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SECTION 1. ENHANCEMENT OF TRANSITION ASSISTANCE PROGRAM. (a) Compulsory Participation in Program.--Effective not later than one year after the date of the enactment of this Act, the Secretary of Defense shall ensure the following: (1) That each member of the Armed Forces who is discharged, released, or otherwise separated from the Armed Forces participates in the Transition Assistance Program of the Department of Defense. (2) That the programs and services of the Transition Assistance Program are accessible by all members of the National Guard and the Reserves. (b) Expansion of Services Under Program.--Effective not later than one year after the date of the enactment of this Act, the Secretary shall ensure that the services provided by the Transition Assistance Program include the following: (1) Employment and training information targeted specifically at the various military grades and at the various military occupational specialties. (2) Expanded emphasis on education benefits available to former members of the Armed Forces, including educational assistance under chapter 33 of title 38, United States Code (commonly referred to as ``Post-9/11 educational assistance''). (3) Enhanced information on the other benefits available to former members of the Armed Forces through the Department of Veterans Affairs. (4) Enhanced training on financial management. (5) Dedicated computer training with TurboTap.org, the VetSuccess Internet website, the USA Jobs Internet website, and any other employment-related Internet websites the Secretary considers appropriate, including, in particular, employment- related Internet websites that focus on jobs for veterans. (6) Dedicated training targeted specifically at members of the National Guard and the Reserves, including training on employment protections and other employment matters under chapter 43 of title 38, United States Code (commonly referred to as the ``Uniformed Services Employment and Reemployment Rights Act''). (c) Reports.-- (1) Report required.--Not later than 6 months after the date of the enactment of this Act, and every six months thereafter for the following 18 months, the Secretary shall submit to the appropriate committees of Congress a report on the status of the implementation of the requirements in subsections (a) and (b). (2) Appropriate committees of congress defined.--In this subsection, the term ``appropriate committees of Congress'' means-- (A) the Committee on Armed Services and the Committee on Health, Education, Labor, and Pensions of the Senate; and (B) the Committee on Armed Services and the Committee on Education and Labor of the House of Representatives. SEC. 2. REPORT ON TRANSITION ASSISTANCE PROGRAM. (a) Report Required.--Not later than 270 days after the date of the enactment of this Act, the Secretary of Defense shall, in consultation with the Secretary of Labor, submit to the appropriate committees of Congress a report on the Transition Assistance Program of the Department of Defense. (b) Elements.--The report required by subsection (a) shall include the following: (1) An analysis of the rates of employment of individuals post-separation from the Armed Forces when compared with the rates of employment of the general population annually since September 11, 2001. (2) A chronological summary of the evolution and development of the Transition Assistance Program since September 11, 2001. (3) A description of efforts to transform the Transition Assistance Program from an end-of-service transition model to a life-cycle model, in which transition is considered throughout the career of a member of the Armed Forces. (4) An analysis of current and future challenges that former members of the Armed Forces face upon entering the civilian workforce, including a survey of the following to identify strengths and shortcomings of the Transition Assistance Program in meeting such challenges: (A) A representational population of transitioning or recently separated members of the Armed Forces. (B) Employers with a history of employing retired or separating members of the Armed Forces. (C) Veterans service organizations and advocacy groups. (5) An assessment of whether the Transition Assistance Program would be more effective if it were provided to members of the Armed Forces earlier before separation. (6) A description of various options for a so-called ``check-in'' mechanism under the Transition Assistance Program in which former members contact the program three months after separation to address questions, including through the use of Internet-based programs. (7) An assessment of the quality of trainers under the Transition Assistance Program. (8) An assessment of the success of marketing the Transition Assistance Program to members of the Armed Forces. (9) Such recommendations as the Secretary of Defense considers appropriate, including recommendations for legislative action, to improve the organization, policies, consistency of quality, and efficacy of the Transition Assistance Program. (c) Appropriate Committees of Congress Defined.--In this section, the term ``appropriate committees of Congress'' means-- (1) the Committee on Armed Services and the Committee on Health, Education, Labor, and Pensions of the Senate; and (2) the Committee on Armed Services and the Committee on Education and Labor of the House of Representatives.

Directs the Secretary of Defense (DOD) to ensure that: (1) each member of the Armed Forces who is discharged, released, or otherwise separated from service participates in DOD's Transition Assistance Program; and (2) such Program's programs and services are also accessible by all members of the National Guard and reserves. Outlines services available under the Program, including employment and training information, available educational benefits, and financial management and computer training. Requires the Secretary to submit to the congressional defense and education committees: (1) four semiannual reports on the status of implementation of requirements under this Act; and (2) a one-time report on the Program's evolution and results.

A Niagara Regional Police officer is in stable condition in a Hamilton hospital after being shot by a fellow police officer in Pelham, Ont., the service says. Around noon Thursday, several officers were investigating a collision that had happened days before in the area of Effingham Street and Roland Road in the rural area southwest of St. Catharines, Ont., when two of the officers became involved in an altercation, according to Monica Hudon, spokesperson for Ontario's Special Investigations Unit. One of the officers, 52 years old, was seriously injured, said Hudon. Niagara police say the officer who was shot has served for 28 years and is assigned to uniform patrol in Welland and Pelham. He was rushed to hospital in critical condition, but the service issued a statement Thursday evening saying he was in stable condition. The officer's name has not been released. SIU working to understand officers' relationship Hudon could not say how many gunshots hit the officer, where he was struck or if both officers fired their weapons. The spokesperson also had no information about what led to the shooting or their relationship. "Understanding what transpired and the relationship between the officers is part of the SIU's investigation," said Hudon. "I can only tell you that there was an altercation, a firearm was discharged and one officer was struck." The SIU is investigating the shooting in Pelham, a rural area southwest of St. Catharines, Ont. (Dave Ritchie/CBC) Niagara Police chief Bryan MacCulloch said he has asked the Ontario Provincial Police to determine if there is any criminal culpability outside of the SIU's scope, but added no arrests have been made in connection with the shooting "The days and weeks ahead will be trying ones for the NRPS family and the community we serve," he said. "I ask for your support for our members and all those involved." The Niagara police said in an earlier statement Thursday afternoon that there was "an incident in Pelham involving members of the NRPS." "An officer has been transported by paramedics from the scene with injuries." The statement did not describe the nature of the incident. "As the SIU is involved we are prohibited from providing further information at this time," the statement reads. Ontario's Special Investigations Unit is looking into a shooting involving two officers on the Niagara's regional police force. (CBC) Ornge Air Ambulance said a person was transported by helicopter from a St. Catharines hospital to a Hamilton trauma centre in critical condition. Eight SIU investigators and three forensic investigators have been assigned to the case, said Hudon, and officers are canvassing for video evidence. "We are interviewing witnesses and we're asking other witnesses to come forward if they have information." The SIU can confirm it is investigating an interaction between two Niagara Regional Police Service officers, and the gunshot wound sustained by one of the officers. SIU spokesperson en route to scene. Scrum early evening. —@SIUOntario Police car was 'head-first in the ditch' She said the SIU has not designated any subject or witness officers as of Thursday evening. The SIU is an arm's-length agency that investigates reports involving police where there has been death, serious injury or allegations of sexual assault. Hudon said the watchdog has investigated cases where a police officer was shot by another officer, but noted it's too early to determine if Thursday's shooting shares any similarities with past incidents. 'The SIU is mandated to investigate any incident involving police where someone has been seriously injured or has died,' a spokesperson said. (Samantha Craggs/CBC) She also made clear why this case falls within the SIU mandate. "The SIU is mandated to investigate any incident involving police where someone has been seriously injured or has died. Whether the person who was injured was a civilian or a police officer, the SIU mandate is invoked anytime that happens." People living in the area said the shooting led to a rush of squad cars racing to the scene in the early afternoon. Robin Zavitz said she was driving home at about 1:30 p.m. when she came across a police blockade. She said she could see a police SUV in a ditch and numerous squad cars nearby. "The police car is head-first in the ditch and there doesn't appear to be any damage to it," Zavitz said. "It's scary when a police officer has been shot in the middle of the day." Zavitz said a police car had been blocking the road at the same intersection all morning, but added the flurry of police activity didn't occur until the early afternoon. Niagara regional police had tweeted earlier Thursday that the road would be partially closed for an investigation. Mike Shepherd was driving home when he came across the same intersection at about 11:30 a.m. An officer was in his squad car, blocking the road eastbound, Shepherd said. "He said they were doing an accident investigation down the road." A little more than an hour later, he said an ambulance rushed by. Niagara's police services board says it's "deeply concerned" about the shooting, but didn't say much else. "The law requires that there be no public comment on or discussion of the specifics of the occurrence under investigation until the SIU investigation and the chief's external review are completed," it said in a statement. But "on behalf of the board," it said, "chair Bob Gale extends our thoughts and prayers to the officers and their families." ||||| A Niagara Regional Police officer is in critical condition after being shot Thursday by a fellow officer during an altercation between the two men in rural Pelham, says provincial Special Investigations Unit spokeswoman Monica Hudon. Hudon made her remarks shortly after 6 p.m. at a news conference on Roland Rd. just west of Effingham St. According to police sources, a Niagara Regional Police officer shot another officer in an argument during a collision reconstruction unit investigation Thursday in rural Pelham, Ont. ( Dave Johnson / The Welland Tribune ) She said officers were in the area conducting a follow-up investigation of a Nov. 12 impaired driving collision in the area of Sulphur Spring Dr. and Roland Rd.. “Around noon there was an interaction between two of the officers and one of the officers was struck by a gunshot,” said Hudon. The nature of the altercation between the officers has not been disclosed. Article Continued Below She couldn’t confirm the number of times the officer, identified by multiple police sources as Const. Nathan Parker, was shot. But those sources told The Standard Parker was hit at least five times. The other officer involved in the incident has been identified by multiple police sources as Det. Sgt. Shane Donovan of the traffic collision reconstruction unit. Hudon did not confirm the officers’ names. Parker is reported to be 52-years-old. Hudon did not have an age for the other officer. Niagara Emergency Medical Services paramedics treated Parker at the scene and transported him to an area hospital. Parker was later transferred by Orgne air ambulance to Hamilton General Hospital where he was listed in critical condition. She also asked that anyone who may have video of the shooting to share it with the SIU or upload it to the SIU website. The SIU investigates all incidents of serious injury or death involving police in Ontario. “Understanding what transpired and the relationship between the two officers is part of the investigation. I can only tell you there was an altercation and a firearm was discharged,” Hudon said. Article Continued Below Asked the exact location of the incident, she said it was in the area of Effingham St. and Roland Rd. “It’s very early in the investigation … we’re in the preliminary stages and it will take time to gather all of the details.” No charges have been laid. Niagara OPP officers were blocking the area around the shooting and Hudon said they were holding the scene for the SIU. There was no word on when Effingham, blocked between Sixteen Rd. and Wessel Dr., and Roland, blocked between Sulphur Spring and just west of Effingham, would be reopened. In a release, NRP Chief Bryan MacCulloch said in the spirit of transparency, he asked the OPP to determine if there was any criminal culpability outside of the SIU’s scope. “The days and weeks ahead will be trying ones for the regional police family and the community we serve. I ask for your support for our members and all those involved,” MacCulloch said. In a release earlier in the day, police said because the SIU is involved the service is prohibited from providing further information. Parker has a long and troubled history with the NRP, having faced at least four disciplinary hearings, three of which involved violence. In 2015, Parker was docked 120 hours’ pay after pleading guilty to discreditable conduct and unnecessary use of force against a prisoner under the Police Services Act. In 2012, Parker was docked 60 hours of pay after pleading guilty to discreditable conduct after pursuing his own investigation into a commanding officer who had been cleared of wrongdoing from a previous incident. Parker was found guilty of using unnecessary force in 2011 and docked 90 days’ pay for arresting a cyclist without cause in 2008. And in 2007, Parker lost a week’s pay after he was found guilty in a disciplinary hearing for pepper-spraying a prisoner who was handcuffed and restrained in the back seat of a cruiser in 2005. The impaired driving collision investigation scene the two officers were at involved an incident that happened Nov. 12 at about 10:54 p.m. It was determined a 19-year-old Pelham man was operating a 2016 Ford Focus with two 19-year-old female passengers when he was unable to negotiate a curve and lost control, entered a ditch and struck a tree. The vehicle burst into flames, and the fire was extinguished by the Pelham fire department. The vehicle was destroyed. The man was able to get out of the car, but the two passengers had to be rescued from the burning vehicle by a local resident and a passing motorist. They both sustained serious injuries, with one later being transported to an out-of-region trauma centre for treatment of critical injuries. Mike Zettel, a reporter with The Tribune’s sister paper Niagara This Week, spoke with Donovan Thursday morning near the investigation scene. “He was very friendly and very helpful,” said Zettel. “Often when a reporter gets to a scene like that, the officer you talk to is just there at the roadblock and might not know anything about the incident. But I got lucky. (Donovan) was able to explain what was going on.” The police service’s union, Niagara Region Police Association, has mobilized to provide support to the impacted officers, police staff and their families. Association president Cliff Priest, who is also an NRP officer, said there haven’t been many cases of NRP officers being shot while on duty, but each one is difficult for the entire service. Dave Johnson is a reporter for The Welland Tribune. Grant LaFleche is an Investigative journalist at the St. Catharines Standard. Read more about: ||||| It was a dark day for policing in Niagara Region and the rest of the province. A Niagara Regional Police constable was in grave condition after being shot in an altercation with a fellow officer who outranked him. The shooting, sources say, followed a “heated argument” and “fist fight” between a constable and a detective sergeant responding to a traffic accident around Roland Rd. and Effingham St. in Pelham, 22 kilometres south of St. Catharines. Wounded Const. Nathan Parker was in hospital fighting for his life Thursday while Det.-Sgt. Shane Donovan was determined to be the subject officer by the province’s Special Investigations Unit (SIU). Sources told the Toronto Sun that Donovan was losing a fight before the shooting. Up to five bullets were allegedly discharged from a police officer’s gun. There have been accidental shootings of police officers by their partners but in his more than 50 years as a Toronto Police officer, newly-named OPP Commissioner Ron Taverner, currently a superintendent, said he can’t recall ever hearing of a case where an officer shot a peer. “It’s very sad and our thoughts are with the Niagara Police today,” he said. The shooting victim, sources say, did not pull a weapon. The SIU confirmed it is investigating an interaction between two Niagara Regional Police Service officers, and one of the cops suffered a gunshot wound. There have been no reports so far of anybody being taken into custody and the SIU is leading the investigation. The SIU can confirm it is investigating an interaction between two Niagara Regional Police Service officers, and the gunshot wound sustained by one of the officers. SIU spokesperson en route to scene. Scrum early evening. — SIU (@SIUOntario) November 29, 2018 “The SIU can confirm it is investigating an interaction between two Niagara Regional Police Service officers, and the gunshot wound sustained by one of the officers,” the SIU said in a tweet. Niagara Regional Police later released a statement explaining the injured officer’s condition has been upgraded to stable. “In the spirit of transparency, I have asked the Ontario Provincial Police to determine if there is any criminal culpability outside of the SIU’s scope,” Chief Bryan MacCulloch said in the statement. “The days and weeks ahead will be trying ones for the NRPS family and the community we serve,” MacCulloch said. “I ask for your support for our members and all those involved.” Sources say there may have been some “bad blood” between the two officers involved. Sources told the Toronto Sun Parker has had a troubled past of police act charges and discipline issues. Policing insiders say Parker racked up Police Services Act convictions, including for violence against prisoners, during his career. He was docked 120 hours in 2015 after pleading guilty to discreditable conduct and unnecessary use of force against a prisoner. In 2012, he was docked 60 hours pay after conducting his own investigation into a commanding officer who had been cleared of wrongdoing from a previous incident. In 2011, Parker was found guilty of using unnecessary force and in 2008, he was docked 90 days pay for arresting a cyclist without cause. In 2007, Parker lost a week’s pay after he was found guilty in a disciplinary hearing for pepper-spraying a handcuffed and restrained prisoner in the backseat of a cruiser in 2005. Police sources say the constable was shot at least three times. Local residents said the incident led to a rush of squad cars racing to the scene in the early afternoon. Robin Zavitz, who lives in the area, said she was driving home around 1:30 p.m. when she came across a police blockade. She said she could see a police SUV in the ditch and numerous squad cars nearby. “The police car is head-first in the ditch and there doesn’t appear to be any damage to it,” Zavitz said. “It’s scary when a police officer has been shot in the middle of the day.” Zavitz said a police car had been blocking the road at the same intersection all morning, but added the flurry of police activity didn’t occur until the early afternoon. Mike Shepherd was driving home earlier in the day when he came across the same intersection around 11:30 a.m. An officer was in his squad car, blocking the road eastbound, Shepherd said. “He said they were doing an accident investigation down the road,” Shepherd added. A little more than an hour later, he said he saw an ambulance rush by. — With files from The Canadian Press [email protected] [email protected]

– A Canadian police officer is hospitalized in stable condition after a fellow cop shot him numerous times during a Thursday altercation, reports the CBC. Det. Sgt. Shane Donovan and Const. Nathan Parker of Niagara Regional Police Services were conducting a follow-up investigation at the scene of a DUI crash in Pelham, Ont., around noon when an argument arose, reports the Toronto Star. It's not clear what the dispute was about, but the Toronto Sun reports that it escalated into a fist fight before Parker was shot at least three times. Ontario Provincial Police Commissioner Ron Taverner described the apparent chain of events as unheard of. "It's very sad and our thoughts are with the Niagara Police today," he said. Per the Sun, there may have been "bad blood" between Donovan and Parker, who pleaded guilty to discreditable conduct and unnecessary use of force against a prisoner in 2015, in the latest of several offences since 2005. In 2012, Parker was also penalized for conducting his own investigation into a commanding officer who'd previously been cleared of wrongdoing.

traditionally , a string is a sequence of letters taken from some alphabet @xmath4 . since we discuss indeterminate strings " in this paper , we begin by generalizing the definition as follows : [ defn - string ] a with base alphabet @xmath4 is either empty or else a sequence of nonempty subsets of @xmath4 . a 1-element subset of @xmath4 is called a letter ; otherwise it is . similarly , a nonempty string consisting only of regular letters is , otherwise . the empty string is regular . all alphabets and all strings discussed in this paper are finite . we denote by @xmath7 the set of all nonempty subsets of @xmath4 , with @xmath8 and @xmath9 . on a given alphabet @xmath4 , there are altogether @xmath10 distinct nonempty strings of length @xmath11 , of which @xmath12 are regular . indeterminate strings were first introduced in a famous paper by fischer & paterson @xcite , then later studied by abrahamson @xcite . in the last ten years or so , much work has been done by blanchet - sadri and her associates ( for example , @xcite ) on `` strings with holes '' that is , strings on an alphabet @xmath4 augmented by a single letter consisting of the @xmath5-element subset of @xmath4 . the monograph @xcite summarizes much of the pioneering work in this area . for indeterminate strings in their full generality , the third and fourth authors of this paper have collaborated on several papers , especially in the contexts of pattern - matching @xcite and extensions to periodicity @xcite . [ defn - match ] two elements @xmath13 of @xmath7 are said to ( written @xmath14 ) if they have nonempty intersection . two strings , ( @xmath15 ) if they have the same length and all corresponding letters match . thus two regular letters match if and only if they are equal . but note that for indeterminate letters @xmath16 , it may be that @xmath14 and @xmath17 , while @xmath18 : think @xmath19 . [ defn - border ] if a string can be written @xmath20 and @xmath21 for nonempty strings , , where @xmath22 , then is said to have a of length @xmath23 . note that choosing @xmath24 yields the empty border of length @xmath25 . the of a string @xmath26 $ ] is an integer array @xmath27 $ ] such that @xmath28 $ ] is the length of the longest border of @xmath29 $ ] . for regular strings , the border array has the desirable property , used in pattern - matching algorithms for more than 40 years @xcite , that any border of a border of is also a border of thus actually specifies every border of every prefix of . for indeterminate strings , however , due to the intransitivity of the match operation , this is not true @xcite ; for example , @xmath30 has a border of length 2 ( @xmath31 ) , and both borders @xmath32 and @xmath33 have a border of length 1 ( @xmath34 and @xmath35 , respectively ) , but has no border of length 1 . to make sense of such situations , the `` prefix array '' becomes important : [ defn - prefix ] the of a string @xmath26 $ ] is the integer array @xmath0 $ ] such that for every @xmath36 , @xmath37 $ ] is the length of the longest prefix of @xmath38 $ ] that matches a prefix of @xmath39 . thus for every prefix array , @xmath1 = n$ ] . apparently the first algorithm for computing the prefix array occurred as a routine in the repetitions algorithm of main & lorentz @xcite ; see also @xcite . a slightly improved algorithm is given in ( * ? ? ? * section 8.4 ) , and two algorithms for computing a `` compressed '' prefix array are described in @xcite . for regular strings the border array and the prefix array are equivalent : it is claimed in @xcite , and not difficult to verify , that there are @xmath40-time algorithms to compute one from the other . on the other hand , as shown in @xcite , for indeterminate strings the prefix array actually allows all borders of every prefix to be specified , while the border array does not @xcite . thus the prefix array provides a more compact and more general mechanism for identifying borders , hence for describing periodicity , in indeterminate strings . in the above example ( [ noborder ] ) , the prefix array of is @xmath41 , telling us that @xmath42 \match \s{u}[1 .. 2]$ ] ( has a border of length 2 ) , hence that @xmath43 \match \s{u}[1]$ ] ( prefix @xmath44 $ ] has a border of length 1 ) and @xmath45 \match \s{u}[2]$ ] ( suffix @xmath42 $ ] has a border of length 1 ) , but , since @xmath46 = 0 $ ] , also that has no border of length 1 . @xcite describes an algorithm that computes the prefix array of any indeterminate string ; in this paper we consider the `` reverse engineering '' problem of computing a string corresponding to a given `` feasible '' array that is , any array that could conceivably be a prefix array : [ defn - feasible ] an integer array @xmath0 $ ] such that @xmath1 = n$ ] and , for every @xmath2 , @xmath47 \le n\+ 1\- i,\ ] ] is said to be . a feasible array that is a prefix array of a regular string is said to be . we will often use the condition @xmath48 \le n\+ 1 $ ] , equivalent to ( [ condition - feasible ] ) . note that there are @xmath49 distinct feasible arrays of length @xmath11 . recalling that there are @xmath50 distinct strings of length @xmath11 for a fixed alphabet size @xmath5 , and applying stirling s inequality @xcite @xmath51 where @xmath52 is the base of the natural logarithm , we see that ( for fixed @xmath5 ) the number of feasible arrays exceeds the number of strings whenever @xmath11 is large enough that @xmath53 the first reverse engineering problem was introduced in @xcite , where a linear - time algorithm was described to compute a lexicographically least string whose border array was a given integer array or to return the result that no such string exists . there have been many such results published since ; for example , @xcite . in @xcite an @xmath54 time algorithm is described to solve the reverse engineering problem for a given feasible array @xmath0 $ ] ; that is , whenever is regular , computing a lexicographically least regular string corresponding to ; and , whenever is not regular , reporting failure . in section [ sect - indet ] , notwithstanding ( [ asymp ] ) , we prove the surprising result that every feasible array is in fact a prefix array of some string ( on some alphabet ) ; further , we characterize the minimum alphabet size of a regular string corresponding to a given prefix array in terms of the largest clique in the negative `` prefix '' graph @xmath55 . we go on to give necessary and sufficient conditions that a given prefix array is regular . section [ sect - graphs ] establishes the duality between strings ( whether regular or indeterminate ) and labelled undirected graphs ; also it provides a characterization of the minimum alphabet size of an indeterminate string in terms of the number of `` independent '' maximal cliques in the associated graph " @xmath6 . section [ sect - conc ] outlines future work . we begin with an immediate consequence of definition [ defn - prefix ] : [ lemm - easy ] let @xmath26 $ ] be a string . an integer array @xmath0 $ ] is the prefix array of @xmath39 if and only if for each position @xmath36 , the following two conditions hold : * @xmath56\big ] \match \s{x}\big[i .. i+ \s{y}[i]-1\big]$ ] ; * if @xmath57 \le n$ ] , then @xmath58 + 1\big ] \not\match \s{x}\big[i + \s{y}[i]\big]$ ] . we now prove the main result of this section . [ lemm - feas ] every feasible array is the prefix array of some string . consider an undirected graph @xmath59 whose vertex set @xmath60 is the set of positions @xmath61 in a given feasible array @xmath62 . the edge set @xmath63 consists of the 2-element subsets @xmath64 such that @xmath65 ; \ k = i+h-1\ ] ] for every @xmath2 . we then define as follows : for each non - isolated vertex @xmath66 , let @xmath67 $ ] be the set of edges incident with @xmath66 ; for each isolated vertex @xmath66 , let @xmath67 $ ] be the loop @xmath68 . let @xmath69 where @xmath70 is the set of loops . we claim that @xmath62 is the prefix array of @xmath26 $ ] . to see this , note that for an index @xmath66 such that @xmath37>0 $ ] , lemma [ lemm - easy](a ) is satisfied by construction . then suppose that for some @xmath37 > 0 $ ] and @xmath71 \le n$ ] , @xmath58\+ 1\big ] \match \s{x}\big[i\+ \s{y}[i]\big]$ ] . but this contradicts lemma [ lemm - easy](b ) , and so @xmath72\+ 1\big ] \not\match \s{x}\big[i\+ \s{y}[i]\big].\ ] ] in case @xmath37 = 0 $ ] , lemma [ lemm - easy](a ) is satisfied vacuously . moreover , @xmath66 is isolated and thus @xmath67 = \{i , i\}$ ] , which does not match @xmath73 $ ] ; consequently , lemma [ lemm - easy](b ) is again satisfied . therefore , @xmath62 coincides with the prefix array of @xmath39 , which is a string over the set @xmath7 of subsets of @xmath4 . + the construction described in this proof yields a string whose prefix array is , but is only one string among many . for example , given the feasible array @xmath74 , this construction yields ( temporarily simplifying the notation ) edges @xmath75 and loops @xmath76 . relabelling these seven edges / loops as @xmath77 respectively , we construct as described in the proof of lemma [ lemm - feas ] : @xmath78 an indeterminate string , when in fact is also the prefix array of the regular string @xmath79 ( and so , by definition [ defn - feasible ] , itself regular ) . [ defn - g ] let @xmath80 be a labelled graph with vertex set @xmath81 consisting of positions in a given feasible array @xmath82 in @xmath83 we define , for @xmath2 , two kinds of edge ( compare lemma [ lemm - easy ] ) : * for every @xmath84 $ ] , @xmath85 is called a ; * @xmath86,i\+ \s{y}[i])$ ] is called a , provided @xmath71 \le n.$ ] @xmath87 and @xmath88 denote the sets of positive and negative edges , respectively . we write @xmath89 , @xmath90 , @xmath91 , and we call @xmath83 the of @xmath62 . if @xmath39 is a string having @xmath62 as its prefix array , then we also refer to @xmath83 as the prefix graph of @xmath39 . + + figures [ graph - ex-1-p][graph - ex-2-n ] show the prefix graphs for @xmath92 from definition [ defn - g ] it is clear that [ rem - py ] for every feasible array , there exists one and only one prefix graph @xmath83 , which therefore may be written @xmath93 ; moreover , @xmath94 if and only if @xmath95 . recall that a graph @xmath96 is said to be if every pair of vertices in @xmath60 is joined by a path in @xmath63 . a ( or , for short ) of @xmath97 is a subgraph @xmath98 formed on a largest subset @xmath99 such that every pair of vertices @xmath100 is joined by a path formed from edges @xmath101 . the graph @xmath102 of figure [ graph - ex-1-p ] has two disjoint connected components , while that of figure [ graph - ex-2-p ] has only one . the basic properties of the prefix graph @xmath93 of a feasible array @xmath0 $ ] are as follows : [ lemm - g ] let @xmath103 be the prefix graph corresponding to a given feasible array . * @xmath87 and @xmath104 are disjoint and @xmath105 where @xmath106 is the number of indices @xmath36 for which @xmath71 = n+1.$ ] for every @xmath2 , either @xmath107 or @xmath108 . * if @xmath109 , where @xmath110 , then @xmath111 = i\- 1 $ ] , and for every @xmath112 , @xmath113 . * @xmath62 is regular if and only if every edge of @xmath55 joins two vertices in disjoint connected components of @xmath114 . * first fix @xmath66 and consider edges @xmath64 , where @xmath115 . if @xmath116 is such an edge , then the edges in @xmath87 must satisfy @xmath117 and therefore are distinct from @xmath118 . this shows that @xmath87 and @xmath104 are disjoint . secondly , @xmath105 since there is exactly one negative edge for each of the possible values of @xmath66 , except those for which @xmath71 = n\+ 1 $ ] . finally , it is easily seen from definition [ defn - g ] that @xmath119 is a positive edge if @xmath37 $ ] is positive , whereas @xmath119 is a negative edge if @xmath37=0 $ ] . * the first statement follows from rewriting definition [ defn - g](b ) with @xmath120 $ ] , the second directly from definition [ defn - g](a ) . * suppose that every negative edge joins two vertices in disjoint connected components of @xmath114 . form a regular string @xmath39 as follows : for each component @xmath121 of @xmath114 , assign a unique identical letter , say @xmath122 , to all positions @xmath67 $ ] for which @xmath123 . we show that @xmath62 is the prefix array of @xmath124 $ ] and therefore that @xmath62 is regular . fix a value @xmath2 . for any @xmath125 such that @xmath126 $ ] , @xmath127 is a positive edge . thus @xmath125 and @xmath128 are in the same component of @xmath114 , and hence @xmath129 = \s{x}[j+i-1]$ ] . we also note that @xmath130 + 1 , \s{y}[i]+i)$ ] is a negative edge ( provided @xmath37\+ i \le n$ ] ) . if so , then by hypothesis @xmath37 + 1 $ ] and @xmath37+i$ ] lie in disjoint components of @xmath114 , so that , by the uniqueness of @xmath122 , @xmath131 + 1\big ] \not\match \s{x}\big[\s{y}[i]+i\big]$ ] . this is precisely what we need in order to conclude that @xmath62 is the prefix array of @xmath124 $ ] . since is regular , so is , as required . + * suppose that is regular , therefore the prefix array of a regular string @xmath39 . now consider any negative edge @xmath132 of the prefix graph @xmath83 of , so that by lemma [ lemm - easy](b ) @xmath133 \not\approx \s{x}[q]$ ] . if @xmath134 and @xmath135 were in the same component of @xmath114 , we would have by lemma [ lemm - easy](a ) a path in @xmath114 joining @xmath134 to @xmath135 consisting of edges @xmath64 such that @xmath136 \match \s{x}[k]$ ] . by the regularity of , this requires @xmath136 = \s{x}[k]$ ] , so that @xmath133 = \s{x}[q]$ ] , a contradiction . from definition [ defn - g ] , we see that @xmath137 can be as small as @xmath25 ( for example , when @xmath138 ) or as large as @xmath139 ( when @xmath140 ) . from lemma [ lemm - g](b ) we see that many of the edges in @xmath87 can be deduced from those in @xmath104 . in fact , if we add an extra node @xmath141 and also , in the cases @xmath142 for which @xmath71 = n\+ 1 $ ] that is , whenever @xmath39 has a border of length @xmath37 = n\+ 1\- i$ ] , add the edges @xmath143 , n+1)$ ] to @xmath104 , then all of @xmath87 can be deduced from @xmath104 . let us call this graph with the additional node and edges the and denote it by @xmath144 with corresponding edge sets @xmath145 and @xmath146 . by lemma [ lemm - g](a ) , @xmath146 consists of exactly @xmath147 edges , which together determine @xmath148 edges in @xmath87 . of course the converse is also true : @xmath87 determines @xmath146 . hence , from remark [ rem - py ] , either @xmath114 or @xmath149 is sufficient to determine a corresponding prefix array . however , a bit more can be said . from lemma [ lemm - g](b ) we see that every edge @xmath150 determines the value @xmath111 $ ] of a position @xmath151 in . thus a simple scan of can identify all positions @xmath152 that are _ not _ determined by @xmath104 ; for all such @xmath152 , it must be true that @xmath153 = n\- h\+ 1 $ ] . in other words @xmath104 determines @xmath146 . writing @xmath154 to mean that @xmath155 can be computed from @xmath156 , and _ vice versa _ , we may summarize this discussion as follows : [ remk - equiv ] @xmath157 : the prefix array and the negative prefix graph provide the same information and so determine the same set of @xmath158not necessarily regular@xmath159 strings . recall @xcite that a in a graph @xmath97 is a complete subgraph @xmath160 of @xmath97 on @xmath161 vertices , while the @xmath162 is the order @xmath161 of the largest clique . we say that a @xmath161-clique is if it is not a subclique of any @xmath163-clique . note that , since every isolated vertex is a complete subgraph , @xmath164 . [ defn - regular - g ] if @xmath62 is a regular feasible array , then its prefix graph @xmath93 is also said to be . we use these ideas to characterize the minimum alphabet size of any regular string with a given prefix graph @xmath83 . consider the edges @xmath165 , of regular @xmath55 , in ascending order of @xmath125 . suppose without loss of generality that is defined on the alphabet @xmath4 of consecutive positive integers ( so that the ordering of is with respect to @xmath4 ) . figure [ alg - greedy ] describes an on - line algorithm assign that , from the sorted list of edges in @xmath55 , computes a lexicographically least string on @xmath166 letters whose prefix graph is @xmath83 . = 0.5in;=3000 assign @xmath167 radix sort the edges @xmath168 , @xmath169 , of @xmath55 by @xmath125 . @xmath170 \la 0 $ ] @xmath171 @xmath11 @xmath172 @xmath173 @xmath129 \la 1 $ ] @xmath174 @xmath175 @xmath176\big ] \la 1 $ ] @xmath177 @xmath178 @xmath179 = 1 $ ] @xmath180 @xmath181 @xmath182 \la 0 $ ] @xmath174 @xmath175 @xmath176\big ] \la 0 $ ] @xmath129 \la \ell$ ] algorithm assign maintains a bit vector @xmath183 that , for each @xmath125 , specifies the letters @xmath67 $ ] that have occurred at positions @xmath150 that is , @xmath184\big ] = 1 $ ] . observe that a new letter @xmath185 is added if and only if vertex @xmath125 has an edge to vertices representing _ all _ previous letters @xmath186 . this is true for every @xmath187 . thus letter @xmath185 is introduced if and only if there are already @xmath161 vertices that form a clique in @xmath55 . consequently the number of letters used by the algorithm to form is exactly @xmath166 . note also that the letter assigned at each position @xmath125 is least with respect to the preceding letters , whether the letter is a new one in the string or not . since the letters are introduced from left to right and never changed , must therefore be lexicographically least with respect to @xmath55 . note further that , since position @xmath125 in the lexicographically least is determined for @xmath188 based solely on preceding positions @xmath169 , it suffices to use @xmath55 rather than the augmented @xmath149 , in accordance with remark [ remk - equiv ] . next consider the time requirement of algorithm assign . since we know from lemma [ lemm - g](a ) that @xmath55 has at most @xmath147 edges , it follows that the radix sort can be performed in @xmath54 time . for the same reason , within the loop , formation of the set @xmath189 also has an overall @xmath54 time requirement . the processing that updates the bit vector @xmath183 , in order to determine the least letter @xmath190 to be assigned to @xmath129 $ ] , requires @xmath191 time , where @xmath175 is the size of @xmath189 , in order to set both @xmath176\big ] \la 1 $ ] and @xmath176\big ] \la 0 $ ] ; in addition the loop requires @xmath192 time in the worst case . since @xmath193 , it follows that the sum of all @xmath194 is @xmath54 , and so the overall time requirement of this processing is @xmath54 . [ lemm - alg ] for a regular prefix graph @xmath83 on @xmath11 vertices , algorithm assign computes in @xmath54 time a lexicographically least string on @xmath166 letters whose prefix graph is @xmath83 . we need to show that the string computed by the algorithm is indeed consistent with @xmath83 ( that is , by remark [ remk - equiv ] , the corresponding prefix array ) . observe that @xmath189 is always empty for @xmath195 , so that therefore the initial assignment @xmath73 \la 1 $ ] is consistent with the subgraph @xmath196 on a single vertex . suppose then that @xmath197 $ ] has been computed by assign for some @xmath198 so as to be consistent with with the subgraph @xmath199 on vertices @xmath200 . for the addition of vertex ( position ) @xmath125 , there are three possibilities : @xmath201 . : : in this case , @xmath129 \la 1 $ ] , the least letter , so that @xmath129 = \s{x}[1]$ ] , and therefore @xmath202 $ ] remains consistent with @xmath203 . * @xmath189 gives rise to @xmath161 distinct letters . * : : here @xmath129 \la t\+ 1 $ ] , a new letter . since this is the first occurrence of @xmath185 in , and since there is no alternative , therefore @xmath202 $ ] is again consistent with @xmath204 and has only the empty border . * @xmath189 gives rise to @xmath205 distinct letters . * : : from the set @xmath189 we know that @xmath197 $ ] has exactly @xmath175 borders not continued to @xmath202 $ ] . the longest of these borders is @xmath206 $ ] . there may be a border of @xmath197 $ ] that is on the other hand actually continued to @xmath202 $ ] . if not , then the assignment @xmath129 \la \ell$ ] is consistent with @xmath204 , where @xmath190 is the least letter not precluded by @xmath189 . suppose then that there exists a border @xmath29 = \s{x}[j\- i\+ 1 .. j]$ ] , @xmath207 . note that while there may be more than one such border , @xmath67 $ ] must be the same for each one , since we suppose that is regular . furthermore , @xmath67 $ ] was chosen by the algorithm to be a minimum letter @xmath208 with respect to the prefix @xmath209 $ ] ; since @xmath210 = \s{x}[1 .. i\- 1]$ ] , the choice of a minimum letter with respect to @xmath197 $ ] must yield @xmath211 , hence also consistent with @xmath204 . therefore by induction the lexicographically least string @xmath202 $ ] is consistent with @xmath204 . we have argued above that is lexicographically least , also that the time requirement of the algorithm is @xmath54 . thus the lemma is proved . notice that the alphabet size determined by assign is least possible , given @xmath83 . instead of assigning letters to positions in , we could just as well have labelled vertices of @xmath83 with these letters ; thus we have [ cor - clique ] the class of regular negative prefix graphs @xmath55 has the property that the chromatic number @xmath158minimum alphabet size@xmath159 @xmath212 for every graph in the class . this property does not hold in general ; in @xcite , for example , it is shown that there exist triangle - free graphs @xmath97 ( @xmath213 ) with arbitrarily large chromatic number . to get a sense of the labelling , consider the following regular prefix array @xmath214 whose corresponding @xmath215 has edges ( sorted as in algorithm assign ) @xmath216 @xmath215 has a single maximal clique , @xmath217 , on four vertices , and the corresponding lexicographically least string is @xmath218 note that @xmath219 contains in addition the edge @xmath220 not required for the lexicographically least . now consider @xmath161-cliques @xmath221 ( not necessarily maximal ) in regular prefix arrays @xmath55 for which @xmath222 , together with regular strings whose prefix graph is @xmath83 . a 1-clique corresponds to a prefix @xmath223 of , where @xmath224 is some ( say , smallest ) letter . then for every 2-clique @xmath225 in @xmath55 , there must exist a corresponding prefix of such that @xmath226 where @xmath227 . similarly , for every 3-clique @xmath228 in @xmath55 , there exists a corresponding prefix of such that @xmath229 where @xmath230 are identical but for distinct rightmost letters @xmath231 and @xmath232 , respectively . in general , for every @xmath161-clique @xmath233 in @xmath55 , there exists a corresponding prefix of such that @xmath234 where @xmath235 are prefixes identical but for rightmost letters @xmath236 and @xmath237 , respectively . thus every @xmath161-clique in regular @xmath55 corresponds to a prefix of the corresponding string that has @xmath238 borders of lengths @xmath239 . the length of this prefix can be minimized by choosing every @xmath240 , @xmath241 , to be empty , so that the strings @xmath242 double in length at each step : hence there exists a prefix graph on @xmath243 vertices ( or , equivalently , a feasible array of length @xmath243 ) whose corresponding strings can not be implemented on less than @xmath161 letters . thus we are able to verify a result given in ( * ? ? ? * proposition 8) : [ lemm - log ] for a given regular feasible array @xmath0 $ ] , a regular string whose prefix array is @xmath62 can be constructed using at most @xmath244 letters . @xcite describes a lemma more complex than algorithm assign , but that does not require a regular prefix array as input : a nonregular feasible array is rejected at the first position detected . we conclude this section with two equivalent necessary and sufficient conditions for to be regular . a string is said to be ( indet , for short ) if and only if its prefix array is not regular . recall from definition [ defn - feasible ] that a feasible array is regular if and only if it is a prefix array of a regular string . thus , for example , the string ( [ reg ] ) , although certainly indeterminate , is not indet because it is consistent with the feasible array @xmath74 that is a prefix array of the regular string @xmath79 . if on the other hand is not regular , then as we have seen ( lemma [ lemm - g](c ) ) there must exist a position @xmath66 such that @xmath67 \match \s{x}[r]$ ] and @xmath67 \match \s{x}[s]$ ] , while @xmath245 \not\match \s{x}[s]$ ] , for some positions @xmath175 and @xmath106 ; in such a case we say that @xmath67 $ ] is . ( in terms of the prefix graph @xmath83 , @xmath246 . ) we state two versions of what is essentially the same lemma ; we prove the second . [ lemm - indet ] suppose that @xmath26 $ ] is a nonempty string with prefix array @xmath62 . then for @xmath36 , @xmath67 $ ] is indet ( and so therefore also ) if and only if there exist positions @xmath175 and @xmath247 such that @xmath248 = r\- 1 $ ] and one of the following holds : * @xmath249 \ge i,\ \s{y}[s\- i\+ 1 ] \ge i$ ] @xmath250 ; * @xmath251 \ge r,\ \s{y}[s\- i\+ 1 ] \ge i$ ] @xmath252 ; * @xmath251 \ge r,\ \s{y}[i\- s\+ 1 ] \ge s$ ] @xmath253 . + + + [ lemm - indeta ] suppose that @xmath26 $ ] is a nonempty string with prefix array @xmath62 . then for @xmath36 , @xmath67 $ ] is indet ( and so therefore also ) if and only if there exist positions @xmath175 and @xmath106 such that one of the following holds : * @xmath254 \ge i,\ \s{y}[s ] \ge i,\ \s{y}[s\- r\+ 1 ] = i\+ r\- 2 $ ] ; * @xmath255 > i,\ \s{y}[s ] \ge i,\ \s{y}[s\+ r\- 1 ] = i\- r$ ] ; * @xmath255 > i,\ s\+ \s{y}[s ] > i,\ \s{y}[s\- r\+ 1 ] = i\- s$ ] . if @xmath67 $ ] is indet , then there must exist positions @xmath256 and @xmath257 such that @xmath67 \match \s{x}[r'],\ \s{x}[i ] \match \s{x}[s'],\ \s{x}[r ' ] \not\match \s{x}[s']$ ] . conversely , if such @xmath256 and @xmath257 exist , then @xmath67 $ ] is indet . without loss of generality , suppose that @xmath258 . then three cases arise depending on the relative values of the distinct integers @xmath259 ( see figure [ fig-3cases ] ) : * @xmath260 since @xmath67 \match \s{x}[r']$ ] and @xmath261 , it follows that @xmath29 \match \s{x}[r'\- i\+ 1 .. r']$ ] , hence that @xmath262 \ge i$ ] ; similarly , @xmath263 \ge i$ ] . since @xmath264 \not\match \s{x}[s']$ ] and @xmath265 , therefore @xmath266 = r'\- 1 $ ] . setting @xmath267 yields the desired result . * @xmath268 since @xmath67 \match \s{x}[r']$ ] and @xmath269 , therefore @xmath270 \match \s{x}[i\- r'\+ 1 .. i]$ ] , and so @xmath271 \ge r'$ ] ; as in ( a ) , @xmath263 \ge i$ ] . also as in ( a ) , @xmath266 = r'\- 1 $ ] . setting @xmath272 yields the result . * @xmath273 as in ( b ) , @xmath271 \ge r'$ ] ; similarly , @xmath274 \ge s'$ ] . as in ( a ) and ( b ) , @xmath266 = r'\- 1 $ ] . setting @xmath275 yields the result . here we extend the ideas of section [ sect - indet ] to establish a remarkable connection between labelled graphs and indeterminate strings . recall that a graph is if and only if it is undirected and contains neither loops nor multiple edges . we define the , @xmath276 , of a string to be the simple graph whose vertices are positions @xmath277 in @xmath39 and whose edges are the pairs @xmath278 such that @xmath67 \approx \s{x}[j]$ ] . thus @xmath279 identifies _ all _ the matching positions in , not only those determined by the prefix array . on the other hand , we may think of each pair @xmath280 as a edge , @xmath67 \not\approx \s{x}[j]$ ] . thus @xmath281 determines all the pairs of positions in that match or do not match each other . it should be noted here that while @xmath6 determines the matchings of positions in , it does not uniquely determine the alphabet of . for example , @xmath282 describes @xmath283 as well as @xmath284 thus a given simple graph @xmath285 with @xmath11 vertices can be the associated graph of distinct strings . another way to generate additional strings is by permuting the vertex labels . given any _ un_labelled @xmath97 , we can generate strings @xmath26 $ ] by labelling the @xmath11 vertices @xmath60 of @xmath97 with integers @xmath61 , and forming a string @xmath39 of which @xmath97 , with this labelling , is the associated graph . thus an unlabelled graph @xmath97 corresponds to a set of strings determined by the @xmath49 possible labellings of @xmath60 . for instance , given the graph ( 100,20)(0,0 ) ( 25,10)(30,10)(1,0)30(65,10 ) ( 85,10 ) there are six possible labellings , three of which , for example ( 280,20)(0,0 ) ( 0,10)(5,10)(1,0)30(40,10 ) ( 60,10 ) ( -2.5,7)1(37.5,7)2(57.5,7)3 ( 100,10)(105,10)(1,0)30(140,10 ) ( 160,10 ) ( 97.5,7)2(137.5,7)3(157.5,7)1 ( 200,10)(205,10)(1,0)30(240,10 ) ( 260,10 ) ( 197.5,7)3(237.5,7)1(257.5,7)2 can be chosen to lead to distinguishable regular strings @xmath286 , respectively . in this case the other three labellings determine the same three strings . consider a given string . suppose that for some position @xmath287 , @xmath288 $ ] matches @xmath289 , \s{x}[i_2 ] , \ldots , \s{x}[i_k]$ ] for some @xmath290 , and matches no other elements of . we say that position @xmath291 is if and only if the entries in positions @xmath292 match each other pairwise . if every position in is essentially regular , we say that itself is . for example , it is easy to verify that @xmath293 though indeterminate , is essentially regular with prefix array @xmath74 . on the other hand , string ( [ reg ] ) , @xmath294 also with prefix array , is not essentially regular . we have [ lemm - union ] a string is essentially regular if and only if the associated graph @xmath6 of is a disjoint union of cliques . thus combinatorics on ( regular , essentially regular ) words is the study of labelled collections of cliques . for example , for @xmath140 , the associated graph @xmath6 is simply the complete graph @xmath295 ; while for such that @xmath67 \match \s{x}[j]\ \rightarrow i = j$ ] , @xmath6 is @xmath11 copies of @xmath296 . more generally , for essentially regular , the number of disjoint cliques in @xmath6 is just the number of distinct letters in a regular string having the same associated graph as , and the order of each clique is the number of times the corresponding letter occurs . recall that a ( sometimes abbreviated mc ) @xmath160 in a graph @xmath96 is a clique that is not a subgraph of any other clique in @xmath97 . thus if @xmath160 is maximal , then for every vertex @xmath125 not in @xmath160 , there exists some vertex @xmath66 of @xmath160 such that @xmath297 . note that every vertex of @xmath97 must belong to at least one maximal clique . [ defn - uid ] let @xmath96 be a finite simple graph , let @xmath189 be the set of all mc in @xmath97 , and let @xmath298 be a smallest subset of @xmath299 such that every edge of @xmath63 occurs at least once in @xmath298 . then the mc in @xmath298 are said to be ( i ) , those in @xmath300 ( d ) . we say that an edge of @xmath97 is a if it belongs to exactly one mc . then every mc that contains a free edge is independent . + + we will see that for the associated graph @xmath301 of a string , the independent mc are closely related to alphabet size . consider for example @xmath302 @xmath6 ( see figure [ graph - ex - gx-1 ] ) has four mc @xmath303 of which , by definition [ defn - uid ] , @xmath304 are independent , since each contains at least one free edge ( @xmath305 , respectively ) . however , @xmath306 is dependent , since its adjacencies all occur elsewhere ( @xmath307 is a subclique of @xmath308 , @xmath309 a subclique of @xmath310 , @xmath311 an edge of @xmath312 , and so every edge of @xmath306 occurs in at least one of the other three cliques ) . thus exactly three of the mc are independent , and we see that ( [ 3lett ] ) has a minimum alphabet of three letters . on the other hand , if @xmath313 ( see figure [ graph - ex - gx-2 ] ) has mc @xmath314 all four of them are independent ( in @xmath315 the edge @xmath311 no longer occurs elsewhere ) , and we claim that no corresponding string can be constructed on fewer than four letters , while @xmath316 achieves the lower bound . [ lemm - minsig ] suppose that a graph @xmath97 has exactly @xmath5 independent maximal cliques . then there exists a string on a base alphabet of size @xmath5 whose associated graph @xmath317 , and on no smaller alphabet . let @xmath318 be the set of independent mc . suppose that initially every @xmath67,\ i = 1,2,\ldots , n$ ] , is empty ; then for @xmath319 , form @xmath320 \la \s{x}[i ] \cup \lambda_s\ ] ] if and only if vertex @xmath66 occurs in @xmath321 , where @xmath322 is a unique regular letter associated with @xmath321 . this ensures that @xmath289 \approx \s{x}[i_2]$ ] if and only if @xmath323 is an edge in one of the independent mc of @xmath97 . since by definition [ defn - uid ] this includes all the edges , it follows that @xmath301 is the associated graph of , a string on a base alphabet of size @xmath5 . suppose that there exists a string on a base alphabet of size @xmath324 , where @xmath325 . but then , since the regular letters in collectively determine all the edges and exactly @xmath326 independent mc in @xmath313 , this means that there exists a set of independent mc in @xmath97 of cardinality @xmath324 , contradicting the condition of definition [ defn - uid ] that @xmath298 is the smallest such subset . this completes the proof . lemma [ lemm - minsig ] has an easy corollary : [ lemm - easier ] suppose that @xmath327 is the associated graph of a string with @xmath5 independent maximal cliques @xmath318 . * if a vertex @xmath328 belongs to exactly @xmath329 of the maximal cliques in @xmath298 , then @xmath330| \ge s$ ] . * if an edge @xmath331 belongs to exactly @xmath329 of the maximal cliques in @xmath298 , then @xmath330 \cap \s{x}[j]| \ge s$ ] . the following simple algorithm might be a candidate to compute a set of independent maximal cliques : * label i every mc that has a free edge ; * alternate steps ( a ) and ( b ) until no new labellings occur : * * label d each unlabelled mc with at least one edge in an mc labelled i ; * * label i each unlabelled mc with at least one edge in an mc labelled d. however , suppose that some subgraph @xmath332 of @xmath97 remains unlabelled after the termination of step 2 of the algorithm . then every edge @xmath333 of @xmath332 must belong to at least two mc of @xmath332 , since otherwise it would have been labelled in step 1 . moreover , any mc containing @xmath333 can not be labelled either i or d , and so @xmath332 can only be a subgraph sharing no edges with the rest of @xmath97 and also containing no free edges . + + to show that such a subgraph can exist , consider the triangulated graph @xmath97 on six vertices @xmath334 , where the only pairs @xmath168 that are _ not _ edges are @xmath335 and @xmath336 , as shown in figure [ graph - ex - gx-4 ] . there are eight mc @xmath337 of which either the first four or the last four can be chosen to be independent , thus by lemma [ lemm - minsig ] yielding a corresponding string on four regular letters . note that every edge occurs in exactly two mc , so that by lemma [ lemm - easier](b ) every position in the corresponding string contains at least two regular letters ; for example , @xmath338 a more complex example is the graph @xmath97 on vertices @xmath339 with maximal cliques @xmath340 , @xmath341 , and 14 others , as shown in figure [ graph - ex - gx-3 ] . the only pairs @xmath168 that are _ not _ edges are @xmath342 and @xmath343 . in this case it turns out that there are six independent mc , for example @xmath344 and so by lemma [ lemm - minsig ] a corresponding string can be constructed using six regular letters ( one letter per mc ) : @xmath345 + these examples show that whenever graphs or subgraphs without free edges exist , the identification of independent mc becomes more difficult . in such cases we know of no algorithm to compute them apart from exhaustive search . thus , while it is straightforward , given , to determine @xmath6 , it is nontrivial , given @xmath97 , to determine a string on a smallest alphabet such that @xmath301 . from lemma [ lemm - union ] it follows that the maximum alphabet size required for an essentially regular string is @xmath11 ; thus to compute from a feasible array is potentially an @xmath54 algorithm and , as shown in @xcite , is actually @xmath54 . however , for indeterminate strings , lemma [ lemm - minsig ] shows that the minimum alphabet size is the number @xmath5 of independent maximal cliques in @xmath6 . a classical result from graph theory @xcite shows that the number of maximal cliques may be as much as @xmath346 , and so an indeterminate string potentially could require an alphabet of exponential size . for example , for @xmath347 , consider the graph @xmath6 on six vertices @xmath348 with nine edges ( @xmath349 ) @xmath350 as shown in figure [ graph - ex - gx-5 ] . each of these edges is a maximal independent 2-clique , and so by lemma [ lemm - minsig ] a corresponding string is @xmath351 defined on an alphabet of nine regular letters with prefix array @xmath352 . note here that information is lost in the transformation from to . the prefix graph @xmath114 corresponding to @xmath353 has the same nine edges @xmath279 , but @xmath55 contains , instead of the six negative edges @xmath354 implied by @xmath279 , just two : @xmath355 . thus by reverse engineering we get the much simpler ( but still necessarily indeterminate ) string @xmath356 whose associated graph @xmath313 has , in addition to the nine edges of @xmath279 , also the four ( now positive ) edges @xmath357 . thus in @xmath313 there are only two maximal cliques , on the vertices 23456 and 1246 , independent of each other , and so by lemma [ lemm - minsig ] can be constructed using @xmath358 regular letters . the fastest known algorithm to compute all maximal cliques is described in @xcite , but of course it must be exponential in the worst case ( @xmath346 maximal cliques ) ; it is not known how many independent maximal cliques can exist in a graph constructed from a prefix array . the graph @xmath114 corresponding to @xmath359 contains seven independent maximal cliques @xmath360 . thus , regarding this graph as an associated graph @xmath6 of some string tells us by lemma [ lemm - minsig ] that seven regular letters would be needed to represent it . in this paper we have explored connections among indeterminate strings , prefix arrays , and undirected graphs , some of them quite unexpected ( by us , at least ) . we believe that many other connections exist that may yield combinatorial insights and thus more efficient algorithms . for example : 1 . how many independent maximal cliques can exist in the associated graph @xmath6 of a string computed ( on a minimum alphabet ) from a given prefix array ? 2 . find an efficient algorithm to compute a string on a minimum alphabet corresponding to a given nonregular prefix array . what classes of graphs @xmath97 exist that , as associated graphs @xmath301 of some string , have fewer than exponential independent maximal cliques , and so therefore may give rise to efficient algorithms for the determination of on a minimum alphabet ? put another way : characterize graphs that have an exponential number of independent maximal cliques . can we recognize strings with associated graphs @xmath6 that have an exponential number of independent maximal cliques ? 5 . can known results from graph theory be used to design efficient algorithms for computing patterns in indeterminate strings ? we are grateful to jean - pierre duval and arnaud lefebvre of the universit de rouen for useful discussions . karl abrahamson , * generalized string matching * , _ 166 _ ( 1987 ) 10391051 . h. bannai , s. inenaga , a. shinohara & m. takeda , * inferring strings from graphs and arrays * , _ mathematical foundations of computer science _ , springer lecture notes in computer science lncs 2747 , b. rovan & p. vojts ( eds . ) ( 2003 ) 208217 . francine blanchet - sadri , _ algorithmic combinatorics on partial words _ , chapman & hall / crc ( 2008 ) 385 pp . francine blanchet - sadri & robert a. hegstrom , * partial words and a theorem of fine and wilf revisited * , _ 2701/2 _ ( 2002 ) 401409 . j. a. bondy & u. s. r. murty , _ graph theory _ , springer ( 2008 ) 651 pp . julien clment , maxime crochemore & giuseppina rindone , * reverse engineering prefix tables * , _ proc . 26th _ , susanne albers & jean - yves marion ( eds . ) ( 2009 ) 289300 . c. bron & j. kerbosch , * algorithm 457 : finding all cliques of an undirected graph * , _ communications of the acm 169 _ ( 1973 ) 575577 . maxime crochemore , christophe hancart & thierry lecroq , _ algorithmique du texte _ , vuibert ( 2001 ) 347 pp . maxime crochemore , christophe hancart & thierry lecroq , _ algorithms on strings _ , cambridge university press ( 2007 ) 392 pp . jean - pierre duval , thierry lecroq & arnaud lefebvre , * border array on a bounded alphabet * , _ 101 _ ( 2005 ) 5160 . michael j. fischer & michael s. paterson , * string - matching and other products * , _ complexity of computation , proc . siam - ams 7 _ ( 1974 ) 113 - 125 . frantisek franek , weilin lu , p. j. ryan , w. f. smyth , yu sun & lu yang , * verifying a border array in linear time * ( preliminary version ) , _ proc . 10th _ , school of computing , curtin university of technology ( 1999 ) 2633 . frantisek franek , shudi gao , weilin lu , p. j. ryan , w. f. smyth , yu sun & lu yang , * verifying a border array in linear time * , _ 42 _ ( 2002 ) 223 - 236 . frantisek franek & w. f. smyth , * reconstructing a suffix array * , _ 176 _ ( 2006 ) 12811295 . jan holub & w. f. smyth , * algorithms on indeterminate strings * , _ proc . 14th _ ( 2003 ) 3645 . jan holub , w. f. smyth & shu wang , * hybrid pattern - matching algorithms on indeterminate strings * , _ london algorithmics and stringology 2006 _ , j. daykin , m. mohamed & k. steinhoefel ( eds . ) , king s college london series _ texts in algorithmics _ ( 2006 ) 115133 . jan holub , w. f. smyth & shu wang , * fast pattern - matching on indeterminate strings * , _ 61 _ ( 2008 ) 3750 . costas s. iliopoulos , manal mohamed , laurent mouchard , katerina g. perdikuri , w. f. smyth & athanasios k. tsakalidis , * string regularities with do nt cares * , _ 101 _ ( 2003 ) 4051 . joseph w. kitchen jr . , _ calculus of one variable _ , addison - wesley ( 1968 ) . m. lothaire , _ applied combinatorics on words _ , cambridge university press ( 2005 ) 610 pp . michael g. main & richard j. lorentz , * an @xmath361 algorithm for finding all repetitions in a string * , _ 5 _ ( 1984 ) 422432 . j. w. moon & l. moser , * on cliques in graphs * , _ israel j. math . 3 _ ( 1965 ) 2328 . dennis moore , w. f. smyth & dianne miller , * counting distinct strings * , _ algorithmica 131 _ ( 1999 ) 113 . james h. morris & vaughan r. pratt , _ a linear pattern - matching algorithm _ , tech . rep . 40 , university of california , berkeley ( 1970 ) . j. mycielski , * sur le colorage des graphes * , _ colloq . math . 3 _ ( 1955 ) 161162 . bill smyth , _ computing patterns in strings _ , pearson addison - 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an integer array @xmath0 $ ] is said to be if and only if @xmath1 = n$ ] and , for every @xmath2 , @xmath3 \le n\+ 1 $ ] . a string is said to be if and only if at least one of its elements is a subset of cardinality greater than one of a given alphabet @xmath4 ; otherwise it is said to be . a feasible array is said to be if and only if it is the prefix array of some regular string . we show using a graph model that every feasible array of integers is a prefix array of some ( indeterminate or regular ) string , and for regular strings corresponding to , we use the model to provide a lower bound on the alphabet size . we show further that there is a 11 correspondence between labelled simple graphs and indeterminate strings , and we show how to determine the minimum alphabet size @xmath5 of an indeterminate string based on its @xmath6 . thus , in this sense , indeterminate strings are a more natural object of combinatorial interest than the strings on elements of @xmath4 that have traditionally been studied . * keywords . * indeterminate string ; regular string ; prefix array ; feasible array ; undirected graph ; minimum alphabet size ; lexicographical order .

the sapho syndrome was first coined and introduced in 1987 by french rheumatologist chamot to a symptom complex consisting of synovitis acne pustulosis hyperostosis osteitis , which till then was known by more than a dozen names over the previous 50 years . although it can occur at any age , it commonly presents during childhood or middle age . the most common presentation is bone pain in a febrile patient associated with dermatological conditions such as pustular psoriasis , acne , and suppurative hidradenitis . natural history of the disease is characterized by osteoarticular involvement and periodic exacerbations and remissions . at present , the exact pathogenesis is unclear . the treatment is difficult and often inadequate . despite a good prognosis , involvement of multiple organ systems an 18-year - old male patient presented to our outpatient department with painful , nodulocystic acne on the face since 9 months , severe pain in both wrist joints and lower back since 30 days , associated with bouts of chills and rigors , which made patient acutely ill . patient 's elder sister had similar cystic acne lesions on the face , without bony pains or systemic symptoms . physical examination revealed grade iv acne on face with multiple cysts , which were acutely tender discharging pus [ figure 1 ] , associated with swelling of right wrist and tenderness over both wrist joints and lumbar spine , with restricted movements due to severe pain . nodulocystic lesions on face before treatment complete blood picture showed mild leukocytosis ( 16,000 cells / mm ) . c - reactive protein ( crp ) levels are elevated at 24 mg / dl , ( normal range < 0.80 mg / dl ) . plain radiograph of the right hand showed evidence of a focal osteopenic area at the distal end of radius . magnetic resonance imaging of the right wrist showed altered signal intensities , at distal metaphyses adjacent to physeal plate on the lateral side of the distal end of radius , suggestive of osteitic lesions . to evaluate the skeleton , technetium-99m - mdp whole body bone scintigraphy ( wbbs ) bone scintigraphy revealed increased metaphyseal uptake in distal radius at both wrists and prominent uptake at sacroiliac joints , vertebral end plates , left 7 costovertebral joint , and in addition , there was increased uptake at bilateral sternoclavicular joints and manubrium sternum , known as bull 's head or bull - horn sign , which is characteristic of sapho syndrome . initially , the patient was treated with nonsteroid anti - inflammatory drugs ( nsaids ) , ceftriaxone and ampicillin later cefpodoxime was started orally at the dose 200 mg twice daily , along with doxycycline 200 mg twice daily and colchicine 0.5 mg twice daily . acne cysts on the face were drained weekly for 3 weeks , with two simultaneous sessions of intralesional injection of triamcinolone acetate ( 0.5 ml of 2.5 mg / ml ) . clindamycin 1% was prescribed as a topical application , along with 2.5% benzoyl peroxide , for acne . the patient responded remarkably to the above treatment and his symptoms subsided in next 4 weeks . at this stage , isotretinoin 20 mg / day was introduced while continuing topical therapy and oral colchicine . by the end of 12 weeks , the lesions on the face flattened [ figure 2 ] and bone pains regressed completely . plain radiograph showed clearance of osteopenic area at the distal end of radius of right hand . sapho syndrome is a complex disorder , characterized by a combination of bone lesions and inflammatory dermatosis associated with pustules , such as pustular psoriasis , palmoplantar pustulosis , fulminant acne , or suppurative hidradenitis . patients typically present with musculoskeletal complaints , such as pain , swelling , and limitations of movement in the affected joints . in young and middle - aged adults the disease is more common in the sternoclavicular region ( 65%90% of patients ) , but can also affect the spine ( 33% ) , pelvis ( 13%52% ) , and long bones ( 30% ) , whereas the ilium and mandible are involved in less than 10% of cases . patients with spinal involvement can present with numbness and radicular pain . in sapho syndrome axial skeleton and costo - sterno - clavicular region is more often affected , compared to localization of inflammation to acral skeleton in chronic recurrent multifocal osteomyelitis , a condition similar to sapho syndrome seen in children . the etiopathogenetic mechanism of sapho syndrome remains unclear , although several hypotheses have been proposed involving bacteriologic , immunologic , and genetic factors . by combining bacteriologic , immunologic , and genetic data , some workers consider sapho syndrome as a reactive osteitis , in which the opportunistic organism such as propionibacterium acnes takes advantage of genetically determined deficiencies in antibacterial defense mechanisms and subsequently induces auto - amplification of the inflammatory response , possibly with an autoimmune component . bacterial cultures are usually negative , with p. acnes being isolated rarely in deep bone biopsy specimens . the diagnosis of sapho syndrome is based on history , characteristic scintigraphic and radiological results , and skin manifestations . any one of the following criteria is regarded as sufficient to diagnose sapho syndrome : ( 1 ) multifocal osteitis with or without skin lesions ; ( 2 ) sterile acute , subacute , or chronic arthritis associated with pustular psoriasis , palmoplantar pustulosis , acne , or suppurative hidradenitis ; and ( 3 ) sterile osteitis combined with one of the skin manifestations . however , the dermatological and skeletal conditions do not always occur in parallel , and they may be separated by a number of years . thus , diagnosing sapho syndrome is difficult in certain cases , particularly if the dermatological manifestations are absent . our patient presented with pustular nodulocystic acne of face and systemic symptoms along with osteitis of multiple joints . wbbs using 99 m tc - methylene - diphosphonate is a sensitive imaging modality that is able to identify its uptake in characteristic regions when changes in radiography are absent or subtly abnormal , is an important tool for the diagnosis of sapho syndrome , particularly for detecting multiple and early bone involvement . , the sternoclavicular junction is the most common site of involvement in adults , followed by the spine and sacroiliac joints . the spinal involvement which was observed in this case along with sacroiliac joint involvement on scintigrapy , is generally reported to have a good prognosis and rarely cause neurological deterioration . high tracer uptake in the sterno - costoclavicular region yields the so - called bull 's head sign , with the manubrium sterni representing the upper skull and the inflamed sterno - clavicular joint with the adjacent claviculae forming the horns . our patient on scintigraphy demonstrated bull head sign indicating increased uptake at these areas [ figure 3 ] , characteristic of sapho syndrome . technetium-99m - mdp whole body bone scintigraphy : showing prominent uptake at bilateral sternoclavicular joints and manubriisterni ( bull horn sign ) and both wrist joints until now , there have been no uniform treatment guidelines for sapho syndrome . current treatment of this illness is multimodal and empirical , and is mainly focused on relieving symptoms . therapy is aimed at symptom relief and mainly includes nsaids and analgesics as firstline agents with or without antibiotics . systemic corticosteroids , disease - modifying antirheumatic drugs , biologicals targeting tumor necrosis factor - alpha and interleukin-1 , and bisphosphonates have all been beneficial in some patients , but ineffective in others , indicating poorly understood multifactorial pathogenesis of sapho syndrome . several studies have supported the effectiveness of intravenous bisphosphonates as a treatment for sapho syndrome , as they exhibit a good response , due to their antiosteoclastic and anti - inflammatory effects that inhibit cytokine secretion by macrophages . in the present case study , nsaids , oral cefpodoxime , doxycycline , colchicine , and intralesional steroids were prescribed simultaneously for first 6 weeks , followed by oral colchicine , isotretinoin , and topical therapy . our patient responded remarkably to the above treatment and his nodulocystic acne , bony lesions and systemic symptoms subsided within 12 weeks . this case presented with a rare combination of acne fulminans and osteitis of multiple joints of axial skeleton . although it is considered that patients with sapho syndrome do not respond well to antibiotic therapy , our patient responded very well to therapy with cefpodoxime , doxycycline , colchicine , and cyst drainage followed by istotretinoin with significant clinical improvement in cystic acne and radiological clearance of osteopenic lesions .

sapho syndrome ( synovitis , acne , pustulosis , hyperostosis , osteitis ) , a rare inflammatory disorder , is an association of distinct skin disorders with pustules with osteoarticular inflammation . its etiology remains unclear , and various treatment regimens frequently fail to control the disease . an 18-year - old male patient presented to the outpatient department with severe nodulocystic acne on the face with pain at both the wrists and lower back associated with high - grade fever and chills . on physical examination , he had severe tenderness at both wrist joints and lower back , along with swelling of right wrist . magnetic resonance imaging revealed osteitis of the distal end of the right radius . technetium-99m - mdp whole body bone scan revealed increased metaphyseal uptake in distal radius on both sides and prominent uptake at the sacroiliac joints , vertebral end plate , left 7th costo - vertebral joint and bilateral sternoclavicular joints and manubrium sternum ( resulting in bull 's head sign , which is characteristic of sapho syndrome ) . he responded very well to a combination therapy of nonsteroid anti - inflammatory drugs , antibiotics , colchicine , and isotretinoin over a 12-week period .

the anti de sitter / conformal field theory ( ads / cft ) correspondence is a powerful method to investigate strongly coupled theories . an interesting application of such duality is the study of systems at finite temperature and density of some conserved quantum number . this is the typical situation in condensed matter physics and in the last few years a considerable amount of work has been dedicated to the development of holographic methods for condensed matter systems ( reviews of which can be found in refs . @xcite ) . in the simplest realizations one deals with einstein s gravitational theory with a negative cosmological constant coupled to a gauge field ( dual to the conserved current ) . while this setup captures some interesting properties of realistic systems , the low temperature behavior has some disturbing features . a classic example , which is perhaps unphysical rather than disturbing , is the fact that the simplest charged black hole solution predicts a nonvanishing entropy in the zero temperature limit . this situation can be improved @xcite by adding a real scalar field @xmath1 ( _ a dilaton _ ) , which interacts with the gauge field by modifying its gauge coupling @xmath2 , = , [ running - coupling ] where @xmath3 , and self - interacts through a potential . this allows for zero entropy at zero temperature . moreover , real scalars of this type are typically present in the low energy limit of string theories and their inclusion may be good if eventually one has to find a stringy embedding . in this work we initiate the study of holographic superfluids and superconductors in dilaton extensions of einstein s gravity . like in the absence of the dilaton , the minimal description of these systems requires a conserved u(1 ) current and a charged condensing operator , which are respectively dual to an abelian gauge field and a charged scalar living on an asymptotically ads space @xcite ( for a review see @xcite ) . then the dilaton can couple directly not only to the gauge field but also to the charged scalar . in the case of superconducting materials the u(1 ) symmetry is gauged while for superfluids is global . in holography a superfluid corresponds to a dirichlet condition for the gauge field at the ads boundary , while a true superconductor can be obtained by imposing a boundary condition of the neumann type @xcite . superfluids can be considered as superconductors in the limit of nondynamical ( electromagnetic ) gauge fields . for the sake of definiteness , we adopt the terminology used in the literature of superconductivity , rather than that of superfluidity . one of the main motivations for holographic superconductivity is the hope to shed light on high-@xmath4 superconductors . experiments indeed imply that these materials can not be entirely described by the weakly coupled theory of bardeen , cooper , and schrieffer ( bcs ) , but they could involve strong coupling . the cuprate high-@xmath4 superconductors can be obtained by doping a mott insulator and in the ( @xmath4 versus `` dopant concentration '' ) phase diagram one can observe an insulator / superconductor transition in the low temperature region @xcite ; therefore the normal ( nonsuperfluid ) phase is expected to be gapped . a transition of this sort has been realized in holography by considering a theory with a compactified extra dimension @xcite ( see also @xcite for the realization of a true superconductor with a dynamical gauge field ) . the size of this extra dimension breaks scale invariance and at low temperatures leads to a gap of charged excitations and thus to an insulator normal phase . one expects to be able to obtain an insulator / sperconductor transition by introducing a dilaton , even in the absence of additional dimensions , because a running dilaton also introduces a scale . we will find that this is indeed the case at low enough temperatures and for some values of the parameters . let us describe in more detail our main results and the organization of the paper . in section [ model ] we will define our einstein - dilaton model coupled to the u(1 ) gauge field and the charged scalar and recall the ads / cft dictionary . here and in the rest of the paper we focus on 2 + 1 dimensional cfts . in the same section we will also review the ( recently found @xcite ) most general static and asymptotically ads planar black hole of the dilaton - gravity system . once we fix the parameters of the model , there is only one solution with active dilaton ( dilaton - bh ) , but the fact that the space is asymptotically ads implies that the schwarzschild black hole ( s - bh ) , which has @xmath5 , is also a solution . therefore , in section [ einstein - dilaton section ] , we compare their free energies as a function of @xmath4 to determine which one is energetically favorable . we find that the s - bh is favorable at high temperatures , while the dilaton - bh dominates in the low temperature region . in the latter phase the dilaton runs logarithmically with the energy and grows from the ultraviolet ( uv ) to the infrared ( ir ) . we then study the ac and dc conductivity by considering an electromagnetic ( em ) perturbation on top of these geometries . the presence of a black hole horizon implies that the system is never perfectly insulating , but for some choices of @xmath6 the dc conductivity is suppressed especially at low temperatures , resembling an insulator . this occurs when the running coupling constant @xmath7 becomes large in the ir and , not surprisingly , links the insulating phase with ir strong coupling . in section [ homogeneoussfphase ] we find superfluid phase transitions by solving the gauge field and charged scalar equations on the fixed dilaton - bh geometry . like for the s - bh @xcite , for each value of the temperature and the other parameters there is a critical temperature @xmath8 below which the charged operator condenses breaking the u(1 ) symmetry . we also study the conductivity in the broken phase and obtain that both the gap of charged excitations and the superfluid density are modified by changing the couplings of the dilaton , in particular the running constant , eq . ( [ running - coupling ] ) . some of the most famous properties of superconductors occur in the presence of external magnetic fields ; therefore we move on and study the magnetic response in the dilaton - bh phase . the same type of analysis in the model without the dilaton has been performed in @xcite . while for superfluids the external and total magnetic fields coincide , they differ substantially in true superconductors . in section [ hscs section ] we study the superconductor case . we directly observe the meissner effect and find vortex solutions , the penetration depth and the critical magnetic fields @xmath9 and @xmath10 . like in the case with no dilaton @xcite , we always find @xmath11 ( the superconductor is of type ii ) and thus this seems to be a rather general prediction of holography . quite interestingly , the known high-@xmath4 superconductors are of this type . crucial differences with respect to the s - bh phase @xcite emerge in the low temperature region , for some choices of @xmath6 ( which , interestingly , lead to an insulating normal phase ) . in these cases the ratio @xmath12 remains finite in the limit of small @xmath0 unlike the s - bh case @xcite and also the penetration depth shows an analogue difference . finally in section [ superlfuids ] we study superfluids in the presence of external rotations and find superfluid vortices in the dilaton - bh phase ; here we find results that are qualitatively similar to those for the s - bh @xcite , although the dilaton generically modify the vortex shape . section [ conclusions - section ] contains some outlook of our work . our model is defined by the usual einstein - dilaton action coupled to a u(1 ) gauge field @xmath13 and a charged scalar @xmath14 : s = d^4x \{116g_n-_^2-|d_|^2 } , [ action ] where @xmath15 is the ricci scalar , @xmath16 the gravitational newton constant , @xmath1 a real scalar ( the dilaton ) and we introduced @xmath17 and @xmath18 . a negative cosmological constant @xmath19 is included in the dilaton potential @xmath20 , and the ads radius is defined by @xmath21 . we define @xmath1 such that @xmath22 . also the dilaton couples to @xmath13 and @xmath14 through two generic functions @xmath23 and @xmath24 and we choose the normalization of the matter fields in a way that @xmath25 . there are no special requirements for the @xmath26 at this level , besides the fact that they should be regular and nonvanishing for any @xmath1 in order for the semiclassical approximation to be valid . for simplicity , we have not added any potential for the charged scalar . the most general static asymptotically ads planar black hole with two - dimensional rotation and translation invariance has the form ds^2=w(z)(-f(z)dt^2+dy^2 + ) , = ( z ) , [ generalbh ] where @xmath27 represents time , @xmath28 and @xmath29 is the holographic coordinate , which we define such that the ads - boundary is located at @xmath30 : for @xmath29 close to zero , @xmath31 , @xmath32 and @xmath1 approximate to @xmath33 , @xmath34 and @xmath35 . this allows us to use the standard ads / cft dictionary , which relates the property of a gravitational theory with those of a cft . in particular the boundary values of @xmath14 and @xmath36 are the sources of a charged operator @xmath37 and the current @xmath38 in the cft side . therefore , if one solves the classical field equations with boundary conditions |_z=0=_0 , a_|_z=0=a _ , [ s - amu ] the green s function for @xmath37 and @xmath38 are given by functional derivatives of the on - shell action with respect to @xmath39 and @xmath40 . for example the vacuum expectation values are given by j_=_z|_z=0 , = d_z |_z=0 . [ operator ] we will work in the limit @xmath41 such that the effect of the gauge field and the charged scalar on the metric and the dilaton can be neglected . in this limit the most general asymptotically ads black hole of the form given in eq . ( [ generalbh ] ) is @xcite w(z)= , ( z)= ( 1+z / l ) , + f(z)=1 + 3()^3\{+(1+z / l)^2}. [ dilaton - bh ] the black hole horizon @xmath42 , defined as usual by @xmath43 , is a function is a function of @xmath44 and @xmath45 only . ] of @xmath44 and @xmath46 . since we want to study the theory at finite temperature , we perform the euclidean continuation to imaginary time @xmath47 with period @xmath48 . the temperature can then be computed with the formula @xmath49 , where a prime denotes a derivative with respect to @xmath29 . when @xmath50 we have @xmath5 and we recover the s - bh : @xmath51 . in this case @xmath52 and we have @xmath53 . if instead @xmath54 the dilaton is active and its backreaction on the metric is nontrivial . this results in a displacement of the horizon and the temperature is no longer given by @xmath55 , but by a more general ( @xmath44-dependent ) expression . it is important to notice that the s - bh is a solution whenever @xmath56 has a negative stationary point . in order to have the dilaton - bh , @xmath54 , one has to consider instead the following family of potentials @xcite v()= _ i=1 ^ 6 v_ie^-_i , where @xmath57 and @xmath58 are given by v_i&=&3 , 12 , ( 1 + ) , + & & 3 , 4(^2 - 1 ) , ( -1 ) , and _ i= + 1 , 1 , -1 , 1- , -1 , --1 respectively , where the @xmath59 signs correspond to @xmath60 and @xmath61 ; the potential is therefore symmetric under @xmath62 and from now on we restrict to @xmath60 . since the black hole is asymptotically ads , this potential has a stationary point for @xmath5 such that @xmath63 . an immediate but important consequence is that one has two black holes for any @xmath54 , the s - bh and the one with active dilaton . for @xmath1 small enough one obtains @xmath64 . notice that the squared mass of @xmath1 is always above the breitenlohner - freedman bound @xcite and therefore @xmath5 is never unstable , but either metastable or stable . in this section we focus on the normal phase , @xmath65 . this , among other things , will help us to understand what kind of superfluid transitions are those described in the rest of the paper . let us compare the free energies of the s - bh and the dilaton - bh to determine which one is energetically favorable , as a function of @xmath4 . the free energy @xmath66 can be computed by evaluating the euclidean action @xmath67 at the solution of interest , f = s_e.[free - energy ] according to this definition it is clear that the free energy of the s - bh is divergent . one reason is that the solution does not depend on the planar coordinates y and therefore @xmath66 goes to infinity as the volume of the plane @xmath68 . this is an infrared divergence and can be avoided by considering the free energy density @xmath69 . there is , however , another source of singularity , due to the fact that the lagrangian evaluated at the s - bh goes as @xmath70 for @xmath29 small enough and the integral includes the point @xmath30 ; however this is an ultraviolet divergence and as such it should cancel in the difference @xmath71 where @xmath72 and @xmath73 are the free energy densities of the dilaton- and s - bh respectively . indeed the dilaton - bh is asymptotically ads and therefore its ultraviolet behavior should coincide with that of the s - bh . we plot the free energy difference in fig . [ phase - transition - d - d - bh ] . we find that if we lower the temperature below a critical value @xmath74 there is a phase transition between the s - bh and the dilaton - bh . since @xmath75 is the only dimensionful parameter , @xmath76 , but the actual value of @xmath74 depends on the dimensionless parameter @xmath44 as well . we observe that the entropy , @xmath77 , approximates to zero at small temperatures . both the s - bh and dilaton - bh phases correspond to systems with nonvanishing conductivity in the cft side . this property can be viewed essentially as a consequence of the black hole horizon ( see below ) . however , as we will see , the dc conductivity can be suppressed for some values of the parameters , resembling an insulator . to compute the conductivity let us consider , on top of these geometries , a small time - dependent perturbation along a spatial coordinate @xmath78 , a_x ( t , z)=(z)e^i(p(z)-t ) , [ wave - decomposition ] which is induced by a small electromagnetic field at the ads - boundary , @xmath79 . here @xmath80 and @xmath81 are real functions of @xmath29 . the system responds creating a current which is linear in @xmath82 : @xmath83 , where @xmath84 is the complex conductivity and @xmath85 the electric field . using the ads / cft dictionary , the first equation in ( [ operator ] ) , we have g^2= p(0)-i . [ sigma ] since this is a linear response problem the conductivity can be computed by solving the linearized maxwell equation _ z(f z_a ( ) _ za_x)+ ^2 a_x= 0 [ linearizedeom ] with appropriate boundary conditions . at the ads - boundary the condition is , as we said , @xmath86 , while at the black hole horizon we impose that the em wave is going towards the horizon ( ingoing boundary condition ) p(z)f(z)1 z = z_h , [ irbc ] as required by regularity @xcite . inserting ( [ wave - decomposition ] ) into ( [ linearizedeom ] ) we obtain an equation whose imaginary part can be solved analytically , to obtain p(z)= ( ) ^2 . [ imeq ] a consequence is that @xmath87 can not be zero without violating eq . ( [ irbc ] ) . therefore the amplitude of the em wave , @xmath88 , acquires an imaginary part which generates a nonvanishing re@xmath89 $ ] . in the fluid mechanical interpretation re@xmath89\neq 0 $ ] corresponds to a fluid , as opposed to a solid which has vanishing re@xmath89 $ ] , as discussed in @xcite . the real part of eq . ( [ linearizedeom ] ) is instead _ z(fz_a_zs ) + fz_a ( _ zs)^2+^2 ( 1-)=0 , [ eq - s ] where @xmath90 to be solved with the regularity boundary conditions s =- z_a , s=- , z = z_h . [ bc - s]once a solution to this equation is found we can compute the real and imaginary part of the conductivity through [ ] = , [ ] = - , [ compute - sigma]where we used eqs . ( [ sigma ] ) and ( [ imeq ] ) . cc a particularly simple case is when there is no direct coupling between the dilaton and the gauge field , @xmath91 , which corresponds to @xmath92 and thus to a frequency - independent re@xmath89 $ ] and to a vanishing im@xmath89 $ ] , both for the s - bh and the dilaton - bh . in this case the dilaton does not have an impact on @xmath84 ; it coincides with that found in @xcite . when @xmath93 depends on @xmath1 the situation is different . a simple way to see it is to take the zero frequency limit . ( [ eq - s ] ) and ( [ bc - s ] ) tell us @xmath94ln@xmath95 for every @xmath29 , which leads to _ 0 [ ] = z_a|_z = z_h , _ 0[]=0 . [ dcsigma]here we see that the dc conductivity can be suppressed or enhanced depending on the function @xmath6 . for the exponential form @xmath96 , the more positive @xmath97 is the bigger the dc conductivity , while a large negative value of @xmath97 corresponds to an approximate insulating behavior . this effect is even stronger at low temperatures where the dilaton is logarithmically large . we have _ 0 [ ] ~t^- , [ sigma - vs - t]where we have remembered that we restrict to the positive sign choice in ( [ dilaton - bh ] ) , without loss of generality . the conductivity can depend on @xmath4 because there is an additional scale in the dilaton phase . it is interesting to notice that for the functions @xmath6 such that the dc conductivity is small the phase transition described in section [ pahses ] is between a conductor at high temperatures and a ( non ideal ) insulator at low temperatures , while in the other cases we observe a transition between two metallic phases ; in particular if we set @xmath98 in eq . ( [ sigma - vs - t ] ) we get a low temperature resistivity that goes linearly in @xmath4 , like for many unconventional ( not bcs ) superconductors . in the high frequency limit , instead , eqs . ( [ eq - s ] ) and ( [ bc - s ] ) tell us that @xmath99 and so eqs . ( [ compute - sigma ] ) imply that @xmath84 converges to the constant value we have in the s - bh phase : re@xmath89=1/g^2 $ ] and im@xmath89=0 $ ] . at high enough energies these systems respond in a universal way . in fig . [ sigma - np ] we give @xmath84 as a function of @xmath100 . a direct coupling between the dilaton and the bulk gauge field gives us a nontrivial frequency dependence of both re@xmath89 $ ] and im@xmath89 $ ] , unlike the s - bh phase ( and the case @xmath101 ) . as suggested by the first equation in ( [ dcsigma ] ) , re@xmath102 $ ] is large ( small ) when @xmath6 is large ( small ) at the horizon . we observe that the same is true for im@xmath89 $ ] . however , while for im@xmath89 $ ] the effect of the dilaton coupling function is strongest at intermediate values of @xmath100 ( as implied by the analytic discussion above ) , for re@xmath89 $ ] we observe the maximum effect at low frequencies . in this section we obtain superfluid phase transitions by introducing a chemical potential . at low temperatures , for the functions @xmath6 such that the normal phase resembles an insulator , these are new insulator / superconductor transitions . in order to obtain superconducting solutions the simplest ansatz is = ( z),a_0=a_0(z ) , [ ansatz ] where @xmath103 is a real function , and the other components of @xmath13 are set equal to zero . a nonvanishing value of @xmath104 is needed in order to have a regular solution for the condensate profile @xmath105 ( see below ) . therefore we consider the following ads - boundary conditions ( see eq . ( [ s - amu ] ) ) _ 0=0 , a_0=. [ uv]the first condition ensures that the u(1 ) breaking is spontaneous , while the chemical potential @xmath106 is needed to have @xmath107 . the regularity at the black hole horizon indeed requires @xmath108 ( in order for @xmath104 to have finite norm ) and therefore @xmath109 would imply @xmath110 everywhere . the field equations for the ansatz in ( [ ansatz ] ) are _ z(w f z _ ( ) _ z ) + a_0 ^ 2 = 0 , _ z(z_a ( ) _ za_0)- ^2 a_0=0 . [ field - equations ] we can now see that @xmath104 is needed : setting @xmath110 would imply either @xmath111 or @xmath112 , which is singular at the black hole horizon . the requirement of regularity gives the following boundary conditions at @xmath42 _ z=0 , a_0=0 . [ ir]the condition @xmath110 ensures that @xmath113 has finite norm @xcite . the second equation in ( [ field - equations ] ) and the regularity of the solution implies that @xmath104 should go to zero at least as fast as @xmath114 and then the second term in the first equation of ( [ field - equations ] ) should vanish at @xmath115 . the remainder of that first equation is a term proportional to @xmath32 , which goes to zero for regular solutions , and one proportional to @xmath116 that can be easily simplified to obtain the first condition in eq . ( [ ir ] ) . we have solved numerically the field equations in ( [ field - equations ] ) with the uv and ir boundary conditions , in ( [ uv ] ) and ( [ ir ] ) respectively . in fig . [ phase - transition - sc- ? ] we give the condensate as a function of the chemical potential . like in @xcite there is a critical chemical potential @xmath117 above which @xmath37 condenses , but here @xmath118 depends on @xmath119 , @xmath44 and the functional form of @xmath120 and @xmath121 . inverting this relation one has the critical temperature of the superfluid phase transition , @xmath8 . we have that @xmath122 is a function of @xmath123 , @xmath44 , @xmath120 and @xmath121 . by computing explicitly the free energy , eq . ( [ free - energy ] ) , one can see that , when it exists , the superconducting solution is energetically favorable with respect to the normal one . we observe that the condensate in fig . [ phase - transition - sc- ? ] seems to diverge as @xmath124 . since increasing @xmath123 for @xmath119 fixed corresponds to exploring the region of small @xmath0 , this suggests that @xmath125 becomes bigger and bigger by decreasing @xmath0 . we notice that neglecting the backreaction of the charged scalar and the gauge field on the metric is still consistent in the strict @xmath126 limit , which we are using throughout this paper limit in a future publication . ] . we now compute the conductivity in the spontaneously broken phase , @xmath127 . most of the equations given in section [ conductivity - section ] are still valid here , but some of them have to be modified because the order parameter is nonvanishing : the linearized maxwell equation , eq . ( [ linearizedeom ] ) , now becomes _ z(f z_a ( ) _ za_x)+ ^2 a_x- z_^2 a_x= 0 . in particular the equation for the modulus of the em wave , parametrized by @xmath128 , is modified to _ z(fz_a_zs ) + fz_a ( _ zs)^2+^2 ( 1-)- z_^2 = 0 [ s - eq - sp ] and has to be solved with the regularity boundary conditions s =- z_a , s= , z = z_h . [ s - bc - sp ] cc cc at very high frequencies , eqs . ( [ s - eq - sp ] ) and ( [ s - bc - sp ] ) indicate that the conductivity should converge to the value in the normal s - bh phase , regardless of the presence of the condensate . this corresponds to the physical fact that at energies much bigger than the condensation scale the system behaves as there were no condensate at all . for lower values of @xmath100 we provide @xmath84 in fig . [ sigma - sp ] . the imaginary part diverges like @xmath129 as @xmath130 , which corresponds , through the kramers - kronig relation [ ( ) ] = - _ -^d,to a delta function in the real part , re@xmath102\sim \pi n_s \delta(\omega)$ ] . this means that the system is superconducting , or a superfluid in the fluid mechanical case . the quantity @xmath131 can be identified with the superfluid density . we also see that the presence of the condensate leads to a superconducting gap in the plot of re@xmath89 $ ] versus @xmath100 , like in the s - bh phase @xcite . in the dilaton phase , however , the gap depends on @xmath6 . from the im@xmath102 $ ] plot we notice that the superfluid density is also changed by such function of the dilaton as we mentioned in the introduction , the distinctive property of superconductors is that the u(1 ) symmetry is gauged rather than global , as opposed to the superfluid case ; all we have discussed so far can be applied equally well to superconductors and superfluids because the dynamics of the gauge field was not important and the condensate ( a u(1 ) breaking field ) only : when we say that the gauge field is ( is not ) dynamical we mean that the backreaction of the condensate on the gauge field has ( has not ) been taken into account , but we do not state anything about the interaction between @xmath132 and the condensate constituents ( whose operators are not explicitly introduced here ) . ] . the purpose of this section is to consider field configurations ( mostly vortices ) where the dynamics of the gauge field is instead crucial . when the gravitational theory is described by einstein s gravity , this has been done in @xcite ; here we will consider the case of dilaton - gravity . in the standard ads / cft correspondence the boundary gauge field is considered as an external source for the u(1 ) current and as such is a nondynamical field , introduced through a dirichlet boundary condition ( the second equation in ( [ s - amu ] ) ) . however , it is possible to promote @xmath40 to a dynamical field by substituting this dirichlet boundary condition with one of the neumann type , which for a 2 + 1 dimensional cft is _ z^ |_z=0 + _ ^|_z=0+j^_ext=0 , [ maxwell2 ] where @xmath133 is an external nondynamical current and we have added a bare boundary kinetic term @xmath134 for generality @xcite . this condition requires to add the following boundary terms to the action in ( [ action ] ) d^4 x _ z=0 . [ extrat ] in the 2 + 1 dimensional case , which we are considering , the bare kinetic term in ( [ maxwell2 ] ) is not necessary @xcite and one can preserve conformal symmetry in the uv . in the absence of such term the dynamical @xmath40 can be considered as an emergent gauge field @xcite . this method to introduce a dynamical gauge field has been originally applied to the holographic superconductor model @xcite ( including diverse dimensions @xcite ) in @xcite and we refer to this paper for further details . it has been subsequently applied to holographic p - wave superconductors @xcite-@xcite in @xcite . it can be applied without any modification to the dilaton - gravity model of holographic superconductors presented here because the bh solutions we consider are all asymptotically ads . let us now look for genuine superconductor vortices with this recipe in mind . the simplest ansatz for the bulk fields is @xcite = ( z , r)e^i n , a_0=a_0(z , r ) , a_=a_(z , r ) [ ansatz - vortex ] and the other components of @xmath113 set equal to zero . in eq . ( [ ansatz - vortex ] ) @xmath135 and @xmath136 are the polar coordinates , @xmath137 , restricted to @xmath138 and @xmath139 , and @xmath140 is an integer . the corresponding field equations are _ z(w f z _ ( ) _ z ) + _ r(r_r ) + z _ ( ) ( - ) & = & 0 , + _ z(f z_a()_z a_)+z_a()r _ r ( _ r a _ ) - w z _ ( ) ^2 ( a_-n ) & = & 0,[eom - vortices ] + _ z ( z_a()_za_0)+ _ r ( r _ r a_0)- ^2 a_0 & = & 0 . requiring regularity we obtain the following boundary conditions at @xmath115 ( with a reasoning similar to that below eq . ( [ ir ] ) ) f(z_h)_z + _ r(r_r ) - & = & 0 , + f(z_h)_z a_+r _ r ( _ r a _ ) - ^2 ( a_-n ) & = & 0,[bch ] + a_0&=&0 , and at @xmath141 _ r a_0&=&0a _ = 0 , + _ r & = & 0 n=0,=0 n0 . [ bcr0 ] for @xmath142 we impose instead the physical condition that the fields should approach the homogeneous superconducting configuration : _ r=0 , _ r a_0=0 , a_=n [ rinftbc].finally let us consider the boundary conditions at @xmath30 . requiring the u(1 ) to be spontaneously broken we impose ( [ uv ] ) , while demanding the magnetic field @xmath143 to be dynamical we have , from eq . ( [ maxwell2 ] ) , _ z a_|_z=0 + r_r(_r a_)|_z=0=0[newbcsc ] , where we have set @xmath144 . cc cc imposing these boundary conditions we have solved numerically eqs . ( [ eom - vortices ] ) by using the comsol package @xcite . solutions of this form correspond to straight vortex lines centered at @xmath141 . for @xmath145 the only solution we find is the homogeneous solution of section [ homogeneoussfphase ] with @xmath146 : this is the famous meissner effect of superconductors . in fig . [ obvsr ] we give the condensate and the magnetic field as a function of @xmath135 for the @xmath147 vortex . we have checked that our solutions respect the model - independent properties given in table [ table ] . cc then we have studied the prediction of our model for the penetration depth @xmath148 and we present it in fig . [ penetration - depth - vs - mu ] . this constant characterizes , among other things , the behavior of @xmath149 far away from the center of the vortex ( see table [ table ] ) and this allows us to extract it from our solutions . let us take @xmath150 for the sake of definiteness . we observe that when @xmath97 is negative enough @xmath148 has a qualitatively different large @xmath106 behavior with respect to the s - bh phase ( and to less negative or positive values of @xmath97 ) . since increasing @xmath123 for a fixed value of @xmath119 corresponds to exploring the region of small @xmath0 , we conclude that the superconductors in the dilaton - bh phase have a qualitatively different low temperature penetration depth . in particular @xmath148 does not increase its value more and more as @xmath0 is decreased , contrary to what happens in the s - bh phase @xcite . in the low @xmath106 region we eventually find that @xmath148 diverges at @xmath151 : this is true in any model of superconductivity because when @xmath152 the condensate becomes small and the ginzburg - landau theory can be applied to predict that divergence . cc moreover , we have extracted the prediction for the first critical field @xmath9 , the minimum value of the external magnetic field @xmath153 for which the system is in the vortex phase . this quantity can be computed with the text book formula given in table [ table ] . there @xmath154 is the u(1 ) gauge constant of the cft in the normal phase , @xmath155 , normalized in a way that the kinetic term of a stationary vector potential in the free energy is @xmath156 ; taking @xmath157 to be constant we obtain = _ 0^z_h dz z_a ( ) . [ e0]we provide @xmath9 as a function of @xmath106 in the left plot of fig . [ hc12-vs - mu ] . in the high @xmath158 ( low @xmath0 ) region we find , like for the penetration depth , substantial qualitative differences compared to the s - bh case if the exponent @xmath97 is negative enough : while for the s - bh ( and for less negative or positive values of @xmath97 ) @xmath159 @xcite , in the other cases @xmath9 remains sizable even at low temperatures . the reason why this occurs is because @xmath160 , whose low temperature behavior depends strongly on whether we are in the scale invariant phase , @xmath5 , or in the phase in which scale invariance is broken , @xmath161 . ( [ e0 ] ) tells us that in the scale invariant phase @xmath162 and so does @xmath9 , but when scale invariance is broken @xmath154 remains finite if @xmath97 is negative enough . from eq . ( [ dilaton - bh ] ) we see that the maximum value of @xmath97 for which this is true is @xmath163 . interestingly , these negative values of @xmath97 lead to an insulator at low temperatures in the normal phase . it is possible to reformulate this discussion in more general terms than exponential @xmath6 : what actually matters here is whether the quantity @xmath164 is small enough for small temperatures ; comparing with eq . ( [ dcsigma ] ) , we see that when this is the case the normal phase tends to be insulating . in the region where @xmath152 we have that @xmath9 decreases and eventually vanishes at @xmath151 : this is a model - independent feature of superconductivity because at the critical point both the superconductive and the vortex configurations go to the normal one . finally , we have analyzed the second critical field @xmath10 , defined as the maximum value of @xmath153 for which we are in the vortex phase . since @xmath165 goes to zero continuously as @xmath166 , the backreaction of @xmath14 on @xmath167 is so small for @xmath168 that one can take @xmath169 and neglect the dynamics of the magnetic field when computing @xmath10 . this means that we can set a dirichlet condition for @xmath170 at the ads - boundary and that @xmath10 is the same for superconductors and superfluids . we will describe explicitly how we computed this quantity in section [ superlfuids ] , but here we present the final result . in fig . [ hc12-vs - mu ] we give @xmath10 and we compare it with @xmath9 . we observe that @xmath10 is always bigger than @xmath9 and therefore there is a finite range of @xmath153 , that is @xmath171 , for which the superconductor is in the vortex phase ( the superconductor is of type ii ) . the holographic superconductor in dilaton - gravity shares this feature with the other holographic superconductors studied so far , based on pure einstein gravity , both in ungapped @xcite and gapped @xcite phases , and therefore it seems , at least to some extent , a universal property of holographic superconductivity . since we are dealing with a type ii superconductor we can conclude that for @xmath172 , but still close enough to @xmath9 , the energetically favorable configuration is the single vortex with @xmath147 , while if @xmath153 increases further , more and more vortices appear until they form a triangular lattice at @xmath173 @xcite . . [ cols= " < , < , < " , ] as we have already said , in the limit in which @xmath40 is nondynamical a superconductor is equivalent to a superfluid . in this section we focus on such limit . in order not to duplicate the symbols , we use the superconductor notation here , but in table [ table ] we give the dictionary to interpret the various quantities in terms of superfluid physics . in particular we are interested in the case in which an external velocity ( denoted by @xmath174 in the lab frame ) is performed on the system . in the formulation of superfluidity we are considering all vectors are expressed in the frame where the external velocity is zero , unless otherwise stated . since superfluids are characterized by being irrotational we focus on constant external angular velocities , where the only nonvanishing component of @xmath174 is a_= r^2 . [ dirichlet]the external angular velocity coincides with @xmath175 . when @xmath167 is small enough the system is in the superfluid state that is irrotational , so the fluid angular velocity is -@xmath176 and @xmath177 . at high @xmath167 superfluidity is eventually broken and @xmath178 ( normal phase ) . for intermediate values of @xmath167 the system is in the vortex phase . to holographically describe this situation we therefore consider once again the ansatz in ( [ ansatz - vortex ] ) . cc cc eq . ( [ dirichlet ] ) can be viewed as a dirichlet boundary condition at @xmath30 . at large ) , we take a large but finite - size system : @xmath179 . ] values of @xmath135 , @xmath180 , we impose instead _ r=0 , _ r a_0=0 , a_=r^2 . [ superfluid - large - r ] the first two conditions correspond to the physical requirement that the field configuration goes to the homogeneous superfluid state at large @xmath135 , while the last one is a simple possibility compatible with the form of @xmath149 given in eq . ( [ dirichlet ] ) . we have numerically @xcite solved eqs . ( [ eom - vortices ] ) with the boundary conditions in eqs . ( [ bch ] ) , ( [ bcr0 ] ) , ( [ uv ] ) , ( [ dirichlet ] ) and ( [ superfluid - large - r ] ) . in fig . [ ojvsr ] we present the corresponding vortex profiles . the minimum value of @xmath167 at which the vortex starts being favorable , called @xmath181 , is known for large @xmath182 and is given in table [ table ] . that formula is model independent and so must be true here in particular . in the infinite volume limit , @xmath183 , we have that @xmath184 ; superfluids are deep type ii superconductors and as such they have the properties mentioned at the end of section [ hscs section ] . as we have already stated , the maximum value of @xmath167 for which the system is in the vortex state , @xmath185 , coincides with that for superconductors . we have computed @xmath10 as the value of @xmath167 at which @xmath186 and provide it as a function of @xmath106 on the right plot of fig . [ hc12-vs - mu ] . we have studied superconductors and superfluids through the ads / cft correspondence with a dilaton in the gravitational theory . our results are summarized in the introductory section . let us provide some outlook of our work here . we have focused on the case in which the charged scalar @xmath14 is massless , this corresponds in the cft side to an operator of dimension 3 . giving @xmath14 a mass would change the dimension of @xmath37 . it may be interesting to do so as this would introduce a third function of the dilaton that represents a running mass . along these lines one could then analyze a more general theory with the given field content having several running constants , which may be useful to identify model - independent features . we found that the holographic superconductors studied here are of type ii , like those without the dilaton @xcite proposed in refs . it would be valuable to know if there is a general reason for this property or , on the other hand , it is possible to engineer a type i superconductor . a more general theory , similar to that mentioned in the paragraph above , could be a good starting point to address this question . the ( non ideal)insulator / superconductor transition that can be realized between the dilaton - bh and the corresponding condensed phase is an alternative to that proposed in ref . @xcite , which exploits a well known deconfined / confined transition @xcite . it is then natural to ask if the properties of the latter scenario ( see for example refs . @xcite ) are shared by the dilaton theories discussed here , for the setup corresponding to an insulator / superconductor transition . * acknowledgments . * we would like to thank andrs anabaln for a very useful correspondence . this work was supported by the eu itn unification in the lhc era " , contract pitn - ga-2009 - 237920 ( unilhc ) and by miur under contract 2006022501 .

we investigate holographic models of superfluids and superconductors in which the gravitational theory includes a dilatonic field . dilaton extensions are interesting as they allow us to obtain a better description of low temperature condensed matter systems . we focus on asymptotically ads black hole configurations , which are dual to field theories with conformal ultraviolet behavior . a nonvanishing value of the dilaton breaks scale invariance in the infrared and is therefore compatible with the normal phase being insulating ( or a solid in the fluid mechanical interpretation ) ; indeed we find that this is the case at low temperatures and if one appropriately chooses the parameters of the model . not only the superfluid phase transitions , but also the response to external gauge fields is analyzed . this allows us to study , among other things , the vortex phase and to show that these holographic superconductors are also of type ii . however , at low temperatures they can behave in a qualitatively different way compared to their analogues without the dilaton : the critical magnetic fields and the penetration depth can remain finite in the small @xmath0 limit . -1.0 cm -0.5 cm -0.5 cm * holographic superfluids and superconductors + in dilaton - gravity * + alberto salvio _ scuola normale superiore and infn , piazza dei cavalieri 7 , 56126 pisa , italy _

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(C) Installation of rumble strips or another warning device, if the rumble strips or other warning devices do not adversely affect the safety or mobility of bicyclists and pedestrians, including persons with disabilities. (D) Installation of a skid-resistant surface at an intersection or other location with a high frequency of crashes. (E) An improvement for pedestrian or bicyclist safety or the safety of persons with disabilities. (F) Construction and improvement of a railway- highway grade crossing safety feature, including the installation of protective devices. (G) The conduct of a model traffic enforcement activity at a railway-highway crossing. (H) Construction of a traffic calming feature. (I) Elimination of a roadside hazard. (J) Installation, replacement, and other improvements of highway signage and pavement markings or a project to maintain minimum levels of retroreflectivity that addresses a highway safety problem consistent with a State strategic highway safety plan. (K) Installation of a priority control system for emergency vehicles at signalized intersections. (L) Installation of a traffic control or other warning device at a location with high crash potential. (M) Transportation safety planning. (N) Collection, analysis, and improvement of safety data. (O) Planning integrated interoperable emergency communications equipment, operational activities, or traffic enforcement activities (including police assistance) relating to work zone safety. (P) Installation of guardrails, barriers (including barriers between construction work zones and traffic lanes for the safety of road users and workers), and crash attenuators. (Q) The addition or retrofitting of structures or other measures to eliminate or reduce crashes involving vehicles and wildlife. (R) Installation of yellow-green signs and signals at pedestrian and bicycle crossings and in school zones. (S) Construction and operational improvements on a high risk rural road (as defined in section 148(a) of title 23, United States Code). (T) Geometric improvements to a road for the purposes of safety improvement. (U) A road safety audit. (V) Roadway safety infrastructure improvements consistent with the recommendations included in the publication of the Federal Highway Administration entitled ``Handbook for Designing Roadways for the Aging Population'' (FHWA-SA-14-015), dated June 2014 (or a revised or updated publication). (W) Truck parking facilities eligible for funding under section 1401 of MAP-21 (23 U.S.C. 137 note; Public Law 112-141). (X) Systemic safety improvements. (Y) Installation of vehicle-to-infrastructure communication equipment. (Z) Pedestrian hybrid beacons. (AA) Roadway improvements that provide separation between pedestrians and motor vehicles, including medians and pedestrian crossing islands. (BB) A physical infrastructure safety project not described in subparagraphs (A) through (AA). (b) New Categorical Exclusions.-- (1) Review of existing categorical exclusions.--The Secretary shall review the categorical exclusions under section 771.117 of title 23, Code of Federal Regulations (or successor regulations), to determine which, if any, are applicable for use by the Secretary in review of projects eligible for assistance under section 202 of title 23, United States Code. (2) Review of tribal transportation safety projects.--The Secretary shall identify tribal transportation safety projects that meet the requirements for categorical exclusions under sections 1507.3 and 1508.4 of title 40, Code of Federal Regulations. (3) Proposal.--The Secretary shall issue a proposed rule, in accordance with sections 1507.3 and 1508.4 of title 40, Code of Federal Regulations, to propose any categorical exclusions identified under paragraphs (1) and (2). (4) Deadline.--Not later than 180 days after the date of enactment of this Act, and after considering any comments on the proposed rule issued under paragraph (3), the Secretary shall promulgate a final rule for the categorical exclusions, in accordance with sections 1507.3 and 1508.4 of title 40, Code of Federal Regulations. (5) Technical assistance.--The Secretary of Transportation shall provide technical assistance to the Secretary in carrying out this subsection. (c) Reviews of Tribal Transportation Safety Projects.-- (1) In general.--The Secretary or the head of another Federal agency responsible for a decision related to a tribal transportation safety project shall complete any approval or decision for the review of the tribal transportation safety project required under the National Environmental Policy Act of 1969 (42 U.S.C. 4321 et seq.) or any other applicable Federal law on an expeditious basis using the shortest existing applicable process. (2) Review of applications.--Not later than 45 days after the date of receipt of a complete application by an Indian tribe for approval of a tribal transportation safety project, the Secretary shall-- (A) take final action on the application; or (B) provide the Indian tribe a schedule for completion of the review described in paragraph (1), including the identification of any other Federal agency that has jurisdiction with respect to the project. (3) Decisions under other federal laws.--In any case in which a decision under any other Federal law relating to a tribal transportation safety project (including the issuance or denial of a permit or license) is required, not later than 45 days after the Secretary has made all decisions of the lead agency under the National Environmental Policy Act of 1969 (42 U.S.C. 4321 et seq.) with respect to the project, the head of the Federal agency responsible for the decision shall-- (A) make the applicable decision; or (B) provide the Indian tribe a schedule for making the decision. (4) Extensions.--The Secretary or the head of an applicable Federal agency may extend the period under paragraph (2) or (3), as applicable, by an additional 30 days by providing the Indian tribe notice of the extension, including a statement of the need for the extension. (5) Notification and explanation.--In any case in which a required action is not completed by the deadline under paragraph (2), (3), or (4), as applicable, the Secretary or the head of a Federal agency, as applicable, shall-- (A) notify the Committee on Indian Affairs of the Senate and the Committee on Natural Resources of the House of Representatives of the failure to comply with the deadline; and (B) provide to the Committees described in subparagraph (A) a detailed explanation of the reasons for the failure to comply with the deadline. SEC. 4. PROGRAMMATIC AGREEMENTS FOR CATEGORICAL EXCLUSIONS. (a) In General.--The Secretary shall enter into programmatic agreements with Indian tribes that establish efficient administrative procedures for carrying out environmental reviews for projects eligible for assistance under section 202 of title 23, United States Code. (b) Inclusions.--A programmatic agreement under subsection (a)-- (1) may include an agreement that allows an Indian tribe to determine, on behalf of the Secretary, whether a project is categorically excluded from the preparation of an environmental assessment or environmental impact statement under the National Environmental Policy Act of 1969 (42 U.S.C. 4321 et seq.); and (2) shall-- (A) require that the Indian tribe maintain adequate capacity in terms of personnel and other resources to carry out applicable agency responsibilities pursuant to section 1507.2 of title 40, Code of Federal Regulations (or successor regulations); (B) set forth the responsibilities of the Indian tribe for making categorical exclusion determinations, documenting the determinations, and achieving acceptable quality control and quality assurance; (C) allow-- (i) the Secretary to monitor compliance of the Indian tribe with the terms of the agreement; and (ii) the Indian tribe to execute any needed corrective action; (D) contain stipulations for amendments, termination, and public availability of the agreement once the agreement has been executed; and (E) have a term of not more than 5 years, with an option for renewal based on a review by the Secretary of the performance of the Indian tribe. Passed the Senate November 29, 2017. Attest: Secretary. 115th CONGRESS 1st Session S. 302 _______________________________________________________________________ AN ACT To enhance tribal road safety, and for other purposes.

John P. Smith Act (Sec. 3) This bill modifies the approval process under the National Environmental Policy Act (NEPA) for tribal transportation safety projects to categorically exclude&nbsp;qualifying projects from requirements to conduct environmental assessments and environmental impact statements. A tribal transportation safety project is one that is eligible for assistance under the tribal transportation program and that: (1) corrects or improves a hazardous road location or feature, or (2) addresses a highway safety problem. The Department of the Interior must: (1) review existing Federal Highway Administration categorical exclusions to determine applicability to tribal transportation program projects, and (2) identify tribal transportation safety projects that meet general categorical exclusion requirements. Interior must establish categorical exclusions for tribal projects consistent with its findings. The bill prescribes requirements for the expedited review and approval of tribal transportation safety projects under NEPA or other federal laws. (Sec. 4) Interior must enter into five-year programmatic agreements with Indian tribes that establish efficient administrative procedures for carrying out environmental reviews for tribal transportation program projects. An agreement may allow a tribe to determine whether a project is categorically excluded from the preparation of an environmental assessment or impact statement under NEPA.

this disease is named after thomas addison , who first described patients affected by this disorder in 1855 , in the book titled on the constitutional and local effects of the disease of supra renal capsule . addison 's disease can present as a life - threatening crisis , because it is frequently unrecognized in its early stages . the basis of addison 's disease has dramatically changed from an infectious cause to autoimmune pathology since its initial description . however , tuberculosis is still the predominant cause of addison 's disease in developing countries . the symptom of addison 's disease begins gradually , chronic worsening fatigue , loss of appetite , generalized weakness , hypotension , and weight loss . the clinical features of hypoadrenocorticism do not actually begin to appear until at least 90% of the glandular tissue has been destroyed . generalized hyperpigmentation of skin is seen , which is classically described as bronzing the hyperpigmentation is generally more prominent on sun - exposed skin and over pressure points , such as the elbows and knees which are caused by increased levels of beta - lipotropin or adrenocorticotropic hormone , each of which can stimulate melanocyte production . hyperpigmentation of the mucous membrane and skin usually proceeds over other symptoms by month to year . vitiligo may also be seen in association with hyperpigmentation in idiopathic addison 's disease due to autoimmune destruction of melanocytes.[46 ] hyponatremia and hyperkalemia are commonly associated with addison 's disease , while hypoglycaemia uncommon . the patient usually complains of gastrointestinal upset with anorexia , nausea , vomiting , diarrhea , and a peculiar craving for salt . adrenal calcification and enlargement are commonly seen in addison 's disease associated with tuberculosis.[79 ] the symptoms of addison ' disease progress slowly and are usually ignored , an event of illness or accident can make the condition worsen and lead to addisonian crisis . sudden penetrating pains in the lower back region , abdomen or legs are symptoms of addisonian crisis with severe vomiting and diarrhea , which is followed by dehydration , low blood pressure and loss of consciousness . the current case not only presents with the typical features of the disorder but also with the extra and particularly unique extensive intraoral pigmentation which is often considered as the initial presentation of the addison 's disease . a 26-year - old female came with the complaint of bleeding gum and bad breath , since last 10 months . patient also gave a history of occasional abdominal pain , amenorrhea , nausea , and vomiting , dysphagia , weight loss and hypotension . she also gave history of sleep disturbances occasionally , which is usually accompanied by the exacerbation of abdominal pain . on clinical examination thin and brittle nail , scanty body hair , hyperpigmentation of skin in the neck [ figure 1 ] and in the lower abdominal region was present . intraoral examination demonstrated pigmentation with bilateral involvement of buccal mucosa , gingival , mucosal surface of lower lip , alveolar mucosa , and hard palate [ figure 2 ] . tongue appears to be smooth with loss of the papilla with pigmentation on the posterior surface [ figure 3 ] . the gingiva appears to be blunt with apical positioning of gingival margins , significant loss of attachment with pocket depth between 3 and 5 mm . hyperpigmentation in the neck and chest region hyperpigmentation in the palate hyperpigmentation and depapillation of the tongue laboratory investigations revealed anemia with hemoglobin level 7.8 g / dl , with normal red blood cell morphology , erythrocyte sedimentation rate ( esr ) 59 mm / h , fasting blood sugar 70 mg / dl . the metabolic profile , including serum urea , creatinine and electrolyte all were within the normal range . anti - hiv , anti hepatitis c virus hepatitis b surface antigen ( hcv hbsag ) factors were negative . based on patient history , clinical findings and laboratory investigations , we reached to the diagnosis of addison 's disease . cortisol replacement in from of methyl prednisolone 10 mg in morning and 5 mg in evening is started , as her condition improved the dose of methyl prednisolone is reduced to 7.5 mg per day . she had an episode of addisonian crisis 3 months after the initial visit and admitted to the hospital , where acute malarial attack was diagnosed to be the precipitating factor . she was managed intravenous fluids , parental supplement glucose , hydrocortisone , and anti - malarial drugs . a variety of pathological processes may cause addison 's disease , which was first described by thomas addison.[13 ] the commonest causes of addison 's disease are autoimmune and tuberculosis . several autoimmune processes can lead to adrenal insufficiency affecting exclusively the adrenal glands or be part of a more complex inherited autoimmune polyglandular syndrome . fungal infection , hemochromatosis , metastatic neoplasm , and x - linked adrenoleukodystrophy are other causes of addison 's disease . several investigators have found dysphagia , fatigue , weight loss and hypotension , abdominal pain , amenorrhea , nausea , and vomiting , thin and brittle nail , scanty body hair in addison 's disease , which is also present in this study.[25791112 ] psychiatric symptoms such as mood disturbances , decreased motivation , and behavior changes are frequently associated with addison 's disease . according to anglin et al . , the etiology of neuropsychiatric symptoms associated with addison 's disease is unknown , but may be related with the disturbances in the electrophysiological , electrolyte , and metabolic activity . in this case , sleep disturbances on periodic exacerbation is present in this case , which is according to the study by lvs et al . one of the hallmark signs of addison 's disease is cutaneous and mucosal hyperpigmentations related to acth melanogenesis action.[35 ] soule reported that the presenting features among 50 patients seen over a 17-year period , as including hyperpigmentation ( 86% ) , weight loss ( 67% ) , abdominal pain ( 20% ) , and diarrhea ( 16% ) . brown patches of gingival , vermillion border of the lips , buccal mucosa , palate , and tongue may represent the first signs of addison 's disease . in this study , pigmentation was present in the neck [ figure 1 ] and in the lower abdominal region with bilateral involvement of buccal mucosa , gingival , mucosal surface of lower lip , and alveolar mucosa . tongue appears to be smooth with loss of the papilla with pigmentation on the posterior surface [ figure 3 ] . lab investigation in this case presented hemoglobin value of 7.8 g / dl , with normal morphology of the erythrocyte , esr was 59 mm / h , and fasting blood sugar level was 70 mg / dl . grinspoon and biller observed decrease hemoglobin percentage , decrease blood sugar level , which is also present in this study . this case is managed by methyl prednisolone initially and later she developed addison crisis and fully recovered after brief hospitalization . the patient is now maintained with methyl prednisolone . addison disease is rare endocrinal disorder , in the developed nations it usually related to auto - immune disorder but in the developing nations it is widely associated with tuberculosis . addison disease is usually associated with dysphagia , fatigue , weight loss , hypotension , abdominal pain , amenorrhea , nausea , vomiting , thin and brittle nail , scanty and body hair . intraorally pigmentation over the gingival , vermillion border of lip , buccal mucosa , palate tongue , is evident and perceived as first sign . as the oral manifestation of the addison 's disease , particularly oral pigmentation may develop earlier than their dermatological counterpart , dental surgeon may be the first medical professional to encounter disease and early diagnosis of the disease essential for proper medical management .

addison 's disease is a rare endocrinal disorder , with several oral and systemic manifestations . a variety of pathological processes may cause addison 's disease . classically , hyperpigmentation is associated with the disease , and intraoral pigmentation is perceived as the initial sign and develops earlier than the dermatological pigmentation . the symptoms of the disease usually progress slowly and an event of illness or accident can make the condition worse and may lead to a life - threatening crisis . in this case , several oral as well as systemic manifestation of the addison 's disease was encountered .

Media playback is unsupported on your device Media caption The BBC's David Willey says the Pope seems serene about his last 12 days in office Tens of thousands of pilgrims have attended St Peter's Square in Rome for one of the final public appearances of Pope Benedict XVI. He is stepping down on 28 February. The Pope recited the Angelus prayer and thanked all those who had prayed for him and shown him support over the past few days since his resignation. The Vatican has said it may hold the conclave that chooses the new pope early, so he can be in place before the start of Holy Week on 24 March. Vatican accommodation The Pope appeared at his study window overlooking St Peter's Square at 11:00 GMT, his first such appearance since announcing his resignation last Monday. The crowd erupted into loud applause and there were chants of "Long live the Pope". One banner in the square read: "We love you". What happens next 17-23 February - Lenten retreat, most normal Vatican functions suspended - Lenten retreat, most normal Vatican functions suspended 24 February - Pope recites Angelus in public for the last time - Pope recites Angelus in public for the last time 27 February - Last weekly audience, in St Peter's Square - Last weekly audience, in St Peter's Square Evening of 28 February - Pope leaves office - Pope leaves office From 15 March - Conclave to elect new Pope In pictures: Crowds greet Pope How many Catholics are there in the world? How does a Pope resign from office? The Pope used his Angelus appearance to urge the faithful to "renew" and "refocus" on God. He said: "The Church calls on all its members to renew themselves... which constitutes a fight, a spiritual battle, because the evil spirit wants us to deviate from the road towards God." The pope spoke in a number of languages; speaking in Spanish, he said: "I beg you to continue praying for me and for the next pope." The BBC's David Willey in Rome says that after the prayer recital on Sunday the Pope plans to spend the rest of the week on a Lenten prayer retreat closeted inside the Apostolic Palace with senior cardinals and bishops. He says the retreat will be a time of reflection about what Pope Benedict's eight-year long papacy has achieved and what are the priorities now facing a Church whose credibility has been seriously harmed by clerical sex abuse scandals. Vatican spokesman Federico Lombardi said earlier: "The Pope is living through these days calmly even though they're very emotional and packed." The Vatican said on Saturday it was considering calls from cardinals to hold the papal conclave earlier than planned, to have a pontiff in place before Holy Week, the most important event in the Christian calendar. Under current rules, the vote cannot be held before 15 March, to give cardinals enough time to travel to Rome. The Vatican is examining the possibility of changing the rule. After his spiritual retreat, the Pope will have very few public engagements. Image caption A banner reads "the immaculate will win" as pilgrims wait for the Pope's blessing He is scheduled to receive Italian President Giorgio Napolitano on 23 February. The Pope will then celebrate Angelus again on 24 February and hold a final audience in St Peter's Square on 27 February. Pope Benedict will be flown to his summer residence of Castel Gandolfo on 28 February and remain there as accommodation in the Vatican is prepared. At 19:00 GMT on 28 February he will no longer by pope. One Vatican official told Reuters news agency it was "absolutely necessary" that Benedict lived in the enclave, "otherwise he might be defenceless". "He wouldn't have his immunity, his prerogatives, his security, if he is anywhere else," the official said. There are concerns he could be cited in relation to legal cases connected with alleged sexual abuses by Catholic Church officials. The 85-year-old pontiff announced his shock resignation last Monday, citing his advanced age as the reason for stepping down. The last pontiff to resign was Pope Gregory XII, who quit in 1415 amid a schism within the Church. ||||| 1 of 28. Pope Benedict XVI waves as he leads the Sunday Angelus prayer in Saint Peter's Square at the Vatican February 17, 2013. Pope Benedict, speaking before a larger than usual crowd at his penultimate Sunday address, asked the faithful to pray for him and for the next pope. VATICAN CITY (Reuters) - Pope Benedict asked the faithful to pray for him and for the next pope, in his penultimate Sunday address to a crowded St. Peter's Square before becoming the first pontiff in centuries to resign. The crowd chanted "Long live the pope!," waved banners and broke into sustained applause as he spoke from his window. The 85-year-old Benedict, who will abdicate on February 28, thanked them in several languages. Speaking in Spanish, he told the crowd which the Vatican said numbered more than 50,000: "I beg you to continue praying for me and for the next pope". It was not clear why the pope chose Spanish to make the only specific reference to his upcoming resignation in his Sunday address. A number of cardinals have said they would be open to the possibility of a pope from the developing world, be it Latin America, Africa or Asia, as opposed to another from Europe, where the Church is crisis and polarized. "I can imagine taking a step towards a black pope, an African pope or a Latin American pope," Cardinal Kurt Koch, a Swiss Vatican official who will enter the conclave to choose the next pope, told Reuters in an interview. After his address, the pope retired into the Vatican's Apostolic Palace for a scheduled, week-long spiritual retreat and will not make any more public appearances until next Sunday. Speaking in Italian in part of his address about Lent, the period when Christians reflect on their failings and seek guidance in prayer, the pope spoke of the difficulty of making important decisions. "In decisive moments of life, or, on closer inspection, at every moment in life, we are at a crossroads: do we want to follow the ‘I', or God? The individual interest, or the real good, that which is really good?" he said. FOR THE GOOD OF THE CHURCH The pope has said his physical and spiritual forces are no longer strong enough to sustain him in the job of leading the world's 1.2 billion Roman Catholics at a time of crisis for the Church in a fast-changing world. Benedict's papacy was rocked by crises over the sex abuse of children by priests in Europe and the United States, most of which preceded his time in office but came to light during it. His reign also saw Muslim anger after he compared Islam to violence. Jews were upset over his rehabilitation of a Holocaust denier. During a scandal over the Church's business dealings, his butler was convicted of leaking his private papers. Since his shock announcement last Monday, the pope has said several times that he made the difficult decision to become the first pope in more than six centuries to resign for the good of the Church. Aides said he was at peace with himself. "In a funny way he is even more peaceful now with this decision, unlike the rest of us, he is not somebody who gets choked up really easily," said Greg Burke, a senior media advisor to the Vatican. "I think that has a lot to do with his spiritual life and who he is and the fact he is such a prayerful man," Burke told Reuters Television. People in the crowd said the pope was a shadow of the man he was when elected on April 19, 2005. "Like always, recently, he seemed tired, moved, perplexed, uncertain and insecure," said Stefan Malabar, an Italian in St. Peter's Square. "It's something that really has an effect on you because the pope should be a strong and authoritative figure but instead he seems very weak, and that really struck me," he said. The Vatican has said the conclave to choose his successor could start earlier than originally expected, giving the Roman Catholic Church a new leader by mid-March. Some 117 cardinals under the age of 80 will be eligible to enter the secretive conclave which, according to Church rules, has to start between 15 and 20 days after the papacy becomes vacant, which it will on February 28. But since the Church is now dealing with an announced resignation and not a sudden death, Vatican spokesman Federico Lombardi said the Vatican would be "interpreting" the law to see if it could start earlier. CONSULTATIONS BEGUN Cardinals around the world have already begun informal consultations by phone and email to construct a profile of the man they think would be best suited to lead the Church in a period of continuing crisis. The Vatican appears to be aiming to have a new pope elected and then formally installed before Palm Sunday on March 24 so he can preside at Holy Week services leading to Easter. New details emerged at the weekend about Benedict's health. Peter Seewald, a German journalist who wrote a book with the pope in 2010 in which Benedict first floated the possibility of resigning, visited him again about 10 weeks ago. "His hearing had deteriorated. He couldn't see with his left eye. His body had become so thin that the tailors had difficulty in keeping up with newly fitted clothes ... I'd never seen him so exhausted-looking, so worn down," Seewald said. The pope will say one more Sunday noon prayer on February 24 and hold a final general audience on February 27. The next day he will take a helicopter to the papal summer retreat at Castel Gandolfo, south of Rome, where he will stay for around two months before moving to a convent inside the Vatican where he will live out his remaining years. (Additional reporting by Hanna Rantala; Editing by Robin Pomeroy)

– Pope Benedict XVI is blessing the faithful from his window overlooking St. Peter's Square for the first time since announcing his resignation, cheered by an emotional crowd of tens of thousands of well-wishers from around the world. Speaking in Spanish, Reuters notes that Benedict implored the crowd, "I beg you to continue praying for me and for the next pope." He triumphantly raised his arms outstretched to the crowd in his second-to-last Angelus blessing before leaving the papacy. A huge banner in the square read: "We love you." The appointment today is one of the most cherished traditions of the Catholic Church, and this moment is one of Benedict's last opportunities to connect with the Catholic masses. The pontiff will spend the rest of the week on a Lenten prayer retreat, reports the BBC.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Green Communities Act''. SEC. 2. FINDINGS; PURPOSES; DEFINITIONS. (a) Findings.--Congress finds the following: (1) Landscaping adds to the economic value and sales appeal of commercial real estate and increases office occupancy rates. (2) Greening can change people's perceptions of their neighborhoods, reduce violence and crime, and increase neighborhood stability. (3) Planting new trees, improving streetscapes, and cleaning vacant lots increases property values. (4) People will stay longer and shop more in shopping districts that are well landscaped. (5) Improvements to neighborhood parks increase the value of single-family homes in the surrounding community. (6) Homes adjacent to vacant lots that are greened have a much higher property value than homes adjacent to vacant lots that have not been greened. (b) Purposes.--The purposes of this Act are to-- (1) promote investment in greening projects and programs as effective economic development tools; (2) connect urban economic development initiatives with environmental initiatives; (3) improve quality of life for city residents; and (4) encourage public-private partnerships. (c) Definitions.--In this Act: (1) Community greening initiatives.--The term ``community greening initiatives'' means programs increasing economic development through environmental improvements. (2) Eligible nonprofit organization.--The term ``eligible nonprofit organization'' means a nonprofit organization that receives a grant under section 4. (3) Eligible program partner.--The term ``eligible program partner'' means a municipality that receives a grant under section 3. (4) Green roof.--The term ``green roof'' means a roof consisting of vegetation and soil or a growing medium planted over a waterproofing membrane. (5) Green stormwater infrastructure.--The term ``green stormwater infrastructure'' means systems and practices that use or mimic natural processes to infiltrate, evapotranspirate, or reuse stormwater on the site where it occurs rather than transporting the water to a stream or treatment facility. (6) Nonprofit organization.--The term ``nonprofit organization'' means an organization that is described in section 501(c)(3) of the Internal Revenue Code of 1986 and exempt from tax under section 501(a) of such Code. (7) Secretary.--The term ``Secretary'' means the Secretary of Commerce. (8) Urban forestry.--The term ``urban forestry'' means an integrated citywide or neighborhood-wide approach to the planting, care, and management of trees in the city or the neighborhood in order to ensure environmental and social benefits for residents. SEC. 3. INITIATIVES FOR ECONOMIC DEVELOPMENT AND GREENING. (a) Grant Authority.--To the extent funds are available, the Secretary, through the Economic Development Administration, shall make grants to municipalities for promoting community greening initiatives. (b) Selection of Eligible Program Partners.--The Secretary, in consultation with the eligible nonprofit organizations, shall select 80 municipalities to receive grants under this section. The Secretary shall ensure that the municipalities meet-- (1) the criteria described by section 209(b) of the Public Works and Economic Development Act of 1965 (42 U.S.C. 3149(b)); or (2) the circumstances described by section 209(c) of such Act (42 U.S.C. 3149(c)). (c) Community Greening Initiatives.--An eligible program partner, with technical assistance and training from an eligible nonprofit organization as provided under section 4(b), shall develop and plan a community greening initiative. Such initiatives may include-- (1) revitalizing municipal parks and public spaces; (2) landscaping community gateways and key corridors; (3) tree plantings and urban forestry projects; (4) comprehensive planning for open space preservation; (5) education, training, and volunteer management concerning community green initiatives; (6) green roof construction; (7) green stormwater infrastructure; or (8) vacant lot management. (d) Implementing Initiatives.-- (1) Completion of developing and planning.--The Secretary may make a grant under this section only to an eligible program partner that has successfully developed and planned a community greening initiative under subsection (c), as determined by the Secretary. (2) Use of funds.--Grants under this section shall be used by an eligible program partner to implement the community greening initiative developed under subsection (c). An eligible program partner may not receive a grant under this section for a community greening initiative that takes more than 2 years to complete. (3) Grant amount.--The Secretary may not award a grant under this section in an amount that is more than $2,000,000. (4) Matching funds.--An eligible program partner receiving a grant under this section shall provide, either directly or through private contributions, non-Federal matching funds equal to not less than 50 percent of the amount of the grant. Such matching funds shall be used for implementing a community greening initiative. (5) Report.--Not later than 60 days after an eligible program partner implements a community greening initiative, the eligible nonprofit organization that assisted the eligible program partner under subsection (c) shall submit to the Secretary a report assessing the implementation of the initiative. SEC. 4. TECHNICAL ASSISTANCE AND TRAINING BY ELIGIBLE NONPROFIT ORGANIZATIONS. (a) Selection of Eligible Nonprofit Organizations.--To the extent funds are available, the Secretary shall make grants to, or enter into contracts with, 5 nonprofit organizations to provide technical assistance and training to eligible program partners. The Secretary shall select nonprofit organizations that have experience with-- (1) planning and implementing projects concerning urban open space, landscape management, and community greening initiatives; (2) land and water conservation; (3) working on the community level; (4) forming partnerships or regional consortiums; (5) urban ecology; and (6) other activities the Secretary considers appropriate. (b) Technical Training and Assistance.--In accordance with section 3(c), eligible nonprofit organizations shall provide eligible program partners with technical assistance and training for the following activities: (1) Developing, planning, implementing, and assessing community greening initiatives. (2) Developing and implementing training and workshops for municipal agencies and local partners. (3) Evaluating the community greening initiative. (c) Period.--A grant or agreement under this section shall be for a period of 5 years. (d) Report to Congress.--Not later than 90 days after the end of each fiscal year for which amounts are made available for grants under this section, the Secretary shall submit to Congress a report on the technical assistance and training provided under this section. Each report shall describe the actions taken by the Secretary to ensure that technical assistance and training is responsive to the needs of eligible program partners. SEC. 5. AUTHORIZATION OF APPROPRIATIONS. (a) In General.--There is authorized to be appropriated to carry out this Act-- (1) $30,000,000 for each of fiscal years 2010, 2013, and 2014; and (2) $90,000,000 for each of fiscal years 2011 and 2012. (b) Reservation of Funds.-- (1) Eligible nonprofit organizations.-- (A) Not less than 85 percent of the amounts made available to carry out this Act for each of fiscal years 2010, 2013, and 2014 shall be made available for technical assistance and training by eligible nonprofit organizations under section 4. (B) Not less than 28 percent of the amounts made available to carry out this Act for each of fiscal years 2011 and 2012 shall be made available for technical assistance and training by eligible nonprofit organizations under section 4. (2) Eligible program partners.--Not less than 66 percent of the amounts made available to carry out this Act for each of fiscal years 2011 and 2012 shall be made available for the planning, developing, and implementing of community greening initiatives by eligible program partners under section 3. (c) Availability of Appropriations.--Funds made available under this Act shall remain available until expended.

Green Communities Act - Directs the Secretary of Commerce, through the Economic Development Administration, to make grants to municipalities to promote community greening initiatives (defined as programs increasing economic development through environmental improvements). Directs the Secretary to select 80 municipalities to receive grants. Requires an eligible program partner to develop and plan such an initiative, which may include revitalizing municipal parks and public spaces, tree plantings, green roof construction, and vacant lot management. Directs the Secretary to make grants to, or enter into contracts with, five nonprofit organizations to provide technical assistance and training to eligible program partners in developing, planning, implementing, and assessing initiatives.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Financial Literacy for Homeowners Act''. SEC. 2. FINDINGS. The Congress finds the following: (1) While expanded access to credit from both prime and subprime lenders has contributed to the highest homeownership rates in the Nation's history, there is growing evidence that some lenders are engaging in predatory lending practices-- excessive front-end fees, single-premium credit life insurance, and exorbitant prepayment penalties--that make homeownership much more costly for families that can least afford it. (2) Borrowers with fair to good credit ratings may be able to obtain loans in the ``prime'' mortgage market, with the lowest interest rates and costs. (3) Borrowers with blemished credit histories obtain mortgage loans in the ``subprime'' mortgage market, with higher interest rates and loan fees than are obtainable in the prime market. Some subprime lenders have been making loans on terms that are regarded as ``predatory''. (4) Predatory lending involves home mortgages, mortgage refinancing, home equity loans, and home repair loans with unjustifiably high interest rates, excessive fees, balloon payments, prepayment penalties, and the imposition of other unreasonable, and sometimes fraudulent, terms. (5) Predatory loans are said to have grown rapidly in minority neighborhoods, often stripping away wealth that may have taken owners decades or a lifetime to accumulate. (6) Some communities that have lacked access to traditional institutions were being victimized by second mortgage lenders, home improvement contractors, and finance companies who peddled high interest rate home equity loans with high loan fees to cash-poor homeowners. Borrowers, who may not have fully understood the terms of the loans, and who may not have been offered adequate disclosures of the loan terms, often have struggled to meet overwhelming mortgage payments and too often ultimately lost their homes through foreclosure. (7) A joint report by the Department of Housing and Urban Development and the Department of the Treasury, issued June 21, 2000, entitled ``Curbing Predatory Home Mortgage Lending'', urged the Congress to adopt legislation that would restrict abusive terms and conditions on high-cost loans, prohibit harmful sales practices in mortgage markets, improve consumer literacy and disclosures, prohibit government-sponsored enterprises from purchasing loans with predatory features, and establish predatory lending as a factor in evaluations for the Community Reinvestment Act of 1977. (8) The joint report proposed a four-point plan to address predatory lending practices, which included improving consumer literacy and disclosures by requiring lenders to recommend that applicants for high-cost loans avail themselves of home mortgage counseling, to disclose credit scores to all borrowers upon request, and to give borrowers more timely and more accurate information on loan costs and terms. (9) A number of government agencies have become involved in addressing various aspects of the predatory lending issue in an attempt to reduce the number of lenders that use high-pressure telemarketing sales techniques and mislead borrowers about increases in interest rates and monthly payments on adjustable rate mortgages. (10) Predatory lending threatens to undo the work of many nonprofit organizations that have worked with lenders and local governments to improve distressed neighborhoods. More needs to be done to assist borrowers who already have predatory loans, to educate consumers about the dangers and pitfalls of entering into a home loan, and to refer consumers to appropriate governmental agencies or consumer protection organizations for assistance. SEC. 3. GRANT PROGRAM FOR EDUCATION AND COUNSELING REGARDING PREDATORY LENDING. (a) In General.--The Secretary of the Treasury may make grants under this section to States, units of general local government, and nonprofit organizations, which shall be used only for costs of carrying out eligible anti-predatory lending activities under subsection (b). (b) Eligible Anti-Predatory Lending Activities.--Amounts from a grant under this section may be used only for carrying out the following activities: (1) Education programs.--For education programs to inform and educate consumers, particularly those most vulnerable to being taken advantage of by predatory and unscrupulous lending practices relating to home loans (such as low-income borrowers and senior citizens), regarding home mortgages, mortgage refinancing, home equity loans, and home repair loans with unjustifiably high interest rates, excessive fees, balloon payments, prepayment penalties, and the imposition of other unreasonable, and sometimes fraudulent, terms. (2) Counseling programs.--For programs, provided only by organizations certified by the Secretary as competent to provide homeownership counseling, that counsel homeowners and prospective homeowners regarding predatory and unscrupulous lending practices relating to home loans. (3) Referral services.--For services that provide referrals, for homeowners and prospective homeowners-- (A) to education and counseling programs described in paragraphs (1) and (2); or (B) to appropriate agencies or authorities responsible for handling consumer complaints, allegations, or requests for assistance regarding predatory and unscrupulous lending practices relating to home loans or for investigating the circumstances surrounding home loans for possible violations of law. (c) Eligibility and Application.--To be eligible for a grant under this section, a State, unit of general local government, or nonprofit organization shall submit to the Secretary an application for a grant in such form and including such information as the Secretary shall require, which shall include such information as the Secretary considers appropriate to ensure that the grant amounts are used for activities eligible under subsection (b). (d) Maximum Grant Amount.--The maximum amount of grant funds that may be provided under this section to any single grantee for any single fiscal year shall be $1,000,000. (e) Selection of Applicants.--The Secretary shall provide for States, units of general local government, and nonprofit organizations to submit applications for grants under this section. The Secretary shall select applications to receive such grants according to selection criteria, which the Secretary shall establish. SEC. 4. TOLL-FREE TELEPHONE NUMBER FOR PREDATORY LENDING COMPLAINTS. The Secretary shall, using any amounts reserved under section 7(1), provide for the establishment, operation, and publication of a nationwide toll-free telephone number to receive consumer complaints regarding predatory and unscrupulous lending practices relating to home loans, provide information about predatory lending, refer borrowers who already have predatory loans to the appropriate governmental agencies or consumer protection organizations for assistance, and coordinate between existing State and nonprofit community organizations to create a resource database of information for consumers. Such toll-free telephone line shall provide for receipt of such consumer complaints and provision of such information at all times only through an actual person and not by pre-recorded or recorded means. SEC. 5. PREDATORY LENDING ADVISORY COUNCIL. (a) Establishment.--There is established in the Department of the Treasury a Predatory Lending Advisory Council (in this section referred to as the ``Council'') to advise the Secretary on policies and issues relating to predatory and unscrupulous lending practices relating to home loans. (b) Membership.--The Council shall be composed of 13 members appointed by the Secretary, who shall include-- (1) 4 members who are representatives of community-based organizations that work with consumers, lenders, and State and local governments to improve distressed neighborhoods, assist borrowers who already have predatory loans, educate consumers about the dangers and pitfalls of entering into a home loan, and refer consumers to appropriate governmental agencies or consumer protection organizations for assistance; (2) 3 members who are officials of State agencies or offices for consumer affairs or consumer protection; (3) 3 members who are private homeowners who are familiar with home mortgages, mortgage refinancing, home equity loans, and home repair loans; and (4) 3 members who are representatives of the private real estate industry, such as realtors, mortgage brokers, and bankers. (c) Terms and Vacancies.--Members of the Council shall serve terms of two years, except that, of the initial members appointed, half shall serve terms of one year and half shall serve terms of two years. A vacancy in the Council shall be filled in the manner in which the original appointment was made. (d) Travel Expenses.--Members of the Council shall serve without compensation but shall receive travel expenses, including per diem in lieu of subsistence, in accordance with sections 5702 and 5703 of title 5, United States Code. (e) Chairperson.--The Secretary shall designate a chairperson of the Council at the time of appointment. (f) Meetings and Hearings.--The Council shall meet upon the call of the chairperson, except that the council shall meet not fewer than 3 times per year. The Council shall have the authority, when a majority of the members deem necessary, to hold public hearings and to take testimony and receive evidence from individuals and organizations. (g) Advisory Functions.--The Council shall provide advice to the Secretary regarding-- (1) the grant program under section 3, including advice regarding criteria for selection of applications to receive grant amounts; (2) the establishment, operation, and publication of the toll-free telephone number under section 4; (3) coordination of activities of the Secretary regarding prevention of predatory and unscrupulous lending practices relating to home loans with such activities of lending institutions; and (4) any other matters regarding predatory and unscrupulous lending practices relating to home loans that the Secretary considers appropriate. (h) Study of Defaults and Foreclosures.--The Council shall conduct an extensive study of the root causes of default and foreclosure of home loans, using as much empirical data as are available. The Council shall submit a report to the Secretary and the Congress, not later than 12 months after the full membership of the Council is first appointed, regarding the results of the study, which shall include recommendations for consumer protection legislation regarding predatory and unscrupulous lending practices relating to home loans. SEC. 6. DEFINITIONS. For purposes of this Act, the following definitions shall apply: (1) Home loan.--The term ``home loan'' means a loan or agreement to extend credit made to a natural person, which loan is secured by a deed to secure debt, security deed, mortgage, security instrument, deed of trust, or other document representing a security interest or lien upon any interest in one- to four-family residential property or a manufactured home, regardless of where made, including the renewal or refinancing of any such loan. Such term includes a home equity line of credit or home improvement loan or other similar agreement. (2) Nonprofit organization.--The term ``nonprofit organization'' has the meaning given such term in section 104(5) of the Cranston-Gonzalez National Affordable Housing Act (42 U.S.C. 12704(5)), except that subparagraph (D) of such section shall not apply for purposes of this Act. (3) Predatory or unscrupulous lending practice.--The term ``predatory or unscrupulous lending practice'' includes-- (A) making any loan that-- (i) is solely based on the borrower's home equity; (ii) is made without regard to the borrower's ability to repay the obligation; and (iii) is unaffordable to the borrower, as may be evidenced by a failure to fully understand the terms of the loans, a failure to offer adequate disclosures of the loan terms, a difficulty in meeting overwhelming mortgage payments, loss of a home through foreclosure, or otherwise; (B) inducing a borrower to refinance a loan repeatedly and charging additional points and fees, even though refinancing may not be in the borrower's interest; and (C) engaging in fraud or deception to conceal the true nature of the loan obligation from an unsuspecting or unsophisticated borrower. (4) Secretary.--The term ``Secretary'' means the Secretary of the Treasury. (5) State.--The term ``State'' means each of the several States, the Commonwealth of Puerto Rico, the District of Columbia, the Commonwealth of the Northern Mariana Islands, Guam, the Virgin Islands, American Samoa, the Trust Territories of the Pacific, or any other possession of the United States. (6) Unit of general local government.--The term ``unit of general local government'' means any city, town, township, parish, village, or other general purpose political subdivision of a State. SEC. 7. AUTHORIZATION OF APPROPRIATIONS. There is authorized to be appropriated for carrying out this Act $55,000,000 for each of fiscal years 2008 through 2012, of which-- (1) not more than $2,000,000 in each such fiscal year shall be for carrying out section 4; and (2) not more than $5,000,000 in each such fiscal year shall be for carrying out section 5. SEC. 8. REGULATIONS. The Secretary may issue any regulations necessary to carry out this Act.

Financial Literacy for Homeowners Act - Authorizes the Secretary of the Treasury to make grants to state and local governments and nonprofit organizations to implement anti-predatory lending activities, including: (1) consumer education programs; (2) certified home ownership counseling programs; and (3) referral services for homeowners and prospective homeowners. Directs the Secretary provide for establishment, operation, and publication of a nationwide toll-free telephone number to receive consumer complaints regarding predatory and unscrupulous lending practices relating to home loans. Establishes the Predatory Lending Advisory Council to: (1) advise the Secretary; and (2) study and report to the Secretary and Congress on the root causes of default and foreclosure of home loans.

fistulation from aorta to gastric conduit after ivor - lewis oesophagectomy is a rare and life threatening condition . reported cases have occurred early post operatively , with a mean post - operative day of presentation of 46 in a review of 23 cases . the majority of these patients presented with a herald bleed ( 93% ) ( 1 ) . early post operative leakage from the suture line of the anastamosis , erosion of the gastric conduit by acidic gastric contents and reduced blood supply to the conduit have been suggested as potential causative factors ( 2,3 ) . thoracic lymphadenectomy , whereby the descending aorta is completely skeletonised , is believed to predispose to fistulation . in this report we present a rare case of the successful treatment of an aorto enteric fistula developing four years after oesophagectomy . a fit and well 71 year old woman presented with a history of reduced appetite and weight loss and was found to have a squamous cell carcinoma of the oesophagus at 30 cm . following restaging an ivor - lewis oesophagectomy was performed with meticulous two field thoraco - abdominal lymphadenectomy . histopathology confirmed a complete pathological response ( mandard regression grade 1 ) to neo - adjuvant therapy ( t0n0 with 0/37 nodes positive ) . there were no immediate post operative complications and she was discharged day 16 post op . over the subsequent three years she was troubled by recurrent dysphagia related to benign anastamotic strictures which required multiple dilatations . acute gastric ulcer seen on endoscopy acute gastric ulcer post treatment with gold probe an endoscopy performed four years post - operatively demonstrated two atypical acute gastric ulcers in the distal stomach ( figure 1 ) , which were treated with a heat probe ( figure 2 ) . two days later she presented as an emergency in hypovolaemic shock following a large volume haematemesis ( haemoglobin of 40g / l ) . an urgent upper gastrointestinal endoscopy revealed a visible vessel at 35 cm forming part of an expansive mass within the gastric conduit . eus demonstrated a heterogeneous mass indenting the gastric conduit , containing a strong doppler signal ( figure 3 ) . an urgent computerised tomography ( ct ) angiogram revealed a type - a thoracic aortic aneurysm with an enteric fistula ( figure 4 ) . the saccular aneurysm of the thoracic aorta was embedded in the gastric conduit . a 28x16 cm valiant ( medtronic ltd , minneapolis , usa ) stent the patient made an excellent recovery and was discharged on the seventh day post stenting . eus examination showing thoracic aneurysm compressing esophagus ct scan showing thoracic aortic aneurysm post operatively the patient developed a low grade stent infection requiring a prolonged course of antibiotics as an outpatient . two years after insertion of the stent she remains well with no further gastrointestinal bleeding and follow up endoscopy has shown intact mucosa at the site of fistula . computerised tomography scanning has demonstrated involution of the aneurysm sac and no endo - leak ( figure 5 ) . aorta - conduit or gastric fistulae are an uncommon complication following oesophagectomy . in this case report we have discussed a patient who developed an aorto - conduit fistula more than four years after an ivor lewis oesophagectomy . in the few cases that have been reported in the literature oesophago - aortic fistulae have presented on average two to three weeks post operatively . eighty two percent ( 82% ) of cases reported presented between the second and sixth weeks postoperatively ( 1 ) . the longest duration between oesophagectomy and presentation of bleed aorta - conduit fistulae tend to present with a triad of symptoms , first described by chiari - strassburgh in 1914 , of chest pain , sentinel haemorrhage and then finally exsanguination following a massive gastro - intestinal haemorrhage ( 5 ) . in a review of 23 reported cases of aorto - conduit fistula 21 patients presented with a herald bleed and only one patient survived operative management of this complication . this presenting symptom may be the only sign prior to massive gastro - intestinal haemorrhage and death . signs of gastro - intestinal bleeding in oesophagectomy patients should raise the suspicion of an aorto - conduit fistula . the latent period between herald bleed and exsanguination has an average duration of ten hours ( 1 ) . proposed aetiology for this complication includes early post operative leakage from the suture line of the anastamosis causing an oesophago - pleural fistula and then an aorto - oesophageal fistula ( 2 ) . this would seem an unlikely cause in the case we have described as four years had passed between the occurrence of the fistula and the original oesophagectomy . erosion of the gastric conduit by highly acidic gastric contents may also predispose to fistula formation ( 3 ) . gastric erosion and ulceration into both the aorta and pericardium from the intra - thoracic portion of the stomach has been reported post oesophagectomy . it is further proposed that chronic infection of these gastric ulcers may be a contributory factor . pathological sections of aorta - oesophageal fistula have shown a granulomatous type inflammation suggestive of mycotic infection complicating ulceration ( 3 ) . indeed this may well have been the cause of the fistula in the case report we have described . an endoscopy performed two days prior to the presentation of the aorto - oesophageal fistula showed two acute atypical looking gastric ulcers .

a 71 year old lady was treated for a squamous cell carcinoma of the oesophagus with neo - adjuvant chemotherapy followed by a two phase ivor - lewis oesophagectomy with two field lymphadenectomy . she presented four years later with life threatening bleeding from a fistula between the thoracic aorta and the gastric conduit , which was treated successfully with a thoracic aortic stent .

NASA / JPL-Caltech / R. Hurt An artist's conception of a free-floating planet that has roughly the mass of Jupiter. Sumi et al. show that these lone worlds, perhaps ejected from the planetary systems of their birth, are probably more common than stars in our galaxy The bitterly fought Pluto wars of a few years back showed that even the experts disagree on what is and what isn't a planet. One thing there's no quarrel about, of course: a planet is, by definition, something that orbits a star. Except, it turns out, when it isn't. Writing in the latest issue of Nature, a team of astronomers is reporting the discovery of 10 objects roughly the size of Jupiter that seem to be on the loose, roaming the galaxy untethered to any star. And while 10 seems to be an insignificant number in a galaxy packed with 200 billion or more stars, the search was an extremely limited one. Unless the observers happened to be absurdly lucky, there could actually be a lot more of these rogue Jupiters — perhaps twice as many as there are stars in the Milky Way. (See the top 50 space moments since Sputnik.) "The implications of this discovery," writes Joachim Wambsganss of the Center for Astronomy at the University of Heidelberg in an accompanying Nature commentary, "are profound." They aren't, however, completely unexpected. As the known number of conventional exoplanets — that is, those that actually do orbit stars — has grown to more than 500 in recent years, astronomers have begun to realize that our well-behaved solar system isn't necessarily typical. Its eight planets orbit the sun in nearly circular orbits, all moving in the same direction as the sun's rotation. But plenty of alien worlds orbit their stars in eccentric, somewhat egg-shaped orbits, and surprising numbers move around their stars in highly tilted orbits as well. (Nonplanet Pluto inscribes just such an inclined and elliptical path.) Some planets even orbit backward. (See pictures of Saturn.) That suggests that sometime in the past, close gravitational encounters with other planets flung them out of their previously conventional orbits. Theorists have predicted for years that such close encounters might also fling planets out into interstellar space. "There's nothing physically mysterious about this," says David Stevenson, a Caltech astronomer who has been working on rogue-planet scenarios for more than a decade. "It's a perfectly natural outcome." (See pictures of five nations' space programs.) Still, he says, it's exciting to see something that had been purely theoretical backed up by hard evidence. It's also notable that these planets were discovered with a technique that sounds like something out of Star Trek. As Albert Einstein explained nearly a century ago, the gravity of a massive object such as a star or a planet warps the space-time that surrounds it. If a ray of light passes close by, the light will be diverted as though it were passing through a giant lens. In the 1930s, Einstein realized that if one star passed in front of another, the closer star could act as a gravitational lens, focusing the light of the more distant star and making it look brighter. We'd never actually see such an effect, conceded Einstein. All stars orbit the center of the galaxy at slightly different speeds, meaning that they are in constant motion relative to one another; the exact lineup necessary to make true lensing occur would happen only very rarely, Einstein believed. For once, though, the great man was wrong. The first gravitational lens was spotted in 1979, and they've become a mainstay of astronomical research ever since. This has aided in the search for exoplanets, as astronomers scan the skies for double flashes — one caused by a foreground star moving in front of a background star, and one following soon after, caused by the orbiting planet. (See TIME's space-shuttle covers.) It's not the most efficient way to discover planets, since you never know when just the right lineup will occur, but about a dozen star-planet pairs have been found with this technique. The 10 free-floating planets revealed themselves the same way, but what distinguished them, says Takahiro Sumi of Osaka University, the study's lead author, is that when they pass in front of a background star, "we don't see any evidence of the host star." Not, at least, within a billion miles or so of the planets, and based on more conventional studies of exoplanets, that suggests that many if not all of the planets indeed have no host star at all. The one caveat offered by both Stevenson and Wambsganss is that while these objects are certainly similar in mass to Jupiter, they could, in fact, be more like small stars, having condensed as the central object out of a swirl of cosmic dust and gas, albeit without sufficient mass to light their nuclear fires. Conventional planets condense out of similar clouds, but they are made up of the leftover dust a parent star didn't use. Some planetary theorists argued that the term "planet" should only apply to the latter, even if two objects have exactly the same mass. (See pictures of Earth from space.) But offsetting that caveat is an even more exciting possibility. If close encounters can throw Jupiter-size planets out of a solar system, they can throw smaller, Earth-size worlds out even more easily — meaning they may outnumber even the hundreds of billions of drifting Jupiters. The brief magnifying flashes they produce would be very hard to detect from the ground, but a proposed space telescope known as the Microlensing Planet Finder could do it — and even find planets as small as Mars. In theory, the mission could fly by 2020. In these days of reduced budgets, however, there's no guarantee that it will actually happen. But if it does, we may soon know what the theorists already suspect: that the Milky Way is teeming with free-range planets of all sizes, floating silently and forlornly in the spaces between the stars. ||||| Newly Found Planets Aren’t Tightly Linked With Solar Systems, Report Says A new class of planets that either aren’t tied to a specific solar system, or are very distantly linked, has been identified by astronomers. The planets were probably ejected from developing planetary systems, said a report today in the journal Nature. The analysis identifies what appears to be 10 free-floating planets roughly the mass of Jupiter, which is about 310 times larger than Earth. Researchers led by astronomer David Bennett, of the University of Notre Dame in Indiana, analyzed observations made of the Milky Way in 2006 and 2007 by a Japan-New Zealand survey. They found 10 potentially orphaned planets, the report said. The analysis, the first evidence of such objects in the galaxy, wasn’t sensitive enough to identify smaller planets, the researchers said. “This tells us something about how planet formation works,” Bennett said in a telephone interview today. “We know planet formation is a violent process. There may be close two- body encounters where one planet gets flung out of the system. Or, if they’re just in distance orbits, there are a lot of planets forming a lot further out.” Free-floating planets are difficult to detect, so the identification of as many as 10 implies more exist, the report suggests. The researchers estimated there may be twice as many free-floaters as there are stars in the sky, or there may be a lot of Jupiter-sized planets very far from their stars. “Our survey is like a population census -- we sampled a portion of the galaxy and, based on these data, can estimate overall numbers in the galaxy,” Bennett said. Finding Free-Floaters The U.S. National Aeronautics and Space Administration, or NASA, will attempt to pinpoint free-floating planets in the Milky Way galaxy during its WFIRST mission, which is currently being planned. WFIRST is designed to study questions in non-sun planets and dark energy research, in part by monitoring changes in brightness to stars made by solar systems, according to the NASA mission page. “Our results suggest that planetary systems often become unstable, with planets being kicked out from their places of birth by close encounters with other planets,” Bennett said in the statement. If they formed on their own, like stars, “then we would have expected to see only one or two of them in our survey instead of 10.” The typical free-floating planet was about 10 astronomical units out, Bennett said. Saturn is 9.5 astronomical units from the sun. Some planets may be in orbit and perpendicular to observers, making it harder to detect their host stars. To contact the reporter on this story: Elizabeth Lopatto in New York at [email protected]. To contact the editor responsible for this story: Reg Gale at [email protected]. ||||| Artist's concept showing a free-floating planet with roughly the mass of Jupiter. These lone worlds, perhaps ejected from the planetary systems of their birth, are probably more common in our galaxy than stars. Astronomers have discovered a whole new class of alien planet: a vast population of Jupiter-mass worlds that float through space without any discernible host star, a new study finds. While some of these exoplanets could potentially be orbiting a star from very far away, the majority of them most likely have no parent star at all, scientists say. And these strange worlds aren't mere statistical anomalies. They likely outnumber "normal" alien planets with obvious parent stars by at least 50 percent, and they're nearly twice as common in our galaxy as main-sequence stars, according to the new study. [Photos: The Strangest Alien Planets] Astronomers have long predicted the existence of free-flying "rogue alien planets." But their apparent huge numbers may surprise many researchers, and could force some to rethink how the planets came to be. "Previous observations of bound planets tell us only about planets which are surviving in orbits now," said study lead author Takahiro Sumi, of Osaka University in Japan. "However, [these] findings inform us how many planets have formed and scattered out." Alien worlds under gravitational lens Sumi and his colleagues made the find using a method called gravitational microlensing, which watches what happens when a massive object passes in front of a star from our perspective on Earth. The nearby object bends and magnifies the light from the distant star, acting like a lens. This produces a "light curve" — a brightening and fading of the faraway star's light over time — whose characteristics tell astronomers a lot about the foreground object's size. In many cases, this nearby body is a star; if it has any orbiting planets, these can generate secondary light curves, alerting researchers to their presence. Before the current study, astronomers had used the gravitational microlensing technique to discover a dozen or so of the nearly 550 known alien planets. (NASA's Kepler mission has detected 1,235 candidate planets by a different method, but they still need to be confirmed by follow-up observations.) Sumi and his team looked at two years' worth of data from a telescope in New Zealand, which was monitoring 50 million Milky Way stars for microlensing events. They identified 474 such events, including 10 that lasted less than two days. The short duration of these 10 events indicated that the foreground object in each case was not a star but a planet roughly the mass of Jupiter. And the signals from their parent stars were nowhere to be found. Independent observations from a telescope in Chile backed up the finds. Either these 10 planets orbit very far from their host stars — more than 10 times the Earth-sun distance — or they have no host stars at all, researchers said. [Infographic: A Sky Full of Alien Planets] Common throughout the galaxy Gravitational microlensing events are rare, because they require the precise alignment of a background star, a massive foreground object and Earth. So the discovery of 10 short-duration events in two years suggests a huge population of these unbound or distantly orbiting Jupiter-mass exoplanets throughout the galaxy, researchers said. Sumi and his team calculated, in fact, that these planets are probably almost twice as common in our own Milky Way as main-sequence stars. And they likely outnumber "normal" planets with known host stars by more than 50 percent. Other studies have established that it's probably pretty rare for huge planets to orbit more than 10 Earth-sun distances from a parent star. So the research team argues that most of the Jupiter-mass planets — at least 75 percent of them — are likely true "rogues," floating through space unbound to a star. Theory predicts that such rogues should exist throughout the galaxy, and other researchers have found evidence of unbound objects that may indeed be orphan planets. But those worlds were much bigger, from three to 10 times Jupiter's mass, and there's a lot of uncertainty in the measurements. Many of the previously detected objects could actually be "failed stars" known as brown dwarfs, Sumi said. Sumi and his colleagues report their results in the May 19 issue of the journal Nature. Rethinking planetary formation theories The newly discovered rogue planets may have formed close to a host star, then been ejected from their solar systems by the gravitational influence of a huge neighbor planet, researchers said. Indeed, such planet-planet interactions are thought to be responsible for the odd, extremely close-in orbits of the giant alien planets known as "hot Jupiters." But the abundance of the seemingly starless worlds may force astronomers to rethink some of their ideas about planet formation, according to Sumi. The "current most recognized planetary formation theory (core accretion model) cannot create so many giant planets," Sumi told SPACE.com in an email interview. "So we need a different theory to create [so] many giant planets, such [as the] gravitational instability model." In the core accretion model, dust coalesces to form a solid core, which later accretes gas around it, creating a planet. The gravitational instability model invokes the rapid collapse of gas, with a core forming later due to sedimentation. The new study should inspire much follow-up research. One of the next steps could involve training more instruments on the microlensing alien planets, further monitoring them for any signs of a parent star. Such work, which may take years, could eventually reveal how many of these worlds actually do have parent stars, and how many are true rogues. "The implications of this discovery are profound," astronomer Joachim Wambsganss, of Heidelberg University, wrote in an accompanying essay in the journal Nature. "We have a first glimpse of a new population of planetary-mass objects in our galaxy. Now we need to explore their proper­ties, distribution, dynamic states and history." You can follow SPACE.com senior writer Mike Wall on Twitter: @michaeldwall. Follow SPACE.com for the latest in space science and exploration news on Twitter @Spacedotcom and on Facebook.

– They're outcasts on a galactic scale, rebels without a star: Astronomers think they have discovered 10 massive planets that defy a standard definition of what it means to be a planet: They orbit no star. What's more, the astronomers believe there are many, many more roaming free about the Milky Way, possibly twice the number of stars in the galaxy, reports Time. The new findings could shed more light on how planets form. "The implications of this discovery are profound," writes a member of the Center for Astronomy in Germany in an accompanying Nature article. Scientists have long speculated that such rogue planets could exist, with one theory being that they got flung away from their own systems because of a too-close-encounter with another planet, explains Bloomberg. Astronomers used a process known as gravitational microlensing to detect the Jupiter-sized objects, and Space.com has more on how it works.

Photo The nasal flu vaccine spray, preferred by millions of anxious parents looking for a needle-free way to get their children immunized against the flu, as well as by adults who would rather not get a flu shot, is ineffective and should not be used in the upcoming flu season. That is the recommendation of the Advisory Committee on Immunization Practices, a committee of experts on immunization that advises the Centers for Disease Control and Prevention. On Wednesday, the committee announced that the nasal vaccine, FluMist, does not work and that children and others should instead get the flu shot. The American Academy of Pediatrics, an influential doctors’ group, endorsed the A.C.I.P.’s recommendation. In clinical practice, most doctors go along with the vaccine recommendations of the C.D.C. and the A.C.I.P. Dr. Melissa Stockwell, an associate professor of pediatrics and public health at Columbia, plans to do just that. “Early studies indicated that the nasal spray might be more effective than the injectable version,” she said. “And a couple of years ago we had a preference for giving the spray. Basically, while we used to have two options, for this upcoming season we’re going to use the injectable version.” Dr. Stockwell also had some advice for parents. “I’m going to tell parents it’s very important that we protect children against the flu. It can be a very serious disease, and all people 6 months and older should get the vaccine. I vaccinate my children, and I recommend it for all my patients. Having FluMist not available doesn’t matter — vaccination is the single most important way we can protect our children and ourselves.” FluMist had been approved for use in people 2 to 49 years old. Because it uses a live, though attenuated, virus, the nasal spray has not been recommended for people who are immune compromised or for pregnant women or nursing mothers. It was first licensed in 2003, after a large randomized controlled trial produced high quality evidence that FluMist was effective. About a third of all children vaccinated for flu have been given the nasal spray. The new recommendation is based partly on preliminary data that came out in late May, gathered during the 2015-16 flu season. It showed that the nasal vaccine had an efficacy of about 3 percent — in other words, it offered virtually no protection at all. By contrast, the injected vaccine, which uses an inactivated form of flu virus, is about 63 percent effective. The problem is that FluMist does not work against the H1N1 strain, which has been circulating more widely in recent years and causes the most serious disease in children. Each year, a new vaccine is formulated to match the most commonly circulating viruses, and efficacy can vary considerably from year to year and from person to person. Early data on FluMist found it just as effective, or even more effective, than the inactivated virus vaccines given by injection. “Then in the 2013-2014 season, the pandemic H1N1 virus came back,” said Brendan Flannery, an epidemiologist with the C.D.C. “That was the first year we could see there was a problem with FluMist. That happened to be the year that the A.C.I.P. recommended the live attenuated vaccine preferentially for children.” At that point, Dr. Flannery said, the manufacturer, AstraZeneca, reformulated the H1N1 component of the vaccine for the 2014-15 flu season But in that season, none of the flu vaccines worked very well, so it was difficult to see any difference between the reformulated FluMist and the injectable vaccines. Finally, in the 2015-16 season, in which the H1N1 strain again predominated, it was clear that FluMist was ineffective against it. “The live version is not working as well as it needs to,” Dr. Flannery said. “Why that is, we don’t know. We hope that the problem with the vaccine will be identified so that the manufacturer can come back with a fixed vaccine.” FluMist has already been produced for the 2016-17 season, but Lisa Grohskopf, a medical officer with the C.D.C., said that demand is hard to predict. “It’s still a licensed vaccine,” she said, “and some may use it anyway. If there is less use as a result of our recommendation, it will be difficult to know how well it works. In order to evaluate a vaccine, you have to have lots of use.” AstraZeneca released a statement disputing the A.C.I.P.’s finding, but said that “AstraZeneca is working with the C.D.C. to better understand its data to help ensure eligible patients continue to receive the vaccine in future seasons in the U.S.” Sales of FluMist in the United States in fiscal year 2015 were $206 million. ||||| (CNN) Flu vaccines are about to get more painful. A Centers for Disease Control and Prevention advisory committee recommended on Wednesday that FluMist, the nasal spray influenza vaccine, should not be used during the upcoming flu season. "To everyone's surprise and increasing consternation, this vaccine has performed quite poorly compared to the injectable vaccine," said Dr. William Schaffner, an infectious disease specialist. An alternative to the standard flu shot, FluMist had been approved for people between the ages of 2 and 49 years old by the Food and Drug Administration. The CDC committee, which includes 15 immunization experts, reviewed data from previous flu seasons, including the most recent season, comparing FluMist with the standard flu shot. The decision must now be approved by the CDC director, Dr. Tom Frieden before taking effect. The FDA first approved the nasal spray in 2003. MedImmune, a subsidiary of London-based AstraZeneca PLC, produces FluMist, a live attenuated influenza vaccine. By contrast, the flu shot is an inactivated influenza vaccine. Though the viruses in FluMist are live, they have been weakened (attenuated, in medical terms) and work by stimulating the immune system. There are two versions of FluMist: one a trivalent vaccine, which protects against three strains of flu virus, and the other a quadrivalent, protecting against four strains. "We agree with [the Advisory Committee on Immunization Practices'] decision today to recommend health care providers and parents use only the inactivated vaccine," Dr. Benard Dreyer, president of the American Academy of Pediatrics, said in a statement. The Pediatric Infectious Disease Society also stated its support during the hearing. Yet, prior to its recent poor performance, all evidence showed the spray worked better than the flu shot in children under the age of 8. And, during those sunny days, the CDC committee expressed a preference for the mist over the shot. "That lasted exactly a year," explained Schaffner. Still, the nasal spray had become a favorite among pediatricians. JUST WATCHED Saving your child from a killer flu Replay More Videos ... MUST WATCH Saving your child from a killer flu 00:59 "Kids in general prefer the FluMist," Atlanta pediatrician Dr. Jennifer Shu said. "I'm the same way; I'm needle-phobic." She said one drawback of the nasal spray is it may cause a runny nose for a day or two. "Half the time, these kids have a runny nose anyway, especially young children," she said. An estimated one-third of all flu vaccinations administered to children are nasal spray, according to the CDC. Pediatricians are likely to be most impacted by Wednesday's recommendation, especially those who have already placed orders for vaccines in advance of the upcoming flu season. "CDC will be working with manufacturers throughout the summer to ensure there is enough vaccine supply to meet the demand," the agency said in a statement. The FDA had been working with MedImmune to determine why the spray had begun to work so poorly. Each February, an FDA committee makes the final decision about which virus strains will go into vaccines sold in America for the coming season. Its decision is based on information from more than 100 countries, where influenza-monitoring centers conduct surveillance of circulating viruses. The committee considers which viruses are making people sick, where those viruses are spreading and how well the previous season's vaccine protects against them. After the committee selects the strains to be used for the vaccine, manufacturers genetically adapt the strains to optimize the vaccine for the production process. Typically, trivalent formulations include two A strains and one B strain, while the quadrivalent formulations add a second B strain. "So the question is whether there's something in the process that alters the strain," Schaffner said. Because the underlying science is so complex, there are no easy answer, he said. Dr. Haihao Sun of the FDA's Office of Pediatric Therapeutics said the inconsistent effectiveness results were a concern to the agency. Join the conversation See the latest news and share your comments with CNN Health on Facebook and Twitter. During the hearing, Dr. Chris Ambrose of MedImmune shared results from the company's 2015-16 influenza vaccine effectiveness study, which found the FluMist quadrivalent vaccine to be 46% effective, compared with the flu shot's 65% effectiveness. However, Dr. Brendan Flannery of the CDC presented data indicating that FluMist had zero effectiveness against one strain of flu. Acknowledging that FluMist offered advantages in the past, especially for children, Sun said the FDA would continue to work with MedImmune. "At this point, we're not ready to take a requirement for changing prescribing information," he said. Wednesday's recommendation is an interim decision that could be reversed when the panel reconsiders it next year with additional data.

– Bad news for needle-hating kids and their accommodating parents: the popular flu vaccine nasal spray FluMist is “ineffective and should not be used in the upcoming flu season," the New York Times reports. That's according to an advisory committee's recommendation to the CDC on Wednesday. FluMist accounts for about a third of all flu vaccinations given to children and was highly recommended at one point, CNN reports. But new data shows it's laughably ineffective against current flu strains to—as one expert puts it—"everyone's surprise and increasing consternation." While flu shots were about 63% effective during last year's flu season, the nasal spray was only about 3% effective. Which, as the Times points out, is "virtually no protection at all." Hopefully pediatricians are stocking up on lollipops.

Supreme Court Justice Clarence Thomas, shown at College of the Holy Cross in Worcester, Mass., in 2012, said of Moira Smith’s groping allegation: “This claim is preposterous and it never happened.” (Michael Dwyer/AP) The 25th anniversary of Justice Clarence Thomas’s confirmation to the Supreme Court has featured testimonials from his supporters, a symposium on his jurisprudence and tributes from conservative legal scholars about his influence on the court. But Thursday brought an unwelcome echo of the sexual harassment allegations that almost derailed his 1991 nomination: An Alaska lawyer told the National Law Journal that Thomas groped her at a dinner party in 1999, when she was a young Truman Foundation scholar in Washington. Through a court spokeswoman, Thomas told the publication: “This claim is preposterous and it never happened.” The woman, Moira Smith, said she decided to make the allegations not because of Thomas but because of Donald Trump. She posted the information on her Facebook page on Oct. 7, hours after the media disclosed that Trump had boasted on tape about grabbing women. “When Justice Thomas touched me inappropriately and without my consent, I was 23 years old — and felt there was nothing I could do,” Smith said in a statement released Wednesday. “Seventeen years later, it is clear that sexual harassment, misconduct and assault continue to be pervasive, having an impact on all women. I choose to speak out now in the hope that this will change.” Smith said she was helping her boss at the dinner party when the incident occurred. Guests contacted by the National Law Journal said they saw nothing untoward. Smith, who posed for a photo with the justice later that night, did not tell them Thomas had grabbed her buttocks. But friends said Smith told them about the alleged groping that same night and the next morning, and they were not surprised when Smith again recounted the incident earlier this month. “I don’t remember the specific timeline,” Amy Hertel Buckley, 39, another Truman scholar at the dinner that night, told The Washington Post. “But when I saw her Facebook post, it was instantly familiar to me. It’s been a long time, but she definitely told me about that after it happened.” Marcia Coyle, the longtime Supreme Court reporter who wrote the story, said Smith did not come forward. Smith initially made her Facebook posting private so that only friends could see it, Coyle said. Smith made it public after friends told her she should. A source told Coyle about the posting — Smith’s Facebook account has now been deactivated — and Coyle interviewed her and others who corroborated her account over a two-week period, according to the NLJ report. The dinner party was held at the Falls Church, Va., home of Louis Blair, then head of the Truman Foundation. It was a scholarship program founded by Congress to identify students “who demonstrate outstanding potential for and who plan to pursue a career in public service.” Smith, now the vice president and general counsel of Enstar Natural Gas Co. in Alaska, was a resident scholar who assisted Blair. Her unofficial duties involved helping coordinate events such as the dinner, which preceded another event at which Thomas was to give an award named for a judge he knew. Buckley said she also helped out at the dinner. Smith told the National Law Journal: “I was setting the place to his right when he reached out, sort of cupped his hand around my butt and pulled me pretty close to him. He said, ‘Where are you sitting?’ and gave me a squeeze. I said, ‘I’m sitting down at the garden table.’ He said, ‘I think you should sit next to me,’ giving me squeezes.” Smith said she was “so confused about what happened” because she liked Thomas but also felt he “had transgressed such a line.” The NLJ report said “her three former housemates during the spring and summer of 1999 each said in interviews they remembered Smith describing inappropriate contact by Thomas after she came home that night from the dinner or early the next morning.” In her Facebook post, Smith said she had been the victim of date rape in college, and also groped by an acquaintance. After hearing the Trump tape, she said, she decided “enough is enough.” She also told the NLJ: “We now know that many men in power take advantage of vulnerable women. That willingness by men in power to take advantage of vulnerable women relies on an unspoken pact that the women will not speak up about it. Why? Because they are vulnerable. Because they are star-struck. Because they don’t want to be whiners. Because they worry about their career if they do speak out. But silence no longer feels defensible; it feels complicit.” [‘It was just awful’: The Clarence Thomas hearings, in the words of those who were there] Thomas’s supporters rallied quickly to his defense, saying the charges were part of an unrelenting attack on the conservative justice. Some tied Smith to Democratic activists and noted that her husband is a former Democratic party official. “The alleged conduct bears no resemblance to the man I worked closely with, whom I still count a friend after nearly 10 years,” Carrie Severino, a former Thomas clerk, wrote on the National Review website. “Those of us who have known the justice or worked with him in any capacity . . . including those who disagree with him, recognize him to be a good and honest man.” Mark Paoletta, a former assistant White House counsel who worked on Thomas’s confirmation, questioned the timing. “I do not consider it a coincidence that this Democratic smear on Justice Thomas comes as he celebrates 25 years on the court, and in the heat of a presidential election.” [For Anita Hill, the Clarence Thomas hearings haven’t really ended] Severino and Paoletta noted that Smith in the past has supported Democrats, and that a former husband worked in the Obama White House. One of the friends who confirmed Smith’s story is a political consultant who works with Democrats. In her statement, Smith said she was motivated by her children. “As the mother of a young daughter and son, I am coming forward to show that it is important to stand up for yourself and tell the truth,” she said. Thomas spoke Wednesday during his remarks at the Heritage Foundation about his own confirmation hearings, marked by the allegations of Anita Hill that he verbally harassed her, and about other confirmation hearings since. “The city is broken in some ways,” Thomas said, adding, “at some point, we have got to recognize that we’re destroying our institutions.” Julie Tate contributed to this report. ||||| Photo WASHINGTON — An Alaska lawyer has accused Justice Clarence Thomas of groping her at a dinner party in 1999, a claim that Justice Thomas called “preposterous.” The lawyer, Moira Smith, who was a 23-year-old Truman Foundation scholar at the time, told The National Law Journal that Justice Thomas had “sort of cupped his hand around my butt and pulled me pretty close to him” as she was making final preparations for the party, in a Washington suburb. Justice Thomas, continuing to squeeze her buttocks, urged her to sit next to him at the dinner, Ms. Smith said. She declined. He asked if she was sure, Ms. Smith recalled. “I said yes, and that was the end of it,” she said. Through a court spokeswoman, Justice Thomas told The National Law Journal that the episode “never happened.” The spokeswoman, Kathleen L. Arberg, said she had nothing to add to that statement. Justice Thomas, 68, took his seat on the court 25 years ago after a searing confirmation battle that also featured accusations of sexual harassment. Advertisement Continue reading the main story Ms. Smith, who is now general counsel of Enstar Natural Gas, declined a request for an interview. But in a statement, she said that while she had felt powerless at the time of the groping, “17 years later, it is clear that sexual harassment, misconduct and assault continue to be pervasive, having an impact on all women.” She added, “I choose to speak out now in the hope that this will change.” In the National Law Journal article, Ms. Smith said her public accusation was prompted by the disclosure this month of a 2005 recording in which Donald J. Trump boasted about kissing women without their consent and groping them. She said she might have been flattered by the attention of a Supreme Court justice had he not been so aggressive. “But it felt somewhat menacing, and I felt vulnerable,” she told Marcia Coyle, a reporter. Three of Ms. Smith’s former housemates and her ex-husband said Ms. Smith had told them about the episode soon after it happened, according to The National Law Journal. But several guests at the dinner — held by the head of the Truman Foundation, which awards scholarships to young people who plan to pursue a career in public service — said they had no recollection of any inappropriate behavior. First Draft Political news and analysis from the staff of The New York Times. Sign-up for free NYT Newsletters Morning Briefing News to start your day, weekdays Opinion Today Thought-provoking commentary, weekdays Cooking Delicious recipes and more, 5 times a week Race/Related A provocative exploration of race, biweekly Please verify you're not a robot by clicking the box. Invalid email address. Please re-enter. You must select a newsletter to subscribe to. Sign Up Receive occasional updates and special offers for The New York Times's products and services. Thank you for subscribing. An error has occurred. Please try again later. View all New York Times newsletters. In Justice Thomas’s confirmation hearing in 1991, Anita Hill, a law professor who had worked for Justice Thomas before he became a judge, said he had tried to date her, used sexual innuendo and described pornographic movies in vivid detail. Justice Thomas, then a federal appeals court judge, responded to the accusations with fury. “This is a circus,” he said. “It’s a national disgrace. And from my standpoint, as a black American, it is a high-tech lynching.” The new accusation is not plausible, said Carrie Severino, a former law clerk to Justice Thomas. “A justice of the U.S. Supreme Court was the guest of honor at a tiny event, surely attracting the sort of swarm the justices tend to attract, yet not a single witness can corroborate Smith’s outlandish story,” Ms. Severino said. Mark Paoletta, who worked in the White House Counsel’s Office during Justice Thomas’s confirmation hearings, said the accusations were motivated by politics. “Justice Thomas has hired more than 30 women law clerks over the years, has worked closely with them day in and day out, and none of them has ever accused him of any inappropriate conduct,” he said. “In fact, they hold him in the highest regard. I do not consider it a coincidence that this Democratic smear on Justice Thomas comes as he celebrates 25 years on the court, and in the heat of a presidential election.” On Wednesday, after hearing of Ms. Smith’s accusations but before they were made public, Justice Thomas was interviewed at the Heritage Foundation. He was generally upbeat and expansive, but he turned serious when asked about his confirmation hearings. Advertisement Continue reading the main story “I think that we have decided that rather than confront the disagreements and the differences of opinion, we’ll simply annihilate the person who disagrees with us,” he said. “I don’t think that’s going to work in a republic, in a civil society.”

– Another accuser says she decided to come forward because of Donald Trump's remarks about woman—but she's accusing Clarence Thomas, not Trump, of groping her. Alaska lawyer Moira Smith says she was a 23-year-old Truman Foundation scholar in Washington when the Supreme Court justice touched her inappropriately at a dinner party in 1999, the Washington Post reports. "I was setting the place to his right when he reached out, sort of cupped his hand around my butt and pulled me pretty close to him," Smith tells the National Law Journal. "He said, 'Where are you sitting?' and gave me a squeeze. I said, 'I'm sitting down at the garden table.' He said, 'I think you should sit next to me,' giving me squeezes." Smith—whose former roommates tell the Journal they remember her talking about the incident—says she felt powerless to do anything at the time but is coming forward now because "sexual harassment, misconduct, and assault continue to be pervasive," the New York Times reports. Anita Hill's accusation of sexual harassment almost cost Thomas his Supreme Court confirmation, which was 25 years ago this week, the Post notes. His supporters described Smith's accusations as a politically motivated attack. Through a spokeswoman, Thomas told the Journal: "This claim is preposterous and it never happened."

A new photograph-analyzing tool quantifies changes made by digital airbrushers in the fashion and lifestyle industry, where image alteration has become the psychologically destructive norm. "Publishers have legitimate reasons to alter photographs to create fantasy and sell products, but they've gone a little too far," said image forensics specialist Hany Farid of Dartmouth University. "You can't ignore the body of literature showing negative consequences to being inundated with these images." In a Nov. 28 Proceedings of the National Academy of Sciences study, Farid and doctoral student Eric Kee debut a computational model developed by analyzing 468 sets of original and retouched photographs. From these, Farid and Kee distilled a formal mathematical description of alterations made to models' shapes and features. Their model then scored each altered photograph on a scale of 1 to 5, with 5 signifying heavy retouching. To validate the scores, Farid and Kee then asked 50 people randomly picked through Amazon's Mechanical Turk task outsourcing service to evaluate the photographs. Computational and human scores matched closely. "Now what we have is a mathematical measure of photo retouching," said Farid. "We can predict what an average observer would say." The researchers started developing their model after learning of the British government's plans to label photographic alterations in advertising. Psychologists have become vocally critical of such images: By employing an arsenal of retouching techniques, from unnaturally slimmed limbs to the old standby of cleaned-up skin, retouchers create unattainable standards of both beauty and normalcy, ultimately leading to self-destructive body image disorders. In June, the American Medical Association urged advertisers to work with activists in developing alteration standards. Setting limits, however, is easier said than done. "One criticism of the British legislation is that they were presenting a blunt instrument. Photographs would be labeled as retouched or not. Anybody knows that there's different types," said Farid. "It's an interesting scientific problem: How much is too much? That got us thinking about whether we could quantify this." Farid and Kee's model doesn't precisely determine a numerical boundary between psychologically appropriate and inappropriate; that's a judgement call to be made by society, Farid said. But they do provide an objective metric for evaluating images and trends. "You look at what photographs looked like in magazines 10 years ago, and there's a huge difference. And that is escalating," said Farid. On the following pages are more images from the study. Image Analysis: Color-coded overlays show the intensity of alteration at different points on a retouched photograph. ||||| Their work is intended as a technological step to address concerns about the prevalence of highly idealized and digitally edited images in advertising and fashion magazines. Such images, research suggests, contribute to eating disorders and anxiety about body types, especially among young women. The Dartmouth research, said Seth Matlins, a former talent agent and marketing executive, could be “hugely important” as a tool for objectively measuring the degree to which photos have been altered. He and his wife, Eva Matlins, the founders of a women’s online magazine, Off Our Chests, are trying to gain support for legislation in America. Their proposal, the Self-Esteem Act, would require photos that have been “meaningfully changed” to be labeled. Photo “We’re just after truth in advertising and transparency,” Mr. Matlins said. “We’re not trying to demonize Photoshop or prevent creative people from using it. But if a person’s image is drastically altered, there should be a reminder that what you’re seeing is about as true as what you saw in ‘Avatar,’ ” the science-fiction movie with computer-generated actors and visual effects. The algorithm developed by Dr. Farid and Mr. Kee statistically measures how much the image of a person’s face and body has been altered. Many of the before-and-after photos for their research were plucked from the Web sites of professional photo retouchers, promoting their skills. The algorithm is meant to mimic human perceptions. To do that, hundreds of people were recruited online to compare sets of before-and-after images and to determine the 1-to-5 scale, from minimally altered to starkly changed. The human rankings were used to train the software. Newsletter Sign Up Continue reading the main story Please verify you're not a robot by clicking the box. Invalid email address. Please re-enter. You must select a newsletter to subscribe to. Sign Up You agree to receive occasional updates and special offers for The New York Times's products and services. Thank you for subscribing. An error has occurred. Please try again later. View all New York Times newsletters. His tool, Dr. Farid said, would ideally be a vehicle for self-regulation. Information and disclosure, he said, should create incentives that reduce retouching. “Models, for example, might well say, ‘I don’t want to be a 5. I want to be a 1,’ ” he said. Yet even without the prod of a new software tool, there is a trend toward Photoshop restraint, said Lesley Jane Seymour, editor in chief of More, a magazine for women over 40. Women’s magazine surveys, said Ms. Seymour, a former editor of Marie Claire and Redbook, show that their readers want celebrities to “look great but real.” “What’s terrific is that we’re having this discussion,” she said. But readers, she added, have become increasingly sophisticated in understanding that photo retouching is widespread, and the overzealous digital transformations become notorious, with the before-and-after images posted online and ridiculed. Advertisement Continue reading the main story “Readers aren’t fooled if you really sculpt the images,” Ms. Seymour said. “If you’re a good editor, you don’t go too far these days. If you give someone a face-lift,” she said, adding, “you’re a fool.”

– Highly altered images of models and celebrities in fashion magazines have come under increasing scrutiny, with France even proposing that all airbrushed pictures come packaged with a health warning. A new tool could make that easier, as it analyzes photographs to detect digital retouching, Wired reports. Publishers have “gone a little too far,” explains the Dartmouth specialist who helped create the tool, adding that there are “negative consequences” associated with a barrage of such images. The new tool would rank images from 1, or barely altered, to 5. It takes into account geometric adjustments (slimming the hips, widening the eyes) as well as photometric adjustments (removing wrinkles, changing skin tone), Mother Nature Network notes. The creators analyzed 468 sets of photos to develop a computational model, which then scored each photo. They then tested the scores by having people evaluate the pictures, and found that the scores they gave closely matched. “Now what we have is a mathematical measure of photo retouching,” the Dartmouth expert explains. “We can predict what an average observer would say.” Such labeling makes more sense than simply labeling whether a photo has been retouched or not, he adds. “Anybody knows that there's different types,” but this tool will address the question, “How much is too much?” The New York Times has an helpful illustration of images ranked 1 through 5.

SECTION 1. MARKET LOSS ASSISTANCE. (a) Assistance Authorized.--The Secretary of Agriculture (referred to in this Act as the ``Secretary'') shall, to the maximum extent practicable, use $4,622,240,000 of funds of the Commodity Credit Corporation to make a market loss assistance payment to owners and producers on a farm that are eligible for a final payment for fiscal year 2001 under a production flexibility contract for the farm under the Agriculture Market Transition Act (7 U.S.C. 7201 et seq.). (b) Amount.--The amount of assistance made available to owners and producers on a farm under this section shall be proportionate to the amount of the total contract payments received by the owners and producers for fiscal year 2001 under a production flexibility contract for the farm under the Agricultural Market Transition Act. SEC. 2. SUPPLEMENTAL OILSEEDS PAYMENT. The Secretary shall use $423,510,000 of funds of the Commodity Credit Corporation to make a supplemental payment under section 202 of the Agricultural Risk Protection Act of 2000 (Public Law 106-224; 7 U.S.C. 1421 note) to producers of the 2000 crop of oilseeds that previously received a payment under such section. SEC. 3. SUPPLEMENTAL PEANUT PAYMENT. The Secretary shall use $54,210,000 of funds of the Commodity Credit Corporation to provide a supplemental payment under section 204(a) of the Agricultural Risk Protection Act of 2000 (Public Law 106- 224; 7 U.S.C. 1421 note) to producers of quota peanuts or additional peanuts for the 2000 crop year that previously received a payment under such section. The Secretary shall adjust the payment rate specified in such section to reflect the amount made available for payments under this section. SEC. 4. SUPPLEMENTAL TOBACCO PAYMENT. (a) Supplemental Payment.--The Secretary shall use $129,000,000 of funds of the Commodity Credit Corporation to provide a supplemental payment under section 204(b) of the Agricultural Risk Protection Act of 2000 (Public Law 106-224; 7 U.S.C. 1421 note) to eligible persons (as defined in such section) that previously received a payment under such section. (b) Special Rule for Georgia.--The Secretary may make payments under this section to eligible persons in Georgia only if the State of Georgia agrees to use the sum of $13,000,000 to make payments at the same time, or subsequently, to the same persons in the same manner as provided for the Federal payments under this section, as required by section 204(b)(6) of the Agricultural Risk Protection Act of 2000. SEC. 5. SUPPLEMENTAL WOOL AND MOHAIR PAYMENT. The Secretary shall use $16,940,000 of funds of the Commodity Credit Corporation to provide a supplemental payment under section 814 of the Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations Act, 2001 (as enacted by Public Law 106-387), to producers of wool, and producers of mohair, for the 2000 marketing year that previously received a payment under such section. The Secretary shall adjust the payment rate specified in such section to reflect the amount made available for payments under this section. SEC. 6. SUPPLEMENTAL COTTONSEED ASSISTANCE. The Secretary shall use $84,700,000 of funds of the Commodity Credit Corporation to provide supplemental assistance under section 204(e) of the Agricultural Risk Protection Act of 2000 (Public Law 106- 224; 7 U.S.C. 1421 note) to producers and first-handlers of the 2000 crop of cottonseed that previously received assistance under such section. SEC. 7. SPECIALTY CROPS. (a) Base State Grants.--The Secretary shall use $26,000,000 of funds of the Commodity Credit Corporation to make grants to the several States and the Commonwealth of Puerto Rico to be used to support activities that promote agriculture. The amount of the grant shall be-- (1) $500,000 to each of the several States; and (2) $1,000,000 to the Commonwealth of Puerto Rico. (b) Grants for Value Of Production.--The Secretary shall use $133,400,000 of funds of the Commodity Credit Corporation to make a grant to each of the several States in an amount that represents the proportion of the value of specialty crop production in the State in relation to the national value of specialty crop production, as follows: (1) California, $63,320,000. (2) Florida, $16,860,000. (3) Washington, $9,610,000. (4) Idaho, $3,670,000. (5) Arizona, $3,430,000. (6) Michigan, $3,250,000. (7) Oregon, $3,220,000. (8) Georgia, $2,730,000. (9) Texas, $2,660,000. (10) New York, $2,660,000. (11) Wisconsin, $2,570,000. (12) North Carolina, $1,540,000. (13) Colorado, $1,510,000. (14) North Dakota, $1,380,000. (15) Minnesota, $1,320,000. (16) Hawaii, $1,150,000. (17) New Jersey, $1,100,000. (18) Pennsylvania, $980,000. (19) New Mexico, $900,000. (20) Maine, $880,000. (21) Ohio, $800,000. (22) Indiana, $660,000. (23) Nebraska, $640,000. (24) Massachusetts,$640,000. (25) Virginia, $620,000. (26) Maryland, $500,000. (27) Louisiana, $460,000. (28) South Carolina, $440,000. (29) Tennessee, $400,000. (30) Illinois, $400,000. (31) Oklahoma, $390,000. (32) Alabama, $300,000. (33) Delaware, $290,000. (34) Mississippi, $250,000. (35) Kansas, $210,000. (36) Arkansas, $210,000. (37) Missouri, $210,000. (38) Connecticut, $180,000. (39) Utah, $140,000. (40) Montana, $140,000. (41) New Hampshire, $120,000. (42) Nevada, $120,000. (43) Vermont, $120,000. (44) Iowa, $100,000. (45) West Virginia, $90,000. (46) Wyoming, $70,000. (47) Kentucky, $60,000. (48) South Dakota, $40,000. (49) Rhode Island, $40,000. (50) Alaska, $20,000. (c) Specialty Crop Priority.--As a condition on the receipt of a grant under this section, a State shall agree to give priority to the support of specialty crops in the use of the grant funds. (d) Specialty Crop Defined.--In this section, the term ``specialty crop'' means any agricultural crop, except wheat, feed grains, oilseeds, cotton, rice, peanuts, and tobacco. SEC. 8. COMMODITY ASSISTANCE PROGRAM. The Secretary shall use $10,000,000 of funds of the Commodity Credit Corporation to make a grant to each of the several States to be used by the States to cover direct and indirect costs related to the processing, transportation, and distribution of commodities to eligible recipient agencies. The grants shall be allocated to States in the manner provided under section 204(a) of the Emergency Food Assistance Act of 1983 (7 U.S.C. 7508(a)). SEC. 9. TECHNICAL CORRECTION REGARDING INDEMNITY PAYMENTS FOR COTTON PRODUCERS. (a) Conditions on Payment to State.--Subsection (b) of section 1121 of the Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations Act, 1999 (as contained in section 101(a) of division A of Public Law 105-277 (7 U.S.C. 1421 note)), and as amended by section 754 of the Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations Act, 2001 (as enacted by Public Law 106-387; 114 Stat. 1549A-42), is amended to read as follows: ``(b) Conditions on Payment to State.--The Secretary of Agriculture shall make the payment to the State of Georgia under subsection (a) only if the State-- ``(1) contributes $5,000,000 to the indemnity fund and agrees to expend all amounts in the indemnity fund by not later than January 1, 2002 (or as soon as administratively practical thereafter), to provide compensation to cotton producers as provided in such subsection; ``(2) requires the recipient of a payment from the indemnity fund to repay the State, for deposit in the indemnity fund, the amount of any duplicate payment the recipient otherwise recovers for such loss of cotton, or the loss of proceeds from the sale of cotton, up to the amount of the payment from the indemnity fund; and ``(3) agrees to deposit in the indemnity fund the proceeds of any bond collected by the State for the benefit of recipients of payments from the indemnity fund, to the extent of such payments.''. (b) Additional Disbursements From the Indemnity Fund.--Subsection (d) of such section is amended to read as follows: ``(d) Additional Disbursement to Cotton Ginners.--The State of Georgia shall use funds remaining in the indemnity fund, after the provision of compensation to cotton producers in Georgia under subsection (a) (including cotton producers who file a contingent claim, as defined and provided in section 5.1 of chapter 19 of title 2 of the Official Code of Georgia), to compensate cotton ginners (as defined and provided in such section) that-- ``(1) incurred a loss as the result of-- ``(A) the business failure of any cotton buyer doing business in Georgia; or ``(B) the failure or refusal of any such cotton buyer to pay the contracted price that had been agreed upon by the ginner and the buyer for cotton grown in Georgia on or after January 1, 1997, and had been purchased or contracted by the ginner from cotton producers in Georgia; ``(2) paid cotton producers the amount which the cotton ginner had agreed to pay for such cotton received from such cotton producers in Georgia; and ``(3) satisfy the procedural requirements and deadlines specified in chapter 19 of title 2 of the Official Code of Georgia applicable to cotton ginner claims.''. (c) Conforming Amendment.--Subsection (c) of such section is amended by striking ``Upon the establishment of the indemnity fund, and not later than October 1, 1999, the'' and inserting ``The''. SEC. 10. INCREASE IN PAYMENT LIMITATIONS REGARDING LOAN DEFICIENCY PAYMENTS AND MARKETING LOAN GAINS. Notwithstanding section 1001(2) of the Food Security Act of 1985 (7 U.S.C. 1308(1)), the total amount of the payments specified in section 1001(3) of that Act that a person shall be entitled to receive for one or more contract commodities and oilseeds under the Agricultural Market Transition Act (7 U.S.C. 7201 et seq.) during the 2001 crop year may not exceed $150,000. SEC. 11. TIMING OF, AND LIMITATION ON, EXPENDITURES. (a) Deadline for Expenditures.--All expenditures required by this Act shall be made not later than September 30, 2001. Any funds made available by this Act and remaining unexpended by October 1, 2001, shall be deemed to be unexpendable, and the authority provided by this Act to expend such funds is rescinded effective on that date. (b) Total Amount of Expenditures.--The total amount expended under this Act may not exceed $5,500,000,000. If the payments required by this Act would result in expenditures in excess of such amount, the Secretary shall reduce such payments on a pro rata basis as necessary to ensure that such expenditures do not exceed such amount. SEC. 12. REGULATIONS. (a) Promulgation.--As soon as practicable after the date of the enactment of this Act, the Secretary and the Commodity Credit Corporation, as appropriate, shall promulgate such regulations as are necessary to implement this Act and the amendments made by this Act. The promulgation of the regulations and administration of this Act shall be made without regard to-- (1) the notice and comment provisions of section 553 of title 5, United States Code; (2) the Statement of Policy of the Secretary of Agriculture effective July 24, 1971 (36 Fed. Reg. 13804), relating to notices of proposed rulemaking and public participation in rulemaking; and (3) chapter 35 of title 44, United States Code (commonly known as the ``Paperwork Reduction Act''). (b) Congressional Review of Agency Rulemaking.--In carrying out this section, the Secretary shall use the authority provided under section 808 of title 5, United States Code. Speaker of the House of Representatives. Vice President of the United States and President of the Senate.

Directs the Secretary of Agriculture to use specified Commodity Credit Corporation (CCC) funds for a market loss assistance payment to farm owners and producers who are eligible for a final FY 2001 production flexibility contract payment (such payment to be proportional to total 2001 flexibility contract payments received).(Sec. 2) Directs the Secretary to use specified CCC funds for supplemental 2000 payments to qualifying: (1) oilseed producers; (2) peanut producers; (3) wool and mohair producers; (4) tobacco producers (payments to Georgia producers may be made only if Georgia provides specified funds for such purpose); and (5) cottonseed producers and first handlers.(Sec. 7) Directs the Secretary to use specified CCC funds for grants to: (1) the States and Puerto Rico for agricultural promotion activities; and (2) the States (in specified amounts) for the value of specialty crop production. Defines "specialty crop" as any crop other than wheat, feed grains, oilseeds, cotton, rice, peanuts, and tobacco.(Sec. 8) Directs the Secretary to use specified CCC funds for grants to cover State transportation, processing, and distribution costs under the Emergency Food Assistance Act of 1983.(Sec. 9) Amends the Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations Act, 1999, as amended by the Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations Act, 2001, respecting Cotton Producer Indemnity Fund payments to Georgia producers and ginners.(Sec. 10) Establishes a $150,000 individual limitation on 2001 loan deficiency payments and marketing loan gains.(Sec. 11) States that expenditures under this Act shall be made by September 30, 2001. Deems any funds remaining unused as of October 1, 2001, to be unexpendable. Rescinds authority to expend such funds as of that date.States that: (1) total expenditures under this Act shall not exceed $5.5 billion; and (2) payments shall be reduced on a pro rata basis if they would exceed such limitation.(Sec. 12) Directs the Secretary and the CCC to promulgate implementing regulations.

SECTION 1. SHORT TITLE. This Act may be cited as the ``FCC Reorganization Act''. SEC. 2. FINDINGS. The Congress finds the following: (1) The Communications Act of 1934 grants the Federal Communications Commission permission to organize ``integrated bureaus'' and ``other divisional organizations'' for the purpose of assisting the Commission in its principal workload. (2) The Federal Communications Commission originally created and organized its bureaus at a time when individual companies offered single, discreet telecommunications services. (3) New communications technologies enable a single company to offer a variety of services (such as cable companies offering video, voice, and data). (4) The organization of the Federal Communications Commission's bureaus based on the type of technology is an obsolete model and is no longer relevant since new technologies provide multiple services. SEC. 3. REGULATORY FUNCTION AND STRUCTURE OF THE FCC. Subsection (b) of section 5 of the Communications Act of 1934 (47 U.S.C. 155(b)) is amended to read as follows: ``(b) Staff Organization.-- ``(1) Authority to organize.--The Commission shall-- ``(A) except as provided in paragraph (3), establish and maintain the bureaus required by paragraph (2); and ``(B) organize the remainder of its staff into-- ``(i) integrated bureaus based on the purposes of the regulation to be administered by such bureau; and ``(ii) such other divisional organizations as the Commission may deem necessary. ``(2) Required divisions.--Except as provided in paragraph (3), the Commission shall establish and maintain the following bureaus and divisions: ``(A) Spectrum management bureau.--A Spectrum Management Bureau with responsibility for all issues relating to electromagnetic spectrum, including spectrum allocation, spectrum interference regulations, unlicensed user regulations, and other general spectrum regulations. ``(B) Government affairs and consumer education bureau.--A Government Affairs and Consumer Education Bureau with responsibility for all issues relating to government relations and consumer education including consumer affairs and outreach, consumer inquiries and complaints, information access and privacy, policy, reference information center, and consumer publications. ``(C) Economic regulations bureau.--An Economic Regulation Bureau with responsibility for all issues relating to economic regulations, including intercarrier compensation, pricing regulations, and media ownership regulations, and the Universal Service Fund/E-rate program. ``(D) Public interest bureau.--A Public Interest Bureau with responsibility for all issues relating to public interest programs, such as Disabled Services, E- 911 regulations, and requirements under the Communications Assistance for Law Enforcement Act. ``(E) Broadcast content bureau.--A Broadcast Content Bureau with responsibility for all issues relating to broadcast content, including broadcast decency and child-friendly television. ``(F) Licensing bureau.--A Licensing Bureau with responsibility for all issues relating to licensing, including spectrum auctions and license renewal ``(G) Enforcement bureau.--An Enforcement Bureau with the same responsibilities such Bureau had on the date of enactment of the FCC Reorganization Act. ``(H) International bureau.--An International Bureau with the same responsibilities such Bureau had on the date of enactment of the FCC Reorganization Act. ``(3) Periodic re-examination.--The Commission shall, at least once after each 5-year interval after the date of enactment of the FCC Reorganization Act-- ``(A) re-examine the organization of the bureaus established under subparagraph (A) and (B)(i) of paragraph (1) to determine whether such organization continues to meet the requirements and needs of the Commission; and ``(B) carry out any reorganization that the Commission determines to be necessary to meet the requirements and needs of the Commission. ``(4) Bureau staffing.--Each bureau established under subparagraph (A) and (B)(i) of paragraph (1) shall include such legal, engineering, accounting, administrative, clerical, and other personnel as the Commission may determine to be necessary to perform its functions.''. SEC. 4. EFFECTIVE DATE; TRANSITION. The amendment made by section 3 is effective 18 months after the date of enactment of this Act, except that the Federal Communications Commission is authorized and required to take actions to begin implementation of, and compliance with, such amendment on such date of enactment.

FCC Reorganization Act - Amends the Communications Act of 1934 to direct the Federal Communications Commission (FCC) to organize its staff into integrated bureaus based on the purposes of the regulations to be administered by such bureau. Requires the following bureaus within the FCC: (1) spectrum management; (2) government affairs and consumer education; (3) economic regulations; (4) public interest; (5) broadcast content; (6) licensing; (7) enforcement; and (8) international. Directs the FCC, at least once every five years, to reexamine such organization and carry out any necessary reorganization.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Veterans Long-Term Care Security Act of 2006''. SEC. 2. REQUIREMENT FOR REPORT TO CONGRESS BEFORE IMPLEMENTATION OF REDUCTION IN PER DIEM RATES FOR CARE PROVIDED TO VETERANS IN STATE HOMES. (a) Requirement for Report.--Subsection (c) of section 1741 of title 38, United States Code, is amended-- (1) by inserting ``(1)'' after ``(c)''; and (2) by adding at the end the following new paragraph: ``(2)(A) If the Secretary proposes to implement a reduction in payments made under this section with respect to a fiscal year the Secretary shall, not later than January 1 of the preceding fiscal year, submit to the Committee on Veterans' Affairs of the Senate and the Committee on Veterans' Affairs of the House of Representatives a report containing a detailed justification of such proposed reduction. ``(B) For purposes of this paragraph, a reduction in payments is-- ``(i) a lack of increase in the rates paid under subsection (a) pursuant to a determination of the Secretary under paragraph (1); or ``(ii) a modification of the eligibility for veterans to receive care in State homes that would, if enacted into law, result in fewer veterans eligible to receive such care in State homes. ``(C) In preparing a report under subparagraph (A), the Secretary shall consult with the heads and appropriate officials of the State and local agencies responsible for the supervision of State homes in each State in which State homes are operated, and representatives of such other organizations with expertise in State home matters as the Secretary determines appropriate. ``(D) A report under subparagraph (A) shall include the following information: ``(i) A specific description of the degree to which the proposed reduction in payments would effect the financial well- being of each State home. ``(ii) A detailed description of the consultation with heads, officials, and representatives required under subparagraph (C), and the results of that consultation. ``(iii) A description of the intent of the Secretary to recover grant amounts under section 8136(a) of this title where a State determines, as a result of the proposed reduction in payments, to close a State home within the period prescribed under that section. ``(iv) A description of the effect of the proposed reduction in payments on the long-term care needs of veterans who receive care in State homes, including a description of the options for long-term care in reasonably proximate facilities available to such veterans and an assessment of the cost of the provision of care for such veterans in such facilities.''. (b) Effective Date.--The amendment made by subsection (a) shall take effect on the date of enactment of this Act, and apply with respect to per diem payments made under section 1741 of title 38, United States Code, on or after such date. SEC. 3. NURSING HOME CARE AND PRESCRIPTION MEDICATIONS IN STATE HOMES FOR VETERANS WITH SERVICE-CONNECTED DISABILITIES. (a) Nursing Home Care.--Subchapter V of chapter 17 of title 38, United States Code, is amended by adding at the end the following new section: ``Sec. 1744. Nursing home care and medications for veterans with service-connected disabilities ``(a)(1) The Secretary shall pay each State home for nursing home care at the applicable rate payable under section 1720 of this title for nursing home care furnished in a non-Department nursing home (as that term is defined in subsection (e)(2) of such section), where such care is provided to any veteran as follows: ``(A) Any veteran in need of such care for a service- connected disability. ``(B) Any veteran who-- ``(i) has a service-connected disability rated at 70 percent or more; and ``(ii) is in need of such care. ``(2) Payment by the Secretary under paragraph (1) to a State home for nursing home care provided to a veteran described in that paragraph constitutes payment in full to the State home for such care furnished to that veteran.''. (b) Provision of Prescription Medicines.--Such section is further amended by adding at the end the following new subsection: ``(b) The Secretary shall furnish such drugs and medicines as may be ordered on prescription of a duly licensed physician as specific therapy in the treatment of illness or injury to any veteran as follows: ``(1) Any veteran in need of such drugs and medicines for a service-connected disability. ``(2) Any veteran who-- ``(A) has a service-connected disability rated at 50 percent or more; ``(B) is provided nursing home care that is payable under subsection (a); and ``(C) is in need of such drugs and medicines.''. (c) Conforming Amendments.-- (1) Criteria for payment.--Section 1741(a)(1) of such title is amended by striking ``The'' and inserting ``Except as provided in section 1744 of this title, the''. (2) Eligibility for nursing home care.--Section 1710(a)(4) of such title is amended-- (A) by striking ``and'' before ``the requirement in section 1710B of this title''; and (B) by inserting ``, and the requirement in section 1744 of this title to provide nursing home care and prescription medicines to veterans with service- connected disabilities in State homes'' after ``a program of extended care services''. (d) Clerical Amendment.--The table of sections at the beginning of chapter 17 of such title is amended by inserting after the item relating to section 1743 the following new item: ``1744. Nursing home care and medications for veterans with service- connected disabilities.''. (e) Effective Date.--The amendment made by this section shall take effect on October 1, 2006. SEC. 4. AUTHORITY TO TREAT CERTAIN HEALTH FACILITIES AS STATE HOMES. (a) Authority.--Subchapter III of chapter 81 of title 38, United States Code, is amended by adding at the end the following new section: ``Sec. 8138. Treatment of certain health facilities as State homes ``(a) The Secretary may treat a health facility as a State home for purposes of subchapter V of chapter 17 of this title if the following requirements are met: ``(1) The facility meets the standards for the provision of nursing home care that is applicable to State homes, as prescribed by the Secretary under section 8134(b) of this title, and such other standards relating to the facility as the Secretary may require. ``(2) The facility is licensed or certified by the appropriate State and local agencies charged with the responsibility of licensing or otherwise regulating or inspecting State home facilities. ``(3) The State demonstrates in an application to the Secretary that, but for the treatment of a facility as a State home under this subsection, a substantial number of veterans residing in the geographic area in which the facility is located who require nursing home care will not have access to such care. ``(4) The Secretary determines that the treatment of the facility as a State home best meets the needs of veterans for nursing home care in the geographic area in which the facility is located. ``(5) The Secretary approves the application submitted by the State with respect to the facility. ``(b) The Secretary may not treat a health facility as a State home under subsection (a) if the Secretary determines that such treatment would increase the number of beds allocated to the State in excess of the limit on the number of beds provided for by regulations prescribed under section 8134(a) of this title. ``(c) The number of beds occupied by veterans in a health facility for which payment may be made under subchapter V of chapter 17 of this title by reason of subsection (a) shall not exceed the number of veterans in beds in State homes that otherwise would be permitted in the State under regulations prescribed under section 8134(a) of this title. ``(d) The number of beds in a health facility in a State that has been treated as a State home under subsection (a) shall be taken into account in determining the unmet need for beds for State homes for the State under section 8134(d)(1) of this title.''. (b) Clerical Amendment.--The table of sections at the beginning of chapter 81 of such title is amended by inserting after the item relating to section 8137 the following new item: ``8138. Treatment of certain health facilities as State homes.''.

Veterans Long-Term Care Security Act of 2006 - Requires the Secretary of Veterans Affairs to submit to the congressional veterans' committees a detailed justification of any proposal to implement a reduction in per diem payments to state nursing homes for care provided to veterans. Directs the Secretary to pay for nursing home care furnished in a non-Department of Veterans Affairs nursing home where such care is provided to any veteran: (1) in need of such care for a service-connected disability; or (2) with a service-connected disability rated at 70 percent or more and in need of such care. Directs the Secretary to furnish such drugs and medicines as ordered by a duly licensed physician for any veteran: (1) in need of such drugs and medicines for a service-connected disability; or (2) with a service-connected disability rated at 50 percent or more in need of such drugs and medicines while being provided nursing home care payable through the Department. Authorizes the Secretary to treat certain health facilities as state homes for purposes of eligibility for payments for care provided to veterans.

it is well - known that hiv - coinfection accelerates the progression of hepatitis c virus ( hcv)-related liver disease . in fact , while some studies have yielded discordant results , most reports and two metaanalyses of nine ( graham cs 2001 ) and 29 studies ( deng l 2009 ) , respectively , have proven a strong association between hiv - coinfection and an increased risk for cirrhosis , end - stage liver disease and death . thus , in cross - sectional studies based on single liver biopsies , patients with lower cd4 cell counts present more advanced stages of fibrosis ( benhamou y 1999 , macas j 2004 , martn carbonero l 2004 ) . likewise , patients with deeper immunosuppression have poorer clinical outcomes than those with higher cd4 counts ( qurishi n 2003 , merchante n 2006 ) . the underlying mechanism of the effect of hiv infection on the progression of hcv - related liver disease is not completely understood . a study , carried out in hepatoma cell lines , have shown that hiv and the surface protein gp120 increase hcv replication and enhance the expression of tgf 1 , a major mediator in fibrogenesis . this effect is blocked by antibodies against co - receptors ccr5 and cxcr4 , as well as using a neutralizing antibody against tgf 1 , indicating that the action of hiv on hcv replication depends on tgf 1 ( lin w 2008 ) . these findings suggest that hiv not only increases the replication of hcv , but also contributes to fibrosis progression . however , in another study , intrahepatic mrna levels of inflammatory cytokines were significantly higher in hiv - positive than in hiv - negative patients harboring hepatitis c , whereas mrna levels of profibrogenic cytokines did not differ between the two groups . these facts support that the accelerated liver disease progression in hiv / hcv - coinfected patients might reflect enhanced intrahepatic inflammatory responses rather than increased local transcription of directly profibrogenic cytokines ( kuntzen t 2008 ) . finally , results reported by our group showed that hiv coinfection increases the expression of fas receptors in hepatocytes of hcv carriers , indicating that hepatocyte apoptosis is enhanced in these patients ( macas j 2005 ) . highly active antiretroviral therapy ( haart ) leads to reconstitution of the immune system , which may improve the control of hcv infection and slow down the subsequent fibrogenesis . however , antiretroviral drugs may also cause several hepatic disorders in the short and long - term , some of them still not well - known . because of this , haart might be either a friend or rather a foe for the liver in hiv / hcv - coinfected patients . overall , the effect of haart on the liver will be the result of the balance between the effects of immune reconstitution and those of liver toxicity . in the following lines , the toxicity of haart , as well as the benefits of this therapy , are analyzed . these episodes of self - limited hypertransaminasemia do not seem to enhance the progression of hcv - related liver disease . thus , in a study of 116 hiv / hcv - coinfected patients with liver biopsy and previous follow - up , patients with advanced fibrosis did not show peak elevations of alt more commonly than subjects without advanced fibrosis ( vergara s 2007 ) . many issues regarding liver damage associated with haart in the long - term are still far from clear . some degree of steatosis is found in up to 70% of liver biopsies from hiv / hcv - coinfected patients , with percentages of patients showing steatosis in more than 30% of hepatocytes which range from 2 - 11% ( mcgovern b 2006 , neau 2007 ) . the factors associated with the presence of steatosis in this population , particularly the role of antiretroviral drugs , are a matter of controversy . it has been reported that ritonavir treated mice have an increase of the active form of sterol regulatory element - binding protein ( srebp)-1c in liver cells , which leads to an increased lipogenesis . in addition , protease inhibitors also slow down the intracelular degradation of apo - b-100 , prompting an overproduction of vldl particles . finally , these drugs may inhibit the ldl receptor - related protein , reducing the clearance of vldl from circulation ( mooser v 2001 ) . however , no study based on liver biopsy has revealed to date an independent association between treatment with protease inhibitors and the presence of steatosis . conversely , the use of dideoxinucleosides , particularly d4 t , has been found to be an independent predictor of liver steatosis in several studies ( mcgovern b 2006 , pascual - pareja jf 2009 , sulkowski 2005 ) . dideoxinucleosides have a high potential for mitochondrial toxicity , which causes defective beta - oxidation of free fatty acids . since steatosis promotes the progression of fibrosis , it is conceivable that hiv / hcv - coinfected patients receiving drugs inducing steatogenesis will develop with time more severe liver fibrosis . hiv - infected patients on haart show higher levels of insulin resistance than those without therapy and healthy controls . this disorder is mainly associated with treatment with protease inhibitors ( brown tt 2005 ) . insulin resistance prompts fibrosis progression in hcv - monoinfected patients . in hiv / hcv - coinfection , a recent study has shown that patients with higher levels of insulin resistance , as measured by the homa method , harbor greater levels of liver stiffness , a reliable marker of fibrosis ( merchante n 2009 ) . this finding supports that insulin resistance is also a cofactor for fibrosis progression in the setting of hiv / hcv coinfection and also provides a rational to think that haart might eventually lead to more severe fibrosis stages . in the few last years , an increasing number of cases of noncirrhotic portal hypertension , observed in hiv - infected patients without hepatitis coinfection , have been reported ( maida i 2006 , schiano d 2007 , mallet v 2007 ) . the underlying liver injury has been nodular regenerative hyperplasia in some of these cases ( mallet v 2007 , maida i 2008 ) and hepatoportal sclerosis ( schiano td 2007 ) in others . this disorder is believed to be associated with long - term exposure to didanosine ( maida i 2006 , mallet v 2007 ) and it seems to improve with the removal of such a drug ( maida i 2008 ) . these data suggest that some antiretroviral drugs may cause unexpected liver diseases after years of exposure . fortunately , these cases seem to be uncommon . to gain additional knowledge on this topic , we have screened 258 hiv - infected patients , without hcv or hbv coinfection , for the presence of liver stiffness equal to or higher than 7.2 kpa by transient elastometry . twenty - nine ( 11% ) fifteen of them accepted to undergo a liver biopsy and all of them , but one , had some degree of liver injury ( figure 1 ) . the most common diagnoses after biopsy were alcoholic liver disease and fibrosis of unknown origin , which reached the stage of cirrhosis in one patient . factors independently associated with liver stiffness equal to or above 7.2 kpa in the multivariate analysis were : prior exposure to didanosine , exposure to abacavir , a daily alcohol intake 50 g / day , age older than 40 years and a cd4 cell count equal to or lower than 200/mm . specifically , the longer the exposure to didanosine , the higher the liver stiffness . these results reinforce the hypothesis that some antiretroviral drugs , like didanosine , may cause liver damage with long - term exposure . diagnosis in hiv - infected patients without hcv or hbv coinfection , showing liver stiffness 7.2 kpa , and who underwent liver biopsy ( n = 15 ) . besides the above - stated potential for liver damage , haart seems to yield clear benefits to the progression of hcv - related liver disease in the short and mid - term . indeed , haart induces recovery of hcv - specific t - cell response to hcv core protein , which parallels with a decline in plasma hcv - rna load in hiv / hcv - coinfected patients ( rohrbach j 2009 ) . thus , studies analyzing single biopsies have shown that less severe liver fibrosis is associated with either haart ( verma s 2006 ) or the consequences of a correct haart , i. e. , higher cd4 cell count ( benhamou y 1999 , macas j 2004 , martn - carbonero l 2004 ) and undetectable plasma hiv - rna load ( bru n 2006 ) . longitudinal studies have provided conflicting results about the effect of haart on the progression of liver fibrosis . thus , a study based on paired biopsies taken from 174 patients belonging to the cohort of the johns hopkins university showed no association between haart and changes in the fibrosis stage ( sulkowski 2007 ) . moreover , a recent study , in which apri was sequentially measured , showed that haart is associated with increasing values of this index over time in hiv / hcv co - infected patients . according to the opinion of the authors , this finding would suggest that patients might be experiencing cumulative hepatotoxicity from antiretrovirals ( moodie eem 2009 ) . to further clarify this topic , we have studied paired biopsies from 135 hiv / hcv - coinfected patients studied in nine hospitals in spain . overall , 44% of patients progressed at least one fibrosis stage of the scheuer 's scoring system , including 56% of those who showed f0 or f1 at the initial biopsy . the factors independently associated with lack of fibrosis progression were low necroinflamatory activity at the first biopsy , longer time from the baseline to the final sample , response to hcv therapy and undetectable plasma hiv - rna between biopsies ( table 1 ) . the latter results show that a correct haart slow down hcv - related fibrosis progression in hiv - coinfected patients . factors associated with progression 1 or more stages between two paired liver biopsies in 135 patients from spain in the multivariate study undetectable hiv rna in 70% determinations during the follow - up . rr ( 95% ci ) : relative risk ( 95% confidence interval ) ; etr : end of treatment response . researchers which have assessed the clinical outcome in patients with hiv / hcv coinfection have uniformly found results consistent with the histological benefit observed in the above - mentioned study . thus , in the bonn and in the san francisco cohorts , haart was associated with a lower liver related mortality ( qurishi n 2003 , bonacini m 2004 ) . this beneficial effect has also been reported even in the most advanced stages of liver disease ( merchante n 2006 ) . accordingly , a greater increase of cd4 cell count after starting haart has been found to be associated with a reduced incidence of liver decompensation and a longer survival ( pineda ja 2007 ) . studies appraising the impact of specific antiretroviral drugs on liver fibrosis progression have yielded conflicting results . in fact , whereas some studies have reported that the rate of fibrosis progression in patients taking protease inhibitors is slower than in those receiving nevirapine ( macas j 2004 ) , other studies have found the opposite results ( berenguer j 2008 ) or no association at all between specific drugs and fibrosis progression ( martin - carbonero 2004 , verma s 2006 ) . however , all these are retrospective studies and inherent biases likely explain the controversial results . this topic will remain unclear , unless a specific randomized clinical trial to assess it is undertaken . the beneficial effect of haart on the progression of hcv infection has made the outcome of liver disease in hiv / hcv - coinfected patients more similar to that of hcv - monoinfected subjects than it used to be before the haart era . thus , a recent metaanalysis , where studies carried out in patients with and without haart were analyzed separately , found that the course of hcv infection continues to be worse in hcv / hiv - coinfected patients taking haart . however the risk ratio for cirrhosis between coinfected and hcv - monoinfected patients has declined from 2.49 in patients without haart to 1.72 in those receiving haart ( thein h 2008 ) . there are data showing that the use of haart is associated with several sorts of liver injuries . this fact is certainly a threat of an increased rate of serious liver disorders in the setting of hiv / hcv - coinfected patients . however , the effects of haart on liver fibrosis progression in these patients are clearly beneficial , at least in the short and mid - term . ithe use of haart is likely one of the reasons why the mortality due to liver disease has stopped increasing among hiv - infected patients seen in places where hcv - coinfection is a major problem ( del valle j 2008 , nez - fernndez c 2009 ) . because of this , the effects of haart on the progression of hcv - related liver disease in coinfected patients largely outweigh the potential risks for long - term toxicity . accordingly , an earlier starting of art in patients with hiv / hcv - coinfection is sufficiently justified .

the overall effect of haart on the liver is the result of the balance between hepatotoxicity and the consequences of immunoreconstitution on the evolution of hiv - associated liver diseases , particularly viral hepatitis . haart may lead to the emergence of acute toxic hepatitis , steatosis , steatohepatitis , liver fibrosis , and noncirrhotic portal hypertension . on the other hand , haart use has been associated with slower fibrosis progression in hiv / hcv - coinfected patients in most studies dealing with this issue . as well , an improvement of the clinical outcome of liver disease has been reported in patients taking haart . for these reasons , the short- and mid - term effects of haart on the liver are mostly beneficial .

groups of galaxies are weak enhancements in the projected galaxy distribution . velocity information from redshift surveys confirms , however , that they are indeed true spatial density enhancements ( e.g. @xcite ; @xcite ; ramella , geller & huchra 1989 ; ramella , pisani & geller 1997 ) , although probably still far from equilibrium ( e.g. @xcite ; @xcite ; @xcite ; moore , frenk & white 1993 ; @xcite ) . groups probe the intermediate scale between galaxies and clusters ( e.g. @xcite ) and can provide important constraints on the amount of dark matter , on the formation and evolution of galaxies , and on the properties of the intergalactic medium ( e.g. @xcite ; @xcite ; @xcite ; @xcite ; @xcite ; @xcite ) . further information about the dynamics of structure formation come from anisotropies of the correlation function in redshift space , which are related to moments of the pairwise velocity distribution . the first moment @xmath7 enters the time evolution equation for the spatial correlation function , and has so far been estimated directly only for the iras 1.2 jy survey ( @xcite ; see also @xcite ; @xcite ) . considerably more attention has been devoted to the second moment @xmath8 , which measures the random motions of galaxies and can be used to constrain @xmath6 via the cosmic virial theorem ( @xcite ; @xcite ; @xcite ; @xcite ) . several authors have shown that @xmath8 is sensitive to the presence of clusters within a survey ( @xcite ; @xcite ; @xcite ; @xcite ) and so requires a large survey volume to obtain a robust and unbiased estimate ( @xcite ; @xcite ; @xcite ; somerville et al . 1997a ; @xcite ) . many early estimates of @xmath8 were substantially below the values predicted by the popular cdm model and its variants ( see e.g. @xcite and references therein ) . larger values were found by mo et al . ( 1993 ) , by marzke et al . ( 1995 ) for the center for astrophysics ( cfa , hereafter ) surveys , and by jing et al . ( 1998 ) for the las campanas redshift survey ( lcrs , hereafter ) . the latter results are for the largest two surveys currently available and suggest that the large velocity bias previously advocated to reconcile cdm models with observations ( e.g. @xcite ; @xcite ; @xcite ) may be unnecessary . comparing the observed distribution of galaxies with models of structure formation is problematic . in particular , if only the dark matter evolution is simulated directly , as is usually the case , then some method must be found to specify the positions , velocities and luminosities of galaxies before `` mock '' redshift surveys can be constructed for direct comparison with real data ( e.g. @xcite ; @xcite ; @xcite ) . kauffmann et al . ( 1998 ; paper i hereafter ) implemented semi - analytic galaxy formation modelling methods on high resolution @xmath0-body simulations of volumes @xmath9 mpc@xmath10 . ( here and below @xmath11 is the hubble constant @xmath12 in units of @xmath13 km s@xmath14 mpc@xmath14 . ) this approach enables us to simulate the physical processes relevant to galaxy formation , evolution and clustering , and to explore different assumptions about processes , like star formation and feedback , which occur on scales below the resolution limit of our @xmath0-body simulations . standard semi - analytic models ( @xcite ; @xcite ; @xcite ; @xcite ; @xcite ; @xcite ) use press - schechter theory ( @xcite ) and its extensions ( @xcite ; @xcite ; @xcite ; @xcite ) to compute the merging history of dark matter halos . within these halos , simple prescriptions , based on observational data and on more detailed simulations , regulate gas cooling rates , star formation rates , stellar population evolution and feedback from stellar winds and supernovae . dynamical friction considerations determine the merging rate among galaxies within a common halo , and so the competition between the formation of spheroids by merging and the formation of disks through cooling of diffuse gas . such models do not , however , provide detailed information about the clustering and the motions of galaxies . in our approach ( see paper i ) , dark matter halos and their evolution through collapse , accretion and merging are followed directly in the @xmath0-body simulations . other processes are then followed as in standard semi - analytic models . diffuse halo gas is assumed to cool and collect in a disk at the centre of each halo . stars form in such disks according to simple , observationally motivated laws . the central galaxy is identified with the most bound particle in the halo . when two or more halos merge , the properties of the central galaxy of the most massive progenitor are transferred to the most bound particle of the remnant . other galaxies from the progenitors become `` satellites '' . these can merge with the central galaxy of the new halo on a time - scale which is related to their progenitor mass as expected from numerical experiments ( e.g. @xcite ) . galaxy properties such as luminosity , colour , stellar and gas mass , star formation rate and morphology evolve according to recipes borrowed from earlier semi - analytic work . we are thus able to analyse clustering as a function of galaxy properties and of redshift ( paper i ; @xcite , paper ii hereafter ) . we investigate two variants of a cold dark matter ( cdm ) universe : the @xmath2cdm model , with cosmological density parameter @xmath1 , shape parameter @xmath15 and hubble constant @xmath16 km s@xmath14 mpc @xmath14 , and the @xmath5cdm model , with @xmath3 , cosmological constant @xmath4 and @xmath17 km s@xmath14 mpc @xmath14 . as discussed in paper i , in order to obtain an approximate match between models and observations , supernova feedback must be very efficient in the @xmath2cdm model , expelling large amounts of the reheated gas and so suppressing the formation of galaxies in low - mass field halos . on the other hand , feedback must be inefficient in the @xmath5cdm models and most reheated gas must be retained in order to produce a sufficient number of luminous galaxies . paper i compared the properties of galaxies in our two models with a variety of present - day observational data , among these the luminosity function in the @xmath18 and @xmath19 bands , the colour distribution , the two - point correlation function , the pairwise velocity dispersion , and the mass - to - light ratios of clusters . the free parameters which control star - formation and feedback in these models were set by fitting the i - band tully - fisher relation of @xcite and the mean gas content of a spiral galaxy at a circular velocity of 220 km s@xmath14 . this `` normalisation '' choice resulted in fiducial models where certain other properties , in particular the luminosity functions , are a relatively poor fit to observation . nevertheless , we used these fiducial models in a follow - up study of the evolution of clustering to high redshift ( paper ii ) and , for consistency , we will continue to use them below , even though it turns out that setting parameters to optimise the luminosity functions gives better fits to the abundance of groups in magnitude - limited redshift surveys . here we extract wide - angle mock surveys from the simulations in order to perform a more detailed analysis of small - scale galaxy clustering . we compare our models with the northern region of the center for astrophysics redshift survey ( cfa2n hereafter ; @xcite ; @xcite ; @xcite ; @xcite ) . the cfa2n covers a volume comparable to the volume of our simulation box . moreover , it provides the largest published catalogue of galaxy groups . we compare the properties of groups in the cfa2n with those of groups extracted from a variety of mock catalogues . in addition , we compare the redshift space correlation functions and the pairwise velocity dispersions of the real and artificial redshift surveys . because our predicted luminosity functions are sensitive to variations of model parameters within their plausible range , it is important to analyse small - scale clustering in ways that are insensitive to the exact luminosities assigned to galaxies . to gain more insight into this question , we compare results for our fiducial models with results from mock surveys of models in which galaxy luminosities are adjusted to reproduce the cfa luminosity function exactly . ( the luminosity _ ranking _ of the simulated galaxies is preserved during this adjustment . ) only the abundance of groups and the fraction of galaxies in groups are strongly affected by this change . even when the cfa luminosity function is reproduced exactly , some differences in small - scale clustering remain between @xmath5cdm and @xmath2cdm , and between both and the cfa2n . such differences may thus provide additional constraints on models . our work is the first attempt to compare a wide - angle redshift survey with simulations where the physics of the formation and evolution of individual galaxies is treated explicitly . previous work has compared the cfa redshift space correlations and group properties with @xmath0-body simulations either by assigning galaxies to dark matter particles according to some high - peak statistical model , or by assigning them to halos based on an assumed halo mass - to - light ratio ( @xcite ; @xcite ; @xcite ; @xcite ; @xcite ) . some recent studies have attempted to simulate galaxy formation in detail but have been forced either to treat volumes which are too small to obtain reliable clustering statistics ( e.g. @xcite ; @xcite ) or to use a resolution which is too poor to follow the formation and evolution of individual galaxies ( e.g. @xcite ; @xcite ) . in our approach , the physical processes important in galaxy formation are treated in a simplified way , but are included _ ab initio _ and are followed throughout the evolution of our models . quantities such as the galaxy luminosity function are thus predictions of our scheme , rather than being imposed as part of the modelling . in paper i , we show how differing assumptions about star formation and feedback affect predictions for such quantities . in sect . [ sec:3dgroup ] , we analyse simulated three - dimensional ( 3d ) groups , defined as sets of galaxies each occupying a single dark halo , and we discuss biases in the spatial and kinematic distributions of the galaxies relative to those of the dark matter . sect . [ sec : mock ] then describes how we extract mock redshift surveys from our simulations , while in sect . [ sec : rsgroup ] we make group catalogues from these mock surveys and investigate how their properties and their relation to `` real '' 3d groups are affected by the parameters which define them . in sect . [ sec : comp ] we compare our simulated groups with groups extracted in the same way from the cfa2n , and we study how this comparison is affected by differences between the simulated and observed luminosity functions . finally , in sect . [ sec : csi ] , we calculate redshift space correlation functions @xmath20 and pairwise velocity dispersions @xmath21 from our mock catalogues and compare with the cfa2n . we conclude in sect . [ sec : disc ] . as discussed in paper i , we identify dark matter halos in our simulations using a friends - of - friends groupfinder which links particles closer than 20% of the mean interparticle separation . the most bound particle in each halo is taken as its centre , and we calculate a radius @xmath22 within which the average mass density is 200 times the critical density . a 3d group of galaxies is then defined as a set of three or more galaxies brighter than some chosen absolute magnitude which lie within @xmath22 of a particular halo centre . groups in the real universe are identified in redshift surveys . below , we will compile mock surveys from our simulations and catalogue groups identified in redshift space . we will then be able to address two issues : ( 1 ) how well the physical properties of redshift space groups correspond to those of 3d groups ; ( 2 ) how well the simulation groups reproduce the properties of groups in the real universe . in this section , we describe the physical properties of the 3d groups . we compare these with the corresponding properties of redshift space groups in sect . [ sec : linking ] . we follow galaxy formation and evolution only in dark matter halos containing at least ten dark matter particles . this resolution limit implies that our galaxy catalogues are complete to a blue band absolute magnitude @xmath23 of about @xmath24 . the luminosity functions of galaxies brighter than this limit are shown in fig . [ fig : lum_fun_cl ] for our two fiducial models . solid , long - dashed , dot - dashed , and dotted lines are schechter function fits to the luminosity functions of the cfa redshift survey ( marzke , huchra & geller 1994 ) , lcrs ( @xcite ) , stromlo - apm ( @xcite ) , and eso slice project ( @xcite ) , respectively . table [ tab : lum_fun ] lists the parameters of schechter function fits to the fiducial models and compares them to those of the cfa survey . as discussed in paper i , our decision to normalise the models to the i - band tully - fisher relation results in both models producing too many bright galaxies . the @xmath2cdm model also produces a faint end slope which is steeper than the data and is a substantially worse fit to the cfa than @xmath5cdm . the total blue luminosity density @xmath25 is @xmath26 for the @xmath2cdm model and @xmath27 for the @xmath5cdm model . marzke et al . ( 1994 ) find @xmath28 for the cfa sample . we will see that this disagreement between the simulated and the observed luminosity functions affects the inferred properties of groups . [ fig : lum_fun_cl ] also shows luminosity functions for galaxies within halos of differing mass @xmath29 within the virial radius @xmath22 . less massive halos ( @xmath30 , thin solid and dotted lines ) contribute mainly to the faint end of the luminosity function . bright galaxies come from large halos ( @xmath31 , long - dashed and short - dashed lines ) . note that these halos show a slight bump in the luminosity function at @xmath32 and @xmath33 , similar to the bump in the luminosity function of several real clusters ( see e.g. @xcite ; @xcite ; @xcite ) including coma ( @xcite ) . in the models , this effect originates from the large merger cross - section of the bright and massive central galaxies which tend preferentially to accrete galaxies of somewhat lower mass . dynamical studies of groups and clusters have always produced mass - to - light ratios @xmath34 which are substantially smaller than that needed globally to close the universe ( e.g. @xcite ; @xcite ) . however , it is not clear that the galaxy populations in groups are representative of the universe as a whole ( see paper i ) . in addition , if galaxies are more strongly clustered than the dark matter , multiplying the mean luminosity density by the typical @xmath34 for groups and clusters can give a highly biased estimate of @xmath6 . indeed , previous work analysing mock surveys drawn from simulations has suggested that high and low density universes produce group catalogues which are not only almost indistinguishable in their observational properties , but also quite similar to the cfa groups ( @xcite ; @xcite ; nolthenius , klypin & primack 1997 ) . to investigate the distribution of galaxies relative to dark matter in rich clusters , figs . [ fig : den_bias ] and [ fig : vel_bias ] compare profiles of density contrast and velocity dispersion for the dark matter and for galaxies of differing luminosity and colour in halos with @xmath35 . in order to compute average profiles for the whole halo sample , we normalise the positions and the velocities of galaxies and dark matter particles to the halo virial radius @xmath22 and to the circular velocity @xmath36 at @xmath22 , respectively . we then compute the average profile by superposing all the halos in our sample and giving equal weight to each galaxy . note that each halo contains a galaxy at its centre . if we keep these central galaxies when computing the average profile , every halo would contribute a galaxy ; we would thus obtain a galaxy number overdensity profile several times larger than the dark matter profile at radii @xmath37 , only because of our arbitrary choice of placing a galaxy at the centre of each dark matter halo . in real clusters , this might not be the case . therefore , we exclude these central galaxies when computing the profiles . this exclusion has no effect at the radii @xmath38 plotted in figs . [ fig : den_bias ] and [ fig : vel_bias ] . the upper part of fig . [ fig : den_bias ] shows mean number overdensity profiles @xmath39 for the dark matter and for galaxy samples split by luminosity and by colour . the lower part gives the bias @xmath40 , the ratio between the galaxy and the dark matter overdensities . in most cases the galaxies are less concentrated than the dark matter , resulting in @xmath40 values less than 1 outside the cluster core . there is no strong dependence of bias on luminosity but there is a variation with colour . we divide galaxies into a red and a blue sample at the median of the colour distribution . red galaxies are more clustered than blue ones , in agreement with the observed morphology - density relation ( @xcite ; @xcite ; @xcite ; @xcite ; see also @xcite ) . blue galaxies are strongly anti - biased ( @xmath41 ) in the @xmath5cdm model , showing relatively little concentration towards the centres of these rich clusters . this is a result of our assumption that galaxies lose their gaseous halos , and so their reservoir of new gas , when they fall into a cluster . they then redden as their interstellar medium is used up and their star formation rate drops . the effect is much weaker in @xmath2cdm because infall of galaxies continues at a high rate until @xmath42 in this model . notice that the number density profiles for the total galaxy population have identical shapes in the two models but are offset in normalisation by about a factor of 3 . it is interesting to compare these results with observed number density profiles @xmath43 derived from the cnoc cluster sample ( @xcite ) and the eso nearby abell cluster survey , enacs ( @xcite ; @xcite ) . to obtain surface density profiles from the models , we assume spherical symmetry and integrate the three - dimensional profiles along a line of sight . at radii @xmath44 , where the number surface density reaches the background value , we approximate the three - dimensional galaxy number density profile with a @xcite profile . in fact , at these radii , galaxies follow the dark matter distribution closely ( figure [ fig : den_bias ] ) . the absolute normalisations are difficult to establish from the observational data . we therefore focus on profile shapes and on the relative distribution of galaxies with different properties . in fact , the observational surveys find different concentrations between red and blue galaxies ( cnoc ) , and between emission - line and non - emission - line galaxies ( enacs ) . in fig . [ fig : surfden ] , we compare these surveys with our models . in the cnoc sample @xmath45 of the galaxies belong to the red subsample . in the enacs sample the non - emission - line and emission - line subsamples contain @xmath46 and @xmath47 of the galaxies , respectively . we split our simulated galaxy samples into red and blue subsamples in such a way as to reproduce these fractions . we normalize both the observed and the model profiles at @xmath48 . for the enacs sample , we assume @xmath49 mpc , the mean value of @xmath22 for the clusters in both our @xmath2cdm and @xmath5cdm models . these surveys give mean profile shapes very similar to those we find here . in addition , the differences between the observed subsamples are intermediate in strength between those predicted by our two models . note however that the results of fig . [ fig : surfden ] are only indicative , because the relative distribution of galaxy subsamples is sensitive to the selection criteria . for example , when the spectra are used to split the enacs sample into early - type non - emission - line and late - type emission - line galaxies , the difference widens ( @xcite ) . finally , fig . [ fig : vel_bias ] shows , for our models , the velocity dispersion ( in units of the circular velocity @xmath36 ) for galaxies within spheres of radius @xmath50 ( in units of @xmath22 ) . these dispersions depend very little on the luminosity of the galaxies and are very similar to the dark matter dispersions . there is a noticeable colour effect , however , which is quite large in the @xmath5cdm model . the velocity dispersions of the red galaxies trace those of the dark matter , whereas blue galaxies have dispersions a factor @xmath51 larger . a similar effect is seen in real clusters ( @xcite ; @xcite ; @xcite ; @xcite , 1998 ) ; it reflects the fact that the few observed blue galaxies have just fallen into the cluster and so are more weakly bound than the red galaxies . the weak velocity bias we find for most galaxy samples is consistent with the similarity between the moments of the pairwise velocity distribution for the galaxies and for dark matter ( see paper i ) . table [ tab : gr_3d ] lists the quartiles of the distributions of a variety of 3d group properties . groups are here defined as halos which contain three or more galaxies brighter than @xmath52 within @xmath22 . the harmonic radius @xmath53 , the one - dimensional velocity dispersion , @xmath54 , and the total luminosity , @xmath55 of galaxy groups are computed directly using the positions , velocities and luminosities of the galaxies . assuming virial equilibrium , we can combine these to derive a virial mass estimate , @xmath56 , and so an estimated virial mass - to - light ratio , @xmath57 . ( we review our definition of these quantities in the appendix . note that @xmath55 includes a correction for galaxies fainter than our absolute magnitude limit . on average , @xmath58 and @xmath59 of the total halo luminosity comes from this correction factor in the @xmath2cdm and @xmath5cdm model respectively . ) in the simulations the virial mass estimate can be compared with the _ true _ mass of the group @xmath29 . the first thing to notice from table [ tab : gr_3d ] is that groups are very similar in the two models . they have slightly larger sizes , lower luminosities and larger velocity dispersions in @xmath5cdm ; these differences combine to give typical @xmath60 values which are two times _ larger _ in the low density model . this surprising result can be attributed primarily to the lower luminosity density in the @xmath5cdm model . if we multiply the median @xmath60 of the groups in each simulation by the mean luminosity density , we can estimate @xmath6 by dividing the result by the appropriate critical density . these estimates @xmath61 are given in the last line of table [ tab : gr_3d ] and in both cases are nearly a factor of 2 smaller than the actual value of @xmath6 . notice that @xmath56 actually overestimates the true group mass systematically . if we use the true median @xmath62 of groups to compute @xmath61 rather than our median virial estimate , we get 0.40 and 0.13 for @xmath2cdm and @xmath5cdm respectively . clearly , the standard assumption that groups have the same mass - to - light ratio value as the universe as a whole is untrue in either model . the bias in mass - to - light ratio is actually a function of group mass as can be seen in fig . 15 of paper i. the simulation boxes have volume @xmath63 mpc@xmath10 and @xmath64 mpc@xmath10 for the @xmath2cdm and the @xmath5cdm models , respectively . both simulations are normalised to match the present day cluster abundance . as a result both simulation boxes contain several clusters of mass @xmath65 . the cfa2n has volume @xmath66 mpc@xmath10 within @xmath67 km s@xmath14 and contains four abell clusters of richness @xmath68 ( including the coma cluster ) with masses @xmath65 . the cfa2n covers the right ascension range @xmath69 $ ] and the declination range @xmath70 $ ] , thereby avoiding regions of strong obscuration . it is clearly well suited for comparison with the simulations . in sect . [ sec : lf ] we showed that the simulated luminosity functions agree rather poorly with the observations . the discrepancy with the cfa luminosity function ( @xcite ) is particularly large because the cfa survey is unusually dense : the normalisation @xmath71 is two times larger and the characteristic magnitude @xmath72 is @xmath73 mag fainter than the average values derived from other surveys . furthermore , the cfa2n is significantly denser than the cfa survey as a whole , presumably because the `` great wall '' dominates this region . in order to understand how the luminosity functions of our models affect the properties of the groups and the redshift space correlation functions we study below , we have constructed mock catalogues from our simulations in two different ways : 1 . we keep the luminosities of the galaxies predicted by the semi - analytic recipes ; we refer to catalogues made using these luminosities as semi - analytic luminosity function ( salf ) catalogues ; 2 . we alter the luminosities of the galaxies in the simulations in order to obtain an exact match to the cfa luminosity function . this is done as follows . for each model we select a set of luminosities from the cfa luminosity function constrained so that their number equals the number of simulation galaxies with original luminosity @xmath74 and their sum equals the simulated volume times the cfa luminosity density . the new luminosities then replace the original ones in such a way that the luminosity ranking of the galaxies is unaltered . for each galaxy we compute the shift from the original to the new luminosity . ninety per cent of the luminosity shifts lie in the ranges @xmath75 $ ] and @xmath76 $ ] magnitudes in the @xmath2cdm and @xmath5cdm models respectively ; the median shifts are 0.8 and @xmath77 magnitudes respectively . we refer to catalogues constructed using these new luminosities as cfa luminosity function ( cfalf ) catalogues . the large scale structure of cfa2n is dominated by the great wall and the coma cluster . the center of coma has celestial coordinates @xmath78 , @xmath79 ( see e.g. @xcite ) and its distance from the milky way is @xmath80 mpc . to compile mock catalogues we place a hypothetical observer at a distance @xmath81h^{-1}$ ] mpc from the most massive cluster within the simulation box . the location of the observer is chosen to coincide with the position of a galaxy with properties similar to the milky way , i.e. a blue band luminosity @xmath82 and mass - to - light ratio @xmath83 ( e.g. @xcite ) . if these values are valid for a fiducial hubble parameter @xmath84 km s@xmath14 mpc@xmath14 , we have @xmath85 . we thus look for a galaxy with magnitude @xmath86 $ ] , stellar mass @xmath87 \times 10^{10 } h^{-1}m_\odot$ ] , and star formation rate sfr@xmath88m_\odot$ ] yr@xmath14 , typical of a normal spiral galaxy ( @xcite ) . we also require that this galaxy belongs to a dark matter halo similar to the local group halo , with total mass @xmath89\times 10^{13 } h^{-1 } m_\odot$ ] and containing no more than 2 galaxies brighter than @xmath90 , the magnitude of m33 . we find 32 and 15 galaxies satisfying these criteria in the @xmath2cdm and @xmath5cdm model respectively . once we have found the observer s galaxy , we rotate the reference frame so that the massive cluster has the coordinates of coma . we then compile a catalogue of galaxies with the same right ascension and declination range as the cfa2n . to each galaxy we assign the radial velocity @xmath91 , where @xmath92 is the galaxy peculiar velocity , @xmath93 is the observer s peculiar velocity , @xmath94 is the relative position between the galaxy and the observer and is in units of km s@xmath14 . the blue absolute magnitude @xmath23 yields the apparent magnitude @xmath95 . we include all galaxies with @xmath96 $ ] km s@xmath14 and @xmath97 $ ] . redshift and magnitude lower cutoffs avoid including faint objects close to the home galaxy . we choose the magnitude limit @xmath98 of our mock redshift surveys as follows . the cfa2n catalogue has a zwicky magnitude limit ( roughly a @xmath18-band magnitude limit ) @xmath99 . because the semi - analytic and the cfa survey luminosity densities differ by more than a factor of two , we fix @xmath98 in the salf catalogues by requiring that the number of galaxies in the mock survey be @xmath100 , the number of galaxies within cfa2n . we obtain @xmath101 for the @xmath2cdm model and @xmath102 for @xmath5cdm . errors in magnitude estimates of the cfa2n catalogue and the scatter in the correlation between blue and zwicky magnitudes make a shift in @xmath98 by @xmath103 mag not at all unreasonable ( see @xcite and references therein ) . the cfalf catalogues have the cfa luminosity function and luminosity density by definition , so , in this case , we set @xmath99 . note that our simulation box is @xmath104 ( @xmath105 ) @xmath106 mpc on a side for the @xmath2cdm ( @xmath5cdm ) model . thus , in order to have a survey with a depth of @xmath107 km s@xmath14 , one periodic replication of the simulation box is required . for @xmath99 , galaxies more distant than 85 ( 141 ) @xmath106 mpc are always brighter than @xmath108 ( @xmath109 ) for @xmath2cdm ( @xmath5cdm ) ; only the brightest galaxies enter the mock catalogue from the replicated regions . since we concentrate in this paper on small scale clustering , we do not expect our results to be seriously affected by this limitation . figs . [ fig : slice_cfa2n ] , [ fig : slice_tcdm ] and [ fig : slice_lcdm ] show the cfa2n catalogue and two typical salf catalogues from the @xmath2cdm and the @xmath5cdm simulations respectively . the @xmath2cdm mock catalogue does not look very much like the real universe . there is too much structure within 5000 km s@xmath14 and the model fails to produce coherent sheets or filaments . these features are common to all our @xmath2cdm mock catalogues . the @xmath5cdm catalogues are in better qualitative agreement with the data . there are large voids and filaments extending across the full survey volume . nevertheless , the structures are not as striking or as sharply defined as in the cfa2n . in addition , there is no structure comparable to the `` great wall '' . we have searched the simulation boxes for coherent sheets of galaxies and have failed to find anything as large as the observed wall ( see also @xcite ) . it is unclear if this is a result of the relatively small volume of our simulations ( particularly @xmath2cdm ) or reflects a significant problem for the cosmological models we have studied . cfalf mock redshift surveys are closer in appearance to the cfa2n because the change in luminosity function forces a distribution of galaxies in redshift closer to that observed ( figure [ fig : slice_lcdm.cfa ] ) . despite this the qualitative differences in large scale structure between the three cases remain . in the following sections , we analyse the cfa2n and mock catalogues extracted from the simulations using identical techniques . we have compiled an ensemble of ten mock catalogues for each simulation in order to assess the robustness of our results . note , however , that since all ten are constructed from the same parent simulation , the scatter between statistics estimated from them will underestimate the true sampling variance . a major problem for the study of groups in the real universe is in finding an objective algorithm to define them , given that only partial knowledge of the phase space coordinates is available in real galaxy catalogues . this algorithm should select groups which correspond as closely as possible to real 3d groups , at least in a statistical sense . in the eighties , two main algorithms were proposed : the hierarchical method ( e.g. @xcite ; @xcite , 1987 ) and the friends - of - friends algorithm ( @xcite ; @xcite ) . we identify groups in our mock catalogues with the friends - of - friends algorithm described by ramella et al . the robustness of methods of this type has been studied by nolthenius & white ( 1987 ) , moore et al . ( 1993 ) , and @xcite . all of these studies used dark matter only @xmath0-body simulations to study the relation between groups selected from mock observational catalogues and genuine virialized systems . their results were very similar to those we find below with careful parameter choices it is possible to arrange a fair correspondence between the two kinds of system and to ensure that the statistical properties of groups estimated from the `` observational '' catalogues are quite similar to those of the `` real '' systems . [ sec : method ] reviews the friends - of - friends algorithm . in sect . [ sec : linking ] , we investigate the dependence of the statistical properties of groups on the linking parameters . in sect . [ sec : comp ] we compare our models with the cfa2n groups . we find that variations of the galaxy luminosity function _ do _ affect the absolute abundances of groups , but have very little effect on their median properties . the friends - of - friends algorithm is an approximate method for identifying systems which lie above a chosen number overdensity threshold . we know galaxy positions in redshift space rather than in real space . we therefore need to use two distinct linking lengths , @xmath110 and @xmath111 , for the radial velocity coordinate and the coordinates projected onto the sky , respectively . when we know the galaxy luminosity function @xmath112 , @xmath111 defines the number overdensity threshold @xmath113^{-1}-1\ ] ] where @xmath114 is the faintest observable absolute magnitude at the fiducial redshift @xmath115 km s@xmath14 within a redshift survey with apparent limiting magnitude @xmath98 . having chosen the threshold @xmath116 and the linking length , @xmath110 , we link each pair of galaxies which satisfies @xmath117 @xmath118 where @xmath119 and @xmath120 are the galaxy radial velocities , @xmath121 is their angular separation and @xmath122^{1/3 } \label{eq : scaling}\ ] ] where @xmath123 $ ] . note that the scaling law in eq . ( [ eq : scaling ] ) has been questioned by many authors . specifically , replacing the power @xmath124 with @xmath125 ( see the argument in @xcite ; @xcite ; @xcite ) drastically reduces the correlation between redshift and velocity dispersion observed in the huchra & geller ( 1982 ) group catalogue . however , part of this correlation is related to a selection effect rather than to the grouping algorithm , because groups with low velocity dispersion usually have few bright galaxies and so can only be seen at low redshift . here , we use eq . ( [ eq : scaling ] ) for consistency with the ramella et al . ( 1997 ) catalogue . one of the goals of identifying groups in the real universe is to estimate their number density as a function of properties such as luminosity or velocity dispersion . to compute the correct abundance of groups , we weight each according to its distance ( @xcite ) . we consider groups with @xmath126 members . we can thus identify a group only when its third - ranked galaxy has absolute magnitude @xmath127 , where @xmath128 is the mean redshift of the group . @xmath129 determines the radius @xmath120 of the sphere within which we could have identified this group . this group contributes with weight @xmath130 to the total abundance of groups , where @xmath131 \label{eq : gr_weight}\ ] ] is the proper volume sampled by the group , to first order in @xmath132 , @xmath133 is the solid angle of the survey and @xmath6 is the ( unknown ) cosmological density parameter . we consider groups with @xmath134 km s@xmath14 ; therefore the first order correction in the volume is 9% at the most , when @xmath1 . note that the simulation galaxy catalogues are complete to @xmath52 . this magnitude sets a minimum redshift @xmath135 : groups closer than @xmath135 could contain galaxies fainter than @xmath23 in a real magnitude limited survey . therefore , we consider only redshift space groups with @xmath136 both in the mock catalogues and in the cfa2n catalogue . from the cfa2n catalogue , ramella et al ( 1997 ) compiled a fiducial group catalogue with linking parameters @xmath137 , and @xmath138 km s@xmath14 . here , we show that in the simulations these linking parameters give groups in redshift space with similar velocity dispersions and luminosities to the 3d groups ( sect 2.3 ) but with substantially larger sizes . these linking parameters will then be adopted for the remainder of our analysis . the accidental inclusion of interlopers is one of the major problems in identifying groups in redshift space . even with full knowledge of the galaxy locations in the six - dimensional phase space , the concept of interloper is ill - defined because groups are not isolated . here , we define interlopers as follows . each 3d group contains only galaxies lying within the same dark halo . each member of a redshift space group is associated with some dark halo , but such a group may contain galaxies belonging to different dark halos . we define the dark halo containing the greatest number of group members as the group halo . all members belonging to another halo are then interlopers , and we define the interloper fraction @xmath139 as the ratio between the number of interlopers and the total number of true members plus interlopers . if all members belong to different dark matter halos , the group is spurious and we set @xmath140 , because the group halo is undetermined . [ fig : link_combmod ] shows the dependence of @xmath139 on the values of the linking parameters @xmath110 and @xmath116 for two salf redshift surveys . all the cfalf and salf mock catalogues we compiled yield similar results . squares show the median of the distribution of @xmath139 ; error bars show the first and third quartiles . the solid square refers to the fiducial catalogue @xmath137 , @xmath138 km s@xmath14 . it is apparent that @xmath139 reaches a minimum when @xmath141 and @xmath110 is small . note that this minimum value is quite large ; more than a third of the assigned members of a typical group are interlopers . [ fig : link_combmod ] also shows that a significant fraction of groups are spurious ; for the preferred values of @xmath116 this fraction is 20 to 30% . we find that @xmath142 of the triplets are spurious , whereas only @xmath143 of the groups with four or more members are spurious . this result agrees with the suggestion of @xcite that the physical association of triplets should be considered uncertain . [ fig : gr_ratio_combmod ] shows how the weighted quartiles of the harmonic radius @xmath53 and of the velocity dispersion @xmath54 vary with the linking parameters which define our catalogues . by weighted quartiles we mean the 25 , 50 and 75% points of the cumulative distribution when each group is assigned weight @xmath130 ( see equation [ eq : gr_weight ] ) ; these should correspond approximately to the quartiles of a volume limited group sample . for comparison we also plot the quartiles of the corresponding distributions for 3d groups as listed in table 2 . these figures show that @xmath53 depends only weakly on @xmath110 and is a decreasing function of @xmath116 ; for @xmath144 it depends little on either linking parameter . on the other hand , @xmath54 is a strong function of @xmath110 for all @xmath116 . this systematic behaviour has been noted in all previous investigations of grouping algorithms ; see trasarti - battistoni ( 1998 ) for a recent discussion . while our fiducial choice , @xmath138 km s@xmath14 , leads to a @xmath54 distribution which is similar to that of the true 3d groups , taking @xmath145 results in @xmath53 distributions which are biased high by about a factor of two . this bias in group size is related to the rather high interloper fraction noted above . if interlopers are excluded when calculating group properties , then the remaining galaxies are , by definition , all members of the same halo and so give a measure of group size which is statistically similar to that found using full 3d information . we demonstrate this in tables [ tab : gr_rs_tcdm ] and [ tab : gr_rs_lcdm ] , which compare the weighted quartiles of the distributions in mock redshift surveys including and excluding interlopers with those of the 3d groups repeated from table [ tab : gr_3d ] . excluding interlopers has little effect on the velocity dispersions of the groups but brings their estimated sizes and mass - to - light ratios into much better agreement with those of the 3d groups unfortunately , of course , it is not possible to exclude interlopers from real redshift survey group catalogues in this fashion . it is curious that in our models this interloper - induced overestimation of @xmath53 in redshift survey groups combines with the overestimation of true group mass by @xmath56 ( see section [ sec:3d - dyn ] ) to almost exactly cancel out the factor of 2.5 difference between the true mass - to - light ratio of groups and the mean mass - to - light ratio of the universe . as a result , as may be seen in tables [ tab : gr_rs_tcdm ] and [ tab : gr_rs_lcdm ] , estimates of @xmath6 obtained by multiplying the ( incorrect ) mean estimated @xmath57 by the average luminosity density are fortuitously quite close to the true value . it is difficult to judge whether this interloper - bias conspiracy will also work in the real universe . some of the tests we carry out below suggest that there is no reason to expect that these two biases should always be of the same order . in this section , we compare our groups with the cfa2n catalogue . the galaxy luminosity function is a fundamental ingredient in constructing mock catalogues and in the friends - of - friends algorithm , so we might expect properties of groups in our simulated redshift surveys to depend strongly on the adopted luminosity function . we show below that this is only partly the case . we investigate how the luminosity function affects group abundances ( sect . [ sec : real_gr ] ) and the dependence of group properties on the linking parameters ( sect . [ sec : cfa_link ] ) . in this section we study how the median group velocity dispersion @xmath54 depends on the linking parameters used to define groups , and we compare with the behaviour seen in the cfa2n survey . the harmonic radius @xmath53 and the total group luminosity @xmath146 are also directly measurable , but , as we have shown , the estimated value of @xmath53 is biased high by interloper contamination , while @xmath146 is insensitive to the linking parameters . on the other hand , the velocity dispersion @xmath54 is not significantly biased by interloper contamination and is sensitive to the linking parameter @xmath110 . moreover , the median @xmath54 is a direct measure of the dynamics of galaxies on small scales , which in turn depends on the underlying mass distribution . the left panels of fig . [ fig : sigma_v0 ] show that the trend of @xmath54 with @xmath110 is similar in all our simulated redshift surveys and appears to be independent both of cosmological model ( @xmath5cdm or @xmath2cdm ) and of the adopted luminosity function ( salf or cfalf ) . the velocity dispersions of the simulated groups are systematically larger than the observed values by an amount which varies from about 10% at low @xmath110 to about 50% at large @xmath110 . this difference is seen in all ten simulated surveys of each model . let us define the grouped fraction @xmath147 as the number of galaxies in groups divided by the total number of galaxies in the catalogue . nolthenius et al . ( 1997 ) suggest using the dependence of the pair ( @xmath147 , @xmath54 ) on @xmath110 at fixed @xmath116 as a diagnostic to discriminate between models . differences in the small - scale dynamics can show up as a shifting of the tracks in the @xmath148 @xmath54 plane . the right panels of fig . [ fig : sigma_v0 ] show such tracks for the cfa2n survey and for our simulated redshift surveys . clearly , the choice of the luminosity function affects @xmath147 strongly but in opposite directions for our two models ; if the salf is used , the @xmath2cdm catalogue is closer than @xmath5cdm to the cfa2n ; with the cfalf , we obtain the opposite result . our models yield a fraction of galaxies in groups systematically lower than the cfa2n sample . when @xmath138 km s@xmath14 , the fraction of galaxies in groups can be from @xmath149 ( cfalf @xmath5cdm ) to @xmath59 ( salf @xmath5cdm ) smaller than in the cfa2n sample . note however that the cfa2n track is less than two standard deviations from the cfalf @xmath5cdm track . [ sec : real_gr ] figs . [ fig : gr_nd_rh ] and [ fig : gr_nd_sigma ] show the abundance of groups as a function of harmonic radius and velocity dispersion derived from our various catalogues . the top panels show results for the semi - analytic luminosity function ( salf ) . the discrepancy with the observations is simply a reflection of the overestimate ( underestimate ) of the total luminosity density of the universe by @xmath2cdm ( @xmath5cdm ) as compared with cfa2n . when we impose the cfa survey luminosity function ( bottom panels ) , the simulation results are in much better agreement with the observations , especially for @xmath5cdm . the change in luminosity function from salf to cfalf has a strong effect on the normalisation of the group abundance function , but rather little effect on its shape . as a result , the median properties of groups do not depend very strongly on the luminosity function . tables [ tab : gr_lf_tcdm ] and [ tab : gr_lf_lcdm ] list the weighted quartiles of galaxy properties in the salf and cfalf catalogues and compare them with the cfa2n values . taking the variations between different mock catalogues into account , the median size and velocity dispersion of groups in the @xmath5cdm simulation agree reasonably well with the observations , if the cfalf is adopted . moreover , we note that , according to our prescription for identifying galaxies in the simulations , the velocity of the central galaxy coincides with that of the dark matter particle with the greatest absolute value of the gravitational potential energy . this particle can move rapidly whereas the central galaxy is plausibly almost at rest with respect to the barycentre of its dark halo . when we replace the central galaxy velocity with the mean velocity of the dark particles within @xmath22 , the median velocity dispersion of groups becomes @xmath150 smaller . this effect is sufficient to bring the cfalf @xmath5cdm model in good agreement with the cfa2n . on the other hand , groups in the @xmath2cdm simulation still have velocity dispersions slightly higher than observed . note that , on average , the difference between the central galaxy velocity and the barycentric velocity of its dark halo is @xmath151 km s@xmath14 . replacing the central galaxy velocity by the barycentric motion has a measurable effect on group dispersions because most groups are triplets and quadruplets . the same replacement does not affect the galaxy pairwise velocity statistics computed in section [ sec : csi ] . for both @xmath2cdm and @xmath5cdm , groups are significantly less luminous than in the real universe . this is a consequence of the presence of the `` great wall '' in the cfa2n region : most of the groups lie within this structure at @xmath152 km s@xmath14 and so have a median redshift @xmath153 km s@xmath14 . in the models , however , the median group redshift is @xmath100 km s@xmath14 , leading to a typical luminosity a factor @xmath154 below that found for the cfa2n . note also that although for the salf catalogues the interloper - bias conspiracy results in estimates of @xmath6 which are quite close to the true values , the same conspiracy does not hold for the cfalf . indeed , when our two simulations are forced to have the same luminosity function they produce group catalogues which are very similar in most of their properties . in particular , they have similar estimated mass - to - light ratios and so lead to similar estimates of @xmath6 despite the factor of 3 difference between the true density values . to probe dynamics of galaxies on nonlinear scales , knowledge of galaxy peculiar velocities is necessary . even for nearby galaxies direct measurements have @xmath155% uncertainties and only a relatively small number of measurements are currently available ( see e.g. @xcite and references therein ) . alternatively , we can study peculiar velocities statistically by using galaxy - galaxy redshift space correlation functions . marzke et al . ( 1995 ) compute such correlation functions for the cfa redshift surveys . here , we analyse our mock catalogues following their procedures which we summarise in the next section . in redshift space , the vector @xmath156 locates a galaxy with redshift @xmath157 and celestial coordinates @xmath158 . for small angular separations ( @xmath159 in our analysis ) , we define the components of the relative separation @xmath160 of a pair of galaxies @xmath161 where @xmath162 . the two - dimensional redshift space correlation function @xmath20 measures the excess probability , compared to a poisson distribution , that a galaxy pair has separation @xmath163 . we estimate @xmath20 by weighting each galaxy according to the minimum variance estimator ( @xcite ) . by inverting @xmath164 , the projection of @xmath20 onto the @xmath165 axis , we can estimate the spatial correlation function @xmath166 . assuming a power - law , @xmath167 , gives @xmath168 , and @xmath169/ \gamma(\gamma/2)$ ] . on non - linear scales , we can then model @xmath20 as ( e.g. @xcite ) @xmath170\}f(r_p,\pi , y)dy \label{eq : csi_conv}\ ] ] where the pairwise velocity distribution @xmath171 is well approximated by the exponential form @xmath172 \label{eq : pairwise}\ ] ] where @xmath173 , and @xmath174 is the pair separation in real space along the line of sight . we model the mean streaming velocity @xmath175 with the scale - invariant solution to the truncated bbgky hierarchy derived by davis & peebles ( 1983 ) , @xmath176 where the constant @xmath177 in the similarity solution . ( [ eq : pairwise ] ) is an excellent approximation to the real distribution on very non - linear scales as already discussed by @xcite and @xcite . ( [ eq : pairwise ] ) also describes both dark matter particles and galaxies in our models quite accurately ( @xcite ) . on mildly non - linear scales , infall skews the distributions . this skewness can be elegantly formalized with an eulerian perturbative approach ( @xcite ) . on the contrary , eq . ( [ eq : v12 ] ) is not a good approximation to the mean streaming velocity measured in the simulations . in sect . [ sec : xi_res ] we will see that the uncertainty on @xmath178 does not strongly affect the estimate of the pairwise velocity dispersion @xmath8 , provided it is not assumed to be zero on all scales . in order to estimate the pairwise velocity dispersion @xmath21 at fixed projected separation @xmath165 , we first determine the spatial correlation function @xmath166 ; we then perform the integral in equation ( [ eq : csi_conv ] ) by assuming @xmath8 constant . note , however , that @xmath8 does depend on @xmath179 because the cosmic virial theorem predicts @xmath180 . however , since @xmath181 , this procedure yields values of @xmath8 in reasonable agreement with those computed with the full three - dimensional information finally , we use the measured @xmath20 to impose the normalisation @xmath182 in equation ( [ eq : pairwise ] ) . this procedure decreases the number of degrees of freedom by one . to estimate errors on @xmath20 we use a bootstrap procedure with 50 resampled samples . estimates of @xmath20 at different separations are correlated . therefore , determining @xmath8 by minimizing the @xmath183 computed directly with eq . ( [ eq : csi_conv ] ) is not the correct procedure . principal component analysis ( @xcite , @xcite ) transforms a set of correlated quantities @xmath184 into a set of uncorrelated quantities @xmath185 . meaningful results come from the standard @xmath183 analysis applied to this latter set . note that the errors of both the original and the transformed data sets are not gaussian distributed . therefore , the confidence levels of the computed @xmath183 should be considered only indicative . [ fig : csi_map ] shows the @xmath20 maps of our salf and cfalf catalogues . at @xmath186 mpc , @xmath20 in the salf @xmath2cdm catalogue is larger than in the cfalf catalogue ; the salf catalogue contains more galaxies in groups and clusters . on the other hand the two @xmath20 maps for the @xmath5cdm model are very similar , perhaps because the differences between the two luminosity functions are smaller . we can quantify the differing behaviour of our two models by looking at the parameters @xmath187 and @xmath188 of the real space correlation function derived by fitting a power law to the projected correlation function @xmath164 . table [ tab : xi ] shows that @xmath187 decreases by @xmath189 from the salf to the cfalf catalogue in the @xmath2cdm model , while in the @xmath5cdm model there is no significant change . none of these models matches the cfa2n parameters satisfactorily , perhaps because the cfa2n yields a correlation length which is significantly larger than in other surveys : cfa2 south and ssrs2 have @xmath190 and @xmath191 mpc respectively ( @xcite ) , while the lcrs gives @xmath192 mpc ( @xcite ) ; these values are close to those of our models . note that cfa2 south also has @xmath193 , so that its correlation function is in close agreement with that of our @xmath5cdm model . we find a similar result by looking at the projection of @xmath20 onto the @xmath194 axis averaged over the @xmath165 interval @xmath195 @xmath196 ( figs . [ fig : xi_tcdm ] and [ fig : xi_lcdm ] ) . independently of the luminosity function , both models predict a correlation amplitude somewhat smaller than that of the cfa2n . typical amplitude ratios between the cfa2n and the models are in the range @xmath197 . these differences are similar to those between the cfa2n and cfa2 south or ssrs2 ( @xcite ) . small variations in @xmath198 translate into large variations in the best fit parameters @xmath8 . in fact , marzke et al . ( 1995 ) show that @xmath8 can vary by a factor as large as three from survey to survey . in fig . [ fig : combine_3sigma ] , solid squares show @xmath21 when the similarity solution for the mean streaming velocity is assumed ( @xmath177 in eq . [ [ eq : v12 ] ] ) . the bold solid line is the @xmath8 of galaxies computed with the full three - dimensional information . the variations in the amplitude and slope of @xmath198 between salf and cfalf catalogues make @xmath8 vary by @xmath199 km s@xmath14 . however , given the sensitivity of @xmath8 , the differences between the models are not significant : both models predict a @xmath21 profile close to that of the cfa2n , independently of the luminosity function adopted . a more robust statistic , e.g. the single - particle - weighted statistic @xmath200 suggested by @xcite , might provide a more convincing comparison . finally , we note that in our models @xmath178 is significantly different from zero at megaparsec scales ; moreover , the similarity solution ( eq . [ [ eq : v12 ] ] ) does not describe its behaviour adequately . however , the estimated @xmath8 are only weakly dependent on the form of @xmath178 . for comparison , we estimate @xmath8 with @xmath201 and @xmath202 mpc which appears to be a better fit to @xmath178 in our simulations . the agreement between the estimated @xmath21 and the three - dimensional profile does not improve substantially ( open triangles in the top panels of fig . [ fig : combine_3sigma ] ) . on the other hand , in agreement with the result of marzke et al . ( 1995 ) , assuming @xmath203 underestimates @xmath21 significantly ( open squares in fig . [ fig : combine_3sigma ] ) . this raises a serious question about the fourier method suggested by @xcite for estimating @xmath21 : this method necessarily assumes @xmath204 . in paper i , we simulated the formation , evolution and clustering of galaxies by combining dissipationless @xmath0-body simulations and semi - analytic models of galaxy formation . we investigated a high density universe ( @xmath2cdm ) and a low density universe with a cosmological constant ( @xmath5cdm ) . here , we extract wide angle mock redshift surveys from these simulations and compare them with the cfa2n redshift survey by compiling catalogues of galaxy groups and by computing the redshift space correlation function @xmath20 . despite their very different @xmath6 values , both models yield a reasonable match to the data , although both appear slightly less clustered than the cfa2n : for example , @xmath59 ( @xmath2cdm ) and @xmath205 ( @xmath5cdm ) of galaxies are in groups rather than the @xmath206 observed ; moreover , the amplitude of @xmath20 is systematically a factor @xmath207 smaller than observed . however , this weaker clustering is similar to that observed in the southern regions of the cfa redshift surveys and in the lcrs , suggesting that galaxies within the cfa2n catalogue might be unusually highly clustered . our semi - analytic modelling predicts luminosity functions which fit the cfa results rather poorly . to test whether this disagreement induces clustering differences between our mock surveys and the cfa2n galaxy catalogue , we impose the cfa survey luminosity function on the models . we find that in fact only the group abundances are strongly affected , becoming substantially closer to those observed in the modified catalogues . quantities connected with the underlying mass distribution , such as the median velocity dispersion of groups or the redshift space correlation function , show less sensitivity to the adopted luminosity function . we compare our models with the cfa2n because ( 1 ) this survey provides the largest catalogue of galaxy groups currently available , and ( 2 ) it covers a volume similar to that we have simulated . however , a coherent two - dimensional structure , the `` great wall '' , dominates the large scale distribution of galaxies in the cfa2n and is not reproduced in our simulations . this structure plays a significant role in determining the typical luminosities of the observed groups and may also affect other group properties . it is unclear whether the apparent deficiency of coherent two - dimensional structure in our mock catalogues is a significant problem for our cosmological models , or reflects cosmic variance and the relatively small size of our simulation boxes . the modest discrepancies between our models and the cfa2n could plausibly disappear when other surveys , covering larger volumes and based on better photometric data become available , and can be compared with simulations of similarly large cosmological volumes . given the limitations of the observational and numerical data we consider in this paper , the agreement between theory and observation is remarkable and demonstrates that present day group dynamics alone give little information about @xmath6 . our preference for @xmath5cdm over @xmath2cdm is based on its better agreement with the observed luminosity functions and tully - fisher relations ( paper i ) and with the observed evolution of clustering ( paper ii ) rather than on any difference in pairwise velocities or in the mass - to - light values implied for groups . on the other hand , these clustering differences reflect observable differences in the evolution of groups and clusters and of their galaxy populations which should be detectable in future surveys to higher redshift . we will investigate these issues more thoroughly in a forthcoming paper . the @xmath0-body simulations were carried out at the computer center of the max - planck society in garching and at the eppc in edinburgh , as part of the virgo consortium project . we thank margaret geller , john huchra and ron marzke for enabling us to compare the cfa2n data directly with these numerical data . we also thank margaret geller , massimo ramella and roberto trasarti - battistoni for several enlightening discussions and an anonymous referee for suggesting improvements in the presentation of our results . during this project , a.d . was a marie curie fellow and held grant erbfmbict-960695 of the training and mobility of researchers program financed by the european community . a.d . also acknowledges support from an mpa guest post - doctoral fellowship . for reference , we review here the formulae we use to compute the physical properties of groups . a system with @xmath0 galaxies has three - dimensional ( 3d ) harmonic radius @xmath208 where @xmath209 are the pairwise galaxy separations . the corresponding harmonic radius for a real system at redshift @xmath128 is @xmath210^{-1}\ ] ] where @xmath121 are the pairwise galaxy angular separations and @xmath12 is the hubble constant . the one - 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this is the third paper in a series which combines @xmath0-body simulations and semi - analytic modelling to provide a fully spatially resolved simulation of the galaxy formation and clustering processes . here we extract mock redshift surveys from our simulations : a cold dark matter model with either @xmath1 ( @xmath2cdm ) or @xmath3 and @xmath4 ( @xmath5cdm ) . we compare the mock catalogues with the northern region ( cfa2n ) of the center for astrophysics ( cfa ) redshift surveys . we study the properties of galaxy groups and clusters identified using standard observational techniques and we study the relation of these groups to real virialised systems . most features of cfa2n groups are reproduced quite well by both models with no obvious dependence on @xmath6 . redshift space correlations and pairwise velocities are also similar in the two cosmologies . the luminosity functions predicted by our galaxy formation models depend sensitively on the treatment of star formation and feedback . for the particular choices of paper i they agree poorly with the cfa survey . to isolate the effect of this discrepancy on our mock redshift surveys , we modify galaxy luminosities in our simulations to reproduce the cfa luminosity function exactly . this adjustment improves agreement with the observed abundance of groups , which depends primarily on the galaxy luminosity density , but other statistics , connected more closely with the underlying mass distribution , remain unaffected . regardless of the luminosity function adopted , modest differences with observation remain . these can be attributed to the presence of the `` great wall '' in the cfa2n . it is unclear whether the greater coherence of the real structure is a result of cosmic variance , given the relatively small region studied , or reflects a physical deficiency of the models .

the crl-2302 ( arpe-19 ) ( atcc , usa ) was used for this study . these human retinal pigment epithelial cells were cultured in dulbecco 's modified eagle 's medium ( dmem ) ( sigma , st louis , mo , usa ) , which is composed of 10% fetal bovine serum ( fbs ) , penicillin ( 100 u / ml ) , streptomycin ( 100 u / ml ) , and nystatin ( 25 ug / ml ) . the cell line was maintained in a humidified incubator in an atmosphere of 95% air and 5% co2 at 37 and the culture medium was changed every 48 hours . the cells were plated in t75 or t150 flasks ( falcon , nj , usa ) and allowed to grow until the cultures were confluent . human retinal pigment epithelial cells were irradiated for 30 seconds with an irradiance of 3.3 mw / cm after removal of serum - free growth medium . uv irradiance was modulated by adjusting lamp output and calibrated with a uv sensor on a uv lamp ( fs-20 t12-uvb , national biological corp . ) . the uvb spectrum was between 280 nm and 320 nm with peak irradiance at 312 nm . human retinal pigment epithelial cells were cultured for 1 day and the experiments were performed on 3 divided groups : the normal control group , which was not exposed to uv light ( group i ) ; the second group , which was exposed to uv light without administration of egcg ( sigma , st louis , mo , usa ) ( group ii ) ; and the third group , which was exposed to uv light with administration of egcg ( group iii ) . egcg was dissolved in dimethyl sulfoxide ( dmso ) ( sigma , st louis , mo , usa ) and added to the culture medium concomitantly with the tnf - a stimulus . five minutes and 1 hour after uv irradiation , different concentration of egcg ( 5 , 10 , 15 , 25 , 50 , and 100 m ) were administered to group iii . after 24 hours incubation , the cell count was determined under a microscope using a counting chamber , cell activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide ( mtt ) assay . briefly , mtt is reduced to purple formazan in the mitochondria of living cells . a solubilizing liquid optical density was measured at 570 nm using a spectrophotometer . to increase the reliability of the data , the data were analyzed for significance using repeated measures , followed by a duncan 's multiple range test of post hoc tests . the data were expressed as a mean percentage of the control value plus s.e.m . a p - value of < 0.05 was considered significant . the crl-2302 ( arpe-19 ) ( atcc , usa ) was used for this study . these human retinal pigment epithelial cells were cultured in dulbecco 's modified eagle 's medium ( dmem ) ( sigma , st louis , mo , usa ) , which is composed of 10% fetal bovine serum ( fbs ) , penicillin ( 100 u / ml ) , streptomycin ( 100 u / ml ) , and nystatin ( 25 ug / ml ) . the cell line was maintained in a humidified incubator in an atmosphere of 95% air and 5% co2 at 37 and the culture medium was changed every 48 hours . the cells were plated in t75 or t150 flasks ( falcon , nj , usa ) and allowed to grow until the cultures were confluent . human retinal pigment epithelial cells were irradiated for 30 seconds with an irradiance of 3.3 mw / cm after removal of serum - free growth medium . uv irradiance was modulated by adjusting lamp output and calibrated with a uv sensor on a uv lamp ( fs-20 t12-uvb , national biological corp . ) . the uvb spectrum was between 280 nm and 320 nm with peak irradiance at 312 nm . human retinal pigment epithelial cells were cultured for 1 day and the experiments were performed on 3 divided groups : the normal control group , which was not exposed to uv light ( group i ) ; the second group , which was exposed to uv light without administration of egcg ( sigma , st louis , mo , usa ) ( group ii ) ; and the third group , which was exposed to uv light with administration of egcg ( group iii ) . egcg was dissolved in dimethyl sulfoxide ( dmso ) ( sigma , st louis , mo , usa ) and added to the culture medium concomitantly with the tnf - a stimulus . five minutes and 1 hour after uv irradiation , different concentration of egcg ( 5 , 10 , 15 , 25 , 50 , and 100 m ) were administered to group iii . after 24 hours incubation , the cell count was determined under a microscope using a counting chamber , cell activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide ( mtt ) assay . briefly , mtt is reduced to purple formazan in the mitochondria of living cells . a solubilizing liquid to increase the reliability of the data , all experiments were repeated 3 times and the average values were obtained . the data were analyzed for significance using repeated measures , followed by a duncan 's multiple range test of post hoc tests . the data were expressed as a mean percentage of the control value plus s.e.m . a p - value of < 0.05 was considered significant . epigallocatechin gallate ( egcg ) effectively protected cultured human retinal pigment epithelial ( rpe ) cells from oxidative - stress - induced cytotoxicity . compared with the control group , which was not exposed to uv irradiation ( fig . 1a ) , exposure to uv irradiation without administration of egcg showed significant cell loss ( fig . 1d ) after uv irradiation , experienced an increased cell count compared with that of the control group . the cell count of cultured human rpe cells after uv irradiation was markedly increased in the egcg administration group , compared with the group that did not receive egcg ( fig . 2 ) . there was no significant relationship between the time to administration of egcg and cell loss ( p=0.279 ) . cell activity of the cultured human rpe cells after uv irradiation was markedly increased with egcg administration , and it increased in a dose - dependent way , as determined by the mtt assay ( fig . significant differences were shown between 5 m ( mean=8.003.630 ) and 10 m ( m=25.835.399 ) and between 10 m ( m=25.835.399 ) and 15 m ( m=58.904.623 ) ( p<0.001 ) . there were no significant differences between 0 m ( m=0.000.000 ) and 5 m ( m=8.003.630 ) ( p=0.260 ) among 15 m ( m=58.904.623 ) , 25 m ( m=61.275.206 ) , 50 m ( m=63.301.871 ) , and 100 m ( m=68.105.229 ) ( p=0.072 ) . in comparison with the group that did not receive egcg , cell activity was increased by approximately 43.9% , 68.1% respectively in 100 m of the egcg administration group . moreover , post - treatment of rpe cells with egcg ( 100 m ) after 1 hour showed significantly reduced cell deaths as a result of uv irradiation . there was a significant relationship between the time to administration of egcg and cell activity ( p=0.001 ) . increasing interest in the health benefits of tea has led to the inclusion of tea extracts in dietary supplements and functional foods . while tea contains a number of bioactive chemicals , it is particularly rich in catechins . the main catechin group consists of eight polyphenolic flavonoid - type compounds : ( + ) -catechin ( c ) , ( -)-epicatechin ( ec ) , ( + ) - gallocatechin ( gc ) , ( -)-epigallocatechin ( egc ) , ( + ) -catechin gallate ( cg ) , ( -)-epicatechin gallate ( ecg ) , ( + ) -gallocatechin gallate ( gcg ) , and ( -)-epigallocatechin gallate ( egcg ) . ( -)-epigallocatechin gallate is the most abundant of the tea catechins and is thought to be responsible for the majority of the green tea extracts 's biological activity , such as its anti - cancer and antioxidant properties.19,20 although a number of in vitro and in vivo studies have shown egcg acts as an antioxidant21 - 24 and an antiapoptotic agent,25 the actual mechanism of its action as an antioxidant remains unclear . importantly , total plasma antioxidant activity has been shown to increase following significant intake of green tea26,27 in laboratory studies . moreover , an increase in plasma catalase activity and a decrease in the nitric oxide levels28 occurred , suggesting that catechins have both direct antioxidant effects and indirect influences on increasing the activity of other antioxidants or enzymes . that catechins like egcg elicit antioxidant actions in a number of ways.29 egcg promotes human keratinocyte survival and inhibits ultraviolet light - induced apoptosis by dual mechanisms , namely by phosphorylating bad protein through erk and akt pathways , respectively , and by increasing the bcl-2 to bax ratio.30 retinal pigment epithelial cells may produce a large amount of oxygen radicals because they consume a large amount of oxygen . these reactive oxygen species may peroxidize the unsaturated fatty acids in cell membranes , damaging the protein and dna , thereby causing oxidative cell injury . an investigation about ultraviolet light and apoptosis in retinal pigment epithelial cells has been performed with various methods . yu et al . suggested the possibility that an oxidative injury by uv irradiation is a cause of apoptosis in retinal pigment epithelial cells.8 although research for suppression and protection against apoptosis of retinal pigmented epithelium is continuing , the correct mechanism has not been identified yet . armd is a leading cause for blindness in developed countries and will be more of a problem as life expectancy increases . support for the involvement of oxidative stress in armd comes from the finding that daily administration of antioxidant vitamins and/or zinc significantly slowed the rate of progression in patients from high risk atrophic armd to neovascular armd.14 a number of age - related pathologies have been attributed to cumulative oxidative damage caused by ros , such as nitric oxide ( no ) , hydrogen peroxide ( h2o2 ) , singlet oxygen , superoxide anion , and hydroxyl radicals . ros arise as by - products of cellular metabolism or photochemical reactions.31,32 furthermore , the oxygen supply to the photoreceptors via the choroidal and retinal vessels can cause an elevated oxygen tension in the retinal pigment epithelium and photoreceptors.33,34 moreover , uv radiation can cause damage to dna , leading to single - strand dna breaks in the retina.4,35 egcg attenuates the effect of an ischemia/ reperfusion insult to the intact retina , where oxidative stress is implicated,37 and to neurons in vitro by h2o2 , an oxidant . it is generally thought that oxidative stress plays a part in the pathogenesis of glaucoma,37,38 initiated by ischemia to the optic nerve head components,39,40 because of a reduced optic nerve head blood supply.40 egcg , besides being a powerful antioxidant,24 also has anti - inflammatory41,42 and vasodilator43 effects ; both inflammation and vasoconstriction36,44 are strongly suspected of playing a part in the pathogenesis of glaucoma . moreover , egcg can intervene in other cellular mechanisms that are relevant to retinal ganglion cell loss in glaucoma , independently from its antioxidant properties . it is known that the oxidative damage to the retinal pigment epithelial cells play an important role in the development of armd and glaucoma . in conclusion , the results of this study have shown that egcg increases the cell count and cell activity after uv irradiation in cultured human retinal pigment epithelial cells ; we can conclude that egcg provides protective effects against uv damage in cultured human retinal pigment epithelial cells . although the results show thategcg can protect human retinal pigment epithelial cells from uv induced damage , further in vivo and in vitro studies investigating areas such as mitochondrial damage , nucleic acid damage , phagocytotic activity after uv exposure in human retinal pigment epithelial cells will be required .

purposeto evaluate the protective effects of epigallocatechin gallate ( egcg ) against uv irradiation in cultured human retinal pigment epithelial ( rpe ) cells.methodsuv irradiation was produced by a uv lamp for 30 seconds with an irradiance of 3.3 mw / cm2 . after 5 minutes and 1 hour , we administered different concentrations of egcg ( 0 , 5 , 10 , 15 , 25 , 50 , 100 um ) . the cell count was determined under a microscope using a counting chamber and the cell activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide ( mtt ) assay.resultsthe cell count of cultured human rpe cells after uv irradiation was markedly increased in the egcg administration group , compared with the non - administrated group . the cell activity of the cultured human rpe cells after uv irradiation was markedly increased in the egcg administration group and was increased in a dose - dependent way as determined by the mtt assay.conclusionsthe administration of egcg increased the cell count and the cell activity after uv irradiation in cultured human retinal pigment epithelial cells ; this suggests that egcg provided protection against uv damage in cultured human retinal pigmented epithelial cells .

CHICAGO — A Chicago couple used their health care business to bilk Medicare out of millions of dollars while also conspiring to force a housekeeper to work against her will, according to an indictment returned in federal court in Chicago. RICHARD TINIMBANG and his wife, MARIBEL TINIMBANG, participated in a $45 million fraud scheme involving three Lincolnwood-based home health care companies owned by Richard Tinimbang’s mother, according to the indictment. The companies paid bribes and kickbacks to obtain Medicare beneficiaries, ignored doctors who refused to certify beneficiaries as being in need of home health care, and falsified medical records to make patients appear sicker than they actually were, the indictment states. The couple and Richard Tinimbang’s mother, JOSEPHINE TINIMBANG, allegedly used proceeds from the fraud to make numerous personal purchases, including shares of stock, vehicles, real estate, and jewelry. Richard Tinimbang, 38, of Chicago, is charged with one count of conspiracy to defraud Medicare, one count of conspiracy to pay or receive health care kickbacks, two counts of paying kickbacks to induce referrals of Medicare beneficiaries, one count of money laundering conspiracy, one count of conspiracy to obtain forced labor, and one count of presenting false statements in an immigration document. Maribel Tinimbang, 40, of Chicago, is charged with one count of conspiracy to defraud Medicare, one count of money laundering conspiracy, and one count of conspiracy to obtain forced labor. An arraignment date has not yet been set. The charges against Richard and Maribel Tinimbang are contained in a third superseding indictment returned last week in U.S. District Court in Chicago. The case is part of a larger health care fraud investigation that previously resulted in charges against 13 others. Three defendants have pleaded guilty and are awaiting sentencing, while the other ten, including Josephine Tinimbang, are awaiting trial. The investigation found that several individuals who worked at three related home health care companies – Donnarich Home Health Care Inc., Josdan Home Health Care Inc., and Pathways Home Health Services LLC – conspired to commit health care fraud and laundered money to conceal the scheme. The fraud started in 2008 and continued into 2014, resulting in a loss to Medicare of $45 million, according to the indictment. Richard and Maribel Tinimbang’s business, Patients First Physical Therapy Inc., purported to provide in-home therapy services to patients of the three companies. The indictment states the couple concealed the money they had pocketed by falsely making it appear to be business expenses, then used it to purchase personal items, including a 5,000-square-foot residence in Lincolnwood. In addition to the health care fraud charges, Richard Tinimbang is accused of submitting fraudulent forms to the U.S. Department of Homeland Security to allow a Filipino woman to legally work in the United States. Richard Tinimbang stated in the form that the woman would be hired as a business analyst at Josdan, thus qualifying her for an H-1B visa. When the woman arrived in the United States, Richard Tinimbang put her to work full time as a nanny and housekeeper for him, his wife and others, the indictment states. The couple allegedly attempted to induce the woman to sign a servitude contract that provided for payment of $66 per day – regardless of the number of hours worked – for a term of seven years. The contract further provided that if the woman quit before the seventh year, she would be required to pay $25,000 in damages, the indictment states. To force the woman to surrender her passport and sign the contract, the couple threatened to send her back to the Philippines without being paid for the work she had already performed, according to the indictment. The indictment was announced by Zachary T. Fardon, United States Attorney for the Northern District of Illinois; Assistant Attorney General Leslie R. Caldwell of the Justice Department’s Criminal Division; Michael J. Anderson, Special Agent-in-Charge of the Chicago Office of the Federal Bureau of Investigation; Lamont Pugh III, Special Agent-in- Charge of the Chicago Regional Office of the U.S. Department of Health and Human Services Office of Inspector General; James D. Robnett, Special Agent-in-Charge of the IRS Criminal Investigation Division in Chicago; James M. Gibbons, Acting Special Agent-in-Charge of the Chicago Office of the U.S. Immigration and Customs Enforcement’s (ICE) Homeland Security Investigations (HSI); James Vanderberg, Special Agent-in-Charge of the Chicago Region of the U.S. Department of Labor’s Office of Inspector General, Office of Labor Racketeering and Fraud Investigations; and Cook County State’s Attorney Anita Alvarez. The investigation was carried out by the Medicare Fraud Strike Force, which consists of agents from the FBI and the U.S. Department of Health and Human Services, and prosecutors from the U.S. Attorney’s Office and the Justice Department’s Fraud Section. The strike force is part of the Health Care Fraud Prevention & Enforcement Action Team (HEAT), a joint initiative between the Justice Department and HHS to prevent fraud and enforce anti-fraud laws around the country. The case was also investigated by the Cook County Human Trafficking Task Force, a multi-disciplinary unit that brings law enforcement agencies together to work on human trafficking cases. The public is reminded that an indictment is not evidence of guilt. The defendants are presumed innocent and are entitled to a fair trial at which the government has the burden of proving guilt beyond a reasonable doubt. If convicted, the Court must impose a reasonable sentence under federal statutes and the advisory U.S. Sentencing Guidelines. The government is represented by Trial Attorney Brooke Harper of the Justice Department’s Criminal Division Fraud Section. To report healthcare fraud or to learn more about it, logon to: StopMedicareFraud.gov . Indictment ||||| The young Lincolnwood couple seemed to have it all: a 5,000-square-foot McMansion, a small fleet of luxury SUVs, $1 million in Facebook stock and a housekeeper and nanny who helped raise their children while they ran a thriving home health care business called "Patients First." But Richard and Maribel Tinimbang's success was built on a lie, according to a federal indictment filed last week that said the Tinimbangs put themselves first, not their patients. Federal authorities say the couple's "nanny" was in fact little more than an indentured servant — a Filipino immigrant whom they had forced to work on threat of deportation — while the couple's main business was bilking taxpayers. Between them, and with the help of Richard Tinimbang's mother, Josephine Tinimbang, and 10 other defendants, the Tinimbangs allegedly committed a $45 million Medicare fraud between 2008 and 2014. According to the indictment, the couple's business, Patients First Physical Therapy, purported to provide in-home therapy services to patients of three other companies in which their family also had a stake, Donnarich Home Health Care, Josdan Home Health Care and Pathways Home Health Care. But the patients they treated often weren't as sick as the Tinimbangs claimed, federal authorities allege. In many cases, the couple and their employees falsified records to make patients appear more ill than they actually were, the indictment states. In others, they paid kickbacks of up to $1,200 for patient referrals, it alleges. The couple are also accused of attempting to force a Filipino immigrant, whom they helped come to the U.S., to work for them illegally. While Richard Tinimbang had sponsored the woman's visa, saying he'd employ her as a $50,000-a-year "business consultant," he in fact employed her as a nanny and housekeeper for just $66 a day, regardless of how many hours she worked, the indictment states. The couple threatened to take her passport, and attempted to induce her to sign a "servitude contract" that would require her to pay them $25,000 if she left within seven years, it adds. Two nurses who worked for the Tinimbangs previously pleaded guilty to their roles in the Medicare fraud scheme, as did a marketer, Sherwin Cubello, who admitted he received $300,000 in bribes and kickbacks from the Tinimbangs for patient referrals. Josephine Tinimbang and seven other co-defendants are awaiting trial. Richard and Maribel Tinimbang, 38 and 40, respectively, did not return calls seeking comment Tuesday morning. They are due to make their first court appearances Thursday. In addition to potential prison terms, the couple face the forfeiture of $45 million, plus the loss of their home, business, stocks and BMW, Land Rover and Mercedes SUVs if convicted. U.S. Attorney Zachary Fardon has made cracking down on Medicare and Medicaid fraud a priority, with several high profile, multimillion-dollar indictments since his 2013 appointment. The Government Accountability Office last year estimated that around $60 billion, or more than 10 percent, of Medicaid payments alone are lost to fraud, waste and other improper payments each year. [email protected] Twitter @kimjnews

– File under Appearances Can Be Deceiving: A Chicago-area couple whose 5,000-square-foot home came complete with a bevvy of luxury SUVs built their empire "on a lie," reports the Chicago Tribune. Richard and Maribel Tinimbang, 38 and 40, are being charged with various counts of conspiracy, paying kickbacks, money laundering, and even forced labor that was all part of an elaborate $45 million Medicare scam, per a Department of Justice press release. The federal indictment filed last week charges that the Tinimbangs used their home health care business "Patients First" to put themselves first and even forced a woman into indentured servitude. An arraignment date hasn't yet been set. The husband and wife are accused of using three home healthcare companies owned by Richard's mother, Josephine Tinimbang, to pay bribes and kickbacks to get Medicare beneficiaries between 2008 and 2014, and of both ignoring doctors who wouldn't certify beneficiaries as needing home health care as well as falsifying records to make patients appear sicker than they were. The DOJ estimates a resulting $45 million hit to Medicare, which afforded the couple their house, vehicles, jewelry, and stock shares. Meanwhile, they allegedly brought a Filipino woman they said would be a business analyst back to the States and paid her $66 a day to serve as their nanny and housekeeper, all while threatening to charge her $25,000 in damages should she leave before seven years were up. Several law enforcement agencies worked together on both the fraud and human trafficking aspects of the case, including the FBI and Department of Health and Human Services. (Check out the enormity of this Medicare fraud bust.)

traditionally , the presence of antibodies against human leukocyte antigen ( hla)-c and dp was considered to be associated with only a low risk of antibody - mediated rejection ( abmr ) in kidney transplantation ( kt ) , because the antigenicities of these proteins are weak . however , the clinical effects of hla - c and -dp donor - specific hla antibodies ( dshas ) have recently been reevaluated . here , we report the case of a retransplant patient with positive flow cytometry crossmatch ( fcxm ) and high level of hla - dp dsha who was desensitized using rituximab , plasmapheresis , and intravenous immunoglobulin . the epitope - based antibody reactivity was identified that the positive b - cell fcxm in our patient was attributable to the specific epitope . the patient underwent a successful retransplantation and has continued to do well for 10 month after kt . if an hla - dp dsha is present , it is important to detect any mismatched hla - dp epitope pretransplantation and to monitor hla - dp levels carefully . according to previous reports , anti - hla - dp dsha can induce abmr soon after transplantation , but such abmr can be prevented by pretransplantation desensitization and careful monitoring of dsha levels . despite immunological advances in transplantation , antibody - mediated rejection ( abmr ) remains the major cause of graft failure after kidney transplantation ( kt ) . the presence of donor - specific anti - human leukocyte antigen ( hla ) antibodies ( dsha ) increases the risk of abmr after kt . however , most clinical studies have focused on antibodies against class i hla - a and -b and class ii hla - dr and -dq rather than against class i hla - c and class ii hla - dp . the clinical implications of anti - hla - c and -dp antibodies in the context of transplantation are less significant because these antigens are expressed at lower levels than other hla antigens . although the levels of mrnas encoding hla - c proteins are similar to those encoding hla - a and - b proteins , but hla - c expression levels on cell surfaces are much lower than those of hla - a and -b . additionally , hla - dp is expressed at a lower level than hla - dr on the endothelial surface of the normal kidney . however , the clinical relevance of anti - hla - c and -dp dshas has recently been reevaluated ; it likely that these antibodies can , in fact , trigger acute abmr . in a previous report , desensitization after kt was unable to overcome the abmr because of the existence of preformed hla - dp dsha . here , we report a case of successful transplantation after desensitization of a patient who expressed a high level of anti - hla - dp dsha and positive flow cytometry crossmatch ( fcxm ) results . a 26-year - old female with end - stage renal disease caused by iga nephropathy received her 1st kidney transplant from her mother in 2008 . hla typing assays detecting the hla - a , -b , drb1 , and dqb1 loci were performed using luminex technology and lifecodes hla sso typing kits ( immucor transplant technology , stamford , ct ) . hla - dpb1 typing was achieved by direct sequencing of exons 2 , 3 , and 4 of hla - dpb1 . the luminex single - antigen bead ( sab ) assay ( lifecodes lsa classes complement - dependent cytotoxicity crossmatching ( cdc - xm ) and fcxm of t- and b - cells were performed before transplantation . the informed consent was given from the patient and the ethical approval was waived for case report . at the time of the 1st kt , 3 antigen mismatches ( hla - a31 , -b75 , and -dpw5 , table 1 ) were evident . the cdc - xm and fcxm tests were both negative , and no anti - hla antibodies were detected by the sab assay . the patient underwent induction therapy with baxiliximab ( simulect ) , followed by tacrolimus ( tacrobell ) , mycophenolate sodium ( myfortic ) , and prednisolone ( solondo ) . however , the patient developed a urinary tract infection 2 years after the 1st kt , and her serum creatinine level increased to 1.75 mg / dl . biopsy of the allograft kidney revealed banff ib / iia acute cell - mediated rejection ( cmr ) . she underwent steroid pulse therapy and received antithymocyte globulin , but cmr was diagnosed on 4 occasions ( in the absence of dsha ) from june 2010 to june 2012 . one year later , her serum creatinine level had increased to 3.65 mg / dl and dsha to b75 , and dpb105 appeared ; the mean fluorescence intensities ( mfis ) were 2617 and 8556 , respectively , according to the sab assay . a 5th kidney biopsy was performed , and she was diagnosed with c4d - negative abmr accompanied by glomerulitis ( g1 ) and peritubular capillaritis ( ptc1 ) . one month later , a 6th biopsy was performed , and acute abmr ( g2 , ptc1 ) associated with c4d - positivity was diagnosed ( fig . 1 ) . after the diagnosis of abmr , she underwent plasmapheresis featuring intravenous immunoglobulin therapy . however , the graft function continued to decline , and her serum creatinine level increased to 5.78 mg / dl . flow chart of the clinical course after the 1st kt showing the levels of serum creatinine and dshas . the initial mfi values for each type of dsha were -b44 ( 1884 ) , -dpb105 ( 14,454 ) , and -dpb119 ( 11,760 ) . after desensitization , the mfi values for each type of dsha decreased to hla - b44 ( 914 ) , -dpb105 ( 5,135 ) , and -dpb119 ( 4,093 ) . the mfi values for each type of dsha were monitored at 3 , 7 , and 20 days after kt and were hla - b44 ( 650 ) , -dpb105 ( 7698 ) , and -dpb119 ( 6180 ) ; hla - b44 ( 747 ) , -dpb105 ( 6295 ) , and -dpb119 ( 4549 ) ; and hla - b44 ( 739 ) , -dpb105 ( 4838 ) , and -dpb119 ( 3590 ) , respectively . abmr = antibody - mediated rejection , atg = antithymocyte globulin , c4d0 = negative c4d staining , c4d1 = minimally positive c4d staining , dsha = donor - specific hla antibody , g = glomerulitis , hla = human leukocyte antigen , ivig = intravenous immunoglobulin , kt = kidney transplantation , mfi = mean fluorescence intensity , mmf = mycophenolate mofetil , mps = mycophenolate sodium , ptc = peritubular capillaritis , tcmr = t cell - mediated rejection . she was evaluated in terms of retransplantation from 2 candidate donors and underwent a 2nd kt ( from her older sister ; candidate donor 1 ) in may 2015 ; the allograft kidney was mismatched at hla - a , -b , -dr , and -dp . during pretransplant evaluation , the cdc - xm status was negative , but both t- and b - cell fcxm were positive ( table 1 ) . anti - hla - b44 , -dpb105 , and -dpb119 dshas were present , as revealed by the sab assay . the luminex c1q assay was also performed at this time , but it was negative . the mfi values of each dsha were 1844 ( hla - b44 ) , 14,454 ( -dpb105 ) , and 11,760 ( -dpb119 ) . the hypervariable region ( hvr ) of hla - dpb1 differed between the recipient and donor at amino acids 84 to 87 of exon 2 . after the 1st kt , only anti - hla - dp antibodies were evident in the class ii pra assay . the epitope triggering antibody production was identified using lifecodes match it antibody software version 1.2.1 ( immucor transplant technology ) as 84 deav ( donor - specific ) ( table 1 ) . the patient had both class i and ii dshas to candidate donor 1 but only a class ii dsha to candidate donor 2 . therefore , the recipient hla - dpb105 dsha reacted with the donor - specific hla - dp antigen of both candidate donors . she was prescribed rituximab at day 7 , and underwent 4 plasmaphereses using a total of 100 mg / kg intravenous immunoglobulin . after desensitization , the mfi values of the dshas fell to 914 ( hla - b44 ) , 5135 ( -dpb105 ) , and 4093 ( -dpb119 ) . after transplantation , immunosuppression was induced with antithymocyte globulin and maintained with tacrolimus ( tacrobell ) , mycophenolated mofetil ( mmf , myrept ) , and prednisolone ( solondo ) . she was capable of immediate urination and the serum creatinine level stabilized at 0.97 mg / dl 10 months after the 2nd kt . the mfis of the dshas were measured 3 , 7 , and 20 days after kt , and were 650 ( hla - b44 ) , 7698 ( -dpb105 ) , and 6180 ( -dpb119 ) ; 747 ( hla - b44 ) , 6295 ( -dpb105 ) , and 4549 ( -dpb119 ) ; and 739 ( hla - b44 ) , 4838 ( -dpb105 ) , and 3590 ( -dpb119 ) , respectively ( fig . hla - dp antigens have been considered to be minimally immunogenic but the incidence of development of anti - hla - dp antibodies after kt was 8% to 45% in previous reports . [ ] development of anti - hla - dp antibodies were associated with transplantation rather than pregnancy or transfusion events . in our patient , anti - hla - dp antibodies developed after hla - dr / dq - matched transplantation . thus , anti - hla - dp antibodies can develop after kt associated with an hla - dp mismatch regardless of the presence of abmr . dshas to hla - dp target immunogenic epitopes in donor - specific hvrs . the clinical importance of matching immunogenic hla - dp epitopes in kt and in patients undergoing hematopoietic stem cell transplantation ( hsct ) has been emphasized . [ ] however , the epitope - matching concept differs between hsct and kt . t - cell epitope - matching at hla - dpb1 is recommended prior to hsct , but hvr matching of hla - dp is recommended before kt . [ ] the hvrs of hla - dpb1 are 6 in number , termed hvr - a to -f ; about 50% of antibodies target hvr - f ( 84 deav ) . [ ] only 7 epitopes ( 35 fc , 56 e , 56 e , 56ee , 57 d , 84 deav , and 85 gpm ) of hla - dp exhibit confirmed antibody reactivity ( according to the hla epitope registry ) , and 3 hvrs ( hvr - b , -c , and -f ) are included in the confirmed epitopes database ( http://www.epregistry.ufpi.br/index/databases/database/dp/ , 2015.06.10 ) . previously , epitope - based matching was thought to be more important than allelic matching of hla - dp antigens prior to kt . both our current results and earlier data support the importance of epitope - based matching of hla - dp antigens ( table 2 ) . the epitope - based antibody reactivity was identified in our patient and the positive b - cell fcxm was attributable to the epitope 84 deav . epitopes mismatched to the donor - specific hla - dp and clinical courses after transplantation as described in previous reports . when using luminex technology , antibody strength may be overestimated because of differences in the extent of antigenic expression between cells and microbeads . in particular , the mfi value of an anti - hla - dpb antibody may differ from that of an actual hla / anti - hla - dpb reaction . therefore , the clinical significance of anti - hla antibodies can not be estimated using only the luminex assay . our patient exhibited a positive b - cell fcxm but a negative cdc - xm . hla - dp antigens are known to be associated with a reduced immunological risk of rejection when the cdc - xm status is negative . however , any correlation between abmr and positive xm data in terms of hla - dp dsha remains controversial . [ ] however , 1 recent report showed that dsha to hla - dp could trigger abmr shortly after kt in the absence of xm positivity . also , abmr can be induced by an antibody reaction to either hla - dpa or -dpb . in addition , positive b cell fcxm status alone ( thus combined with negative cdc - xm status ) can trigger both early and late allograft failure . recent data have shown that hla - dp dsha are more relevant in the context of acute abmr and a positive fcxm status than are dsha to hla - a , b , dr , or dq . therefore , the positive b cell fcxm status was a poor prognostic marker after transplantation in our patient . in our present case , the patient underwent desensitization before transplantation , because she was positive for fcxm and exhibited high - level dsha associated with hla - dp . after transplantation , the patient was stable , thus without abmr , for 10 months . according to previous reports , anti - hla - dp dsha can induce abmr soon after transplantation , but such abmr can be prevented by pretransplantation desensitization and careful monitoring of dsha levels , as in our case . however , the long - term clinical impact of anti - hla - dp dsha requires further evaluation . in conclusion , hla - dp antibodies usually develop in the posttransplant status and are of clinical significance . therefore , hla - dp dsha levels should be evaluated , especially if retransplantation is planned . it is important to identify mismatched hla - dp epitopes pretransplantation and to carefully monitor anti - hla - dp antibody levels . such donor - specific epitope antibodies can induce abmr shortly after transplantation . however , acute abmr developing shortly after transplantation can be prevented by pretransplant desensitization accompanied by close monitoring .

abstractbackground : traditionally , the presence of antibodies against human leukocyte antigen ( hla)-c and dp was considered to be associated with only a low risk of antibody - mediated rejection ( abmr ) in kidney transplantation ( kt ) , because the antigenicities of these proteins are weak . however , the clinical effects of hla - c and -dp donor - specific hla antibodies ( dshas ) have recently been reevaluated.methods:here , we report the case of a retransplant patient with positive flow cytometry crossmatch ( fcxm ) and high level of hla - dp dsha who was desensitized using rituximab , plasmapheresis , and intravenous immunoglobulin.results:the epitope - based antibody reactivity was identified that the positive b - cell fcxm in our patient was attributable to the specific epitope . the patient underwent a successful retransplantation and has continued to do well for 10 month after kt.conclusion:if an hla - dp dsha is present , it is important to detect any mismatched hla - dp epitope pretransplantation and to monitor hla - dp levels carefully . according to previous reports , anti - hla - dp dsha can induce abmr soon after transplantation , but such abmr can be prevented by pretransplantation desensitization and careful monitoring of dsha levels .

absorbing states , i.e. , states which systems may fall into but never escape from , and phase transitions into them are expected to be ubiquitous in nature . for instance , spreading or contamination processes like fires or epidemics exhibit such transitions when the propagation rate changes : initially active ( infected ) regions eventually disappear forever at low rates , i.e. , the absorbing state is reached , while they can be sustained ( pandemic regime ) for fast - enough propagation . examples abound far beyond : hundreds of numerical models , describing , e.g. , catalytic reactions , granular flows , and calcium dynamics in living cells , to name but a few , have been shown to exhibit such absorbing phase transitions @xcite . such phase transitions also naturally arise from general problems such as synchronization @xcite , self - organized criticality @xcite , spatiotemporal intermittency @xcite , and depinning @xcite . the vast majority of these transitions share the same critical behavior , that of the `` directed percolation '' ( dp ) class @xcite , as long as they are continuous . deep theoretical issues underpin this situation . whereas universality is well understood for systems in thermodynamic equilibrium , this is still not the case for systems driven out of equilibrium , where even the relevant ingredients determining the class are not well understood . in this context , absorbing phase transitions are central because of their genuine nonequilibrium character , since absorbing states directly imply violation of the detailed balance . janssen and grassberger @xcite conjectured that the dp universality class contains all continuous transitions into a single effective absorbing state in the absence of any extra symmetry or conservation law . the dp class thus appears as the simplest , and most common case , as testified by overwhelming numerical evidence . however , the situation has been quite different in experiments . over the last twenty years and more , a number of experiments have been performed in situations where dp - class transitions would be theoretically expected , but they have always yielded mixed and/or partial results with limited accuracy @xcite ( table [ tbl : earlierexperiments ] ) . this lack of fully convincing experimental realizations , in contrast with the wealth of numerical results , has been found surprising and a matter of concern in the literature @xcite . recently , though , studying a spatiotemporal intermittency regime occurring in turbulent liquid crystals , we found a transition whose complete set of static critical exponents match those of the dp class @xcite . the goal of the present paper is to provide a comprehensive report on this transition including not only a more complete description of experiments designed to investigate the static critical behavior , but also new experiments giving access to dynamic critical behavior . lllllllll ( 1 + 1)d system & size & @xmath0 & @xmath1 & @xmath2 & @xmath3 & @xmath4 & refs . + annular rayleigh - bnard & @xmath5 & & @xmath6 & & @xmath7 & @xmath8 & @xcite + annular rayleigh - bnard & @xmath9 & & @xmath6 & @xmath6 & @xmath10 & @xmath11 & @xcite + linear rayleigh - bnard & @xmath12 & @xmath13 & @xmath14 & @xmath14 & @xmath15 & @xmath16 & @xcite + interface roughening & & & & & & @xcite + viscous fingering & @xmath17 & @xmath18 & & & @xmath19 & @xmath20 & @xcite + vortices of fluid & @xmath21 & @xmath6 & & & & @xmath22 & @xcite + taylor - deen & @xmath23 & @xmath24 & @xmath25 & @xmath26 & @xmath27 & @xmath28 & @xcite + taylor - couette & @xmath29 & @xmath30 & @xmath31 & & @xmath32-@xmath33 & & @xcite + granular flow & & & & & & @xcite + torsional couette & & @xmath34 & @xmath35 & & & & @xcite + ferrofluidic spikes & @xmath36 & @xmath13 & @xmath37 & @xmath38 & @xmath39 & @xmath40 & @xcite + lateral heat convection in annulus & @xmath41 & @xmath42 & @xmath43 & @xmath44 & & & @xcite + dp & & @xmath45 & @xmath46 & @xmath47 & @xmath48 & @xmath49 & @xcite + & & & & & + ( 2 + 1)d system & size & @xmath0 & @xmath1 & @xmath2 & @xmath3 & @xmath4 & refs . + liquid columns & @xmath50 & @xmath51 & & & & & @xcite + dsm1-dsm2 ( present paper ) & @xmath52 & @xmath53 & @xmath54 & @xmath55 & @xmath56 & @xmath57 & + dp & & @xmath58 & @xmath59 & @xmath60 & @xmath61 & @xmath62 & @xcite + the paper is organized as follows . we first illustrate the coarse - grained dynamics of the turbulent regime of electroconvection studied and our basic experimental setup ( sec . [ sec : setup ] ) , with further details on image analysis given in the appendix . to characterize the critical behavior , we perform three series of experiments : ( a ) steady - state experiment under constant applied voltages ( sec . [ sec : steadystate ] ) , ( b ) critical - quench experiment starting from fully active initial conditions ( sec . [ sec : criticalquench ] ) , and ( c ) critical - spreading experiment starting from a single active seed , prepared with a novel experimental technique using pulse laser , developed in this work ( sec . [ sec : criticalspreading ] ) . in sec . [ sec : summary ] , our results are summarized and we discuss why clear dp - class critical behavior is observed rather easily in our system , contrary to many other experiments performed in the past in this context . we work on the electrohydrodynamic convection of nematic liquid crystals , which occurs when a thin layer of liquid crystal is subjected to an external voltage strong enough to trigger the carr - helfrich instability @xcite . this is _ a priori _ a suitable system to study critical behavior thanks to its possibly large aspect ratio , fast response time , and easy controllability . we focus on the transition between two turbulent regimes , called dynamic scattering modes 1 and 2 ( dsm1 and dsm2 ) , observed successively upon increasing the root - mean - square amplitude of the voltage @xmath63 at relatively low frequencies @xcite . the difference between dsm1 and dsm2 lies in their density of topological defects in the director field [ fig . [ fig : dsm1dsm2](a ) ] . in the dsm2 state , a large quantity of these defects , called disclinations , are present @xcite . they elongate and split constantly under the shear due to the fluctuating turbulent flow around . in dsm1 , on the other hand , disclinations are present but kept smaller than the critical size and disappear immediately . their density thus remains very low . the many disclinations in dsm2 lead to the loss of macroscopic nematic anisotropy and to a lower light transmittance than in dsm1 . our basic experimental setup is shown in fig . [ fig : setup ] . the sample cell is made of two parallel glass plates spaced by a polyester film of thickness @xmath64 . both inner surfaces are covered with transparent electrodes of size @xmath65 , coated with polyvinyl alcohol and then rubbed in order that molecules are planarly aligned in the @xmath66 direction , defined thereby . the cell is filled with @xmath67-(4-methoxybenzylidene)-4-butylaniline ( mbba ; purity @xmath68 , tokyo chemical industry ) doped with 0.01 wt.% of tetra-@xmath69-butylammonium bromide . the temperature of the cell is kept constant carefully by a handmade thermocontroller , composed of heating wires and peltier elements controlled by a proportional - integral - derivative feedback loop with a lock - in amplifier [ fig . [ fig : setup](b ) ] . windows of the thermocontroller are made of sapphire in order to improve the spatial homogeneity of the temperature . throughout each series of experiments , the cell temperature is maintained at @xmath70 with fluctuations typically of a few @xmath71 , unless otherwise stipulated , measured by three thermistors placed at different positions close to the cell . we observe the electroconvection through the transmitted light from a handmade stabilized light source made of light - emitting diodes , recorded by a charge - coupled device camera . the observed region is a central rectangle of size @xmath72 ( fig . [ fig : setup ] , inset ) . since there is a minimum linear size of dsm2 domains , @xmath73 @xcite , we can roughly estimate the number of effective degrees of freedom at @xmath74 for the convection area and @xmath75 for the observation area . note that the meaningful figure is that of the total system size , which is at least four orders of magnitude larger than in earlier experimental studies ( table [ tbl : earlierexperiments ] ) . in the following , we vary @xmath63 and fix the frequency at @xmath76 , at roughly one third of the cutoff frequency @xmath77 which separates the conducting and the dielectric regimes of electroconvection @xcite . disclinations being topological defects , the spontaneous nucleation of dsm2 in a dsm1 domain is in principle forbidden . it is indeed an essentially unobservable rare event , except along the edges of the electrode and for very high voltages , far from the range investigated in the present paper . therefore , the fully dsm1 state serves as an absorbing state . on the other hand , dsm2 domains introduced externally , or present initially in the system can remain sustained in the bulk for large enough voltages , but eventually disappear for voltages lower than a certain threshold @xmath78 . closely above @xmath78 , a regime of spatiotemporal intermittency ( sti ) is observed , with dsm2 patches moving around on a dsm1 background [ fig . [ fig : dsm1dsm2](b ) , and movie s1 of ref . the basic dynamics of the observed sti is illustrated in fig . [ fig : dsm1dsm2](d ) : active dsm2 patches evolve in space - time essentially by contamination of neighboring inactive ( absorbing ) dsm1 regions and by relaxation into the dsm1 state . this suggests an absorbing phase transition induced by change in rates of both elementary processes @xcite , which are functions of the applied voltage here . the order parameter @xmath79 is then simply the ratio of the surface occupied by active dsm2 regions to the whole area . prior to any analysis , we must distinguish dsm2 domains from dsm1 . this binary reduction can be easily performed by our eyes , so we automated it , based on the facts that dsm2 domains have lower transmittance , longer time correlations , and have a minimum area of @xmath80 @xcite ( see appendix for details ) . a typical result is shown in fig . [ fig : dsm1dsm2](c ) , and in movie s2 of ref . figure [ fig : dsm1dsm2](e ) displays spatiotemporal diagrams obtained this way , showing how dsm2 patches evolve in the steady state . this supports the qualitative dynamics illustrated in fig . [ fig : dsm1dsm2](d ) and indeed looks like the directed percolation of , say , water in a porous medium under gravitational field . we first observe sti in the steady state under constant voltage @xmath63 , in the range of @xmath81 . the voltage for the onset of steady roll convection ( williams domain ) is @xmath82 . spatiotemporal distributions of dsm2 patches are recorded over the period @xmath83 , which is longer than @xmath84 correlation times defined from the fluctuations of the order parameter @xmath85 . as a function of @xmath63 in the steady state . inset : same data in logarithmic scales . errorbars indicate the standard deviation of fluctuations in @xmath85 and @xmath63 . blue dashed lines are fitting curves . ] figure [ fig : steadystaterho ] shows the time - averaged order parameter @xmath86 , i.e. , the average fraction of dsm2 . it shows that the transition is continuous and that @xmath86 scales algebraically near the critical point . fitting these data with the usual scaling form @xcite @xmath87 the critical voltage @xmath78 and the critical exponent @xmath0 are found to be @xmath88 where the numbers in parentheses indicate the range of errors in the last digits @xcite . our estimate @xmath89 is in good agreement with the value for @xmath90-dimensional dp , @xmath91 @xcite . we then measure the distributions of the sizes @xmath92 and durations @xmath93 of inactive ( dsm1 ) regions , or intervals between two neighboring active ( dsm2 ) patches . histograms are made separately for each spatial direction , @xmath94 and @xmath95 , to take account of the anisotropy of dsm1 @xcite . care is also taken to compensate missing intervals due to the finite observation window : since an interval of size @xmath92 may not be captured within a frame of size @xmath96 , i.e. , either edge of the interval may not be in the frame , with probability @xmath97 , the unbiased distributions @xmath98 are estimated from the observed ones by @xmath99 @xcite . the results are shown in fig . [ fig : steadystatedsm1dist ] . we find that the dsm1 distributions decay algebraically within the observed length / time scale for voltages very close to criticality , while for higher voltages they start to decay exponentially from certain characteristic length / time scales , as expected for continuous absorbing phase transitions @xcite . the observed power - law decays are fitted as @xmath100 and @xmath101 with @xmath102 where @xmath103 and @xmath104 indicate the exponent @xmath3 measured in the @xmath66 and @xmath105 direction , respectively . these exponents are directly connected to the fractal dimensions @xmath106 of the dsm2 clusters measured in the corresponding direction as @xmath107 . the critical exponents @xmath3 and @xmath4 for dp can be estimated using scaling relations with the order parameter exponent @xmath0 and the correlation length / time exponents @xmath1 and @xmath2 , namely @xcite , @xmath108 they give @xmath109 and @xmath110 for @xmath90 dimensions @xcite . although the existence of slight discrepancies of order @xmath111 in eq . is suggested from numerical studies @xcite , our estimates in eq . agree with values expected for the dp class at any rate . moreover , the dsm1 distributions allow estimating correlation length and time scales , @xmath112 and @xmath113 , respectively , from their exponential tails shown in fig . [ fig : steadystatedsm1dist](d - f ) . fitting distributions with an empirical form @xcite @xmath114 with powers @xmath3 and @xmath4 fixed at the estimates in eq . , we obtain the results shown in fig . [ fig : steadystatenu ] . both @xmath112 and @xmath113 show algebraic divergence @xmath115 near criticality as expected , except for the first two points in fig . [ fig : steadystatenu](c ) , which deviate from the power law presumably due to finite length of movies ( @xmath116 ) used to count the distributions . fitting eq . to the data in scaling regions ( the first five points for @xmath117 and all the points except the first two for @xmath113 ) , we obtain @xmath118 they are in good agreement with the dp values @xmath119 and @xmath120 @xcite . in addition , the facts that no significant anisotropy is found between @xmath121 and @xmath122 and that they can be even shorter than the cell depth @xmath64 [ fig . [ fig : steadystatenu](a , b ) ] suggest that distributions of dsm2 patches are practically not influenced by the anisotropy of dsm1 @xcite and by the existence of coherent roll structure of width roughly @xmath123 behind dsm1 @xcite . on the other hand , distributions of sizes of active ( dsm2 ) patches do not show any long range correlations even close to criticality [ fig . [ fig : steadystatedsm2dist](a , b ) ] . it implies that the local recession of dsm2 into dsm1 sketched in fig . [ fig : dsm1dsm2](d ) is indeed always present . the effective relaxation rate can be directly estimated , just as an inverse of the characteristic time @xmath124 from the exponential tail of the temporal dsm2 distribution , shown in fig . [ fig : steadystatedsm2dist](c ) . the characteristic time @xmath124 increases linearly with @xmath63 except for high voltages , where it is not simply determined from the dynamics of individual patches because of the saturation of the dsm2 fraction ( fig . [ fig : steadystaterho ] ) . in particular , it exhibits no sign of criticality . all these observations are consistent with , e.g. , the dynamics of the so - called contact process @xcite ( depicted in fig . [ fig : dsm1dsm2](d ) ) , a prototypical model showing a dp - class transition @xcite , indicating that such process indeed governs the coarse - grained dynamics of our sti regime in liquid crystal turbulence . similarly , the spatial distributions of dsm2 sizes yield characteristic length scales @xmath125 and @xmath126 [ fig . [ fig : steadystatedsm2dist](c ) ] . although they appear to be also dominated by the relaxation process , as suggested from an effectively constant ratio @xmath127 [ inset of fig . [ fig : steadystatedsm2dist](c ) ] , they clearly show anisotropy [ fig . [ fig : steadystatedsm2dist](c ) ] , as opposed to the correlation lengths @xmath121 and @xmath122 estimated from dsm1-size distributions [ fig . [ fig : steadystatenu](a , b ) ] . this implies that the contamination process of dsm2 is indeed driven by the anisotropic , fluctuating shear flow of surrounding dsm1 . the larger effective contamination rate in @xmath66 is in line with the fact that the turbulent structure of dsm1 remains mainly in the @xmath66-@xmath128 plane @xcite , but at odds with the global elliptic shape of growing dsm2 nuclei , longer in @xmath105 , observed for higher voltages @xcite . both would be explained if we assume that turbulent flow behind is faster and more correlated in the @xmath105 direction , but further studies are necessary on this point . a typical experiment performed usually on numerical models showing absorbing phase transitions is the critical decay of active patches from fully active initial conditions @xcite . in such critical - quench experiments , correlation length and time grow in time , and , as long as they remain much smaller than the system size , scaling estimates are free from finite - size effects . experiments are performed as follows : we first apply @xmath129 to the cell and wait until it is entirely invaded by dsm2 domains . we then suddenly decrease the applied voltage to a value in the range of @xmath130 , i.e. , near @xmath78 , and observe the time decay of activity for @xmath131 . we repeat this @xmath132 times for each @xmath63 and average the results over this ensemble . on critical quenching . ( a ) @xmath85 versus @xmath133 , for @xmath134 , @xmath135 , @xmath136 , @xmath137 from bottom left to top right . the curve for @xmath138 ( showing the longest power - law regime ) is indicated by a thick line . ( b ) same data with rescaled axes @xmath139 and @xmath140 , showing data collapsing . for @xmath78 , @xmath141 , and @xmath2 , we use values measured in the experiment [ eqs . and ] , but a collapse of similar quality is obtained also with dp - class exponent values . the dashed curve indicates the dp universal scaling function @xmath142 obtained numerically from the contact process . ] we first measure the decay of the order parameter @xmath85 after the quench [ fig . [ fig : criticalquenchrho](a ) ] . as expected , @xmath85 decays exponentially with a certain characteristic time for lower voltages , converges to a finite value for higher voltages , and in - between at @xmath143 , it decays algebraically over the whole observation time . a simple scaling ansatz implies the following functional form for @xmath85 in this case : @xmath144 where @xmath145 is the deviation from criticality and @xmath146 is a universal scaling function . from the slopes of the algebraic regimes for the three @xmath63 values closest to the threshold , we estimate @xmath147 note that @xmath78 measured here is slightly higher than in the steady - state experiments . in fact , the roll convection onset @xmath148 was also higher . we believe this is because of possible slight shift in the controlled temperature , and also of the ageing of our sample , a well known property of mbba , during the days which separated the two sets of experiments . on the other hand , no measurable shift of @xmath78 was detected during a given set of experiments . we also confirmed that @xmath78 here is consistent with a threshold roughly estimated from steady state just before the critical - quench experiments . our estimate of the critical exponent @xmath141 is again in good agreement with the dp value @xmath149 @xcite . furthermore , the scaling form of eq . implies that the time series @xmath85 for different voltages collapse on a single curve @xmath146 when @xmath140 is plotted as a function of @xmath139 . our data do collapse reasonably well [ fig . [ fig : criticalquenchrho](b ) ] , where the upper and lower branches correspond to @xmath150 and @xmath151 , respectively . it is compared and found in good agreement with the universal scaling function @xmath146 of the dp class [ dashed curve in fig . [ fig : criticalquenchrho](b ) ] , calculated numerically from the @xmath90-dimensional contact process . it shows that the decay of dsm2 patches is governed by this dp universal function , except for the very early stage where it is influenced by microscopic features of the liquid crystal , as expected . at @xmath152 , measured in the critical - quench experiments . raw data in the inset are collapsed with rescaled axes @xmath153 and @xmath154 . dashed line shows the estimated asymptotic algebraic decay . ] we also measure the autocorrelation function @xmath155 , defined as @xmath156 where @xmath157 denotes average in space and over ensembles . during the critical decaying process , @xmath155 is not a function of @xmath158 ( inset of fig . [ fig : criticalquenchageing ] ) but scaled rather by @xmath153 , a feature sometimes referred to as `` ageing '' in the literature @xcite . our data can be collapsed ( fig . [ fig : criticalquenchageing ] ) using the expected scaling form @xmath159 with @xmath160 both are in agreement with dp values @xmath161 and @xmath162 , estimated from the scaling relations @xcite @xmath163 where @xmath164 is the spatial dimension . the dynamic aspect of critical behavior can also be characterized using first - passage quantities @xcite . one of these is the local persistence probability @xmath165 , defined as the probability that the local state at a given point in space has not changed until time @xmath133 , which typically shows a power - law decay @xmath166 . the non - trivial local persistence exponent @xmath167 is known to be in general independent of usual critical exponents such as @xmath168 , and far less is known about its universality , mainly due to the fact that persistence is a quantity involving an infinite - point correlation function . in the context of dp , local persistence is measured from the probability that initially inactive `` sites '' do not become active up to time @xmath133 . ( the persistence of activity is always dominated by the local relaxation into the inactive state and shows only exponential decay , similarly to fig . [ fig : steadystatedsm2dist ] . ) initial conditions are typically set to be random in numerical studies @xcite , which is , however , impossible in this experiment at present . we therefore consider , as `` initial condition '' for the local persistence , configurations chosen at some moment @xmath169 during the critical quench and measure the persistence probability @xmath170 . in the critical - quench experiments . the initial time is @xmath171 for the main panel and @xmath172 for the inset . the applied voltages are in ascending order from top to bottom . dashed lines are guides to eye with the same slope . ] the scaling regime for the order parameter decay observed in fig . [ fig : criticalquenchrho ] starting only after times of typically @xmath30-@xmath173 , we further limit ourselves to @xmath169 values larger than this microscopic , non - universal time . typical results are shown for @xmath171 in fig . [ fig : criticalquenchpersistence ] . the local persistence probability @xmath165 is found to converge to a finite constant for @xmath174 and to decay exponentially for @xmath175 , as expected from numerical studies of absorbing phase transitions @xcite . at criticality , @xmath165 decays algebraically ( again beyond some time of the order of @xmath169 ) with @xmath176 the value of @xmath167 for @xmath90-dimensional dp is still a matter of debate , with different estimates in past numerical studies : @xmath177 @xcite , @xmath178 @xcite , and very recently @xmath179 , found with an improved algorithm @xcite . our value , which is rather robust with respect to changing the initial conditions and the initial time ( fig . [ fig : criticalquenchpersistence ] ) , is in agreement with all numerical estimates to our accuracy . in order to complete the characterization of the dynamic critical behavior of the dsm1-dsm2 transition , we performed critical spreading experiments , which start from a single seed of active , dsm2 region . this allows to measure other critical exponents , such as the one governing the scaling of the probability @xmath180 that a cluster starting from a single active seed survives forever : @xmath181 , known to serve as another order parameter characterizing absorbing phase transitions @xcite . the two exponents @xmath0 and @xmath182 are known to be equal to each other for the dp class , thanks to an extra symmetry linked to time - reversal , the so - called rapidity symmetry @xcite . this symmetry also implies that @xmath183 where @xmath184 is defined from the time decay of the survival probability at threshold , @xmath185 . we stress , however , that the rapidity symmetry and the resulting scaling relations do not hold generically in absorbing phase transitions . although a value of @xmath182 consistent with dp was suggested from the critical scaling of hysteresis loops in the dsm1-dsm2 transition @xcite , it remains important to assess all spreading exponents as accurately and independently as possible , in order to complete our characterization of dp - class critical behavior and check directly the rapidity symmetry . in contrast to numerical simulations , it is not easy , in experiments , to prepare an initial , single , localized seed of dsm2 in an otherwise homogeneous dsm1 system . we developed an experimental technique for nucleating a dsm2 patch artificially , using a pulse laser . of the molecules ( squares and circles , respectively ) . error bars denote the @xmath186 confidence intervals assuming the binomial distribution . ( inset ) typical spatiotemporal diagram of nucleated dsm2 cluster for @xmath187 . scales are @xmath188 in space and @xmath189 in time . ] the experimental setup for the critical - spreading experiments is schematically shown in fig . [ fig : expsetupspreading ] . we emit @xmath190-@xmath191 pulses of nd : yag laser ( minilase ii 20hz , new wave research ) , focused by an objective lens ( @xmath192 , na @xmath193 , uplanfln , olympus ) , into the cell . using its third harmonic at @xmath194 , around which mbba has a broad absorption band @xcite , and reducing its energy to roughly @xmath195 at the cell , we can indeed nucleate dsm2 from the absorbing dsm1 state ( inset of fig . [ fig : dsm2nucleation ] ) without any observable damage to the sample . figure [ fig : dsm2nucleation ] shows the probability of the dsm2 nucleation induced by emitting five successive laser pulses at @xmath196 . the nucleation probability increases with voltage and is significantly higher for laser polarized along the mean director field . this confirms that nucleation is indeed brought about by the laser absorption of mbba , since its absorbance is higher along the long axis of the molecule @xcite . moreover , the electronic structure of mbba reveals that the ultraviolet absorption band stems from the c n and c c bonds between the aniline and benzyliden rings and is strongly coupled with twist angles there @xcite . we therefore speculate that absorption of ultraviolet laser pulses might lead to a sudden conformation change in the molecular structure , creating a topological defect and thus triggering a dsm2 nucleation . we perform the critical - spreading experiments with the technique above . for each measurement we emit ten successive pulses polarized along the molecules ( in the @xmath66 direction ) , with which dsm2 is always nucleated for voltages of interest . in order to make reliable statistics for the survival probability , it is necessary to repeat experiments at least hundreds of times for each voltage . this led us to improve further the temperature control of the cell , both in short and long time scales . this is achieved by placing the thermocontroller in a thermally - insulated chamber ( fig . [ fig : expsetupspreading ] ) , made of plastic foam stage , wall , and ceiling , whose temperature inside is kept constant by circulating constant - temperature water . the cell temperature is finally stabilized at @xmath197 with fluctuations at most @xmath198 over two weeks . this allows us to repeat the experiment @xmath199-@xmath200 times for each voltage in the range of @xmath201 . the roll convection onset and the critical voltage roughly measured in steady state were @xmath202 and @xmath203 , respectively . we measure not only the survival probability @xmath204 but also the volume @xmath205 and the mean square radius @xmath206 of dsm2 clusters , averaged over all the repetitions , even if the cluster dies before time @xmath133 . the following relations are then expected from the scaling ansatz @xcite : @xmath207 where @xmath208 are universal scaling functions . the experimental results are shown in fig . [ fig : criticalspreadingresults ] . except for @xmath206 where all the data are almost overlapping , which is also typically the case in simulations of dp - class models , the data show opposite curvatures below and above a certain voltage . seeking for the curve with the longest algebraic regime in @xmath205 , which is statistically most reliable , we locate the critical voltage @xmath78 at @xmath209 we then measure the three critical exponents @xmath210 from the algebraic regime for three voltages around @xmath78 , yielding @xmath211 all of them are in good agreement with the dp exponents , @xmath212 , and @xmath213 @xcite . this confirms the scaling relations expressing the rapidity symmetry . it is further confirmed by plotting the ratio of the survival probability @xmath204 to the dsm2 fraction @xmath85 in the critical - quench experiments [ inset of fig . [ fig : criticalspreadingresults](a ) ] , which shows that the two order parameters become asymptotically proportional to each other @xmath214 with the coefficient @xmath215 . we also tested data collapse [ fig . [ fig : criticalspreadingresults](d - f ) ] , which provides reasonable results given the limited statistical accuracy of the data . the obtained scaling functions coincide satisfactorily with those of the @xmath90-dimensional contact process [ dashed curves in fig . [ fig : criticalspreadingresults](d - f ) ] . as in the data collapse of @xmath85 [ fig . [ fig : criticalquenchrho](b ) ] , the collapsed data show typical time scales above which the corresponding quantities are governed by the dp scaling functions . we have performed three series of experiments , namely , steady - state experiments , critical - quench experiments , and critical - spreading experiments , to characterize the critical behavior of the dsm1-dsm2 transition in liquid crystal turbulence . table [ tbl : summaryexponents ] summarizes the main results . we have measured in total 12 critical exponents with reasonable accuracy , typically over a few orders of magnitude of power - law regimes . all of the measured exponent values agree within a few percent with those defining the dp universality class . given that most of them are theoretically linked through scaling relations , we can equivalently say that we have experimentally confirmed those scaling relations , 8 in total , that connect the measured exponents ( table [ tbl : summaryscalingrelations ] ) . among them , we have confirmed in particular the rapidity symmetry @xmath183 , providing also the asymptotic amplitude of the ratio between the two order parameters , @xmath215 . moreover , we have also tested the expected scaling forms of eqs . , , - through data collapse , and found them in good agreement with numerically - obtained dp universal scaling functions . based on all these results , we conclude that the dsm1-dsm2 transition constitutes an unambiguous experimental realization of an absorbing phase transition in the dp universality class . ? = ? .summary of the measured critical exponents [ cols="<,<,<,<,<",options="header " , ] we now return to our initial remark concerning the surprising scarcity of experimental realizations of dp - class transitions ( table [ tbl : earlierexperiments ] ) . one central difficulty lies in the necessity to avoid , as much as possible , quenched disorder , which is known to be relevant . it is theoretically known that such disorder does affect dp criticality and even destroys it for strong disorder @xcite . recent theoretical and numerical studies show that even weak disorder changes the asymptotic critical behavior @xcite , but the characteristic length / time scale separating dp and disordered , so - called `` activated '' critical behavior grows fast with decreasing strength of disorder @xcite . it is therefore important to work with systems made of macroscopic units , where quenched disorder is expected to be negligible . we consider that the quenched disorder in our system , which may take the form of inhomogeneities in the electrodes or impurities in the sample , is also sufficiently weak . still , our dsm1-dsm2 transition seems to be the only fully convincing one . three factors explain , in our view , why our experiments provided such clear dp scaling laws . \(a ) _ large system size and fast response_. as already mentioned , one great advantage to work with electroconvection is that very large aspect ratios can easily be realized . the number of effective degrees of freedom of our cell is @xmath52 , which is orders of magnitude larger than any earlier experiment ( table [ tbl : earlierexperiments ] ) . this considerably suppresses finite - size effects and allows to observe scaling on several orders of magnitude . similarly , the typical microscopic timescales of liquid crystals are very short ( of the order of @xmath216 ) , providing accurate statistics in reasonable laboratory time . \(b ) _ almost perfectly absorbing state_. the condition for being an absorbing state , i.e. , that the system can _ never _ escape once it entered , appears to be somewhat too strict from the experimental point of view . indeed , spontaneous nucleation of the active state seems to have been present at least in some of the past experiments @xcite , which blurs the critical behavior beyond some finite scales . on the other hand , our active state , dsm2 , consists of topological defects , whose spontaneous formation is in principle forbidden . of course this may occur in practice , as suggested from the observation of vanishing hysteresis at the dsm1-dsm2 transition @xcite , but the nucleation rate remains so low that we can not directly observe it , constituting an almost perfectly absorbing state . ( c ) _ fluctuating absorbing state_. in most earlier experiments and numerical studies , the absorbing state has been essentially fluctuation - free , or laminar . this is indeed a natural choice suggested from the minimal theory of dp , and causes of course no problem in numerical studies . in experiments , however , such absorbing states may typically cause long - range effects through the rigidity of their laminar pattern and/or the propagation of soliton - like objects , which may further reduce the effective system size and even break dp scaling @xcite . in contrast , our absorbing state , dsm1 , is itself a fluctuating , turbulent state . long - range interactions are then likely to be killed by the local turbulent fluctuations of dsm1 , which may have led to the observation of clean dp critical behavior . it is noteworthy to remark that the chat - manneville coupled map lattice @xcite , a deterministic numerical model for absorbing phase transitions with a non - chaotic ( laminar ) absorbing state , exhibits non - dp critical behavior probably due to soliton - like objects propagating through laminar regions . interestingly , an elementary modification to render its absorbing state itself chaotic does lead to dp scaling @xcite . in conclusion , we have experimentally found that the dsm1-dsm2 transition in the electroconvection of nematic liquid crystals , showing an absorbing transition into spatiotemporal intermittency , clearly belongs to the dp universality class . both static and dynamic critical behavior has been investigated with the help of the newly developed experimental technique to create a seed of dsm2 , confirming a total of 12 critical exponents , 5 scaling functions , 8 scaling relations , and in particular the rapidity symmetry , in full agreement with those characterizing the dp class in @xmath217 dimensions . we hope that this first clear and comprehensive experimental realization of a dp - class transition will trigger further studies of absorbing phase transitions and of related situations with genuinely non - equilibrium critical properties . in this respect the recent works of cort _ et al . _ @xcite and of mangan _ et al . _ @xcite are especially encouraging , concerning experiments and realistic situations , respectively , for absorbing transitions with a conserved field . the authors are grateful to i. dornic , f. ginelli , j. a. hoyos , s. kai , and n. oikawa for fruitful discussions . we would also like to thank m. henkel and g. i. menon for drawing our attention to ageing and ref . @xcite and to local persistence , respectively . this work is supported in part by grant - in - aid for scientific research ( 18068005 ) and for jsps fellows . every analysis presented in the paper is performed using binarized images , where dsm2 domains are distinguished from the absorbing dsm1 background . we give here a detailed description of the binarizing algorithm we used . the binarization is carried out in the following manner : ( a ) we prepare three successive images taken at 15 frames per second , and remove the inhomogeneity of the incident light intensity . ( b ) we then normalize the obtained intensity @xmath218 of the three images with respect to mean @xmath219 and standard deviation @xmath220 of the dsm1 intensity at a given voltage , namely @xmath221 . note that we can separately measure the intensity of the fully dsm1 state even above the threshold @xmath78 , since dsm1 always appears first when the voltage is applied . ( c ) since dsm2 domains have lower transmittance than dsm1 , we extract the regions where the normalized intensity is less than a certain threshold @xmath222 . here we chose @xmath223 , determined so as to obtain a good agreement with direct visual observations , particularly in movies . ( d ) taking into consideration that dsm2 domains move much slower than the local intensity fluctuations in dsm1 ( recall that dsm1 is itself a turbulent state ) and that the minimum dsm2 area is @xmath80 @xcite , where @xmath123 is the depth of the cell , we take the logical intersection ( `` and '' operator ) of the three successive images , and then remove clusters with area smaller than @xmath80 . clusters are screened out in this way , and their binarized images in the middle frame are used as final images . in other words , the intersection is used only for comparison with the minimum area . ( e ) finally , we cut off the periphery of the image of width @xmath224 , since this region is biased in the step ( d ) . the size of the binarized images reduces to @xmath225 , which roughly corresponds to @xmath226 effective degrees of freedom . we confirmed that the chosen threshold ( @xmath223 ) works well all over the range of voltages we investigate , and that no dsm2 region is falsely detected when binarizing images of the fully dsm1 phase . typical results of the binarization are shown in fig . [ fig : dsm1dsm2](c ) and ( e ) , and movie s2 of ref . @xcite , where we can confirm that dsm2 domains are precisely detected . for the critical - spreading experiments presented in sec . [ sec : criticalspreading ] , we have slightly modified the binarization algorithm in order to detect dsm2 patches originating only from the prepared seed , and not to miss them . to this end , we have reduced the intensity threshold @xmath227 to @xmath228 , and instead , binarized only within a target region , defined from positions of dsm2 patches in previous images ( position of the seed for the first image ) and assumed maximal displacement of dsm2 , which is chosen to be much larger than the actual displacement , namely , @xmath123 during successive two images taken at @xmath229 fps and extrapolated diffusively . we again confirmed that binarized images from a single set of parameters closely follow the actual evolution of dsm2 patches for all the voltages of interest . a typical result is shown in the inset of fig . [ fig : dsm2nucleation ] . the deviation from criticality is measured in terms of @xmath230 instead of @xmath63 by convention , since the dielectric torque that drives the electroconvection is proportional to @xmath230 @xcite . the results do not change if @xmath231 is used . confidence intervals of the critical exponents given in the present paper are determined as follows . ( a ) for values estimated from a finite number of independent data points [ eqs . and ] , @xmath186 confidence intervals in the sense of student s t are provided . ( b ) for values estimated from a continuous curve [ eqs . , , , , ] , range of fitting is varied within reasonable regions , and both the dependence on fitting regions and the confidence interval from each fitting are incorporated in the final estimate of error . when the threshold is simultaneously determined [ eqs . and ] , uncertainty in the estimate of the threshold is also considered . ( c ) for values determined from data collapsing [ eq . ] , we provide the range of values of the exponent with which no systematic shift in data collapsing is seen . ( d ) for values derived from an equation , the range of error is estimated by the law of propagation of error . ( e ) for values cited from literature , we simply borrow the range of errors provided by the corresponding authors . this correction was not made in ref . although algebraic decays in the distributions are not much influenced , this correction is significant to have exponential decays in sufficiently large scales to estimate the correlation length and time .

this is a comprehensive report on the phase transition between two turbulent states of electroconvection in nematic liquid crystals , which was recently found by the authors to be in the directed percolation ( dp ) universality class [ k. a. takeuchi _ et al . _ , phys . rev . lett . * 99 * , 234503 ( 2007 ) ] . we further investigate both static and dynamic critical behavior of this phase transition , measuring a total of 12 critical exponents , 5 scaling functions , and 8 scaling relations , all in full agreement with those characterizing the dp class in 2 + 1 dimensions . developing an experimental technique to create a seed of topological - defect turbulence by pulse laser , we confirm in particular the rapidity symmetry , which is a basic but nontrivial consequence of the field - theoretic approach to dp . this provides the first clear experimental realization of this outstanding , truly out - of - equilibrium universality class , dominating most phase transitions into an absorbing state .

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The radio personality and reporter Emmanuel Dzotsi spent a year working on the forthcoming season, for which they were given permission to record inside courtrooms, judges’ chambers, back hallways, and attorneys’ offices. The show will take listeners through the sometimes unsettling ways in which crimes are investigated and tried. “Every case Emmanuel and I followed, there came a point where we thought: No, this can’t be how it works,” said Koenig in a press release. “And then we were like, Oh! Oh my god. This is how it works! This is how it happens! People who work in the system, or have been through the system, they know this. But millions more people do not. And for the past year I’ve had this urgent feeling of wanting to kind of hold open the courthouse door, and wave people inside. Because things are happening — shocking things, fascinating things — in plain sight.” The first two episodes will debut on Sep 20, with each additional episode premiering weekly on Thursdays. Several stories will be highlighted over the course of the season, with some being wrapped into a single episode and others unveiled over multiple installments. Serial is heading back to court—this time, in Cleveland. Season Three, coming September 20. https://t.co/0O60tPrtxS — Serial (@serial) September 5, 2018 Get a sneak peek of the new season at the link above. Listeners can hear Serial for free via podcast apps such as Apple Podcasts, Google Podcasts, and Pandora. ||||| The team behind podcast hit “Serial” are premiering the latest season of the investigative series — digging into the inner workings of Cleveland’s criminal-court system — later this month. The first two episodes of “Serial” season 3 will debut Sept. 20, with subsequent episodes to be released weekly on Thursdays. Instead of telling a single story over the course of the show, as the first two seasons did, the third run will follow many different stories with some spanning two or even three episodes. When “Serial” first launched in 2014, the spinoff of NPR’s “This American Life” became an overnight podcasting success. In the first season, Sarah Koenig narrated an investigation into the 2000 conviction of Adnan Syed for the murder of his girlfriend, Hae Min Lee, in Baltimore. (The show led to a judge’s ruling granting Syed a retrial, which remains pending.) Season 2 of “Serial” documented the story of Bowe Bergdahl, a U.S. soldier who was captured by the Taliban. The first two seasons of “Serial” have been downloaded more than 340 million times. Now, with season 3, “Serial” tells the stories of ordinary cases as they wind through the justice system in Cleveland. Producers said they chose Cleveland because they were given an unusual level of access to record inside courtrooms, judges’ chambers, hallways and attorneys’ offices. For the latest season, Koenig and reporter Emmanuel Dzotsi — an Ohio native and former “This American Life” fellow — spent more than a year in the city, looking at small criminal cases like marijuana possession and disorderly conduct and more serious ones including felonies. The duo say they documented various manipulations, distortions and justifications that they say produced a disparity between what people did and what they were punished for. Related 'Serial' Podcast Exposes Epic Dysfunction in Cleveland’s Criminal Justice System YouTube Stars Alisha Marie, Remi Cruz Launch Dishy New Podcast (EXCLUSIVE) The show comes from Serial Productions, formed by the podcast’s original producers in 2017, and is partnered with “This American Life,” which is produced in collaboration with Chicago Public Media. The executive producer of “Serial” is Julie Snyder, who also created the company’s “S-Town” podcast with Brian Reed that launched last year. “Every case Emmanuel and I followed, there came a point where we thought: ‘No, this can’t be how it works,’” Koenig said in a prepared statement. “People who work in the system, or have been through the system, they know this. But millions more people do not. And for the past year I’ve had this urgent feeling of wanting to kind of hold open the courthouse door and wave people inside. Because things are happening — shocking things, fascinating things — in plain sight.” Ira Glass, host of “This American Life” who serves as an editor for “Serial,” commented that even the early drafts of season 3 left him with “this dumbass, fanboy ‘OMG it’s ‘Serial’! feeling” that reflected Koenig’s “deeply ‘Serial’-ish, super-methodical, annoyingly well-reasoned investigation into the deeper truths that underlie all the stories.” “Serial” season 3 will be available as a free download via apps including Apple Podcasts and Google Podcasts, and also will be available free on Pandora via an exclusive streaming partnership. After subscribing, listeners will automatically receive all episodes as they are released. The new season is exclusively sponsored by jobs site ZipRecruiter. The third season of “Serial” is expected to be around 10 episodes, but that’s subject to change. Listen to the audio trailer for season 3 at serialpodcast.org. Pictured above: Emmanuel Dzotsi (l.) and Sarah Koenig

– Serial is taking on the criminal courts. Breaking from its format for the first two seasons of focusing on a single story, the investigative podcast will follow several cases from inside the Cleveland criminal court system for its third season, per Entertainment Weekly. Some stories will be wrapped up in one episode while others will span multiple episodes. "For the past year I've had this urgent feeling of wanting to kind of hold open the courthouse door, and wave people inside. Because things are happening—shocking things, fascinating things—in plain sight," says host Sarah Koenig, who joins reporter Emmanuel Dzotsi on the trip inside courtrooms, judges' chambers, and attorneys' offices. The first two of 10 expected episodes are out Sept. 20, per Variety.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Access to Competitive Power Act of 2007''. SEC. 2. ESTABLISHMENT OF EQUAL ACCESS AND TREATMENT WITH RESPECT TO FEDERAL POWER RESOURCES. Section 212(i) of the Federal Power Act (16 U.S.C. 824k(i)) is amended-- (1) by redesignating paragraphs (2) through (5) as paragraphs (3) through (6), respectively; (2) by striking the subsection designation and heading and all that follows through the end of paragraph (1) and inserting the following: ``(i) Establishment of Equal Access and Treatment With Respect to Federal Power Resources.-- ``(1) Definition of generator.--In this subsection, the term `generator' means-- ``(A) the Bonneville Power Administration; ``(B) the Southeastern Power Administration; ``(C) the Western Area Power Administration; ``(D) the Southwestern Power Administration; and ``(E) the Tennessee Valley Authority. ``(2) Authority and duties of commission.-- ``(A) In general.--Pursuant to sections 210, 211, and 213, the Commission-- ``(i) may order the administrator or board of directors, as applicable, of any generator to provide transmission service, including by establishing the terms and conditions of the service; and ``(ii) shall ensure that-- ``(I) the provisions of otherwise applicable Federal laws shall continue in full force and effect and shall continue to be applicable to the system; ``(II) the rates for the transmission of electric power on the system of each Federal power marketing agency-- ``(aa) are administered in accordance with applicable Federal law, other than sections 210, 211, and 213; and ``(bb) are not unjust, unreasonable, or unduly discriminatory or preferential, as determined by the Commission. ``(B) Tennessee valley authority rates.-- ``(i) In general.--Notwithstanding any other provision of law, the Commission shall have jurisdiction over the rates, terms, and conditions of the provision of transmission service in interstate commerce by the Tennessee Valley Authority. ``(ii) Tariff.--Notwithstanding any other provision of law, pursuant to sections 205 and 206, the Board of Directors of the Tennessee Valley Authority shall have on file with the Commission an open access transmission tariff that contains just, reasonable, and not unduly preferential or discriminatory rates, terms, and conditions for the provision of transmission service in interstate commerce by the Tennessee Valley Authority.''; (3) in paragraph (3) (as redesignated by paragraph (1))-- (A) by striking ``(3) Notwithstanding'' and inserting the following: ``(3) Procedure for determinations.--Notwithstanding''; (B) in the matter preceding subparagraph (A), by inserting ``of a Federal power marketing agency'' after ``service''; and (C) in subparagraph (A)-- (i) by striking ``when the Administrator of the Bonneville Power Administration either'' and inserting ``if the Administrator of any Federal power marketing agency''; and (ii) by striking ``on the Federal Columbia River Transmission System''; (4) in paragraph (4) (as redesignated by paragraph (1))-- (A) by striking ``(4) Notwithstanding'' and inserting the following: ``(4) Judicial review.--Notwithstanding''; (B) by striking ``the Administrator of the Bonneville Power Administration'' and inserting ``the Administrator of a Federal power marketing agency''; and (C) by striking ``United States Court of Appeals'' and all that follows through the end of the paragraph and inserting ``United States court of appeals of jurisdiction of the Federal power marketing agency.''; (5) in paragraph (5) (as redesignated by paragraph (1)), by striking ``(5) To the extent the Administrator of the Bonneville Power Administration'' and inserting the following: ``(5) Exception.--To the extent that an Administrator of a Federal power marketing agency''; (6) in paragraph (6) (as redesignated by paragraph (1))-- (A) by striking ``(6) The Commission'' and inserting the following: ``(6) Prohibition.--The Commission''; and (B) by striking ``the Administrator of the Bonneville Power Administration'' and inserting ``the Administrator of a Federal power marketing agency''. SEC. 3. EQUITABILITY WITHIN TERRITORY RESTRICTED ELECTRIC SYSTEMS. Section 212(j) of the Federal Power Act (16 U.S.C. 824k(j)) is amended-- (1) by striking ``With respect to'' and inserting the following: ``(1) In general.--Except as provided in paragraph (2), with respect to''; (2) by striking ``electric utility:'' and all that follows through ``electric utility.'' and inserting ``electric utility.''; and (3) by adding at the end the following: ``(2) Exception.--Paragraph (1) and subsection (f) shall not apply to any area served at retail by a distributor that-- ``(A) on October 24, 1992, served as a distributor for an electric utility described in paragraph (1); and ``(B) before December 31, 2006, provided to the Commission a notice of termination of the power supply contract between the distributor and the electric utility, regardless of whether the notice was later withdrawn or rescinded. ``(3) Stranded costs.--An electric utility described in paragraph (1) that provides transmission service pursuant to an order of the Commission or a contract may not recover any stranded cost associated with the provision of transmission services to a distributor. ``(4) Rights of distributors.-- ``(A) Notice not provided.--A distributor described in paragraph (2) that did not provide a notice described in paragraph (2)(B) by December 31, 2006, may-- ``(i) construct, own, and operate any generation facility, individually or jointly with another distributor; and ``(ii) receive from any electric utility described in paragraph (1) partial requirements services, unless the cumulative quantity of energy provided by the electric utility exceeds a ratable limit that is equal to a proxy for load growth on the electric utility, based on-- ``(I) the total quantity of energy sold by each affected agency, corporation, or unit of the electric utility during calendar year 2006; and ``(II) a 3-percent compounded annual growth rate. ``(B) Notice provided.-- ``(i) In general.--A distributor described in paragraph (2) that provided a notice described in paragraph (2)(B) by December 31, 2006, may-- ``(I) construct, own, and operate any generation facility, individually or jointly with another distributor; ``(II) receive from any electric utility described in paragraph (1) partial requirements services; ``(III) receive from any electric utility described in paragraph (1) transmission services that are sufficient to meet all electric energy requirements of the distributor, regardless of whether an applicable contract, or any portion of such a contract, has been terminated under this section; and ``(IV) not later than 180 days after the date of enactment of this paragraph, elect to rescind the notice of termination of the distributor without the imposition of a reintegration fee or any similar fee. ``(ii) Treatment.--On an election by a distributor under clause (i)(IV), the distributor shall be entitled to all rights and benefits of a distributor described in subparagraph (A). ``(5) Right to retain access to services.-- ``(A) Definitions.--In this paragraph: ``(i) Affected distributor.--The term `affected distributor' means a distributor that receives any electric service or power from at least 2 generators. ``(ii) Generator.--The term `generator' means an entity referred to in any of subparagraphs (A) through (E) of subsection (i)(1). ``(B) Retention of services.--An affected distributor may elect to retain any electric service or power provided by a generator, regardless of whether an applicable contract, or any portion of such a contract, has been terminated under this section. ``(C) Effect of notice of termination.-- ``(i) In general.--The provision or execution by an affected distributor of a notice of termination described in paragraph (2)(B) with 1 generator shall not affect the quantity of electric service or power provided to the affected distributor by another generator. ``(ii) Price.--The price of electric services or power provided to an affected distributor described in clause (i) shall be equal to the price charged by the applicable generator for the provision of similar services or power to a distributor that did not provide a notice described in paragraph (2)(B). ``(D) Transmission service.--On an election by an affected distributor under subparagraph (B) to retain an electric service or power, the affected distributor shall be entitled to receive from a generator transmission service to 1 or more delivery points of the affected distributor, as determined by the affected distributor, regardless of whether an applicable contract, or any portion of such a contract, has been terminated under this section.''. SEC. 4. STUDY OF PRIVATIZATION OF TENNESSEE VALLEY AUTHORITY. (a) Study.--The Comptroller General of the United States shall conduct a study of the costs, benefits, and other effects of privatizing the Tennessee Valley Authority. (b) Report.--Not later than 180 days after the date of enactment of this Act, the Comptroller General of the United States shall submit to Congress a report that describes the results of the study conducted under this section. SEC. 5. STUDY OF DEBT LEVEL OF TENNESSEE VALLEY AUTHORITY. (a) Study.--The Comptroller General of the United States shall conduct a study of the financial structure of, and the amount of debt held by, the Tennessee Valley Authority, which (as of February 1, 2007) is approximately $25,000,000,000. (b) Report.--Not later than 180 days after the date of enactment of this Act, the Comptroller General of the United States shall submit to Congress a report that describes the results of the study conducted under this section.

Access to Competitive Power Act of 2007 - Amends the Federal Power Act to authorize the Federal Energy Regulatory Commission (FERC) to order transmission service by the administrator or board of directors of the Bonneville, Southeastern, Western Area, and Southwestern Power Administrations, and the Tennessee Valley Authority (TVA). Grants FERC jurisdiction over the rates, terms, and conditions of TVA's provision of transmission service in interstate commerce. Requires the TVA Board of Directors to file with FERC an open access transmission tariff containing just, reasonable, and not unduly preferential or discriminatory rates, terms, and conditions. Prohibits certain territory-restricted electric utilities from recovering stranded costs associated with the provision of transmission services to a distributor. Authorizes distributors which, by December 31, 2006, gave notice of termination of a power supply contract with a territory-restricted electric utility (such as TVA) to negotiate partial requirements services with such utility, as well as receive sufficient transmission services. Allows such distributors also to elect to rescind a termination notice without imposition of a reintegration or similar fee. Authorizes distributors that did not give a termination notice by such date to receive partial requirements services from any such utility, subject to specified requirements. Allows a distributor receiving any electric service or power from at least two generators to elect to retain it regardless of whether an applicable contract, or portion of it, has been terminated. Directs the Comptroller General to study and report to Congress on: (1) the costs, benefits, and other effects of privatizing the TVA; and (2) the TVA's financial structure, as well as the amount of debt it holds.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Valley Forge Museum of the American Revolution Act of 1998''. SEC. 2. FINDINGS AND PURPOSE. (a) Findings.--Congress finds that-- (1)(A) Valley Forge National Historical Park, formerly a State park, was established in 1976 as a unit of the National Park System under Public Law 94-337 (16 U.S.C. 410aa et seq.); and (B) the National Park Service acquired various parcels of land and structures associated with the Park, including a visitor center, from the Commonwealth of Pennsylvania; (2) the Park maintains an extensive collection of-- (A) artifacts, books, and other items relating to the 1777-1778 winter encampment of General George Washington's Continental Army at Valley Forge; (B) artifacts of military life from the Revolutionary War era; (C) important archaeological resources; and (D) numerous structures and associated artifacts; (3) between 1982 and 1997, the National Park Service completed a general management plan, long-range interpretive plan, and strategic business plan for the Park that establish goals and priorities for management of the Park; (4) the plans-- (A) identify inadequacies in the Park's visitor center and interpretive programs; (B) call for development of a new or significantly renovated visitor center that would make the collection accessible to the public through exhibits and research facilities; and (C) call for improving the interpretation of the landscape and improving the circulation of visitors into and through the Park; (5) the Valley Forge Historical Society-- (A) was established in 1918 as a nonprofit organization to preserve and interpret for future generations the significant history and artifacts of the American Revolution in the historic setting of Valley Forge; (B) has amassed valuable holdings of artifacts, art, books, and other items relating to the 1777-1778 encampment, the American Revolution, and the American colonial era; and (C) continues to pursue additional important collections through bequests, exchanges, and acquisitions; (6)(A) as of the date of enactment of this Act, the Society's collection is housed in a facility that is inadequate to properly maintain, preserve, and display the ever-growing collection; and (B) the Society is interested in developing an up-to-date museum and education facility; (7) the Society and the National Park Service have discussed the idea of a joint museum, education facility, and visitor center that would-- (A) directly support the historical, educational, and interpretive activities and needs of the Park and such activities and needs of the Society; (B) combine 2 outstanding museum collections; and (C) provide an enhanced experience at Valley Forge for visitors, scholars, and researchers; (8) under section 1602 of the Transportation Equity Act for the 21st Century (112 Stat. 262), $3,000,000 was set aside to construct access roads and parking facilities for such a joint museum, education facility, and visitor center at Valley Forge; and (9) the Society has proposed to raise funds to construct a new museum, education facility, and visitor center on Park property that would be planned, developed, and operated jointly with the National Park Service. (b) Purpose.--The purpose of this Act is to authorize the Secretary of the Interior to enter into an agreement with the Society to construct and operate, in cooperation with the Secretary, a museum within the boundary of the Park. SEC. 3. DEFINITIONS. In this Act: (1) Agreement.--The term ``agreement'' means the agreement described in section 4(a). (2) Museum.--The term ``Museum'' means the Valley Forge Museum of the American Revolution described in section 4. (3) Park.--The term ``Park'' means Valley Forge National Historical Park. (4) Secretary.--The term ``Secretary'' means the Secretary of the Interior. (5) Society.--The term ``Society'' means the Valley Forge Historical Society. SEC. 4. VALLEY FORGE MUSEUM OF THE AMERICAN REVOLUTION. (a) Authorization.--In administering the Park, the Secretary may enter into an agreement under appropriate terms and conditions with the Society to facilitate the planning, construction, and operation of the Valley Forge Museum of the American Revolution on Federal land within the boundary of the Park. (b) Activities of Society.--The Agreement shall authorize the Society-- (1) to operate the Museum in cooperation with the Secretary; (2) to provide at the Museum, to visitors to the Park, programs and services relating to the story of Valley Forge and the American Revolution; and (3) acting as a private nonprofit organization, to engage in activities appropriate for operation of a museum, including charging fees, conducting events, and selling merchandise, tickets, and food to visitors to the Museum. (c) Activities of Secretary.--The Agreement shall authorize the Secretary to carry out at the Museum activities relating to the management of the Park, including provision of appropriate visitor information and interpretive facilities and programs relating to the Park. (d) Use of Revenues.--Revenues from the facilities and services of the Museum shall be used to offset the expenses of operation of the Museum. (e) Museum Structures.--The Agreement shall authorize the Society to occupy and use any structure constructed at the Park for the purposes of the Museum during the term specified in the Agreement and subject to the following terms and conditions: (1) Conveyance to united states.--The Society shall convey to the United States all right, title, and interest in each such structure. (2) Conditions on occupancy and use.--The right of the Society to occupy and use each such structure-- (A) shall be for the purposes of-- (i) exhibiting, preserving, and interpreting artifacts associated with the Valley Forge encampment and the impact of the encampment on the American Revolution; (ii) enhancing the experience of visitors to the Park; and (iii) conducting the activities of the Society consistent with the mission of the Society; and (B) shall not be transferred without the consent of the Secretary. (3) Other terms and conditions.--The Agreement shall include such other terms and conditions as the Secretary considers appropriate. SEC. 5. PRESERVATION AND PROTECTION. Nothing in this Act authorizes the Secretary or the Society to take any action in derogation of the preservation and protection of the values and resources of the Park.

Valley Forge Museum of the American Revolution Act of 1998 - Authorizes the Secretary of the Interior, in administering the Valley Forge National Historical Park, to enter into an agreement with the Valley Forge Historical Society to facilitate the planning, construction, and operation of the Valley Forge Museum of the American Revolution on Federal land within the boundary of the Park.

most of the endodontic failures occur due to the microorganisms which persists after the conventional treatment or due to the entry of the same through coronal leakage.1 the success of surgical endodontics is again determined by the apical seal which prevents the entry of microorganisms and the tissue fluid in the periapical region in either direction . numerous materials have been tested previously for the apical seal such as amalgam , glass ionomer cement , zinc oxide eugenol based cements,2 and mineral trioxide aggregate ( mta).3 mta has all the properties of root end filling material except its handling properties because of long setting time of 2 h 45 min and the requirement of additional moisture for activation of setting reaction.4 in this series of development , many new materials have been added and tried as root - end filling materials such as bioaggregate , ceramicrete5 and biodentine.6 biodentine is a new material based on calcium silicate technology . the powder contains dicalcium silicate , tricalcium silicate , calcium carbonate and iron oxide , and zirconium oxide filler . liquid consists of calcium chloride which is acting as accelerator and a polymer which is acting as a water reducing agent.7 due to its better handling properties with a setting time of around 45 min,7 this material can be alternatively used as a retrograde filling material . pawar et al . , successfully treated a large periapical lesion using biodentine as retrofilled material in their 18 months follow - up case there is no evidence of any study which compares the marginal adaptation of biodentine by hand manipulation . hence , this study was carried out to compare the sealing ability of biodentine as a root end filling material by two different manipulation techniques using stereomicroscopy . sixty ( n = 60 ) ( figure 1 ) extracted maxillary anterior teeth with completely formed apices and straight canals were taken for this study and were divided into two groups of 30 each for performing the study . cleaning and shaping were done using iso standardized 2% k file till 50 number apically and thereafter till 80 number coronally . between each sequential filing rc help after cleaning and shaping , paper points was used to dry the root canals and then obturated with gutta - percha by lateral compaction technique . the quality of obturation was assessed by radiographs and access cavities were sealed with composite resin restorative material after 24 h. an apical resection at 90 to the long axis of the tooth was made at 3 mm from the end of the root . root - end cavities of 3 mm were prepared with a straight fissure diamond bur . then the root end restoration was done with biodentine ( figure 2 ) by manipulating with trituration method in group i and by hand manipulation in group ii . then tooth surface were coated with nail varnish except at the apex and were allowed to dry . the specimens were then immersed in 2% methylene blue for 24 h. following this the teeth were rinsed for 15 min under distilled water . sectioning was done in mesiodistal direction and samples were observed under stereo microscope at high magnification and microleakage was evaluated in millimeters . the scores are given according to the dye penetration as follows : 0 no dye penetration ( figure 3 ) figure 3no dye penetration.1 dye penetration between 0 mm and 1 mm ( figure 4 ) figure 4dye penetration between 0 mm and 1 mm.2 dye penetration between 1 mm and 2 mm ( figure 5 ) figure 5dye penetration between 1 mm and 2 mm.3 dye penetration between 2 mm and 3 mm ( figure 6 ) . 0 no dye penetration ( figure 3 ) figure 3no dye penetration . 1 dye penetration between 0 mm and 1 mm ( figure 4 ) figure 4dye penetration between 0 mm and 1 mm . dye penetration between 0 mm and 1 mm . 2 dye penetration between 1 mm and 2 mm ( figure 5 ) figure 5dye penetration between 1 mm and 2 mm . 3 dye penetration between 2 mm and 3 mm ( figure 6 ) . figure 6dye penetration between 2 mm and 3 mm . mann whitney test was used for comparing penetration score between mechanical trituration and hand manipulation . p < 0.05 considered to be statistically significant ( table 1 and graph 1 ) . in group i , 14 samples showed no dye penetration whereas in group ii all the samples showed some amount of dye penetration . 13 samples showed 1 mm dye penetration in group i compared to only 7 samples in group ii . 16 samples showed 2 mm dye penetration in group ii compared to 3 samples in group i. none of the samples in group i showed 3 mm dye penetration . there was highly statistical significant difference observed between group i and group ii ( p < the post - surgical healing of periradicular tissues depends upon the removal of all the irritants from the area surrounding the apex and stopping the entry of the newer ones into the area . the root - end filling material serves as a barrier for the possible irritants against reentering into the periapical region . gartner and dorn9 suggested that an ideal root - end filling material should provide a three - dimensional seal to prevent leakage of microbial irritants into the periapical tissues . in addition , the material should be compatible with apical tissues , provide long - term stability and good handling properties . the selection of material depends on the physical and biological properties such as sealing ability , biocompatibility , and handling characteristics . mta is used as root - end filling material since inception and showed better sealing properties than amalgam , super ethoxybenzoic acid and vitremer irrespective of the type of root - end cavity preparation.10 - 13 although mta is showing good results as retrograde filling material , but it has certain limitations also such as long setting time and high cost.14,15 the basic constituents of biodentine is same as compare to mta . the manufacturers claim that it 's modified xpowder composition i.e. , the addition of setting accelerators and softeners , a new pre dosed capsule formulation for use in a mixing device largely improve the physical properties of the material making it more user - friendly . as there is no literature available comparing the manipulation techniques for biodentine as a root - end filling material , so we compared the sealing ability with different manipulation techniques . the results of this study showed that both ( trituration and hand manipulation ) techniques exhibited microleakage , but the extent of microleakage was significantly less in biodentine manipulated mechanically when compared to hand manipulation . this can be attributed to the fact that mechanical trituration produces a more homogenous mix as compare to manual mixing . furthermore , the water powder ratio will be altered in manual mixing resulting in non - homogenous mix . within the limits of this study , the following conclusions were drawn : more microleakage was seen when biodentine was manually manipulated as compared to machine trituration . further , studies should be conducted in order to suggest a proper powder to liquid ratio for proper hand manipulation of the material as in trituration lot of material is wasted .

background : the study was aimed to evaluate the microleakage of biodentine using two different manipulation methods by dye penetration.materials and methods : a total of 60 single - rooted human maxillary permanent teeth were cleaned and obturated with gutta - percha using lateral condensation method . standardized root - end cavities were prepared after apical resection . all teeth were divided randomly into two groups of 30 specimens and were filled with biodentine by trituration and hand manipulation methods . the samples were coated with varnish and immersed in 1% methylene blue dye for 72 h. then the teeth were sectioned longitudinally and observed under a stereomicroscope . the depth of dye penetration was measured in millimeters.results:there was highly statistical significant difference observed between group i and group ii ( p < 0.001 ) when dye penetration scores were compared.conclusion:more microleakage was seen when biodentine was manually manipulated as compared to machine trituration .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Veterans Educational Opportunities Enhancement Act of 2001''. SEC. 2. PERMITTING AN ELECTION TO REDUCE BASIC PAY OVER A PERIOD OF TWO YEARS. (a) In General.--The first sentence of sections 3011(b) and 3012(c) of title 38, United States Code, are each amended by striking ``$100 for each of the first 12 months'' and inserting ``$50 for each of the first 24 months''. (b) Effective Date.--The amendments made by subsection (a) shall apply to individuals who first become a member of the Armed Forces or first enter on active duty as a member of the Armed Forces on or after the date that is 90 days after the date of the enactment of this Act. SEC. 3. PERMITTING WITHDRAWAL OF ELECTION NOT TO ENROLL UNDER THE MONTGOMERY GI BILL. (a) In General.--Chapter 30 of title 38, United States Code, is amended by inserting after section 3018C the following new sections: ``Sec. 3018D. Opportunity for active-duty personnel to withdraw election not to enroll ``(a) Notwithstanding any other provision of this chapter, each qualified individual (described in subsection (b)) may withdraw an election made under section 3011(c)(1) or 3012(d)(1) of this title not to receive educational assistance under this chapter during an open period (described in subsection (c)). The qualified individual shall withdraw such election in accordance with this section and on such form as the Secretary of Defense shall prescribe for such purpose. ``(b) A qualified individual referred to in subsection (a) is an individual who meets each of the following requirements: ``(1) The individual first became a member of the Armed Forces or first entered on active duty as a member of the Armed Forces on or after the date of the enactment of this section. ``(2) The individual continues to serve, without a break in service, the period of service which, at the beginning of the open period, such individual was obligated to serve. ``(3) The individual-- ``(A) serves the obligated period of service described in paragraph (2); ``(B) before completing such obligated period of service, is discharged or released from active duty for (i) a service-connected disability, (ii) a medical condition which preexisted such service and which the Secretary determines is not service connected, (iii) hardship, or (iv) a physical or mental condition that was not characterized as a disability and did not result from the individual's own willful misconduct but did interfere with the individual's performance of duty, as determined by the Secretary of each military department in accordance with regulations prescribed by the Secretary of Defense (or by the Secretary of Transportation with respect to the Coast Guard when it is not operating as a service of the Navy); or ``(C) before completing such obligated period of service, is (i) discharged or released from active duty for the convenience of the Government after completing not less than 20 months of continuous active duty under that period of obligated service, if such period was less than three years, or 30 months of continuous active duty under that period of obligated service, if such period was at least three years, or (ii) involuntarily discharged or released from active duty for the convenience of the Government as a result of a reduction in force, as determined by the Secretary concerned in accordance with regulations prescribed by the Secretary of Defense (or by the Secretary of Transportation with respect to the Coast Guard when it is not operating as a service in the Navy). ``(4) Before applying for benefits under this section, the individual-- ``(A) completes the requirements of a secondary school diploma (or equivalency certificate); or ``(B) successfully completes (or otherwise receives academic credit for) the equivalent of 12 semester hours in a program of education leading to a standard college degree. ``(5) Upon completion of such obligated period of service, the individual-- ``(A) is discharged from service with an honorable discharge, is placed on the retired list, is transferred to the Fleet Reserve or Fleet Marine Corps Reserve, or is placed on the temporary disability retired list; ``(B) continues on active duty; or ``(C) is released from active duty for further service in a reserve component of the Armed Forces after service on active duty characterized by the Secretary concerned as honorable service. ``(c) The open period referred to in subsection (a) with respect to a qualified individual is as follows: ``(1) Subject to paragraph (2), such period is the 90-day period preceding the date of the termination of the initial obligated period of active duty required of the individual under section 3011 or 3012 of this title. ``(2) In the case of a discharge or release under subparagraph (B) or (C) of subsection (b)(3), such period is the 90-day period preceding the anticipated date of such discharge or release. ``(d)(1) Subject to the succeeding provisions of this subsection, with respect to a qualified individual who withdraws, under subsection (a), an election under section 3011(c)(1) or 3012(d)(1) of this title-- ``(A) the basic pay of the qualified individual shall be reduced (in a manner determined by the Secretary concerned) until the total amount by which such basic pay is reduced equals $1,200; or ``(B) to the extent that basic pay is not so reduced before the qualified individual's discharge or release from active duty as specified in subsection (b)(5), the Secretary concerned shall collect from the qualified individual an amount equal to the difference between $1,200 and the total amount of reductions under subparagraph (A), which shall be paid into the Treasury of the United States as miscellaneous receipts. ``(2) In the case of an individual described in clause (B) or (C) of subsection (b)(3) whose discharge or release from active duty prevents the reduction of the basic pay of such individual by $1,200, an amount less than $1,200. ``(e) With respect to qualified individuals referred to in subsection (d)(1)(B), no amount of educational assistance allowance under this chapter shall be paid to the qualified individual until the earlier of the date on which the Secretary concerned collects the applicable amount under clause (i) of such subsection. ``(f) A withdrawal under subsection (a) is irrevocable. ``(g) The Secretary concerned shall provide for notice of the opportunity under this section to withdraw an election made under section 3011(c)(1) or 3012(d)(1) of this title.''. (b) Conforming Amendments.--(1) Sections 3011(c)(1) and 3012(d)(1) of such title are each amended by striking ``Any individual'' in the third sentence and inserting ``Subject to section 3018D, any individual''. (2) Section 3017(b)(1) of such title is amended to read as follows: ``(1) the total of-- ``(A) the amount reduced from the individual's pay under section 3011(b), 3012(c), 3018(c), 3018A(b), 3018B(b), 3018C(b), 3018C(e), or 3018D(d) of this title; ``(B) the amount reduced from the individual's retired pay under section 3018C(e) or 3018D(d) of this title; ``(C) the amount collected from the individual by the Secretary under section 3018B(b), 3018C(b), 3018C(e), or 3018D(d) of this title; and ``(D) the amount of any contribution made by the individual under section 3011(e) or 3012(f) of this title, less''. (c) Clerical Amendment.--The table of sections at the beginning of chapter 30 of such title is amended by inserting after the item relating to section 3018C the following new item: ``3018D. Opportunity for active-duty personnel to withdraw election not to enroll.''. SEC. 4. OPPORTUNITY FOR CERTAIN ACTIVE-DUTY PERSONNEL TO ENROLL UNDER THE MONTGOMERY GI BILL. (a) In General.--Chapter 30 of title 38, United States Code, as amended by section 3(a), is further amended by inserting after section 3018D the following new section: ``Sec. 3018E. Opportunity for certain active-duty personnel to enroll ``(a)(1) Notwithstanding any other provision of this chapter, during the one-year period beginning on the date of the enactment of this section, a qualified individual (described in subsection (b)) may make an irrevocable election under this section to become entitled to basic educational assistance under this chapter. ``(2) The Secretary of each military department shall provide for procedures for a qualified individual to make an irrevocable election under this section in accordance with regulations prescribed by the Secretary of Defense for the purpose of carrying out this section or which the Secretary of Transportation shall provide for such purpose with respect to the Coast Guard when it is not operating as a service in the Navy. ``(b) A qualified individual referred to in subsection (a) is an individual who meets each of the following requirements: ``(1) The individual first became a member of the Armed Forces or first entered on active duty as a member of the Armed Forces before July 1, 1985. ``(2) The individual has served on active duty without a break in service since the date the individual first became such a member or first entered on active duty as such a member. ``(3) The individual is serving on active duty during the one-year period referred to in subsection (a)(1). ``(4) The individual, before applying for benefits under this section, has completed the requirements of a secondary school diploma (or equivalency certificate) or has successfully completed (or otherwise received academic credit for) the equivalent of 12 semester hours in a program of education leading to a standard college degree. ``(5) The individual, when discharged or released from active duty, is discharged or released therefrom with an honorable discharge. ``(c)(1) Subject to the succeeding provisions of this subsection, with respect to a qualified individual who makes an election under this section to become entitled to basic educational assistance under this chapter-- ``(A) the basic pay of the qualified individual shall be reduced (in a manner determined by the Secretary concerned) until the total amount by which such basic pay is reduced is $2,700; and ``(B) to the extent that basic pay is not so reduced before the qualified individual's discharge or release from active duty as specified in subsection (b)(5), at the election of the qualified individual-- ``(i) the Secretary concerned shall collect from the qualified individual; or ``(ii) the Secretary concerned shall reduce the retired or retainer pay of the qualified individual by, an amount equal to the difference between $2,700 and the total amount of reductions under subparagraph (A), which shall be paid into the Treasury of the United States as miscellaneous receipts. ``(2)(A) The Secretary concerned shall provide for an 18-month period, beginning on the date the qualified individual makes an election under this section, for the qualified individual to pay that Secretary the amount due under paragraph (1). ``(B) Nothing in subparagraph (A) shall be construed as modifying the period of eligibility for and entitlement to basic educational assistance under this chapter applicable under section 3031 of this title. ``(d) With respect to qualified individuals referred to in subsection (c)(1)(B), no amount of educational assistance allowance under this chapter shall be paid to the qualified individual until the earlier of the date on which-- ``(1) the Secretary concerned collects the applicable amount under clause (i) of such subsection; or ``(2) the retired or retainer pay of the qualified individual is first reduced under clause (ii) of such subsection. ``(e) The Secretary, in conjunction with the Secretary of Defense, shall provide for notice of the opportunity under this section to elect to become entitled to basic educational assistance under this chapter.''. (b) Conforming Amendments.--Section 3017(b)(1) of such title, as amended by section 3(b), is further amended in each of subparagraphs (A), (B), and (C)-- (1) by striking ``or'' before ``3018D(d)''; and (2) by inserting ``, or 3018E(c)'' before ``of this title''. (c) Clerical Amendment.--The table of sections at the beginning of chapter 30 of such title, as amended by section 3(c), is further amended by inserting after the item relating to section 3018D the following new item: ``3018E. Opportunity for certain active-duty personnel to enroll.''.

Veterans Educational Opportunities Enhancement Act of 2001 - Amends Federal veterans' benefits provisions to allow the basic pay reduction for entitlement to veterans educational assistance under the Montgomery GI Bill to be taken over two years (currently one year).Allows the withdrawal of an election not to receive such assistance during a specified open period for an individual who: (1) first becomes a member or enters into active service on or after the enactment of this Act; (2) continues to serve the period of obligated service without a service break; (3) before completing such period, is discharged or released from duty for a service-connected disability, a preexisting medical condition, a hardship, a physical or mental condition that did not result from the individual's own willful misconduct, or for the convenience of the Government; (4) completes the requirements of a secondary school diploma or equivalency certificate or 12 semester hours toward a standard college degree; and (5) is discharged honorably or placed on one of specified retirement lists. Provides a basic pay reduction for entitlement to such assistance.Provides an opportunity for certain active-duty military personnel who first became a member of the armed forces before July 1, 1985, to enroll for such assistance during an open period under eligibility requirements very similar to those above, and requires a similar basic pay reduction for such assistance.

this work was mostly funded by the inserm , france , the university of fribourg , switzerland , and by grants from the european community ( r - gnosis , fp7/health - f3 - 2011 - 282512 , and magic - bullet , fp7/health - f3 - 2001 - 278232 ) .

we report here the first identification of the worldwide spread of klebsiella pneumoniae carbapenemase-2-producing and carbapenem - resistant k. pneumoniae clone st258 in turkey , a country where the distantly - related carbapenemase oxa-48 is known to be endemic . worryingly , this isolate was also resistant to colistin , now considered to be the last - resort antibiotic for carbapenem - resistant isolates .

WASHINGTON (AP) — U.S. employers slowed their hiring in July, adding 157,000 jobs, a solid gain but below the healthy pace they maintained in the first half of this year. The Labor Department says the unemployment rate ticked down to 3.9 percent from 4 percent. That's near an 18-year low of 3.8 percent reached in May. Employers added an average of 224,000 new workers in the first six months of this year, a faster pace than in 2017. The pickup has impressed many economists because it's happening late in the economic expansion, which has entered its 10th year and is now the second-longest in U.S. history. The economy grew in the April-June quarter at its fastest pace in four years. Business and consumers are optimistic, suggesting solid hiring is likely to continue. ||||| Stock-market investors got another sign that inflation isn't rising so fast that the Federal Reserve will have to alter its pace of interest-rate hikes to keep the economy from overheating. The Labor Department's July jobs report showed wages grew 2.7% from a year earlier, a modest gain that economists had expected and below the 2.9% level that had spooked investors in January's report. "Wages are moving up but we're not seeing a spike in wages that would concern the market about a sudden rise in inflation," said Evan Brown, director of asset allocation at UBS Asset Management. "There's not much of a reaction in markets at the moment." S&P 500 futures are down slightly since the jobs report was released Friday morning.

– US employers slowed their hiring in July, adding 157,000 jobs, a solid gain but below the healthy pace they maintained in the first half of this year and down from expectations of 190,000 jobs. The Labor Department says the unemployment rate ticked down to 3.9% from 4%. That's near an 18-year low of 3.8% reached in May. Employers added an average of 224,000 new workers in the first six months of this year, a faster pace than in 2017, reports the AP. The pickup has impressed many economists because it's happening late in the economic expansion, which has entered its 10th year and is now the second-longest in US history. The economy grew in the April-June quarter at its fastest pace in four years. Business and consumers are optimistic, suggesting solid hiring is likely to continue. Average hourly earnings are up 0.3% to $27.05, putting the year-over-year gain at 2.7%. The Wall Street Journal characterizes wage growth as "sluggish in recent months even as the unemployment rate has fallen to the lowest level in decades."

SECTION 1. SHORT TITLE. This Act may be cited as the ``Interstate Transportation of Municipal Waste Act of 1993''. SEC. 2. INTERSTATE TRANSPORTATION OF MUNICIPAL WASTE. Subtitle D of the Solid Waste Disposal Act (42 U.S.C. 6941 et seq.) is amended by adding at the end the following new section: ``interstate transportation of municipal waste ``Sec. 4011. (a) Authority To Restrict Out-of-State Municipal Waste Imports.-- ``(1) Authority to prohibit.--(A) Except as provided in subparagraph (B), a Governor may prohibit the disposal of out- of-State municipal waste in any landfill or incinerator that is subject to the jurisdiction of the Governor. ``(B) The authority to prohibit disposal of out-of-State municipal waste shall not apply to-- ``(i) landfills in operation on the date of enactment of this section that-- ``(I) received during calendar year 1991 documented shipments of out-of-State municipal waste; and ``(II) are in compliance with all applicable Federal and State laws (including any Federal or State rule or regulation) relating to design and location standards, leachate collection, ground water monitoring, and financial assurance for closure and post- closure and corrective action; ``(ii) proposed landfills that, prior to January 1, 1993, received-- ``(I) an approval from either the affected local government or the local solid waste planning unit to receive municipal waste generated outside the jurisdiction of the affected local government, the solid waste planning unit, or the State in which the landfill is located; and ``(II) a notice of decision from the State to grant a construction permit; or ``(iii) incinerators in operation on the date of enactment of this section that-- ``(I) received, during calendar year 1991, documented shipments of out-of-State municipal waste; ``(II) are in compliance with the applicable requirements of section 129 of the Clean Air Act (42 U.S.C. 7429); and ``(III) are in compliance with all applicable Federal and State laws (including any Federal or State rule or regulation) relating to facility design, operations, and emissions. ``(2) Authority to limit.--Beginning with calendar year 1993, a Governor may-- ``(A) limit the quantity of out-of-State municipal waste received for disposal at each landfill or incinerator in the State to an annual quantity equal to the quantity of out-of-State municipal waste received for disposal at the landfill or incinerator during the calendar year 1991 or 1992, whichever is less; and ``(B) limit the disposal of out-of-State municipal waste at each landfill or incinerator in the State that received, during calendar year 1991 or 1992, documented shipments of more than 50,000 tons of out-of-State municipal waste representing more than 30 percent of all municipal waste received at the landfill or incinerator during the calendar year, by limiting the quantity of out-of-State municipal waste received for disposal at such landfill or incinerator to an annual quantity not greater than 30 percent of all municipal waste received at the landfill or incinerator during calendar year 1991 or 1992, whichever is less; ``(C) prohibit the disposal of out-of-State municipal waste in landfills that do not meet all applicable Federal and State laws (including any Federal or State rule or regulation) relating to design and location standards, leachate collection, ground water monitoring, and financial assurance for closure and post-closure and corrective action; and ``(D) prohibit the disposal of out-of-State municipal waste in incinerators that do not meet all applicable Federal and State laws (including any Federal or State rule or regulation) relating to facility design, operations, and emissions. ``(3) Authority to further limit.--Beginning with calendar year 1997, a Governor may further limit the disposal of out-of- State municipal waste as provided in paragraph (2)(B) by reducing the 30 percent annual quantity limitation to 20 percent in each of calendar years 1998 and 1999, and to 10 percent in each succeeding calendar year. ``(4) Authority with respect to industrial waste.--A Governor may exercise the authority provided in paragraphs (1), (2), and (3) with respect to any industrial waste that is to be disposed of at a landfill or incinerator that receives municipal solid waste. ``(5) Applicability and discrimination provisions.--Any limitation imposed by the Governor under paragraph (2)(A), paragraph (2)(B), or paragraph (3)-- ``(A) shall be applicable throughout the State; and ``(B) shall not discriminate against any shipments of out-of-State municipal waste on the basis of State of origin. ``(6) Determination of quantity of out-of-state municipal waste received in states exercising authority.--(A) Any Governor who intends to exercise the authority provided in this subsection shall, within 120 days after the date of enactment of this section, submit to the Administrator information documenting the quantity of out-of-State municipal waste received for disposal in the State of the Governor during calendar years 1991 and 1992. ``(B) On receipt of the information submitted pursuant to subparagraph (A), the Administrator shall notify the Governor of each State and the public and shall provide a comment period of not less than 30 days. ``(C) Not later than 180 days after the date of enactment of this section, the Administrator shall publish a list of the quantity of out-of-State municipal waste that was received during calendar years 1991 and 1992, at each landfill and incinerator in each State in which the Governor intends to exercise the authority provided in this subsection. ``(b) Authority To Restrict In-State Municipal Waste Exports.--(1) Except as provided in paragraph (2), a Governor of a State may limit or prohibit the exportation outside the State of municipal waste generated in the State, in accordance with the comprehensive waste management plan of the affected local solid waste planning unit, or, if such a plan does not exist, in accordance with State law. ``(2) A Governor may not limit or prohibit the exportation of materials consisting solely of materials that have been separated from municipal waste for recycling. ``(c) Delegation of Authority to Local Governments.--A Governor may delegate authority provided by subsection (a) or (b), or both, to an affected local government or to a local solid waste planning unit, if a local solid waste planning unit exists under State law. ``(d) Designation of Affected Local Government.--Within 90 days after the date of the enactment of this section, the Governor shall designate which entity listed in subsection (e)(1) shall serve as the affected local government for actions taken under subsections (a) and (b). If the Governor fails to make a designation, the affected local government for actions taken under this section shall be the city, town, borough, county, parish, or other political subdivision created pursuant to State law with primary jurisdiction over the land or the use of the land on which the landfill or incinerator concerned is located. ``(e) Definitions.--For purposes of this section: ``(1) The term `affected local government' means the elected officials of the city, town, borough, county, parish, or other political subdivision in which a landfill or incinerator is located. ``(2) The term `affected local solid waste planning unit' means a political subdivision of a State with authority relating to solid waste management planning in accordance with State law. ``(3) The term `out-of-State municipal waste' means, with respect to a State, municipal waste generated outside of the State. The term includes municipal waste generated outside of the United States. ``(4) The term `municipal waste' means refuse (and refuse- derived fuel) generated by the general public or from a residential, commercial, institutional, or industrial source (or any combination thereof), consisting of paper, wood, yard wastes, plastics, leather, rubber, or other combustible or noncombustible materials such as metal or glass (or any combination thereof). The term does not include-- ``(A) any solid waste identified or listed as a hazardous waste under section 3001; ``(B) any solid waste, including contaminated soil and debris, resulting from a response action taken under section 104 or 106 of the Comprehensive Environmental Response, Compensation, and Liability Act (42 U.S.C. 9604 or 9606) or a corrective action taken under this Act; ``(C) any metal, pipe, glass, plastic, paper, textile, or other material that has been separated or diverted from municipal waste and has been transported into the State for the purpose of recycling or reclamation; ``(D) any solid or industrial waste that is-- ``(i) generated by an industrial facility; and ``(ii) transported for the purpose of treatment, storage, or disposal to a facility that is owned or operated by the generator of the waste, or is located on property owned by the generator of a company with which the generator is affiliated; ``(E) any solid waste generated incident to the provision of service in interstate, intrastate, foreign, or overseas air transportation; ``(F) any medical waste that is segregated from or not mixed with municipal waste; or ``(G) any material or product returned from a dispenser or distributor to the manufacturer for credit, evaluation, or possible reuse. ``(5) The term `industrial waste' means waste generated from manufacturing or industrial processing operations that is not identical to municipal waste with respect to the physical and chemical state of the waste and the composition of the waste. The term includes construction and demolition debris.''. SEC. 3. TABLE OF CONTENTS AMENDMENT. The table of contents of the Solid Waste Disposal Act is amended by adding at the end of the items relating to subtitle D the following new item: ``Sec. 4011. Interstate transportation of municipal waste.''.

Interstate Transportation of Municipal Waste Act of 1993 - Amends the Solid Waste Disposal Act to authorize a State Governor to prohibit the disposal of out-of-State municipal waste in any landfill or incinerator in the State. Exempts from a Governor's authority to prohibit the disposal of out-of-State waste: (1) landfills that received documented shipments of such waste in 1991 and are in compliance with Federal and State laws relating to design and location standards, leachate collection, groundwater monitoring, and financial assurance for closure and post-closure and corrective action; (2) proposed landfills that, prior to January 1, 1993, received an approval from the affected local government or solid waste planning unit to receive municipal waste generated outside the jurisdiction of the local government, planning unit, or State and a State notice of decision to grant a construction permit; or (3) incinerators that received documented shipments of such waste during 1991 and are in compliance with performance standards under the Clean Air Act and Federal and State laws relating to facility design, operations, and emissions. Authorizes State Governors, beginning in 1993, to further limit the quantity of out-of-State waste received for disposal, or the disposal of such waste, at specified landfills and incinerators. Applies the authorities of this Act to industrial waste to be disposed of at landfills or incinerators that receive municipal solid waste. Prohibits discrimination against shipments of out-of-State waste on the basis of State of origin. Authorizes a State Governor to limit or prohibit the exportation outside the State of municipal waste generated within the State.

the existence of variability in the x - ray emission from active galactic nuclei ( agns ) , on time - scales of days to years , was established roughly three - decades ago ( e.g. * ? ? ? * and references therein ) . variations on time - scales shorter than this are also common . the launch of _ exosat _ , with its long orbit , meant that well - sampled x - ray light curves could be obtained for time - scales of minues to days . the power - spectra generated from _ light curves could be described by an unbroken power - law ( e.g. * ? ? ? * ; * ? ? ? archival observations spanning weeks to months showed that , for two objects , the power - law flattened at low frequencies @xcite . more recently , _ rxte _ and _ xmm - newton _ observations have shown that the power - spectra of agn light curves exhibit broken power - law shapes very similar to those seen in galactic black - hole x - ray binaries ( e.g. * ? ? ? * ; * ? ? ? * ) . as well as power - spectral density , the _ excess variance _ can be used to characterise the x - ray variability ( e.g. * ? ? ? excess variance is defined as the variance in the light curve not due to statistical fluctutations . the window function affects the excess variance less than it does the power - spectral density . therefore , the excess variance is an especially useful quantity for the description of light curves containing many gaps . an anti - correlation was found between excess variance and luminosity for a sample of agns observed by the _ advanced satellite for cosmology and astrophysics _ ( _ asca _ ) @xcite . later work using _ asca _ data found that , for a given luminosity , the x - ray light curves of narrow - line seyfert 1 ( nls1 ) galaxies exhibit a larger excess variance than broad - line seyfert 1 ( bls1 ) galaxies @xcite . this result can be explained if , for a given luminosity , the nls1s have a lower black - hole mass than the bls1s . a lower mass results in faster variations , and this is seen as a larger excess variance . alternatively , other properties of the variability , not just the time - scale , might differ between nls1s and bls1s . these alternatives can be tested through examining the dependence of the excess variance on black - hole mass . the relationship between excess variance and black - hole mass , for seyfert 1 galaxies and quasi - stellar objects ( qsos ) , has been studied using _ asca _ data ( time - scale @xmath0 d ) @xcite . these studies revealed an anti - correlation between mass and variance . moreover , the narrow - line ( nl agns ) and broad - line ( bl agns ) objects followed the same relation . this relation could be explained if the power - spectrum is an unbroken power - law [ @xmath1 with @xmath2 @xcite . an investigation using _ rxte _ data ( time - scale @xmath3 d ) presents a different picture @xcite . the bls1s , and the nls1 mcg6 - 30 - 15 , follow a variance mass relation that is consistent with a universal power - spectral shape . this ` average ' spectrum comprises a twice - broken power - law which breaks from @xmath4 to @xmath5 at the so - called ` low - frequency break ' , and from @xmath6 to @xmath7 at the ` high - frequency break ' . the break frequencies are inversely proportional to black - hole mass , and the amplitude , when represented in power@xmath8frequency space , is constant . this power - spectral shape resembles that seen in the black - hole binary cyg x-1 in the low / hard state . the other nls1 in the sample , ngc 4051 , _ did not _ follow the above relation . the excess variance of ngc 4051 was consistent with a singly - broken power - law , breaking from @xmath6 to @xmath7 , with a break frequency that is @xmath9 times higher than for bls1s . this shape is similar to that seen in cyg x-1 in the high / soft state . a power - spectral analysis of ngc 4051 , using _ rxte _ ( time - scale @xmath10 years ) and _ xmm - newton _ ( time - scale @xmath11 ks ) data , confirms that ngc 4051 is indeed an analogue to high state binaries @xcite . moreover , in plots of high - frequency break versus black - hole mass , the nls1s were found to have systematically higher break frequencies than the bls1s @xcite . the excess variance versus luminosity relation for the bls1 galaxies can be explained as a consequence of the variance - mass relation if the bls1s radiate at @xmath12 per cent of the eddington luminosity @xcite . the location of ngc 4051 in the variance - luminosity plane is consistent with that object radiating at @xmath13 per cent eddington @xcite . these results from _ rxte _ and _ xmm - newton _ suggest that the power - spectral properties of agn depend on black - hole mass _ and _ at least one other parameter . the dependence with mass is perhaps the least surprising , since we expect the size of the emission region and , therefore , the variability time - scale to scale with mass . a useful step forward , then , is to account for this mass dependence and investigate how the x - ray variability depends on other parameters . this is best achieved through maximising the sample size and minimising observational scatter . the _ asca _ satellite was launched into a 96 minute orbit on 1993 february 20 and ceased observing on 2000 july 14 @xcite . the satellite comprised four x - ray telescopes and four corresponding focal - plane instruments @xcite . there were two solid - state imaging spectrometers ( sis0 and sis1 ) @xcite and two gas imaging spectrometers ( gis2 and gis3 ) @xcite . the effective energy ranges were 0.510 kev and 0.710 kev for the sis and gis instruments , respectively . the tartarus database contains products for all _ asca _ observations with targets designated as agn @xcite . the products comprise sis and gis event files , images , spectra , and light curves . version 2 is presently available at goddard space flight centre ( gsfc ) , and consists of 529 observing sequences . we are updating and improving the database to include data collected after 1999 january . the revised database will consist of 614 sequences with a total of 375 objects . version 3 of tartarus is to be made available at gsfc and imperial college london . we are conducting a systematic timing analysis of the light curves in the tartarus database . tartarus is well suited to such a project because it contains data for a large sample of objects . the overall aim of the project is to uncover any correlations that exist between the properties of the x - ray variability and other parameters . we have begun the project by investigating those agn for which the black - hole mass has been estimated . we present here some preliminary results of an investigation between excess variance and black - hole mass . our work is similar to that conducted using _ rxte _ data as described in the previous section . .name , type and black - hole mass for each object having at least 1 valid tartarus light curve . the objects exhibiting significant variability are listed first . [ cols="<,^,^,^,^ " , ] we restricted our analysis to narrow- and broad - line agn . our sample contains seyfert 1 galaxies and qsos . we do not differentiate between seyfert galaxies and qsos , but we shall simply refer to each object as either a narrow- or broad - line agn @xcite . we used the ` rms spectrum ' @xcite reverberation - mapping mass estimate if available , otherwise we used the mass estimate determined from the optical luminosity ( e.g * ? ? ? the objects in our sample , along with their black - hole masses , are listed in table [ tab : objinfo ] . the mass measurements with no error bars were estimated via the optical luminosity . the uncertainty in these measurements is about 0.5 dex @xcite . objects with @xmath14 km s@xmath15 were classified as nl agns @xcite . the variance in a light curve is equal to the integral of the power - spectral density between the frequency limits set by the time resolution and duration of the light curve . therefore , the use of different binnings and durations per object will introduce artificial scatter . we wish to minimize this scatter . therefore , we used a time resolution of 256 s for all light curves , and restricted them to be between 30 and 40 ks in duration . a sample of measurements of the excess variance of a red - noise process will possess a large scatter about their mean ( * ? ? ? * see also the following section ) . this scatter is , of course , reduced by averaging over many realizations . therefore , in our analysis , light curves longer than 40 ks were subdivided into many shorter segments . this allowed us to maximize the number of variance measurements per object . we extracted a 210 kev combined sis0 and sis1 light curve for each object . we only used light curves comprising at least 20 bins , with each bin having no fewer than 20 counts . some light curves , having being initially extracted , contained some bins having fewer than 20 counts . in these cases , we excised bins from the light curve , on the basis of fractional exposure , so that only valid bins remained . the invalid bins could thus be removed from the light curve without introducing bias . there were 29 objects for which we had at least a single valid light curve segment . these objects are listed in table [ tab : objinfo ] . we determined the @xmath16 corresponding to the hypothesis of a constant counting rate for each segment . we then summed all of the @xmath16s and degrees - of - freedom for each object , and thereby tested whether that object exhibited variability . we detected variability in 16 objects at the 95 per cent confidence significance level ( see table [ tab : objinfo ] ) . we are yet to determine the upper limits for those objects in which variability was not detected . for the 8 objects having at least 5 measurements of excess variance , the uncertainty in the mean variance was measured from the observed scatter in those measurements . the standard deviation of the scatter about the mean was found to be @xmath17 per cent of the mean . we used this relation to assign uncertainties for the 8 objects having fewer than 5 variance measurements . a plot of log@xmath18 of the excess variance versus log@xmath18 of the black - hole mass is presented in fig . [ fig : xrt2003plot ] . the open and filled circles indicate the nl agns and bl agns , respectively . the stars indicate the masses of the 13 objects in we did not detect variability . the solid line in fig . [ fig : xrt2003plot ] shows the expected variance assuming a twice - broken power - law . we determined this using the relation found from _ _ data for bls1s @xcite , except that we also accounted for red - noise leak . the dashed lines indicate the rough range of the expected variance based on the errors from the _ rxte _ analysis . the nl agns and bl agns follow roughly the same relation . this conclusion was also reached with previous analyses of _ asca _ data @xcite . we note again that our analysis is an improvement over the previous work because we have calculated the excess variance from light curves having nearly the same length . the next step in our work is to include the gis data in our analysis to improve our signal - to - noise and increase the number of valid light curves . we will also investigate the variance mass relationship in different energy bands . most importantly , our future work will involve simulations similar to those used in modeling agn power - spectra ( e.g. * ? ? ? this will allow us to account for the sampling of the light curves and , thereby , permit a robust comparison with a hypothesised universal power spectrum . moreover , we shall quantify the extent to which the mean excess variance of each object differs from the expected variance . these residuals can then be examined against other parameters , such as mass - accretion rate . in this way , we can investigate the extent to which various parameters , other than black - hole mass , are associated with the x - ray variability . markowitz , a. , edelson , r. , vaughan , s. , uttley , p. , george , i. m. , griffiths , r. e. , kaspi , s. , lawrence , a. , mchardy , i. , nandra , k. , pounds , k. , reeves , j. , schurch , n. , and warwick , r. , _ apj _ , * 593 * , 96114 ( 2003 ) . serlemitsos , p. , jalota , l. , soong , y. , kunieda , h. , tawara , y. , tsusaka , y. , suzuki , h. , sakima , y. , yamazaki , t. , yoshioka , h. , furuzawa , a. , yamashita , k. , awaki , h. , itoh , m. , ogasaka , y. , honda , h. , and uchibori , y. , _ pasj _ , * 47 * , 105114 ( 1995 ) . gendreau , k. , _ x - ray ccds for space applications : calibration , radiation hardness , and use for measuring the spectrum of the cosmic x - ray background _ , ph.d . thesis , massachusetts institute of technology ( 1995 ) . ohashi , t. , ebisawa , k. , fukazawa , y. , hiyoshi , k. , horii , m. , ikebe , y. , ikeda , h. , inoue , h. , ishida , m. , ishisaki , y. , ishizuka , t. , kamijo , s. , kaneda , h. , kohmura , y. , makishima , k. , mihara , t. , tashiro , m. , murakami , t. , shoumura , r. , tanaka , y. , ueda , y. , taguchi , k. , tsuru , t. , and takeshima , t. , _ pasj _ , * 48 * , 157170 ( 1996 ) . turner , t. j. , nandra , k. , turcan , d. , and george , i. m. , `` tartarus - an asca agn database , '' in _ aip conf . proc . 599 : x - ray astronomy : stellar endpoints , agn , and the diffuse x - ray background _ , 2001 , pp . 991994 .

the tartarus database contains products for 529 _ asca _ observations of active galactic nuclei . we have been updating tartarus to include observing sequences conducted after 1999 january . the revised database will contain products for 375 objects , with a total of 614 observing sequences . we have begun a systematic timing analysis of the tartarus light curves . we present here some preliminary results of an investigation into the relation between excess variance and black - hole mass . having optimised our analysis to minimize the scatter in the variance measurements , we find that the narrow - line active galactic nuclei follow roughly the same relation as the broad - line objects . address = astrophysics group , imperial college london , blackett laboratory , prince consort road , london sw7 2aw , united kingdom address = astrophysics group , imperial college london , blackett laboratory , prince consort road , london sw7 2aw , united kingdom address = department of physics , university of crete , 71 003 , heraklion , greece , altaddress = iesl , forth - hellas , 71 110 , heraklion , crete , greece address = laboratory for high energy astrophysics , code 660 , nasa goddard space flight center , greenbelt , md 20771 , altaddress = university of maryland , baltimore county , 1000 hilltop circle , baltimore , md 21250

hepatitis c virus ( hcv ) is a small , hepatotropic , positive - strand rna virus with a genome of approximately 9.6 kb in length.1,2 the hcv genome consists of a single open reading frame that encodes viral proteins and a 5 and 3 noncoding region ( ncr ) . the 5 ncr contains the internal ribosome entry site that initiates the translation of the hcv genome into a single polyprotein;2 the 3 ncr is required for efficient hcv rna replication,3 as it has a specific tripartite structure : a variable region that is important for efficient rna replication ; a poly(u / uc ) tract of variable length ; and a highly conserved x tail.46 studies have demonstrated that the conserved elements in the 3 ncr , including a minimal poly(u ) tract of about 25 bases , are essential for hcv replication in cell culture and in vivo.710 although the detailed mechanisms by which the 3 ncr elements act on rna replication are not clear , it is likely that binding of one or more viral or host proteins to this rna structure is necessary to establish the replication complex.11 the open reading frame encodes a polyprotein precursor of about 3000 amino acids that is cleaved by host and viral proteases into three structural proteins ( core , e1 , and e2 ) and seven nonstructural proteins ( p7 , ns2 , ns3 , ns4a , ns4b , ns5a , and ns5b ) ( fig . 1).3,12 hcv has six major genotypes and each genotype contains numerous variants.13 each genotype has its own epidemiologic characteristics . genotype 1 is predominant in america14,15 and europe,16,17 followed by genotypes 2 and 3;18,19 and genotype 4 is the most common genotype in africa and the middle east,2022 and is often seen among immigrants or indigenous injection drug users in north america and europe.23,24 genotype 5 is mainly distributed in south africa25 and genotype 6 has been found primarily in asia.2628 hcv infection is a major cause of liver disease , with a high possibility of chronic infection . if left untreated , chronic hcv infection frequently results in progressive fibrosis , cirrhosis , and an increased risk of hepatocellular carcinoma.2 the most recent report from the world health organization estimates that about 150 million people worldwide are chronically infected with hepatitis c virus ( www.who.int ) . unfortunately , there is still no effective vaccine for hcv.29 to date , the standard of care for chronic hcv infection in most countries is combination therapy with pegylated interferon ( ifn ) and ribavirin . however , the sustained virologic response ( svr ) rate is just 4050% in patients infected with hcv genotype 1 and 80% in patients infected with hcv genotypes 2 or 3.2,30,31 since 2011 , treatment for hcv infection has been improved by adding one of the hcv nonstructural protein ns3/4a serine protease inhibitors , telaprevir or boceprevir , to pegylated ifn and ribavirin.32 this regimen improves the svr to 75% in patients infected with hcv genotype 1.33 ns3/4a serine protease plays at least two roles in the hcv life cycle . first , it is responsible for cleaving the hcv polypeptide into individual viral proteins ; it is essential for viral replication and virion assembly.32,34,35 second , ns3/4a protease inhibits the innate immune response to facilitate hcv persistence . therefore , ns3/4a protease is a good target for inhibitors that inhibit hcv replication and restore the host 's innate immunity . following the successful determination of the crystal structure of ns3/4a protease , small molecules specifically binding to the catalytic site of the ns3/4a protease were developed34 and two protease inhibitors , telaprevir and boceprevir , are now used to treat hcv infection in some countries . although protease inhibitor - based therapy significantly improves the svr,32,34 the high cost , severe adverse events , and rapid emergence of resistance mutations associated with these drugs limit their use in the developing countries where treatment is needed most.34 therefore , there is a pressing need to identify new treatment options that are cost- and clinically effective for all hcv genotypes . micrornas ( mirnas ) belong to a noncoding gene family involved in eukaryotic posttranscriptional gene regulation.3639 transcription of mirna genes forms primary transcripts ( pri - mirnas ) that usually contain a hairpin structure . the stem - loop structure is then cleaved by an rnaseiii - like enzyme called drosha , together with its binding partner dgcr8 ( digeorge syndrome critical region 8) , to yield precursor mirnas ( pre - mirnas ) that are subsequently transferred from the nucleus to the cytoplasm with the help of exportin-5 . in the cytoplasm , pre - mirnas are processed by dicer rna polymerase iii into a duplex structure , from which one strand is separated and functions as the guide strand ( functional strand ) to be loaded together with argonaute proteins into an rna - induced silencing complex that recognizes and binds to the target mrna . the other strand is degraded and nonfunctional ( fig . 2).36,4044 mirna exerts its function by degrading the target mrna ( if the mirna has perfect base pairing with its target mrna ) or inhibiting mrna translation ( if there is only partial pairing).4547 the human genome encodes more than 1500 mirnas ( www.mirbase.org , released january 2012 ) . each mirna can regulate numerous target genes and each mrna is likely to be regulated by several mirnas.48,49 the interaction of mirnas and their target mrnas results in a complex network that is involved in almost every cell process , including development , differentiation , proliferation , death , disease pathology , and antiviral defence.5053 most recently , increasing evidence suggests that cellular mirnas and other components of the mirna pathway can interact with viruses at multiple levels to influence viral replication.54,55 in this review , we summarize the mirnas involved in hcv infection and their proposed connection with antiviral innate immunity . type i ifn is a major player in the innate immune response , and is induced through pathways mediated by two distinct pathogen - associated molecular - pattern receptors : toll - like receptors ( tlrs ) and retinoic acid - inducible gene i ( rig - i)/melanoma differentiation - associated gene 5 . the mirnas mir-155 and mir-146a / b have been shown to be involved in these pathways.56 the potential target genes of mir-146a , such as interleukin-1 receptor - associated kinase 1 and 2 , tnf receptor - associated factor 6 , rig - i , and ifn - regulatory factor 5 , play a critical role in these type i induction pathways.57 inducible expression of mir-155 has been observed in both bacterial and viral infections , and may act as a negative feedback regulator of the tlr pathway to dampen the innate immune response.5860 in addition , mir-155 has been shown to be involved in carcinogenesis.6164 two oncogenic viruses , kaposi 's sarcoma - associated herpesvirus and the avian -herpesvirus marek 's disease virus type 1 , can encode mir-155 mimics mir - k12 - 11 and mir - m4 , respectively.6567 both of the virus - encoded mirnas share high sequence similarity with mir-155 and therefore function as an ortholog of cellular mir-155.6568 although numerous lines of evidence point to the fact that more and more mirnas are involved in host innate immunity either directly or indirectly,53,55,69,70 we are just at the very start of understanding the diverse roles of mirna in regulating host immunity . more studies are needed to understand how cellular mirnas interact with the antiviral innate immune response . type i ifn plays an irreplaceable role in anti - hcv defense . quite interestingly , as the key player in hcv therapy , ifn treatment can rapidly modulate the expression of numerous cellular mirnas.71 using microarray technology , pedersen et al . analyzed the expression of cellular mirnas in ifn - stimulated cells and found that the expression levels of about 30 mirnas were altered ( increased or decreased).71 furthermore , they analyzed the sequence of these mirnas and hcv genomic rna and identified eight ifn -induced mirnas ( mir-1 , -30 , -128 , -196 , -296 , -351 , -431 , and -448 ) that matched with hcv genome perfectly . functional assays showed that overexpression of these mirnas by transfection of the mirna mimics reproduced the antiviral effect of ifn in huh7 cells , while their neutralization with anti - mirnas dampened the antiviral effects of ifn against hcv.71 similarly , another independent study reported that mir-196 inhibited hcv rna replication in hcv replicon cells ( genotypes 1b and 2a).72 both studies illustrated that one of the mechanisms for ifn inhibition of hcv rna replication is probably the induction of cellular mirnas that can directly degrade hcv rna . in addition to the ifn - inducible mirnas described above , there are many other mirnas that can also inhibit hcv replication . for example , the overexpression of mir-199a has been reported to suppress hcv rna replication , while inhibition by a specific antisense oligonucleotide upregulated viral replication in two cell lines bearing the replicons hcv-1b or -2a.73 in addition to the direct inhibition , some mirnas inhibit hcv rna replication indirectly by activating the ifn pathway . for example , mir-130a has been shown to be able to inhibit hcv replication in both replicon ( genotype 1b ) and jfh1 infectious models . transfected mir-130a mimic into cultured huh7.5.1 cells stably expressing an hcv genome and found that replication of hcv rna was significantly inhibited.74 further studies showed that the expression levels of type i ifns ( ifn and ifn ) were significantly increased . as huh7.5.1 cells are deficient in both tlr3 and rig - i , two important mediators of type i ifn induction , these cells can not recognize hcv infection and , as a result , almost no type i ifns are produced following virus infection . these results imply that mir-130a may inhibit hcv replication indirectly , probably by restoring the host innate immune response in tlr3- and rig - i - deficient cells.74 however , other investigators have demonstrated that hcv infection upregulates mir-130a , and that interferon - induced transmembrane protein 1 ( ifitm1 ) is a direct target for this mirna : knockdown of mir-130a enhanced ifitm1 expression and reduced hcv replication.75 this study demonstrated that hcv evades innate immune attack by decreasing antiviral ifitm1 expression through mir-130a . since li et al found mir-130a up - regulated the ifn expression , the expression of the ifn - stimulated gene ifitm1 should increase ( although not tested in their study ) . these two studies reached seemingly contradictory results , which may indicate that mir-130a has more than one target , and the interaction of this mirna with the host innate immune system is complex . in any case , the interaction between mir-130a and the host innate immune system deserves further study . mir-122 is the most abundant liver - specific mirna , accounting for around 70% of the total mirna content in mammalian liver tissue.76 it is undetectable in other tissues in mice.76 studies have demonstrated that mir-122 acts as a regulator of fatty - acid metabolism in mouse liver,77 and reduced mir-122 levels are associated with hepatocellular carcinoma.7881 in addition , of all the mirnas , mir-122 is unique in its stimulatory , not inhibitory , role in hcv replication.82 the discovery that mir-122 is required for hcv replication linked a host mirna to a human infectious disease for the first time.83 the role of mir-122 in hcv replication was first reported by jopling et al . in 2005.82 they sequestrated mir-122 with antisense oligonucleotides and found that hcv rna accumulation decreased.82 in addition , they also identified two target sites in the hcv 5 untranslated region that are necessary for hcv replication . since then , a large number of elegant studies have been performed to show that the interaction between mir-122 and viral 5ncr is essential to promote hcv replication.8488 the role of mir-122 as an important , possibly essential , host factor for hcv production makes it an attractive candidate for antiviral therapy . modified antisense agents and small - molecule inhibitors have been developed as potential new lead compounds for drug discovery.89 most recently , treatment with miravirsen ( spc3649 ) efficiently suppressed hcv genotype 1a and 1b infections in chimpanzees , with no evidence of viral resistance or side effects.90 miravirsen , a locked nucleic acid modified dna phosphorothioate antisense oligonucleotide of mir-122 , has also been trialed in patients with chronic hcv genotype 1 , with the results showing a dose - dependent reduction in hcv rna levels without the occurrence of viral resistance.91 in addition to targeting hcv rna directly , yoshikawa et al . found that overexpression of mir-122 suppresses the activity of ifn - stimulated response element ( isre ) while significantly silencing mir-122-enhanced ifn - induced isre activity.92 isres are specific nucleotide sequences located in the promoters of ifn - stimulated genes that encode antiviral proteins and can induce transcription of these genes by binding with ifn - stimulated gene factor 3.93 furthermore , yoshikawa et al . found that silencing mir-122 decreased the expression of suppressor of cytokine signaling , a negative regulator of ifn signaling , in mouse liver , leading to increased ifn anti - hcv activity.92 this study indicates that the anti - hcv effect of mir-122 might also be mediated by decreasing the expression of antiviral proteins or increasing negative regulators of cytokine production . most recently , it has been reported that mir-141 , which can be induced by hcv infection , may also be necessary for efficient hcv replication.94 mir-141 belongs to the mir-200 family , which is believed to play an essential role in tumor suppression by inhibiting epithelial transfected an mir-141 mimic or antagonist into hcv1a - infected hepatocytes to increase or deplete intracellular mir-141 expression , respectively.94 the results showed that overexpression of mir-141 enhanced hcv replication , while depletion of mir-141 inhibited virus replication . meanwhile , they identified dlc-1 ( deleted in liver cancer 1 ) as one of the target genes.94 increasing mir-141 decreased dlc-1 protein levels without a parallel decrease in dlc-1 mrna levels , suggesting that mir-141 primarily targets translational inhibition of dlc-1.94 dlc-1 encodes a member of the rho - gtpase activating protein ( gap ) family of proteins . the rho - gap proteins can specifically catalyze the conversion of the active gtp - bound rhoa protein into the inactive gdp - bound protein.97,98 active rhoa protein is required for ras - mediated tumorigenic transformation,99 and rho - gaps may therefore act as important negative regulators in human carcinogenesis . in hepatocellular carcinoma , homozygous deletion or loss of dlc-1 mrna expression usually occurs in vivo and in vitro.98,100 in addition , restoration of dlc-1 in hepatoma cell lines lacking dlc-1 results in reduced cell proliferation as well as reduced metastatic activity.100 since hcv - infected cells express mir-141 , and its overexpression significantly suppresses dlc-1 expression,94 the results indicate the presence of a novel mechanism of hcv infection - associated mirna - mediated regulation of a tumor suppressor protein , which is worth further exploration . mirnas involved in hcv infection and their interactions with the innate immune system are summarized in table 1 . hcv , hepatitis c virus ; ifn , interferon ; isre , interferon - stimulated response element ; mirna , microrna type i ifn plays an irreplaceable role in anti - hcv defense . quite interestingly , as the key player in hcv therapy , ifn treatment can rapidly modulate the expression of numerous cellular mirnas.71 using microarray technology , pedersen et al . analyzed the expression of cellular mirnas in ifn - stimulated cells and found that the expression levels of about 30 mirnas were altered ( increased or decreased).71 furthermore , they analyzed the sequence of these mirnas and hcv genomic rna and identified eight ifn -induced mirnas ( mir-1 , -30 , -128 , -196 , -296 , -351 , -431 , and -448 ) that matched with hcv genome perfectly . functional assays showed that overexpression of these mirnas by transfection of the mirna mimics reproduced the antiviral effect of ifn in huh7 cells , while their neutralization with anti - mirnas dampened the antiviral effects of ifn against hcv.71 similarly , another independent study reported that mir-196 inhibited hcv rna replication in hcv replicon cells ( genotypes 1b and 2a).72 both studies illustrated that one of the mechanisms for ifn inhibition of hcv rna replication is probably the induction of cellular mirnas that can directly degrade hcv rna . in addition to the ifn - inducible mirnas described above , there are many other mirnas that can also inhibit hcv replication . for example , the overexpression of mir-199a has been reported to suppress hcv rna replication , while inhibition by a specific antisense oligonucleotide upregulated viral replication in two cell lines bearing the replicons hcv-1b or -2a.73 in addition to the direct inhibition , some mirnas inhibit hcv rna replication indirectly by activating the ifn pathway . for example , mir-130a has been shown to be able to inhibit hcv replication in both replicon ( genotype 1b ) and jfh1 infectious models . transfected mir-130a mimic into cultured huh7.5.1 cells stably expressing an hcv genome and found that replication of hcv rna was significantly inhibited.74 further studies showed that the expression levels of type i ifns ( ifn and ifn ) were significantly increased . as huh7.5.1 cells are deficient in both tlr3 and rig - i , two important mediators of type i ifn induction , these cells can not recognize hcv infection and , as a result , almost no type i ifns are produced following virus infection . these results imply that mir-130a may inhibit hcv replication indirectly , probably by restoring the host innate immune response in tlr3- and rig - i - deficient cells.74 however , other investigators have demonstrated that hcv infection upregulates mir-130a , and that interferon - induced transmembrane protein 1 ( ifitm1 ) is a direct target for this mirna : knockdown of mir-130a enhanced ifitm1 expression and reduced hcv replication.75 this study demonstrated that hcv evades innate immune attack by decreasing antiviral ifitm1 expression through mir-130a . since li et al found mir-130a up - regulated the ifn expression , the expression of the ifn - stimulated gene ifitm1 should increase ( although not tested in their study ) . these two studies reached seemingly contradictory results , which may indicate that mir-130a has more than one target , and the interaction of this mirna with the host innate immune system is complex . in any case , the interaction between mir-130a and the host innate immune system deserves further study . mir-122 is the most abundant liver - specific mirna , accounting for around 70% of the total mirna content in mammalian liver tissue.76 it is undetectable in other tissues in mice.76 studies have demonstrated that mir-122 acts as a regulator of fatty - acid metabolism in mouse liver,77 and reduced mir-122 levels are associated with hepatocellular carcinoma.7881 in addition , of all the mirnas , mir-122 is unique in its stimulatory , not inhibitory , role in hcv replication.82 the discovery that mir-122 is required for hcv replication linked a host mirna to a human infectious disease for the first time.83 the role of mir-122 in hcv replication was first reported by jopling et al . in 2005.82 they sequestrated mir-122 with antisense oligonucleotides and found that hcv rna accumulation decreased.82 in addition , they also identified two target sites in the hcv 5 untranslated region that are necessary for hcv replication . since then , a large number of elegant studies have been performed to show that the interaction between mir-122 and viral 5ncr is essential to promote hcv replication.8488 the role of mir-122 as an important , possibly essential , host factor for hcv production makes it an attractive candidate for antiviral therapy . modified antisense agents and small - molecule inhibitors have been developed as potential new lead compounds for drug discovery.89 most recently , treatment with miravirsen ( spc3649 ) efficiently suppressed hcv genotype 1a and 1b infections in chimpanzees , with no evidence of viral resistance or side effects.90 miravirsen , a locked nucleic acid modified dna phosphorothioate antisense oligonucleotide of mir-122 , has also been trialed in patients with chronic hcv genotype 1 , with the results showing a dose - dependent reduction in hcv rna levels without the occurrence of viral resistance.91 in addition to targeting hcv rna directly , yoshikawa et al . found that overexpression of mir-122 suppresses the activity of ifn - stimulated response element ( isre ) while significantly silencing mir-122-enhanced ifn - induced isre activity.92 isres are specific nucleotide sequences located in the promoters of ifn - stimulated genes that encode antiviral proteins and can induce transcription of these genes by binding with ifn - stimulated gene factor 3.93 furthermore , yoshikawa et al . found that silencing mir-122 decreased the expression of suppressor of cytokine signaling , a negative regulator of ifn signaling , in mouse liver , leading to increased ifn anti - hcv activity.92 this study indicates that the anti - hcv effect of mir-122 might also be mediated by decreasing the expression of antiviral proteins or increasing negative regulators of cytokine production . most recently , it has been reported that mir-141 , which can be induced by hcv infection , may also be necessary for efficient hcv replication.94 mir-141 belongs to the mir-200 family , which is believed to play an essential role in tumor suppression by inhibiting epithelial transfected an mir-141 mimic or antagonist into hcv1a - infected hepatocytes to increase or deplete intracellular mir-141 expression , respectively.94 the results showed that overexpression of mir-141 enhanced hcv replication , while depletion of mir-141 inhibited virus replication . meanwhile , they identified dlc-1 ( deleted in liver cancer 1 ) as one of the target genes.94 increasing mir-141 decreased dlc-1 protein levels without a parallel decrease in dlc-1 mrna levels , suggesting that mir-141 primarily targets translational inhibition of dlc-1.94 dlc-1 encodes a member of the rho - gtpase activating protein ( gap ) family of proteins . the rho - gap proteins can specifically catalyze the conversion of the active gtp - bound rhoa protein into the inactive gdp - bound protein.97,98 active rhoa protein is required for ras - mediated tumorigenic transformation,99 and rho - gaps may therefore act as important negative regulators in human carcinogenesis . in hepatocellular carcinoma , homozygous deletion or loss of dlc-1 mrna expression usually occurs in vivo and in vitro.98,100 in addition , restoration of dlc-1 in hepatoma cell lines lacking dlc-1 results in reduced cell proliferation as well as reduced metastatic activity.100 since hcv - infected cells express mir-141 , and its overexpression significantly suppresses dlc-1 expression,94 the results indicate the presence of a novel mechanism of hcv infection - associated mirna - mediated regulation of a tumor suppressor protein , which is worth further exploration . mirnas involved in hcv infection and their interactions with the innate immune system are summarized in table 1 . hcv , hepatitis c virus ; ifn , interferon ; isre , interferon - stimulated response element ; mirna , microrna mirnas are endogenous , short , noncoding rnas that function at the posttranscriptional ( mrna ) level through mrna degradation or inhibition of translation . host mirnas play various important roles in many cellular processes , including host innate immunity and cell defense . increasing lines of evidence suggest that many mirnas are involved in the viral life cycle . for hcv , mirnas can either stimulate or inhibit viral rna replication through distinct mechanisms . in the past few years , many studies have focused on identifying differentially expressed mirnas before and after hcv infection . identifying their target mrnas remains a great challenge , as a complex network of interaction exists between mirnas and mrnas . although high - throughput screening methods such as genome - wide association studies and microarrays may reveal the complicated network of regulation and eventually identify targets for intervention , functional studies will have to be performed to validate these targets experimentally . remarkably , the advent of anti - mir-122 drugs is opening a new era for hcv therapy . although many mirnas have been identified in vitro , and the function of many of these has not been verified in vivo , mirnas have great potential as therapeutic targets for viral infection , in addition to many other diseases .

hepatitis c virus ( hcv ) infection is a major global health problem . there is no effective vaccine and the current treatment regimen with pegylated interferon and ribavirin is associated with significant adverse events . therefore , there is an urgent need to identify new antiviral targets for hcv therapy . in recent years , a growing number of micrornas ( mirnas ) have been reported to be able to regulate hcv replication and infection by interacting with the hcv genome directly or by regulating host innate immunity to build a nonspecific antiviral state within cells . in this review , we discuss hcv virology and standard of care followed by mirna in general , and then give a brief overview of mirnas involved in hcv infection and discuss their potential application as a therapeutic option for the treatment of hcv infection .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Protecting Children Against Crime Act of 2003''. SEC. 2. NO STATUTE OF LIMITATIONS FOR CHILD ABDUCTION AND SEX CRIMES. (a) Statute of Limitations.-- (1) In general.--Chapter 213 of title 18, United States Code, is amended by adding at the end the following: ``Sec. 3297. Child abduction and sex offenses ``Notwithstanding any other provision of law, an indictment may be found or an information instituted at any time without limitation for any offense under section 1201 involving a minor victim, and for any felony under chapter 109A, 110, or 117, or section 1591.''. (2) Clerical amendment.--The table of sections at the beginning of chapter 213 of title 18, United States Code, is amended by adding at the end the following new item: ``3297. Child abduction and sex offenses.''. (b) Application.--The amendments made by this section shall apply to the prosecution of any offense committed before, on, or after the date of the enactment of this section. SEC. 3. REGISTRATION OF CHILD PORNOGRAPHERS IN THE NATIONAL SEX OFFENDER REGISTRY. (a) Jacob Wetterling Crimes Against Children and Sexually Violent Offender Registration Program.--Section 170101 of subtitle A of title XVII of the Violent Crime Control and Law Enforcement Act of 1994 (42 U.S.C. 14071(a)) is amended-- (1) by striking the section heading and inserting the following: ``SEC. 170101. JACOB WETTERLING CRIMES AGAINST CHILDREN AND SEXUALLY VIOLENT OFFENDER REGISTRATION PROGRAM.''; and (2) in subsection (a)(3)-- (A) in clause (vii), by striking ``or'' at the end; (B) by redesignating clause (viii) as clause (ix); and (C) by inserting after clause (vii) the following: ``(viii) production or distribution of child pornography, as described in section 2251, 2252, or 2252A of title 18, United States Code; or''. (b) Authorization of Appropriations.--There are authorized to be appropriated to the Department of Justice, for each of fiscal years 2004 through 2007, such sums as may be necessary to carry out the amendments made by this section. SEC. 4. GRANT PROGRAM FOR NEW TECHNOLOGIES TO IMPROVE AMBER ALERT COMMUNICATIONS PLANS. (a) Program Required.--The Attorney General of the United States shall carry out a program to provide grants to States for the development or enhancement of programs and activities for the support of AMBER Alert communications plans. (b) Activities.--Activities funded by grants under the program under subsection (a) may include the development and implementation of new technologies to improve AMBER Alert communications. (c) Federal Share.--The Federal share of the cost of any activities funded by a grant under the program under subsection (a) may not exceed 50 percent of the total cost thereof. (d) Distribution of Grant Amounts on Geographic Basis.--The Attorney General shall, to the maximum extent practicable, ensure the distribution of grants under the program under subsection (a) on an equitable basis throughout the various regions of the United States. (e) Administration.--The Attorney General shall prescribe requirements, including application requirements, for grants under the program under subsection (a). (f) Authorization of Appropriations.-- (1) In general.--There is authorized to be appropriated to the Department of Justice $5,000,000 for each of fiscal years 2004 through 2007, to carry out this section. (2) Availability.--Amounts appropriated pursuant to the authorization of appropriations in paragraph (1) shall remain available until expended. SEC. 5. NATIONAL RESEARCH COUNCIL STUDY AND REPORT CONCERNING ON-LINE PORNOGRAPHY. (a) Study.--The National Research Council of the National Academy of Sciences shall conduct a study of-- (1) the extent to which it is possible for Internet service providers to monitor Internet traffic to detect illicit child pornography sites on the Internet, and the extent to which they do so; (2) the extent to which purveyors use credit cards to facilitate the sale of illegal child pornography on the Internet; (3) which credit card issuers have in place a system to facilitate the identification of purveyors who use credit cards to facilitate the sale of illicit child pornography; and (4) options for encouraging greater reporting of such illicit transactions to law enforcement officials. (b) Report to Congress.--Not later than 12 months after the date of enactment of this Act, the National Research Council shall submit a report to the Congress on the study conducted under subsection (a). SEC. 6. SEVERABILITY. If any provision of this Act, an amendment made by this Act, or the application of such provision or amendment to any person or circumstance is held to be unconstitutional, the remainder of this Act, the amendments made by this Act, and the application of the provisions of such to any person or circumstance shall not be affected thereby.

Protecting Children Against Crime Act of 2003 - Amends the Federal criminal code to provide that no statute of limitations shall apply for specified child abduction and sex offenses.Amends the Jacob Wetterling Crimes Against Children and Sexually Violent Offender Registration Act to provide for the registration in the national sex offender registry of persons who produce or distribute child pornography.Requires the Attorney General to carry out a program to provide grants to States for the development or enhancement of programs and activities for the support of AMBER Alert communications plans.Directs the National Research Council of the National Academy of Sciences to study: (1) the extent to which Internet service providers can and do monitor Internet traffic to detect illicit child pornography sites; (2) the extent to which purveyors use credit cards to facilitate the sale of illegal child pornography on the Internet; (3) which credit card issuers have a system to facilitate the identification of such purveyors; and (4) options for encouraging greater reporting of such illicit transactions to law enforcement officials.

GRAND JUNCTION — Investigators say the device at the center of a fatal bungee accident at an indoor recreation park in western Colorado was functioning properly. The Grand Junction Daily Sentinel reports the Colorado Department of Labor and Employment worked with the manufacturer to test the device and is now investigating other reasons for the Jan. 4 fall that killed 20-year-old Ciara Romero. The woman was participating in a 70-foot (21-meter) bungee-jump feature at Get Air at the Silo when she fell. Participants climb one of the silo’s towers, then transfer to a wooden platform and jump off while attached to a rope. Users fall for about 20 feet (6 meters) and are caught by the device and lowered slowly to the ground. Get Air says it is cooperating with investigators. Information from: The Daily Sentinel ||||| GRAND JUNCTION, Colo. - News Channel 5 has obtained the Grand Junction Police Department's investigation into the death of Ciara Romero at the Get Air Silo Trampoline Park. The GJPD has announced no criminal charges will be filed. Romero was one of a group of five using the "Quick Jump" free fall device on January 4th and by multiple accounts from witnesses and employees, Romero was hesitant to jump. "She was hesitant you know, pretty freaked out," the employee at the bottom of the silo told police, "Kind of scared, but excited to go." Employees at both the top and the bottom of the silo told police they were "confident" the harness had been attached properly. Video reviewed by police shows the employee at the top of the silo pulling up on the harness with force to confirm it was attached. The report says at one point Romero sat down. Afterwards, the employee at the top checked the harness again. "I saw the carabiner that was attached to her harness. It caught like it was normally supposed to," the employee at the bottom of the Silo told police. "I saw that she was falling much faster and so I just instinctively tried to get underneath her." Multiple people at Get Air rushed to help, including a former ICU nurse. That person recalled checking for a pulse and felt a light one initially as well as hearing a gasping breath. The former nurse checked for a pulse again, but was unable to find one, and began two rounds of CPR. The employee at the top of the Silo, noticeably shaking when talking to police the report notes, said it was possible Romero's hand slipped and opened the carabineer during the initial jump but thought that would have been difficult to do. "[They are] designed to be difficult to remove with someone's body weight keeping tension on the line," the employee told police. A GJPD officer investigated the carabiner to find that it can be opened with one or two hands. "I found the carabiner to be relatively easy to open with one hand and believe a patron could inadvertently open the device with out knowing," Detective Heil said in the report, noting no flaws or damage on the device. The Colorado Department of Labor and Employment is investigating this incident as well and tells News Channel 5 they expect the results this week.

– Authorities in Colorado are investigating how a 20-year-old nurse died in a bungee jump accident—when the equipment was apparently working properly. Ciara Romero died after a fall Jan. 4 at the 70-foot Get Air attraction at the Silo Trampoline Park in Grand Junction, the Denver Post reports. The jump requires participants to jump off a tower connected to a rope attached to a harness. After free-falling for around 20 feet, they are supposed be caught by the device and slowly lowered to the ground. The Grand Junction Sentinel reports that in results confirmed by state investigators, the company that makes the device says it carried out tests and the "device, webbing, and triple-locking carabiner were found to be intact, and functioning normally." State investigators say they will now focus on witness statements, and the Grand Junction Police Department says no criminal charges will be filed. According a a police report seen by News Channel 5, employees and other witnesses said Romero was reluctant to jump. "She was hesitant, you know, pretty freaked out," one employee told police, "Kind of scared, but excited to go." Video shows employees checking to make sure the harness was properly attached, the report says. The report states that an employee told investigators that it was possible Romero's hand could have slipped and opened the carabiner. The employee said this would have been very difficult, though an officer wrote that he "found the carabiner to be relatively easy to open with one hand" and believes it could have happened accidentally.

one of the important results in the theory of derivations in banach bimodules is the theorem of j. r. ringrose on automatic continuity of every derivation acting on a @xmath1-algebra @xmath0 with values in a banach @xmath0-bimodule @xcite . this theorem extends the well - known result that every derivation of a @xmath1-algebra @xmath0 is automatically norm continuous @xcite . in the case when @xmath0 is an @xmath2-algebra ( in particular , @xmath3-algebra ) , every derivation on @xmath0 is inner @xcite , @xcite . significant examples of @xmath3-modules are non - commutative symmetric spaces of measurable operators affiliated with a von neumann algebra . at the present time the theory of symmetric spaces is actively developed ( see , e.g. @xcite , @xcite ) and it gives useful applications both in the geometry of banach spaces and in the theory of unbounded operators . every non - commutative symmetric space is a solid linear space in the @xmath4-algebra @xmath5 of all @xmath6-measurable operators affiliated with a von neumann algebra @xmath0 , where @xmath6 is a faithful normal semifinite trace on @xmath0 @xcite . the algebra @xmath5 equipped with the natural topology @xmath7 of convergence in measure generated by the trace @xmath6 is a complete metrizable topological algebra . in its turn the algebra @xmath5 represents a solid @xmath4-subalgebra of the @xmath4-algebra @xmath8 of all locally measurable operators , affiliated with a von neumann algebra @xmath0 @xcite , @xcite , in addition , the latter algebra @xmath8 with the natural topology @xmath9 of convergence locally in measure is a complete topological @xmath4-algebra @xcite . in @xcite there are established significant results in description of derivations of these algebras . in particular , it is proved that for every @xmath9-continuous derivation @xmath10 acting on the algebra @xmath8 there exists @xmath11 , such that @xmath12 $ ] for all @xmath13 , that is the derivation @xmath10 is inner . one of the main corollary of this result provides a full description of derivations @xmath10 acting from @xmath0 into a banach @xmath0-bimodule @xmath14 of locally measurable operators affiliated with @xmath0 . more precisely it is shown that any derivation an a von neumann algebra @xmath0 with values in a banach @xmath0-bimodule @xmath14 is inner @xcite . in the present paper we establish the similar property of derivations in more general case when @xmath14 is a quasi - normed @xmath0-bimodule of locally measurable operators affiliated with @xmath0 . the proof proceed in several stages . firstly , in section 2 we establish the version of ringrose theorem for arbitrary quasi - normed @xmath1-bimodules without the assumption of their completeness . after that in section 3 we supply the proof of the main result of the present paper ( theorem [ t_mbm ] ) showing that every derivation @xmath15 is necessarily inner , i.e. @xmath16 for some @xmath17 . in particular , @xmath10 is a continuous derivation from @xmath18 into @xmath19 . in addition , the operator @xmath20 may be chosen so that @xmath21 , where @xmath22 is the modulus of concavity of the quasi - norm @xmath23 . we use terminology and notations from the von neumann algebra theory @xcite and the theory of locally measurable operators from @xcite . let @xmath24 be the @xmath4-algebra of all bounded linear operators acting in a hilbert space @xmath25 , and let @xmath26 be the identity operator on @xmath25 . let @xmath0 be a von neumann algebra acting on @xmath25 , and let @xmath27 be the centre of @xmath0 . denote by @xmath28 the lattice of all projections in @xmath0 and by @xmath29 the set of all finite projections in @xmath0 . a densely - defined closed linear operator @xmath30 affiliated with @xmath0 is said to be _ measurable _ with respect to @xmath0 if there exists a sequence @xmath31 such that @xmath32 and @xmath33 for every @xmath34 , where @xmath35 is the domain of @xmath30 and @xmath36 is the set of all natural numbers . the set @xmath37 of all measurable operators is a unital @xmath4-algebra over the field @xmath38 of complex numbers with respect to strong sum @xmath39 , strong product @xmath40 and the adjoint operation @xmath41 @xcite . a densely - defined closed linear operator @xmath30 affiliated with @xmath0 is called _ locally measurable _ with respect to @xmath0 if there is a sequence @xmath42 such that @xmath43 and @xmath44 for all @xmath34 . the set @xmath8 of all locally measurable operators ( with respect to @xmath0 ) is a unital @xmath4-algebra over the field @xmath38 with respect to the same algebraic operations as in @xmath37 , in addition @xmath0 and @xmath37 are @xmath4-subalgebras of @xmath8 . for every subset @xmath45 , the set of all self - adjoint ( respectively , positive ) operators in @xmath46 is denoted by @xmath47 ( respectively , @xmath48 ) . the partial order in @xmath49 is defined by its cone @xmath50 and is denoted by @xmath51 . let @xmath30 be a closed linear operator with the dense domain @xmath35 in @xmath25 , let @xmath52 be the polar decomposition of the operator @xmath30 , where @xmath53 and @xmath54 is a partial isometry in @xmath24 such that @xmath55 is the right support @xmath56 of @xmath30 . it is known that @xmath13 ( respectively , @xmath57 ) if and only if @xmath58 ( respectively , @xmath59 ) and @xmath60 @xcite . for every @xmath13 the projection @xmath61 , where @xmath62 and @xmath56 are left and right supports of @xmath30 respectively , is called the support of @xmath30 . if @xmath63 , then the spectral family of projections @xmath64 for @xmath30 belongs to @xmath0 @xcite , in addition , @xmath65 . denote by @xmath66 the @xmath1-norm in the von neumann algebra @xmath0 . we need the following property of partial order in the algebra @xmath8 . * proposition 6.1 ) [ mchext ] let @xmath0 be a von neumann algebra acting on the hilbert space @xmath25 , @xmath67 and @xmath68 . then @xmath69 for some @xmath70 , in particular , @xmath71 . now , let us recall the definition of the local measure topology . if @xmath0 is a commutative von neumann algebra , then @xmath0 is @xmath4-isomorphic to the @xmath4-algebra @xmath72 of all essentially bounded measurable complex - valued functions defined on a measure space @xmath73 with the measure @xmath74 satisfying the direct sum property ( we identify functions that are equal almost everywhere ) ( see e.g. ( * ? ? ? * ch . 1 ) ) . the direct sum property of a measure @xmath74 means that the boolean algebra @xmath75 of all projections of a commutative von neumann algebra @xmath72 is order complete , and for any non - zero @xmath76 there exists a non - zero projection @xmath77 such that @xmath78 , where @xmath79 , @xmath80 and @xmath81 , when @xmath82 . consider the @xmath4-algebra @xmath83 of all measurable almost everywhere finite complex - valued functions defined on @xmath73 ( functions that are equal almost everywhere are identified ) . define on @xmath84 the local measure topology @xmath85 , that is , the hausdorff vector topology , whose base of neighbourhoods of zero is given by @xmath86 @xmath87 where @xmath88 , @xmath89 , @xmath90 . the topology @xmath85 does not change if the measure @xmath74 is replaced with an equivalent measure @xcite . now let @xmath0 be an arbitrary von neumann algebra and let @xmath91 be a @xmath4-isomorphism from @xmath27 onto the @xmath4-algebra @xmath72 . denote by @xmath92 the set of all measurable real - valued functions defined on @xmath73 and taking values in the extended half - line @xmath93 $ ] ( functions that are equal almost everywhere are identified ) . let @xmath94 be a dimensional function on @xmath95 @xcite . for arbitrary scalars @xmath96 and a set @xmath97 , @xmath90 , we set @xmath98 @xmath99 it was shown in @xcite that the system of sets @xmath100 defines a hausdorff vector topology @xmath9 on @xmath8 such that the sets of form a neighbourhood base of an operator @xmath13 . the topology @xmath9 on @xmath8 is called the _ local measure topology_. it is known that @xmath101 is a complete topological @xmath4-algebra , and the topology @xmath9 does not depend on a choice of dimension function @xmath102 and on a choice of @xmath4-isomorphism @xmath91 ( see e.g. @xcite , @xcite ) . let us mention the following important property of the topology @xmath9 . * proposition 2.5 ) [ p2_2 ] the von neumann algebra @xmath0 is dense in @xmath103 . let @xmath0 be a semifinite von neumann algebra acting on the hilbert space @xmath25 , let @xmath6 be a faithful normal semifinite trace on @xmath0 . an operator @xmath104 is called _ @xmath6-measurable _ if for any @xmath105 there exists a projection @xmath106 such that @xmath107 and @xmath108 . the set @xmath5 of all @xmath6-measurable operators is a @xmath4-subalgebra of @xmath37 and @xmath109 . if the trace @xmath6 is finite , then @xmath110 . let @xmath7 be the _ measure topology _ @xcite on @xmath5 whose base of neighbourhoods of zero is given by @xmath111 the pair @xmath112 is a complete metrizable topological @xmath4-algebra . here , the topology @xmath7 majorizes the topology @xmath9 on @xmath5 and , if @xmath6 is a finite trace , the topologies @xmath7 and @xmath9 coincide @xcite . let @xmath0 be a @xmath1-algebra with identity @xmath26 and @xmath113 be an arbitrary bimodule over @xmath0 with bilinear mappings @xmath114 such that @xmath115 for all @xmath116 . by introduction of algebraic operation @xmath117 , the @xmath0-bimodule @xmath113 become a complex linear space . recall that a real function @xmath118 on a complex linear space @xmath113 is called a _ quasi - norm _ on @xmath113 , if there exists a constant @xmath119 such that for all @xmath120 the following properties hold : @xmath121 . @xmath122 ; @xmath123 . @xmath124 ; @xmath125 . @xmath126 . the couple @xmath127 is called a quasi - normed space and the least of all constants @xmath128 satisfying the inequality @xmath125 above is called the modulus of concavity of the quasi - norm @xmath118 and denoted by @xmath129 . every quasi - normed space @xmath127 is a locally bounded hausdorff topological vector space ( see e.g. @xcite ) . if an @xmath0-bimodule @xmath113 is equipped with a quasi - norm @xmath130 , then the couple @xmath131 is called a quasi - normed @xmath0-bimodule if for all @xmath132 the equality @xmath133 holds , where @xmath66 is the @xmath1-norm on @xmath0 . let @xmath113 be an @xmath0-bimodule over a @xmath1-algebra @xmath0 . a linear mapping @xmath134 is called a _ derivation _ , if @xmath135 for all @xmath136 . a derivation @xmath134 is called _ inner _ , if there exists an element @xmath137 , such that @xmath138=dx - xd$ ] for all @xmath139 . if @xmath131 is a quasi - normed @xmath0-bimodule , then , by every inner derivation @xmath134 is a continuous linear mapping from @xmath140 into @xmath131 . in the following theorem we show that every derivation @xmath141 is continuous and strengthen the ringrose theorem by omitting the assumption of completeness of the space @xmath131 . our proof uses the original proof of j.ringrose ( * ? ? ? * theorem 2 ) . [ t_ring ] let @xmath131 be a quasi - normed @xmath0-bimodule . then every derivation @xmath141 is a continuous mapping from @xmath140 into @xmath131 . set @xmath142 exactly as in ( * ? ? ? * theorem 2 ) we obtain that @xmath143 is a two - sided ideal in @xmath0 . since @xmath144 we have @xmath145 let us show that @xmath143 is a closed ideal in @xmath0 . let @xmath146 and @xmath147 as @xmath148 . then every @xmath149 is a continuous mapping from @xmath0 into @xmath113 and for every fixed @xmath150 we have @xmath151 the principle of uniform boundedness ( see e.g. ( * ? ? ? * theorem 2.8 ) ) implies that @xmath152 is continuous , that is @xmath153 . thus , @xmath143 is a closed two - sided ideal in @xmath0 . now , we show that the restriction @xmath154 is continuous . suppose the contrary . then there exists a sequence @xmath155 such that @xmath156 set @xmath157 . then @xmath158 by ( * ? ? ? * lemma 1 ) there exists @xmath159 with @xmath160 such that @xmath161 . hence , @xmath162 that is the mapping @xmath163 is unbounded . that contradicts the inclusion @xmath164 . thus , the restriction @xmath154 is a continuous mapping . next , we claim that the quotient algebra @xmath165 is finite - dimensional . assume the contrary and as in ( * ? ? ? * theorem 2 ) choose a sequence @xmath166 such that @xmath167 since @xmath168 the mapping @xmath169 is unbounded , therefore there exist @xmath170 such that @xmath171 by setting @xmath172 we have @xmath173 and @xmath174 . the inequality @xmath175 implies that @xmath176 now , using the inequality @xmath177 we obtain that @xmath178 that is a contradiction , thus the quotient algebra @xmath165 is finite - dimensional . therefore , @xmath0 is a direct sum @xmath179 , where @xmath180 is a finite - dimensional subspace in @xmath0 and @xmath143 is a closed ideal in @xmath140 . since the restrictions @xmath154 and @xmath181 are continuous it follows that the derivation @xmath182 is continuous too . in this section we establish the main result of the present paper , which give description of all derivations acting on a von neumann algebra @xmath0 with values in a quasi - normed @xmath0-bimodule @xmath14 of locally measurable operators affiliated with @xmath0 . let @xmath0 be an arbitrary von neumann algebra . a linear subspace @xmath14 of @xmath8 , is called an @xmath0-bimodule of locally measurable operators if @xmath183 whenever @xmath184 and @xmath185 . it is clear that @xmath14 is a bimodule over the @xmath1-algebra @xmath0 in the sense of section 3 . if @xmath14 is a @xmath0-bimodule of locally measurable operators , @xmath186 and @xmath187 is the polar decomposition of operator @xmath30 then @xmath188 and @xmath189 . in addition , by proposition [ mchext ] every @xmath0-bimodule satisfies the following condition @xmath190 if an @xmath0-bimodule of locally measurable operators @xmath14 is equipped with a quasi - norm @xmath191 , satisfying the inequality , then @xmath192 is called a _ quasi - normed @xmath0-bimodule of locally measurable operators_. examples of quasi - normed @xmath0-bimodules of locally measurable operators , which are not normed @xmath0-bimodules , are the noncommutative @xmath193-space @xmath194 associated with a faithful normal semifinite trace @xmath6 for @xmath195 . recall that two projections @xmath199 are called equivalent ( notation : @xmath200 ) if there exists a partial isometry @xmath150 such that @xmath201 and @xmath202 . for projections @xmath199 notation @xmath203 means that there exists a projection @xmath204 such that @xmath205 . let @xmath222 be an arbitrary derivation , that is @xmath10 is a linear mapping such that @xmath135 for all @xmath136 . in ( * lemma 3.1 ) it is proved that @xmath223 and @xmath224 for all @xmath225 . in particular , @xmath226 and the restriction @xmath227 of the derivation @xmath10 to @xmath228 is a derivation on @xmath228 with values in @xmath229 . let @xmath10 be a derivation from @xmath0 with values in a @xmath0-bimodule @xmath14 of locally measurable operators . let us define a mapping @xmath230 by setting @xmath231 , @xmath232 . a direct verification shows that @xmath233 is also a derivation from @xmath0 with values in @xmath14 . a derivation @xmath10 is said to be _ self - adjoint _ , if @xmath234 . every derivation @xmath10 from @xmath0 with values in a @xmath0-bimodule @xmath14 of locally measurable operators can be represented in the form @xmath235 , where @xmath236 are self - adjoint derivations from @xmath0 with values in @xmath14 . for the proof of the assertion that every derivation @xmath237 is inner we need the following significant theorem establishing that every @xmath9-continuous derivation acting on the @xmath4-algebra @xmath8 is inner . for application of the theorem [ t1 ] in our case , when @xmath10 is a derivation acting on @xmath0 with values in quasi - normed @xmath0-bimodule @xmath238 of locally measurable operators , we need @xmath9-continuity of @xmath10 . in the following proposition [ p4 ] using theorem [ t_ring ] we prove this property of derivation @xmath10 . let @xmath6 be a faithful normal finite trace @xmath6 on the von neumann algebra @xmath0 . in this case , the algebra @xmath0 is finite . moreover , @xmath239 , @xmath240 and @xmath103 is an @xmath241-space @xcite . since the trace @xmath6 is finite , we have that @xmath240 , and therefore it is sufficient to show that @xmath245 . suppose the contrary . passing to a subsequence , if necessary , we may choose @xmath246 such that @xmath247 for all @xmath34 . set @xmath253 it is clear that @xmath254 . since @xmath255 the set @xmath256 is an orthocomplemented complete modular lattice , and therefore @xmath256 is a continuous geometry @xcite . in particular , @xmath257 consequently , for all @xmath34 there exists an integer @xmath258 such that @xmath259 . set @xmath260 . the sequence of projections @xmath261 is increasing , moreover , @xmath262 and @xmath263 therefore , @xmath264 . by proposition [ pe4 ] we have @xmath265 since the sequence @xmath266 is increasing , the last inequality implies that @xmath267 for all @xmath34 . using the convergence @xmath264 we obtain @xmath268 , that contradicts . * lemma 6.8 ) [ l_e4 ] if @xmath0 is a von neumann algebra with a faithful normal finite trace @xmath6 , @xmath270 and @xmath244 , then there exists a subsequence @xmath271 such that @xmath272 , where @xmath273 and @xmath274 . [ p4 ] let @xmath0 be a von neumann algebra with a faithful normal finite trace @xmath6 , let @xmath238 be a quasi - normed @xmath0-bimodule of locally measurable operators and let @xmath10 be a derivation on @xmath8 such that @xmath275 . then the derivation @xmath10 is @xmath9-continuous . since the restriction @xmath281 of the derivation @xmath10 to the von neumann algebra @xmath0 is a derivation from @xmath0 into the quasi - normed @xmath0-bimodule @xmath238 , by theorem [ t_ring ] we have @xmath282 . lemma [ l_e2 ] implies that @xmath283 . * theorem 1 ) [ t_bs ] let @xmath0 be a von neumann algebra and @xmath287 . then there exist a self - adjoint operator @xmath288 in the centre of the @xmath4-algebra @xmath8 and a family @xmath289 of unitary operators from @xmath0 such that @xmath290 let @xmath0 be a von neumann algebra and let @xmath238 be a quasi - normed @xmath0-bimodule of locally measurable operators . then any derivation @xmath15 is inner , that is there exists an element @xmath20 such that @xmath138,x\in\mathcal{m}$ ] , in addition @xmath21 . if @xmath291 or @xmath292 then @xmath293 may be chosen so that @xmath294 . choose pairwise orthogonal central projections @xmath297 such that @xmath298 + @xmath299 , @xmath300 is a properly infinite von neumann algebra and on every von neumann algebra @xmath301 exists a faithful normal finite trace . by ( * theorem 3.3 ) the derivation @xmath302 is @xmath303-continuous . since the von neumann algebra @xmath301 is finite with a faithful normal finite trace and for the derivation @xmath304 the inclusion @xmath305 holds , proposition [ p4 ] implies that @xmath306 is also @xmath307-continuous for all @xmath308 . therefore , by ( * ? ? ? * corollary 2.8 ) , the derivation @xmath295 is @xmath9-continuous . by theorem [ t1 ] the derivation @xmath295 is inner , that is there exists an element @xmath11 , such that @xmath309 $ ] for all @xmath13 . it is clear that @xmath310=\overline{\delta}(\mathcal{m})=\delta(\mathcal{m})\subset \mathcal{e}$ ] . let us show that we can choose @xmath20 such that @xmath138 $ ] for all @xmath139 . by theorem [ t_bs ] and taking @xmath315 in ( [ e_bs ] ) we obtain that there exist self - adjoint operators @xmath316 in the centre of the @xmath4-algebra @xmath8 and unitary operators @xmath317 such that @xmath318|\geq |a_i - c_i|,\ i=1,2.\ ] ] since @xmath319\in\mathcal{e}$ ] and @xmath14 is @xmath0-bimodule of locally measurable operators we have that @xmath320 , @xmath321 ( see ) . therefore @xmath322 . since @xmath316 are central elements from @xmath8 it follows that @xmath323=[d , x]$ ] for all @xmath139 . now , suppose that @xmath291 . in this case , @xmath324=[d , x]-[d , x^*]^*=\delta(x)-(\delta(x^*))^*=\delta(x)-\delta^*(x)=0 $ ] for any @xmath139 . consequently , the operator @xmath325 commutes with every elements from @xmath0 , and by proposition [ p2_2 ] , @xmath326 is a central element in the algebra @xmath8 . therefore we may suggest that @xmath138,\ x\in\mathcal{m}$ ] , where @xmath327 . according to theorem [ t_bs ] there exist @xmath328 from the centre of the algebra @xmath8 and a family @xmath289 of unitary operators from @xmath0 such that @xmath329|\geq ( 1-\varepsilon)|a - c|.\ ] ] for @xmath330 and @xmath315 we have @xmath331|=2|[-id , u_{1/2}]|=2[d , u_{1/2}]\in\mathcal{e}.\ ] ] consequently , @xmath332 , moreover , @xmath333=[ia , x]=[b , x]\ ] ] for all @xmath139 . since @xmath334|=|[d , u_\varepsilon]|=|\delta(u_\varepsilon)|,\ ] ] it follows that @xmath335 for all @xmath105 , that implies the inequality @xmath336 . now , suppose that @xmath339 and @xmath340 . equality ( [ e1 ] ) implies that @xmath341 consequently , @xmath342 similarly , @xmath343 . since @xmath344 , @xmath345 , there exist @xmath346 , such that @xmath347,\ im(\delta)(x)=[d_2,x]$ ] for all @xmath139 and @xmath348 , @xmath321 . taking @xmath349 , we have that @xmath20 , @xmath350+i[d_2,x]=[d , x]$ ] for all @xmath139 , in addition @xmath21 . let @xmath0 be a semifinite von neumann algebra and let @xmath6 be a faithful normal semifinite trace on @xmath0 . let @xmath5 be the @xmath4-algebra of all @xmath6-measurable operators affiliated with @xmath0 . for each @xmath351 and @xmath352 we define the decreasing rearrangement ( or generalised singular value function ) by setting @xmath353 let @xmath14 be a linear subspace in @xmath5 equipped with a quasi - norm @xmath196 satisfying the following condition : @xmath354 in this case , the pair @xmath19 is called _ quasi - normed symmetric spaces of @xmath6-measurable operators_. it is easy to see that every quasi - normed symmetric space of measurable operators is a quasi - normed @xmath0-bimodule of locally measurable operators , and therefore theorem [ t_mbm ] implies the following [ c_last ] let @xmath19 be a quasi - normed symmetric spaces of @xmath6-measurable operators , affiliated with a semifinite von neumann algebra @xmath0 with a faithful semifinite normal trace @xmath6 . then any derivation @xmath355 is continuous and there exists @xmath20 such that @xmath138 $ ] for all @xmath139 and @xmath356 p.g . dodds , t.k . dodds and b. de pagter , _ noncommutative banach function spaces _ z. , * 201 * ( 1989 ) , 583597 . kadison and j.r . ringrose , _ fundamentals of the theory of operator algebras ii _ , academic press , orlando , 1986 . n.j . kalton , n.t . peck , j.w . roberts , _ an f - space sampler , _ london math . lecture notes 89 . cambridge univ . press . 1985 . n.j . kalton , f.a . sukochev , _ symmetric norms and spaces of operators . _ j. reine angew . , * 621 * ( 2008 ) , 81121 . i.kaplansky , _ any orthocomplemented complete modular lattice is continuous geometry _ , ann , * 61 * ( 1955 ) , 524542 . d.olesen , _ derivations of @xmath2-algebras are inner _ , pacific j. math . , * 53 * ( 1974 ) , no.1 , 555561 . j. r.ringrose , _ automatic continuity of derivations of operator algebras _ , j.london math . soc . , * 5 * ( 1972 ) , no . 2 , 432438 .

we prove that every derivation acting on a von neumann algebra @xmath0 with values in a quasi - normed bimodule of locally measurable operators affiliated with @xmath0 is necessarily inner .

a 65-year - old lady referred to our center for managing an abdominal pain she had for a 6 months period and right side adnexal mass . imaging studies revealed a solid and cystic mass in right adnexa m. 1086564 mm indistinguishable from uterine border . total hysterectomy with bilatereal salpigo - oopherectoy in association with complete staging procedure was done . ovarian masses , m. 10 6 and 6 5 cm , respectively , with frozen pelvis was found in laparatomy . gross examination of the received specimens revealed multiple discrete tumoral tissue m. up to 3 cm in diameter . opening of the uterus showed an endometrial polyp m. 5 mm in diameter with soft consistency . microscopic examination of the specimens revealed bilateral high grade ovarian serous carcinoma ( figure 1a ) , endometrial polyp with small foci of serous carcinoma ( figure 1b ) , massive full thickness myometrial invasion by the serous tumor ( figure 1c ) , lymphovascular space involvement , omentum metastasis , metastatic lymph nodes and positive ascetic fluid for malignant cells . the invasive foci in the myometrium were positive for p53 ( figure 1c ) , estrogen receptor and progesterone receptor . in contrast the foci of serous carcinoma in the endometrial polyp were negative for p53 ( figure 1d ) . unfortunately we missed the carcinomatous foci of the endometrial polyp in ki-67 , estrogen receptor and progesterone receptor staining due to repeated sections for ihc staining . high grade ovarian serous carcinoma ( a ) , the endometrial polyp with small foci of serous carcinoma ( b ) , myometrial invasion by the serous carcinoma showing p35 positive staining ( c ) and small focus of serous papillary carcinoma in the endometrial polyp with negative p53 staining ( d ) . a 53-year - old lady with chief complaint of vaginal bleeding for 6 months period referred for further evaluation . ultrasound study revealed mild increased endometrial thickness ( 10 mm ) with no remarkable change in the cervix , myometrium or adnexa . endometrial biopsy was done and histologic examination revealed endometrial clear cell carcinoma with serous carcinoma components in association with fragments of endometrial polyp m. up to 5 mm in diameter ( figure 2a , 2b ) . gross examination of the specimens revealed unremarkable endometrial cavity and the myometrium , cervix and ovaries showed no pathologic change . microscopic examination of the endometrium showed endometrial glands with dysplstic nuclei and clear cytoplasm ( clear cell glandular dysplasia ) with no invasive component ( figure 2c ) . the received omentum , lymph nodes , peritoneal biopsies , and peritoneal washing cytology were negative for malignancy . foci of endometrial clear cell carcinoma in the endometrial biopsy ( a ) , a fragment of endometrial polyp in the endometrial biopsy ( b ) , clear cell endometrial glandular dysplasia , emgd ( c ) and positive p53 reaction in the clear cell carcinoma ( d ) . a 65-year - old lady referred to our center for managing an abdominal pain she had for a 6 months period and right side adnexal mass . imaging studies revealed a solid and cystic mass in right adnexa m. 1086564 mm indistinguishable from uterine border . total hysterectomy with bilatereal salpigo - oopherectoy in association with complete staging procedure was done . ovarian masses , m. 10 6 and 6 5 cm , respectively , with frozen pelvis was found in laparatomy . gross examination of the received specimens revealed multiple discrete tumoral tissue m. up to 3 cm in diameter . opening of the uterus showed an endometrial polyp m. 5 mm in diameter with soft consistency . microscopic examination of the specimens revealed bilateral high grade ovarian serous carcinoma ( figure 1a ) , endometrial polyp with small foci of serous carcinoma ( figure 1b ) , massive full thickness myometrial invasion by the serous tumor ( figure 1c ) , lymphovascular space involvement , omentum metastasis , metastatic lymph nodes and positive ascetic fluid for malignant cells . the invasive foci in the myometrium were positive for p53 ( figure 1c ) , estrogen receptor and progesterone receptor . in contrast the foci of serous carcinoma in the endometrial polyp were negative for p53 ( figure 1d ) . unfortunately we missed the carcinomatous foci of the endometrial polyp in ki-67 , estrogen receptor and progesterone receptor staining due to repeated sections for ihc staining . high grade ovarian serous carcinoma ( a ) , the endometrial polyp with small foci of serous carcinoma ( b ) , myometrial invasion by the serous carcinoma showing p35 positive staining ( c ) and small focus of serous papillary carcinoma in the endometrial polyp with negative p53 staining ( d ) . a 53-year - old lady with chief complaint of vaginal bleeding for 6 months period referred for further evaluation . ultrasound study revealed mild increased endometrial thickness ( 10 mm ) with no remarkable change in the cervix , myometrium or adnexa . endometrial biopsy was done and histologic examination revealed endometrial clear cell carcinoma with serous carcinoma components in association with fragments of endometrial polyp m. up to 5 mm in diameter ( figure 2a , 2b ) . gross examination of the specimens revealed unremarkable endometrial cavity and the myometrium , cervix and ovaries showed no pathologic change . microscopic examination of the endometrium showed endometrial glands with dysplstic nuclei and clear cytoplasm ( clear cell glandular dysplasia ) with no invasive component ( figure 2c ) . the received omentum , lymph nodes , peritoneal biopsies , and peritoneal washing cytology were negative for malignancy . foci of endometrial clear cell carcinoma in the endometrial biopsy ( a ) , a fragment of endometrial polyp in the endometrial biopsy ( b ) , clear cell endometrial glandular dysplasia , emgd ( c ) and positive p53 reaction in the clear cell carcinoma ( d ) . a 65-year - old lady referred to our center for managing an abdominal pain she had for a 6 months period and right side adnexal mass . imaging studies revealed a solid and cystic mass in right adnexa m. 1086564 mm indistinguishable from uterine border . total hysterectomy with bilatereal salpigo - oopherectoy in association with complete staging procedure was done . ovarian masses , m. 10 6 and 6 5 cm , respectively , with frozen pelvis was found in laparatomy . gross examination of the received specimens revealed multiple discrete tumoral tissue m. up to 3 cm in diameter . opening of the uterus showed an endometrial polyp m. 5 mm in diameter with soft consistency . microscopic examination of the specimens revealed bilateral high grade ovarian serous carcinoma ( figure 1a ) , endometrial polyp with small foci of serous carcinoma ( figure 1b ) , massive full thickness myometrial invasion by the serous tumor ( figure 1c ) , lymphovascular space involvement , omentum metastasis , metastatic lymph nodes and positive ascetic fluid for malignant cells . the invasive foci in the myometrium were positive for p53 ( figure 1c ) , estrogen receptor and progesterone receptor . in contrast the foci of serous carcinoma in the endometrial polyp were negative for p53 ( figure 1d ) . unfortunately we missed the carcinomatous foci of the endometrial polyp in ki-67 , estrogen receptor and progesterone receptor staining due to repeated sections for ihc staining . high grade ovarian serous carcinoma ( a ) , the endometrial polyp with small foci of serous carcinoma ( b ) , myometrial invasion by the serous carcinoma showing p35 positive staining ( c ) and small focus of serous papillary carcinoma in the endometrial polyp with negative p53 staining ( d ) . a 53-year - old lady with chief complaint of vaginal bleeding for 6 months period referred for further evaluation . ultrasound study revealed mild increased endometrial thickness ( 10 mm ) with no remarkable change in the cervix , myometrium or adnexa . endometrial biopsy was done and histologic examination revealed endometrial clear cell carcinoma with serous carcinoma components in association with fragments of endometrial polyp m. up to 5 mm in diameter ( figure 2a , 2b ) . gross examination of the specimens revealed unremarkable endometrial cavity and the myometrium , cervix and ovaries showed no pathologic change . microscopic examination of the endometrium showed endometrial glands with dysplstic nuclei and clear cytoplasm ( clear cell glandular dysplasia ) with no invasive component ( figure 2c ) . the received omentum , lymph nodes , peritoneal biopsies , and peritoneal washing cytology were negative for malignancy . foci of endometrial clear cell carcinoma in the endometrial biopsy ( a ) , a fragment of endometrial polyp in the endometrial biopsy ( b ) , clear cell endometrial glandular dysplasia , emgd ( c ) and positive p53 reaction in the clear cell carcinoma ( d ) . in a series including 455 patients with endometrial polyp diagnosed by hysteroscopy , endometrial adenocarcinoma was found in 2.7% , although they did not indicate the type of reported malignancy.15 in another study , all of the 13 malignancies reported in the endometrial polyps were well to moderately differentiated endometriod adenocarcinoma.16 although uterine serous carcnoma is an uncommon cancer , it accounts for a disproportionate number of endometrial cancer deaths . in a series studied by hamilton et al , these tumors accounted for 10% of endometrial tumors , but comprised 39% of endometrial cancer deaths.17 its tendency for early spread results in upstaging of 50% to 70% of clinically stage i cancers at the time of operation.18 presentation of 19.7% and 31.1% of patients with uterine serous carcinoma in stage ii - iii , respectively in one study confirms the common perception that this histotype of endometrial carcinoma carry a worse prognosis due to advanced disease at the time of diagnosis.19 the first case reported here shows the coexistence of high grade bilateral ovarian serous carcinoma and small foci of invasive serous carcinoma in the endometrial polyp . although metastatic spread to this endometrial polyp should be considered in differential diagnosis , the high tendency of primary endometrial serous carcinoma to develop in endometrial polyps must be emphasized . in a study , 13 cases of primary endometrial serous carcinoma had developed in endometrial polyps and all of them except for one were limited to the endometrial polyps.20 on the other hand , although apparently these lesions were limited in the polyps in the present study , extrauterine spread was found in four cases , three of which were microscopic . even in the so - called intraepithelial form of serous carcinoma ( endometrial intraepithelial carcinoma ) , the predilection and tendency for extra uterine spread has been noted.2124 in addition , minimal uterine serous carcinoma ( including serous carcinoma with invasion limited to the endometrium and endometrial intraepithelial carcinoma ) were found to involve endometrial polyps in 88% of the cases ( 35/40 ) and were confined to the polyp in 53% ( 21/40).24 in an interesting case report that included 5 cases , the authors reported endometrial serous carcinoma confined to an endometrial polyp with ovarian vascular involvement.25 for this reason clement and young recommended that eic should be considered as small foci of serous carcinoma and stressed that pathologists should indicate its malignant potential in the pathology report when it is unaccompanied by typical serous carcinoma and note its size and location.26 it means that in all forms of uterine serous carcinoma including eic , surgical staging should be performed regardless its location or limitation on endometrial polyp . recently , it has been proposed that the term eic should be discarded as a precursor lesion for endometrial serous carcinoma due to its well recognized potential for extra uterine spread . furthermore , endometrial glandular dysplasia ( emgd ) has been proposed recently as a true precursor lesion for endometrial serous carcinoma.27 in the our recent study emgd was found in five out of 25 cases of endometrial serous carcinoma developed in endometrial polyp ( unpublished data ) . coexisting involvement of the endometrium or ovary is found in 10% and 5% of women with ovarian and endometrial cancer , respectively.28 although the presence of multifocal or multi - centric serous neoplaia is possible , identical p53 mutation in multiple sites indicates metastatic origin.29 in this case , positivity of tumor nests in the myometrium and negativity of the small foci of serous papillary carcinoma in the polyp for p53 favours independent primary tumors in both endometrium and ovaries ( figure 1c , 1d ) . in the second case like the first one , the endometrial clear cell carcinoma had been developed in an endometrial polyp in association with clear cell emgd . the criteria most commonly used for identification of serous emgd are glands or groups of small glands in superficial endometrium or a flat layer of superficial epithelium . since the level of atypia in these foci is not at the level of serous carcinoma , these lesions do not fit the designation of eic . the typical changes in emgd foci are nucleomegaly ( 2 - 4 times of resting endometrium nuclei ) , variably conspicuous nuclei , nuclear loss of polarity and changeable nuclear hyperchromasia.30 clear cell emgd is characterized by small glands or segments of slowly progressing nuclear atypia . based on grade of nuclear atypia , the grades of these lesions vary from 1 to 3 . histologically , the lesions lined by cells with atypical nuclei and clear or eosinophilic cytoplasm were considered grade 3 while the lesions with grade 1 or 2 nuclear atypia were designated clear cell emgd.31 based on the molecular and immunohistochemical studies in this background,32 it is reasonable to consider that emgd may be the true precancerous lesion of endometrial serous carcinoma on the assumption that serous carcinogenesis in the endometrium is also identical to other carcinogenetic processes in terms of stepwiss progressing rather than de novo arising from resting endometrium . in summary , this paper reported two cases of type ii endometrial carcinoma in dualistic model of endometrial carcinogenesis in association with presumed precursor lesion in one case developed on endometrial polyp . it should be emphasized that endometrial polyps especially the symptomatic and larger one and the polyps developed in postmenopausal patients have tendency to show malignant change . therefore , careful histologic examination of these lesions to find premalignant and malignant lesions should be emphasized .

endometrial polyps are common pathologic findings in gynecologic pathology practice . although malignant changes in these lesions are uncommon , numerous studies confirmed this association especially with endometrial serous and clear cell carcinoma . two cases of malignant endometrial polyps in association with presumed precursor lesion in one of them are presented .

three charged leptons are known , the electron and the heavier @xmath0 and @xmath1 leptons @xcite . relations between their mass values have been proposed @xcite . it is therefore interesting to note that the empirical formula @xmath2 , where @xmath3 is the mass of the electron , gives @xmath4 mev / c@xmath5 which is 0.5 per cent off the mass of the @xmath0-lepton @xcite , and @xmath6 mev / c@xmath5 which is 1.2 per cent off the mass of the @xmath1-lepton @xcite . that this formula reproduces the mass values of @xmath0 and of @xmath1 fairly well for integer values of @xmath7 as if @xmath7 is a quantum number suggests that @xmath0 and @xmath1 are excited states of the electron . if so , the electron would have to be a complex system of some constituents , e.g. rishons / preons @xcite . the electron and the proton are both stable particles . while a proton has constituents , has an electron constituents ? if so , and if they by analogy to the three quarks in a proton were two @xmath8 with electric charge @xmath9 each , and one @xmath10 with electric charge @xmath11 , where each @xmath8 and @xmath10 has lepton number @xmath12 , then a system with one @xmath8 and two @xmath10 could correspond to a neutrino . an @xmath13 system with lepton number zero could correspond to a boson . if @xmath8 and @xmath14 analogous to quarks may be `` dressed '' as proposed in fig.1 , an @xmath13 system may decay to a @xmath15 pair . `` spectators '' and `` leading particles '' are seen in @xmath16 reactions where a beam proton collides with the neutron in the deuteron with its proton as spectator @xcite , and in @xmath17 reactions with a leading meson due to a dressed spectator quark @xcite . if @xmath18 and @xmath19 have some structure , leading spectator constituents could by analogy be expected also in e.g. @xmath15 collisions . if they by analogy to quarks may be `` dressed '' , they may be observed . if one @xmath8 of a colliding @xmath18 is scattered and dressed to be an @xmath13 boson which decays to an @xmath15 pair , with the remaning @xmath20 system as a spectator which is dressed to be an @xmath21 electron as proposed in fig.2 , the result is trident production , i.e. @xmath22 . tridents have been observed @xcite and discussed from theoretical point of view @xcite . our fig.2 suggests an additional production model . our empirical mass formula and model for trident production suggest that electrons may have an inner structure and some constituents . particle data booklet 2004 , lbnl and cern , and phys . b * 592 * , 1(2004 ) . a.o.barut , phys . rev . lett . * 42 * , 1251 ( 1979 ) . p.caldirola , lett . nuovo cim . * 27 * , 225 ( 1980 ) . h.terazawa and m.yasue , phys . b * 307 * , 383 ( 1993 ) . y.koide , arxiv : hep - ph/0506247 v1 , 2005 . h.harari , phys . b * 86 * , 83 ( 1979 ) , and scientific american * 248 * , 48 ( 1983 ) . m.a.shupe , phys . b * 86 * , 87 ( 1979 ) . j.dugne , s.fredriksson , and j.hansson , europhys . lett . * 57 * , 188 ( 2002 ) . s.fredriksson , arxiv : hep - ph/0309213 v2 , sep . a.j.buchmann and m.l.schmid , phys . d * 71 * , 055002(2005 ) , and references therein . a.breakstone , e - print arhive : physics/0602118 , 2006 , and references therein . v.bakken and t.jacobsen , nuovo cim . a * 61 * , 219 ( 1981 ) , and references therein . f.balestra et al . , phys . b * 217 * , 43 ( 1989 ) . f.balestra et al . , phys . scripta * 43 * , 9 ( 1991 ) . p.h.fowler , d.h.perkins and c.f.powell , the study of elementary particles by the photographic method , pergamon press , london 1959 , and references therein . g.reading henry , phys . rev . * 154 * , 1534 ( 1967 ) , k.a.thompson and p.chen , slac pub 7776 ( 1998 ) , t.adams et al . , hep - ex/9811012 , 9 nov 1998 , and references therein .

for integer values of its free parameter , an empirical formula reproduces fairly well the mass values of the @xmath0 and @xmath1 leptons as if they were excited states of the electron . trident production might possibly be due to constituent collisions . pacs : 14.60.cd , 14.60.ef , 14.60.fg , 14.60.hi

SECTION 1. OVERSIGHT OF BROKERS AND DEALERS. (a) Definitions.--Title I of the Sarbanes-Oxley Act of 2002 is amended by adding at the end the following new section: ``SEC. 110. DEFINITIONS. ``For the purposes of this title, and notwithstanding section 2: ``(1) Audit.--The term `audit' means an examination of the financial statements of any issuer, broker, or dealer by an independent public accounting firm in accordance with the rules of the Board or the Commission (or, for the period preceding the adoption of applicable rules of the Board under section 103, in accordance with then-applicable generally accepted auditing and related standards for such purposes), for the purpose of expressing an opinion on such statements. ``(2) Audit report.--The term `audit report' means a document or other record-- ``(A) prepared following an audit performed for purposes of compliance by an issuer, broker, or dealer with the requirements of the securities laws; and ``(B) in which a public accounting firm either-- ``(i) sets forth the opinion of that firm regarding a financial statement, report, or other document; or ``(ii) asserts that no such opinion can be expressed. ``(3) Professional standards.--The term `professional standards' means-- ``(A) accounting principles that are-- ``(i) established by the standard setting body described in section 19(b) of the Securities Act of 1933, as amended by this Act, or prescribed by the Commission under section 19(a) of that Act (15 U.S.C. 17a(s)) or section 13(b) of the Securities Exchange Act of 1934 (15 U.S.C. 78a(m)); and ``(ii) relevant to audit reports for particular issuers, brokers, or dealers, or dealt with in the quality control system of a particular registered public accounting firm; and ``(B) auditing standards, standards for attestation engagements, quality control policies and procedures, ethical and competency standards, and independence standards (including rules implementing title II) that the Board or the Commission determines-- ``(i) relate to the preparation or issuance of audit reports for issuers, brokers, or dealers; and ``(ii) are established or adopted by the Board under section 103(a), or are promulgated as rules of the Commission. ``(4) Broker.--The term `broker' means a broker (as such term is defined in section 3(a)(4) of the Securities Exchange Act of 1934 (15 U.S.C. 78c(a)(4))) that is required to file a balance sheet, income statement, or other financial statement under section 17(e)(1)(A) of such Act (15 U.S.C. 78q(e)(1)(A)), where such balance sheet, income statement, or financial statement is required to be certified by a registered public accounting firm. ``(5) Dealer.--The term `dealer' means a dealer (as such term is defined in section 3(a)(5) of the Securities Exchange Act of 1934 (15 U.S.C. 78c(a)(5))) that is required to file a balance sheet, income statement, or other financial statement under section 17(e)(1)(A) of such Act (15 U.S.C. 78q(e)(1)(A)), where such balance sheet, income statement, or financial statement is required to be certified by a registered public accounting firm. ``(6) Self-regulatory organization.--The term `self- regulatory organization' has the same meaning as in section 3(a)(26) of the Securities Exchange Act of 1934 (15 U.S.C. 78c(a)(26)).''. (b) Establishment and Administration of the Public Company Accounting Oversight Board.--Section 101 of such Act is amended-- (1) by striking ``issuers'' each place it appears and inserting ``issuers, brokers, and dealers''; (2) in subsection (a), by striking ``public companies'' and inserting ``companies''; and (3) in subsection (a), by striking ``for companies the securities of which are sold to, and held by and for, public investors''. (c) Registration With the Board.--Section 102 of such Act is amended-- (1) by striking ``Beginning 180 days after the date of the determination of the Commission under section 101(d), it'' and inserting ``It''; (2) in subsections (a) and (b)(2)(G), by striking ``issuer'' each place it appears and inserting ``issuer, broker, or dealer''; and (3) by striking ``issuers'' and inserting ``issuers, brokers, and dealers''. (d) Auditing and Independence.--Section 103(a) of such Act is amended-- (1) in paragraph (1), by striking ``and such ethics standards'' and inserting ``such ethics standards, and such independence standards''; (2) in paragraph (2)(A)(iii), by striking ``describe in each audit report'' and inserting ``in each audit report for an issuer, describe''; and (3) in paragraph (2)(B)(i), by striking ``issuers'' and inserting ``issuers, brokers, and dealers''. (e) Inspections of Registered Public Accounting Firms.--Section 104 of such Act is amended-- (1) in subsection (a), by striking ``issuers'' and inserting ``issuers, brokers, and dealers''; (2) in subsection (b)(1)(A), by inserting before the semicolon the following ``or more than 100 brokers and dealers''; and (3) in subsection (b)(1)(B), by striking ``100 or fewer issuers'' and inserting ``issuers, brokers, or dealers, but is not described in subparagraph (A)''. (f) Investigations and Disciplinary Proceedings.--Section 105(c)(7)(B) of such Act is amended-- (1) by striking ``any issuer'' each place it appears and inserting ``any issuer, broker, or dealer''; and (2) by striking ``an issuer under this subsection'' and inserting ``a registered public accounting firm under this subsection''. (g) Foreign Public Accounting Firms.--Section 106 of such Act is amended-- (1) by striking ``issuer'' and inserting ``issuer, broker, or dealer''; and (2) by striking ``issuers'' and inserting ``issuers, brokers, or dealers''. (h) Funding.--Section 109 of such Act is amended-- (1) in subsection (c)(2), by striking ``subsection (i)'' and inserting ``subsection (j)''; (2) in subsection (d)(2), by striking ``allowing for differentiation among classes of issuers, as appropriate'' and inserting ``and among brokers and dealers that are not issuers, in accordance with subsection (h), and allowing for differentiation among classes of issuers and brokers and dealers, as appropriate''; (3) by redesignating subsections (h), (i), and (j) as subsections (i), (j), and (k), respectively; and (4) by inserting after subsection (g) the following new subsection: ``(h) Allocation of Accounting Support Fees Among Brokers and Dealers.-- ``(1) In general.--Any amount due from brokers and dealers that are not issuers (or a particular class of such brokers and dealers) under this section to fund the budget of the Board shall be allocated among and payable by such brokers and dealers (or such brokers and dealers in a particular class, as applicable). A broker or dealer's allocation shall be in proportion to the broker or dealer's net capital compared to the total net capital of all brokers and dealers that are not issuers, in accordance with the rules of the Board. ``(2) Obligation to pay.--Every broker or dealer shall pay the share of a reasonable annual accounting support fee or fees allocated to such broker or dealer under this section.''. (i) Referral of Investigations to a Self-Regulatory Organization.-- Section 105(b)(4)(B) of the Sarbanes-Oxley Act of 2002 is amended-- (1) by redesignating clauses (ii) and (iii) as clauses (iii) and (iv), respectively; and (2) by inserting after clause (i) the following new clause: ``(ii) to a self-regulatory organization, in the case of an investigation that concerns an audit report for a broker or dealer that is subject to the jurisdiction of such self- regulatory organization;''. (j) Use of Documents Related to an Inspection or Investigation.-- Section 105(b)(5)(B)(ii) of such Act is amended-- (1) in subclause (III), by striking ``and''; (2) in subclause (IV), by striking the comma and inserting ``; and''; and (3) by inserting after subclause (IV) the following new subclause: ``(V) a self-regulatory organization, with respect to an audit report for a broker or dealer that is subject to the jurisdiction of such self-regulatory organization,''. SEC. 2. EFFECTIVE DATE. The amendments made by this Act shall take effect 180 days after the date of the enactment of this Act.

Amends the Sarbanes-Oxley Act of 2002 to extend the regulatory jurisdiction of the Public Company Accounting Oversight Board to audit reports prepared by a domestic registered or foreign public accounting firm regarding issuers, brokers and dealers, and any companies subject to securities laws (currently only issuers and public companies). Directs the Board to: (1) establish standards for independence to be used by a registered public accounting firm; and (2) conduct annual inspections to assess compliance of each registered public accounting firm that regularly provides audit reports for more than 100 brokers and dealers. Declares it shall be unlawful for any person that is suspended or barred from being associated with a registered public accounting firm to willfully become, or remain associated with any broker or dealer (as well as, under current law, any issuer) in an accountancy or financial management capacity. Prescribes a formula for mandatory allocation among non-issuer brokers and dealers of accounting support fees due from them to fund the budget of the Board. Authorizes the Board to: (1) refer an investigation to a self-regulatory organization if the investigation concerns an audit report for a broker or dealer subject to the organization's jurisdiction; and (2) make available to the organization documents or information related to such an investigation or an inspection.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Health Freedom for Seniors Act''. SEC. 2. TRANSFER OF REQUIRED MINIMUM DISTRIBUTION FROM RETIREMENT PLAN TO HEALTH SAVINGS ACCOUNT. (a) Transfer From Retirement Plan.-- (1) Individual retirement accounts.--Section 408(d) of such Code is amended by adding at the end the following new paragraph: ``(10) Required minimum distribution transferred to health savings account.-- ``(A) In general.--In the case of an individual who has attained the age of 70\1/2\ and who elects the application of this paragraph for a taxable year, gross income of the individual for the taxable year does not include a qualified HSA transfer to the extent such transfer is otherwise includible in gross income. ``(B) Qualified hsa transfer.--For purposes of this paragraph, the term `qualified HSA transfer' means any distribution from an individual retirement plan-- ``(i) to a health savings account of the individual in a direct trustee-to-trustee transfer, ``(ii) to the extent such distribution does not exceed the required minimum distribution determined under section 401(a)(9) for the distribution calendar year ending during the taxable year. ``(C) Application of section 72.--Notwithstanding section 72, in determining the extent to which an amount is treated as a distribution for purposes of paragraph (1), the entire amount of the distribution shall be treated as includible in gross income without regard to paragraph (1) to the extent that such amount does not exceed the aggregate amount which would have been so includible if all amounts in all individual retirement plans of the individual were distributed during such taxable year and all such plans were treated as 1 contract for purposes of determining under section 72 the aggregate amount which would have been so includible. Proper adjustments shall be made in applying section 72 to other distributions in such taxable year and subsequent taxable years. ``(D) Coordination.--An election may not be made under subparagraph (A) for a taxable year for which an election is in effect under paragraph (9).''. (2) Other retirement plans.--Section 402 of the Internal Revenue Code of 1986 is amended by adding at the end the following new subsection: ``(m) Required Minimum Distribution Transferred to Health Savings Account.-- ``(1) In general.--In the case of an individual who has attained the age of 70\1/2\ and who elects the application of this subsection for a taxable year, gross income of the individual for the taxable year does not include a qualified HSA transfer to the extent such transfer is otherwise includible in gross income. ``(2) Qualified hsa transfer.--For purposes of this subsection, the term `qualified HSA transfer' means any distribution from an retirement plan-- ``(A) to a health savings account of the individual in a direct trustee-to-trustee transfer, ``(B) to the extent such distribution does not exceed the required minimum distribution determined under section 401(a)(9) for the distribution calendar year ending during the taxable year. ``(3) Application of section 72.--Notwithstanding section 72, in determining the extent to which an amount is treated as a distribution for purposes of paragraph (1), the entire amount of the distribution shall be treated as includible in gross income without regard to paragraph (1) to the extent that such amount does not exceed the aggregate amount which would have been so includible if all amounts in all eligible retirement plans of the individual were distributed during such taxable year and all such plans were treated as 1 contract for purposes of determining under section 72 the aggregate amount which would have been so includible. Proper adjustments shall be made in applying section 72 to other distributions in such taxable year and subsequent taxable years. ``(4) Eligible retirement plan.--For purposes of this subsection, the term `eligible retirement plan' has the meaning given such term by subsection (c)(8)(B) (determined without regard to clauses (i) and (ii) thereof).''. (b) Transfer to Health Savings Account.-- (1) In general.--Subparagraph (A) of section 223(d)(1) of such Code is amended by striking ``or'' at the end of clause (i), by striking the period at the end of clause (ii)(II) and inserting ``, or'', and by adding at the end the following new clause: ``(iii) unless it is in a qualified HSA transfer described in section 408(d)(10) or 402(m).''. (2) Excise tax inapplicable to qualified hsa transfer.-- Paragraph (1) of section 4973(g) of such Code is amended by inserting ``or in a qualified HSA transfer described in section 408(d)(10) or 402(m)'' after ``or 223(f)(5)''. (c) Effective Date.--The amendments made by this section shall apply to distributions made after the date of the enactment of this Act, in taxable years ending after such date.

Health Freedom for Seniors Act - Amends the Internal Revenue Code to allow tax-free transfers of required distributions after age 70 1/2 from an individual retirement account (IRA) and other tax-exempt retirement accounts to a health savings account.&nbsp; Exempts such transfers from the excise tax on excess contributions to tax-favored accounts and annuities.

neisseria gonorrhoeae ( ngo ) or gonococcus , a gram - negative diplococcus , is the etiological agent of the sexually transmitted bacterial infection ( sti ) gonorrhoea . gonorrhea is the second most frequent sti worldwide , where the total number of new cases of gonorrhea in adults was estimated to be 106.1 million cases out of 498.9 million with sti . clinical data also indicates that previous gonococcal infections do not improve immune response in patients with reinfection , which suggest that immunological memory is not induced by gonococcus . since the ineffective immune response against gonococcus is multifactorial , it has been hypothesized that it could be the sum of different mechanisms . one of them may be related to genital tissue properties , such as immune privileged site in the female tract [ 3 , 4 ] , while the other could involve evasion mechanisms intrinsically developed by the bacteria , such as phase and antigenic variations , epitope mimicry , and phagosome subversion to overcome immune defence . on the other hand , ngo has several mechanisms for evading complement - mediated defences , such as los sialylation and binding of porb molecules to the complement cascade inhibitors factor h and complement factor 4b - binding protein ( c4bp ) . the current data suggest that ngo is able to suppress the protective innate cellular immune response at different levels . even though phagocytosis by neutrophils ( pmn ) is generally a dead end for bacteria , it has been demonstrated that the number of intracellular ngo cells and the number of bacteria per intracellular phagosome inside neutrophils increase over time [ 1012 ] . moreover , ngo use multiple mechanisms to defend themselves against other ros ; nonoxidative antibacterial factors of pmn must act on the bacteria , which implies that these factors are not sufficient to clear infection . on the other hand , macrophages ( m ) and dendritic cells ( dc ) are critical cells in the innate immune response ; it has been showed that ngo potently inhibits the ability of antigen - primed bone - marrow - derived dc ( bmdc ) to trigger t - cell proliferation by inducing expression of both immunosuppressive cytokines and tolerance - inducing cell surface protein . recent findings of our laboratory have demonstrated that human monocyte - derived macrophages ( mdm ) were induced to a m2 profile when they were infected with ngo . no significant differences were observed in il-1 levels in comparison to gonococcus - treated macrophages and m0-macrophages suggesting that ngo could trigger insufficient il-1 levels to activate innate immune response , which leads to chronic inflammatory condition with no pathogen destruction . il-1 is described as a proinflammatory cytokine that is crucial for host - defense responses to infection and injury . il-1 needs two independent signals to be properly active and functionally released : a priming step where a first signal in response to pathogen associated molecular patterns ( pamp ) induces pro - il-1 expression and a second signal which transforms pro - il-1 in its mature and functional form ( il-1 ) for proper release . this second signal is mediated by a protein complex named inflammasome , which prompts activation of the il-1 converting enzyme caspase-1 , although it has been shown in other cells like pmn that production of il-1 is not entirely dependent on caspase-1 and several serine proteases including cg , ne , and pr3 can also process pro - il-1 . in macrophages , multiple distinct bacterial products signals stimulate the nlrp3 inflammasome , resulting in the proteolytic activation of caspase-1 [ 2022 ] . nlrp3 has a tripartite structure with a pamp / danger associated molecular patterns ( damp ) sensing c - terminal leucine - rich repeat ( lrr ) , a central nucleotide binding ( or nacht ) domain , and an n - terminal pyrin domain ( pyd ) . the pyd domain of nlrp3 recruits the adaptor molecule apoptosis - associated speck - like protein containing a caspase recruitment domain ( asc ) , which recruits pro - caspase-1 and produces caspase-1 activation . thus , the searching for strategies to overcome this disruption is an important goal to be addressed . to date , three models of nlrp3 activation in response to microbial ligands have been proposed : k efflux , lysosomal rupture , and ros production [ 2527 ] . additionally , endogenous damp such as extracellular atp on macrophages produces a variety of cellular effects , including a maturation and release of il-1 by inflammasome activation . atp can be secreted under a broad range of conditions including antigen presentation and macrophage interaction with bacteria or microbial products such as lps . in vitro studies have demonstrated that atp ligation of the p2x7 also stimulates killing of intracellular chlamydiae and mycobacteria in infected macrophages [ 3032 ] . in addition , gingival epithelial cells infected with p. gingivalis secrete il-1 only after stimulation with extracellular atp . therefore , we tested the hypothesis that the addition of an exogenous source of atp promotes the il-1 processing and release during ngo infection in human monocyte - derived macrophages ( mdm ) . we demonstrated that atp stimulation increases the secretion of il-1 in ngo - infected mdm . interestingly , high levels of il-1 did not correlate with the activation of inflammasome - mediated caspase-1 , as previously observed in other microorganisms [ 3335 ] suggesting that atp - induced il-1 secretion could be acting at the level of mechanisms related to vesicle trafficking or pore formation . the study was approved by the scientific ethics committee of hospital clnico universidad de chile ( approval number 58 ) . after sample collection , a trial number was assigned to each donor with their demographic data and the database was anonymised . neisseria gonorrhoeae p9 - 17 strain used in this study was kindly provided by dr . gonococcal vials were taken from frozen stocks , plated on thayer martin plates ( laboratoriolinsan , chile ) , and cultured at 37c in 5% co2 for 18 to 20 hours . human monocytes were obtained from normal blood donor buffy coats by two - step gradient centrifugation followed by an additional step using rosettesep human monocyte enrichment cocktail ( stemcell technologies ) . monocyte - derived macrophages ( mdm ) were obtained by culturing monocytes ( 84% cd14 ) for 7 days in rpmi 1640 ( gibco , invitrogen corporation ) supplemented with 10% fbs ( hyclone ) , 50 u / ml penicillin , 50 g / ml streptomycin ( gibco invitrogen ) , and 50 ng / ml of m - csf ( miltenyibiotec ) in 6-well plates at a density of 2 10 cells per well . the necessary amount of atp ( product number a6419 sigma - aldrich , mo , usa ) for experiment was weighed in a eppendorf tube . ten minutes before cells stimulation , atp was diluted in nonsupplemented rpmi-1640 medium to generate a 10 mm atp solution . then atp solution was filtered using syringe filter ( pore size 0.2 m ) and it was immediately added to the cells to reach a 5 mm concentration . mdm were infected with ngo at a multiplicity of infection ( moi ) of 100 for 4 hours at 37c and 5% co2 . then cultures were treated with gentamicin ( 100 g / ml ) ( invitrogen corp . , carlsbad , ca ) to kill extracellular bacteria for 2 h at 37c and 5% co2 . medium was replaced by nonsupplemented ( serum - free and antibiotic - free ) rpmi and then 5 mm atp ( sigma - aldrich , mo , usa ) was added and incubated for 30 minutes at 37c 5% co2 . finally , the supernatants were collected for il-1 , while cells were lysed for rna extraction . il-1 levels were measured in supernatants immediately after 30-minute treatment with atp by enzyme - linked immunosorbent assays using elisa ready - set - go ! ( ebioscience , usa , sensitivity 2 pg / ml ) , according to the manufacturer 's instructions . reverse transcription ( 5 g ) was performed using the transcriptor first - strand cdna synthesis kit following the manufacturer 's recommendations ( roche applied science , mannheim , germany ) . to quantify the mrna expression of il-1 , nlrp3 , asc , and casp-1 , 50 ng of cdna was amplified by quantitative real - time pcr using the appropriate primers and the sybrgreen master mix ( fermentas ) in a stepone real - time pcr system ( applied biosystems , california , usa ) . the cycle program used was 95c for 10 min , followed by 40 cycles of 95c for 15 s , 60c for 30 s , and 72c for 30 s. primer sequences were as follows : 5-cttcctttccagtttgctgc-3 forward and 5-tctcgcagtccacttccttt-3 reverse for nlrp3 , 5-agtttcacaccagcctggaa-3 forward and 5-ttttcaagctggcttttcgt-3 reverse for asc , 5-gcccaagtttgaaggacaaa-3 forward and 5-ggtgtggaagagcagaaagc-3 reverse for casp-1 , 5-ctgtcctgcgtgttgaaaga-3 forward and 5-ttgggtaatttttgggatctaca-3 reverse for il-1 , and 5-ctaacacgggaaacctcac-3 forward and 5-cgctccaccaactaagaacg-3 reverse for 18s . the fold change in expression of the target gene relative to the 18s endogenous control was set at 2 , where ct = ( cttarget ct18s ) stimulated ( cttarget ct18s ) unstimulated . a fam - flica caspase-1 assay kit ( immunochemistry technologies ) flica was diluted and added to wells containing infected , atp - treated or nontreated cells . the cells were cultured for 4 hours and mdm were then collected and subjected to flow - cytometric analysis ( facscalibur , becton - dickinson , san diego , ca , usa ) to quantify the percentage of fam - flica - positive mdm . apoptosis of mdm cells was measured using an fitc annexin v apoptosis detection kit with 7-aad ( biolegend ) . macrophages were grown on 12 mm coverslips in 24-well plates and were treated using same conditions of cell culture previously described . after 30 minutes of atp stimulation , cells supernatant was removed and coverslips were washed twice with sterile pbs 1x and then cells were fixed with 4% paraformaldehyde in 100 mm pipes buffer ph 6.8 , containing 40 mm koh , 2 mm egta , and 2 mm mgcl2 for 30 minutes . then , cells were washed three times with washing solution ( 50 mmtris buffer ph 7.6 containing 0.15 n nacl and 0.1% sodium azide ) and permeabilized with 0.1% triton x-100 in washing solution for 10 min , washed twice , and then blocked with 2% bovine serum albumin for 60 min . intracellular il-1 was evaluated by staining cells with an anti - il-1 rb pab at 1 : 100 dilution ( ab2105 , abcam , usa ) , followed by a goat anti - rabbit igg ( h+l ) secondary antibody , alexa fluor 488 conjugate ( a11008 , life technologies ) at 1 : 100 dilution . coverslips were washed twice and mounted on microscope slides with dako fluorescent mounting medium ( dako north america inc . , ca , usa ) and samples were visualized with a confocal microscopy ( carl zeiss , model lsm700 ) . previous findings of our laboratory showed that il-1 present in supernatants from ngo- infected macrophages at different mois was not significantly different from nonstimulated mdm . to further explore in those results , we aimed to detect the presence of il-1 from mdm infected with ngo at 100 moi . as shown in figure 1(a ) , macrophages infected with ngo did not show more il-1 secretion than noninfected macrophages . indeed , il-1 secretion by macrophages exposed to lps was much more than il-1 secreted by ngo - infected macrophages . however , when total mrna levels of pro - il-1 were assessed by qpcr , we observed that pro - il-1 rna levels were highly induced in response to gonococcal infection ( figure 1(b ) ) , indicating that ngo is able to trigger the signaling pathway to start pro - il-1 synthesis . since the synthesis of mature il-1 depends on the activation of nlrp3 inflammasome signaling pathway as a second signal , we aimed to stimulate the nlrp3 inflammasome in ngo - infected mdm using a cognate agonist ( atp ) , to establish whether gonococcus are modifying nlrp3 inflammasome activity . our results showed that the low levels of secreted il-1 from ngo - infected mdm were increased in presence of atp ( figure 2 ) . the use of atp was able to induce a similar cytokine production in ngo - infected mdm as lps stimulated mdm . since one of the strategies adopted by bacterial pathogens is the inflammasome subversion and the use of atp contributes to the host immune response against intracellular bacteria , through its ability to stimulate p2x7-dependent il-1 secretion , we decided to study whether inflammasome components nlrp3 , asc , and caspase-1 ( casp-1 ) might be modified by the atp treatment in infected mdm . data obtained from 4 independent experiments showed that atp only modified the rna expression levels of nlrp3 in infected mdm , while the levels of asc and casp-1 showed no significant differences with nonstimulated infected cells ( table 1 ) . caspase-1 activation is necessary to process pro - il-1 onto mature il-1 , but atp was not able to produce transcriptional activation of casp-1 ; thus we assessed if atp is able to modify caspase-1 activity in ngo - infected mdm , using a fluorescent inhibitor probe fam - yvad - fmk to label active caspase-1 enzyme . data obtained from 3 independent experiments showed that atp treatment of ngo - infected mdm was not able to induce the activation of caspase-1 in infected cells ( figure 3 ) . although trypan blue staining showed that most cells were viable after infection and atp treatment , we performed a fitc annexin v ( av ) with 7-aminoactinomycin ( 7-aad ) apoptosis detection assay to monitor atp - induced cell pyroptosis . considering that the feature of pyroptosis is the positive staining with av in contrast to negative 7-aad staining , we compared the percentage of av 7-aad cells . atp was able to induce an early stage of apoptosis in gonococcus - infected mdm ( figure 4 ) . since nlrp3 inflammasome is not involved in the atp - induced il-1 secretion in gonococcus - infected mdm , we aimed to observe the ability of atp to induce a nonclassical il-1 secretion by microvesicles formation . ngo - infected mdm treated with atp were observed for intracellular distribution of mature il-1 by immunofluorescence using confocal microscopy . notably , atp treatment of ngo - infected mdm defined an increase of positive staining for il-1 with a distinctive pattern of distribution ( figure 5(c ) ) as a focus formation towards membrane . the current data suggest that ngo produce lack of induction of protective immune response in macrophages and dendritic cell [ 14 , 15 , 42 ] . recent findings of our laboratory have recognized that mdm are induced to a m2 profile when they are infected with ngo and do not reach significant differences in il-1 levels between gonococcus - treated macrophages and m0-macrophages . in this work , we confirmed the lower levels of il-1 in ngo - infected human mdm ( figure 1(a ) ) . our data differ with those reported by duncan et al . which showed that ngo can promote nlrp3 activation and il-1 secretion in human macrophages thp-1 cells . this discrepancy might be explained by the remarkable difference between thp-1 cell line ( monocytic nature ) and macrophages . the increase in the constitutive caspase-1 activation and subsequent il-1 secretion by monocytes following tlr stimulation is well recognized , whereas macrophages require a second signal . moreover , we showed that macrophages skewed from the m1 to m2 states , when infected with ngo , have low levels of the toll - like receptor-4 ( tlr-4 ) , which has been shown to play a key role in the induction of inflammatory pathways . our first results showed lower levels of mature il-1 in ngo - infected human mdm supernatants . however , when we looked at transcript level , we showed a sizable induction of il-1 rna upon gonococcal infection ( figure 1(b ) ) . the differences in transcription versus translation of il-1 induced by gonococcus in mdm cells could be due to disruption in inflammasome activity as shown in others pathogens . since atp contributes to the host immune response against intracellular bacteria through its ability to stimulate il-1 secretion , we showed that atp treatment of gonococcus - infected mdm cells is able to restore il-1 secretion ( figure 2 ) as shown in gingival epithelial cells infected with p. gingivalis , which only secrete il-1 after stimulation with extracellular atp . after having established the effect of atp on il-1 production by gonococcus - treated mdm , we examined the mrna expression of nlrp3 inflammasome - associated genes : nlrp3 , asc , and casp-1 to assess inflammasome transcriptional activity in presence of atp . only the nlrp3 transcript was upregulated in ngo - infected mdm cells treated with atp ( table 1 ) . to date , the exact action mechanism of atp on transcription of inflammasome is unknown . however , it is not surprising that expression of nlrp3 was affected by atp , because the atp release may act as a danger signal to mobilize intracellular calcium , further modulating nf-b activation acting through a p2y receptor / phospholipase - c / calcium signaling pathway . in this context , the existence of binding sequences to nf-b has been demonstrated in the nlrp3 promoter in murine macrophages . interestingly , we did not detect any changes in transcription levels of asc and casp-1 in ngo - infected macrophages treated with atp ( table 1 ) . the nonchange in levels of expression of asc and casp-1 could be explained because unlike nlrp3 , its transcriptional regulation is not associated with myd88 and nf-b . in line with this , we think that the absence of changes in transcription level of asc could be affecting caspase-1 activity in response to atp , because the function of adaptor protein asc is enabling the activation of caspase-1 in inflammasome . indeed , asc macrophages secreted much less mature il-1 than their wild - type counterparts in s. typhimurium - induced caspase-1 activation model . although we did not observe changes in transcription levels of casp-1 , we assessed the caspase-1 activity in ngo - infected mdm cells treated with atp . we did not observe any changes in caspase-1 activity between infected mdm cells with or without atp . interestingly , in our model of mdm cells , infection with ngo does not induce pyroptosis compared with uninfected mdm cells , unlike what is reported by duncan et al . , who showed that ngo infection promotes nlrp3-dependent thp-1 cell death via pyronecrosis . however , when infected mdm cells were treated with atp , we observed an induction of early apoptotic cells ( av 7aad ) . even though pyroptosis is caspase-1-dependent , we do not discard other mechanisms that induce apoptosis . as showed by previous works , extracellular atp induces apoptotic signaling in different cells types using different pathways that link purinergic receptors to induce apoptosis and necrosis [ 5355 ] . our results showed that atp was not able to activate caspase-1 at rna and protein level in ngo - infected macrophages ( table 1 and figure 3 ) . since pro - il-1 and pro - il-18 are the substrates in vitro and in vivo of caspase-1 , we hypothesize that il-1 secretion induced by atp in ngo - infected macrophages could be at an alternative level from pro - il-1 processing by nlrp3 inflammasome . in a recent report studying porphyromonas gingivalis - infected mice macrophages , il-1 secretion was inhibited by the pathogen fimbriae through inflammasome independent p2x7r mechanisms , suggesting that , in this pathological context , the il-1 absence was due to unknown secretory signaling pathway involving p2x7r . using confocal microscopy , we attempted to localize the presence and distribution of mature il-1 , where it was clearly visible that ngo - infected mdm induced a pattern of the mature il-1 arrangement with stained points dispersed in the cells . this dispersion of mature il-1 as stained points was changed to concentrated and polarized points ( figure 5 ) . since the secretion mechanism to il-1 does not correspond to the classic cytokine er - golgi pathway and its secretion could be carried by intracellular vesicles , secretion lysosome exocytosis , or direct passing through the cellular membrane , we speculate that one of the possibilities in the downmodulation of il-1 secretion by gonococcus could be due to a mechanism related to pore formation . indeed , during pyroptosis , pores open in the cell membrane and this structural change could promote the cellular release of interleukin-1 . moreover , as shown by pelegrin and surprenant , pannexin-1 ( panx1 ) could be a functional link between p2x7r - activated large pore formation and cytokine release in macrophage . in this sense , the activation of p2x7-receptor triggers the recruitment of an accessory pore - forming mechanism [ 59 , 60 ] ; the panx1 protein knockdown and panx1-mimetic inhibitory peptide are able to block atp - mediated il-1 release in mouse and human macrophage . this issue was not assessed in this work and further studies are required to investigate this phenomenon . in this work , we demonstrated that n. gonorrhoeae probably evades host defence by not activating the nlrp3 inflammasome in macrophages and showed that extracellular atp is likely to act at the level of vesicle trafficking or pore formation . a better understanding of mechanisms that produce the il-1 downmodulation by gonococcus will further contribute to the advance of our knowledge on n. gonorrhoeae pathogenesis and let us find a therapeutic strategy for treatment of gonococcus infection .

neisseria gonorrhoeae ( ngo ) has developed multiple immune evasion mechanisms involving the innate and adaptive immune responses . recent findings have reported that ngo reduces the il-1 secretion of infected human monocyte - derived macrophages ( mdm ) . here , we investigate the role of adenosine triphosphate ( atp ) in production and release of il-1 in ngo - infected mdm . we found that the exposure of ngo - infected mdm to atp increases il-1 levels about ten times compared with unexposed ngo - infected mdm ( p < 0.01 ) . however , we did not observe any changes in inflammasome transcriptional activation of speck - like protein containing a caspase recruitment domain ( card ) ( asc , p > 0.05 ) and caspase-1 ( casp1 , p > 0.05 ) . in addition , atp was not able to modify caspase-1 activity in ngo - infected mdm but was able to increase pyroptosis ( p > 0.01 ) . notably atp treatment defined an increase of positive staining for il-1 with a distinctive intracellular pattern of distribution . collectively , these data demonstrate that atp induces il-1 secretion by a mechanism not related to the nlrp3/asc / caspase-1 axis and likely is acting at the level of vesicle trafficking or pore formation .

thyroid nodules are common in the general population with a prevalence of 5% - 7% ( by palpation ) . the estimated prevalence of clinically inapparent thyroid nodules ( by ultrasound ) is even higher , around 20% to 76% with similar prevalence in autopsy studies . the initial evaluation of thyroid nodules commonly involves thyroid function tests , an ultrasound ( usg ) , and fine needle aspiration biopsy ( fnab ) . on fnab , 60% 80% of the nodules are classified as benign , and 3.5% 5% as malignant . these require further evaluation to distinguish between follicular adenoma ( fa ) , adenomatoid hyperplasia , follicular thyroid carcinoma ( ftc ) , and follicular variant of papillary thyroid carcinoma ( ptc ) , and these patients currently have to undergo ( diagnostic ) surgery , which will eventually detect thyroid malignancy in about 20% of these patients . this means that 80% of the thyroid fnab samples that were classified as indeterminate by cytology will undergo an unnecessary diagnostic thyroidectomy , which has its own risk of complications . thus , there is a need to better delineate this indeterminate category . in this article , we attempt to review the available literature on the molecular markers , which are increasingly being studied for their diagnostic utility in assessing thyroid nodules . the various molecular markers consist of gene mutations , gene re arrangements , rna - based assays , and immunohistochemical markers . genetic mutations and gene re- arrangements braf mutationthe map kinase pathway ( mapk pathway ) is an intracellular signaling pathway , which plays a fundamental role in cell functions like proliferation , differentiation , apoptosis , survival , and , tumorigenesis when aberrantly activated . the t1799a point mutation , which causes the v600e amino acid change in the braf protein , is the most common , accounting for more than 90% of all the braf gene mutations . braf mutations are the most commonly detected abnormality in ptc , and are seen in about 45% of sporadic adult cases but less frequently ( 0% - 12% ) in pediatric and radiation - induced tumors . in addition to papillary carcinomas , this mutation is also found in poorly - differentiated and anaplastic carcinomas . it is rarely seen in the follicular carcinomas ( 1% - 2% ) or benign thyroid nodules , and hence it seems to be a specific marker for ptc . also , it may assist prognostically , as patients with braf - positive ptcs have been shown to have more aggressive disease at presentation , with higher rates of extrathyroidal extension , lymph node metastasis , and tumor recurrence after initial treatment.when studied as a diagnostic marker , a meta - analysis of 18 studies on braf mutations showed that the rate of malignancy in braf - positive nodules tested by fna was 99.8% . importantly , 15% to 39% of these braf - positive fna samples were indeterminate or non - diagnostic by cytology , demonstrating its utility in establishing a definitive diagnosis of cancer in nodules with indeterminate cytology.ras mutationras proteins are positioned at the inner surface of the plasma membrane where they transduce extracellular ligand - mediated stimuli to a cascade of cytoplasmic proteins and map kinases , which , in turn , influence cell growth , differentiation , and apoptosis . ras mutation are the second most common mutation found in thyroid cancers , and the most common type of ras mutations in thyroid cancer is the n-2-ras mutation in codon 61 . the frequency of ras mutations ranges from 0.9% to 23.9% in ftc , 0.6% to 15.2 % in benign follicular adenomas , and these are very rare in colloid nodules ( 1% - 2.5% ) and papillary carcinoma ( 0.3% to 5% ) . these mutations , especially those of k - ras , are also a marker for aggressive cancer behavior , large tumor size , vascular invasion , and distant metastasis.when studied as a diagnostic marker in fna , ras mutation was found to confer a 87.5% probability of malignancy , including a 62.5% probability of a ptc ( mainly follicular variant ) and a 25% probability of a ftc , thus justifying the recommendation of surgery for patients with ras - positive nodules . however , 12.5% of benign follicular adenomas are false positive for ras mutation , and these may be precursors of ftc , as has been shown in some mouse models.ret-ptc re - arrangementthe ret proto - oncogene encodes a cell membrane tyrosine - kinase receptor protein . the ret - ptc gene represents an intra - chromosomal gene re - arrangement wherein the ret tyrosine - kinase ( ret - tk ) domain gets fused to the 5-terminal region of a heterologous gene , producing fusion genes that give rise to a constitutively activated form . ret - ptc re - arrangements were identified in ptcs before ret was recognized as the susceptibility gene for multiple endocrine neoplasia 2 ( men2 ) . there are now at least 15 types of ret - ptc re - arrangements involving ret and 10 different genes , the commonest being ret - ptc1 and ret - ptc 3 . they are also known to occur in follicular adenomas , adenomatous goiter , and in hashimoto 's thyroiditis , though in such instances , the pathology is heterogeneous while in ptc , there is clonal evolution of ret / ptc positive cells.carol et al . observed that the identification of ret / ptc gene re - arrangements as an adjunct to cytology in fnacs refined the diagnosis of ptc in 60% of cases that would otherwise have been considered indeterminate and in 33% of those considered insufficient for cytological diagnosis.pax8/ppar rearrangementpax8/ppar re - arrangement is a result of t(2;3)(q13;p25 ) translocation that leads to the fusion between the pax8 gene and the peroxisome proliferator - activated receptor ( ppar ) gene.pax8/ppar re - arrangement is described to be present in 26% - 40% of ftc , variably from 0% - 37% in follicular variant of ptc and much less in hurthle cell carcinoma ( 1 in 30 in one study ) and hyperplastic nodules . ftc patients with ppar re - arrangement more frequently have vascular invasion , areas of solid / nested tumor histology , and previous non - thyroid cancers . thus , pax8/ppar re - arrangement typically correlates with the presence of malignancy , although in prospective studies , only a few positive cases have been reported so far.use of a combination of markerscurrently , no single genetic marker is specific and sensitive enough to reliably make a diagnosis of benign versus malignant lesion , and hence there may be an advantage using a combination of these markers . , studied a of 1,056 consecutive thyroid fna samples with indeterminate cytology for determination of braf , ras , ret / ptc , and pax8-ppar. they reported that in specific categories of indeterminate cytology , i.e. atypia / flus ( follicular lesion of undetermined significance ) , follicular neoplasm / suspicious for a follicular neoplasm , and suspicious for malignant cells , the detection of any mutation conferred the risk of malignancy of 88% , 87% , and 95% , respectively , as against the risk of malignancy based on cytology alone was 14% , 27% , and 54% , respectively . the risk of cancer in mutation - negative nodules was 6% , 14% , and 28% , respectively . the overall cancer rate for mutation - negative status was 6% , and among these , only 2.3% were invasive and 0.5% had extra - thyroidal extension . hence , they recommended total thyroidectomy in mutation - positive status . for mutation - negative patients , recently reviewed and re - analyzed the literature including 16 studies with 1 mutation [ e.g. , braf or ret / ptc ] and 4 studies that have analyzed combination of several mutations ( braf , ras , ret / ptc , and pax8/ppar ) . more importantly , they excluded the samples with fna cytological diagnosis of suspicious of malignancy since these have high chances of malignancy ( 50% - 70% ) and might falsely inflate the performance of molecular markers . for these 4 studies , which were re - analyzed , the combined sensitivity and specificity were 63.7% and 98% , respectively . there were 5 false positives in the 4 studies and in all of them , the ras mutations were detected in follicular adenomas , and the postulated explanation was that it might be a precursor of malignancy on the background of hashimoto 's thyroiditis.one such panel for analysis of combination of markers , which is commercially available , is the asuragen mirinform molecular panel , which includes various mutations in braf , ras and ret - ptc and pax8-pparg gene re - arrangements . rna - based markers micro rna ( mirna)micrornas are 21 to 22 nucleotide segments of non - coding rna that have a key role in post - transcriptional gene regulation ( mainly inhibitory ) through complementary binding that mediates the translation and degradation of messenger rna.many studies have found up - regulation of different mirnas in ptcs using microarray , out of which mir-221 and -222 are the most consistently up - regulated in ptcs while mir-1 , -191 , -486 , and -451 are consistently down-regulated.nikiforova et al . observed that the most up - regulated mirnas in conventional ftcs were mir-187 , -224 , -155 , -222 , and -221 , and those in oncocytic variants were mir-187 , -221 , -339 , -183 , -222 , and -197 . they observed that when at least one mirna was overexpressed more than 2-fold , the sensitivity of tumor detection was 100% , specificity 94% , and accuracy 95% , whereas when 3 or more mirnas were up - regulated , the sensitivity of tumor detection was 88% , specificity 100% , and accuracy 98%.however , no large - scale , prospective , multicenter trial investigating microrna has yet been performed . presently , microrna testing of thyroid aspirates is not commercially available and is offered only through research protocols.thyroid stimulating hormone receptor mrnabecause thyroid cancer cells express functional tsh receptors ( tshr ) , tshr - mrna in peripheral blood might serve as a tissue / cancer - specific marker . tshr - m rna is used as a peripheral blood marker in the follow up of patients of well - differentiated thyroid malignancy.the diagnostic value of circulating tshr mrna , for pre - operative detection of differentiated thyroid carcinoma ( dtc ) in patients with thyroid nodules , was evaluated in 258 subjects ( with 51 normal subjects ) , by chia et al . they demonstrated a sensitivity of 90% and specificity of 80% of tsh mrna to predict malignancy , especially in those with indeterminate cytology on fnac.gene expression ( micro array ) analysisunlike single gene mutations or re - arrangements , microarray diagnostic tests can detect hundreds of expressed genes . it involves the use of multi - gene expression classifiers that assess gene expression from mrna isolated from needle washings during a standard fna procedure.based on the previous work by chudova et al . on whole genome assays , alexander et al . conducted a large , prospective , multicenter validation study of a gene expression classifier using 167 genes on 265 indeterminate nodules and found 92% sensitivity with a specificity of 52% to diagnose malignancy . were 95% , 94% , and 85% , respectively.however , the analysis revealed 7 aspirates with false negative results , some of which might be due to insufficient sampling of the nodule . they suggested that due to high negative predictive value , the gec can be used as a rule out test to avoid unnecessary surgeries . this gene classifier ( veracyte affirma gec ) is available commercially after the above validation study.immunohistochemical markersin recent years , immunohistological markers like galectin-3 , hbme-1 , fibronectin- , cited-1 , and cytokeratin-19 have been investigated for their role in discrimination between benign and malignant nodules . however , they have not been adopted in routine practice , mainly because of different methods used and because these markers show prominent overlap between follicular adenoma and differentiated thyroid carcinomas.other markersthere are certain other potential markers like trk mutations ( too low prevalence of < 5 % in ptcs ) , ubch10 and hmga2 and htert , which are awaiting further large scale studies . map kinase pathway ( mapk pathway ) is an intracellular signaling pathway , which plays a fundamental role in cell functions like proliferation , differentiation , apoptosis , survival , and , tumorigenesis when aberrantly activated . the t1799a point mutation , which causes the v600e amino acid change in the braf protein , is the most common , accounting for more than 90% of all the braf gene mutations . braf mutations are the most commonly detected abnormality in ptc , and are seen in about 45% of sporadic adult cases but less frequently ( 0% - 12% ) in pediatric and radiation - induced tumors . in addition to papillary carcinomas , this mutation is also found in poorly - differentiated and anaplastic carcinomas . it is rarely seen in the follicular carcinomas ( 1% - 2% ) or benign thyroid nodules , and hence it seems to be a specific marker for ptc . also , it may assist prognostically , as patients with braf - positive ptcs have been shown to have more aggressive disease at presentation , with higher rates of extrathyroidal extension , lymph node metastasis , and tumor recurrence after initial treatment.when studied as a diagnostic marker , a meta - analysis of 18 studies on braf mutations showed that the rate of malignancy in braf - positive nodules tested by fna was 99.8% . importantly , 15% to 39% of these braf - positive fna samples were indeterminate or non - diagnostic by cytology , demonstrating its utility in establishing a definitive diagnosis of cancer in nodules with indeterminate cytology.ras mutationras proteins are positioned at the inner surface of the plasma membrane where they transduce extracellular ligand - mediated stimuli to a cascade of cytoplasmic proteins and map kinases , which , in turn , influence cell growth , differentiation , and apoptosis . ras mutation are the second most common mutation found in thyroid cancers , and the most common type of ras mutations in thyroid cancer is the n-2-ras mutation in codon 61 . the frequency of ras mutations ranges from 0.9% to 23.9% in ftc , 0.6% to 15.2 % in benign follicular adenomas , and these are very rare in colloid nodules ( 1% - 2.5% ) and papillary carcinoma ( 0.3% to 5% ) . these mutations , especially those of k - ras , are also a marker for aggressive cancer behavior , large tumor size , vascular invasion , and distant metastasis.when studied as a diagnostic marker in fna , ras mutation was found to confer a 87.5% probability of malignancy , including a 62.5% probability of a ptc ( mainly follicular variant ) and a 25% probability of a ftc , thus justifying the recommendation of surgery for patients with ras - positive nodules . however , 12.5% of benign follicular adenomas are false positive for ras mutation , and these may be precursors of ftc , as has been shown in some mouse models.ret-ptc re - arrangementthe ret proto - oncogene encodes a cell membrane tyrosine - kinase receptor protein . the ret - ptc gene represents an intra - chromosomal gene re - arrangement wherein the ret tyrosine - kinase ( ret - tk ) domain gets fused to the 5-terminal region of a heterologous gene , producing fusion genes that give rise to a constitutively activated form . ret - ptc re - arrangements were identified in ptcs before ret was recognized as the susceptibility gene for multiple endocrine neoplasia 2 ( men2 ) . there are now at least 15 types of ret - ptc re - arrangements involving ret and 10 different genes , the commonest being ret - ptc1 and ret - ptc 3 . they are also known to occur in follicular adenomas , adenomatous goiter , and in hashimoto 's thyroiditis , though in such instances , the pathology is heterogeneous while in ptc , there is clonal evolution of ret / ptc positive cells.carol et al . observed that the identification of ret / ptc gene re - arrangements as an adjunct to cytology in fnacs refined the diagnosis of ptc in 60% of cases that would otherwise have been considered indeterminate and in 33% of those considered insufficient for cytological diagnosis.pax8/ppar rearrangementpax8/ppar re - arrangement is a result of t(2;3)(q13;p25 ) translocation that leads to the fusion between the pax8 gene and the peroxisome proliferator - activated receptor ( ppar ) gene.pax8/ppar re - arrangement is described to be present in 26% - 40% of ftc , variably from 0% - 37% in follicular variant of ptc and much less in hurthle cell carcinoma ( 1 in 30 in one study ) and hyperplastic nodules . ftc patients with ppar re - arrangement more frequently have vascular invasion , areas of solid / nested tumor histology , and previous non - thyroid cancers . thus , pax8/ppar re - arrangement typically correlates with the presence of malignancy , although in prospective studies , only a few positive cases have been reported so far.use of a combination of markerscurrently , no single genetic marker is specific and sensitive enough to reliably make a diagnosis of benign versus malignant lesion , and hence there may be an advantage using a combination of these markers . , studied a of 1,056 consecutive thyroid fna samples with indeterminate cytology for determination of braf , ras , ret / ptc , and pax8-ppar. they reported that in specific categories of indeterminate cytology , i.e. atypia / flus ( follicular lesion of undetermined significance ) , follicular neoplasm / suspicious for a follicular neoplasm , and suspicious for malignant cells , the detection of any mutation conferred the risk of malignancy of 88% , 87% , and 95% , respectively , as against the risk of malignancy based on cytology alone was 14% , 27% , and 54% , respectively . the risk of cancer in mutation - negative nodules was 6% , 14% , and 28% , respectively . the overall cancer rate for mutation - negative status was 6% , and among these , only 2.3% were invasive and 0.5% had extra - thyroidal extension . hence , they recommended total thyroidectomy in mutation - positive status . for mutation - negative patients , recently reviewed and re - analyzed the literature including 16 studies with 1 mutation [ e.g. , braf or ret / ptc ] and 4 studies that have analyzed combination of several mutations ( braf , ras , ret / ptc , and pax8/ppar ) . more importantly , they excluded the samples with fna cytological diagnosis of suspicious of malignancy since these have high chances of malignancy ( 50% - 70% ) and might falsely inflate the performance of molecular markers . for these 4 studies , which were re - analyzed , the combined sensitivity and specificity were 63.7% and 98% , respectively . there were 5 false positives in the 4 studies and in all of them , the ras mutations were detected in follicular adenomas , and the postulated explanation was that it might be a precursor of malignancy on the background of hashimoto 's thyroiditis.one such panel for analysis of combination of markers , which is commercially available , is the asuragen mirinform molecular panel , which includes various mutations in braf , ras and ret - ptc and pax8-pparg gene re - arrangements . the map kinase pathway ( mapk pathway ) is an intracellular signaling pathway , which plays a fundamental role in cell functions like proliferation , differentiation , apoptosis , survival , and , tumorigenesis when aberrantly activated . the t1799a point mutation , which causes the v600e amino acid change in the braf protein , is the most common , accounting for more than 90% of all the braf gene mutations . braf mutations are the most commonly detected abnormality in ptc , and are seen in about 45% of sporadic adult cases but less frequently ( 0% - 12% ) in pediatric and radiation - induced tumors . in addition to papillary carcinomas , this mutation is also found in poorly - differentiated and anaplastic carcinomas . it is rarely seen in the follicular carcinomas ( 1% - 2% ) or benign thyroid nodules , and hence it seems to be a specific marker for ptc . also , it may assist prognostically , as patients with braf - positive ptcs have been shown to have more aggressive disease at presentation , with higher rates of extrathyroidal extension , lymph node metastasis , and tumor recurrence after initial treatment . when studied as a diagnostic marker , a meta - analysis of 18 studies on braf mutations showed that the rate of malignancy in braf - positive nodules tested by fna was 99.8% . importantly , 15% to 39% of these braf - positive fna samples were indeterminate or non - diagnostic by cytology , demonstrating its utility in establishing a definitive diagnosis of cancer in nodules with indeterminate cytology . ras proteins are positioned at the inner surface of the plasma membrane where they transduce extracellular ligand - mediated stimuli to a cascade of cytoplasmic proteins and map kinases , which , in turn , influence cell growth , differentiation , and apoptosis . ras mutation are the second most common mutation found in thyroid cancers , and the most common type of ras mutations in thyroid cancer is the n-2-ras mutation in codon 61 . the frequency of ras mutations ranges from 0.9% to 23.9% in ftc , 0.6% to 15.2 % in benign follicular adenomas , and these are very rare in colloid nodules ( 1% - 2.5% ) and papillary carcinoma ( 0.3% to 5% ) . these mutations , especially those of k - ras , are also a marker for aggressive cancer behavior , large tumor size , vascular invasion , and distant metastasis . when studied as a diagnostic marker in fna , ras mutation was found to confer a 87.5% probability of malignancy , including a 62.5% probability of a ptc ( mainly follicular variant ) and a 25% probability of a ftc , thus justifying the recommendation of surgery for patients with ras - positive nodules . however , 12.5% of benign follicular adenomas are false positive for ras mutation , and these may be precursors of ftc , as has been shown in some mouse models . ret - ptc re - arrangement the ret proto - oncogene encodes a cell membrane tyrosine - kinase receptor protein . the ret - ptc gene represents an intra - chromosomal gene re - arrangement wherein the ret tyrosine - kinase ( ret - tk ) domain gets fused to the 5-terminal region of a heterologous gene , producing fusion genes that give rise to a constitutively activated form . ret - ptc re - arrangements were identified in ptcs before ret was recognized as the susceptibility gene for multiple endocrine neoplasia 2 ( men2 ) . there are now at least 15 types of ret - ptc re - arrangements involving ret and 10 different genes , the commonest being ret - ptc1 and ret - ptc 3 . they are also known to occur in follicular adenomas , adenomatous goiter , and in hashimoto 's thyroiditis , though in such instances , the pathology is heterogeneous while in ptc , there is clonal evolution of ret / ptc positive cells . carol et al . observed that the identification of ret / ptc gene re - arrangements as an adjunct to cytology in fnacs refined the diagnosis of ptc in 60% of cases that would otherwise have been considered indeterminate and in 33% of those considered insufficient for cytological diagnosis . pax8/ppar rearrangement pax8/ppar re - arrangement is a result of t(2;3)(q13;p25 ) translocation that leads to the fusion between the pax8 gene and the peroxisome proliferator - activated receptor ( ppar ) gene . pax8/ppar re - arrangement is described to be present in 26% - 40% of ftc , variably from 0% - 37% in follicular variant of ptc and much less in hurthle cell carcinoma ( 1 in 30 in one study ) and hyperplastic nodules . ftc patients with ppar re - arrangement more frequently have vascular invasion , areas of solid / nested tumor histology , and previous non - thyroid cancers . thus , pax8/ppar re - arrangement typically correlates with the presence of malignancy , although in prospective studies , only a few positive cases have been reported so far . use of a combination of markers currently , no single genetic marker is specific and sensitive enough to reliably make a diagnosis of benign versus malignant lesion , and hence there may be an advantage using a combination of these markers . nikiforov et al . , studied a of 1,056 consecutive thyroid fna samples with indeterminate cytology for determination of braf , ras , ret / ptc , and pax8-ppar. they reported that in specific categories of indeterminate cytology , i.e. atypia / flus ( follicular lesion of undetermined significance ) , follicular neoplasm / suspicious for a follicular neoplasm , and suspicious for malignant cells , the detection of any mutation conferred the risk of malignancy of 88% , 87% , and 95% , respectively , as against the risk of malignancy based on cytology alone was 14% , 27% , and 54% , respectively . the risk of cancer in mutation - negative nodules was 6% , 14% , and 28% , respectively . the overall cancer rate for mutation - negative status was 6% , and among these , only 2.3% were invasive and 0.5% had extra - thyroidal extension . hence , they recommended total thyroidectomy in mutation - positive status . for mutation - negative patients , recently reviewed and re - analyzed the literature including 16 studies with 1 mutation [ e.g. , braf or ret / ptc ] and 4 studies that have analyzed combination of several mutations ( braf , ras , ret / ptc , and pax8/ppar ) . more importantly , they excluded the samples with fna cytological diagnosis of suspicious of malignancy since these have high chances of malignancy ( 50% - 70% ) and might falsely inflate the performance of molecular markers . for these 4 studies , which were re - analyzed , the combined sensitivity and specificity were 63.7% and 98% , respectively . there were 5 false positives in the 4 studies and in all of them , the ras mutations were detected in follicular adenomas , and the postulated explanation was that it might be a precursor of malignancy on the background of hashimoto 's thyroiditis . one such panel for analysis of combination of markers , which is commercially available , is the asuragen mirinform molecular panel , which includes various mutations in braf , ras and ret - ptc and pax8-pparg gene re - arrangements . micro rna ( mirna)micrornas are 21 to 22 nucleotide segments of non - coding rna that have a key role in post - transcriptional gene regulation ( mainly inhibitory ) through complementary binding that mediates the translation and degradation of messenger rna.many studies have found up - regulation of different mirnas in ptcs using microarray , out of which mir-221 and -222 are the most consistently up - regulated in ptcs while mir-1 , -191 , -486 , and -451 are consistently down-regulated.nikiforova et al . observed that the most up - regulated mirnas in conventional ftcs were mir-187 , -224 , -155 , -222 , and -221 , and those in oncocytic variants were mir-187 , -221 , -339 , -183 , -222 , and -197 . they observed that when at least one mirna was overexpressed more than 2-fold , the sensitivity of tumor detection was 100% , specificity 94% , and accuracy 95% , whereas when 3 or more mirnas were up - regulated , the sensitivity of tumor detection was 88% , specificity 100% , and accuracy 98%.however , no large - scale , prospective , multicenter trial investigating microrna has yet been performed . presently , microrna testing of thyroid aspirates is not commercially available and is offered only through research protocols.thyroid stimulating hormone receptor mrnabecause thyroid cancer cells express functional tsh receptors ( tshr ) , tshr - mrna in peripheral blood might serve as a tissue / cancer - specific marker . tshr - m rna is used as a peripheral blood marker in the follow up of patients of well - differentiated thyroid malignancy.the diagnostic value of circulating tshr mrna , for pre - operative detection of differentiated thyroid carcinoma ( dtc ) in patients with thyroid nodules , was evaluated in 258 subjects ( with 51 normal subjects ) , by chia et al . they demonstrated a sensitivity of 90% and specificity of 80% of tsh mrna to predict malignancy , especially in those with indeterminate cytology on fnac.gene expression ( micro array ) analysisunlike single gene mutations or re - arrangements , microarray diagnostic tests can detect hundreds of expressed genes . it involves the use of multi - gene expression classifiers that assess gene expression from mrna isolated from needle washings during a standard fna procedure.based on the previous work by chudova et al . on whole genome assays , alexander et al . conducted a large , prospective , multicenter validation study of a gene expression classifier using 167 genes on 265 indeterminate nodules and found 92% sensitivity with a specificity of 52% to diagnose malignancy . were 95% , 94% , and 85% , respectively.however , the analysis revealed 7 aspirates with false negative results , some of which might be due to insufficient sampling of the nodule . they suggested that due to high negative predictive value , the gec can be used as a rule out test to avoid unnecessary surgeries . this gene classifier ( veracyte affirma gec ) is available commercially after the above validation study.immunohistochemical markersin recent years , immunohistological markers like galectin-3 , hbme-1 , fibronectin- , cited-1 , and cytokeratin-19 have been investigated for their role in discrimination between benign and malignant nodules . however , they have not been adopted in routine practice , mainly because of different methods used and because these markers show prominent overlap between follicular adenoma and differentiated thyroid carcinomas.other markersthere are certain other potential markers like trk mutations ( too low prevalence of < 5 % in ptcs ) , ubch10 and hmga2 and htert , which are awaiting further large scale studies . micrornas are 21 to 22 nucleotide segments of non - coding rna that have a key role in post - transcriptional gene regulation ( mainly inhibitory ) through complementary binding that mediates the translation and degradation of messenger rna . many studies have found up - regulation of different mirnas in ptcs using microarray , out of which mir-221 and -222 are the most consistently up - regulated in ptcs while mir-1 , -191 , -486 , and -451 are consistently down - regulated . observed that the most up - regulated mirnas in conventional ftcs were mir-187 , -224 , -155 , -222 , and -221 , and those in oncocytic variants were mir-187 , -221 , -339 , -183 , -222 , and -197 . they observed that when at least one mirna was overexpressed more than 2-fold , the sensitivity of tumor detection was 100% , specificity 94% , and accuracy 95% , whereas when 3 or more mirnas were up - regulated , the sensitivity of tumor detection was 88% , specificity 100% , and accuracy 98% . however , no large - scale , prospective , multicenter trial investigating microrna has yet been performed . presently , microrna testing of thyroid aspirates is not commercially available and is offered only through research protocols . thyroid stimulating hormone receptor mrna because thyroid cancer cells express functional tsh receptors ( tshr ) , tshr - mrna in peripheral blood might serve as a tissue / cancer - specific marker . tshr - m rna is used as a peripheral blood marker in the follow up of patients of well - differentiated thyroid malignancy . the diagnostic value of circulating tshr mrna , for pre - operative detection of differentiated thyroid carcinoma ( dtc ) in patients with thyroid nodules , was evaluated in 258 subjects ( with 51 normal subjects ) , by chia et al . they demonstrated a sensitivity of 90% and specificity of 80% of tsh mrna to predict malignancy , especially in those with indeterminate cytology on fnac . gene expression ( micro array ) analysis unlike single gene mutations or re - arrangements , microarray diagnostic tests can detect hundreds of expressed genes . it involves the use of multi - gene expression classifiers that assess gene expression from mrna isolated from needle washings during a standard fna procedure . based on the previous work by chudova et al . on whole genome assays , alexander et al . conducted a large , prospective , multicenter validation study of a gene expression classifier using 167 genes on 265 indeterminate nodules and found 92% sensitivity with a specificity of 52% to diagnose malignancy . . however , the analysis revealed 7 aspirates with false negative results , some of which might be due to insufficient sampling of the nodule . they suggested that due to high negative predictive value , the gec can be used as a rule out test to avoid unnecessary surgeries . this gene classifier ( veracyte affirma gec ) is available commercially after the above validation study . immunohistochemical markers in recent years , immunohistological markers like galectin-3 , hbme-1 , fibronectin- , cited-1 , and cytokeratin-19 have been investigated for their role in discrimination between benign and malignant nodules . however , they have not been adopted in routine practice , mainly because of different methods used and because these markers show prominent overlap between follicular adenoma and differentiated thyroid carcinomas . there are certain other potential markers like trk mutations ( too low prevalence of < 5 % in ptcs ) , ubch10 and hmga2 and htert , which are awaiting further large scale studies . henry et al . recently analyzed and concluded that using molecular markers for cytologically indeterminate thyroid nodules can potentially avoid almost three fourths of currently performed surgeries in patients with benign nodules . compared with the current practice based on cytological findings alone , use of this test may result in lower overall costs and modestly improved quality of life for these patients . to summarize , the optimal management of patients with thyroid nodules with indeterminate cytology is plagued by the lack of highly sensitive and specific diagnostic modalities . the molecular markers as described above definitely would help to optimize the management of such patients . the management algorithm that can be proposed taking into account the sensitivity , specificity , positive and negative predictive values of the various markers available ( as suggested by carolina et al . ) is as shown in figure 1 . algorithm for approach to thyroid nodules with molecular markers however , there are certain limitations to be considered . there is a need for standardization of methods of dna and rna ( including mirna ) extraction and sensitive methods of mutation analysis . though some studies have predicted it to be cost - effective , the cost would be a prohibitive concern , especially in a resource - limited setting like that in our country . moreover , these markers are limited by low sensitivity ( around 70% in different studies ) , which is expected , as the panels could detect only known mutations . hence , in order to reduce the high number of avoidable , diagnostic thyroid surgeries , there is a need to find more markers that can reliably identify about 50% of the lesions , which are malignant but are currently mutation - negative and especially those 80% of benign nodules in the follicular proliferation / indeterminate cytology . the sampling error and inadequacy of sampling during fnab would continue to limit the efficacy of the molecular diagnostics . nevertheless , the scope of molecular markers in the diagnosis of thyroid nodules seem promising , especially in the cytologically indeterminate class .

thyroid nodules are common in the general population with a prevalence of 5 - 7% the initial evaluation of thyroid nodules commonly involves thyroid function tests , an ultrasound ( usg ) and fine needle aspiration biopsy ( fnab ) . the optimal management of patients with thyroid nodules with indeterminate cytology is plagued by the lack of highly sensitive and specific diagnostic modalities in this article we attempt to review the available literature on the molecular markers which are increasingly being studied for their diagnostic utility in assessing thyroid nodules . the various molecular markers consist of gene mutations , gene re arrangements , rna based assays and immunohistochemical markers . the molecular markers definitely would help to optimise the management of such patients .

electromagnetic production of strange baryons has long been of interest because of the fact that such data can provide unique information about the flavor dependence of nucleon excited states , eventually leading to a better understanding of the theory of qcd . unfortunately , progress in understanding the production mechanism has been slow , in no small part because of the lack of high quality data . with the recent availability of a high quality , continuous electron beam at jefferson laboratory , precise new measurements are now achievable over a wide kinematic range @xcite . in addition to providing information on the elementary production reaction , such data will also be a benchmark for future investigations of hyperon - nucleon interactions with nuclear targets . in this paper , we present new cross section data on the reaction @xmath9 from jefferson lab experiment e93 - 018 , that were acquired at values of the square of four - momentum transfer , @xmath10 , between 0.5 and 2.0 ( gev / c)@xmath7 . at each value of @xmath10 , cross sections were obtained at three different values of the virtual photon polarization @xmath8 , allowing a separation of the cross section into its longitudinal ( l ) and transverse ( t ) components . results for the @xmath3 channel were previously reported in ref . however , in order to provide an internally consistent comparison between the two reaction channels , we also present a reanalysis of the @xmath3 data . the differences between the two analyses will be discussed in detail in section [ sec : mc ] : here we use a direct comparison of the experimental data to simulated yields in order to extract the cross section . the result is a significantly smaller longitudinal contribution and a weaker @xmath10 dependence than was previously reported . after a brief introduction and a detailed description of the experiment and analysis , the data will be compared to isobaric models of meson electroproduction described below . exploratory measurements of kaon electroproduction were first carried out between 1972 and 1979 @xcite . in ref . @xcite the longitudinal and transverse contributions to the @xmath3 and @xmath4 cross sections were separated for three values of @xmath10 . two values of @xmath8 were measured for each kinematic setting with relatively poor statistical precision , and the uncertainties in the l / t separated results were large . in ref . @xcite , the measurements were focused on pion electroproduction , but a sample of kaons was also acquired , from which cross sections were extracted . these measurements provided the first determination of the qualitative behavior of the kaon cross sections and were the basis for the development of modern models of kaon electroproduction . theoretical models all attempt to reproduce the available data from both kaon production and radiative kaon capture , while maintaining consistency with su(3 ) symmetry constraints on the coupling constants @xcite . the energy regime addressed by these models is low enough that they are formulated using meson - nucleon degrees of freedom . the most recent theoretical efforts can be divided into two categories , isobaric models and those that use regge trajectories . the approach taken in the isobaric models is to explicitly calculate kaon production amplitudes from tree - level ( _ i.e. _ , only one particle exchanged ) processes . a typical selection of diagrams considered is depicted in figure [ fig : kdiagrams ] . for example , in david _ et al . _ @xcite , the authors sum over @xmath11-channel nucleon resonances up to and including spin 5/2 , @xmath12-channel hyperon resonances of spin 1/2 , and @xmath13-channel kaon resonances k@xmath14(892 ) and k1(1270 ) . in the wjc model @xcite , a different selection of @xmath11 and @xmath12 channel resonances is included ( both limited to spin 3/2 ) . mart _ et al . _ @xcite include the lowest lying @xmath15- and @xmath16-wave resonances , plus an additional resonance @xmath17 for which there appears to be evidence from kaon photoproduction @xcite , although alternative interpretations of the data have been put forth in @xcite and @xcite . the various isobaric models share the property that they initially include only spin 1/2 baryonic resonances ( although the specific resonances differ ) and determine the remaining coupling constants from performing phenomenological fits to the data . the coupling constants , which are the parameters of the theory , are not well - constrained due to the lack of available data . because of this , one sees differences in the various models for quantities such as @xmath18 . one issue that these differences reflect is that the various models disagree on the relative importance of the resonances entering the calculation . further details on the various isobaric models can be found in @xcite . -channel ( @xmath18 , etc ... ) are shown explicitly . note that the @xmath11-channel processes involving @xmath19 resonances are forbidden by isospin conservation for @xmath3 production.,width=316 ] models based on regge trajectories @xcite were developed in the early 1970 s to describe pion photoproduction data , of which there is a relative abundance . this approach has recently been revisited by vanderhaegen , guidal , and laget ( vgl ) @xcite . here , the standard single particle feynman propagator , @xmath20 , is replaced by a regge propagator that accounts for the exchange of a family of particles with the same internal quantum numbers @xcite . the extension of the photoproduction model to electroproduction is accomplished by multiplying the gauge invariant @xmath13-channel k and k@xmath14 diagrams by a form factor ( the isobaric models such as wjc also include electromagnetic form factors , however the functional forms used differ between models @xcite ) . for the vgl model this is given as a monopole form factor , @xmath21 where @xmath22 are mass scales that are essentially free parameters , but can be fixed to fit the high @xmath10 behavior of the separated electroproduction cross sections , @xmath23 and @xmath24 . for both the isobaric and regge approaches , precise experimental results for longitudinal / transverse separated cross sections are important for placing constraints on the free parameters within the models , hopefully giving insight into the reaction mechanisms . an additional motivation for performing measurements of l / t separated cross sections in kaon electroproduction is to determine the @xmath10 dependence of the k@xmath25 electromagnetic form factor . if it can be demonstrated that @xmath26 is dominated by photon absorption on a ground state kaon , the k@xmath25 form factor can be extracted through a measurement of the @xmath13-dependence of the longitudinal component of the cross section . this technique has been used to determine the @xmath27 electromagnetic form factor , including a recent new measurement @xcite . while the kaon form factor may not be able to be extracted from the data presented here , it is the subject of other recently completed measurements at jefferson laboratory @xcite . finally , historically there has been interest in the ratio of @xmath28 transverse cross sections , which is linked to contribution of sea quarks to nucleon structure @xcite . within the context of the parton model , isospin arguments would lead one to expect the @xmath28 transverse cross section ratio at forward kaon cm angles to approach 0 with increasing bjorken @xmath29 if the kaon production mechanism is dominated by the photon interacting with single valence @xmath12 quark . when sea quarks are included in the nucleon s initial state , the approach to 0 is expected to be more rapid . measurement of of @xmath30 over a broad range of @xmath29 may provide information about the intrinsic @xmath31@xmath11 content of the proton . the elementary kaon electroproduction reaction studied here , @xmath1 + @xmath0 @xmath32 @xmath33 + @xmath34 + ( @xmath3 or @xmath4 ) , is shown in figure [ fig : peekdiag ] . an incident electron ( @xmath1 ) with lab energy @xmath35 , scatters by radiating a virtual photon ( @xmath36 ) . the scattered electron ( @xmath33 ) travels at a polar angle @xmath37 in the laboratory frame with respect to the direction of the incident beam , defining the scattering plane . the virtual photon carries momentum @xmath38 and energy @xmath39 and interacts with a target proton to form a kaon ( k@xmath25 ) and a hyperon ( y , here either a @xmath3 or @xmath4 ) . the kaon travels at a polar angle @xmath40 in the laboratory frame with respect to the virtual photon direction and is also detected . the reaction plane , defined by the produced kaon and produced hyperon , makes an angle @xmath41 with respect to the scattering plane . , between the scattering and reaction planes with respect to the direction of the virtual photon.,width=316 ] the exclusive five - fold differential electroproduction cross section can be expressed in terms of a virtual photoproduction cross section , @xmath42 , multiplied by a virtual photon flux factor , @xmath43 @xcite . the cross section is written in terms of the scattered electron energy , @xmath44 , electron lab frame solid angle , @xmath45 , and kaon center - of - momentum frame ( cm ) solid angle , @xmath46 as @xmath47 with @xmath48 here the cm frame is that of the ( virtual photon + proton ) system , and that the cm frame counterparts to lab variables will be denoted with an asterisk superscript . in this expression , @xmath49 is the fine structure constant ( @xmath501/137 ) , @xmath51 is the proton mass , @xmath5 is the total energy of the ( virtual photon + proton ) system , @xmath10 is the square of the four - momentum transfer carried by the virtual photon , and @xmath8 is the polarization of the virtual photon , given by @xmath52 where @xmath53 is the virtual photon three - momentum . because the beam and target were unpolarized , and no outgoing polarization was measured , the virtual photoproduction cross section can be decomposed into four terms : @xmath54 where @xmath55 is the cross section due to transversely polarized virtual photons , @xmath56 is due to longitudinally polarized virtual photons , and @xmath57 and @xmath58 are interference terms between two different polarization states . if one integrates the cross section over all @xmath59 , the interference terms vanish leaving only the combined contributions from the transverse and longitudinal cross sections , @xmath60 . by measuring the cross section at several values of the virtual photon polarization , @xmath8 , the cross sections @xmath55 and @xmath56 can be separated . the experimental setup described here was such that at each of the four values of @xmath10 , the full range in @xmath61 was accessible at three different values of the virtual photon polarization , @xmath8 , as listed in table [ tab : kinematics ] . the data were fitted using the linear dependence between ( @xmath62 ) and @xmath8 . the intercept and slope of the fitted line were used to extract @xmath55 and @xmath56 for each @xmath10 , for both the @xmath3 and @xmath63 channels . .kinematical settings measured in e93 - 018 . note that there are three settings of the virtual photon polarization , @xmath8 , for each of four values of @xmath10 . data were taken in the @xmath3 and @xmath4 channels simultaneously . for ease of discussion , the settings have been labeled as point 1 through point 12 in increasing order of @xmath10 , and with increasing order of @xmath8 within each @xmath10 setting . the quantities ( p@xmath64,@xmath65 ) and ( p@xmath66,@xmath67 ) are the central momentum and angle settings of the two spectrometers used for electron and kaon detection , respectively . [ cols="^,^,^,^,^,^,^,^,^ " , ] for the @xmath68 process , shown with the linear fit to the data that allows separation into the longitudinal and transverse components.,width=316 ] for the @xmath69 process . the lines are the fit to the data , allowing separation of the longitudinal and transverse components . , width=316 ] it should be noted that the data for e93 - 018 were taken in parallel with another experiment in which angular distributions of kaon electroproduction from hydrogen and deuterium were studied . in a few cases the kinematic settings were very similar , and comparisons were made with cross sections extracted from the analysis of @xcite . they are in excellent agreement ( within 2.5% ) , when scaled to the same @xmath10 and @xmath5 values using eq . [ eq : bebekq ] and [ eq : dmkw ] . as a function of @xmath10 . the ratio is shown in panel ( c ) . the data are compared to calculations of @xcite ( solid line ) and @xcite ( dashed line ) . the open diamond data are from @xcite , and the solid diamond photoproduction data point is from @xcite.,width=316 ] as a function of @xmath10 . the ratio is shown in panel ( c ) . the calculations are again from @xcite ( solid line ) and @xcite ( dashed line ) . the open diamond data are from @xcite , and the solid diamond photoproduction data point is from @xcite.,width=316 ] /@xmath3 cross sections as a function of @xmath10 , separated into longitudinal ( a ) and transverse ( b ) components , compared with the same two calculations as above.,width=316 ] as described in the introduction , several model calculations of @xmath3 and @xmath4 electroproduction cross sections , using parameters fit to previous data , are available . we have chosen to compare our data to the models in @xcite ( wjc ) and @xcite , for which calculations were readily available in the form in which the data are presented here . the parameters of each model were constrained by global fits to previously obtained unpolarized photo- and electroproduction data , and , through crossing arguments , to kaon radiative capture . for the @xmath3 channel , the wjc model reproduces reasonably well the trends in both the longitudinal and transverse components ( figs . [ fig : lambda - t - sep](a ) and [ fig : lambda - t - sep](b ) , respectively ) , although the transverse component is underpredicted . the calculation of ref . @xcite qualitatively reproduces the transverse piece , which is constrained by the photoproduction point , but not the longitudinal component . one possible cause for the discrepancy could be the lack of knowledge of the @xmath10 dependence of the baryon form factors entering in the @xmath11-channel @xcite . in their study of kaon electroproduction , david _ et al . _ , observed that @xmath70 was sensitively dependent on the choice of baryon form factors , while rather insensitive to the reaction mechanism @xcite , whereas the unpolarized cross section alone did not depend strongly on the baryon form factors . for @xmath71 , the transverse component is underestimated by both models and thus the ratio is overestimated ( see fig . [ fig : sigma - t - sep ] ) . the strong peak in @xmath72 implied by the wjc model is not observed in our data . the magnitude of this peak in the wjc model is very sensitive to the cm energy , @xmath5 , of the reaction , indicating that there are strong resonance contributions in the model . as in the case of the @xmath3 channel , it is likely that the form factors and the strengths of the various resonances entering the model could be modified in order to give better agreement with the data . in general , models for the @xmath4 channel are harder to tune than for the @xmath3 because of the influence of isovector @xmath73 resonances ( of spin 1/2 and 3/2 in the model ) in the @xmath4 channel and because of the lower quality / quantity of available data . the ratio of the longitudinal cross sections for @xmath28 ( fig . [ fig : lamsig_wjc](a ) ) appears to mildly decrease with increasing @xmath10 . this could arise , for example , from differences in the behavior of the @xmath74 and @xmath75 form factors , if the longitudinal response is dominated by @xmath13-channel processes . we note that while regge trajectory models are not expected to work well at the rather low cm energies of our data , which are still within the nucleon resonance region , our highest @xmath10 results are in reasonable agreement with the calculation of @xcite , both in the unseparated cross sections and in the l / t components . at lower momentum transfer our data indicate a larger longitudinal component to the @xmath4 cross sections than predicted by their model , perhaps indicative of the larger number of resonance contributions to the @xmath4 channel . the ratio of the transverse cross sections for @xmath28 ( fig . [ fig : lamsig_wjc](b ) ) shows a mild decrease above @xmath76 gev@xmath7 . however , the inclusion of the desy photoproduction data on the plot shows that there is likely a rapid decrease in @xmath77 for @xmath10 below 0.5 ( gev / c)@xmath7 . this lower momentum region may be of interest for further study , particularly in the @xmath4 channel . rosenbluth separated kaon electroproduction data in two hyperon channels , @xmath78 and @xmath79 , have been presented . these results are the most precise measurements of the separated cross sections @xmath23 and @xmath24 made to date , particularly for the @xmath4 channel , and will help constrain theoretical models of these electroproduction processes . such data allow access to baryon excitations that couple strongly to final states with strangeness but weakly to @xmath80-n systems . they also allow the possibility of mapping out the @xmath10 evolution away from the photoproduction point , thereby providing a means to extract electromagnetic form factors and detailed information about the excited state wave functions . used in conjunction with models they will allow one to learn more about the reaction dynamics of strangeness production . the southeastern universities research association ( sura ) operates the thomas jefferson national accelerator facility for the united states department of energy under contract de - ac05 - 84er40150 . this work was also supported by the department of energy contract no . w-31 - 109-eng-38 ( anl ) and by grants from the national science foundation . we also acknowledge informative discussions with c. bennhold . see , for example , jefferson laboratory experiments e89 - 004 ( r. schumacher ) , e89 - 043 ( l. dennis ) , e93 - 030 ( k. hicks ) , e99 - 006 and e00 - 112 ( d. carman ) , and e98 - 108 ( p. markowitz ) , and e91 - 016 ( b. zeidman , contact ) . t. mart and c. bennhold , phys . c * 61 * , 012201(r ) ( 2000 ) . the code to calculate the cross sections at our specific kinematics was provided by t. mart . at the time of this writing , the version of the code provided at http://www.kph.uni-mainz.de/maid/kaon/kaonmaid.html had known errors and therefore was not used . mohring , ph.d . thesis , university of maryland ( 1999 ) , ( unpublished ) . it should be noted that an error was recently found in the calculation of the kaon s survival probability in the thesis analysis , which accounts for the majority of the difference between the cross sections presented here and those in the thesis .

we report measurements of cross sections for the reaction @xmath0(@xmath1,@xmath2)y , for both the @xmath3 and @xmath4 hyperon states , at an invariant mass of @xmath5=1.84 gev and four - momentum transfers @xmath6 ( gev / c)@xmath7 . data were taken for three values of virtual photon polarization @xmath8 , allowing the decomposition of the cross sections into longitudinal and transverse components . the @xmath3 data is a revised analysis of prior work , whereas the @xmath4 results have not been previously reported .

a range of ii - vi semiconductor nanoheterostructures has been synthesized , including spherical core - shell particles , seeded nanorods , and seeded tetrapods . these heterostructures allow for sophisticated manipulation of photons and carriers at the nanoscale and exhibit many interesting phenomena , including extremely high extinction coefficients , polarized emission and high quantum yields . the synthesis of multicomponent nanostructures requires precise control over the composition , phase , shape , size , and connectivity of each component . control over these various factors relies largely on the ability to independently modulate the rate of nucleation and growth . one strategy to achieve independent control over nucleation and growth is to separate these two processes into separate synthetic steps . here , we will show how small seeds of cdse generated under reaction conditions optimized for nucleation and growth of spherical nanocrystals can then be transferred to a second flask where the growth of cds occurs under reaction conditions optimized for anisotropic growth of rod - shaped arms . by tuning the crystal structure of the cdse seed from wurtzite to zinc - blende , we will demonstrate how the morphology of cdse / cds heterostructures grown under similar conditions can be changed from a nanorod to a tetrapod , highlighting the precise control over phase , shape , and size afforded by state - of - the - art nanoparticle synthesis methods . nanostructures of the cadmium chalcogenides have served as a useful model - system for the development of new synthetic techniques , as this material system has been intensively explored ; although the synthesis of a particular nanostructure is shown in this video protocol , the same techniques are applicable to the synthesis of numerous other nanostructures . small differences in the techniques and reagents employed in nanoparticle syntheses have been shown to create dramatic differences in the final product . for instance , the temperature ramp rate and impurities present during the synthesis have been shown to dramatically impact the size and shape of the nanocrystals . with identification of the specific factors to which the synthetic procedures are highly sensitive , the reproducibility of nanocrystal syntheses continues to improve . this detailed video protocol is intended to help new practitioners in the field avoid many common pitfalls associated with the synthesis of nanoparticles . please use all appropriate safety practices when performing a nanocrystal reaction including the use of engineering controls ( fume hood , glovebox ) and personal protective equipment ( safety glasses , gloves , lab coat , full - length pants , closed - toe shoes ) . preparation of cadmium ( ii ) myristate cadmium myristate can be synthesized in either an ex situ or in situ method , achieving similar results . ex situ preparation of cadmium myristate dissolve 0.240 g sodium hydroxide and 1.370 g myristic acid in 240 ml methanol.separately , dissolve 0.617 g cadmium nitrate tetrahydrate in 40 ml methanol.add the cadmium nitrate solution drop - wise ( ~1 drop / sec ) to the stirring ( 800 rpm ) sodium myristate solution using an addition funnel.filter the solution . g myristic acid in 5 ml 1-octadecene ( ode ) in a 50 ml 3-neck round bottom flask with a stir bar.heat the solution to 250 c under inert gas while stirring ( 800 rpm ) until the solution becomes a pale yellow color . carefully swirl the solution as necessary to remove excess cdo from the sidewalls of the flask . leaving this solution at elevated temperature beyond this point will cause it to become an undesired black color.cool the solution to room temperature for use in subsequent reactions . ex situ preparation of cadmium myristate dissolve 0.240 g sodium hydroxide and 1.370 g myristic acid in 240 ml methanol.separately , dissolve 0.617 g cadmium nitrate tetrahydrate in 40 ml methanol.add the cadmium nitrate solution drop - wise ( ~1 drop / sec ) to the stirring ( 800 rpm ) sodium myristate solution using an addition funnel.filter the solution . dissolve 0.240 g sodium hydroxide and 1.370 g myristic acid in 240 ml methanol . separately , dissolve 0.617 g cadmium nitrate tetrahydrate in 40 ml methanol . add the cadmium nitrate solution drop - wise ( ~1 drop / sec ) to the stirring ( 800 rpm ) sodium myristate solution using an addition funnel . combine 39 mg cadmium oxide ( cdo ) with 0.137 g myristic acid in 5 ml 1-octadecene ( ode ) in a 50 ml 3-neck round bottom flask with a stir bar.heat the solution to 250 c under inert gas while stirring ( 800 rpm ) until the solution becomes a pale yellow color . carefully swirl the solution as necessary to remove excess cdo from the sidewalls of the flask . leaving this solution at elevated temperature beyond this point will cause it to become an undesired black color.cool the solution to room temperature for use in subsequent reactions . combine 39 mg cadmium oxide ( cdo ) with 0.137 g myristic acid in 5 ml 1-octadecene ( ode ) in a 50 ml 3-neck round bottom flask with a stir bar . heat the solution to 250 c under inert gas while stirring ( 800 rpm ) until the solution becomes a pale yellow color . carefully swirl the solution as necessary to remove excess cdo from the sidewalls of the flask . leaving this solution at elevated temperature beyond this point will cause it to become an undesired black color preparation of top : se precursor combine 58 mg selenium powder with 0.360 g tri - n - octylphosphine ( top ) under an inert atmosphere.sonicate until the selenium powder is fully dissolved , yielding an optically clear solution . alternatively , the solution can also be heated to 100 c in order to fully dissolve the selenium . use proper glassware or a glove box to prevent exposure of the solution to air during sonication or heating . combine 58 mg selenium powder with 0.360 g tri - n - octylphosphine ( top ) under an inert atmosphere . alternatively , the solution can also be heated to 100 c in order to fully dissolve the selenium . use proper glassware or a glove box to prevent exposure of the solution to air during sonication or heating . preparation of top : s precursor combine 0.160 g elemental sulfur with 1.853 g top.heat to 50 c under an inert atmosphere until the solution is optically clear . cool to room temperature for future use . combine 0.160 g elemental sulfur with 1.853 g top . synthesis of wurtzite cdse ( w - cdse ) nanocrystals combine 3.0 g trioctylphosphine oxide ( topo ) , 280 mg n - octadecylphosphonic acid ( odpa ) , and 60 mg cdo with a stir bar in a 25 ml 3-neck round bottom flask equipped with a thermocouple ( inserted in a custom glass adapter or punctured through a rubber septum ) , a reflux condenser , and a rubber septum . inspect all glassware for defects prior to use due to the high temperature of reaction and potential need for rapid cooling . assemble all glass - to - glass joints with high temperature vacuum grease.degas the mixture at 150 c under vacuum for 1 hr while stirring ( 800 rpm).heat the solution to 300 c under inert gas to form an optically clear solution . allow the solution to become optically clear again.add 1.5 g top drop - wise to the solution and raise the temperature to 370 c.rapidly inject top : se solution using a syringe with a large diameter ( 14 g ) needle . the rapid injection will create a sharp nucleation event , promoting a narrow size distribution.let the reaction proceed for the desired duration , as the size of the w - cdse nanocrystal can be tuned by adjusting the reaction time . immediately cooling after the injection will yield nanocrystals of ~2 - 2.5 nm in diameter whereas reacting the solution for 3 and 5 min will yield ~3 nm and ~4 nm diameter nanocrystals , respectively.remove the heating mantle and rapidly cool the flask using a stream of compressed air . care should be taken when rapidly cooling a flask from elevated temperatures as the thermal shock may break the glassware . for this reason , the use of a water bath for rapid cooling is strongly discouraged.add 10 ml of anhydrous methanol to the solution when the temperature is below 60 c to flocculate the nanocrystals . add anhydrous methanol until the solution becomes turbid and centrifuge.repeat a similar cleaning procedure ( step 2.1.9 ) using a different solvent / nonsolvent pair : hexane / isopropanol . this helps prevent situations in which the nanocrystals and precursors precipitate simultaneously.disperse the cleaned precipitate in a small volume ( a few milliliters ) of anhydrous toluene . the use of a small volume of solvent here will avoid the need to concentrate the particles as an additional step prior to their use in the seeded growth of cds.confirm the wurtzite crystal structure of the cdse nanocrystals by x - ray diffraction this step is strongly encouraged due to the polymorphism of cdse and the strong dependence on the structure of the cdse seed for the resulting heterostructures.dilute a small aliquot of the w - cdse stock solution by a known dilution factor and acquire a uv - vis absorption spectrum.determine the w - cdse nanocrystal diameter and extinction coefficient based upon the first exciton absorbance according to the following formulas : d = ( 1.612210)- ( 2.657510)+ ( 1.624210) - ( 0.4277) + 41.57 = 5857(d ) where d is the diameter ( nm ) of the w - cdse nanocrystal , is the wavelength ( nm ) of the first excitonic absorption peak , and is the extinction coefficient ( l / molcm ) of nanocrystals at the first exciton.determine the concentration of the w - cdse nanocrystal stock solution using the absorbance at the first excitonic absorption peak in accordance with beer - lambert s law and the appropriate dilution factor.to prepare w - cdse for the growth of seeded rods , combine 0.5 g top with a volume of the w - cdse nanocrystal stock solution corresponding to 10 mol of w - cdse nanocrystals . the use of a small volume of toluene for the w - cdse stock solution in a prior step ( 2.1.11 ) should lead to only a small amount of toluene , on the order of microliters , in the seed solution used for the injection . the injection of larger volumes of volatile organic solvents , such as toluene , at temperatures substantially above their boiling point poses a safety hazard and will adversely affect the nanocrystal product due to large drops in reaction temperatures . combine 3.0 g trioctylphosphine oxide ( topo ) , 280 mg n - octadecylphosphonic acid ( odpa ) , and 60 mg cdo with a stir bar in a 25 ml 3-neck round bottom flask equipped with a thermocouple ( inserted in a custom glass adapter or punctured through a rubber septum ) , a reflux condenser , and a rubber septum . inspect all glassware for defects prior to use due to the high temperature of reaction and potential need for rapid cooling . degas the mixture at 150 c under vacuum for 1 hr while stirring ( 800 rpm ) . heat the solution to 300 c under inert gas to form an optically clear solution . add 1.5 g top drop - wise to the solution and raise the temperature to 370 c . rapidly inject top : se solution using a syringe with a large diameter ( 14 g ) needle . the rapid injection will create a sharp nucleation event , promoting a narrow size distribution . let the reaction proceed for the desired duration , as the size of the w - cdse nanocrystal can be tuned by adjusting the reaction time . immediately cooling after the injection will yield nanocrystals of ~2 - 2.5 nm in diameter whereas reacting the solution for 3 and 5 min will yield ~3 nm and ~4 nm diameter nanocrystals , respectively . remove the heating mantle and rapidly cool the flask using a stream of compressed air . care should be taken when rapidly cooling a flask from elevated temperatures as the thermal shock may break the glassware . for this reason , the use of a water bath for rapid cooling is strongly discouraged . add 10 ml of anhydrous methanol to the solution when the temperature is below 60 c to flocculate the nanocrystals . repeat a similar cleaning procedure ( step 2.1.9 ) using a different solvent / nonsolvent pair : hexane / isopropanol . disperse the cleaned precipitate in a small volume ( a few milliliters ) of anhydrous toluene . the use of a small volume of solvent here will avoid the need to concentrate the particles as an additional step prior to their use in the seeded growth of cds . this step is strongly encouraged due to the polymorphism of cdse and the strong dependence on the structure of the cdse seed for the resulting heterostructures . dilute a small aliquot of the w - cdse stock solution by a known dilution factor and acquire a uv - vis absorption spectrum . determine the w - cdse nanocrystal diameter and extinction coefficient based upon the first exciton absorbance according to the following formulas : d = ( 1.612210)- ( 2.657510)+ ( 1.624210) - ( 0.4277) + 41.57 = 5857(d ) where d is the diameter ( nm ) of the w - cdse nanocrystal , is the wavelength ( nm ) of the first excitonic absorption peak , and is the extinction coefficient ( l / molcm ) of nanocrystals at the first exciton . determine the concentration of the w - cdse nanocrystal stock solution using the absorbance at the first excitonic absorption peak in accordance with beer - lambert s law and the appropriate dilution factor . to prepare w - cdse for the growth of seeded rods , combine 0.5 g top with a volume of the w - cdse nanocrystal stock solution corresponding to 10 mol of w - cdse nanocrystals . the use of a small volume of toluene for the w - cdse stock solution in a prior step ( 2.1.11 ) should lead to only a small amount of toluene , on the order of microliters , in the seed solution used for the injection . the injection of larger volumes of volatile organic solvents , such as toluene , at temperatures substantially above their boiling point poses a safety hazard and will adversely affect the nanocrystal product due to large drops in reaction temperatures . synthesis of zinc - blende cdse ( zb - cdse ) nanocrystals combine 0.17 g cadmium myristate and 37 ml ode with a stir bar in a 50 ml 3-neck round bottom flask equipped with a thermocouple ( inserted in a custom glass adapter or punctured through a rubber septum ) , a reflux condenser , and a rubber septum . inspect all glassware for defects prior to use due to the high temperature of reaction . assemble all glass - to - glass joints with high temperature vacuum grease.degas the solution under vacuum at 90 c for 1 hr while stirring ( 800 rpm ) . subsequently , cool the solution to room temperature under inert gas.briefly remove the rubber septum and add 33 mg selenium dioxide powder to the flask . replace the septum . degas the solution under vacuum at 50 c for 15 min.heat to 240 c at a ramp rate of approximately 10 c / min under inert gas . as the temperature rises , the solution will begin to change color , progressing from yellow to red.add a previously degassed solution of 1 ml oleic acid and 1 ml oleylamine in 4 ml ode drop - wise when the solution reaches 240 c.react the solution for 30 min at 240 c . the size of the zb - cdse nanocrystals can be tuned by modifying the reaction time . take aliquots for absorption and photoluminescence spectra to monitor particle growth if desired.remove the heating mantle and cool to room temperature . transfer the crude solution to an inert atmosphere glove box and split the reaction mixture into 20 ml fractions in centrifuge vials.add 10 ml anhydrous acetone to each vial and centrifuge solutions to isolate the nanocrystals.pour off the supernatant and redisperse the precipitate in anhydrous toluene . add acetone until the solution becomes turbid and centrifuge.repeat a similar cleaning procedure ( step 2.2.9 ) using a different solvent / nonsolvent pair : chloroform / methanol . this helps prevent situations in which the nanocrystals and precursors precipitate simultaneously.disperse the cleaned precipitate in a small volume ( a few milliliters ) of anhydrous chloroform . the use of a small volume of solvent here will avoid the need to concentrate the particles as an additional step prior to their use in the seeded growth of cds.after cleaning the particles , confirm the zinc - blende crystal structure of the cdse nanocrystals by x - ray diffraction this step is strongly encouraged due to the polymorphism of cdse and the strong dependence on the structure of the cdse seed for the resulting heterostructures.dilute a small aliquot of the zb - cdse stock solution by a known dilution factor and acquire a uv - vis absorption spectrum.determine the zb - cdse nanocrystal diameter and extinction coefficient based upon the first exciton absorbance according to the following formulas : = 19300 ( d ) where d is the diameter ( nm ) of the zb - cdse nanocrystal , eg the band gap energy ( ev ) corresponding to the first excitonic absorption peak , and is the extinction coefficient ( l / molcm ) of nanocrystals at 340 nm.determine the concentration of the zb - cdse nanocrystal stock solution using the absorbance at 340 nm in accordance with beer - lambert s law and the appropriate dilution factor.combine 0.5 g top with a volume of the zb - cdse nanocrystal stock solution corresponding to 10 mol of zb - cdse nanocrystals to prepare zb - cdse injection for the growth of seeded tetrapods . the use of a small volume of chloroform for the zb - cdse stock solution in a prior step ( 2.2.11 ) should lead to only a small amount of chloroform , on the order of microliters , in the seed solution used for the injection . the injection of larger volumes of volatile organic solvents , such as chloroform , at temperatures substantially above their boiling point poses a safety hazard and will adversely affect the nanocrystal product due to large drops in reaction temperatures . combine 0.17 g cadmium myristate and 37 ml ode with a stir bar in a 50 ml 3-neck round bottom flask equipped with a thermocouple ( inserted in a custom glass adapter or punctured through a rubber septum ) , a reflux condenser , and a rubber septum . inspect all glassware for defects prior to use due to the high temperature of reaction . degas the solution under vacuum at 90 c for 1 hr while stirring ( 800 rpm ) . remove the rubber septum and add 33 mg selenium dioxide powder to the flask . replace the septum . heat to 240 c at a ramp rate of approximately 10 c / min under inert gas . as the temperature rises , the solution will begin to change color , progressing from yellow to red . add a previously degassed solution of 1 ml oleic acid and 1 ml oleylamine in 4 ml ode drop - wise when the solution reaches 240 c . the size of the zb - cdse nanocrystals can be tuned by modifying the reaction time . transfer the crude solution to an inert atmosphere glove box and split the reaction mixture into 20 ml fractions in centrifuge vials . add 10 ml anhydrous acetone to each vial and centrifuge solutions to isolate the nanocrystals . pour off the supernatant and redisperse the precipitate in anhydrous toluene . add acetone until the solution becomes turbid and centrifuge . repeat a similar cleaning procedure ( step 2.2.9 ) using a different solvent / nonsolvent pair : chloroform / methanol . disperse the cleaned precipitate in a small volume ( a few milliliters ) of anhydrous chloroform . the use of a small volume of solvent here will avoid the need to concentrate the particles as an additional step prior to their use in the seeded growth of cds . after cleaning the particles , confirm the zinc - blende crystal structure of the cdse nanocrystals by x - ray diffraction . this step is strongly encouraged due to the polymorphism of cdse and the strong dependence on the structure of the cdse seed for the resulting heterostructures . dilute a small aliquot of the zb - cdse stock solution by a known dilution factor and acquire a uv - vis absorption spectrum . determine the zb - cdse nanocrystal diameter and extinction coefficient based upon the first exciton absorbance according to the following formulas : = 19300 ( d ) where d is the diameter ( nm ) of the zb - cdse nanocrystal , eg the band gap energy ( ev ) corresponding to the first excitonic absorption peak , and is the extinction coefficient ( l / molcm ) of nanocrystals at 340 nm . determine the concentration of the zb - cdse nanocrystal stock solution using the absorbance at 340 nm in accordance with beer - lambert s law and the appropriate dilution factor . combine 0.5 g top with a volume of the zb - cdse nanocrystal stock solution corresponding to 10 mol of zb - cdse nanocrystals to prepare zb - cdse injection for the growth of seeded tetrapods . the use of a small volume of chloroform for the zb - cdse stock solution in a prior step ( 2.2.11 ) should lead to only a small amount of chloroform , on the order of microliters , in the seed solution used for the injection . the injection of larger volumes of volatile organic solvents , such as chloroform , at temperatures substantially above their boiling point poses a safety hazard and will adversely affect the nanocrystal product due to large drops in reaction temperatures . synthesis of cdse / cds seeded nanorods combine 207 mg cdo , 1.08 g odpa , 3.35 g topo , and 15 mg propylphosphonic acid ( ppa ) with a stir bar in a 25 ml 3-neck round bottom flask equipped with a thermocouple ( inserted in a custom glass adapter or punctured through a rubber septum ) , a reflux condenser , and a rubber septum . inspect all glassware for defects prior to use due to the high temperature of reaction . assemble all glass - to - glass joints with high temperature vacuum grease.degas the solution under vacuum at 120 c for 30 min while stirring ( 800 rpm).heat the solution to 320 c under inert gas to form an optically clear solution . degas the solution under vacuum for 1 hr at 120 c.after degassing and complexing the reaction solution , heat the mixture to 340 c under inert gas . inject 1.5 g top drop - wise and let the temperature recover to 340c.rapidly inject 0.65 g top : s using a syringe with a large diameter ( 14 g ) needle.20 seconds after the top : s injection , rapidly inject w - cdse solution ( 10 mol w - cdse nanocrystals in 0.5 g top ) using a syringe with a large diameter ( 14 g ) needle.adjust the reaction temperature to 320 c . after 10 min at 320 c , remove the heating mantle and cool the solution.add ~10 ml anhydrous toluene to the flask when the temperature is around 100 c to prevent solidification of the topo.transfer the crude solution to a centrifuge vial . the purification of the crude solution of seeded rods can be performed in an inert atmosphere glovebox or ambient conditions , if desired , as the overgrowth of cds enhances the environmental stability of the nanocrystals . add an equal volume of anhydrous ethanol to flocculate the nanocrystals and centrifuge.pour off the supernatant and redispersed the precipitate in hexane / octylamine ( 8:1 by volume ) . redisperse precipitate in anhydrous toluene.occasionally , solutions of seeded rods will form a gel during the cleaning process . if this occurs , add a few drops of octylamine to dissolve the gel and continue the cleaning procedure . note : the length of the nanorods can be tuned by changing the concentration of injected cdse seeds ; higher seed concentrations lead to shorter rods . adjusting the top : s concentration will vary the rod diameter and length ; higher top : s concentration produces longer , thinner rods . combine 207 mg cdo , 1.08 g odpa , 3.35 g topo , and 15 mg propylphosphonic acid ( ppa ) with a stir bar in a 25 ml 3-neck round bottom flask equipped with a thermocouple ( inserted in a custom glass adapter or punctured through a rubber septum ) , a reflux condenser , and a rubber septum . inspect all glassware for defects prior to use due to the high temperature of reaction . assemble all glass - to - glass joints with high temperature vacuum grease . degas the solution under vacuum at 120 c for 30 min while stirring ( 800 rpm ) . heat the solution to 320 c under inert gas to form an optically clear solution . after degassing and complexing the reaction solution , heat the mixture to 340 c under inert gas . rapidly inject 0.65 g top : s using a syringe with a large diameter ( 14 g ) needle . 20 seconds after the top : s injection , rapidly inject w - cdse solution ( 10 mol w - cdse nanocrystals in 0.5 g top ) using a syringe with a large diameter ( 14 g ) needle . adjust the reaction temperature to 320 c . after 10 min at 320 c , add ~10 ml anhydrous toluene to the flask when the temperature is around 100 c to prevent solidification of the topo . the purification of the crude solution of seeded rods can be performed in an inert atmosphere glovebox or ambient conditions , if desired , as the overgrowth of cds enhances the environmental stability of the nanocrystals . pour off the supernatant and redispersed the precipitate in hexane / octylamine ( 8:1 by volume ) . if this occurs , add a few drops of octylamine to dissolve the gel and continue the cleaning procedure . note : the length of the nanorods can be tuned by changing the concentration of injected cdse seeds ; higher seed concentrations lead to shorter rods . adjusting the top : s concentration will vary the rod diameter and length ; higher top : s concentration produces longer , thinner rods . synthesis of cdse / cds seeded tetrapods combine 207 mg cdo , 1.08 g odpa , 3.35 g topo , and 50 mg ppa with a stir bar in a 25 ml 3-neck round bottom flask equipped with a thermocouple ( inserted in a custom glass adapter or punctured through a rubber septum ) , a reflux condenser , and a rubber septum . inspect all glassware for defects prior to use due to the high temperature of reaction . assemble all glass - to - glass joints with high temperature vacuum grease.degas the solution under vacuum at 120 c for 1 hr while stirring ( 800 rpm).heat the solution to 280 c under inert gas to form an optically clear solution . carefully swirl the solution to remove excess cdo from the sidewalls of the flask . degas the solution under vacuum for 1 hr at 120 c.after degassing and complexing the reaction solution , heat the mixture to 300 c under inert gas . inject 1.5 g top drop - wise and let the temperature recover to its initial value.rapidly inject 0.65 g top : s using a syringe with a large diameter ( 14 g ) needle.40 seconds after the top : s injection , rapidly inject zb - cdse solution ( 10 mol zb - cdse nanocrystals in 0.5 g top ) using a syringe with a large diameter ( 14 g ) needle.raise the reaction temperature to 315 c at a rate of 1 c / min . after 20 min at 315 c , remove the heating mantle and cool.add anhydrous toluene to the flask when the temperature is around 100 c to prevent solidification of the topo.transfer the crude solution to a centrifuge vial . the purification of the crude solution of seeded tetrapods can be performed in an inert atmosphere glovebox or ambient conditions , if desired , as the overgrowth of cds enhances the environmental stability of the nanocrystals . add anhydrous acetone until the solution becomes turbid and centrifuge.pour off the supernatant and redisperse the precipitate in hexane / octylamine ( 8:1 by volume ) . add anhydrous acetone until the solution becomes turbid and centrifuge.repeat the purification of the tetrapods twice more using toluene and acetone as the solvent and nonsolvent , respectively . store the tetrapods in toluene.separate tetrapods from undesired nanorod byproducts by centrifuging toluene solutions at 12,000 x g for 30 min to develop a concentration gradient due to the mass difference between rods and tetrapods . carefully remove and discard the upper layers , which contain mainly rods . note : the length of the tetrapod arms can be tuned by changing the injection seed concentration ; higher seed concentrations produce shorter arms . the growth time can be used to adjust the arm diameter ; longer growth times increase the diameter of the arms . see reference for details . the yield of tetrapods can be varied by using different amounts of ppa in the initial reaction mixture . combine 207 mg cdo , 1.08 g odpa , 3.35 g topo , and 50 mg ppa with a stir bar in a 25 ml 3-neck round bottom flask equipped with a thermocouple ( inserted in a custom glass adapter or punctured through a rubber septum ) , a reflux condenser , and a rubber septum . inspect all glassware for defects prior to use due to the high temperature of reaction . degas the solution under vacuum at 120 c for 1 hr while stirring ( 800 rpm ) . heat the solution to 280 c under inert gas to form an optically clear solution . after degassing and complexing the reaction solution , heat the mixture to 300 c under inert gas . inject 1.5 g top drop - wise and let the temperature recover to its initial value . rapidly inject 0.65 g top : s using a syringe with a large diameter ( 14 g ) needle . 40 seconds after the top : s injection , rapidly inject zb - cdse solution ( 10 mol zb - cdse nanocrystals in 0.5 g top ) using a syringe with a large diameter ( 14 g ) needle . raise the reaction temperature to 315 c at a rate of 1 c / min . add anhydrous toluene to the flask when the temperature is around 100 c to prevent solidification of the topo . the purification of the crude solution of seeded tetrapods can be performed in an inert atmosphere glovebox or ambient conditions , if desired , as the overgrowth of cds enhances the environmental stability of the nanocrystals . pour off the supernatant and redisperse the precipitate in hexane / octylamine ( 8:1 by volume ) . repeat the purification of the tetrapods twice more using toluene and acetone as the solvent and nonsolvent , respectively . store the tetrapods in toluene . separate tetrapods from undesired nanorod byproducts by centrifuging toluene solutions at 12,000 x g for 30 min to develop a concentration gradient due to the mass difference between rods and tetrapods . carefully remove and discard the upper layers , which contain mainly rods . note : the length of the tetrapod arms can be tuned by changing the injection seed concentration ; higher seed concentrations produce shorter arms . the growth time can be used to adjust the arm diameter ; longer growth times increase the diameter of the arms . see reference for details . the yield of tetrapods can be varied by using different amounts of ppa in the initial reaction mixture . preparation of cadmium ( ii ) myristate cadmium myristate can be synthesized in either an ex situ or in situ method , achieving similar results . ex situ preparation of cadmium myristate dissolve 0.240 g sodium hydroxide and 1.370 g myristic acid in 240 ml methanol.separately , dissolve 0.617 g cadmium nitrate tetrahydrate in 40 ml methanol.add the cadmium nitrate solution drop - wise ( ~1 drop / sec ) to the stirring ( 800 rpm ) sodium myristate solution using an addition funnel.filter the solution . g myristic acid in 5 ml 1-octadecene ( ode ) in a 50 ml 3-neck round bottom flask with a stir bar.heat the solution to 250 c under inert gas while stirring ( 800 rpm ) until the solution becomes a pale yellow color . carefully swirl the solution as necessary to remove excess cdo from the sidewalls of the flask . leaving this solution at elevated temperature beyond this point will cause it to become an undesired black color.cool the solution to room temperature for use in subsequent reactions . ex situ preparation of cadmium myristate dissolve 0.240 g sodium hydroxide and 1.370 g myristic acid in 240 ml methanol.separately , dissolve 0.617 g cadmium nitrate tetrahydrate in 40 ml methanol.add the cadmium nitrate solution drop - wise ( ~1 drop / sec ) to the stirring ( 800 rpm ) sodium myristate solution using an addition funnel.filter the solution . dissolve 0.240 g sodium hydroxide and 1.370 g myristic acid in 240 ml methanol . separately , dissolve 0.617 g cadmium nitrate tetrahydrate in 40 ml methanol . add the cadmium nitrate solution drop - wise ( ~1 drop / sec ) to the stirring ( 800 rpm ) sodium myristate solution using an addition funnel . combine 39 mg cadmium oxide ( cdo ) with 0.137 g myristic acid in 5 ml 1-octadecene ( ode ) in a 50 ml 3-neck round bottom flask with a stir bar.heat the solution to 250 c under inert gas while stirring ( 800 rpm ) until the solution becomes a pale yellow color . carefully swirl the solution as necessary to remove excess cdo from the sidewalls of the flask . leaving this solution at elevated temperature beyond this point will cause it to become an undesired black color.cool the solution to room temperature for use in subsequent reactions . combine 39 mg cadmium oxide ( cdo ) with 0.137 g myristic acid in 5 ml 1-octadecene ( ode ) in a 50 ml 3-neck round bottom flask with a stir bar . heat the solution to 250 c under inert gas while stirring ( 800 rpm ) until the solution becomes a pale yellow color . carefully swirl the solution as necessary to remove excess cdo from the sidewalls of the flask . leaving this solution at elevated temperature beyond this point will cause it to become an undesired black color . preparation of top : se precursor combine 58 mg selenium powder with 0.360 g tri - n - octylphosphine ( top ) under an inert atmosphere.sonicate until the selenium powder is fully dissolved , yielding an optically clear solution . alternatively , the solution can also be heated to 100 c in order to fully dissolve the selenium . use proper glassware or a glove box to prevent exposure of the solution to air during sonication or heating . combine 58 mg selenium powder with 0.360 g tri - n - octylphosphine ( top ) under an inert atmosphere . alternatively , the solution can also be heated to 100 c in order to fully dissolve the selenium . use proper glassware or a glove box to prevent exposure of the solution to air during sonication or heating . preparation of top : s precursor combine 0.160 g elemental sulfur with 1.853 g top.heat to 50 c under an inert atmosphere until the solution is optically clear . cool to room temperature for future use . combine 0.160 g elemental sulfur with 1.853 g top . synthesis of wurtzite cdse ( w - cdse ) nanocrystals combine 3.0 g trioctylphosphine oxide ( topo ) , 280 mg n - octadecylphosphonic acid ( odpa ) , and 60 mg cdo with a stir bar in a 25 ml 3-neck round bottom flask equipped with a thermocouple ( inserted in a custom glass adapter or punctured through a rubber septum ) , a reflux condenser , and a rubber septum . inspect all glassware for defects prior to use due to the high temperature of reaction and potential need for rapid cooling . assemble all glass - to - glass joints with high temperature vacuum grease.degas the mixture at 150 c under vacuum for 1 hr while stirring ( 800 rpm).heat the solution to 300 c under inert gas to form an optically clear solution . carefully swirl the solution to remove excess cdo from the sidewalls of the flask . allow the solution to become optically clear again.add 1.5 g top drop - wise to the solution and raise the temperature to 370 c.rapidly inject top : se solution using a syringe with a large diameter ( 14 g ) needle . the rapid injection will create a sharp nucleation event , promoting a narrow size distribution.let the reaction proceed for the desired duration , as the size of the w - cdse nanocrystal can be tuned by adjusting the reaction time . immediately cooling after the injection will yield nanocrystals of ~2 - 2.5 nm in diameter whereas reacting the solution for 3 and 5 min will yield ~3 nm and ~4 nm diameter nanocrystals , respectively.remove the heating mantle and rapidly cool the flask using a stream of compressed air . care should be taken when rapidly cooling a flask from elevated temperatures as the thermal shock may break the glassware . for this reason , the use of a water bath for rapid cooling is strongly discouraged.add 10 ml of anhydrous methanol to the solution when the temperature is below 60 c to flocculate the nanocrystals . transfer the solution to a vial under inert gas and centrifuge.decant the solution . discard the supernatant and redisperse the precipitate in anhydrous toluene . add anhydrous methanol until the solution becomes turbid and centrifuge.repeat a similar cleaning procedure ( step 2.1.9 ) using a different solvent / nonsolvent pair : hexane / isopropanol . this helps prevent situations in which the nanocrystals and precursors precipitate simultaneously.disperse the cleaned precipitate in a small volume ( a few milliliters ) of anhydrous toluene . the use of a small volume of solvent here will avoid the need to concentrate the particles as an additional step prior to their use in the seeded growth of cds.confirm the wurtzite crystal structure of the cdse nanocrystals by x - ray diffraction this step is strongly encouraged due to the polymorphism of cdse and the strong dependence on the structure of the cdse seed for the resulting heterostructures.dilute a small aliquot of the w - cdse stock solution by a known dilution factor and acquire a uv - vis absorption spectrum.determine the w - cdse nanocrystal diameter and extinction coefficient based upon the first exciton absorbance according to the following formulas : d = ( 1.612210)- ( 2.657510)+ ( 1.624210) - ( 0.4277) + 41.57 = 5857(d ) where d is the diameter ( nm ) of the w - cdse nanocrystal , is the wavelength ( nm ) of the first excitonic absorption peak , and is the extinction coefficient ( l / molcm ) of nanocrystals at the first exciton.determine the concentration of the w - cdse nanocrystal stock solution using the absorbance at the first excitonic absorption peak in accordance with beer - lambert s law and the appropriate dilution factor.to prepare w - cdse for the growth of seeded rods , combine 0.5 g top with a volume of the w - cdse nanocrystal stock solution corresponding to 10 mol of w - cdse nanocrystals . the use of a small volume of toluene for the w - cdse stock solution in a prior step ( 2.1.11 ) should lead to only a small amount of toluene , on the order of microliters , in the seed solution used for the injection . the injection of larger volumes of volatile organic solvents , such as toluene , at temperatures substantially above their boiling point poses a safety hazard and will adversely affect the nanocrystal product due to large drops in reaction temperatures . combine 3.0 g trioctylphosphine oxide ( topo ) , 280 mg n - octadecylphosphonic acid ( odpa ) , and 60 mg cdo with a stir bar in a 25 ml 3-neck round bottom flask equipped with a thermocouple ( inserted in a custom glass adapter or punctured through a rubber septum ) , a reflux condenser , and a rubber septum . inspect all glassware for defects prior to use due to the high temperature of reaction and potential need for rapid cooling . degas the mixture at 150 c under vacuum for 1 hr while stirring ( 800 rpm ) . heat the solution to 300 c under inert gas to form an optically clear solution . add 1.5 g top drop - wise to the solution and raise the temperature to 370 c . rapidly inject top : se solution using a syringe with a large diameter ( 14 g ) needle . the rapid injection will create a sharp nucleation event , promoting a narrow size distribution . let the reaction proceed for the desired duration , as the size of the w - cdse nanocrystal can be tuned by adjusting the reaction time . immediately cooling after the injection will yield nanocrystals of ~2 - 2.5 nm in diameter whereas reacting the solution for 3 and 5 min will yield ~3 nm and ~4 nm diameter nanocrystals , respectively . remove the heating mantle and rapidly cool the flask using a stream of compressed air . care should be taken when rapidly cooling a flask from elevated temperatures as the thermal shock may break the glassware . for this reason , the use of a water bath for rapid cooling is strongly discouraged . add 10 ml of anhydrous methanol to the solution when the temperature is below 60 c to flocculate the nanocrystals . discard the supernatant and redisperse the precipitate in anhydrous toluene . add anhydrous methanol until the solution becomes turbid and centrifuge . repeat a similar cleaning procedure ( step 2.1.9 ) using a different solvent / nonsolvent pair : hexane / isopropanol . disperse the cleaned precipitate in a small volume ( a few milliliters ) of anhydrous toluene . the use of a small volume of solvent here will avoid the need to concentrate the particles as an additional step prior to their use in the seeded growth of cds . this step is strongly encouraged due to the polymorphism of cdse and the strong dependence on the structure of the cdse seed for the resulting heterostructures . dilute a small aliquot of the w - cdse stock solution by a known dilution factor and acquire a uv - vis absorption spectrum . determine the w - cdse nanocrystal diameter and extinction coefficient based upon the first exciton absorbance according to the following formulas : d = ( 1.612210)- ( 2.657510)+ ( 1.624210) - ( 0.4277) + 41.57 = 5857(d ) where d is the diameter ( nm ) of the w - cdse nanocrystal , is the wavelength ( nm ) of the first excitonic absorption peak , and is the extinction coefficient ( l / molcm ) of nanocrystals at the first exciton . determine the concentration of the w - cdse nanocrystal stock solution using the absorbance at the first excitonic absorption peak in accordance with beer - lambert s law and the appropriate dilution factor . to prepare w - cdse for the growth of seeded rods , combine 0.5 g top with a volume of the w - cdse nanocrystal stock solution corresponding to 10 mol of w - cdse nanocrystals . sonicate briefly if needed to redisperse the w - cdse nanocrystals in top . the use of a small volume of toluene for the w - cdse stock solution in a prior step ( 2.1.11 ) should lead to only a small amount of toluene , on the order of microliters , in the seed solution used for the injection . the injection of larger volumes of volatile organic solvents , such as toluene , at temperatures substantially above their boiling point poses a safety hazard and will adversely affect the nanocrystal product due to large drops in reaction temperatures . synthesis of zinc - blende cdse ( zb - cdse ) nanocrystals combine 0.17 g cadmium myristate and 37 ml ode with a stir bar in a 50 ml 3-neck round bottom flask equipped with a thermocouple ( inserted in a custom glass adapter or punctured through a rubber septum ) , a reflux condenser , and a rubber septum . inspect all glassware for defects prior to use due to the high temperature of reaction . assemble all glass - to - glass joints with high temperature vacuum grease.degas the solution under vacuum at 90 c for 1 hr while stirring ( 800 rpm ) . subsequently , cool the solution to room temperature under inert gas.briefly remove the rubber septum and add 33 mg selenium dioxide powder to the flask . replace the septum . degas the solution under vacuum at 50 c for 15 min.heat to 240 c at a ramp rate of approximately 10 c / min under inert gas . as the temperature rises , the solution will begin to change color , progressing from yellow to red.add a previously degassed solution of 1 ml oleic acid and 1 ml oleylamine in 4 ml ode drop - wise when the solution reaches 240 c.react the solution for 30 min at 240 c . the size of the zb - cdse nanocrystals can be tuned by modifying the reaction time . take aliquots for absorption and photoluminescence spectra to monitor particle growth if desired.remove the heating mantle and cool to room temperature . transfer the crude solution to an inert atmosphere glove box and split the reaction mixture into 20 ml fractions in centrifuge vials.add 10 ml anhydrous acetone to each vial and centrifuge solutions to isolate the nanocrystals.pour off the supernatant and redisperse the precipitate in anhydrous toluene . add acetone until the solution becomes turbid and centrifuge.repeat a similar cleaning procedure ( step 2.2.9 ) using a different solvent / nonsolvent pair : chloroform / methanol . this helps prevent situations in which the nanocrystals and precursors precipitate simultaneously.disperse the cleaned precipitate in a small volume ( a few milliliters ) of anhydrous chloroform . the use of a small volume of solvent here will avoid the need to concentrate the particles as an additional step prior to their use in the seeded growth of cds.after cleaning the particles , confirm the zinc - blende crystal structure of the cdse nanocrystals by x - ray diffraction this step is strongly encouraged due to the polymorphism of cdse and the strong dependence on the structure of the cdse seed for the resulting heterostructures.dilute a small aliquot of the zb - cdse stock solution by a known dilution factor and acquire a uv - vis absorption spectrum.determine the zb - cdse nanocrystal diameter and extinction coefficient based upon the first exciton absorbance according to the following formulas : = 19300 ( d ) where d is the diameter ( nm ) of the zb - cdse nanocrystal , eg the band gap energy ( ev ) corresponding to the first excitonic absorption peak , and is the extinction coefficient ( l / molcm ) of nanocrystals at 340 nm.determine the concentration of the zb - cdse nanocrystal stock solution using the absorbance at 340 nm in accordance with beer - lambert s law and the appropriate dilution factor.combine 0.5 g top with a volume of the zb - cdse nanocrystal stock solution corresponding to 10 mol of zb - cdse nanocrystals to prepare zb - cdse injection for the growth of seeded tetrapods . the use of a small volume of chloroform for the zb - cdse stock solution in a prior step ( 2.2.11 ) should lead to only a small amount of chloroform , on the order of microliters , in the seed solution used for the injection . the injection of larger volumes of volatile organic solvents , such as chloroform , at temperatures substantially above their boiling point poses a safety hazard and will adversely affect the nanocrystal product due to large drops in reaction temperatures . combine 0.17 g cadmium myristate and 37 ml ode with a stir bar in a 50 ml 3-neck round bottom flask equipped with a thermocouple ( inserted in a custom glass adapter or punctured through a rubber septum ) , a reflux condenser , and a rubber septum . inspect all glassware for defects prior to use due to the high temperature of reaction . degas the solution under vacuum at 90 c for 1 hr while stirring ( 800 rpm ) . subsequently , cool the solution to room temperature under inert gas . briefly remove the rubber septum and add 33 mg selenium dioxide powder to the flask . heat to 240 c at a ramp rate of approximately 10 c / min under inert gas . as the temperature rises , the solution will begin to change color , progressing from yellow to red . add a previously degassed solution of 1 ml oleic acid and 1 ml oleylamine in 4 ml ode drop - wise when the solution reaches 240 c . the size of the zb - cdse nanocrystals can be tuned by modifying the reaction time . transfer the crude solution to an inert atmosphere glove box and split the reaction mixture into 20 ml fractions in centrifuge vials . add 10 ml anhydrous acetone to each vial and centrifuge solutions to isolate the nanocrystals . pour off the supernatant and redisperse the precipitate in anhydrous toluene . add acetone until the solution becomes turbid and centrifuge . repeat a similar cleaning procedure ( step 2.2.9 ) using a different solvent / nonsolvent pair : chloroform / methanol . this helps prevent situations in which the nanocrystals and precursors precipitate simultaneously . disperse the cleaned precipitate in a small volume ( a few milliliters ) of anhydrous chloroform . the use of a small volume of solvent here will avoid the need to concentrate the particles as an additional step prior to their use in the seeded growth of cds . after cleaning the particles , confirm the zinc - blende crystal structure of the cdse nanocrystals by x - ray diffraction . this step is strongly encouraged due to the polymorphism of cdse and the strong dependence on the structure of the cdse seed for the resulting heterostructures . dilute a small aliquot of the zb - cdse stock solution by a known dilution factor and acquire a uv - vis absorption spectrum . determine the zb - cdse nanocrystal diameter and extinction coefficient based upon the first exciton absorbance according to the following formulas : = 19300 ( d ) where d is the diameter ( nm ) of the zb - cdse nanocrystal , eg the band gap energy ( ev ) corresponding to the first excitonic absorption peak , and is the extinction coefficient ( l / molcm ) of nanocrystals at 340 nm . determine the concentration of the zb - cdse nanocrystal stock solution using the absorbance at 340 nm in accordance with beer - lambert s law and the appropriate dilution factor . combine 0.5 g top with a volume of the zb - cdse nanocrystal stock solution corresponding to 10 mol of zb - cdse nanocrystals to prepare zb - cdse injection for the growth of seeded tetrapods . the use of a small volume of chloroform for the zb - cdse stock solution in a prior step ( 2.2.11 ) should lead to only a small amount of chloroform , on the order of microliters , in the seed solution used for the injection . the injection of larger volumes of volatile organic solvents , such as chloroform , at temperatures substantially above their boiling point poses a safety hazard and will adversely affect the nanocrystal product due to large drops in reaction temperatures . synthesis of cdse / cds seeded nanorods combine 207 mg cdo , 1.08 g odpa , 3.35 g topo , and 15 mg propylphosphonic acid ( ppa ) with a stir bar in a 25 ml 3-neck round bottom flask equipped with a thermocouple ( inserted in a custom glass adapter or punctured through a rubber septum ) , a reflux condenser , and a rubber septum . inspect all glassware for defects prior to use due to the high temperature of reaction . assemble all glass - to - glass joints with high temperature vacuum grease.degas the solution under vacuum at 120 c for 30 min while stirring ( 800 rpm).heat the solution to 320 c under inert gas to form an optically clear solution . carefully swirl the solution to remove excess cdo from the sidewalls of the flask . degas the solution under vacuum for 1 hr at 120 c.after degassing and complexing the reaction solution , heat the mixture to 340 c under inert gas . inject 1.5 g top drop - wise and let the temperature recover to 340c.rapidly inject 0.65 g top : s using a syringe with a large diameter ( 14 g ) needle.20 seconds after the top : s injection , rapidly inject w - cdse solution ( 10 mol w - cdse nanocrystals in 0.5 g top ) using a syringe with a large diameter ( 14 g ) needle.adjust the reaction temperature to 320 c . after 10 min at 320 c , remove the heating mantle and cool the solution.add ~10 ml anhydrous toluene to the flask when the temperature is around 100 c to prevent solidification of the topo.transfer the crude solution to a centrifuge vial . the purification of the crude solution of seeded rods can be performed in an inert atmosphere glovebox or ambient conditions , if desired , as the overgrowth of cds enhances the environmental stability of the nanocrystals . add an equal volume of anhydrous ethanol to flocculate the nanocrystals and centrifuge.pour off the supernatant and redispersed the precipitate in hexane / octylamine ( 8:1 by volume ) . redisperse precipitate in anhydrous toluene.occasionally , solutions of seeded rods will form a gel during the cleaning process . if this occurs , add a few drops of octylamine to dissolve the gel and continue the cleaning procedure . note : the length of the nanorods can be tuned by changing the concentration of injected cdse seeds ; higher seed concentrations lead to shorter rods . adjusting the top : s concentration will vary the rod diameter and length ; higher top : s concentration produces longer , thinner rods . combine 207 mg cdo , 1.08 g odpa , 3.35 g topo , and 15 mg propylphosphonic acid ( ppa ) with a stir bar in a 25 ml 3-neck round bottom flask equipped with a thermocouple ( inserted in a custom glass adapter or punctured through a rubber septum ) , a reflux condenser , and a rubber septum . inspect all glassware for defects prior to use due to the high temperature of reaction . degas the solution under vacuum at 120 c for 30 min while stirring ( 800 rpm ) . heat the solution to 320 c under inert gas to form an optically clear solution . carefully swirl the solution to remove excess cdo from the sidewalls of the flask . allow the solution to become optically clear again . after degassing and complexing the reaction solution , heat the mixture to 340 c under inert gas . rapidly inject 0.65 g top : s using a syringe with a large diameter ( 14 g ) needle . 20 seconds after the top : s injection , rapidly inject w - cdse solution ( 10 mol w - cdse nanocrystals in 0.5 g top ) using a syringe with a large diameter ( 14 g ) needle . adjust the reaction temperature to 320 c . after 10 min at 320 c , remove the heating mantle and cool the solution . add ~10 ml anhydrous toluene to the flask when the temperature is around 100 c to prevent solidification of the topo . the purification of the crude solution of seeded rods can be performed in an inert atmosphere glovebox or ambient conditions , if desired , as the overgrowth of cds enhances the environmental stability of the nanocrystals . pour off the supernatant and redispersed the precipitate in hexane / octylamine ( 8:1 by volume ) . if this occurs , add a few drops of octylamine to dissolve the gel and continue the cleaning procedure . note : the length of the nanorods can be tuned by changing the concentration of injected cdse seeds ; higher seed concentrations lead to shorter rods . adjusting the top : s concentration will vary the rod diameter and length ; higher top : s concentration produces longer , thinner rods . synthesis of cdse / cds seeded tetrapods combine 207 mg cdo , 1.08 g odpa , 3.35 g topo , and 50 mg ppa with a stir bar in a 25 ml 3-neck round bottom flask equipped with a thermocouple ( inserted in a custom glass adapter or punctured through a rubber septum ) , a reflux condenser , and a rubber septum . inspect all glassware for defects prior to use due to the high temperature of reaction . assemble all glass - to - glass joints with high temperature vacuum grease.degas the solution under vacuum at 120 c for 1 hr while stirring ( 800 rpm).heat the solution to 280 c under inert gas to form an optically clear solution . carefully swirl the solution to remove excess cdo from the sidewalls of the flask . allow the solution to become optically clear again.cool the solution to 120 c . degas the solution under vacuum for 1 hr at 120 c.after degassing and complexing the reaction solution , heat the mixture to 300 c under inert gas . inject 1.5 g top drop - wise and let the temperature recover to its initial value.rapidly inject 0.65 g top : s using a syringe with a large diameter ( 14 g ) needle.40 seconds after the top : s injection , rapidly inject zb - cdse solution ( 10 mol zb - cdse nanocrystals in 0.5 g top ) using a syringe with a large diameter ( 14 g ) needle.raise the reaction temperature to 315 c at a rate of 1 c / min . after 20 min at 315 c , remove the heating mantle and cool.add anhydrous toluene to the flask when the temperature is around 100 c to prevent solidification of the topo.transfer the crude solution to a centrifuge vial . the purification of the crude solution of seeded tetrapods can be performed in an inert atmosphere glovebox or ambient conditions , if desired , as the overgrowth of cds enhances the environmental stability of the nanocrystals . add anhydrous acetone until the solution becomes turbid and centrifuge.pour off the supernatant and redisperse the precipitate in hexane / octylamine ( 8:1 by volume ) . add anhydrous acetone until the solution becomes turbid and centrifuge.repeat the purification of the tetrapods twice more using toluene and acetone as the solvent and nonsolvent , respectively . store the tetrapods in toluene.separate tetrapods from undesired nanorod byproducts by centrifuging toluene solutions at 12,000 x g for 30 min to develop a concentration gradient due to the mass difference between rods and tetrapods . note : the length of the tetrapod arms can be tuned by changing the injection seed concentration ; higher seed concentrations produce shorter arms . the growth time can be used to adjust the arm diameter ; longer growth times increase the diameter of the arms . see reference for details . the yield of tetrapods can be varied by using different amounts of ppa in the initial reaction mixture . combine 207 mg cdo , 1.08 g odpa , 3.35 g topo , and 50 mg ppa with a stir bar in a 25 ml 3-neck round bottom flask equipped with a thermocouple ( inserted in a custom glass adapter or punctured through a rubber septum ) , a reflux condenser , and a rubber septum . inspect all glassware for defects prior to use due to the high temperature of reaction . degas the solution under vacuum at 120 c for 1 hr while stirring ( 800 rpm ) . heat the solution to 280 c under inert gas to form an optically clear solution . after degassing and complexing the reaction solution , heat the mixture to 300 c under inert gas . inject 1.5 g top drop - wise and let the temperature recover to its initial value . rapidly inject 0.65 g top : s using a syringe with a large diameter ( 14 g ) needle . 40 seconds after the top : s injection , rapidly inject zb - cdse solution ( 10 mol zb - cdse nanocrystals in 0.5 g top ) using a syringe with a large diameter ( 14 g ) needle . raise the reaction temperature to 315 c at a rate of 1 c / min . add anhydrous toluene to the flask when the temperature is around 100 c to prevent solidification of the topo . the purification of the crude solution of seeded tetrapods can be performed in an inert atmosphere glovebox or ambient conditions , if desired , as the overgrowth of cds enhances the environmental stability of the nanocrystals . pour off the supernatant and redisperse the precipitate in hexane / octylamine ( 8:1 by volume ) . repeat the purification of the tetrapods twice more using toluene and acetone as the solvent and nonsolvent , respectively . store the tetrapods in toluene . separate tetrapods from undesired nanorod byproducts by centrifuging toluene solutions at 12,000 x g for 30 min to develop a concentration gradient due to the mass difference between rods and tetrapods . carefully remove and discard the upper layers , which contain mainly rods . note : the length of the tetrapod arms can be tuned by changing the injection seed concentration ; higher seed concentrations produce shorter arms . the growth time can be used to adjust the arm diameter ; longer growth times increase the diameter of the arms . see reference for details . the yield of tetrapods can be varied by using different amounts of ppa in the initial reaction mixture . absorption spectra , photoluminescence ( pl ) spectra , x - ray diffraction ( xrd ) patterns , and transmission electron microscopy ( tem ) images were collected for the seeds ( figure 1 ) and the final heterostructures ( figure 2 ) . the absorption and pl spectra ( a , b ) absorption ( black ) and pl ( red ) spectra with inset of tem images of wurtzite and zinc - blende cdse nanocrystals , respectively . ( c , d ) x - ray diffraction patterns of wurtzite and zinc - blende cdse nanocrystals with the line patterns of corresponding bulk materials provided for reference . ( a , b ) tem images of cdse / cds nanorods and cdse / cds tetrapods , respectively . ( e , f ) absorption ( black ) and pl ( red ) spectra of cdse / cds nanorods and tetrapods . the optical spectra for the w - cdse and zb - cdse seeds exhibit clear excitonic absorption ( figures 1a and 1b ) as the seeds are highly monodisperse ; the energy of the first exciton corresponds to diameters of 3.3 nm and 3.6 nm for w - cdse and zb - cdse , respectively . the seeds also exhibit strong photoluminescence , with quantum yields ranging from approximately 3 - 30% , depending on the method of preparation of the sample ; for instance , a greater number of cleaning steps tends to remove the surface ligands and lead to lower quantum yields . the narrow full width at half - maximum of the pl peak ( 31 nm and 33 nm for the w - cdse and zb - cdse nanocrystals , respectively ) is consistent with size distributions of 5 - 10% . the x - ray diffraction patterns collected for the seeds ( figures 1c and 1d ) confirm that they are of the desired phase . the wurtzite phase has clear reflections at 41.1 and 53.8 that are absent for the zinc - blende phase . the differences in the crystal structure of the cdse seeds lead to dramatically different morphologies of the final heterostructure ( figures 2a and 2b ) . w - cds nucleates and grows from the ( 001 ) and ( 00 ) facets of the w - cdse , leading to a final rod - shaped particle since there is uniaxial growth . in contrast , w - cds nucleates and grows off the { 111 } facets of zb - cdse . of the eight { 111 } facets , four exhibit lower coordinative saturation than the others ; as a result , we observe more rapid growth of w - cds off of these four facets , which leads to a tetrapod morphology . the seeded rods and tetrapods display high crystallinity , corresponding to wurtzite cds as confirmed by xrd ( figures 2c and 2d ) . because the cds portion of the heterostructures is much larger compared to the cdse seed , the absorption due to the seeds is a small percentage of the overall absorption . as a result , the heterostructures absorb weakly at wavelengths longer than 500 nm , where the majority of absorption is due to the cdse seed ( figures 2e and 2f ) . at wavelengths shorter than 500 nm , absorption is dramatically enhanced since the larger bandgap cds begins to absorb significantly . the extinction coefficients for the seeds are on the order of 10 mcm , while the rods and tetrapods have significantly enhanced extinction coefficients of 10 mcm and 10 mcm , respectively . for both the rods and tetrapods , the first excitonic transition for the heterostructures is red - shifted compared to the bare seeds ( figures 2e and 2f ) since the electrons and holes are spread out over a larger particle . depending on the particular size of the components of the heterostructure and the resulting band structure , the hole tends to be somewhat confined to the seed while the electron is more free to move throughout the entire particle . as a result , recombination occurs away from the particle surface , leading to quantum yields for rods above 75% and for tetrapods between 35 - 70% , which are significantly higher than that of the bare cdse seeds . furthermore , the inorganic passivation from the cds on the cdse seeds provides enhanced environmental stability . we have demonstrated a method for controlling the final morphology of a nanoscale heterostructure via control over the crystal structure of the seed . this same seeded - growth approach has already been applied to a wide range of structures , and we expect that the types of heterostructures that can be synthesized by this approach will continue to expand .

we demonstrate a method for the synthesis of multicomponent nanostructures consisting of cds and cdse with rod and tetrapod morphologies . a seeded synthesis strategy is used in which spherical seeds of cdse are prepared first using a hot - injection technique . by controlling the crystal structure of the seed to be either wurtzite or zinc - blende , the subsequent hot - injection growth of cds off of the seed results in either a rod - shaped or tetrapod - shaped nanocrystal , respectively . the phase and morphology of the synthesized nanocrystals are confirmed using x - ray diffraction and transmission electron microscopy , demonstrating that the nanocrystals are phase - pure and have a consistent morphology . the extinction coefficient and quantum yield of the synthesized nanocrystals are calculated using uv - vis absorption spectroscopy and photoluminescence spectroscopy . the rods and tetrapods exhibit extinction coefficients and quantum yields that are higher than that of the bare seeds . this synthesis demonstrates the precise arrangement of materials that can be achieved at the nanoscale by using a seeded synthetic approach .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Disaster Recovery Improvement Act''. SEC. 2. ADDITIONAL MITIGATION ASSISTANCE. Section 404 of the Robert T. Stafford Disaster Relief and Emergency Assistance Act (42 U.S.C. 5170c) is amended by adding at the end the following: ``(d) Additional Mitigation Assistance.-- ``(1) In general.--If, at the time of a declaration of a major disaster, the affected State has in effect and is actively enforcing throughout the State an approved State building code, the President may increase the maximum total of contributions under this section for the major disaster, as specified in subsection (a), by an amount equal to 5 percent of the estimated aggregate amount of grants to be made (less any associated administrative costs) under this Act with respect to the major disaster. ``(2) Submission.--To be eligible for an increased Federal share under paragraph (1), a State, at least once every 4 years, shall submit its State building code to the President for approval. ``(3) Approval.--The President shall approve a State building code submitted under paragraph (2) if the President determines that the building code-- ``(A) is consistent with the most recent version of a nationally recognized model building code; ``(B) has been adopted by the State within 4 years of the most recent version of the nationally recognized model building code; and ``(C) uses the nationally recognized model building code as a minimum standard. ``(4) Definitions.--In this subsection, the following definitions apply: ``(A) Actively enforcing.--The term `actively enforcing' means effective jurisdictional execution of all phases of a State building code in the process of examination and approval of construction plans, specifications, and technical data and the inspection of new construction or renovation. ``(B) Nationally recognized model building code.-- The term `nationally recognized model building code' means a building code for residential and commercial construction and construction materials that-- ``(i) has been developed and published by a code organization in an open consensus type forum with input from national experts; and ``(ii) is based on national structural design standards that establish minimum acceptable criteria for the design, construction, and maintenance of residential and commercial buildings for the purpose of protecting the health, safety, and general welfare of the building's users against natural disasters. ``(C) State building code.--The term `State building code' means requirements and associated standards for residential and commercial construction and construction materials that are implemented on a statewide basis by ordinance, resolution, law, housing or building code, or zoning ordinance. At a minimum, such requirements and associated standards shall apply-- ``(i) to construction-related activities of residential building contractors applicable to single-family and two-family residential structures; and ``(ii) to construction-related activities of engineers, architects, designers, and commercial building contractors applicable to the structural safety, design, and construction of commercial, industrial, and multifamily structures. ``(5) Regulations.--Not later than 180 days after the date of enactment of this subsection, the President, acting through the Administrator of the Federal Emergency Management Agency, shall issue such regulations as may be necessary to carry out this subsection.''. SEC. 3. EXPEDITED PAYMENTS. Section 406 of the Robert T. Stafford Disaster Relief and Emergency Assistance Act (42 U.S.C. 5172) is amended by adding at the end the following: ``(f) Expedited Payments.-- ``(1) Grant assistance.--In making a contribution under subsection (a)(1), the President shall provide not less than 50 percent of the President's initial estimate of the Federal share of assistance as an initial payment in accordance with paragraph (2). ``(2) Date of payment.--Not later than 60 days after the date of the estimate described in paragraph (1), and not later than 90 days after the date on which the State or local government or owner or operator of a private nonprofit facility applies for assistance under this section, the initial payment described in paragraph (1) shall be paid.''. SEC. 4. DEBRIS REMOVAL. (a) Debris Management Plans.--Section 407(d) of the Robert T. Stafford Disaster Relief and Emergency Assistance Act (42 U.S.C. 5173(d)) is amended by adding at the end the following: ``The Federal share shall be increased by 5 percent for States and local governments that (1) have a debris management plan approved by the Administrator; and (2) have prequalified 2 or more debris and wreckage removal contractors before the date of declaration of the major disaster. To qualify for the increased Federal share under the preceding sentence, a debris management plan shall be resubmitted to the Administrator for approval every 4 years.''. (b) Financial Incentives for Debris Recycling.--Section 407 such Act (42 U.S.C. 5173) is amended by adding at the end the following: ``(f) Debris Recycling.-- ``(1) In general.--A grant recipient under subsection (a)(2) may use funds from the grant for the costs of recycling debris and wreckage resulting from a major disaster, including the sorting of such materials. ``(2) Value of salvaged material.-- ``(A) Retention of financial benefits.--A grant recipient under subsection (a)(2) may retain any financial benefit received from the salvage of recycled debris or wreckage. ``(B) Treatment of financial benefits.--Any such financial benefit shall not be considered to be program income for purposes of section 13.25 of title 44, Code of Federal Regulations (or any successor regulation). ``(C) Contracts.--Any arrangement between a grant recipient under subsection (a)(2) and a contractor in which the contractor will retain possession of recyclable materials shall be reflected in the contractor's bid price. ``(3) Reporting.-- ``(A) Recipients that recycle debris.--A grant recipient under subsection (a)(2) that recycles debris or wreckage during disaster operations shall submit to the Administrator of the Federal Emergency Management Agency a written description of what the recipient did to recycle the debris or wreckage, the volume of the debris or wreckage that was recycled, and the monetary or nonmonetary benefits received, if any. ``(B) Recipients that do not recycle debris.--A grant recipient under subsection (a)(2) that chooses not to recycle debris or wreckage during disaster operations shall submit to the Administrator a written statement describing why this option was not used.''. SEC. 5. APPEALS PROCESS. (a) Timing.--Section 423(b) of the Robert T. Stafford Disaster Relief and Emergency Assistance Act (42 U.S.C. 5189a(b)) is amended by striking ``90 days'' and inserting ``60 days''. (b) Regulations.--The Administrator shall issue rules regarding the information that must be provided to an applicant in the event that a project worksheet is denied. The required information shall include, at a minimum-- (1) all reasons for which the project worksheet was denied; (2) the specific items, if any, in the project worksheet that are disputed; and (3) a description of any additional information the applicant needs to provide. SEC. 6. INDIVIDUAL ASSISTANCE FACTORS. In order to provide more objective criteria for evaluating the need for assistance to individuals and to speed a declaration of a major disaster or emergency under the Robert T. Stafford Disaster Relief and Emergency Assistance Act (42 U.S.C. 5121 et seq.), not later than 180 days after the date of enactment of this Act, the Administrator of the Federal Emergency Management Agency, in cooperation with representatives of State and local emergency management agencies, shall review, update, and revise through rulemaking the factors considered under section 206.48 of title 44, Code of Federal Regulations, to measure the severity, magnitude, and impact of a disaster. SEC. 7. HOUSEHOLD PETS AND SERVICE ANIMALS. Section 502(a) of Robert T. Stafford Disaster Relief and Emergency Assistance Act (42 U.S.C. 5192(a)) is amended-- (1) by striking ``and'' at the end of paragraph (7); (2) by striking the period at the end of paragraph (8) and inserting ``; and''; and (3) by adding at the end the following: ``(9) provide assistance for rescue, care, shelter, and essential needs-- ``(A) to individuals with household pets and service animals; and ``(B) to such pets and animals.''.

Disaster Recovery Improvement Act - Amends the Robert T. Stafford Disaster Relief and Emergency Assistance Act to authorize the President to increase the maximum total contributions for a major disaster by 5% under such Act if, at the time of a declaration of a major disaster, the affected state has in effect and is actively enforcing an approved building code. Sets forth state building code submission and approval requirements, including use of the nationally recognized model building code as a minimum standard. Directs the President, in making a contribution to a state or local government or a person that owns a nonprofit facility for repair, restoration, and replacement of a damaged facility, to provide not less than 50% of the President's initial estimate of the federal share as an initial payment. Provides for expedited payments. Requires the federal share for debris removal to be increased by 5% for states and local governments that have: (1) a debris management plan approved by the Administrator of the Federal Emergency Management Agency (FEMA); (2) prequalified two or more debris and wreckage removal contractors before the date of declaration of the major disaster; and (3) resubmitted such plan to the Administrator for approval every four years. Allows a recipient of a debris removal grant to: (1) use funds for the costs of recycling debris and wreckage resulting from a major disaster; and (2) retain any financial benefit received from the salvage. Increases the period for appeals of disaster assistance decisions. Directs the Administrator to review, update, and revise the factors considered to measure the severity, magnitude, and impact of a disaster. Authorizes the President to provide emergency assistance to pets and animals and their owners.

three demographic and health surveys ( dhs ) were conducted in ethiopia , in 2000 , 2005 and 2011 . results of these surveys were reported at the national level ( 13 ) , allowing examinations of demographic patterns ( 49 ) and topic - specific analyses ( 10,11 ) . however , the demographic impacts of population mobility on fertility and mortality have not been analyzed . as a result , the short- and long - term demographic impacts of migrations , in particular , the impacts of government - sponsored resettlement of the 1980s , 1990s , and 2000s remain largely unknown . this study aims to help fill this knowledge gap using a point - in - time analysis together with a longitudinal approach that compares reported numbers of births for settlers and non - settlers in gambella administrative region . gambella region was selected because it tops the list of destinations of government - sponsored resettlement dating back to the 1970s ( 12 ) . the neighboring region of benishangul - gumuz served as a control ( figure 1 ) . both regions have hosted settlers , refugees and internally displaced persons over the years , and have similar lowland climates and vegetations ( 1320 ) , but gambella 's proportion of the settler population is much larger . map showing the study and control areas the study has two main objectives : 1 ) to examine the possible impacts of government - sponsored resettlement on birthrates in gambella administrative region , and 2 ) to show the usefulness of using a neighboring administrative region with similar demographis , socio - economic and environmental characteristics as control ( figure 1 ) . we used a longitudinal approach and a point - in - time multivariate analysis in which women were placed in five - year age cohorts . the sample - based dhs 2000 , 2005 , and 2011 data were obtained from http://dhsprogram.com/data/datasetadmin/login_main.cfm following an online application for download . the enumeration areas in ethiopia 's last two censuses served as the sampling frame ( 13 ) . there were 876 women between the age of 1549 in gambella 's 2000 sample , 921 women in the 2005 sample , and 1,215 women in the 2011 sample . three variables were analyzed : 1 ) age of women at the birth of the first child , 2 ) the number of children born within five years of the 2000 and 2005 surveys , and 3 ) the number of children ever born . the 2000 and 2005 dhs have duration of residence information but the 2011 dhs does not . six records with missing duration of residence values were excluded in the 2000 sample , and 11 cases were excluded in the 2005 sample . the statistical software sas was used to conduct a multivariate analysis of variance ( manova ) . manova is simply an analysis of variance ( anova ) with two or more dependent variables . whereas anova tests for the difference in means between two or more groups , manova tests for the difference in two or more vectors of means ( 21 ) . it can be interpreted as the proportion of the variance in the outcomes that is not explained by an effect ( 21 ) . to calculate wilk 's lambda for each characteristic root , one has to calculate 1/(1 + the characteristic root ) , then find the product of these ratios . pillai 's trace is the other measure ( 21 ) . to calculate pillai 's trace , each characteristic root is divided by 1 + the characteristic root , and then the sums of these ratios are summarized . it is the sum of the roots of the product of the sum - of - squares matrix of the model and the sum - of - squares matrix of the error for the two linear regression functions and is a direct generalization of the f statistic in anova ( 21 ) . the hotelling - lawley trace is calculated by summing the characteristic roots listed in the output . roy 's greatest root is the largest of the roots of the product of the sum - of - squares matrix of the model and the sum - of - squares matrix of the error for the two linear regression functions . because it is a maximum , it can behave differently from the other three test statistics . as a general rule , in instances where the other three are not significant and roy 's is significant , the effect should be considered non - significant ( table 1 ) . number and percentage of women respondents in gambella , benishangul - gumuz , and nationally by 5 year age group ( ethiopian demographic survey , 2011 ) age distribution of sample women : figure 1 shows the percentage distribution of sample women in the 2011 dhs by five - year age groups . differences in age distribution between women interviewees nationally , those in gambella and those in benishangul - gumuz were not statistically significant ( figure 1 ) . the proportion of women under 30 years of age was 60.8% nationally , 62.5% in benishangul - gumuz , and 57.8% in gambella . the main difference is in the length of time various age cohorts of women had lived in their places of interview by the time of dhs 2011 . analysis of data from all three surveys showed significantly higher proportions of nonnatives in gambella 's 2011 dhs than nationally or in benishangul - gumuz . duration of residence : results of dhs 2000 show that 1519 year old nonnatives represented 20.1% of the population nation - wide , 19.1% in benishangul - gumuz , and 41.8% in gambella . for 2024 year olds , the proportions of nonnatives at the national level , in benishangul - gumuz , and in gambella were 35.3 , 29.6 and 66.6% respectively , suggesting a minority status for 2024 year old females in gambella but not nationally or in benishangul - gumuz . for the 2529 year old females , the respective proportions of nonnative females were 42.7 , 39.0 , and 65.6% . nonnative 3034 year old females were also a majority in gambella ( 54.4% ) but a minority nationally ( 43.7% ) and in benishangul - gumuz ( 45.6% ) . by the time of dhs 2000 , the proportion of females residing in places of interview for less than 10 years was 28.0% nationally , 23.2% in benishangul - gumuz , and 44.0% in gambella . the proportions with length of stay between 10 and 19 years were 7.0% nationally , 5.6% in benishangul - gumuz , and 12.6% in gambella . duration of residence and age of respondents at the birth of their first child : the dots in figure 2 show how old an individual female interviewee was at the birth of her first child . the line graphs show the average age of women at the birth of the first child by duration of residence . a focus on the extreme age groups ( 1519 and 4549 ) reveals generational differences in the effect of duration on age at first birth . three observations emerge : a ) in both gambella and benishangul - gumuz , there is no difference in age at first birth between natives and nonnatives for the 1519 age group , b ) in both gambella and benishangul - gumuz , there is a difference in age at first birth between natives and nonnatives for the 4549 age group and c ) the difference is in opposite directions with native 4549 year olds having a lower average age at first birth than nonnatives in any duration group in gambella while nonnatives had a higher age at first birth than natives in any duration group in benishangul - gumuz . the effect of duration of residence on age at first birth in gambella is statistically significant ( p < .0001 ) ( table 1 ) . age of respondent at first birth by age at the time of survey and duration of residence ( dhs , 2000 ) duration of residence and childbearing during the five years prior to dhs 2000 : one fifth ( 20.7 % ) of respondents had two or more births during the five years prior to dhs 2000 nationally , 24.9% in benishangul - gumuz and 15.6% in gambella . on the other hand , the proportion of female respondents who only had one birth during that period was 26.5% nationally , 26.7% in benishangul - gumuz , and 36.6% in gambella . for gambella , the difference by duration of residence is statistically significant ( p<.0001 ) ( table 1 ) . figure 3 reveals significant effect of duration of residence in gambella , but not in benishangul - gumuz . total children ever born by age at the time of survey and duration of residence nonnatives in the 3034 age group were between the ages of 10 and 14 at the time of arrival prior to 1980 . the 2.0 children per woman deficit for the 3034 year - olds at dhs 2000 could be explained by the disruptive effects of resettlement . there is no native - nonnative difference for the two age groups in benishangul - gumuz . the native - nonnative difference in gambella also applies to the 3539 , 4044 and 4549 year age groups , with nonnatives reporting approximately two additional lifetime births than natives . this pattern is largely absent in benishangul - gumuz , where most curves representing the average number of children by women 's age and duration cohorts are overlapping ( figure 4 ) . number of births in the five years prior to dhs 2000 by age and by duration of residence figure 5 presents a comprehensive longitudinal picture . the table portion combines findings from all the three demographic surveys by using the number of births in the last five years variable for the entire 16-year period ( the five years preceding dhs 2000 to the end of dhs 2011 ) , and by tracking age cohorts of women . the six - year - interval for 2005 to 2011 was made possible by reclassification of single age distributions using sas . this approach provided an opportunity to follow recent reproductive histories of an age cohort using the number of births in the last five years variable as proxy . the graph portion of figure 5 shows the percentages of women who had two or more births in the five years prior to dhs 2000 , dhs 2005 , and dhs 2011 . gambella 's position during the three surveys is noteworthy for the shift from a bottom position in 2000 to the second highest in 2011 . for instance , 43.9% and 23.3% of women aged 2529 in benishangul - gumuz and gambella had two or more births respectively during dhs 2000 . at 33% percentage of women who had two or more births in the five years prior to dhs 2000 , dhs 2005 , and dhs 2011 ( top graph ) and the number of children born per woman by age group of respondents between 1995 and 2011 ( bottom table ) univariate and multivariate analyses of variance : a summary univariate analysis based on a point - in - time dhs 2000 data is provided for gambella followed by a multivariate analysis of variance ( manova ) ( table 1 ) . results of the manova with all the three dependent variables in combination and the duration of residence as the independent variable show a statistically significant effect . the null hypothesis for each of these tests is the same : the independent variable has no effect on any of the dependent variables . duration of residence ( coded v013 ) is the independent variable in both the univariate and the multivariate analysis . the first dependent variable considered was total number of children ever born ( code v201 ) . we obtained an r - square of 0.53 , a root mse of 1.65 , a coefficient of variation of 45.20 and a mean value of 3.65 . the second dependent variable in the univariate analysis was number of births in the five years prior to dhs 2000 ( code v208 ) , giving a r - square of 0.24 , a root mse of 0.67 , a coefficient of variation of 72.48 and a mean of 0.92 . the third dependent variable in the univariate analysis was age of respondent at first birth ( code v212 ) ( r - square 0.11 , root mse 3.47 , coefficient of variation 18.88 , mean of 18.42 ) . all three results were statistically significant ( p < 0.0001 ) ( table 1 ) . no studies are available regarding the impacts of large scale resettlement on birth rates . by achieving its two main objectives of showing the fertility effects of resettlement in gambella and of demonstrating the advantages of using a neighboring region as control we adopted a dual approach of longitudinal age - cohort tracking on the one han and a point - in - time multivariate analysis on the other , to examine the possible demographic impacts of resettlement in gambella region . both the dual approach and the use of benishangul - gumuz as control represent a methodological improvement in the analysis of dhs data . our overall finding is that resettlement has the effect of reducing the number of lifetime births for women who arrived at young ages , but not on women who were past the mid - point of their reproductive years at the time of arrival . the effect of resettlement on women just coming into marriageable ages at the time of arrival is unlikely to be the singular reason gambella has a lower total fertility rate ( tfr ) than benishangul - gumuz ( 13 ) . we are not able to show whether or not settler - native differentials existed in contraceptive prevalence ( 5 ) , or if gambella 's sociopolitical factors ( 13 , 15 , 16 and 18 ) differentially affected birth rates among settlers . we analyzed reproductive histories using a count of lifetime births and recent fertility based on the 16-year period starting with five years prior to dhs 2000 and ending at the conclusion of dhs 2011 . the picture for gambella is complex , and specific results depended on whether the focus was on cumulative numbers of lifetime births or on recent fertility . our analysis traced the reproductive histories of the 1970s and 80s arrivals based on age at the time of dhs 2000 . the comparison between women in the 3034 and 4044 age groups is particularly noteworthy . for 4044 year - olds , the total number of births is higher among nonnatives in the 20 + duration group than among natives by about 1.5 lifetime births per woman . the reverse is true for 3034 year olds in the 20 + years ' duration group . here this is not surprising given that nonnatives in the 3034 age groups were aged 1014 at the time of arrival prior to 1980 . the 2.0 lifetime births per woman deficit for the 3034 year old nonnatives could be thought of as resulting from the disruptive effects of resettlement . supporting evidence comes from the absence of native - nonnative differences for the two age groups in our control region , benishangul - gumuz . the higher cumulative lifetime births in gambella also apply to 3539 , 4044 and 4549 year - olds where approximately two additional births were registered for nonnatives than for natives . in other words , the disruptive effect of resettlement on child birth was limited to women who were younger than 35 years of age at dhs 2000 . settler women aged 40 or higher at dhs 2000 had higher lifetime births in any duration group than native born women . these findings do not apply to benishangul - gumuz where native - born women have higher lifetime births than nonnatives in any age or duration group . a different portrait emerges when recent reproductive performances ( births in the five years preceding the three surveys ) are analyzed . the picture from gambella 's dhs 2000 is one of an initial deficit for age cohorts of nonnatives compared to natives ; a deficit which is then made up over a period of 16 years ( five years prior to dhs 2000 through the end of dhs 2011 ) . results of the multivariate analysis with duration of residence as the independent variable and three dependent variables ( age at the time of first birth , number of births in the five years within five years of the 2000 and 2005 surveys and lifetime births ) showed a statistically significant effect of duration of residence when based on a point - in - time analysis of gambella 's dhs 2000 . however , a longitudinal age cohort analysis showed the duration effect as moderating over time . the moderation is reflected in the absence of significant native - nonnative differences in the number of children ever born when five - year age cohorts are followed from dhs 2000 to the dhs 2011 . the longitudinal approach followed in figure 5 shows the success settler women in gambella achieved in making up for the deficits recorded in dhs 2000 . for example , 2024 year old females in benishangul - gumuz started with a five - year average of 0.66 births in 2000 and ended with a cumulated total of 2.02 births for the 16 year period ( five years prior to dhs 2000 through dhs 2011 ) . their counterparts in gambella started with a lower five year average of 0.56 in 2000 but had matched the 16-year cumulated total for women in benishangul - gumuz by the end of the 16-year period in 2011 . we recommend that the length of stay variable be reinstated in ethiopia 's future dhs surveys to capture the effects of population mobility on birth rates and other demographic variables . monitoring of the possible impacts of mobility on health and death is also dependent on the inclusion of the length of stay variable .

backgroundthis study aims to examine the possible impacts of resettlement on birth rates by using the length of stay variable in the 2000 demographic and health survey ( dhs).methodsdata in all three rounds of gambella administrative region 's demographic and health surveys ( dhs ) are analyzed . the neighboring administrative region of benishangul - gumuz is used as a control . the multivariate analysis of variance ( manova ) is applied with duration of residence as a categorical independent variable . the statistical software sas is used.resultsin a univariate analysis of gambella 's dhs 2000 , duration of residence has a significant effect on mothers ' age at first birth ( p < 0.001 ) , the number of children born within the five years of the survey ( p<0.001 ) , and the total number of children ever born ( p<0.001 ) . in the manova analysis , the duration effect on all three is also statistically significant ( p<0.001).discussionresettlement had a disruptive effect on birth rates among females who were just coming into marriageable ages in places of origin but were resettled to gambella . although the disruptive effects waned over time , the initial shortfall resulted in reduced overall lifetime births for settler women who were not past the midpoint of their reproductive years at arrival.conclusionbased on the reproductive history of female settlers with different duration of residence in the resettlement schemes , we recommend the reinstatement of the length of residence question in future dhs surveys in ethiopia to allow a longitudinal tracking of demographic trends among nonnative populations .

but the role of submucous fibroids which are reported in 5%-18% of patients as a causal factor for infertility is likely . submucous fibroids are postulated to cause menometrorrhagia , preterm delivery , postpartum hemorrhage , and puerperal infection . in their submucosal location , myomas can be treated exclusively using surgical procedures and they may be accessible by operative hysteroscopy : the standard minimally invasive surgical approach . though a large number of reports have been published on laparoscopic and laparotomic myomectomy , the studies available regarding hysteroscopic myomectomy are few in number by comparison . a few retrospective studies published in 1990s have demonstrated successful reproductive outcome after hysteroscopic removal of submucous myomas in infertile women . the aim of this retrospective study was to evaluate the subsequent fertility and outcome of pregnancy after hysteroscopic myomectomy according to ( a ) the characteristics of submucous fibroids and ( b ) association with intramural fibroids . the study was conducted during a period of 6 years from 2004 march to 2010 march . this was a retrospective cohort study . in order to assess the other associated causes of infertility , patients were evaluated by follicular study , hormonal assessment , semen analysis , and laparoscopy . the details of subsequent fertility were obtained from hospital records and direct information from patients . all infertile patients with submucous fibroids confirmed on three - dimensional ( 3d ) ultrasound . only those patients who had a follow - up of at least 12 months from the day of surgery were included . submucous fibroids were classified based on european society of gynaecological endoscopy into type 0-whole of fibroid inside the uterine cavity . of these , 37 patients who were subfertile and fulfilled our criteria were included . in infertile patients , the duration of infertility ranged from 12 to 108 months , the mean duration being 42 months . pre - operative treatment with leuprolide 3.75 mg once a month for 2 months were given in two cases when the size of fibroid was 4 cm . all myomectomies were performed under general anesthesia . in all 37 patients , resectoscope ( 26 fr , karl storz , tuttlingen , germany ) with a bipolar wire loop the intrauterine pressure was controlled by hamou hysteromat , karl storz , tuttlingen , germany . resection was carried out under video control from fundus to os using cutting current . for each patient , intra- and postoperative complications such as hemorrhage , perforation , or intravasation of fluid medium into circulation was recorded . all these patients had a postoperative sonogram at the end of 3 months to evaluate the completion of the procedure . postoperative estrogen and progesterone was given in four patients , when the affected endometrial surface was too broad . fertility was analyzed according to the type of fibroids , size , number of myomas , associated intramural fibroids , associated factors contributing to infertility , and time to conception using spss software . analysis was performed using chi - square test and chi - square test modified by yates . all infertile patients with submucous fibroids confirmed on three - dimensional ( 3d ) ultrasound . duration of infertility more than or equal to 12 months . only those patients who had a follow - up of at least 12 months from the day of surgery were included . submucous fibroids were classified based on european society of gynaecological endoscopy into type 0-whole of fibroid inside the uterine cavity . a total of 48 patients had undergone hysteroscopic myomectomy during the study period . of these , 37 patients who were subfertile and fulfilled our criteria were included . in infertile patients , the duration of infertility ranged from 12 to 108 months , the mean duration being 42 months . pre - operative treatment with leuprolide 3.75 mg once a month for 2 months were given in two cases when the size of fibroid was 4 cm . all myomectomies were performed under general anesthesia . in all 37 patients , resectoscope ( 26 fr , karl storz , tuttlingen , germany ) with a bipolar wire loop the intrauterine pressure was controlled by hamou hysteromat , karl storz , tuttlingen , germany . for each patient , intra- and postoperative complications such as hemorrhage , perforation , or intravasation of fluid medium into circulation was recorded . all these patients had a postoperative sonogram at the end of 3 months to evaluate the completion of the procedure . postoperative estrogen and progesterone was given in four patients , when the affected endometrial surface was too broad . fertility was analyzed according to the type of fibroids , size , number of myomas , associated intramural fibroids , associated factors contributing to infertility , and time to conception using spss software . analysis was performed using chi - square test and chi - square test modified by yates . the mean patient age was 32 years ( range : 24 to 40 years ) . the mean duration of infertility was 42 months ( range : 12 to 108 months ) . the most common symptoms were menorrhagia which was present in seven patients and dysmenorrhea / pelvic pain in five patients . of the 37 patients , the average time taken for the procedure was 54 mins ( range : 20 - 180 ) including associated laparoscopy and the treatment of intraoperative complications . the average duration of hospital stay was 40 h. removal of subserous myoma was performed in 14 cases . all cases of intramural fibroids found close to endometrium or distorting endometrium as previously diagnosed by 3d or four - dimensional ultrasound and intramural fibroids more than 4 cm were resected by simultaneous laparoscopy performed in nine cases . two of the patients with intramural myoma had undergone hysteroscopic myomectomy as part of pre in vitro fertilization ( ivf ) workup and intramural myomectomy was not performed in them . the size of intramural fibroids was 3 and 2.5 cm in these cases . there were two complications in this series ( 5.4% ) . one patient had intraoperative hemorrhage which was controlled with intrauterine foleys for 8 h and one pint of blood transfusion . a total of 11 patients conceived after hysteroscopic myomectomy , that is , 29.7% . of the 37 patients , endometriotic cystectomy or fulguration of deposits was done for them , three had polycystic ovaries which were punctured , two had associated male factor infertility , and three had tubal pathology . in contrast , in those with submucous fibroids with no other identifiable cause , 40% conceived . the value , though substantially higher than those with multifactorial infertility , was not statistically significant [ table 1 ] . pregnancy outcome in patients according to associated infertility factors in our study population , 33.3% of patients with type 0 submucous fibroids conceived , while 25% of those with type 1 conceived . pregnancy outcome according to the type of myomas of the 37 , 28 patients had only one , six had two submucous fibroids , and three patients had three submucous myomas . none of the patients with three or more submucous fibroids conceived . of those with only one submucous fibroid , 32.1% conceived , while in those with two or more submucous myomas , only 22% conceived . thus , conception varied inversely with the number of myomas , though this was not found to be statistically significant [ table 3 ] . pregnancy outcome according to number and size of submucous fibroids the mean number of myomas removed was 1.343 ( range : 1 - 3 ) . in those with size less than 3 cm , 24.3% and those with fibroids mor than 3 cm , -50% conceived [ table 3 ] . thus , it was found that removal of submucous fibroids more than 3 cm has a beneficial effect on fertility , though this was not statistically significant . eight out of the 26 patients with submucous myoma alone conceived , while among those with associated intramural fibroids , three patients conceived . the conception rate was higher in those without associated intramural myoma-30.7% when compared to those with associated intramural myoma-27.6% and this was found to be statistically significant p = 0.045 . nine of the 11 patients with an intramural myoma had undergone a intramural myomectomy . in the remaining two patients , the size of intramural myoma was less than 4 cm and had undergone hysteroscopy as part of pre ivf workup and intramural myomectomy was not performed in them . of the nine patients operated , there were three pregnancies , that is , 33.3% . but due to the small size of the sample ( n = 2 ) , a comparison was not possible between the two groups . the miscarriage rate was found to be much higher in patients with associated intramural myoma-33.3% versus those with no associated intramural myoma-12.5% . however , this was not found to be statistically significant tab . the mean time taken to conceive was increased significantly in those with intramural fibroids than those without intramural fibroid [ table 4 ] . fertility according to the presence of associated intramural fibroids of the 37 patients analyzed , 23 had primary infertility and 14 had secondary infertility . eight ( 34.7% ) of those with primary infertility conceived , while three ( 21.42% ) of those with secondary infertility conceived . endometriotic cystectomy or fulguration of deposits was done for them , three had polycystic ovaries which were punctured , two had associated male factor infertility , and three had tubal pathology . in contrast , in those with submucous fibroids with no other identifiable cause , 40% conceived . the value , though substantially higher than those with multifactorial infertility , was not statistically significant [ table 1 ] . pregnancy outcome in patients according to associated infertility factors in our study population , 33.3% of patients with type 0 submucous fibroids conceived , while 25% of those with type 1 conceived . of the 37 , 28 patients had only one , six had two submucous fibroids , and three patients had three submucous myomas . none of the patients with three or more submucous fibroids conceived . of those with only one submucous fibroid , 32.1% conceived , while in those with two or more submucous myomas , only 22% conceived . thus , conception varied inversely with the number of myomas , though this was not found to be statistically significant [ table 3 ] . the mean number of myomas removed was 1.343 ( range : 1 - 3 ) . less than 3 cm , 24.3% and those with fibroids mor than 3 cm , -50% conceived [ table 3 ] . thus , it was found that removal of submucous fibroids more than 3 cm has a beneficial effect on fertility , though this was not statistically significant . eight out of the 26 patients with submucous myoma alone conceived , while among those with associated intramural fibroids , three patients conceived . the conception rate was higher in those without associated intramural myoma-30.7% when compared to those with associated intramural myoma-27.6% and this was found to be statistically significant p = 0.045 . nine of the 11 patients with an intramural myoma had undergone a intramural myomectomy . in the remaining two patients , the size of intramural myoma was less than 4 cm and had undergone hysteroscopy as part of pre ivf workup and intramural myomectomy was not performed in them . of the nine patients operated , there were three pregnancies , that is , 33.3% . but due to the small size of the sample ( n = 2 ) , a comparison was not possible between the two groups . the miscarriage rate was found to be much higher in patients with associated intramural myoma-33.3% versus those with no associated intramural myoma-12.5% . however , this was not found to be statistically significant tab . the mean time taken to conceive was increased significantly in those with intramural fibroids than those without intramural fibroid [ table 4 ] . of the 37 patients analyzed , 23 had primary infertility and 14 had secondary infertility . eight ( 34.7% ) of those with primary infertility conceived , while three ( 21.42% ) of those with secondary infertility conceived . in our experience , the pregnancy rate after hysteroscopic myomectomy in infertile patients was 29.7% . little data are available about fertility after hysteroscopic myomectomy for submucous myoma . in a series of 13 infertile women by corson and brooks , the pregnancy rates after the procedure as reported by various studies have been described in table 5 . summary of studies reporting on the reproductive outcome after hysteroscopic myomectomy many of these series report better results than those achieved in the present study . nevertheless , the current results are similar to those reported in two studies , namely a pregnancy rate of 33.5% in 31 women ( bernard et al . ) and a rate of 28.7% in 14 women ( hucke et al . ) . all these studies thus conclusively prove that submucous fibroids are associated with infertility and their removal considerably improves fertility . the pregnancy rate was 40% when the myoma was the only apparent cause , compared with 22.7% with the presence of additional factors . we found that the results are best with type 0 fibroids-33.3% and the rates drastically fell with increasing intramural extension . the reduction in fertility rates with increasing intramural extension was also reported in a study by ioannis et al . , it was a small study that looked at 25 patients . they found a fertility rate of 57.15% in type 0 , 42.8% in type 1 , and 25% in type 2 fibroids . paradoxically , in the current study , the rate was higher among those with larger myomas ( 30 mm ) . this observation is important ; indeed , the large size of the myoma was in these cases the sole factor for infertility , and reinforced the fact that myomas could be a cause of infertility . similar results were obtained in a myomectomy via laparotomy series ( sudik et al . ) , while another group ( varasteh et al . ) reported similar findings when using hysteroscopy , with a cumulative pregnancy rate of 25% for myomas < 20 mm and 75% for those > 30 mm . these results offer indirect proof that large myomas are a valid cause of infertility , mainly because of the mechanical distortion and the dystrophy that they cause . the pregnancy rate was significantly higher in those without associated intramural fibroids than those with intramural fibroids in our study even after their correction . comparing those patients in whom intramural fibroids were left alone with those in whom they were corrected however , the sample size was too small ( n = 2 ) to make any statistical inference . in the current study , 75% of the pregnancies occurred during the 1 year , with a mean surgery to conception time span of 4 months . this short delay of conception has also been observed by others ( rosenfeld ; goldenberg et al . ) . it is , therefore , strongly recommended that patients attempt to conceive soon after the procedure . . they also found a statistically significant negative correlation of intramural myomas with term delivery rate and early conception after hysteroscopic myomectomy . the rate of miscarriage was found to be higher in patients with associated intramural fibroid when compared with those without intramural fibroid- 33.3% versus 12.5% . however , the difference was not statistically significant . this result is in accordance with those of matsunaga and shiota which suggests that myomas increase the risk of miscarriage . the difference could not be due to cavity distortion as that was corrected by laparohysteroscopy . therefore , the results reinforce the hypothesis that other mechanisms may contribute like endometrial atrophy , hyperplasia , vascular factors , and inflammation . in fertile women , expression of molecular markers of endometrial receptivity hoxa11 , leukemia - inhibiting factor , and basic transcriptional element - binding protein 1 rises during luteal phase with the peak occurring during implantation window . in a study by shokrazadeh and alizadeh , endometrial levels of hoxa11 , lif , and bteb1 m rna were significantly reduced in infertile patients with uterine fibroid as compared with healthy fertile controls at the time of implantation . other causes implicated are adhesion molecules , epidermal growth factor , insulin like growth factor , and transforming growth factor present in fibroids . several groups ( fahri et al . ; eldar - geva et al . ; stovall et al . ; have suggested that submucosal leiomyomas and fibroids distorting the endometrial cavity were associated with a reduction in the efficacy of assisted reproduction technique cycles due to reduced implantation and delivery rates ( pritts et al . ) ( home and crithchley ) and that myomectomy should be completed prior to ivf cycles . our results were also analyzed according to the type of infertility . in the present study , completely intracavitary myomas and absence of other contributing factors seem to be the best prognostic factors for further fertility . removal of large myomas ( more than 3 cm ) has a much more beneficial effect on fertility than small ones . the mechanisms by which leiomyomas interfere with fertility are unclear , but presence of intramural myomas was found to impair delivery rate and fertility in our study . since in the majority of patients in this series , intramural myomas which cause cavity distortion and large intramural myomas had been removed previously or by simultaneous laparoscopy , an independent assessment of their effect on fertility and pregnancy outcome was not possible . however , based on this study , removal of associated intramural myomas seems to be a wise option in patients undergoing hysteroscopic myomectomy who are desirous of childbearing .

background : submucosal myomas are associated with infertility and may be treated by hysteroscopic resection.objective:the aim of this retrospective study was to analyze 37 subfertile patients who unnderwent hysteroscopic myomectomy in a tertiary care center with particular regard to their postprocedure reproductive outcome.materials and methods : the entire patient group ( n = 37 ) underwent the procedure between march 2004 and march 2010 . the submucosal myomas were type 0 ( n = 27 ) , type 1 ( n = 8) , and type 2 ( n = 2 ) . the mean myoma size was 2.1 cm ; mean duration of the procedure was 54 mins and mean follow - up was 26 10 months . 22 patients had one or more associated infertility factors.results:the complication rate was 5.4% . 11 patients ( 29.7% ) conceived after the procedure . the pregnancy rate was better when myoma was the exclusive etiology of infertility ( 40% ) , when the myoma was completely intracavitary ( 33.3% ) , when the lesion was 30 mm in size ( 50% ) , and there were no associated intramural fibroids.conclusion:hysteroscopic myomectomy is a safe procedure to enhance fertility especially in cases with unexplained infertility .

antibiotic resistance is a public health problem that , arguably , has the potential to destroy the efficacy of all antibiotics in the next 1020 years . there is , therefore , an urgent need for new drugs , especially ones that might be more resistance - resistant . one possible approach to achieving this goal is to move away from targeting the direct killing of pathogens to inhibiting their virulence , because this might lead to a decreased life or death . a second approach would be to develop more drugs that target pathogen cell membranes . an example of this type of drug would be the antifungal amphotericin , which functions by binding to ergosterol ( which is not present in human cell membranes ) . a third and well - known approach is to employ combination therapies , although the problems associated with finding two new drugs active against two new targets are clearly significant . this could involve series inhibition , in which targets would be in the same metabolic pathway ( figure 1 , left ) , parallel inhibition , in which the targets would be unrelated but an inhibitor might mimic a common substrate or would affect , for example , a membrane function ( figure 1 , middle ) , or network inhibition , in which many targets in series and/or in parallel could be involved ( figure 1 , right ) . while challenging , many drugs that have been effective in monotherapy do in fact have multiple targets while single - target drugs ( many of which are used in treating tuberculosis ) are often only effective in combination therapies . series ( in the same metabolic pathway ) , parallel ( unrelated pathways or dna / membrane targets ) , or network ( series and parallel target ) inhibition . in this work , we consider the mechanism(s ) of action of the new antituberculosis drug 1 ( chart 1 ) , currently in phase ii clinical trials . this drug candidate appeared of interest because it contains a c10 isoprenoid ( geranyl ) side chain together with a strongly basic ( ethylenediamine ) fragment , a likely cationic center , suggesting that it might act as a carbocation isostere for a transition state / reactive intermediate in isoprenoid biosynthesis and , as with other inhibitors of isoprenoid biosynthesis , it might be involved in multitargeting.1 was developed in a synthesis / screening program in which 64 000 ethylenediamine analogues of the antituberculosis drug ethambutol ( 2 ) were synthesized . 1 was 4 more active than any of the other leads developed , having a minimum inhibitory concentration ( mic ) of 0.71.56 m against m. tuberculosis ( h37rv , erdman , and drug - resistant strains ) , and insights into its mode of action recently became available when the target of sq109 was proposed to be mmpl3 , a trehalose monomycolate ( tmm ) transporter , an essential membrane protein that transports tmm into the cell envelope . this conclusion was based on the observation that several m. tuberculosis mutants produced via serial passage with several 1-like inhibitors had mutations in the mmpl3 gene and cross - resistance to 1 , although these latter effects were rather small . more intriguingly , no spontaneous resistant mutants were obtained when using 1 , suggesting the possibility of multiple targets . that idea is supported by the observation that 1 also has activity against other bacteria , e.g. , helicobacter pylori(14 ) as well as against the yeast candida albicans , neither of which possess the mmpl3 gene , suggesting again that other 1 targets are harbored by these organisms and , potentially , by m. tuberculosis . in this work , we synthesized a series of analogues of 1 in which we varied the adamantane headgroup and the ethylenediamine linker ( varying the possible charge centers ) , chart 1 . all compounds were screened against a panel of bacteria ( m. tuberculosis , m. smegmatis , escherichia coli , staphylococcus aureus , and bacillus subtilis ) , two yeasts ( saccharomyces cerevisiae and candida albicans ) , a malaria parasite ( plasmodium falciparum ) , and a human cell line ( mcf-7 ) , to establish antibacterial , antifungal and antimalarial structure activity relationships and to assess mammalian cell toxicity . in addition , we investigated a subset of compounds for activity against a series of putative targets , isoprenoid biosynthesis enzymes , in addition to investigating the effects of these compounds on respiration , atp synthesis , and the proton motive force ( pmf ) . to investigate which features contribute to the activity of 1 against a broad range of organisms , we synthesized 1 and the 11 analogues ( 313 ) shown in chart 1 in which the ethylenediamine linker was replaced by ethanolamine , choline , propanolamine , ethylene glycol , or glycolic amide moieties ( providing linkers with potentially 0 , 1 , or 2 positive charges ) , as well several head group as expected , 1 had potent activity against m. tuberculosis with an mic of 0.10.2 g / ml ( table 1 ) . interestingly , the n - geranyl ethanolamines 3 and 13 were more potent ( mic values as low as 0.020.05 g / ml ) , indicating that the presence of two nitrogens was not essential for activity . the o - geranyl ethanolamine derivative ( 4 ) had activity similar to that of 1 ( 0.2 g / ml ) , table 1 . with the n - geranyl ethanolamines ( 3 , 13 ) , activity was about 30-fold higher than with ethambutol ( 2 ) . the ethylene glycol ( 5 ) was far less active ( 50 g / ml ) , as was the glycolic amide 9 ( 12 g / ml ) . thus , the most active compounds all contain one strongly basic nitrogen in the linker region , with most activity being found with the two n - geranyl ethanolamines 3 and 13 ( table 1 ) , with 3 being 45 times more active than that of 1 . the results ( table 1 ) show that overall activity against m. smegmatis is less than that observed against m. tuberculosis , as can also be seen in the heat map shown in figure 2a . there is , however , a very high correlation coefficient ( r = 0.9 , figure 2b ) between the pic50 (= log10 ic50 ) values for m. tuberculosis and m. smegmatis , indicating a similar mechanism of action , leading to our use of m. smegmatis in several mechanism of action studies , as described below . inhibition of cell growth for m. tuberculosis ( mt ) , m. smegmatis ( ms ) , s. aureus ( sa ) , b. subtilis ( bs ) , e. coli ( ec ) , s. cerevisiae ( sc ) , c. albicans ( ca ) , p. falciparum ( pf ) , and a human cell line ( mcf-7 ) by 1 , 313 . red = strong inhibition ; yellow = moderate inhibition ; green = weak / no inhibition . ( b ) correlation r values for cell growth inhibition pic50 (= log10 ic50 , m ) or pmic = ( log10 mic , m ) between all systems investigated . all 12 compounds ( 1 , 313 ) were then tested against three other bacteria : s. aureus , b. subtilis , and e. coli , table 1 . with s. aureus ( the methicillin - resistant s. aureus ( mrsa ) usa300 strain ) , 1 itself had little activity ; however , the n - geranyl ethanolamines 3 , 12 , 13 and the n - geranyl propanolamine 6 all had mic values of 8 g / ml , while the other analogues were much less active ( mic > 32 g / ml ) . a similar pattern of activity was seen against b. subtilis , with the three ethanolamines ( 6 , 12 , 13 ) exhibiting the highest levels of activity . in addition , unlike with s. aureus , 1 itself had activity ( 7.6 g / ml , table 1 ) . with e. coli , 1 , the n - geranyl ethanolamine ( 3 ) and the n - geranyl propanolamine ( 6 ) were all quite active , with ic50 values of 23 g / ml , table 1 . moreover , there was a modest correlation ( r = 0.5 ) between the m. tuberculosis ( or m. smegmatis ) pmic values and those found with e. coli , figure 2b . these results again indicate that at least one basic amine , most likely a cationic center , is required for best activity ; plus , there must be a target or targets other than mmpl3 in e. coli because the mmpl3 gene is absent in this organism . bioinformatics searches did locate uncharacterized mmpl3-like genes in s. aureus and b. subtilis , but it remains to be seen if the corresponding proteins are targeted by our compounds . we next tested all 12 compounds ( 1 , 313 ) for activity against s. cerevisiae and c. albicans . as can be seen in table 1 and figure 2a , 1 and the ethanolamines 3 , 6 , 11 , and 13 had activity in the 13 g / ml range , with 1 and 13 being the most potent , having an ic50 1 g / ml . with c. albicans , 1 was most active , followed by the ethanolamines 3 and 13 . not unexpectedly , there was a high correlation between the pic50 values seen between s. cerevisiae and c. albicans ( r = 0.8 ; table 1 and figure 2b ) . a modest correlation between the pic50 values for the yeasts and e. coli or b. subtilis is also apparent ( r = 0.60.7 , figure 2b ) , suggesting the possibility of target conservation between fungi and bacteria . because a recognizable mmpl3 gene is absent in the fungi , these results again indicate an alternate target or targets . these results also lead to the idea that there could be additional targets in m. tuberculosis , which would help explain the very low mic values observed and the inability to induce resistance via serial passage , as noted by tahlan et al . , although multiple - targeting does not necessarily guarantee improved potency . the results with the bacteria and fungi then suggested the possibility that the growth of other organisms ( protozoa ) might also be inhibited by 1 or its analogues . to evaluate antiprotozoal activity we screened all 12 compounds ( 1 , 313 ) against the intraerythrocytic form of the malaria parasite , plasmodium falciparum . as can be seen in table 1 , 1 had a 1 g / ml activity against p. falciparum , and the three ethanolamines ( 3 , 4 , and 6 ) also had good activity . as viewed on the heat map ( figure 2a ) , inhibition of m. tuberculosis cell growth is strongest but is followed by p. falciparum ( in the intraerythrocytic assay ) and in each case where there is activity against p. falciparum ( 2 , 3 , 4 , 6 , 7 ) , the inhibitors ( chart 1 ) are expected to carry a + 1 charge , as with the best m. tuberculosis growth inhibitors . when compared to growth inhibition results with a human cell line ( mcf-7 ; table 1 ) , we see that activity against the human cells is much weaker than against p. falciparum and , of course , against m. tuberculosis . we calculate a therapeutic index ( ti ) , defined as : of 18 for 1 against p. falciparum and 40 for 3 , while for m. tuberculosis we find ti = 120 ( 1 ) and ti = 900 ( 3 ) , suggesting that these and related analogues may also be promising p. because the human cell growth assays are carried out in the presence of 10% fetal bovine serum ( fbs ) , we tested three of the most active compounds ( 1 , 3 , 13 ) against e. coli in the presence or absence of 10% fbs . there was only a 1.6 0.07 increase in the ic50 , meaning that , as expected , serum binding is small and quite similar for each of these compounds . we next sought to explore what the additional targets for these compounds might be in cells that lack mmpl3 . the general patterns of activity seen with the compounds described above have some similarities across the diverse organisms investigated in that at least one cationic center , or perhaps more importantly a protonatable nitrogen , is required for activity . in m. tuberculosis , 1 is thought to act by inhibiting mmpl3 , a tmm transporter , although as noted by tahlan et al . this seems quite likely because in most cases these other organisms lack mmpl3 or a clearly identifiable orthologue , and do not utilize tmm , as is also the case with h. pylori . given that protonated geranylamines might be good isosteres for transition states or reactive intermediates in enzymes involved in isoprenoid biosynthesis ( scheme 1 ) , we investigated if 1 could inhibit any of the following enzymes : m. tuberculosis cis - farnesyl diphosphate synthase ( rv1086 ) ; m. tuberculosis cis - decaprenyl diphosphate synthase ( rv2361 ) ; p. vivax geranylgeranyl diphosphate synthase ( ggpps ) ; s. aureus and e. coli undecaprenyl diphosphate synthases ( uppss ) , s. aureus farnesyl diphosphate synthase ( fpps ) , and human ggpps . in essentially all cases , ic50 values were 50 m . the exception was human ggpps , which was inhibited by 1 ( the only compound with two basic groups ) with a 4.5 m ic50 . these enzymes are all so - called cis or trans-head - to - tail prenyltransferases and the presence of the two ( as opposed to one ) hydrophobic domains ( in addition to the cationic center ) might not be required for enzyme inhibition . there are , however , other prenyl transferases that might be targeted in which two hydrophobic domains , together with a carbocation center , would better mimic transition states / reactive intermediates . these would include the so - called head - to - head prenyl transferases , as well as some of the enzymes involved in quinone biosynthesis . there are demonstrated or putative head - to - head prenyl transferases in m. tuberculosis ( rv3397c ) , m. smegmatis , ( mycsm_04912 ) , s. aureus ( crtm ) , b. subtilis ( yisp ) , s. cerevisiae ( squalene synthase , sqs ) , and c. albicans ( sqs ) and in humans ( sqs ) , but no homologous proteins can be found by standard blast searches in p. falciparum . the products ( where known ) of these enzymes vary , and not all are essential for survival in vitro . nevertheless , we tested a subset of compounds ( 1 , 3 , 4 ) for activity against either sacrtm or human sqs , finding only weak activity ( 100 m ) in all cases . these results support the notion that the head - to - head prenyl transferases are unlikely cell growth inhibition targets of our compounds in these organisms . cis - fpps and trans - fpps , upps , and dpps are not inhibited by 1 but crtm is , and crtm-1 structures have been reported ( pdb i d 4ea1 , 4ea2 ) and serve as models for mena inhibition . the other obvious candidates are the enzymes involved in quinone biosynthesis ( scheme 2 ) or quinone utilization . we thus next investigated the two quinone biosynthesis enzymes , mena and meng , both of which are likely to utilize cationic transition states / reactive intermediates during catalysis . mena ( ec 2.5.1.74 , 1,4-dihydroxy-2-naphthoate polyprenyl transferase ) catalyzes the isoprenylation of 1,4-dihydroxy-2-naphthoic acid by long chain isoprenoid diphosphates , scheme 2 , and mena is of interest as an m. tuberculosis drug target . in an initial set of experiments we tested three potent m. tuberculosis and m. smegmatis growth inhibitors ( 1 , 3 , and 13 ) in the m. smegmatis mena ( msmena ) membrane fragment inhibition assay described previously , finding ic50 values of 6 m ( table 2 ) . typical dose response curves are shown in figure s1a , supporting information . while this assay revealed only modest activity , the observation that mena activity was in fact inhibited by the three most potent inhibitors is a potentially important one because this inhibition might be expected to inhibit electron transfer / atp synthesis , of particular importance in nonreplicating / persister cells , and to contribute to cell growth inhibition beyond that seen with mmpl3 inhibition alone . what was also of interest was that 1 had similar activity ( ic50 = 9 m , in the same assay as used here ) against mena to that we reported previously with ro 48 - 8071 , a lipophilic amine that decreases menaquinone biosynthesis and blocks m. tuberculosis as well as m. smegmatis cell growth . these growth inhibition effects with ro 48 - 8071 ( as well as the inhibition of respiration ) were reported previously to be reversed in both organisms by addition of 400 m menaquinone-4 ( mk-4 ) or phylloquinone to the medium . ic50 in m , m. smegmatis membrane fraction ( figure s1 , supporting information ) . ic50 in m , from methylene blue reduction assay ( figure s3 , supporting information ) . ic50 in m , from disc3(5 ) assay ( figure s7 , supporting information ) . ic50 in m , expressed e. coli mena ( figure s2 , supporting information ) . . ic50 in m , measured with e. coli imvs ( figures s4 and s5 , supporting information ) . n.d . : not determined a second possible target is meng ( ec 2.1.1.163 , 2-polyprenyl-1,4-naphthoquinone methyltransferase ) which carries out the s - adenosylmethionine ( sam)-dependent methylation of demethylmenaquinone ( the product of the mena reaction ) . as with mena , the meng reaction is inhibited by 1 and the potent ethanolamine analogues 3 , 13 ( table 2 , and figure s1b , c , supporting information ) , with ic50 in the 613 m range . unlike the c - alkylations with prenyl diphosphates , the meng reaction uses sam ( as a c1 source ) , and mg is not required . with 1 binding to meng , the cationic center in the inhibitor might mimic a cationic transition state / reactive intermediate , although another possibility is that the cationic center simply mimics the sam s - methyl sulfonium group . thus , both mena and meng are inhibited in vitro by 1 and its analogues , which can be expected to supplement mmpl3-based inhibition in the mycobacteria , as well as provide alternative targets in some of the organisms that lack the mmpl3 gene . moreover , inhibition of two sequential targets ( series inhibition ) in a biosynthetic pathway can often be quite effective because the product of the first reaction is the substrate for the second reaction . we next used an expressed e. coli mena ( hereafter ecmena ) detergent - based assay to obtain inhibition data for all 12 inhibitors , table 2 , and figure s2 , supporting information . interestingly , the most potent inhibitor was 3 ( ic50 = 400 nm ) , and 3 was also the most potent inhibitor of m. tuberculosis cell growth ( and , within experimental error , of e. coli cell growth , table 1 ) . we additionally found that there was a moderate correlation between e. coli cell growth inhibition and ecmena inhibition with an r = 0.43 ( using pic50 = log10 ic50 , both values in m ) values , suggesting that mena inhibition may be involved in cell growth inhibition . as described below , the experimental vs predicted e. coli cell growth inhibition correlation increased to r = 0.77 with the incorporation of a second experimental parameter , ph collapse . the structure of mena is not known , but it is predicted to be a transmembrane protein containing about nine -helices , as shown in figure 3a . using modern structure prediction programs such as phyre2 that are secondary - structure based , mena is predicted ( figure 3b ) to adopt basically all the same -helical folds as found in farnesyl diphosphate synthase and crtm ( the s. aureus dehydrosqualene synthase ) but where one n- and two c - terminal helices ( transmembrane helices 1 , 8 , and 9 in figure 3a ) are not modeled , figure 3b . a total of 198 residues ( 68% ) are , however , modeled at a predicted > 90% accuracy , and the predicted structure has the closest similarity to the crystal structure of farnesyl diphosphate synthase from methylococcus capsulatus ( pdb i d 3ts7 ) , although remarkably there is only a 10% residue identity . the first and second aspartate - rich motifs essential for mg binding and catalysis in fpps and crtm are located in very similar regions in the mtmena model , as shown in the superposition with crtm in figure 3c ( orange spheres = conserved asps in ecmena model ; blue spheres = asp - rich motif in crtm ) . this then suggests , based on the 1crtm x - ray structure , the binding sites for 1 ( pink ) shown in figure 3c . the two asp - rich domains in mena are also highly conserved , as shown by a scorecons analysis ( table s1 , supporting information ) . although only a computational prediction , it is of interest that the highest scoring phyre2 prediction is found with a prenyl transferase enzyme that is known to utilize a carbocation mechanism , consistent with the experimental observation that only cationic species inhibit mena . ( b ) transmembrane helices in phyre2 model of mtmena ( helices s1 , s8 , and s9 from a are not modeled ) . ( c ) mena model ( cyan ) and crtm ( green , pdb : 4ea1 , n- and c - terminal helices are removed ) . we next measured the activity of 1 against both actively growing ( m. tuberculosis h37rv ) and nonreplicating ( streptomycin - starved m. tuberculosis 18b ) mycobacteria , using a resazurin microplate reduction assay ( rema ; figure 4 ) . 1 had a mic of 0.15 g / ml against actively replicating h37rv in this assay , as expected . it also displayed activity against the nonreplicating streptomycin - starved 18b strain ( where mmpl3/tmm transport is presumably not involved because there is no cell growth ) , and the effects of 1 on both strains were affected by mk-4 addition ( figure 4 ) . in the h37rv aerobic assay , the mic shifted from 0.15 g / ml in the absence of mk-4 ( figure 4a ) to 1 g / ml when the medium was supplemented with 1 mm menaquinone , consistent with a role for 1 in inhibiting quinone biosynthesis and/or electron transport . as noted above , a remarkably similar effect was seen previously with ro 48 - 8071 , another lipophilic amine , at 400 m mk-4 , for both m. tuberculosis and m. smegmatis . the effect of 1 against nonreplicating ( streptomycin - starved 18b ) bacteria , as seen by rema as a decrease in fluorescence ( lack of resazurin reduction to the highly fluorescent red resorufin ) above a 1 concentration of 1 g / ml was also blocked by mk-4 addition ( figure 4b ) . the activity of 1 against nonreplicating ( streptomycin - starved 18b ) cells was confirmed by plating and counting cfu after 7 days of drug exposure ( figure 4c ) with normal 7h9 medium or with 7h9 medium containing 1 mm mk-4 . as can be seen in figure 4c , 1 at 1 g / ml had essentially no effect on ( nonreplicating ) bacterial activity in the presence of mk-4 and only a small effect in the absence of mk-4 . however , at 10 g / ml 1 , while there was again a small effect on activity in the presence of mk-4 , cell activity in the absence of mk-4 was reduced by 4 log units , consistent with a role for 1 in blocking respiration and hence atp synthesis . ( a ) aerobic m. tuberculosis h37rv growth inhibition in the presence of increasing mk-4 concentrations , measured by rema . ( b ) as in a but with nonreplicating m. tuberculosis 18b . ( c ) m. tuberculosis 18b cells were plated after 7 days of drug exposure with ( gray ) or without ( black ) mk-4 . concentrations are in g / ml . the results described above show that 1 has activity against not only the two mycobacteria ( m. tuberculosis and m. smegmatis ) but also a range of other bacteria , fungi , and a protozoan , each of which lack a bioinformatically recognizable mmpl3 gene . in m. tuberculosis and m. smegmatis , inhibition of mena / meng would inhibit respiration , resulting in a decrease in atp biosynthesis . this could help explain how 1 increases the level of tmm given that mmpl3 is a tmm transporter of the rnd family of efflux pumps , many of which are powered by the pmf . restated , 1 might exhibit an indirect action upon the tmm transporter by removing its power source ( the proton motive force ) , in addition to directly binding to , and inhibiting , the transporter . this indirect action could be accomplished in one of two ways : ( 1 ) blocking respiration ( by depletion of menaquinone by inhibition of mena or meng or by directly inhibiting a component of the electron transport chain ) ; ( 2 ) a direct effect on the pmf ( + ph , where is the membrane potential and ph , the ph gradient ) . the possibility of the involvement of the pmf is suggested from the results of a number of studies in which lipophilic bases ( e.g. , amiodarone , local anesthetics , and nsaids ) can act as uncouplers . in addition , there could also be multidrug targeting affecting mmpl3 ( or efflux pumps ) , mena , meng , and the pmf , which would be expected to produce potent inhibition of cell growth / respiration / atp synthesis , as well as a low rate of resistance . in earlier work , we showed that several mena inhibitors , analogues of ro 48 - 8071 , blocked respiration in m. tuberculosis and m. smegmatis ( as evidenced by inhibiting the reduction of methylene blue ) , that there was a correlation between cell growth inhibition and respiration inhibition , and that the effects of the inhibitors could ( at least in part ) be reversed by adding mk-4 at the 400 m level . we thus next tested all compounds for their effects on methylene blue reduction , in m. smegmatis ( figure s3 , supporting information ) , finding that there was a moderate correlation between pmic (= log10 mic , mic in m ) for cell growth inhibition and the pic50 (= log10 ic50 , ic50 in m ) for inhibition of whole cell respiration inhibition ( r = 0.55 ) for all 12 compounds ( tables 1 and 2 ) . these results suggest the possibility of a direct effect on electron transport ( because the effects observed are rapid : tens of minutes ) , blocking respiration , consistent with the mk-4 rescue experiments . the nature of the target or targets involved are beyond the scope of this current study , but we did carry out preliminary experiments with 1 against a series of dehydrogenases by monitoring the reduction of the artificial electron acceptor mtt ( 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2h - tetrazolium bromide ) . we used an m. smegmatis membrane preparation and a variety of substrates including nadh ( measuring both complex i and alternative nadh dehydrogenases , ndh-2 ) , deamino - nadh ( measuring complex i activity but not ndh-2 ) , succinate ( measuring succinate dehydrogenase ) , malate ( measuring quinone - dependent malate dehydrogenase ) , and lactate ( measuring lactate dehydrogenase ) . ic50 values for 1 were in general 30 g / ml , the exception being malate dehydrogenase ( ic50 = 10 g / ml ) , results that suggest that more than one - electron - transfer protein may be involved , in cells , with the inhibitors mimicking quinone substrates . the results presented above show that 1 and its analogues inhibit mena , meng , electron transfer proteins , and respiration and that mk-4 can rescue cell growth or activity , the relatively high ic50s for enzyme inhibition / respiration ( when compared to cell growth inhibition ) being suggestive of multiple targeting . what is of particular interest about all of the results described above is that they seem to point in one direction : respiration , offering a possible explanation for the previous observation that tmm accumulates ( with 1 ) , in m. tuberculosis , due to mmpl3 inhibition . this mmpl3 inhibition could be due to direct binding or a more indirect effect on the pmf / atp synthesis . to test the hypothesis that 1 and its analogues might collapse the pmf , we first used e. coli inverted membrane vesicles ( imvs ) , essentially as described by haagsma . the results obtained with sf6847 , one of the most potent uncouplers known , are shown in figure 5a and indicate a very rapid ( seconds ) collapse in ph , as reported by haagsma et al . the same effect was seen with 1 and analogues that have potent activity in cell growth inhibition , while inactive ( diether / amide ) analogues ( e.g. , 5 ) had no effect , figure 5b , figures s4 and s5 , supporting information . the effects on the collapse in ph were seen in vesicles in which the ph gradient was driven by either atp hydrolysis or by electron transport in the presence of succinate or nadh . using oxonol vi as a probe , we also found that in e. coli imvs ( positive inside ) was collapsed ( figure s6a ) by the same compounds , and there was a correlation between the collapse of the membrane potential and the collapse in ph ( using acma fluorescence ; table 2 ; r = 0.79 , figure s6b , supporting information ) . this is consistent with these lipophilic cations acting as protonophores , carrying protons across the membrane lipid bilayer , with only compounds containing a basic nitrogen supporting the uncoupling activity . ( a ) ( d ) effects of 3 on atp biosynthesis of effect in m. smegmatis cells . we found similar pmf effects in intact m. smegmatis cells in which there was a collapse in ( positive outside ) , as measured by using disc3(5 ) fluorescence , figure s7 , supporting information . addition of 1 or the potent analogues to m. smegmatis cells resulted in an immediate increase in disc3(5 ) fluorescence , indicating a collapse of . as can be seen in figure s7b , supporting information , 1 collapses the membrane potential in a dose - dependent manner with an ec50 of 20 g / ml . the ec50 for one of the most potent cell growth inhibitors 13 was 15 g / ml . in addition to these investigations of collapse in intact cells , we investigated ph collapse in intact m. smegmatis cells , using p nmr spectroscopy . phosphorus nmr chemical shifts are sensitive indicators of local ph values . as can be seen in figure s8a , supporting information , the p nmr chemical shift of phosphate inside m. smegmatis is 0.35 ppm downfield from external pi , and from these chemical shifts , the internal and external ph values can be determined : results are shown in figure s8b , supporting information . there is a ph = 0.26 ( inside more basic ) in wild type m. smegmatis cells , but this ph gradient is collapsed by the uncoupler cccp ( m - chlorophenylcarbonyl cyanide phenylhydrazone ) , by the antiporter nigericin , and by 1 and 13 , while as expected , the k ionophore valinomycin has no effect . the effects of 1 and the other potent analogue thus leads to collapse of as well as ph in both inverted vesicles and in whole cells . this collapse in the pmf , in cells , can be expected to result in an inhibition of atp synthesis , as is indeed found experimentally ( figure 5d ) with the potent lead , 3 . in addition , the collapse of the proton motive force is expected to inhibit activity of the mmpl3/tmm transporter . any quantitative analysis of cell growth inhibition based on enzyme inhibition or another property ( e.g. , ph collapse ) is of course challenging , but it should be possible to use the multidescriptor approach described previously with , in this case , no purely mathematical descriptors being required . we thus use eq 1:1where pic50(a ) is log10 ( ic50 , a ) for enzyme or property a ( such as mena inhibition ) , and b is a second property , e.g. , ph collapse . we show by way of examples in figures 6a , b , three - dimensional plots for e. coli cell growth inhibition : log ic50 = f ( mena , ph ) , and for m. smegmatis : log mic = f ( respiration , ) , where we find correlation coefficients of r = 0.82 ( e. coli ) and r = 0.72 ( m. smegmatis ) values for the experimental - versus - predicted cell growth inhibition results . in previous work we investigated correlations between cell and enzyme activity ( pic50 ) assays in 10 diverse systems finding on average an r = 0.32 for the 10 cell / enzyme correlations , similar to the r = 0.43 we find for the mena alone / e . incorporation of the second parameter ( the percentage of ph collapse ) increases the r to 0.77 , suggesting the importance of multitargeting , in e. coli . the correlation is worse for m. smegmatis due , perhaps , to the omission of an mmpl3 term , expected to be particularly important in the mycobacteria . experimental ( red circles ) and computed ( colored plane ) results for cell growth inhibition based on eq 1 . ( a ) e. coli cell growth inhibition predicted using mena , ph collapse ( ic50s in m , r for the model = 0.77 ) . ( b ) m. smegmatis growth inhibition using respiration ( methylene blue assay ) and collapse ( mic and ic50s in m , r for the model = 0.64 ) . the results presented above show that e. coli mena is inhibited by 1 and its analogues and that there is a correlation between mena inhibition and cell growth inhibition ( in m. smegmatis ) , suggesting that diverse menas may be inhibited by these compounds . however , this result is perhaps surprising in that in e. coli , mena is not an essential gene for aerobic growth because ubia can be used in aerobic respiration . one possibility is that ecubia might also be inhibited by 1 ( and its analogues ) . while we have not yet investigated this experimentally , what we have found is that mtmena , ecmena , and ecubia are all predicted ( using the phyre2 program ) to have an fpps / ggpps - like structure . in all three cases the structures are predicted to contain a central fpps / gpps - like catalytic domain ( comprising 2/3 of the overall amino acid sequence ) that has close similarity to the same two ( soluble ) prenyl synthases : methylococcus capulatus fpps and lactobacillus brevis ggpps . predicted sequence identity investigations have shown that mena and ubia have moderate homology , but correlations with fpps and ggpps were not made in those studies because the actual sequence identities are very low , about 1016% . however , secondary - structure - based algorithms do permit accurate structure predictions , even when residue identities are low . these previous bioinformatics studies also demonstrated that another class of proteins , protoporphyrin ix farnesyl transferases ( e.g. , heme o synthase ) , have significant sequence homology to the mena / ubia proteins , and all three classes of proteins are mg - dependent prenyl transferases . once again , the structure of heme o synthase is not known but is predicted to be another nine - helix transmembrane protein with a central fpps / ggpps - like core , suggesting that mena , ubia , and protoporphyrin ix farnesyl transferases are all likely to be inhibited by 1 and related systems . mmpl3 is thought to be a target for 1 ( and other diverse inhibitors ) , blocking tmm transport . it has also been shown that mmpl3 together with a related protein , mmpl11 , is associated with heme uptake . however , both are membrane proteins and are predicted to have 1112 transmembrane helices . using the phyre2 program , we find with mmpl3 that 653 residues ( 69% coverage ) are predicted with 100% confidence to have the structure shown in figure 7a and with mmpl11 , 642 residues ( 66% coverage ) are predicted with 100% confidence to have the structure shown in figure 7b . both structures are very similar to those found in cation efflux pumps such as cusa ( pdb i d 3ko7 ) and multidrug efflux pumps such as the acriflavin resistance protein b ( acrb ; pdb i d 1oy8 ) , although the c - terminus ( 1/3 of the total protein ) is not modeled in either mmpl3 or mmpl11 . the transmembrane hydrophobic domains are shown in figure 7c , d ( in white / light orange ) . 1 as well as several other inhibitors ( figure 7e ) has been proposed to target mmpl3 ( detected by sequencing mutants that arose under drug pressure ) , but the sites of these mutations , shown as blue spheres in figure 7f , are spread throughout the protein , suggesting , perhaps , multisite targeting of mmpl3/11 as an additional basis for the lack of resistant mutations with 1 . overall , however , the effects of 1 on the pmf and respiration , the menaquinone - reversal experiments , activity against diverse organisms as well as the ability to make generally good predictions of cell activity without mmpl3 inhibition data suggests that mmpl3 may not be the primary target for 1 , in m. tuberculosis . ( c ) phyre2 predictions showing hydrophobic residues ( white / gray ) and their proposed relation to the membrane for mmpl3 . ( d ) phyre2 predictions showing hydrophobic residues ( white / gray ) and their proposed relation to the membrane for mmpl11 . ( e ) structure of representative m. tuberculosis growth inhibitors that are thought to target mmpl3 and ( f ) sites of resistance mutations ( blue spheres ) in mmpl3 . we show in figure 8 a summary of the proposed sites of action for 1 and its analogues in m. tuberculosis and in m. smegmatis . some of these targets are also present in the other pathogens investigated but not in human cells . in addition to its previously proposed role in targeting mmpl3 , 1 and its analogues also inhibit mena and meng and , as described above , the inhibition of m. tuberculosis cell growth or activity is rescued by mk-4 . we also find that the pmf is inhibited by the most active compounds , which act as protonophores / uncouplers . this results in a decrease in atp synthesis and , we propose , decreased activity of mmpl3/11 , helping explain the accumulation of tmm ( with 1 ) . mena , meng targeting can affect respiration / electron transfer ; pmf ( ph , ) collapse leads to decreased atp biosynthesis , reduction in pmf / atp - powered transporters ( e.g. , mmpl3 ) , increased tmm accumulation , and decreased cell wall biosynthesis . this multiple - targeting is perhaps best thought of as involving network inhibition in which both series and parallel paths are involved ( figure 1c ) because at least in the mycobacteria , mena , meng , electron transport , ph , , and mmpl3 ( and presumably other pumps dependent on the pmf ) can all be affected . there are , of course , likely to be differences in the mechanisms of action of different inhibitors in different organisms ( and in the same organisms under different growth conditions ) , although effects on the pmf are expected to be quite common because they are based on more physical properties , rather than purely enzyme inhibition . the uncoupling effects we observe could also help explain the growth inhibition seen in human cell lines , as could inhibition of the human mena , ubia , and meng / ubie orthologues : ubiad1 , coq2 , and coq3 . also of interest are the likely differences in time scales ( and concentrations ) for the different reactions involved . the effects on the collapse in and ph are very rapid - on the seconds to minutes time scale and are observed ( in vesicle experiments ) at low m concentrations , for the most active species . the effects on respiration as determined by methylene blue reduction ( in intact cells ) are also rapid , typically observable in minutes , and may reflect the time required for inhibitors to enter the cell and accumulate ( because they could also be actively pumped out ) . little is known about the rate of menaquinone turnover , but it is likely that several cell divisions are required for a large reduction in menaquinone levels , so while mena / meng inhibition may be rapid , the effects on cell growth may take many hours or ( with m. tuberculosis ) days to occur likewise , because mmpl3 is thought to be involved in cell wall biosynthesis , its inhibition would also be expected to result in observable effects on growth inhibition on a time scale of hours to days . the results we have described above are of interest for drug discovery against tuberculosis , as well as against other bacterial , fungal , and protozoan pathogens , for several reasons . we synthesized a series of analogues of the antituberculosis drug 1 in which we varied the nature of the ethylenediamine linker to provide cationic , protonatable , and neutral species , and in addition we varied the adamantyl headgroup . the most active compound against m. tuberculosis was 5 more potent than was 1 and was also less toxic to an mcf-7 human cell line . we tested all compounds against a panel of bacteria , fungi , and a protozoan parasite , and the results obtained showed that at least one cationic ( or basic ) group was essential for activity . the most potent activity was against m. tuberculosis ( mic = 0.020.05 g / ml ) and the intraerythrocytic form of the malaria parasite , p. falciparum ( ic50 = 30 ng / ml ) . to explore possible targets , we tested several compounds for activity against a panel of cis- and trans - prenyl transferases ( cis - fpps , fpps , dpps , ggpps , upps , crtm , and sqs ) as well as against the menaquinone biosynthesis enzymes , mena and meng . activity was seen against mena and meng , and we proposed a structural model for the mena active site , as well as a likely binding site for 1 . in addition , we found that menaquinone ( mk-4 ) rescued both aerobic h37rv m. tuberculosis cell growth and the activity of nonreplicating m. tuberculosis ( streptomycin - starved 18b ) . we found that 1 as well as several analogues inhibited oxygen consumption in m. smegmatis , and there was a correlation between oxygen consumption and cell growth inhibition . we tested 1 and each of the 11 analogues for their effects on the pmf ( ph and ) in fluorescence - based assays , as well as in some cases in intact cells ( via p nmr ) . the results obtained showed that 1 and the most potent cell growth inhibitors collapsed both and ph , and there were good correlations between experimental and predicted cell growth inhibition results based on mena/ph ( e.coli ) and respiration/ ( m. smegmatis ) . taken together , the results obtained suggested a model for 1/analogue activity in mycobacteria in which the increase in tmm levels seen on treatment with 1 have a contribution from ( indirectly ) inhibiting the tmm transporter mmpl3 by blocking the pmf / atp biosynthesis . overall , the results are of general interest because they indicate that 1 ( and its analogues ) can have diverse effects : on o2-consumption / electron transport / mena / meng inhibition ; on , ph , and atp biosynthesis , likely helping to explain activity against non - mmpl3-containing pathogens such as h. pylori , c. albicans , and , here , p. falciparum . moreover , the possibility of developing more potent compounds that can inhibit these targets is of general interest in the context of developing drug leads that are resistance resistant , due to multitargeting . moisture - sensitive reactions were performed under an inert atmosphere ( dry nitrogen ) with dried solvents . reactions were monitored by tlc using merck silica gel 60 f-254 thin - layer plates . flash column chromatography was carried out on merck silica gel 60 ( 230400 mesh ) . h nmr and c nmr spectra were recorded on varian ( palo alto , ca ) unity spectrometers at 400 and 500 mhz for h and at 100 and 125 mhz for c. coupling constants ( j ) are reported in hertz . high - resolution mass spectra ( hrms ) were recorded in the university of illinois mass spectrometry laboratory . hplc / ms was performed using an agilent lc / msd trap xct plus system ( agilent technologies , santa clara , ca ) with an 1100 series hplc system including a degasser , an autosampler , a binary pump , and a multiple - wavelength detector . all final compounds were 95% pure as determined by elemental analysis , analytical hplc / ms analysis , or qnmr analysis . qnmr spectra were recorded using varian ( palo alto , ca ) 500 mhz unity spectrometers with 1,3,5-trimethoxybenzene as the internal total - spin - count quantitation standard ; 60 pulse excitation , 60 s recycle delay , 1.0 hz line - broadening due to exponential multiplication , and 16 accumulations . qnmr data were processed using mnova nmr software ( mestrelab , escondido , ca ) . all nmr spectra ( including qnmr spectra ) are provided in the supporting information . mena and meng inhibition assays were carried out using m. smegmatis membrane fragments . in addition , we used an expressed , purified e. coli mena , as described below . vitamins k1 and k2 and kanamycin were purchased from sigma - aldrich ( st . s - adenosyl - l-[methyl - c]methionine ( c - sam ) obtained from perkin - elmer ( 47 mci / mmol ) . dmk8 was prepared from an e. coli ubie mutant ( cgsc # 11636 ) , which accumulates dmk8 , and was purchased from the e.coli genetic stock center , yale university ( http://cgsc.biology.yale.edu ) . meng assays were conducted using the membrane fractions prepared from m. smegmatis grown in 7h9 medium ( supplemented with oleic acid , albumin , dextrose , and 0.05% tween 80 ) . washed cells were resuspended in buffer a ( 50 mm mops ph 7.9 , 5 mm mgcl2 , 5 mm dl - dithiothreitol ( dtt ) , 10% glycerol ( v / v ) ) and disrupted by probe sonication on ice with a sanyo soniprep 150 ( 10 cycles of 60 s on and 90 s off ) . the whole cell lysate was centrifuged at 27 000 g for 20 min at 4 c . the supernatant was further centrifuged at 100 000 g ( for 2 h at 4 c ) in an optima tlx ultracentrifuge ( beckman ) . the membrane - enriched pellet was washed with buffer a followed by ultracentrifugation at 100 000 g. the washed pellet was resuspended in buffer a , divided into aliquots , and frozen at 80 c . the membrane protein concentration was estimated by using a bca protein assay kit ( pierce ) . assay mixtures ( 100 l ) contained 100 mm tris - hcl ph 8.0 , 1 mm dtt , 5 mm mgcl2 , 0.1% chaps , 600 ng of dmk8 , 40 m radiolabeled sam , and varying concentrations of inhibitor 1 ( 0 to 25.0 g / ml ) . reactions were initiated by the addition of 50100 g of m. smegmatis membrane protein and incubated at 37 c for 1 h. reactions were stopped by the addition of 0.1 m acetic acid in methanol ( 0.5 ml ) , and radiolabeled products were extracted with hexane ( 2 3 ml ) . pooled extracts were washed with 1 ml of water , evaporated to dryness under a n2 stream , and dissolved in chcl3/ch3oh ( 2:1 v / v ) . an aliquot was subjected to liquid scintillation counting ( ls 6500 , beckman coulter ) ; a second aliquot and authentic standards ( dmk8 and mk9 ) were subjected to reverse - phase tlc ( whatman kc 18f silica gel 60 a ) developed in acetone / water ( 97:3 ) . standards were visualized under uv light , and distribution of radioactivity was detected by phosphorimaging ( typhoon trio , amersham biosciences ) and quantified with imagequant tl v2005 software ( amersham biosciences ) . the gene encoding ecmena with a n - terminal strep tag was amplified by polymerase chain reaction ( pcr ) with forward primer 5-gacgacgacaagatgagcgcgtggagccatccgcagtttgaaaaaggcggtggcagcgcggagaatctttattttcagggcgctggtgc-3 and reverse primer 5-gaggagaag cccggttattatgctgcccactggcttaggaatat-3 , and then cloned into the pet46 ek / lic vector . the recombinant plasmid was transformed to e. coli c43 ( de3 ) and the protein induced with 1 mm isopropyl thiogalactopyranoside ( iptg ) at 37 c for 5 h. the cell paste was harvested by centrifugation at 7000 g and resuspended in buffer a containing 25 mm tris - hcl , ph 7.5 , 150 mm nacl , and 20 mm imidazole . a cell lysate was prepared with a jnbio pressure cell ( jn-3000 plus ) , the membrane , and soluble proteins being separated by ultracentrifugation at 150 000 g for 1.5 h. the resulting pellet was solubilized by incubation in buffer a supplemented with 1% ( w / v ) ddm detergent overnight at 4 c . the latter solution was centrifuged ( 100 000 g for 1 h at 4 c in a beckman ti70 rotor ) and the supernatant loaded onto a ni - nta column and washed with buffer a containing 0.05% ddm . the buffer and gradient for the ni - nta column were 25 mm tris , ph 7.5 , 150 mm nacl , 0.05% ddm , and 20500 mm imidazole . the protein was then loaded onto a strep - tactin ( iba ) column equilibrated with washing buffer containing 100 mm tris - hcl , ph 8.0 , 150 mm nacl , 1 mm edta , and 0.05% ddm and washed with five column volumes of washing buffer . ecmena was finally eluted with eluting buffer containing 100 mm tris - hcl , ph 8.0 , 150 mm nacl , 1 mm edta , 0.05% ddm , and 2.5 mm desthiobiotin . the purified protein was finally concentrated to 5 mg ml in a 25 mm tris - hcl , ph 7.5 , 150 mm nacl , 0.05% ddm buffer . inhibition of ecmena was carried out using an hplc - based protocol . typically , 2.5 g of ecmena in 100 l of reaction buffer ( 25 mm tris - hcl , 0.1% triton x-100 , 250 m mgcl2 , 10 mm dtt , ph = 7.5 ) was incubated with inhibitors for 30 min at 22 c . 1,4-dihydroxy-2-naphthoic acid ( dhna ) and farnesyl diphosphate ( fpp ) were then added to the enzyme solution to a final concentration of 150 m each . the reaction was incubated at 37 c for 3 h before quenching with 50 l of 0.1 m acetic acid in methanol containing 50 m menaquinone-4 ( mk-4 , sigma - aldrich ) as an internal standard . after centrifugation , 500 l of organic layer was collected and dried under nitrogen then dissolved in 200 l of methanol . twenty microliters of the methanol solution was then subjected to hplc analysis ( 0.1% formic acid in h2o to 0.1% formic acid in ch3cn , uv : 325 nm , 250 l / min ) . the amount of the mena reaction product demethylmenaquinone-3 ( dmmk-3 ) was determined by comparison of integrated peak areas between dmmk and the internal standard mk-4 . ic50 values were estimated by using origin 6.1 software to analyze the dose response curves . subtilis atcc 6051 , e. coli atcc 29425 , and saccharomyces cerevisiae atcc 208352 were purchased from the american type culture collection . the c. albicans strain was cai-4 ; the p. falciparum strain was 3d7 and the human cell line mcf-7 ( breast adenocarcinoma ) , obtained from the national cancer institute . all 12 compounds ( 1 , 313 ) were assayed for inhibition of m. tuberculosis cell growth as described previously . we measured the activity of 1 against both actively growing m. tuberculosis ( h37rv ) and nonreplicating m. tuberculosis ( streptomycin - starved 18b ) using a resazurin microplate reduction assay . response curves were investigated using medium that was supplemented with 0 , 10 , 100 , and 1000 m menaquinone ( mk-4 , sigma - aldrich ) in the presence of between 10 ng / ml and 10 g / ml 1 . the activity of 1 against nonreplicating 18b was determined after 7 days of drug exposure by plating the culture followed 28 days later by cfu counting after plating serial dilutions on 7h10 agar plates ( difco ) . c. albicans growth inhibition was carried out according to a reported protocol except that ypd media was used instead of rpmi 1640 . ic50 values for e. coli growth inhibition were determined by using a broth microdilution method . the culture was then diluted 500-fold into fresh lb medium and 100 l inoculated into each well of a 96-well flat - bottom culture plate ( corning inc . the starting concentration of each compound was 0.3 mm , and this was 2 serially diluted to 292 nm . an mtt ( ( 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ) cell proliferation assay ( atcc ) was then carried out to obtain bacterial viability dose response curves . briefly , 10 l of mtt reagent was added into each well , followed by incubation for 24 h until a purple precipitate was visible . then , 100 l of detergent reagent was added , and the plates were incubated in the dark at 22 c for 2 h. absorbance was measured at 570 nm and a nonlinear regression analysis carried out using origin 6.1 software . ic50 values for b. subtilis growth inhibition were determined by using a microbroth dilution method . a stationary starter culture of b. subtilis was diluted 50-fold into fresh lb broth and grown to an od600 of 0.4 . the culture was then diluted 500-fold into fresh lb medium to give a working solution , and then 100 l of working solution was transferred to each well of a 96-well flat - bottom culture plate ( corning inc . , corning , ny ) . inhibitors were then added at 0.5 mm and 2 serial diluted to 500 nm , the volume and solvent composition constant . plates were incubated for 1216 h at 37 c , and the absorbance at 600 nm was determined . a nonlinear regression analysis was carried out using origin 6.1 to obtain the ic50 values . the protocol was the same as for b. subtilis except that ypd instead of lb was used as the culture medium , and the 96-well plates were incubated for 48 h instead of 1216 h. we determined ic50 values for p. falciparum growth inhibition using the intraerythrocytic assay described previously . compounds were half - log serial diluted using cell culture media into 96-well tc - treated round - bottom plates ( corning inc . , corning , ny ) . cells were plated at a density of 5000 cells / well and then incubated under the same culture conditions for 2 days at which time an mtt ( ( 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ) cell proliferation assay ( atcc , manassas , va ) was performed to obtain dose response curves . dehydrogenase activity in m. smegmatis membranes was measured by using the mtt ( ( 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ) reduction assay in the presence of 5 mm kcn . mtt reduction was followed at 570 nm , after addition of the different substrates ( nadh , succinate , malate , or lactate ) . oxygen concentration was monitored at 37 c using a ysi model 53 oxygen electrode ( yellow springs instrument co. , yellow springs , oh ) equipped with a temperature - controlled 1.8 ml electrode chamber . the reaction mixture consisted of sodium phosphate buffer , ph 7.5 , 50 mm nacl , and 200400 g / ml membranes . the concentration of oxygen in the air - saturated buffer was taken to be 250 m , and the reaction was initiated by injecting 200 m nadh . the electron transport rates are expressed as mol of nadh oxidized or mol of o2 ( mol enzyme ) s. membranes were incubated with different concentrations of inhibitors for 5 min prior to nadh addition . the effects of inhibitors on were determined by fluorescence quenching of the potential - sensitive probe 3,3-dipropylthiodicarbocyanine ( disc3(5 ) ) . m. smegmatis were grown for 8 h in middlebrook 7h9-adc - tween 80 medium and diluted to an od600 of 0.3 in the same medium plus 10 mm glucose and 1 m nigericin . different concentrations of 1 and its analogues were added to the bacterial suspension , and changes in fluorescence due to the disruption of were continuously monitored with a fluorescence spectrophotometer ( fluostar omega , bmg labtech ) employing an excitation wavelength of 643 nm and an emission wavelength of 666 nm , at 30 c . m. smegmatis were grown for 8 h in middlebrook 7h9-adc - tween 80 and diluted to an od600 of 2 . different concentrations of 1 and its analogues were added and atp / adp ratios determined ( abcam ; adp / atp ratio assay kit , catalog number : ab65313 ) after 10 and 60 min of incubation at 37 c , 200 rpm . atp and adp were extracted from 50 l of cell suspension by adding trichloroacetic acid ( tca ) to a final concentration of 0.5% . after 5 min , tae ( tris acetic acid edta ) buffer was added to neutralize the system by diluting the sample 5-fold . the atp and adp cell concentrations were measured according to the manufacturer s protocol . e. coli imvs were prepared by three passages through a precooled french pressure cell at 20 000 psi . the lysate was centrifuged at 14 000 g at 4 c for 20 min to remove unbroken cells . the supernatant was centrifuged at 370 000 g at 4 c for 1 h , and the pellet , consisting of the imvs , was washed with 50 mm mops after the second centrifugation step , membranes were resuspended in 50 mm mops koh ( ph 7.5 ) , 2 mm mgcl2 , 10% glycerol , and stored at 80 c . imvs ( 0.1 mg / ml membrane protein ) were preincubated at 37 c in 10 mm hepes koh ( ph 7.5 ) , 100 mm kcl , 5 mm mgcl2 containing 2 m acma , and the baseline was monitored for 5 min . the reaction was then initiated by adding 1 mm atp or 5 mm succinate . when the signal had stabilized , 1 or its analogues were added and proton translocation was measured , fluorimetrically . the -sensitive fluorophore oxonol vi ( 1,5-bis(5-oxo-3-propylisoxazol-4-yl)pentamethine oxonol ) was used to determine if 1 and its analogues were able to dissipate the membrane potential in imvs . imvs ( 0.1 mg / ml membrane protein ) were added to assay buffer : 10 mm mops after a few seconds , 0.5 mm nadh was added to initiate respiration - dependent generation of ( positive inside ) , and the resultant quenching of oxonol vi fluorescence was monitored at 37 c . uncoupling by inhibitors was estimated based on their ability to dissipate the established , measured as the dequenching of the fluorescence signal . m. smegmatis was grown to a cell density of 10 cells / ml in a total volume of 500 ml in a 4 l erlenmeyer flask with constant shaking at 37 c in difco middlebrook 7h9 media supplemented with oleic acid / albumin / dextrose and 0.05% tween 80 . cells were harvested by centrifugation , and the pellet was washed twice with 5 mm phosphate buffer , ph 6.8 . the cell pellet was then resuspended in 200 l of the same buffer and 500 l of the resulting cell slurry transferred to a 5 mm nmr tube . chemical shifts were referenced with respect to 85% phosphoric acid in d2o in a coaxial capillary . p nmr spectra were obtained using a varian inova 300 ( at 121.5 mhz ) using 60 pulse excitation , proton decoupling , and a 1 s recycle time . a total of 1024 scans were accumulated corresponding to approximately a 60 min total data acquisition time ( without aeration ) . the peak corresponding to the -phosphate of atp ( at 10.5 ppm ) and the inorganic phosphate peaks of interest ( in the region of 01.5 ppm ) were used to calculate the internal and external ph using the following equation , where d is the distance between the -phosphate of atp and the inorganic phosphate peak , in ppm .

we report the discovery of a series of new drug leads that have potent activity against mycobacterium tuberculosis as well as against other bacteria , fungi , and a malaria parasite . the compounds are analogues of the new tuberculosis ( tb ) drug sq109 ( 1 ) , which has been reported to act by inhibiting a transporter called mmpl3 , involved in cell wall biosynthesis . we show that 1 and the new compounds also target enzymes involved in menaquinone biosynthesis and electron transport , inhibiting respiration and atp biosynthesis , and are uncouplers , collapsing the ph gradient and membrane potential used to power transporters . the result of such multitarget inhibition is potent inhibition of tb cell growth , as well as very low rates of spontaneous drug resistance . several targets are absent in humans but are present in other bacteria , as well as in malaria parasites , whose growth is also inhibited .

for approximately the past three decades , analysis of collisionally - excited forbidden lines in the optical / uv wavelength region has been the primary means of determining the physical conditions and element abundances in regions and planetary nebulae ( pne ) . studies of these emission lines have been a fundamental source of data for the study of the chemical evolution of galaxies other than the milky way and for comparison with models of stellar nucleosynthesis . for almost as long a time , however , there has been the nagging question of the reliablity of such abundance measurements . the crux of the problem is that collisionally - excited lines in the optical / uv part of the spectrum have large excitation energies ( 1 - 10 ev ) , and thus the excitation rates are acutely sensitive to electron temperature . @xcite pointed out that if significant fluctuations about an average temperature are present , the collisionally - excited line emission will be weighted toward hotter regions because of the exponential dependence on @xmath7 , while the balmer recombination lines will be preferentially produced in cooler regions because of the inverse dependence on @xmath7 . in this case , ion abundances derived from the forbidden lines could be systematically underestimated by a large amount . it has not yet been demonstrated definitively that significant deviations from a smoothly - varying temperature structure exist in photoionized nebulae , other than the gradients expected from ionization / thermal equilibrium models . determining whether such temperature fluctuations exist and their magnitude is challenging observationally , and it is strongly debated whether temperature fluctuations have a significant effect on abundance determinations based on collisionally - excited lines ( see mathis 1995 for a balanced discussion ) . it is often suggested that observations of recombination lines from the heavy elements would provide more reliable measures of element abundances than the commonly observed collisionally - excited lines . this is because recombination lines have very similar dependences on electron temperature , so the ratio of a given recombination line to , say , h@xmath2 is nearly independent of @xmath7 . thus , heavy element abundances could be calculated from recombination lines with virtually no systematic uncertainties , in principle . the main drawback is that recombination lines from elements heavier than he are intrinsically faint , typically less than 1% of h@xmath2 , because of the direct scaling of the emissivities with ion abundance . as a result , few measurements of heavy element recombination lines have been published . nevertheless , improved spectrographs and detectors have enabled high quality measurements of heavy element recombination lines , particularly , to be made in recent years @xcite . at the same time , improved computations of effective recombination coefficients for transitions of heavy element recombination lines ( e.g. , storey 1994 ) have made the analysis more reliable . for the orion nebula , @xcite found that recombination lines gave somewhat higher o@xmath3/h@xmath8 than the [ ] collisionally - excited lines , and interpreted this in terms of modest temperature fluctuations . on the other hand , @xcite have found that and [ ] yield spectacularly discrepant o@xmath3 abundances in the planetary nebulae ( pne ) ngc 7009 and ngc 6153 with the lines giving abundances 5 - 6 times larger than those derived from [ ] . these differences are so large that they can not be accounted for in the context of the @xcite small temperature fluctuation formulation . we have been obtaining new measurements of recombination lines in pne to further understand the cause of the - [ ] discrepancy . in @xcite ( hereafter paper ii ) , we will present measurements of integrated lines and derived abundances for a sample of ten pne , and compared these abundances with published results based on [ ] . the main results from paper ii are summarized in @xcite and @xcite . in particular , we find : ( 1 ) a wide range of values for the difference between - and [ ] - derived abundances ( @xmath9log o@xmath3/h@xmath8 anywhere between 0.0 and 0.8 dex ) ; ( 2 ) an inverse correlation between @xmath9log o@xmath3/h@xmath8 and nebular diameter ; and ( 3 ) that lines arising from levels populated mainly by dielectronic recombination are especially enhanced . in a companion program , we have obtained deep long - slit observations of some pne to study and compare the spatial distribution of both and [ ] emission , in the hope that this would provide new clues toward understanding the source of the abundance discrepancies . in this paper we describe the results for the largest object in our sample , the ring nebula ngc 6720 . we have observed several galactic planetary nebulae in long - slit mode in order to study the spatial distribution of emission from both the recombination lines and [ ] forbidden lines . these observations were obtained on the clear nights 6 - 7 june 1999 with the 2.3 m bok reflector at steward observatory , using the boller & chivens spectrograph . the spectrograph has a 1200@xmath10800 loral ccd with 15@xmath11 m pixels , corresponding to 083 per pixel at the detector . the four - arcminute long slit thus covers about 285 rows on the detector . we used an 832 line / mm grating in second order to cover the spectral range 4150 - 5000 . with a 25 slit , the spectral resolution was in the range 2.1 - 2.3 , with the best resolution set at approximately 4650 . in our ring nebula observations , the spatial profiles of stars along the slit had a fwhm of approximately 25 . we centered the long slit on the ngc 6720 central star , with the slit at a position angle of 91@xmath12 , where the pa is measured from n through e. we made four 15-minute exposures at this position . the two - dimensional data were processed by standard methods . the wavelength solution for the spectra was determined from the positions of he - ar lines from calibration lamp observations taken through the same spectrograph setup . the root - mean - square residuals from a fourth - order polynomial solution were approximately 0.1 . the object frames were divided by a normalized flat - field constructed by combining observations of the illuminated dome and the twilight sky . the spectra were corrected for atmospheric extinction using standard kitt peak national observatory extinction coefficients ; and finally , the spectra were placed on a relative photometric scale using a spectrometer sensitivity function derived from observations of standard stars from the list of @xcite . note that because of the narrow slit , absolute spectrophotometry was not possible ; however , the relative end - to - end photometric calibration is good to about 3% ; the flat - field uncertainty adds another 1% to the errors . after calibration , the four individual frames were combined to form a single image , and the sky background was subtracted . at this time we also extracted a section of the frame 131 pixels ( 109 ) wide containing only the bright emission from the nebula ( along the east - west direction ) , and rectified the image to align the centroid of the central star with the rows of the image , to ensure that features in each emission line lined up spatially . we saw no variation in the background between the four separate observations , so we averaged the frames before subtracting the background to improve the signal / noise for the sky determination . the sky level along each column was determined by a linear fit to the background in regions along each column outside the bright part of the nebula . note that the ring nebula has an extended halo outside the bright inner nebula @xcite . the faint emission from this halo is seen in the brightest lines in our spectrum , h@xmath2 , h@xmath13 , and [ ] 4959 . the halo emission extends across the entire slit ; however , this emission has a surface brightness of less than 1% of the surface brightness in the bright shell . therefore , subtraction of the halo component will have little effect on the line ratios we derive in the inner nebula . the final processing of the data involved extracting spatial cuts of various emission lines from the image . the extraction method was similar to that used for extracting one - dimensional stellar spectra , except that we did the extraction along lines of constant wavelength . as part of the extraction we subtracted the nebular and stellar continuum by fitting to line - free regions of continuum near the wavelengths of each extracted emission line . the result was an array of pure emission line flux vs. spatial position for each extracted line . note that continuum subtraction by this method does not take into account absorption lines in the central star spectrum , or in starlight scattered by dust within the nebula , that may coincide with an emission line . the effect of stellar absorption will manifest itself as peculiar emission line ratios at the position of the central star , and in general we will exclude the regions including the central star from the discussion ; the effects of scatterd starlight will be much smaller , and in any case would mean that the permitted lines are systematically even stronger than observed . figure 1 shows examples of extracted spatial profiles for a few emission lines . figure 2 shows an expanded view of the spectral region around 4661 for two different positions along the slit . figure 2 shows that , although [ ] @xmath14658 is significantly stronger than @xmath14661 in the inner part of the ring nebula , the two lines are readily distinguished and can be deconvolved accurately . we can estimate the interstellar reddening along the slit from the h@xmath13/h@xmath2 intensity ratio . this ratio depends slightly on the nebular electron temperature @xmath7 . for ngc 6720 @xmath7 is between 10,000 k and 12,000 k @xcite ; in this range of @xmath7 , the h@xmath13/h@xmath2 ratio is 0.47 @xcite . the relation between observed and reddened line ratios is given by @xmath14 where i@xmath15 and i@xmath16 are the observed and intrinsic line intensities , and f(@xmath1 ) @xmath17 f(h@xmath2 ) = 0.13 for @xmath1 = h@xmath13 , from the average interstellar reddening curve of @xcite . the coefficient @xmath18 ( or , more commonly , @xmath18(h@xmath2 ) ) is then the logarithmic ` extinction ' at h@xmath2 more accurately , a combination of absorption and scattering . figure 3(a ) shows the spatial variation of @xmath18(h@xmath2 ) we derive along the slit for ngc 6720 . generally , we see values for @xmath18 ranging between 0.1 and 0.2 along the slit , with possibly a slow increase from east to west along the slit . the reddening values we derive are consistent with the values obtained by @xcite and @xcite . note the spike at the position of the central star , where the line ratio is very likely affected by stellar absorption . note also the steep upturn at the e end and the downturn at the w end . we suspect these steep changes are not real , but artifacts resulting from small misalignment of the h@xmath2 and h@xmath13 extractions , combined with a small variation of the focus , at positions where the nebular surface brightness profile is declining rapidly ( see figure 1 ) . nevertheless , the correction for reddening relative to h@xmath2 is small for all lines in our observed spectral region along most of the slit , less than 10% over the region @xmath1938 from the central star . this is illustrated in figure 3(b ) , where we show the ratio of i(h@xmath13)/0.47 i(h@xmath2 ) . if there were no reddening , this ratio would be close to unity ; figure 3(b ) shows that this ratio is within 10% of unity over the region where the emission is bright . if we ratio lines in the blue half of the spectrum to h@xmath13 and those in the redward half to h@xmath2 , the error accrued is less than 5% over the regions of interest in the nebula . in the end , we chose this method to correct the line intensities . the regions of the nebula beyond @xmath1940 from the central stars have too low s / n for the faint lines to contribute to our analysis , so we will exclude them from the following discussion . our spectrum includes the [ ] 4711 , 4713 doublet ; the ratio of these two lines is sensitive to the electron density @xmath20 , similar to the [ ] 6717 , 6731 pair . there is one complication in using the [ ] ratio : the 4711 line is blended with the 4713 line at low resolution . this is apparent in our spectrum by a larger line width for the 4711 line , as well as a shift in wavelength from the inner nebula , where [ ] is strong and weak , to the outer ring where predominates . we can correct for the 4713 contamination by subtracting a scaled version of the 4471 line profile . @xcite estimated @xmath20 from [ ] line ratios in the ring , obtaining values of 200 - 600 @xmath21 . at these densities , collisional excitation has a small effect on the 4713/4471 line ratio , so we choose to neglect it . for @xmath7 @xmath5 10,000 k , the 4713/4471 intensity ratio is 0.11 , based on the emissivities computed by @xcite . assuming a constant temperature in the zone , we multiply the 4471 fluxes by 0.11 , then subtract the result from the 4711 line fluxes . the correction to the 4711 fluxes are small for the inner nebula , where emission is faint , and greatest in the outermost parts of the nebula . we estimated @xmath20 from two regions on either side of the central star , using the atomic code described by @xcite , assuming an electron temperature @xmath7 = 11,000 k. east of the central star , the mean [ ] ratio was [email protected] ( where the error is the rms scatter about the mean ) , which corresponds to @xmath20 = 740@xmath19250 @xmath21 , while west of the central star , the [ ] ratio was [email protected] , which yields @xmath20 = 660@xmath19500 @xmath21 . these values are consistent with the densities obtained by @xcite , @xcite and @xcite . @xcite derived densities approximately twice as large as ours ; however , this is the result of using atomic data for [ ] that are now out of date . we have re - computed @xmath20 using barker s data and the shaw & dufour program , and obtain densities similar to the ones we obtain from [ ] . since we observe both [ ] 4363 and [ ] 4959 we can estimate the electron temperature @xmath7 across the nebula . figure 4(a ) plots the variation of @xmath7 derived from the [ ] ratio , showing a smooth increase in @xmath7 from the shell to the interior of the nebula , from about 10,000 k in the shell to about 12,000 k in the center . this behavior is in good agreement with that derived by @xcite . for comparison , we plot in figure 4(b ) the [ ] @xmath14959/h@xmath2 line ratio across the slit . we note several features in the plot . first , the line ratio shows only a slow variation across most of the nebula , with a shallow minimum in the center . second , we see a steep decline in [ ] /h@xmath2 at about 36 from the central star in both directions . this most likely corresponds to the transition from o@xmath3 to o@xmath8 near the edge of the bright shell . third , [ ] /h@xmath2 increases again outside the bright shell , corresponding to the inner halo region , which evidently has rather high excitation and/or high ionization along these sightlines . note that the minima in @xmath7 do not correspond to the minima in [ ] /h@xmath2 , but rather lie just interior to the low - excitation zones . @xmath7 then appears to increase a bit in the region of low [ ] /h@xmath2 ; this increase may be a result of radiation hardening combined with inefficient cooling in the low - ionization zone of the nebula . the signal / noise in our 4363 line observation is too low to determine @xmath7 in the halo region . now that we have established the variation of @xmath7 across ngc 6720 , we can proceed to determine abundances for the ions of interest . for this study , we will derive abundances relative to h@xmath8 for o@xmath3 ( from both [ ] 4959 and 4661 ) , c@xmath3 ( from 4267 ) , he@xmath8 , and he@xmath3 , as a function of position along our slit . since the electron densities across the nebula are relatively small , we can assume the low - density limit and compute the ion abundances analytically . the abundance of any ion relative to h@xmath8 derived from the ratio of the intensity of a transition @xmath1 to the intensity of h@xmath2 is given by @xmath22 where @xmath23 represents the volume emission coefficient for a given emission line @xmath1 . for collisionally - excited lines in the low - density limit , the analysis in section 5.9 of @xcite applies . the volume emission coefficient for a collisionally - excited line is given by @xmath24 where @xmath25 is the collision strength for the transitions observed , @xmath26 is the statistical weight of the lower level , and @xmath27 is the excitation energy of the upper level . for [ ] we use the collision strengths from @xcite , interpolated to a temperature of 11,000 k ; the collision strength for the 4959 , 5007 lines varies by only 8% between 10,000 k and 15,000 k , so the assumption of a constant @xmath25 introduces only a small error . for recombination lines , the emission coefficient is given by @xmath28 where @xmath29(@xmath1 ) is the effective recombination coefficient for the recombination line @xmath1 . for the 4661 line , we use the effective recombination coefficient derived by @xcite for ls - coupling in case b. for h and we used the recombination coefficients from @xcite , while for we used the emissivities computed by @xcite . we employ a value @xmath29 ( @xmath14661)/@xmath29(h@xmath2 ) = 1.29 for @xmath7 = 10,000 k ; this ratio varies by only 4% between 10,000 k and 15,000 k. similarly , @xmath30 ( @xmath14686 ) = 11.9@xmath30(h@xmath2 ) for @xmath7 = 11,000 k , varying by only 9% between 10,000 k and 20,000 k , and @xmath30 ( @xmath14471 ) = 0.501@xmath30(h@xmath2 ) at @xmath7 = 10,000 k and @xmath20 = 100 @xmath21 ; collisional excitation increases @xmath30(@xmath14471 ) by only 5% at @xmath20 = 10@xmath31 @xmath21 @xcite . given the relatively low densities we derive for the ring , and the small variation across the nebula , we can neglect collisional excitation of . finally , we computed c@xmath3 abundances from the 4267 line using the case b effective recombination coefficient from @xcite and @xcite . at @xmath7 = 10,000 k , @xmath29 ( @xmath14267)/@xmath29(h@xmath2 ) @xmath5 9.1 figure 5 shows a comparison of the spatial distribution of the [ ] 4959 emission and the 4661 emission in the ring . it is readily apparent that the [ ] and lines have distinctly different spatial distributions . the [ ] emission essentially follows the h@xmath2 emission , peaking slightly interior to the h@xmath2 peak , consistent with the ring - like morphology of the nebula . in contrast , the emission peaks @xmath32 the [ ] -emitting region . this behavior is remarkable - if the @xmath14661 emission arises mainly from radiative recombination of o@xmath3 to o@xmath8 , then one would predict that the emission would peak @xmath33 from the central star than the [ ] emission , where the ionization decreases . clearly , the and [ ] emission lines arise under dissimilar conditions . in figure 6 we show the computed o@xmath3 abundances as derived from the forbidden lines and the recombination lines , using the electron temperatures shown in figure 4(a ) . again , we see that o@xmath3 as derived from [ ] peaks in the shell while o@xmath3 derived from the recombination line is more concentrated toward the center of the nebula . to demonstrate that the results are not a result of low signal / noise in the 4661 line , we also plot in figure 6 the abundances we obtain from binned ( summed over 8 - 12 ) spectra extracted at several intervals along the slit . the agreement between the binned spectra and the point - by - point measurements is excellent . another thing that is apparent upon inspection of figure 6 is that the discrepancy between the [ ] and abundance results is not constant ; the discrepancy is much larger for the central regions of the nebula , where o@xmath3 ( ) is as much as ten times larger than o@xmath3 ( [ ] ) , than in the bright shell , where the difference is not more than a factor of two . similar behavior has also been seen by @xcite in the planetary nebula ngc 6153 , another shell - like nebula . this suggests a common origin for the forbidden - line / recombination - line abundance discrepancy . the helium abundance derived from our observations is shown in figure 7 , with the total he / h plotted as the solid line and the he@xmath3 contribution as the dashed lines . the plot shows that the helium abundance remains rather constant across the ring nebula , apart from possibly a small upturn at the edges of the shell . this increase is seen in he@xmath8 , and may be due to the assumption of a constant electron density across the shell ; however , the effect is not large . the average helium abundance we derive , he / h @xmath5 0.12 , is about 10% smaller than that derived by @xcite , he / h @xmath5 0.135 . the reason for the discrepancy is not clear . we do agree , however , that the helium abundance is essentially constant across the ring . finally , in figure 8 we display the c@xmath3 abundances derived from our measurements of @xmath14267 , compared with the o@xmath3 derived from . the c@xmath3 abundance shows an increase toward the nebula center similar to that of o@xmath3 , although the increase is not as strong . we find that c@xmath3/o@xmath3 @xmath5 1 in the bright shell , decreasing to @xmath5 0.5 ( approximately the solar value ) in the center . this variation could be due to ionization effects ( increasing importance of c@xmath34 in the interior ) , a real c / o abundance variation across the nebula , or a variation in the emission mechanism . note that the c@xmath3 abundance in the shell is similar to that derived for ngc 6720 ( c / h @xmath5 6@xmath1010@xmath35 ) from the ] 1908 feature by @xcite . @xcite derived c@xmath3 abundances in the ring nebula from measurements of @xmath14267 and from @xmath36 measurements of ] @xmath11908 . he found that the abundances derived from these two lines differed by a large factor in the central part of the ring nebula , but that the difference decreased radially outward and essentially disappeared in the bright shell . this behavior is very similar to what we see for abundances derived from and [ ] . this suggests a common mechanism affecting emission lines from both o@xmath3 and c@xmath3 . our long - slit observations of the ring nebula demonstrate that the and [ ] lines have very different spatial distributions . the big surprise is that the peak recombination line emission occurs in the region interior to the [ ] zone , in contrast to the expectations if the emission is the result of radiative recombination of o@xmath3 . either the lines are enhanced in the inner nebula or the electron temperature derived from [ ] is greatly overestimated in the nebular interior . in paper ii , we identify other surprising results . we find that the size of the - [ ] abundance discrepancy , @xmath9 log(o@xmath3/h@xmath8 ) , is anticorrelated with pn diameter and mean emission measure . we also see that lines that arise from levels populated mostly by dielectronic recombination are more discrepant than other lines when compared with the forbidden lines . these results , together with our new observations of the ring nebula , must be giving us important clues regarding the origin of the discrepancy between the recombination lines and the forbidden lines . here we discuss some of the possible mechanisms for producing the abundance discrepancies ; other possibilities will be examined in paper ii . temperature fluctuations have been invoked to explain why collisionally - excited lines give lower abundances than the recombination lines @xcite . nevertheless , the abundance discrepancies observed in ngc 7009 @xcite , ngc 6153 @xcite , and the ring nebula ( this paper ) are so large that they are are no longer in the regime where peimbert s formalism of small temperature fluctuations applies . for example , in the ring nebula we find that the lines yield abundances as much as ten times larger than the [ ] lines in the center of the nebula . if we assume that the lines give the correct abundances , we can estimate the magnitude of temperature fluctuations needed to obtain the same abundances from the [ ] lines . forcing the [ ] lines to give the same abundances requires an average temperature @xmath37 @xmath5 6,500 k in the center of the nebula , and @xmath37 @xmath5 9,000 k in the shell , whereas we derived @xmath4 [ ] @xmath5 12,000 k in the center and @xmath4 [ ] @xmath5 10,000 k in the shell . using the @xmath38 formalism of @xcite , these temperature differences imply @xmath38 @xmath5 0.03 in the shell and @xmath38 @xmath5 0.16 in the center of the nebula ! @xmath38 = 0.16 corresponds to rms temperature variations of @xmath1940% . it is difficult to imagine how such wild temperature variations could go unobserved [ see fig . 4(a ) ] . still , we saw in figure 4(a ) that there is a radial gradient in t [ ] within the ring nebula . this variation could give rise to a noticeable @xmath38 term if the temperature measured from the summed spectrum differs significantly from the emission - measure - weighted average temperature . we compare the [ ] temperature derived from the ring nebula spectrum summed along the entire slit with the average [ ] temperature weighted by the [ ] @xmath14959 intensity along the slit . the temperature derived from the full - slit spectrum is 10,950 k , while the emission - weighted average temperature is 10,860 k. using equation ( 4 ) of @xcite , the measured difference in t [ ] corresponds to @xmath38 = 0.003 . this is too small to have a significant impact on abundances . nevertheless , such gradients in @xmath7 are likely to be common in regions and pne , and should be taken into account whenever possible . @xcite have also argued that temperature fluctuations are unable to account for the large discrepancy between forbidden - line and recombination - line abundances in ngc 6153 . they derived @xmath7 from both the [ ] lines and from the balmer jump / line ratio in ngc 6153 ; the balmer jump temperature was determined to be 3000 k smaller than the [ ] temperature . nevertheless , @xcite found that this difference in @xmath7 could account for only one - third of the factor of nine difference in the derived o@xmath3 abundances in ngc 6153 . furthermore , they found that abundances derived from @xmath39 measurements of collisionally - excited [ ] , [ ] , and [ ] ir fine - structure lines agree very well with the results from corresponding optical forbidden lines . since the ir fine - structure lines have a very weak temperature dependence compared to the optical forbidden lines , it is difficult to reconcile the good agreement in ir and optical abundances with the idea of significant temperature fluctuations . these results and ours are evidence that temperature fluctuations can not account entirely for the large differences between recombination lines and forbidden lines in pne . shocks can provide a source of additional heating for a photoionized gas , and have been proposed as a mechanism to account for temperature fluctuations @xcite . shocks can heat a photoionized plasma by transforming the kinetic energy of a flow ( e.g. , a stellar wind ) into random thermal energy , and strong shocks heat the ambient medium to very high temperatures . high - excitation lines such as [ ] 4363 would be preferentially enhanced behind shocks in photoionized nebulae . @xcite showed that an interstellar shock superposed on the spectrum of an region could lead to a spuriously high measured electron temperature , and thus to underestimated abundances from collisionally - excited lines in the optical spectrum . in a pn , a shock front is expected to be formed at the interface between a fast stellar wind from the central star and the slowly - expanding circumstellar envelope . the fast stellar wind would carve out a hot bubble in the interior of the nebula which would emit primarily in x - rays . clear evidence for such hot bubbles has been found recently for a small number of pne from x - ray imaging @xcite . evidence that shocks enhance temperatures in photoionized gas in an observable way is generally lacking , however . physically , a shock is an extremely thin structure , only a few particle mean free paths thick ; the high - temperature recombination zone downstream from the shock is generally only a few times 10@xmath40 cm deep in interstellar shock models @xcite . therefore , one might expect the shock front to be manifested by a sharp , narrow spike in the spatial profile of @xmath7 . examination of figure 4 shows that we observe no sharp jumps in @xmath7 across the ring , only a smooth increase from the shell to the center . the rms deviations from this smooth profile are less than 200 k. one must consider that the spatial resolution of our data , 2@xmath415 @xmath5 2@xmath1010@xmath42 cm at a distance of 600 pc , is larger than the expected width of the shock cooling zone , and that we are observing a temperature averaged along a chord through the nebula . another problem that must be considered is the structure of the pn and its effect on the propagation of the shock . @xcite has simulated the radiation - gas dynamical evolution of a pn in the context of the interacting - winds model @xcite . these models begin with a slowly - expanding red giant wind . the pn expansion is initiated by the onset of a slow , high - density `` superwind '' which lasts a few thousand years , creating a dense shell of gas around the central star . following the end of the superwind , a high - velocity , low - density `` fast wind '' ensues , clearing out a central cavity and exposing the hot stellar core . frank followed the gas dynamics and ionization / thermal evolution of the nebula simultaneously . in the model , the fast wind drives a shock into the superwind , creating a hot central bubble . the low density in the bubble allows radiation from the hot stellar remnant to penetrate and ionize the dense shell . the high pressure in the hot bubble drives a forward shock into the dense shell . figure 2 of @xcite shows a snapshot of the dynamical , thermal , and ionization properties of the nebula at a point which is comparable to the current state of the ring nebula . at this stage , the nebula is fully ionized , and the temperature profile in the dense shell is determined by radiative cooling and heating . at this point , the forward shock is nearly isothermal and does not produce a noticeable temperature jump . this behavior is consistent with the lack of a temperature discontinuity in our observations of the ring nebula . however , a sharp jump in @xmath4 is seen at the contact discontinuity between the hot bubble and the dense shell in frank s models . one might then expect to see sharp jump in observed @xmath7 at this point in a pn . we do not observe such a jump in the ring , but this may be due to insufficient spatial resolution . considering the results of our observations and frank s models leads us to conclude that shocks can not explain the large discrepancy between forbidden - line and recombination - line abundances , although shocks should be present . spectroscopic observations with better spatial resolution should show whether shocks produce any significant effect on temperature profiles in pne . @xcite and @xcite suggested that abundance inhomogeneities could produce anomalously strong recombination lines from heavy elements in pne . if the central region of the pn contains hydrogen - depleted material , the metal - rich interior would be expected to have a low electron temperature due to strong cooling by ir fine - structure line emission . thus , optical forbidden lines would be weakened in this region while the recombination lines are enhanced . the optical forbidden lines would be produced mainly in the h - rich shell and would reflect the conditions and abundances there . a number of observable consequences result from this model . first , it might be expected that the central nebula would be enriched in helium as well , if the c and o enhancements result from incomplete mixing of he - burning products . figure 7 , however , shows that this is not the case for the ring nebula he / h is essentially constant across the nebula . alternatively , one might hypothesize that the central region is enhanced in c and o by a wind from a h- and he- depleted central star . however , the central star of the ring nebula is classified as h - rich @xcite . second , one would expect the observed @xmath7 to decrease toward the center of the nebula . from figure 4 , however , we see that @xmath7 @xmath43 toward the center . one could get around this by arguing that the derived temperature toward the center does not reflect the conditions in the interior , but rather in the shell projected along the line of sight . such a condition could occur if the nebula were shaped like a lozenge or an ellipsoid with the minor axis along the line of sight to the central star . in this configuration , gas near the minor axis would be closer to the central star and be subject to a stronger ionizing radiation field ( i.e. , a higher ionization parameter ) , and thus would have a higher @xmath7 . this configuration conflicts with the model for the ring presented by @xcite . based on the measured velocity field in the nebula , they argue that the ring is a prolate ellipsoid with the major axis pointing at a small angle to the line of sight , a configuration roughly orthogonal to the one discussed above . finally , ir fine - structure line measurements do not show much evidence for the large abundance enhancements needed to explain the observed recombination line emission @xcite . ( see also the discussion in section 5.1 . ) from the above discussion , we conclude that the strong recombination line emission in the central region of the ring does not reflect an h - poor , metal - enriched interior . @xcite have also considered the question of abundance inhomogeneities . they first determined that simple density inhomogeneities in a nebula with homogenous abundances could not account consistently for the strengths of forbidden lines , recombination lines , and the balmer line ratios in ngc 6153 . they next considered super - metal - rich ( smr ) condensations , and found that they could account for the emission line strengths in ngc 6153 with a model having dense , h - depleted inclusions that occupy a very small fraction of the volume . in this model , the heavy element recombination lines arise predominantly in the cool , dense condensations , while the forbidden lines are emitted primarily in the hotter , low - density component . @xcite were able to produce models of this kind that were able to reproduce the strengths of the recombination lines as well as the optical , uv , and ir collisionally - excited lines . chemical inhomogeneities might be expected in a pn , since c , n , and he are produced in different regions of the progenitor star . convective mixing during the red giant phase could homogenize the pn envelope , but such mixing might never be complete , especially in very late stages prior to envelope ejection . hydrodynamic instabilities would promote clumping in the gas , and a clumpy stellar wind may eject chemically inhomogeneous knots of gas . evidence for knots of h - depleted material is seen in several pne , for example abell 30 @xcite . on the other hand , there are a number of difficulties with this model as an explanation for the apparent abundance discrepancies . @xcite noted the difficulty of maintaining the postulated dense knots in pressure equilibrium with the surrounding nebula . another difficulty is the roughly equal enhancements of c , n , o , and ne in the recombination line emission . this is inconsistent with the nucleosynthesis predicted for pn progenitors , which generally synthesize c , n , and he , but not o or ne . in paper ii , we show that the difference between forbidden - line and recombination - line abundances in pne is inversely correlated with the nebular emission measure and diameter : in compact , high - surface - brightness pne the forbidden lines and recombination lines give essentially identical abundances , while large , low - surface - brightness pne show large abundance discrepancies . this result suggests that the discrepancy between forbidden lines and recombination lines is apparent only when a pn is large and evolved . it is difficult to imagine why hydrogen - depleted knots would condense out of the pn only at late times . if hydrogen - depleted clumps were present in the ejected envelope one would expect them to be present at early times as well . evaporation of grains from dense globules can not produce the smr clumps required enhanced recombination lines are seen not only for o and c , but also for n and ne , which largely do not condense onto grains . one possibility is a clumpy stellar wind from an h - poor central star , and indeed , the central star of ngc 6153 shows o vi emission indicating an h - depleted wind . however , as noted above , the ring nebula central star is h - rich . obviously , a better understanding of the ejection and clumping of material in the nebula is needed to determine if this model can successfully account for pn emission . an obvious consequence of the smr knot model is that one might expect to see strong recombination lines associated with the presence of dense knots . numerous small cometary knots have been observed in the helix nebula ngc 7293 @xcite , and have been identified as elongated , dense , dusty globules with a surface photoilluminated by the central star @xcite . their origin has not been determined yet , and spectroscopic data on physical conditions and metallicities are not yet available . however , they ( or the shadow regions behind them ) are logical places to look for emission anomalies , such as enhanced recombination line emission . imaging with the _ hubble space telescope _ has revealed the presence of dusty , possibly cometary , knots in the ring nebula as well . we have extracted wfpc-2 images of the ring nebula from the _ hst _ archive ( taken under program go-7632 ) . we obtained images in f502n ( [ ] @xmath15007 ) , f658n ( [ ] @xmath16584 ) , and f469n ( @xmath14686 ) . the three individual exposures in each filter were combined and mosaiced after removing cosmic rays and image defects . we combined the final filter images to highlight the dusty globules . ( the stsci office of public outreach web site oposite.stsci.edu has a nice color image of the ring nebula which clearly shows the dusty knots . ) we rotated the image so that the e - w direction was aligned with the horizontal axis , and overlaid our spectrograph slit on the image . the upper panel of figure 9 shows a negative composite image of ngc 6720 in the f469n , f502n , and f658n filters , with our slit outlined . numerous dusty knots are seen in this image , beginning about 20@xmath0 from the central star . high - resolution ir imaging of ngc 6720 shows that bright h@xmath44 s(1 ) emission follows the rings of dusty knots @xcite , indicating the presence of neutral and molecular material as well . the lower panel in figure 9 shows the distribution of o@xmath3/h@xmath8 across this section of the ring . comparison with the upper panel shows that the peak of the recombination line emission does not coincide with the region of dusty knots , but rather lies interior to the rings of knots . the discrepancy between the abundance derived from and that derived from [ ] is largest in the innermost regions and is declining in the regions where the dusty knots are seen . although the spatial resolution of our spectrum is poor compared to the _ hst _ imaging , we conclude that the knots observed in the ring are not the primary source for the enhanced recombination emission . any metal - rich knots of the kind proposed by @xcite must be largely invisible at _ hst _ resolution . we show in paper ii ( also dinerstein , lafon & garnett 2000 and garnett & dinerstein 2001 ) that some lines yield much larger o@xmath3 abundances than other lines . in particular , the 4590 , 4596 lines from multiplet 15 are especially strong . the levels that these lines arise from are populated mainly by dielectronic recombination ( dr ) . the large abundances obtained from these lines , even after taking into account the low - temperature dielectronic recombination rates @xcite , indicate that low - temperature dielectronic recombination at nebular temperatures does not account for the great strength of the lines . we therefore investigate the possibility that the dielectronic recombination rates in the affected pne could be severely underestimated . this could be the case if the rate coefficients to upper levels are grossly underestimated ( which does not seem very likely for all of the ions involved ) , or if there is a component of dielectronic recombination that is not accounted for in standard pn emission models . we hypothesize that this could be high - temperature dielectronic recombination in a hot central bubble ; dielectronic recombination rates are enhanced by as much as a factor of ten at @xmath4 @xmath5 10@xmath6 k compared to the rates at nebular temperatures of @xmath5 10@xmath31 k @xcite . the spatial distribution of emission in our long - slit observations the ring nebula would appear to be consistent with this hypothesis . the lines are strongest just interior to the main shell , in the region where the interface between a hot bubble and the denser ionized shell would be expected . the spatial profile of the emission peak is fairly broad , perhaps broader than might be expected from such a transition layer ; however , we have not accounted for the relatively low spatial resolution of the spectra nor for the effects of nebular geometry . unfortunately , no x - ray images of the ring nebula exist , so we have no information on the presence or absence of hot gas . at what temperature would the recombination coefficient be large enough to account for the increased emission ? let us assume that the emission in the main shell represents the intrinsic o@xmath3 abundance of ( 7@xmath191)@xmath1010@xmath35 , at a temperature of 10,000 k. the maximum derived o@xmath3 abundance is ( 24@xmath192)@xmath1010@xmath35 , or about 3.5 times the abundance in the shell . equality of abundance would then imply that the recombination coefficient in the inner nebula is higher by the same factor . based on the theoretical recombination coefficients tabulated by @xcite , this is true if the material producing the excess emission is at @xmath4 @xmath5 65,000 k. similarly , the c@xmath3 abundance in the inner nebula is about twice as large as that in the shell . the recombination rate for @xmath45 is a factor two larger at @xmath4 @xmath5 35,000 k than the rate at 10,000 k. on the other hand , @xcite points out that the high-@xmath4 dr rate from these ls - coupling calculations may be underestimated by perhaps a factor of 1.5 - 2 because of missing autoionizing levels , which would act in favor of our model . one difficulty that arises is that any o@xmath3 ions recombining in this hot zone would be expected to emit very strongly in [ ] and a large increase in @xmath7 and in the forbidden line strengths might be observed . this problem could be mitigated if the density in the hot zone is very small ; the contribution to [ ] emission from the hot zone would then be overwhelmed by the strong emission from the main shell . we can check this by comparing the collisional excitation rates for [ ] with the recombination rates as a function of temperature . for the enhanced dr model to work , two conditions must be satisfied : first , there must be a temperature regime in which the recombination rate @xmath46 increases faster with increasing @xmath7 than the collisional excitation rate @xmath47 , at temperatures where dr dominates ; and second , there must be a temperature regime in which @xmath46/@xmath47 exceeds the value of this ratio at 10,000 k , the electron temperature we measure in the shell of the ring . figure 10 shows the results of a comparison of recombination rates to collisonal excitation rates for o@xmath3 , where we plot @xmath48 vs temperature for both [ ] @xmath494959,5007 and @xmath14363 . here we have computed the total recombination rate and assumed that the effective recombination rates to individual levels scale identically . we used the radiative recombination rates formulated by @xcite , together with the dielectronic recombination rates from @xcite and @xcite to estimate @xmath46 . the collisional rates @xmath50 were computed using the averaged temperature - dependent collision strengths of @xcite , @xcite , and @xcite . figure 10 shows that while the first condition listed above is met , the second is not . the plot shows that @xmath46 does increase faster than @xmath47 in the range 4.4 @xmath51 log @xmath4 @xmath51 5.5 . on the other hand , while we do see that @xmath46/@xmath47(@xmath494959,5007 ) for log @xmath4 = 5.1 - 5.7 exceeds the ratio at 10@xmath31 k , the largest difference is only about 0.1 dex . this is not nearly enough to explain the large difference between recombination line abundances and forbidden line abundances in ngc 6720 . furthermore , figure 10 shows us that for log @xmath4 @xmath52 4.5 @xmath46/@xmath47(@xmath14363 ) never exceeds the value at 10@xmath31 k. in order for this model to work , the theoretical dr rates would have to be increased by a large factor , which appears to be outside the estimated uncertainties in current dr rate calculations . we are thus forced at the present time to conclude that the recombination / collisonal excitation ratio can not be increased sufficiently by the presence of hot gas , for any combination of gas temperatures , to account for the observations , at least with conventional physics . we have demonstrated in this paper that the and [ ] lines in the ring nebula have distinctly different spatial distributions in the nebula ; similar results have been found by @xcite for ngc 6153 . the permitted line emission peaks closer to the central star than the forbidden line emission . this spatial distribution appears to be inconsistent with a model in which the permitted lines arise mainly from radiative recombination of o@xmath3 in the transition zone to o@xmath8 in the bright shell . in order to force the abundances from the [ ] lines to agree with those derived from would require such large temperature fluctuations that it would be difficult to hide them . furthermore , it is difficult to reconcile large temperature fluctuations with the good agreement between optical and far - ir measurements of forbidden lines in ngc 6153 . thus , it appears clear that temperature fluctuations can not account for most of the discrepancy between forbidden - line and recombination - line abundances in planetary nebulae . nor do we find that c@xmath3 and o@xmath3 derived from the optical recombination lines have similar overabundances relative to those obtained from the collisionally - excited lines in the ring nebula . comparing our c@xmath3 abundance with that obtained by @xcite from the uv ] lines , we find that the rl abundance for c@xmath3 is about a factor of two higher , while for o@xmath3 the rls give an abundance that is a factor of four higher than that derived from [ ] . thus it appears that the cause of the abundance discrepancy need not apply equally to all of the species . based on the enhanced strengths of multiplet 15 , the correlation of the abundance discrepancy with nebular size ( paper ii , garnett & dinerstein 2001 ) , and the spatial distribution of the emission , we proposed that dielectronic recombination in a hot gas bubble might greatly enhance the emission rates of the permitted lines above the rates at nebular temperatures . a comparison of recombination rates versus collisional excitation rates for o@xmath3 showed , however , that the increase in recombination rates due to dielectronic recombination at @xmath7 @xmath5 10@xmath6 k is not enough to overcome the increase in collisionally - excited emission . unless the theoretical dr rates are greatly underestimated , this does not appear to be a viable explanation for the recombination line - forbidden line discrepancy . in any case , our results suggest that we need to understand better the effects of dr on recombination line strengths in general . a model in which the recombination emission arises mainly in cold , h - depleted clumps @xcite could explain the enhanced recombination line emission in pne , although we are unable to find a close correlation between enhanced emission and the locations of dusty globules in the ring nebula . furthermore , we would also need to understand why such clumps are only seen in the larger , more evolved pne . perhaps this is a selection effect related to the surface brightness . spectroscopy and imaging with high spatial resolution of other pne should provide more clues to the nature of the relation between recombination line enhancement and nebular diameter . unfortunately , we are not able to convincingly reconcile any of the proposed models to explain the rl enhancements with all of the observations of ngc 6720 and ngc 6153 . we present our results here in the hope that it will inspire new thinking on the physics behind emission processes in photoionized nebulae . what are the consequences for abundance measurements from forbidden lines ? the results are a bit mixed at the present time . the agreement in abundances derived from optical / uv forbidden lines and ir lines measured by @xmath39 for ngc 6153 @xcite offers strong evidence that temperature fluctuations do not have sufficient magnitude to significantly affect forbidden - line abundances . on the other hand , there is a significant discrepancy between the balmer discontinuity temperature and the [ ] temperature in ngc 6153 . it is possible that this discrepancy merely reflects variations in temperature across the nebula . as we have seen , the [ ] temperature is not constant across the ring nebula , and such a variation is expected based on ionization models . a detailed observational study of the spatial profile of various temperature indicators across nebulae would provide a clearer picture of the temperature variation within planetary nebulae . we thank a. frank , j. mathis , and g. shields for very helpful and stimulating discussions , bob benjamin for assistance in deriving the results shown in figure 10 , and the anonymous referee for several useful comments . the work of drg is supported by nasa ltsa grant nag5 - 7734 , while hld acknowledges support from nsf grant ast 97 - 31156 .

we present new long - slit ccd spectra of permitted lines and [ ] forbidden lines in the ring nebula ngc 6720 . these observations provide spatially - resolved information on both and [ ] over the 70@xmath0 diameter of the main shell . we find significant differences in the spatial distribution of the lines and [ ] @xmath14959 . the [ ] emission follows the h@xmath2 emission measure , peaking slightly radially inward from the h@xmath2 peak . the emission peaks inside the [ ] emission . this suggests that radiative recombination may not be the primary mechanism for producing the lines . o@xmath3 abundances derived from lines are 5 - 10 times larger , than those derived from [ ] in the region within 20@xmath0 of the central star . outside of this region , however , the and [ ] derived abundances agree to within 0.2 - 0.3 dex . the electron temperature derived from [ ] lines rises smoothly from about 10,000 k in the outer shell to about 12,000 k in the center ; we see no evidence for a temperature jump that would be associated with a shock . if temperature fluctuations are responsible for the discrepancy in o@xmath3 abundances , the average temperature would have to be approximately 6,500 k in the he@xmath3 zone and about 9,000 k in the outer shell in order to force the [ ] -derived abundance to equal that derived from . this would conflict with ionization models for pne which predict that the temperature is higher in the he@xmath3 region close to the ionizing star . we therefore argue that temperature fluctuations can not explain the abundance discrepancy . a comparison of the spatial distribution of emission with the location of dusty knots shows that the recombination lines do not peak where the dense knots are located , creating difficulties for models which explain the recombination line / forbidden line discrepancy by density fluctuations . we examine the possibility high - temperature dielectronic recombination in a central hot bubble enhances the recombination line strengths in the central part of the nebula . however , comparison of recombination rates with collisional excitation rates shows that the increase in recombination emission due to dielectronic recombination at @xmath4 @xmath5 10@xmath6 k is not sufficient to overcome the increase in collisonally - excited emission . we are unable to find a completely satisfactory model to explain the discrepancy between recombination line and forbidden line abundances .

lanthanum carbonate ( lc ) is a non - calcium , non - aluminum phosphate binder used to treat hyperphosphatemia in end - stage renal disease . there , this cation binds with phosphate to produce lanthanum phosphate , which is excreted with the feces . it has been reported that lanthanum is absorbed and deposited in many organs in a rat model . in humans , however , lc is considered safe because its absorption in the gastrointestinal tract is reported to be minimal [ 2 , 3 ] . recently , two japanese groups reported lanthanum deposits in the gastric or duodenal mucosa of the patients treated with lc [ 4 , 5 ] . the patients exhibited no adverse effects from the deposits , but it is necessary to clarify whether lanthanum phosphate compounds are just deposited in the stomach or whether they are absorbed there and transported throughout the body . an 81-year - old woman with a history of partial gastrectomy for early gastric cancer 7 years earlier was admitted to our hospital for treatment of gastric cancer . because of diabetic nephropathy , she had received hemodialysis three times a week for 1 year and had taken lc ( one 250 mg chewable tablet after each meal ) for 7 months . she complained of gastric discomfort and underwent endoscopic examination of the stomach , which revealed three tumors . histological examination of the resected specimens showed that all three tumors ( diameter , 215 mm ) were well - differentiated tubular adenocarcinomas located in intestinal metaplastic mucosa with no submucosal invasion . all the tumors were resected completely . in the lamina propria of the mucosa , however , we noticed many macrophages with abundant cytoplasm containing some basophilic material ( figure 1a and b ) . the macrophages were found grouped just beneath the epithelium and were widespread in the intestinal metaplastic mucosa , including in the neoplastic lesion ( figure 1c ) . energy - dispersive x - ray spectroscopy ( sem - eds ) and transmission electron microscopy - eds . in the macrophages , we found lanthanum deposits with a spectrum similar to that of lc ( figure 1d ) . also , sem - eds showed that the lymph node contained lanthanum ( figure 2a d ) . an elemental map of phosphorus and lanthanum indicates that they were deposited together ( figure 1e and f ) . because the patient continued to take lanthanum after gastrectomy , we measured the plasma lanthanum concentration , which was 0.47 ng / ml ( within the range of values in a control group of patients on dialysis who took lanthanum as a phosphate binder ) . three years after the surgery , the patient has shown no signs of recurrence and had no notable illness . fig . 1.light micrograph and transmission electron microscope energy - dispersive x - ray spectroscopy ( tem - eds ) results of the gastric mucosa . ( a ) gastric mucosa of non - neoplastic area showing accumulation of macrophages in the lamina propria . ( b ) high - power magnification of ( a ) , showing macrophages with abundant granular cytoplasm with some eosinophilic materials ( indicated by arrows ) . ( d ) tem bright - field image of a macrophage showing deposits around the nucleus ( indicated by arrows ) . ( e ) eds spectrum showing the presence of lanthanum ( la ) and phosphorus ( p ) in the area analyzed ( indicated by the ( f ) deposits indicated by the + in ( d ) correspond to la and p. fig . ( a ) macrophages with granular cytoplasm in the lymph node ( indicated by arrows ) . ( b ) sem image of the lymph node showing bright elements ( indicated by arrows ) . ( c ) eds spectrum showing the presence of la and p at the area analyzed ( indicated by the light micrograph and transmission electron microscope energy - dispersive x - ray spectroscopy ( tem - eds ) results of the gastric mucosa . ( a ) gastric mucosa of non - neoplastic area showing accumulation of macrophages in the lamina propria . ( b ) high - power magnification of ( a ) , showing macrophages with abundant granular cytoplasm with some eosinophilic materials ( indicated by arrows ) . ( d ) tem bright - field image of a macrophage showing deposits around the nucleus ( indicated by arrows ) . ( e ) eds spectrum showing the presence of lanthanum ( la ) and phosphorus ( p ) in the area analyzed ( indicated by the ( f ) deposits indicated by the + in ( d ) correspond to la and p. light micrograph and sem - eds results of a regional lymph node . ( a ) ( b ) sem image of the lymph node showing bright elements ( indicated by arrows ) . ( c ) eds spectrum showing the presence of la and p at the area analyzed ( indicated by the there have been few reports of lanthanum being detected in patients who took lc orally [ 4 , 5 , 79 ] . lymph nodes had been the only tissue with histologically confirmed lanthanum deposition in humans , but the pathway to the lymph nodes remains unclear . however , lanthanum deposits were recently found and histologically confirmed in the gastric or duodenal mucosa of patients who took lc orally [ 4 , 5 ] . the authors of those reports [ 4 , 5 ] observed no apparent clinical problems arising from the lanthanum deposits but did not report long - term patient outcomes . here , we report the case of a patient with lanthanum deposits in the stomach and a regional lymph node . the histological findings of the stomach are similar to those in the previous two reports . in those studies , the findings were from gastroduodenal biopsies or endoscopic submucosal dissection specimens , so regional lymph nodes were not examined . in our case , the stomach had many macrophages in the lamina propria , whereas the lymph node did not have many ; therefore , these findings suggest that lanthanum is not just deposited in the stomach , but also absorbed there and possibly transported via lymph flow . in general , the plasma lanthanum concentration of dialysis patients who took lanthanum as a phosphate binder is higher than healthy individuals because of little absorption of lanthanum from the intestine and the plasma lanthanum concentration of our patient is the same as that of dialysis patients that were reported in the literature . therefore , we can not rule out the possibility that absorbed lanthanum is transported from the intestine to the stomach . however , blood flow from the intestine usually reaches the liver via the portal vein , not the stomach , unless the patient suffers from liver cirrhosis . our patient did not suffer from liver disease , so it is unlikely that blood flow goes from the intestine to the stomach . furthermore , lanthanum absorbed in the intestine is transported by blood flow , so the possibility that lanthanum is carried from the intestine to the lymph nodes seems to be low . this is why we considered that lanthanum was absorbed in the stomach and transported via lymph flow . as of this writing , our patient has shown no adverse reaction associated with continuous use of lc for 3 years , but it remains unclear whether deposits of lanthanum compounds throughout the body are harmful ; therefore , further investigation of similar cases is needed . in the past reports of histologically confirmed lanthanum deposits in human gastric mucosa [ 4 , 5 ] , the duration of lc treatment was at least 1 year 9 months , far longer than our patient 's lc treatment ( 7 months at the time of surgery ) . our patient had a history of partial gastrectomy for early gastric cancer 7 years earlier ; therefore , this second occurrence of gastric cancer suggests susceptibility to gastric cancer . also , the macrophages were found mainly in the atrophic mucosa with metaplastic epithelia , which is considered to be an initial step toward carcinogenesis . in gastric epithelia with intestinal metaplasia , the expression of claudin , which is a core protein of tight junctions , is reported to differ from that in normal gastric epithelia . this difference could also cause the increased permeability possibly leading to lanthanum deposition or absorption in the gastric mucosa . in fact , we encountered another patient who had taken lc for years and died from malignant lymphoma without gastric involvement , and we found no such macrophages . this patient 's gastric mucosa showed no atrophy or intestinal metaplasia , suggesting that these metaplastic changes are associated with lanthanum deposition . in summary , we have reported the case of a patient who had lanthanum phosphate deposits in the gastric mucosa and a regional lymph node , suggesting that lanthanum was absorbed in the stomach and carried via lymph flow .

lanthanum carbonate ( lc ) is an orally administered phosphate binder . its absorption is generally thought to be minimal . we report here the case of an 81-year - old woman who underwent subtotal gastrectomy for gastric cancer after receiving hemodialysis for 1 year and taking lc for 7 months . lanthanum phosphate compounds were found histologically in the gastric mucosa and a regional lymph node and confirmed by scanning and transmission electron microscopy energy - dispersive x - ray spectroscopy . these findings suggest that lanthanum is absorbed in the stomach and transported via lymph flow . this observation could prove helpful in future investigation of lanthanum disposition .

A Winona State University student and gymnast who died late Monday at a Fountain City restaurant was remembered Tuesday for her warm, outgoing personality, a smile that brightened the darkest room and the competitive drive she’d use to encourage her teammates. Brooke Baures, 21, was found dead Monday night in a Fountain City restaurant in an incident involving a food-service elevator. Details of how she died were not available Tuesday, though police said they did not suspect foul play or any criminal activity. The WSU senior competed three seasons for the gymnastics team and earned All-America honors in 2013. “Brooke had a magnetic personality and a smile that would light up the gym,” WSU gymnastics coach Beckie Rolbiecki said. “She was a sparkplug of a competitor and an ambitious, dedicated teammate. “She was one of those athletes who warmed your heart when you’d see her walk into the gym. It’s so hard for all of us to comprehend.” The Buffalo County Sheriff’s Department received a 911 call shortly before 8 p.m. Monday from the WingDam Saloon & Grill, and when first responders arrived they discovered Baures’ body in the restaurant’s food service elevator, according to the Fountain City Police Department. Baures was an employee at the restaurant. Baures was pronounced dead at the scene, said Fountain City Police Chief Jason Mork. The Fountain City Police Department is investigating Baures’ death, with assistance from the sheriff’s department and county coroner. Mork said he could not speak further about the incident and investigation until he’s able to meet with family members and the autopsy is completed. Mork said the food elevator, commonly referred to as a dumbwaiter and located off the kitchen, runs between the first and second floors of the restaurant and is generally used to transport bulk food for parties and other events in the space. The opening to the elevator is about three feet by three feet, he said, and was not designed for employees to enter. The lifting mechanism works similar to an electric garage door, he said. Dumbwaiter incidents are extremely rare, according to the federal Occupational Safety and Health Administration, which maintains online databases for workplace-related injuries and deaths. According to the OSHA database there have been just two incidents, both fatal, in the United States between 2003 and 2013, the date range the digital records cover. Amanda Schabacker, manager at the WingDam, said the restaurant was closed Tuesday but declined further comment. 'Grateful for the gift of her' It’s the second time in five months the WSU athletic department mourned the loss of a student athlete. In July, incoming football transfer Shawn Afryl collapsed and died due to a medical condition during a conditioning workout. The athletic department — not just the gymnastics program — was in a state of shock Tuesday. Baures, a social work major from Chetek, Wis., was loved by many. “She was one of those kids who touched a lot of people and who was very well liked,” said WSU athletic director Eric Schoh, who remembered Baures popping into his office just to see how he was doing. “She was a big part of the gymnastics team, but also the athletic department. She knew athletes across the whole department.” Former teammates remember her team-first attitude during competitions. “She was the most selfless teammate I ever had,” said Katie Seehusen, a 2014 graduate, who’ll remember Baures most for the joy and laughs she brought to those long road trips during the season. “She was always right up there, the first one to greet you when you were done with your routine.” Stephanie Wojton, another recent graduate, said Baures made her a better gymnast, and both qualified for the NCGA National Championship together in beam in 2013. “We both made it to the second day,” Wojton said. “It was really great to share that with her. I wouldn’t have wanted to share it with anyone else.” Wojton and Baures were inseparable that season, getting to practice early, commandeering the sound system and blaring whatever music they would want. One song, in particular, meant a lot to both of them — Sarah Evans’ “A Little Bit Stronger.” “We would work on our moves on the beam, dance to our routine, and pretty much just belt out the words,” Wojton said. “That song means a lot to me now.” Both Wojton and Seehusen looked up to Baures, even though they were older. “She was the one person in my life I could go to for everything,” Wojton said. Baures was to be a captain this season but left the team in mid-October. The split was amicable on both sides, Schoh said, adding that Baures wanted to focus on other things. Her presence will remain with the team this season, Rolbiecki said. “I told the team today that she isn’t with us physically, but each of you are changed because of her presence,” she said. “Each of you have gained something by your connectivity to her and cherish that.” The team was set to compete in an exhibition Friday night at UW-La Crosse. It wasn’t decided as of Tuesday night whether or not that meet will still happen. The regular season begins Jan. 8 in Alaska. The first home meet is scheduled for Jan. 23 against UW-Eau Claire. “Our team is distraught and grieving and torn,” Rolbiecki said. “Our hearts go out to the family, and our wish is that they somehow can come to terms with this loss and recall the beauty of their wonderful daughter. “I’m just grateful for the gift of her, that she came and passed through my doors and I got to know the wonderful person that she was. It was a true blessing for me to have those three years with her.” ||||| MINNEAPOLIS (WCCO) — A 21-year-old Winona State University student was discovered dead inside a bar’s dumbwaiter Monday evening, according to the Fountain City Police Department. Shortly before 8 p.m., the Buffalo County Sheriff’s Office received a 911 call from WingDam Bar and Saloon in Fountain City, Wisconsin. When authorities arrived, they discovered the body of an employee identified as Brooke Baures in the food service elevator. Baures’ gymnastic coach, Becki Rolbiecki, calls her a stand-out athlete who went to Nationals and was named All American all three years at Winona State. “She’s one of those once-in-a-lifetime athletes,” Rolbiecki said. “Her work ethic inspired everybody in the gym because she just went all out and gave her all every practice.” Rolbiecki said Baures was an all-around gymnast, but she concentrated on the bars and beam, and her future. “Awesome team person, you know. Very compassionate and caring person, a good listener, a good friend, a good mentor,” Rolbiecki said. “We had lots of conversations and lots of discussions about life and love and wishes and dreams and hopes.” Baures planned to become a social worker, a desire she took so seriously. Rolbiecki says she decided to pursue an internship rather than gymnastics her senior year. She also worked part-time at WingDam Saloon and Grill. Police say part of her job included getting service items from the dumbwaiter that runs between the floors of the bar. While police don’t know yet how Baures became trapped, they have ruled out foul play. Winona State University Athletic Director Eric Schoh met with the gymnastic team before they went to see Baures’ family in Wisconsin. “A lot of tears, a lot of hang-in-there’s, a lot of thoughts and prayers and a lot of hugs,” Schoh said. Rolbiecki says the team’s thoughts and prayers go out to Baures family. “She was such a gift, she loved life,” Rolbiecki said. Baures went to high school in Cameron, Wisconsin. The gymnastics team and other students are planning a candle light vigil for Baures Wednesday night at 8 p.m. at the gazebo on campus. Police think they’ll know more Wednesday about how the accident happened. OSHA has been contacted, and the agency says there have only been two fatal dumbwaiter accidents in the U.S. in the past 10 years.

– A college gymnast is dead after what appears to be a freak accident at the restaurant where she worked: Brooke Baures was found in its dumbwaiter, reports NBC Chicago. The body of the 21-year-old senior at Winona State University in Minnesota was discovered Monday evening in the food elevator of the WingDam Saloon & Grill in nearby Fountain City, Wisconsin. Police say they don't suspect foul play, reports the Winona Daily News, though authorities haven't spelled out what they think happened. Part of Baures' job was collecting items from the dumbwaiter that runs between floors, reports CBS Local. “Brooke had a magnetic personality and a smile that would light up the gym,” says WSU's gymnastics coach. “She was a sparkplug of a competitor and an ambitious, dedicated teammate." The school was planning a candlelight vigil tonight for Baures, who planned to be a social worker upon graduation.

as cataract and refractive surgery are increasingly performed , the surgeons ' skills as well as the precision of ocular measurements are important in order to satisfy patients ' expectations . central corneal thickness ( cct ) is critical in designing vision correction surgeries such as laser in situ keratomileusis ( lasik ) , as well as in glaucoma diagnosis and other corneal diseases [ 16 ] . measurements of the anterior chamber depth ( acd ) , which is defined as the distance from the corneal epithelium to the anterior surface of the crystalline lens , and the aqueous depth ( ad ) , which is defined as the distance from the corneal endothelium to the anterior surface of crystalline lens , have many clinical applications . the acd measurement is used , for example , by the holladay 2 formula , whereas the ad measurement is critical for the selection of patients undergoing phakic intraocular lens implantation . anterior segment optical coherence tomography ( visante as - oct , carl zeiss meditec , dublin , ca , usa ) has been clinically used for several years for anterior segment measurement and has high resolution . it is based on low coherence interferometry and uses the light source of a 1310 nm superluminescent light - emitting diode . the visante as - oct is widely used to measure the corneal thickness and acd . the al - scan is a newly introduced optical biometer that can measure six parameters within 10 seconds , including cct , acd , axial length ( al ) , corneal keratometry ( k ) , white - to - white ( wtw ) , and pupil diameter ( pd ) . it uses the principle of the scheimpflug imaging to measure cct and acd and an 830 nm infrared laser diode for al . previous studies had reported highly repeatable and reproducible measurements of al , k values , and acd with this new device [ 914 ] . few studies have investigated the accuracy and agreement of al - scan with other instruments [ 9 , 10 , 1315 ] . this is the first study to compare the ocular measurements obtained by the al - scan and the visante as - oct . sixty - three eyes of 63 healthy subjects ( 36 men , 27 women ) were enrolled in the study . mean age ( standard deviation , sd ) was 23 3.83 years ( range : 1832 years ) . mean refraction error was 4.41 2.12 d ( range : 0.5 d to 9.00 d ) . the exclusion criteria were age < 18 years , previous ocular surgery , anterior or posterior pathology , contact lens usage ( within 4 weeks for rigid contact lens and within 2 weeks for soft contact lens ) , and astigmatism > 3.0 d. before enrolment , each patient underwent a complete ophthalmological examination , including visual acuity , intraocular pressure measurement , anterior segment evaluation , and fundus examination . this study was approved by the review board of the eye hospital of wenzhou medical university and performed according to the declaration of helsinki . al - scan uses the principle of the scheimpflug imaging to measure cct and acd with 470 nm monochromatic light emitted from an led . the anterior chamber single - scan mode was used to measure the cct and acd with visante oct . the depth and width of the scanning field were 6.0 mm and 16.0 mm , respectively . the scan was obtained when a vertical white line along the center of the cornea was visible . the calibrated caliper function was used to calculate the acd and ad [ 16 , 17 ] . all measurements were taken between 10:00 and 17:00 and were completed within 15 minutes for each patient . spss software version 21.0 ( ibm corporation , armonk , ny , usa ) and medcalc statistical software v14.8.1 ( medcalc software , inc . , the kolmogorov - smirnov test was performed to check the data distribution for each device . the paired t - test was used to evaluate the difference between the measurements of each device . the range of agreement was shown with 95% limits of agreement ( loa ) , which stands for the mean difference 1.96 sd . the mean cct , acd , and ad measured by al - scan were 538.59 27.37 m , 3.70 0.30 mm , and 3.16 0.30 mm , respectively . the visante oct showed 536.14 26.61 m for cct , 3.71 0.29 mm for acd , and 3.17 0.29 mm for ad . although there was a statistically significant difference in the mean cct measurements between the two devices , it was clinically insignificant ( table 1 ) . good agreement was found between the two devices for cct with a maximum boundary value of 95% loa of 14.35 m ( figure 1 ) . the acd and ad measurements of al - scan and visante oct were similar ( p > 0.05 ) and had good agreement with the 95% loa range of 0.15 to 0.12 mm ( figures 2 and 3 ) . accurate quantitative measurements of cct , acd , and ad provide valuable clinical information and are important for preoperative assessment , surgical planning , and follow - up in phakic iol implantation . ultrasound ( us ) is typically widely used for measuring these parameters [ 19 , 20 ] . but , nowadays , noncontact devices such as the visante as - oct are more popular in measuring ocular parameters . the al - scan is a recently released , noncontact , imaging instrument using partial coherence interferometry ( pci ) and the scheimpflug principle with good repeatability and reproducibility . the scheimpflug camera with a 470 nm led is used for measuring the cct and anterior chamber in the al - scan . our data is the first study to suggest that the visante as - oct and the al - scan have good agreement for measuring cct , acd , and ad . previous studies have investigated the al - scan and compared it to other instruments , mainly the iolmaster . since the iolmaster is unable to directly measure the corneal thickness , no prior data for comparing cct were available . ethnic variation was found in previous studies when cct values were measured ; chinese , caucasians , hispanics , and filipinos had comparable cct measurements , whereas japanese had significantly thinner corneas than caucasians , chinese , filipinos , and hispanics . the differences also existed between the anterior chamber of chinese and caucasians [ 2123 ] . so we are more focused on the repeatability results rather than the mean measurement values . . showed high repeatability of cct values by the al - scan in both normal and keratoconic groups . although its reproducibility was not better than other available scheimpflug systems , the al - scan showed excellent and comparable repeatability and reproducibility in most ocular parameters ' measurements [ 1012 , 24 , 25 ] . thus , it was useful to review and compare the currently used devices such as pentacam ( oculus , wetzlar , germany ) , galilei ( ziemer , port , switzerland ) , and sirius ( costruzione strumenti oftalmici , florence , italy ) as they all use the principle of the scheimpflug imaging to measure the cct despite the lack of direct comparison between the al - scan and other scheimpflug systems . a recent analysis showed that the total measurement error of visante oct for cct was 7.88 m , while the error was 9.85 m , 7.05 m , 2.64 m , and 4.76 m for ultrasound , pentacam , galilei , and sirius , respectively . . showed low coefficients of repeatability and reproducibility and high intraclass correlation coefficients of the cct measurement by visante oct . in our recent prospective studies on three different scheimpflug imaging systems and one oct , high repeatability and good agreement for cct measurement were also demonstrated [ 28 , 31 ] . however , o'donnell et al . showed that the 95% loa for pentacam and visante oct were 25.61 to 49.11 m . in the current study , the visante oct provided slightly thinner cct than al - scan , which was also seen between visante and pentacam by nemeth et al . , and our max boundary of 95% loa was 14.35 m , demonstrating very good agreement between the two devices . the scheimpflug and oct measure cct by different optical and physical techniques : the pentacam used 475 nm blue light , visante oct used 1310 nm diode laser , and al - scan used 470 nm led , which might contribute to the differences in the results . besides , the anterior corneal surface also influences the demarcating boundary , which results in differences . a previous study had shown that the total measurement error of iolmaster for acd was 0.06 mm and the error of visante oct , pentacam , and galilei was all approximately 0.05 mm . as compared to the iolmaster 500 , the acd was 3.17 0.12 mm by al - scan and 3.12 0.11 mm by iolmaster , with a minor difference of 0.13 0.04 mm and high correlation between al - scan and iolmaster 500 in measuring acd . srivannaboon et al . also showed a small difference indicating good agreement between al - scan and iolmaster with a loa range of 0.24 to 0.19 mm , which was similar to the results of our previous comparison between the al - scan and iolmaster . nemeth et al . , wang et al . , and lavanya et al . showed that the acd measurements by oct were 3.11 0.33 mm , 3.76 0.21 mm , and 3.14 0.34 mm , respectively , in normal adults and presented good agreement with ultrasound or scheimpflug or iolmaster . . demonstrated that acd measured by visante oct had deeper but not clinically important values than iolmaster . reported high correlation between pentacam and visante oct in measuring acd , which was similar in keratoconus in a study by yazici et al . . in our current study , the 95% loa range was even narrower for acd or ad measurements indicating better agreement between al - scan and visante oct than that between al - scan and iolmaster or between al - scan and galilei . in our current study we simultaneously measured acd and ad modes , which is more comprehensive than other studies that only analyzed one mode . in clinical settings , acd and the intraocular pressure are important parameters for glaucoma screening and diagnosis . however , the acd values are the summation of cct and ad values . since acd values can be affected by cct measurement , the method used for measuring cct , the accuracy of cct measurement , corneal edema , and other aspects related to cct results will influence the precision of acd . thus , it was meaningful to assess the agreement of these parameters between the two devices in a single study . we only included healthy unoperated eyes and further investigations are needed to assess both instruments for other categories of patients ( such as those affected with keratoconus or previous refractive surgery ) . mydriasis would influence changes in the cornea and anterior chamber , so further studies will be performed to evaluate the performance of the biometer after pupil dilation . this study found a clinically insignificant difference between the two devices for the measurement of cct . the al - scan and visante as - oct have good agreement in measuring cct , acd , and ad , and their results can be interchangeably used in the clinical setting .

purpose . to compare between a new optical biometer ( al - scan , nidek co. , aichi , japan ) and an anterior segment optical coherence tomographer ( visante as - oct , carl zeiss meditec , dublin , usa ) for measuring central corneal thickness ( cct ) , anterior chamber depth ( acd ) , and aqueous depth ( ad ) . methods . sixty - three eyes of 63 normal subjects were examined with al - scan and visante as - oct in this prospective study . one eye per subject was measured three times with both devices to record their cct , acd , and ad . all procedures were performed by the same operator . agreement between the two devices was assessed using paired t - tests , bland - altman plots , and 95% limits of agreement ( loa ) . results . the mean cct , acd , and ad measured by al - scan were 538.59 27.37 m , 3.70 0.30 mm , and 3.16 0.30 mm , respectively . the mean values obtained by the visante oct were 536.14 26.61 m for cct , 3.71 0.29 mm for acd , and 3.17 0.29 mm for ad . the mean cct by the al - scan was higher than that obtained by the visante as - oct ( difference = 2.45 6.07 m , p < 0.05 ) . the differences in acd and ad measurements were not statistically significant . the 95% loa of cct , acd , and ad were between 9.44 and 14.35 m , 0.15 and 0.12 mm , and 0.15 and 0.12 mm , respectively . conclusions . since these two devices were comparable for measuring cct , acd , and ad , their results can be interchangeably used in the clinic .

it has been known for over a decade that the star - formation rate density in the universe peaked around redshifts @xmath20 ( e.g. , * ? ? ? * ; * ? ? ? more recently , the advent of bolometer arrays in the sub - millimeter ( sub - mm ) as well as the _ spitzer space telescope _ , have established that the contribution of ultra - luminous infrared galaxies ( ulirgs ) to the star - formation rate density in the universe rises sharply with redshift out to @xmath21 ( e.g. , * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? although ulirgs in the local universe are known to be rare @xcite and have long been thought to arise from a major merger of two gas - rich disk galaxies ( e.g. , * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? * ) , their nature and role in galaxy evolution at high redshift is not yet well - understood . the primary obstacle to studying ulirgs at high - redshift has been one of identification ( caused in large part by faintness at optical wavelengths ) . surveys to identify ulirgs have either been limited to small areas on the sky ( e.g. , the sub - mm common user bolometer array half degree survey , shades ; * ? ? ? * ) , low - spatial resolution imaging ( e.g. , the balloon - borne large aperture submillimeter telescope ; * ? ? ? * ) or are sensitive to mid - infrared ( mid - ir ) radiation which is far from the peak of the spectral energy distribution ( sed ) of the ulirg ( e.g. , * ? ? ? * ) . each of these techniques produce samples of objects that are sufficiently faint at far - ir and sub - mm wavelengths that follow - up observations have been time - consuming and therefore limited to a modest number of objects , both in terms of determining redshifts ( e.g. , * ? ? ? * ) and measuring important quantities such as accurate positions ( e.g. , * ? ? ? * ; * ? ? ? * ) , morphologies ( e.g. , * ? ? ? * ; * ? ? ? * ; * ? ? ? * ) , and gas and dust masses ( e.g. , * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? this situation is now being remedied following the launch of the _ herschel space observatory _ ( _ herschel_@xmath22 ) . with a large array of sensitive detectors at 70@xmath0 m , 100@xmath0 m , 160@xmath0 m , 250@xmath0 m , 350@xmath0 m , and 500@xmath0 m , the photodetector array camera and spectrometer and spectral and photometric imaging receiver on _ herschel _ are well - suited to surveying large areas of the sky at wavelengths that are ideal for the detection of ulirgs in the redshift range @xmath23 . the widest such survey is known as the _ herschel _ astrophysical terahertz large area survey ( h - atlas ; * ? ? ? * ) and covers 550 deg@xmath24 of sky as the largest open - time key project , reaching 5@xmath25 sensitivities of 130 mjy at 100@xmath0 m , 120 mjy at 160@xmath0 m , 32 mjy at 250@xmath0 m , 36 mjy at 350@xmath0 m , and 45 mjy at 500@xmath0 m @xcite . the wide area coverage of h - atlas makes it ideal for building statistically significant samples of rare galaxies . one such example that has been particularly fruitful thus far is the selection of gravitationally lensed objects . these are systems where the light from a distant source ( in this case , a ulirg at @xmath26 ) is deflected by a foreground lens ( typically an early type galaxy or group of galaxies ) in such a way that the background ulirg appears to have its angular size and brightness increased . several authors have predicted that the sub - mm is an efficient waveband to identify lensing systems due to the steep number counts of galaxies selected at sub - mm and mm wavelengths ( smgs ) ( e.g. , * ? ? ? * ; * ? ? ? * ; * ? ? ? * ) . additionally , the fact that most smgs lie at @xmath12 @xcite increases the probability that an interloping galaxy will lie along the line - of - sight . recently , @xcite have shown that a selection at 500@xmath0 m of @xmath27mjy sources within the 14.4 deg@xmath24 science demonstration phase field of h - atlas identifies strongly lensed systems , low-@xmath28 spiral galaxies @xcite , and higher-@xmath28 active galactic nuclei ( agn ) that are radio - bright and show a synchrotron emission spectrum even into the spire bands . shallow ground - based optical and radio imaging can be used to remove the latter two classes of objects , leaving only the strongly lensed systems . the h - atlas source catalog already extends to @xmath29deg@xmath24 ( phase 1 catalog ; dunne et al . , in prep . ) . this paper focuses on one source of particular interest drawn from the phase 1 catalog : h - atlas j142413.9 + 022304 ( this object is denoted i d 141 in * ? ? ? * hereafter , we refer to it as g15v2.779 ) . spire photometry of this source shows that it is one of the brightest detected so far in _ herschel _ wide - field surveys and that its sed peaks at wavelengths greater than 500@xmath0 m , suggesting that it lies at @xmath30 . this source has been the target of significant follow - up efforts : the plateau de bure interferometer ( pdbi ) has detected millimeter ( mm ) and sub - mm co emission lines which imply that the redshift of this source is @xmath31 , while data from the atacama pathfinder experiment ( apex ) have shown that the dominant cooling line in this galaxy is [ cii ] emission @xcite . this makes this one of the few smgs known at @xmath32 @xcite . in addition , a faint counterpart ( @xmath33 ab ) is detected in both the sloan digital sky survey ( sdss dr7 , * ? ? ? * ) and the united kingdom infrared deep sky survey ( ukidss , * ? ? ? * ) that has a photometric redshift of @xmath34 @xcite . altogether , the evidence favors a scenario in which the background source is a smg at high redshift that is being gravitationally lensed by an object at intermediate redshift , consistent with the lensing hypothesis of @xcite . recent observations by the submillimeter array ( sma ) have shown an elongation along the southeast northwest direction , possibly an indication of interesting morphological features on scales smaller than @xmath35 @xcite . in this paper , we present high - spatial resolution ( @xmath36 ) sma imaging at 880@xmath0 m , keck adaptive optics ( ao ) @xmath37-band imaging , and gemini multi - object spectrograph - south ( gmos - s ) optical spectroscopy of this object and demonstrate their utility for constraining a detailed model of the lens - source system . we use the sma , keck , and gemini data to probe the source size and magnification factor as well as the luminous plus dark matter mass of the lensing galaxies . the magnification factor is a critical parameter , since it is needed to understand intrinsic properties of the background smg such as its ir luminosity ( @xmath38 , integrated over 8 - 1000@xmath0 m ) as well as molecular gas and dust masses ( @xmath39 and @xmath40 ) . g15v2.779 is an example of a gravitationally lensed system discovered in h - atlas that permits the simultaneous study of obscured star - formation at high redshift as well as the nature of light and dark matter in galaxies at intermediate redshift . when the h - atlas catalogs are complete , we expect to have @xmath41 candidate lensed systems . in addition , systems identified from the _ herschel _ multi - tiered extragalactic survey could bring this total to 500 such objects discovered by _ herschel_. recent efforts using near - ir imaging to push to fainter sub - mm flux densities and grow the list of candidates up to @xmath42 appear promising @xcite . using similar selection techniques , the south pole telescope ( spt ) has identified a sample of @xmath43 candidate lensed smgs within the initial 87 deg@xmath24 survey @xcite . the final survey area will cover 2000 deg@xmath24 and is expected to provide a sample of @xmath44 lensed smgs . due to the selection at 1.4 mm , the spt sample of lensed smgs will be complementary to the _ herschel _ sample in the sense that it will be biased towards higher redshift or cooler dust temperatures . together , both the _ herschel _ and spt samples offer the opportunity to expand upon the legacy of work on strongly lensed galaxies over a similar redshift range undertaken as part of the center for astrophysics arizona space telescope lens survey ( castles ; * ? ? ? * ) , the cosmic lens all - sky survey ( class ; * ? ? ? * ; * ? ? ? * ) , and the jodrell bank very large array gravitational lens survey ( jvas ; * ? ? ? * ) by increasing the sample size of such systems by 1 - 2 orders of magnitude . in comparison to lensed systems selected via optical spectroscopy ( e.g. , the sloan lens advanced camera for surveys or slacs and the baryon acoustic oscillation survey emission - line lensing survey or bells ; * ? ? ? * ; * ? ? ? the ( sub-)mm selection is highly complementary in that it identifies ( 1 ) lensed galaxies that are both more luminous and at higher redshift ; and ( 2 ) lensing galaxies that span a wider range in optical brightness ( in particular , they do not need to be bright enough to be detected in sdss - iii spectroscopy ) . throughout this paper we assume @xmath4571 km s@xmath46 mpc@xmath46 , @xmath47 , and @xmath48 . at @xmath2 , this results in a scaling of 6.9 kpc arcsec@xmath46 . sma imaging data of g15v2.779 was initially obtained as a short observation conducted in the compact array configuration on 2010 june 16 ( @xmath49 hrs on - source integration time , see * ? ? ? * ) . these data yielded a robust detection of the target and provided a total flux density measurement at 880@xmath0 m of @xmath50 mjy . the data also pinpointed the location of the _ herschel _ source : ra 14:24:13.98 , dec + 02:23:03.45 ( j2000.0 ) and with a beamsize of 2@xmath51 hinted at an elongation in the northwest southeast direction ( @xmath52 degrees east of north ; * ? ? ? * ) . subsequent data in the very extended array configuration were obtained on 2011 january 4 and 6 ( @xmath53 hrs in total , max baseline length of 475 m ) . extended array configuration data were obtained to improve _ uv _ coverage on 2011 january 28 ( @xmath54 hrs , max baseline length of 226 m ) . atmospheric opacity was low ( @xmath55 ) and phase stability was good ( phase errors less than 30@xmath56 ) . we optimized the sma single - polarization 345 ghz receivers for continuum detection by tuning the primary local oscillator to 339.58 ghz and an intermediate frequency coverage of 48 ghz , providing a total of 8 ghz bandwidth ( considering both sidebands ) . the observations did not cover the nearest co emission line , co(@xmath57 ) at about 351 ghz since that frequency is near the high end of the range of the sma 345 ghz receivers and would have compromised the sensitivity of our continuum observations . we used the interactive data language ( idl ) mir package to calibrate the _ uv _ visibilities . the blazar 3c279 was used as the primary bandpass calibrator while titan was used as the absolute flux calibrator . the nearby quasars 1337@xmath58129 ( @xmath59jy , 19 degrees from target ) and 1512@xmath58090 ( @xmath60jy , 17 degrees from target ) were used for phase gain calibration . the quasar 1458 + 042 ( @xmath61jy , 9 degrees from target ) was observed to provide an independent check of the reliability of the calibration , particularly phase transfer . for imaging , we used the multichannel image reconstruction , image analysis , and display ( miriad ) software package @xcite with natural weighting for maximum sensitivity . this resulted in an elliptical gaussian beam with a full - width half - maximum ( fwhm ) of @xmath62 and position angle of 62.4 degrees east of north . figure [ fig : imaging ] shows the sma image of this source ( combining compact , extended and very extended array configurations ) in red contours . the sub - mm emission is resolved into two bright emission regions to the southeast and northwest of the lensing galaxies . these emission regions have peak intensities of @xmath63 mjy beam@xmath46 and @xmath64 mjy beam@xmath46 , respectively ( quoted 1@xmath25 uncertainties do not include the estimated absolute calibration uncertainty of 10% ) . the peaks are located at positions of ( ra=14:24:14.006 , dec=+02:23:02.81 ) and ( ra=14:24:13.938 , dec=+02:23:04.40 ) , respectively ( the uncertainty in the relative position of these peaks is @xmath65 ) . in addition , there is a background of complex substructure that , together with the two bright emission regions , sums to a total flux density of @xmath66 mjy and is likely to be produced by gravitational lensing . m emission centroid ) . red contours highlight sma 880@xmath0 m dust continuum emission from the lensed smg at @xmath2 ( drawn at -2 , 2 , 4 , 6 , ... times the 1@xmath25 rms level , where @xmath67 mjy ) . the size of the sma beam ( fwhm @xmath68 ) is shown by the black hatched ellipse at the bottom left corner of the plot . the greyscale background shows keck ao @xmath1-band imaging which has resolved the lens into two early type galaxies . [ fig : imaging],scaledwidth=45.0% ] we obtained a 1920 sec @xmath1-band image of g15v2.779 on 2011 april 13 ( ut ) as part of program i d c213n2l ( pi : h. fu ; e.g. , * ? ? ? * ) with the keck ii laser guide - star adaptive - optics system ( lgsao ; * ? ? ? an @xmath69 magnitude star 26@xmath70 south of g15v2.779 served as the tip - tilt reference star . the expected strehl ratio is about 0.17 at the source position . we used the second generation near - infrared camera ( nirc2 ) at @xmath71 pixel@xmath46 scale and executed a nine - point dithering pattern with 3@xmath70 dithering steps . three 80 sec exposures were obtained at each dithering position . the natural seeing was about @xmath72 . we used our own idl program to reduce the images . after dark subtraction and flat - fielding , sky background and object masks were updated iteratively . for each frame , after subtracting a scaled median sky , the residual background was removed with b - spline models . in the last iteration , we discarded the three frames of the poorest image quality and corrected the nirc2 geometric distortion using the solution of p. b. cameron before combining the aligned frames . the resolution of the final image is @xmath73 in fwhm , as measured from the stellar source @xmath74 northwest of g15v2.779 . astrometry was determined from sdss photometric sources inside the 40@xmath70 field of view and carries 1@xmath25 uncertainties in an absolute sense of @xmath75 ( in fact , we show in section [ sec : results ] that the tightest constraints on the astrometry are derived directly from the lens modeling ) . the flux scale in the image was normalized such that the total flux of the two lensing galaxies matches that seen in the ukidss @xmath76-band data , where the two galaxies have a total magnitude of @xmath77 . the grayscale of figure [ fig : imaging ] shows the keck ao @xmath1-band image of g15v2.779 . the backgound smg is undetected , while the two foreground lensing galaxies are detected at high significance . the ao imaging indicates the secondary lens galaxy is located 0@xmath78025 east and 0@xmath78327 south of the primary . a galfit decomposition of the two sources seen in the keck image into srsic components indicates that a de vaucouleurs profile is appropriate for both the northern and southern galaxies . in fact , the best - fit models have @xmath79 , but this is probably due to faint , large - scale fluctuations in the background sky level hereafter , we assume @xmath80 for both galaxies for simplicity . figure [ fig : galfit ] shows the best - fit galfit model and the residuals after subtracting the model from the data . table [ tab : galfitresults ] contains the best - fit parameters from the galfit modeling and their 1@xmath25 uncertainties . these are underestimates of the true errors as they do not account for degeneracies between the parameters . the two lensing galaxies are highly compact , with effective radii of @xmath81 kpc and @xmath82 kpc . the northern galaxy has @xmath83 ( vega mag ) and the southern galaxy has @xmath84 ( vega mag ) . -band image ( as in figure [ fig : imaging ] ) . _ middle _ : best - fit galfit model ( assuming @xmath85 for both lensing galaxies ) . _ right _ : residuals obtained after subtracting the best - fit model from the keck data . both morphologies are consistent with early - type galaxies . [ fig : galfit],scaledwidth=45.0% ] the background source is not detected inside a @xmath86 radius , implying a 5@xmath25 limit of @xmath87 ( vega mag ) . this corresponds to a flux density 5@xmath25 limit of @xmath88jy . this level of faintness in the near - ir is frequently an indication of @xmath32 systems ( e.g. * ? ? ? * ; * ? ? ? if differential magnification effects are insignificant ( i.e. , @xmath89 ) , then this implies a 500@xmath90 m to @xmath1-band flux density ratio of @xmath91 . at @xmath2 , this corresponds roughly to rest - frame 100@xmath90 m to @xmath92-band . an interesting comparison example is mrk 231 , a heavily obscured ulirg in the local universe that has a 100@xmath90 m to @xmath92-band flux density ratio of @xmath93 . this value is about a factor of 3 - 4 lower than g15v2.779 , suggesting that the obscuration in g15v2.779 is extreme . in section [ sec : bg ] , we will compare the obscuration in g15v2.779 with other @xmath26 smgs . lccc @xmath94 ( vega ) & @xmath95 & @xmath96 + @xmath97 & 4 & 4 + @xmath98 ( kpc ) & @xmath99 & @xmath100 + @xmath101 & @xmath102 & @xmath103 + @xmath104 ( deg ) & @xmath105 & @xmath106 + [ tab : galfitresults ] long - slit spectroscopic observations of g15v2.779 were taken using the gemini gmos - south instrument on the night of 2011 march 6 , under photometric conditions as part of programme gs-2011a - q-57 ( pi : d. j. b. smith ) . two observations of 1800 seconds each were made through a 2@xmath70 slit , using the r400 grating and the og515 blocking filter , with dithering both in the wavelength direction and along the slit to minimize the effects of bad columns and gaps between the gmos - s chips . the central wavelengths for the two observations were 630 and 635 nm , and flat field observations were interspersed between the observations at each wavelength setting , as recommended by the gemini observatory . cuar arc lamp exposures were taken for the purposes of wavelength calibration , using the same instrumental setup as for the science exposures , and the spectral resolution obtained was @xmath1076.0 . a position angle of 330@xmath56 east of north was chosen to place the slit along the major axis of the extension seen in the sma and pdbi observations , and the ccd was binned by 4 pixels in both the spectral and spatial directions . the long - slit data were reduced using the iraf gemini gmos reduction routines , and following the standard gmos - s reduction steps in the example taken from the gemini observatory webpages . since the primary aim of these observations was to obtain a spectroscopic redshift and measure of the balmer/4000 break for the lensing source ( or sources ) , flux calibration was not performed . figure [ fig : gmos ] shows the optical spectrum of g15v2.779 obtained with gemini gmos - s . because the slit width is 2@xmath70 , both lensing galaxies are included in this spectrum . a strong break at observed - frame 6350 is obvious in the spectrum . two narrow emission lines on either side of this break coincide with atmospheric features and are likely not produced by astronomical sources . the break in the spectrum likely corresponds to a balmer/4000 break and suggests that both lensing galaxies are at @xmath108 ( the redshift and error were estimated using a by - eye comparison of the observed spectrum with a synthesized simple stellar population with solar metallicity and an age of 5 gyr ; * ? ? ? we note that without spatially resolved spectroscopy it is not possible to confirm that both lensing galaxies are located at the same redshift . the ratio of the flux density longward and shortward of the break is known as the @xmath109 value and is a measure of the average age of the stars within the galaxies . we use the definition from @xcite and measure @xmath110 ( we adjust the wavelength window longward of the break to avoid the portion of the spectrum affected by atmospheric emission lines ) . this value is typical of galaxies dominated by old stellar populations ( 5 - 10 gyr , depending on metallicity ; * ? ? ? * ) . and are selected to avoid the cyan regions . the background source is hidden by dust at these wavelengths , but both foreground lens galaxies lie within the 2@xmath70 gmos - s slit . the spectrum shows a strong , abrupt break at an observed - frame wavelength of @xmath111 , likely corresponding to the balmer/4000@xmath22 break and implying a lens redshift of @xmath112 . the strength of the break implies the lensing galaxies are dominated by old stars ( 5 - 10 gyr , depending on metallicity ; * ? ? ? [ fig : gmos],scaledwidth=45.0% ] the combination of good sensitivity and high spatial resolution provided by the sma and keck ao data ( probing the emission from the lensed and lensing galaxies , respectively ) permits a detailed study of the parameters of the lensing model that describe this system . the lensed emission is detected only in the sma data . since the sma is an interferometer , the surface brightness map of the lensed emission is obtained with incomplete _ uv _ coverage , implying that surface brightness is not necessarily conserved and that the pixel - to - pixel errors in the map are correlated . furthermore , the lensed emission observed by the sma comprises multiple , resolved components . for these reasons , it is important to compare model and data in the visibility plane rather than the image plane . we make use of the publicly available gravlens software @xcite to map emission in the source plane to the image plane for a given lensing mass distribution . using this software , a model of the lensed emission is constructed based on the density profile of the lens assumed here to be two singular isothermal ellipsoids ( one for each galaxy seen in the keck ao imaging ) , the morphology of the source taken here to be a srsic profile , and the position of the source relative to the lens . although the srsic profile represents a crude simplification of the true background source morphology , we use it here because it permits a test of the variation in the lensing properties ( e.g. , magnification of the background source ) as a function of variation in the nature of the source ( e.g. , half - light radius ) . later in this section , we discuss how our best - fit parameters change when a second source is added to the source plane . the gravlens lens model ( with a single source in the source plane ) contains 15 free parameters : the position of the source relative to the sma 880@xmath90 m emission centroid ( @xmath113 and @xmath114 ) , the intrinsic flux of the source ( @xmath115 ) , the half - light radius of the source ( @xmath116 ) , the srsic index of the source ( @xmath117 ) , the ellipticity ( defined as @xmath118 ) and position angle of the source ( @xmath119 and @xmath120 ) , the position of the primary lens relative to the sma emission centroid ( @xmath121 and @xmath122 ) , the mass of the primary lens ( parameterized in terms of the angular einstein radius , @xmath123 ) , the ellipticity and position angle of the primary lens ( @xmath124 and @xmath125 ) , and the einstein radius , ellipticity , and position angle of the secondary lens ( @xmath126 , @xmath127 , and @xmath128 ) . the 1-@xmath25 absolute astrometric accuracy between the sma and keck images is @xmath129 , so in our modeling efforts we allow the position of the lens to vary by as much as @xmath130 in both ra and dec ( i.e. , 2@xmath25 in each direction ) . in fact , the constraints from the lens model are significantly tighter than @xmath129 , as we show below . we make use of the keck ao @xmath1-band data and fix the position of the secondary lens relative to the primary at @xmath131 and @xmath132 ( rotational astrometric uncertainties between the sma and keck ao images are sub - dominant to translational uncertainties ) . furthermore , we use our galfit results and constrain the ellipticity and position angle of the lenses to be within 3@xmath25 of the best - fit galfit values ( as given in table [ tab : galfitresults ] . we tested models in which the mass of each foreground lensing galaxy was allowed to vary as well as models in which the mass of the secondary lens was fixed to be equal to one - half that of the primary lens . this latter choice assumes that both lens galaxies are located at the same redshift @xmath133 and is supported by the ground - based gemini gmos - s spectrum of g15v2.779 ( see section [ sec : gmos ] ) . high - spatial resolution optical or near - ir spectroscopy are needed to resolve the two lensing galaxies and provide a definitive test of the validity of our assumptions . for a given set of model parameters , gravlens generates a surface brightness map of the lensed emission . this surface brightness map can then be used as input to miriad s uvmodel task , which computes the fourier transform of the image and samples the resulting visibilities in a way that matches the sampling of the actual observed sma visibility dataset ( @xmath134 ) to produce a `` simulated visibility '' dataset ( @xmath135 ) . the quality of fit for a given set of model parameters is determined from the chi - squared value ( @xmath136 ) according to the following equation : @xmath137 where @xmath138 is the 1@xmath25 uncertainty level for each visibility and is determined from the system temperatures ( this corresponds to a natural weighting scheme ) . because the measured visibilities are complex , we compute both @xmath139 and @xmath140 and measure the total @xmath136 as the sum of the real and imaginary components . we employ a markov chain monte carlo ( mcmc ) technique to sample the posterior probability density function ( pdf ) of our model parameters . in particular , we use the emcee code @xcite to implement the mcmc analysis . the algorithm adopted by emcee was originally presented in @xcite and uses an affine - invariant ensemble sampler to obtain significant performance advantages over standard mcmc sampling methods . here , we summarize the behavior of the ensemble sampler technique . the available parameter space is searched using a set of @xmath141 walkers . during iterations of the mcmc , each walker selects another walker from the ensemble and identifies a new position in parameter space based on the positions of both walkers ( this is known as a `` stretch move '' ) . once a new position has been found , the posterior pdf is computed and compared to that of the previous position . new positions with higher probability ( i.e. , lower @xmath136 ) are always accepted ; those with lower probability are _ sometimes _ accepted . after a sufficient number of iterations ( @xmath142 ) , the ensemble of walkers samples the parameter space in a way that reflects the posterior pdf . the mean and variance of each parameter can then be measured directly from the history of walker positions . we employ a `` burn - in '' phase with @xmath143 and @xmath144 ( i.e. , 50,000 samplings of the posterior pdf ) that is used to identify the best - fit model position . this position is then used to initialize the `` final '' phase with @xmath145 and @xmath146 ( i.e. , 10,000 samplings of the posterior pdf ) . to ensure that the posterior pdf was sampled with a sufficient number of iterations , we computed the autocorrelation time for each parameter in a given ensemble of walkers and found that it was of order unity for each parameter . this implies that we have 10,000 independent samplings of the posterior pdf , more than enough to obtain a robust measurement of the mean and uncertainty on each parameter of the model . during each mcmc iteration , we also measure the magnification factor @xmath90 ( we follow the nomenclature in the smg literature here and use @xmath90 to refer to the total magnification obtained by summing over all individual lensed components ) using the following method . first , we take the unlensed , intrinsic source model and measure the total flux density ( @xmath147 ) within an elliptical aperture ( @xmath148 ) centered on the source with ellipticity and position angle equal to that of the source model and with a semi - major axis length of @xmath149 . next , we take the lensed image of the best - fit model and measure the total flux density ( @xmath150 ) within the aperture @xmath151 , where @xmath152 is determined by using gravlens to map @xmath153 in the source plane to @xmath152 in the image plane ( using the lens parameters which correspond to the best - fit model ) . the magnification is then computed simply as @xmath154 . the best - fit value and 1@xmath25 uncertainty are drawn from the posterior pdf as with the other parameters of the model . the best - fit model ( assuming a fixed mass ratio between the primary and secondary lens ) produced by gravlens is shown in figure [ fig : modeling ] and demonstrates that many of the features present in the sma imaging can be reproduced in detail by gravlens . the panel on the left shows the sma imaging overlaid on the inverted , deconvolved map of the best - fit model visibilities . the panel on the right shows the residual image obtained by inverting and deconvolving the residual visibilities ( i.e. , the cleaned map of the difference between the model and data visibilities ) . the model fits the two brightest components in the sma image ( the peaks to the southeast and northwest ) , but fails to reproduce fully the peaks in the map to the northeast and southwest . we measure the following parameters of interest from the model : @xmath155 , @xmath156 , @xmath157 , @xmath158 , @xmath159 ( this position is within 1@xmath25 of the position indicated from the keck ao astrometry ) , @xmath160 , @xmath161 , @xmath162 , @xmath163 kpc , @xmath164 , and @xmath165 degrees east of north . the best - fit model has @xmath166 and 144191 degrees of freedom . these constraints on model parameters are reported in table [ tab : lensingresults ] . also reported in table [ tab : lensingresults ] are the results obtained when the mass of the secondary is allowed to vary relative to the primary . the uncertainties on the mass of each individual lensing galaxy are significantly larger in this case because our lens model constrains the sum of the masses of the two lensing galaxies . the constraint on the sum of the masses is @xmath167 ( consistent with the results from models where the mass ratio has been fixed ) . the gemini gmos - s optical spectrum provides evidence that the two lensing galaxies are both @xmath168 . under that assumption , the secondary is significantly less luminous and hence likely to be significantly less massive . therefore , for the remainder of the paper we have assumed a 2:1 mass ratio between the primary and secondary . spatially resolved spectroscopy of the lensing galaxies is needed to prove the validity of this assumption . lcccc @xmath169 ( @xmath70 ) & @xmath170 & @xmath171 & @xmath172 + @xmath173 ( @xmath70 ) & @xmath174 & @xmath175 & @xmath176 + @xmath177 ( kpc ) & @xmath178 & @xmath179 & @xmath180 + @xmath181 & @xmath182 & @xmath182 & @xmath183 + @xmath184 & @xmath185 & @xmath186 & @xmath187 + @xmath188 ( deg ) & @xmath189 & @xmath190 & @xmath191 + @xmath192 ( @xmath70 ) & & & @xmath193 + @xmath194 ( @xmath70 ) & & & @xmath195 + @xmath196 ( kpc ) & & & @xmath197 + @xmath198 & & & 0.5a + @xmath199 & & & @xmath200 + @xmath201 ( deg ) & & & @xmath202 + @xmath121 ( @xmath70 ) & @xmath203 & @xmath204 & @xmath205 + @xmath206 ( @xmath70 ) & @xmath207 & @xmath208 & @xmath209 + @xmath123 ( @xmath70 ) & @xmath210 & @xmath211 & @xmath212 + @xmath126 ( @xmath70 ) & @xmath195 & @xmath213 & @xmath213 + @xmath90 & @xmath214 & @xmath215 & @xmath216 + @xmath136 & 217796.9 & 217799.1 & 217769.2 + @xmath217 & 144190 & 144191 & 144185 + a srsic index of secondary source is fixed at @xmath218 . see section [ sec : results ] for details . [ tab : lensingresults ] the residual map in figure [ fig : modeling ] shows that our single - source model fails to account for the secondary peaks in the map to the northeast and southwest as well as a faint ring of emission partially lined up with the tangential critical curve . we investigated whether adding an additional source in the source plane near the tangential caustic would improve the ability of the model to match these secondary peaks . the new model has six new parameters : the flux of the second source ( @xmath219 ) , the position of the second source relative to the sma emission centroid ( @xmath192 and @xmath220 , constrained to be within @xmath221 of the tangential caustic ) , half - light radius of the second source ( @xmath196 ) , the ellipticity of the second source ( @xmath199 ) , and the position angle of the second source ( @xmath201 ) . initial tests of the two - source model showed that the fitting routine struggled to identify the best - fit model consistently unless the srsic index of the second source was fixed at @xmath218 ( i.e. , a gaussian profile ) , so that is what we have adopted here . figure [ fig : merger ] shows the results obtained with the two - source model and table [ tab : lensingresults ] contains the best - fit model parameters and their 1@xmath25 uncertainties . the best - fit model has @xmath222 and 144185 degrees of freedom . the magnification factor is @xmath223 , and the einstein radii of the two lenses are @xmath224 and @xmath225 , values that are very similar to those obtained with the single - source model . these are the parameters of greatest interest , so it is reassuring that they are relatively insensitive to the exact morphology of the background source . the position of the primary background source is also relatively robust between the two models we have tested , with ( @xmath226 , @xmath227 ) relative to the sma emission centroid . the secondary source is less well - constrained , having a position of @xmath228 , @xmath229 . this position places the secondary source near a caustic , implying that it has experienced a high degree of magnification and has a much lower intrinsic luminosity than the primary source . the primary source maintains a broad profile intermediate between a disk and an elliptical , while the second source is compact ( @xmath230 kpc ) . in both the single - source and two - source models , the best - fit residual maps show emission to the southwest in the sma data that the model fails to reproduce . this could be an indication of the presence of a third source in the source plane , but an examination at that level is beyond the scope of this paper . overall , the agreement between the single - source and two - source model results is encouraging . for the remainder of the paper , we use the results from our single - source model , since it provides nearly as good a fit to the data as the two - source model ( @xmath231 ) but requires six fewer free parameters . our major conclusions are insensitive to whether the single - source or two - source model is used . it is interesting that the magnification factor we have measured is somewhat lower than might be expected based on the velocity dispersion and observed luminosity of co emission lines in g15v2.779 . studies of co(@xmath232 ) emission lines in both lensed and unlensed smgs have found a correlation between the intrinsic ( i.e. , unlensed ) co(@xmath232 ) line luminosity and the fwhm of the emission line ( harris et al . , submitted ; bothwell et al . , in prep . ) . while co(@xmath232 ) data are not yet available for g15v2.779 , higher @xmath233 lines have indicated fwhm@xmath234km@xmath235s@xmath46 and @xmath236km@xmath22s@xmath237pc@xmath24 . according to the correlation identified in the previous studies , this fwhm value would imply an ( unlensed ) line luminosity of @xmath238km@xmath22s@xmath237pc@xmath24 . however , assuming a typical sub - thermal co(@xmath239 ) to co(@xmath232 ) conversion factor ( e.g. , harris et al . , in submitted . ) , our measurement of @xmath90 would indicate @xmath240km@xmath22s@xmath237pc@xmath24 . possible explanations for this include either an unusual co(@xmath239)/co(@xmath232 ) ratio , a large intrinsic scatter in the luminosity line - width relations in these systems , or a difference in the size - scale of the co(@xmath232 ) and the far - ir emitting regions , leading to @xmath241 not being equal to @xmath242 . in this section , we discuss the implications of our results for the nature of g15v2.779 . we begin with a focus on the background source and end with the foreground lens properties . the magnification factor of the background source is a parameter that is critical to the derivation of any intrinsic property of the source . the properties that we consider here are the total ir luminosity ( @xmath38 ) , the sfr , the projected ir luminosity surface density ( @xmath243 ) , the dust mass ( @xmath40 ) , and the molecular hydrogen gas mass ( @xmath244 ) . we compute @xmath38 as the integral under the full sed as reported in @xcite , divided by @xmath90 . differential magnification effects are an important consideration when computing @xmath38 . initial studies indicate that when the magnification factor at any given wavelength is modest ( @xmath245 ) , then differential magnification effects are expected to have a minimal influence on the inferred ir luminosity @xcite . the contribution from the lensing galaxies to @xmath38 is likely to be minimal , given that they are both early - type galaxies at @xmath246 . we find an intrinsic ir luminosity of @xmath247 , a value that likely makes g15v2.779 one of the intrinsically brightest known smgs ( with an intrinsic , un - lensed sub - mm flux density of @xmath248mjy ) . using the standard conversion from @xmath38 to sfr , this corresponds to a sfr of @xmath249yr@xmath46 . this value assumes that all of the ir luminosity originates from star - formation rather than agn . hence this value should be regarded as an upper limit on the true sfr , although it should be noted that measurements of the radio luminosity suggest a far - ir to radio flux ratio that is consistent with starburst dominated galaxies @xcite . the srsic index of the background source ( @xmath250 ) is intermediate between an exponential disk profile ( @xmath251 ) and a de vaucouleurs ( @xmath80 ) profile . the source is significantly extended , having a half - light radius of @xmath252kpc . this implies a de - projected ir luminosity surface density ( computed as @xmath253 , where @xmath254 ) of @xmath255kpc@xmath256 . this range of values for @xmath243 places g15v2.779 within the `` normal star - forming '' class of galaxies at @xmath257 and is significantly below that of local ulirgs ( which have @xmath243 values in the range @xmath258kpc@xmath256 ; * ? ? ? this may be a clue that unlike local ulirgs , the intense , dust - enshrouded burst of star - formation that is occurring in g15v2.779 may not be driven by a major merger . to compute the apparent ( i.e. , un - corrected for lensing ) dust mass , @xcite perform a single - temperature , optically thin , modified black - body fit to the far - ir and sub - mm sed of g15v2.779 ( following * ? these authors find a dust mass of @xmath259 , using the best - fit dust temperature of @xmath260k and a mass absorption coefficient of @xmath261@xmath262g@xmath46 . if instead an optically thick modified black - body is used to fit the data , the inferred dust mass decreases by nearly a factor of 2 . our measurement of @xmath90 implies dust masses @xmath263 ( using the values reported in * ? ? ? the uncertainty in the dust mass is dominated by systematic uncertainties related to the unknown optical depth at far - ir wavelengths and the unconstrained mass opacity coefficient and is at least a factor of a few . the measured dust mass is similar ( though at the top end ) to those estimated for other high-@xmath28 smgs and also for the most massive @xmath264 galaxies in h - atlas @xcite . to quantify the interstellar medium properties in this object , @xcite use a spherical , single - component , large velocity gradient ( lvg ) model to fit simultaneously the co(@xmath265 ) , co(@xmath239 ) , and co(@xmath266 ) emission lines . assuming a conversion factor of @xmath267k@xmath235km@xmath235s@xmath237pc@xmath268 to go from @xmath269 to @xmath270 , @xcite find gas masses of @xmath271 . using our measurement of @xmath90 , we find @xmath272 . note that there is some evidence that @xmath273 may be higher for less dense systems at high-@xmath28 relative to local ulirgs @xcite . if this is indeed the case , then the gas mass would be even larger . given the large dust mass ( even with the optically thick fit ) , this is not unreasonable . this gas mass is a factor of @xmath274 larger than the typical gas mass found in un - lensed smgs @xcite , 2.5 - 9 times larger than two lensed sources discovered in the h - atlas sdp @xcite , and a factor of @xmath274 larger than a lensed source from hermes @xcite . g15v2.779 appears to be a very massive , highly star - forming galaxy at @xmath275 . table [ tab : smgproperties ] summarizes the properties of g15v2.779 and compares them with unlensed smgs at @xmath26 . g15v2.779 bears a close resemblence to gn20 , having similar @xmath38 , @xmath39 , @xmath276 , @xmath116 , @xmath277 , and @xmath243 values . however , there is an important difference : gn20 is much more luminous in the rest - frame optical than g15v2.779 . in terms of visual extinction ( @xmath278 ) , g15v2.779 is most similar to gn10 , which has @xmath279 . however , gn10 is less luminous and has only an upper limit on its source size . the fact that g15v2.779 is clearly extended on scales @xmath280 kpc and yet maintains a covering fraction near unity indicates an impressive quantity of dust , consistent with the dust mass measurements described above . one feature all of these @xmath26 smgs share in common is @xmath243 values that are 1 - 2 orders of magnitude lower than those of ulirgs in the local universe . this may be an indication that the physical mechanisms driving the prodigious luminosities in these systems may be different from what occurs at @xmath281 . theories attempting to explain the behavior of these systems must also account for the short gas depletion timescales ( possibly via strong inflow of gas from the inter - galactic medium ; e.g. * ? ? ? * ) , as the estimated sfrs will consume all of the available gas within @xmath282 myr in all of these galaxies . lcccccccccc g15v2.779 & @xmath283 & @xmath284 & lowfg & @xmath285 & & @xmath286 & @xmath287 & @xmath179 & @xmath288 & @xmath289 + gn10a & @xmath290 & @xmath291 & lowg & @xmath292 & @xmath293 & @xmath294 & @xmath295 & @xmath296 & @xmath297 & @xmath298 + gn20b & @xmath299 & @xmath300 & lowg & @xmath301 & @xmath302 & @xmath303 & @xmath304 & @xmath305 & @xmath302 & @xmath306 + gn20.2ab & @xmath307 & @xmath308 & lowg & @xmath309 & @xmath310 & @xmath303 & @xmath311 & @xmath296 & @xmath312 & @xmath298 + j1000 + 0234c & @xmath313 & @xmath314 & lowg & @xmath315 & @xmath309 & @xmath316 & @xmath317 & @xmath318 & @xmath319 & @xmath320 + j033229.4d & @xmath321 & @xmath322 & lowh & @xmath323 & @xmath324 & @xmath325 & @xmath326 & @xmath305 & @xmath327 & @xmath320 + aztec-3e & @xmath328 & @xmath329 & lowg & @xmath330 & @xmath331 & @xmath303 & @xmath332 & @xmath312 & @xmath333 & @xmath334 + a@xcite b@xcite c@xcite d@xcite e@xcite f880@xmath90 m size @xmath280 kpc gradio to ir luminosity ratio consistent with star - formation dominated galaxies hweak nv , 24@xmath90 m , and near - uv emission inconsistent with agn [ tab : smgproperties ] we use the standard equations from @xcite to compute the mass of the lens galaxies @xmath335 , finding @xmath336 ( recall that we have assumed @xmath337 ) . independent mass estimates can be obtained using the correlation between @xmath338-band luminosity and @xmath335 given in @xcite . at @xmath339 , the observed @xmath28-band corresponds almost exactly to the rest - frame @xmath338-band . the ground - based @xmath28-band magnitude of the two lenses together is @xmath340 @xcite , corresponding to a rest - frame @xmath338-band luminosity of @xmath341 . assuming the rest - frame @xmath338-band luminosity ratio between the two lens galaxies is the same as that in the observed @xmath1-band , the @xmath342 correlation observed from the slacs lenses @xcite implies lens masses of @xmath343 and @xmath344 , consistent with our lens model estimates of @xmath345 and @xmath346 . an alternative estimate of the lens masses is to use the @xmath338-band luminosities along with a mass - to - light ratio derived from synthesized stellar populations . the optical spectrum of g15v2.779 shows a strong balmer/4000 break ( @xmath347 ) , typical of galaxies dominated by old stellar populations ( 5 - 10 gyr , depending on metallicity ; * ? ? ? a synthesized stellar population with an age of 5 gyr , a chabrier imf , and no dust extinction has a mass - to - light ratio of @xmath348 . thus , the inferred stellar masses of the two lensing galaxies are @xmath349 and @xmath350 . there is evidence at the 1.5@xmath25 level that the lens and mass estimates are greater than the stellar mass estimates . this may be reasonable considering the small stellar sizes ( half - light radii of @xmath351 kpc ) relative to the einstein radius of each system ( @xmath352 kpc ) . figure [ fig : castlesboss ] shows that g15v2.779 has two of the faintest ( in @xmath353-band ) and lowest mass ( at this redshift ) lensing galaxies found in current surveys of gravitationally lensed systems ( e.g. , castles , class , slacs , and bells ; * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? this is an indication that wide - field surveys with _ herschel _ will be useful for identifying lensing systems where the lensing galaxy is faint in the optical , either due to being low - mass or being very distant . this is generally true for source - selected lensing surveys ( e.g. , class , h - atlas , and a portion of castles ) , whereas lens - selected lensing surveys ( e.g. , slacs and bells ) tend to be biased towards brighter and more massive foreground galaxies . both g15v2.779 lens galaxies have early - type morphologies with small half - light radii ( @xmath351 kpc ) . such systems appear to be commonplace at @xmath354 , but become increasingly rare at lower redshifts ( e.g. , * ? ? ? however , given the small separation between the two lensing galaxies ( @xmath355 kpc ) , it is likely that they are about to merge together ( dissipationless mergers often do not have obvious signs of interaction even at these separations ; e.g. , see * ? ? ? simple virial arguments suggest that this process could lead to a doubling of the radius while the mass only increases by 50% @xcite . such a result would make the size of the merged system consistent with similarly massive galaxies at @xmath356 ( e.g. , * ? ? ? * ) as well as more typical of lensing galaxies found in castles , class , slacs , and bells . overall , these observations are consistent with the dissipationless ( `` dry '' ) merging stage of the two - phase galaxy evolution scenario outlined in @xcite . in this picture , the progenitors of massive galaxies undergo intense in - situ star - formation from @xmath357 to @xmath21 that leads to compact , elliptical galaxies with little or no reservoirs of gas for future star - formation . from @xmath21 to the present - day , massive galaxies undergo dry merging and increase their sizes such that they evolve onto the mass - size relation observed in local early - type galaxies . -band magnitudes as a function of redshift . note that g15v2.779 is significantly fainter in @xmath353-band than any of the galaxies in bells . _ bottom _ : mass within the einstein radius as a function of redshift . g15v2.779 is less massive than all bells galaxies at @xmath358 . this demonstrates that as a source - selected lens survey ( similar to class and part of castles ) , h - atlas will be less biased towards massive , bright lensing galaxies than lens - selected surveys like slacs or bells . h - atlas and other _ herschel _ wide - field surveys will help identify lens systems at intermediate redshifts where the galaxy in the foreground is particularly faint , either due to having a low mass or lieing at high redshift ( or both , as appears to be the case for g15v2.779 ) . [ fig : castlesboss],scaledwidth=45.0% ] we use high - spatial resolution imaging obtained with the sma at 880@xmath90 m and keck ao at @xmath1-band to perform a detailed gravitational lens modeling of g15v2.779 , an smg at @xmath275 identified by _ herschel _ in the h - atlas survey . we present a gemini gmos - s optical spectrum of g15v2.779 that suggests that the two foreground galaxies are at @xmath112 . this analysis provides important measurements of the nature of both the background smg and the foreground lenses . we summarize our findings below . we employ a visibility - plane lens modeling analysis and find a magnification factor of @xmath359 for the background source . this measurement is significantly lower than what had been previously assumed for this source and indicates that not all of the brightest lens candidates identified by _ herschel _ have high magnification factors . this value of @xmath90 implies an intrinsic infrared luminosity of @xmath360 . the best - fit model for the background source favors radial profiles that are intermediate between exponential disks and de vaucouleurs . the half - light radius of the background source is @xmath361kpc . this size measurement implies a de - projected ir luminosity surface density of @xmath255kpc@xmath256 . this number is typical of @xmath257 ulirgs and hylirgs but 10 - 100 times lower than ulirgs in the local universe . this may be an indication that the formation mechanism for this source could be different from @xmath281 ulirgs , which are thought to arise from major mergers of gas - rich disk galaxies . higher - spatial resolution data with improved sensitivity are needed to favor one of these models over the other . our measurement of @xmath90 , in conjunction with previous observations of co emission lines and the far - ir sed , indicates a gas mass of @xmath362 and a dust mass of @xmath363 . these values are factors of 2.5 - 9 times larger than other lensed galaxies studied to date but are comparable to other @xmath26 smgs . they indicate that g15v2.779 hosts a massive reservoir of molecular gas that is fueling a prodigious , but likely short - lived ( @xmath282 myr ) period of star - formation . the foreground lenses have einstein radii of @xmath364 and @xmath365 . these imply lens masses of @xmath366 and @xmath367 . the lensing galaxies have sizes of @xmath368kpc and lie at a redshift of @xmath369 . the gravitational potential from both galaxies may include a significant contribution from dark matter . they are separated by 2 kpc and will likely merge into a single early - type galaxy with a larger size that will make the resultant system consistent with other early - types at @xmath370 . together , the sma , keck , and gemini data have established that g15v2.779 is a smg at @xmath275 modestly lensed by a pair of early - type galaxies at @xmath168 . our results highlight the bounty of information that can be obtained via a multi - wavelength approach to studying strongly lensed smgs at high redshift . more sensitive and higher - spatial resolution imaging of the lensed emission is needed to improve the constraints on the parameters of the gravitational lensing model and test competing models for the powering mechanism in this source ( e.g. , major merger vs. secular processes ) . this will become feasible in the near future when baseline lengths of @xmath371 km become available with alma . _ hst _ spectroscopy is needed to confirm that the lensing galaxies both lie at @xmath246 , to measure their velocity dispersions , and to improve their stellar mass estimates . the results described in this paper are based on observations obtained with _ , an esa space observatory with science instruments provided by european - led principal investigator consortia and with important participation from nasa . herschel_-atlas is a project with _ herschel _ , which is an esa space observatory with science instruments provided by european - led principal investigator consortia and with important participation from nasa . the h - atlas website is http://www.h - atlas.org/. us participants in h - atlas acknowledge support from nasa through a contract from jpl . rsb acknowledges support from the sma fellowship program . hf , ac , jlw and sk acknowledge support from nsf career ast-0645427 . we thank the referee for a thorough review of the manuscript which resulted in a stronger paper overall . the ground - based follow - up observations were obtained at the sma , at the w. m. keck observatory , and at the gemini south observatory . the sma is a joint project between the smithsonian astrophysical observatory and the academia sinica institute of astronomy and astrophysics and is funded by the smithsonian institution and the academia sinica . the authors wish to recognize and acknowledge the very significant cultural role and reverence that the summit of mauna kea has always had within the indigenous hawaiian community . we are most fortunate to have the opportunity to conduct observations from this mountain . based on observations obtained at the gemini observatory , which is operated by the association of universities for research in astronomy , inc . , under a cooperative agreement with the nsf on behalf of the gemini partnership : the national science foundation ( united states ) , the science and technology facilities council ( united kingdom ) , the national research council ( canada ) , conicyt ( chile ) , the australian research council ( australia ) , ministrio da cincia , tecnologia e inovao ( brazil ) and ministerio de ciencia , tecnologa e innovacin productiva ( argentina ) . facilities : sma , keck , gemini - south . , r. j. , teuben , p. j. , & wright , m. c. h. 1995 , in astronomical society of the pacific conference series , vol . 77 , astronomical data analysis software and systems iv , ed . r. a. shaw , h. e. payne , & j. j. e. hayes , 433+

we present high - spatial resolution imaging obtained with the submillimeter array ( sma ) at 880@xmath0 m and the keck adaptive optics ( ao ) system at @xmath1-band of a gravitationally lensed sub - millimeter galaxy ( smg ) at @xmath2 discovered in the _ herschel _ astrophysical terahertz large area survey . the sma data ( angular resolution @xmath3 ) resolve the dust emission into multiple lensed images , while the keck ao @xmath1-band data ( angular resolution @xmath4 ) resolve the lens into a pair of galaxies separated by @xmath5 . we present an optical spectrum of the foreground lens obtained with the gemini - south telescope that provides a lens redshift of @xmath6 . we develop and apply a new lens modeling technique in the visibility plane that shows that the smg is magnified by a factor of @xmath7 and has an intrinsic infrared ( ir ) luminosity of @xmath8 . we measure a half - light radius of the background source of @xmath9kpc which implies an ir luminosity surface density of @xmath10kpc@xmath11 , a value that is typical of @xmath12 smgs but significantly lower than ir luminous galaxies at @xmath13 . the two lens galaxies are compact ( @xmath14kpc ) early - types with einstein radii of @xmath15 and @xmath16 that imply masses of @xmath17 and @xmath18 . the two lensing galaxies are likely about to undergo a dissipationless merger , and the mass and size of the resultant system should be similar to other early - type galaxies at @xmath19 . this work highlights the importance of high spatial resolution imaging in developing models of strongly lensed galaxies discovered by _

A former cop believed to be Golden State Killer may have been arrested but the Bay Area still has some serial killers on the loose. A 72-year-old former officer, Joseph James DeAngelo, may now face consequences for at least some of the 12 murders and roughly 50 rapes he allegedly committed across California in the late 1970s. But the same can’t be said for of the state’s mystery serial killers. California has many grisly, disturbing and high-profile crimes in its history, but here are a few of the high-profile killers who were never apprehended. The Zodiac Killer The Zodiac Killer did far less damage than the Golden State Killer but is more widely known, to put it mildly. He was believed to have killed five people between 1968 and 1969, mostly in Northern California, all while bragging about his deeds in letters sent to the San Francisco Police Department, the San Francisco Examiner, and other local papers. It’s one mystery that officials don’t seem optimistic about solving as they believe the suspect may have already died. In 2014, a Lousiana man became the latest to claim that he knew who the killer was — his biological father who died in 1984. The man sure gained a lot of attention for the book he wrote about his supposed murderous father, but the claims were not proven. Though the Zodiac Killer’s terror is largely in the past, younger generations can feel an inkling of it by watching David Fincher’s gripping film Zodiac. The Doodler Similar to the Golden State and Zodiac killers, this one also hits close to home — specifically, the Castro. The first known victim of the Doodler — also known as the Black Doodler due to the color of his skin in sketches — was found on Ocean Beach in 1974. For roughly the next year, at least five gay men were stalked and stabbed by the suspect. Though he has been credited with up to 14 murders, the deadly nature of the 1970s for gay men means the Doodler is sadly not the only murderer at the time. Frightened witnesses wouldn’t go on the record for fear of being outed and the only suspect walked. No other suspect was identified but if the killer is still alive, he would be in his early-to-mid 60s. Santa Rosa Hitchhiker Murders As SF Weekly previously reported, the Sonoma County Sheriff in 1975 tried linking the Zodiac Killer to murders in Santa Rosa, which he probably would have gladly taken credit for while trying to up his notoriety. But the true killer of eight young girls, most of whom were raped, was never identified. The victims were found from 1972 to 1979 and ranged from 13 to 20 years old. Zodiac Killer suspect Leigh Allen reportedly lived in Santa Rosa near where the bodies were found, and Ted Bundy was also a suspect in hitchhiker murders before his credit card history cleared him. San Diego homeless killer A more recent unsolved killing spree took the lives of some of our most vulnerable people. The killer attacked dozens of homeless men and an elderly woman in the summer of 2016, leaving four of them dead and setting two of them on fire. That July, Jon David Guerrero — who had a history of criminal charges and mental illness — was detained and later charged. He was found mentally incompetent to stand trial last July and the case has been suspended, according to The San Diego Union-Tribune. That’s plenty to disturb you for now, dear reader. Sweet dreams. ||||| (CNN) A young serial killer stalked San Francisco's gay community in the mid-1970s. He would sketch strangers in bars, strike up conversations, leave with those strangers and then, police say, stab them to death. He became known as "The Doodler." His last known victim died in the summer of 1975: The decomposing body was found near the 16th tee of a picturesque golf course that borders the Pacific Ocean. The victim's pants were unzipped. His face was eaten by maggots. Police released a sketch of a suspect a few months later. They repeatedly questioned one man. But the Doodler was never caught. Now, more than 40 years later, the San Francisco Police Department says it has a suspect. Three men were assaulted but somehow managed to escape the Doodler's clutches, the lead inspector on the case at the time told reporters: a well-known entertainer, a European diplomat, and a third man who left the city and didn't respond to police calls. They gave police descriptions of the Doodler. "We have a suspect in the assault that spawned the sketch," Inspector Dan Cunningham says. Police at the time were convinced that assailant was the Doodler, but Cunningham is now working to confirm the details. "I'm still connecting the dots," he said. "I'm working to see if that assault is actually connected to the murders." And Cunningham is now looking for the diplomat. "I'm waiting to determine if this person is still alive," he says. In the 1970s, detectives said the Doodler might have butchered as many as 14 people. "I'm looking at five murders," says Cunningham, who recently took charge of the department's cold case unit. "But I'd be a fool to say he didn't do more." A police artist has updated the sketch: aging the Doodler, drawing him as he might look now. The updated sketch will be released, says Cunningham, "once I've got all my ducks in a row." If he's still alive, the Doodler will be in his early 60s. Cunningham will also work with the SFPD crime lab, hoping modern forensic technology might manage to extract a usable DNA sample from evidence gathered at two Doodler crime scenes 43 years ago. "We made a lot of effort to collect a lot of blood samples at that time," says Inspector Kenneth Moses, who worked at the lab in the 1970s. "If there's no moisture, there will be no decomposition," says Moses. "And it was standard procedure then to dry samples thoroughly." Cold cases warm up The Doodler is one of a number of cold cases now creeping back into the spotlight after a suspect in the so-called Golden State Killer case was arrested in April thanks to advances in DNA technology. He's accused of a string of robberies, rapes and killings committed across California in the 1970s and 1980s. The suspect, Joseph DeAngelo, was arrested six days after investigators surreptitiously swabbed his car door, collecting a DNA sample that reportedly matched samples gathered at crime scenes decades ago. DeAngelo, now 72 years old, is married with children and was living near the scenes of some of his crimes. At a court appearance in late April he did not enter a plea. JUST WATCHED Tissue led to Golden State Killer case arrest Replay More Videos ... MUST WATCH Tissue led to Golden State Killer case arrest 01:01 Authorities in Vallejo, California, also hope DNA technology might now lead them to the Zodiac Killer, who killed at least five people in the Bay Area in the late-1960s. Detectives have reportedly sent two letters written by the killer to a crime lab for analysis. The Vallejo Police Department and mayor's office did not return repeated calls for comment. Across the bay, Cunningham, who grew up in San Francisco, remembers the Doodler case from his childhood. "Two of the bodies were found near where two of my aunts lived," he says. A series of grisly killings The first of the Doodler's alleged victims to be found was Gerald Cavanagh, a 50-year-old who had worked in a mattress factory. According to the coroner's report, he never married. Cavanagh's body was found early one January morning in 1974, lying at the water's edge on Ocean Beach where Golden Gate Park meets the Pacific. The coroner states that Cavanagh's corpse was, "Lying on the sand, in a supine position. ... There were multiple stab wounds. ... There was an apparent defense wound on the left little finger." Cavanagh had been stabbed 16 times. "I know the case. I remember the case," says Cunningham, who in January began wading through the Doodler case files, cross-referencing details with the scant media coverage from the time. There are four other corpses on Cunningham's list. Joseph Stevens, a 27-year-old drag queen, was the next to die. His body was found by a dog walker in Golden Gate Park early one morning in June 1974. Stevens had been stabbed five times. According to the coroner's report, "Approximately 10 feet west of the deceased's feet was a large disturbed area of brush, with a pool of blood. There were drag marks from this point to where the deceased was found, indicating that an altercation had taken place." Less than two weeks later, another early morning walker found another body on Ocean Beach: Claus Christmann, a 31-year-old German. According to the coroner, "The deceased's pants were unzipped and open." The report details multiple stab wounds on Christmann's neck and shoulders, "In a manner which seemed as though the assailant had attempted to decapitate the deceased." A police bulletin released regarding those first three killings reads, in part: "Victims one and two have homosexual propensities and due to underclothing and makeup in victim number three's pocket he also may have the same propensities." Police said the third victim, Claus Christmann, was wearing "orange bikini shorts" at the time of his death. According to the coroner, he was married. In the summer of 1975 two more bodies were found. Frederick Capin, a registered nurse in his early 30s, was found stabbed to death beside the highway that runs parallel to Ocean Beach. The coroner notes, "There was dried blood smeared on the soles of both shoes, on the hands, about the face and upper torso, anterior, lateral and posterior." Capin was wearing a corduroy jacket and a striped "Picasso" shirt when he died. A month later, the fifth and final corpse was found in bushes near the 16th tee of the Lincoln Park Golf Course, a little to the northeast of Ocean Beach. "Deceased had no underpants and his blue pants were unzipped," wrote the coroner. The dead man was Harald Gullberg, a 67-year-old Swedish sailor. Five men had been found dead within 4 miles of each other, all within 18 months. "There was fear among gay men," says Randy Alfred, news editor at The Sentinel, a gay newspaper. "Particularly among men who were attracted maybe to the young hustler types." The search for the killer A few months after Gullberg's death, the SFPD released the artist's sketch and a description of the suspect. Inspector Rotea Gilford, the lead investigator on the case, told The Sentinel that the suspect "often sits in bars doodling caricatures and cartoons on napkins." Sometimes referred to as the Black Doodler, he was described at the time as African-American, between 19 and 22 years old, slender, a little shy of 6 feet, and frequently wore "a Navy-type watch cap." The Sentinel was one of the few media outlets covering the story at the time. The Zodiac Killer was still big news. And in 1973 and 1974 the so-called Zebra Murders plagued the city: A group of black, Muslim men were killing white victims. Some in the gay community wondered if the police were taking the Doodler killings seriously. "There was a feeling they would have given it a lot more attention if the victims had been white society women from Pacific Heights," says Alfred. "Baloney," says Moses, who worked in the SFPD crime lab. "I wouldn't say any case got less attention, was forgotten about," he said. "That's just not how the system works." In January 1976, the San Francisco Chronicle ran a story about the Doodler and two days later a suspect was arrested. According to The Sentinel, he was detained "outside a Tenderloin bar last Friday night after a bar patron called to report that a man fitting the composite drawing furnished by the SFPD had entered the bar and was offering to draw sketches of patrons." According to the paper, "The man was carrying a butcher knife and a book of sketches when the police nabbed him." Police questioned the man repeatedly, The Sentinel reported at the time. The paper quoted an unnamed police source as saying the suspect had confessed the killings to a psychiatrist. "He's having difficulty with his sexuality," Gilford told The Chronicle at the time. "He's probably ashamed of what he's doing. Homosexuality has never been accepted in the black community. ... The guilt he is experiencing causes him to want to erase the acts he's committed." "That was a very popular meme in police circles at the time," says Alfred. "And it was probably true. In some cases." Police had a strong suspect, and they had three still-living witnesses. But those three men refused to testify. "My feeling is they don't want to be exposed as homosexuals," Gilford told the UPI wire service. An Associated Press headline read: "Murder suspect free because gays silent." Iconic gay rights activist and politician Harvey Milk told the AP, "I can understand their position. I respect the pressure society has put on them." Gay sex was illegal in California until January 1976, and discrimination in jobs and housing was still rife. "There was still a long history of mistrust between gay men and the police force," says Alfred. "I mean, the homicide detective might have been in the vice squad two years ago when he busted you." Many of the officers involved in the Doodler investigation, and many of the witnesses, have died in the 43 years since the Doodler's last suspected hit. Gilford died in 1998. Cunningham is well aware the clock is ticking to solve this case. "The DNA is going to be important," he says. "A lot is going to have to depend on the crime lab."

– The San Francisco Police Department might be close to finally catching the Doodler, a 1970s serial killer more savage than his nickname might suggest. The killer is believed to have killed at least five gay men and possibly up to 14 in 1974 and 1975, SF Weekly reports. Police say the killer would approach men in bars, sketch them, and leave with them. The victims were stabbed multiple times; one was nearly decapitated. The bodies were left in the open in locations including beaches and golf courses. Inspector Dan Cunningham, who recently took charge of San Francisco's cold case unit, tells CNN they have a suspect and are now "connecting the dots." Cunningham says he is trying to track down a European diplomat believed to be one of three people who were assaulted by the Doodler and survived. The victims provided information that helped police create a sketch. But fearing their sexuality would be exposed, they refused to testify when a man matching the suspect's description was arrested outside a bar with a butcher knife and a book of sketches, meaning the man, who is apparently still the main Doodler suspect, was never charged. Cunningham says he plans to work with the crime lab to see if a usable DNA sample can be taken from 43-year-old crime scene evidence. If the suspect is still alive, he would now be in his early 60s. Cunningham says he plans to release an updated sketch of the suspect when he has "all his ducks in a row."

extrahepatic biliary duct duplication , also commonly called duplicated common bile duct ( dcbd ) , is exceptionally rare and mostly turn to be unexpected finding during surgery exposing surgeons to unusual surprises leading to iatrogenic bile duct injuries ( bdi ) . this anomaly has been reported to be associated with multiple disorders including cholelithiasis , choledocholithiasis , choledochal cyst , pancreatobiliary maljunction ( pbm ) and malignancy . recognition of the existence of this anomaly is important to prevent iatrogenic biliary injury and most importantly help in making the right surgical decision . after the first case of dcbd reported by vesalius in 1543 , numerous cases of different variants have been reported in the english literature across the globe [ 25 ] . only seven out of nine variants currently described in the literature can be classified by available classification systems . presented here - in , is a new variant of dcbd discovered after iatrogenic bile duct injury during laparoscopic cholecystectomy . the importance of recognition of its existence to avoidance bdi during surgery coupled with the need for a comprehensive classification system to encompass newly discovered variants are highlighted . a 64-year - old female presented to the surgical emergency unit with a day 's history of right upper quadrant pain . her physical examination revealed right upper quadrant tenderness with no rebound tenderness or muscular guarding . laboratory test showed leukocytosis of 17 10/l and elevated c - reactive protein of 51 mg / l ( 05 ml abdominal ultrasound revealed thickened gallbladder ( gb ) wall ( 4.7 mm ) with a 25 mm gallstone . a diagnosis of acute calculous cholecystitis was made and intravenous fluid and antibiotic treatment were initiated . gb wall was found to be inflamed with omental adhesions . using the critical view of safety approach , after careful dissection of the gb from the liver bed small amount of bile was observed oozing from a spot proximal to the ligated cystic duct stump . irrigation of the spot revealed a small tear at what was thought to be the common hepatic duct . a 5-fr drainage catheter ( 50 cm long , 1.4 mm in diameter ) was placed into the opened duct and exteriorized through the mid - clavicular 5 mm port site for post - operative drainage . a tube cholangiography done on post - operative day 7 showed duplication of the common hepatic duct proximal to the cystic duct stump with the injury occurring on the right - sided duct ( fig . was taken which confirmed the presence of the duplicated common hepatic duct with the cystic duct stump distal to the duplication ( fig . her post - operative course was uneventful with an average biliary drainage output of about 300 ml . drainage tube was clamped on post - operative day 9 and finally removed 4 weeks after surgery . figure 1:cholangiogram showing the double duct originating from the hepatic hilus with injury on the right duct . figure 2:mrcp showing the double common bile duct , cystic duct stump and pancreatic duct . cholangiogram showing the double duct originating from the hepatic hilus with injury on the right duct . the wide variation in morphology of reported cases of dcbd has posed a great challenge in its precise anatomical definition and classification . proposed modified classification system describes five groups , with subtypes , involving seven variants as depicted in fig . 3 . in the case presented here - in , the anomaly was discovered post - operatively by tube cholangiography following iatrogenic bile duct injury during laparoscopic cholecystectomy . the double ducts were noted to originate from the hepatic duct confluence separately and rejoined distally with the cystic duct noted to open into the unified duct ( figs 1 and 2 ) . this variant appears to be different from previously reported type v in which the cystic duct opens into the right duct before joining the left duct . literature review showed similar reported cases of inadvertent bdi associated with dbcd during surgery [ 6 , 7 ] and other configurations that could not be classified with existing classification systems [ 3 , 5 , 8 ] [ fig . 4 ] . these reports reaffirm and underscore the importance of prior knowledge of the existence of this anomaly and careful dissection within the hepato - gastroduodenal ligament to avoid bdi , particularly during laparoscopic cholecystectomy . the clinical importance of this anomaly lies with its association with conditions such as cholecysto - choledocholithiasis and choledochal cyst , the risk of malignant transformation and the risk of exposing patients to biliary injury during surgery , if not detected pre - operatively . the type of malignant transformation seems to be directly related to the drainage site of the ducts ( gastric , duodenal or pancreatic ) and the presence of pbm . in a review of 47 cases in the japanese literature , yamashita et al . reported an incidence of cholelithiasis in 28% , choledochal cyst in 11% , pbm in 30% and malignancy in 26% of the cases . review of 24 cases in the chinese literature also revealed cholelithiasis in 37% , choledocholithiasis in 79% , choledochal cyst in 33% and pbm in 8% of the reported cases . the high incidence of gallstone formation associated with this anomaly is thought be due to bile stasis and repetitive cholangitis resulting from reflux of gastrointestinal content into the anomalous duct . figure 3:modified double common bile duct classification proposed by choi et al . type i : cbd separated by septum ; type ii : cbd that bifurcates to drain separately ; type iii : double biliary drainage without extrahepatic communication channels ( without [ iiia ] or with [ iiib ] intrahepatic connecting channels ) ; type iv : double biliary drainage with one or more extrahepatic communication channels ; type v : single biliary drainage of double extrahepatic bile ducts without ( va ) or with ( vb ) communication channels . sahu et al.(b ) variant described by kosar et al.(c ) variant described in current report . type i : cbd separated by septum ; type ii : cbd that bifurcates to drain separately ; type iii : double biliary drainage without extrahepatic communication channels ( without [ iiia ] or with [ iiib ] intrahepatic connecting channels ) ; type iv : double biliary drainage with one or more extrahepatic communication channels ; type v : single biliary drainage of double extrahepatic bile ducts without ( va ) or with ( vb ) communication channels . sahu et al.(b ) variant described by kosar et al.(c ) variant described in current report . extrahepatic bile duct duplication could be a recipe for disaster during surgery and a prior knowledge of its existence is important to avoid inadvertent bdi . a thorough review of all reported variants is needed for a comprehensive classification system of clinical significance .

abstractduplicated common bile duct , often associated with conditions like lithiasis , biliary cysts and pancreatobiliary maljunction , could result in highly morbid and potentially fatal biliary injuries . precise preoperative diagnosis and classification still remain a challenge . a female patient undergoing emergency laparoscopic cholecystectomy for acute calculous cholecystitis sustained iatrogenic bile duct injury . a drainage tube was placed into the injured duct for post - operative conservative management . post - operative tube cholangiogram revealed a double common bile duct with cystic duct opening distally . this was identified as a new variant not previously reported or classified . however rare , duplicated common bile duct could result in serious iatrogenic bile duct injury if unidentified during surgery . knowledge of its existence is essential to avoid such injuries as preoperative diagnosis still remains a challenge . a thorough clinical and morphological study of previously reported variants is needed for a comprehensive classification to encompass newly discovered variants .

lipids play key roles in many biological processes ; ranging from a structural role in membranes to signaling , in addition to being sources of metabolic energy ( bohdanowicz and grinstein 2013 ; van meer and sprong 2004 ; van meer et al . , 2008 ) . malaria infection is initiated when plasmodium sporozoites enter the mammalian host through the bite of an infected female anopheles mosquito . during a blood meal , 10100 sporozoites are deposited under the skin of the host and travel to the liver , where they infect hepatocytes . each sporozoite resides in a hepatocyte for 214 days ( 2 days for p. berghei and 7 days for p. falciparum ) , multiplying into > 10,000 merozoites , which are then released in the bloodstream to infect red blood cells , initiating the symptoms of malaria ( prudncio et al . , the rapid replication of plasmodium parasites in hepatocytes requires important lipid resources to support organelle and membrane neogenesis , the growth of the parasitophorous vacuole membrane ( pvm ) , and possibly the maintenance of host cell and parasite homeostasis and survival ( prudncio et al . , 2006 ) . such demand is likely to be satisfied by import of hepatocyte lipids , as well as by de novo synthesis by the apicoplast fatty acid synthesis ii ( fas ii ) system ( ralph et al . , 2004 ) and the plethora of parasite - encoded phospholipid biosynthetic enzymes ( dchamps et al . , 2010 ) . transcriptomic studies revealed that the apicoplast - resident enzymes involved in the fas ii system are upregulated throughout liver stage infection ( tarun et al . , 2008 ) . while these and other enzymes of the pyruvate dehydrogenase complex are critical for the formation of infective merozoites , parasites lacking these enzymes initiate replication in the liver normally ( pei et al . , 2010 ; vaughan et al . , 2009 ; yu et al . , 2008 ) . likewise , parasites deficient in octanoyl - acp transferase or lipoic acid protein ligase ( lipb ) , a limiting enzyme in the derivation of lipoic acid from a major fas ii product , octanoyl - acp , show a similar phenotype . in addition , p. yoelii parasites deficient in glycerol-3-phosphate dehydrogenase and glycerol-3-phosphate acyltransferase , key enzymes in the synthesis of the phospholipid precursor phosphatidic acid , develop normally , but again do not form merozoites ( lindner et al . , 2014 ) . these data imply that , despite the ability to synthesize fatty acids de novo , plasmodium depends on host lipids during part or the entire pre - erythrocytic cycle . our previous work revealed that host genes involved in lipid metabolism are transcriptionally modulated during plasmodium intrahepatic development ( albuquerque et al . , 2009 ) . also , scavenger receptor binding protein 1 , a membrane protein important for cellular cholesterol homeostasis , is key for in vitro infection ( rodrigues et al . , 2008 ; plasmodium parasites scavenge cholesterol from the host irrespective of whether it has been internalized via the ldl receptor or synthesized de novo . inhibition of either source of host cholesterol decreased the cholesterol content in merozoites but did not have any effect on liver stage development . on the other hand , scavenging of lipoic acid from the host cell into parasite mitochondria was shown to be critical for p. berghei survival in hepatocytes ( allary et al . the contribution of host cell lipid metabolic pathway(s ) to the establishment of a successful infection in hepatocytes is largely unexplored . aiming at understanding the dynamics of lipids during plasmodium liver stage infection , we performed shotgun mass spectrometry analysis of the total cellular lipidome in p. berghei - infected versus noninfected cells at different points throughout infection . these analyses revealed major alterations in lipids involved in storage and membrane biogenesis , including phosphatidylcholine ( pc ) , one of the major membrane phospholipids . combining targeted silencing of host genes involved in de novo pc synthesis with visualization of host pc , we show that plasmodium uptakes host - derived pc and that the activity of the two host de novo pc synthesis pathways is critical for the establishment of plasmodium in the mammalian liver . to assess whether changes in gene expression of major lipid biosynthetic pathways in the host and the parasite transcriptomes ( albuquerque et al . , 2009 ; tarun et al . , 2008 ) correlated with changes in the total lipidome of hepatocytes upon infection with plasmodium sporozoites , we performed quantitative shotgun lipidomics experiments on p. berghei - infected and noninfected huh7 hepatoma cells ( figure 1a ) . initial mass spectrometry analysis of noninfected huh7 cells showed that the amount of lipids extracted was proportional to the number of cells used and that the minimal number of cells necessary to detect major lipid classes was 10 cells ( figure s1 available online ) . due to the low infectivity of plasmodium sporozoites , we isolated gfp - expressing p. berghei - infected and noninfected cells by fluorescence - activated cell sorting ( facs ) ( prudncio et al . , 2008 ) at 25 , 35 , and 45 hr ( h ) after infection , which are representative time points of early parasite replication , liver schizogony , and the early cellularization process leading to the formation of individual merozoites . the number of cells used in this study ranged from 4.5 to 30 10 per sample . the relative abundance or total abundance of each lipid class was expressed as molar percentage of total lipidome or normalized as the total lipid per number of cells at any given time , respectively ( figure s1 ) . major and significant alterations in the lipidome of p. berghei - infected cells were observed ( see table s1 for entire raw data ) . the neutral lipids triacylglycerol ( tag ) , diacylglycerol ( dag ) , and cholesterol esters ( ces ) were increased at 25 hr after infection ; however , at later time points their levels had subsided to those of control cells ( figures 1b and s1 ) . additionally , an enrichment of pc , the main structural membrane phospholipid , was observed in infected cells throughout infection , concomitant with a persistent and significant decrease in the levels of all anionic phospholipids : phosphatidylethanolamine ( pe ) , phosphatidylserine ( ps ) , phosphatidic acid ( pa ) , and phosphatidylinositol ( pi ) ( figure 1b ) . altogether , the lipidomic data suggest that key aspects of hepatic lipid metabolism such as lipogenesis / lipolysis , in addition to phospholipid headgroup remodeling pathways , are actively engaged during plasmodium infection of hepatocytes . our lipidomic analyses revealed a significant enrichment in the neutral lipids tag , ce , and dag in p. berghei - infected cells at 25 hr after infection , although this was no longer the case at later time points ( figure 1b ) . both tag and ce are stored in organelles called lipid droplets ( lds ) ( listenberger et al . during periods of increased lipogenesis , de - novo - synthesized or medium - derived fatty acids are channeled either into the glycerol-3-phosphate pathway to form dag , which are then converted to tag by dgat1 or dgat2 ( shi and cheng 2009 ) , or conjugated to free cholesterol by acyl - coa : cholesterol acyltransferase ( acat1/2 ) to form ce ( chang et al . , 2001 ) fat stored in lds is catabolized by neutral lipases to liberate free fatty acids ( figure s2 ) . to assess the functional relevance of the observed changes , we first examined p. berghei infection in mice deficient in enzymes involved in ce and tag synthesis . p. berghei load was similar in the livers of acat1 and acat2 , when compared to littermate wild - type ( wt ) controls ( figure s2 ) . additionally , knockdown of dgat1 and dgat2 using sirna in huh7 cells did not influence the level of infection ( figure s2 ) , in spite of a strong reduction in both tag and ce in cells with reduced expression of dgat2 ( figure s2 ) . finally , due to the decline in tags at 35 hr and 45 hr after infection , we also determined whether hydrolysis of tags in p. berghei - infected cells could provide building blocks for pathways active at later stages of liver stage infection . however , p. berghei liver infection was not affected in mice deficient in atgl ( zimmermann et al . , 2004 ) when compared to wt controls , in spite of the visible increase in ld size and a significant accumulation of tag , as shown by oil red o staining and ms analysis , respectively ( figure s2 ) . taken together , these data suggest that plasmodium liver stage infection is independent of host ce biosynthesis and tag biosynthetic and lipolytic pathways . since pc was highly enriched in infected cells ( figures 1b and s1 ) , we next investigated whether this phospholipid could play a role during plasmodium intrahepatic parasitism . the bulk of pc ( as well as pe ) is synthesized by the kennedy pathway for which choline phosphate cytidyltransferase ( pcyt or ct ) is the rate - limiting enzyme ( kennedy and weiss 1956 ) ( figure 2a ) . strikingly , downregulation of host cell ct using sirna in huh7 cells ( figure s3 ) greatly reduced p. berghei infection ( figure 2a ) . the parasite liver load 48 hr after intraveneous injection of p. berghei sporozoites was also significantly lower in ct liver - specific deficient mice ( ct-lko ) ( jacobs et al . , 2004 ) , as compared to that of ct-flox littermate mice ( figure 2b ) . we further characterized the effect of ct depletion on infection by immunofluorescence microscopy analysis of thick liver sections . the number of p. berghei exo - erythrocytic forms ( eefs ) was significantly reduced in ct-lko liver sections compared to ct-flox controls ( figure 2c ) , with no differences in eef size ( figures 2d and 2e ) . importantly , this effect on parasite numbers could not be ascribed to a defect in initial invasion of hepatocytes , as there was no difference in liver infection at 6 hpi between ct-lko and ct-flox littermate mice ( figure 2f ) . the decrease in infection in ct-lko mice only became apparent at 24 hpi ( figure 2f ) . in addition to the kennedy pathway , the sequential trimethylation of pe by phosphatidylethanolamine n - methyltransferase ( pemt ) , which is predominantly expressed in the liver , contributes about 20% of de novo pc synthesis ( ridgway and vance 1987 ) . downmodulation of pemt using sirna in huh7 cells ( figure s3 ) led to a decrease in p. berghei infection ( figure 2a ) . similarly , the livers of mice deficient in pemt ( pemt ) showed a decreased parasite load compared to wt littermates , as measured by qrt - pcr of p. berghei 18s rrna ( figure 2 g ) . as before , this reduction in parasite load correlated with a significant decrease in p. berghei numbers in the livers of pemt mice ( figure 2h ) , without any effect on eef size ( figure 2i ) . in an attempt to disrupt both routes of pc biosynthesis , we used pemt mice fed on a choline - deficient diet . while a choline - deficient diet alone ( administered to pemt mice ) did not affect infection , it had a significant impact on parasite liver load in pemt mice ( figure 2 g ) . on the other hand , exogenous administration of cdp - choline to ct-lko mice ( niebergall et al . , 2011 ) was sufficient to revert the impairment of p. berghei liver infection caused by depletion of ct ( figure 2b ) . altogether , and despite the ability of plasmodium to synthesize pc from choline scavenged from the host cell ( dchamps et al . , 2010 ) , our data clearly show that de novo pc synthesis by the host cell is essential for plasmodium hepatocyte infection . we next employed click chemistry detection to assess usage and distribution of pc in plasmodium eefs at different time points after infection ( see experimental procedures ; figure s4 ) . prelabeled huh7 cells ( with propargylcholine , alkyne - tagged choline ) infected with p. berghei sporozoites were analyzed by confocal microscopy . choline - containing products were seen not only within the eef ( figure s4 ) but also in the parasite plasma membrane ( ppm ) and pvm , as confirmed by colocalization with circumsporozoite ( cs ) ( figure s4 ) and uis4 ( upregulated in sporozoites ) , ppm , and pvm proteins , respectively . intense staining of lipid - rich regions was observed at later time points ( 4048 hr ) after infection , and as the parasite underwent schizogony , each daughter nucleus was surrounded by choline - stained membranes ( figure s4 ) . while these observations show that the parasite uses choline or choline - containing products from the host cell , it is possible that the parasite might take up free choline ( and not pc ) previously hydrolyzed from choline - containing molecules . indeed , propargylcholine is metabolized to pc , ether - lysophosphatidylcholine and lyso - phosphatidylcholine ( lyso - pc ) ( jao et al . , 2009 ) . thus , we next used a nonhydrolyzable ether - lyso - pc to determine whether plasmodium is capable of using host pc directly . the pattern of ether - lyso - pc distribution was similar to that of propargylcholine described above ( figure 3a ) . these results establish that the parasite takes up pc from the host cell throughout infection and without prior hydrolysis . subcellular characterization of the lipid - rich domains within eefs revealed that these structures likely correspond to parasite endoplasmic reticulum ( er ) and not the apicoplast , as evidenced by the colocalization of ether - lyso - pc with the p. berghei er - resident protein bip ( figure 3b ) but not with the apicoplast - resident protein atg8 ( figure 3c ) . additionally , ether - lyso - pc prelabeling of hepg2 cells , which support efficient merosome release upon pvm breakdown as it occurs in malaria infections in vivo , shows that host pc associates with ppm / pvm , intravacuolar membranous structures , and individual merozoites visualized by immune staining with anti - msp1 antibodies ( figure s4 ) . click labeling on live detached merosomes also showed distinct propargylcholine staining of individual merozoites ( figure s4 ) . uptake of pc from the host cell into p. berghei eefs was also observed in mouse primary hepatocytes ( figure s4 ) . similar results were obtained when an azido - tetramethylrhodamine was used in the click cyclo - addition reaction instead of azido - sulfo - bodipy , showing that the reporter fluorophore does not affect the pattern of pc distribution ( figure s4 ) . next , we assessed whether the use of pc from host cell also occurs during pre - erythrocytic development of the human pathogen p. falciparum in micropatterned human primary hepatocytes ( march et al . , host - derived pc associated with p. falciparum eefs as early as 1.5 days after infection , with a distinct perinuclear staining in all eefs examined ( figure 3d ) . we next sought to determine the mechanism by which host pc contributes to the establishment of parasite infection in hepatocytes . several studies using distinct knockout parasites lines that exhibit defects in pvm formation and remodeling show a decrease in the number of parasites able to complete liver stage development ( aly et al . , 2008 ; ishino et al . , 2005 ; labaied et al . , 2007 ; mueller et al . , 2005a , 2005b , silvie et al . , 2008 ; van dijk et al . , 2005 ; van schaijk et al . , additionally , we have recently shown that treatment of liver stage parasites with a class of drugs called torins impairs trafficking of plasmodium pvm - resident proteins resulting in elimination of those parasites ( hanson et al . , 2013 ) . given our observations that host pc localizes to the pvm throughout infection and that parasite numbers decrease sharply when the pc - biosynthetic activity of the host cell is compromised , we hypothesized that reduction of pc at the pvm might impair the insertion and/or maintenance of plasmodium pvm - resident proteins , leading to parasite elimination . indeed , it is well established that the pc / pe ratio in membranes affects the membrane protein content ( li et al . , 2006 ) . thus , we next analyzed the expression of uis4 , a plasmodium protein known to localize to the pvm and to be essential during liver stage ( mueller et al . , 2005b ) , in primary hepatocytes deficient for ct. the amount of uis4 was significantly reduced in the pvm of ct-deficient hepatocytes , when compared to wt hepatocytes ( figures 4a and 4b ) , in spite of similar transcriptional expression of the uis4 gene ( figure 4c ) . thus , our data suggest that the insertion of host pc into the pvm is critical for the parasite to maintain the protein composition of this essential membrane and avoid host cell intrinsic elimination mechanisms . how plasmodium parasites modulate the host cell environment during the liver stage , in order to survive long enough to generate the large numbers of merozoites that are released into the blood , is still poorly understood . inside each this rapid proliferation rate implies that sufficient lipids are available to support both the enlargement of the pvm and membrane neogenesis for newly formed merozoites . we hypothesized that the inherent ability of hepatocytes to mobilize lipids may be critical during plasmodium infection of the liver . our quantitative determination of the lipid composition of p. berghei - infected hepatocytes at different time points after initial infection revealed that pc is the only phospholipid enriched in relative abundance in infected cells with a concomitant decline in the relative abundance of pe , ps , pa , and pi . in addition , confocal microscopy showed that plasmodium parasites continuously accumulate host pc . using target - specific sirnas , in addition to ct- and pemt - deficient mice , we showed that the host de novo pc biosynthetic machinery is indispensable for plasmodium intrahepatic infection , despite its ability to synthesize pc de novo ( dchamps et al . , 2010 ) . our data show that intracellular development of the parasite correlates with increased synthesis of the major structural phospholipid , pc , both through the kennedy and the pemt pathways , but ps decarboxylase activity does not seem to be required , as pe and ps levels declined at all time points examined . considering that pc is the major structural phospholipid of eukaryotic membranes and that host pc is used by the parasite throughout infection , it was surprising that , despite a profound impairment in parasite survival , knockout of ct did not affect parasite growth or merozoite formation . these observations suggest that compensatory pc biosynthetic pathways , such as the pemt and lands cycle ( lands 1958 ; ridgway and vance 1987 ) , or other proteins either from the host or parasite side might be engaged during this process . also surprising is the fact that while the lipidomics data show a significant increase in lipids typically associated with lds ( namely tag and ce ) , an organelle used by many pathogens as a source of structural lipids and energy ( chandak et al . , 2010 ; cocchiaro et al . , 2008 ; kumar et al . , 2006 ; miyanari et al . , 2007 ) , ablation of key enzymes involved in ce and tag synthesis or lipolysis does not disturb any aspect of the infection . ld biogenesis represents a conserved cellular response to infection ( melo and dvorak 2012 ) in macrophages but does not seem to play a direct role in plasmodium infection of hepatocytes . the exo - erythrocytic stage of plasmodium infection occurs within host hepatocytes , a cell type with a phenomenal capacity to support lipid metabolism . notably , lack of de novo synthesis of a single phospholipid , pc , in the host cell strongly affects parasite survival inside hepatocytes . we show that reduction of pc availability directly reflects on the protein composition of the pvm , as noted by a significant decrease on the levels of the pvm - resident protein uis4 , which implicates pc in pvm remodeling . given that host pc was found to colocalize with the parasite er , another plausible scenario is that pc depletion affects the trafficking of proteins to the parasite surface . we can not exclude that other mechanisms might be in place to explain why host pc is so important for infection . still , the pvm constitutes the critical interface between the parasite and a potentially hostile host cell environment , and the presence of plasmodium proteins on the pvm was shown to be indispensable for the parasite to avoid elimination by the host cell ( hanson et al . , 2013 ) , providing a likely explanation as to why host pc plays such a critical role in parasite survival . c57bl6 mice were purchased from jackson laboratory , and all experiments were performed in strict compliance to the guidelines of our institution 's animal ethics committee and the federation of european laboratory animal science associations ( felasa ) . hepg2 , huh7 cells , and primary hepatocytes were cultured in supplemented dulbecco s modified eagle s medium ( dmem ) , rpmi 1640 , and william 's medium , respectively , as described in liehl et al . gfp- , rfp- , or luciferase - expressing p. berghei sporozoites were dissected from salivary glands of infected female anopheles stephensi mosquitoes into dmem medium prior to be added to cells or injected into mice for in vitro and in vivo infections . infection in vitro was assessed as previously described using a multiplate reader ( infinite m200 from tecan , switzerland ) or a bd lsr fortessa cytometer ( franke - fayard et al . , 2004 ; noninfected and gfp - expressing p. berghei - infected cells were gated on the basis of their different fluorescence intensity as previously established ( albuquerque et al . , 2009 ; prudncio et al . , 2008 ) . cells were collected by facs sorting , and total cellular lipid was extracted from sorted cells as previously described ( sampaio et al . , 2011 ) . human huh7 hepatoma cells were reverse transfected with 30 nm of target - specific or control sirna sequences ( table s2 ) according to the manufacturer 's instructions ( ambion , life technologies ) . the efficiency of knockdown was assessed by quantitative rt - pcr ( table s3 ) . host cells seeded on glass coverslips were metabolically prelabeled with 500 propargylcholine or 20 m of a nonhydrolyzable pc , ether - lyso - pc ( kuerschner et al . , 2012 ) , for 812 hr . cells were then infected with rfp - expressing p. berghei anka sporozoites , as previously described . after fixation , click cyclo - addition reaction with sulfo - azido - bodipy was carried out as described elsewhere ( gaebler et al . , 2013 ; p < 0.05 , p < 0.01 , and p < 0.0001 .

summaryduring invasion , plasmodium , the causative agent of malaria , wraps itself in a parasitophorous vacuole membrane ( pvm ) , which constitutes a critical interface between the parasite and its host cell . within hepatocytes , each plasmodium sporozoite generates thousands of new parasites , creating high demand for lipids to support this replication and enlarge the pvm . here , a global analysis of the total lipid repertoire of plasmodium - infected hepatocytes reveals an enrichment of neutral lipids and the major membrane phospholipid , phosphatidylcholine ( pc ) . while infection is unaffected in mice deficient in key enzymes involved in neutral lipid synthesis and lipolysis , ablation of rate - limiting enzymes in hepatic pc biosynthetic pathways significantly decreases parasite numbers . host pc is taken up by both p. berghei and p. falciparum and is necessary for correct localization of parasite proteins to the pvm , which is essential for parasite survival . thus , plasmodium relies on the abundance of these lipids within hepatocytes to support infection .

anxiety disorders ( ads ) are the most common type of psychiatric disorders , with a mean incidence of 18.1% and a lifetime prevalence of 28.8% ( kessler et al 2005 ) . ads results in a great economic burden as it was estimated that they account for a $ 42.3 billion annual cost in the united states , with over 50% of the total sum directed towards nonpsychiatric medical treatment costs ( greenberg et al 1999 ) . moreover , wang and colleagues ( 2005 ) , in the national comorbidity survey replication , pointed out that only about 37% of patients with ads utilize any form of health services , including psychiatric consultation ( 13% ) , other mental health practitioners ( 16% ) , or primary care physicians ( 24.3% ) . to date , it is well established that patients suffering of ad may also have a high comorbidity with mood disorders , with up to 90% of patients experiencing some kind of depressive disorder in their lifetime with these two disorders sharing some neurobiological mechanisms such as abnormalities in the 5ht1a receptor function ( nutt and stein 2006 ) . due the involvement of multiple neurobiological systems , several classes of medications the main classes include benzodiazepines , tricyclic antidepressants ( tca ) , buspiron hydrochloride , selective serotonin reuptake inhibitors ( ssris ) , noradrenergic and specific serotonergic drug ( nassa ) , and dual - reuptake inhibitors of serotonin and noradrenaline ( snris ) ( goodman 2004 ; gambi et al 2005 ; shearer 2007 ; sheehan and sheehan 2007 ) . it has been demonstrated that a novel agent acting on gaba neurotransmission , pregabalin , was effective in the treatment of generalized anxiety disorder ( gad ) ( rickels et al 2005 ) and , in 2006 , it was officially approved in european union for the treatment of gad . however , some of these drugs do not have a favorable profile in the long - term treatment of ad . in fact , even if benzodiazepines can be useful for the immediate alleviation of anxiety , their effectiveness for long - term management has been questioned because of concerns about tolerance , dependency , and remission rates ( pollack 2001 ) . the ssris are preferred in the treatment of ad because of greater safety and tolerability an to date are licensed for the treatment of several ad including panic disorder ( pd ) , gad , obsessive - compulsive disorder ( ocd ) , and social anxiety disorder ( sad ) ( vaswani et al 2003 ) . however , despite their favorable profile of side effects , these drugs may cause some adverse effects that may be problematic for some patients such as sexual dysfunction , risk of bleeding , hyponatremia , discontinuation symptoms , and increased bodyweight ( westenberg and sandner , 2006 ; williams et al 2006 ) . in fact , it has been reported that patients with ad are more sensible to side effects of psychopharmacological treatment ( bandelow et al 2006 ) . furthermore , although patients with gad respond to ssris , the minority of patients actually achieve remission with these treatments ( pollack 2001 ) . in this context , the development of snris ( venlafaxine and duloxetine ) has been particularly useful . as a dual - acting intervention that targets two neurotransmitter systems the purpose of this review was to elucidate current facts and views about the role of the novel snri duloxetine in the treatment of ad . searches of the medline database from 1988 through january 2008 and the psycinfo / embase database from 1988 through january 2008 were conducted , restricted to the english language . the search term duloxetine was combined with anxiety , generalized anxiety disorder , obsessive - compulsive disorder , panic disorder , phobia , social anxiety disorder , and post - traumatic stress disorder to identify relevant original research and review articles . all citations were screened , and the full texts of peer - reviewed journal articles considered relevant to the purposes of the review were obtained . duloxetine [ ly248686 , ( + ) -n - methyl-3-(1-naphthalenyloxy)-2-thiophenepropanamine ] , a relatively new antidepressant drug , was discovered in 1988 by wong and colleagues and released in august 2004 . duloxetine is an inhibitor of the reuptake of serotonin ( 5-hyroxytryptamine ; 5ht ) and noradrenaline ( na ) , both in vitro and in vivo ( wong et al 1993 ) . duloxetine has demonstrated a relatively evenly balanced and potent inhibition of both the 5ht and ne reuptake at the transport sites and a weak effect on dopamine reuptake in both in vitro and in vivo studies ( pitsikas 2000 ; wong 1998 ; wong and bymaster 2002 ) . duloxetine lacks significant affinity for muscarinic , histamine h1 , alpha-1-adrenergic , dopamine d2 , 5ht1a , 5ht1b , 5ht1d , 5ht2a , 5ht2c , gaba , glutamate and opioid receptors ( wong et al 1993 ; bymaster et al 2001 ) . moreover , duloxetine does not exert its action through the inhibition of monoamine oxidase ( mao ) . absorption of duloxetine begins two hours after oral administration , and the maximum concentration in plasma ( c - max ) is achieved in approximately six hours ( bymaster et al 2003 ) . the estimated volume of distribution is 1640 l , although there was large variability among subjects ( sharma et al 2000 ) . duloxetine is highly protein bound ( 96% ) , primarily to albumin or 1-acidglycoprotein ( bymaster et al 2003 ) . duloxetine undergoes extensive metabolism , but the major circulating metabolites have not been shown to contribute significantly to the pharmacologic activity of duloxetine itself ( westanmo et al 2005 ) . it is metabolized primarily by cytochrome p-450 ( cyp ) isoenzymes 2d6 and 1a2 ( bymaster et al 2003 ) . duloxetine has a mean plasma half - life of 12 hours ( sharma et al 2000 ) . duloxetine was approved by the us food and drug administration ( fda ) in august 2004 for the treatment of major depressive disorder ( mdd ) . it has been suggested that , due to a more balanced inhibition of 5-ht and ne reuptake , duloxetine can provide enhanced benefits in relieving depression . it has also been hypothesized that duloxetine has less affinity for other receptors ( eg , muscarinic ) that are held responsible for the numerous adverse events of other antidepressants . several studies have established the safety and efficacy of duloxetine in the treatment of mdd ( detke et al 2002 ; nemeroff et al 2002 ; lewis - fernandez et al 2006 ; shelton et al 2007 ) . for an exhaustive review of efficacy and tolerability of duloxetine in mdd see frampton and plosker ( 2007 ) . moreover , as duloxetine enhances urethral striated sphincter activity and increases bladder capacity in an in vivo cat bladder irritation model , this snri seems to be efficacious in the treatment of stress urinary incontinence ( moore 2004 ) . duloxetine has not been approved for stress urinary incontinence in the usa , but has been approved for stress urinary incontinence in the european union since august 2004 . in september even if the exact mechanism of central pain inhibition of duloxetine is , to date , not well known , it is thought to be related to potentiation of adrenergic and serotoninergic activity in the central nervous system ( wernicke et al 2006 ) . it has been widely demonstrated that mdd is associated with altered regulation of both 5-ht and na neurotransmission and that acting on these two systems both separately or simultaneously may lead to therapeutic effects . moreover , it is also well known that clinical observations demonstrate a significant degree of overlap in symptoms associated with mdd and ads ( baldwin et al 2002 ) . although the precise mechanisms underlying the pathogenesis of anxiety remain unclear , a lot of evidences support decreased serotonergic function in both depression and anxiety . studies conducted on patients suffering of ads have pointed out that a dysregulation of 5-ht neurotransmission such as low 5-ht turnover rate , is believed to play a role in the manifestation of symptoms of anxiety ( graeff et al 1997 ; wrase et al 2006 ) . additionally , there have been reports of reduced serotonin transporter ( sert ) binding in patients with gad ( iny et al 1994 ) . consistent with these notions , antidepressants that enhance serotonergic neurotransmission , such as the ssris , have been found to be effective in treating some ads , as above specified . moreover , several genetic studies have demonstrated associations between certain polymorphisms in the 5-ht gene and anxiety traits as well as gad ( lesch et al 1996 ; ohara et al 1999 ) . in addition , the short allele of the 5-ht gene linked polymorphic region has been associated with a greater activation of the amygdala in response to fearful face stimuli in healthy subjects ( hariri et al 2002 ) . the role of na in anxiety is less clear , but many lines of evidence support the hypothesis that na neurotransmission is involved in anxiety ( morilak et al 2005 ) . na has been shown to modulate activity in regions of the brain that are involved in anxiety , such as the amygdala and the locus coeruleus ( van bockstaele 2000 ) . in addition , increases in 3-methoxy-4-hydrophenylglycol ( mhpg ; a metabolite of na ) and hypersecretion of na in plasma and cerebrospinal fluid have been associated with anxiety states ( bremner et al 1996 ) . clinical evidences , including results from studies that have evaluated the anxiolytic efficacy of agents that modulate noradrenergic neurotransmission , are consistent with the involvement of na in ads ( stahl et al 2005 ) . also preclinical studies have suggested anxiolytic effects for duloxetine . using the mouse zero maze anxiety model , troelsen and colleagues ( 2005 ) compared the effects of chronic administration of several antidepressants , including tricyclics , ssris , and snris . duloxetine demonstrated a significant anxiolytic effect via reduction in all of the animal behaviors associated with anxiety . the chronic duloxetine treatment regimen also resulted in a considerable reduction in serotonin transporters ( sert ) density in the cortex after duloxetine whereas citalopram , amitriptyline and reboxetine were not anxiolytic after chronic treatment and induced a small or no reduction in sert density . these findings were also confirmed by mirza and colleagues ( 2007 ) who showed that duloxetine and fluoxetine both reduced sert density in mice cortex and induced anxiolytic - like effects . moreover , duloxetine also reduced noradrenaline transporter ( net ) density in mice cortex , with increased anxiolytic - like effects . moreover , as it has been demonstrated that duloxetine may antagonize the p - chloroamphetamine - induced depletion of 5-ht in the rat brain ( wong et al 1993 ) , preventing also the depletion of ne induced by 6-hydroxydopamine in mice hearts and in the hypothalamus of rats ( fuller et al 1994 ) , this may account for its action on anxiety symptoms : in addition , using microdialysis , it has been shown that acute systemic duloxetine administration may cause a large increase in extracellular levels of 5-ht and ne especially in the hypothalamus and cortex ( engleman et al 1995 ; kihara and ikeda 1995 ) . kasamo and colleagues ( 1996 ) found that duloxetine inhibits the spontaneous firing of both the dorsal raphe 5-ht and the locus coeruleus ne neurons , indicating an increased availability of these neurotransmitters in the immediate vicinity of their somatodendritic receptors regulating their firing activity . the course of gad appears , for its own nature , to require long - term treatment ( rynn and brawman - mintzer 2004 ) . with this consideration , ssris and selective serotonin and noradrenaline reuptake inhibitors ( snris ) the snri venlafaxine has been approved for gad by the fda as was shown to be effective in double - blind clinical trials ( rickels et al 2000 ) . efficacy of duloxetine on anxiety symptoms , especially in the treatment of gad , has become object of investigation starting from the observation that duloxetine was effective in reducing anxiety symptoms associated with mdd . dunner and colleagues ( 2003 ) analyzed all the placebo - controlled studies of duloxetine in mdd but focused on four trials in which duloxetine was superior to placebo on the primary outcome measure of the hamilton depression rating scale ( ham - d ) total score , with anxiety symptoms assessed using the ham - d anxiety / somatization subfactor and the anxiety - psychic item ( ham - d item 10 ) . they concluded that duloxetine was effective in treating a broad spectrum of symptoms associated with depression , including mood , anxiety , and painful physical symptoms . in particular , they pointed out that duloxetine caused a rapid relief of anxiety symptoms associated with depression . more recently , fava and colleagues ( 2007 ) investigated the efficacy and tolerability of duloxetine in the treatment of anxious versus nonanxious depression with anxious depression defined by a ham - d anxiety / somatization factor score 7 . they observed that duloxetine treatment was associated with a significantly greater reduction in total ham - d scores and ham - d anxiety / somatization factor scores among patients with anxious depression with the latter showing a significantly shorter median time to response than patients with nonanxious depression . , also duloxetine has been approved by fda for the treatment of gad and the double - blind , placebo - controlled , large sample ( > 100 patients ) studies of duloxetine in the treatment of gad are summarized in table 1 . overall , all these studies demonstrated that duloxetine was more effective than placebo and , at least , equal effective than venlafaxine xr in the treatment of gad . moreover , russell and colleagues ( 2007 ) reported the effectiveness of duloxetine in improving not only anxiety symptoms , but also pain severity and patient functioning in adults with gad , who presented with clinically significant pain symptoms . interestingly , the data of the study of hartford and colleagues ( 2007 ) , koponen and colleagues ( 2007 ) and rynn and colleagues ( 2008 ) were also analyzed globally in two studies . in the first , endicott and colleagues ( 2007 ) pooled data of these three clinical studies to report the efficacy of duloxetine in reducing role impairments and in enhancing wellbeing in patients with gad and found that duloxetine consistently reduced role functioning disabilities associated with gad and enhanced patients quality of life and well - being . in addition , summarizing efficacy of the same three clinical studies , allgulander and colleagues ( 2007 ) concluded that , considering a sample of more than 1100 patients , duloxetine was efficacious for reducing anxiety severity and for increasing patients overall role functioning in gad . moreover , pollack and colleagues ( 2008 ) , pooling data from three double - blind , placebo - controlled clinical trials that examined the efficacy of duloxetine in gad ( hartford et al 2007 ; koponen et al 2007 ; rynn et al 2008 ) , found that patients with gad experience significant and substantial impairment in three domains of quality of life : global role functioning , subjective well - being , and perceived health . using the criterion of improvement to community values , patients treated with duloxetine were more likely to achieve this outcome on each quality of life measure . however , it should be considered that all of the clinical trials were for short - term ( 910 weeks ) acute treatment and therefore longer trials are necessary to determine the extended response and maintenance of effect from duloxetine treatment in gad . to date , there are no long - term studies that examined whether the clinical efficacy of venlafaxine in treating gad is maintained for 6 months or longer . moreover , as patients with gad frequently have comorbid psychiatric and medical illnesses and these trials excluded significant psychiatric and medical comorbidity , results of these studies should be extended also to , for example , primary - care settings to adding evidences to the generalizability of result to general patient population . despite growing evidences about a good efficacy of duloxetine in the treatment of gad , there is a relative lacking of data of its potential efficacy in other ads such as pd , sad , ocd , and post - traumatic stress disorder ( ptsd ) . in fact , for these disorders , there are only case reports that have suggested a potential efficacy . crippa and zuardi ( 2006 ) reported a case of a 26-year - old woman with pd and agoraphobia successfully treated with duloxetine whereas luis blay and black ( 2007 ) showed a good clinical response in a 38-year - old man with ocd with a successful 1-year follow - up . recently dellosso and colleagues ( 2008 ) reported the cases of four patients with treatment - resistant ocd who were switched from ssris to duloxetine and followed up for 12 weeks . at the endpoint , three out of four patients showed a clinically significant improvement of the oc symptoms ( 35% on the y - bocs score ) , whereas the clinical features of the fourth patient remained unchanged . again crippa and colleagues ( 2007 ) pointed out that duloxetine treatment at 120 mg / day was efficacious to reduce brief social phobia scale scores in two women with sad . concerning ptsd , a case report showed an exacerbation of ptsd symptoms with use of duloxetine in a 53-year - old married vietnam veteran , but this patient was also affected by bipolar disorder and this may potentially explain the finding along with sustained noradrenergic effects of this medication ( deneys and ahearn 2007 ) . on the other hand , hanretta and malek - ahmadi ( 2007 ) reported a case of 38-year - old woman with treatment - resistant mdd and ptsd who was successfully treated with electroconvulsive therapy along with a duloxetine olanzapine combination . the duloxetine treatment was generally well tolerated in the three studies of gad where data on tolerability were available ( allgulander et al 2007 ; endicott et al 2007 ) . nausea was the most frequent adverse effect reported by the patients in the studies of gad . treatment groups did not differ significantly in their overall study completion rates , which were 64.8% for duloxetine and 68.1% for placebo . the rate of discontinuation due to adverse event was 15.6% for the duloxetine group ( mostly due to nausea and vomiting ) . duloxetine is a promising treatment for ads that may be employed to obtain patient remission than merely response ( getting the patient 50% better ) . the emerging data suggests that dual action agents may have greater efficacy in getting the patients with gad to remission . however , the clinical efficacy of this drug will be more evident once will be more widely prescribed and used in the community by physicians . the results of trials evaluating the use duloxetine in the treatment of gad are supportive on its efficacy on this disorder without severe adverse effects . despite its clinical efficacy and fda approval for the treatment of gad , surprisingly , to date , the long term efficacy of duloxetine has not been yet investigated deeply and therefore further studies on long - term period are needed . apart from some interesting case reports , no studies are , to date , present in literature about duloxetine and other ads . therefore , the clinical efficacy and the relative good tolerability of duloxetine in other ads than gad may be further investigated with double blind placebo - controlled studies in order to widen the therapeutic spectrum of ads .

anxiety disorders ( ads ) are the most common type of psychiatric disorders , with a mean incidence of 18.1% and a lifetime prevalence of 28.8% . pharmacologic options studied for treating ads may include benzodiazepines , tricyclic antidepressants ( tca ) , selective serotonin reuptake inhibitors ( ssris ) , noradrenergic and specific serotonergic drug ( nassa ) and dual - reuptake inhibitors of serotonin and norepinephrine ( snris ) . in this context , the development of snris ( venlafaxine and duloxetine ) has been particularly useful . as a dual - acting intervention that targets two neurotransmitter systems , these medications would appepar promising for the treatment of ads . the purpose of this review was to elucidate current facts and views about the role of duloxetine in the treatment of ads . in february 2007 , duloxetine was approved by fda for the treatment of generalized anxiety disorder ( gad ) . the results of trials evaluating the use duloxetine in the treatment of gad are supportive on its efficacy even if further studies on long - term use are needed . apart from some interesting case reports , no large studies are , to date , present in literature about duloxetine and other ads such as panic disorder , social anxiety disorder , obsessive - compulsive disorder and post - traumatic stress disorder . therefore , the clinical efficacy and the relative good tolerability of duloxetine may be further investigated to widen the therapeutic spectrum of ads .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Commission on the Accountability and Review of Federal Agencies Act''. SEC. 2. ESTABLISHMENT OF COMMISSION. (a) Establishment.--There is established the Commission on the Accountability and Review of Federal Agencies (hereafter in this Act referred to as the ``Commission''). (b) Membership.-- (1) Number and appointment.-- (A) In general.--The Commission shall be composed of 7 members appointed by the President as follows: (i) One in consultation with the Speaker of the House of Representatives. (ii) One in consultation with the minority leader of the House of Representatives. (iii) One in consultation with the majority leader of the Senate. (iv) One in consultation with the minority leader of the Senate. (v) Three other members. (B) Ex officio members.--The President may appoint up to 4 Members of Congress (up to 2 from each House) as nonvoting ex officio members of the Commission. (c) Period of Appointment; Vacancies.--Members shall be appointed for the life of the Commission. Any vacancy in the Commission shall not affect its powers, but shall be filled in the same manner as the original appointment. (d) Initial Meeting.--Not later than 30 days after the date on which all members of the Commission have been appointed, the Commission shall hold its first meeting. (e) Meetings.--The Commission shall meet at the call of the chairperson. (f) Quorum.--A majority of the members of the Commission shall constitute a quorum, but a lesser number of members may hold hearings. SEC. 3. DUTIES OF THE COMMISSION. (a) Definition.--The term ``agency'', as used in this section, has the meaning given the term ``executive agency'' under section 105 of title 5, United States Code. (b) In General.--The Commission shall-- (1) evaluate all agencies and programs within those agencies, using the criteria under subsection (c); and (2) submit to Congress-- (A) a plan with recommendations of the agencies and programs that should be realigned or eliminated; and (B) proposed legislation to implement the plan under subparagraph (A). (c) Criteria.-- (1) Duplicative.--If 2 or more agencies or programs are performing the same essential function and the function can be consolidated or streamlined into a single agency or program, the Commission shall recommend that the agency or program be realigned. (2) Wasteful or inefficient.--The Commission shall recommend the realignment or elimination of any agency or program that has wasted Federal funds by-- (A) egregious spending; (B) mismanagement of resources and personnel; or (C) use of such funds for personal benefit or the benefit of a special interest group. (3) Outdated, irrelevant, or failed.--The Commission shall recommend the elimination of any agency or program that-- (A) has completed its intended purpose; (B) has become irrelevant; or (C) has failed to meet its objectives. (d) Report.-- (1) In general.--Not later than 2 years after the date of enactment of this Act, the Commission shall submit to the President and Congress a report that includes-- (A) the plan described under subsection (b)(1) with supporting documentation for all recommendations; and (B) the proposed legislation described under subsection (b)(2). (2) Use of savings.--The proposed legislation under paragraph (1)(B) shall provide that all funds saved by the implementation of the plan under paragraph (1)(A) shall be used for deficit reduction. (3) Relocation of federal employees.--The proposed legislation under paragraph (1)(B) shall provide that if the position of an employee of an agency is eliminated as a result of the implementation of the plan under paragraph (1)(A), the affected agency shall make reasonable efforts to relocate such employee to another position within the agency or within another Federal agency. SEC. 4. POWERS OF THE COMMISSION. (a) Hearings.--The Commission or, at its direction, any subcommittee or member of the Commission, may, for the purpose of carrying out this Act-- (1) hold such hearings, sit and act at such times and places, take such testimony, receive such evidence, and administer such oaths as any member of the Commission considers advisable; (2) require, by subpoena or otherwise, the attendance and testimony of such witnesses as any member of the Commission considers advisable; and (3) require, by subpoena or otherwise, the production of such books, records, correspondence, memoranda, papers, documents, tapes, and other evidentiary materials relating to any matter under investigation by the Commission. (b) Issuance and Enforcement of Subpoenas.-- (1) Issuance.--Subpoenas issued under subsection (a) shall bear the signature of the chairperson of the Commission and shall be served by any person or class of persons designated by the chairperson for that purpose. (2) Enforcement.--In the case of contumacy or failure to obey a subpoena issued under subsection (a), the United States district court for the judicial district in which the subpoenaed person resides, is served, or may be found, may issue an order requiring such person to appear at any designated place to testify or to produce documentary or other evidence. Any failure to obey the order of the court may be punished by the court as a contempt of that court. (c) Information From Federal Agencies.--The Commission may secure directly from any Federal department or agency such information as the Commission considers necessary to carry out this Act. Upon request of the chairperson of the Commission, the head of such department or agency shall furnish such information to the Commission. (d) Postal Services.--The Commission may use the United States mails in the same manner and under the same conditions as other departments and agencies of the Federal Government. SEC. 5. COMMISSION PERSONNEL MATTERS. (a) Compensation of Members.-- (1) Non-federal members.--Except as provided under subsection (b), each member of the Commission who is not an officer or employee of the Federal Government shall not be compensated. (2) Federal officers or employees.--All members of the Commission who are officers or employees of the United States shall serve without compensation in addition to that received for their services as officers or employees of the United States. (b) Travel Expenses.--The members of the Commission shall be allowed travel expenses, including per diem in lieu of subsistence, at rates authorized for employees of agencies under subchapter I of chapter 57 of title 5, United States Code, while away from their homes or regular places of business in the performance of services for the Commission. (c) Staff.-- (1) In general.--The chairperson of the Commission may, without regard to the civil service laws and regulations, appoint and terminate an executive director and such other additional personnel as may be necessary to enable the Commission to perform its duties. The employment of an executive director shall be subject to confirmation by the Commission. (2) Compensation.--Upon the approval of the chairperson, the executive director may fix the compensation of the executive director and other personnel without regard to chapter 51 and subchapter III of chapter 53 of title 5, United States Code, relating to classification of positions and General Schedule pay rates, except that the rate of pay for the executive director and other personnel may not exceed the maximum rate payable for a position at GS-15 of the General Schedule under section 5332 of such title. (3) Personnel as federal employees.-- (A) In general.--The executive director and any personnel of the Commission who are employees shall be employees under section 2105 of title 5, United States Code, for purposes of chapters 63, 81, 83, 84, 85, 87, 89, and 90 of that title. (B) Members of commission.--Subparagraph (A) shall not be construed to apply to members of the Commission. (d) Detail of Government Employees.--Any Federal Government employee may be detailed to the Commission without reimbursement, and such detail shall be without interruption or loss of civil service status or privilege. (e) Procurement of Temporary and Intermittent Services.--The chairperson of the Commission may procure temporary and intermittent services under section 3109(b) of title 5, United States Code, at rates for individuals which do not exceed the daily equivalent of the annual rate of basic pay prescribed for level V of the Executive Schedule under section 5316 of such title. SEC. 6. TERMINATION OF THE COMMISSION. The Commission shall terminate 90 days after the date on which the Commission submits the report under section 3(d). SEC. 7. CONGRESSIONAL CONSIDERATION OF REFORM PROPOSALS. (a) Definitions.--In this section-- (1) the term ``implementation bill'' means only a bill which is introduced as provided under subsection (b), and contains the proposed legislation included in the report submitted to Congress under section 3, without modification; and (2) the term ``calendar day'' means a calendar day other than 1 on which either House is not in session because of an adjournment of more than 3 days to a date certain. (b) Introduction; Referral; and Report or Discharge.-- (1) Introduction.--On the first calendar day on which both Houses are in session, on or immediately following the date on which the report is submitted to Congress under section 3, a single implementation bill shall be introduced (by request)-- (A) in the Senate by the majority leader of the Senate, for himself and the minority leader of the Senate, or by Members of the Senate designated by the majority leader and minority leader of the Senate; and (B) in the House of Representatives by the Speaker of the House of Representatives, for himself and the minority leader of the House of Representatives, or by Members of the House of Representatives designated by the Speaker and minority leader of the House of Representatives. (2) Referral.--The implementation bills introduced under paragraph (1) shall be referred to any appropriate committee of jurisdiction in the Senate and any appropriate committee of jurisdiction in the House of Representatives. A committee to which an implementation bill is referred under this paragraph may report such bill to the respective House without amendment. (3) Report or discharge.--If a committee to which an implementation bill is referred has not reported such bill by the end of the 15th calendar day after the date of the introduction of such bill, such committee shall be immediately discharged from further consideration of such bill, and upon being reported or discharged from the committee, such bill shall be placed on the appropriate calendar. (c) Floor Consideration.-- (1) In general.--When the committee to which an implementation bill is referred has reported, or has been discharged under subsection (b)(3), it is at any time thereafter in order (even though a previous motion to the same effect has been disagreed to) for any Member of the respective House to move to proceed to the consideration of the implementation bill, and all points of order against the implementation bill (and against consideration of the implementation bill) are waived. The motion is highly privileged in the House of Representatives and is privileged in the Senate and is not debatable. The motion is not subject to amendment, or to a motion to postpone, or to a motion to proceed to the consideration of other business. A motion to reconsider the vote by which the motion is agreed to or disagreed to shall not be in order. If a motion to proceed to the consideration of the implementation bill is agreed to, the implementation bill shall remain the unfinished business of the respective House until disposed of. (2) Amendments.--An implementation bill may not be amended in the Senate or the House of Representatives. (3) Debate.--Debate on the implementation bill, and on all debatable motions and appeals in connection therewith, shall be limited to not more than 10 hours, which shall be divided equally between those favoring and those opposing the resolution. A motion further to limit debate is in order and not debatable. An amendment to, or a motion to postpone, or a motion to proceed to the consideration of other business, or a motion to recommit the implementation bill is not in order. A motion to reconsider the vote by which the implementation bill is agreed to or disagreed to is not in order. (4) Vote on final passage.--Immediately following the conclusion of the debate on an implementation bill, and a single quorum call at the conclusion of the debate if requested in accordance with the rules of the appropriate House, the vote on final passage of the implementation bill shall occur. (5) Rulings of the chair on procedure.--Appeals from the decisions of the Chair relating to the application of the rules of the Senate or the House of Representatives, as the case may be, to the procedure relating to an implementation bill shall be decided without debate. (d) Coordination With Action by Other House.--If, before the passage by 1 House of an implementation bill of that House, that House receives from the other House an implementation bill, then the following procedures shall apply: (1) Nonreferral.--The implementation bill of the other House shall not be referred to a committee. (2) Vote on bill of other house.--With respect to an implementation bill of the House receiving the implementation bill-- (A) the procedure in that House shall be the same as if no implementation bill had been received from the other House; but (B) the vote on final passage shall be on the implementation bill of the other House. (e) Rules of the Senate and the House of Representatives.--This section is enacted by Congress-- (1) as an exercise of the rulemaking power of the Senate and House of Representatives, respectively, and as such it is deemed a part of the rules of each House, respectively, but applicable only with respect to the procedure to be followed in that House in the case of an implementation bill described in subsection (a), and it supersedes other rules only to the extent that it is inconsistent with such rules; and (2) with full recognition of the constitutional right of either House to change the rules (so far as relating to the procedure of that House) at any time, in the same manner, and to the same extent as in the case of any other rule of that House. SEC. 8. AUTHORIZATION OF APPROPRIATIONS. There are authorized to be appropriated such sums as may be necessary for each of fiscal years 2010 through 2013 for carrying out this Act.

Commission on the Accountability and Review of Federal Agencies Act - Establishes the Commission on the Accountability and Review of Federal Agencies to: (1) evaluate executive agencies and their programs; and (2) submit to Congress a plan recommending agencies and programs that should be realigned or eliminated and proposing implementing legislation. Requires the Commission to recommend: (1) realignment where a function performed by two or more agencies or programs can be consolidated; (2) realignment or elimination of any agency or program that has wasted federal funds; and (3) elimination of any agency or program that has completed its purpose, become irrelevant, or failed to meet objectives.

a wealth of observational evidence indicates the existence of considerably more mass in galaxies and clusters of galaxies than we see in stars and gas . the source of the missing mass has been a problem since zwicky s 1937 measurement of the masses of extragalactic systems @xcite . given the evidence from galaxy clusters , galaxy dynamics and structure formation , big - bang nucleosynthesis , and the cosmic microwave background that baryons can only account for @xmath2 of this matter , most of it must be nonbaryonic . although neutrinos provide the cosmological density of dark matter if their masses sum to @xmath3 ev , such particles can not ( essentially from the pauli principle ) have a sufficiently high phase - space density to account for galactic dark - matter halos @xcite ; moreover , such masses are now inconsistent with neutrino - mass measurements @xcite . theorists have thus taken to considering for dark - matter candidates new physics beyond the standard model . to date , the most promising candidates those that appear in fairly minimal extensions of the standard model and which coincidentally have a cosmological density near the critical density are a weakly - interacting massive particle ( wimp ) , such as the neutralino , the supersymmetric partner of the photon , @xmath4 boson , and/or higgs boson @xcite , or the axion @xcite . a considerable theoretical literature on the properties and phenomenology of these particles has arisen , and there are considerable ongoing experimental efforts to detect these particles . in the absence of discovery of such particles , it may be well worth exploring other possibilities . thus , an alternative line of investigation takes a more model - independent approach and seeks to explore phenomenologically the possible properties of a dark - matter particle . along these lines , for example , constraints to strongly - interacting dark matter were considered in ref . @xcite ; self - interacting dark matter has been considered @xcite , and some have studied whether dark matter might be charged @xcite or have a millicharge @xcite . our investigation follows in spirit the latter possibility . in particular , dark matter is so called because the coupling to photons is assumed to be nonexistent or very weak , or else we would have presumably seen such particles either through absorption or emission of radiation or in laboratory experiments . in this paper , we ask the question , `` how dark is ` dark ' ? '' in other words , how weak must the coupling of the dark - matter particle to the photon be in order to be consistent with laboratory and astrophysical constraints ? in the work on millicharged particles , a dark - matter coupling to photons was assumed to arise from a tiny charge . in this paper we consider the possibility that the dark matter possesses an electric or magnetic dipole moment . the punch line , illustrated in fig . [ fig : concord ] , is that a dirac particle with an electric or magnetic dipole moment of order @xmath5 cm with a mass between an mev and a few gev can provide the dark matter while satisfying all experimental and observational constraints . cm , where @xmath6 is the electron charge . for reference , the bohr magneton @xmath7 cm in these units . also note that we work in rationalized gaussian units so that the fine - structure constant @xmath8 , and in particle - physics units ( @xmath9 ) @xmath10 and @xmath11 . ] in the following section , we introduce the effective lagrangian for the dipolar dark matter ( ddm ) interaction with photons . we discuss the relic abundance in section [ section3 ] . section [ section4 ] presents constraints on dark - matter dipole moments and masses that arise from direct searches at low - background detectors as well as constraints from high - altitude experiments . section [ section5 ] discusses constraints due to precision tests of the standard model , while section [ section6 ] discusses constraints due to the cosmic microwave background and the growth of large - scale structure . we provide some concluding remarks in section [ section7 ] . an appendix provides details of the calculation of the drag force between the baryon and ddm fluids used in section [ section6 ] . a particle with a permanent electric and/or magnetic dipole moment must have a nonzero spin ; we thus consider spin-1/2 particles . moreover , majorana particles can not have permanent dipole moments , so we consider dirac fermions . since the spin and the magnetic dipole are both axial vectors , a magnetic dipole moment can arise without violating any discrete symmetries . however , the electric dipole moment is a vector and thus requires time - reversal and parity violation . the effective lagrangian for coupling of a dirac fermion @xmath12 with a magnetic dipole moment @xmath13 and an electric dipole moment @xmath14 to the electromagnetic field @xmath15 is @xmath16 at energies low compared to the dark - matter mass , the photon is blind to distinctions between @xmath13 and @xmath14 ( unless time - reversal - violating observables are considered ) . hence , we can discuss limits to @xmath14 which equally apply to @xmath13 , except where noted . on dimensional grounds , we expect the electric dipole moment to be @xmath17 cm , where @xmath18 is the proton mass . similar arguments also apply to the magnetic dipole moment . this limit is shown as the perturbative bound in fig . [ fig : concord ] , as violation of this bound would signal some non - trivial or non - perturbative field configuration . as we will see below , more rigorous but slightly weaker upper limits can be set with unitarity arguments . these upper limits already simplify our analysis . the phenomenology of charged dark - matter particles is determined largely by the ability of these particles to form atom - like bound states with electrons , protons , or each other . however , dipolar dark matter can not form such bound states . a neutral particle with a magnetic moment will not form bound states with charged particles . curiously enough , a neutral particle with an electric dipole moment ( edm ) can indeed form a bound state with an electron , as first noted by no less than fermi and teller @xcite , but only if the dipole moment is greater than @xmath19 cm ( assuming @xmath20 ) where @xmath21 is the bohr radius . for smaller values of the dipole , the electron `` sees '' both poles of the dipole and finds no stable orbit . this critical electric dipole moment scales inversely with the dipole - electron reduced mass , so a bound state with a proton can occur if the dipole mass is @xmath22 and @xmath23 cm . as we will see below , such values for the edm can not occur for a pointlike ddm . likewise , the weakness of the dipole - dipole interaction prevents the formation of any stable dark - matter atoms . the first cosmological constraint is that from big - bang nucleosynthesis ( bbn ) . bbn requires that the effective number of relativistic degrees of freedom at @xmath24 mev does not exceed the equivalent of roughly 0.2 neutrino species @xcite . since the particles we are considering are dirac particles , they act like two effective neutrino species and thus can not be relativistic and in equilibrium at bbn . generally , such considerations rule out @xmath25 mev , and so we restrict our attention in fig . [ fig : concord ] to masses above an mev . strictly speaking , if the dipole moment is @xmath26\lesssim 10^{-22}\,e$ ] cm , and if the particle has no other interactions with standard - model particles , then a particle of mass @xmath27 mev can decouple at a temperature @xmath28 gev , and if so , it will evade the bbn limit . ddm particles can exist in thermal equilibrium in the early universe when the temperature @xmath29 , and their interactions will freeze out when @xmath30 drops below @xmath31 resulting in some cosmological relic abundance . the mass density of relic ddm particles is fixed by the cross section @xmath32 for annihilation to all lighter particles times the relative velocity @xmath33 through ( see , e.g. , eq . ( 5.47 ) in ref . @xcite ) , @xmath34 \over 21},\end{aligned}\ ] ] where @xmath35 assuming that annihilation takes place ( as it does in our case ) through the @xmath36 wave . here , @xmath37 is the effective number of relativistic degrees of freedom at the temperature @xmath38 of freezeout . for the interaction of eq . ( [ lint ] ) , ddm anti - ddm pairs can annihilate to either two photons or to charged particle - antiparticle pairs through the diagrams shown in figs . [ fig : ddtophotons ] and [ fig : ddtoff ] . the cross sections for these two processes ( to lowest order in @xmath33 ) are @xmath39 where @xmath40=[{\cal d,\ , m}]/(10^{-17}~e~{\rm cm})$ ] , and @xmath41 . here , @xmath42 is the effective number of fermion - antifermion pairs with mass @xmath43 , @xmath44 is the charge of fermion @xmath45 , and @xmath46 is the number of color degrees of freedom for fermion @xmath45 . ( @xmath47 for electrons . ) in the standard model , annihilation can also occur to @xmath48 pairs above threshold . for @xmath49 , fermions are the dominant final state . the present - day mass density of ddm particles thus depends primarily on the dipole moment . if such particles are to account for the dark matter , then @xmath50 @xcite , and @xmath51 cm for @xmath52gev . the full mass dependence of this result is shown in fig . [ fig : concord ] . the cross sections in eq . ( [ eqn : ann ] ) are @xmath36-wave cross sections . according to partial - wave unitarity , the total @xmath36-wave annihilation cross section must be @xmath53 @xcite , so that @xmath54 , fixed by the cross section for annihilation to two photons . this limit is shown in fig . [ fig : concord ] , as is the more stringent , but less rigorous , limit @xmath55 . of course , the present - day mass density of ddm particles could differ from the estimates obtained above . to obtain these results , we assumed ( 1 ) that the dipole interaction with photons is the only interaction of these particles ; and ( 2 ) that there is no particle - antiparticle asymmetry . it is reasonable to assume that in any realistic model , a dark - matter dipole interaction will arise from loop diagrams involving other standard - model and new particles . if so , then there may be other contributions to the annihilation cross sections . in this case , the relic abundance will be smaller than we have estimated above . we thus conclude that if there is no particle - antiparticle asymmetry , our estimates should be treated as an upper bound to the relic abundance , and the @xmath56 curve in fig . [ fig : concord ] should thus be considered an upper limit to the desired values of @xmath14 and @xmath13 . on the other hand , the relic abundance could also be increased if exotic processes increase the expansion rate during freezeout @xcite . if there is an asymmetry between @xmath12 and @xmath57 , then the relic abundance is increased relative to our estimate . in this case , however , the present - day universe should contain predominantly either particles or antiparticles . although there is no _ a priori _ reason to expect there to be a particle - antiparticle asymmetry , the observed baryon - antibaryon asymmetry might lead us to expect an analogous dark - matter asymmetry , should the dark matter be composed of dirac particles . it is possible such asymmetries have a common origin . finally , we have assumed above that the particles freeze out when they are nonrelativistic . however , as the dipole moment is lowered for a given mass , freezeout occurs earlier . if the dipole moment is reduced beyond a certain value , and if there are no other couplings to standard - model particles , then freezeout will be relativistic . these particles will then be roughly as abundant as photons , and they will overclose the universe by huge margins unless their masses are @xmath27 few ev ; even in this case they will violate constraints to hot dark matter from the cmb and large - scale structure , and they will also be unable , from the tremaine - gunn argument , to make up the dark matter in galactic halos . the transition from nonrelativistic to relativistic freezeout occurs ( again , assuming no non - dipole interactions with standard - model particles ) for @xmath58 gev for @xmath59 mev , and for @xmath60 mev , at @xmath61 mev . the diagram for scattering of a ddm particle with a particle of charge @xmath62 occurs through the exchange of a photon , as shown in fig . [ fig : dn ] ( not unlike the electron - neutron interaction @xcite ) . in the nonrelativistic limit , the differential cross section for this process is given by , @xmath63 where @xmath33 is the relative velocity . through this interaction the ddm might produce a signal in a direct - detection experiment . although the total cross section is formally infinite , the divergence comes from the small - momentum - transfer scatterings that will be screened by atomic electrons . roughly speaking , then , the ddm - nucleus elastic - scattering cross section will be @xmath64 @xmath65 , using @xmath66 . current null searches in germanium detectors [ @xmath67 correspond for masses @xmath68 gev to a rough upper limit to the cross section @xmath69 @xmath65 @xcite , thus ruling out any dipole moment @xmath70 . this is shown in fig . [ fig : concord ] as the horizontal dashed line at @xmath71 cm . note that the cross - section limit depends ( and increases ) with mass at higher masses ; the curve appears as a horizontal line simply because of the break in scale on the @xmath72 axis . this seems like a very stringent limit , especially considering the value , @xmath73 , favored for the correct cosmological density . however , if the dipole moment becomes large enough , the particles will be slowed in the rock above the detector and thus evade detection in these underground experiments . in order to determine the magnitude of the dipole moment for this to occur , we need to calculate the stopping power @xmath74 for the particle as it passes through the atmosphere and then the rock . since elastic scattering takes place through exchange of a photon , it leads to a long - range interaction and , as we have seen above , a formally divergent elastic - scattering cross section . the calculation of the stopping power thus parallels that for ionization loss due to coulomb collisions , with two important differences . first of all , since the long - range force is @xmath75 , as opposed to @xmath76 for rutherford scattering , stopping occurs via scattering from nuclei , rather than electrons . second , since this interaction falls more rapidly with radius than the coulomb interaction , the stopping power is due primarily to hard scatters at small impact parameter , rather than soft scatters at a wide range of impact parameters . our result for the stopping power due to scattering from nuclei of charge @xmath77 is @xmath78 where the kinetic - energy transfer in a single collision is @xmath79 , @xmath80 is the depth , and @xmath81=m_\chi m_n(m_\chi+m_n)^{-1}$ ] is the reduced mass . for very weak wimp interactions with nuclei , the most restrictive limits on the wimp - proton cross section ( the smallest upper bounds ) are obtained from null searches from experiments that are deepest underground ( so as to reduce the background ) . however , the most restrictive constraints on the cross section at the upper end of the excluded range of cross sections will come from the shallowest underground experiment with a null result . from eq . ( [ eqn : dedx ] ) , we find that the dark - matter particles will only penetrate to a depth @xmath82 where @xmath83 is the initial dark - matter kinetic energy and @xmath84 is the final energy . for a stopped particle , @xmath85 . however , the particle only needs to lose enough energy for @xmath84 to drop below the detection threshold for a particular experiment . equating the maximum kinetic energy transferable in a collision ( @xmath86 ) to the threshold detectable nuclear - recoil energy ( @xmath87 ) , we find the velocity must be slowed to @xmath88 ^ 2 $ ] , where @xmath89 is the mass of the nuclei in the detector , and @xmath90 $ ] is the ddm - nucleus reduced mass . hence , the final dark - matter energy must be @xmath91 ^ 2 $ ] . so far we have assumed that the particle loses energy but is not significantly deflected in each scatter ; this will be a good approximation if @xmath92 . however , when @xmath93 gev , the dark - matter particle may be backscattered upon encountering a terrestrial nucleus , rather than simply being slowed without deflection . in this case , the particle will diffuse , undergoing @xmath94 scatters before coming to rest . if so , the penetration depth will be reduced by an additional factor of @xmath95 . we thus replace @xmath96 $ ] in our expression for the penetration depth . then , for a given shielding thickness @xmath97 , in meters water equivalent ( mwe ) , we invert the expression for the stopping distance to obtain the following bound on the dipole strength : @xmath98 ^ 2 } e_{\rm th } \over { e^2 \over 2 \pi } l \sum_i f_i z_i^2 { \mu[m_\chi , m_i]^2 \over m_i^2 } [ 1 + ( m_i/2 m_\chi)^{1/2 } ] } \label{dscatteringbound}\ ] ] where the index @xmath99 sums over the composition of the shielding material , and @xmath100 is the fractional composition by weight . we use a realistic model of the composition of the earth ( chemical composition by weight : o [ 46.6% ] , si [ 27.7% ] , al [ 8.1% ] , fe [ 5% ] , ca [ 3.6% ] , na [ 2.8% ] , k [ 2.6% ] , mg [ 2.1% ] ) and atmosphere ( @xmath101 mwe consisting of a 4:1 ratio of nitrogen to oxygen ) , although the resulting bounds do not change substantially if we ignore the atmosphere and approximate the earth s crust as entirely composed of si . we take the initial ddm velocity to be 300 km sec@xmath102 . the shallowest underground experiment with a strong null result is the stanford underground facility ( suf ) run of the cryogenic dark matter search ( cdms ) @xcite , which was situated at a depth of 16 mwe . with a detector energy threshold of @xmath103 kev , it is sensitive to ddm masses down to @xmath104 gev . near this threshold we find that ddm particles are stopped by the shielding for @xmath105 . this bound grows more prohibitive with increasing mass , as illustrated in fig . [ fig : concord ] . the cryogenic rare event search with superconducting thermometers ( cresst ) @xcite , though at a depth of 3800 mwe , extends to slightly lower masses , having a detector threshold energy @xmath106 kev . near @xmath107gev the minimum dipole strength is @xmath108 . however , there are no limits from underground experiments for ddm masses below 1 gev . two airborne experiments unobscured by the atmosphere or rock which have closed the windows on some forms of strongly - interacting dark matter @xcite , also restrict dark - matter dipole moments . to determine the predicted signal at a detector , we recast eq . ( [ eqn : dn ] ) as the cross section per energy transfer , whereby @xmath109 . the event rate ( per time , energy , and unit mass of detector ) is @xmath110 where @xmath111 is the number of nuclei per gram of material . the silicon semiconductor detector flown on a balloon in the upper atmosphere by rich _ _ @xcite observed an event rate of @xmath112 nuclear recoils in the lowest energy bin at @xmath113kev . for dark - matter masses above the threshold @xmath114gev , we thus require @xmath115 . the x - ray quantum calorimeter ( xqc ) detector flown on a rocket by mccammon _ @xcite , was designed to probe the soft x - ray background . however , it serendipitously provides a tight constraint on dipolar dark matter . to predict the expected number of events , we start by computing the number of ddm particles that could impinge on the detector : @xmath116 , where @xmath117 is the galactic number density of dark - matter particles , @xmath33 is their velocity , the cross - sectional area of the xqc detector is @xmath118@xmath119 , and the rocket flight was about @xmath120seconds . the chief property of the xqc detector is the @xmath121 m thick si substrate above the thermistor , providing a target of @xmath122nuclei/@xmath119 . thus , the event / energy count @xmath123 integrated over the 25100 ev energy bin gives a predicted @xmath124 events compared to the @xmath125 observed events . since the detector has a @xmath126ev threshold , energy transfer by dark - matter particles as light as @xmath127gev can be detected . altogether , the balloon and rocket experiments exclude a wide range of dipole strengths and masses , as illustrated in fig . [ fig : concord ] . we now consider the limits placed on ddm due to precision tests of the standard model . our use of perturbation theory is valid provided the energy scale of the interaction @xmath128 satisfies @xmath129 . in addition , we require that the ddm mass satisfies @xmath130 , equivalent to the unitary bound @xcite , which ensures the self - consistency of the local operator in eq . ( [ lint ] ) . indeed , if @xmath131 is the energy scale at which a dipole is generated then one generally expects @xmath132 . in @xmath133 we assume that all interacting particles with masses greater than @xmath131 have been integrated out . consequently , one must have at least @xmath134 for the dark matter to be dynamical , which also yields @xmath135 . the interaction in eq . ( [ lint ] ) contributes to the photon propagator via the diagram shown in fig . [ fig : photon - prop ] . the photon - ddm interaction vertices are either both electric or magnetic dipolar ; the mixed diagram where one vertex is magnetic and the other is electric is proportional to @xmath136 for photons with equal momenta . the sum of the diagrams produces the following contribution to the photon vacuum - polarization tensor : @xmath137 where the photon momentum is taken to be small , @xmath138 ( resulting in @xmath139 ) , and @xmath140 is the renormalization scale , which should be smaller than @xmath131 . we take @xmath141 tev for our estimates . with this self - energy correction , the photon propagator for @xmath142 can be written as @xmath143 the second term above generates a correction to the muon gyromagnetic ratio @xmath144 . interestingly , this contribution is not explicitly suppressed by the ddm mass . in view of recent measurements @xcite and comparison with the sm predictions , we require that @xmath145 does not exceed @xmath146 , whereby @xmath147 cm . the order of magnitude of this result can be obtained on dimensional grounds , if we consider that the ddm dipole moment contributes to @xmath148 via at least a two - loop graph ( see fig . [ fig : mug2 ] ) , with two electromagnetic couplings and two dipole couplings . including a factor @xmath149 per loop , one obtains the estimate , @xmath150 where @xmath128 is the characteristic energy scale for the process . in the case of the muon , @xmath151 , which reproduces the rigorous result to within an order of magnitude . furry s theorem tells us that in evaluating radiative corrections to a process one should only keep the diagrams with an even number of photons attached to a closed loop . contributions with an odd number of photons attached sum to zero . on the other hand , one must have an odd number of time - reversal - odd ( t - odd ) edm vertices in the ddm loop to generate a t - odd operator . these considerations show that the lowest - order non - vanishing diagram must have four photons attached to the ddm loop ; diagrams with two photons attached , similar to the one in fig . [ fig : mug2 ] , vanish ( see above ) . out of the four photons attached to the ddm loop , either one or three can have edm coupling to ddm . note that in this scenario both electric and magnetic ddm moments are necessary to generate a dipole moment for a sm fermion . with these considerations in mind , the lowest - order three - loop diagram that induces an edm for a charged fermion is shown in fig . [ fig : edm ] . one obtains the following estimate for the induced electric dipole moment : @xmath152 { e^3 m_f^3\over ( 16\pi^2)^3}\ln^2{m_\chi\over m_f},\ ] ] where a possible double - logarithmic enhancement is included . for the electron , the present limit is @xmath153 cm , which implies @xmath154 cm for @xmath155 gev and @xmath156 . for smaller @xmath31 the limit becomes weaker . there are constraints on the edms of other systems , such as the neutron and the mercury atom . it is non - trivial to translate such constraints into limits on the underlying interaction . in case of the neutron , one may attempt to treat the neutron as a point particle for virtual - photon energies below @xmath157gev . for higher loop momenta , photons begin seeing the quarks and the contribution to the edm becomes suppressed by the quark masses . in this case one may use the above equation with @xmath158 and no logarithmic enhancement , in order to estimate the neutron edm : @xmath159 { e^3|\kappa_n|^3 m_n^3\over ( 16\pi^2)^3 } < 6 \times 10^{-26}~e~{\rm cm},\ ] ] which results in the limit @xmath160 cm ( assuming @xmath161 . in the above equation , @xmath162 is the magnetic moment of the neutron . it appears because the neutron is neutral , and couples to the photon in fig . [ fig : edm ] via a magnetic - moment interaction . the limit for the edm of the mercury atom is much stronger than the neutron , @xmath163 cm . unfortunately , the mercury atom is a complicated system for which the edm is influenced by many sources . therefore , we leave the hg limit for future study . the ddm can contribute to the running of the fine - structure constant for momenta ranging up to the @xmath4 mass . such running will affect the relationship between the fermi constant @xmath164 , the mass of the @xmath165 boson , and the fine - structure constant at zero momentum : @xmath166 where @xmath167 is a correction calculable in a given theory . the interaction in eq . ( [ lint ] ) modifies the standard expression for @xmath167 , whereby @xmath168 . in the standard model @xmath169 . on the other hand , one can use experimentally measured values for @xmath170 , @xmath171 , and @xmath164 in eq . ( [ eqn : wbosonmass ] ) to infer @xmath172 , which gives @xmath173 at the 95% confidence level . therefore , we obtain the limit @xmath174 cm . a full calculation of the vacuum polarization yields the constraint shown in fig . [ fig : concord ] . this turns out to be the strongest constraint due to precision tests of the standard model . the ddm will contribute to various @xmath4-pole observables through two - loop diagrams similar to the one shown in fig . [ fig : zpole ] , at the level @xmath175 . requiring that these contributions do not exceed the @xmath176 precision to which @xmath4-pole observables are typically known @xcite results in the constraint @xmath177 cm . note that in order for perturbation theory to apply for energies @xmath178 , one must have @xmath179 , which means @xmath180 cm . interestingly , consistency with a perturbative treatment at the @xmath4 pole imposes much stronger constraints on the ddm than the @xmath4-pole observables themselves . if kinematically allowed , ddm can be directly produced in various scattering and decay experiments . in this case one may use the missing energy " signature to constrain the ddm couplings . here , we consider missing - energy constraints from both low - energy ( @xmath181 and @xmath182 meson decays ) as well as collider ( lep , cdf ) experiments . searching for light ( @xmath183 gev ) dark matter using missing - energy signatures in rare @xmath181 meson decays was originally suggested in ref . @xcite . there , data from babar @xcite and cleo @xcite were used to set a limit @xmath184 [ derived from @xmath185 ) ] . this limit can be used to constrain the dipole moments of dark matter . the diagram for @xmath186 decay is shown in fig . [ fig : bk - missing](a ) . the rate for this decay can be related to the photon - exchange contribution to @xmath187 shown in fig . [ fig : bk - missing](b ) . since the graphs have identical topologies , the difference in rates will come from the difference in effective couplings and the final - state phase - space integrals . one can estimate , @xmath188 where @xmath189 stand for the corresponding final - state phase - space integrals , and @xmath190 gev is the @xmath181 mass . belle @xcite and babar @xcite find @xmath191 . since the ratio of the phase - space integrals is of order unity , and since in the absence of accidental cancellations @xmath192 , one obtains the constraint @xmath193 which leads to @xmath194 cm . this constraint is relevant for @xmath195 gev . rare @xmath182 decays can be treated in a similar manner . the relevant branching ratios are @xmath196 and @xmath197 @xcite . the resulting constraint on the dipole moment is @xmath198 cm . this constraint applies for @xmath199 gev . we see that constraints from @xmath181 and @xmath182 decays are not competitive with other constraints shown in fig . [ fig : concord ] . a typical example of a process where ddm can be directly produced in a collider experiment is shown in fig . [ fig : coll - missing ] . here , two fermions @xmath45 scatter to produce a final state containing some set of visible particles @xmath200 ( photon , multiple jets , etc . ) along with particles that are not detected . in the sm , the latter are neutrinos . limits on the rate for such processes have been set by , e.g. , the l3 and cdf collaborations @xcite . at lep , @xmath200 consisted of a single photon whereas at cdf it consisted of one or more hadronic jets . in order to translate constraints from collider experiments into limits on ddm couplings one needs an analytical expression for the rate for @xmath201 . naive application of the effective lagrangian in eq . ( [ lint ] ) would result in upper limits from these missing - energy searches of roughly @xmath202 cm . however , this constraint does not actually exclude larger values of the dipole moments . indeed , as discussed above , perturbation theory will break down when the energy scale for the process @xmath203 satisfies @xmath204 . this means that missing - energy searches from l3 ( @xmath205 gev ) and cdf ( @xmath206 tev ) can not be used to probe effective dipole moments @xmath207 cm and @xmath208 cm , respectively , unless the underlying physics that gives rise to the dipole moment is specified . important constraints can be obtained for millicharged particles from the lamb shift @xcite and from a targeted experiment at slac @xcite . we have checked , however , that due to the different energy dependence of the photon - dipole vertex , as opposed to the photon - millicharge vertex , the ddm - induced correction to the lamb shift is small for dipole moments not eliminated by other precision measurements , such as the running of the fine - structure constant . likewise , although the slac experiment is in principle sensitive to neutral particles with a dipole , the production and energy deposition of dipole particles is sufficiently small , for dipole moments consistent with accelerator experiments , to evade detection in the slac experiment . we now consider the effects of the interaction @xmath133 on the evolution of cosmological perturbations and their resulting imprints on the matter power spectrum and the cmb . a dipole moment can induce a coupling of the dark matter to the baryon - photon fluid by scattering from photons through the diagrams shown in fig . [ fig : ddmphoton ] , or by scattering from protons , helium nuclei , and/or electrons through the diagram shown in fig . [ fig : dn ] . what we will show below is that the dark matter is coupled to the baryon - photon fluid at early times , and decouples at later times . when the dark matter is coupled to the photon - baryon fluid , the pressure of the plasma resists the growth of gravitational potential wells . thus , the short - wavelength modes of the density field that enter the horizon at early times will have their growth suppressed relative to the standard calculation resulting in a suppression of small - scale power . the evolution of the longer - wavelength modes that enter the horizon after the dark matter has decoupled remain unaffected . before presenting the results of our detailed analysis , we begin with some simple estimates . we first show that ddm - photon scattering is negligible compared with ddm - baryon scattering in providing the drag force between the ddm fluid and the baryon - photon fluid . to do so , we first estimate the drag force per unit mass ( i.e. , the deceleration ) on a ddm particle that moves with a velocity @xmath209 with respect to the rest frame of a blackbody at temperature @xmath30 . the diagrams in fig . [ fig : ddmphoton ] will lead to a photon - ddm scattering cross section @xmath210 . considering that the momentum transfer to the ddm particle in each scatter is @xmath211 and that the difference of the fluxes of photons moving in the same versus opposite direction to the ddm particle is @xmath212 , we conclude that the deceleration due to photon scattering is @xmath213 . we next estimate @xmath214 , the drag force per unit mass due to ddm - proton scattering . we first note that the peculiar velocity of the baryon - photon fluid ( obtained from the continuity equation ) in the early universe will be @xmath215 , where @xmath216 is the hubble parameter , @xmath217 is the physical wavenumber of the mode in question , and @xmath218 is the amplitude of the fractional density perturbation . since @xmath219 for modes inside the horizon , we must have @xmath220 . on the other hand , the proton thermal velocity dispersion is @xmath221 before recombination . thus , for the early times of interest to us here , the relative velocity between the ddm and the baryon - photon fluid is small compared with the thermal proton velocities . thus , the appropriate relative velocity to use in eq . ( [ eqn : dn ] ) in estimating the proton - ddm cross section is @xmath222 , resulting in a ddm - proton cross section @xmath223 . the momentum transfer per scatter is @xmath224 , where @xmath140 is the proton - ddm reduced mass , and the difference of the fluxes of protons moving with as opposed to against the ddm fluid is @xmath225 , where @xmath226 is the proton density . the drag force per unit mass on the ddm fluid due to scattering with protons is thus @xmath227 . we also conclude from the appearance of @xmath140 in this result that drag due to scattering from electrons is negligible compared with baryon drag . since @xmath228 and @xmath229 , we find @xmath230 as opposed to @xmath231 . thus , at early times , photon drag dominates while baryon drag dominates at later times . the transition occurs at a temperature @xmath24 gev for values of @xmath31 and @xmath14 of interest to us , and such high temperatures correspond to ( comoving ) horizon scales considerably smaller than the distance scales ( @xmath232 mpc ) probed by large - scale structure . we can thus neglect photon drag . from @xmath233 we infer a deceleration time for the ddm fluid @xmath234 . since this decreases more rapidly than the hubble time @xmath235 ( where @xmath236 gev is the planck mass ) , we conclude that ddm particles are tightly coupled to the plasma at early times and then are decoupled at later times . with these rough estimates , the transition temperature is @xmath237 suggesting that power on scales smaller than @xmath238 mpc will be suppressed . the @xmath239 dependence of the ratio of the deceleration and expansion times suggests furthermore that the small - scale suppression will change gradually , rather than exponentially , with wavenumber @xmath217 . knowing that the linear - theory power spectrum is measured and roughly consistent with scale invariance down to distances @xmath240mpc leads us to conclude that dipole moments @xmath241 cm will be ruled out . strictly speaking , when @xmath242 , the detailed calculation must take into account the velocity dispersion of the ddm particles ; our detailed calculation below includes these effects . as seen below , the detailed analysis leads to a slightly stronger constraint . the standard calculation of perturbations in an expanding universe requires solution of the combined einstein and boltzmann equations for the distribution functions of the dark matter , baryons , photons , and neutrinos including all relevant standard - model interactions ( see , e.g. , refs . @xcite and references therein ) . since the perturbations are initially very small , linear perturbation theory is an excellent approximation ; this allows us to solve the perturbation equations in fourier space at each wavenumber @xmath217 independently of all other wavenumbers ( modes are uncoupled ) . the scattering of photons and baryons by ddm through the interaction @xmath133 influences the growth of cosmological perturbations by introducing additional collision terms to the boltzmann equations , which ultimately result in a drag force between the ddm and the colliding species in the equations describing the cosmological fluid ( see , e.g. , refs . @xcite , which consider similar effects ) . below we present the exact perturbation equations including the effects of dark matter with electric or magnetic dipole moments . since solutions to these equations are numerically intensive when photons and baryons are tightly coupled through compton scattering , we also discuss the equations appropriate for solving for the ddm , photon , and baryon perturbations during the epoch of tight coupling . in the synchronous gauge the equations describing the evolution of baryons , photons , and dark matter with an electric or magnetic dipole moment are @xmath243 while the evolution equations for the density contrast @xmath244 for each species @xmath245 are as in the standard case @xcite , as discussed above , the evolution equations for the fluid - velocity perturbations have additional drag - force terms due to the photon - ddm interaction . note that in these equations and what follows the variable @xmath246 is the divergence of the fluid velocity in fourier space , @xmath247 is the shear , @xmath248 is the intrinsic sound speed , and @xmath249 and @xmath250 are the background number and energy densities of a particular species @xmath251 , respectively . the variable @xmath252 is the trace of the scalar metric perturbation in fourier space ( not to be confused with the hubble parameter ) , @xmath253 is the cosmological scale factor , and an overdot represents a derivative with respect to the conformal time @xmath254 . furthermore , @xmath255 is the thomson cross section , while @xmath256 is the appropriately thermally - averaged ddm - photon cross section , which can be obtained from the differential cross section @xcite , @xmath257 for photon - ddm scattering . as argued above , the photon - ddm drag term is small , and we consider it no further in eq . ( [ exact_eqn ] ) . the quantity @xmath258 is the appropriate thermally - averaged cross section times relative velocity for the baryon - ddm coupling , and @xmath259 is the relative efficiency for coupling to helium nuclei compared to protons . appendix a provides a derivation of this collision coefficient . in these expressions , @xmath260 is the cosmological helium mass fraction ( approximating @xmath261 ) , @xmath262 is the average thermal speed of the protons , @xmath263 is the average thermal speed of the ddm , and @xmath264 , @xmath265 , and @xmath266 are the photon , baryon , and ddm temperatures respectively . the dark - matter temperature evolves according to @xmath267 where @xmath268 is the same as the expression given in eq . ( [ sigmavdb ] ) with the replacement of @xmath269 by @xmath270 which is given by the expression in eq . ( [ withy ] ) with the factor @xmath271 replaced by @xmath272 ^ 2 $ ] . the final term , describing the dark matter heating by photons , is important at very early times . for the dipole strength and mass range considered , the influence is manifest only on very small length scales , below the range of interest . at early times , the ddm temperature @xmath273 , but at later times , when the ddm decouples , @xmath274 drops relative to @xmath275 . the ddm - proton cross section is @xmath276 , which leads to @xmath277 . as a result , we can not directly apply the results of ref . @xcite , wherein a velocity - independent dark matter - baryon interaction was assumed . however , we have verified that we recover their results if we take a velocity - independent cross section as the source of dark - matter baryon drag . at early times when @xmath278 the rapid scattering of baryons and photons forces these species to have nearly equal fluid velocities , and consequently the solution of the equations shown in eq . ( [ exact_eqn ] ) is numerically intensive . following standard procedures @xcite we derive a set of equations to leading order in the ( conformal ) compton scattering time @xmath279 that are appropriate for evolving the fluid variables through this epoch of tight coupling . we first write down an equation for the time derivative of @xmath280 which is usually termed the baryon - photon ` slip ' to leading order in @xmath279 , @xmath281,\end{aligned}\ ] ] where we have introduced the ( conformal ) ddm - baryon scattering time @xmath282 , and @xmath283 . it is useful to separate this equation as a sum of the terms not containing @xmath284 ( this is just the time derivative of the standard slip , which we denote @xmath285 ) , and the new terms introduced by the ddm coupling , @xmath286,\end{aligned}\ ] ] where @xmath287 is the parameter that controls how strongly the new interaction affects the evolution of the slip . in terms of these definitions the baryon - velocity evolution equation is @xmath288 + r_{\gamma b } \left[\dot{s}_{b \gamma}+ \beta\left(\dot{\theta}_\chi - \frac{1}{2}\frac{\dot{a}}{a}(\theta_\chi-\theta_b)\right ) \right ] \right\}.\end{aligned}\ ] ] the photon - evolution equation is then given by the exact expression @xmath289 \\ \nonumber & + k^2\left(\frac{1}{4}\delta_{\gamma } - \sigma_{\gamma}\right ) . \label{theta_g_tc}\end{aligned}\ ] ] we use these equations to follow the initial evolution of the baryon and photon fluid variables and switch to the exact equations of eq . ( [ exact_eqn ] ) at later times . for the evolution of the ddm fluid variables we always use the exact form of eq . ( [ exact_eqn ] ) . in fig . [ fig : power ] we show the linear matter power spectrum and in fig . [ fig : cmb ] we show the angular power spectrum of the cmb for several values of the dipole moment and for ddm mass @xmath290 gev . physically , the effects of ddm on the matter power spectrum and cmb can be simply understood . prior to matter - radiation equality the photons have a much larger density than the baryons or the ddm and so to a first approximation completely drive the behavior of the baryon perturbations through compton scattering . in turn , the baryon perturbations drive the behavior of the ddm perturbations , very efficiently before ddm decoupling so that the ddm density contrast @xmath291 on scales that enter the horizon during this epoch track the oscillations of the baryon - photon fluid before growing , and less efficiently after ddm decoupling so that the baryons simply cause a drag on the growth of @xmath291 . in either case the matter power spectrum is suppressed relative to the standard case . the behavior of the cmb angular power spectrum can be similarly understood . roughly speaking , the coupling of the ddm and baryons increases the effective baryon loading of the plasma at early times so that the cmb power spectra look similar to those from high - baryon models . this is of course an imperfect correspondence as modes of larger wavelength enter the horizon when the coupling is weaker , and so at later and later times the evolution of the photon perturbations becomes more and more like the standard - cdm case . but due to geometrical projection effects modes of wavenumber @xmath217 contribute to all @xmath292 where @xmath293 is the angular - diameter distance to the last - scattering surface , and so the effects of ddm on small length scales can be noticed even on relatively large angular scales in the cmb . as the effect of ddm on the cmb may be partially degenerate with other cosmological parameters , we have explored a parameter space that allows us to constrain @xmath31 and @xmath294 after marginalizing over other cosmological parameters . we consider flat @xmath131cdm models and our chosen parameter space is the dark - matter density @xmath295 , the baryon density @xmath296 , the hubble parameter @xmath252 in units of @xmath297 , the optical depth @xmath298 to the last - scattering surface , and the primordial spectral index @xmath299 . we have employed the markov chain monte carlo technique ( see , e.g. , ref . @xcite ) to efficiently explore this parameter space , taking the most recent results from sdss @xcite , wmap @xcite , cbi @xcite , vsa @xcite , and sne ia @xcite as our data . note that although ddm has no effect on observations of type ia supernovae , we include these data because the other parameters we allow to vary are constrained by these observations . we conclude using a relative - likelihood test that cosmological measurements lead to the bound shown in fig . [ fig : concord ] . the numerical calculations confirm the qualitative behavior discussed above . dipole moments as large as @xmath300 , near the upper end of our allowed parameter space , are thus cosmologically viable . ddm particles in the galactic halo can annihilate to two photons through the diagrams shown in fig . [ fig : ddtoff ] . since halo particles move with velocities @xmath301 km sec@xmath302 , the photons produced will be very nearly monoenergetic with energies equal to the ddm - particle rest mass . the intensity at earth of such gamma rays is obtained by integrating the emissivity , @xmath303 , where @xmath117 is the ddm number density , along the given line of sight . the intensity is largest toward the galactic center , where the dark - matter density is largest . in this direction , the gamma - ray intensity is then @xcite , @xmath304 where @xmath305 is a scaled integral of @xmath306 along a line of sight toward the galactic center . the numerical coefficient is one - half that from ref . @xcite since we have here particle - antiparticle annihilation rather than majorana annihilation . roughly speaking , @xmath307 for cored - isothermal - sphere models of the galactic halo , while @xmath305 can extend up to @xmath308 for navarro - frenk - white profiles @xcite ; i.e. , uncertainty in the dark - matter distribution in the inner galaxy leads to an uncertainty of two orders of magnitude in the predicted flux . we thus expect @xmath309 to constrain dipole moments from non - observation of a gamma - ray line , we choose to use the most conservative estimate , @xmath310 for the dimensionless line integral . moreover , we are not aware of any egret analysis that places limits in particular to a line flux . we thus obtain very conservative limits by using the binned continuum fluxes for the _ total _ gamma - ray flux listed in table 1 of ref . @xcite and noting that a line flux in that bin can not exceed the measured continuum flux . the egret limits apply for masses @xmath311 , and range from @xmath312 for @xmath60 gev to @xmath313 for @xmath314 gev , as shown in fig . [ fig : concord ] . again , a few caveats are in order . first of all , our limit is quantitatively conservative we chose the halo model that produces the lowest flux , and a detailed egret analysis would probably yield a line - flux limit lower than what we have assumed . on the other hand , the strong dependence @xmath315 of the predicted flux on the dipole moment guarantees that the upper limit to the acceptable dipole moment will not depend quite so strongly on these details . second , if @xmath316 in the mass range 100 mev to 1 gev , then the correct cosmological abundance most likely requires a particle - antiparticle asymmetry . if so , then the annihilation rate in the halo could be reduced far below the values we have obtained above . we conclude by noting that with the increased sensitivity of the gamma - ray large area space telescope ( glast ) , a detailed search for a line flux , and the possibility that the actual halo model provides a more generous annihilation rate , an observable glast signature may exist for masses @xmath317 gev and dipole moments as low as @xmath318 . in this paper we have considered the cosmology and phenomenology of dark - matter particles with a nonzero magnetic or electric dipole moment . we have found that information from precision tests of the standard model , direct dark - matter searches , gamma - ray experiments , and the cmb and large - scale structure restrict the dipole moment to be @xmath319\lesssim3\times10^{-16}\,e$ ] cm for masses @xmath60 few gev and @xmath319\lesssim 10^{-24}\,e$ ] cm for larger masses . some of the allowed regions of parameter space may soon be probed with glast and with future more sensitive direct - detection experiments . the electromagnetic interactions of these particles with nuclei are coherent . moreover , these particles can not annihilate directly to neutrinos . therefore , searches for energetic neutrinos from decays of the products of @xmath320 annihilation in the sun or earth are thus likely to provide less sensitive probes than direct searches @xcite . moreover , if there is a particle - antiparticle asymmetry , then the energetic - neutrino flux could be reduced without altering the direct - detection rate . we have restricted our attention to particles with masses @xmath59 mev , with the notion that lower - mass particles will violate bbn limit , as discussed toward the end of section [ sec : theory ] . we also consider masses @xmath59 mev , as particles of lower mass will almost certainly undergo relativistic freezeout and thus lead to unacceptable dark - matter candidates . however , as also noted above that if an @xmath60 mev particle has a dipole moment @xmath319\lesssim 10^{-22}\,e$ ] cm and no other interactions with ordinary matter , then it might still be consistent with bbn . of course , such a particle will , assuming standard freezeout , have a mass density many orders of magnitude larger than the dark - matter density . but suppose we were to surmise that the dark - matter density was fixed by some other mechanism . e.g. , suppose the dipole was sufficiently weak that it never came into equilibrium . in this case , an additional constraint to the dark - matter dipoles can be obtained from energy - loss arguments applied to stars in globular clusters . such arguments eliminate dipole moments @xmath319 \lesssim 6\times10^{-23}\,e$ ] cm for masses @xmath321 kev @xcite . we have also considered constraints from astrophysical phenomena such as the stability of the galactic disk , lifetime of compact objects , and annihilations in the solar neighborhood @xcite , and find that these constraints on the mass and interaction strengths are not competitive with those presented here . it would be of interest to attempt to embed this scenario in a consistent particle physics model . we might find links between baryonic and non - baryonic matter abundances , the dark matter electric dipole moment and the cp violation needed for baryogenesis , and the magnetic moments of dark matter and baryons . however , such model building is beyond the scope of the present study . our approach throughout has been entirely phenomenological , as we have been motivated by the desire to answer the question , how dark is ` dark ' ? " we thank s. golwala , j. albert , and m. zaldarriaga for useful discussion . ks acknowledges the support of a canadian nserc postgraduate scholarship . this work was supported in part by nasa nag5 - 9821 and doe de - fg03 - 92-er40701 ( at caltech ) and nsf phy-0099543 ( at dartmouth ) . md and rc thank caltech for hospitality during the course of this investigation . to determine how the cosmological perturbation equations for baryons and dark matter are altered when we bestow the dark matter with a magnetic or electric dipole moment , we must formally evaluate the collision operator of the general - relativistic boltzmann equation in a given gauge @xcite for the dipole interaction of eq . ( [ lint ] ) . we have completed this calculation in detail , and find that the dipole interaction produces a drag force proportional to the relative velocity @xmath322 of the dark - matter and baryon fluids . as the relative velocity is gauge invariant in linear perturbation theory and all scatterings are local processes , we may thus take a simpler , more physically transparent approach and just evaluate this drag force using nonrelativistic statistical mechanics . it is this approach we now present . we wish to calculate the drag force per unit mass , or deceleration , due to collisions with protons to the dark - matter fluid as it passes through the baryon - photon fluid . comoving scales @xmath323 mpc enter the horizon when the cosmological temperature is @xmath324 ev , when the ddm particles ( which are restricted to @xmath59 mev ) are nonrelativistic . we may thus consider thermal velocity distributions for nonrelativistic baryons and dark matter . since the drag force can only depend on the dark - matter baryon relative velocity , we take the baryon fluid to be at rest and the dark - matter fluid to have a velocity of magnitude @xmath209 in the @xmath325 direction . then , the proton phase - space distribution is @xmath326 where @xmath327 is the proton velocity dispersion and @xmath226 the proton number density , and @xmath328,\ ] ] is the dark - matter phase - space distribution , with @xmath329 . recall also that we expect @xmath330 , as discussed above . the drag force per unit mass is obtained by integrating the momentum transfer per collision over all collisions between protons and dark - matter particles . from the symmetry of the problem , the deceleration of the dark - matter fluid will be in the @xmath325 direction , and it will have a magnitude , @xmath331 here @xmath332 is the scattering angle in the center - of - mass frame , and @xmath333 is the difference between the final and initial @xmath80 component of the dark - matter particle velocity ; the difference is the same in the center - of - mass and laboratory frames . the differential cross section @xmath334 is that given in eq . ( [ eqn : dn ] ) . consider an individual scattering event . let @xmath170 be the angle that @xmath335 makes with the @xmath325 direction ; this is then the angle that @xmath336 makes with the @xmath325 axis in the center - of - mass frame , and the magnitude of the initial and final dark - matter velocities in the center - of - mass frame is @xmath337 , where latexmath:[$v\equiv @xmath325 component of the dark - matter velocity in the center - of - mass frame is then @xmath339 . the scattering angles @xmath340 and @xmath341 are then the polar and azimuthal angles that the scattered dark - matter velocity make with the initial velocity in the center - of - mass frame . by rotating this coordinate system by an angle @xmath170 about the @xmath342 axis to align it with the laboratory @xmath325 axis , we find @xmath343 . thus , @xmath344 completing the integral in eq . ( [ eqn : ax ] ) in the limit @xmath345 , we find @xmath346 taking into account the definition @xmath347 , this drag force leads to the drag - force term in eqs . ( [ exact_eqn ] ) , ( [ sigmavdb ] ) , and ( [ withy ] ) , when including the simple corrections for a mass fraction @xmath348 of helium . p. de bernardis . _ et al . _ , nature * 404 * , 955 ( 2000 ) ; s. hanany _ _ , astrophys . j. lett . * 545 * , l5 ( 2000 ) ; n. w. halverson _ et al . _ , j. 568 , 38 ( 2002 ) ; b. s. mason _ _ , astrophys . j. * 591 * , 540 ( 2003 ) ; a. benoit _ _ , astron . astrophys . * 399 * , l2 ( 2003 ) . d. n. spergel _ et al . _ , astrophys . j. suppl . * 148 * , 175 ( 2003 ) . c. bird , p. jackson , r. kowalewski , and m. pospelov , arxiv : hep - ph/0401195 . b. aubert _ et al . _ [ babar collaboration ] , arxiv : hep - ex/0304020 . t. e. browder _ et al . _ [ cleo collaboration ] , phys . rev . lett . * 86 * , 2950 ( 2001 ) [ arxiv : hep - ex/0007057 ] . k. abe _ et al . _ [ belle collaboration ] , phys . * 88 * , 021801 ( 2002 ) [ arxiv : hep - ex/0109026 ] . b. aubert _ et al . _ [ babar collaboration ] , arxiv : hep - ex/0107026 . p. achard _ et al . _ [ l3 collaboration ] , phys . b * 587 * , 16 ( 2004 ) ; d. acosta [ cdf collaboration ] , phys . rev . lett . * 92 * , 121802 ( 2004 ) ; t. affolder _ et al . _ [ cdf collaboration ] , phys . lett . * 88 * , 041801 ( 2002 ) .

we consider the consequences of a neutral dark - matter particle with a nonzero electric and/or magnetic dipole moment . theoretical constraints , as well as constraints from direct searches , precision tests of the standard model , the cosmic microwave background and matter power spectra , and cosmic gamma rays , are included . we find that a relatively light particle with mass between an mev and a few gev and an electric or magnetic dipole as large as @xmath0 cm ( roughly @xmath1 ) satisfies all experimental and observational bounds . some of the remaining parameter space may be probed with forthcoming more sensitive direct searches and with the gamma - ray large area space telescope .

SECTION 1. SHORT TITLE. This Act may be cited as the ``National Security Letter Reform Act of 2005''. SEC. 2. JUDICIAL REVIEW OF NATIONAL SECURITY LETTERS. (a) In General.--Chapter 223 of title 18, United States Code, is amended by inserting after section 3510 the following: ``Sec. 3511. Judicial review of requests for information ``(a) Petition by Recipient.-- ``(1) In general.--The recipient of a request for records, a report, or other information under section 2709(b) of this title, section 626(a) or (b) or 627(a) of the Fair Credit Reporting Act, section 1114(a)(5)(A) of the Right to Financial Privacy Act, or section 802(a) of the National Security Act of 1947 may, in the United States district court for the district in which that person or entity does business or resides, petition for an order modifying or setting aside the request. ``(2) Court action.--The court may modify or set aside a request under this section if compliance would be unreasonable or oppressive. ``(b) Modifications of Nondisclosure Requirement.-- ``(1) Petitions.--The recipient of a request for records, a report, or other information under section 2709(b) of this title, section 626(a) or (b) or 627(a) of the Fair Credit Reporting Act, section 1114(a)(5)(A) of the Right to Financial Privacy Act, or section 802(a) of the National Security Act of 1947, may petition any court described in subsection (a) for an order modifying or setting aside a nondisclosure requirement imposed in connection with such a request. ``(2) Within 1 year.-- ``(A) In general.--If the petition under paragraph (1) is filed not later than 1 year after the request for records, a report, or other information under section 2709(b) of this title, section 626(a) or (b) or 627(a) of the Fair Credit Reporting Act, section 1114(a)(5)(A) of the Right to Financial Privacy Act, or section 802(a) of the National Security Act of 1947, the court may modify or set aside such a nondisclosure requirement if it finds that there is no reason to believe that disclosure may endanger the national security of the United States, interfere with a criminal, counterterrorism, or counterintelligence investigation interfere with diplomatic relations, or endanger the life or physical safety of any person. ``(B) Effect of certification.--The certification made at the time of the request that disclosure may endanger the national security of the United States or interfere with diplomatic relations shall be treated as conclusive under this paragraph unless the court finds that the certification was made in bad faith. ``(3) After 1 year.-- ``(A) In general.--If the petition is filed 1 year or more after the request for records, a report, or other information under section 2709(b) of this title, section 626(a) or (b) or 627(a) of the Fair Credit Reporting Act, section 1114(a)(5)(A) of the Right to Financial Privacy Act, or section 802(a) of the National Security Act of 1947, the issuing officer, within 90 days of the filing of the petition, shall either terminate the nondisclosure requirement or recertify that disclosure may result in danger to the national security of the United States, interference with a criminal, counterterrorism, or counterintelligence investigation, interference with diplomatic 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or 627(a) of the Fair Credit Reporting Act, section 1114(a)(5)(A) of the Right to Financial Privacy Act, or section 802(a) of the National Security Act of 1947. ``(f) Review of Government Submission.--In all proceedings under this section, the court shall, upon the Federal Government's request, review the submission of the Government, which may include classified information, ex parte and in camera.''. (b) Chapter Analysis.--The chapter analysis for chapter 223 of title 18, United States Code is amended by inserting at the end the following: ``3511. Judicial review of request for information.''. SEC. 3. CONFIDENTIALITY OF NATIONAL SECURITY LETTERS. (a) Title 18.--Section 2709(c) of title 18, United States Code, is amended to read: ``(c) Prohibition of Certain Disclosure.-- ``(1) In general.--If the Director of the Federal Bureau of Investigation, or his designee in a position now lower than Deputy Assistant Director at Bureau headquarters or a Special Agent in Charge in a Bureau field office designated by the Director, certifies that otherwise there may result a danger to the national security of the United States, interference with a criminal, counterterrorism or counterintelligence investigation, interference with diplomatic relations, or danger to the life or physical safety of any person, no wire or electronic communications service provider, or officer, employee, or agent thereof, shall disclose to any person (other than those to whom such disclosure is necessary in order to comply with the request or an attorney to obtain legal advice with respect to the request) that the Federal Bureau of Investigation has sought or obtained access to information or records under this section. ``(2) Notice.--A request under this section shall notify the person or entity to whom the request is directed of the nondisclosure requirement under paragraph (1). ``(3) Disclosure.--Any recipient of a request under this section disclosing to those persons necessary to comply with the request or to an attorney to obtain legal advice with respect to the request shall inform such persons of any applicable nondisclosure requirements. Any person who receives such a disclosure under this subsection shall be subject to the same prohibitions on disclosure as under paragraph (1).''. (b) Confidentiality of Disclosures to FBI.--Section 626(d) of the Fair Credit Reporting Act (15 U.S.C. 1681u(d)), as so designated by section 214(a)(1) of the Fair and Accurate Credit Transactions Act of 2003 (Public Law 108-159, 117 Stat. 1980), is amended to read as follows: ``(c) Confidentiality.-- ``(1) In general.--If the Director of the Federal Bureau of Investigation, or the designee thereof in a position not lower than Deputy Assistant Director at Bureau headquarters or a Special Agent in Charge in a Bureau field office designated by the Director, certifies that otherwise there may result a danger to the national security of the United States, interference with a criminal, counterterrorism, or counterintelligence investigation, interference with diplomatic relations, or danger to the life or physical safety of any person, no consumer reporting agency, or officer, employee, or agent of a consumer reporting agency-- ``(A) shall disclose to any person (other than those to whom such disclosure is necessary in order to comply with the request or an attorney to obtain legal advice with respect to the request), that the Federal Bureau of Investigation has sought or obtained the identity of financial institutions or a consumer report respecting any consumer under subsection (a), (b), or (c); and ``(B) shall include in any consumer report any information that would indicate that the Federal Bureau of Investigation has sought or obtained such information on a consumer report. ``(2) Notice.--A request under this section shall notify the person or entity to whom the request is directed of the nondisclosure requirement under paragraph (1). ``(3) Prohibitions applicable to further disclosures.--Any recipient of a request under this section disclosing to those persons necessary to comply with the request or to an attorney to obtain legal advice with respect to the request shall inform such persons of any applicable nondisclosure requirements. Any person who receives such a disclosure under this subsection shall be subject to the same prohibitions on disclosure as under paragraph (1).''. (c) Confidentiality of Disclosures to Other Government Agencies.-- Section 627(c) of the Fair Credit Reporting Act (15 U.S.C. 1681v(c), as so designated by section 214(a)(1) of the Fair and Accurate Credit Transactions Act of 2003 (Public Law 108-159, 117 Stat. 1980), is amended to read as follows: ``(c) Confidentiality.-- ``(1) In general.--If the head of a government agency authorized to conduct investigations or intelligence or counterintelligence activities or analysis related to international terrorism, or the designee thereof, certifies that otherwise there may result a danger to the national security of the United States, interference with a criminal, counterterrorism, or counterintelligence investigation, interference with diplomatic relations, or danger to the life or physical safety of any person, no consumer reporting agency, or officer, employee, or agent of a consumer reporting agency, shall disclose to any person (other than those to whom such disclosure is necessary in order to comply with the request or an attorney to obtain legal advice with respect to the request), or specify in any consumer report, that a government agency has sought or obtained access to information under subsection (a). ``(2) Notice.--A request under this section shall notify the person or entity to whom the request is directed of the nondisclosure requirement under paragraph (1). ``(3) Prohibitions applicable to further disclosures.--Any recipient disclosing to those persons necessary to comply with a request or to an attorney to obtain legal advice with respect to the request shall inform such persons of any applicable nondisclosure requirements. Any person who receives such a disclosure under this subsection shall be subject to the same prohibitions on disclosure as under paragraph (1).''. (d) Right to Financial Privacy Act.--Section 1114(a)(5)(D) of the Right to Financial Privacy Act (12 U.S.C. 3414(a)(5)(D)) is amended to read as follows: ``(D) Prohibition of certain disclosure.-- ``(i) If the Director of the Federal Bureau of Investigation, or the designee thereof in a position not lower than Deputy Assistant Director at Bureau headquarters or a Special Agent in Charge in a Bureau field office designated by the Director, certifies that otherwise there may result a danger to the national security of the United States, interference with a criminal, counterterrorism, or counterintelligence investigation, interference with diplomatic relations, or danger to the life or physical safety of any person, financial institution, or officer, employee, or agent of such institution, shall disclose to any person (other than those to whom such disclosure is necessary in order to comply with the request or an attorney to obtain legal advice with respect to the request) that the Federal Bureau of Investigation has sought or obtained access to a customer's or entity's financial records under this paragraph. ``(ii) A request under this subsection shall notify the person or entity to whom the request is directed of the nondisclosure requirement under paragraph (1). ``(iii) Any recipient disclosing to those persons necessary to comply with the request or to an attorney to obtain legal advice with respect to the request shall inform such persons of any applicable nondisclosure requirement. Any person who receives such a disclosure under this subsection shall be subject to the same prohibitions on disclosure as under clause (i).''. (e) NSA.--Section 802(b) of the National Security Act of 1947 (50 U.S.C. 436(b)) is amended to read as follows: ``(b) Prohibition of Certain Disclosure.-- ``(1) In general.--If an authorized investigative agency described in subsection (a) certifies that otherwise there may result a danger to the national security of the United States, interference with a criminal, counterterrorism, or counterintelligence investigation, interference with diplomatic relations, or danger to the life or physical safety of any person, no governmental or private entity, or officer, employee, or agent of such entity, may disclose to any person (other than those to whom such disclosure is necessary in order to comply with the request or an attorney to obtain legal advice with respect to the request) that such entity has received or satisfied a request made by an authorized investigative agency under this section. ``(2) Notice.--The request shall notify the person or entity to whom the request is directed of the nondisclosure requirement under paragraph (1). ``(3) Disclosure.--Any recipient disclosing to those persons necessary to comply with the request or to an attorney to obtain legal advice with respect to the request shall inform such persons of any applicable nondisclosure requirement. Any person who receives a disclosure under this subsection shall be subject to the same prohibitions on disclosure under paragraph (1).''. SEC. 4. VIOLATION OF NONDISCLOSURE PROVISIONS OF NATIONAL SECURITY LETTER. Section 1510 of title 18, United States Code, is amended by adding at the end the following: ``(e) Penalty.--Whoever knowingly violates section 2709(c)(1) of this title, sections 626(d) or 627(c) of the Fair Credit Reporting Act (15 U.S.C. 1681u(d) or 1681v(c)), section 1114(a)(3) or 1114(a)(5)(D) of the Right to Financial Privacy Act (U.S.C. 3414(a)(3) or 3414(a)(5)(D)), or section 802(b), of the National Security Act of 1947 (50 U.S.C. 436(a)(5)(D)), or section 802(b) of the National Security Act of 1947 (50 U.S.C. 436(b)) shall be imprisoned for not more than 1 year, and if the violation is committed with the intent to obstruct an investigation or judicial proceeding, shall be imprisoned for not more than 5 years.''.

National Security Letter Reform Act of 2005 - Establishes procedures for judicial review of national security letters (NSLs). Authorizes: (1) the recipient of a request for records or other information under federal criminal code provisions concerning counterintelligence access to telephone toll and electronic communication transactional records, the Fair Credit Reporting Act, the Right to Financial Privacy Act, or the National Security Act of 1947 to petition the U.S. district court for an order modifying or setting aside the request; and (2) the court to modify or set aside a request if compliance would be unreasonable or oppressive. Sets forth provisions regarding: (1) challenges to NSL nondisclosure requirements; (2) compelling compliance; and (3) closed hearings, filings under seal, and court review of classified information. Prohibits a wire or electronic communications service provider from disclosing that the Federal Bureau of Investigation (FBI) has sought or obtained access to information or records if the Director of the FBI certifies that such disclosure may result in a danger to national security, interference with a criminal counterterrorism or counterintelligence investigation, interference with diplomatic relations, or a danger to the life or physical safety of any person. Sets penalties for violations of NSL nondisclosure provisions where committed with intent to obstruct an investigation or judicial proceeding.

Image credit: Barbara Kinney Secretary of State Hillary Clinton’s mother, Dorothy Howell Rodham, died Tuesday morning, shortly after midnight. She was 92. Clinton canceled trips to London and Turkey Monday in order to stay by her sick mother’s side in Washington, D.C., and was with her mother when she died. “She was a warm, generous and strong woman,” the Clinton family said in a statement. “An intellectual; a woman who told a great joke and always got the joke; an extraordinary friend and, most of all, a loving wife, mother and grandmother.” Rodham is survived by her three children and four grandchildren. Despite her daughter’s public life, Rodham stayed largely out of the spotlight, granting only one televised interview, which aired on “The Oprah Winfrey Show” in 2004. She last appeared in public for her granddaughter Chelsea Clinton’s 2010 wedding to Marc Mezvinsky. When asked during her 2007 presidential bid who was her greatest inspiration, Clinton cited her mother. “More personally, I owe it to my mother, who never got a chance to go to college, who had a very difficult childhood but who gave me a belief that I could do whatever I set my mind,” Clinton said during a Democratic primary debate. Clinton’s daughter Chelsea, also cited Rodham as her “inspiration,” saying in a recent interview with Yahoo! News that she tried to talk to her grandmother every day. “My grandmother has had a remarkable life and overcame challenges when she was a child that I cannot even imagine,” Clinton said. “And her determination to build a better life for her children and then sort of that determination that my mother and my father then had to build a better life for me is something that I feel elevated by.” In her autobiography, “Living History,” Hillary Clinton wrote that her mother was “essentially abandoned” by her grandmother as a young girl. Rodham was sent to live with her grandparents at the age of 8, and left home at 14 to work as a nanny. After marrying Hugh Rodham, a traveling salesman, in 1942, Rodham became a stay-at-home mom. Clinton would later describe her as a “classic homemaker.” “Her story was a quintessentially American one, largely because she wrote it herself,” the Clinton family said in Tuesday’s statement. “She overcame abandonment and hardship as a young girl to become the remarkable woman she was.” Rodham, who has lived with Bill and Hillary Clinton outside Washington since 2006, fell ill Monday night. She died at Georgetown University Hospital, surrounded by family, according to the Clinton family’s statement. ||||| Dorothy Rodham, mother of Secretary of State Hillary Rodham Clinton and former President Bill Clinton's mother-in-law, died Tuesday at age 92 after an illness. FILE - In a July 14, 1992 file photo, Hillary Clinton, right, and her mother Dorothy Rodham are shown in their New York hotel room. Dorothy Rodham died shortly after midnight on Tuesday, Nov. 1, 2011... (Associated Press) FILE - In a Saturday, June 7, 2008 file photo, Dorothy Rodham, mother of Sen. Hillary Rodham Clinton, D-N.Y., wipes away a tear as her daughter addresses supporters at the National Building Museum in... (Associated Press) FILE -In this May 1, 2008 file photo, then-Democratic presidential hopeful Sen. Hillary Rodham Clinton, D-N.Y., right, helps her mother, Dorothy Rodham, walk up to the stage during a campaign event in... (Associated Press) The family said Rodham died shortly after midnight, surrounded by her family in Washington. The secretary of state cancelled a planned trip to London and Istanbul to be at her mother's side. Dorothy Rodham was a witness to her daughter's political victories and defeats. She avoided the spotlight and rarely gave interviews about herself or her daughter and son-in-law, the former president. A notable exception was her daughter's 2008 bid for the Democratic nomination for president. She appeared with her daughter in primary states, particularly at events focusing on women's issues. Clinton cited her mother in at least one ad during the campaign, saying that her mother had taught her to stand up for herself and to stand up for those who needed help. As Clinton battled Barack Obama for the nomination in April 2008, Rodham joined her daughter and granddaughter at a campaign event at Haverford College, Pa. Then 88, Rodham didn't speak at the event, but Hillary Clinton noted that her mother lived with her and "always has a lot of great ideas about what we need to be doing," drawing chuckles from the audience. When Clinton ended her campaign during a speech in June 2008 at Washington's National Building Museum, her mother watched from off stage and wiped a tear as Clinton conceded the nomination to Obama. The following February, Rodham was on hand as her daughter was sworn in as Obama's secretary of state. Dorothy Howell Rodham was born in Chicago in 1919, the daughter of a city firefighter. In her autobiography, "Living History," Hillary Clinton described her mother's childhood as lonely and loveless. The Howells shuttled Dorothy and her younger sister, Isabelle, among relatives and schools. She was 8 when her parents divorced in 1927 and she was sent with her sister to live with their paternal grandparents in Alhambra, Calif. Her grandmother could be cruel when not ignoring young Dorothy, Clinton wrote. Rodham left her grandparents' home at 14 when she found room and board as a mother's helper to another family. After graduating from high school, she returned to Chicago on her mother's promise of helping to pay for a college education if she lived with her and her new husband. After that promise was unfulfilled, Rodham supported herself with a job in an office. "I'm still amazed at how my mother emerged from her lonely early life as such an affectionate and levelheaded woman," Clinton wrote. She met Hugh E. Rodham, a native of Scranton, Pa., who had found work in Chicago as a traveling salesman. They courted for several years before marrying in 1942. Besides their daughter, they raised two sons, Hugh and Tony. The Clinton family plans a private memorial service for Rodham. Clinton has often credited her mother with inspiring her, saying Rodham overcame adversity and abandonment in her own early life. ||||| Our condolences to Secretary of State Hillary Rodham Clinton, whose mother passed away this morning. Dorothy Rodham, often credited by her daughter for her success in public life, was 92. "She overcame abandonment and hardship as a young girl to become the remarkable woman she was," said a statement from the Clinton family: "A warm, generous and strong woman; an intellectual; a woman who told a great joke and always got the joke; an extraordinary friend and, most of all, a loving wife, mother and grandmother." The former first lady had canceled a planned State Department trip to Europe to be with her mother. Mrs. Rodham is also survived by her son-in-law, former president Bill Clinton. The funeral will be private. In an obituary, The Washington Post described Mrs. Rodham as "a suburban Chicago homemaker who endured a devastating childhood and served as an inspiration to her daughter, Hillary Rodham Clinton, one of the most accomplished women in U.S. history:" Mrs. Rodham spent decades as a familiar but unflashy presence alongside her daughter, Hillary Rodham Clinton, and son-in-law, Bill Clinton. She accompanied them to Arkansas, where Bill Clinton was governor, and then to Washington as the Clinton family fortunes rose. Sturdy and down-to-earth, Mrs. Rodham was known among family friends for her sense of humor and curiosity, traits she passed on to her eldest child at an early age. Later in life, she grew close to her grandchildren, especially Chelsea. Mrs. Rodham never worked outside the home, raising three children in the suburban enclave of Park Ridge, Ill., under the watchful eye of her husband, a conservative Republican who owned a drapery-making business. In a restrictive household dominated by its patriarch, Mrs. Rodham funneled ambition and a passion for learning to her only daughter, who has long credited her mother with giving her the tools -- and toughness -- to enter politics. During her presidential campaign in 2008, Hillary Clinton said she owed her inspiration to one person: "My mother, who never got a chance to go to college, who had a very difficult childhood, but who gave me a belief that I could do whatever I set my mind." Dorothy Howell was born June 4, 1919, in Chicago, the eldest of two daughters of Edwin Howell Jr., a firefighter, and Della Murray. Her parents' marriage turned violent. After their divorce in the late 1920s, they sent their daughters -- Dorothy and Isabelle -- alone on a train to California to live with their paternal grandparents. They were severe and unpredictable disciplinarians. The full statement from the Clinton family:

– Dorothy Rodham, Hillary Clinton’s mother, died shortly after midnight, surrounded by her family at Georgetown University Hospital in Washington, the Clinton family announced today. She was 92, and had been living with her daughter in Washington since 2006. Clinton canceled a planned trip to London and Istanbul to be with her when she fell ill last night, ABC News reports. In its statement, the family said Rodham “overcame abandonment and hardship … to become the remarkable woman she was.” They asked well-wishers to make a donation in her name to George Washington Hospital, the Heifer Project, or a local charity of their choice. Rodham had mostly avoided the spotlight during her daughter and son-in-law’s political careers, but did appear alongside Clinton a few times during her campaign for the Democratic nomination in 2008, the AP notes. Click through the gallery for photos from Rodham's life.

It's here!! Nicki Minaj and Meek Mill have finally blessed us with their sexy spread for GQ's October issue! And besides the two claiming they're not actually engaged, it seems this editorial is really what's going to convince people to take their relationship seriously. Related: Nicki Shows Off Her Killer Body In A Mesh Outfit! After all, the Anaconda rapper never did a shoot with her ex, Safaree Samuels! Anyway, we got a glimpse of the rappers' spread in their BTS video, but the actual pictures are way hotter!! Just take a peek at Nicki's Alexander Wang outfit and Giuseppe Zanotti heels! Need we say more?? So read on for the HIGHlights and get to know these two better. Oh, and to hear their thoughts on the MTV VMAs controversy, Drake, and MORE... [Image via Ellen von Unwerth/GQ.] ||||| Lindsay Lohan Lifetime Producers Worried Sick -- THEY DON'T GET IT! EXCLUSIVE Sources close to's Lifetime movie tell TMZ ... producers have been in hysterics these past few weeks over LiLo's latest hijinks, and we're left to wonder ... WHY?!?!?!According to our sources, producers were particularly upset over her car accident on PCH. We're told the producers have five big concerns:-- The company that insures the movie might bail-- Her probation could be violated for lying to the cops-- She could be prosecuted for lying to police-- She could crash her car again-- She's going to clubs where bad things happenBut here's the thing ... when has a Lifetime movie ever gotten this much press (besides the one where played a hooker )? And don't they know ... nothing bad ever REALLY happens to Lindsay.$10 says "Liz & Dick" is the most watched program in the network's history. ||||| Never a dull moment in the life of Lindsay Lohan and those she comes into contact with: Two Hollywood unions are investigating working conditions on the set of "Liz & Dick," the actress' Lifetime movie, after Lohan was found unresponsive and required medical attention and two crew members left the project. "Liz & Dick" tells the story of Elizabeth Taylor and Richard Burton. Filming the project has proven somewhat difficult for Lohan, who was not only the subject of hospitalization rumors (Lohan was later said to be asleep -- not unconscious -- and never went to the hospital) but also crashed her car while driving in Los Angeles. Two other crew members were actually sent to the hospital for exhaustion and dehydration. Lohan tweeted that she had been working 85 hours in four days. SAG-AFTRA confirmed to THR that they were looking into the matter and said they were not yet prepared to report their findings. Though IATSE declined comment to THR, sources said that union's agents were indeed looking into the matter. As for Lohan, reports of concerned family members continue to surface. One industry source told The Huffington Post that Lohan was viewed as a "ticking time bomb," a macabre reference the source explained by adding, "If Lindsay hadn’t been making a movie, who would have called for help? As soon as filming wraps, she will be all alone again." The 25-year-old actress is under a great deal of pressure to orchestrate a comeback before her star -- already tarnished by multiple run-ins with the legal system -- fades beyond repair. Earlier: Lohan's on-set wardrobe malfunction, the whole story of her medical scare and family and friends concerns. Also on HuffPost: ||||| The seed for this crawl was a list of every host in the Wayback Machine This crawl was run at a level 1 (URLs including their embeds, plus the URLs of all outbound links including their embeds) The WARC files associated with this crawl are not currently available to the general public.

– Though they should have known what they were in for the moment they hired her, the producers of Lindsay Lohan's upcoming Lifetime movie are reportedly "hysterical" over the actress' recent car crash and exhaustion incident. Sources tell TMZ the producers are particularly worried they may lose their insurance over the car crash, or that Lindsay could face legal issues for lying to police … or that she could simply get into yet more trouble of some other sort, whether car-related or nightclub-related. They're probably also not too happy that LiLo's explanation for her exhaustion ("working 85hours in 4days, and being up all night shooting," she tweeted) ended up getting the working conditions on the set investigated by two Hollywood unions. But Perez Hilton notes that some crew members say Lohan was exaggerating, and absolutely "did not work 85 hours in four days." TMZ points out that this is quite a bit of publicity, however, and that Lifetime could end up quite happy if it boosts the ratings for Liz & Dick. For more, click to listen to the 911 call made over Lohan's exhaustion.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Greenhouse Gas Observation and Analysis System Act''. SEC. 2. PURPOSES. The purposes of this Act are-- (1) to establish a comprehensive national greenhouse gas observation and analysis system to support verification of greenhouse gas emissions; (2) to establish a baseline characterizing the influence of current and past greenhouse gas emissions on atmospheric composition; and (3) to provide a scientifically robust record of atmospheric greenhouse gas concentrations. SEC. 3. ESTABLISHMENT OF GREENHOUSE GAS OBSERVATION AND ANALYSIS SYSTEM. (a) In General.--The Administrator shall establish a greenhouse gas observation and analysis system that will offer the resolution and widespread coverage required to verify reduction and mitigation of greenhouse gases. In establishing the system, the Administrator shall coordinate with the Department of Commerce's National Institute of Standards and Technology, the National Aeronautics and Space Administration, the National Science Foundation, the Department of Energy, the Department of Agriculture, and the United States Geological Survey. (b) System Components.--The system-- (1) shall be an operational and scientifically robust greenhouse gas observation and analysis system that includes local and regional ground-based observations, space-based observations, carbon-cycle modeling, greenhouse gas inventories, meta-analysis, and extensive data integration and distribution to provide quantitative information about sources, sinks, and fluxes of greenhouse gases at relevant temporal and spatial scales; and (2) shall be capable of-- (A) differentiating between source and sink exchanges; (B) identifying types of emissions (fossil-fuel and non-fossil fuel sources); and (C) tracking agricultural and other sinks; and (3) shall include-- (A) sustained ground, sea, and air-based measurements; (B) sustained space-based observations; (C) measurements of tracer, including isotopes and non-carbon dioxide gases; (D) carbon cycle monitoring; (E) carbon cycle modeling; (F) traceability to the International System of Units; and (G) data assimilation and analysis. (c) Coordination.--The Administrator shall, to the extent appropriate-- (1) facilitate coordination of-- (A) observations and modeling; (B) data and information management systems, including archive and access; and (C) the development and transfer of technologies to facilitate the evaluation of greenhouse gas emission reductions, offsets, and other mitigation strategies; (2) coordinate with the National Institute of Standards and Technology to make sure that the greenhouse gas observation and analysis system is based upon quantitative measurements traceable to international standards; and (3) coordinate with other Federal agencies and international organizations and agencies involved in international or domestic programs. SEC. 4. SYSTEM PLAN. (a) In General.--Not later than 1 year after the date of enactment of this Act, the Administrator shall, in coordination with the agencies described in section 3, develop and submit a plan for an integrated and comprehensive greenhouse gas observation and analysis system to the Senate Committee on Commerce, Science, and Transportation and the House of Representatives Committee on Science and Technology. (b) Plan Requirements.--The plan shall-- (1) identify and describe current national and international greenhouse gas observation networks, modeling, and data analysis efforts; (2) contain an inventory of agency data relevant to greenhouse gases; (3) assess gaps, conflicts, and opportunities with respect to the matters described in paragraphs (1) and (2); (4) establish priorities, define agency roles, and make recommendations on necessary capacity and capabilities for-- (A) ground, sea, and air-based measurements; (B) sustained space-based observations; (C) measurements of tracer, including isotopes and non-carbon dioxide gases; (D) carbon cycle monitoring; (E) carbon cycle modeling; (F) measurement traceability and comparability; (G) data assimilation and analysis; and (H) data archive management and data access; and (5) establish and define mechanisms for ensuring continuity of domestic and international greenhouse gas measurements, and contribute to international efforts to build and operate a global greenhouse gas information system, in coordination with the World Meteorological Organization and other international organizations and agencies, as appropriate. SEC. 5. REPORTS. The Administrator shall, not less than every 4 years after the date of enactment of this Act and in coordination with the agencies described in section 3, submit a report to the Senate Committee on Commerce, Science, and Transportation and the House of Representatives Committee on Science and Technology that includes-- (1) an analysis of the progress made toward achieving the goals and objectives of the plan outlined in section 4; (2) an evaluation of the effectiveness of the system; (3) recommendations concerning modifications to the system; (4) an analysis of the consistency of reported greenhouse gas emission reductions with independent observations of atmospheric and Earth-system trends; and (5) an update on changes or trends in Earth-system sources and sinks of greenhouse gases. SEC. 6. AGREEMENTS. (a) In General.--The Administrator may enter into and perform such contracts, leases, grants, cooperative agreements, or other agreements as may be necessary to carry out the purposes of this Act. (b) Specific Authority.--Notwithstanding any other provision of law, the Administrator may-- (1) enter into long-term leases of up to 20 years for the use of unimproved land to site small shelter facilities, antennae, and equipment including weather, tide, tidal currents, river, and air sampling or measuring equipment; (2) enter into long-term licenses of up to 20 years at no cost to site facilities and equipment including weather, tide, tidal currents, river, and air sampling or measuring equipment; (3) acquire (by purchase, lease, or otherwise), lease, sell, and dispose of or convey services, money, securities, or property (whether real, personal, intellectual, or of any other kind) or an interest therein; (4) construct, improve, repair, operate, maintain, outgrant, and dispose of real or personal property, including buildings, facilities, and land; and (5) waive capital lease scoring requirements for any lease of space on commercial antennas to support weather radio equipment, air sampling, or measuring equipment. (c) Certain Leased Equipment.--Notwithstanding any other provision of law, rule, or regulation, leases of antenna or equipment on towers or other structures shall be considered operating leases for the purpose of capital lease scoring. SEC. 7. EFFECT ON OTHER LAWS. Nothing in this Act shall be construed to supersede or alter the existing authorities of any Federal agency with respect to Earth science research or greenhouse gas mitigation. SEC. 8. DEFINITIONS. In this Act: (1) Administrator.--The term ``Administrator'' means the Administrator of the National Oceanic and Atmospheric Administration. (2) Earth-system.--The term ``Earth-system'' means the Earth's biosphere, including the ocean, atmosphere, and soils that influence the amounts of greenhouse gas in the atmosphere. (3) Greenhouse gas.--The term ``greenhouse gas'' means a gas in the atmosphere that increases the radiative forcing of the Earth-atmosphere system. (4) International system of units.--The term ``International System of Units'' means the modern metric system of units established in 1960 by the 11th General Conference on Weight and Measures. (5) Radiative forcing.--The term ``radiative forcing'' means the measure of the influence that a substance or process has in altering the balance of incoming and outgoing energy in the Earth-system. (6) Sink.--The term ``sink'' means the removal of a greenhouse gas from the atmosphere. (7) Source.--The term ``source'' means the emission of a greenhouse gas into the atmosphere. (8) System.--The term ``system'' means the national greenhouse gas observation and analysis system established under section 3. (9) Tracer.--The term ``tracer'' means an atmospheric substance that can be used to assess or determine the origin of a greenhouse gas. SEC. 9. AUTHORIZATION OF APPROPRIATIONS. There are authorized to be appropriated to the Secretary of Commerce such sums as appropriate to carry out this Act.

Greenhouse Gas Observation and Analysis System Act - Directs the Administrator of the National Oceanic and Atmospheric Administration (NOAA) to establish a greenhouse gas observation and analysis system that will offer the resolution and widespread coverage required to verify reduction and mitigation of greenhouse gases. Requires the system to: (1) be an operational and scientifically robust greenhouse gas observation system that provides quantitative information about sources, sinks, and fluxes of greenhouse gases at relevant temporal and spatial scales; (2) be capable of differentiating between source and sink exchanges, identifying types of emissions, and tracking agricultural and other sinks; and (3) include sustained ground, sea, and air-based measurements, sustained space-based observations, measurements of tracer, carbon cycle monitoring and modeling, traceability to the International System of Units, and data assimilation and analysis. Directs the Administrator to develop and submit to specified congressional committees a plan for an integrated and comprehensive greenhouse gas observation and analysis system, which shall: (1) describe current greenhouse gas observation networks, modeling, and data analysis efforts; (2) contain an inventory of agency data relevant to greenhouse gases; (3) assess gaps, conflicts, and opportunities with respect to such efforts and data; (4) establish priorities, define agency roles, and make recommendations on necessary capacity and capabilities for measurements, monitoring, modeling, analysis, and data management; (5) establish mechanisms for ensuring continuity of greenhouse gas measurements; and (6) contribute to international efforts to build and operate a global greenhouse gas information system. Requires the Administrator to report to Congress every four years on the effectiveness of the system, progress in achieving plan objectives, the consistency of reported greenhouse gas emissions with independent observations, and changes in Earth-system sources and sinks of greenhouse gases.

the parent compounds of iron pnictide superconductors such as bafe@xmath7as@xmath7 and srfe@xmath7as@xmath7 exhibit a tetragonal - to - orthorhombic structural transition at @xmath0 followed by development of collinear antiferromagnetic ( af ) order along the @xmath12-axis of the orthorhombic lattice below @xmath10 [ left inset in fig . 1(a ) and @xmath13 @xcite . upon electron - doping via partially substituting fe by co or ni to form bafe@xmath14as@xmath3 ( @xmath15 co , ni ) , the nearly coupled structural and magnetic phase transitions in bafe@xmath7as@xmath7 become two separate second order phase transitions at @xmath0 and @xmath10 ( @xmath16 ) that decrease in temperature with increasing @xmath17 @xcite . on the other hand , the coupled first order structural and magnetic phase transitions in srfe@xmath7as@xmath7 @xcite , while decreasing in temperature with increasing @xmath17 in srfe@xmath14as@xmath3 , remain coupled first order transitions leading up to superconductivity @xcite . because the structural and magnetic phase transitions in bafe@xmath14as@xmath3 and srfe@xmath14as@xmath3 occur below room temperature , iron pnictides in the orthorhombic af ground state will form twin domains with af bragg peaks appearing at the in - plane @xmath18 and @xmath19 positions in reciprocal space [ right inset in fig . 1(a ) ] @xcite . to probe the intrinsic electronic properties of these materials , one can apply uniaxial pressure along one axis of the orthorhombic lattice to obtain single domain samples @xcite . indeed , transport measurements on uniaxial pressure detwinned electron - doped bafe@xmath14as@xmath3 ( @xmath15 co , ni ) reveal in - plane resistivity anisotropy in the af state that persists to temperatures above the zero - pressure @xmath10 and @xmath0 @xcite . on the other hand , similar transport measurements on uniaxial pressured detwinned srfe@xmath14as@xmath3 ( @xmath15 co , ni ) indicate vanishingly small resistivity anisotropy at temperatures above the zero pressure coupled @xmath10 and @xmath0 @xcite . figure 1(b ) compares temperature dependence of the resistivity anisotropy [ defined as @xmath20 , where @xmath21 and @xmath22 are resistivity along the @xmath12 and @xmath23 axis of the orthorhombic lattice , respectively ] obtained under 20 mpa uniaxial pressure for bafe@xmath7as@xmath7 , bafe@xmath5ni@xmath6as@xmath7 , srfe@xmath5ni@xmath6as@xmath7 , and srfe@xmath7as@xmath7 . consistent with earlier works @xcite , we find that resistivity anisotropy is much larger in bafe@xmath7as@xmath7 and bafe@xmath5ni@xmath6as@xmath7 at temperatures above @xmath10 . although resistivity anisotropy in the paramagnetic state of the iron pnictides under applied uniaxial pressure suggests the presence of an electronic nematic phase that breaks the in - plane fourfold rotational symmetry ( @xmath24 ) of the underlying tetragonal lattice @xcite , much is unclear about the microscopic origin of the in - plane resistivity anisotropy and electronic nematic phase @xcite . since neutron scattering experiments reveal that uniaxial pressure necessary to detwin the sample also increases @xmath10 of the system , the observed in - plane resistivity anisotropy above the zero pressure @xmath10 and @xmath0 may arise from the increased @xmath10 and intrinsic anisotropic nature of the collinear af phase @xcite . furthermore , while it is generally assumed that the uniaxial pressure for sample detwinning has negligible effect on the lattice parameters of the iron pnictides @xcite , the precise effect of uniaxial pressure on structural distortion of these materials is unknown . from neutron extinction effect measurements , a uniaxial pressure is suggested to push structural fluctuations related to the orthorhombic distortion to a temperature well above the zero - pressure value of @xmath0 @xcite , similar to the effect on the resistivity anisotropy @xcite . to understand the microscopic origin of the in - plane resistivity anisotropy in the paramagnetic state @xcite , it is important to establish the effect of a uniaxial pressure on the magnetic and structural phase transitions of bafe@xmath14as@xmath3 and srfe@xmath14as@xmath3 , and determine if the electronic anisotropy in the paramagnetic tetragonal phase of iron pnictides is intrinsic @xcite , or entirely due to the symmetry breaking uniaxial pressure applied to the materials @xcite . it is also important to deduce what role the nature of the af transition plays in the nematic susceptibility @xcite and how the latter depends on the uniaxial pressure . ni@xmath25as@xmath7 with arrows marking @xmath26 and @xmath27 samples described in the present study . the af , pm , ort , tet , ic , sc are antiferromagnetic , paramagnetic , orthorhombic , tetragonal , incommensurate , and superconducting states , respectively @xcite . the left inset shows the direction of the applied uniaxial pressure ( marked by the vertical arrows ) and the spin arrangements of fe in the af ordered iron pnictides , where @xmath12 and @xmath23 are the orthorhombic axes . the right inset shows the corresponding reciprocal lattice . all the marked positions have af or nuclear bragg peaks for a twinned sample , while the positions marked by open symbols have vanishing scattering intensity for a detwinned sample . ( b ) temperature dependence of the resistivity anisotropy for bafe@xmath1ni@xmath2as@xmath3 and srfe@xmath1ni@xmath2as@xmath3 ( @xmath28 ) under @xmath29 mpa . ( c ) summary of temperature dependence of the uniaxial pressure induced lattice distortion at @xmath30 mpa [ @xmath31 for bafe@xmath1ni@xmath2as@xmath3 ( @xmath4 ) and srfe@xmath5ni@xmath6as@xmath7 . the actual data for @xmath32 are normalized to 20 pma assuming a linear relationship between uniaxial pressure and @xmath33 . uniaxial pressure induced lattice distortion vanishes rapidly below @xmath10 marked by the vertical dashed lines in ( b ) and ( c ) . , width=264 ] in this paper , we use neutron resonance spin echo ( nrse ) @xcite and larmor diffraction @xcite to study the effect of uniaxial pressure on the structural and magnetic phase transitions in electron doped iron pnictides bafe@xmath1ni@xmath2as@xmath3 with @xmath34 @xcite and srfe@xmath5ni@xmath6as@xmath7 @xcite , and in the isovalently doped bafe@xmath7(as@xmath8p@xmath9)@xmath7 @xcite . while the underdoped bafe@xmath5ni@xmath6as@xmath3 ( @xmath35 k and @xmath36 k ) exhibits a second - order af transition below @xmath0 , srfe@xmath5ni@xmath6as@xmath7 has coupled first - order structural and magnetic phase transitions at @xmath37 k @xcite . the electron overdoped bafe@xmath38ni@xmath39as@xmath3 ( @xmath40 k ) and isovalently doped bafe@xmath7(as@xmath8p@xmath9)@xmath7 ( @xmath41 k ) have a paramagnetic tetragonal structure at all temperatures without static af order . figure 1(c ) summarizes the key experimental result of the present work , where the temperature dependences of the uniaxial pressure induced orthorhombic lattice distortion @xmath42 are determined using neutron larmor diffraction for bafe@xmath7as@xmath7 , bafe@xmath5ni@xmath6as@xmath3 , srfe@xmath5ni@xmath6as@xmath7 , and bafe@xmath38ni@xmath39as@xmath3 [ we defined the lattice distortion @xmath43 with @xmath12 and @xmath23 being the orthorhombic lattice parameters ] . remarkably , the magnitude of our determined structural nematic susceptibility @xmath44 in figure 1(c ) is comparable in all three materials that have a structural phase transition , unlike the very different values of the resistivity anisotropy displayed in figure 1(b ) . comparing these results with those of the elastoresistance and nematic susceptibility obtained from transport @xcite and from elastic shear modulus / ultrasound spectroscopy measurements @xcite , we conclude that the resistivity anisotropy in the paramagnetic phase of the iron pnictides depends sensitively on whether the underlying magnetic phase transition is first or second order . we also find a strong coupling between the uniaxial pressure induced lattice distortion and the electronic nematic susceptibility , and have to be cautious in directly relating resistivity anistropy to the nematic order parameter in the iron pnictides . for the zero ( @xmath45 ) and uniaxial pressured ( @xmath46mpa ) bafe@xmath5ni@xmath6as@xmath7 . @xmath10 is @xmath47k for an unpressured sample ( blue diamonds ) . upon applying uniaxial pressure of @xmath46 mpa , the @xmath10 is enhanced to @xmath48k and the sample becomes @xmath49 detwinned as seen by puma and trisp measurements . ( b ) the energy line width ( half - width - at - half - maximum , @xmath50 ) of the magnetic bragg peak @xmath51 measured by nrse using trisp for bafe@xmath5ni@xmath6as@xmath7 . the blue and red dashed lines indicate @xmath10 in @xmath45 and @xmath52 mpa unaixial pressure , respectively . the slight larger errors of @xmath50 near @xmath10 is due to low statistics data . , width=264 ] our experiments were carried out using conventional thermal triple - axis spectrometer puma and three axes spin echo spectrometer ( trisp ) at the forschungsneutronenquelle heinz maier - leibnitz ( mlz ) , garching , germany . the principles of nrse and larmor diffraction are described elsewhere @xcite . single crystals of bafe@xmath1ni@xmath2as@xmath3 , srfe@xmath1ni@xmath2as@xmath7 , and bafe@xmath7(as@xmath8p@xmath9)@xmath7 were grown by self - flux method as described before @xcite . we define the momentum transfer @xmath53 in the three - dimensional reciprocal space in @xmath54 as @xmath55 , where @xmath56 , @xmath57 , and @xmath58 are miller indices and @xmath59 , @xmath60 , @xmath61 with @xmath62 , and @xmath63 for bafe@xmath1ni@xmath2as@xmath3 . in this notation , the af bragg peaks should occur at @xmath64 ( @xmath65 ) positions in reciprocal space of a completely detwinned sample [ right inset in fig . 1(a ) ] . for neutron scattering experiments , single crystals are aligned in either the @xmath66 $ ] @xcite or @xmath67 $ ] zone . we first discuss the effect of uniaxial pressure on the collinear af order in bafe@xmath14as@xmath3 . in previous neutron scattering work on bafe@xmath1co@xmath2as@xmath3 , the n@xmath68el temperature ( @xmath10 ) was found to be pushed to higher temperature under uniaxial strain field , forming a broader magnetic transition @xcite . moreover , it seems that the increase in @xmath10 depends on the annealing condition @xcite . although the @xmath10 enhancement was attributed to uniaxial strain aligned fluctuating magnetic domains , the effect of uniaxial pressure on the ordered moment remains elusive and the nature of the @xmath10 enhancement is still under debate @xcite . by aligning single crystals in the @xmath69\times [ 0,1,1]$ ] scattering plane @xcite , we were able to determine @xmath10 , detwinning ratio , as well as the ordered moment of the system under zero and finite uniaxial pressures . figure 2(a ) shows temperature dependence of the @xmath70 and @xmath71 magnetic scattering intensity for bafe@xmath5ni@xmath6as@xmath3 obtained using puma [ left axis in fig . 2(a ) ] and trisp ( right axis ) . the two sets of data are in excellent quantitative agreement with each other . under the applied uniaxial pressure of @xmath72 mpa , the nel temperature increases from @xmath73 k ( at @xmath45 ) to @xmath74 k. the magnetic scattering intensity [ fig . 2(a ) ] in the @xmath70 peak becomes approximately twice as large as in the twinned sample , whereas the @xmath71 peak vanishes , suggesting that the sample is completely detwinned and the applied uniaxial pressure does not significantly affect the ordered moment . to test whether the @xmath10 increase is an intrinsic feature of the system , we note that the magnetic order parameter under uniaxial pressure has a round tail around @xmath10 @xcite , suggesting that the @xmath10 enhancement could arise from enhanced slow spin dynamics ( critical scattering ) under inhomogeneous uniaxial strain field and can not be resolved by conventional triple - axis neutron diffraction due to its coarse energy resolution ( @xmath75 mev ) . to clarify the nature of the increase in @xmath10 , we have measured the energy line - width ( @xmath76 , [ see fig . 2(b ) ] ) of the quasielastic scattering for magnetic reflection @xmath77 using high energy resolution ( @xmath78 @xmath79ev ) nrse at trisp @xcite . as seen in figure 2(b ) , the @xmath50 at all measured temperatures are resolution limited , indicating that the increase in magnetic scattering intensity below @xmath74 k is elastic ( @xmath80ev ) , and an intrinsic nature of the system . in sev eral iron pnictides under different uniaxial pressures obtained from neutron larmor diffraction experiments @xcite . ( a ) temperature dependence of @xmath81 in fwhm for the @xmath82 bragg reflection of bafe@xmath7as@xmath7 at @xmath45 and 20 mpa . the solid line above @xmath10 is a fit using curie - wiess formalism [ @xmath83 , where @xmath84 and @xmath85 are fitting parameters ] . ( b ) similar data for srfe@xmath5ni@xmath6as@xmath7 . the vertical blue and red dashed lines in ( a ) and ( b ) mark the @xmath10 of the sample at zero and finite pressure , respectively . ( c ) similar data for bafe@xmath5ni@xmath6as@xmath7 , where the vertical green and blue dashed lines mark @xmath10 and @xmath0 , respectively , at zero pressure . the open green and yellow squares mark measurements of fwhm under zero pressure ( fresh ) at the @xmath82 and @xmath86 bragg peaks , respectively . the pink solid circles are identical measurements under @xmath87 mpa uniaxial pressure on @xmath82 . the solid green diamonds are data after uniaxial pressure is released . the vertical red dashed line indicate the peak position of the fwhm under @xmath88 mpa . ( d ) temperature dependence of fwhm in @xmath81 for bafe@xmath7(as@xmath8p@xmath9)@xmath7 at @xmath45 mpa ( solid green circles ) , bafe@xmath38ni@xmath39as@xmath7 at @xmath45 ( solid green diamonds ) and 14 mpa ( solid red circles ) . , width=264 ] to determine the effect of uniaxial pressure on the tetragonal - to - orthorhombic phase transition in iron pnictides , we carried out neutron larmor diffraction experiments capable of measuring minor change of lattice spacing @xmath89 and its spread @xmath90 with a resolution better than @xmath91 in @xmath81 [ inset in fig . 3(a ) ] @xcite . we focus on @xmath82 and @xmath86 nuclear bragg reflections corresponding to a @xmath92-spacing @xmath93 , which we measured in bafe@xmath1ni@xmath2as@xmath3 ( @xmath34 ) , srfe@xmath5ni@xmath6as@xmath7 , and bafe@xmath7(as@xmath8p@xmath9)@xmath7 both on freshly prepared samples ( uniaxial pressure @xmath45 ) and under uniaxial pressure ( @xmath94 mpa ) . figure 3 shows the temperature and pressure dependence of the @xmath92 spread for these samples . the @xmath92 spread are characterized by the fwhm ( full - width - half - maximum ) of the lattice spacing distribution @xmath95 , which is assumed to be gaussian distribution @xcite . the diamonds in figure 3(a ) show temperature dependence of the fwhm for bafe@xmath7as@xmath7 at zero pressure . similar to bafe@xmath5ni@xmath6as@xmath3 @xcite , temperature dependence of fwhm follows a curie - wiess form and peaks around the zero - pressure value of @xmath96 . upon application of a uniaxial pressure @xmath29 mpa , the magnitude of fwhm increases at all temperatures and now peaks at an enhanced @xmath97 k [ fig . 3(a ) ] . figure 3(b ) shows similar data for srfe@xmath5ni@xmath6as@xmath7 , where there are coupled strong first order structural and af phase transitions at @xmath98 k @xcite . compared with bafe@xmath7as@xmath7 , where the af phase transition is weakly first order and structural transition is second order @xcite , the af and structural transition induced changes in fwhm are much smaller and confined to temperatures close to @xmath96 in srfe@xmath5ni@xmath6as@xmath7 [ fig . 3(b ) ] . under a uniaxial pressure @xmath29 mpa , however , both the fwhm and @xmath10 increase dramatically with solid lines showing curie - wiess fits to the data . for bafe@xmath5ni@xmath6as@xmath3 , application of a @xmath87 mpa uniaxial pressure transforms temperature dependence of the fwhm , which forms a broad peak above the zero - pressure value of @xmath0 . upon releasing the uniaxial pressure [ @xmath99 released , filled green diamonds in fig . 3(c ) ] , the system goes back to the original unpressured fresh state . figure 3(d ) compares temperature dependence of the fwhm for electron overdoped bafe@xmath38ni@xmath39as@xmath3 and bafe@xmath7(as@xmath8p@xmath9)@xmath7 , where both materials are in the paramagnetic tetragonal state without static af order . the weak temperature dependence of fhwm in these materials suggests that the large temperature dependence of fwhm in af ordered bafe@xmath1ni@xmath2as@xmath3 ( @xmath28 ) and srfe@xmath5ni@xmath6as@xmath7 is due to a strong magnetoelastic coupling . although application of a @xmath100 mpa uniaxial pressure on bafe@xmath38ni@xmath39as@xmath3 increases the absolute value of fwhm , it is still weakly temperature dependent [ fig . 3(d ) ] . to further demonstrate the impact of uniaxial pressure on the tetragonal - to - orthorhombic structural transition in bafe@xmath1ni@xmath2as@xmath3 ( @xmath34 ) and srfe@xmath5ni@xmath6as@xmath7 , we compare in figure 4 temperature dependence of the lattice parameters along the orthorhombic @xmath12 and @xmath23 axis directions under zero and finite uniaxial pressure . we first discuss results for bafe@xmath1ni@xmath2as@xmath3 with @xmath101 [ fig . 4(a ) , 4(b ) ] and 0.03 [ fig . 4(c ) and 4(d ) ] . at @xmath45 , the lattice parameters have @xmath102 at temperatures above @xmath0 ( tetragonal phase ) and decrease linearly with decreasing temperature [ open diamonds and hexagons in fig . 4(a ) and 4(c ) ] . upon application of a uniaxial pressure , the system becomes orthorhombic at all temperatures and the orthorhombic structural transition becomes a crossover [ filled diamonds and hexagons in fig . 4(a ) and 4(c ) ] . figures 4(b ) and 4(d ) show temperature dependence of the lattice orthorhombicity @xmath43 at different uniaxial pressures for @xmath101 , and 0.03 , respectively . for unpressured fresh samples ( @xmath45 ) , and after the pressure has been released , the tetragonal structure becomes orthorhombic below @xmath0 and the af order below @xmath10 further enhances the lattice orthorhombicity @xcite . upon applying the uniaxial pressure @xmath87 , 15 , and 20 mpa , the temperature dependence of the lattice orthorhombicity becomes remarkably similar to that of the @xmath103 elastoresistance and nematic susceptibility of bafe@xmath14as@xmath3 obtained from transport @xcite and elastic shear modulus / ultrasound spectroscopy measurements @xcite , respectively . to understand the temperature dependence of the pressure - induced lattice orthorhombicity described in figs . 4(b ) and 4(d ) , we consider the ginzburg - landau free energy formalism used in previous works @xcite : @xmath104 = f_0 + \frac{a}{2}(t - t_0)\varphi^2 + \frac{\tilde{b}}{4}\varphi^4 + \frac{c_{66,0}}{2}\delta^2 - \lambda \delta\varphi - p\delta , \label{eq.landau}\ ] ] where the electronic nematic order parameter @xmath105 is coupled linearly to the orthorhombic lattice distortion @xmath33 . it then follows that ( see appendix @xcite ) @xmath106 where @xmath107 is the bare elastic constant that has no strong temperature dependence and @xmath99 is the conjugate uniaxial pressure ( stress ) @xcite . in the absence of the elasto - nematic coupling ( @xmath108 ) , the nematic susceptibility @xmath109 $ ] is characterized by the curie - weiss temperature @xmath110 . upon considering the coupling between the nematic order parameter @xmath105 and the structural lattice distortion @xmath33 ( or equivalently , the elastic shear strain @xmath111 ) , the elastic susceptibility takes on the form @xcite : @xmath112 with the renormalized nematic transition temperature @xmath113 that is increased compared to the bare curie - weiss temperature @xmath110 . the pressure - induced lattice distortions in figs . 4(b ) and 4(d ) can be well described by the curie - weiss functional form @xcite . therefore , uniaxial pressure induced orthorhombic lattice distortion and its temperature dependence in undoped and underdoped bafe@xmath1ni@xmath2as@xmath3 are directly associated with the nematic susceptibility @xcite . since the external uniaxial pressure explicitly breaks the tetragonal lattice symmetry , it turns the nematic transition at @xmath114 into a crossover , as is clearly seen in fig . if the in - plane resistivity anisotropy in electron underdoped iron pnictides indeed arises from the coupling of the uniaxial - pressure induced lattice distortion @xmath33 with the nematic susceptibility , it would be interesting to determine the effect of similar uniaxial pressure on the electron overdoped sample , where the resistivity anisotropy is known to be much weaker @xcite . figures 4(e ) and 4(f ) summarize the outcome of the neutron larmor diffraction experiments on uniaxial pressured bafe@xmath38ni@xmath39as@xmath3 , which is tetragonal ( @xmath102 ) and non - magnetic at all temperatures in zero pressure @xcite . figure 4(e ) shows temperature dependence of the lattice parameter changes along the @xmath12-axis ( @xmath115 ) and @xmath23-axis ( @xmath116 ) under a uniaxial pressure of @xmath100 mpa . for comparison , the thermal contraction of aluminum is also shown @xcite . figure 4(f ) shows the temperature dependence of the orthorhombic lattice distortion @xmath33 , which reveals a clear anomaly at @xmath117 consistent with ultrasonic spectroscopy measurements @xcite . while the applied uniaxial pressure induces orthorhombic lattice distortion at 230 k , the magnitude of the lattice distortion , @xmath118 , is about 5 times smaller than that of bafe@xmath7as@xmath7 and bafe@xmath5ni@xmath6as@xmath3 at 230 k. on cooling to 20 k , @xmath33 in bafe@xmath38ni@xmath39as@xmath3 increases to @xmath119 , while @xmath33 in bafe@xmath7as@xmath7 and bafe@xmath5ni@xmath6as@xmath3 becomes @xmath120 near @xmath0 [ fig . 4(b ) and 4(d ) ] , an order of magnitude larger than that of the electron overdoped compound . to understand how a uniaxial pressure affects the first order nature of the structural and magnetic phase transitions in srfe@xmath5ni@xmath6as@xmath7 , we compare in fig . 4(g ) and 4(h ) temperature dependence of the lattice parameters and orthorhombicity under the zero and finite uniaxial pressure . at zero pressure , the first order nature of the structural transition is clearly seen in hysteresis of temperature dependence of the lattice parameters and distortion [ fig . 4(g ) and 4(h ) ] . upon application of @xmath121 mpa uniaxial pressure , the lattice orthorhombicity no longer displays the first order transition at @xmath0 , but instead becomes a crossover , similar to that observed in the undoped and underdoped bafe@xmath1ni@xmath2as@xmath3 [ see figs . 4(b ) and 4(d ) ] . assuming that the application of the modest uniaxial pressure @xmath29 mpa can be considered in the linear - response regime @xcite , we can estimate the elastic susceptibility from the finite difference @xmath122 and compare it among the different compounds in the iron pnictide family . figure 1(c ) compares temperature dependence of @xmath123 for bafe@xmath1ni@xmath2as@xmath3 ( @xmath34 ) and srfe@xmath5ni@xmath6as@xmath7 normalized for @xmath124 . for af ordered bafe@xmath1ni@xmath2as@xmath3 ( @xmath28 ) and srfe@xmath5ni@xmath6as@xmath7 , the magnitudes of the pressure - induced lattice orthorhombicity are similar in the paramagnetic phase and vanish rapidly upon entering into the af ordered state . furthermore , the @xmath123 decreases for the iron pnictides with reduced @xmath10 , and are much smaller for bafe@xmath38ni@xmath39as@xmath3 . it is well known that the effect of increasing electron - doping in bafe@xmath14as@xmath3 is to suppress the static af order and to eliminate the low - temperature lattice orthorhombicity @xcite . at zero pressure , bafe@xmath7as@xmath7 first exhibits a second - order structural transition from the high - temperature paramagnetic tetragonal phase to a paramagnetic orthorhombic phase at @xmath0 , followed by a discontinuous further orthorhombic structural distortion and weakly first order af phase transition at @xmath10 ( @xmath125 ) due to magnetoelastic coupling @xcite . upon ni - doping in bafe@xmath1ni@xmath2as@xmath3 , the structural and magnetic phase transitions are gradually separated and suppressed [ fig . 1(a ) ] , and become second order in nature @xcite . upon application of a uniaxial pressure , the @xmath24 rotational symmetry of the tetragonal lattice is broken . since the tetragonal - to - orthorhombic symmetry of the underlying lattice can only be broken once , @xmath0 will become a crossover regardless the magnitude of the applied pressure , as our findings in figs . 3 and 4 corroborate . the same conclusion holds for srfe@xmath5ni@xmath6as@xmath7 where the first - order structural transition becomes a crossover [ see figs . 4(g ) and 4(h ) ] . therefore , both bafe@xmath1ni@xmath2as@xmath3 and srfe@xmath5ni@xmath6as@xmath7 under uniaxial pressure can only exhibit af phase transition . we note that our measurements and theoretical landau ginzburg analysis do not rely on the microscopic nature of the nematic order parameter @xmath105 . in particular , they apply equally well to the so - called ising spin nematic scenario @xcite or the orbital order interpretation of nematicity @xcite . in fact , the ferro - orbital order @xmath126 is always linearly coupled @xcite to the ising spin nematic order parameter @xmath127 , so the orbital order is generically present whenever @xmath128 , although there are theoretical indications that the converse is not always true . in other words , the orbital order can exist in the absence of static af order @xcite , as is known to be the case in fese @xcite . in either case , the application of external uniaxial stress renders the nematic transition a crossover , so that the lattice distortion @xmath33 and consequently @xmath105 are both finite above the zero - stress value of @xmath0 . in this light , the electronic anisotropy seen in the magnetic torque @xcite and scanning tunneling microscopy @xcite measurements above @xmath0 without explicit external uniaxial pressure is likely due to intrinsic local strain in these materials which breaks the @xmath24 rotational symmetry of the paramagnetic tetragonal phase . indeed , local strain - induced effect has recently been observed in free standing bafe@xmath7as@xmath7 above @xmath10 and @xmath0 @xcite . the key finding of the present work is that undoped bafe@xmath7as@xmath7 , as well as bafe@xmath5ni@xmath6as@xmath3 and srfe@xmath5ni@xmath6as@xmath7 all exhibit similar magnitudes of the pressure - induced lattice orthorhombicity [ fig . 1(c ) and fig . 4 ] and fwhm of @xmath81 near @xmath10 ( fig . this indicates that these samples experience similar strain field under nominally similar applied uniaxial pressure , thus suggesting that the doped ni impurities do not play an important role in determining the strain field inside the sample . theoretically , the electronic anisotropy of the iron pnictides is expected to couple linearly to the lattice orthorhombicity @xmath33 @xcite , as captured by the effective landau free energy in eq . ( [ eq.landau ] ) . the curie - weiss like temperature dependence of the uniaxial pressure induced lattice distortion [ fig . 1(c ) ] is consistent with the temperature dependence of the nematic susceptibility @xmath129 in eq . ( 3 ) and agrees with the results of young s modulus measurements @xcite . this gives us confidence that in the effective landau description @xcite , the uniaxial pressure - induced lattice distortion @xmath33 has a component proportional to the electronic nematic order parameter @xmath105 via eq . ( 2 ) , where one expects @xmath130 in zero pressure ( @xmath45 ) . since @xmath33 has similar magnitude in bafe@xmath7as@xmath7 , bafe@xmath5ni@xmath6as@xmath3 , and srfe@xmath5ni@xmath6as@xmath7 ( see fig . 4 ) , one would also expect comparable values of @xmath105 in all three compounds . so if one uses the resistivity anisotropy @xmath20 as a proxy for the nematic order parameter , as has been widely used in the literature @xcite , how does one then explain the resistivity anisotropy differences in bafe@xmath14as@xmath3 @xcite and a much smaller resistivity anisotropy above @xmath10 [ fig . 1(b ) ] in srfe@xmath14as@xmath3 family of materials @xcite ? the bare value of the elastic shear modulus @xmath107 that enters eq . ( [ eq.delta ] ) has no strong temperature dependence @xcite and from the curie - weiss fits of the nematic susceptibility to eq . ( [ eq.suscept ] ) , we find it to be roughly the same in all three compounds , @xmath131 gpa @xcite . the only remaining unknown variable is the elasto - nematic coupling constant @xmath132 , which could be material - dependent but not temperature - dependent @xcite . it is thus very challenging to explain the qualitatively different temperature dependence of the resistivity anisotropy in bafe@xmath5ni@xmath6as@xmath3 [ monotonic , blue diamonds in fig . 1(b ) ] from that in bafe@xmath7as@xmath7 and in srfe@xmath5ni@xmath6as@xmath7 [ both non - monotonic , with a maximum at or just below @xmath0 ] . one possible explanation for the non - monotonic temperature dependence of the resistivity anisotropy , recently proposed in the context of fese @xcite , is to assume a temperature dependent coefficient of proportionality between @xmath134 and @xmath105 : @xmath135 such that @xmath136 tends to zero as @xmath137 , whereas @xmath138 is expected to increase monotonically below @xmath0 as the temperature is lowered ( consider for instance the mean - field result @xmath139 for the second order phase transition ) . even with the introduction of @xmath136 in eq . ( [ eq.rho ] ) , which has a meaning of the temperature - dependent scattering function , it is extremely difficult to explain the much lower value of @xmath134 in srfe@xmath5ni@xmath6as@xmath7 compared to bafe@xmath7as@xmath7 and bafe@xmath5ni@xmath6as@xmath3 . in fact , from the curie - weiss fits of the susceptibility data , we estimate the elasto - nematic coupling constant @xmath132 to be a factor of @xmath140 smaller in srfe@xmath5ni@xmath6as@xmath7 compared to bafe@xmath5ni@xmath6as@xmath3 @xcite . given the comparable magnitudes of @xmath33 between the two compounds [ see fig . 4(d ) and 4(h ) ] , one would then expect the nematic order parameter @xmath105 to be a factor of @xmath140 greater in srfe@xmath5ni@xmath6as@xmath7 , to ensure that the left - hand side of eq . ( 2 ) remains of the same magnitude . and yet the resistivity anisotropy @xmath141 paints a diametrically opposite picture , being much smaller in srfe@xmath5ni@xmath6as@xmath7 . we propose that a likely resolution of this dilemma lies in the nature of the magnetic phase transition which we have so far neglected in our analysis . indeed , it is well established that structural and magnetic phase transitions in srfe@xmath14as@xmath3 are coupled first order transitions that decrease with increasing @xmath17 before vanishing near optimal superconductivity @xcite , while electron - doped bafe@xmath7as@xmath7 has second order magnetic and structural phase transitions @xcite . although application of a uniaxial pressure renders the structural transition a crossover , the first order nature of the magnetic transition means a vanishing critical regime with suppressed low - energy spin fluctuations at temperatures near @xmath10 , compared with those of bafe@xmath14as@xmath3 where the af phase transition is second order . one expects the scattering of electrons on the magnetic fluctuations , and hence the resistivity , to therefore be smaller in the vicinity of the first - order magnetic transition , as is the case in srfe@xmath14as@xmath3 . we thus conclude that the vanishing resistivity anisotropy above @xmath10 in the uniaxial pressure detwinned srfe@xmath14as@xmath3 ( compared with those of bafe@xmath14as@xmath3 ) is likely rooted in the first order nature of the af phase transition . this is also consistent with the increased paramagnetic resistivity anisotropy on moving from bafe@xmath7as@xmath7 to bafe@xmath142co@xmath143as@xmath3 @xcite , where the magnetic transition changes from weakly first order to second order @xcite . similarly , the lack of large resistivity anisotropy in the paramagnetic state of uniaxial pressured ba@xmath144k@xmath25fe@xmath7as@xmath7 @xcite , ba@xmath144na@xmath25fe@xmath7as@xmath7 @xcite , and ca@xmath144la@xmath25fe@xmath7as@xmath7 @xcite is likely due to the first order nature of the paramagnetic to af phase transition in these materials . the phenomenological landau theory can be extended to include the coupling between nematicity @xmath105 and the magnetic order parameter @xcite , and our theoretical analysis shows @xcite that the resulting uniaxial pressure - induced lattice distortion @xmath145 reproduces semi - quantitatively the experimental findings in fig . we conclude that the in - plane resistivity anisotropy found in the paramagnetic state of iron pnictides depends sensitively on the nature of the magnetic phase transition and a strong elasto - nematic coupling between the uniaxial pressure induced lattice distortion and the electronic nematic susceptibility . we caution that while the resistivity anisotropy @xmath134 and its dependence on the shear strain can be successfully used to extract the quantity proportional to the nematic susceptibility @xcite , care should be taken when equating @xmath134 with the nematic order parameter itself . in particular , the non - monotonic temperature dependence of @xmath134 and its sensitivity to the nature of the magnetic phase transition remain relatively little explored and deserve further experimental and theoretical studies . we thank a. e. b@xmath146hmer , j. h. chu , jiangping hu , and qimiao si for helpful discussions . the neutron scattering work at rice is supported by the u.s . nsf - dmr-1308603 , nsf - dmr-1362219 , and dmr-1436006 ( p.d . ) . is supported by the u.s . nsf career award ( dmr-1350237 ) . this work is also supported by the robert a. welch foundation grant nos . c-1839 ( p.d . ) and c-1818 ( a.h.n . ) . the work at the institute of physics , chinese academy of sciences is supported by ministry of science and technology of china ( 973 project : 2012cb821400 and 2011cba00110 ) , national natural science foundation of china projects 11374011 and 91221303 and the strategic priority research program ( b ) of the chinese academy of sciences grant no . xdb07020300 . the iron pnictide single crystals used in present study were prepared by self - flux method @xcite . the samples have been characterized by resistivity , magnetization , and neutron scattering measurements . figures 5 and 6 show the basic characterizations of bafe@xmath5ni@xmath6as@xmath3 and srfe@xmath5ni@xmath6as@xmath3 samples , respectively . the basic characteristics of the bafe@xmath3as@xmath3 and bafe@xmath38ni@xmath39as@xmath3 samples can be found elsewhere @xcite . ( b ) temperature derivative of the magnetic susceptibility , showing clearly the structural and magnetic phase transitions . ( c ) temperature dependence of the @xmath147 magnetic ( green diamonds ) and @xmath148 nuclear ( red squares ) bragg peak intensity @xcite . the extinction release of the @xmath149 bragg reflection is sensitive to the change of structural distortion and used to determine the @xmath0 . combining the results in ( a)-(c ) , the @xmath10 and @xmath0 are determined as shown in the green and red vertical dashed lines , respectively.,width=264 ] figure 5(a ) shows temperature dependence of the zero field cooled ( zfc ) and field cooled ( fc ) magnetic susceptibility @xmath150 . figure 5(b ) is temperature derivative of @xmath150 , @xmath151 . figure 5(c ) shows temperature dependence of the magnetic @xmath70 bragg peak ( green diamonds ) and @xmath148 nuclear bragg intensity ( red squares ) . these results establish @xmath10 ( green dashed line ) and @xmath0 ( red dashed line ) of bafe@xmath5ni@xmath6as@xmath3 . the @xmath10 was determined as @xmath152 k from magnetic order parameter of the @xmath70 magnetic bragg peak [ fig . 5(c ) ] and temperature dependent magnetization measurements [ fig . the structural transition temperature @xmath0 is estimated from a feature shown in the magnetization , [ fig . 5(b ) ] , and the neutron extinction release of the @xmath149 nuclear bragg peak intensity [ fig . 5(c ) ] @xcite . ( b ) temperature dependence of the @xmath82 nuclear bragg peak intensity measured for warming and cooling . the dramatic increase of the @xmath153 bragg reflection signals the change of structural distortion near @xmath0 @xcite.,width=264 ] figure 6(a ) shows temperature dependent resistivity @xmath154 and its derivative @xmath155 for srfe@xmath5ni@xmath6as@xmath3 . the dip of the @xmath155 at @xmath156 k indicates the concomitant structural and magnetic transition , different from the two features for the separated @xmath10 and @xmath0 in bafe@xmath5ni@xmath6as@xmath3 . figure 6(b ) is temperature dependence of the @xmath153 nuclear bragg peak intensity . the dramatic increase of the peak intensity also signals the structural transition . the observed intensity hysteresis is consistent with first order nature of the structural and magnetic phase transition . large single crystals were selected and cut into rectangular shapes along the orthorhombic @xmath157 $ ] and @xmath158 $ ] directions by a high precession wire saw . the well - cut samples were placed inside a uniaxial pressure device with @xmath23 axis being the direction of the applied pressure @xcite . the applied uniaxial pressures for the the samples range from @xmath159 mpa to @xmath160 mpa , as described before . in order to measure temperature and pressure dependence of orthorhombic lattice distortion @xmath161 , the samples were mounted in the @xmath67 $ ] scattering plane , where orthorhombic @xmath82 and @xmath86 bragg reflections can be measured . the effects of uniaxial pressure on tetragonal - to - orthorhombic structural transition and uniaxial - pressure induced lattice orthorhombicity can be probed directly via measuring temperature and pressure dependence of the @xmath82 and @xmath86 reflections by neutron larmor diffraction . for magnetic measurements , the bafe@xmath5ni@xmath6as@xmath3 sample was mounted in the @xmath162\times [ 1,-1,0]$ ] scattering plane , where both the @xmath70 and @xmath71 magnetic bragg peaks can be reached @xcite . neutron spin echo ( nse ) technique has been demonstrated to be an effective method to measure the slow dynamics ( quasielastic scattering ) with an extremely high energy resolution ( @xmath163ev or even to @xmath164 nev ) @xcite . by combining triple axes spectrometer and neutron resonance spin echo ( nrse ) technique , the trisp spectrometer at the forschungsneutronenquelle heinz maier - leibnitz ( mlz ) is capable of measuring the lifetime of excitations with an energy resolution @xmath165ev in the range of about @xmath166ev @xcite . directions are clearly marked . ( b ) schematic diagram for the neutron larmor diffraction measurements . for nrse , the neutron precession direction in @xmath167 is opposite to that of @xmath168 . in neutron larmor diffraction , the neutron precession directions are same in @xmath167 and @xmath168.,width=302 ] for @xmath169 and @xmath170 . the solid lines are consine fittings of the data using eq . ( b ) @xmath171 for various temperatures . the solid lines are fittings by eq . the brown dashed line shows a drawing of eq . ( 10 ) with @xmath172ev for comparison purpose . the corresponding lorentzian @xmath173 are shown as the solid green and brown lines in the inset.,width=264 ] compared with typical neutron scattering experiments where @xmath174 ( @xmath175 ) is usually measured , neutron spin echo measures @xmath176 or @xmath177 , where @xmath99 is the polarization of the scattered neutrons , which is the time fourier transform of the @xmath174 and thus provides direct information of @xmath178(*q*,@xmath179 ) such as energy line - width ( lifetime ) and intensity @xcite . the basic principle of nse can be understood in a simplified picture as shown in figure 7(a ) . we assume neutrons polarized along the @xmath180 direction with a velocity @xmath181 enter the first arm of nse spectrometer with a constant magnetic field @xmath182 [ fig . the precession angle in the first arm ( @xmath167 ) is then @xmath183 , where @xmath184hz@xmath185 is the gyromagnetic ratio of neutron , @xmath167 is the length of the first neutron guide arm , and @xmath186 is the time for neutron to travel through the first arm . after interactions with the sample , some neutrons are scattered into different energy with velocity @xmath187 . in the second arm ( @xmath168 ) , the neutron spin will precess along the opposite direction , generating @xmath188 . assuming @xmath189 and @xmath190 , @xmath191 , the net phase after passing through both field regions will be @xmath192 . since neutron energy transfer is @xmath193 , the net phase can be written as @xmath194 where @xmath195 is defined as @xmath196 note @xmath195 is not a physical time but a quantity determined by specific parameters of the spectrometer , with the dimension of time . the polarization along @xmath180 direction of the scattered neutrons can be analyzed and detected [ fig . the average polarization @xmath197 for neutrons with energy transfer @xmath198 is @xmath199 thus @xmath197 is the cosine fourier transform of @xmath178(*q*,@xmath179 ) for @xmath179 and has been shown equal to the intermediate scattering function @xmath200(*q*,@xmath201 ) . therefore , the @xmath195 dependent polarization @xmath171 , that is , @xmath200(*q*,@xmath201 ) , provide direct information about @xmath178(*q*,@xmath179 ) @xcite . in the nrse , the precession fields and spin flippers are replaced by four short bootstrap r - f spin flipper coils [ c1-c4 in fig . 7(b ) ] , which can improve the energy resolution by a factor of 4 compared with the nse with the same * b * and @xmath58 . the neutrons only precess in bootstrap while keep their spin directions in @xmath167 and @xmath168 . @xmath168 can be tuned by translating the flipper @xmath202 , by which the intensity with respect to the position of @xmath202 , @xmath203 , can be measured . for a fixed @xmath201 , the measured intensity can be described as @xmath204\big]\text{,}\label{eq:8}\\\ ] ] where @xmath99 is the polarization , @xmath205 is the averaged intensity of the scattered beam , @xmath206 is the period of the intensity modulation , and @xmath207 is the reference position of @xmath202 . the measurements of the @xmath171 for bafe@xmath5ni@xmath6as@xmath3 under @xmath72 mpa are summarized in figure 8 . figure 8(a ) shows the intensity modulations for @xmath208 and @xmath209 of * * q**=@xmath70 at @xmath210 k. the polarizations are obtained through fitting the data by eq . the fitted @xmath171 for different temperatures are plotted in figure 8(b ) . assuming the possible broadening in energy of the magnetic reflections is caused by some slow dynamics ( quasielastic scattering ) , the corresponding @xmath173 can be described by a simple lorentzian : @xmath211 where @xmath50 ( @xmath76 ) ( half width at half maximum ) is the line - width of the quasielastic scattering ( @xmath212 ) . followed by eq . ( 9 ) , the @xmath171 should be fitted by the fourier transform of eq . ( 9 ) : @xmath213 all the @xmath171 in our measurements can be well described by this exponential decay , as shown in figure 8(b ) . the fitted energy line - widths @xmath50 are less than @xmath214ev , meaning the signal are resolution limited at the measured temperatures . the comparison between @xmath173 for resolution limited ( @xmath215ev ) and @xmath172ev is shown in the inset of figure 8(b ) , as a reference . the temperature dependence of @xmath50 is shown in figure 2(b ) of the main text , which must have values greater than zero . the large error bars for the values of @xmath50 near @xmath10 are due to experimental uncertainties of @xmath171 in fig . 8(b ) . for bafe@xmath5ni@xmath6as@xmath3 . ( a ) comparison of @xmath218 at @xmath219 between @xmath220 k and @xmath221 k with @xmath87 mpa . ( b ) @xmath218 for the @xmath82 and @xmath86 reflections measured at @xmath222 k with @xmath87 mpa . the inset shows the gaussian distribution of the @xmath92 spacing . ( c ) temperature dependence of the @xmath218 for the @xmath82 peak at @xmath45 . @xmath218 for the two @xmath92 spacings shows clear modulation which can be fitted by eq . ( 14 ) ( solid curves ) due to the twinning caused by the tetragonal - to - orthorhombic structural transition.,width=283 ] ) dependent polarizations across the structural transition for bafe@xmath3as@xmath3 . the solid green curves are fits of the @xmath218 by one or multi gaussian @xmath92 spacing distribution models . ( e)-(h ) are the @xmath92 spacing distributions in @xmath92 space . the orthorhombic , coexisting two different orthorhombic and tetragonal phases can be determined for @xmath223 to @xmath224 k , respectively.,width=283 ] we now turn to the neutron larmor diffraction measurements . larmor diffraction is a neutron larmor precession technique capable of measuring lattice spacing expansion and spread with a resolution better than @xmath91 in term of @xmath81 . it is sensitive to minor change of lattice spacing @xmath92 but insensitive to sample mosaicity and not much affected by slight misalignment @xcite . the total precession phase ( @xmath225 ) dependent polarizations [ @xmath218 ] can be used to determine the @xmath92 spread and the splitting between multiple @xmath92 spacings with small differences , such as the peak splitting caused by the tetragonal - to - orthorhombic structural transitions in iron pnictides @xcite . figure 7(b ) is a schematic of larmor diffraction . the spin flippers are tuned to be parallel with the diffracting planes and the neutron precession directions in @xmath167 and @xmath168 are the same . assuming @xmath189 , the total neutron precession phase is @xmath227 . from the bragg law @xmath228 , and the neutron velocity @xmath229 , the total larmor phase @xmath225 can be written as @xmath230 consequently , the variation of the larmor phase is proportional to the change of the @xmath92 spacing ( caused by external or thermal effect ) , that is @xmath231 for @xmath92 change induced thermal expansion , the evolution of @xmath218 at different temperatures and the relative change of the @xmath225 ( @xmath232 ) can be obtained by fitting the intensity modulations @xmath233 using eq . ( 8) , where the modulations are measured by scanning @xmath234 near @xmath207 [ fig . 7(b ) and fig . the @xmath232 between different temperatures ( or pressures/@xmath235s ) can be used to determine the evolution of the lattice spacings . to facilitate data analysis , @xmath232 between two neighbouring conditions should be kept within @xmath236 . figure 9 is an example of lattice thermal expansion at @xmath237 of bafe@xmath5ni@xmath6as@xmath3 . the difference in @xmath234 ( @xmath238 ) between @xmath239 k and @xmath240 k , @xmath238 , can be converted to lattice expansions according to eq . ( 11 , 12 ) . in present measurements , @xmath241 mm is equivalent to @xmath242 in @xmath81 , with resolution @xmath243 . note lattice expansion measurements is only valid for single @xmath92 spacing at one @xmath235 . systems showing coexisting multiple @xmath92 spacings around the same @xmath235 with small differences between them can not be measured by this method . besides the lattice expansion measurements , the @xmath244 in a wide range of @xmath225 has been demonstrated to be the fourier transform of the lattice spacing distribution [ @xmath95 ] @xcite . for a single - gaussian distribution of @xmath92 with fwhm=@xmath246 , the @xmath218 can be derived as @xmath247 where the fwhm represents the magnitude of the @xmath92 spread . it is usually expressed in term of @xmath81 . the data shown in the figure 3 of the main text are temperature dependence of the fwhm ( lattice spacing spread ) . all of our @xmath218 for single @xmath92 spacing are well described by this model , resulting in a gaussian distribution of the @xmath92 values . figure 10 shows the @xmath218 of bafe@xmath5ni@xmath6as@xmath3 under @xmath248 mpa and their fittings by eqs . ( 13),(14 ) . a clear difference between @xmath220 k and @xmath249 k in figure 10(a ) indicates different fwhm of the @xmath92 spread . figure 10(b ) compares @xmath218 for the @xmath82 and @xmath86 reflections at @xmath222 k. the corresponding fwhms of the @xmath92 distributions are also shown as an inset . their differences suggest that the @xmath92 spread along the pressure - applied orientation is much larger . as@xmath7 and srfe@xmath5ni@xmath6as@xmath3 . the open green diamond in ( a ) marks the temperature range showing four @xmath92 spacings . the open red diamonds in ( b ) show the persistence of the tetragonal phase into the orthorhombic phase , indicative of a first - order structural transition , consistent with previous reports . the vertical blue dashed lines mark the structural transitions.,width=283 ] figure 10(c ) shows temperature dependence of @xmath218 for an un - pressured bafe@xmath5ni@xmath6as@xmath3 sample . its evolution at high temperature ( @xmath250 k ) indicates the broadening of the @xmath92 spread . below @xmath47 k , clear modulations are seen in @xmath218 . this is caused by the peak splitting of the orthorhombic @xmath153 and @xmath251 reflections in a twinned sample . for systems showing two or more coexisting @xmath92 spacings around some @xmath235 , their @xmath92 spacing distribution functions are superposition of multiple gaussian distributions . in this case , the interference between different @xmath92 spacings will appear and can be used to identify the specific values and spread of the involved @xmath92 spacings . where @xmath255 here we assume both @xmath92 spacings have the same @xmath246 . @xmath12 and @xmath256 denote the populations of the @xmath252 and @xmath253 . @xmath257 is the lattice distortion . the definition of @xmath258 is similar with the orthorhombic lattice distortion @xmath259 in iron pnictides , with @xmath258 = @xmath260 @xcite . the @xmath218 at @xmath261 k and @xmath262 k in figure 10(c ) are well described by eq . the fitted lattice distortions and @xmath92 spreads are shown in figure 3 and 4 of the main text . the resolution in determining @xmath258 here depends on the range of @xmath225 and the @xmath92 spread of the sample since the dips of the polarization is critical for fitting @xmath258 . the resolution of @xmath258 for two @xmath92 spacings is @xmath263 in the present work . thus the possible distortions at temperatures slightly lower than @xmath36 k [ such as the @xmath264 k data shown in figure 10(c ) ] in bafe@xmath5ni@xmath6as@xmath3 can not be distinguished from the broadening of the @xmath92 spread . figure [ fig:11 ] are @xmath218 for temperatures across the structural transition of the bafe@xmath3as@xmath7 sample . @xmath218 in figure [ fig:11](a ) is a beating pattern caused by interference between two @xmath92 spacings below @xmath0 , similar with that shown in figure 10(c ) . the corresponding @xmath92 spacing distributions are shown in figure [ fig:11](e ) . the orthorhombic distortions can be determined as @xmath265 . upon warming the sample to @xmath266 k , a temperature slightly lower than @xmath0 , a more complicated pattern [ fig . [ fig:11](b ) ] indicates the coexistence of four @xmath92 spacings [ fig . [ fig:11](f ) ] . this is consistent with the coexisting orthorhombic antiferromagnetic ( @xmath267 ) and orthorhombic paramagnetic ( @xmath268 ) phases revealed by high resolution x - ray diffraction measurements @xcite . the four-@xmath92 spacing model of @xmath171 can be derived analytically ( not shown here ) and fit the data very well . figure [ fig:11](c ) and ( g ) are results for @xmath269 , where the @xmath268 is indistinguishable and only one broad @xmath92 spread can be fitted . here , the orthorhombic antiferromagnetic phase ( @xmath267 ) is about to disappear , suggesting this temperature is near @xmath0 . for temperature higher than @xmath0 in figure [ fig:11](d ) and ( h ) , only one @xmath92 spacing is observed , indicating the system enters into the paramagnetic tetragonal phase . in figure [ fig:11](a , b ) , the magnitude of the lattice distortions determines the beating periods ( overall line shape ) and the relative populations of different @xmath92 spacings control whether the polarization can reach zero at dips . in the present study , the overall line shapes of all @xmath171 are well fitted by specific multiple ( @xmath270 ) @xmath92 spacing models [ green curves in figure [ fig:11](a)-(d ) ] , indicating that the lattice distortions are well determined . the orthorhombic lattice distortions for bafe@xmath3as@xmath7 and srfe@xmath5ni@xmath6as@xmath3 obtained from larmor diffraction measurements of @xmath218 are shown in figure [ fig:12 ] . these results are consistent with previous results measured by x - ray diffraction @xcite . the error bars in figures 3 and 4 of the main text are fitting errors of the raw data at different temperatures according to formulas discussed above . spread of bafe@xmath1ni@xmath2as@xmath3 and srfe@xmath5ni@xmath6as@xmath3 measured with finite uniaxial pressure . @xmath10 and @xmath0 are marked as blue ( and green ) vertical dashed lines . the red dashed line marks the temperature with the maximum of the fwhm.,width=283 ] another interesting discovery is the doping dependent @xmath92 spread anisotropy under uniaxial pressure . the samples shown in figure 13 exhibit similar temperature dependence of the @xmath92 spread between @xmath153 and @xmath251 , suggesting that the difference of @xmath92 spread between @xmath12 and @xmath23 is trivial . however , we note that the fwhm of @xmath251 , along the uniaxial pressure direction , is much larger than @xmath12 in underdoped samples [ fig . 13(a)-13(c ) ] . this may be attributed to an inhomogeneous distribution of the pressure induced strain field . however , we find very small differences in @xmath92 spread between @xmath153 and @xmath251 in the overdoped bafe@xmath38ni@xmath39as@xmath3 [ fig . 13(d ) ] , suggesting the @xmath92 spread anisotropy between @xmath12 and @xmath23 is non - trivial and may be associated with antiferromagnetic / structural instability or even nematic susceptibility in underdoped samples . the young s modulus @xmath271 along the @xmath23-axis ( @xmath272 ) can be estimated by @xmath273 , where @xmath33 is pressure induced lattice distortion . at @xmath274k , the @xmath271 for bafe@xmath7as@xmath7 , bafe@xmath5ni@xmath6as@xmath7 and bafe@xmath38ni@xmath39as@xmath7 estimated from our neutron larmor diffraction experiments are @xmath275 gpa , @xmath275 gpa and @xmath276 gpa , respectively . compared with the shear modulus @xmath277 obtained by ultrasound spectroscopy @xcite , the estimated @xmath271 for @xmath101 and @xmath278 are @xmath279 larger . these differences are mainly caused by the errors in our estimation of the applied pressure @xmath99 through measuring compressed spring distances and estimated spring constant @xcite . however , they will not affect temperature dependence of the pressure - induced fhwm of @xmath81 and its comparison with other iron pnictides , thus will not alter the conclusions of our experiments . in order to understand the distinct behavior of the observed lattice distortion in srfe@xmath5ni@xmath6as@xmath280compared to bafe@xmath5ni@xmath6as@xmath280[see fig . 1(c ) in the main text ] , we write down the landau free energy incorporating the electronic nematic order parameter @xmath105 , coupled magnetoelestically to the lattice distortion @xmath281 , as well as to the antiferromagnetic order parameter @xmath282 : @xmath283 + t_0 \tilde{f}[m,\varphi],\ ] ] where @xmath284 = \frac{a}{2}\frac{t - t_0}{t_0}\varphi^2 + \frac{b}{4 t_0}\varphi^4 + \frac{c_{66,0}}{2t_0}\delta^2 - \frac{\lambda}{t_0 } \delta\varphi - \frac{p\delta}{t_0 } \label{eq.phi - delta}\ ] ] here we chose to normalize the free energy by the curie - weiss temperature @xmath110 associated with the quadratic @xmath285 term ( if @xmath110 is negative , it is replaced by @xmath286 ) . treating the electronic nematic order parameter @xmath105 as a dimensionless variable , this has an advantage that all the coefficients in the free energy are dimensionless ( here we choose , without loss of generality , ) . the remaining landau expansion parameters can be fixed from the experiment . indeed , it is convenient to express the external uniaxial stress @xmath99 in terms of the dimensionless stress variable @xmath287 . then , the last three terms in eq . ( [ eq.phi-delta ] ) can be written as follows : @xmath288\ ] ] minimizing the free energy with respect to @xmath33 , we find @xmath289 from the minimization with respect to @xmath105 , it is easy to obtain @xmath290 and now the shear modulus @xmath291 becomes @xmath292 in other words the elastic modulus gets renormalized from its bare value @xmath107 by virtue of the elasto - nematic coupling @xmath132 . equivalently , it follows from the above equation that the inverse nematic susceptibility also gets renormalized from its bare value @xmath293 : @xmath294 where @xmath295 is the renormalized curie weiss temperature . one can now cast eq . ( [ eq.c66 ] ) above the transition temperature @xmath114 into the form @xmath296 which is eq . ( 3 ) in the main text . we now use this eq . ( [ eq.suscept ] ) to fit the data for the pressure - induced distortion @xmath297 [ fig . 1(c ) in the main text ] , extracting the values of @xmath110 and @xmath298 which we quote in table [ table ] for bafe@xmath7as@xmath7 and srfe@xmath5ni@xmath6as@xmath280 . we now turn to the question of the strength of the elasto - nematic coupling constant @xmath132 . the unknown dimensionless parameter @xmath299 in eq . ( [ eq.delta ] ) can be fixed from the ratio @xmath300 in zero external stress ( @xmath301 ) . substituting the typical value of @xmath302 in srfe@xmath5ni@xmath6as@xmath280and bafe@xmath5ni@xmath6as@xmath280and choosing the value of the nematic order parameter @xmath303 deep inside the nematic phase for convenience , we find @xmath304 . as for the value of @xmath305 itself , it can also be fixed from the experiment since @xmath132 enters in eq . ( [ eq.nematic-suscept ] ) to renormalize the curie - weiss temperature . therefore , one obtains . plugging in the values of @xmath298 and @xmath110 from our fittings of the lattice distortions ( table [ table ] ) , we obtain @xmath306 for srfe@xmath5ni@xmath6as@xmath280and @xmath307 for bafe@xmath7as@xmath308 , in other words the effective electron - lattice coupling is about @xmath309 times weaker in srfe@xmath5ni@xmath6as@xmath280compared to the bafe@xmath310as@xmath7 compounds . for bafe@xmath5ni@xmath6as@xmath280 , the quality of our data was insufficient to accurately determine the bare curie weiss temperature @xmath110 ( we were only able to determine @xmath311 k ) . however , from the estimated @xmath312 k by the elastic measurements @xcite , we can deduce the approximate value of the coupling constant @xmath313 , similar in magnitude to undoped bafe@xmath7as@xmath7 . we now turn our attention to the magneto - nematic coupling . on symmetry grounds , nematic order parameter must couple to @xmath314 ( since magnetization breaks time - reversal symmetry , and @xmath105 does not ) . this can be shown explicitly by considering the magnetization @xmath315 on the two sublattices composed of the next - nearest neighbor sites of the square lattice , in which case the nematic order parameter couples linearly to the product @xmath316 [ ] . note that this conclusion holds independently of whether the microscopic origin of nematicity is purely magnetic @xcite or orbital @xcite . the magnetic phase transition itself may be intrinsically second order , as in bafe@xmath310as@xmath7 compounds , or first order , as in srfe@xmath5ni@xmath6as@xmath280 , ba@xmath144(k , na)@xmath25fe@xmath7as@xmath7 , and ca@xmath144la@xmath25fe@xmath7as@xmath7 . below we consider both possibilities : @xmath317\!\ ! & = & \!\ ! \frac{u}{2}(t - t_{n,0})m^2 - \frac{v}{4}m^4 + \frac{w}{6}m^6 - \mu\varphi m^2 \phantom{xxx } \label{eq.first } \\ \tilde{f}_2[m,\varphi]\ ! \!&=&\!\ ! \frac{u}{2}(t - t_{n,0})m^2 + \frac{v}{4}m^4 - \mu\varphi m^2 \label{eq.second}\end{aligned}\ ] ] since we are after the qualitative consequences of the magneto - nematic coupling , the precise values of the landau coefficients are not essential ( we take @xmath318 and @xmath319 for concreteness ) . ) or 2nd order ( eq . [ eq.second ] ) magnetic phase transition coupled to the nematic order parameter @xmath105 . the blue dashed curve is shifted to the left by @xmath320 for clarity . these results should be compared to the neutron data in fig . 1c in the main text.,scaledwidth=44.0% ] having introduced the landau formalism above , we now study the effect of the applied external stress @xmath99 on the behavior of the lattice distortion . the calculated temperature dependence of @xmath321 is shown in figure [ fig.delta-eps ] for the realistic strain @xmath30 mpa and is shown to depend crucially on the nature of the magnetic phase transition . indeed , the only difference between the two curves is the sign in front of the quartic @xmath322 terms in eqs . ( [ eq.first ] ) and ( [ eq.second ] ) , while all the other landau expansion parameters are kept the same ( the two curves are offset horizontally for clarity ) . note that for small @xmath99 , @xmath323 is proportional to the nematic susceptibility , which is expected to diverge at @xmath298 according to eq . ( [ eq.suscept ] ) . both curves in fig . [ fig.delta-eps ] exhibit an enhanced nematic susceptibility on approaching @xmath298 , as expected . the main difference is the shape of the curve on approaching the transition , which has a distinct asymmetric `` lambda '' shape in the case of the second - order magnetic transition , and resembles closely the experimentally measured @xmath321 for bafe@xmath5ni@xmath6as@xmath280 in fig . 1c ( see main text ) . by contrast , the nel transition is first order in srfe@xmath5ni@xmath6as@xmath280 , and the experimental behavior in fig . 1(c ) is close to the calculated sharp increase seen in our model ( solid line in fig . [ fig.delta-eps ] ) . therefore , the landau free energy results corroborate our conclusion that the nature of the magnetic transition is crucial to the observed temperature dependence of the lattice distortion . we note in passing that for sufficiently strong coupling constant @xmath79 , the magnetic transition becomes weakly first - order even if the intrinsic free energy has positive @xmath322 term in eq . ( [ eq.second ] ) . this is likely the explanation for the observed change of the nature of the magnetic transition from weakly first order in bafe@xmath7as@xmath308to second order upon co doping @xcite . however for the values of the coupling constants in fig . [ fig.delta-eps ] , this effect is imperceptible and the main difference between the two curves is due to the different intrinsic nature of the magnetic phase transition depending on the sign of the quartic term in eqs . ( [ eq.first ] ) and ( [ eq.second ] ) . we have verified that for the significantly larger values of the coupling constant ( @xmath324 in eq . [ eq.second ] ) , it is indeed possible to obtain the shape similar to the dashed line in fig . [ fig.delta-eps ] because the magnetic transition becomes effectively first order . in either case , our conclusions remain intact . the resistivity anisotropy @xmath325 has been widely used as a proxy for the electronic nematic order parameter in the iron pnictides @xcite . however in some compounds , in particular in srfe@xmath5ni@xmath6as@xmath280 , the resistivity anisotropy is vanishingly small immediately above @xmath10 [ see fig . 1(b ) in the main text ] , whereas it is much larger in bafe@xmath310as@xmath7 . this is puzzling because the lattice distortion is comparable in both cases [ fig . 1(c ) ] and , according to eq . ( [ eq.delta ] ) , one expects the lattice distortion @xmath33 to be proportional to the nematic order parameter . coupled to either first or second order magnetic phase transition . note that in both cases , the bare @xmath326 term is positive , however the nematic transition is rendered first order ( solid curve ) when coupled to the first order magnetic order parameter in eq . ( [ eq.first]).,scaledwidth=44.0% ] to shed more light on this apparent inconsistency , we have plotted in figure [ fig.phi ] the temperature dependence of the nematic order parameter @xmath105 under the uniaxial stress @xmath30 mpa . the two curves correspond to the first- and second - order nature of the magnetic transition , respectively , and the landau parameters were kept the same in both cases ( except for the sign of the quartic term in eq . [ eq.first ] and [ eq.second ] ) . above the transition temperature , @xmath327 , the values of @xmath105 are predictably small , but importantly , they are identical in the two cases . in fact , the main difference lies in the temperature dependence immediately below @xmath0 . from fig . [ fig.phi ] , it would appear that in this regime , the nematic order parameter should be smaller for the second - order phase transition , however this is diametrically opposite from the comparison between bafe@xmath5ni@xmath6as@xmath280and srfe@xmath7as@xmath7 in fig . 1(b ) ( see main text ) , where the magnetic transition in bafe@xmath5ni@xmath6as@xmath280is second order , yet resistivity anisotropy is much larger . this qualitative observation can be made sharper by considering eq . ( [ eq.delta ] ) , where the coupling constant @xmath132 is estimated from experiment to be a factor of @xmath328 larger in bafe@xmath5ni@xmath6as@xmath280and bafe@xmath7as@xmath308compared to srfe@xmath5ni@xmath6as@xmath280 , whereas the elastic modulus @xmath131 gpa is similar in all three materials . then , bafe@xmath7as@xmath308is expected to have at least a factor of 5 larger lattice distortion compared to srfe@xmath5ni@xmath6as@xmath280 , assuming that @xmath105 is the same in both materials . if one now equates the resistivity anisotropy with the nematic order parameter @xmath105 , as has commonly been done in the literature @xcite , then one is forced to conclude that @xmath105 must be about 4 times larger in bafe@xmath7as@xmath308due to the larger resistivity anisotropy [ see fig . 1(b ) ] . taken together , one would expect the lattice distortion @xmath33 to be a factor of @xmath329 larger in bafe@xmath7as@xmath308and in bafe@xmath5ni@xmath6as@xmath280compared to srfe@xmath5ni@xmath6as@xmath280(factor of 4 due to larger resistivity anisotropy , times factor of 5 due to larger @xmath132 ) . and yet this clearly contradicts the experimental evidence in fig . 1(c ) , according to which the lattice distortion is almost the same in all three materials . one possible way out of this dilemma is that the landau theory may not be applicable to describe the nematicity in the pnictides . however , given the excellent semi - quantitative agreement that landau theory provides for the lattice distortion ( fig . [ fig.delta-eps ] above ) and its well documented success describing the elastic shear modulus measurements @xcite , such a conclusion is perhaps not well justified . rather , a much more plausible conclusion is that resistivity anisotropy is a poor substitute for the nematic order parameter . while it is plausible that the two quantities are proportional to each other , as follows from the nematic susceptibility measurements @xcite , the coefficient of proportionality need not be constant and can have a strong temperature dependence ( and likely material dependence ) , as suggested recently by tanatar _ _ in the recent study on fese @xcite . this material displays a non - monotonic temperature dependence of the resistivity anisotropy with a peak below @xmath0 , qualitatively similar to bafe@xmath7as@xmath308 . further theoretical and experimental studies are necessary to elucidate the precise relationship of the resistivity anisotropy and the nematic order parameter in the iron pnictides and chalcogenides . direct microscopic measurements of the nematic order parameter , for instance using the angle - resolved photoemission spectroscopy ( arpes ) to probe the orbital splitting , combined with the uniaxial pressure measurements , would be desirable . m. yi , d. h. lu , j .- h . chu , j. g. analytis , a. p. sorini , a. f. kemper , b. moritz , s .- k . mo , r. g. moore , m. hashimoto , w .- s . lee , z. hussain , t. p. devereaux , i. r. fisher , and z .- x . shen , pnas * 108 * , 6878 ( 2011 ) . d. hu , x. y. lu , w. l. zhang , h. q. luo , s. l. li , p. p. wang , g. f. chen , f. han , s. r. banjara , a. sapkota , a. kreyssig , a. i. goldman , z. yamani , ch . niedermayer , m. skoulatos , r. georgii , t. keller , p. s. wang , w. q. yu , and p. c. dai , phys . lett . * 114 * , 157002(2015 ) .

we use neutron resonance spin echo and larmor diffraction to study the effect of uniaxial pressure on the tetragonal - to - orthorhombic structural ( @xmath0 ) and antiferromagnetic ( af ) phase transitions in iron pnictides bafe@xmath1ni@xmath2as@xmath3 ( @xmath4 ) , srfe@xmath5ni@xmath6as@xmath7 , and bafe@xmath7(as@xmath8p@xmath9)@xmath7 . in antiferromagnetically ordered bafe@xmath1ni@xmath2as@xmath3 and srfe@xmath5ni@xmath6as@xmath7 with @xmath10 and @xmath0 ( @xmath11 ) , a uniaxial pressure necessary to detwin the sample also increases @xmath10 , smears out the structural transition , and induces an orthorhombic lattice distortion at all temperatures . by comparing temperature and doping dependence of the pressure induced lattice parameter changes with the elastoresistance and nematic susceptibility obtained from transport and ultrasonic measurements , we conclude that the in - plane resistivity anisotropy found in the paramagnetic state of electron underdoped iron pnictides depends sensitively on the nature of the magnetic phase transition and a strong coupling between the uniaxial pressure induced lattice distortion and electronic nematic susceptibility .

in the ` standard ' model of long - duration , soft - spectrum gamma - ray bursts ( grbs ; e.g. @xcite ) , the prompt high - energy emission arises in ultra - relativistic ( bulk lorentz factor @xmath2 ) , highly collimated ( opening half - angle of a few degrees ) jets . the high lorentz factors are inferred from the requirement of a sufficiently low opacity to photon - photon annihilation or to scattering by photon annihilation - produced electron - positron pairs ( e.g. * ? ? ? the high collimation makes it possible to reduce the total flow energy down to values that are comparable to the energy of stellar explosions . as the jets make their way through the interstellar medium they sweep the ambient gas into a thin relativistic shell that itself becomes a strong source of electromagnetic radiation . after a sufficiently large amount of gas is swept up , the shell begins to decelerate . simplified models of this interaction predict that a panchromatic break would then occur in the afterglow light curve , provided that @xmath3 , where @xmath4 is the jet opening half - angle . the detection of such ` jet breaks ' on time scales of @xmath5 day in several ( primarily long / soft ) grb afterglows has been a key reason for the widespread adoption of the jet model for these sources . the observed break parameters have made it possible to deduce the opening half - angle of these jets . the inferred values are strongly model dependent , although they usually lie the range of @xmath6 ( e.g. * ? ? ? * ; * ? ? ? although more recent observations by the _ swift _ satellite have revealed that late - time panchromatic jet breaks are not that common and that various aspects of the jet model may need to be modified ( e.g. * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? * ) , these breaks remain the strongest evidence for collimated outflows in grb sources . the supernova connection of long / soft grbs provides strong support for theoretical models of their jet engines that invoke dying massive and rapidly rotating stars . these models are generally divided into two groups depending on the mechanism of jet acceleration . in the first group the acceleration is driven by the thermodynamic pressure of plasma heated to ultra - relativistic temperatures via the annihilation of neutrinos and antineutrinos emitted by the accretion disk formed around the central black hole , thus tapping the disk thermal energy . in the second group the acceleration is driven by magnetic stresses , tapping the rotational energy of the disk or the central compact object ( neutron star or black hole ) . at present , both the magnetic and the thermal mechanisms seem possible , although the lack of detection of a thermal component in the spectra of some grbs is consistent with the notion that , at least in certain cases , the outflow is initially magnetically dominated @xcite . the magnetic jet acceleration mechanism has been the subject of theoretical study for many years . due to the mathematical complexity of magnetohydrodynamics ( mhd ) , which is even more pronounced in the relativistic limit , it has been possible to find analytical and semi - analytical solutions only for a rather limited number of problems characterized by a high degree of symmetry . in fact , there is only one available _ exact _ solution of the relativistic mhd equations including thermal and magnetic effects , the self - similar model of @xcite . the advance of numerical methods for relativistic mhd during the last decade has opened a new direction of study that has already resulted in significant progress ( e.g. * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? * ) . in particular , @xcite investigated the magnetic acceleration of ultra - relativistic flows within channels of prescribed geometry , @xmath7 ( where @xmath8 and @xmath9 are dimensionless cylindrical coordinates ) , determined by the shape of coordinate surfaces of elliptical coordinates . such shapes correspond to power - law distributions of the confining pressure that can approximate the expected distributions in the envelopes of the progenitor stars in both the collapsar and the magnetar scenarios ( which correspond to the dying star leaving behind a black hole or a neutron star , respectively ) as well as the effect of a confining disk wind . among other results , they found that in the case of a gradually widening channel , @xmath10 , the acceleration is not efficient , whereas in the case of a channel with gradually increasing collimation , @xmath11 , the acceleration is effective but the asymptotic flow obeys the inequality @xmath12 . these numerical results have been strengthened by complementary theoretical analyses @xcite , which led to the question of whether the magnetic models can accommodate the jet breaks at all . recently , a similar numerical study was carried out by @xcite , who confirmed the findings of @xcite . they have , however , also considered a somewhat modified setup , wherein at some distance from the origin , roughly corresponding to the stellar surface , the channel geometry changes from progressively collimating to progressively de - collimating . in this setup @xcite observed a remarkable change in the jet behaviour : beyond the point where the geometry changed , the jet speed underwent a strong boost that was accompanied only by a very small increase in the jet opening angle . as a result , the asymptotic flow had @xmath13 , which made it possible for late - time jet breaks to occur . the exact shape of the channel above the transition point did not seem to matter . in this paper we describe ( section [ simulations ] ) simulations that confirm the results of @xcite and then analyse ( section [ interpretation ] ) the underlying physical mechanism . we discuss and summarize our results in section [ conclusion ] . the numerical method is exactly the same as in @xcite and we refer the reader interested in technical details to that paper . here we only remark that our numerical code is based on the godunov - type scheme for relativistic mhd @xcite and that we look for steady - state axisymmetric solutions using time - dependent simulations with time - independent boundary conditions . for our purpose we selected model b1 from @xcite , for which the channel shape parameter is @xmath14 . this model describes a cold flow with values of the field - line constant @xmath15 , defined as the energy flux per unit rest - mass energy flux , as large as @xmath16 . this constant sets the upper limit on the lorentz factor that can be achieved in this model via ideal mhd mechanism .. ] the initial ratio of the poynting flux to the hydrodynamic energy flux is @xmath17 , as the initial lorentz factor , @xmath18 , is close to unity , corresponding to a sub - alfvnic flow . the base rotation is uniform , with the dimensionless light - cylinder radius @xmath19 being @xmath20 ; we used the distance of the inlet boundary from the origin as the unit of length . to examine the effect of changing the channel shape , we map the solution at @xmath21 and @xmath22 onto the inlet boundary of a new grid corresponding to a conical channel of the same local radius and with a vertex located at the origin . in this way we introduce a change in the channel shape to a profile that results in less collimation . we then proceed with the simulations on the new grid , following the same procedure as in model b1 . the two solutions obtained in this way , which we denote as b1a and b1b , are analysed below . [ lorentz ] shows the overall geometry as well as the shape of the magnetic surfaces and the evolution of the lorentz factor in models b1 and b1b . one can see that , in contrast with the situation in model b1 , the field lines in model b1b straighten out . one might think that this reflects the conical shape of the channel , but this is not so . in fact , the jet is separated from the channel wall by a near vacuum . this is the reason why the red - coloured boundary layer in the right panel of fig . [ lorentz ] is free from magnetic field lines . a similar separation has been seen in model e of @xcite and , we believe , also in the simulations of @xcite . as a result , the wall and the jet are causally disconnected and the precise shape of the wall does not matter . in model b1b the jet lorentz factor approaches its maximum possible value @xmath23 at the jet boundary , signalling a total conversion of the poynting flux . the acceleration is weaker in the jet interior but , as one can clearly see in fig . [ lorentz ] , it is still more effective than in model b1 . this is further illustrated in the left panel of fig . [ sigma ] , which compares the acceleration in both models along the magnetic surface enclosing @xmath24 of the jet s total poloidal magnetic flux . in the case of model b1a , where the channel opens up much earlier , the jet also passes through a phase of rapid acceleration . however , the acceleration slows down dramatically when the jet enters the phase of ballistic expansion . as a result , the final lorentz factor in this model is even lower than in model b1 . as one can see from fig . [ lorentz ] , the opening angle of the jet does not change much after passing the point where the channel widens , in agreement with the results of @xcite . thus , the product @xmath25 , where @xmath26 is the local opening half - angle , is expected to increase following the rapid increase of the lorentz factor . this is indeed the case , as one can see in the right panel of fig . [ sigma ] . in model b1b this product is much larger than in model b1 , approaching values that are @xmath1 near the jet boundary . concluding this section , we reiterate that our results are in very good agreement with those obtained in @xcite , thus confirming that the effect is real and must have a robust physical basis . once the jet separates from the wall in models b1a and b1b it enters the phase of free expansion and eventually becomes a ballistic conical outflow with radial streamlines . during the transition from the one regime to the other a strong fast - magnetosonic rarefaction wave propagates into the jet . since at this point the jet is causally connected ( see * ? ? ? * ) , the wave is not confined to a boundary layer but propagates all the way to the jet core . this is clearly seen in fig . [ pressure ] , which compares the distributions of the magnetic pressure @xmath27 ( where @xmath28 is the magnetic field amplitude in the comoving frame ) in models b1 and b1b downstream from the channel - widening point . the observed jet acceleration is apparently related to the properties of this wave . in fact , this phenomenon has already been seen in other numerical simulations of both purely hydrodynamic and magnetized flows @xcite . here we elucidate its physical nature by considering a simpler one - dimensional problem of relativistic expansion into vacuum in a slab geometry . the rarefaction wave in this case is described by a self - similar solution known as a ` simple wave ' . although such a flow is not identical to the one in our simulated jets , it nevertheless captures the underlying physical mechanism . consider a quasilinear hyperbolic system @xmath29 where @xmath30 is a vector of dependent variables , e.g. the gas pressure , density , etc . , and @xmath31 is an @xmath32 matrix . when the initial ( @xmath33 ) configuration describes two uniform states separated by a discontiniuty at @xmath34 ( a riemann problem ) , the system allows self - similar solutions that depend only on @xmath35 . in general , the solution involves a combination of shock and rarefaction waves , but in the case of expansion into vacuum it describes a single rarefaction wave ( a simple wave ) . in terms of the new independent variable @xmath36 , the system of equations ( [ h - system ] ) reduces to @xmath37 where @xmath38 is the unit matrix . this equation has the form of the characteristic equation for the matrix @xmath39 , and thus @xmath36 is equal to one of the eigenvalues of @xmath39 , @xmath40 with @xmath41 being the corresponding right eigenvector . each eigenvalue represent the phase speed of a particular wave , whereas the right eigenvector determines the connection between the variations of the dependent variables that are induced by the wave . equation ( [ sw - eq ] ) can be conveniently written as @xmath42 integrating this system , one finds @xmath43 , where @xmath44 , and then equation ( [ eq - of - char ] ) ( the equation of characteristics ) can be used to obtain @xmath45 . the systems of equations for relativistic hydrodynamics and for relativistic mhd can be written in the form of equation ( [ h - system ] ) . the eigenvalues and eigenvectors for all hyperbolic waves can be found , for example , in @xcite and @xcite . simple waves have been analysed in @xcite for purely hydrodynamic flows and in @xcite for magnetized flows in which the magnetic field is tangential to the discontinuity and orthogonal to the flow velocity . consider a simple one - dimensional problem with plane geometry describing the evolution of an initial discontinuity that separates a uniform magnetized cold plasma at rest on the left and vacuum on the right . this problem is related to the transverse expansion of our simulated jets after they lose external support , as seen in the jet comoving frame . the discontinuity decays into a single wave , namely the simple fast - magnetosonic rarefaction wave . the left front of this wave ( the head ) propagates into the left state with the local fast - magnetosonic speed and the right front ( the tail ) moves into vacuum with some finite terminal speed . in such a simple geometry , the lorentz force only involves the magnetic pressure , and the equations of mhd reduce to those of hydrodynamics of an ideal gas with a polytropic index @xmath46 . in this case the effective sound speed @xmath47 is equal to the fast - magnetosonic speed , which satisfies @xmath48 where @xmath49 is the rest - mass density and @xmath50 is the local magnetization parameter . this property allows us to utilize the results obtained for the corresponding problem in relativistic gas dynamics . in particular , the integration of equation ( [ sw - eq1 ] ) yields the integral across the rarefaction @xmath51 @xcite , where @xmath52 is the local flow speed . this equation can be used to deduce @xmath53 , the wave s expansion speed into vacuum . specifically , by equating the value of the above invariant as derived from the given left state to the value obtained at the boundary with the vacuum ( where @xmath54 ) , one finds @xmath55 @xmath56 for example , if in the left state , where @xmath57 , we have @xmath58 , and hence @xmath59 , then the lorentz factor of expansion into vacuum is @xmath60 . next , consider another reference frame that moves along the initial discontinuity with a lorentz factor @xmath61 this corresponds to the jet source frame in our simulations . the lorentz factor of plasma at the right front of the rarefaction wave in this frame is @xmath62 which in our example is three times larger than @xmath61 . thus , the seemingly weak acceleration in the jet frame may correspond to a huge boost in the jet source frame : in our example the lorentz factor increases from @xmath63 to the left of the rarefaction wave to @xmath64 at the boundary with vacuum . this is the essence of the acceleration mechanism that operates in the free expansion regime of the jet simulations . however , the jet expansion problem can not be completely reduced to the one considered here since it is inherently two dimensional ( see section [ bunching ] and appendix [ appb ] ) . the results can therefore be expected to be _ quantitatively _ different , as one can readily verify . indeed , along a magnetic surface of a steady jet the energy flux per unit rest mass flux is conserved , which for a cold flow leads to the integral @xmath65 where @xmath66 and where @xmath61 and @xmath67 represent the initial jet lorentz factor and magnetization , respectively . thus , the lorentz factor at the tail of the rarefaction wave , where the magnetization has decreased to zero , has to be @xmath68 . in contrast , equations ( [ exp_gamma ] ) and ( [ lor ] ) imply that @xmath69 , where @xmath67 is the magnetization of the undisturbed left state of the riemann problem ( which we identify with the initial magnetization in the steady - jet problem ) . here we consider a more complicated riemann problem where the velocity of the left state is not zero but has a component tangent to the discontinuity , @xmath70 . this corresponds to the jet expansion as seen in the jet source frame . the magnetic field of the left state is @xmath71 , where @xmath72 corresponds to the jet azimuthal magnetic field as measured in the comoving frame . in addition , we no longer assume that the left state is cold , which will allow us to compare the purely hydrodynamic and mhd cases . in the rarefaction wave @xmath73 and @xmath74 . this case has been analysed in @xcite . integration of the simple wave equations ( [ sw - eq1 ] ) leads to the integrals @xmath75 @xmath76 @xmath77 and @xmath78 where @xmath79 is the specific entropy , @xmath80 is the @xmath9-component of the 4-velocity , @xmath81 is the generalized specific enthalpy and @xmath82^{1/2 } \frac{{c_{\rm f}}}{c } \ .\ ] ] here @xmath83 is the fast - magnetosonic speed in the direction normal to the magnetic field as measured in the fluid frame , with @xmath84 @xmath85 is the alfvn speed , with @xmath86 @xmath87 is the sound speed , with @xmath88 and @xmath89 is the specific enhalpy . the function @xmath90 is a function of density only and the other variables are eliminated via the integrals ( [ is ] ) , ( [ ib ] ) and ( [ iz ] ) for a given equation of state . the values of these integrals are dictated by the left state of the problem . in particular , @xmath91 where @xmath92 and @xmath93 in these expressions we use the index ` @xmath94 ' to indicate the left state variables as this state corresponds to the undisturbed jet . also , @xmath67 is the magnetization parameter and @xmath95 is the energy integral that incorporates a thermal contribution ( see * ? ? ? * ) . in this case the characteristics equation ( [ eq - of - char ] ) yields @xmath96^{-1/2}. \label{eq - char1}\ ] ] this result has a straightforward interpretation . on the left - hand side one immediately recognizes the relativistic expression for the addition of velocities , whereas the right - hand side gives the speed of a fast - magnetosonic wave as measured in a frame that moves along the @xmath97 axis with the same speed as the fluid , i.e. @xmath52 ( see appendix [ eq20 ] ) . the procedure for constructing the self - similar solutions using the above analytical results is the following . > from equations ( [ is])([ip ] ) and the equation of state , one finds the functions @xmath98 , @xmath99 , @xmath100 , @xmath101 and the thermal pressure @xmath102 . , the enthalpy is @xmath103 p$ ] , in which case equation ( [ is ] ) becomes @xmath104const . ] finally , equation ( [ eq - char1 ] ) allows one to obtain @xmath105 . in particular we find that the head of the rarefaction wave propagets with the speed @xmath106^{-1/2 } , \nonumber \end{aligned}\ ] ] whereas the wave s tail advances with the speed @xmath107 although in general the solutions can only be found numerically , one can derive fully analytic results in the ultra - relativistic limit , as follows . from , equation ( [ iz ] ) one has @xmath108 for highly relativistic jets @xmath109 and @xmath110 . furthermore , @xmath111 and @xmath112 as @xmath113 . equation ( [ uz ] ) then yields @xmath114 the lorentz factor at the tail of the rarefaction wave ( i.e. at the boundary with vacuum ) is thus found to equal the value expected in a steady jet , as discussed in section [ case1 ] . the generalized one - dimensional riemann problem considered here ( case 2 ) therefore provides a better representation of the simulated two - dimensional jet problem than the simpler model considered above ( case 1 ) . + + + + in our jet simulations we deal with cold ( @xmath115 ) , super fast - magnetosonic ( @xmath116 ) , relativistic ( @xmath117 ) jets . in this limit we have @xmath118 equation ( [ uz ] ) then gives @xmath119 whereas equation ( [ ib ] ) yields @xmath120 combining the last two results we find that @xmath121 moreover , in this limit the integral in equation ( [ ip ] ) assumes a simple analytic form . specifically , when @xmath115 and @xmath122 we have @xmath123 and thus @xmath124^{1/2 } \ , . \nonumber \end{aligned}\ ] ] in the super fast - magnetosonic regime @xmath116 and @xmath125 . this makes it possible to simplify the expression for @xmath90 even further , @xmath126 which leads to @xmath127 . \nonumber \end{aligned}\ ] ] this shows that @xmath110 , which enables us to approximate the left side of this equation as @xmath128 and write @xmath129\ , . \label{exp_speed}\ ] ] for the jet problem this implies that the jet opening half - angle @xmath130 increases only by the amount @xmath131 these considerations imply that the product @xmath132 can increase to values that are significantly greater than 1 and that this occurs mainly on account of the increase in @xmath133 . this is indeed the behaviour seen in our jet simulations . the rarefaction acceleration process has been seen in numerical simulations of both unmagnetized and magnetized flows and a number of conclusions have been drawn about the role of the magnetic field @xcite . as both cases may have applications in astrophysics , we are motivated to extend our analysis and investigate the role of the magnetic field in the rarefaction mechanism a bit further . in particular , it is interesting to see if the presence of strong magnetic fields can lead to some observationally identifiable features . to check on ths we have derived self - similar solutions of the riemann problem described in section [ case2 ] for four different left states : a cold mhd flow , a hot mhd flow and two purely hydrodynamic ( hd ) flows with different values of @xmath61 . in all of these cases the magnitude of the energy flux per unit rest - mass energy flux @xmath95 is kept the same . the lorentz factor near the boundary with the vacuum approaches this value , independently of the other characteristics of the rarefaction wave ( see equation [ boundary - g ] ) . however , the spatial distribution of the lorentz factor near the right boundary turns out to be quite sensitive to the magnetization of the left state . [ raref_gammacont ] shows the results of the numerical integrations for an ideal gas with polytropic index @xmath134 . if we compare the properties of the cold mhd flow ( first column ) with those of the hd flow ( third column ) we see that the acceleration is much stronger in the cold mhd case . in the first place this is due to the fact that , in the mhd case , the acceleration occurs over a larger volume of the jet . this is simply a reflection of the difference in the speeds of the rarefaction wave s head in the hd case it is determined by the sound speed @xmath135 , whereas in the mhd case it is determined by the fast - magnetosonic speed @xmath83 , which can approach the speed of light . a second reason for the difference between the mhd and hd cases has to do with the dependence of the ( generalized ) specific enthalpy on the mass density . whereas @xmath136 is proportional to the mass density @xmath49 , @xmath137 is proportional to @xmath138 . as the density drops across the rarefaction wave , the magnetic energy declines much faster than the thermal energy , which explains the relative inefficiency of the hydrodynamic case . for example , in the hd flow shown in the third column of fig . [ raref_gammacont ] , the density is @xmath139 at @xmath140 , but the value of @xmath137 is still 2 ( meaning that the lorentz factor is only a half of its maximum value , @xmath141 ) . in contrast , in the cold mhd case @xmath136 is only @xmath142 at the same value of the density , meaning that @xmath133 is already @xmath143 . note that the time dependence of the density of a particular fluid parcel is different in the two cases . as shown in appendix [ append_approx ] , in the mhd case the density drops with time as @xmath144 , whereas in the hd case it declines faster ( @xmath145 ) due to the higher speed of the tail of the rarefaction . nevertheless , the ( generalized ) specific enthalpy in the mhd and hd cases is proportional to @xmath144 and @xmath146 , respectively , implying that the increase of the lorentz factor is much stronger in the former case . the above interpretation of the rarefaction - acceleration mechanism is consistent with the general analysis of the acceleration of cold , steady - state jets presented in @xcite , where it was shown that the bulk flow acceleration is intimately related to the shape of the field ( or stream ) lines through the ` bunching function ' @xmath147 where @xmath8 is the cylindrical distance from the rotation axis , @xmath148 is the amplitude of the poloidal magnetic field and @xmath149 is the magnetic flux function . in the super fast - magnetosonic regime the lorentz factor increases when @xmath150 decreases . specifically , one can show that @xmath151 where @xmath152 is the distance measured along the poloidal magnetic field lines and the effective rest - mass @xmath153 is constant on magnetic flux surfaces ( see appendix [ appb ] ) . the coefficient in front of the derivative on the left hand side of this equation vanishes at the fast - magnetosonic critical surface which , in the highly relativistic limit , implies @xmath154 . thus , in the super fast - magnetosonic regime , acceleration corresponds to a decrease in @xmath150 , whereas in the sub fast - magnetosonic regime it corresponds to an increase in the bunching function . this is analogous to the transonic hydrodynamic flow in a de laval nozzle , with @xmath155 playing the role of the nozzle cross section . equation ( [ bf ] ) shows that , for @xmath150 to decrease , @xmath148 should decrease faster than @xmath156 , i.e. the separation between neighbouring magnetic flux surfaces should increase with distance faster than @xmath8 , their cylindrical radius . in confined flows , such as model b1 and the other cases studied in @xcite , this is realised through the stronger collimation of the inner flux surfaces relative to the outer ones . for this reason , the acceleration mechanism at work in such flows can be dubbed the _ collimation mechanism_. and the amplitude of poloidal magnetic field decreases faster than @xmath156 . , width=302 ] the acceleration mechanism that operates in models b1a and b1b during the transition to the ballistic regime is different from the collimation mechanism in that it involves a rarefaction wave , and we therefore dub it the _ rarefaction mechanism_. in this process , the rarefaction wave that is launched at the jet boundary at the point where the channel widens reaches the jet axis much further downstream . therefore , the outer field lines straighten much closer to the source than the inner ones ( see fig . [ ill ] ) . the net effect is again that @xmath148 decreases faster than @xmath156 . inspection of models b1a and b1b shows that the magnetic bunching function indeed decreases along the magnetic field lines ( see fig . [ s ] ) and that in both of these models the flow becomes super fast - magnetosonic well upstream of the channel widening point . our numerical simulations confirm the discovery by @xcite of the additional fast acceleration of relativistic jets during the transition from a confined to an unconfined regime . we have analyzed the acceleration mechanism and concluded that it is related to the sideways expansion of the jet that is triggered by the elimination of support from the confining wall . this expansion does not lead to a significant increase of the jet opening angle because of the high mach number that the flow has already attained by the time it reaches the location where the channel opens up . the induced rarefaction wave is nevertheless strong enough to lead to the conversion of a large fraction of the remaining magnetic energy into kinetic energy of bulk motion . the rarefaction - acceleration mechanism and its potential relevance to relativistic astrophysical flows were previously considered by @xcite and @xcite for unmagnetized and magnetized flows , respectively . as discussed in section [ hdvsmhdsection ] , the slow expansion of the left front of the rarefaction and the weak dependence of the enthalpy on the density in a hydrodynamic outflow , as compared to the faster expansion and stronger dependence of the magnetic energy on the density in mhd cases , is evidently behind the finding of @xcite that this acceleration mechanism is more efficient in mhd outflows than in purely hydrodynamic ones . although this mechanism operates even in newtonian flows , its role there is not that important . this is because a high fast - magnetosonic mach number in the newtonian regime implies that most of the magnetic energy has already been converted into kinetic energy of bulk motion , so the effect of any additional acceleration is rather insignificant even if it involves a full conversion of the remaining magnetic energy . the situation is different in the relativistic case since the flow can remain magnetically dominated even in the highly super fast - magnetosonic regime . note in this connection that the gradual increase of the lorentz factor of an unmagnetized long / soft grb outflow as it first emerges from underneath the surface of the associated progenitor star ( e.g. * ? ? ? * ) has a different origin than the rarefaction acceleration considered here . in the unmagnetized case , a ` cocoon ' of moderately relativistic , shocked jet and stellar material that formed while the outflow was confined within the star is the first component to be revealed . the second component to emerge is the faster shocked jet material that occupies the region between the jet head and the reverse shock that was induced by the interaction of the outflow with the stellar envelope . finally , the unshocked , high - velocity jet itself comes out . the behaviour of the latter component after it leaves the star is initially influenced by the presence of the ` shielding ' cocoon gas . whether significant rarefaction acceleration could occur under these circumstances even in a jet that reaches the stellar surface with a measurable fraction of its thermal energy not yet converted into kinetic energy remains to be investigated . we have shown that when the rarefaction wave propagates inside the jet it produces a region where the separation between neighbouring poloidal magnetic surfaces increases faster than their cylindrical radius . this is a common feature of magnetic acceleration in the super fast - magnetosonic regime and is also a characteristic of the magnetic acceleration process of externally confined flows by the collimation mechanism . however , there are also significant differences between these two mechanisms . most importantly , acceleration by the collimation mechanism can be sustained over many decades in distance and produces asymptotic flows with @xmath157 , whereas the rarefaction mechanism continues only for as long as it takes for the rarefaction wave to cross the jet ( of the order of the current jet length in our numerical models ) , and subsequently the flow enters a phase of ballistic expansion wherein the magnetic acceleration is so slow that it can be ignored . we emphasize that the present study has involved axisymmetric simulations . a fully three - dimensional ( 3d ) treatment is needed to address the issue of stability , although we note that the results to date ( e.g. * ? ? ? * ) indicate that magnetically accelerated relativistic jets basically remain stable as they propagate away from the source . it is also not yet entirely clear whether the acceleration / collimation properties of 3d outflows remain the same as in the axisymmetric case , but , at least on the basis of newtonian simulations ( e.g. * ? ? ? * ) , it appears that the acceleration efficiency remains roughly the same . the most effective magnetic acceleration of steady flows could be achieved via a combination of both mechanisms first the collimation mechanism produces a flow with @xmath157 , and then the rarefaction mechanism provides additional acceleration , resulting in a particle - dominated ( @xmath158 ) flow . model b1b is an illustrative example of such a combination ( see fig . [ sigma ] ) , and it is interesting to examine whether it could in principle be realized in long / soft grb sources . if the jet originates from a rapidly rotating black hole then the light cylinder radius is of the order of a few gravitational radii , @xmath159 cm for a @xmath160 black hole . if the confining medium is the stellar envelope , the collimation mechanism operates up to @xmath161 . a quick inspection of fig . [ sigma ] shows that this corresponds to the channel widening point in our model b1b . thus , it may indeed be possible to accelerate long / soft grb flows to the high lorentz factors indicated by observations , with @xmath162 decreasing to values @xmath163 ( as happens in this example on scales @xmath164 cm ) . however , it seems unlikely that the low magnetization ( @xmath165 ) required for effective dissipation in the internal - shocks model for the prompt @xmath166-ray emission can be attained in this scenario , which suggests that magnetic energy dissipation might need to be invoked to explain this emission ( e.g. * ? ? ? if the initial magnetization @xmath167 is very high , well above @xmath168 , the jet will still be magnetically dominated when it enters the ballistic regime . as pointed out by @xcite , the rarefaction - acceleration mechanism can in principle give rise to magnetically accelerated outflows that satisfy @xmath3 . in the standard model of uniform grb jets , this condition allows a late ( on a time scale @xmath169 day ) panchromatic jet break in the afterglow light curve . however , as the asymptotic structure of magnetically accelerated jets is far from being uniform , further investigation is required to fully establish this result . furthermore , in some of the grb sources detected by _ swift _ there have been indications of an early ( on a time scale of @xmath5hr ) jet break ( e.g. * ? ? ? * ; * ? ? ? * ) , corresponding to @xmath170 and @xmath171 , as predicted by pure collimation - acceleration models @xcite . if these inferences are corroborated by further observations , the reasons why certain long / soft grb sources show no evidence of rarefaction acceleration will need to be clarified . it is , however , also conceivable that the acceleration of jets that exhibit a late break in the afterglow lightcurve is predominantly thermal , since in this case the value of @xmath172 is not limited as in the magnetic acceleration scenario . one may , however , be able to distinguish between the thermal and magnetic mechanisms at least in some cases based on other observational diagnostics , such as the appearance of a photospheric emission component ( e.g. * ? ? ? this issue could potentially be further illuminated by studies of short / hard grb afterglows . since the outflows in the latter sources evidently do not propagate through a stellar envelope , the rarefaction - acceleration mechanism would not operate in this case ( or at least not in the same way as in long / soft grb sources ) . if short / hard grb outflows are accelerated predominantly by magnetic stresses , this suggests that there should be no late - time breaks in their afterglow lightcurves ( or at least fewer than in the case of long / soft grbs ) . while the data on short / hard grb afterglows are still sparse ( e.g. * ? ? ? * ) , this prediction could in principle be tested as more such afterglows are observed . ssk was supported by the stfc grant `` a rolling programme of astrophysical research at leeds '' . nv acknowledges partial support by the special account for research grants of the national and kapodistrian university of athens . ak was partially supported by a nasa astrophysics theory program grant . aloy m. a. , rezzolla l. , 2006 , apj , 640 , l115 anile a. m. , 1989 , relativistic fluids and magneto - fluids , cambridge univ . press , cambridge anile a. m. , pennisi s. , 1987 , ann . henri poincar , 46 , 27 bucciantini n. , quataert e. , arons j. , metzger b. d. , thompson t. a. , 2008 , mnras , 383 , l25 bucciantini n. , quataert e. , arons j. , metzger b. d. , thompson t. a. , arons j. , del zanna l. , 2009 , mnras , 396 , 2038 daigne f. , drenkhahn g. , 2002 , a&a , 381 , 1066 kamble a. , misra k. , bhattacharya d. , sagar r. , 2009 , mnras , 394 , 214 s. s. , 1999 , mnras , 303 , 343 s. s. , 2001 , mnras , 326 , l41 s. s. , 2004 , mnras , 350 , 1431 s. s. , barkov m. v. , 2007 , mnras , 382 , 1089 s. s. , barkov m. v. , 2009 , mnras , 397 , 1153 s. s. , barkov m. v. , vlahakis n. , knigl a. , 2007 , mnras , 380 , 51 s. s. , vlahakis n. , knigl a. , barkov m. v. , 2009 , mnras , 394 , 1182 liang e .- w . , racusin j. l. , zhang b. , zhang b .- b . , burrows d. n. , 2008 , apj , 675 , 528 lithwick y. , sari , r. , 2001 , apj , 555 , 540 lyubarsky y. , 2009 , apj , 698 , 1570 lyutikov m. , blandford r. d. , 2003,arxiv : astro - ph/0312347 mart j. m. , mller e. , 1994 , j. fluid mech . , 258 , 317 mckinney j. c. , 2006 , mnras , 368 , 1561 mckinney j. c. , blandford r. d. , 2009 , mnras , 394 , l126 mszros p. , 2006 phys . , 69 , 2259 mizuno y. , hardee p. , hartmann d. h. , nishikawa k .- zhang b. , 2008 , apj , 672 , 72 moll r. , 2009 , a&a , 507 , 1203 morsony b. j. , lazzati d. , begelman m. c. , 2007 , apj , 665 , 569 nakar e. , 2007 , phys . , 442 , 166 panaitescu a. , 2007 , mnras , 379 , 331 piran t. , 2005 , rev . , 76 , 1143 racusin j. l. , et al . , 2009 , apj , 698 , 43 rhoads j. e. , 1999 , apj , 525 , 737 romero , r. , mart , j. m. , pons , j. a. , ibez , j. m. , miralles , j. a. 2005 , j. fluid mech . , 544 , 323 ryde f. , et al . , 2010 , apj , 709 , l172 sari r. , piran t. , halpern j. p. , 1999 , apj , 519 , l17 tchekhovskoy a. , narayan r. , mckinney j. c. , 2008 , mnras , 388 , 551 tchekhovskoy a. , narayan r. , mckinney j. c. , 2009a , apj , 699 , 1789 tchekhovskoy a. , narayan r. , mckinney j. c. , 2009b , arxiv0909.0011 n. , 2004 , apj , 600 , 324 n. , knigl a. , 2003 , apj , 596 , 1080 b. , peer a. , 2009 , apj , 700 , l65 the derivation of the characteristics equations that yield the phase speeds of relativistic mhd waves can be found in a number of references ( e.g. * ? ? ? * ; * ? ? ? * ; * ? ? ? for the fast - magnetosonic waves the result is @xmath173=0\ , , \end{array } \label{i1}\ ] ] where @xmath174 is the generalized enthalpy and @xmath175 is the magnetic field 4-vector ( see equations 29 and a20 in @xcite ) . in order to have compact equations we employ in this appendix geometric units in which @xmath176 . the components of @xmath175 can be obtained given the magnetic field and flow velocity 3-vectors via @xmath177 in the problem under consideration @xmath178 and @xmath179 . moreover , in the frame comoving with the fluid along the @xmath97 axis @xmath180 and equation ( [ i1 ] ) yields @xmath181^{-1 } . \label{i3}\ ] ] here we use a tilde to indicate quantities in the comoving frame ( comoving only in the @xmath97 direction ) . using the equations of lorentz transformation we find @xmath182 where @xmath183 and @xmath133 are the flow parameters as measured in the frame of the initial discontinuity and where @xmath184 and @xmath185 describe the motion of the comoving frame . since @xmath186 , this equation yields @xmath187 where @xmath188 . substituting this result into equation ( [ i3 ] ) , we obtain @xmath189^{-1}. \label{i6}\ ] ] thus , the right - hand side of equation ( [ eq - char1 ] ) is indeed the fast - magnetosonic wave speed as measured in a frame that comoves with the fluid along the @xmath97 axis . the riemann problem considered in section [ case2 ] is described by equations ( [ is])([ip ] ) and ( [ eq - char1 ] ) . here we add that one can follow the wordline of a fluid parcel initially located at @xmath190 , by integrating the equation @xmath191 which follows from the definition @xmath35 . the dimensionless time @xmath192 , for times @xmath193 ( i.e. after the head of the rarefaction wave has already passed @xmath194 ) , is given by @xmath195 the expressions for the lorentz factor @xmath133 and the expansion speed @xmath52 as functions of the density @xmath49 in the cold @xmath196 , ultra - relativistic @xmath197 limit have already been derived in section [ case2 ] and are given by equations ( [ lor1 ] ) and ( [ exp_speed ] ) , respectively . using the same simplifications , we can find the density and the lorentz factor as functions of @xmath198 . equation ( [ eq - char1 ] ) can be writen as @xmath199 \,,\ ] ] implying @xmath200 for the head and @xmath201 for the tail of the rarefaction wave . the lorentz factor is @xmath202 , with @xmath203 \,,\ ] ] found by inverting equation ( [ xoverctsimple ] ) . we can also express the lorentz factor as a function of the dimensionless time @xmath204 , since equation ( [ teq ] ) implies @xmath205 the resulting expression is @xmath206 similar approximations in the purely hydrodynamic limit ( @xmath207 ) imply @xmath208 -{\cal i } \left[\left(2-\gamma\right)\left(h_j-1\right)\varrho^{\gamma-1}\right ] } { \mu_j \left(\gamma-1\right)^{1/2}\left(2-\gamma\right)^{1/2 } } \ , , \nonumber \\ { \cal i } \left[\zeta\right ] \equiv \zeta^{1/2 } \left(1+\zeta\right)^{1/2 } + \ln \left[\zeta^{1/2}+\left(1+\zeta\right)^{1/2}\right ] \ , , \\ \frac{x}{ct}=\frac{v_x}{c } -\frac{1}{\gamma } \left [ \frac{\left(\gamma-1\right)\left(h_j-1\right)\varrho^{\gamma-1 } } { 1+\left(2-\gamma\right)\left(h_j-1\right)\varrho^{\gamma-1 } } \right]^{1/2 } \ , , \\ t = \gamma_j \varrho^{-(\gamma+1)/2 } \left [ \frac{1+\left(2-\gamma\right)\left(h_j-1\right)\varrho^{\gamma-1 } } { \left(\gamma-1\right)\left(h_j-1\right ) } \right]^{1/2 } \ , , \label{timehd}\end{aligned}\ ] ] where @xmath209 . ( note that , for @xmath210 and @xmath211 , we recover the cold mhd case considered in section [ hd ] . ) for @xmath134 and @xmath133 significantly larger than @xmath212 , equation ( [ timehd ] ) simplifies to @xmath213 subtituting this result into equation ( [ gammahd ] ) , we infer the dependence of the lorentz factor on @xmath204 , @xmath214 comparing the results ( [ gam_analmhd ] ) and ( [ gam_analhd ] ) , we see that the rarefaction - acceleration process is faster in the mhd case than in a purely hydrdynamic flow . this is part of the reason for why this mechanism is more efficient in mhd jets , as discussed in section [ hdvsmhdsection ] . at distances from the central source where the flow can be considered cold and the azimuthal velocity small , the component of the momentum equation along the motion can be written as where @xmath49 is the rest - mass density , @xmath8 is the cylindrical coordinate , @xmath216 is the azimuthal component of the magnetic field , @xmath152 is the arclength along a poloidal field ( or stream ) line , and derivatives with respect to @xmath152 are taken along a given field line ( see e.g. equation 20 in @xcite ) . we can further simplify equation ( [ momentum - v_p ] ) by using two integrals of motion , the mass flux per unit magnetic flux @xmath217 and the angular velocity of magnetic field lines @xmath218 ( see e.g. section 2.1 in @xcite ) . using their expressions in the limit of a small azimuthal velocity , we have @xmath219 equation ( [ momentum - v_p ] ) can be written in the form of a momentum equation of a point particle in a potential field : @xmath220 the effective rest mass , @xmath153 , is inversely proportional to the magnetization , @xmath221 and the effective potential energy is related to the bunching function , @xmath222 the corresponding energy equation can be written as @xmath223 where the integral of motion @xmath15 represents the total energy flux per unit rest - mass energy flux . the bunching function @xmath150 is directly connected to the geometry of the flow . the cross sectional area between two neighbouring flux surfaces @xmath224 and @xmath225 is @xmath226 . thus , the function @xmath150 is proportional to @xmath227 over this area and decreases whenever the flow expands in such a way that this area increases faster than @xmath227 ( @xcite ; see also section 5.1 in @xcite ) . the evolution of @xmath150 is determined by the transfield component of the momentum equation ; it depends on the external pressure that confines the jet ( or , equivalently , on the shape of the ` wall ' that defines its outer boundary ) . since the potential depends not only on @xmath150 but also on the velocity , it is useful to separate out the effect of geometry in the equation of motion . combining equations ( [ momentum1 ] ) , ( [ potential ] ) and ( [ integral ] ) we can write @xmath228 the resulting critical point corresponds to the fast magnetosonic surface , where @xmath229 and @xmath154 ( in the relativistic regime where @xmath230 ) . acceleration in the super - fast ( sub - fast ) magnetosonic regime corresponds to decreasing ( increasing ) @xmath150 , respectively . if at some point the curvature of the jet boundary suddently increases , the adjustment of the magnetic field from the old to the new curvature corresponds to a fast expansion and decrease of the bunching function . this is precisely the effect of the _ rarefaction wave _ analysed in section [ interpretation ] . as an example , suppose that the initial shape is parabolic , @xmath231 , and the final shape is conical , @xmath232 , as shown in fig . [ ill ] . the variables @xmath233 and @xmath234 are functions of @xmath224 and can be found from a smooth matching of the magnetic field along the transition surface @xmath235 ( dotted line in fig . [ ill ] ) . downstream from this surface the bunching function @xmath150 declines as @xmath236 ( see equation 35 and the related discussion in @xcite for further details ) . the appearance of the variable @xmath237 in the equation describing the conical boundary ( @xmath238 ) is crucial for enablig the additional acceleration ( by making @xmath239 ) : this is elaborated in the discussion of the difference between ` type i conical ' ( in which @xmath240 ) and ` type ia conical ' ( in which @xmath241 ) shapes in @xcite ; similar categories exist for parabolic shapes as well ( type i , ia , ii and iia ) . although the adopted channel shape in model b1b is a simple cone whose vertex is located at the origin , the field lines clearly have a ` type i conical ' shape , i.e. their projection crosses the @xmath242 axis at @xmath243 with @xmath244 ( see the right panel of fig . [ lorentz ] and fig . [ ill ] ) . equation ( [ eq_for_s ] ) fits well the curves seen in fig . [ s ] . in one decade or so in cylindrical distance downstream from the transition radius @xmath245 , the bunching function drops from @xmath246 to @xmath247 . the difference @xmath248 ( @xmath249 corresponds to a difference @xmath250 in the potential energy and thus to an acceleration @xmath251 .

when a magnetically dominated super fast - magnetosonic long / soft gamma - ray burst ( grb ) jet leaves the progenitor star , the external pressure support will drop and the jet may enter the regime of ballistic expansion , during which additional magnetic acceleration becomes ineffective . however , recent numerical simulations by tchekhovskoy et al . have suggested that the transition to this regime is accompanied by a spurt of acceleration . we confirm this finding numerically and attribute the acceleration to a sideways expansion of the jet , associated with a strong magnetosonic rarefaction wave that is driven into the jet when it loses pressure support , which induces a conversion of magnetic energy into kinetic energy of bulk motion . this mechanism , which we dub _ rarefaction acceleration _ , can only operate in a relativistic outflow because in this case the total energy can still be dominated by the magnetic component even in the super fast - magnetosonic regime . we analyse this process using the equations of relativistic mhd and demonstrate that it is more efficient at converting internal energy into kinetic energy when the flow is magnetized than in a purely hydrodynamic outflow , as was found numerically by mizuno et al . we show that , just as in the case of the magnetic acceleration of a collimating jet that is confined by an external pressure distribution the _ collimation acceleration _ mechanism the rarefaction - acceleration process in a magnetized jet is a consequence of the fact that the separation between neighbouring magnetic flux surfaces increases faster than their cylindrical radius . however , whereas in the case of effective collimation - acceleration the product of the jet opening angle and its lorentz factor does not exceed @xmath0 , the addition of the rarefaction - acceleration mechanism makes it possible for this product to become @xmath1 , in agreement with the inference from late - time panchromatic breaks in the afterglow light curves of long / soft grbs . mhd relativity methods : numerical gamma - rays : bursts

in the context of cold dark matter dominated ( cdm ) , hierarchical clustering cosmology , large galaxies are formed from the merging and accretion of small , less massive progenitors ( clumps ) . the exact role played by this substructure in the formation of galaxies is still unclear , and there remain unresolved several very important and fundamental issues that are closely related to the role of these clumps . the angular momentum content of galaxies is a fundamental parameter . cosmological n - body simulations have verified the proposal that tidal torques between proto - galaxies generate angular momentum ( peebles 1969 ) , and have shown that the dimensionless spin parameter @xmath0 has a well - defined mean value of @xmath1 , independent of the details of the power spectrum of density fluctuations ( efstathiou & jones 1979 ; aarseth & fall 1980 ; barnes & efstathiou 1987 ; warren _ et al . _ 1992 ; steinmetz & bartelmann 1995 ; cole & lacey 1996 ) . since the spin parameter @xmath2 is much smaller for present day ellipticals indeed equal to the value of @xmath1 of a typical dark halo than is the value of @xmath2 for spirals , while the effective radius for spirals is comparable to that of ellipticals at a given luminosity ( fall 1980 ) , it is important to know how the ellipticals succeed in losing angular momentum , compared to the expectation of smooth collapse and spin - up within a dark halo ( fall & efstathiou 1980 ) while still dissipating the same amount of binding energy as do proto - spirals . on the other hand , there exists an angular momentum problem in that while disks are formed in fully self - consistent hierarchical - clustering simulations , the angular momentum transport inherent in the merging process produces disks that are too centrally - concentrated and contain too little angular momentum compared with observed spirals ( e.g. navarro & benz 1991 ; evrard , summers & davis 1994 ; vedel , hellsten & sommer - larsen 1994 ; navarro & steinmetz 1997 ) . indeed standard analytic and semi - analytic models of the formation of spiral galaxies show that extended disks , as observed , form through detailed angular momentum conservation , with proto - disk material retaining the same value of specific angular momentum as the dark halo ( e.g. white & rees 1978 ; fall & efstathiou 1980 ; gunn 1982 ; jones & wyse 1983 ; dalcanton , spergel & summers 1997 ; mo , mao & white 1998 ; zhang & wyse 2000 , silk 2001 ) . hence models must retain angular momentum for spirals , while losing it for ellipticals . mergers and the associated gravitational torques and angular momentum transport clearly play a role . however , detailed merger simulations of two disk galaxies have shown that there are difficulties with the simplest merger picture of how ellipticals form ( bendo & barnes 2000 ; cretton , naab , rix & burkert 2001 ) , in that equal mass mergers seem to produce too much kinematic misalignment , while in unequal mass mergers the strong signatures of the more massive disk survive . what are the effects of substructure such as gas clouds , stellar ( globular ? ) clusters , dwarf galaxies or sub - halos which fall later into the galactic - scale potential well ? do they significantly change the angular momentum distribution and further change the final galaxy classification ? an analytical approach will have difficulties in dealing with this problem , although the secondary infall model is successful in describing the smooth post - collapse halo profile ( gunn & gott 1972 ; gunn 1977 ; filmore & goldreich 1984 ; hoffman & shaham 1985 ; bertschinger & watts 1988 ; zaroubi , naim & hoffman 1996 ) . however , numerical simulations have the capability of treating the formation and the non - linear evolution of dark halos in a cosmological context ( quinn , salmon & zurek 1986 ; zurek , quinn & salmon 1988 ; quinn & zurek 1988 ; warren _ et al . _ 1992 ; dubinski & carlberg 1991 ) . these studies show that the angular momentum and binding energy are indeed redistributed , in an orderly manner , during the relaxation of the halos ( quinn & zurek 1988 ) . further , during the merging process inherent in hierarchical clustering , baryonic substructure can lose angular momentum to the dark halo ( frenk _ et al . _ 1985 ; zurek , quinn & salmon 1988 ; barnes 1988 ; navarro & steinmetz 1997 ; navarro , frenk & white 1995 ; ) . zurek , quinn & salmon ( 1988 ) suggest that whether the baryonic clumps are gas clouds ( and hence dissipative ) or stellar could be an important criterion in determining whether the forming galaxy will become a spiral or an elliptical . proposed solutions to the problem with disks , within the context of cdm cosmologies , have included delaying the onset of disk formation until after the merging process is essentially complete , by appeal to suitable ` feedback ' from the first stars ( weil , eke & efstathiou 1998 ) , but this solution must address the old age for disk stars in the solar neighborhood ( e.g. edvardsson _ et al . _ 1993 ; wyse 1999 ) and in the outer parts of the m31 disk ( ferguson & johnson 2001 ) , in addition to the observation of apparently fully - formed disks at redshifts above unity ( brinchmann & ellis 2000 ) with a tully - fisher relation that is essentially indistinguishable from that of present - day disks , apart from passive evolution . the density and mass of the substructure are clearly important , and a major motivation for the present work is to quantify the effects of substructure of a range of each . further , when is substructure disrupted and why ? another issue we seek to clarify is how much of the angular momentum change seen in the cosmological simulations is due to the boundary conditions , namely that the system under study is not closed . it is hard to separate the effects of the real angular momentum transfer from clumps to halo from the angular momentum gain by the accretion of material or the torques applied by the neighboring environment or the later infall of dark matter . thus it is worthwhile to study , as here , the evolution of angular momentum in isolated systems . in the isolated n - body simulations by barnes ( 1988 ) of the encounter of two galaxies , it is found that the dark halo can extract some angular momentum from other components . in this paper , we shall extend such n - body studies of the dynamical evolution to analyse the evolution of a system of clumps in a larger , smooth , isolated system . our simulations have relevance beyond a forming proto - galaxy . we may address the dynamical processes occurring in a virialized system with substructure , such as a cluster of galaxies or a single galaxy and its retinue of dwarf companion galaxies . the relative importance of the effects of the dissipationless collapse of the overall system , tidal disruption of clumps , dynamical friction of clumps , clump - clump heating and merging can possibly be related to the formation of cd galaxies in clusters of galaxies , to the formation of central density cusps in dark halos , to the triaxial nature of dark halos , to the formation of substructure composed of disrupted debris in the outer halo regions of galaxies , etc . thus we initiated a consistent comparison among these dynamical processes in the context of galaxy formation . in section 2 , we present the parameters of our n - body simulations . section 3 contains a discussion of our expectations for the dynamics of the substructure based on analytic calculations and comparisons with the n - body simulations , while section 4 discusses the angular momentum content and transport . the internal kinematics of the different components are discussed in section 5 , while their morphology is discussed in section 6 . section 7 summarizes our conclusions . the more technical aspects are given in the appendices . we adopt a numerical n - body code based on the hierarchical tree algorithm ( barnes & hut 1986 ; hernquist 1987 ) . our simulations study the dynamical evolution of a number of clumps embedded in a smooth dark halo . due to the collisionless property of the particles used in our n - body simulation , it should be emphasized that the clump can represent either stellar or dark matter depending on our interpretation of the physical entity . the initial dark halo profile is modelled with either the hernquist profile ( hernquist 1990 ) or the plummer profile ( plummer 1911 ) , the details of which are given in appendix a. the hernquist profile , with @xmath3 at the centre and @xmath4 at large radius , was introduced as being , when projected , close to the observed surface brightness profiles of elliptical galaxies , and is close to the mass profile seen in hierarchical clustering simulations ( the nfw profile ; navarro , frenk & white 1997 ) , which has a cuspy centre , @xmath3 ( though flatter than the @xmath5 behaviour of high - resolution simulations ; ghigna _ et al . _ 2000 ) , and @xmath6 at large radius . the plummer profile has close to a harmonic potential in the core ( only slowly varying density ) and @xmath7 at large radius . in all realisations , each clump is simulated with a plummer profile . we ran simulations of systems in initial equilibrium plus out - of - equilibrium systems that underwent an initial collapse . in order to study the angular momentum behaviour of the clumps and the dark halo , we require that the system contain enough angular momentum , consistent with the cosmological initial conditions expected , i.e. @xmath8 ( e.g. efstathiou & jones 1979 ; barnes & efstathiou 1987 ) . first , we build the dark halo with no streaming velocity . then , we add some angular momentum about the @xmath9 direction , which is defined to be the axis of the halo . the orbital rotation velocity added to each particle is the component projected on the equatorial plane of a constant fraction , @xmath10 , of the circular velocity where the particle is located , i.e. , @xmath11 , where @xmath12 is the angle between @xmath13 and @xmath14 . we further stretch the spherical profile to an oblate profile with ellipticity @xmath15 ( warren _ et al . assuming , if the system is virialized , that the flattening is only caused by the addition of rotation , we adopt the empirical relation @xmath16 , which may be seen by noting the scaling of the rotation parameter @xmath17 for isotropic systems flattened by rotation ( binney & tremaine 1987 ) . with this choice of @xmath10 , the initial spin parameter of the halo in the virialized simulations ( with the virial ratio @xmath18 , where @xmath19 is the total kinetic energy and @xmath20 is the total potential energy ) is @xmath21 . the collapse simulation models ( with the virial ratio @xmath22 ) have @xmath23 . in order to achieve an initial condition suitable for pre - collapse , i.e. with small @xmath24 , we decrease the total velocity of the dark halo particles and the velocity of each clump by a factor of @xmath25 for @xmath22 . no internal rotation is added to the clumps , which are spherical . the distribution of clumps is chosen to follow the dark halo profile with similar treatment of the flattening and rotation velocity . for the simulation models with the same number of clumps , we require the orbital characteristics for the clumps be the same with the exception of models b and e ( see table 1 ) . the parameter values of interest for our simulations are given in table [ tab : parameter ] . the total number of particles in our simulations ranged from 20,000 to 120,000 , with smooth dark halo particles and clump particles having an equal mass . the total number of clumps , @xmath26 , varied from 5 to 80 and the total clump mass fraction , @xmath27 , varied from 5% to 100% . these ranges were chosen to study the effect of clumpiness on the outcome of the simulations . the core radius of a clump ( a plummer sphere ) is set to achieve the chosen density contrast , @xmath28 , the ratio of the mean density within the half mass radius of the clump to that of the whole system ( dark matter plus the clumps ) . we vary the density parameter @xmath29 ( with @xmath30 ) over the range of 3 to 64 in our simulations , to study the effects of global tides in disrupting the clumps . a value of three for the density contrast is the minimum expected for a system to withstand global tides ( the roche criterion ) . the total mass of the system is normalized to be unity . the unit of distance is the core size of the dark halo ( @xmath31 , see appendix a ) and we further set the gravitation constant @xmath32 . with these units and as detailed in appendix a , the mean crossing time for a hernquist halo is 5.3 , while that for a plummer halo is 2.1 , and the simulations are run for @xmath33 crossing times , or approximately a hubble time in physical units . it is convenient to express some of our parameters , such as the clump mass fraction @xmath27 , the number of clumps @xmath26 , density contrast of each clump @xmath28 , and crossing time @xmath34 , in terms of dimensionless quantities . from our definition of the density contrast of the clump , the ratio of the half mass radius of a clump to that of the whole system can be written as r _ c / r _ h = f^1/3 n^-1/3_c ( ) ^-1/3 . the ratio of the one - dimensional internal velocity dispersion of the clump and the halo is @xmath35 . this can be further written as _ c/_h = f^1/3 n^-1/3_c ( ) ^1/6 . as demonstrated in appendix b , while there may well be spurious clump heating effects in our simulations , due to the limited number of particles used , they do not pose a problem for our analysis . the softening - length in the treecode is set at @xmath36 , where @xmath37 is the number of particles used in each clump . this relatively large value is chosen to suppress the unphysical two - body relaxation ( white 1978 ) which otherwise could occur due to the small number of particles used in each clump ( ranging from 150 to 2400 ) . figure [ fig : relax ] shows the mass profiles for examples of unperturbed clumps consisting of 150 particles ( from simulation a ) and 900 particles ( from simulation h ) at the beginning ( solid line ) and the end ( dashed line ) of our simulations . the radius of a given mass fraction does not change much even for the clump with 150 particles , demonstrating that indeed relaxation effects are not important . in this section , we describe the methods we used in calculating the quantities of physical interest , such as the angular momentum , the properties of the debris from the disrupted clumps , and the ellipticity or triaxiality , density and kinematics of the clumps and the halo . in calculating the angular momentum , one needs to choose the origin carefully . here we calculate the angular momentum of the different components of the system in two ways , relative to the centre of mass of the whole system and relative to the highest density point of the dark halo . the centre of mass of the whole system can be calculated directly , while the highest density point of the dark halo can be searched for in an iterative way : first we choose the centre of mass of the whole system as the starting point @xmath38 , and calculate the centre of mass @xmath39 of the dark halo particles contained within a radius @xmath40 relative to the point @xmath38 . then we adopt the point @xmath39 as the next starting point to repeat the above process until the centre of mass converges ; then we decrease the radius @xmath41 by half and repeat the first step . after several iterations of these two steps , the highest density point is located when the search radius @xmath41 has decreased greatly . throughout this paper we adopt the highest density point as the origin when calculating other physical quantities such as the density profile , ellipticity and kinematics . the debris disrupted from each clump is calculated in an iterative way : at some timestep , e.g. initially , for each clump we know those particles still bound to that clump ; at the next timestep we check which of those particles remain bound to the clump , and we assign the unbound particles to the debris . we repeat this process at each timestep until the end of the simulation is reached or the clump is completely disrupted . it should be noted that our simulation code is not designed to search for merging events , which would require a more sophisticated algorithm that includes a check on a merging criterion at each timestep of the integration . thus the ` debris ' we identify could include some clump particles that are no longer bound to their initial clump due to the fact that this initial clump has merged with another clump , and the particles are bound to the new merger remnant , rather than being truely unbound . in other words , we do not re - assign particles to a new , larger clump should one clump be subsumed in another . we simply keep track of whether the particles remain bound or not to the initial clump . however , our calculation of the debris would be inaccurate only in a very few cases in which the merging process is very efficient . in addition , when identifying debris , we ignore the possibility that a clump can capture particles that were removed from another clump , but this is not an important process for our simulations which do not include a dissipative component . the intrinsic triaxiality of the final dark halo or debris component is calculated in a simple way . we calculate the moment of inertia formed by the relevant particles within a chosen radius ( e.g. half mass radius ) . from the eigenvalues of the moment of inertia @xmath42 , we can fit the moment of inertia with a triaxial ellipsoid with the intrinsic axial ratios @xmath43 and @xmath44 where @xmath45 . it can be calculated that @xmath46 and @xmath47 where @xmath48 and @xmath49 . the intrinsic axial ratios calculated in this way can be slightly overestimated compared to their real values , but provide a consistent comparison among our simulations . the ellipticity of the projected ( surface density ) images of the final dark halo or debris can be calculated in a more direct way , for a range of viewing angles . we calculate an isodensity contour map by assigning a gaussian density profile to each particle , with width proportional to the softening length . then we simply fit the contour with the ellipse to obtain the axial ratio @xmath50 and the ellipticity @xmath51 . the radial density profile is calculated by dividing the particles into radial bins , each containing equal numbers of particles ( about 16 ) . the velocity dispersion and rotation velocity are calculated by the conventional approach . we can study the dynamical evolution of clumps that contain enough particles . the study of the dynamics of substructure has applications on both the galaxy size scale , where star clusters , gas clouds and dwarf satellite galaxies play the role of clumps ( fall & rees 1977 ) , and the galaxy cluster scale , where galaxies play the role of clumps ( dressler 1984 ) . it is also related to the ` undermerging ' problem that has emerged recently , in that high - resolution cdm cosmological simulations predict too many surviving dark matter satellites around halos of the size of our galaxy ( klypin _ et al . _ 1999 ; moore _ et al . _ 1999 ) ) . the dynamical processes associated with the evolution of these clumps we shall investigate are global tidal stripping , dynamical friction , and merging and close encounters between clumps . we first derive expectations , based on analytic arguments , for the roles these dynamical processes have played and on which parameters they depend , for the virialized models . a preliminary comparison between these theoretical estimates and our simulations is provided at the end of the section . snapshots of each model are plotted in figures 27 . we derived analytic expectations for the amplitudes of the various processes we believe are operating in the simulations , to gain an understanding of the results . many processes are working together , often with the same net result ( disruption of the clumps ) , which would greatly complicate the interpretation of the n - body simulations in the absence of analytic insight . global tides due to the spatial variation of the underlying large - scale dark halo potential provide an important mechanism for the disruption of substructures as they orbit through the dark halo . analytical studies of the tidal effect on a clump show that , for a given clump orbit , the disruption efficiency depends on the ratio between the clump density to the mean density of halo within the pericentre of the clump orbit ( e.g. king 1962 ; binney & tremaine 1987 ; johnston , hernquist & bolte 1996 ) . the tidal radius of the clump , during its disruption , is the roche radius at which its gravity is equal to the tidal force exerted by the dark halo , which roughly scales as r_tide ~()^1/3 r , where @xmath52 is the pericentre distance . for our simulations , we expect that the clumps with density contrast @xmath53 should suffer more efficient tidal disruption than those with @xmath54 . for a clump in a circular orbit at the half mass radius of the dark halo , the fraction of mass contained within the tidal radius is @xmath55 for @xmath54 and @xmath56 for @xmath57 . since the clumps in our models are each represented by a plummer profile , which has a fairly constant density core ( see appendix a ) , while the dark halo is represented typically by a hernquist profile , which has a cuspy central density profile , the minimum pericentre distance for the approximately constant density core to be disrupted is @xmath58 for @xmath59 and @xmath60 for @xmath61 . the merging cross section between a pair of identical spherical clumps has been studied by makino & hut ( 1997 ) numerically , using a variety of mass profiles for the clumps . they find that in a cluster of clumps with one - dimensional velocity dispersion @xmath62 the number of merging events per unit time per unit volume , @xmath63 , is given by _ m = n^2 r^2_c vi _ c r_0(x ) = n^2 r^2_c vi _ h r_0(x ) , where @xmath64 , with @xmath65 and @xmath66 being the one - dimensional velocity dispersion of the system of clumps ( the halo ) and the internal velocity dispersion of a clump respectively , @xmath67 is the number density of the clumps within the half mass radius of the dark halo , @xmath68 is the virial radius of the clump , and the dimensionless quantity @xmath69 with @xmath70 and @xmath71 for clumps with a plummer profile . written this way , one can see explicitly a strong dependence of the merging rate on the parameter @xmath72 ( the ratio of the internal velocity dispersions of halo and clump ) . the number of merging events per unit time , @xmath73 , expected in our simulations can be estimated by the product of @xmath63 and the volume within the half mass radius of the halo profile ( equal to the half mass radius of the system of clumps ) . after some algebraic manipulations using equations ( 1 ) and ( 2 ) given in section 2.2 and the scalings in appendix a , we obtain r_m = r^3 _ h r_m 0.47 f^2 r_0(x ) . thus the number of merging events per halo crossing time is @xmath74 , and depends fairly strongly on the clump mass fraction , @xmath27 , but with only a weak residual explicit dependence on the parameter @xmath72 ( many parameters are interdependent ) . in the limit of a high relative velocity compared to internal velocity dispersion , @xmath75 , which is approximately valid for all our models , @xmath76 . this limit does not favour mergers , and results in the number of merging events per halo crossing time being @xmath77 for @xmath78 , @xmath79 for @xmath80 and @xmath81 for @xmath82 . we can also estimate the merging timescale for a clump . for a given clump within the half - mass radius of the halo , the probability of it merging with another clump per unit time is @xmath83 . thus the merging time scale is t_m = n / r_m= t_hc . it should be emphasized that the internal velocity dispersion ratio of the halo to the clump , @xmath72 , itself depends on the clump mass fraction @xmath27 , the clump number @xmath26 and the density contrast @xmath28 by equation ( 2 ) . we can see here that , given the values of the model parameters , the merging time scale is only very weakly dependent on the density contrast , which is instead a crucial factor for the efficiency of the global tidal stripping . merging between clumps is an important effect for large values of the clump mass fraction , @xmath27 , and for small numbers of clumps , @xmath84 . in our models with @xmath85 , the merging effect is very small with @xmath86 , while for larger @xmath87 , merging can be important , and the minimum merging timescale is @xmath88 ( model i ) . the merging rate calculated above is the mean quantity at the initial half mass radius . further , it does not take into account other dynamical effects , such as global tidal effects and close encounters , that can greatly decrease the calculated merging rate ( makino & hut 1997 ) . the effects of global tides can decrease the merging cross section by tending to tear apart a pair of clumps which , if isolated , would have merged . similarly , the local tides from a third clump can also act to tear apart a merging pair of clumps . furthermore , the subsequent nonlinear evolution in the presence of other more important dynamical processes can make the estimated merging timescale change quickly with time . we will see the limitation of this analytic estimate when we compare with the simulations below . disruption of clumps can also be caused by close encounters with other clumps . similarly to the discussion given in section 2.3.2 , we can estimate this clump disruption timescale as follows : for a given clump , the heating rate is e = , where @xmath67 is the mean clump number density within the half mass radius of the dark halo , and all other parameters are as defined above . as discussed in appendix b2 , we adopt @xmath89 and @xmath90 . thus the clump disruption timescale due to clump - clump heating is given by : t_c - c = 0.03 f^-4/3 n^1/3_c ( _ cl/_0 ) ^1/3 t _ hc . thus clump - clump heating is important for a large clump mass fraction , @xmath27 , small clump number , @xmath26 , and low density contrast , @xmath28 . we have @xmath91 for model a , and @xmath92 for model b. however , we should keep in mind that the above calculation could overestimate the effects of clump - clump heating . the choice of @xmath93 is uncertain . further , the impulse approximation holds only for @xmath94 if the impact parameter @xmath95 is chosen to be @xmath96 . if the encounter time is too long compared with the clump internal crossing time , particles in the clump may adiabatically respond to the encounter , hence the encounter could leave no net effects ( binney & tremaine 1987 ) . this could possibly explain the apparent inconsistency between our analytic estimates for the clump - clump merging effect and the clump - clump heating effect ( equations ( 6 ) and ( 8) ) , in that they both become more important with large clump mass fraction and small numbers of clumps . from equation ( 2 ) , we can see that @xmath97 also tends to be large for a large clump mass fraction and a small number of clumps ( provided that @xmath98 ) . when @xmath99 increases above @xmath100 , our prediction of the clump - clump heating effect in equation ( 8) becomes invalid , and the clump - clump heating effect will decrease quickly while the merging effect will increase continuously . the above arguments can be understood in terms of three different regimes depending on the value of the encounter speed , basically equivalent to the role of @xmath65 . ( 1 ) in the case that the encounter speed @xmath101 is very high , the two clumps will not merge and the clumps are just heated somewhat during the fast encounter . ( 2 ) in the case that the encounter speed is just slightly reduced , it can be envisioned that the chance for merging is slightly increased , and the heating effect is also slightly enhanced since the duration of the encounter is slightly longer . ( 3 ) in the case that the encounter velocity is very low , the merging rate is greatly increased , and the heating effect can be inhibited , since if the duration of the encounter is long enough compared to the internal crossing timescale in the clump , the clump just adiabatically responds during the encounter and returns to the initial state after the encounter . dynamical friction can drive clumps to the centre of the dark halo , where they can be tidally disrupted more easily . the slowing down of the clumps also can increase their merging cross - section . at the same time this process can extract angular momentum from the clumps , and transfer it to the dark halo . since chandrasekhar ( 1943 ) introduced the concept of dynamical friction , namely that an object moving through an infinite and homogeneous medium made of small mass particles suffers a drag force , there have been many studies on this subject by numerical simulations ( e.g. white 1978 , 1983 ; lin & tremaine 1983 ; bontekoe & van albada 1987 ; zaritsky & white 1988 ; hernquist & weinberg 1989 ; van den bosch _ et al . _ 1999 ) and analytical methods ( e.g. tremaine 1981 ; tremaine & weinberg 1984 ; weinberg 1989 ; maoz 1993 ; domnguez - tenreiro & gmez - flechoso 1998 ; colpi , mayer & governato 1999 ; tsuchiya & shimada 2000 ) . an overview of past work is given by cora , muzzio & vergne ( 1997 ) . in spite of the difficulties encountered in the study of dynamical friction , many authors find chandrasekhar s formula is a remarkably good approximation ( e.g. velazquez & white 1999 ) . adopting chandrasekhar s formula the deceleration of a clump is then = - , where t^-1_df=16 ^2 g^2 m_p ( m_c+m_p ) , and @xmath102 is the mass of a background halo particle , @xmath103 is the mass of the clump , @xmath104 is the velocity of the clump , @xmath105 is the phase - space number density of the background halo medium , and @xmath106 is the ratio between the maximum and minimum impact parameters @xmath107 . using the values at the half mass radius , we can immediately see that the characteristic dynamical friction time , t_df t_hc t_hc scales inversely with the mass of a clump ( @xmath108 , with the total mass normalized to unity as here ) . in applying these formulae to our simulations with virialized initial conditions , @xmath18 , and for which the dark halo is taken to follow the hernquist profile , we have chosen to use the phase space distribution function given by hernquist ( 1990 ) , hence ignoring the angular momentum dependence of the distribution function . the phase - space density of the dark halo is then as detailed in appendix c. for a clump initially on a circular orbit at the half mass radius , the dynamical friction time calculated as in appendix c is @xmath109 analyses of the orbital eccentricities of substructure in spherical potentials have found that for isotropic distribution functions the typical orbital eccentricity is @xmath110 ( van den bosch _ et al . _ 1999 ) . with this value the dynamical friction time is decreased by a factor of up to 2 , and the typical dynamical friction time for our computed models should then be t_df ~0.08 t _ hc . thus dynamical friction is more important for a large clump mass fraction ( provided @xmath111 ) and a small number of clumps , giving a large mass for each clump . this dependence on @xmath27 and @xmath26 in a general sense is consistent with that of clump - clump merging in all parameter ranges and that of clump - clump heating in some restricted parameter ranges . for our models with @xmath112 , dynamical friction is not important , with @xmath113 . for our models with @xmath114 , dynamical friction is not important for @xmath78 , with @xmath115 , but for @xmath80 it becomes important , with @xmath116 . for our models with @xmath117 , dynamical friction is important , with @xmath118 for @xmath119 and @xmath120 for @xmath80 . it should be emphasized that efficient dynamical friction leads to significant angular momentum loss from the clumps , and thus can drive clumps to the centre , where global tidal effects are stronger . thus the net efficiency of tidal stripping by the global potential includes a dependence on the clump mass fraction and number of clumps similar to that of dynamical friction . it should be noted that the above analysis is mainly applicable to virialized models . for the pre - collapse models , the disruption of clumps due to the collapse process itself dominates . for the plummer dark halo profile , the details of the calculation of dynamical friction from section 3.1.4 are not applicable , but the scaling should be the same as in the hernquist models . thus , for ease of comparison , the dynamical friction time is normalized to the crossing time scale at the half mass radius , as are all timescales . as noted earlier , all models with the same number of clumps have the same orbital characteristics for the clumps , with the exception of models b and e. thus it should be the different choices of our three free parameters the density contrast @xmath121 , the clump mass fraction @xmath27 and the number of clumps @xmath26 that are responsible for differences in the evolution of the different models . the most important uncertainty in the comparison of the theoretical predictions with our simulation results comes from two factors that enter the determination of the theoretical clump - clump heating timescale , namely the normalization quantity , @xmath93 , and the use of the impulse approximation even for relatively large values of @xmath99 . however , there are also uncertainties in the analysis of our simulations . our code is not designed to follow the merging events that occur throughout the simulations , and as mentioned above , the ` debris ' includes both particles genuinely removed from clumps and orbiting freely in the global potential and the remnants of merging clumps . thus in our analysis , both heating and merging produce debris . as a rough estimate of the mean disruption timescale of a clump in the simulations , we simply use the time required for the disruption of half of the clump mass . table [ tab : timescale ] lists , for the virialized models only , all the timescales , in units of @xmath122 , calculated from our analytic expressions , together with the disruption time of half of the mass in clumps measured from our simulations . the reader should note that the relative importance of the processes has not be derived from the simulations explicitly . [ timescales ] shows the dependence of various processes on the mass of the clump , and also on the mass fraction in clumps , @xmath27 , the latter denoted by the symbol size . the discussion of each virialized model is given in turn below : \(1 ) for model a , since @xmath123 , the impulse approximation is valid in our calculation of the clump - clump heating timescale @xmath124 . indeed , the dominant dynamical process is clump - clump heating and the analytic prediction is quite consistent with the simulation result . \(2 ) for model b , again clump - clump heating is the dominant dynamical process . however our analytic estimate of @xmath124 is a factor of 3 below the simulation result . this can be understood since @xmath125 and thus we are in the regime of marginal applicability of the impulse approximation , and we may have underestimated @xmath124 . \(3 ) for model c , we can see @xmath126 and thus our underestimate of @xmath124 could be significant , possibly by as much as the factor of 30 needed for consistency with the simulation result . it is also possible that @xmath127 is underestimated by the factor of 2 discrepancy with the simulation result . the dominant processes appear to be merging and clump - clump heating . \(4 ) for model g , @xmath128 , and again we find our apparent underestimate of @xmath124 is about a factor of 3 . the dominant process is apparently dynamical friction or possibly clump - clump heating . note that dynamical friction acts to drive clumps to the centre , where they will be tidally disrupted more easily . \(5 ) for model h , @xmath129 , and again we have an apparent underestimate of @xmath124 by about a factor of 20 , and an underestimate of @xmath127 by a factor of 2 . the dominant process appears to be dynamical friction . \(6 ) for model i , @xmath130 , sufficiently close to unity that our underestimate of @xmath124 could be very significant . we can simply assume that there is no clump - clump heating for this case ( adiabatic encounters ) . the dominant physical process is then merging of the clumps . as can be seen from figure [ fig : vic20hern ] , in this model all the clumps finally merge into two large systems . since in this case the ` debris ' is mainly in these two merging remnants , we do not calculate the disruption time in the simulation . \(7 ) for model m , @xmath128 , and we again assume our underestimate of @xmath124 is about a factor of 3 . as noted above , our analytic estimates of the dynamical friction timescale are not applicable for plummer profiles , but as a rough estimate we can adopt the value from the equivalent hernquist profile model g. the dominant processes are clump - clump heating and possibly dynamical friction . \(8 ) for model n , as above , we adopt the dynamical friction timescale from the corresponding hernquist profile model h. the velocity dispersion ratio is @xmath129 , and again the anaytic expressions have apparently underestimed @xmath124 by about a factor of 20 , and @xmath127 by about a factor of 2 . the dominant process is dynamical friction . \(9 ) for model o , again the ratio of velocity dispersion is sufficiently close to unity ( @xmath130 ) that we assume there is no clump - clump heating . the only possible dominant physical process is merging of clumps , and the analytic estimate of @xmath127 is apparently underestimated by a factor of 4 . \(10 ) for model s , @xmath131 . the dominant disruption processes are global tidal effects and clump - clump heating . \(11 ) for model t , @xmath132 . again we assume our underestimate of @xmath124 is about a factor of 3 . the dominant disruption processes are global tidal effects and clump - clump heating . \(12 ) for model w , @xmath133 , and the analytic underestimate of @xmath124 is at least a factor of 10 . the only dominant process is dynamical friction . \(13 ) for model x , @xmath134 , again sufficiently high that we ignore the clump - clump heating effect . again we assume our underestimate of @xmath127 is about a factor of 2 . the possible dominant processes are dynamical friction and merging . from the above , we can see that the modification to our analytic expression for the clump - clump heating timescale @xmath124 should be performed in a consistent way : for @xmath135 , no modification is needed ; for @xmath136 , we multiply by a factor of 3 ; for @xmath137 , we multiply by a factor of 10 ; for @xmath138 , we multiply by a a factor of 30 ; for @xmath139 , we ignore the clump - clump heating effect ( i.e. make the timescale infinite ) . from the above we can see that the merging timescale @xmath127 should be multiplied by a factor of 2 for all values of the velocity - dispersion ratio . from the comparison of the analytic theoretical predictions with our simulation results , we can see that with some reasonable and consistent modifications to our theoretical estimate of the timescale for clump - clump heating and merging , we can reach rough consistency with the estimates measured from our simulations . this allows us to develop an understanding of the dependence of the various processes of global tidal stripping , clump - clump heating , clump - clump merging and dynamical friction on the number of clumps , mass fraction of clumps and density contrast of a clump in the halo . in general , a decrease in the number of clumps and an increase in the clump mass fraction can increase the velocity dispersion ratio of clump to halo , and can further increase directly or indirectly the efficiency of all four processes , if the ratio is much smaller than the order of unity . for larger values of this velocity dispersion ratio , the efficiency of the clump - clump heating process drops quickly , while the merging process becomes more important , and the dynamical friction becomes more important as long as clump mass fraction is less than 50% . a decrease in the density contrast between clump and halo can enhance the disruptive effects of global tides , and of clump - clump heating ( if the velocity dispersion ratio of clump to halo is much less than unity ) . all the simulations have good conservation of total angular momentum and of total energy . the total angular momentum is conserved relative to the initial origin and to the centre of the total mass . when significant substructure is involved , as here , the calculation of angular momentum can be complicated by two factors . the first is that the smooth dark matter component and the clump component do not always share the same centre of mass . the second is that the centre of mass of the smooth dark matter component does not always correspond to its highest density point which is usually taken to be the centre of the relevant system , the galaxy or the cluster of galaxies due to the fact that the dark halo density profile to be simulated does not decrease with radius fast enough , e.g. for hernquist models , @xmath140 , and the simulation can only allow a limited number of particles to be distributed to infinity . the first factor is possibly non - trivial , since though using many clumps can make their centre of mass more closely coincide with that of the smooth component , there do exist physical environments , such as clusters of galaxies , in which indeed a small number of clumps are embedded in a smooth component . the second factor however is artificial ; the few particles in the outermost regions have a distribution that is more extended and asymmetric , and thus have more weight in the determination of the centre of mass . this problem could possibly be avoided by making the density profile decrease more rapidly with radius , e.g. , applying a cutoff radius . indeed , our simulations show that the coincidence between the centre of mass of the dark halo and the highest density point is better for the plummer profile than for the hernquist profile . table [ tab : ang1 ] lists the different measures of the angular momentum contents of our computed models , with the exception of the models with a clump mass fraction @xmath141 . the quantity @xmath142 , in column 7 , is defined as _ cl = , where @xmath143 and @xmath144 are the initial and final angular momentum , calculated relative to the highest density point of the dark matter , of the @xmath145th clump . it should be noted that any direct comparison between the plummer models and the hernquist models should use the halo crossing time as the time unit ; the final times here are fixed in these units for each of the plummer models and the hernquist models . we can see from the entries in this table that shifting the origin from the centre of mass of the total system , to the highest density point of the dark matter , can produce apparent non - conservation of the total angular momentum ; this arises since the highest density point of the dark matter defines a non - inertial frame . a real physical change in angular momentum with respect to the centre of mass of the total system occurs for each of the clumps and the dark matter ( compare the changes with the estimated errors ) . this ensures that the angular momentum exchange between the clump component and dm component is real ( barnes 1988 ) . however , from the observational point of view , or in cosmological simulations , the angular momentum is rather calculated relative to the highest density point of the dm . thus the question we want to ask is whether the angular momentum of the clumps changes significantly when measured in this way . this remains non - trivial since , for example , if a clump is extremely far from the centre , and thus it contains most of the angular momentum of the clumpy component , no matter how efficient is the angular momentum transfer from the remaining clumps to the dark matter , the angular momentum change of the total clump system will be very small . thus we must address not only the total angular momentum change of the clumps but also the angular momentum change of each individual clump . the parameter @xmath142 is useful in quantifying the mean angular momentum change of an individual clump . figures [ fig : clumpejvi ] and [ fig : clumpejco ] show the binding energy and angular momentum for each individual clump . it should be noted that in our simulations in which the smooth ( dark matter ) component has a plummer profile , the initial direction of the angular momentum vector of the clumpy component is in the opposite direction to that of the dm component . this is simply a result of the random assignment of the initial velocity , leading to negative values of the angular momentum for ( several of ) the clumps at large radius . from the plots of models m and p ( figure [ fig : clumpejvi ] and figure [ fig : clumpejco ] respectively ) we can see this fluctuation leads to a lower initial specific angular momentum than in the hernquist models . thus the total angular momentum of the clumps can be changed drastically compared to its initial value , even if the change of angular momentum of an individual clump is slight . thus we conclude that @xmath142 is a more robust parameter to measure changes in angular momentum than is the percentage change of the total angular momentum of the clumps , especially for the plummer models . from the entries in table [ tab : ang1 ] we can see that @xmath142 for all the collapse models is much larger than most of the virialized models . by checking individual clumps , as illustrated in figures [ fig : clumpejvi ] and [ fig : clumpejco ] , we find that clumps close to the centre have significant angular momentum loss , while the clumps at large distance can have significant angular momentum change gains and losses in collapse cases . for the virialized models a , s , b , g , w and t , @xmath142 is small , while for the remaining virialized models @xmath142 is large . we list the dynamical friction time and the time for half of the mass in clumps to be disrupted , in units of @xmath122 , for these models , in increasing order of the value of @xmath142 , in table [ tab : smallangchange ] . we can see that there are two factors that determine the angular momentum change @xmath142 : the dynamical friction time and the disruption time . generally , long dynamical friction times and short disruption times produce small values of @xmath142 . as discussed in section 3.1.4 , dynamical friction acts to drive clumps to the centre , with loss of angular momentum of the clumps . on the other hand , efficient disruption of a clump , especially due to processes unrelated to dynamical friction such as clump - clump heating or global tidal effects , helps to decrease the mass of the clump , which slows down the dynamical friction process , and thus can decrease the angular momentum loss . in the extreme case , a clump will no longer suffer dynamical friction after being disrupted completely . thus the angular momentum change is most significant for those massive clumps moving slowly , close to the centre , that are dense enough to withstand disruption by tides . for the collapse models , the large value of @xmath142 is caused by not only dynamical friction , but also by dynamical mixing during the post - collapse relaxation , which can redistribute both the binding energy and the angular momentum ( quinn & zurek 1988 ) . we plot the lindblad diagram for the smooth dm component for models k and d in figure [ fig : lindblad ] . the most bound @xmath146 of the dm particles are divided into nine equal size bins , sorted by the binding energy of each particle at the end of the simulation . we plot the vector angular momentum @xmath147 , and the scalar angular momentum @xmath148 , for each bin . we can see that for all the collapse models , regardless of the clump mass fraction or number of clumps , they show the same behaviour , in that inner , more - bound material loses angular momentum @xmath149 , while outer , less - bound material gains angular momentum @xmath149 . the scalar angular momentum @xmath150 increases for each bin . this result is consistent with previous results for the redistribution of angular momentum in protogalaxies ( quinn & zurek 1988 ) . the clumps close to the centre are disrupted quickly during the collapse , but still suffer significant angular momentum loss , both while still bound in clumps and after disruption . this material becomes more bound to the halo . for those clumps that survive the collapse , subsequent disruption and dynamical friction effects occur , as discussed above for the case of an initially virialized system . in addition , the final dark matter distribution is triaxial ( see section 6.2 below ) and exerts a torque that helps transfer angular momentum between clumps and the dark matter , and between the inner and outer regions ( resulting in the angular momentum loss from the inner debris ) . in the context of galaxy formation , the quantity of interest is the total angular momentum change , over a hubble time , of the baryonic component ( here given by the clumps ) . however as can be seen from table [ tab : ang1 ] , the total angular momentum @xmath149 of all the clumps does not change as much as would be expected from the parameter @xmath142 , except for model y and all the plummer models . for the plummer models , as we discussed above , the large change in the total angular momentum of the clumpy component is due to the particular random choice of the initial ( low ) specific angular momentum of this component . as an upper limit , we may adopt the parameter @xmath142 as the estimate of the angular momentum change for the clump system . our simulations show that the total angular momentum of the clumpy component does not change significantly in a hubble time for a small clump mass fraction and a large number of clumps , but does change significantly ( quantified by @xmath142 in table 3 being greater than @xmath151 ) in models with few and massive clumps ; compare model g with model h , or model s with model t , or model b with model x. such a high amplitude of angular momentum loss from proto - disk material can not allow a spiral to form that matches observation . thus we conclude that spiral galaxies _ can _ be formed through the accretion of many , but small , clumps , that conserve angular momentum in the process , but can not be formed in an environment that contains only a few , but large , clumps ( cf . silk & wyse 1993 ) . in all of the collapse models the kinematic properties for the dark halo component are similar , regardless of the different parameter values . from figure [ fig : dmvre10coc20d3f04 ] , we can see that after collapse the radial velocity dispersion @xmath152 increases at all radii , but the increase is larger in the central regions than at large radius . the other components of the velocity dispersion tensor , @xmath153 and @xmath154 , increase less than does @xmath152 , with @xmath153 slightly larger than @xmath154 , and they do not increase significantly at large radius . thus the final ratios @xmath155 and @xmath156 decrease with increasing radius . however , at the centre , the velocity ellipsoid approaches isotropy , i.e. @xmath157 . the rotation velocity , @xmath158 , increases , while @xmath159 decreases . @xmath160 decreases during the collapse in the central regions but is fairly constant in time at large radius . the lindblad diagram for the dark halo component is shown in figure [ fig : lindblad ] , and shows that for the most bound energy bin the scalar angular momentum @xmath161 increases , despite the fact that the amplitude of the vector angular momentum @xmath147 decreases . the different behaviours of the scalar and the vector angular momenta for the most bound energy bin can be explained by noting that individual particles can gain angular momentum in addition to kinetic energy , but can be deflected isotropically in direction during the post - collapse relaxation process , thus the vector angular momentum of all the particles in that energy bin decreases . as for the virialized models , there are no significant changes for the dark halo component . the kinematic properties of the clump debris for each model are somewhat different , but regardless of the parameter values , the velocity ellipsoid properties are similar to those of the dark halo component , especially in the central regions . figure [ fig : dedmvre10coc20d3f04 ] shows the same quantities for the debris as does figure [ fig : dmvre10coc20d3f04 ] for its dark halo . in the outer regions , the debris is largely still composed of many streams formed from the disrupted clumps . to illustrate , figure [ fig : phase ] plots @xmath162 and @xmath163 at the final time for the clump particles within a box of diameter of @xmath164 located at the coordinate ( 4,4,0 ) ( beyond the half - mass radius ) for model u. the different symbols indicate membership of different initial individual clumps ; in this example the box contains several streams , which are composed of eight different disrupted clumps . the density profiles of the disrupted clumps for all the collapse simulations follow the profiles of the dark matter , the surface density profile of which can be best fit by the @xmath165 law . this result is consistent with the early studies of van albada ( 1982 ) , which demonstrated that no matter how clumpy the pre - collapse initial condition is , the final profile is consistent with the de vaucouleurs @xmath165 law , provided the collapse factor is large enough ( the virial ratio @xmath22 ) . however , in the virialized simulations , the density profile of the debris can be different from that of the dark matter . figures [ fig : rhodensity ] and [ fig : sigdensity ] show the density profile and surface density profile for the debris ( normalized to their values at the debris half - mass radius ) . the solid lines correspond to the collapse cases , while the dashed lines correspond to the virialized cases . the density profile for model h shows a peak at some distance from the centre , due to the presence of a merger remnant there . we can see that , once normalized , the profiles of the debris in all the models are very similar . at the central regions , the density profile of the virialized models is slightly shallower than that of the collapse models . at the normalized distance @xmath166 , i.e. at one - tenth of the half - mass radius , @xmath167 for collapse models while @xmath168 for virialized models . at the very centre , due to the different resolutions for our different models , we can only infer that the central density profile is cuspy . the models with the plummer profile for the dark halo behave somewhat differently . figure [ fig : plumdendedm ] shows the final density profiles of the debris and of the dark matter for models m and n. these demonstrate that the central density of the debris can be larger than that of the dark halo component , and the central density profile of the debris is cuspy and does not have a ( approximately ) constant density core , in contrast to the dark halo profile . the initial and final density profiles of each component for models m and n are shown in figure [ fig : plumdenall ] . since the distribution of the clumpy components initially follows the same plummer profile as does the dark matter , the initial density profile including all components is approximately a plummer profile . the final density profile , including all components , shows a cuspy structure at the central region , for example at @xmath169 , model m has central profile @xmath170 and model n has central profile @xmath168 . a larger clump mass fraction ( model n ) leads to a steeper central density profile and a higher normalization , compared to the results with a lower clump mass fraction ( model m ) . this is because in the former case dense and massive clumps can move to the centre through dynamical friction without being significantly disrupted , and thus can contribute to the mass and density profile at the centre . this result has the application , in cdm cosmology , that the merging into a lower density parent halo of a number of higher density subhalos can produce a final cuspy and dense halo . furthermore , how cuspy and dense the final halo is depends mainly on the number of subhalos in the parent halo and the density contrast of a subhalo to the parent halo , both of which are related to the density fluctuation power spectrum index , @xmath67 , for @xmath171 . this provides an explanation for the central cuspy density profiles of halos found in cosmological numerical simulations , as the consequence of the self - limiting merging / accretion of small , dense halos , as suggested by syer and white ( 1998 ) . it is well - known that the surface density profile of a cd galaxy in its outer regions is systematically above the @xmath165 law that fits the more central parts . recent n - body simulations of groups of 50 galaxies studied by garijo , athanassoula & garca - gmez ( 1997 ) show that a giant central galaxy can be formed if there is a initial seed galaxy at the centre . further , these authors find that their virialized models produce a giant central galaxy with such a cd envelope . previous studies of the formation of cd galaxies , using non - cosmological n - body simulations of isolated clusters of galaxies , ( richstone & malumuth 1983 ; bode _ et al . _ 1994 ) concentrated on identifying the relative roles of stripping , merging and collapse . can a cd galaxy be formed by the galaxies that were disrupted at the cluster centre or by galaxies that merged with the central galaxy ? does the formation of a cd galaxy happen before , or after , the collapse of the cluster ? dubinski ( 1998 ) explored the formation of brightest cluster galaxies through the merging of several massive galaxies , in the context of hierarchical clustering cosmologies , but still failed to create the characteristic extended envelope of cd galaxies . one might expect that a larger clump mass fraction and a small number of clumps can lead to efficient merging or disruption of galaxies , which are plausibly important processes to form cd galaxies . though our simulations do only explore a limited parameter space , they include a simulation with only five clumps with a mass fraction of 40% , and also one with only twenty clumps with a mass fraction of unity . neither formed a cd . all our giant central galaxies can be fit by an @xmath165 law very well , over a range of more than 4 orders of magnitude in surface density . we speculate that collapse and small - scale structure alone can not produce cd galaxies . it is plausible that the continuous later infall of large galaxies could provide a mechanism to form cd galaxies . cdm - dominated cosmological n - body simulations show the protohalos are usually triaxial ( warren _ et al . _ 1992 ; dubinski & carlberg 1991 ) with the tendency to be prolate , and with the mean ratio of minor to major axes , @xmath172 , approximately 0.5 at small radius . the study of tremblay & merritt ( 1995 ; merritt & tremblay 1996 ) of the intrinsic shapes of elliptical galaxies found that bright ellipticals ( @xmath173 ) are systematically rounder than faint ellipticals , with the ratio of minor to major axes , @xmath172 , peaked at 0.75 for bright ellipticals , while for faint ellipticals @xmath172 is peaked at 0.65 . small ellipticals also tend to be flattened by rotation ( davies _ et al . _ 1983 ; rix , carollo & freeman 1999 ) rather than by anisotropic stellar velocity dispersions . studies of the collapse of a proto - galaxy with some initial triaxiality have explored the possibility that angular momentum can be transferred from the inner halo to the outer parts ( subramanian 1988 ; curir , diaferio & de felice 1993 ; curir & diaferio 1994 ) . our simulations study the evolution of a system of clumps embedded in a smooth dark halo with an initial oblate profile , and thus we do not address the question of the role of any initial triaxiality , but rather investigate what parameters determine the triaxiality of the final system . we first investigate the level of flattening of various components that can be due to rotation , by comparing the ellipticity with the ratio of rotation to velocity dispersion . the ellipticity , @xmath174 , is calculated from the projected isodensity contour of the simulation particles from sixteen different viewing angles . the central line - of - sight velocity dispersion , @xmath175 , and rotational streaming velocity , @xmath176 , are also calculated for these viewing angles , and the ratio @xmath177 formed . in figure [ fig : contourvrvde ] we plot the location of each viewing angle on the ( @xmath177,@xmath174 ) plane for models j , g , u and k. since the morphology of the debris generally follows that of dark halo , here we just show the dark halo measured in this way . from figure [ fig : contourvrvde ] we can see for the collapse cases the value @xmath177 is decreased significantly and the system becomes anisotropic . for model u , with low density contrast between the clumps and the halo , the ellipticity increases , while for model k , with large clump mass fraction , the ellipticity decreases . the virialized cases are actually initially marginally out of equilbrium , and generally evolve such that the ellipticity and @xmath177 are decreased , to make the system rounder and more isotropic ( remember these simulations are constructed to be initially close to isotropic and flattened by rotation ) . the three - dimensional shapes can be calculated from the moments of inertia , giving the triaxiality for both dark halo and debris . as we discussed in section 2.4 , this technique for calculating the axial ratio systematically underestimates the flattening . for example , the initial flattening of the dark halo in all simulations is @xmath178 , while the calculation from the moment of inertia gives @xmath179 . however , since we are interested more in _ trends _ in the dependence of final triaxiality on the initial conditions , such a systematic overestimate is not a problem . table [ tab : triaxial ] summarizes the values of @xmath50 and @xmath172 in the simulations , with as usual @xmath180 where a , b and c are calculated from the eigenvalues of the moment of inertia tensor within the half mass radius as described in section 2.4 . from table [ tab : triaxial ] , and fig . [ shapes ] we can see that : \(a ) all the collapse models show some level of triaxiality for both the dark halo component and the debris component . cases with a large clump mass fraction ( @xmath181 ) are slightly rounder than the cases with small clump mass fraction ( @xmath78 ) . for the completely clumpy cases ( @xmath141 ) the final shape of the debris is very spherical , with the exception of the collapse model with a initial plummer profile ( model r ) . the triaxiality for the low density contrast cases , such as models u and v , is more significant than that of high density contrast cases , such as models j and k. the triaxiality for models with a small number of clumps , such as models y and z , is less significant than that for those with a large number of clumps , such as models j and k , or d and e. also we should note that , for our choice of initial configuration , the clump mass fraction is weakly correlated with the value of the virial ratio , @xmath24 , for the collapse models . actually the real collapse factor for all the collapse models is almost a constant . for the pure clump models with @xmath141 , calculating a modified virial ratio ( denoted @xmath182 ) by excluding the clump internal kinetic energy and potential energy , we have @xmath183 . so , for our models , it is the level of clumpiness , rather than the collapse factor , that determines the triaxiality of the final systems . large values of the clump density contrast , large clump mass fractions , and small numbers of ( massive ) clumps all indicate that clumpiness is important ; a higher level of ` clumpiness ' makes the final system rounder . clearly , the collapse factor will also affect the triaxiality of the final system . \(b ) for the virialized cases , the final shape of the dark matter component is oblate with @xmath184 , slightly rounder than its initial configuration ; the shape of the debris component is close to oblate , with @xmath185 and @xmath186 . as we can see from the virialized cases , which is an extreme case of approximately zero collapse factor , the final system tends to be oblate or round . this result implies that the generation of triaxiality requires thin box orbits , or radial orbits , that get very close to the centre . in this case the collapse is mostly radial and creates a lot of triaxiality ; more clumpiness disrupts these radial orbits . this suggests that giant ellipticals , which tend to be rounder than small ellipticals , may be formed in a more clumpy environment than are small ellipticals , but this inference is complicated by the fact that the small ellipticals tend to be oblate , with significant dissipation being implicated ( e.g. wyse & jones 1984 ; rix _ et al . _ 1999 ) . the existence of a population of intracluster stars in the core region of the virgo cluster , detected through planetary nebulae ( mndez _ et al . _ 1997 ) and red giant stars ( ferguson , tanvir & von hippel 1998 ) indicates that the stripping of stars from cluster galaxies , through the multiple disruption processes that we discussed above , is a reality during the formation of clusters of galaxies . in addition , m87 , the giant elliptical in the virgo cluster , exhibits a broad , diffuse and extended ` fan ' in surface brightness at a projected distance of around 100 kpc from its centre . the accretion of a small stellar satellite with @xmath187 of the mass of m87 , with small impact parameter , can allow the formation of a surface brightness feature like this ( weil , bland - hawthorn & malin 1997 ) . even in our galaxy , large overdensities of a - stars ( yanny _ et al . _ 2000 ) and rr lyrae stars ( ivezic et al . 2000 ) are observed in the halo at distance of up to 60 kpc from the galactic centre , through the analysis of sloan digital sky survey imaging data ( yanny _ et al . this structure may be tidal debris from the sagittarius dwarf spheroidal galaxy ( ibata _ et al . the observation of substructure in the outer halo can be useful in constraining the formation history of galaxies . from figures 21 and [ fig : substructure ] we can see that in the outer halo region of our simulations there are indeed prominent streams from the disrupted clumps , seen in surface density . these unrelaxed streams can account for the over - density above the @xmath165 law seen at the very outer regions in figure [ fig : sigdensity ] . a detailed study of the substructure is a mathematical challenge needing a serious treatment , but as a first step we adopt a simple approach to explore its presence and evolution . to quantify the lumpiness of substructure as it might be observed , the concept of the filling factor of disrupted clumps - the fraction of sky containing one or more streams - was introduced by tremaine ( 1993 ) and used by many authors subsequently in studying the evolution of tidally disrupted stellar systems ( johnston 1998 ; helmi & white 1999 ) . the shortcoming of the filling factor as a measure of streaming is that it can become significantly larger than unity as streams wrap around the sky . here we introduce a different measure of inhomogenities in the debris , restricting our analysis to the spatial part of phase space ( the complications in velocity space are illustrated in figure [ fig : phase ] ) . we define the quantity @xmath188 , defined as the fraction of the debris which is in regions with overdensity above some critical value , or @xmath189 , restricting the calculation to regions beyond a critical radius @xmath190 projected onto the celestial sphere . at a given time @xmath191 , the critical radius @xmath190 is chosen to be the radius where @xmath192 , where @xmath193 is the circular velocity at radius @xmath194 , and @xmath195 is a free parameter of the order of unity . this critical radius can be regarded as the division between the inner , smooth debris where mixing is complete , and the outer regions where mixing is incomplete . though the assumption is over - simplified , a visual check of figure [ fig : cparameter ] justifies a choice of @xmath196 . for collapse cases , we have approximately @xmath197 respectively for @xmath198 , while for virialized cases @xmath199 , for times @xmath200 . it should be noted that we do not have any ` baryons ' that were not initially in clumps , so that all the unbound clump particles are ` debris ' ; in the interpretation of the evolution of substructure in a galaxy like the milky way , the entire field halo would be debris , and we are quantifying the structure in that debris . we simply divide the sky into a number of cells of equal solid angle . the average number of debris particles in each cell is @xmath201 . if the cell has more than @xmath202 debris particles , then it is counted as a region of overdensity . if @xmath203 , the overdensity of @xmath204 can be used to indicate the existence of streaming structure in that cell , since the density fluctuation is then greater than 3@xmath205 , with @xmath206 . thus an accurate calculation of @xmath188 requires that both the number of cells and the number of debris particles be large enough . however , this condition is not satisfied in many of our simulations . thus here we can only give a rough estimate of @xmath188 for the simulations with large clump mass fraction , using @xmath207 and @xmath208 . table [ tab : eta ] summarizes the values of @xmath188 at different times for our simulations , with the conclusion that for our models @xmath188 is more or less a constant , with a value varying only from about @xmath209 to @xmath210 . by checking the number of distinct overdense regions on the celestial sphere used in calculating @xmath188 , and also by a visual check of the snapshots of the models for 5 , 20 , and 80 clumps , we can see that , not surprisingly , the number of streams correlates with the number of clumps . the disruption of clumps is more efficient for collapse cases , resulting in streams that are more radially aligned compared to those formed in our virialized models . the observations of streams in phase space in the outer halos of galaxies are thus potentially important in constraining the formation history of galaxies , especially in determining the abundance of accreted substructure of different sizes and densities , through comparison with simulations . in this paper , we use n - body simulations to study the evolution of clumps , or substructure , embedded in non - dissipative , isolated dark halos . we ran 26 different combinations of 4 independent free parameters , namely the clump mass fraction , the number of clumps , the density contrast of clump to halo and the initial virial ratio . we also investigated two different density profiles for the smooth dark halo component , the cuspy hernquist profile and the ( approximately ) constant - density core plummer profile . for the initial virialized systems , we derived analytic estimates for the importances of various dynamical processes that occured in our simulations , such as global tidal stripping , clump - clump heating , clump - clump merging and dynamical friction , including explicit dependence on the 4 independent free parameters . these analytic estimates were used to gain physical insight , and a comparison between our numerical results and our analytical estimate showed general agreement . with an increase in the mass fraction of clumps and a decrease in the number of clumps , the velocity dispersion ratio of a clump to the halo increases , and all the dynamical processes become more efficient in a general sense , provided this velocity dispersion ratio is still much less than one . as this velocity dispersion ratio increases close to unity , the heating effect by close encounters between clumps becomes less important , while other dynamical processes continue to become more important . we find that due to the angular momentum transport seen , spiral galaxies can not be formed in a system with a large clump mass fraction and a small number of clumps . our simulations show that the angular momentum of the clumpy component does not change significantly in a hubble time for a small mass fraction in the clumps and a large number of clumps . this result confirms the standard formation scenario for disk galaxies , in that the merging history of spirals is restricted to the accretion of many , small systems , still conserving their specific angular momentum . this is similar in some aspects to the model of vitvitska et al . ( 2001 ) , who find that one may also end up with ellipticals with rapidly spinning halos , especially if only a small number of massive clumps are involved in the final merging events . the final density profile , starting with clumps embedded in a smooth plummer component , shows a rather steep inner part , depending on the clump mass fraction . thus our experiments support the explanation for the origin of the central cusps in the density profiles of halos in cosmological numerical simulation as the consequence of self - limiting merging of small dense halos , as suggested by syer and white ( 1998 ) . the surface density profile of the debris formed from the disrupted clumps can be best fit by the de vaucouleurs law for all our simulations . thus our simulations do not produce cd galaxies , a deficiency which suggests that the formation of cd galaxies reauires conditions outside the parameter ranges covered by our simulations . plausibly the formation of the outer envelope characteristic of cds requires some later infall of large galaxies into the central regions of the cluster , possibly enhanced by dynamical friction . the iso - density contours of both the dark halo and debris are consistently triaxial after the collapse , even though the initial configurations are oblate . the triaxiality of the final system is found to depend on the clumpiness of the initial system . a high level of clumpiness , such as having only a few , but massive , clumps , helps to produce a round system . this further suggests that giant ellipticals , which tend to be rounder than small ellipticals , may be formed in a more clumpy environment than small ellipticals . we introduced a new measure of ` streams ' in the final system , and found that persistent signatures of disrupted clumps in the outer halo can , at an overdensity of @xmath211 , cover 10% to 20% of the sky . the properties of these streams depend on the initial conditions in an intuitive way , in that the number of streams correlates with the number of initial clumps , and their orientation is more radial in collapse simulations . some extensions of our work that would further our understanding of the role of substructure in the formation of galaxies and of cluster of galaxies include n - 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dimensional velocity dispersion @xmath205 , defined by @xmath229 . these are related by @xmath230 . we first discuss the effects of two - body relaxation , for which the two bodies can be two particles both from a single clump , or two particles with one from a clump and the other from the dark halo , or two particles both from the dark halo . then we discuss the heating effect of a clump by dark halo particles . first we just consider the case that the clump is isolated , i.e. the two bodies under consideration are both from a single clump . we know the evaporation timescale is usually 100 times the relaxation timescale ( binney & tremaine 1987 ) for a given maxwellian system ; this sets the timescale over which a clump could suffer evaporative mass loss if the two - body relaxation time is too short compared to the simulation time . the two - body relaxation time in a single clump is ( sellwood 1987 ) @xmath231 where the @xmath37 is the number of particles in a single clump , @xmath232 is the softening - length and @xmath233 is the internal crossing time within a clump . the softening - length in the treecode is set at @xmath234 ; this relatively large value is chosen to suppress the unphysical two - body relaxation ( white 1978 ) , which otherwise could occur due to the small number of particles used in each clump ( ranging from 150 to 2400 ) . in terms of the halo crossing time , this two - body relaxation time can be written as @xmath235 thus the two - body relaxation time in a single clump is shorter , in terms of the halo crossing time , for larger values of the density contrast @xmath28 . this poses a limitation for us in exploring the parameters for clumps of large density contrast , in addition to the limitation from the cpu time used , which is determined by the total number of particles . for our computed models with @xmath236 and @xmath237 , we have @xmath238 . in the worst case , with @xmath239 and @xmath240 , we have @xmath241 . since our simulation time is about @xmath242 , generally our clumps should suffer somewhat from two - body relaxation effects , which can lead to some internal manifestation of collisional behaviour such as mass segregation ( to which we are insensitive since we have adopted equal mass particles ) . however , we do not expect there to be significant mass loss due to evaporation effects , not only because the estimated evaporation time scale is very long compared to our simulation time , but also due to the fact that adoption of a softening - length can inhibit evaporation . furthermore , we are not interested , in this study , in the evolution of the internal structure of the clump , and thus our chosen parameter values are acceptable . next , we turn to consideration of two - body relaxation in the dark halo , i.e. the two bodies participating in the two - body relaxation are both from the dark halo . similarly to the expressions above , we have @xmath243 where @xmath244 is the number of particles in the dark halo . typically @xmath245 . thus the two - body relaxation effect in the halo can be ignored . in addition to the possible evaporation of clump particles due to two - body heating between two particles within the same clump , there is another heating process we should consider , caused by two - body heating between a halo particle and a clump particle ( carlberg 1994 ; van kampen 1995 ) . the disruption time due to this heating process is @xmath246 for our simulations , this disruption time is much longer than the total integration time ; for a typical model , @xmath247 and we can safely ignore this heating effect too . numerical limitations resulting from a small number of particles can lead not only to unwelcome collisional effects as discussed above , but also can lead to spurious heating effects within clumps . while in our simulations we have both halo particles and clump particles of the same mass , we shall consider the more general case of unequal particles , and indeed of a heavier halo particle . as a ( heavy ) dark halo particle passes by or through a clump , it can tidally heat the clump , and the clump can eventually be disrupted ( carlberg 1994 ) . one can roughly estimate the magnitude of this effect by using the impulse approximation , provided the duration of the encounter is short compared to the internal crossing time of the clump ( binney & tremaine 1987 ) . the binding energy of the clump is given by @xmath248 . for a given clump , the heating rate is e = , where @xmath102 is the mass of one dark halo particle , @xmath249 is the mean number density of the dark halo particles within the half mass radius of the dark halo , @xmath250 is the mass of the clump , @xmath251 is the mean - square radius of the clump , @xmath65 is the one - dimensional velocity dispersion of the dark halo and @xmath252 is the minimum impact parameter . the size of the single dark halo particle can be set to the value of the softening length @xmath232 . since @xmath253 , we can choose @xmath254 to include head - on encounters , thus modifying the above equation by multiplying a factor of @xmath89 ( binney & tremaine 1987 ) . the appropriate value of @xmath255 is somewhat uncertain , since , for example , for the plummer profile @xmath93 is divergent . the heating rate however remains finite . this result can be understood in the following way : the heating by such a close encounter causes the particles in the clump to gain a velocity increment proportional to their projected distance from the centre of the clump , and thus while the inner particles are essentially unaffected , the outermost particles , though few in number , can gain most of the kinetic energy , resulting in their removal from the clump . thus in the calculation of @xmath93 , we should ignore those particles lying too far from the clump centre . here we adopt @xmath93 to be @xmath256 . after some algebraic manipulations using the relations in section 2.2 and appendix a , we have that the clump disruption timescale , due to halo particle - clump heating , is t_p - c = 0.03 n_tot f^2/3 n^-2/3_c ( _ cl/_0 ) ^1/3 t _ hc , where @xmath257 is the total number of particles used in the simulation . for the worst case ( model s ) with @xmath78 , @xmath258 , @xmath259 and @xmath260 , we have @xmath261 . so again this particle - clump heating effect can be ignored in our simulations . as discussed in the text ( section 3.1.3 ) , the physical clump - clump heating effect is much more important . we estimate the expected amplitude of dynamical friction under the conditions we simulated by adopting , for hernquist profile halos , the phase space distribution function he derived , which neglects angular momentum . this is f(e)= k_0(q ) , where k_0(q)= , where @xmath213 is the core radius of the halo , @xmath262 , @xmath263 , and @xmath264 is the specific energy of a halo particle . . then we have v^2= v^2_g- 2v^2_g q^2 . since @xmath266 is non - negative for all @xmath267 , where @xmath268 is the escape velocity , and if the clump is moving with velocity @xmath104 less than the escape velocity at radius r , we can simply substitute for @xmath266 in equation ( 10 ) . with @xmath269 ( symbols defined in section 3.1.4 ) , we have ^v_m_0 f(v ) v^2 dv = f_0(x , v_m ) with f_0(x , v_m ) = ^q_v=0_q_v = v_m ( - q^2 ) ^1/2 k_0(q ) q dq where @xmath270 and @xmath271 . thus the characteristic dynamical friction timescale becomes t^-1_df = f_0(x , v_m ) to obtain the exact dynamical friction time from the above equations , for given initial conditions , one needs to integrate over time for the time - dependent orbit ( e.g. cora , muzzio & vergne 1997 ) . while it is generally assumed that orbits are quickly circularized by dynamical friction , and thus that the chandrasekhar formula for circular orbits may be applied , this is not always a good assumpotion ( van den bosch _ et al . _ 1999 ) . however , there are some empirical relations derived from numerical studies ( see a short summary in colpi _ et al . _ 1999 ) that relate the dynamical friction time calculated numerically for a particle on a given initial orbit , i.e. @xmath272 and @xmath273 , to the prediction using the circular orbit approximation , giving @xmath274 , where @xmath275 , and @xmath276 is the angular momentum of a particle on a circular orbit with the same binding energy . the parameter @xmath174 is simply dependent on the orbit eccentricity only , while @xmath277 can range from 0.4 to 0.8 . for a typical orbital eccentricity of @xmath278 , the circular orbit approximation provides an overestimate by a factor of around 2 . we then assume that a clump is initially moving on a circular orbit with @xmath279 ( tsuchiya & shimada 2000 ) , and modify the estimates of the dynamical friction timescales by this factor of two . then from equation ( 9 ) in the main text , the specific angular momentum loss rate should be equal to the torque caused by the dynamical friction at radius @xmath194 , and we have = - r. it can be further written as = - . with some algebraic manipulation , the dynamical friction time can be expressed as t_df= b(x_0 ) where b(x_0)= ^x_0_0 dx , and @xmath280 is the initial radius . the appropriate value of @xmath281 can be calculated as ( white 1976 ) = ^b_max_0 d^3 dd ^2 , where @xmath282 is the mass profile of a clump , here given by the plummer law . the maximum impact parameter is chosen to be the half mass radius of the dark halo , @xmath283 . thus = ( + 1 ) + ( - 1 ) where @xmath284 is the core radius of the clump plummer profile . for our computed models , typically @xmath285 . lrccccrrr model & @xmath24 & @xmath26 & @xmath28 & @xmath27 & @xmath99 & dark halo & @xmath286 & @xmath37 + a & 1.07 & 80 & 58 & 0.1 & 0.21 & hernquist & 108000 & 150 + b & 0.91 & 80 & 38 & 0.4&0.31 & hernquist & 36000 & 300 + c & 1.35 & 80 & 64 & 1 & 0.46 & hernquist & 0 & 300 + d & 0.11 & 80 & 58 & 0.1&0.21 & hernquist & 108000 & 150 + e & 0.13 & 80 & 38 & 0.4 & 0.31 & hernquist & 36000 & 300 + f & 0.31 & 80 & 64 & 1 & 0.46 & hernquist & 0 & 300 + g & 1.05 & 20 & 58 & 0.1&0.34 & hernquist & 54000 & 300 + h & 0.95 & 20 & 38 & 0.4&0.50 & hernquist & 27000 & 900 + i & 1.20 & 20 & 64 & 1 & 0.74 & hernquist & 0 & 1000 + j & 0.11 & 20 & 58 & 0.1&0.34 & hernquist & 54000 & 300 + k & 0.17 & 20 & 38 & 0.4&0.50 & hernquist & 27000 & 900 + l & 0.48 & 20 & 64 & 1 & 0.74 & hernquist & 0 & 1000 + m & 1.05 & 20 & 58 & 0.1&0.34 & plummer & 54000 & 300 + n & 0.89 & 20 & 38 & 0.4&0.50 & plummer & 27000 & 900 + o & 1.17 & 20 & 64 & 1 & 0.74 & plummer & 0 & 1000 + p & 0.11 & 20 & 58 & 0.1&0.34 & plummer & 54000 & 300 + q & 0.40 & 20 & 38 & 0.4&0.50 & plummer & 27000 & 900 + r & 0.48 & 20 & 64 & 1 & 0.74 & plummer & 0 & 1000 + s & 1.06 & 20 & 2.7 & 0.1 & 0.20&hernquist & 54000 & 300 + t & 0.95 & 20 & 1.8 & 0.4 & 0.30&hernquist & 27000 & 900 + u & 0.11 & 20 & 2.7 & 0.1&0.20 & hernquist & 54000 & 300 + v & 0.13 & 20 & 1.8 & 0.4&0.30 & hernquist & 27000 & 900 + w & 1.08 & 5 & 61 & 0.05&0.43 & hernquist & 114000 & 1200 + x & 0.8 & 5 & 38 & 0.4&0.79 & hernquist & 9000 & 1200 + y & 0.13 & 5 & 58 & 0.1&0.53 & hernquist & 36000 & 800 + z & 0.27 & 5 & 38 & 0.4&0.79 & hernquist & 18000 & 2400 + lcccccc model & @xmath287 & @xmath288 & @xmath289 & @xmath290 & @xmath99 & inferred dominant processes + a & 667 & 10.8 & 71 & 12.8 & 0.21 & c - c + b & 16.7 & 1.5 & 26.7 & 5.1 & 0.31 & c - c + c & 6.7 & 0.52 & @xmath291 & 18.3 & 0.46 & merge , c - c + g & 167 & 6.8 & 17.8 & 15.1 & 0.34 & c - c , df + h & 10.4 & 0.93 & 6.7 & 6.6 & 0.50 & df + i & 1.7 & 0.33 & @xmath291 & n / a & 0.74 & merge + m & 167 & 6.8 & n / a & 26.7 & 0.34 & c - c , df ( ? ) + n & 10.4 & 0.93 & n / a & 9.0 & 0.50 & df ( ? ) + o & 1.7 & 0.33 & @xmath291 & 9.0 & 0.74 & merge + s & 167 & 2.4 & 17.8 & 2.5 & 0.20 & tides , c - c + t & 10.4 & 0.33 & 6.7 & 2.5 & 0.30 & tides , c - c + w & 167 & 11.0 & 8.4 & 11.3 & 0.43 & df + x & 2.6 & 0.6 & 1.7 & 4.5 & 0.79 & df , merge + lrrrrccrrrc model & state & @xmath292 & @xmath293 & @xmath294 & @xmath295 & @xmath142 & @xmath296 & @xmath297 & @xmath298 & @xmath299 + a & i & -0.6083 & -0.04536 & -0.5630 & @xmath300 & @xmath301 & -0.6007 & -0.03910 & -0.5616 & @xmath302 + & f & -0.6244 & -0.04769 & -0.5767 & & & -0.6020 & -0.04306 & -0.5589 & + & ( f - i)/i & @xmath303 & @xmath304 & @xmath305 & & & @xmath306 & @xmath209 & @xmath307 & + b & i & -0.6200 & -0.3169 & -0.3030 & @xmath308 & @xmath309 & -0.6254 & -0.3121 & -0.3132 & @xmath310 + & f & -0.6203 & -0.3215 & -0.2988 & & & -0.6250 & -0.3083 & -0.3167 & + & ( f - i)/i & @xmath311 & @xmath312 & @xmath313 & & & @xmath314&@xmath315 & @xmath316 & + d & i & -0.1904 & -0.01480 & -0.1756 & @xmath317 & @xmath318 & -0.1923 & -0.01511 & -0.1771 & @xmath319 + & f & -0.1991 & -0.01689 & -0.1822 & & & -0.1930 & -0.01869 & -0.1743 & + & ( f - i)/i & @xmath320 & @xmath321 & @xmath322 & & & @xmath323 & @xmath324 & @xmath325 & + e & i & -0.1951 & -0.09930 & -0.09583 & @xmath308&@xmath326 & -0.1963 & -0.09864 & -0.09762 & @xmath310 + & f & -0.1948 & -0.08726 & -0.1076 & & & -0.1980 & -0.08917 & -0.1088 & + & ( f - i)/i & @xmath327&@xmath328 & @xmath329 & & & @xmath330 & @xmath331 & @xmath332 & + g & i & -0.6092 & -0.04577 & -0.5635 & @xmath300&@xmath333 & -0.6172 & -0.05260 & -0.5646 & @xmath334 + & f & -0.6202 & -0.04794 & -0.5722 & & & -0.6170 & -0.04282 & -0.5742 & + & ( f - i)/i & @xmath335&@xmath336 & @xmath337 & & & @xmath338 & @xmath339 & @xmath340 & + h & i & -0.4822 & -0.1763 & -0.3059 & @xmath341&@xmath326 & -0.4818 & -0.1686 & -0.3133 & @xmath342 + & f & -0.3726 & -0.1135 & -0.2590 & & & -0.4803 & -0.1990 & -0.2813 & + & ( f - i)/i & @xmath343&@xmath344 & @xmath345 & & & @xmath346 & @xmath347 & @xmath348 & + j & i & -0.1943 & -0.01615 & -0.1782 & @xmath349&@xmath350 & -0.1968 & -0.01810 & -0.1787 & @xmath351 + & f & -0.1970 & -0.01725 & -0.1798 & & & -0.1969 & -0.01557 & -0.1814 & + & ( f - i)/i & @xmath352 & @xmath353 & @xmath330 & & & @xmath354 & @xmath355 & @xmath312 & + k & i & -0.1544 & -0.05766 & -0.09673 & @xmath341&@xmath356 & -0.1530 & -0.05386 & -0.09900 & @xmath342 + & f & -0.1721 & -0.06048 & -0.1116 & & & -0.1503 & -0.04253 & -0.1078 & + & ( f - i)/i & @xmath332 & @xmath357 & @xmath358 & & & @xmath359 & @xmath360 & @xmath361 & + m & i & -0.2708 & 0.002488 & -0.2732 & @xmath362&@xmath363 & -0.2702 & 0.003379 & -0.2736 & @xmath364 + & f & -0.2700 & 0.004062 & -0.2740 & & & -0.2702 & 0.003606 & -0.2738 & + & ( f - i)/i & @xmath346 & @xmath365 & @xmath366 & & & @xmath367 & @xmath368 & @xmath311 & + n & i & -0.1367 & 0.01071 & -0.1474 & @xmath369&@xmath370 & -0.1293 & 0.02120 & -0.1505 & @xmath371 + & f & -0.1311 & 0.01484 & -0.1459 & & & -0.1292 & 0.01630 & -0.1455 & + & ( f - i)/i & @xmath372 & @xmath373 & @xmath364 & & & @xmath374 & @xmath375 & @xmath376 & + p & i & -0.08585 & 0.000555 & -0.08641 & @xmath377&@xmath378 & -0.08566 & 0.0008716 & -0.08653 & @xmath364 + & f & -0.08550 & -0.003074 & -0.08242 & & & -0.08560 & -0.003251 & -0.08235 & + & ( f - i)/i & @xmath379 & @xmath380 & @xmath381 & & & @xmath374 & @xmath382 & @xmath383 & + lrrrrccrrrc model & state & @xmath292 & @xmath293 & @xmath294 & @xmath295 & @xmath142 & @xmath296 & @xmath297 & @xmath298 & @xmath299 + q & i & -0.04355&0.003064 & -0.04661&@xmath384&@xmath385 & -0.04112&0.006532 & -0.04765 & @xmath386 + & f & -0.04193&-0.006918&-0.03501 & & & -0.04143&-0.006248 & -0.03518 & + & ( f - i)/i & @xmath387 & @xmath388 & @xmath389 & & & @xmath390 & @xmath391 & @xmath392 & + s & i & -0.6082 & -0.04469 & -0.5635 & @xmath393&@xmath332 & -0.6162 & -0.05164 & -0.5646 & @xmath394 + & f & -0.6189 & -0.04763 & -0.5712 & & & -0.6159 & -0.04354 & -0.5723 & + & ( f - i)/i & @xmath335 & @xmath395 & @xmath352 & & & @xmath396 & @xmath386 & @xmath352 & + t & i & -0.4812 & -0.1754 & -0.3059 & @xmath397&@xmath398 & -0.4817 & -0.1684 & -0.3133 & @xmath342 + & f & -0.4435 & -0.1548 & -0.2897 & & & -0.4809 & -0.1666 & -0.3143 & + & ( f - i)/i & @xmath369&@xmath328 & @xmath399 & & & @xmath400 & @xmath401 & @xmath366 & + u & i & -0.1933 & -0.01512 & -0.1768 & @xmath402&@xmath403 & -0.1958 & -0.01720 & -0.1786 & @xmath361 + & f & -0.1953 & -0.01605 & -0.1792 & & & -0.1953 & -0.01606 & -0.1792 & + & ( f - i)/i & @xmath401 & @xmath404 & @xmath404 & & & @xmath346&@xmath405 & @xmath366 & + v & i & -0.1533 & -0.05657 & -0.09673 & @xmath341&@xmath406 & -0.1526 & -0.05356 & -0.09907 & @xmath342 + & f & -0.1730 & -0.05907 & -0.1140 & & & -0.1519 & -0.05269 & -0.09919 & + & ( f - i)/i & @xmath309 & @xmath407 & @xmath347 & & & @xmath408&@xmath325 & @xmath409 & + w & i & -0.6251 & -0.01217 & -0.6130 & @xmath410&@xmath411 & -0.6169 & -0.001880 & -0.6151 & @xmath366 + & f & -0.6117 & -0.01168 & -0.6000 & & & -0.6174 & -0.01037 & -0.6070 & + & ( f - i)/i & @xmath412 & @xmath387 & @xmath412 & & & @xmath354 & @xmath413 & @xmath414 & + x & i & -0.4011 & -0.09584 & -0.3052 & @xmath324&@xmath415 & -0.3678 & -0.08759 & -0.2802 & @xmath324 + & f & -0.3306 & -0.1236 & -0.2070 & & & -0.3675 & -0.1068 & -0.2607 & + & ( f - i)/i & @xmath416 & @xmath417 & @xmath418 & & & @xmath419 & @xmath420 & @xmath384 & + y & i & -0.1829 & -0.007196 & -0.1757 & @xmath421&@xmath422 & -0.1786 & -0.004523 & -0.1741 & @xmath423 + & f & -0.1780 & -0.001705 & -0.1763 & & & -0.1762 & 0.0009680 & -0.1771 & + & ( f - i)/i & @xmath424 & @xmath425 & @xmath366 & & & @xmath414 & @xmath426 & @xmath335 & + z & i & -0.1264 & -0.03001 & -0.09640 & @xmath324 & @xmath427 & -0.1404 & -0.04144 & -0.09896 & @xmath428 + & f & -0.1668 & -0.03264 & -0.1342 & & & -0.1425 & -0.01930 & -0.1232 & + & ( f - i)/i & @xmath429 & @xmath430 & @xmath373 & & & @xmath312 & @xmath431 & @xmath324 & + lcccc model & @xmath432 & @xmath433 & @xmath434 & @xmath435 + a & 0.99 & 0.81 & 0.95 & 0.71 + b & 0.99 & 0.86 & 0.96 & 0.83 + c & n / a & n / a & 0.98 & 0.88 + d & 0.66 & 0.56 & 0.63 & 0.54 + e & 0.72 & 0.61 & 0.68 & 0.62 + f & n / a & n / a & 0.97 & 0.80 + g & 0.99 & 0.84 & 0.97 & 0.86 + h & 0.97 & 0.88 & 0.94 & 0.80 + i & n / a & n / a & n / a & n / a + j & 0.68 & 0.57 & 0.67 & 0.53 + k & 0.88 & 0.70 & 0.83 & 0.62 + l & n / a & n / a & 0.96 & 0.92 + m & 0.99 & 0.85 & 0.95 & 0.70 + n & 0.99 & 0.88 & 0.98 & 0.81 + o & n / a & n / a & 0.95 & 0.90 + p & 0.69 & 0.59 & 0.61 & 0.52 + q & 0.82 & 0.61 & 0.70 & 0.50 + r & n / a & n / a & 0.73 & 0.70 + s & 0.98 & 0.82 & 0.88 & 0.80 + t & 0.98 & 0.82 & 0.91 & 0.80 + u & 0.63 & 0.51 & 0.61 & 0.54 + v & 0.75 & 0.55 & 0.76 & 0.60 + w & 0.99 & 0.83 & 0.95 & 0.55 + x & 0.98 & 0.90 & 0.92 & 0.80 + y & 0.76 & 0.61 & 0.67 & 0.59 + z & 0.88 & 0.84 & 0.86 & 0.80 + z & 0.08 & 0.11 & 0.12 + s & 0.1 & 0.155 & 0.165 + h & 0.11 & 0.13 & 0.12 + t & 0.115 & 0.12 & 0.135 + k & 0.125 & 0.155 & 0.14 + v & 0.13 & 0.13 & 0.18 + e & 0.135 & 0.175 & 0.16 + y & 0.135 & 0.145 & 0.13 + b & 0.14 & 0.12 & 0.125 + u & 0.145 & 0.17 & 0.145 + w & 0.15 & 0.17 & 0.16 + g & 0.155 & 0.125 & 0.13 + j & 0.165 & 0.16 & 0.12 + d & 0.165 & 0.14 & 0.175 + x & 0.17 & 0.235 & 0.105 + a & 0.17 & 0.15 & 0.18 +

the evolution of substructure embedded in non - dissipative dark halos is studied through n - body simulations of isolated systems , both in and out of initial equilibrium , complementing cosmological simulations of the growth of structure . we determine by both analytic calculations and direct analysis of the n - body simulations the relative importance of various dynamical processes acting on the clumps , such as the removal of material by global tides , clump - clump heating , clump - clump merging and dynamical friction . the ratio of the internal clump velocity dispersion to that of the dark halo is an important parameter ; as this ratio approaches a value of unity , heating by close encounters between clumps becomes less important while the other dynamical processes continue to increase in importance . our comparison between merging and disruption processes implies that spiral galaxies can not be formed in a proto - system that contains a few large clumps , but can be formed through the accretion of many small clumps ; elliptical galaxies form in a more clumpy environment than do spiral galaxies . our results support the idea that the central cusp in the density profiles of dark halos is the consequence of self - limiting merging of small , dense halos . this implies that the collapse of a system of clumps / substructure is not sufficient to form a cd galaxy , with an extended envelope ; plausibly subsequent accretion of large galaxies is required . the post - collapse system is in general triaxial , with rounder systems resulting from fewer , but more massive , clumps . persistent streams of material from disrupted clumps can be found in the outer regions of the final system , and at an overdensity of around 0.75 , can cover 10% to 30% of the sky . = cmcsc10 200v_200 a&a , # 1to 0pt#1

for the purpose of this study we used a high - resolution simulation of a two - component dwarf galaxy orbiting in the gravitational potential of the milky way ( klimentowski et al . 2007 , 2009a ) . the dwarf progenitor of total mass @xmath1 consisted of a baryonic disk embedded in a dark matter halo . the initial mass of the disk was @xmath2 and the mass of the nfw dark matter halo was @xmath3 . the dwarf galaxy was placed on an eccentric orbit around the host galaxy with apocenter to pericenter ratio of @xmath4 kpc and the disk initially inclined by 45@xmath5 to the orbital plane . the evolution was followed for 10 gyr corresponding to five orbital times . the host galaxy was modelled by a static gravitational potential assumed to have the present - day properties of the milky way as described by mass model a1 of klypin et al . ( 2002 ) . during the evolution the dwarf galaxy is strongly affected by the tidal field of the host which results in a significant mass loss , the morphological transformation from a disk to a bar and then a spheroid and the transition from the streaming to the random motion of the stars . at all times , including the final stage , the core of the dwarf galaxy remains gravitationally bound but is surrounded by pronounced tidal tails and its shape departs from spherical . if dwarf spheroidal galaxies of the local group indeed formed as envisioned by this so - called tidal stirring scenario ( mayer et al . 2001 , 2007 ) , these effects must be taken into account when modeling their masses . here we provide quantitative estimates of the biases imposed by the contamination of kinematic samples by unbound stars from the tails and by the departures from sphericity of the stellar component . the left panel of fig . [ fig1 ] shows a kinematic sample of a thousand stars randomly selected from the final output of the simulation ( where the dwarf galaxy is at apocenter ) . this mock data set shows line - of - sight velocities as a function of the projected distance @xmath6 as would be measured by a distant observer . the observation is made along the tidal tails , which is a typical orientation of the debris for an observer placed near the center of the milky way ( klimentowski et al . only the data within the standard velocity cut - off of @xmath7 ( where @xmath8 is the central velocity dispersion of the stars ) from the systemic velocity of the dwarf are shown . from this data set we obtain the velocity dispersion profile shown in the middle panel of fig . [ fig1 ] with gray data points with sampling errors . we then fit to this profile the solutions of the jeans equation for spherical systems , assuming that mass traces light ( the distribution of stars is measured for the same line of sight ) , and adjusting two parameters : the total mass @xmath9 and the anisotropy parameter of stellar orbits @xmath10 . the best - fitting solution is shown as a gray line in the middle panel of fig . [ fig1 ] and the constraints on @xmath9 and @xmath11 are shown with the gray @xmath12 and @xmath13 contours in the right panel of fig . [ fig1 ] . the increase of the velocity dispersion profile for @xmath14 kpc is due to the contamination of the sample by unbound stars from the tidal tails . note that the true values of the mass and anisotropy of this dwarf galaxy within a sphere of @xmath15 kpc measured in the simulation are respectively @xmath16 and @xmath17 ( okas et al . 2010 ) . the use of the contaminated sample thus leads to an overestimate of the mass and an underestimate of the anisotropy ( tangential rather than mildly radial orbits are inferred ) . the amount of this bias will depend on the actual orientation of the tails and the initial velocity cut - off applied to the sample , but the presented example shows that it can be quite large . since the fit is rather bad one may try to improve it by introducing a more extended dark matter halo . the tidal stirring scenario predicts , however , that tidally affected dwarfs do not possess such halos and their mass approximately traces light ( mayer et al . 2001 , okas et al . 2010 ) . .,width=604 ] the problem is solved when the kinematic sample is cleaned of interlopers ( klimentowski et al . 2007 , okas et al . 2008 , okas 2009 ) . the stars marked by the gray dots in the left panel of fig . [ fig1 ] have been removed by a scheme based on assigning a maximum velocity allowed for a star at a given @xmath6 which was extensively tested on simulated data ( klimentowski et al . the resulting velocity dispersion profile ( black points in the middle panel of fig . [ fig1 ] ) is then no longer increasing with radius and our simple two - parameter model fits the data much better . the best - fitting mass and anisotropy ( black contours in the right panel of fig . [ fig1 ] ) obtained in this case are in very good agreement with the real values . the products of tidal stirring are typically non - spherical . in the example discussed here the distribution of the stars in the final stage is a prolate spheroid with the short - to - long axis ratio of 0.6 ( klimentowski et al . the shape affects the velocity distribution in the dwarf which retains some of the radial orbits characteristic of the long - lasting bar - like phase of the evolution where the axis ratio was much smaller . [ fig2 ] shows the maps of the line - of - sight velocity dispersion of the stars seen along the long ( @xmath18 ) and the two short ( @xmath19 and @xmath20 ) axes ( from the left to the right panel ) . the dispersion is larger when viewed along the @xmath18 axis and it decreases more steeply with radius . the same effect is seen in fig . [ fig3 ] where we plot the velocity dispersion profiles measured in a traditional way , in concentric shells of projected radius @xmath6 : when measured along the long axis of the stellar component the dispersion reaches higher values in the center and decreases more steeply with @xmath6 . note that here only the stars within the sphere of radius @xmath15 kpc were used so no contamination from the tidal tails is present and all profiles decrease with radius . in addition , we used all ( i.e. almost 38 thousand ) stars , rather than a sample of a thousand to avoid the noise due to sampling errors ( those are then too small to be visible in fig . [ fig3 ] and are not shown ) . as in the previous section , we fitted the dispersion profiles with the solutions of the jeans equation for spherical systems , adjusting the total mass and anisotropy , assuming that mass follows light ( the stellar density profile was fitted separately for every line of sight ) . for the view along @xmath18 the mass within 1.7 kpc is overestimated by 7% , for the view along @xmath19 and @xmath20 it is underestimated by 17 - 18% . interestingly , the anisotropy is recovered almost perfectly , with the best - fitting values within the range of @xmath21 - 0.3 in all cases ( okas et al .

using a high resolution @xmath0-body simulation of a two - component dwarf galaxy orbiting in the potential of the milky way , we study two effects that lead to significant biases in mass estimates of dwarf spheroidal galaxies . both are due to the strong tidal interaction of initially disky dwarfs with their host . the tidal stripping of dwarf stars leads to the formation of strong tidal tails that are typically aligned with the line of sight of an observer positioned close to the host center . the stars from the tails contaminate the kinematic samples leading to a velocity dispersion profile increasing with the projected radius and resulting in an overestimate of mass . the tidal stirring of the dwarf leads to the morphological transformation of the initial stellar disk into a bar and then a spheroid . the distribution of stars in the dwarf remains non - spherical for a long time leading to an overestimate of its mass if it is observed along the major axis and an underestimate if it seen in the perpendicular direction .

a central model behind the theoretical description of competition among dissimilar species was introduced by @xcite . in the model , species are characterized by their niche position @xmath0 , which measures a trait being relevant for the exploitation of a distributed resource . as examples , the niche value @xmath0 may represent body size of predators , where the distributed resource are preys with their size distribution , or @xmath0 could be beak sizes of birds , in which case the resource could be seeds of different sizes . mathematically this leads to a lotka - volterra type of competition equation , where the competition coefficients are function of the distance between species on the niche axis @xmath1 . this competition kernel is usually taken to be a gaussian function of the niche difference ( also called normal curve ) . the implication of this choice is the central topic of this paper . the model was originally proposed as part of the hypothesis of limiting similarity , namely that competing species can coexist only if they are sufficiently different from each other @xcite . a mathematical analysis of the model revealed that arbitrarily similar species could in fact coexist in some cases . however adding further effects to the model , like noise ( @xcite , but see @xcite ) or extinction thresholds @xcite , impose a limit to the similarity between species . this sensitivity to second order effects has led to the conclusion that the model , in its original form , is structurally unstable when used to predict limits of similarity @xcite . the competition model has also been applied to describe coevolving species @xcite and used in some formulations of the theory of island biogeography @xcite . more recently the same type of model has been simulated numerically and used as a basis for dynamical models of sympatric speciation @xcite , food web assembly and evolution @xcite , elucidating the relation between competition and predator - prey interactions @xcite , and for explaining lumped size distributions of species @xcite . for a more extensive review of the biological applications and the generalization of the model see @xcite . the competition model has been fundamental for the development of basic principles in theoretical ecology and it is relevant to achieve a full understanding of its technical aspects . in almost all applications of the model the chosen competition kernel is gaussian . this choice facilitates mathematical analysis , and was justified because the exact shape of the kernel was thought to have no influence on the fundamental results of the model . however , recent work has shown that the equilibrium solution can be one of two fundamentally different types , depending on the form of the competition kernel @xcite . one class of competition kernels preserves all species initially introduced in the system , with adjustments only in their relative abundance . the final equilibrium is a state with species closely spaced and with roughly similar abundances ( if the carrying capacity is also uniform ) . another class of competition kernels leads to the species being lumped in dense groups ( in some cases groups are formed by single species ) , separated by empty regions on the niche axis . subsequent invasion of new species in these ` exclusion zones ' is not possible due to competitive exclusion . the condition for uniform distribution of species is to have a _ positive definite _ competition kernel ( see definition below ) . this criterion is automatically fulfilled when the kernel is constructed from the overlap of the species utilization of the resource @xcite . if the kernel is not positive definite , a lumpy species distribution with exclusion zones emerges . the concern about this discovery is that , even though the gaussian kernel is ecologically sound , it is exactly marginal between the two regimes . this indicates that numerical inaccuracies and/or secondary ecological effects may violate the positive definiteness of the competition kernel and cause a transition from a uniform to a lumpy species distribution . the objective of this paper is to raise awareness in the theoretical ecology community of the potential pitfalls and subtleties associated with the use of gaussian competition kernels or other marginal choices . to illustrate this , the consequences of the marginal nature of the gaussian kernel in the competition model are explored , in the idealized case of a uniform carrying capacity . first , the sensitivity to ecologically relevant effects that may lead to lumpy distributions are examined . then we examine the sensitivity to the details of numerical implementation . in the last section , we discuss the relevance of our results for the applications of the model . the competition model considers @xmath2 interacting populations , each utilizing a common distributed resource @xmath1 according to a utilization function @xmath3 , @xmath4 . the dynamics of the abundance of species @xmath5 , @xmath6 , is described by a lotka - volterra set of competition equations : @xmath7 where the growth rate ( considered to be the same for all species ) is set to one for simplicity , and the carrying capacity @xmath8 is uniform . competition in ( [ eq : lv ] ) is described by competition coefficients @xmath9 which are constructed from the overlap of utilization functions of competing species @xcite : @xmath10 a justification of ( [ eq : interaction ] ) rests upon considering the probability that consumer @xmath5 meets consumer @xmath11 @xcite . often , utilization functions are ignored , and the competition coefficients are postulated directly . it is usually assumed that species @xmath5 has an optimal exploitation of the resource at a value @xmath12 , and the competition coefficients are taken to depend on the difference between the optimal resource values of two competing species , @xmath13 , such that we can introduce the so - called competition kernel , @xmath14 . here we use a family of competition functions described by a parameter @xmath15 : @xmath16 which contains the gaussian kernel when @xmath17 , or the exponential one when @xmath18 . the width of the kernel @xmath19 gives the range of competition on the niche axis . incidentally the gaussian kernel is obtained from eq . ( [ eq : interaction ] ) when the utilization functions are also gaussian and of the form @xmath20 with @xmath21 . when @xmath22 the kernels are more peaked around @xmath23 and for @xmath24 they become more box - like ( see fig . [ fig : patterns ] ) . note that when competition coefficients are constructed by the formula ( [ eq : interaction ] ) , i.e. from the overlap of two utilization functions , they are always _ positive definite _ , meaning that @xmath25 for any set of numbers @xmath26 @xcite or , equivalently , that the fourier transform of @xmath27 , defined as @xmath28 , does not take negative values . this property holds for the family of kernels ( [ eq : alpha ] ) for @xmath29 , but not for @xmath24 ( fig . [ fig : patterns ] ) . the gaussian kernel is therefore marginal in the sense that , corresponding to the limit case @xmath17 , even a very small perturbation may violate its positive definite character , generally believed to be an ecological requirement arising from expression ( [ eq : interaction ] ) . an intuitive explanation for the appearance of the exclusion zones for @xmath24 is the following . interaction kernels with large @xmath15 have a box - like shape . in these cases species compete very strongly with other species , roughly within a distance @xmath30 from their own niche value . species with a niche @xmath1 in that range will therefore not be able to invade the resident species , leading to the exclusion zones between them . when @xmath15 is decreased , the resident species compete less and less with neighbouring species , until the exclusion zones disappear , leading to the possibility of continuous coexistence . understanding the fact that the transition occurs at @xmath17 , and also the coexistence of more than one species in each cluster , requires a mathematical stability analysis of the model . consider the uniform solution , in which many species having the same abundance are densely packed in niche space . now perturb each population by a small quantity @xmath31 , which can be either positive or negative . if the competition kernel is not positive defined , there are sets of perturbations such that @xmath32 is less than zero . one can show that such perturbations are amplified by the dynamics @xcite , making the uniform solution unstable . the system will then evolve to a clustered state , where the distance between clusters is proportional to the interaction range @xmath19 . we mention here that a possible generalization is to consider multi - dimensional niche spaces . this possibility would complicate the mathematical notation but does not introduce qualitative changes . stability in a multi - dimensional niche space still depends on the positive definiteness of the competition kernel . in particular , a multi - dimensional gaussian competition kernel is still marginal in the sense described above . we simulated the model ( [ eq : lv ] ) with competition kernel ( [ eq : alpha ] ) for 1000 generations and @xmath33 species initially at random niche positions . the width of the kernel is @xmath34 and the carrying capacity is @xmath35 . the niche range is taken to be @xmath36 $ ] . the standard mathematical way to avoid effects due to the borders of the niche space is to adopt periodic boundary conditions ( e.g. @xcite ) . these are introduced for mathematical convenience and aim at modeling species far from endpoints in a large niche space . adopting periodic boundary conditions means that niche space is circular , so that when the interaction kernels extends beyond the left edge at @xmath37 , it enters back into the right side at @xmath38 and vice versa . periodic boundaries therefore mimic an infinite system by considering the niche segment @xmath39 $ ] as embedded in an array of repeated copies of itself . mathematically , this is properly implemented by making a kernel wrap , i.e. substitute @xmath27 in ( [ eq : alpha ] ) with @xmath40 , where the sum runs from @xmath41 . we call this implementation `` fully periodic boundary conditions '' , to distinguish it from another possibility considered below . under fully periodic boundary conditions , the stability properties of the uniform solution are the same as in the infinite system . simulations using the competition kernel ( [ eq : alpha ] ) with @xmath42 ( exponential ) , @xmath43 ( gaussian ) and @xmath44 ( box - like ) illustrate the uniform species distributions for @xmath18 and @xmath17 , and the lumped species clusters for @xmath45 ( fig . [ fig : patterns ] ) . the configurations in fig . [ fig : patterns ] are still transient states and , at longer times , configurations with @xmath46 become more uniform , whereas the periodically spaced clusters of species for @xmath24 become thinner until they contain only a single species . in any case , from the initial stages until the final equilibrium , the main difference between the dynamics for the two classes of competition kernel is unchanged : for @xmath46 all initial species are preserved , leading to dense and evenly distributed configurations , whereas ` exclusion zones ' develop for @xmath24 leading to lumped species distributions . a natural question is whether the marginal nature of gaussian competition can be brought on by secondary ecological effects . we have checked that adding a small immigration rate does not produce lumpy distributions . adding noise or an extinction threshold ( i.e. species are removed when their populations fall below a threshold ) result in a limit to similarity between species , but does not lead to clustering @xcite . this also happens in non marginal cases with @xmath47 , where the minimum distance between species is unrelated to the competition range @xmath19 . effect of species extinction , invasion , and speciation was simulated by eliminating species below a given population threshold , and introducing invading species at a fixed rate . if they are introduced at random locations in niche space no patterns are observed . if invading species are introduced close to existing ones , modeling evolutionary change and speciation @xcite , the system ends with a lumped species distribution , even for @xmath17 ( fig . [ fig : immigration ] ) . however , the same mechanism has no effect if an exponential competition kernel ( @xmath18 ) is chosen . the interpretation is that evolutionary effects favor the formation of lumpy species distributions , but only when the competition kernel is close to the gaussian limiting case . generations with speciation and extinction . species whose population goes below @xmath48 are removed from the system . every @xmath49 generations new species are introduced close to an existing one . the parent species is chosen with a probability proportional to its population ; the distance of the new species to its parent is drawn from a gaussian distribution of zero mean and spread @xmath50 . the new species @xmath11 is introduced with a population uniformly drawn from the interval @xmath51 $ ] . ( left panel ) gaussian kernel ( @xmath17 ) and ( right panel ) exponential kernel ( @xmath18 ) . simulations are performed with fully periodic boundary conditions . @xmath35 and @xmath52.,width=302 ] the most obvious numerical simplification is to only partially implement the periodic boundary conditions , by omitting the kernel wrap around the niche interval , that is , using @xmath27 , with @xmath53 being the minimum of the two possible distances among species @xmath5 and @xmath11 ( @xmath54 and @xmath55 ) , instead of the periodic kernel @xmath56 . the resulting effective kernel is gaussian but truncated at @xmath57 , making it no longer positive definite . although the shapes of @xmath27 and @xmath56 are still very similar for the parameters used here ( @xmath52 ) , the change immediately leads to lumped species distributions ( fig . [ fig : numerical ] ) . in contrast , for @xmath18 ( or any other values of @xmath47 which we have checked ) , changing @xmath56 by @xmath27 has no noticeable effect . qualitatively , the dynamics for truncated gaussian kernels resembles the outcome when the exponent of the competition kernel is perturbed just slightly . e.g. using @xmath58 instead of @xmath17 also leads to lumped species distributions , even when fully periodic boundary conditions are implemented ( not shown ) . while the mathematical analysis of `` evolutionary diffusion '' is rather complicated and results can be obtained only in the framework of simple models @xcite , the effect of truncation on the different kernels may be analyzed in more depth and is discussed in the next subsection . species after @xmath59 generations with ( left panel ) gaussian competition kernel with fully periodic boundary conditions , and ( right panel ) with truncated gaussian competition kernel ( see text ) . @xmath35 and @xmath52 . , width=302 ] we have numerically shown in the previous section that truncation leads to radically different results for the gaussian and exponential kernel . this may be surprising when realizing that neither the truncated gaussian nor the truncated exponential kernel are positive defined . the explanation of the different result comes from the wavelength of the modes @xmath60 for which the fourier transform of the kernel @xmath61 takes negative values , as it determines the distance between lumps @xcite . to find these wavelengths , we start from the gaussian case and show what is the effect of truncating the kernel at a distance @xmath62 ( which we take now to be the niche - space size , previously scaled to be 1 ) : @xmath63,\ ] ] where @xmath64 is the error function , and @xmath65 stands for complex conjugate . we impose @xmath66 , so we can get a simpler expression by expanding the error function , yielding @xmath67\ ] ] from the previous expression we see that the wavenumbers that give negative modes are order @xmath68 . we now check the same effect in the exponential case : @xmath69 in this case the instability occurs for large wavenumbers , proportional to @xmath70 . we checked numerically that kernels with @xmath47 behave like the @xmath18 case , with the wavenumber of the first negative mode growing exponentially with the size of the niche space . summarizing , the kernels we considered develop an instability due to the truncation , but at very different frequencies : very high for the exponential kernel ( exponential in the ratio between the system size and the kernel range ) compared with the gaussian ( proportional to the same ratio ) . the consequence is that , already when the size of the niche space is large but not extremely large compared with the competition distance ( like the cases considered here , @xmath71 ) , the unstable mode in the exponential case has a wavelength being much smaller than the interspecies distance , and is thus unable to generate patterns . the model ( [ eq : lv])-([eq : alpha ] ) provides a very abstract representation of competition . both empirical observations and theoretical approaches , based on explicit consideration of the coupled consumer - resource dynamics , lead to competition coefficients which are quite different from gaussian @xcite , except in a few particular cases . even so , the qualitative outcome of the model does not depend on the exact shape of the competition kernel , but only on its positive or non - positive definite character . we have restricted our considerations primarily to the basic model ( [ eq : lv ] ) with gaussian interaction kernel and constant carrying capacity since it is the simplest implementation , allowing to illustrate in a clear setting the importance of @xmath72 and the issues caused by the choice of a marginal competition kernel . the basic model with competition coefficients obtained from the overlap of utilization functions , which yields always positive definite kernels , allows for dense species distributions with no limits to similarity . this fundamental solution may be changed by three different effects : 1 ) effects stemming from the competition kernel being no longer positive definite lead to lumpy species distributions . clusters of species will appear , separated by exclusion zones in niche space with a spacing proportional to the width of the competition kernel @xmath19 ; 2 ) second order ecological effects like noise , species heterogeneity , evolutionary effects , or the introduction of an extinction threshold lead to a limit to the similarity with the spacing between species being independent of @xmath19 ; 3 ) under a non constant carrying capacity , patterns of unevenly spaced species , lumpy or not , may appear . this lead @xcite to conclude that `` the not - very - smooth nature of the carrying capacity seems to be essential for limiting similarity '' . notice that also some types of smooth , but non - uniform , carrying capacities may originate lumped distributions @xcite the first case arises when the competition kernel is not positive definite . the main point of this paper is that , when the competition kernel is the marginal gaussian , the model becomes very sensitive to additional effects that may lead to lumpy species distribution . as an example , we demonstrated that a simple representation of evolutionary diffusion @xcite may lead to patterns in the gaussian case . this effect is similar to that of evolutionary dynamics under assortative mating which shown to lead to lumpy species distributions @xcite . it is worth mentioning that , in the context of evolutionary dynamics , the fact that the presence of clusters depends of the choice of the competition kernel has been recently demonstrated @xcite . patterns can also result from numerical approximations , such as truncating the tails of a gaussian competition kernel . this effect is probably the underlying mechanism behind species clustering observed in recent numerical work @xcite , which was used to explain observed lumpy distributions @xcite . additional ecological effects have been identified however @xcite which make the species groups a robust phenomenon ( see @xcite for analytical solutions of this type ) . in any case , these spurious effects can be avoided by paying attention to numerical details or by using a competition kernel which is not marginal , e.g. one with @xmath73 , which in practice is almost indistinguishable from the gaussian one . it is worth mentioning that analytical ( i.e. not numerical ) results are not affected by the marginal nature of the gaussian kernel , both in relation to limiting similarity @xcite , coevolution @xcite or criteria for sympatric speciation @xcite . the marginal nature of gaussian competition kernel may however affect numerical work on food web evolution and assembly @xcite . since a non - positive definite competition kernel leads to lumpy species distributions a natural question is whether a non - positive definite kernel can result from hypothesis on ecological interactions . this case is often neglected in the literature , since assuming eq . ( [ eq : interaction ] ) automatically leads to a positive definite competition kernel @xcite . however , as emphasized in @xcite and references therein , under quite general assumptions one should introduce two different utilization - like functions : a _ sensitivity _ function @xmath74 , describing the effect of the resource at @xmath1 on the growth of species @xmath5 , and an _ impact _ function @xmath75 , describing the depletion of resources produced by @xmath5 . then , the competition coefficients depend on the overlap of these two quantities @xmath76 , and reduce to ( [ eq : interaction ] ) only if the sensitivity and impact functions are proportional , with the constant of proportionality being the ecological efficiency . when the ecological efficiency is a function of @xmath1 , and the sensitivity and impact functions are no longer proportional , the competition kernel may cease to be positive definite @xcite . the third mechanism is that of a non - constant carrying capacity @xmath77 , which has been explored by @xcite . they found that some choices of carrying capacity leads to an irregular species lumping . the effect of non - constant carrying capacity in conjunction with both positive and non - positive definite competition kernels was explored by @xcite . the emerging picture is that the two mechanisms are independent . the cases in which a non - constant carrying capacity leads to uniform species distributions can also be destabilized by a non - positive definite kernel . this means that the mechanism explored here is not a particularity of constant carrying capacity but is present also in more general settings . it has been suggested that the effect of cutting the kernel is similar to that of having a finite niche space , i.e. of a box - like carrying capacity @xcite . however , this analogy does not hold to a rigorous mathematical analysis , which has demonstrated that lumps may appear when the carrying capacity is non - constant , but that this effect is not mathematically equivalent to a cut kernel @xcite . moreover , recent results @xcite show how the effect of closed boundaries depend on the details of the boundary shape , so that the box - like case is not representative of a general finite niche space . having outlined the reasons that may cause the three different outcomes , the question arises if it is possible to infer whether one effect or the other is at play from the result of a numerical integration of the competition model . it can be difficult to distinguish between a uniform distribution of discrete species and a lumpy one when lumps are very narrow and close . here , the fact that in the lumpy distribution the spacing of the lumps is proportional to the width of the competition kernel @xmath19 can be used . if changing @xmath19 results in a change in the distance between species proportional to @xmath19 , the effect is due to a non - positive definite competition kernel and vice versa . in the case where the effect is due to the carrying capacity being non - constant the spacing of species is usually more irregular @xcite . to summarize : in line with previous works we have found that the case of continuous coexistence ( no limits to similarity ) may be limited by a variety of effects , specially for the gaussian kernel which has a marginal character . we have underlined that there are different ways to limit similarity , some leading to lumpy species distributions and others not . we hope that this article will increase the awareness in the theoretical ecological community of the potential subtleties associated with the use of the gaussian competition kernel . even though this functional form appears to be natural , in particular for analytical work , it may not be the most prudent choice for numerical exploration of the niche model . c.l . and e.h - g . acknowledge support from project fisicos ( fis2007 - 60327 ) of mec and feder and nest - complexity project patres ( 043268 ) . k.h.a was supported by the danish research council , grant no . 272 - 07 - 0485 baptestini em , de aguiar mam , bolnick di and arajo ms ( 2009 ) . the shape of the competitition and carrying capacity kernels affects the likelihood of disruptive selection . jour theo biol , doi:10.1016/j.tbi.2009.02.023 .

a central model in theoretical ecology considers the competition of a range of species for a broad spectrum of resources . recent studies have shown that essentially two different outcomes are possible . either the species surviving competition are more or less uniformly distributed over the resource spectrum , or their distribution is lumped ( or clumped ) , consisting of clusters of species with similar resource use that are separated by gaps in resource space . which of these outcomes will occur crucially depends on the competition kernel , which reflects the shape of the resource utilization pattern of the competing species . most models considered in the literature assume a gaussian competition kernel . this is unfortunate , since predictions based on such a gaussian assumption are not robust . in fact , gaussian kernels are a border case scenario , and slight deviations from this function can lead to either uniform or lumped species distributions . here we illustrate the non - robustness of the gaussian assumption by simulating different implementations of the standard competition model with constant carrying capacity . in this scenario , lumped species distributions can come about by secondary ecological or evolutionary mechanisms or by details of the numerical implementation of the model . we analyze the origin of this sensitivity and discuss it in the context of recent applications of the model .

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The preceding sentence shall be applied based on amounts shown on the original applicable District of Columbia franchise or income tax return. ``(h) Section Not To Apply to Estates and Trusts.--This section shall not apply to an estate or trust. ``(i) Regulations.--The Secretary shall prescribe such regulations as may be necessary or appropriate to carry out the purposes of this section.'' (b) Conforming Amendments.-- (1) Paragraph (1) of section 55(c) of such Code is amended by adding at the end the following: ``Such regular tax shall be determined without regard to section 59B.'' (2) The table of parts for subchapter A of chapter 1 of such Code is amended by adding at the end the following new item: ``Part VIII. Limitation on tax imposed on residents of the District of Columbia.'' (c) Effective Date.--The amendments made by this section shall apply to taxable years ending after the date of the enactment of this Act.

District of Columbia Economic Recovery Act - Amends the Internal Revenue Code to set forth a limitation on the income tax imposed on individuals who are residents of the District of Columbia. Specifies that the limitation is the sum of: (1) 15 percent of so much District-sourced income as exceeds the exemption amount; and (2) the average rate of the non-District-sourced adjusted gross income. Sets forth definitions, including for "resident of the District of Columbia" and "exemption amount." Provides for the tax treatment of certain sources of income.

among the important ( yet ill - understood ) diagnostics of stellar nucleosynthesis and the subsequent chemical enrichment of the interstellar medium ( ism ) is the @xmath5n/@xmath0n isotopic ratio . the production of @xmath5n is thought to involve a combination of secondary sources , such as the cold cno cycle in main sequence stars , and primary ones , such as hot bottom burning in asymptotic giant branch ( agb ) stars , while @xmath0n is thought to be synthesized almost exclusively as a secondary nuclide , e.g. , through the hot cno cycle associated with nova outbursts . various sources of @xmath5n and @xmath0n have been incorporated into models of galactic chemical evolution ( gce ; e.g. , tosi 1982 ; romano & matteucci 2003 ; kobayashi et al . 2011 ) , which commonly predict that the @xmath5n/@xmath0n ratio should increase with galactocentric radius . millimeter - wave emission studies of nitrogen - bearing molecules and their isotopologues in warm dense clouds of the galactic disk have indeed revealed such a trend ( e.g. , dahmen et al . 1995 ; wilson 1999 ; adande & ziurys 2012 ) . adande & ziurys ( 2012 ) , who examined millimeter observations of cn and hnc in 11 molecular clouds , and reevaluated previous observations of hcn , inferred a nitrogen isotopic ratio for the solar neighborhood of @xmath7 from the gradient seen in their data . other determinations of the @xmath5n/@xmath0n ratio in the local ism sometimes give quite different results , however , suggesting that the ratios may be affected by chemical fractionation . hily - blant et al . ( 2013a , 2013b ) found significant differences in the nitrogen isotopic ratios derived from observations of cn and hcn isotopologues in dark molecular cloud cores . an overall ratio of @xmath8 was obtained for cn , while hcn exhibited ratios between 140 and 360 . the authors interpreted these results as evidence of fractionation and presented model calculations that they propose can explain the observations . daniel et al . ( 2013 ) studied a suite of nitrogen - bearing molecules and their isotopologues in the dark cloud barnard 1 , finding no evidence for nitrogen fractionation , which they suggest may be linked to the relatively high gas kinetic temperature ( @xmath9 k ) in the innermost part of the b1b cloud . their molecular abundances were found to be consistent with a @xmath5n/@xmath0n ratio of @xmath10300 for the parental molecular cloud , in agreement with the adande & ziurys ( 2012 ) result obtained for warmer sources in the local ism . for comparison , lucas & liszt ( 1998 ) obtained a nitrogen isotopic ratio of @xmath11 for diffuse molecular gas seen in absorption from hcn toward the extragalactic continuum source b0415@xmath12379 . in this letter , we present a new approach to estimating the nitrogen isotopic ratio in the local ism ; we report the first detection of c@xmath0n in diffuse molecular gas from an analysis of cn absorption lines in the optical spectra of background o and b - type stars . specifically , we examine high quality optical spectra of hd 73882 , hd 154368 , hd 169454 , and hd 210121 , which have distances in the range @xmath13 @xmath14 0.21.1 kpc and color excesses of @xmath15 @xmath14 0.31.1 mag . the diffuse molecular clouds probed by these sight lines have high enough kinetic temperatures ( @xmath16 k ; e.g. , sonnentrucker et al . 2007 ) that chemical fractionation is not expected to be important . furthermore , the amount of visual extinction through the clouds ( @xmath17 mag ; valencic et al . 2004 ; rachford et al . 2009 ) is small enough that selective photodissociation of n@xmath18 should not play a significant role ( heays et al . these measurements have the potential therefore to yield the most accurate @xmath5n/@xmath0n ratio to date for material within the solar neighborhood ( @xmath19 kpc ) . the observations examined here were previously discussed by ritchey et al . ( 2011 ) , who studied @xmath2cn/@xmath3cn and @xmath2ch@xmath4/@xmath3ch@xmath4 ratios along 13 lines of sight through diffuse molecular clouds . upon further examination of those data , it was realized that for four sight lines with very strong cn absorption lines , a weak feature between the main @xmath2cn and @xmath3cn absorption components might be due to the c@xmath0n isotopologue . the relevant data , acquired using the ultraviolet and visual echelle spectrograph ( uves ) of the very large telescope ( vlt ) , were obtained from the european southern observatory ( eso ) science archive facility and were reduced with the uves pipeline software ( as described in more detail in ritchey et al . the spectra have very high signal - to - noise ratios ( s / n @xmath10 12002000 per resolution element near 3875 ) and a resolution of approximately 3.5 km s@xmath20 ( @xmath21 ) . figure 1 presents the vlt / uves spectra for the four directions in the vicinity of the cn @xmath22@xmath23@xmath24 ( 0 , 0 ) @xmath25(0 ) line . the grey line in each panel indicates the profile synthesis fit originally obtained by ritchey et al . ( 2011 ) . in each case , it is apparent that there is extra absorption between the main @xmath2cn and @xmath3cn components that is not adequately accounted for by the synthetic spectrum . the expected isotope shift for the c@xmath0n @xmath25(0 ) line from laboratory spectroscopy is + 0.121 or + 9.4 km s@xmath20 ( colin & bernath 2012 ; sneden et al . 2014 ) , which is consistent with the position of this weak additional feature ( except in the case of hd 210121 ; see below ) . however , before we can claim a detection of the c@xmath0n isotopologue , we must first consider the possibility that the extra absorption arises from an additional cloud contributing a weak @xmath2cn @xmath25(0 ) component . to this end , we examined the @xmath26@xmath23@xmath24 ( 0 , 0 ) lines of ch and ch@xmath4 , which were also covered by the uves spectra ( see figures 2 and 3 ) . the first step in the analysis was to synthesize the ch lines , including as many weak additional absorption components beyond the main component as were necessary to provide a good fit . as in ritchey et al . ( 2011 ) , we used the profile synthesis routine ismod ( e.g. , sheffer et al . 2008 ) , which determines best - fitting values for the velocities , @xmath27-values , and column densities of the absorption components through an iterative rms - minimizing procedure . the goodness of fit was evaluated by comparing the residuals to the noise in the continuum regions . after fitting the ch lines , we reexamined the ch@xmath4 fits from ritchey et al . ( 2011 ) to determine if any additional components needed to be included . ( only toward hd 154368 did we see the need to include an additional weak ch@xmath4 component . ) for these ch@xmath4 syntheses , the @xmath2ch@xmath4/@xmath3ch@xmath4 ratio was held fixed at 74.4 , i.e , the mean value obtained by ritchey et al . ( 2011 ) from mcdonald observatory data . these fits are not significantly better or worse than ones where the ratio was allowed to vary , illustrating the difficulties one encounters when attempting to derive @xmath2ch@xmath4/@xmath3ch@xmath4 ratios from these vlt / uves spectra ( see ritchey et al . nonetheless , absorption from @xmath3ch@xmath4 had to be included at some level because in certain cases ( i.e. , toward hd 154368 and hd 169454 ) this absorption overlaps with weak additional @xmath2ch@xmath4 components blueward of the main components . the next step was to use the component structure derived for ch and ch@xmath4 ( see table 1 ) to determine which of the weak additional components might need to be included in the cn syntheses . in general , we retained only the strongest of the additional ch components if there was evidence of absorption at those velocities in the cn profile . in many cases , the components not included have @xmath28(ch@xmath4 ) @xmath29 @xmath28(ch ) , suggesting that the ch in those clouds is associated with ch@xmath4 rather than with cn ( e.g. , zsarg & federman 2003 ) . toward hd 169454 , there is a weak ch component at @xmath30 = + 16.7 km s@xmath20 that is shifted by + 10.9 km s@xmath20 with respect to the main component at @xmath30 = + 5.8 km s@xmath20 . this shift is close to the expected isotope shift of + 9.4 km s@xmath20 for c@xmath0n . however , we do not believe that the absorption seen in the cn profile at this velocity is due to an additional component of @xmath2cn . the cloud in question has @xmath28(ch@xmath4)/@xmath28(ch ) @xmath29 1.0 , and @xmath27(ch ) @xmath29 @xmath27(ch@xmath4 ) , indicating that the ch in this case is ch@xmath4-like rather than cn - like ( lambert et al . 1990 ; pan et al . 2005 ) . such gas should have very little ( if any ) associated cn . none of the other sight lines have a ch component that in the cn profile could be mistaken for c@xmath0n . toward hd 210121 , there is a weak ch component shifted by + 8.5 km s@xmath20 relative to the main component . however , there is no evidence for this component in the cn profile , and , moreover , c@xmath0n is not significantly detected in this direction ( see section 3 ) . we have made several improvements to the analysis of the cn features in the present work compared to our previous analysis of these spectra ( ritchey et al . most importantly , we have adopted an updated set of @xmath31-values and wavelengths for all of the relevant cn transitions , using data from the recently - published cn line lists ( brooke et al . 2014 ; sneden et al . in addition , we now explicitly account for the splitting in the cn @xmath25(0 ) feature , which is a blend of the @xmath32(0 ) and @xmath33(0 ) lines . we adopt a splitting of 0.0039 or 0.30 km s@xmath20 , with the former line having an @xmath31-value twice that of the latter ( federman et al . 1984 ; brooke et al . 2014 ) . the isotope shifts for the @xmath3cn and c@xmath0n @xmath25(0 ) features were held fixed at the values derived from laboratory spectroscopy . for @xmath3cn , the expected isotope shift is + 0.168 or + 13.0 km s@xmath20 ( ram & bernath 2011 ; sneden et al . the column densities and @xmath27-values of the main @xmath2cn absorption components were determined through simultaneous fits to the @xmath25(0 ) lines of the ( 0 , 0 ) and ( 1 , 0 ) bands of the cn @xmath22@xmath23@xmath24 system . spectra covering the cn ( 1 , 0 ) band near 3580 were obtained from archival vlt / uves observations , which generally employed a different instrumental setup and have somewhat lower resolution than the spectra covering the ( 0 , 0 ) band near 3875 ( see ritchey et al . the @xmath27-values derived for the main @xmath2cn absorption components were used to fit the corresponding @xmath3cn and c@xmath0n absorption features . the final component structures obtained for ch@xmath4 , ch , and cn are given in table 1 , where the ch@xmath4 and cn column densities refer only to the dominant isotopologue . table 2 provides the column densities and resulting ratios of the cn isotopologues for the main absorption components . uncertainties in the derived column densities account for both photon noise and errors in continuum placement . for the main absorption components , the column density uncertainties also include contributions related to the errors in the derived @xmath27-values . corrections for optical depth are the dominant source of error for the very strong @xmath2cn absorption lines seen here . ritchey et al . ( 2011 ) discussed the sensitivity of the @xmath2cn column densities to very small changes in @xmath27 . however , the @xmath27-value related uncertainties were not explicitly included in the errors reported in that paper . here , we formally include column density uncertainties based on the errors in the @xmath27-values , which are very well constrained as a result of our simultaneous fits to the strong ( 0 , 0 ) and weak ( 1 , 0 ) @xmath25(0 ) lines ( see table 1 ) . from a careful analysis of the component structure along each line of sight , we find that absorption from the c@xmath0n isotopologue is confidently detected in three out of the four directions studied . for hd 210121 , the extra absorption between the main @xmath2cn and @xmath3cn absorption features is mostly due to an additional component of @xmath2cn , which is apparent in the ch profile as well . the @xmath34 upper limit on the equivalent width of the c@xmath0n line in this direction is @xmath35(c@xmath0n ) @xmath36 m . for the other directions , we find c@xmath0n equivalent widths of @xmath37 m ( hd 73882 ) , @xmath38 m ( hd 154368 ) , and @xmath39 m ( hd 169454 ) , corresponding to @xmath40 , @xmath41 , and @xmath42 detections , respectively . the weighted mean c@xmath5n / c@xmath0n ratio for the three sight lines where c@xmath0n is detected is @xmath6 . since the diffuse molecular clouds toward our target stars have relatively high kinetic temperatures ( @xmath16 k ) and the visual extinctions are relatively low ( @xmath17 mag ) , the c@xmath5n / c@xmath0n ratios we derive should not be affected by chemical or photochemical fractionation ( see below ) . our mean value should therefore be representative of the ambient @xmath5n/@xmath0n ratio in the local ism . in principle , two processes could drive the c@xmath5n / c@xmath0n ratio away from the ambient @xmath5n/@xmath0n ratio in interstellar clouds . isotope selective photodissociation of n@xmath18 could alter the atomic @xmath5n/@xmath0n ratio from which all other nitrogen - bearing molecules are produced . however , the detailed analysis by heays et al . ( 2014 ) indicates that significant reductions in @xmath5n/@xmath0n , resulting from enhancements in @xmath5n@xmath18/@xmath5n@xmath0n , occur only at relatively large extinctions ( i.e. , @xmath43 mag ) . our targets have line - of - sight extinctions in the range @xmath44 @xmath14 0.83.6 mag ( e.g. , valencic et al . 2004 ; rachford et al . 2009 ; see table 2 ) . chemical fractionation ( e.g. , hily - blant et al . 2013b ) involving ion - molecule reactions leading to nitrogen hydride ions , which are precursors in the formation of cn ( e.g. , federman et al . 1994 ) , requires gas temperatures of @xmath1010 k. however , the clouds probed by our targets have temperatures ( from analyses of c@xmath18 rotational excitation ; e.g. , sonnentrucker et al . 2007 ) of @xmath45 k ( hd 73882 , hd 154368 , and hd 169454 ) and @xmath46 k ( hd 210121 ) . the @xmath2cn/@xmath3cn ratios for the sight lines studied here have been revised slightly compared to the ratios given in ritchey et al . ( 2011 ) , as a result of the updated @xmath31-values that we adopt and the inclusion of absorption from the c@xmath0n isotopologue , among other changes ( see section 2 ) . however , the new results do not significantly alter the conclusions of ritchey et al . the weighted mean value of @xmath2cn/@xmath3cn from our new determinations for hd 73882 , hd 154368 , hd 169454 , and hd 210121 is @xmath47 . if we include results for the other sight lines analyzed by ritchey et al . ( 2011 ) , based on the same set of @xmath31-values as used here , then the weighted mean @xmath2cn/@xmath3cn ratio we obtain is @xmath48 . ( the lower mean value for this larger sample results from the inclusion of several sight lines with markedly low @xmath2cn/@xmath3cn ratios ; such ratios are presumably a consequence of selective photodissociation of co , which can be important at relatively low values of @xmath44 ; e.g. , visser et al . 2009 ) . in either case , we find that the mean @xmath2cn/@xmath3cn ratio for local diffuse molecular clouds is in good agreement with other estimates for the @xmath2c/@xmath3c ratio in the local ism ( e.g. , wilson 1999 ; milam et al . 2005 ) . milam et al . ( 2005 ) , examining millimeter - wave observations of cn , co , and h@xmath18co in dense molecular clouds , inferred a carbon isotopic ratio for the solar neighborhood of @xmath49 from a fit to the @xmath2c/@xmath3c gradient with galactocentric distance . a similar correspondence is seen for the @xmath5n/@xmath0n ratio . our mean value of c@xmath5n / c@xmath0n for local diffuse clouds ( @xmath6 ) is in good agreement with the nitrogen isotopic ratio derived for the solar neighborhood by adande & ziurys ( 2012 ) from their fit to the galactic gradient in @xmath5n/@xmath0n ( @xmath7 ) . the close correspondence between the @xmath2c/@xmath3c and @xmath5n/@xmath0n ratios that we derive for local diffuse molecular clouds ( from the analysis of optical interstellar absorption lines ) and those measured for dense molecular clouds in the solar neighborhood ( from millimeter observations ) indicates that these values accurately reflect the ambient ratios in the present - day local ism . in contrast , the @xmath2c/@xmath3c and @xmath5n/@xmath0n ratios attributed to the sun and/or the protosolar nebula are both higher than the present - day interstellar ratios , presumably because the ism has been enriched with the products of stellar nucleosynthesis since the formation of the solar system some 4.6 gyr ago . marty et al . ( 2011 ) , reporting on solar wind data acquired by the _ mission , measured a @xmath5n/@xmath0n ratio of @xmath50 , from which they derived a value of @xmath51 for the protosolar nebula . our mean value of c@xmath5n / c@xmath0n for the local ism ( @xmath6 ) , when compared with the protosolar nebula value of @xmath5n/@xmath0n , implies that a @xmath0n enrichment of @xmath1060% has occurred over the last 4.6 gyr . a comparable study of the @xmath2c/@xmath3c ratio from the _ genesis _ mission has yet to be reported ( d. s. burnett 2014 , private communication ) . however , this ratio is obtainable for the solar photosphere from infrared co lines : scott et al . ( 2006 ) reported @xmath2c/@xmath3c = @xmath52 and ayres et al . ( 2013 ) determined a ratio of @xmath2c/@xmath3c = @xmath53 using different simulations of the solar granulation . since the local interstellar value of @xmath2c/@xmath3c is @xmath1070 , this implies that a @xmath3c enrichment of @xmath1030% has occurred since the formation of the sun . interpretation of the evolution of the @xmath2c/@xmath3c and @xmath5n/@xmath0n ratios requires identification of the principal sources responsible for the synthesis of these isotopes . a recent comprehensive model of galactic chemical evolution , which sought to reproduce the isotopic ratios seen in the sun and in other stars throughout the galaxy , was presented by kobayashi et al . ( 2011 ) . in constructing their model , kobayashi et al . consider all of the major sources of stellar nucleosynthesis , including stellar winds , agb and super - agb stars , type ia supernovae , core - collapse supernovae ( including hypernovae ) , and pair - instability supernovae , and describe recipes for the initial mass function and the star formation histories . the @xmath2c/@xmath3c ratio predicted by the kobayashi et al . model at [ fe / h ] = 0 is @xmath1089 , in very good agreement with the solar ratio . however , the predicted @xmath5n/@xmath0n ratio at [ fe / h ] = 0 is @xmath102500 , which is significantly larger than the ratio inferred for the protosolar nebula . kobayashi et al . remark that this discrepancy for @xmath5n/@xmath0n is most likely due to the fact that nova nucleosynthesis is not included in their model . the gce models of romano & matteucci ( 2003 , 2005 ) , on the other hand , do include contributions from novae , along with the standard sources of stellar nucleosynthesis . these authors adjusted the contributions from novae so that the solar isotopic ratios ( i.e. , @xmath2c/@xmath3c , @xmath5n/@xmath0n , and @xmath54o/@xmath55o ) were reproduced at the appropriate time . with this adjustment , their gce models account well for the observed decreases in the @xmath2c/@xmath3c and @xmath5n/@xmath0n ratios over the 4.6 gyr between the formation of the sun and the present . the yields from novae for @xmath3c , @xmath0n , and @xmath55o are predicted to be dependent on the mass of the c - o or o - ne white dwarf and the degree of mixing between the accreted envelope and the surface of the white dwarf on which the explosion occurs ( jos & hernanz 1998 ) . the key nuclear process is the hot cno cycle . if , as romano & matteucci ( 2005 ) assert , `` novae are at present the only candidates for producing @xmath0n in a galaxy , '' future studies of @xmath0n in gas and stars in the milky way and other galaxies are to be encouraged . we thank peter bernath and don burnett for helpful comments related to this work . the research presented here was supported by nasa grant nnx10ad80 g ( s.r.f . ) , and by the kenilworth fund of the new york community trust ( a.m.r . ) . thanks the robert a. welch foundation of houston , tx for support through grant f-634 . adande , g. r. , & ziurys , l. m. 2012 , apj , 744 , 194 ayres , t. r. , lyons , j. r. , ludwig , h .- , et al . 2013 , apj , 765 , 46 brooke , j. s. a. , ram , r. s. , western , c. m. , et al . 2014 , apjs , 210 , 23 colin , r. , & bernath , p. f. 2012 , j. mol . spectrosc . , 273 , 30 dahmen , g. , wilson , t. l. , & matteucci , f. 1995 , a&a , 295 , 194 daniel , f. , grin , m. , roueff , e. , et al . 2013 , a&a , 560 , a3 federman , s. r. , danks , a. c. , & lambert , d. l. 1984 , apj , 287 , 219 federman , s. r. , strom , c. j. , lambert , d. l. , et al . 1994 , apj , 424 , 772 heays , a. n. , visser , r. , gredel , r. , et al . 2014 , a&a , 562 , a61 hily - 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( 2011 ) , while the black line shows the fit obtained in this work . the position of the main absorption component in @xmath2cn is indicated by a longer tick mark , while shorter tick marks give the positions of weak additional @xmath2cn components included in the fit . the positions of the main @xmath3cn and c@xmath0n components are also indicated.,scaledwidth=100.0% ] @xmath23@xmath24 ( 0 , 0 ) lines toward hd 73882 , hd 154368 , hd 169454 , and hd 210121 ( @xmath57 ) . plotting symbols are the same as in figure 1 . the position of the main ch absorption component is indicated by a longer tick mark , while shorter tick marks give the positions of weak additional components included in the fit.,scaledwidth=100.0% ] @xmath26@xmath23@xmath24 ( 0 , 0 ) lines toward hd 73882 , hd 154368 , hd 169454 , and hd 210121 ( @xmath58 ) . plotting symbols are the same as in figure 1 . the positions of the main absorption components in @xmath2ch@xmath4 and @xmath3ch@xmath4 are indicated by longer tick marks , while shorter tick marks give the positions of weak additional components included in the fit . the two ch@xmath4 isotopologues are assumed to have identical component structure and to exhibit a @xmath2ch@xmath4/@xmath3ch@xmath4 ratio of 74.4 ( see the text).,scaledwidth=100.0% ] lccccccccccc hd 73882 & & & & & + 1.0 & @xmath59 & 0.2 & & @xmath230.5 & @xmath60 & 0.2 + & + 5.6 & @xmath61 & 2.8 & & + 5.9 & @xmath62 & 1.4 & & + 6.1 & @xmath63 & @xmath64 + & + 10.2 & @xmath65 & 1.9 & & + 12.1 & @xmath66 & 0.2 & & + 12.6 & @xmath60 & 0.2 + hd 154368 & @xmath2312.9 & @xmath67 & 0.5 & & @xmath2312.9 & @xmath68 & 1.8 & & @xmath2313.4 & @xmath69 & 0.2 + & @xmath236.8 & @xmath70 & 1.4 & & @xmath237.0 & @xmath71 & 1.9 & & & & + & + 2.4 & @xmath72 & 2.0 & & + 3.8 & @xmath73 & 2.6 & & + 4.2 & @xmath74 & 2.6 + & + 6.5 & @xmath75 & 1.9 & & + 5.7 & @xmath76 & 1.1 & & + 5.7 & @xmath77 & @xmath78 + & + 11.5 & @xmath79 & 4.5 & & + 12.3 & @xmath80 & 1.1 & & & & + hd 169454 & @xmath232.3 & @xmath81 & 5.5 & & @xmath233.3 & @xmath82 & 4.0 & & @xmath232.8 & @xmath83 & 1.6 + & & & & & + 1.1 & @xmath84 & 1.6 & & + 1.5 & @xmath85 & 0.6 + & + 5.6 & @xmath86 & 2.7 & & + 5.8 & @xmath87 & 1.3 & & + 6.2 & @xmath88 & @xmath89 + & & & & & + 10.2 & @xmath90 & 2.0 & & + 12.1 & @xmath60 & 0.8 + & + 15.4 & @xmath91 & 1.9 & & + 16.7 & @xmath92 & 3.3 & & & & + & & & & & + 22.7 & @xmath93 & 1.6 & & & & + & & & & & + 27.2 & @xmath94 & 0.2 & & & & + hd 210121 & @xmath237.3 & @xmath95 & 1.6 & & @xmath236.1 & @xmath96 & 1.5 & & @xmath236.2 & @xmath97 & @xmath98 + & @xmath232.7 & @xmath99 & 2.6 & & @xmath232.2 & @xmath100 & 0.8 & & @xmath231.8 & @xmath101 & 0.4 + & & & & & + 2.4 & @xmath102 & 2.0 & & & & + lccccccc hd 73882 & @xmath103 & @xmath63 & @xmath104 & @xmath105 & @xmath106 & @xmath107 + hd 154368 & @xmath108 & @xmath77 & @xmath109 & @xmath110 & @xmath111 & @xmath112 + hd 169454 & @xmath113 & @xmath88 & @xmath114 & @xmath115 & @xmath116 & @xmath117 + hd 210121 & @xmath118 & @xmath97 & @xmath119 & @xmath120 & @xmath121 & @xmath122 +

we report the first detection of c@xmath0n in diffuse molecular gas from a detailed examination of cn absorption lines in archival vlt / uves spectra of stars probing local diffuse clouds . absorption from the c@xmath0n isotopologue is confidently detected ( at @xmath1 ) in three out of the four directions studied and appears as a very weak feature between the main @xmath2cn and @xmath3cn absorption components . column densities for each cn isotopologue are determined through profile fitting , after accounting for weak additional line - of - sight components of @xmath2cn , which are seen in the absorption profiles of ch and ch@xmath4 as well . the weighted mean value of c@xmath5n / c@xmath0n for the three sight lines with detections of c@xmath0n is @xmath6 . since the diffuse molecular clouds toward our target stars have relatively high gas kinetic temperatures and relatively low visual extinctions , their c@xmath5n / c@xmath0n ratios should not be affected by chemical fractionation . the mean c@xmath5n / c@xmath0n ratio that we obtain should therefore be representative of the ambient @xmath5n/@xmath0n ratio in the local interstellar medium . indeed , our mean value agrees well with that derived from millimeter - wave observations of cn , hcn , and hnc in local molecular clouds .

a 23-year - old healthy female was admitted to our hospital with a new - onset tender bulge in her left groin , associated with subjective fevers and chills . four days prior to presentation , she noted a sudden protrusion in her left groin with associated pain . given worsening pain and intermittent nausea , she presented to our emergency room . on admission , physical examination revealed a soft , non - distended abdomen that was tender to palpation in the left lower quadrant . a soft , mobile , exquisitely tender , and non - reducible mass laboratory data were notable for a leukocyte count of 6.7 , a hematocrit of 36.9 and a lactate of 1.4 in the setting of normal electrolytes . an outside ultrasound showed an avascular complex cystic lesion measuring 2.1 cm in the left groin . a subsequent computed tomography scan of the abdomen and pelvis revealed a tubular cystic structure along the left inguinal canal , coursing along the expected path of the round ligament , without surrounding fat stranding or herniation of bowel loops . given her symptoms and the unclear etiology of the hernia , she was admitted to the hospital and taken to the operating room for exploration ( fig . 1 ) . in the operating room , a 6-cm dark purple cystic structure was visualized within the sac of an indirect inguinal hernia , travelling along the round ligament down toward the mons pubis ( fig . 2 ) . the cystic structure was dissected away from the round ligament and the cyst was opened and noted to contain clear liquid . ultimately , the patient underwent left indirect inguinal hernia repair , with gore bio a absorbable mesh , and excision of a left inguinal hydrocele of the round ligament . final pathology revealed fibromuscular tissue lined by mesothelium consistent with a hernia sac and a hydrocele with concordant endometriosis . the patient 's post - operative course was uneventful and she was discharged home on post - operative day 1 . figure 2:purple cystic structure within the sac of an indirect inguinal hernia , travelling along the round ligament down towards the mons pubis . left indirect inguinal hernia . purple cystic structure within the sac of an indirect inguinal hernia , travelling along the round ligament down towards the mons pubis . endometriosis is defined as the presence of ectopic endometrial glands and stroma at extrauterine sites . it is a relatively common , benign , estrogen - dependent disorder that affects 10% of women of reproductive age . it is characterized by chronic pain , severe dysmenorrhea and infertility , although the disease may be asymptomatic or discovered incidentally . endometriosis can affect almost any organ system , although most ectopic implants are located in the pelvis . extrapelvic endometriosis is a rare disease entity that may cause a variety of unusual symptoms , including pain and physiologic dysfunction , dependent on the location and size of lesions as well as the organ system affected . it has been described at multiple sites including the gastrointestinal tract , urinary tract , thoracic cavity , central nervous system , umbilicus , skin ( including abdominal wall incisions and episiotomy scars ) and inguinal canal . inguinal endometriosis is a condition characterized by the presence of endometrial stroma and glands in the extraperitoneal portion of the round ligament and in the surrounding connective and lymphatic tissues . first described in 1986 , it is an extremely rare affliction with < 60 cases reported in the literature . typically , patients are in their reproductive years , with a peak incidence between 3040 years , and present with tender inguinal swelling . inguinal endometriosis is difficult to recognize and thus often confused with more common conditions such as hernias , lymphadenopathy , granulomas , soft tissue tumors , cysts and hydroceles . catamenial symptoms , such as variation in size and tenderness of the mass , are present in 50% of cases and should raise the index of suspicion for inguinal endometriosis . in many cases , the patient is brought to the operating room with a preoperative diagnosis of incarcerated hernia and the endometriosis is discovered incidentally or on histologic examination . in over 90% of cases , inguinal endometriosis occurs on the right side . the endometriosis most often affects the extraperitoneal portion of the round ligament and is rarely found in association with occult hernias . however , in a minority of cases , inguinal endometriosis can coincide with inguinal hernias and other groin pathology , increasing the diagnostic difficulty . in one series , 37% of patients suffered from inguinal endometriosis associated with a groin hernia . the presence of isolated endometriosis contained within a left - sided inguinal hernia sac has , to our knowledge , never been reported . in all but two cases reported in the literature , or 91% of cases , the treatment of choice for both inguinal hernias and inguinal endometriosis is surgical excision . in order to be locally curative , surgical excision must include the removal of the extraperitoneal portion of the round ligament . given the high concordance of pelvic endometriosis , concurrent diagnostic laparoscopy or post - operative referral to a gynecologist is indicated to evaluate for other lesions and the extent of endometriosis . in some cases , there may be a role for hormonal suppression with oral contraceptives or gnrh agonists . our patient underwent complete excision of a left inguinal hydrocele of the round ligament and repair of left indirect inguinal hernia with mesh . she was started on hormonal therapy with an oral contraceptive and subsequently referred to a gynecologist for subsequent evaluation of her newly documented endometriosis . all authors were members of the clinical team who saw the patient and treated the patient at the beth israel deaconess medical center . the case report was written in large part by k.a . with contributions from all other authors .

endometriosis is a common gynecologic disorder wherein ectopic endometrial glands and stroma are found at extrauterine sites . extrapelvic endometriosis is a well - documented , yet rare , disease entity that can affect almost any organ system . inguinal endometriosis is an extremely rare disease entity characterized by tender inguinal swelling . here we report a case of a sudden - onset and acutely painful left inguinal hernia with concordant endometriosis . a review of the literature is presented . the presence of isolated endometriosis contained within a left - sided inguinal hernia sac has , to our knowledge , never been reported . often diagnosed incidentally or on histologic examination , general surgeons should consider inguinal endometriosis in the differential diagnosis of inguinal masses , even in the absence of catamenial symptoms . surgical excision , with gynecologic follow - up , is locally curative and the treatment of choice for inguinal endometriosis .

gamma - rays are an important tool for studying the cosmos ; unlike cosmic rays ( crs ) , they point back to their sources and can identify remote acceleration regions . air cherenkov telescopes have identified numerous sources of high - energy ( @xmath8 tev ) gamma - rays ( see e.g. @xcite ) : within our galaxy , gamma - rays have been observed coming from supernova remnants ( snrs ) , pulsar wind nebulae ( pwne ) , binary systems , and the galactic center . extra - galactic sources include starburst galaxies and active galactic nuclei ( agns ) . surface air - shower arrays like milagro have performed all - sky searches for tev gamma - rays . although these detectors are less sensitive to point sources than air cherenkov telescopes , they have identified several galactic pointlike and extended sources @xcite . interactions of crs with interstellar matter and radiation in the galaxy produce a diffuse flux . hadrons interacting with matter produce neutral pions , which decay into gamma rays , while cr electrons produce gamma - rays via inverse compton scattering on the radiation field . milagro has measured this diffuse galactic flux in the tev energy range with a median energy of 15 tev and reported an excess in the cygnus region , which might originate from crs from local sources interacting with interstellar dust clouds @xcite . icecube s predecessor amanda - ii has also looked for tev photons from a giant flare from sgr 1806 - 20 , using 100 gev muons . amanda s large muon collection area compensated for the small cross - section for photons to produce muons @xcite . at higher energies , extra - galactic sources are unlikely to be visible , because more energetic photons are predicted to interact with cosmic microwave background radiation ( cmbr ) , and with infrared starlight from early galaxies , producing @xmath9 pairs @xcite . at 1 pev , for example , photon propagation is limited to a range of about 10 kpc . it is unknown whether galactic accelerators exist that can produce gamma rays of such high energy , but an expected flux results from interaction of ( extragalactic ) crs with the interstellar medium ( ism ) and dense molecular clouds . to date , the best statistics on photons with energies in the range from @xmath0300 tev to several pevs come from the chicago air shower array - michigan muon array ( casa - mia ) , built at the dugway proving ground in utah . casa consisted of 1089 scintillation detectors placed on a square array with 15 m spacing . mia consisted of 1024 scintillation counters buried under about 3 m of earth , covering an area of 2500 m@xmath10 . it served as a muon veto , with a threshold of about 0.8 gev . casa - mia set a limit on the fraction of photons in the cosmic - ray flux of @xmath11 at energies above 600 tev @xcite . the experiment also sets a limit of @xmath12 on the fraction of photons in the cr flux coming from within 5@xmath13 of the galactic disk @xcite at 310 tev . this is near the theoretical expectation due to cosmic - ray interactions with the interstellar medium . for a northern hemisphere site like casa - mia , ref . @xcite predicts a gamma - ray fraction of @xmath14 for the average gas column density . in this work , we present a new approach for detecting astrophysical pev gamma rays , based on data of the surface component , icetop , and the in - ice array of icecube . icetop measures the electromagnetic component of air showers , while the in - ice array is sensitive to muons that penetrate the ice with energies above 500 gev . while most cr showers above 1 pev contain many muons above this threshold , only a small fraction of pev gamma - ray showers carry muons that are energetic enough to reach the in - ice array . therefore , gamma - ray candidates are selected among muon - poor air showers detected with icetop and whose axis is reconstructed as passing through the in - ice array . this approach of selecting muon - poor showers as gamma - ray candidates is fundamentally different from the earlier amanda - ii gamma - ray search described above , which was only sensitive to gamma - ray showers that _ do _ contain high energy muons ( @xmath15 gev ) . we present a limit on the gamma - ray flux coming from the galactic plane , based on one year of data with half of the icecube strings and surface stations installed . we also discuss the sensitivity of the completed detector . icecube consists of a @xmath0km@xmath10 surface air shower array and 86 strings holding 60 optical modules each , filling a physical volume of a km@xmath16 . the region in the center of the buried detector is more densely instrumented . see text for details . ] icecube ( see fig . [ fig : detector ] ) is a particle detector located at the geographic south pole . the in - ice portion consists of 86 strings that reach 2450 m deep into the ice . most of the strings are arranged in a hexagonal grid , separated by @xmath0125 m. each of these strings holds 60 digital optical modules ( doms ) separated by @xmath0 17 m covering the range from 1,450 m to 2,450 m depth . eight strings form a denser instrumented area called deepcore . the doms detect cherenkov light produced by downward - going muons in cosmic - ray air showers and from charged particles produced in neutrino interactions . the data used in this analysis was collected in 2008/9 , when the 40 strings shown in fig . [ fig : layout ] were operational . each dom is a complete detector system , comprising a 25 cm diameter hamamatsu r7081 - 02 phototube @xcite , shaping and digitizing electronics @xcite , calibration hardware , plus control electronics and power supply . most of the buried pmts are run at a gain of @xmath17 . digitization is initiated by a discriminator , with a threshold set to 0.25 times the typical peak amplitude of a single photoelectron waveform . each dom contains two separate digitizing systems ; the analog transient waveform digitizer ( atwd ) records 400 ns of data at 300 megasamples / s , with a 14 bit dynamic range ( divided among 3 parallel channels ) , while the fast analog - to - digital converter ( fadc ) records 6.4 @xmath18s of data at 40 megasamples / s , with 10 bits of dynamic range . a system transmits timing signals between the surface and each dom , providing timing calibrations across the entire array of about 2 ns @xcite . the icetop surface array @xcite is located on the surface directly above the in - ice detectors . it consists of 81 stations , each consisting of two ice - filled tanks , about 5 m apart . for the 2008 data used here , 40 stations were operational ( ic40 , see fig . [ fig : layout ] ) . each tank is 1.8 m in diameter , filled with ice to a depth of about 90 cm . the tanks are initially filled with water , and the freezing of the water is controlled to minimize air bubbles and preserve the optical clarity of the ice . each tank is instrumented with two doms , a high - gain dom run at a pmt gain of @xmath19 , and a low - gain dom , with a pmt gain of @xmath20 . the two different gains were chosen to maximize dynamic range ; the system is quite linear over a range from 1 to @xmath21 photoelectrons . a station is considered hit when a low - gain dom in one tank fires in coincidence with a high - gain dom in the other ; the thresholds are set to about 20 photoelectrons . when an in - ice dom is triggered it sends a local coincidence ( lc ) message to its nearest two neighbors above and nearest two neighbors below . if the dom also receives an lc message from one of its neighbors within 1 @xmath18s it is in hard local coincidence ( hlc ) . in that case the full waveform information of both the atwd and fadc chip is stored . for ic40 and earlier configurations , isolated or soft local coincidence ( slc ) hits were discarded . in newer configurations , the slc hits are stored albeit with limited information . keeping the full waveforms would require too much bandwidth , since the rate of isolated hits per dom due to noise is @xmath0500 hz . instead , only the three fadc bins with the highest values and their hit times are stored . in sec . [ sec : ic40ana ] we present a gamma - ray analysis of the ic40 dataset . in sec . [ sec : fullsensitivity ] we study the expected sensitivity of the full icecube detector , and discuss how the inclusion of slc hits increases the background rejection . map of location of all 86 strings of the completed icecube detector . the blue dots represent the 40 string configuration that is used for this analysis . at surface level each of these 40 strings is complemented by an icetop station consisting of two tanks . the large ( red ) circles indicate the ` inner strings ' of the ic40 configuration . ] we create a sample of gamma - ray candidates by selecting air showers that have been successfully reconstructed by icetop and have a shower axis that passes through the icecube instrumented volume . the geometry limits this sample to showers having a maximum zenith angle of @xmath030 degrees . since icecube is located at the geographic south pole , the field of view ( fov ) is roughly constrained to the declination range of @xmath22 to @xmath23 degrees , as shown in fig . [ fig : fov ] . this fov includes the magellanic clouds and part of the galactic plane . gamma - rays at pev energies are strongly attenuated over extra - galactic distances , thus limiting the observable sources to those localized in our galaxy . at distances of @xmath0 50 kpc and @xmath060 kpc , the pev gamma - ray flux from the large and small magellanic cloud is suppressed by several orders of magnitude . the contours in the background of fig . [ fig : fov ] are the integrated neutral atomic hydrogen ( hi ) column densities under the assumption of optical transparency based on data from the leiden / argentine / bonn survey @xcite . these densities are not incorporated into the analysis and are only plotted to indicate the galactic plane . we do expect , however , that gamma - ray sources are correlated with the hi column density . firstly , galactic cr accelerators are more abundant in the high density regions of the galaxy . secondly , the gamma - ray flux of ( extra-)galactic crs interacting with the ism naturally correlates with the column density . however , it has to be noticed that this correlation is not linear , because of the attenuation of gamma - rays over a 10 kpc distance scale . furthermore , the column densities do not include molecular hydrogen which can also act as a target for crs . contours of integrated neutral atomic hydrogen ( hi ) column densities @xcite , in galactic coordinates ( flat projection ) . the blue circle indicates the gamma - ray fov for icecube in the present ic40 analysis . the red rectangle indicate the regions for which casa - mia @xcite has set an upper limit on the galactic diffuse photon flux in the 100 tev @xmath24 1 pev energy range . icecube s fov is smaller but covers a different part of the galactic plane , close to the galactic center . ] the gamma - ray candidate events are searched for in a background of cr showers that have exceptionally few muons or are directionally misreconstructed . in the latter case the muon bundle reaches kilometers deep into the ice but misses the instrumented volume . this background is hard to predict with monte carlo ( mc ) simulations . cosmic - ray showers at pev energies and with a low number of energetic muons are rare . for example , at 1 pev less than 0.1% of the simulated showers contain no muons with an energy above 500 gev , approximately what is needed to reach the detector in the deep ice when traveling vertically . determining how many hadronic showers produce a signal in a buried dom would require an enormous amount of mc data to reach sufficient statistics , plus very strong control of the systematic uncertainties due to muon production , propagation of muons and cherenkov photons through the ice , and the absolute detector efficiencies . it would also have to be able to accurately predict the errors in air shower reconstruction parameters . for example , this analysis is very sensitive to the tails of the distribution of the error on the angular reconstruction of icetop . even mc sets that are large enough to populate these tails are not expected to properly describe them . to avoid these issues , we determine the background directly from data . as a result , we are not able to measure a possible isotropic contribution to the gamma - ray flux , because these gamma - rays would be regarded as background . instead , we search for localized excesses in the gamma - ray flux . we search for a correlation of the arrival directions of the candidate events with the galactic plane , and scan for point sources . the acceptance of icetop-40 is a complex function of azimuth and zenith due to its elongated shape and the requirement that the axis of the detected shower passes through ic40 ( with the same elongated shape ) . however , since the arrival time is random ( there are no systematic gaps in detector uptime w.r.t . sidereal time ) the reconstructed right ascension ( ra ) of an isotropic flux of cr showers is uniform . the correct declination distribution of the background is very sensitive to the number of background showers introduced by errors in the icetop angular reconstruction of the air shower as a function of the zenith angle , and is taken to be unknown . however , the flat distribution of background over ra is enough to allow for a search for gamma - ray sources . recently , icecube found an anisotropy in the arrival direction of crs on the southern hemisphere @xcite . these deviations with ra have been established for samples of crs with median energies of 20 tev and 400 tev . the two energy ranges show a very different shape of the anisotropy , but the level of the fractional variations in flux is at a part - per - mil level for both @xcite . an anisotropy with comparable magnitude in the pev energy range is too small to affect this analysis ( the ic40 final sample contains 268 events ) . between april 5 2008 and may 20 2009 , icecube took data with a configuration of 40 strings and 40 surface stations ( ic40 ) , using several trigger conditions based on different signal topologies . this analysis uses the 8 station surface trigger , which requires a signal above threshold in both tanks of at least 8 icetop stations . an additional signal in icecube is not required for this trigger , but all hlc hits in the deep detector within a time window of 10 @xmath25 before and after the surface trigger are recorded . the air shower parameters are reconstructed from the icetop hits with a series of likelihood maximization methods . the core position is found by fitting the lateral distribution of the signal , using @xmath26 where @xmath27 is the signal strength , @xmath28 is the distance to the shower axis , @xmath29 is the fitted signal strength at the reference distance @xmath30 m , @xmath31 is the slope parameter reflecting the shower age , and @xmath32 is a constant determined from simulation @xcite . signal times are used to find the arrival direction of the air shower . the time delay due to the shape of the shower plane is described by the sum of a gaussian function and a parabola , both centered at the shower core , which yields a resolution of @xmath33 for ic40 . the relationship between the reconstructed energy @xmath34 and @xmath29 is based on mc simulations for proton showers and depends on the zenith angle . icecube data is processed in different stages : in the first two levels the raw data is calibrated and filtered , and various fitting algorithms are applied , of which only the icetop reconstruction described above is used in this analysis . in the selection of photon shower candidates from the data sample we distinguish two more steps : level three ( l3 ) and level four ( l4 ) . level three includes all the conditions on reconstruction quality , geometry and energy that make no distinction between gamma - ray showers and cr showers . the l4 cut is designed to separate gamma rays from crs . two parameters are used to constrain the geometry and ensure the shower axis passes through the instrumented volume of icecube . the icetop containment parameter @xmath35 is a measure for how centralized the core location is in icetop . when the core is exactly in the center of the array @xmath36 , while @xmath37 means that it is exactly on the edge of the array . more precisely , @xmath38 means that the core would have been on the edge of the array if the array would be @xmath39 times its actual size . the string distance parameter @xmath40 is the distance between the point where the shower reaches the depth of the first level of doms and the closest inner string . inner string , in this sense , means a string which is not on the border of the detector configuration . ic40 has 17 inner strings ( see fig . [ fig : layout ] ) . the l3 cuts are : * quality cut on lateral distribution fit : @xmath41 ( cf . [ eq : latfit ] ) * geometry cut : @xmath42 * geometry cut : @xmath43 * energy cut : @xmath44 the energy and geometry cuts are optimized in a later stage ( sec . [ sec : gptest ] ) . the l4 stage imposes only one extra criterion to the event : there should be no hlc hits in icecube . this removes most of the cr showers , if @xmath45 is chosen sufficiently high . the remaining background consists of cr showers with low muon content and mis - reconstructed showers , the high energy muons from which do not actually pass through icecube . the event sample after the l4 cut might be dominated by remaining background but it can be used to set an upper limit to the number of gamma - rays in the sample . since the event sample after l3 cuts is certainly dominated by crs , the ratio between the number of events after l4 and l3 cuts can be used to calculate an upper limit to the ratio of gamma - ray - to - cr showers . the remaining set of candidate gamma ray events is tested for a correlation with the galactic plane ( sec . [ sec : gptest ] ) and the presence of point like sources ( sec . [ sec : pssearch ] ) . first , the results of simulations are presented , which provide several quantities needed for sensitivity calculations . although we determine the background from data only , simulations are needed to investigate systematic differences in the detector response to gamma - ray showers and cosmic - ray showers . more specifically , we are interested in the energy reconstruction of gamma - ray showers , the fraction of gamma - ray showers that is rejected by the muon veto system , and a possible difference in effective detector area between both types of showers . gamma - ray and proton showers are simulated with corsika v6.900 , using the interaction models fluka 2008 and sybill 2.1 for low and high energy hadronic interactions , respectively . for both primaries 10,000 showers are generated within an energy range of 800 tev to 3 pev with a @xmath46 spectrum . because the shower axes are required to pass through icecube , the zenith angle is restricted to a maximum of 35 degrees . the observation altitude for icetop is 2835 m. atmospheric model msis-90-e is used , which is south pole atmosphere for july 01 , 1997 . seasonal variations in the event rate are of the order of 10% @xcite . the detector simulation is done with the icetray software package . each simulated shower is fed into the detector simulation ten times with different core positions and azimuthal arrival direction , for a total of 100,000 events for both gamma rays and protons . this resampling of showers is a useful technique for increasing the statistics when examining quantities like the resolution of the energy reconstruction of icetop . however , it can not be used for quantities with large shower - to - shower variations , such as the number of high energy muons . ratio between reconstructed and true energy of simulated gamma - ray showers as a function of their true energy . at low energies the overestimation of the gamma - ray energy is largely due to a bias effect of the eight - station filter . at higher energies , this overestimation decreases . ] distribution of true energy of gamma - ray ( red , solid ) and proton ( blue , dotted ) showers for an energy cut at @xmath47 pev , weighted to a @xmath48 spectrum . ] the energy of gamma - ray showers is overestimated by the reconstruction algorithm . [ fig : ereco ] shows the distribution of the logarithm of the ratio between the reconstructed and true primary energy as function of true energy , weighted to a @xmath48 spectrum . there are two reasons for the energy offset . first , there is a selection effect of the eight - station filter , which has a bias ( below a few pev ) towards showers that produce relatively large signals in the icetop tanks . this also affects the reconstructed energy of cr showers . at higher energies , the offset decreases but the reconstructed energy of gamma - ray showers is still slightly overestimated because the energy calibration of icetop is performed with respect to proton showers . figure [ fig : ethresh ] shows the distribution of true energies of gamma - ray and proton showers for the energy cut @xmath47 pev ( which will be adopted in sec . [ sec : gptest ] ) . after this cut , 95% of the gamma - ray showers have a true energy above 1.2 pev , while 95% of the proton showers have an energy above 1.3 pev . the fraction of gamma - ray showers that is falsely rejected because the showers contain muons that produce a signal in icecube is found by applying the cuts to the mc simulation . after applying the l3 cuts ( defined in sec . [ sec : gptest ] ) to the simulated gamma - ray sample there are 737 events left in the sample , of which 121 produce a signal in icecube . taking into account an energy weighting of @xmath48 , this corresponds to 16% . showers that have no energetic muons can still be rejected if an unrelated signal is detected by icecube . this could be caused by noise hits or unrelated muon tracks that fall inside the time window . this noise rate is determined directly from the data and leads to 14% signal loss . the total fraction of gamma - ray showers that is falsely rejected is therefore 28% . finally , because the composition , shower size and evolution of gamma - ray and cr showers are different , one might expect a difference in the number of triggered stations and the quality of the reconstruction , which could lead to different effective areas . such an effect would be of importance when calculating the relative contribution of gamma - rays to the total received flux . we compare the effective area for gamma rays and protons by counting the number of events that are present at l3 . we compensate for the energy reconstruction offset by reducing the reconstructed gamma - ray energy by a factor 1.16 . the ratio of the effective area for gamma - rays to that for protons is then found to be 0.99 . it should be emphasized that we do not use the simulation to determine the number of muons and their energy distribution from cr showers . this would require a simulation set that includes heavier nuclei instead of protons only . moreover , various hadronic interaction models generate significantly different muon fluxes @xcite . instead , this analysis estimates the rate of cr showers that do not trigger icecube using the data itself . the ic40 data set consists of 368 days of combined icecube and icetop measurements . the data from august 2009 is used as a burn sample , which means that it is used to tune the parameters of the analysis . after this tuning the burn sample is discarded and the remaining data is used for the analysis . icecube is sensitive to gamma rays above 1 pev . earlier searches by casa - mia in a slightly lower energy range ( 100 tev 1 pev ) with better sensitivity have not established a correlation of gamma - rays with the galactic plane ( see fig . [ fig : sensgalp ] ) . for a galactic diffuse flux below the casa - mia limit @xcite no gamma rays are expected in the ic40 burn sample . however , icecube observes a different part of the galactic plane ( see fig . [ fig : fov ] ) , close to the galactic center , so the possibility exists that previously undetected sources or local enhancements in cr and dust densities create an increase in the flux from that part of the sky . in order to find a possible correlation of candidate events in our burn sample to the galactic plane , different sets of l3 cut parameters are applied to find a set that produces the most significant correlation . afterwards , the cut parameters are fixed and the burn sample is discarded . the fixed cut parameters are then used in the analysis of the rest of the ic40 data set to test whether the correlation is still present . note that these cuts are applied at l3 , so they affect both the event samples after l3 and l4 cuts . this is important because the ratio between the number of events after l4 and l3 cuts is used to calculate the ratio between gamma ray and cr showers . there are three cut parameters that are optimized by using the burn sample : @xmath45 , @xmath49 and @xmath50 . this is done by scanning through all combination of parameters within the following range : 600 tev @xmath51 2 pev with steps of 100 tev , @xmath52 with steps of 0.1 , and 50 m @xmath53 m with steps of 10 m. for each combination , the number of events @xmath54 in the burn sample after the l4 cut , located in the source region , is counted . the source region is defined as within 10 degrees of the galactic plane . then , the data set is scrambled multiple times by randomizing the ra of each data point . for each scrambled data set the number of events in the source region is again counted . the best combination of cut parameters is the set which has the lowest fraction of scrambled data sets for which this number is equal to or higher than @xmath54 . the result of the scan is given in the three panels of fig . [ fig : optim ] . for each cut parameter the fraction of scrambled data sets that has a number of events in the source region equal to or exceeding the amount in the original data set is plotted for different cut values . for each plot the values of the other two cut parameters are kept constant at their optimal value . the actual search is done in three dimensions . the ratio is lowest for @xmath55 pev , @xmath56 and @xmath57 m. with this combination of cuts only 0.011% of the scrambled data sets produce an equal or higher number of events in the source region . note that while this procedure of optimizing cuts should be effective in the presence of sufficient signal , the small fraction obtained here and its erratic behavior with changing cut values are consistent with fluctuations of the background cr distribution alone , given the large number of possible cut combinations which were scanned . nonetheless , the cut parameter values found with this procedure seem very reasonable ( similar values are found with an alternative method , see sec . [ sec : fullsensitivity ] ) . the optimized cuts are applied to the complete ic40 data set minus the burn sample . there are 268 candidate events of which 28 are located in the source region . figure [ fig : skymap ] is a map of the sky showing all 268 events . the colors in the background indicate the integrated hi column densities , cf . [ fig : fov ] ( see discussion sec . [ sec : principle ] ) . these are meant to guide the eye and are not part of the analysis . the significance of the correlation with the galactic plane is tested by producing data sets with scrambled ra . an equal or higher number of source region events is found in 21% of the scrambled data sets , corresponding to a non - significant excess of + 0.9@xmath58 . we follow the procedure of feldman & cousins @xcite to construct an upper limit for the ratio of gamma rays to crs . the background is determined by selecting a range of ra that does not contain the source region . within this range the data points are scrambled multiple times and for each scrambled set the number of events in a pre - defined region of the same shape and size as the source region is counted . this yields a mean background of 24.13 events for the source region . using a 90% confidence interval , the upper limit on the number of excess gamma rays from this region is 14 . since 28% of gamma - ray showers are rejected by the veto from the buried detector , the maximum number of excess gamma - rays from the galactic plane is @xmath59 . from fig . [ fig : ethresh ] , it is known that the energy cut corresponds to a threshold of 1.2 pev for gamma - rays , and 1.3 pev for protons . given that at l3 the sample is dominated by cr showers , and assuming a cr and gamma - ray power law of @xmath60 , a 90% c.l . upper limit of @xmath61 on the ratio of gamma - ray showers to cr showers in the source region can be derived in the energy range 1.2 6.0 pev . the upper bound of 6.0 pev is the value for which 90% of the events are inside the energy range . this value falls outside the range for which gamma - ray showers were simulated . however , there is no indication that the energy relation plotted in fig . [ fig : ereco ] behaves erratically above 3 pev . this is a limit on the average excess of the ratio of gamma - rays to crs in the source region with respect to the rest of the sky , i.e. a limit on the galactic component of the total gamma - ray flux . a possible isotropic component is not included . systematic uncertainties lead to a 18% variation of the upper limit , as determined in sec . [ sec : systerror ] . an additional search for point - like sources tests the possibility that a single source dominates the pev gamma - ray sky . this source does not necessarily lie close to the galactic plane . an unbinned point source search is performed on the sky within the declination range of @xmath62 to @xmath63 , using a method that follows @xcite . the region within 5 degrees around the zenith is omitted , because the method relies on scrambled data sets that are produced by randomizing the ra of the events . close to the zenith this randomization scheme fails due to the small number of events . the data is described by an unknown amount of signal events on top of a flat distribution of background events . in an unbinned search , a dense grid of points in the sky is scanned . for each point a maximum likelihood fit is performed for the relative contribution of source events over background events . for a particular event @xmath64 the probability density function ( pdf ) is given by @xmath65 where @xmath66 is the number of events that is associated to the source , @xmath67 is the background pdf , and @xmath68 is the two - dimensional gaussian source pdf , in which @xmath69 is the space angle between the event and the source test location , and @xmath70 is the angular resolution of icetop . the background pdf @xmath67 is only dependent on the zenith angle , and is derived from the zenith distribution of the data . for each point in the sky there is a likelihood function @xmath71 and associated test statistic @xmath72 which is maximized for @xmath66 . in the optimization procedure , @xmath66 is allowed to have a negative value , which mathematically corresponds to a local flux deficit . the procedure is similar to the search method for the neutrino point sources with icecube @xcite , except that the source and background pdf do not contain an energy term . because the range of energies in the event sample is relatively small ( 90% of the events have an energy between 1 and 6 pev ) , an energy pdf is unlikely to improve the sensitivity . distribution of the largest value of @xmath73 observed in each scrambled data set . the red dotted line indicated the value for @xmath73 that corresponds to the hottest spot in the data . ] figure [ fig : pointsources ] displays a map of the sky with declination between @xmath62 and @xmath63 showing the events in this region and contours of the test statistic @xmath73 . the maximum value is @xmath74 at @xmath75 and ra@xmath76 , corresponding to a fit of @xmath77 signal events . the overall significance of this value for @xmath73 is found by producing @xmath78 scrambled data sets by randomizing the ra of each event . figure [ fig : hotspots ] shows the distribution of @xmath73 associated to the hottest spot in each scrambled data set . the median test statistic value for the hottest spot in the scrambled data sets is @xmath79 , so the actual data set is consistent with a flat background . upper limits on the gamma - ray flux can be derived for each point in the sky by assuming that all events are gamma - rays . since many events are in fact muon - poor or misreconstructed showers , this leads to a conservative upper limit . because the acceptance of ic40 decreases as a function of declination ( see fig . [ fig : acceptance ] ) , the limit is more constraining at lower declination . figure [ fig : pointsourceslimits ] is a sky map of the 90% c.l . upper limit in the energy range @xmath80 pev for @xmath4 source spectra . point source fluxes are excluded at a level of @xmath5 @xmath6s@xmath7tev@xmath7 depending on source declination . corrections for signal efficiency and detector noise are taken into account . systematic uncertainties lead to a 18% variation of the upper limit . since this analysis derives the background from data , the systematic uncertainties due to the background estimation are small . the previously discussed cosmic - ray anisotropy measurement ( see sec . [ sec : principle ] and @xcite ) is too small to have an impact on this analysis . since there are no systematic gaps in detector uptime with respect to sidereal time - of - day in our sample , the coverage of ra is homogeneous . therefore , we focus on the systematic uncertainties in the signal efficiency , due to uncertainties in the surface detector sensitivity , and in the muon production rate for photon showers . the uncertainty in the surface detector sensitivity is studied in ref . @xcite ; table 2 there gives the uncertainties for hadronic showers as a function of shower energy and zenith angle . although there are differences between hadronic and electromagnetic showers , most factors that contribute to this figure apply to both types of showers . strongly contributing factors include atmospheric fluctuations , calibration stability and uncertainties in response of detector electronics ( pmt saturation and droop ) . the contribution from the uncertainty in modeling the hadronic interaction is clearly different for electromagnetic showers , and is discussed below . for @xmath81 pev , and zenith angle less than 30@xmath82 , there is a 6.0% systematic uncertainty in energy , and a 3.5% systematic uncertainty in flux . for an @xmath48 spectrum , a 6.0% uncertainty in energy translates into a 17.0% uncertainty in flux , or , adding in quadrature , 17.4% flux uncertainty . the uncertainty in the muon production from hadronic showers emerges from theoretical uncertainties . it depends on the hadronic photoproduction and electroproduction cross - sections for energies between 10 tev and 6 pev . figure 1 of @xcite compares two cross - sections from two different photoproduction models , and finds ( for water with a similar atomic number and mass number as air ) , a difference that rises from about 20% at 10 tev to 60% at 1 pev . the bulk of the particles in the shower are at lower energies , so we adopt a 20% uncertainty on the muon production rate via photoproduction . in addition , there is also a contribution of muon pair creation . to reach the in - ice doms , muons need at least 500 gev . at 1 tev , the fractional contribution of muon pair creation is @xmath83% @xcite . since muon pair production is not included in sybill 2.1 , we arrive at 30% uncertainty in total muon production rate . this uncertainty is applied to the 16% of photon showers that are lost because they contain muons for a final 4.8% uncertainty in sensitivity due to the unknown muon production cross - section . we add the uncertainties due to detector response and muon production in quadrature , and arrive at an overall 18 % uncertainty in sensitivity . the sensitivity of the full icecube detector to a gamma - ray flux from the galactic plane benefits from multiple improvements that can be made with respect to the analysis presented above . in this section we use preliminary data from the ic79 configuration ( 79 strings , 73 surface stations , 2010/2011 ) to estimate the sensitivity that the full icecube detector can reach in 5 years . since the full detector ( ic86 : 86 strings and 81 surface stations ) is slightly larger than the ic79 configuration , the predicted sensitivity will be slightly underestimated . also , the new cuts proposed below are not yet optimized , as this would require the actual ic86 data set . this analysis is very sensitive to the quality of the core reconstruction . if the shower core is not reconstructed accurately , a muon bundle that passes outside the in - ice array might be incorrectly assumed to be aimed at the detector . because of the absence of a signal in the in - ice doms , the event is then misinterpreted as a gamma - ray candidate . a more accurate core reconstruction algorithm has been developed for icetop and will improve the cr rejection in post - ic40 analyses . in addition , the angular resolution of the larger array is improved , increasing the sensitivity to point sources . the slc mode ( which is available since ic59 , see sec . [ sec : detector ] ) increases the sensitivity to cr showers with low muon content . a muon with just enough energy to reach icecube , might not emit enough cherenkov light to trigger multiple neighboring doms . by tightening the l4 cut so that no slc hits are allowed to be present in the data , the efficiency with which cr showers can be rejected increases . at the same time , actual gamma - ray showers may be rejected in case of a noise hit in a single dom . to keep this chance low , slc hits only count as veto hits if they can be associated to the shower muon bundle both spatially and temporally . figure [ fig : slchits ] shows the distribution of isolated hits in the complete detector as a function of time relative to the arrival time of the air shower as measured by icetop . the plots show data at l3 level , applying the same cut values as in the ic40 analysis . the left plot shows the distribution of slc hits for all events , while the right plot shows the same distribution but restricted to the subset of events which contain _ only _ slc hits , i.e. events with no hlc hits . hits associated with the muon bundle are seen throughout the detector , although the number of hits varies with depth because of variations in the optical properties of the ice due to naturally varying levels of contaminants such as dust , which attenuate cherenkov photons the large number of isolated hits in the two bottom rows is an edge effect : the doms have fewer neighbors , so the chance for a hit to be isolated increases . in principle , the same effect could occur at the top two rows . however , the muon bundle deposits more energy in this region and the probability for any hit to have neighbor hits is larger here . the muon - poor showers that produce no hlc hits ( right - hand plot ) can still cause some isolated hits in the top of the detector . these events can be removed with an additional cut on slc hits . because isolated hits can also be produced by noise , only a small area is selected in which slc hits are used as a veto . a simple additional l4 cut is that all events are removed that have an slc hit meeting the following three criteria : * it is within 200 m from the reconstructed shower axis , * it is within a time window of 4.87.5 @xmath18s after the shower arrival time , and * it is in one of the six top layers of doms ( spanning a vertical extend of 85 m ) . note that the lower bound of the time window ( 4.8 @xmath18s ) corresponds to the time it takes for a muon traveling vertically to reach the top layer of in - ice doms starting from the surface . muons from an inclined shower will arrive even later . the number of background events that are discarded in the l4 cut is increased by @xmath030% , while the slc noise rate in the data implies a decrease in signal efficiency of @xmath05% . with the completed detector it will be possible to optimize the slc cuts further by making the time window dependent on zenith angle and dom depth . the effect of this optimization was not yet studied here . for the ic40 analysis the cut parameters were optimized to increase the detection probability of a possible correlation of gamma rays with the galactic plane . to increase the sensitivity of future searches with the completed ic86 configuration , the cut values were re - evaluated to increase the number of candidate events without losing background rejection power . this was achieved by evaluating the ratio between the number of events after l3 and l4 cuts . while the l3 event sample is completely dominated by crs , the l4 sample is a combination of possible gamma - ray showers , muon - poor cr showers and misreconstructed cr showers . the fraction of gamma - rays and muon - poor crs in the detected events is independent from the cuts on geometry parameters @xmath40 and @xmath35 . the number of misreconstructed cr showers , on the other hand , will increase if the geometry cut values are chosen too loosely . therefore , the ratio between the number of l4 and l3 events as a function of the cut parameter should be flat up to some maximum value after which it starts to increase . this maximum value is the preferred cut value since it maximizes the number of candidate events without lowering the background rejection power . it also maximizes the fov , as looser geometry cuts imply a larger maximum zenith angle . figure [ fig : ratios ] shows the number of l3 ( red ) and l4 ( blue ) events together with their ratio ( black dotted line ; right - hand axis ) as a function of the three main cut parameters ( with the other cut parameters kept constant at their final value ) . the rejection efficiency for @xmath40 is fairly stable up to 60 m. the number of events rapidly decreases above this value , while the rejection becomes worse . in this case , the alternative method of optimization yields the same result as the method used in the ic40 analysis . for the containment size @xmath35 the ratio remains stable up to the edge of the array ( @xmath37 ) after which it starts to rise . it appears the cut can be relaxed with respect to the ic40 analysis . in the following we will use @xmath57 m and @xmath84 . the efficiency of the energy cut increases , as expected , with increasing energy , leveling off around @xmath0 2.0 pev . since the total number of events falls off rapidly for increasing energy , the most sensitive region will be @xmath85 pev . however , since the spectra of possible sources in this energy regime are unknown , it is not clear what energy cut would produce the optimal sensitivity . instead , the sensitivity is calculated for ten energy bins in the range 110 pev ( see fig . [ fig : sensgalp ] ) . acceptance ( effective area integrated over solid angle ) for showers with an axis through both icetop and icecube for ic40 , @xmath35=0.8 ( black ) , and ic86 , @xmath35=1.0 ( blue ) . ] with a larger array the acceptance , defined here as the effective area integrated over the solid angle of each 1@xmath82 bin in zenith angle , increases considerably . because of the condition that the shower axis has to be inside the instrumented area of both icecube and icetop , the increase is especially dramatic at larger zenith angles . fig . [ fig : acceptance ] shows the acceptance for ic40 with @xmath86 and the complete ic86 array with @xmath87 . not only does the acceptance increase at large zenith angles , the range of possible zenith angles is also extended ( to @xmath88 ) . this extends the fov to cover a larger part of the galactic plane and probe an area closer to the galactic center . the galactic center itself is still outside the fov at @xmath89 , corresponding to a zenith angle of @xmath90 . the sensitivity that can be reached with 5 years of data from the completed icecube configuration can be estimated with preliminary data from ic79 . it is assumed that the fraction of gamma - rays that are missed due to noise hits is the same as in the ic40 analysis . the full detector obviously has more noise hits , but this can be compensated by refining the in - ice cut by only allowing vetoes from doms that can be associated to the shower muon bundle in space and time ( cf . the slc cut described above ) . the sensitivity is calculated by producing scrambled data sets with randomized ra . figure [ fig : sensgalp ] shows the 90% c.l . sensitivity to a diffuse flux from within 10 degrees of the galactic plane that can be achieved with 5 years of full detector data . the blue dashed line indicates the integrated limit between 1 and 10 pev , while the blue dots indicate the sensitivity in six smaller energy bins . the upper limits found by casa - mia and ic40 ( present work ) are also included in the plot . the kascade @xcite results are not included since they set a limit on the all - sky gamma - ray flux . figure [ fig : sensps ] shows the sensitivity to point sources that is possible with 5 years of icecube data . the sensitivity is a strong function of declination because the acceptance decreases at larger zenith angles . point sources are expected to lie close to the galactic plane which reaches its lowest declination at @xmath91 . within the icecube field of view there are several pwne and other gamma - ray sources detected by h.e.s.s . @xcite , listed in table [ table : sources ] . for these sources no significant cut - off was observed up to the maximum energy of 10 tev , where statistics gets low . the blue dots indicate the flux that these sources would have at 1 pev if their spectrum remains unchanged up to that energy . no correction for gamma - ray attenuation between the source and observer has been applied in this calculation . the extrapolation over two order of magnitude causes large uncertainties in the gamma - ray flux due to propagation of the errors on the spectral indices . existing limits ( red triangles for casa - mia and purple line for present ic40 analysis ) and icecube sensitivity to a diffuse gamma - ray flux from a region within 10 degrees from the galactic plane . the blue dashed line indicates the five year sensitivity of the completed detector , while the blue dots represent the sensitivity in smaller energy bins . ] icecube 5 year sensitivity to point sources as a function of declination . the solid ( dashed ) black line indicates the sensitivity to an @xmath92 flux . the dashed red line indicates the lowest declination reached by the galactic plane . the blue points indicate the flux at 1 pev with extrapolated uncertainties of the sources listed in table [ table : sources ] in the absence of a cut - off . ] [ cols="<,<,<,<,<,<",options="header " , ] we have presented a new method of searching for high energy gamma - rays using the icecube detector and its surface array icetop . one year of data from ic40 was used to perform a search for point sources and a galactic diffuse signal . no sources were found , resulting in a 90% c.l . upper limit on the ratio of gamma rays to cosmic rays of @xmath61 for the flux coming from the galactic plane region ( @xmath93 ) in the energy range 1.2 6.0 pev . point source fluxes with @xmath4 spectra have been excluded at a level of @xmath5 @xmath6s@xmath7tev@xmath7 depending on source declination . the full detector was shown to be much more sensitive , because of its larger size , improved reconstruction techniques and the possibility to record isolated hits . this analysis offers interesting observation possibilities . icecube can search for a diffuse galactic gamma - ray flux with a sensitivity comparable to casa - mia , but at higher energies . this sensitivity is reached , however , by studying a much smaller part of the galactic plane than casa - mia . icecube is therefore especially sensitive to localized sources , which might be galactic accelerators or dense targets for extragalactic crs . the h.e.s.s . and cangaroo - iii @xcite telescopes have found several high energy gamma - ray sources in icecube s fov . most of these sources are identified as or correlated with pwne . their energy spectrum has been measured up to a couple of tens of tev . at this energy , statistics become low and for most sources no cut - off has been established . if these spectra extend to pev energies without a break , icecube will be able to detect them . it is also possible that an additional spectral component in the pev energy range is present if a nearby dense molecular cloud acts as a target for the pwn beam @xcite . icecube will be able to study these systems and place constraints on their behavior at very high energies , or possibly detect pev gamma - rays for the first time . we acknowledge the support from the following agencies : u.s . national science foundation - office of polar programs , u.s . national science foundation - physics division , university of wisconsin alumni research foundation , the grid laboratory of wisconsin ( glow ) grid infrastructure at the university of wisconsin - madison , the open science grid ( osg ) grid infrastructure ; u.s . department of energy , and national energy research scientific computing center , the louisiana optical network initiative ( loni ) grid computing resources ; national science and engineering research council of canada ; swedish research council , swedish polar research secretariat , swedish national infrastructure for computing ( snic ) , and knut and alice wallenberg foundation , sweden ; german ministry for education and research ( bmbf ) , deutsche forschungsgemeinschaft ( dfg ) , research department of plasmas with complex interactions ( bochum ) , germany ; fund for scientific research ( fnrs - fwo ) , fwo odysseus programme , flanders institute to encourage scientific and technological research in industry ( iwt ) , belgian federal science policy office ( belspo ) ; university of oxford , united kingdom ; marsden fund , new zealand ; australian research council ; japan society for promotion of science ( jsps ) ; the swiss national science foundation ( snsf ) , switzerland . a. borione , m. a. catanese , m. c. chantell , c. e. covault , j. w. cronin , b. e. fick , l. f. fortson , j. fowler _ et al . _ , astrophys . j. * 493 * , 175 - 179 ( 1998 ) . f. a. aharonian , astrophysics & space science * 180 * , 305 ( 1991 ) . r. abbasi _ et al . _ [ icecube collaboration ] , nucl . instrum . * a618 * , 139 - 152 ( 2010 ) . r. abbasi _ et al . _ [ icecube collaboration ] , nucl . instrum . * a601 * , 294 - 316 ( 2009 ) . a. achterberg _ et al . _ [ icecube collaboration ] , astropart . * 26 * , 155 - 173 ( 2006 ) . f. halzen and s. r. klein , rev . instrum . * 81 * , 081101 ( 2010 ) r. abbasi _ et al . _ [ icecube collaboration ] , [ astro - ph/1207.6326 ]

gamma - ray induced air showers are notable for their lack of muons , compared to hadronic showers . hence , air shower arrays with large underground muon detectors can select a sample greatly enriched in photon showers by rejecting showers containing muons . icecube is sensitive to muons with energies above @xmath0500 gev at the surface , which provides an efficient veto system for hadronic air showers with energies above 1 pev . one year of data from the 40-string icecube configuration was used to perform a search for point sources and a galactic diffuse signal . no sources were found , resulting in a 90% c.l . upper limit on the ratio of gamma rays to cosmic rays of @xmath1 for the flux coming from the galactic plane region ( @xmath2 ; @xmath3 ) in the energy range 1.2 6.0 pev . in the same energy range , point source fluxes with @xmath4 spectra have been excluded at a level of @xmath5 @xmath6s@xmath7tev@xmath7 depending on source declination . the complete icecube detector will have a better sensitivity , due to the larger detector size , improved reconstruction and vetoing techniques . preliminary data from the nearly - final icecube detector configuration has been used to estimate the 5 year sensitivity of the full detector . it is found to be more than an order of magnitude better , allowing the search for pev extensions of known tev gamma - ray emitters .

Art is a cry of distress from those who live out within themselves the destiny of humanity … Inside them turns the movement of the world; only an echo of it leaks out – the work of art Arnold Schoenberg, 1910. Austrian composer Arnold Schoenberg, like many gifted artists throughout history, suffered for his art. Popular artists of the modern era have kept this tradition alive. For all the superficial glamour of the pop music world, let us not delude ourselves - today’s popular music scene is brutal. The “pop-cultural scrap heap”, to borrow journalist Drew Magary’s term, is piled high with the dead or broken bodies of young musicians whose personal and musical aspirations collided with the aspirations of those occupying the commercial edifices erected around them, which turn them into income-generating commodities whose role is to satisfy capricious and ever-changing consumer demands. Many of those musicians end up feeling suffocated, caged and possessed by their minders, exploiters and fans. And many end up dead. How big a problem is the pop music industry, really? The rock scene is a volatile mix of glamour, instant wealth, risk-taking, rebellion and psychological distress accompanied by taken-for-granted assumptions that pop musicians will live dangerously, abuse substances and die early. Journalist Amanda Hooten, writing about Robbie Williams, identifies the components of the “classic rock’n’roll script” as “sex, drugs, rehab and bitterness”. Blogger Jacob Katel expresses the same sentiments in a more forthright manner: [d]ead rock stars are a dime a dozen. They usually drink themselves to death, overdose on narcotics, crash cars, or get on faulty aircraft with drunk pilots … Previous research does not answer the question Why do so many pop musicians die young? Few studies have systematically examined the popular musician population to ascertain the extent of the problems codified in the media comments above. Existing studies are limited in scope. Adrian Barnett, for example, tested the “27 club hypothesis”. Tucker, Faulkner and Horvath only included a narrow sample of the population, that is, musicians who died between 1959 and 1967. A John Moores University study only looked at artists with top rating albums. At the other end of the scale, the study reported by Howard Sounes in his book 27 is over-inclusive as it covers not only performing musicians but also songwriters, record producers, managers and promoters. New research AAP Photo I’ve undertaken the first population study of performing pop musicians (n=12,665) from all popular genres who died between 1950 and June 2014 of whom 90.6% (11,478 musicians) were male. Data on age, circumstances and manner of death were accessed from over 200 sources, including The Dead Rock Stars’ Club; Nick Tavelski’s (2010) Knocking on Heaven’s Door: Rock Obituaries, Pop star mortality; R.I.P. Encyclopaedia Metallicum; Voices from the Dark Side for Dead Metal Musicians; Wikipedia’s List of Dead Hip Hop Artists and Hip Hop obituaries; I went to rapper death websites, Dead Punk Stars and similar sites for all popular music genres. The genres I covered included African, ballad, bluegrass, blues, Cajun, calypso, Christian pop, conjunto, country, doo-wop, electroclash, folk, funk, Gospel, hard rock, hip hop, honky tonk, indie, jazz, Latin, metal, new wave, polka, pop, psychedelic, punk, punk-electronic, rock rap, reggae, rhythm and blues, rock ‘n’ roll, rockabilly, ska, soul, swamp, swing, techno, western and world music. Longevity, suicide, homicide and accidental death rates in pop musicians I examined four outcomes – longevity and the proportion of deaths by suicide, homicide and non-intentional injury or accident. Longevity was determined by calculating the average age of death for each musician by sex and decade of death. These averages were then compared with population averages by sex and decade for the US population (per 100,000) (see Figure 1, below). Figure 2 (below) provides a graphical summary of percentages of musicians who died by decade from each of the three causes of death studied; these are juxtaposed with deaths in the US population from the same causes by decade. All comparisons shown in these figures were highly statistically significantly different from the US population. The pop music scene is toxic and needs rehabilitation The results of this study are disturbing. Across the seven decades studied, popular musicians’ lifespans were up to 25 years shorter than the comparable US population. Accidental death rates were between five and 10 times greater. Suicide rates were between two and seven times greater; and homicide rates were up to eight times greater than the US population. This is clear evidence that all is not well in pop music land. Why is this so? The pop music “scene” fails to provide boundaries and to model and expect acceptable behaviour. It actually does the reverse – it valorises outrageous behaviour and the acting out of aggressive, sexual and destructive impulses that most of us dare only live out in fantasy. The music industry needs to consider these findings to discover ways of recognising and assisting young musicians in distress. At the very least, those who make their livings from these young people need to learn to recognise early signs of emotional distress, crisis, depression and suicidality and to put some support systems in place to provide the necessary assistance and care. The Conversation is currently running a series on Death and Dying. ||||| Many famous musicians died at 27. Professor Diana Kenney says the theory of the 27 Club doesn’t stack up, but rock stars do die younger. She speaks to WSJ’s Ramy Inocencio. Photo: AP CANBERRA, Australia—The so-called 27 Club boasts some of the music industry’s biggest names, including Kurt Cobain, Jimi Hendrix, Janis Joplin, Amy Winehouse and Jim Morrison. Rock-and-pop superstardom is one requirement for entry; the other, much less enviable qualification is premature death. The theory, popularized in music journals, is that 27 is the age at which rock musicians are most at risk of an untimely death. But the author of a new Australian study argues that the theory doesn’t stack up. While musicians do often lead far shorter lives than their fans, the average age of death is much higher than 27. ‘The industry itself actually supports outrageous behavior.’ — Dianna Kenny After tracing music-world deaths since 1950 and plotting them against the wider U.S. population, Dianna Kenny found that the average male musician dies in his late 50s, compared with 75 for men outside the industry during the period. Female musicians live a little longer—into their early 60s, but still well short of 80, the average age at death for American women over the relevant time period. ENLARGE Warren Mason, Kurt Cobain's first guitar teacher, signs an image of the musician during Kurt Cobain Day on Feb. 20, 2014, in Aberdeen, Wash., U.S. Associated Press “The 27-Club hypothesis is a myth,” says Ms. Kenny, a researcher in psychology and music at the University of Sydney. “There’s no one particular age compared with the normal population that is more vulnerable.” Her academic study isn’t the first to delve into untimely rock-star deaths, but it claims to be only one that examines as many as 12,665 musicians who have died over the past six decades. The researcher studied musical genres ranging from jazz, rock and blues to techno, rap and ballads. Of the musicians whose deaths she tabulated since rock 'n' roll’s rise in the 1950s, more than 90% were male. Ms. Kenny says fatal accidents in the music industry occur at twice—and suicides at three times—the general average. “The industry itself actually supports outrageous behavior. Drugs are very prevalent—young musicians often take uppers to perform and then party all night with alcohol and drugs,” Ms. Kenny said, adding that the stresses of touring also cut lives short. ENLARGE Based on her experience in psychology, Ms. Kenny says the music industry often fails to provide enough emotional support or guidance to vulnerable young people coming into the field. , many of whom are from broken homes or have experienced some degree of emotional disruption. “As they are climbing the ladder to stardom they dream of being at the peak and that all of their psychological problems will somehow be relieved by adoration and squillions of dollars,” she says. “What they actually come to is a sense of emptiness and an incredibly demanding lifestyle, where everybody is telling them what to do.” ‘The 27-Club hypothesis is a myth.’ —Dianna Kenny The number of suicides among musicians started to decline after hitting a peak in 1994 around the death of Kurt Cobain, the guitarist and hard-living lead singer of rock-band Nirvana, says Ms. Kenny. Still, she says more needs to be done to ensure that young people, particularly, have a better idea of what they are getting into. Television talent shows are particularly concerning, she says, with even children sometimes finding themselves propelled to stardom almost overnight. “Children lose their sense of being children in those environments,” she adds. ENLARGE A portrait of late British singer Amy Winehouse by Canadian singer Bryan Adams at his photo exhibition on the outskirts of Lisbon, Portugal, Oct. 14. European Pressphoto Agency Write to Rob Taylor at [email protected]

– The idea that rock stars die young is actually true, according to a new study out of Australia. Though most rock stars don't enter the so-called "27 Club," whose members all died at that age (Kurt Cobain, Jimi Hendrix, Janis Joplin, Amy Winehouse, Jim Morrison), the study finds that they do die much earlier than the average person. Researchers looked at 12,665 music industry deaths since 1950 and found that the average male musician lives just into his late 50s, while the average female musician lives only into her early 60s, the Wall Street Journal reports. Compare that to the average age of death for American men (75) and women (80) who are not in the industry. The study found that the rates of suicide, homicide, and fatal accidents are all significantly higher among rock stars than among the general population, the lead researcher writes at the Conversation. "Across the seven decades studied, popular musicians' lifespans were up to 25 years shorter than the comparable US population," she writes. Why? She thinks it has to do with the lifestyle. "The industry itself actually supports outrageous behavior. Drugs are very prevalent—young musicians often take uppers to perform and then party all night with alcohol and drugs," she tells the Journal. Add that to the general stress of touring, and you have a recipe for disaster—particularly because the industry doesn't provide enough emotional support, she says. Rock stars "dream of being at the peak and that all of their psychological problems will somehow be relieved by adoration and squillions of dollars. What they actually come to is a sense of emptiness and an incredibly demanding lifestyle, where everybody is telling them what to do." (Lonely people also may not live as long.)

MOLALLA, Ore. – Clackamas County Sheriff Craig Roberts apologized Thursday after one of his deputies shot and killed a family’s pony last month. “We made a mistake,” Roberts said in a statement. “Other actions could and should have been taken.” At about 9 a.m. Thursday, Feb. 19, a deputy was called to an area along Highway 213 on a report that a horse may have been hit by a car. The deputy reported that he saw a “very old” horse that “couldn’t stand” even though it was trying to do so. The deputy said he couldn’t determine where the horse came from and could not locate its owner. In his report, the deputy said “it appeared (the horse) was nursing one front leg and a rear leg.” The deputy said he called the humane society, a local veterinarian, and a supervisor to seek advice in determining what he should do. The deputy said after describing his observations to his supervisor, his supervisor agreed with him that the horse needed to be put down. The deputy then killed the horse with his shotgun. That horse, a 30-year-old American Miniature Horse named Gir, belonged to Crista Fitzgerald. After learning that her horse had been put down without her permission, Fitzgerald said there was no good reason to kill her pony and that her vet determined there was nothing wrong with it. Fitzgerald wanted a second opinion and sent Gir’s body to Oregon State University’s veterinary lab on Feb. 25. The lab determined the pony had no broken bones and was in excellent condition despite having arthritis. In his statement of apology, Roberts said, “We offer our sincere condolences to the Fitzgerald family. … “We have approached the family about exploring ways to make this as right as we can. And we are examining our own procedures when dealing with this sort of situation in the future.” But Adam Fitzgerald, Crista’s husband, told KATU News Thursday afternoon that they haven’t heard from anyone at the sheriff’s office since Monday night, when an investigator came to their home to pick up the OSU report. He said the sheriff’s office has talked to them about making things right, but Adam Fitzgerald said he feels like it is an attempt to just silence them. Fitzgerald said the family plans to sue the sheriff’s office, citing discrepancies in the police report. He said the bullet gauge used to shoot the pony was different than the gun the deputy said he used. Sheriff Roberts' statement: I grew up with horses and livestock in Clackamas County, and understand their profound value. We offer our sincere condolences to the Fitzgerald family. As detailed in the report, a judgment call was made in the field to humanely euthanize the animal; ultimately, other actions could and should have been taken. We made a mistake. We have approached the family about exploring ways to make this as right as we can. And we are examining our own procedures when dealing with this sort of situation in the future. Craig Roberts Clackamas County Sheriff ||||| MOLALLA, Ore. -- A Clackamas county family wants to know why a sheriff's deputy shot and killed their beloved pony. They claim it happened without them knowing, and for no good reason. Crista Fitzgerald said her family’s 30 year-old American Miniature Horse, named Gir, was fine - except for his old age. Gir was so healthy he was able to escape from his stall in a Molalla barn sometime overnight on February 18. "I locked his stall door, and I always do a double check. The next morning I came back out before I had class in the morning, which is around 10, and he was gone,” she said. Fitzgerald knew Gir couldn’t have gone far from the barn. "We started knocking door-to-door. And the first house we came to he was laying in their yard,” she explained. She thought Gir was taking a nap, but it turns out he took a couple bullets instead "We walked up closer and I bent down to pet him, and that's when I saw the pool of blood behind his cheek bones. The neighbor came out and told us she had called the sheriff's department and they put him down,” Fitzgerald said. "When I called the officer he said that he had gotten out on the highway and gotten hit by a car and broke both of his back legs,” she said. Clackamas County Sheriff Office spokesman Sgt. Nathan Thompson tells KATU News the officer did believe the horse had broken legs from being hit by a car. Thompson also said he believes the deputy called the Oregon Humane Society to ask about euthanizing the horse before he shot it. A spokeswoman for OHS tells KATU News the deputy never called them. Thompson also said the deputy called a local veterinarian to ask about euthanizing the horse. KATU News reporter Hillary Lake contacted the vet about that call. He confirmed he did talk to the deputy, that his office offered assistance in euthanizing the horse, but that the officer said he would “take care of the problem on his own” and call a rendering service himself. Thompson said the deputy made the decision to shoot the horse after also consulting his supervisor. “There wasn't very much I could say at that point because they shot the pony. I mean, i didn't know how to react,” Fitzgerald said. She didn't believe Gir was hit by a car or that it had broken legs as the neighbor told the deputy, and the sheriff’s office claims. "My vet said there was absolutely nothing wrong with him,” she said. So she sent Gir's body to Oregon State University's veterinary lab on February 25 for a second opinion. The report says Gir died by gunshot, had no broken bones except for a fractured jaw caused by a bullet, and was in excellent body condition considering he had arthritis. "If I had gone out and shot the pony I’d be in jail right now. That's cruel,” Fitzgerald said. The Clackamas County Sheriff's Office is investigating the shooting because Fitzgerald’s husband filed a report. The Oregon Humane Society can’t confirm if it started, and then stopped, an animal cruelty investigation into Gir’s shooting. But the hardest part of this loss for her is explaining to her children why they can't ride Gir anymore. "He was part of our family…There's no way to replace him,” she said. ||||| The family does not accept the deputy's explanation for euthenizing the animal A Molalla husband and wife say they are planning to consult a lawyer after a Clackamas County Sheriff’s deputy shot and killed their 30 year-old American Miniature Horse. Crista and Adam Fitzgerald said the horse, named Gir, had escaped its barn sometime during the early morning hours of Feb. 19 and was found lying in a neighbor’s yard, 150 yards down the road, around 8:30 a.m. Sgt. Nate Thompson, a sheriff’s office spokesman, said the deputy who was dispatched to the scene believed the horse had been hit by a car and was suffering from broken hind legs. He said the deputy did not shoot the horse until after consulting a veteranarian, the deputy’s supervisor and the Oregon Humane Society, a process that took hours. “What happened is this — we were called out there by a citizen who was calling about a severely distressed horse that the caller believed had been hit by a car,” Thompson said Wednesday, March 4. “The caller, who was the property owner, said the horse was found in the front yard, but they did not know who owned the horse and had never seen the horse before.” Thompson said the horse was unable to get to its feet the entire time the deputy was there, which was for more than an hour. Both the person who found the horse and the deputy believed it had been hit by a car because of the stress the horse was suffering. “We called a vet and also the Humane Society and drew on resources to find out what to do with this animal,” Thompson said. “The animal had been in severe distress for hours, so they decided to euthenize it in the most humane way available, and it’s something we normally do.” Crista Fitzgerald, however, said she didn't believe the family’s horse was hit by a car or that its legs had been broken. The Fitzgeralds sent the horse’s body to Oregon State University's veterinary lab on Feb. 23 for an autopsy. According to the autopsy report, dated Feb. 26, the diagnosis was death by gunshot; severe degenerative joint disease. “This animal was in excellent body condition, indicating that the severe degenerative joint disease ("arthritis") present was not interfering with willingness or ability to eat,” the report states. “The only bone fractures detected were associated with euthanasia by gunshot.” The report states at least two gunshots to the throat area fractured the horse’s jaw and some skull bones. “The trajectory of the bullets (at least two) are not aligned with the commonly accepted path as described by the AVMA (American Veterinary Medical Association) for humane euthenasia by firearm,” the report states. To the Fitzgeralds, the deputy’s explanation for shooting their horse is unacceptable. “It wasn’t that Gir couldn’t stand up, it was probably that he didn’t want to,” Adam Fitzgerald said. ‘He was a stubborn horse. We were late getting out to the barn that day, and he didn’t get his pain medication – he normally got it twice a day, once in the morning and once at the end of the day. So he probably was sore after walking 150 yards. He laid down in the sun, ate some grass and then moved on again to their yard and laid back down.” Fitzgerald said that a local veteranarian was right down the road when the incident took place. “He offered his assistance, and the officer declined several times and said that he would take care of the problem on his own,” Fitzgerald said. “The veterinary office asked if the officer knew how to properly euthanize a horse, and he said yes. Now the Fitzgeralds are trying to raise enough money to hire a lawyer. “People keep calling us, saying you need to get a lawyer,” Adam said. “We are not trying for monetary compensation, although that would be nice, but we just want to make sure this won’t happen again.” The family, which owns four other horses, has owned Gir four or five years, and the pony had been passed on from their oldest daughter to their youngest daughter. “My youngest is a shy little girl with social issues,” he said. “But if you ask her about her pony, she will open right up. So it helped her with issues like that.” Fitzgerald said the sheriff’s office has stayed in touch with the family and told him and his wife the case is being investigated. “They haven't told us anything else about what will happen to the officer, or what the outcome will be,” he said. “But I’ve been asked about monetary compensation – what the horse is worth. The Fair Market Value is nothing — he was 30 years old — but that doesn’t take care of the fact he was a well-loved pony, a member of the family. “This whole situation is messed up, and it could have been avoided if the officer had contacted me or my wife,” Fitzgerald said. “I’m in the military, deployed three times to Iraq. I am high enough on the food chain that I send soldiers out, and one of the practices in the military, if there’s any kind of threat in the area, we make sure our troops are ready to handle that situation. So I would expect the police to provide the training needed to handle this kind of situation, especially in an area like Molalla, where there are thousands of horses.” Thompson said following this incident, the Clackamas County Sheriff’s Office has been “looking into this, to see what kinds of things we can do better to take care of these things.” “We are also working to partner with people in the community, and we talked with the owner of the horse about this, to try to develop resources in case deputies come into one of these situations again,” he said. To complicate matters, according to Fitzgerald, the Clackamas County Sheriff Office has received a threat from a Molalla-area man who claims he is an army sniper in retirement since 2009. “He said he would have no problem looking for the neighbor who found the horse and the officer who did the shooting,” Fitzgerald said.

– A beloved elderly pony that escaped from his barn stall and went for a stroll one night was shot dead by police for no good reason, according to a furious family in Oregon. A neighbor called police after she found Gir, a 30-year-old American Miniature Horse, lying in her yard in Clackamas County last month. Police say a deputy fatally shot the horse after deciding it had been hit by a car, had two broken legs, and was unable to stand, according to KATU—but owners Crista and Adam Fitzgerald sent it to a veterinary lab for a second opinion and discovered it was in good health apart from arthritis and didn't have any broken bones. "It wasn't that Gir couldn't stand up, it was probably that he didn't want to," Adam Fitzgerald tells the Portland Tribune. "He was a stubborn horse. We were late getting out to the barn that day, and he didn't get his pain medication." Police say the deputy called his supervisor and a veterinarian before deciding to euthanize the horse, but the vet tells KATU that the officer rejected his offer of assistance and said he would "take care of the problem on his own." Authorities also say the deputy called the humane society first, but the Oregon Humane Society says it never got a call. "This whole situation is messed up," Fitzgerald tells the Tribune, saying that since there are thousands of horses in the area, police should have more training in handling these situations. Gir, he says, "was a well-loved pony, a member of the family," and had been passed down from his older daughter to his younger daughter. Thursday, the county sheriff apologized to the family, admitted a mistake had been made, and said his office is "exploring ways to make this as right as we can," KOMO reports. (These cops, on the other hand, saved a dog that had been shot and tied to railroad tracks.)

this is particularly true during early childhood as oral health can influence overall health and well - being . keeping primary teeth healthy is essential as those who suffer from caries in their preschool years are more likely to experience caries throughout childhood and adolescence [ 2 , 3 ] . early childhood caries ( ecc ) is decay affecting the primary dentition of children < 72 months of age [ 4 , 5 ] . several groups have been found to be at a high risk for ecc including first nations and aboriginal children , refugees and newcomers , and those experiencing poverty [ 69 ] . prevalence rates for ecc in several distinct canadian pediatric populations have been reported with most groups exhibiting rates above 40% . for instance , urban and on - reserve first nations and aboriginal children are reported to have high rates , sometimes reaching 8090% of the population with many meeting the definition of severe early childhood caries ( s - ecc ) , a more rampant form of ecc [ 810 ] . meanwhile nearly 40% of rural hutterite children other groups in canada such as vietnamese children , immigrants from south asia , and portuguese - speaking immigrants have been reported to experience ecc [ 1214 ] . however , still very little is known about the oral health of newcomers , although anecdotal conversations with practitioners would suggest a high level of dental needs . there is a growing realization that newcomers are at increased risk for caries as the american academy of pediatric dentistry ( aapd ) has included a question on immigrant status in their caries - risk assessment tool ( cat ) . one - size - fits - all approaches and strategies that have worked with the general population often have little impact on reducing the incidence of ecc in high - risk populations and may not be effective with distinct cultural groups . even if it were possible to reach all high - risk children and provide them with tailored programming , the desired behavioural change may not take place ( despite the increase in knowledge offered by traditional oral health approaches ) . differing practices and views on oral health , which may be related to cultural diversity , may contribute to increased caries risk . many aspects of cultural diversity can influence oral hygiene routines , diet , health beliefs , reaction to pain , and access to care , factors which may in turn affect oral health status [ 17 , 18 ] . if a person belongs to a cultural group that does not define poor oral health as abnormal , they may lack both information about oral health and access to care and may not comply with professional recommendations for treatment [ 18 , 19 ] . there is a growing realization that qualitative research methods are useful in identifying how knowledge and ideas develop and operate within a given cultural context . overall , there is limited qualitative research on the topic of ecc and the promotion of early childhood oral health ( ecoh ) among cultural minority groups in north america [ 21 , 22 ] . there is a growing realization that qualitative research methods may be helpful to uncover family and cultural issues that influence infant and preschool oral health . having an appreciation of different cultural views may allow for focused outreach and promotion activities [ 23 , 24 ] . while known barriers to good oral health include a lack of funds to seek dental care ( especially with newcomer populations ) , the effect of knowledge and beliefs on child oral health is less well understood . parental and caregiver lack of knowledge of and negative attitude towards preschool oral health have been found to be associated with increased caries experience in their young children . the purpose of this pilot study was to examine the knowledge and beliefs of parents and caregivers from four different cultural groups with respect to ecoh and ecc . the ultimate goal was to use these findings to assist in tailoring ongoing promotional activities to improve ecoh and prevent ecc . a qualitative study design using focus groups was chosen to explore parent and caregiver views on ecoh and ecc from four different cultural groups . this pilot study was undertaken by the healthy smile happy child ( hshc ) partnership that has been promoting ecoh in manitoba , canada , since 2000 . the partnership adopted and maintains a community engagement approach to address ecc and has been guided by three pillars : community development , health promotion and education and evaluation [ 2628 ] . focus groups were selected as health promotion programs can often be strengthened through participatory planning approaches that allow participants to voice their experiences and opinions . the project team recognized the value of focus groups and the different findings that can be obtained using such an approach . four pilot focus groups involving parents and caregivers of children < 6 years of age were held . each focus group involved a different cultural group and was held in southern manitoba , canada . a nonprobabilistic approach to recruitment using a convenience sample of participants was selected . the four groups included parents and caregivers from an urban aboriginal community , a rural hutterite colony in southwest manitoba , a refugee group in the city of winnipeg , and an urban group of recent newcomer immigrants to the city of winnipeg , manitoba . these four distinct groups were selected as children from these communities often experience a higher burden of ecc than the mainstream population . aboriginal participants were recruited through an aboriginal head start program and an organization providing culturally relevant preventive and supportive programming to families . hutterite participants were recruited with the help of a teacher and research assistant who was a member of a hutterite colony and who had an existing working relationship with the department of pediatrics and child health at the university of manitoba . the hutterite live on colonies and are a communal branch of anabaptists ( like the amish and mennonites ) . finally , the newcomer focus group participants were recruited from an english - as - an - additional - language ( eal ) program in winnipeg , canada . participants were landed immigrants , who had an english benchmark of at least four and who had been in canada for at least one year . the team facilitating the focus groups included a qualitative research consultant and a hshc staff member . the study was approved by the university of manitoba health research ethics board and followed established community research protocols . the research team made notes on a flipchart during the discussions while the hshc team member took additional notes . participants were invited to review the notes and to correct , delete , or add to any inaccurate or inadequate representations of their comments . participants in the urban focus groups were provided with bus tickets and all participants received a small honorarium . focus group discussions followed a sequence of guiding questions from a semistructured tool developed by the hshc partnership as follows . if i said that someone 's child had healthy teeth , what would that mean to you?is it important for kids to have healthy teeth in your culture?what do you think makes very young kids get cavities or decay in their baby teeth?do you think whether or not a child 's baby teeth are healthy makes any difference to their overall health ? if yes , ask how or in what ways.where did you learn how to take care of your babies ' or young children 's teeth?has anyone ever learned about dental care for babies or very young kids at any of the programs they attend?has anyone read any pamphlets or brochures about dental health for babies or young kids?what do you think is the best way to get information out to parents and families about dental health for babies or young kids?how do you take care of your babies ' or young children 's teeth?are there any specific practices that your culture does to keep children 's teeth healthy?what helps you keep your babies ' or young children 's teeth healthy?are there any things that make it hard for you to take care of your babies ' or young children 's teeth?does anyone here have children who have had problems with their teeth?what kinds of problems did they have?what did you do about it?does anyone here know any kids who have had dental surgery ? if yes , ask what that was like for the kids and the families.is there one thing that somebody ( anybody government , health workers , family members , the people in this room , or anyone else you can think of ) could do to help parents and caregivers take care of young children 's teeth ? what would it be?is there anything else that you would like to tell me about what we talked about today ? if i said that someone 's child had healthy teeth , what would that mean to you ? is it important for kids to have healthy teeth in your culture?what do you think makes very young kids get cavities or decay in their baby teeth ? what do you think makes very young kids get cavities or decay in their baby teeth ? do you think whether or not a child 's baby teeth are healthy makes any difference to their overall health ? if yes , ask how or in what ways . where did you learn how to take care of your babies ' or young children 's teeth has anyone ever learned about dental care for babies or very young kids at any of the programs they attend?has anyone read any pamphlets or brochures about dental health for babies or young kids?what do you think is the best way to get information out to parents and families about dental health for babies or young kids ? has anyone ever learned about dental care for babies or very young kids at any of the programs they attend ? has anyone read any pamphlets or brochures about dental health for babies or young kids ? what do you think is the best way to get information out to parents and families about dental health for babies or young kids ? are there any specific practices that your culture does to keep children 's teeth healthy?what helps you keep your babies ' or young children 's teeth healthy?are there any things that make it hard for you to take care of your babies ' or young children 's teeth ? are there any specific practices that your culture does to keep children 's teeth healthy ? what helps you keep your babies ' or young children 's teeth healthy ? are there any things that make it hard for you to take care of your babies ' or young children 's teeth ? what kinds of problems did they have?what did you do about it?does anyone here know any kids who have had dental surgery ? if yes , ask what that was like for the kids and the families . what kinds of problems did they have ? is there one thing that somebody ( anybody government , health workers , family members , the people in this room , or anyone else you can think of ) could do to help parents and caregivers take care of young children 's teeth ? is there anything else that you would like to tell me about what we talked about today ? questions of particular interest included what good oral health means for their child , their experiences with dental problems like ecc , and how they learned to care for their children 's teeth . another area of interest was whether there were any practices unique to their cultures relating to caring for young children 's teeth . additional probing questions were used as needed to elicit specific details or clarification . notes and recordings from each focus group were transcribed verbatim and analyzed independently using thematic analysis by two members of the team . when analyzing the data , transcripts from each of the participant groups were examined independently , drawing out participants ' responses to the overarching research questions . themes that emerged in each cultural group were reported separately so that findings would be more practical to inform existing and future oral health promotion and research activities . a total of 40 parents and caregivers participated in this pilot study , including nine in the aboriginal focus group and 14 in the hutterite focus group . eight were residents of the community where the focus group was held while the additional six resided at a different colony . participants originated from countries in africa , the middle east , and western asia including chad , congo , ethiopia , iraq , morocco , nigeria , and somalia . six people participated in the immigrant focus group and were from africa and western asia including congo , eritrea , nigeria , and sudan . aboriginal participants described healthy teeth as being clean , free from decay , and not falling out . participants referred to a link between oral health and temperament , stating thatif they have a toothache , they 're going to be all upset and miserable , crying , in pain and if they have a cavity , then they 're going to be crabby . if they have a toothache , they 're going to be all upset and miserable , crying , in pain and if they have a cavity , then they 're going to be crabby . if they have healthy teeth , they wo n't be grouchy . however , another participant felt that baby teeth are of little value as they are going to fall out anyway . one was a mother 's diet during pregnancy and the other was the use of bottles and bottle - feeding . one participant expressed,everything you eat when you 're pregnant , everything that goes in your mouth , your baby gets it everything you eat when you 're pregnant , everything that goes in your mouth , your baby gets it some participants believed that giving children a bottle at bedtime or naptime causes caries . while several participants had heard this before , a few stated that they did not believe this to be true . participants generally learned how to care for their children 's teeth from their mothers , grandparents , and friends . one participant described how her grandparents tought her to use a facecloth and infant toothbrush to clean her babies ' gums and teeth . another indicated that she learned about using infant toothbrushes and toothpaste and the importance of antenatal oral health by attending a community - based healthy baby program . this included uncooperative children , the cost and inability to purchase oral hygiene supplies , and lack of time . one participant expressed , it 's hard with my kids to get them to brush their teeth . some caregivers indicated that they had little difficulty in getting their child to cooperate in brushing , though one parent noted that despite this her child still developed caries in her front teeth . three participants in the aboriginal group had at least one child or family member who had experienced s - ecc and underwent dental surgery under general anesthesia ( ga ) . one stated that her child 's teeth had rotted before she reached the age of two because she did not have enough enamel and had surgery to remove these teeth . the mother of a three - year - old described the surgery experience as awful . another stated that her niece had all her teeth removed when she was four years old.her teeth rotted really quickly . by the time she was three years old , her top and her bottom was just black , like on posters you see of tooth decay . her teeth rotted really quickly . by the time she was three years old , her top and her bottom was just black , like on posters you see of tooth decay . many of the parents indicated that they had difficulty in getting their children to see the dentist . for some , it was because they had been scared or hurt during previous dental encounters or feared needles . unfortunately , one mother admitted that her son has five cavities right now because he wo n't go to the dentist . this fear of the dentist led two parents to agree that it might be better if the dentist were to simply use a gas to just knock [ their children ] out . aboriginal participants shared information about traditional medicines and practices such as the use of herbal and traditional medicines when babies have rotten teeth . one had taken her child to a traditional healer because of the way the gums looked and had informed the dentist of this . however , participants suggested that before incorporating any traditional knowledge or medicines into programming and prevention activities , it is important to first seek permission from an elder to share knowledge and teachings . sharing information on a one - to - one basis and making use of existing parental networks were described by participants as effective ways to promote ecoh within the urban aboriginal community . it was suggested that front - line workers , such as public health nurses and dentists , begin making home visits . talk to children in school about taking care of teeth and the [ traditional ] medicines . hutterite participants identified four factors they believed influenced oral health : oral hygiene , intake of junk food , use of fluoride , and genetics . some participants felt that brushing and rinsing may be more important than a child 's intake of candy and treats.you can have a kid who does not eat candy and does not brush or a kid who eats lots of candy and brushes and the kid who eats a lot of candy will be better off . you can have a kid who does not eat candy and does not brush or a kid who eats lots of candy and brushes and the kid who eats a lot of candy will be better off . participants were not aware of colonies that fluoridate their drinking water , but noted that fluoride does occur naturally in the water of some colonies . other colonies use water that has been treated by reverse osmosis to remove minerals and one participant wondered whether or not this might affect oral health as it removes fluoride from the water . one mother pointed out that even in colonies where parents are making quite a bit of an effort to care for children 's teeth , a lot of kids have to fill their teeth . another stated that , while they did not remember ever brushing their teeth as children , they never had cavities and wondered if this might be due to genetics . it was noted that , on several occasions , the children 's temperaments hindered oral hygiene . specifically , children were often too tired , grumpy , or simply unwilling to brush their teeth . parents and caregivers also expressed difficulty in making the time to help or encourage their children to brush their teeth due to their own fatigue . i never give her candy , but she gets it from everybody else ! one caregiver acknowledged that she only cleans her children 's teeth once a day , even though she knows it is recommended to wipe the teeth after each feeding . her attempt to reduce the risk of decay was to give her baby water to drink , a practice that other parents in the group seemed to share . as one parent pointed out , it is important to clean babies ' mouths because there are something like 8 or 9 [ sugar ] cubes per cup of breast milk , only slightly less than juice . participants admitted that it can be painful and traumatic for children when they have cavities , which can affect their quality of life : if [ children ] have bad teeth , how can they eat ? one participant 's four - year - old daughter had been complaining of a toothache so she took her to a dentist who found a whole mouth full of problems . she needed five teeth filled and another two removed.i never want to go through it again seeing her in all this pain and you can not do anything at all . seeing her going into the operating room , they 're going to put her to sleep and what if she never wakes up ? and all of those things i never want to go through it again seeing her in all this pain and you can not do anything at all . seeing her going into the operating room , they 're going to put her to sleep and what if she never wakes up ? and all of those things those who had learned about oral health through presentations in their communities were willing to share information with other family members . for instance , one passed along information to family members that you should not give a bottle to a child over one year of age . while participants felt empowered to share with family and friends , they indicated that they might feel uncomfortable about sharing information with others whom they did not know well . participant 1 : i would n't dream of , if i see someone giving a baby a bottle , a two - year old , saying , do you know that 's not healthy ? participant 2 : of course not . participant 1 : if i know them but not if i did not know them . participant 3 : i might if i knew them a little say do you know that this could cause this or that . participant 2 : but it 's always better if they get it from somebody higher up . participant 1 : i would n't dream of , if i see someone giving a baby a bottle , a two - year old , saying , do you know that 's not healthy ? participant 2 : of course not . participant 1 : if i know them but not if i did not know them . participant 3 : i might if i knew them a little say do you know that this could cause this or that . participant 2 : but it 's always better if they get it from somebody higher up . participant 1 : like at a meeting or a workshop . participant 4 : that 's non - confrontational . they appeared to value a personal , one - to - one connection style of learning . nothing propels you more to try to help your child than to see the results of non - caring , like pictures of decayed teeth . however , they did say that if language is too high tech , nobody 's going to read it . the community kitchen seems to be an established area for information sharing in hutterite colonies . they recommended strategies like a parenting blog , forum , or an email list serve or contact list as ways to disseminate information . caregivers from this colony also indicated that public health nurses could take a more active role in providing information . those in the immigrant group felt that good oral health meant the absence of swelling , pain , and broken teeth . if the first set of teeth starts bad then that will transfer to new [ adult ] teeth . some in the refugee group felt that the health of baby teeth is important and explained that there is a relationship between overall health and healthy teeth . two refugee participants believed that genetic factors play a role in the process of decay , with one referring to the high occurrence of bad teeth in her family . the consumption of sweets , lack of oral hygiene , and the use of bottles were also identified as contributing factors in caries development . participants also mentioned the inability to control their children 's intake of sweets at school , which makes it difficult for them to care for their children 's teeth . milk and dairy products were identified as good choices for children due to their calcium content . one mother from the immigrant group shared how she managed to curb her daughter 's intake of sweets : sometimes you need to scare them . my daughter likes chocolate and sugar . when she has cereal , i give her a little sugar but she wants more . i tell her that if i give her more sugar , when i take her to the dentist , he 'll remove all her teeth now , sometimes she says do not put sugar ! sometimes you need to scare them . my daughter likes chocolate and sugar . when she has cereal , i give her a little sugar but she wants more . i tell her that if i give her more sugar , when i take her to the dentist , he 'll remove all her teeth now , sometimes she says do not put sugar ! immigrant participants believed that regular visits to the dentist or doctor were important practices . however , those in the refugee group did not necessarily share this view , as one participant stated that children do not need to go to the dentist unless they are experiencing dental problems . one immigrant mother mentioned how the dentist recommended that she give her daughter a cup rather than a bottle as her daughter 's teeth had turned black . other participants agreed that children should start using a cup at an early age instead of bottles . they described cleaning their babies ' gums and tongue using a cloth , warm water and salt , baking soda , glycerin , or cotton wool . the majority of participants indicated they had first learned about oral health care from family members and friends and later from medical practitioners in their home countries . children of participants from the immigrant focus group were reported to have had few dental problems . the mother described her experience:[the ] family doctor , when my child 's tooth was a little black , he told me to go to dentist and gave address but no other information . he said to brush all the time and i do not have to feed her by the bottle . so i have to feed her by the cup and you have to clean always her teeth . [ the ] family doctor , when my child 's tooth was a little black , he told me to go to dentist and gave address but no other information . he said to brush all the time and i do not have to feed her by the bottle . so i have to feed her by the cup and you have to clean always her teeth . participants in both groups spoke about the practice of using a twig from a specific tree to clean teeth , stating that it has the additional benefit of being natural and chemical - free . sewak and reported that the plant has lots of benefits for your teeth . the twig is reportedly very effective : sometimes a brush wo n't get everything , but that one will take everything off . as one participant stated , it 's part of the obligation . as part of islam there is a saying from our prophet that if i would have told any human being that these are the obligations that you must do , i would have encouraged them to clean their teeth five times a day . there is a saying from our prophet that if i would have told any human being that these are the obligations that you must do , i would have encouraged them to clean their teeth five times a day . participants suggested that oral health promotion activities could be delivered through existing programs , classes , daycares , schools , and organizations in which parents are already involved ( such as eal classes or programs for moms and tots).that 's a good reason to use community centres they can bring parents out , tell them what you want to say , what they need to do . for people who do not understand the language that 's a good reason to use community centres they can bring parents out , tell them what you want to say , what they need to do . for people who do not understand the language , it 's better for them to see it with their eyes . some indicated that they would appreciate getting information from a healthcare provider with experience and knowledge whom they could easily trust . there was general agreement that some refugee caregivers might prefer someone who is like them or who knows their language . the purpose of this pilot study was to gain an initial understanding of views on ecoh that may assist in shaping effective and appropriate culturally proficient promotional activities and materials targeting specific communities within an increasing diverse population . even though the intent of these pilot focus groups was not to contrast findings between the different cultural groupings , it was interesting that there were some differences and apparent similarities . for instance , when asked what contributes to caries in young children , participants in the aboriginal group identified bottles and bottle - feeding along with prenatal diet as being important while hutterite participants identified a lack of fluoride in the drinking water , junk food , and genetics . meanwhile , newcomer participants mentioned sweets , a lack of oral hygiene , and genetics . one apparent similarity between some of the groups related to barriers to regularly cleaning their children 's teeth was seen as both participants in the aboriginal and hutterite groups mentioned a lack of time as well as their children 's temperament and uncooperativeness . with regard to promoting ecoh each group mentioned the importance of reaching parents and making personal connections but offered unique suggestions ranging from including aboriginal elders to share traditional knowledge , the use of workshops and health - education materials with the hutterites , and using laypeople in newcomer communities to including oral health messages in existing programs providing assistance to these families . each focus group yielded useful suggestions on how to possibly promote oral health and engage members of their cultural community . two specific issues were identified , namely , seeking permission from an elder to incorporate traditional medicine or knowledge into programming and the elder 's actual role in information sharing . these findings are consistent with those of a study examining cultural factors affecting children 's oral health , which found that elders and their wisdom were highly respected . they discussed concerns of passing on information to strangers and the importance of using a nonjudgmental approach as some felt guilty that their child required dental surgery . they felt that appropriate methods included the use of pamphlets , posters , and e - mail updates . this resembles a health - education model rather than health promotion and community development approaches and is not recommended for groups with low literacy levels , language barriers , or limited access to computers . hutterite communities have a unique lifestyle as they live communally with community ownership of most goods . communal living allows for less control over some aspects of living as compared to other groups , as is evident with shared meals , dress , and lack of individual finances . this lifestyle may impact their access to oral hygiene supplies and dental care . as decision - making occurs at the community elder level it is important to note that women in hutterite culture play a key role in making decisions about health [ 11 , 30 ] . we previously reported that hutterite mothers had a highly accurate view of their children 's oral health . both hutterite and refugee participants believed that genetics play a role in ecc development . while there is a proven increase in dental agenesis in the hutterite population , presently there is no literature to substantiate a genetic predisposition to caries with this group . this belief is likely based on the fact that some genetically associated diseases , such as muscular dystrophy and cystic fibrosis , are more prevalent in or exclusive to the hutterite population [ 32 , 33 ] . some genetic conditions do affect enamel and dentin formation , which can decrease host resistance to caries ( e.g. amelogenesis imperfecta ) . however , there is now emerging evidence supporting a genetic predisposition to caries in some populations [ 3436 ] . the belief that hereditary factors contribute to caries is not exclusive to our study , as these views were also held by latino immigrant caregivers in another investigation . regardless of the role that genetics play , it is important to increase parental awareness of the numerous factors involved in caries development so that they can minimize their children 's caries risk . interestingly , some participants in the aboriginal group did not believe that putting children to sleep with a bottle could cause caries . other reports have suggested that some parents may not understand this and may routinely give their infants and toddlers bottles at bedtime [ 23 , 37 ] . in a recent qualitative study , nurses reported that parents often do not associate bottle - feeding with caries . our findings also suggest that there may be some misconceptions about general infant feeding that require clarification . for instance , participants from the hutterite group stated that breast milk is high in sugar . while breast milk does contain a certain amount of natural sugar , breast milk itself is not cariogenic . a recent review suggests that there is inconclusive evidence to support a relationship between breastfeeding and ecc . however , while some studies have reported that breastfeeding may be protective against caries other studies have reported that prolonged breastfeeding and nocturnal breastfeeding may increase the risk . the canadian dental association 's recent position statement on breastfeeding supports this practice but emphasizes the importance of regular oral hygiene once primary teeth begin to erupt . therefore , it may be important to involve parents and grandparents in oral health promotion activities to equip them with essential oral - health - related information that they can then pass on to younger generations . a move towards family - centred care ( which encourages the involvement of all members of a patient 's circle , both familial and social ) would assist in meeting the needs of this group . in our study this was surprising , as the group identified public health nurses as a possible messenger of oral health information . immigrant participants possessed a good level of understanding about ecoh and few had children who developed ecc . healthy immigrant effect , which suggests that the healthiest are more likely to migrate and be granted residence in another country . participants in this focus group held differing opinions about who should deliver information to members of their community . while some felt that professionals would be best as they trust them , others believed that lay workers in the community would be better suited to promote ecoh . for instance , participants from each group identified that the difficulty in cleaning their children 's teeth and limiting sugar intake were challenges to keeping their children 's mouths healthy . similar findings were also reported in a recent study involving african newcomers to canada as they expressed concern over their inability to keep their children from eating sugar and candies and fighting with their children to brush their teeth . refugee participants believed that few of their children had dental issues and suggested that children really only need to visit the dentist when they experience a dental problem or toothache . similarly , another report has suggested that the perceived need for dental care may be low among african newcomers as they mainly rely on their own assessments , toothaches , and advanced signs of caries to indicate the need for dental care rather than the established early warning signs of ecc . additional evidence supports these findings , as certain groups have been found to seek dental care only after their children begin to experience pain . seeking preventive dental care may not be the cultural norm [ 21 , 46 ] . however , focus groups with a similar population of canadian newcomers have suggested that oral hygiene may not be a priority , as they believe that oral health is ultimately dictated by god 's will . perhaps the involvement of religious institutions and leaders may be a worthwhile avenue to explore for continuing work with this population . language is key to effective and safe communication and therefore must play a critical role if ecoh is to be effectively tailored to specific populations . participants suggested that using individuals from their own cultural group to deliver oral health messages would be effective . language barriers have a larger influence on how one successfully interacts with the health care system than cultural beliefs . language is affected by cultural and historical context and is often about sharing and validating realities . given the obvious language barriers that exist for newcomer populations , participants in the immigrant and refugee groups also suggested that providing visual information and resources may be useful in sharing key messages about ecoh . as rates of immigration continue to grow , cultural groups are less likely to have access to health professionals who share the same beliefs and understandings of health and disease , language , and experiences . linguistically appropriate care can be achieved when a provider shares an understanding of the experiences of the community . perhaps the use of interpreters at dental care appointments can help to pass along oral health messages . this service exists in some community - based dental programs in the winnipeg region . for practitioners to provide culturally responsive care they require awareness of cultural beliefs and practices while recognizing that care still needs to be provided based on an assessment of the individual . health promotion workers should continue to learn about distinct cultural groups while recognizing that communication and individual beliefs will still have an impact on knowledge acquisition and behavioural change . this approach will help shape health promotion activities and develop prevention strategies targeted to unique at - risk groups . if we are going to reduce the impact of ecc on these groups , we must ensure that preventive strategies are adapted as necessary and incorporate their suggestions . due to our sampling approach , the findings are not generalizable to the entire communities participating in our study as these findings may not be reliable and reproducible if more representative samples were recruited . further , those agreeing to participate may have been those with a greater appreciation and awareness of oral health . participation was not restricted to only parents and caregivers of children who were affected by ecc , which may have resulted in an overrepresentation of those whose children were actually in good dental health . the small numbers of participants and the pilot nature of this work also prohibit comparisons between groups . language issues proved to be a large hurdle in the focus group process , as several participants spoke english as an additional language . this was particularly evident in both focus groups with parents and caregivers who were refugees or other immigrants . while all individuals in the immigrant focus group spoke english well , the majority of participants in the refugee group had limited english skills and relied on other participants to translate for them . the reliance on these individuals as translators constituted another source of error , as the information obtained by researchers was , in a sense , passed through an intermediate party which had interpretive control . the interpreters had control over what they communicated as the content and meaning of their language peers ' responses . while the immigrant and refugee focus groups were somewhat heterogeneous in terms of country of origin , it can be argued that all participants in each respective group shared similarity as they self - identified as being either an immigrant or refugee . participants in this study may have already had some understanding of ecc through exposure to the hshc initiative or other resources . regardless , the information obtained during these focus group sessions is extremely valuable and provides useful insight into the best ways to promote ecoh amongst these at - risk populations . the hshc partnership understands that meaningful community development requires that attention be paid to cultural proficiency for meaningful community engagement , the development of interventions , oral health promotion , and health education . culturally and linguistically proficient approaches must be developed for at - risk communities if they are to fully participate in prevention and promotional activities . developing culturally proficient and therefore relevant approaches to oral health promotion and caries prevention requires an understanding of diversity . cultural proficiency can be enhanced by increasing awareness of the views and beliefs of cultural groups . this pilot work will certainly help to inform our further qualitative and quantitative research and outreach activities with these different groups , especially immigrants and refugees to manitoba , canada . there is a growing need for further qualitative investigation with larger samples of parents , especially those whose children have experienced ecc , to gain their perspectives . this would also assist in the development of questions for use in survey instruments and caries - risk assessment tools for these cultural groups . since little is known about the true oral health status of refugee and immigrant newcomers to manitoba , baseline studies on the prevalence of ecc and associated risk factors are warranted . at the present time we are using these findings to assist us in developing pictorial - based ecoh promotion materials for newcomer populations these pilot focus group sessions were useful in identifying potential barriers to ecoh , sources of oral - health information , oral health - related misconceptions , and how to best reach each community with ecoh messages . caregivers identified several barriers to maintaining ideal early childhood oral health including the child 's temperament , finances , and inability to control sugar intake . however , both religion and genetics were found to influence the perception of oral health in some groups . misconceptions regarding breast milk and bottle use were present . while participants from the refugee group believed that dental visits were only necessary if dental pain or problems were experienced . one - on - one discussions , use of parental networks , and the use of laypeople from similar cultural backgrounds were suggested as ways to promote oral health . the immigrant and refugee group placed emphasis on the use of visuals for those with language barriers while the hutterite participants recommended a more traditional health - education focused approach . the findings from this paper have provided some initial insight into the oral - health - related knowledge and beliefs of these high - risk cultural groups . these insights will help to inform planning of ecc prevention and research strategies , which can be tailored to specific populations .

objectives . several groups in manitoba , canada , experience early childhood caries ( ecc ) , including aboriginal , immigrant , and refugee children and those from select rural regions . the purpose of this pilot study was to explore the views of parents and caregivers from four cultural groups on early childhood oral health and ecc . methods . a qualitative descriptive study design using focus groups recruited parents and caregivers from four cultural groups . discussions were documented , audio - recorded , transcribed , and then analyzed for content based on themes . results . parents and caregivers identified several potential barriers to good oral health practice , including child 's temperament , finances , and inability to control sugar intake . both religion and genetics were found to influence perceptions of oral health . misconceptions regarding breastfeeding and bottle use were present . one - on - one discussions , parental networks , and using laypeople from similar backgrounds were suggested methods to promote oral health . the immigrant and refugee participants placed emphasis on the use of visuals for those with language barriers while hutterite participants suggested a health - education approach . conclusions . these pilot study findings provide initial insight into the oral health - related knowledge and beliefs of these groups . this will help to inform planning of ecc prevention and research strategies , which can be tailored to specific populations .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Empowering Our Local Communities Act of 2007''. SEC. 2. CERTAIN KILLINGS BY ILLEGAL ALIENS. (a) In General.--Chapter 51 of title 18, United States Code, is amended by adding at the end the following: ``Sec. 1123. Certain killings by illegal aliens ``Whoever, being an alien who is unlawfully present in the United States, commits manslaughter while under the influence of alcohol and while operating a motor vehicle, which has been shipped, transported or traveled in or affecting interstate or foreign commerce, shall be subject to a fine under this title and imprisoned not less than 5 nor more than 40 years.''. (b) Clerical Amendment.--The table of sections at the beginning of chapter 51 of title 18, United States Code, is amended by adding at the end the following new item: ``1123. Certain killings by illegal aliens.''. SEC. 3. IMPROPER ENTRY BY, OR PRESENCE OF, ALIENS. Section 275 of the Immigration and Nationality Act (8 U.S.C. 1325) is amended-- (1) in the section heading, by inserting ``unlawful presence;'' after ``improper time or place;''; (2) in subsection (a)-- (A) by striking ``Any alien'' and inserting ``Except as provided in subsection (b), any alien''; (B) by striking ``or'' before (3); and (C) by inserting after ``concealment of a material fact,'' the following: ``or (4) is otherwise present in the United States in violation of the immigration laws or the regulations prescribed thereunder,''. SEC. 4. INSTITUTIONAL REMOVAL PROGRAM (IRP). (a) Continuation and Expansion.-- (1) In general.--The Department of Homeland Security shall continue to operate and implement the program known as the Institutional Removal Program (IRP) which-- (A) identifies removable criminal aliens in Federal and State correctional facilities; (B) ensures such aliens are not released into the community; and (C) removes such aliens from the United States after the completion of their sentences. (2) Expansion.--The institutional removal program shall be extended to all States. Any State that receives Federal funds for the incarceration of criminal aliens shall-- (A) cooperate with officials of the institutional removal program; (B) expeditiously and systematically identify criminal aliens in its prison and jail populations; and (C) promptly convey such information to officials of such program as a condition for receiving such funds. (b) Authorization for Detention After Completion of State or Local Prison Sentence.--Law enforcement officers of a State or political subdivision of a State have the authority to-- (1) hold an illegal alien for a period of up to 14 days after the alien has completed the alien's State prison sentence in order to effectuate the transfer of the alien to Federal custody when the alien is removable or not lawfully present in the United States; or (2) issue a detainer that would allow aliens who have served a State prison sentence to be detained by the State prison until personnel from United States Immigration and Customs Enforcement takes the alien into custody, as required by law. (c) Technology Usage.--Technology such as video conferencing shall be used to the maximum extent possible in order to make the Institutional Removal Program (IRP) available in remote locations. Mobile access to Federal databases of aliens, such as IDENT, and live scan technology shall be used to the maximum extent practicable in order to make these resources available to State and local law enforcement agencies in remote locations. (d) Authorization of Appropriations.--There is authorized to be appropriated to carry out the institutional removal program-- (1) $100,000,000 for fiscal year 2008; (2) $115,000,000 for fiscal year 2009; (3) $130,000,000 for fiscal year 2010; (4) $145,000,000 for fiscal year 2011; and (5) $160,000,000 for fiscal year 2012. SEC. 5. TRAINING OF STATE AND LOCAL PERSONNEL PERFORMING IMMIGRATION FUNCTIONS. (a) Authorization of Appropriations.-- (1) In general.--To carry out paragraph (2), there are authorized to be appropriated $40,000,000 for fiscal year 2008, to remain available until September 30, 2009. (2) Use of funds.--From amounts made available under paragraph (1), the Secretary of Homeland Security may reimburse a State or political subdivision for the expenses described in paragraph (4). (3) Eligible recipients.--A State, or a political subdivision of a State, is eligible for reimbursement under paragraph (2) if the State or political subdivision-- (A) has entered into a written agreement described in section 287(g) of the Immigration and Nationality Act (8 U.S.C. 1357(g)) under which certain officers or employees of the State or subdivision may be authorized to perform certain functions of an immigration officer; and (B) desires such officers or employees to receive training from the Department of Homeland Security in relation to such functions. (4) Expenses.--The expenses described in this subsection are actual and necessary expenses incurred by the State or political subdivision in order to permit the training described in paragraph (3)(B) to take place, including expenses such as the following: (A) Costs of travel and transportation to locations where training is provided, including mileage and related allowances for the use of a privately owned automobile. (B) Subsistence consisting of lodging, meals, and other necessary expenses for the personal sustenance and comfort of a person required to travel away from the person's regular post of duty in order to participate in the training. (C) A per diem allowance paid instead of actual expenses for subsistence and fees or tips to porters and stewards. (D) Costs of securing temporary replacements for personnel traveling to, and participating in, the training. (b) Clarification.--Nothing in this Act or any other provision of law shall be construed as making any immigration-related training a requirement for, or prerequisite to, any State or local law enforcement officer exercising that officer's inherent authority to assist in the apprehension, arrest, detention, or transfer to Federal custody of illegal aliens during the normal course of carrying out their law enforcement duties. (c) Report.-- (1) In general.--Not later than 18 months after the date of enactment of this Act, the Secretary of Homeland Security shall submit to the Congress a report describing the usefulness and effectiveness of the program under section 287(g) of the Immigration and Nationality Act (8 U.S.C. 1357(g)). (2) Contents.--The report under paragraph (1) shall address the following: (A) The number of States and political subdivisions of States participating in such program. (B) The number of States and political subdivisions of States that have engaged in discussions with the Department of Homeland Security regarding such program. (C) A description of how useful and effective the program is, including data on apprehensions of aliens who are unlawfully present in the United States. (D) A description of any hardships faced by States and political subdivisions as participants of the program. (E) A description of the steps the Secretary of Homeland Security is taking, and any plan the Secretary has formulated, to encourage the participation of States and political subdivisions in such program.

Empowering Our Local Communities Act of 2007 - Amends the federal criminal code to impose a minimum mandatory prison term of five years and a maximum term of 40 years on any illegal alien who commits manslaughter while operating a motor vehicle under the influence of alcohol. Amends the Immigration and Nationality Act to impose criminal penalties on individuals present in the United States in violation of immigration laws. Requires the Department of Homeland Security to continue to operate and implement the Institutional Removal Program for the identification and removal from the United States of criminal aliens. Requires such program to be extended to all states. Authorizes states to detain criminal aliens after the completion of their prison sentences to effectuate their transfer to federal custody. Authorizes appropriations for the training of state and local government officers or employees to perform certain functions of a federal immigration officer.

describing accurately the thermodynamics and structure of fluids with short ranged inter - particle potentials has been a long standing problem in liquid state theory . various methods have been developed to attack the problem . they can be divided into two categories . one category is based on integral equation theory(iet ) and the other is based on thermodynamic perturbation theory(tpt ) @xcite . methods based on iet take into account correlations between particles and aim at accurate description of structural properties of liquids i.e. , the radial distribution function ( rdf ) , direct correlation function ( dcf ) etc . the iets involve solving the ornztein - zernike equation(oze ) coupled with a closure relation . thermodynamic properties like internal energy and pressure are obtained as integrals of rdf . but inside the two phase region , most of the closures do not have a solution@xcite . apart from this , the iet method suffers from lack of thermodynamic consistency between the energy , virial and compressibility routes . various closure relations were proposed to minimize the inconsistency@xcite . also closures with adjustable parameters have been proposed to enforce thermodynamic consistency by adjusting them . the requirement of consistency makes the computations complicated . despite the improvements , accurate description of thermodynamic and structural properties of simple liquids with narrow potentials is still lacking . in earlier formulations of tpt , the structure and thermodynamic properties of reference system are assumed to be known and the thermodynamic properties of actual system are obtained as a small perturbation over the reference system . the structure of the reference system and the actual system are assumed to be the same . within this approach , it is not possible to go beyond second order term in the perturbation series as they require higher order correlation functions@xcite . zhou@xcite developed a method in which the helmholtz free energy of the system is written as a series over coupling parameter @xmath0 . this method requires derivatives of the radial distribution function ( rdf ) at @xmath1 . zhou calculated the derivatives using finite - difference method and could obtain terms in the perturbation series up to sixth order@xcite . however , as one goes to higher and higher orders , errors due to numerical differentiation creep in and the data sets of derivatives of rdf require additional smoothing to remove fluctuations . so it is difficult to get derivatives of rdf to arbitrary order . on the other hand , for very short - ranged inter - particle potentials , the convergence of the free energy series becomes very slow and requires higher order terms to be evaluated . recently , we addressed the problem in a more fundamental way combining the ideas of iet and tpt . we assumed that the rdf and the dcf of a system can be written as taylor series in coupling parameter @xmath0 at @xmath2 . we showed that the terms in taylor series of both rdf and dcf ( i.e. , their derivatives ) can be obtained by solving a simple set of equations obtained by differentiating the oze and the generalized closure @xmath3 @xmath0 . the formula for free energy given by zhou can be derived within our formalism apart from the rdf and dcf of the actual system . within this approach we obtained dcf , rdf and lvpds for square well ( sw ) fluids of various ranges up to seventh order . by comparing the third , fifth and seventh order versions of our theory , we concluded that the perturbation series for helmholtz free energy has practically converged by seventh order . however , the series for rdf and dcf did nt converge for low densities and low temperatures for narrow square well fluids by seventh order . even though the helmholtz free energy series has converged , we found that there was significant deviation of the obtained lvpd using seventh order tpt from simulation results for narrow sw fluids . the deviation and slow convergence could be because of two reasons : firstly , we neglected the derivatives of bridge function @xmath3 @xmath0 in our calculations and secondly the error in the bridge function we have chosen for calculation . also , in our previous work , we were able to obtain the rdf and dcf inside the spinodal and close to the critical region without any problems of convergence of the iteration scheme even though our numerical scheme is very simple . this raises questions about the existence of the solution to oze inside the spinodal region . according to sarkisov@xcite , solutions to oze exist in the spinodal region also . however , the iet methods available are not convergent in that region . the rdf and dcf in the two - phase region find applications in the density functional theory of fluids @xcite . one example is the calculation of surface tension . this calculation requires the dcf in the two phase region . as the iets does nt have solution in some part of the lvpd , earlier calculations of surface tension were done using an interpolation formula given by ebner @xmath4@xcite to obtain @xmath5 inside the two - phase region . in present paper , we address these issues using a generalized version of our method with application to sw fluids . we use the bridge function proposed by sarkisov@xcite with slight modification for sw fluids@xcite and include its derivatives @xmath3 @xmath0 in the calculation . we obtain rdfs , isotherms and lvpds for sw fluids of various ranges and compare with those obtained from iet and simulations . we also calculate the surface tension for sw fluids of ranges @xmath6 , @xmath7 and @xmath8 using the expression obtained from the square gradient functional for helmholtz free energy and compare with simulation results . as an application of our theory to non - hard sphere reference systems , we apply it to lennard - jones ( lj ) fluid . we use the sarkisov bridge function for both reference system and perturbation part . the rdfs , isotherms and lvpd for lj fluid are obtained and compared with those obtained from iet and simulations wherever available . the paper is organized as follows . in section ii we discuss the method briefly . in section iii we apply the theory to sw fluids to lj fluids and the results are analyzed . the paper is concluded in section iv . basic theory is the same as explained in reference[12 ] except for a generalization to include derivatives of bridge function in the calculation . consider a fictitious system at temperature @xmath9 and density @xmath10 with interaction potential @xmath11 given by @xmath12 @xmath0 is a coupling parameter . when @xmath2 , the fictitious system becomes reference system with interaction potential @xmath13 . a non - zero @xmath0 will add a perturbation to @xmath13 as shown in the above equation . @xmath14 corresponds to the potential of the system under consideration . we postulated that the rdf and dcf of the system with potential @xmath15 can be written as a mclaurin series in @xmath0 , that is , @xmath16 @xmath17 hereafter we shall denote @xmath18 partial derivative of any function @xmath19 @xmath20 as @xmath21 . the radial distribution function can be written as @xmath22 where @xmath23 is the indirect correlation function defined as @xmath24 and @xmath25 is the total correlation function of the fictitious fluid . @xmath26 is called the potential of mean force . the expression for @xmath27 in eq.([gg ] ) is exact@xcite . @xmath28 called the bridge function @xcite . since @xmath29 , and hence @xmath30 , as well as @xmath31 are expanded in a series in @xmath0 , the correlation function @xmath23 is also a series in @xmath0 . the @xmath18 order coefficient in its series is given by @xmath32 . generally , @xmath33 is chosen as a function of @xmath34 . several approximations to @xmath28 in terms of @xmath23 are available @xcite in literature . the general expression for @xmath18 order derivative of @xmath35 from eq.([gg ] ) is @xmath36\ ; \phi^{(n - m)}(\zeta , r)\ ; g^{(m)}(\zeta , r ) , \ ; n \geq \;1 \label{g - def - n}\ ] ] where @xmath37 $ ] is the binomial coefficient . the derivatives @xmath38 are given by @xmath39 where @xmath40 is the kronecker delta . the derivatives @xmath41 can be computed using eq.([g - def - n ] ) in a recursive manner , using @xmath38 either from initial guess or previous iteration . since @xmath42 its @xmath18 order derivative is @xmath43 to get another set of relations between @xmath44 and @xmath45 , we consider the ornstein zernike equation ( oze ) in fourier space : @xmath46 where @xmath47 and @xmath48 are the fourier transforms of @xmath49 and @xmath50 , respectively . also , structure factor @xmath51 is defined as @xmath52 therefore , using above equation in oze i.e. , eq.([oze ] ) we get @xmath53 now , differentiating eq.([sfac ] ) @xmath54-times , we get @xmath55\ ; \rho\ ; \sum_{m=0}^{(n-1 ) } [ c_m^n]\ ; c^{(n - m)}(\zeta , k)\ ; s^{(m)}(\zeta , k ) , \ ; n \geq 1 \label{sfac - n-1}\ ] ] using eq.([sh ] ) the derivatives of @xmath56 are expressed as @xmath57 thus in order to obtain up to @xmath58 order term in taylor series expansion of both @xmath59 and @xmath60 , @xmath61 coupled linear equations in real - space and @xmath61 coupled linear equations in fourier space have to be solved simultaneously with @xmath2 . for example , to obtain taylor series expansion up to second term , the set of four equations given by @xmath62 have to be solved ( where @xmath63 is @xmath64 ) . the cpe for helmholtz free energy density @xmath65 of a homogeneous fluid at a given temperature @xmath9 is given by @xcite @xmath66 where @xmath67 is the free energy density of the reference system . for notational simplicity we do not show temperature dependence of @xmath65 explicitly hereafter . substituting eq.([g - series ] ) in eq.([f ] ) and integrating over @xmath0 , we get @xmath68 here we have used the shortened notation for the derivatives @xmath69 which is readily obtained as @xmath70 . thus the method provides the dcf , rdf as well as the free energy density . the taylor series of rdf truncated up to second order gives third order cpe for @xmath71 . the numerical procedure we used is as explained in our previous paper@xcite and is not repeated here . eq.([f1 ] ) has been first derived by zhou@xcite in a different way . seventh order version of above mentioned theory is applied to sw fluids . we used the closure proposed by sarkisov with slight modification by mendoub@xcite . @xmath72 where @xmath73 and @xmath74 is the hard sphere diameter . we obtained the rdf and dcf of the reference system using the same bridge function by solving the oze using a similar procedure as explained above to maintain consistency . reduced units ( @xmath75 , where @xmath76 is the well depth and @xmath74 is hard sphere diameter ) are used throughout the paper . for convenience , we denote @xmath77 , @xmath63 by @xmath78 , @xmath79 respectively and @xmath59 , @xmath60 by @xmath5 , @xmath80 respectively . in fig.([1 ] ) we compare @xmath80 obtained using @xmath81 order version of our tpt and that obtained through iet@xcite for sw fluid of range @xmath82 for densities @xmath83 and @xmath84 and temperature @xmath85 . clearly , there is negligible difference between results obtained using present method and those obtained from iet . also , the agreement with simulation results is good . we observed that except for very low temperatures and low densities , results of fifth order and seventh order tpts have negligible deviation showing that the taylor series has converged . convergence of the iteration scheme has been good in the whole phase diagram . @xmath80 obtained by our method for sw fluid of range @xmath6 in the spinodal region at @xmath86 and @xmath87 is shown in fig.([1 ] ) . above observations show that the present method may be viewed as an alternative way of solving the oze . in fig.([2 ] ) we give plots of lvpd for sw fluids of ranges @xmath6 and @xmath7 respectively obtained using seventh order version of tpt with and without including the derivatives of bridge function in the calculations . we used the carnahan - starling(cs ) expression for helmholtz free energy density of the reference system . our results are compared with simulations , those obtained from iet@xcite and our previous results using malijevsky - labik brdige function neglecting the derivatives of bridge function . results of the present calculations are very much improved in the liquid part of the lvpd over those of mendoub @xcite . the main reason for this improvement is the use of the cs expression for free energy density . a comparison of the lvpds obtained by including derivatives of the bridge function in the calculation and those obtained by neglecting them shows that the correction due to the derivatives becomes important close to the critical region and along the liquid side of the phase diagram . neglecting them leads to shifting of the critical point to high density region . in fig.([3 ] ) , pressure isotherms obtained using @xmath88 , @xmath89 and @xmath81 order tpt for sw fluids of extremely short ranges @xmath90 and @xmath91 are plotted for temperatures @xmath92 and @xmath93 respectively . the figures depict that the @xmath88 order results are much closer to the simulation results . however , a comparison of the three versions shows that the series is indeed convergent at each density point . but it is converging to a point away from the simulation results . this is because of the inaccuracy of the bridge function for very short ranged fluids . thus the apparent closeness of the third order tpt results to the simulation results is spurious . possibility of obtaining @xmath5 in two phase region opens up applications in density functional theory(dft ) of liquids . one simple application is calculation of surface tension of liquids . we use the @xmath5 obtained from seventh order version of tpt to obtain surface tension for sw fluids . formula for surface tension is obtained by yang et . @xcite from square - gradient functional for helmholtz free energy of inhomogeneous fluids . a brief derivation is as follows : the square - gradient approximation for helmholtz free energy functional of an inhomogeneous liquid occupying volume @xmath94 at temperature @xmath9 is given by @xmath95 = \int d\vec r\ \ { f(\rho(\vec r ) ) + f_g(\rho(\vec r))|\nabla \rho(\vec r)|^2 \ } \label{sg - f}\ ] ] where @xmath71 is helmholtz free energy density of homogeneous liquid . the second term is the effect of inhomogeneity . @xmath96 is the number density in an infinitesimal volume around @xmath97.@xmath98 $ ] , @xmath99 and @xmath100 are all functions of @xmath9 even though the dependence is not shown explicitly . the coefficient @xmath101 of gradient term also referred as influence parameter is @xmath102 = \frac{1}{12\beta}\int d\vec r ' r'^2 c [ \rho(\vec r ) , r ' ] \label{f - g - rho - vec}\ ] ] we assume that liquid - vapor interface is flat and that @xmath103-axis is normal to the interface pointing out into the vapor from the liquid . in such a case , eq.([sg - f ] ) becomes @xmath104 = a\int dz \ \ { f(\rho(z ) ) + f_g(\rho(z))\left |\frac { d\rho(\vec r)}{dz}\right |^2 \ } \label{sg - f2}\ ] ] where @xmath105 is the surface area . grand free energy of the system is given as @xmath106 = f[\rho(z ) ] - \mu n \label{gp}\ ] ] where @xmath107 is the chemical potential of the system and @xmath61 is the total number of particles minimizing @xmath108 @xmath3 @xmath10 we get @xmath109 = \frac{d\gamma(\rho)}{dz } \label{v}\ ] ] where @xmath110 is the grand free energy density . integrating above eq.([v ] ) with boundary conditions @xmath111 gives @xmath112^{1/2 } \label{drdz}\ ] ] where @xmath113 and @xmath114 are coexisting liquid and vapor densities for temperature @xmath9 under consideration . surface tension @xmath115 can be calculated using the formula @xmath116 using eq.([drdz ] ) in above equation gives @xmath117 ^ 2 \label{s2}\ ] ] in the above equations @xmath118 may be replaced by @xmath119 also as both have same value . above explained formalism is applied to sw fluids of ranges @xmath7 , @xmath120 and @xmath8 with @xmath5 obtained from seventh order tpt as explained above . fig.([4 ] ) shows @xmath121 as a function of @xmath10 for different temperatures for sw fluid of range @xmath6 . from fig.([4 ] ) it can be seen that @xmath121 becomes negative at high densities which is unphysical . this might be an artifact of the approximate bridge function used . however , within the binodal , where @xmath101 is required for the calculation of surface tension(s ) , it is positive . surface tensions obtained from our calculation are plotted as a function of @xmath9 in fig.([5 ] ) . our results compare well with simulations except close to the critical temperatures . the theoretical formalism explained in section ii is general and can be applied to non - hard sphere reference systems also . as an example , we applied the theory to lennard jones(lj ) fluid . the lennard jones potential was split into reference and perturbation parts according to the weeks chandler and anderson ( wca)@xcite method . in this case , we used for @xmath122 , the expression proposed by sarkisov @xcite which is same as eq.([b - m ] ) with @xmath123 where @xmath124 is the minimum energy point of the lennard - jones potential . the @xmath78 and @xmath79 of the reference system are obtained by solving the oze with the same bridge function . thus , in effect , we solved the oze for lj fluid with the above bridge function using the perturbation method . in fig.([6 ] ) , we compare the @xmath80 of lj fluid obtained from seventh order tpt with simulation results . there is excellent agreement between the theory and simulation results for the cases shown except for a slight deviation in the case of lowest temperature . in fig.([7 ] ) , equation of state(eos ) of lj fluid for various temperatures obtained using seventh order tpt is compared with those obtained by solving oze by sarkisov@xcite . pressure(p ) is obtained using the virial formula given by @xmath125 values obtained by our method matched with negligible deviation from those given by sarkisov . in this case also , using our method we could obtain the pressure for all density points in the phase diagram , as @xmath80 at any point in the phase diagram could be calculated . again , even close to the critical region , the same numerical procedure was sufficient whereas iets face numerical convergence problems in this region . in fig.([8 ] ) , lvpd of lj fluid is shown and compared with simulation results . we plotted the lvpd obtained in two ways . one is obtained by maxwell construction of pressure isotherm obtained using eq.([pvir ] ) which is the so called virial route . alternatively , lvpd is also obtained using the energy route . it is obtained as follows : pressure isotherm of the reference fluid is obtained using eq.([pvir ] ) with @xmath13 . from this , helmholtz free energy density of the reference fluid is obtained from the formula below @xmath126 once the reference free energy is obtained , method described in section ii can be applied to get the free energy density of the required system . the pressure isotherm is obtained by differentiating the helmholtz free energy @xmath3 volume of the system . maxwell construction is done to get the coexistence points . from the figure , it can be seen that the lvpd obtained from both the routes differ slightly along the liquid part of coexistence curve . also , there is some deviation of both lvpds from the simulation results . this is due to the bridge function used . even though sarkisov bridge function is supposed to be quiet accurate , there is some inconsistency between various thermodynamic routes . imposition of the thermodynamic consistency between various routes as a constraint would solve the problem and may improve the accuracy of the results . this can be done in a straight - forward way within the theory presented in the paper . we have generalized the tpt of fluids based on coupling parameter expansion to include the derivatives of the bridge function . the applications presented in the paper let us conclude the following points.(i ) inclusion of derivatives of the bridge function in the tpt has a significant effect on structural and thermodynamic properties of liquids . ( ii ) if accurate reference system data is available , it can be used in the tpt to improve the accuracy of the results over those of iet . ( iii ) the present method may be viewed as an alternative way of solving the oze with the advantage that solution can be obtained in the whole phase diagram . i am indebted to dr . s.v . g. menon for introducing me to the subject when he was in theoretical physics division , b.a.r.c . i thank dr . d. m. gaitonde for useful comments and discussions . 99 j. p. hansen , and i. r. mcdonald , theory of simple liquids , academic press , london , 2006 . p. m. w. cornelisse , c. j. peters and j. de swaan arons , j. chem . 106 , 9820 ( 1997 ) and references therein . j. m. bomont , recent advances in the field of integral equation theories , + adv . in chem . 139 , john wiley and sons j. a. barker and d. henderson , j. chem . 47 , 2856(1967 ) ; rev . , 48 , 587 , 1976 . s. zhou , phys . e 74 , 031119(2006 ) s. zhou , phys . e 77 , 041110(2008),j . 130 , 054103 ( 2009 ) g. sarkisov j. chem . 114 , 9496 ( 2001 ) r. evans , adv . in phys . 28 , 143(1979 ) c. ebner , w. f. saam , and d. stroud , phys . a 14 , 2264 ( 1976 ) . n. f. carnahan and k. e. starling , j. chem . 51 , 635 ( 1969 ) e. b. el mendoub , j. f. wax , i. charpentier , n. jakse , mol . phys . 106 , 2667(2008 ) a. sai venkata ramana and s. v. g. menon , phys . e 87 , 022101 ( 2013 ) arthur j. m. yang , paul d. fleming and julian h. gibbs , j. chem . 63 , 3732(1976 ) john d. weeks , david chandler and hans c. andersen , j. chem . 54 , 5237(1971 ) j. largo , j. r. solana , s. b. yuste , and a. santos , j. chem 122 , 084510 ( 2005 ) l. vega , e. de miguel , l. f. rull , g. jackson and i. a. mclure , j. chem . 96 , 2296 ( 1992 ) fernando d. rio , e. avalos , r. espindola , l. f. rull , g. jackson and s. lago , mol . 100 , 2531 ( 2002 ) s. zhou , j.r . solana phys . phys . 11 , 11528(2009 ) jayant k. singh , david a. kofke and jeffrey r. errington , j. chem . 119 , 3405(2003 ) r. lopez - rendon , y. reyes , and p. orea , j. chem . 125 , 084508 ( 2006 ) l. verlet , phys . 165 , 201(1968 ) a. lofti , j. vrabec , and j. fisher , mol . 76 , 1319 ( 1992 )

the coupling parameter expansion in thermodynamic perturbation theory of simple fluids is generalized to include the derivatives of bridge function with respect to coupling parameter . we applied seventh order version of the theory to square - well ( sw ) and lennard - jones(lj)fluids using sarkisov bridge function . in both cases , the theory reproduced the radial distribution functions obtained from integral equation theory ( iet ) and simulations with good accuracy . also , the method worked inside the liquid - vapor coexistence region where the iets are known to fail . in the case of sw fluids , the use of carnahan - starling expression for helmholtz free energy density of hard - sphere reference system has improved the liquid - vapor phase diagram(lvpd ) over that obtained from iet with the same bridge function . the derivatives of the bridge function are seen to have significant effect on the liquid part of the lvpd . for extremely narrow sw fliuds , we found that the third order theory is more accurate than the higher order versions . however , considering the convergence of the perturbation series , we concluded that the accuracy of the third order version is a spurious result . we also obtained the surface tension for sw fluids of various ranges . results of present theory and simulations are in good agreement . in the case of lj fluids , the equation of state obtained from the present method matched with that obtained from iet with negligible deviation . we also obtained lvpd of lj fluid from virial and energy routes and found that there is slight inconsistency between the two routes . the applications lead to the following conclusions . in cases where reference system properties are known accurately , the present method gives results which are very much improved over those obtained from the iet with the same bridge function . in cases where reference system data is not available , the method serves as an alternative way of solving the ornstein- zernike equation with a given closure relation with the advantage that solution can be obtained throughout the phase diagram with a proper choice of the reference system .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Civil War Sesquicentennial Commission Act''. SEC. 2. FINDINGS AND PURPOSE. (a) Findings.--Congress makes the following findings: (1) The American Civil War was a defining experience in the development of the United States. (2) The people of the United States continue to struggle with issues of race, civil rights, the politics of federalism, and heritage which are legacies of the Civil War and Reconstruction. (3) There is a resurgence of interest in the Civil War that is evidenced by the multitude of publications, exhibits, reenactments, research organizations, Internet and multimedia resources, historic parks, and preservation associations focused on the Civil War. (4) The years 2011 through 2015 mark the sesquicentennial of the Civil War. (5) The sesquicentennial of the Civil War presents a significant opportunity for Americans to recall and reflect upon the Civil War and its legacy in a spirit of reconciliation and reflection. (6) The United States Civil War Center at Louisiana State University, Louisiana, and the Civil War Institute at Gettysburg College, Pennsylvania, have been designated by the Federal Government to plan and facilitate the commemoration of the sesquicentennial of the Civil War. (7) The State of Virginia-- (A) witnessed more Civil War military engagements on its soil than any other State; (B) hosts more historic sites related to the Civil War than any other State; and (C) is home to the Pamplin Historical Park and the National Museum of the Civil War Soldier and the Virginia Center for Civil War Studies at Virginia Polytechnic Institute and State University, both of which are nationally recognized centers of expertise in the study of the Civil War. (8) The African American Civil War Museum located in Washington, DC, is the only museum in the Nation dedicated to the study and understanding of the role of African Americans in the Civil War. (b) Purpose-.-- The purpose of this Act is to establish a Civil War Sesquicentennial Commemoration Commission to-- (1) ensure a suitable national observance of the sesquicentennial of the Civil War; (2) cooperate with and assist States and national organizations with programs and activities for the observance of the sesquicentennial of the Civil War; (3) assist in ensuring that any observance of the sesquicentennial of the Civil War is inclusive and appropriately recognizes the experiences and points of view of all people affected by the Civil War; and (4) provide assistance for the development of programs, projects, and activities on the Civil War that have lasting educational value. SEC. 3. CIVIL WAR SESQUICENTENNIAL COMMEMORATION COMMISSION. The Secretary of the Interior shall establish a commission to be known as the Civil War Sesquicentennial Commemoration Commission (hereafter in this Act referred to as the ``Commission''). SEC. 4. COMPOSITION OF THE COMMISSION. (a) In General.--The Commission shall be composed of 25 members as follows: (1) Government members.--The Commission shall include-- (A) 2 Members of the House of Representatives appointed by the Speaker of the House of Representatives; (B) 2 Members of the Senate appointed by the President pro tempore of the Senate, in consultation with the majority leader and the minority leader of the Senate; (C) the Secretary of the Interior or the designee of the Secretary; (D) the Secretary of the Smithsonian Institution, or the designee of the Secretary; (E) the Secretary of the Department of Education, or the designee of the Secretary; (F) the Chairman of the National Endowment for the Humanities, or the designee of the Chairman; (G) the Archivist of the United States, or the designee of the Archivist; (H) the Librarian of Congress, or the designee of the Librarian; and (I) the Director of the National Park Service, or the designee of the Director. (2) Private members.--The Commission shall include-- (A) 5 members appointed by the President from among individuals who are representative of the corporate community; and (B) 9 individuals, appointed by the President, from among persons who by reason of education, training, and experience, are experts on the Antebellum, Civil War, and Reconstruction eras, including-- (i) 6 individuals with expertise in history; (ii) 1 individual with specific expertise in art history, historic preservation, or a related field; (iii) 1 individual with expertise in anthropology, cultural geography, sociology, or a related field; and (iv) 1 individual with expertise in political science, law, economics, or a related field. (b) Terms.--Members shall be appointed for the life of the Commission. (c) Vacancies.--Any vacancy in the Commission shall not affect its powers, and shall be filled in the same manner as the original appointment. (d) Initial Appointments.--The appointment of the members of the Commission shall be made not later than 60 days after the date of the enactment of this Act. SEC. 5. GENERAL PROVISIONS. (a) Meetings.-- (1) Initial meeting.--Not later than 60 days after the date on which all members of the Commission have been appointed, the members appointed under subparagraphs (A) and (B) of section 4(a)(2) shall call the first meeting of the Commission. (2) Subsequent meetings.--The Commission shall hold subsequent meetings at the call of the chairperson. (b) Chairperson and Vice Chairperson.--At the initial meeting, the Commission shall elect a Chairperson and Vice Chairperson from among its voting members. (c) Quorum.--A majority of voting members shall constitute a quorum, but a lesser number may hold meetings. (d) Voting.-- (1) In general.--The Commission shall act only on an affirmative vote of a majority of the voting members of the Commission. (2) Nonvoting members.--The individuals appointed under subparagraphs (A) and (B) of section 4(a)(1) shall be nonvoting members, and shall serve only in an advisory capacity. SEC. 6. DUTIES OF THE COMMISSION. (a) Activities Related to the Sesquicentennial.--The Commission shall-- (1) plan, develop, and carry out programs and activities appropriate to commemorate the sesquicentennial of the Civil War; (2) encourage interdisciplinary examination of the Civil War; (3) facilitate Civil War-related activities throughout the United States; (4) encourage civic, historical, educational, economic, and other organizations throughout the United States to organize and participate in activities to expand the understanding and appreciation of the significance of the Civil War; (5) coordinate and facilitate the public distribution of scholarly research, publications, and interpretations of the Civil War; (6) provide technical assistance to States, localities, and nonprofit organizations to further the commemoration of the sesquicentennial of the Civil War; (7) develop programs and facilities to ensure that the sesquicentennial commemoration of the Civil War results in a positive legacy and long-term public benefit; and (8) encourage the development and conduct of programs designed to involve the international community in activities that commemorate the Civil War. (b) Plans and Report.-- (1) Strategic plan and annual performance plans.--The Commission shall prepare a strategic plan in accordance with section 306 of title 5, United States Code, and annual performance plans in accordance with section 1115 of title 31, United States Code, for the activities of the Commission carried out under this Act. (2) Reports.-- (A) Annual report.--The Commission shall submit to Congress an annual report that contains a list of each gift, bequest, or devise with a value of more than $250, together with the identity of the donor of each such gift, bequest, or devise. (B) Final report.--Not later than December 30, 2015, the Commission shall submit to Congress a final report that contains-- (i) a summary of activities of the Commission; (ii) a final accounting of funds received and expended by the Commission; and (iii) the findings and recommendations of the Commission. SEC. 7. GRANT PROGRAM. (a) Grants Authorized.--The National Endowment for the Humanities shall award grants under this section for the uses described in subsection (b). (b) Use of Grants.--Grants awarded under this section shall be used for appropriate activities relating to the sesquicentennial of the Civil War. (c) Consideration.--In awarding grants under this section, the National Endowment of the Humanities shall consider established university, museum, or academic programs with national scope that sponsor multidisciplinary projects, including those that concentrate on the role of African Americans in the Civil War. SEC. 8. POWERS OF THE COMMISSION. (a) In General.--The Commission may-- (1) solicit, accept, use, and dispose of gifts, bequests, or devises of money or other real or personal property for the purpose of aiding or facilitating the work of the Commission; (2) appoint any advisory committee as the Commission considers appropriate for the purposes of this Act; (3) authorize any voting member or employee of the Commission to take any action that the Commission is authorized to take under this Act; (4) procure supplies, services, and property, and make or enter into contracts, leases, or other legal agreements to carry out this Act (except that any contracts, leases, or other legal agreements entered into by the Commission shall not extend beyond the date of the termination of the Commission); and (5) use the United States mails in the same manner and under the same conditions as other Federal agencies. SEC. 9. PERSONNEL MATTERS. (a) Compensation of Members.--Members of the Commission, and members of any advisory committee appointed under section 8(a)(2), shall serve without compensation. (b) Travel Expenses.--Members of the Commission, and members of any advisory committees appointed under section 8(a)(2), shall be allowed travel expenses, including per diem in lieu of subsistence, at rates authorized for an employee of an agency under subchapter I of chapter 57 of title 5, United States Code, while away from the home or regular place of business of the member in the performance of the duties of the Commission. (c) Staff.-- (1) In general.--The Chairperson of the Commission may, without regard to civil service laws (including regulations), appoint and terminate an executive director and such other additional personnel as are necessary to enable the Commission to perform the duties of the Commission. (2) Confirmation of executive director.--The employment of an executive director shall be subject to confirmation by the Commission. (3) Compensation.-- (A) In general.--Except as provided in subparagraph (B), the Chairperson of the Commission may fix the compensation of the executive director and other personnel without regard to the provisions of chapter 51 and subchapter III of chapter 53 of title 5, United States Code, relating to classification of positions and General Schedule pay rates. (B) Maximum rate of pay.--The rate of pay for the executive director and other personnel shall not exceed the rate payable for level V of the Executive Schedule under section 5316 of title 5, United States Code. (d) Detail of Government Employees.-- (1) In general.--At the request of the Commission, the head of any Federal agency may detail, on a reimbursable or nonreimbursable basis, any of the personnel of the agency to the Commission to assist the Commission in carrying out the duties of the Commission under this Act. (2) Civil service status.--The detail of an employee under paragraph (1) shall be without interruption or loss of civil service status or privilege. (e) Volunteer and Uncompensated Services.-- Notwithstanding section 1342 of title 31, United States Code, the Commission may accept and use voluntary and uncompensated services as the Commission determines necessary. (f) Support Services.--The Director of the National Park Service shall provide to the Commission, on a reimbursable basis, such administrative support services as the Commission may request. (g) Procurement of Temporary and Intermittent Services.--The Chairperson of the Commission may procure temporary and intermittent services under section 3109(b) of title 5, United States Code, at daily rates for individuals which do not exceed the daily equivalent of the annual rate of basic pay prescribed for level V of the Executive Schedule under section 5316 of such title. (h) FACA Nonapplicability.--Section 14(b) of the Federal Advisory Committee Act (5 U.S.C. App.) shall not apply to the Commission. (i) Termination.--The Commission shall terminate on the date that is 90 days after the date on which the Commission submits its report under section 6(b)(2). SEC. 10. AUDIT OF COMMISSION. The Inspector General of the Department of the Interior shall perform an annual audit of the Commission and shall make the results of the audit available to the public. SEC. 11. AUTHORIZATION OF APPROPRIATIONS. (a) In General.--There is authorized to be appropriated to carry out this Act (other than section 7) $200,000 for each of the fiscal years 2005 through 2016. (b) Grants.--There is authorized to be appropriated $3,500,000 to the National Endowment for the Humanities to provide grants under section 7, to remain available until expended.

Civil War Sesquicentennial Commission Act - Directs the Secretary of the Interior to establish a Civil War Sesquicentennial Commission to plan, develop, and carry out programs and activities appropriate to commemorate the sesquicentennial of the Civil War, and to carry out other specified duties. Directs the National Endowment for the Humanities to award grants for appropriate activities relating to the Civil War sesquicentennial, and to consider for such grants university, museum, or academic programs with national scope that sponsor multidisciplinary projects, including those that concentrate on the role of African Americans in the Civil War.

The year 2015 will be slightly longer after the Paris Observatory announced it was adding a leap second to clocks this summer. On June 30, dials will read 11:59:60 as clocks hold their breath for a second to allow the Earth’s rotation to catch up with atomic time. Atomic time is constant, but the Earth’s rotation is gradually slowing down by around two thousandths of a second per day. It is the task of scientists and officials at the International Earth Rotation Service based in France to monitor the planet's rotation and tweak time where necessary. Some years the Earth runs bang on time and no adjustment is needed. Software companies are already bracing themselves for problems. When the last leap second was added in 2012 Mozilla, Reddit, Foursquare, Yelp, LinkedIn, and StumbleUpon all reported crashes and there were problems with the Linux operating system and programmes written in Java. Many computing systems use the Network Time Protocol, or NTP, to keep themselves in sync with the world’s atomic clocks. But most are not programmed to deal with an unexpected extra second. Google has even developed a special technique to deal with what it refers to as a ‘leap smear’ where it gradually adds milliseconds to its system clocks prior to the official arrive of the leap second. "The Earth is slowing down a little bit," said Nick Stamatakos, the chief of Earth Orientation Parameters at the US Naval Observatory. "Atomic clocks keep very accurate time. The measurements are telling us 'Oh, they're slowing down'" The first leap second was added in 1972, and it will be the 26th time it has been added to clocks in history. It means the rotation of the Earth will have slowed 26 seconds compared to the time measured on atomic clocks. "They add an extra second to something called UTC (Coordinated Universal Time) in order to make sure the rate of UTC is the same as atomic time," he said. Adding the leap second will mean that at 11:59:59pm on June 30 for one second clocks will read 11:59:60pm. "For that day [June 30] there'll be 86,401 seconds, instead of 86,400 seconds. The length of the day for you and I and everyone on the Earth will have an extra second," added Mr Stamatakos. Leap seconds are rarer these days than they were when the practice of adding seconds first began. From 1972 to 1979, at least one second was added every year. Leap seconds were added six times throughout the 1980s. But there will only have been four leap seconds added since 1999. The US wants to get rid of leap seconds claiming they're too disruptive to precision systems used for navigation and communication. At a conference in Geneva in 2012 delegates argued that precisely timed money transactions could go astray or vehicles could be sent tens of metres out of position if they are a second out in their measurement of time But Britain opposes the change, saying that it would forever break the link between our concept of time and the rising and setting of the Sun. It would also spell the end for Greenwich Mean Time, which is measured by the time at which the Sun crosses the Greenwich Meridian and was adopted in Britain in 1847 Experts also fear that once this link is broken it could never be restored because although the Earth's timekeeping systems are built to accommodate the occasional leap second, adding a leap minute or hour to global time would be virtually impossible. Rory McEvoy, Curator of Horology, Royal Observatory Greenwich, said: "Since antiquity the Earth’s rotation has provided us with our timescale – it is the Earth’s rotation that gives us our most basic unit of time, the solar day. "In the early 20th century civil time, Greenwich Mean Time (GMT), was disseminated by radio signal. The clocks connected to the radio transmitters were constantly checked and adjusted, when necessary, according to astronomical determination of time. "This setup did not require leap seconds. It was only after the redefinition of the si second in 1967, when it became an issue because it was based on atomic timekeeping (more accurate than the Earth). It was felt that civil time, Co-ordinated Universal Time (UTC), should correspond with Earth rotation. In 1972 the first leap second was added to UTC to correct the disparity. "The Earth’s speed of rotation has a tendency to slow – caused principally because of the relationship between Earth and the moon – but it can speed up. There is a possibility that a negative leap second could be added to UTC. "The abolition of the leap second is being considered and after around 12 years of discussion there may be a decision made later this year." ||||| Because Earth's rotation is slowing ever so slightly, we occasionally need to add an extra second to re-sync our super-precise atomic clocks to our planet's rotation. But you know who's not on board with that? Those damn computers, whose operating systems just can't handle it. The last time we added a leap second in 2012, it wreaked havoc across the Internet. Leap seconds are governed by the Paris-based International Earth Rotation Service, which this week announced its plan to make June 30, 2015 one second longer. This will be the 26th such leap second added since 1972. Advertisement In those intervening decades, though, we've become ever more dependent on computers and GPS systems that need to keep exact time—making the task ever more fraught. In 2012, the act of adding a simple second took down Mozilla, Reddit, Foursquare, Yelp, LinkedIn, and StumbleUpon, according to the Telegraph. And yes, Gizmodo was not spared either. It mostly has to do with NTP, or the Network Time Protocol computers use to sync with atomic clocks. If a computer sees the same second twice in a row, it logically thinks something went very wrong. There are fixes to this, but they've obviously not been implemented across the board. Apparently, the Telegraph reports, there's been some controversy over whether to keep adding leap seconds. U.S. delegates have argued that "precisely timed money transactions could go astray or vehicles could be sent tens of metres out of position if they are a second out in their measurement of time." It's amazing to think that our world is so interconnected but fragile that a single second could send hiccups rippling through the system. Advertisement But, perhaps, more frighteningly, if we don't keep adding leap seconds, the primordial link between our notion of a day and the rotation of the Earth could be forever disrupted. Experts also fear that once this link is broken it could never be restored because although the Earth's timekeeping systems are built to accommodate the occasional leap second, adding a leap minute or hour to global time would be virtually impossible. After all, what is a day? Is it 24 hours exactly? Is it one complete revolution of the Earth? Armed with our super-precise modern instruments, we find ourselves asking basic questions about our world. [The Telegraph] Top image: Janaka Dharmasena/Shutterstock

– The powers that be in the world of time management have decreed that the world needs to gain an extra second this year. More precisely, the folks at the International Earth Rotation Service in Paris have decided to add one second to June 30, 2015, to sync our atomic clocks to the Earth's slowing rotation, reports Phys.org. It's called a "leap second," and this will be the 26th one since the 1970s. The problem is that the last time this happened, in 2012, it caused all kinds of problems for all kinds of websites. "If a computer sees the same second twice in a row, it logically thinks something went very wrong," explains Gizmodo. "There are fixes to this, but they've obviously not been implemented across the board." Google has developed a work-around in which it "gradually adds milliseconds to its system clocks prior to the official arrive of the leap second," reports the Telegraph, though it's not clear whether other sites will follow suit. Meanwhile, the US is pushing for the end of leap seconds altogether, given their potential to wreak havoc with financial transactions, navigation, and communication in general. A decision could come later this year, but opponents such as Britain argue that the move has the hard-to-fathom potential to mess up our notion of telling time by the rising and setting of the sun—eventually our clocks would be noticeably out of whack with the Earth's rotation. "Another possibility," writes Bob Yirka at Phys.org, is "to maintain a dual system, one for technologists, the other for everybody else." (This might be the most precise clock on the planet.)

however despite the introduction of more advanced surgical techniques , there remains a significant risk of complications and death from surgical procedures ( 1 ) . previous studies have shown that over 50% of surgical complications are avoidable ( 2 ) . in addition , the importance of effective teamwork has been established and been shown to improve outcome ( 3 ) . consequently , the world health organisation ( who ) developed the surgical safety checklist in 2008 ( 4 ) . following the introduction of the who surgical safety checklist , a large global multi - centre study demonstrated a 40% reduction in complications and death following surgery ( 5 ) . the use of this checklist is now recommended for all patients undergoing surgery in the uk by the national patient safety agency . a large number of invasive and interventional procedures are now performed outside the theatre environment . many of the factors contributing to surgical complications and serious untoward incidents are present when performing invasive procedures and/or administrating sedation in other environments . consequently , there is an increasing requirement to utilise safety checklists for all invasive procedures . the indications , guidelines and protocols for transoesophageal echocardiography are well established ( 6 , 7 , 8) . transoesophageal echocardiography is generally considered to be low risk but is occasionally associated with serious complications including oesophageal perforation , transmission of infection and death ( < 0.01% ) ( 9 ) . adherence to the british society of echocardiography ( bse ) guidance on toe probe cleaning and disinfection ( 10 ) is important to reduce the risk of transmission of infection between patients . in addition , the bse has produced guidance on the use of safe sedation during toe ( 11 ) . the incidence of complications may be further reduced by implementation and adherence to a safety checklist together with effective team working . the current who surgical safety checklist was designed for use within the theatre environment and hence is not directly relevant for use in toe . this document produced by the british society of echocardiography and the association of cardiothoracic anesthetists aims to outline a procedure specific safety checklist for toe ( who checklist , see section on who checklist given at the end of this article ) . the form is designed to be printed on a double - sided a4 page and can be filed in the patient medical records once it has been completed . however , the form can be adapted for use locally or converted into an electronic format for use in an electronic patient record if necessary . in keeping with the format of the who safety checklist , the procedure has been broken down into three phases , corresponding to patient checks , immediately pre - procedure and post - procedure checks . there is also an appendix to be completed if the toe is being performed under general anaesthesia . in order to complete the checklist effectively , it is important that one member of the team assumes responsibility for completion of each stage of the checklist . , it is important that the patient verbally confirms their identity and the intended procedure in their own words . during the time out phase , all team members should be present and should confirm their name and role . if the team is unchanged during a list , this stage can be performed at the start of the list but does not need repetition for each patient . immediately pre - procedure , the team should reconfirm that the correct patient is about to undergo the correct procedure and outline any anticipated difficulties for each patient . once the procedure has been completed , appropriate handover to the recovery team and any specific instructions should be given and all documentation completed . it is anticipated that the use of this checklist will ensure a consistent process is followed when performing toe . the authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this guideline . this guideline did not receive any specific grant from any funding agency in the public , commercial or not - for - profit sector .

the world health organisation ( who ) launched the surgical safety checklist in 2008 . the introduction of this checklist resulted in a significant reduction in the incidence of complications and death in patients undergoing surgery . consequently , the who surgical safety checklist is recommended for use by the national patient safety agency for all patients undergoing surgery . however , many invasive or interventional procedures occur outside the theatre setting and there are increasing requirements for a safety checklist to be used prior to such procedures . transoesophageal echocardiography ( toe ) is an invasive procedure and although generally considered to be safe , it carries the risk of serious and potentially life - threatening complications . strict adherence to a safety checklist may reduce the rate of significant complications during toe . however , the standard who surgical safety checklist is not designed for procedures outside the theatre environment and therefore this document is designed to be a procedure - specific safety checklist for toe . it has been endorsed for use by the british society of echocardiography and the association of cardiothoracic anaesthetists .

SECTION 1. SHORT TITLE. This Act may be cited as the ``National Discovery Trails Act of 1996''. SEC. 2. NATIONAL TRAILS SYSTEM ACT AMENDMENTS. (a) National Discovery Trails Established.--Section 3(a) of the National Trails System Act (16 U.S.C. 1242(a)) is amended by inserting after paragraph (4) the following: ``(5) National discovery trails, established under section 5, which will be extended, continuous interstate trails so located as to provide for outstanding outdoor recreation and travel and to connect representative examples of America's trails and communities. National discovery trails should provide for the conservation and enjoyment of significant natural, cultural, and historic resources associated with each trail and should be so located as to represent metropolitan, urban, rural, and back-country regions of the Nation. The appropriate Secretary shall administer national discovery trails in cooperation with a nonprofit organization.''. (b) Designation of the American Discovery Trail as a National Discovery Trail.--Section 5(a) of such Act (16 U.S.C. 1244(a)) is amended-- (1) by redesignating the paragraph relating to the California National Historic Trail as paragraph 18; (2) by redesignating the paragraph relating to the Pony Express National Historic Trail as paragraph 19; and (3) by adding at the end the following: ``(20) The American Discovery Trail, a trail of approximately 6,000 miles extending from Cape Henlopen State Park in Delaware to Point Reyes National Seashore in California, traveling through Delaware, Maryland, Washington, DC, West Virginia, Ohio, and Kentucky, where near Cincinnati it splits into 2 routes. The Northern Midwest route winds through Ohio, Indiana, Illinois, Iowa, Nebraska, and Colorado, and the Southern Midwest route explores Indiana, Illinois, Missouri, Kansas, and Colorado. After rejoining in Denver, Colorado, the route continues through Colorado, Utah, Nevada, and California. The trail is generally described in volume 2 of the National Park Service feasibility study dated June 1995 which shall be on file and available for public inspection in the office of the Director of the National Park Service, Department of the Interior, Washington, DC. The American Discovery Trail shall be administered by the Secretary of the Interior in cooperation with a nonprofit organization and other affected land managing agencies. No lands or interests outside the exterior boundaries of federally administered areas may be acquired by the United States solely for the American Discovery Trail. This trail is exempted from sections 5(d), 7(e), 7(f), and 7(g).''. (c) Comprehensive National Scenic Trail Plan.--Section 5(e) of such Act (16 U.S.C. 1244(e)) is amended by striking the first sentence through ``as part of the system,'' and inserting ``Within two complete fiscal years of the date of enactment of legislation designating a national scenic trail, except for the Continental Divide National Scenic Trail and the North Country National Scenic Trail, or a national discovery trail, except for the American Discovery Trail, as part of the system,''. (d) Comprehensive Plan for American Discovery Trail.--Section 5 of such Act (16 U.S.C. 1244) is amended by adding at the end the following: ``(g) The Secretary of the Interior shall enter into arrangements with a nonprofit organization to submit (within 3 complete fiscal years after the date of the enactment of this subsection) a comprehensive plan for the protection, management, development, and use of the American Discovery Trail, to the Committee on Resources of the United States House of Representatives and the Committee on Energy and Natural Resources of the United States Senate. The Secretary shall ensure that the comprehensive plan does not conflict with any existing agency direction and that the nonprofit organization consults with affected Federal land-managing agencies, the Governors of the affected States, county and local political jurisdictions, and local organizations maintaining components of the trail. Mandatory components of the comprehensive plan include-- ``(1) specific objectives and practices to be observed in the administration and management of the trail, including the identification of all significant natural, historical, and cultural resources to be preserved, model agreements necessary for joint trail administration among and between interested parties, and an identified carrying capacity of the trail and a plan for its implementation; ``(2) a trail protection plan to preserve the values for which the trail is being established and recognized by the Federal Government; ``(3) general and site-specific development plans, including anticipated costs; and ``(4) the process to be followed by the nonprofit organization in partnership with the Secretary of the Interior to mark the trail under section 7(c) of this Act.''. SEC. 3. CONFORMING AMENDMENTS. The National Trails System Act is amended-- (1) in section 2(b) (16 U.S.C. 1241(b)), by striking ``scenic and historic'' and inserting ``scenic, historic, and discovery''; (2) in the section heading to section 5 (16 U.S.C. 1244), by striking ``and national historic'' and inserting ``, national historic, and national discovery''; (3) in section 5(a) (16 U.S.C. 1244(a))-- (A) by striking ``and national historic'' and inserting ``, national historic, and national discovery''; and (B) by striking ``and National Historic'' and inserting ``, National Historic, and National Discovery'' ; (4) in section 5(b) (16 U.S.C. 1244(b)), by striking ``or national historic'' and inserting ``, national historic, or national discovery''; (5) in section 5(b)(3) (16 U.S.C. 1244(b)(3)), by striking ``or national historic'' and inserting ``, national historic, or national discovery''; (6) in section 5(d) (16 U.S.C. 1244(d)), by striking ``or national historic'' and inserting ``, national historic, or national discovery''; (7) in section 7(a)(2) (16 U.S.C. 1246(a)(2)), by striking ``and national historic'' and inserting ``, national historic, and national discovery''; (8) in section 7(b) (16 U.S.C. 1246(b)), by striking ``or national historic'' each place such term appears and inserting ``, national historic, or national discovery''; (9) in section 7(c) (16 U.S.C. 1246(c))-- (A) by striking ``or national historic'' each place such term appears and inserting ``, national historic, or national discovery''; and (B) by striking ``and national historic'' and inserting ``, national historic, and national discovery''; (10) in section 7(d) (16 U.S.C. 1246(d)), by striking ``or national historic'' and inserting ``, national historic, or national discovery''; (11) in section 7(e) (16 U.S.C. 1246(e)), by striking ``or national historic'' each place such term appears and inserting ``, national historic, or national discovery''; (12) in section 7(f)(2) (16 U.S.C. 1246(f)(2)), by striking ``or Historic'' and inserting ``, Historic, or Discovery''; (13) in section 7(h)(1) (16 U.S.C. 1246(h)(1)), by striking ``or national historic'' and inserting ``, national historic, or national discovery''; and (14) in section 7(i) (16 U.S.C. 1246(i)), by striking ``or national historic'' and inserting ``, national historic, or national discovery''.

National Discovery Trails Act of 1996 - Amends the National Trails System Act (the Act) to provide that national discovery trails established under the Act shall be components of the National Trails System. Provides that such trails shall be extended, continuous interstate trails located so as to provide for outdoor recreation and travel and to connect representative examples of America's trails and communities. Designates the 6,000-mile American Discovery Trail (established by this Act) as a national discovery trail. Provides that the Trail shall extend from Cape Henlopen State Park in Delaware to Point Reyes National Seashore in California, traveling northern and southern routes from Cincinnati, Ohio, to Denver, Colorado. Exempts the Trail from comprehensive national scenic trail plan requirements under the Act, but requires the Secretary of the Interior to enter into arrangements with a nonprofit organization to submit to specified congressional committees, within three fiscal years after this Act's enactment, a comprehensive plan for the protection, management, development, and use of the Trail.

SECTION 1. SHORT TITLE. This Act may be cited as the ``First-Time Homebuyer Affordability Act of 2001''. SEC. 2. FINDINGS AND POLICY. (a) Findings.--The Congress finds that-- (1) it is desirable to make funds available from individual retirement plans to encourage first time home ownership, and (2) the tax and penalty on the premature withdrawal of funds from individual retirement plans are substantial impediments to making such funds available for that purpose. (b) Policy.--It is the policy of the Congress to remove impediments to home investment by first-time homebuyers by permitting owners of individual retirement plans to direct the trustees of such plans to invest plan funds as home equity or debt in the homes of such owners or in the home of family members who are first-time homebuyers. SEC. 3. CERTAIN RETIREMENT PLANS AUTHORIZED TO MAKE EQUITY INVESTMENTS IN PRINCIPAL RESIDENCES FOR FIRST-TIME HOMEBUYERS. (a) Exemption From Prohibited Transaction Rules.--Section 4975 of the Internal Revenue Code of 1986 (relating to tax on prohibited transactions) is amended by redesignating subsections (h) and (i) as subsections (i) and (j), respectively, and by inserting after subsection (g) the following new subsection: ``(h) Special Rule for Home Equity Participation Arrangements.-- ``(1) In general.--The prohibitions provided in subsection (c) shall not apply to any qualified home equity participation arrangement to the extent that the amount paid to acquire the ownership interest referred to paragraph (2)(A) does not exceed $10,000. ``(2) Qualified home equity participation arrangement.--For purposes of this subsection-- ``(A) In general.--The term `qualified home equity participation arrangement' means an arrangement-- ``(i) under which the trustee of an individual retirement plan, at the direction of the eligible participant, shall acquire an ownership interest in any dwelling unit which within a reasonable period of time (determined at the time the arrangement is executed) is to be used as the principal residence for a first- time homebuyer, and ``(ii) which meets the requirements of subparagraph (B) of this paragraph. ``(B) Ownership interest requirement.--An arrangement shall meet the requirements of this subparagraph if the ownership interest described in subparagraph (A)-- ``(i) is a fee interest in such property (and, in the case of an arrangement which is not otherwise at arm's length, the trustee's fee interest would be reasonable in an arm's length arrangement), ``(ii) by its terms requires repayment in full upon the sale or other transfer of the dwelling unit, and ``(iii) may not be used as security for any loan secured by any interest in the dwelling unit. ``(3) Definitions.--For purposes of this subsection-- ``(A) Eligible participant.--The term `eligible participant' means an individual on whose behalf an individual retirement plan is established. ``(B) First-time homebuyer.--The term `first-time homebuyer' means an individual who-- ``(i) is an eligible participant or qualified family member, and ``(ii) had (and if married, such individual's spouse had) no present ownership interest in a principal residence at any time during the 2-year period before the date of the arrangement. ``(C) Qualified family member.--The term `qualified family member' means a child (as defined in section 151(c)(3)), parent, or grandparent of the eligible participant (or such participant's spouse). Section 152(b)(2) shall apply in determining if an individual is a parent or grandparent of an eligible participant (or such participant's spouse). ``(D) Acquisition; etc.-- ``(i) Acquisition.--The term `acquisition' includes construction, reconstruction, and improvement related to such acquisition. ``(ii) Acquisition cost.--The term `acquisition cost' has the meaning given such term by section 143(k)(3). ``(E) Principal residence.--The term `principal residence' has the same meaning as when used in section 121.''. (b) Effective Date.--The amendment made by this section shall apply to arrangements entered into after the date of the enactment of this Act. SEC. 4. LOANS USED TO ACQUIRE PRINCIPAL RESIDENCES FOR FIRST-TIME HOMEBUYERS. (a) Individual Retirement Plans.--Section 408(e) of the Internal Revenue Code of 1986 (relating to tax treatment of accounts and annuities) is amended by adding at the end thereof the following new paragraph: ``(7) Loans used to purchase a home for first-time homebuyers.-- ``(A) In general.--Paragraph (3) shall not apply to any qualified home purchase loan made by an individual retirement plan. ``(B) Qualified home purchase loan.--For purposes of this paragraph, the term `qualified home purchase loan' means a loan-- ``(i) made by the trustee of an individual retirement plan at the direction of the individual on whose behalf such plan is established, ``(ii) the proceeds of which are used for the acquisition of a dwelling unit which within a reasonable period of time (determined at the time the loan is made) is to be used as the principal residence for a first-time homebuyer, ``(iii) which by its terms requires interest on the loan to be paid not less frequently than monthly, ``(iv) which by its terms requires repayment in full not later than the earlier of-- ``(I) the date which is 15 years after the date of acquisition of the dwelling unit, or ``(II) the date of the sale or other transfer of the dwelling unit, ``(v) which by its terms treats-- ``(I) any amount required to be paid under clause (iii) during any taxable year which is not paid at the time required to be paid, and ``(II) any amount remaining unpaid as of the beginning of the taxable year beginning after the period described in clause (iv), as distributed during such taxable year to the individual on whose behalf such plan is established and subject to section 72(t)(1), and ``(vi) which bears interest from the date of the loan at a rate not less than 2 percentage points below, and not more than 2 percentage points above, the rate for comparable United States Treasury obligations on such date. Nothing in this paragraph shall be construed to require such a loan to be secured by the dwelling unit. ``(C) Limitation on amount of loans.--The amount of borrowings to which paragraph (3) does not apply by reason of this paragraph shall not exceed $10,000. ``(D) Denial of interest deduction.--No deduction shall be allowed under this chapter for interest on any qualified home purchase loan. ``(E) Definitions.--For purposes of this paragraph-- ``(i) First-time homebuyer.--The term `first-time homebuyer' has the meaning given such term by section 4975(h)(3)(B). ``(ii) Acquisition.--The term `acquisition' has the meaning given such term by section 4975(h)(3)(D)(i). ``(iii) Principal residence.--The term `principal residence' has the same meaning as when used in section 121. ``(iv) Date of acquisition.--The term `date of acquisition' means the date-- ``(I) on which a binding contract to acquire the principal residence to which subparagraph (B) applies is entered into, or ``(II) on which construction, reconstruction, or improvement of such a principal residence is commenced.''. (b) Prohibited Transaction.--Section 4975(d) of the Internal Revenue Code of 1986 (relating to exemptions from tax on prohibited transactions) is amended by striking ``or'' at the end of paragraph (14), by striking the period at the end of paragraph (15) and inserting ``; or'', and by inserting after paragraph (15) the following new paragraph: ``(16) any loan that is a qualified home purchase loan (as defined in section 408(e)(7)(B)).''. (c) Effective Date.--The amendments made by this section shall apply to loans made after the date of the enactment of this Act.

First-Time Homebuyer Affordability Act of 2001 - Amends the Internal Revenue Code to make the tax on prohibited transactions inapplicable to a qualified home equity participation arrangement (one in which up to $10,000 in an individual retirement plan is used to acquire an ownership interest in a dwelling unit that is to be used as the principal residence for a first-time homebuyer). Requires such ownership interest to be a fee interest requiring full repayment. Defines "first-time homebuyer" as an individual on whose behalf an individual retirement plan is established (eligible participant) or a family member (child, parent, or grandparent) who had no present ownership interest in a principal residence during the two-year period before the date of the arrangement.Allows the use of amounts in an individual retirement plan to make loans of up to $10,000 to purchase a home for a first-time homebuyer on behalf of an eligible participant or a family member. Prohibits a related interest deduction.

magnetars are a class of neutron stars powered by the decay of their ultrastrong magnetic fields ( duncan & thompson 1992 ) . if they are isolated , magnetars are believed to appear as persistent pulsars in the x - rays , with occasional episodes of bursting activity in the hard x - rays / soft @xmath0-rays . anomalous x - ray pulsars ( axps ) and soft gamma - ray repeaters ( sgrs ) are thought to be the observational manifestations of magnetars : their steady spin - down , quasi - thermal x - ray spectra , bursts , and the absence of binary companions all lend support to this identification ( see , e.g. , kouveliotou et al . 1998 ; mereghetti , israel , & stella 1998 ; woods et al . 1999 ; zel , psaltis , & kaspi 2001 ; gavriil & kaspi 2002 ; gavriil , kaspi , & woods 2003 ) . the absence , until recently , of detectable emission from axps and sgrs in longer wavelengths constrained all such studies to the x - rays and @xmath0-rays . in the last few years , faint counterparts of four axps have been detected in ir and optical wavelengths ( hulleman , van kerkwijk , & kulkarni 2000 , 2004 ; hulleman et al . 2001 ; israel et al . 2002 , 2003 ; wang & chakrabarty 2002 ) but no counterparts have yet been observed for sgrs , due at least in part to the high extinction along the line of sight to these sources ( corbel et al . 1997 , 1999 ; vrba et al.2000 ; kaplan et al . 2001 , 2002 ; eikenberry et al . 2001 ; wachter et al . the axp counterparts were found to be variable , with fluxes possibly correlated with the bursting activity ( kaspi et al.2003 ) , had rising spectra in @xmath1 ( hulleman et al . 2004 ; see fig . 1 below ) , and showed pulsations at the stellar spin frequency ( kern & martin 2002 ) . these long - wavelength detections have been used to argue strongly against the presence of accretion disks and companion stars around axps ( hulleman et al . 2000 ; perna , hernquist , & narayan 2000 ) . however , no predictions have been made so far for the expected long - wavelength emission from a magnetar , which can be tested against observations ( see eichler , gedalin , & lyubarsky 2002 for a preliminary discussion ) . in this _ letter _ , we discuss the strong constraints imposed by the observed ir and optical brightness of axps on any magnetar emission model . in particular , we argue that the long - wavelength emission can not originate from the surface of the neutron star . we suggest that synchrotron emission from energetic particles in the magnetosphere at @xmath2 stellar radii is responsible for this emission . the brightness and limits inferred from the optical and ir observations of axps and sgrs can be used to place stringent constraints on the mechanisms that can give rise to this emission within the magnetar model . the most robust constraint comes from imposing the thermodynamic limit on the surface emission from a neutron star . if the source of energy that powers the optical / ir emission is in the interior of the neutron star , the emitted radiation will be reprocessed in the thermalized surface layers of the star . for such processes , the maximum flux that can emerge from the star is equal to the flux of blackbody radiation at the temperature @xmath3 at optical depth unity . for a source at a distance of 5 kpc observed at a frequency of @xmath4 hz , the blackbody limit is @xmath5 where @xmath6 is the radius of the neutron star . models of magnetar atmospheres indicate that the temperature at the thermalization depth of optical / ir photons is @xmath7 kev in an atmosphere of @xmath8 kev , which reproduces the x - ray spectra of axps ( zel 2001 , 2003 ) . the constraint imposed on the emission models by equation ( 1 ) is illustrated in figure 1 for the case of axp 4u 0142@xmath961 , which has been detected over the widest range of optical / ir wavelengths . this source has a period of @xmath10 s , a period derivative of @xmath11 s s@xmath12 , and an uncertain distance of @xmath13 kpc or @xmath14 kpc ( see zel et al . 2001 and references therein ) . for this discussion , we set @xmath15 kpc . as figure 1 shows , the maximum possible flux from the surface of the neutron star 4u 0142@xmath961 is smaller by orders of magnitude than the observed optical flux for any reasonable value of the surface temperature . indeed , for the blackbody limit to be comparable to the optical flux , the temperature of the emitting layers needs to exceed 1 mev . at this temperature , the cooling of the neutron star would proceed via neutrino and not photon emission . moreover , it would yield an x - ray spectrum inconsistent with the observations . these strongly argue against a magnetar surface emission model for the optical / ir emission of axps . an upper limit on the size of the emitting region can be obtained by considering the large amplitude of pulsations at the stellar spin frequency observed at optical wavelengths for 4u 0142@xmath961 ( kern & martin 2002 ) . for coherent pulsations to be produced at @xmath10 s , the size of the emitting region has to be smaller than the light travel distance @xmath16 , which also coincides with the size of the light cylinder . therefore , the optical / ir emission of axps must be magnetospheric in origin . note that these limits apply in either the case of emission from or reprocessing of stellar radiation by the magnetosphere . the source of energy that powers the optical / ir emission is more difficult to constrain . however , contrary to the case of the high - energy emission which requires a source of magnetic energy , it is significant that rotational energy alone is sufficient to account for the observed long - wavelength brightness of axps . this is illustrated in figure 1 for the case of 4u 0142@xmath961 , where the horizontal line corresponds to the maximum flux that can be observed at earth from processes powered by rotational energy losses , i.e. , @xmath17 in this equation , @xmath18 is the rotational luminosity and @xmath19 is the moment of inertia of the neutron star . further observations of axps in uv wavelengths may be able to distinguish between the magnetic and rotational energy as the source of the long - wavelength emission . in the previous section , we argued that the optical / ir emission from axps should originate within their magnetospheres . in this section , we show that synchrotron emission from a goldreich - julian density of electrons in a dipole magnetic field geometry at @xmath2 neutron star radii can reproduce the observed long - wavelength properties of axps . in the magnetosphere of a rotating neutron star , the quasi steady - state distribution of charges is given by ( goldreich & julian 1969 ) @xmath20 where @xmath21 is the local magnetic field at radius @xmath22 , @xmath23 is the electric charge , and @xmath24 is the speed of light . the acceleration mechanism and the resulting energy distribution of these charges is largely unknown . in this section , we will assume a mono - energetic distribution of electrons characterized by a lorentz factor @xmath0 . we will also assume a magnetic field strength with a dipolar radial profile @xmath25 where @xmath26 is the magnetic field strength at the stellar surface . this distribution of energetic charges in the stellar magnetic field emits synchrotron radiation with an integrated power @xmath27 where @xmath28 is the thompson cross - section and @xmath29 is the velocity of the electrons in units of @xmath24 . in this calculation , we assume that , at each radius , all the power is emitted at the fundamental synchrotron frequency @xmath30 where @xmath31 is the mass of the electron . note that the classical expression for the synchrotron emissivity is sufficient for the magnetic field strengths that generate the optical / ir frequencies . under these assumptions , the photon - frequency dependent luminosity can be calculated as @xmath32 4 \pi r^2 dr,\ ] ] which yields @xmath33 this luminosity corresponds to a flux at earth of @xmath34 the predictions of this model for the case of 4u 0142@xmath961 are shown in figure 2 . the optical spectrum of this source , which approximately follows a @xmath35 dependence , can be fit very well with a mono - energetic distribution of electrons characterized by @xmath36 we discuss the effects of relaxing some of the approximations made in this section and its implications for the ir spectra of axps in the next section . in this _ letter _ , we described a model of the optical / ir emission of axps in which a distribution of energetic electrons in the neutron star magnetosphere emits synchrotron radiation . this model can naturally reproduce the observed brightness and the rising spectra of axps . in the calculations reported above , we have made some simplifying assumptions that may affect the quantitative predictions of the model . first , we did not take into account the angular dependence of the magnetic field and of the emitted radiation . relaxing this assumption will result in a brightness and spectrum that depends on the relative orientation of the magnetic axis and the observer . moreover , it will naturally give rise to pulsations of the long - wavelength emission at the stellar spin frequency . second , we have assumed a mono - energetic distribution of electrons throughout the magnetosphere . allowing for a radial profile of the electron lorentz factor @xmath0 will affect the slope of the optical / ir spectrum and may give rise to spectral breaks at frequencies characteristic of the acceleration and cooling mechanisms in the magnetosphere . the source of energy and the mechanism of particle acceleration in the magnetosphere of a magnetar are open questions . the long - wavelength observations of axps may provide within this model clues towards distinguishing between various possibilities . if the source of this radiation is dissipation of the rotational energy of the neutron star , then equation ( 2 ) provides an upper limit on the flux of magnetospheric synchrotron photons ( see the dashed line in fig . 2 ) . this , in return , sets an upper limit on the frequency of synchrotron radiation at @xmath37 hz for the parameters of 4u 0142@xmath961 . combining this limit with equation ( 6 ) and the best - fit value of the parameter @xmath38 ( see fig . 2 ) results in a lower limit on the emission radius of @xmath39 g@xmath40 . the observations of 4u 0142@xmath961 , in this framework , require that either the particles do not radiate at smaller radii or that particle acceleration takes place at large distances from the neutron star surface , possibly due to the formation of bound positronium states ( leinson & prez 2000 ) at the stronger magnetic fields close to the star . the inferred ir spectrum of 4u 0142@xmath961 is flatter than its optical spectrum ( hulleman et al . 2004 ) . this can be achieved for a radial distribution of lorentz factors that rises locally with increasing radius . such an energy distribution would strongly suggest that the particles are accelerated at @xmath41 and lose energy via synchrotron radiation as they follow field lines back toward the star . if the low - frequency radiation is powered by magnetic energy , such a configuration may naturally arise from the dissipation of alfvn waves in the magnetospheres of magnetars ( thompson & duncan 1996 ) . because of the much larger reservoir of magnetic energy , the optical spectrum may extend to higher frequencies than in the case of rotation power . observations of axps and sgrs in uv wavelengths will be important in distinguishing between different mechanisms . note also that the optical and ir observations of 4u 0142@xmath961 were not carried out simultaneously and may point to a change in the magnetic field configuration in time . simultaneous and/or repeat observations may also provide additional clues to the nature of the emission . this magnetospheric model can also account for a number of other observed properties of the optical / ir emission of axps . as mentioned above , the magnetic field geometry and the angular dependence of synchrotron emission gives rise to pulsations at the stellar spin frequency as observed ( kern & martin 2002 ) . the optical / ir flux is also likely to be polarized due to the strong beaming of synchrotron emission but a quantitative prediction for the degree of polarization requires including in the calculations the angle dependences discussed above . observations that search for polarization of the optical emission may help further constrain the magnetospheric model . in addition , the optical / ir emission will naturally respond to the changes in the magnetic field strength , configuration , or spin - down rate following an sgr - like burst . the timescale for this flux enhancement will be dictated by the rearrangement of magnetic field lines which are anchored in the neutron star crust and thus will proceed at a slower pace than any characteristic timescale in the magnetosphere . such correlated changes have been observed following the burst of 1e 2259@xmath9586 ( kaspi et al . 2003 ) . finally , because of its proposed magnetospheric origin , the low - energy emission of axps is expected to correlate with the rate of rotational or magnetic energy losses . the absolute luminosities of axps in the ir are very hard to infer observationally because of the unknown distances and the effects of the large interstellar absorption to these sources . to minimize these uncertainties , we have normalized the unabsorbed ir flux in the k band to the unabsorbed persistent x - ray flux at @xmath42 hz . the intrinsic x - ray luminosities of axps are expected to be similar between the sources and not to depend strongly on the magnetic field strength . even though such a luminosity clustering is difficult to infer from the data , their quasi - thermal spectra with similar color temperatures and the fact that the emitting areas should all be comparable to the surface area of a neutron star point to such a theoretical expectation . the inferred flux ratios are plotted against the observed rate of rotational energy loss in figure 3 ( see israel et al . 2003 and references therein for the data ) . the overall correlation provides additional support to the model of magnetospheric optical / ir emission of axps discussed here . i thank chryssa kouveliotou , peter woods , and sandeep patel for stimulating discussions and their hospitality during my visit to msfc where this work was initiated , as well as for their detailed comments on the manuscript . i thank sandeep patel also for his help with the axp data files . i am grateful to dimitrios psaltis for his help , scientific and otherwise , while completing this work . i acknowledge support by nasa through hubble fellowship grant hf-01156 from the space telescope science institute , which is operated by the association of universities for research in astronomy , inc . , under nasa contract nas 5 - 26555 .

a number of anomalous x - ray pulsars ( axps ) have recently been detected in the optical / ir wavelengths . we use their inferred brightness to place general constraints on any model for this emission within the magnetar framework . we find that neutron - star surface emission can not account for the observations and that the emission must be magnetospheric in origin . we propose a model for the optical / ir emission in which a distribution of energetic electrons in the neutron - star magnetosphere emits synchrotron radiation . this model can naturally reproduce the observed brightness and the rising spectra of axps as well as the observed pulsations at the stellar spin frequency and the correlation of the ir flux with their bursting activity .

the problem of a random walk on a two - dimensional lattice with a single interior source point and absorbing boundaries was first considered by courant _ _ @xcite in 1928 where general properties of the solution were discussed . this problem was solved exactly in 1940 @xcite for the case of random walks on a square lattice with rectangular absorbing boundaries . the problem on a triangular lattice with finite absorbing boundaries was considered in 1963 @xcite where the exact solution was given for an approximation of the problem using straight boundaries rather than the true zig - zag boundaries of the triangular lattice . indeed the authors of this paper remarked that `` an explicit solution of the difference equation can hardly be obtained if these boundary conditions are used . '' other variants of the problem on the square lattice have been solved exactly @xcite however the problem on the triangular lattice with true zig - zag triangular lattice boundaries has remained unsolved . in this paper we give the exact solution for this problem . the problem of random walks on finite lattices with absorbing boundaries is fundamental to the theory of stochastic processes @xcite and has numerous applications . these include potential theory @xcite , electrical networks @xcite , surface diffusion @xcite and diffusion - limited aggregation ( dla ) @xcite . for example , the exact results for the square lattice problem @xcite have been used to expedite the growth of large dla clusters on the square lattice @xcite and the formulae derived in this paper could similarly be used on the triangular lattice . a schematic illustration showing random walk pathways ( dashed lines ) on an equi- angular triangular lattice is shown in fig . 1 . a natural co - ordinate system for the triangular lattice is to label the lattice vertices by the intersection points @xmath0 of horizontal straight lines @xmath1 and slanted straight lines @xmath2 parallel to the @xmath3 axis shown in fig . 1 . in this co - ordinate system the expectation that a random walk on the lattice visits a site @xmath0 , before exiting at a finite boundary , is given by the non - separable difference equation @xmath4.\end{aligned}\ ] ] in this paper we adopt a different co - ordinate system , which may at first appear less natural but it has the advantage that the governing equations are separable . in the co - ordinate system used here we label the vertices of the triangular lattice by the intersection points @xmath0 of horizontal straight lines @xmath1 and vertical zig - zag lines @xmath2 ( see fig . 2 ) . in the absence of any source terms the expectation that a random walker visits a lattice site @xmath0 is given by the coupled homogeneous difference equations @xmath5,\label{feq}\\ \hat f(p , q)&=&\frac{1}{6}\left [ f(p-1,q)+\hat f(p , q-1)+f(p+1,q)\right.\nonumber\\ & & \quad \left . + f(p+1,q+1 ) + \hat f(p , q+1)+ f(p-1,q+1)\right],\label{fhateq}\end{aligned}\ ] ] where @xmath6 denotes the field value at an even @xmath3 co - ordinate and @xmath7 denotes the field value at an odd @xmath3 co - ordinate . this separation of even and odd field equations , which is not necessary for the problem on the square lattice , is central to our solution below . now consider a source term at @xmath8 and absorbing boundaries at @xmath9 and @xmath10 . in section 3 we give the solution for the case where @xmath11 is odd . the same methods can be used with slightly altered equations to obtain the solution for @xmath12 even . the special case of the strip with @xmath13 has been detailed elsewhere @xcite . following mccrea and whipple @xcite we construct separate solutions , @xmath14 for @xmath15 and @xmath16 for @xmath17 . the absorbing boundary conditions are thus given by @xmath18 the ommision of a subscript @xmath19 or @xmath20 in the above indicates that the same equations are satisfied by both @xmath21 and @xmath22 . at @xmath23 we have the matching conditions @xmath24 finally , with the inclusion of the source term , we have the coupled inhomogeneous field equations at @xmath23 , @xmath25,\\ 6\hat f_i(p , b)&=&6\delta_{p , a}(a \mbox{mod } 2)\nonumber\\ & & + \left[f_i(p-1,b)+\hat f_i(p , b-1)+f_i(p+1,b)\right.\nonumber\\ & & \left . \quad + f_{ii}(p+1,b+1 ) + \hat f_{ii}(p , b+1)+f_{ii}(p-1,b+1)\right].\end{aligned}\ ] ] in section iii we present the solutions to eqs . ( 1)(12 ) . the probabilities for the random walking particle to be absorbed at any specified point on one of the four boundaries , @xmath26 , are readily obtained by averaging over the nearest neighbour expectation values subject to the boundary conditions , eqs . ( 3)(8 ) . for example , @xmath27;\nonumber\\ & & \qquad\quad k=1,\ldots \frac{m+1}{2}.\end{aligned}\ ] ] we begin by solving the homogenous equations , eqs . ( 1),(2 ) , subject to the absorbing boundary conditions , eqs . ( 3),(4 ) . the homogenous field equations separate , on using @xmath28 into @xmath29 where @xmath30 and @xmath31 are separation constants . the two coupled equations for @xmath32 and @xmath33 can be readily decoupled into separate equations @xmath34 where @xmath35 is an integer . this second order linear difference equation for @xmath36 on a lattice of even ( odd ) integers has the solution @xmath37 where @xmath38 and @xmath39 and @xmath40 are arbitrary . it follows that the solution of @xmath41 ( with @xmath3 even ) corresponding to the boundary conditions , eqs . ( 3),(4 ) , is @xmath42 with @xmath43 the solution for @xmath44 ( with @xmath3 odd ) now follows from eq . ( 17 ) as @xmath45 equations ( 16 ) and ( 17 ) can also be decoupled for @xmath46 and @xmath47 resulting in the same fourth order linear difference equation in each case ; @xmath48 the zeroes of the corresponding characteristic quartic polynomial are in reciprocal pairs leading to the solutions @xmath49 where @xmath50 the coefficients @xmath51 may be chosen arbitrarily with the coefficients @xmath52 then determined by substituting eqs . ( [ qeq ] ) , ( [ qhateq ] ) into eq . ( 16 ) or eq . ( 17 ) . from eq . ( 17 ) we obtain @xmath53 where @xmath54 by combining eqs . ( 14),(15),(20),(22),(24),(25),(28),(29 ) we can write the solutions to the field equations , eqs . ( [ feq ] ) , ( [ fhateq ] ) , that satisfy the boundary conditions , eqs . ( 3),(4 ) , in the form @xmath55,\\ & & \nonumber\\ & & \hat f(p , q;a , b , c , d)=\sum_{j=1}^m\sin\left(\frac{\pi j p}{m+1}\right ) \cos\left(\frac{\pi j}{m+1}\right)\nonumber\\ & & \quad\times\left [ a_j{\mathrm{e}}^{\alpha q}({\mathrm{e}}^\alpha+1 ) + b_j{\mathrm{e}}^{-\alpha q}({\mathrm{e}}^{-\alpha } + 1)\right.\nonumber\\ & & \qquad\left . + c_j{\mathrm{e}}^{\beta q}({\mathrm{e}}^\beta+1)+ d_j{\mathrm{e}}^{-\beta q}({\mathrm{e}}^{-\beta}+1)\right],\end{aligned}\ ] ] where @xmath56 are arbitrary . before imposing the remaining absorbing boundary conditions , eqs . ( 5)(8 ) , we represent the solutions in the two regions : @xmath57 ; @xmath58 by @xmath59 the absorbing boundary conditions , eqs . ( 5)(8 ) , can be used to eliminate @xmath60 . after an appropriate re - normalization of the coefficients @xmath61 this yields @xmath62,\label{fi } \\ & & \nonumber\\ \hat f_i(p , q)&=&\sum_{j=1}^m\sin\left(\frac{\pi j p}{m+1}\right ) \cos\left(\frac{\pi j}{m+1}\right)\nonumber\\ & & \times\left[\hat a_i(q,\alpha,\beta)a_j+\hat a_i(q,-\alpha,\beta)b_j\right ] , \label{fihat}\\ & & \nonumber\\ f_{ii}(p , q)&=&\sum_{j=1}^m\sin\left(\frac{\pi j p}{m+1}\right)\nonumber\\ & & \times\left[a_{ii}(q,\alpha,\beta)\tilde a_j+a_{ii}(q,-\alpha,\beta ) \tilde b_j\right],\label{fii}\\ & & \nonumber\\ \hat f_{ii}(p , q)&=&\sum_{j=1}^m\sin\left(\frac{\pi j p}{m+1}\right ) \cos\left(\frac{\pi j}{m+1}\right)\nonumber\\ & & \times\left[\hat a_{ii}(q,\alpha,\beta)\tilde a_j+ \hat a_{ii}(q,-\alpha,\beta)\tilde b_j\right],\label{fiihat}\end{aligned}\ ] ] where @xmath63 and the function @xmath64 the coefficients defined in eq . ( 36 ) which are shown as implicit functions of @xmath65 and @xmath66 are also functions of @xmath67 via eqs . ( 21),(26),(27 ) . equations ( [ fi])([fiihat ] ) , are general solutions to the coupled homogeneous field equations , eqs . ( 1),(2 ) , that satisfy all of the absorbing boundary conditions , eqs . ( 3)(8 ) . by using the two matching conditions , eqs . ( 9),(10 ) , the four arbitrary constants , @xmath68 , can be reduced to two arbitrary constants , @xmath69 say . the solutions in region ii can then be written as @xmath70,\\ & & \nonumber\\ \hat f_{ii}(p , q)&=&\sum_{j=1}^m\sin\left(\frac{\pi j p}{m+1}\right ) \cos\left(\frac{\pi j}{m+1}\right)\nonumber\\ & & \times\left[\hat a_{ii}^\star(q,\alpha,\beta)a_j + \hat a_{ii}^\star(q,-\alpha , \beta)b_j\right],\end{aligned}\ ] ] where @xmath71 and @xmath72 finally the remaining arbitrary constants @xmath69 are determined from the requirement that the solutions satisfy the coupled inhomogeneous field equations , eqs . ( 11),(12 ) . this step is facilitated using the identity @xmath73 explicitly we find : + i ) @xmath74 even , @xmath75 ii ) @xmath74 odd , @xmath76 and @xmath77 our solution for the triangular lattice site expectation values with absorbing boundary conditions and a source point is finally given by eqs . ( 32),(33 ) in region i and eqs . ( 41),(42 ) in region ii . the relevant quantities appearing in these equations are defined through the series of equations , eqs . ( 21),(26),(27),(36)(40),(43)(46),(48)(50 ) . consider the case of a triangular lattice with @xmath78 and a source at @xmath79 ( fig . 2 ) . in the approximation to this problem using straight edge boundaries and the @xmath0 co - ordinate system of keberle and montet @xcite this problem corresponds to ; @xmath80 . we have calculated expectation values at the nearest neighbour lattice sites around the source and absorption probabilities at the boundaries ; ( a ) using our exact results above , and ( b ) using the results of keberle and montet @xcite for the approximation to the problem their equations ( 7a ) , ( 7b ) , ( 7c ) . in this small model lattice system we found that the straight line boundary approximation provides reasonable results for expectation values near the source ( accurate to within a few percent ) but provides poor results for the absorption probabilities ( table 1 ) . note that the ` absorption probabilities ' for the zig - zag boundary co - ordinates which are inside the straight line boundary of keberle and montet @xcite are not true probabilities in their solution . @*5l @xmath81(a)&&&(b)&@xmath82&.012247&&@xmath83&.019609 + @xmath84&.035646&&@xmath85&.039949 + @xmath86&.054827&&@xmath87&.057904 + @xmath88&.063296&&@xmath89&.065834 + @xmath90&.056686&&@xmath91&.059209 + @xmath92&.039811&&@xmath93&.042817 + @xmath94&.020737&&@xmath95&.024583 + @xmath96&.005743&&@xmath97&.007903 + @xmath98&.026040&&@xmath99&.033624 + @xmath83&.013797&&@xmath84&.036214 + @xmath100&.069523&&@xmath101&.088151 + @xmath85&.021476&&@xmath88&.053888 + @xmath102&.005743&&@xmath103&.015276 + @xmath104&.040253&&@xmath105&.051612 + @xmath106&.015039&&@xmath107&.038562 + @xmath108&.059725&&@xmath109&.075927 + although our solution is somewhat unwieldly , we have nevertheless solved the underlying field equations for random walks on a finite triangular lattice with a single interior source point and zig - zag absorbing boundaries and have thus calculated the associated absorption probabilities . this problem was previously considered to be intractable @xcite . we hope that our result will inspire further work in this area .

the problem of a random walk on a finite triangular lattice with a single interior source point and zig - zag absorbing boundaries is solved exactly . this problem has been previously considered intractable . # 1 epsf.sty

gout is a disease characterized by joint and kidney inflammation caused by high levels of uric acid in the bloodstream and tissues . uric acid is water soluble and is normally eliminated by the kidneys in quantities between 600 and 700 mg / day when the organism receives a normal diet . plasma concentrations of uric acid higher than 6 mg / dl and 7 mg / dl in women and men , respectively , cause hyperuricemia . this medical condition may be caused by a diet rich in proteins , fat , and alcohol as well as hereditary factors ( inborn errors of purine - pyrimidine metabolism ) . there are other diseases associated to hyperuricemia such as type 2 diabetes which , in the presence of higher levels of uric acid , causes insulin absorption resistance in tissues , increase of nephropathy progression , and tumor lysis syndrome ( tls ) [ 24 ] . urate oxidase ( uricase , ec 1.7.3.4 ) is an enzyme with copper bonds that catalyze the oxidative opening of the purine ring of uric acid to form allantoin which is 510 times more soluble than uric acid [ 5 , 6 ] . rasburicase ( fasturtec / elitek ) is a market name given to the aspergillus flavus urate oxidase expressed in saccharomyces cerevisiae which has been approved for clinical use . studies showed that rasburicase is more effective than other drugs in the treatment of hyperuricemia due to low incidence of hypersensibility reaction [ 7 , 8 ] . urate oxidase is also used as a reagent in clinical diagnostic kits for enzymatic determination of uric acid . native enzyme may be obtained from several microorganisms of the genus micrococcus , brevibacterium , streptomyces , candida , bacillus , pseudomonas , arthrobacter , and aspergillus [ 915 ] . urate oxidase from thermophilic bacillus sp . tb-90 has been extensively studied for diagnostic purposes since it exhibits high activity and thermostability in a wide range of phs . purified recombinant bacillus subtilis urate oxidase has been tested with success in a biochip system for diagnostic purposes . in this case , the puclm gene was cloned in - frame with the maltose - binding protein ( mpb ) coding sequence resulting in a large protein fusion ( ~98 kda ) which was not significantly overexpressed in escherichia coli . this result prompted us to employ a different approach to improve the expression of b. subtilis urate oxidase in e. coli by using a smaller 6x his tag which would also enable simple and fast purification of the recombinant enzyme for further biochemical characterization and large - scale production . bacillus subtilis subtilis lmd 69.3 was used as a source of the urate oxidase gene . for heterologous expression , e. coli bl21 ( de3 ) plyss and the expression vector pet21a ( novagen ) ni sepharose 6 fast flow ( ge healthcare ) resin was used to purify recombinant urate oxidase . plasmid extraction was performed by the use of qiaprep spin mini kit ( qiagen ) . b. subtilis chromosomal dna was extracted as described elsewhere . the urate oxidase coding sequence ( 1485 pb ) was obtained by pcr using primers pucl5 ( 5-cggatccatgttcacaatggatgacctg -3 ) and pucl3 ( 5-gctcgagggctttcaggctccgacat-3 ) which were designed based on the b. subtilis puclm gene sequence ( genebank gi : 32468813 ) . primer pucl5 contained a bamhi site ( underlined ) and the translation initiation codon ( bold ) , whereas pucl3 incorporated an engineered xhoi site ( underlined ) . amplification was performed using the following conditions : 30 cycles of 1 minute at 94c , 45 seconds at 50c , and 1.5 minutes at 72c . the sequence of the cloned gene was verified by automated dna sequencing on the genetic analyzer mega bace 1000 ( ge healthcare ) using the mega bace dye terminator kit . plasmid pgemuri was digested with bamhi and xhoi and the puclm gene was ligated into pet21a digested with the same enzymes . because primer pucl3 lacks a stop codon , the urate oxidase gene was cloned in - frame with the 6x his tag coding sequence present in pet21a . the resulting plasmid , peturi , was used to transform e. coli bl21 ( de3 ) plyss . a single e. coli colony transformed with peturi was inoculated in 6 ml luria - bertolin ( lb ) medium containing 100 g / ml ampicillin and incubated at 37c with shaking ( 200300 rpm ) overnight . five milliliters of this preculture were transferred to 50 ml of lb medium in a 250 ml shake flask . the culture was grown under the same condition until od600 reached 0.6 when iptg was added to a final concentration of 1 mm . one milliliter samples were collected at different intervals and cell pellet was resuspended in 50 l of sds - page sample buffer and boiled for 5 minutes prior to gel electrophoresis analysis . protein samples were separated on 12% sds - page gels and electroblotted onto pvdf membrane . the membrane was blocked with 5% milk in 10 mm tris - hcl with 150 mm nacl ( ph 8.0 ) and 0.1% tween 20 ( tbst ) for 2 hours at room temperature . the membrane was then incubated for 2 hours at room temperature with monoclonal mouse antipoly histidine ap antibody diluted 1 : 1000 in tbst . after three washes with tbst , bands were visualized by using the nbt / bcip detection method . in order to purify and analyze the recombinant protein , one bacterial clone was induced with 1 mm iptg in 100 ml lb during 3 hours . the cells were harvested by centrifugation at 5000 rpm for 20 minutes at 4c . cell pellet ( 1.5 g ) was resuspended in 2 ml lysis buffer ( 10 mm imidazole , 50 mm nah2po4 [ ph 8.0 ] , 300 mm nacl ) and lysed by sonication ( 6 cycles of 10 seconds of pulses at 45% amplitude59w ) . the suspension was centrifuged at 13000 rpm for 10 minutes and the supernatant loaded into an ni - nta column with a volume of 1 ml resin preequilibrated in lysis buffer . the column was washed 8 times with 1 ml wash buffer ( 20 mm imidazole , 50 mm nah2po4 [ ph 8.0 ] , 300 mm nacl ) and 4 times with 500 l elution buffer ( 200 mm imidazole , 50 mm nah2po4 [ ph 8.0 ] , 300 mm nacl ) . molecular mass determinations were performed on an ultraflex ii spectrometer ( bruker daltonics ) using lyophilized sample dissolved in milli - q water and mixed separately with two different saturated matrices solutions , -cyano-4-hydroxycinnanic acid , and 3,5-dimethoxy-4-hydroxycinnamic acid ( sinapinic acid ) . hydrogen peroxide reacts with 4-aminoantipyrine and 3,5-dichloro-2-hydroxybenzenesulfonic acid and forms quinoneimine , a red compound that is detected by an increase in absorbance at 555 nm . the enzymatic reaction was carried out at 37c and contained 200 l uric acid solution ( 10 mg in 100 ml of 10 mm tris - hcl , ph 8.0 ) , 50 l distilled water , and 50 l enzyme samples . after 15-minute reaction , the reagent solution ( 4 mm 4-aminoantipyrine , 2 mm 3,5-dichloro-2-hydroxybenzenesulfonic acid , 2 mm horseradish peroxidase , and 10 mm tris - hcl buffer ) was added , incubated at room temperature for 5 minutes , and measured at 555 nm . one unit of urate oxidase activity was defined as the amount of enzyme that catalyzes the transformation of 1 mol of urate per minute at 37c ( ph 8.0 ) . urate oxidase activity was calculated using the math formula found at the kikkoman biochemicals website ( http://www.kikkoman.co.jp/bio/e/common/rinsyou.html ) . enzyme activity as a function of ph was tested with 50 mm sodium citrate for the followings values of ph : 2.5 , 3.0 , 4.5 , 5.0 ; 50 mm sodium phosphate for ph values 6.0 and 7.0 ; 50 mm tris - hcl for ph values 8.0 , 9.0 and 10.0 . the optimum temperature was evaluated by measuring urate oxidase activity for 30 minutes at different temperatures : 25 , 37 , 40 , 60 , and 80c . the effect of temperature on enzyme stability was determined by measuring the residual activity after 0 , 12 , 24 , 48 and 72 hours of preincubation in 10 mm tris - hcl ( ph 8.0 ) at 20 , 4 and 37c . a ~1.5 kb amplicon corresponding to the b. subtilis puclm gene was successfully cloned , sequenced and transferred to the bacterial expression vector pet21a ( data not shown ) . in order to analyze the kinetics of urate oxidase expression , a colony of e. coli cells harbouring peturi was grown to mid - log and induced with iptg for 0 , 15 , 30 , 60 , 90 , and 120 minutes . samples analyzed by sds - page revealed a ~60 kda induction band ( figure 1(a ) ) . the size of this band was consistent with the predicted mass of the recombinant enzyme . western blot analysis showed that the induction band represented a protein which contained a 6x his tag ( figure 1(b ) ) . two smaller ( < 50 kda ) and less abundant bands were also observed in the western blot ( figure 1(b ) ) . induction profile showed a progressive accumulation of the enzyme starting 15 minutes after addition of iptg and reaching the highest peak 90 minutes later . after induction in 100 ml , the cleared cell lysate was chromatographed in a ni - nta resin column in order to purify recombinant urate oxidase in a single - step . fractions collected in different steps of purification were analyzed by sds - page ( figure 2 ) . in order to optimize the purification procedure of the enzyme different elution buffers containing increasing concentrations of imidazole ( 50 , 100 , 150 , 200 mm ) after elution with 200 mm imidazole , a predominant band with an apparent molecular mass of ~60 kda was observed ( figure 2 , lane 6 ) . the data presented in table 1 shows that the enzyme was purified with a 2.1 fold increase in specific activity with a yield of ~58% as compared to the crude extract . maldi - tof / ms analysis of the purified enzyme fraction revealed two major ions m+h = 58675 da and its double charged m+2h = 29338.1 da ( figure 3 ) . the effects of ph and temperature on enzyme activity are shown in figures 4(a ) and 4(b ) , respectively . purified urate oxidase showed maximum activity at ph 8.0 and 37c ( figure 4(b ) ) . as shown in figure 5 , the residual activity was practically constant at 20c and 4c after a 72 hours incubation period but was significantly affected by incubation at 37c . urate oxidase is a enzyme conserved in many species ranging from microorganisms to mammals ; however , primates have lost this activity as consequence of evolutionary gene mutations [ 20 , 21 ] . this enzyme catalyzes the oxidative reaction that converts urate to allantoin , a more soluble and easily excreted compound . due to this property urate oxidase many sources of urate oxidase are available , but commercial production may be hampered by low productivity and difficulties in protein purification for clinical applications [ 22 , 23 ] . dna technology has been employed to overcome these difficulties by expressing urate oxidase genes in heterologous systems . in b. subtilis the genes for purine degradation are clustered at positions 284 to 285 in the genome map [ 25 , 26 ] . mutational analysis of this region showed that inactivation of puclm resulted in a defect in the utilization of guanosine , hypoxanthine , and uric acid and was thus proposed to code for urate oxidase . although the protein coded from the pulm gene shows amino acid identity to other urate oxidases , this similarity is restricted to the c - terminal domain ( amino acids 171494 ) with the highest identities being with bacillus sp . tb-90 ( 66% ) , bacillus clausii ( 63% ) , and bacillus fastidiosus ( 55% ) . it has been proposed that the first 170 amino acids correspond to a peroxide reductase domain that could be involved in the removal of hydrogen peroxide , a product of the oxidation of uric acid to allantoin catalyzed by urate oxidase . unlike eukaryotic urate oxidases and similar to bacillus sp . tb-90 , the b. subtilis enzyme does not have the typical type 2 copper binding motif h - x - h - x - f . in this work , the puclm was successfully expressed in e. coli in a soluble and active form . this result is particular important for the commercial production of this enzyme since it eliminates the laborious denaturing / refolding steps often necessary to solubilize proteins present as inclusion bodies . furthermore , the strategy used in this work involved the fusion of b. subtilis urate oxidase to a 6x his tag in order to allow simple one - step purification using ni - nta column . a derivation of this method using ni ion - chelating magnetic beads to increase yield was reported for the purification of recombinant bacillus sp . the results presented in table 1 show that the recombinant enzyme was purified almost to homogeneity and the yield was about 58% as compared to the crude extract . this yield was close to that reported for commercial rasburicase ( 61% ) and native b. subtilis urate oxidase ( 67% ) [ 28 , 29 ] . the smaller protein contaminants that copurified with the recombinant enzyme represent minor breakdown products because they were recognized by the antipoly histidine antibody ( figure 1(b ) ) . the recombinant enzyme was submitted to biochemical characterization ( molecular mass determination , thermostability , optimum temperature and ph ) and in vitro enzymatic activity . the experimental molecular mass value of 58675 da obtained by maldi - tof / ms for the recombinant enzyme is close to the theoretical values calculated for the predicted recombinant protein ( 58.9 kda ) . the optimum temperature ( 37c ) and ph ( 8.0 ) were similar to that observed with a. flavus urate oxidase produced in e. coli and the b. subtilis mpb - uricase fusion protein . in enzymatic assays the b. subtilis urate oxidase exhibited a specific activity of 39 iu / mg protein , a value higher than those observed for other urate oxidase described in the literature under optimal conditions . for example , native b. subtilis urate oxidase specific activity was 5.29 iu / mg protein , the specific activity for the a. flavus urate oxidase expressed in e. coli was 26.96 iu / mg and the commercial rasburicase was 26.98 iu / mg protein . the stability of the recombinant enzyme at the temperatures used to store commercial enzymatic diagnostic kits ( 20c and 4c ) was evaluated and the enzyme kept 80% of its residual activity after 72 hours of pre - incubation . however , at 37c , 50% of the residual activity was lost after 12 hours which is in agreement with the rasburicase half life of 19 hours reported in humans [ 30 , 31 ] . it has been proposed that the human body temperature is responsible for the shorter circulating half - time exhibited by recombinant urate oxidase [ 30 , 31 ] . the results presented in this work showed the feasibility of producing soluble recombinant urate oxidase at high levels . the purity of the enzyme together with its high activity and thermostability shows that the production of the b. subtilis urate oxidase in e. coli should be considered for the development of diagnostic kits and for clinical purposes .

urate oxidase ( ec 1.7.3.3 ) is an enzyme involved in purine metabolism which is used in the treatment of gout and as diagnostic reagent for detection of uric acid . in order to produce this enzyme in large quantities for biotechnological purposes , the gene coding for the bacillus subtilis urate oxidase was cloned and heterologously expressed in escherichia coli . time course induction in e. coli showed an induced protein with an apparent molecular mass of 60 kda . soluble recombinant enzyme was purified in a single - step procedure using ni - nta column . the enzyme was purified 2.1-fold with a yield of 56% compared to the crude extract . maldi - tof analysis revealed an ion with a mass of 58675 da which is in agreement with the expected mass of the recombinant protein . the purified enzyme showed an optimal ph and temperature of 8.0 and 37c , respectively , and retained 90% of its activity after 72 hours of incubation at 20c and 4c .

transverse pattern formation , autosolitons and cavity solitons have been the subject of intense research in nonlinear optics in the last two decades since their original predictions @xcite . unlike in other fields of science , transverse patterns and dissipative solitons find useful applications in photonics such as optical memories , delay lines and optical registers @xcite . cavity solitons counterparts in the propagation direction have also been shown to generate passive mode - locking in fiber lasers @xcite . formation of transverse spatial structures in quadratic nonlinear cavities was predicted first in optical parametric oscillators ( opos ) @xcite and later extended to second harmonic generation @xcite . early predictions in opos were confined to the degenerate case where signal and idler fields have the same frequency . experimental evidence of pattern formation was indeed found in triply resonant degenerate opos close to the confocal cavity configuration @xcite and via conical emissions @xcite . confirmation of the predictions of @xcite was provided in a broad - aperture degenerate opos in a plane - mirror mini - cavity @xcite . degenerate opos also display phase domain dynamics and dark - ring cavity solitons @xcite . finally , opo models for non - degenerate type - ii cases in doubly or triply resonant cavity configurations have also been shown to display self - organization and pattern formation @xcite . transverse instabilities in the case of non - degenerate , singly resonant opos ( sropos ) , where the signal field is the only resonated field in an optical cavity , have been less discussed in the literature . on the theoretical side pattern formation in sropos is expected to replicate results of the complex ginzburg - landau laser case @xcite . on the experimental side cw sropo configurations are notoriously difficult to operate because of high oscillation thresholds ( typically several watts ) in common birefringent crystals @xcite . quasi - phase matching in periodically poled materials has , however , considerably reduced operation thresholds of cw sropos @xcite allowing for diode @xcite and fiber @xcite laser pumping for spectroscopy applications . a major advantage of cw sropos is that their wide tunability is monotonic and not affected by mode jumps typical of doubly or triply resonant configurations . in this paper we investigate the formation and dynamics of transverse structures in sropos . we first derive a mean - field model in section [ mfl ] where the nonlinearity is of sinc@xmath0 form in agreement with early studies of sropo steady states emissions @xcite . the analysis builds on approaches that describe and integrate the propagation equations inside the opo crystal @xcite by considering transverse effects and by carefully separating the mean - field and close - to - threshold approximations . the final model equations are capable of describing transverse pattern formation in the presence of pump depletion , signal - idler recombination and external seeding close to the signal frequency . external seeding proves to be of fundamental importance for transverse structures in sropos since , in its absence , changes of the cavity length are compensated by changes in the signal ( and idler ) frequency thus nullifying the common mechanism of turing pattern formation in off - resonant optical systems @xcite . in section [ pwss ] plane - wave steady states and their stability are analyzed in the sropo models with external seeding , close to and far from threshold . these studies confirm that no pattern formation should be expected without a detuned external seed . analytical expressions for the location in the parameter space of the loss of stability of homogeneous solutions to spatially modulated structures are then provided in section [ tupf ] . the thresholds for pattern formation when changing the seeding intensity are then compared with those obtained from numerical integration of the sropo dynamical equations with excellent agreement . section [ otcs ] investigates when spatially periodic spatial structures break down to either optical turbulence for small seeding intensities or to cavity solitons for large pump and seeding intensities . optical turbulence is demonstrated to be the mechanism which generates rogue waves in the spatio - temporal evolution of the output fields . finally , bright and dark cavity solitons are found in multistable configurations with localized hexagonal and honeycomb patterns . we consider parametric down conversion in a @xmath1 crystal of length @xmath2 at perfect phase matching , a condition that can also describe the average effect of quasi - phase matching in periodically poled crystals . in this case the propagation of the pump , signal and idler fields in the crystal along the @xmath3 direction are described by @xcite : @xmath4 where @xmath5 with @xmath6 are the slowly varying amplitudes of pump , signal and idler fields , respectively , with wave - numbers @xmath7 and @xmath8 is the transverse laplacian operator along the @xmath9 and @xmath10 directions perpendicular to the propagation axis @xmath3 . the frequency constraint @xmath11 is rewritten as @xmath12 where @xmath13 , @xmath14 and the effective coupling parameter @xmath15 is given by @xmath16 where @xmath1 is the second order susceptibility of the crystal , @xmath17 is the common refractive index of the three waves that guarantees phase matching and @xmath18 is the speed of light in vacuum . with a single partially reflecting mirror @xmath19 and containing a parametric down - conversion crystal of length @xmath2 . ] we assume that the parametric down conversion crystal is contained in an optical cavity of length @xmath20 where the signal field is the only one to be resonated ( see figure [ fig : sropo ] ) . the steps involved in taking the mean - field approximation are the same as those reported in @xcite although in the sropo case there is only one resonated field . the final equation for the normalized signal field reads as : @xmath21 where we have introduced @xmath22 and the parameters @xmath23 here , @xmath19 is the output mirror reflectivity , @xmath24 is the frequency of the longitudinal cavity mode closest to the signal frequency @xmath25 and @xmath26 is a complex input field of frequency @xmath27 close to @xmath25 , normally known as the seeding . the usual mean - field limit procedure requires high reflectivity @xmath19 and involves an expansion in longitudinal fourier modes and the requirement that all terms , including the nonlinear one , are independent of the longitudinal variable @xmath3 . the @xmath28variation per pass of the resonated signal field , @xmath29 , can be neglected when it is affected by the average of the propagation of the pump and idler waves along the crystal @xcite , i.e. @xmath30 to obtain an explicit dependence of pump and idler fields along the direction of propagation we consider the first and third equations of the system ( [ propequ ] ) and neglect diffraction in the crystal : @xmath31 where the signal amplitude @xmath29 is now independent of @xmath3 . by taking the second derivative of ( [ eqn : s1 ] ) and using ( [ eqn : s2 ] ) , one obtains @xmath32 which shows that the pump field oscillates along the propagation direction with a frequency that depends on the signal intensity @xmath33 . integrating this equation we find @xmath34 where @xmath35 is the amplitude of the pump field at the entrance of the crystal @xcite . from ( [ eqn : s1 ] ) , @xmath36 in agreement again with @xcite . we can now calculate the spatial average ( [ average ] ) : @xmath37 and insert it into ( [ mfl2 ] ) : @xmath38 by expanding in longitudinal fourier modes and retaining only the longitudinal mode closest to @xmath25 , corresponding to @xmath39 , we finally obtain : @xmath40 \end{aligned}\ ] ] where @xmath41 finally , we renormalize the transverse space variables @xmath9 and @xmath10 by dividing them by @xmath42 , the time variable by multiplying it by @xmath43 and the field amplitudes according to @xmath44 to obtain @xmath45 the analysis of eq . ( [ sropo ] ) is the main focus of the research presented here . it will be referred to as the _ sinc@xmath0 model _ since @xmath46 . we note that in sropo configurations the frequency of the signal field , @xmath25 , is tuneable by corresponding changes of the idler frequency , @xmath47 , while maintaining the energy conservation condition @xmath48 . this means that with no external seeding ( @xmath49 ) the detuning @xmath50 is also zero since the sropo tunes its signal frequency to the closest longitudinal cavity mode @xmath24 . with an external seeding different from zero and detuned with respect to the cavity , it is advantageous to consider the external frequency @xmath27 as reference and introduce @xmath51 under these conditions @xmath26 should be considered to be real and equation ( [ sropo ] ) remains unchanged . it is interesting to investigate the behavior of the pump and idler fields inside the opo crystal as provided by eqs . ( [ e0 ] ) and ( [ e2 ] ) . figure [ fig : cp ] shows the pump and idler intensities during propagation for three sample values of @xmath52 , namely 1.2 , 2.0 and 8.0 . while at @xmath53 ( black lines ) the changes of pump and idler per pass are limited , for @xmath54 ( red lines ) and @xmath55 ( blue lines ) they are substantial . in particular , full pump depletion and substantial back - conversion of signal and idler fields into the pump are clearly visible in figure [ fig : cp ] for @xmath55 . in the sropo case these phenomena are not incompatible with the mean field approximation and are at the base of the sinc@xmath0 nonlinearity of model ( [ sropo ] ) . the mean field approximation implies that the signal intensity remains almost constant with respect to its input value during propagation in the @xmath1 medium with large changes taking place over several cavity round - trips . no such constrains apply to pump and idler fields as shown in fig . [ fig : cp ] . note that the cos@xmath0 and sin@xmath0 nature of the pump and idler intensities , respectively , guarantees conservation of the energy density in every point along the sropo crystal . energy conservation in turn guarantees the validity of the manley - rowe relations about the variations of the energy densities @xmath56 per field along the crystal : @xmath57 since @xmath58 . these facts are a - posteriori confirmations that the physical processes described in eqs . ( [ propequ ] ) are compatible with the application of the mean - field limit to the signal field even for large values of the pump and seeding intensities . close to the signal generation threshold it is possible to obtain partial differential equations in the mean - field limit where the nonlinear terms are in a polynomial form and thus easier to analyze . the scaling of the mean field limit requires that the nonlinear coefficient per pass , @xmath59 , has to be of the order of the mirror transmittivity , @xmath60 . this implies that the argument of the @xmath61 term in equation ( [ av2 ] ) may become large for large signal intensities without breaking the mean - field conditions . close to threshold , however , the signal intensity satisfies @xmath62 and the @xmath61 term can be approximated by a power expansion . in this case pump and idler display small changes per pass across the crystal meaning that pump depletion and back - conversion do not take place in a single pass . equations ( [ e0 ] ) and ( [ e2 ] ) , however , tell us that while the pump can be approximated to first order to a constant value @xmath35 , the idler has to grow along @xmath3 from its initial value . this is in agreement with previous analysis below threshold where the important noise term is associated with the idler fluctuations at the entrance of the crystal @xcite . in the case of sropos close to threshold , we can approximate @xmath63 and @xmath64 in ( [ e0 ] ) and ( [ e2 ] ) with @xmath65 by using these expressions to evaluate the average ( [ average ] ) one obtains : @xmath66 by repeating the same steps of the mean - field limit as described in the previous subsection we obtain : @xmath67 which describes the spatio - temporal behaviour of the sropo close to threshold in the presence of an external seeding @xmath26 and will be referred to as the _ cubic model_. as mentioned in section [ mfl ] , when there is no external seeding , @xmath49 , the detuning is zero since the sropo automatically adjusts its frequency to the closest cavity resonance . the plane wave steady - state intensities , @xmath68 , are implicit for the sinc@xmath0 model ( see @xcite ) and explicit for the cubic model : @xmath69 the steady - state signal intensity of the sropo as a function of the pump intensity , @xmath52 , is shown in figure [ fig : ss ] for the sinc@xmath0 model ( solid line ) and the cubic approximation ( dashed line ) . these are trivially complemented by the zero - intensity state that is stable below threshold , @xmath70 , and unstable above . in the cubic case the stationary intensity above threshold asymptotes to the value @xmath71 for large pump intensities and is always stable . the steady - state curve for the sinc@xmath0 model , on the other hand , becomes multivalued at large values of the input pump intensity ( @xmath72 , not shown here ) @xcite . here , however , we are interested in values of the pump intensity below @xmath73 , as these are more realistic with respect to present state - of - the - art of broad area sropo realisations . in this regime it is possible to prove that , above threshold , the non - zero steady - state intensities in the sinc@xmath0 model are also stable @xcite . note that when comparing the sinc@xmath0 and the cubic models , there is a substantial difference between their steady - state intensities even below @xmath74 . at twice above threshold this difference becomes considerable and the close to threshold ( cubic ) model has to be discarded . analogously to lasers , the field phase is decoupled from the steady - state equations and is affected by fluctuations and drift processes . when there is external seeding , @xmath75 , the phase of the sropo locks to that of the external beam , depending on the magnitude of the detuning @xmath50 and the input intensity . such behavior strongly differs from that of @xmath49 . in the case of @xmath76 the steady - state intensities are given by @xmath77\ ] ] where @xmath78 for the sinc@xmath0 and cubic models , respectively . the steady - state curves of the sropo intensity versus the input intensity become s - shaped , a behavior typical of injected optical systems , as shown in section [ tupf ] . for the cubic model without diffraction it is possible to obtain analytical results . for example , for @xmath79 the plane - wave steady - state curves are s - shaped , and the positions of the turning points @xmath80 $ ] and @xmath81 $ ] can be determined by finding the maxima and minima of ( [ sswseed ] ) : @xmath82 \ , .\ ] ] and then using these values in ( [ sswseed ] ) . at resonance , @xmath83 , the turning points are located at : @xmath84 & = & \left [ 0,3 ( |e_0|^2 - 1)/|e_0|^2 \right ] \\ \left[(e_{in}^2)^-,i_s^-\right ] & = & \left [ 4 ( |e_0|^2 - 1)^3 / ( 9 |e_0|^2 ) , \right . \nonumber \\ & & \left . ( |e_0|^2 - 1 ) / ( 3 |e_0|^2)\right ] \nonumber \ , .\end{aligned}\ ] ] note that the @xmath85 turning point at resonance corresponds to the zero seeding case of sropo intensity given by eq . ( [ ssnoin ] ) . the linear stability analysis of the steady - states given in the previous section produces two stability eigenvalues : @xmath86 where for the sinc@xmath0 model @xmath87 and for the cubic model @xmath88 for the sinc@xmath0 model , the stability eigenvalues are implicit functions of the steady - state intensity , @xmath68 . it is , however , easy to display the stability of the stationary states graphically along the s - shaped curves by picking increasing values of @xmath68 , evaluating @xmath89 and reporting the stability result on the diagram , as displayed in figures [ fig : pfe02_2 ] and [ fig : pfe02_8 ] . here black solid lines correspond to two negative real eigenvalues ( sinks ) , turquoise solid lines to stable complex eigenvalues ( foci ) , dot - dashed blue lines to at least one positive real eigenvalue ( saddles or sources ) and red dashed lines to complex eigenvalues with positive real part ( unstable foci ) . in terms of bifurcations , the intersection of a black solid line and a blue dot - dashed line signals a saddle - node bifurcation , while the transition of a turquoise solid line into a red dashed line signals a hopf bifurcation . we find that the turning points of the s - shaped curves always correspond to either saddle - node ( the @xmath90 $ ] points ) or saddle - source ( the @xmath91 $ ] points ) bifurcations corresponding to a change of sign of one real eigenvalue . for the cubic model this fact can be demonstrated analytically . in the lowest branch of the s - curve , the two real eigenvalues turn complex ( see the red dashed line in figures [ fig : pfe02_2 ] and [ fig : pfe02_8 ] ) . this means that the lowermost part of the s - curve is hopf unstable . ( color online ) plane wave steady - state stability and pattern formation for ( a ) the sinc@xmath0 model ( [ sropo ] ) of a sropo and ( b ) the cubic model ( [ sropob ] ) of a sropo close to threshold . the solid ( black ) , dot - dashed ( blue ) and dashed ( red ) lines correspond to stable , unstable and hopf unstable plane wave steady states , respectively . the black dotted ( black dashed ) lines correspond to the minimum and maximum of the intensity of stationary hexagonal ( roll ) patterns . the vertical dotted line corresponds to the instability of hexagons leading to optical turbulence . parameters are @xmath92 and @xmath93 . all variables are dimensionless . , title="fig:",scaledwidth=52.0% ] ( color online ) plane wave steady - state stability and pattern formation for ( a ) the sinc@xmath0 model ( [ sropo ] ) of a sropo and ( b ) the cubic model ( [ sropob ] ) of a sropo close to threshold . the solid ( black ) , dot - dashed ( blue ) and dashed ( red ) lines correspond to stable , unstable and hopf unstable plane wave steady states , respectively . the black dotted ( black dashed ) lines correspond to the minimum and maximum of the intensity of stationary hexagonal ( roll ) patterns . the vertical dotted line corresponds to the instability of hexagons leading to optical turbulence . parameters are @xmath92 and @xmath93 . all variables are dimensionless . , title="fig:",scaledwidth=52.0% ] in this section we describe instabilities of the stationary states of the sropo to transverse perturbations due to diffraction with and without external seeding . by moving to the spatial fourier space of the transverse wave - vector @xmath94 and repeating the linear stability steps of the previous section , we obtain the two stability eigenvalues of ( [ evalues ] ) but with the detuning @xmath50 replaced by @xmath95 which introduces an explicit dependence on the transverse spatial scale . we start with the analysis of possible turing instabilities without external seeding ( @xmath49 ) and with zero detuning @xmath83 . in this case , the evaluation of the stability eigenvalues with the appropriate factor ( [ thetak ] ) is done only at the values of @xmath68 given by ( [ ssnoin ] ) . in the cubic case the eigenvalues reduce to : @xmath96 the largest eigenvalue has a zero value for the plane - wave case , @xmath97 , corresponding to the uncoupled phase of the sropo models without seeding as studied in the previous section . for large wave - vectors the eigenvalues can become complex , i.e. one may observe damped oscillations . however , the presence of diffraction can not make the real part of the eigenvalues positive which means that , for the sropo alone , there are no spatio - temporal instabilities and hence no pattern formation . we obtain the same result for the sinc@xmath0 model within the pump intensity ranges studied here although the implicit nature of the steady - state ( [ ssnoin ] ) requires straightforward numerical evaluations of the stability eigenvalues for given wave - vectors @xmath94 . we now consider the case of external seeding where the detuning , @xmath50 , can be non - zero . by using the expressions ( [ evalues ] ) with @xmath50 replaced by @xmath98 ( [ thetak ] ) one observes that the transverse wave - vector can destabilise the system only when it counterbalances the detuning and that this is most effective when @xmath99 i.e. the off - resonance mechanism for pattern formation typical of optical systems @xcite . we refer to the off - resonance mechanism as turing pattern formation since it has been demonstrated that all the requirements of turing instabilities are fully satisfied @xcite . the condition ( [ offresonance ] ) provides us with the value along the steady - state curves at which we expect pattern formation to occur , @xmath100 . this value simply corresponds to the steady - state value of the plane wave solution at zero detuning ( [ ssnoin ] ) since for @xmath101 the stability eigenvalues ( [ evalues ] ) reduce to @xmath102 , where @xmath103 and @xmath104 are given by ( [ absinc ] ) for the sinc@xmath0 model and ( [ abcube ] ) for the cubic model . by tracing a horizontal line at the @xmath100 value on the diagrams of figures [ fig : pfe02_2 ] and [ fig : pfe02_8 ] one obtains the corresponding value of @xmath105 of the seeding intensity where the turing instability takes place . the bifurcation from the homogeneous states to steady transverse patterns is obtained when decreasing the seeded amplitude @xmath26 so that the locked plane wave state progressively approaches the upper turning point of the s - shaped steady - state curve ( the @xmath90 $ ] point ) . before reaching it , the stationary plane wave intensity reaches the value @xmath100 and a stationary roll pattern is formed supercritically while a hexagonal pattern is formed subcritically in agreement with @xcite . this bifurcation scenario is in agreement with early analysis of complex ginzburg - landau models in the presence of injection @xcite ) although our cubic model does not contain diffusion or purely imaginary nonlinearities . it is also in remarkable agreement with numerical simulations , as demonstrated in section [ num ] . we have also investigated instabilities of the plane wave to pattern structures for large values of both the input pump and the seeding intensity as shown in fig . [ fig : pfe02_8 ] . these instabilities have no counterpart in the close - to - threshold regime and can be estimated analytically by using the stability eigenvalues ( [ evalues ] ) with ( [ absinc ] ) and @xmath101 for the most unstable wave - vector ( [ offresonance ] ) . figure [ fig : lambdaplus ] shows the instability eigenvalue @xmath106 versus the stationary sropo intensity for different values of the input pump @xmath52 . above a threshold value of @xmath107 ( corresponding to a critical value of @xmath108 ) , there is a range of values of the sropo intensity where the plane wave solution is unstable to spatial patterns . the limit values of the sropo intensity are the zeroes of the @xmath106 curve shown in figure [ fig : lambdaplus ] with the lower ( upper ) intersection corresponding to an instability when increasing ( decreasing ) the seeding intensity . ( color online ) stability eigenvalue @xmath106 versus the sropo stationary intensity . parameters are @xmath109 , @xmath110 ( lowermost dashed - dotted blue line ) , @xmath111 ( solid black line ) , @xmath112 ( dashed black line ) , @xmath113 ( dotted black line ) , @xmath114 ( uppermost dashed - dotted black line ) and @xmath115 ( uppermost solid red line ) . all variables are dimensionless.,scaledwidth=50.0% ] in figure [ fig : instabregime ] we show the plane - wave instability range in the parameter space of the sropo intensity versus the seed intensity for different values of the pump intensity . in section [ num ] we show that the bifurcations at the boundaries of the instability ranges are subcritical in nature and that there are extended regions of bistability between patterns and stable plane waves to support cavity solitons . the ranges displayed in fig . [ fig : instabregime ] provide a minimum size of the parameter region where pattern formation is expected . for example , the plane - wave instability range for @xmath115 evaluated analytically from the stability eigenvalues is approximately between @xmath116 and @xmath117 ( see fig . [ fig : instabregime ] ) while the numerical simulations find stable patterns between @xmath118 and @xmath119 because of subcriticality ( see fig . [ fig : pfe02_8 ] ) . ( color online ) plane wave instability regions to spatial patterns in the ( seed intensity , sropo intensity ) parameter space . parameters are @xmath109 , @xmath111 ( solid black line ) , @xmath112 ( dashed black line ) , @xmath113 ( dotted black line ) , @xmath114 ( uppermost dashed - dotted black line ) and @xmath115 ( uppermost solid red line ) . all variables are dimensionless.,scaledwidth=50.0% ] we have first numerically integrated the sinc@xmath0 ( [ sropo ] ) and cubic ( [ sropob ] ) models for @xmath92 and @xmath93 . we have started with relatively large values of the seeding amplitude , @xmath120 , where the stable plane - wave solution has been recovered . by progressively decreasing @xmath26 , a supercritical roll pattern is observed to appear at around @xmath121 , @xmath122 for the sinc@xmath0 model and @xmath123 , @xmath124 for the cubic model , in excellent agreement with the theoretical predictions given in section [ tupf ] . by further decreasing the seeding intensity , the amplitude of the roll pattern increases ( see black dashed lines in fig . [ fig : pfe02_2 ] until it merges into a hexagonal structure . having located the hexagonal pattern ( see fig . [ fig : patterns ] ( a ) for its transverse intensity structure ) , we have traced it with increasing and decreasing values of the external seeding intensity . ( color online ) intensity of transverse patterns in a sropo . ( a ) hexagons for @xmath125 . ( b ) hexagons for @xmath116 . ( c ) rolls for @xmath126 . ( d ) honeycombs for @xmath127 . parameters are @xmath115 and @xmath109 . all variables are dimensionless.,scaledwidth=45.0% ] for small seeding intensities , figures [ fig : pfe02_2 ] and [ fig : pfe02_8 ] show the maximum and minimum intensity of the hexagonal pattern ( dotted lines ) and show that these change linearly with decreasing seeding intensity . the bifurcation back to the steady plane - wave solution is subcritical although the regime of sub - critical bistability is very small and difficult to detect on the scales of the diagrams . when further decreasing the external seeding , one observes a sudden destabilisation of the hexagonal pattern into a region of optical turbulence . the abrupt transition from stable patterns to turbulence is clearly displayed in figures [ fig : pfe02_2 ] and [ fig : pfe02_8 ] by the almost vertical line on the right hand side of these diagrams that corresponds to a sudden jump in the values of the minima and maxima intensities observed in the transverse section during the turbulent evolution . for larger values of the input pump , @xmath52 , new regions of pattern formation arise in the sropo with seeding in a way similar to what has been described for nascent optical bistability @xcite . these new regions can only be observed in the sinc@xmath0 model since the cubic model can only display stable plane wave solutions for large @xmath52 and large @xmath128 . moreover , the cubic model is not accurate away from threshold . for the numerical simulations presented here we have selected the value of @xmath115 where the minimum size of the pattern region is more than 15% of the maximum value of the seed intensity in order to guarantee relevance to possible experimental realizations . in fig . [ fig : pfe02_8 ] we present the intensities of the observed patterns together with the steady - state plane wave curves for the selected value of @xmath115 . at low seed intensities the phenomenology is similar to that described for @xmath92 above . however , at larger seeding intensities the upper branch of the s - shaped plane - wave steady - state curve suddenly increases . the steady - state first develops damped oscillations and then becomes unstable to a hopf bifurcation ( see dashed red lines around the seed intensity of 23 in figure [ fig : pfe02_8 ] ) . around such bifurcation , a new region of stationary patterns develops . we have identified rolls r ( solid lines ) , hexagons h@xmath129 ( dotted lines ) and honeycombs h@xmath130 ( dashed lines ) . the intensities of the different transverse patterns are displayed in figure [ fig : patterns ] . we note that none of the patterns observed at large input pumps and seeding intensities are present in the cubic model . finally , pattern bistability is observed between rolls and hexagons and rolls and honeycombs . when the seeding is small , the input energy is not sufficient to lock the sropo to the external laser . these unlocked regimes are typical of lasers with injected signals @xcite . the larger the detuning , @xmath50 , between the external laser and the sropo cavity , the larger the seed intensity necessary for locking . since the lower branch of the s - shaped steady - state curves is always hopf unstable for small seeding , one expects to observe dynamical regimes where locking and unlocking alternate in space and time . in comparison with purely temporal systems , the presence of transverse degrees of freedom elongates the locking region to lower values of the seeding intensity , as displayed in figures [ fig : pfe02_2 ] and [ fig : pfe02_8 ] where stable hexagons are observed well into the region where plane wave solutions are unstable . as the seeding intensity is decreased , unlocking eventually takes place and stable patterns develop defects @xcite that induce first phase and then amplitude instabilities . the resulting regime corresponds to optical turbulence since one observes a sudden ( exponential ) decrease of the spatio - temporal correlation function @xcite @xmath131 } { { \rm re}\left[\langle e({\bf r},t ) e^*({\bf r},t ) \rangle - \langle e({\bf r},t ) \rangle \langle e^*({\bf r},t ) \rangle \right]}\end{aligned}\ ] ] where @xmath132 and @xmath133 identify separate positions on the transverse plane , @xmath134 , @xmath135 denotes the real part and @xmath136 corresponds to temporal averages . such behavior is demonstrated in figure [ fig : corr ] where the correlation function @xmath137 is calculated for the hexagonal pattern ( dashed line ) , the turbulent regimes for @xmath92 ( solid line ) and @xmath115 ( dot - dashed line ) . fitting exponentials to the correlation functions shows that in the turbulent regimes the correlation length is reduced by at least a factor of six . in the regime of optical turbulence , large variations of the sropo intensity are observed in both space and time . in figures [ fig : pfe02_2 ] and [ fig : pfe02_8 ] we display the range of variation of the sropo intensity at a given time @xmath138 at the onset of optical turbulence . the wide increase in the maximum sropo intensity when changing the seed strength below the hexagon instability is clearly visible . to characterize the regime of optical turbulence we have considered the temporal evolutions of the maximum sropo intensity , the spatial average of the sropo intensity and its standard deviation . as displayed in figure [ fig : turb2and8 ] , the spatial statistics is large enough to guarantee probability distributions of well defined averages and deviations . larger values of the pump power increase the size of the probability distribution of the sropo intensity and that of the fluctuations of its maximum value ( compare figures [ fig : turb2and8](a ) and ( b ) ) . such increase results in the occurrence and propagation of transverse rogue waves . following the generally accepted definition of rogue waves in systems with injection @xcite , we plot the temporal evolution of @xmath139 corresponding to transverse pulse maxima , @xmath140 , above or below a threshold given by the average value of the intensity , @xmath141 , plus eight times the standard deviation , @xmath142 , of the sropo intensity for the sinc@xmath0 model in the dashed - dotted red lines of figures [ fig : turb2and8](a ) and ( b ) . the presence of peaks of a rogue wave is signalled by positive values of @xmath143 @xcite . with pump intensities a few times above threshold ( figure [ fig : turb2and8](a ) ) , the rogue wave test fails ( @xmath143 remains negative ) and the optical turbulence generated by the unlocking of the seed laser and the sropo is relatively mild . with larger values of the pump power , however , rogue waves are commonplace and affect the spatio - temporal evolution of the sropo field for long durations of the temporal evolution ( see figure [ fig : turb2and8](b ) ) . when comparing these results with those related to lasers with injections @xcite , we note that our simulations are fully spatio - temporal and show that the material dynamics , typical of semiconductor media , is not essential in the generation and maintenance of rogue waves during optical turbulence . the main mechanism underlying rogue waves in sropos is the absence of locking between master and slave devices leading to intermittent phase jumps . full investigations of optical turbulence in injected ( seeded ) optical devices will be presented elsewhere . finally , we have studied the presence and stability of cavity solitons ( cs ) in sropos with a particular focus on localised structures induced by the sinc@xmath0 nonlinearity , i.e. away from threshold and with large seeding from an external laser . cs have been described in a variety of opo devices without seeding from degenerate @xcite to non - degenerate triply resonant configurations @xcite . cs in degenerate opos have also been numerically extended to include the presence of seeding @xcite . in the case of the non - degenerate sropos investigated here , the resonance condition of sropo operation rules out any cs in the absence of seeding . it is then important to stress that all cs solutions described in this section are due to the external seeding field and have no counterpart in the case of @xmath49 . since we have introduced the sinc@xmath0 nonlinearity in spatio - temporal models of sropos to describe self - organization when pump depletion and back conversion take place , we focus here on cs in the limit of large pump powers . from figures [ fig : pfe02_8 ] and [ fig : instabregime ] we see that there are broad ranges of the parameter space where bistability between the plane wave solution and pattern structures is observed . for example , we find coexistent hexagons and homogeneous solutions for @xmath144 between 19.98 and 21.90 and coexistent honeycombs and homogeneous solutions for @xmath144 between 26.00 and 28.09 . note that we even observe tri - stability among plane waves , hexagons and rolls for @xmath144 between 21.25 and 21.90 and among plane waves , honeycombs and rolls for @xmath144 between 26.00 and 26.52 . in the two wide regions of homogeneous - pattern bistability we have been able to locate single peak ( bright ) and single trough ( dark ) cs as shown for example in figure [ fig : cs ] ( a ) and ( d ) , respectively . the onset and nature of these cs are again similar to those observed in nascent optical bistability @xcite . together with the single unit bright and dark cs we have also found many multi - peak @xcite and multi - trough localized structures that correspond to clusters of cs ( also referred to as localized patterns @xcite ) . a few examples of these bright and dark clusters are displayed in figure [ fig : cs ] . the range of existence of single unit cs and cs clusters is displayed in figure [ fig : csrange ] . snaking of both bright and dark cs is observed with stability branches of larger and larger clusters approaching the pattern stability lines in the parameter space ( see figure [ fig : csrange ] ) . the details of the bifurcations and of the number of branches of bright and dark cs for changing @xmath52 are too long to be described here and will be the subject of a future publication . ( color online ) stable bright ( a)-(c ) and dark ( d)-(f ) cs configurations of the sropo model ( [ sropo ] ) . parameters are @xmath115 , @xmath109 , @xmath145 for ( a)-(c ) , @xmath146 for ( d ) and @xmath147 for ( e)-(f ) . all variables are dimensionless . , scaledwidth=45.0% ] self - organization and pattern formation in opos has been known for a number of years in degenerate @xcite or doubly or triply resonant non - degenerate configurations @xcite . the case of a widely non - degenerate sropo has , however , been overlooked because of experimental limitations , now overcome , and the fact that off - resonance operation is inhibited because of its intrinsic tuneability . here we have shown that under the action of a detuned injection close to the signal frequency , one can find an extremely rich variety of self - organized structures , from regular co - existing patterns to clusters of cs and even optical turbulence . in particular , we have derived mean field models for sropos with external seeding and shown that , away from threshold , cubic nonlinearities should be replaced by sinc@xmath0 terms . the sinc@xmath0 nonlinearity is capable of describing regimes of pump depletion and back - conversion . in these regimes , the external seeding generates hexagonal , roll and honeycomb patterns as well as bright and dark cs . note that cs in sropos offer positional control associated to the generation of entangled photons with vastly different frequencies . in contrast to laser systems , the fast material dynamics of @xmath1 media makes a sropo with external seeding an ideal candidate for comparisons between theory and experiments of optical self - organization . the fast material dynamics is also beneficial to the investigation of spatio - temporal structures in the regime of short pulse generation where many of the results presented here can find useful extensions . these investigations together with the full characterization of the turbulent regimes will be the subject of future communications . we thank j. lega for useful discussions . we acknowledge financial support from the eu grant hideas . amy acknowledges financial support from the uk engineering and physical sciences research council ( epsrc ) . c. bonatto , m. feyereisen , s. barland , m. giudici , c. masoller , j. r. rios leite and j. r. tredicce , phys . lett . * 107 * , 053901 ( 2011 ) ; j. zamora - munt , b. garbin , s. barland , m. giudici , j. r. rios leite , c. masoller and j. r. tredicce , phys . a * 87 * , 035802 ( 2013 ) .

spatio - temporal dynamics of singly resonant optical parametric oscillators with external seeding displays hexagonal , roll and honeycomb patterns , optical turbulence , rogue waves and cavity solitons . we derive appropriate mean - field equations with a sinc@xmath0 nonlinearity and demonstrate that off - resonance seeding is necessary and responsible for the formation of complex spatial structures via self - organization . we compare this model with those derived close to the threshold of signal generation and find that back - conversion of signal and idler photons is responsible for multiple regions of spatio - temporal self - organization when increasing the power of the pump field .

SANTA CLARA, Calif. -- San Francisco 49ers linebacker Aldon Smith was charged Wednesday with three felony counts of illegal possession of an assault weapon in a case stemming from a party at his home in June 2012. The Santa Clara County district attorney's office said in announcing the charges that Smith, 24, is expected to surrender later this month. He is on an indefinite leave of absence from the defending NFC champion 49ers while undergoing treatment for substance abuse at an in-patient facility following a DUI arrest Sept. 20. "We've been aware of the incident, the serious nature of it. We're all accountable for our actions, good and bad," 49ers coach Jim Harbaugh said Wednesday. "There's a process, due process, that will take place. I don't feel any need to comment further on it." When asked whether Smith -- who set a franchise record with 19.5 sacks last season -- would play again this season, Harbaugh said only, "I don't have any need to further comment on it." On Monday, the coach said he had traded a few text messages with Smith, saying, "Heard that things are going very well, very positive reports back." If convicted, Smith could face up to four years and four months in jail, the district attorney's office said. "The preamble to the assault weapons law states that each assault weapon 'has such a high rate of fire and capacity for firepower that its function as a legitimate sports or recreational firearm is substantially outweighed by the danger that it can be used to kill and injure human beings,'" District Attorney Jeff Rosen said. "California's prohibition of these powerful weapons is not about hunting or target practice. It is about interrupting the long history of death, carnage and grief assault weapons have inflicted on California communities." Smith also is likely to face a suspension from the NFL, perhaps pushed back to next season or after his legal issues are resolved. "The 49ers organization is aware of the recent developments with Aldon arising from an incident at his home in 2012," the team said in a statement Wednesday. "We recognize the serious nature of this situation, as does Aldon, and will continue to monitor it closely. As this is an ongoing legal matter, we will have no further comment." Last month, Smith and former teammate Delanie Walker were named in a lawsuit filed in Santa Clara County Superior Court by a Northern California man who said he was shot at a party at Smith's house on June 29, 2012. [+] Enlarge Jeff Gross/Getty Images Aldon Smith has been charged with three felony counts of illegal possession of an assault weapon, stemming from a party at his home in June 2012. The players charged a $10 admission and $5 per drink, the lawsuit said. Smith and now-Tennessee Titans tight end Walker, 29, were allegedly intoxicated when they fired gunshots into the air off a balcony while trying to end the party, the lawsuit said. Walker will not be charged, deputy district attorney Brian Buckelew told The (Nashville) Tennessean. "Delanie Walker did not shoot one of the assault weapons. Delanie Walker did shoot a handgun, and that was after gang members had already started shooting at Aldon's garage," Buckelew told the newspaper. "So the purpose of Delanie Walker shooting up in the air was to try and get the gang members out of there. It could be viewed as self-defense, or a reasonable means to try and dissipate a crazy situation." Before the 49ers' 2012 home opener last September, Smith was a passenger in a car during an accident in Santa Clara County in which the driver swerved to avoid hitting a deer. Smith sustained a cut beneath his right eyebrow. He apologized and insisted he had grown up. Smith, selected seventh overall in the 2011 draft out of Missouri, had previously been arrested on suspicion of DUI in January 2012 in Miami shortly after the 49ers lost in the NFC title game. He is on the reserve non-football injury list while in rehab, and there is no NFL minimum for number of games he must miss while on the list. Smith played in a 27-7 home loss to the Indianapolis Colts on Sept. 22 and had five tackles just two days after he was arrested and jailed on suspicion of DUI. Smith apologized for his behavior after the game. Information from The Associated Press was used in this report. ||||| 49er Aldon Smith hit with felony gun charges 49ers linebacker Aldon Smith had his off-field troubles deepen Wednesday when he was charged with illegally possessing three assault weapons he bought over the counter in Arizona - including two rifles he allegedly purchased a day before a road game in 2011 during his rookie season. Santa Clara County prosecutors also charged Smith with misdemeanor drunken driving Wednesday in connection with a Sept. 20 crash in San Jose - an incident that reportedly prompted him to enter a treatment facility and step away from the team indefinitely. Smith, 24, is expected to surrender this month to face the felony gun charges filed in county Superior Court. If convicted, he could face a sentence ranging from no time in custody to four years and four months behind bars, authorities said. How the cases will affect Smith on the field remains unknown. In the past, NFL players have returned to successful careers after convictions for criminal charges including drug dealing, obstruction of justice and dogfighting. The three gun counts leveled against Smith stem from a party at his house in the foothills east of San Jose during which he was stabbed and two people were shot. Investigators who responded to the violence and searched the rented home found the prohibited firearms, according to Santa Clara County prosecutors. window._taboola = window._taboola || []; _taboola.push({ mode: 'thumbnails-c', container: 'taboola-interstitial-gallery-thumbnails-3', placement: 'Interstitial Gallery Thumbnails 3', target_type: 'mix' }); _taboola.push({flush: true}); Photo: Associated Press Image 1 of / 3 Caption Close Image 1 of 3 In a photo provided by the San Jose Police Department, San Francisco 49ers linebacker Aldon Smith appears in a booking photo. Smith was arrested Friday Sept. 20, 2013, in San Jose, Calif., on suspicion of driving under the influence and marijuana possession, authorities said. (AP Photo/San Jose Police Department) less In a photo provided by the San Jose Police Department, San Francisco 49ers linebacker Aldon Smith appears in a booking photo. Smith was arrested Friday Sept. 20, 2013, in San Jose, Calif., on suspicion of ... more Photo: Associated Press Image 2 of 3 49ers linebacker Aldon Smith also has been charged with misdemeanor drunken driving for a Sept. 20 crash in San Jose. 49ers linebacker Aldon Smith also has been charged with misdemeanor drunken driving for a Sept. 20 crash in San Jose. Photo: Marcio Jose Sanchez, Associated Press Image 3 of 3 49er Aldon Smith hit with felony gun charges 1 / 3 Back to Gallery More than 100 people were at the party on June 29, 2012, but Smith decided to end it after someone brandished a gun at a bartender, prosecutors said. Smith told a group of guests to leave and was closing his garage door when someone fired three shots that lodged in the back of the garage, investigators said. Smith went to a bedroom, retrieved a .45-caliber handgun and fired a shot into the air, authorities said. He reopened the garage door, but people were still congregating outside. Prosecutors said that as Smith walked out of the garage, someone uttered a "gang slur," prompting Smith to tell the group, "This is my house. I'm Aldon Smith." The visitors still did not leave, and some told Smith that they didn't care who he was, authorities said. A partygoer, Steven Barba, 27, then allegedly used a knife to stab Smith twice. Barba has been charged with assault, gun possession and gang enhancements. Delanie Walker, a former 49ers tight end who also was at the party, then fired the same .45-caliber handgun into the air, authorities said. Another person returned fire, striking two guests, Ronndale Esporlas and Aaron Reyes, who suffered serious injuries and are suing Smith and Walker, who now plays for the Tennessee Titans. As this was happening, someone went into Smith's bedroom, removed an assault weapon and "carried it around the party," investigators said. After the party, sheriff's deputies searched the home and found five weapons, including four rifles, as well as "several additional large-capacity magazines strewn about the floor of Smith's bedroom." There was expended and unexpended ammunition in a bedside table, authorities said. None of the five weapons was registered with the state Department of Justice, investigators said, and three rifles were determined to be illegal assault weapons under California law. Prosecutors described those three guns as an Armalite AR10-T .308-caliber rifle, a Bushmaster ACR chambered for 5.56mm NATO cartridges and a Bushmaster Carbon 15 .223-caliber rifle. Investigators determined that Smith had purchased the three firearms in Arizona in 2011. He bought two of them from a gun dealer in Phoenix on Dec. 10, 2011, the day before the 49ers played the Arizona Cardinals in Glendale, investigators said, adding that even if the weapons were purchased in Arizona by an Arizona resident, the weapons are illegal to possess in California. Under California's assault-weapons ban, enacted in 1989, certain models of semiautomatic rifles and pistols are prohibited - as well as others with certain characteristics. For example, guns with detachable magazines can't have any of a number of features that give them added functions or make them easier to handle, such as forward grips and folding stocks. Regulators say looser gun-buying laws in Nevada, Arizona and other nearby states allow many forbidden weapons to be brought into California. In the drunken-driving case, Smith allegedly crashed his car into a tree while driving with a blood-alcohol level of 0.15 percent, nearly twice the legal limit. Prosecutors charged him Wednesday with two misdemeanor counts of drunken driving and accused him of driving with a false license plate, an infraction. 49ers head coach Jim Harbaugh said Wednesday, "We're all accountable for our actions, good and bad." In a statement , 49ers officials said they were aware of the developments. "We recognize the serious nature of this situation, as does Aldon, and will continue to monitor it closely," the team said. "As this is an ongoing legal matter, we will have no further comment."

– Embattled 49ers star Aldon Smith has been charged with three counts of illegally possessing assault weapons, stemming from a party-turned-shootout at his San Jose-area abode last year. According to prosecutors, Smith, 24, was hosting upward of 100 people at his home last June when someone pulled a gun on the party's bartender, the San Francisco Chronicle reports. Smith decided it was time to break up the party—and toward that end, fired a .45 caliber handgun into the air. Far from taking the hint, the partygoers refused to leave; one instead pulled a knife and stabbed Smith twice. Smith's then-teammate Delanie Walker grabbed Smith's gun and fired it in the air again—only this time another person shot back, hitting two guests. When police arrived, they found five guns, including assault rifles, which are illegal in California, and high-capacity magazines. Smith is expected to surrender himself later this month; he's already on an indefinite leave of absence from the 49ers thanks to a drunk driving incident, according to ESPN.

the possibility of pion condensation in nuclear medium was suggested by a. b. migdal for the first time in the 1970s @xcite . thereafter , many studies @xcite of `` in - medium '' pion properties have been performed due to the important consequences in subnuclear physics @xcite , in the physics of neutron stars @xcite , supernovas @xcite , and the heavy ion collisions @xcite . these analysis considered the pion as an elementary object but we know that they can be considered as nambu - goldstone bosons generated by chiral symmetry breaking . hence the internal structure and the mass of the pion can be sensitive to the quantum chromodynamics ( qcd ) vacuum modifications in the finite density environment @xcite ; moreover the finite baryon density , and even the isospin density arising from the neutrality condition , can modify the structure of the qcd ground state , and it can in turn produce significant modifications of the pion properties in the medium . in this work @xcite , we present the possibility of a charged pion ( @xmath5 ) condensation starting from a _ microscopic _ model which is built with quarks as the constituents of pions , and which exhibits chiral symmetry restoration at the finite quark chemical potential @xmath6 or temperature @xmath7 . we derive an appropriate criterion for @xmath5 condensation , that we use to show the fragility of the @xmath5 condensation with respect to explicit chiral symmetry breaking via a finite current quark mass . the conditions for the onset of @xmath5 condensation at finite density are investigated using the nambu jona - lasinio ( njl ) model of qcd . we find that the threshold for @xmath5 condensation for noninteracting elementary pion gas is @xmath8 ( @xmath9 ) for positive ( negative ) @xmath10 , where @xmath10 is the electric chemical potential and @xmath4 the in - medium pion mass . finally , we clarify the effect of the current quark mass in the electrically neutral ground state , and the effect of a non - vanishing @xmath10 in presence of a finite current quark mass . based on these analyses , we conclude that @xmath5 condensation is forbidden in realistic neutral quark matter within this effective model . the njl lagrangian of the model is given for a two - flavor quark matter at a finite chemical potential @xcite @xmath11~ , \label{eq : lagr}\end{aligned}\ ] ] here @xmath12 denotes the electron field , and @xmath13 is the quark spinor with dirac , color and flavor indices ( implicitly summed ) . the bare quark mass is @xmath14 and @xmath15 the coupling constant . the electrical chemical potential @xmath10 is necessary to keep the system electrically neutral @xcite , while @xmath16 serves as the isospin chemical potential in the hadron sector , @xmath17 . the quark chemical potential matrix @xmath18 is defined in flavor - color space as @xmath19 , where @xmath20 denotes the identity matrix in color space , @xmath6 is the quark chemical potential related to the conserved baryon number . in the mean field approximation ( mfa ) , we examine the possibility that the ground state develops condensation in the @xmath21 and/or @xmath22 channels , where @xmath23 denotes the pauli matrices . due to the absence of driving forces , we find @xmath24 is always zero . for convenience we denote @xmath25 and @xmath26 . in the numerical analyses , we have fixed @xmath27 mev and @xmath28 so that the model reproduces @xmath29 mev , @xmath30 , and @xmath31 mev in the vacuum with @xmath32 mev . the pion condensation `` in the vacuum '' ( @xmath33 ) has been investigated with the chiral perturbation approach @xcite and within njl model @xcite . in both studies the threshold for the onset of the condensation is found to be @xmath34 , i.e. , when the absolute value of the electric chemical potential equals the vacuum pion mass . we now consider neutral quark matter at @xmath35 and @xmath36 and we want to study the relation between the threshold of @xmath5 condensation at finite density and the in - medium pion masses in the neutral ground state ( for further recent studies at finite baryon and/or isospin chemical potential see also refs . @xcite ) . in ref . @xcite , it is shown that at the physical point @xmath32 mev , there is no room for @xmath5 condensation in the neutral phase ( similar results obtained also in ref . even though the picture changes when the current mass is lowered , for our discussion it is enough to state that we consider a current quark mass of the order of 10 kev . in fig . [ fig : masse ] we plot @xmath37 and @xmath38 in the neutral phase as a function of @xmath6 . in this figure @xmath39 , @xmath40 denote the in - medium pion masses defined by the poles of the pion propagators in the rest frame , computed in the randomt phase approximation ( rpa ) to the bethe - salpeter ( bs ) equation . the positive and negative solutions of the bs equation in @xmath41 corresponds to the excitation gaps for @xmath42 and @xmath43 , which are @xmath44 and @xmath45 , respectively . from fig . [ fig : masse ] we notice that the transition to the pion condensed phase is of second order and it occurs at the point where @xmath46 . for a more detailed mathematical discussion of the numerical results shown in fig . [ fig : masse ] we refer to @xcite . , the pion condensate @xmath38 , and meson masses as a function of @xmath6 at @xmath36 in the neutral phase for a toy value of the current quark mass @xmath47 kev.,width=264 ] in the past years , a large number of the analysis about @xmath5 condensation have been performed in the chiral limit . in this section we investigate the role of the finite current quark mass in @xmath5 condensation . in order to do this , we set the cutoff @xmath49 and the coupling @xmath15 to the values specified above and we treat @xmath0 as a free parameter . as a consequence , the pion mass at @xmath50 , @xmath51 in the following , is a free parameter as well . plane.,width=264 ] in fig . [ fig : phasempi ] we report the phase diagram in @xmath52 plane in the neutral case . the solid line represents the border between the two regions where chiral symmetry is broken and restored . the bold dot is the critical endpoint of the first order transition . the shaded region indicates the region where @xmath5 condensation occurs . in the chiral limit @xmath53 our results are in good agreement with those obtained in ref . indeed , there exist two critical values of the quark chemical potential , @xmath54 and @xmath55 , corresponding to the onset and vanishing of @xmath5 condensation , respectively . when the current quark mass increases , a shrinking of the shaded region occurs till the point @xmath56 for @xmath57 , corresponding to a current quark mass of @xmath58 . hence the gapless @xmath5 condensation is extremely fragile with respect to the symmetry breaking effect of the current quark mass . plane at @xmath32 mev.,width=264 ] as a final investigation , in fig . [ fig : phasediag ] we report the phase diagram of quark matter in the @xmath59 plane when the current quark mass is tuned to @xmath32 mev . at each value of @xmath59 we compute the chiral and pion condensates by minimization of the thermodynamical potential . the solid line represents the first order transition from the @xmath5 condensed phase to the chiral symmetry broken phase without the @xmath5 condensate . the bold dot is the critical endpoint for the first order transition , after which the second order transition sets in . the dashed line indicates the first order transition between the two regions where chiral symmetry is broken and restored , respectively . the dot - dashed line is the neutrality line @xmath60 which is obtained by requiring the global electrical neutrality condition , @xmath61 . the neutrality line manifestly shows the impossibility of finding a @xmath5 condensate , in this physical situation . we have studied the pion condensation in two - flavor neutral quark matter using the nambu jona - lasinio model of qcd at finite density . we have investigated the role of electric charge neutrality , and explicit symmetry breaking via quark mass , both of which control the onset of the charged pion condensation . we show that the equality between the electric chemical potential and the `` in - medium '' pion mass , @xmath62 , as a threshold , persists even for a composite pion system in the medium , provided the transition to the pion condensed phase is of the second order ( the same qualitative picture has been found also in a recent analysis in the massive gross - neveu model @xcite ) . moreover , we have found that the pion condensate in neutral quark matter is extremely fragile to the symmetry breaking effect via a finite current quark mass @xmath0 , and is ruled out for @xmath0 larger than the order of 10 kev . a final comment is in order . in this study the contribution to finite baryon density comes only from the constituent quarks and not from nucleons . the presence of nucleons may make the pion condensation even less favorable . the reason can be found in the tomozawa - weinberg pion - nucleon interaction , which is isospin odd , giving rise to a repulsive pion self - energy at the physical situation where the neutron density is larger than the proton density ( see ref . @xcite ) . for this reason an interesting investigation may consider the pion condensation with the presence of nucleon degrees of freedom within njl model ( see ref . @xcite for useful prescriptions ) . sawyer , phys . * 29 * , 382 ( 1972 ) ; d.j . scalapino , phys . * 29 * , 386 ( 1972 ) . g. baym and d.k . campbell in : _ mesons and nuclei _ , v. 3 , eds . m. rho and d. wilkinson ( north holland , 1979 ) . j. b. hartle , r. f. sawyer and d. j. scalapino , astrophys . j. * 199 * , 471 ( 1975 ) ; a. b. migdal , g. a. sorokin , o. a. markin and i. n. mishustin , phys . b * 65 * , 423 ( 1976 ) ; o. maxwell , g. e. brown , d. k. campbell , r. f. dashen and j. t. manassah , astrophys . j. * 216 * , 77 ( 1977 ) ; a. ohnishi , d. jido , t. sekihara and k. tsubakihara , phys . c * 80 * , 038202 ( 2009 ) . h. abuki , m. ciminale , r. gatto , n. d. ippolito , g. nardulli and m. ruggieri , phys . d * 78 * , 014002 ( 2008 ) ; h. abuki , m. ciminale , r. gatto , g. nardulli and m. ruggieri , phys . d * 77 * , 074018 ( 2008 ) ; h. abuki , r. anglani , r. gatto , g. nardulli and m. ruggieri , phys . d * 78 * , 034034 ( 2008 ) . d. ebert and k. g. klimenko , arxiv:0911.1944 [ hep - ph ] . m. matsuzaki , arxiv:0909.5615 [ hep - ph ] ; j. o. andersen , l. t. kyllingstad and k. splittorff , arxiv:0909.2771 [ hep - lat ] ; h. abuki , r. gatto and m. ruggieri , phys . d * 80 * , 074019 ( 2009 ) ; d. ebert and k. g. klimenko , arxiv:0902.1861 [ hep - ph ] ; h. abuki , t. brauner and h. j. warringa , eur . j. c * 64 * , 123 ( 2009 ) .

we have studied the phenomenology of pion condensation in 2-flavor neutral quark matter at finite density with nambu jona - lasinio ( njl ) model of qcd . we have discussed the role of the bare quark mass @xmath0 and the electric chemical potential @xmath1 in controlling the condensation . the central result of this work is that the onset for @xmath2-condensed phase occurs when @xmath3 reaches the value of the in - medium pion mass @xmath4 provided the transition is of the second order , even for a composite pion system in the medium . finally , we have shown that the condensation is extremely fragile with respect to the explicit chiral symmetry breaking via a finite current quark mass .

helium is the second most abundant element in the universe , and its emission and opacity help determine the structure of any interstellar cloud . its abundance relative to hydrogen can be measured within a few percent since the emissivities of h i and he i lines have similar dependences on temperature and density . this makes it an indicator of both stellar and primordial nucleosynthesis ( pagel 1997 ) . a good discussion of the history of calculations of the helium recombination spectra is given by benjamin , skillman , & smits ( 1999 , hereafter bss99 ) , who present new calculations - the current standard in the field . yet much progress has been made since the work by smits ( 1991 , 1996 ) upon which the bss99 results depend . we implement these improvements , present a new set of predictions , and compare our results with those of bss99 . the differences are large enough to impact continuing attempts to estimate the primordial helium abundance ( peimbert _ et al _ 2002 ) . the basic physical processes have been described by brocklehurst ( 1972 ) and bss99 . here we will describe the differences between bss99 and our new numerical representation of the helium atom , which is a part of the spectral simulation code cloudy ( ferland _ et al _ 1998 ) . this model resolves all terms , @xmath0 , up to an adjustable maximum principal quantum number @xmath1 , followed by a pseudolevel , @xmath2 , in which all @xmath3 terms are assumed to be populated according to statistical weight and collapsed " into one . we set recombinations into the collapsed level equal to the convergent sum of recombinations from @xmath4 to @xmath5 . in the low - density limit , the collapsed level increases the emissivities of our benchmark lines ( the same 32 lines given in bss99 ) by 0.4% , on average , with @xmath1=100 . the decays from states with @xmath6 are most sensitive to this correction for system truncation . the strong optical line @xmath7 is corrected upward by 1.3% . at finite densities collisional processes force the populations of very highly excited states into local thermodynamic equilibrium ( lte ) . in this case the adequacy of the method used to compensate for truncation is unimportant . we find the corrections negligible for @xmath8 @xmath9 and @xmath1=100 . consequently , the uncertainties in the results presented in section 3 are due to the uncertainties in atomic data , especially the often substantial uncertainties in collisional rates affecting terms not in lte at given conditions . there are several differences in atomic data for radiative processes between bss99 and the present work . the transition probabilities and radiative recombination coefficients are obtained from oscillator strengths and photoionization cross - sections . bss99 uses the oscillator strengths calculated by kono & hattori ( 1984 ) . while these agree very well with the essentially exact oscillator strengths of drake ( 1996 ) , drake presents a much larger set , up to and including @xmath10=10 and @xmath11=7 , which we adopt . hummer & storey ( 1998 , hereafter hs98 ) have presented _ ab initio _ calculations of threshold photoionization cross - sections up to @xmath10=4 . bss99 uses cross - sections from topbase ( cunto , 1993 ) , while we use the more accurate hs98 values . the dominant remaining uncertainties in radiative data are in oscillator strengths involving low @xmath11 states ( with @xmath12 ) and photoionization cross - sections for low @xmath11 states ( with @xmath13 ) . hs98 also illustrates the method , originally discussed by seaton ( 1958 ) , of calculating threshold photoionization cross - sections by extrapolating absorption oscillator strengths to the threshold energy of a given level . this method has been used in the present work , based on the oscillator strengths from drake , to extend the _ ab initio _ cross - sections of hs98 to greater @xmath10 . differences in collisional data between bss99 and the current work are also significant . for low-_n _ transitions for which there are _ ab initio _ calculations , bss99 uses the collision strengths of sawey & berrington ( 1993 ) . we replace these , where available , with the results of the close - coupling calculation by bray _ et al _ ( 2000 ) , which include continuum states not considered in the @xmath14-matrix calculations by sawey & berrington . for _ l_-changing collisions bss99 uses two different treatments : seaton ( 1962 , hereafter s62 ) for low-@xmath11 transitions , and pengelly & seaton ( 1964 , hereafter ps64 ) otherwise neither of these treatments allows for angular momentum transfers greater than one unit , and both apply when the projectile velocity is greater than the velocity of the bound electron . the r.m.s . electron and projectile velocities in conditions considered by bss99 , assuming proton colliders , are @xmath15 where @xmath16 is the fine structure constant , _ c _ is the speed of light , and @xmath17 is the screened nuclear charge . dividing the latter by the former , we arrive at the expected value of the reduced velocity as a function of temperature and principal quantum number @xmath18 for typical nebular temperatures this reduced velocity will be of order or less than unity for proton colliders for all @xmath19 150 ; the treatment of ps64 is applicable only for greater @xmath10 , and it greatly overestimates _ l_-mixing cross - sections when used outside its range of validity ( macadam , rolfes , & crosby 1981 ) . vrinceanu & flannery ( 2001 , hereafter vf01 ) give a ( classical ) theory of _ l_-changing collisions and claim exact solutions in the limit that the intrashell transition is induced by slow distant collisions . their treatment allows naturally for angular momentum changes greater than unity . ( at a sufficiently high reduced velocity large angular momentum transfers are strongly suppressed and the theory goes to the optically allowed limit with which ps64 is concerned . ) we use equation 41 of kazansky & ostrovsky ( 1996 ) for the angle , @xmath20 , swept out by the projectile . a physical basis for the necessary large impact parameter cutoff in the theory follows from equating the stark and quantum - defect precession frequencies . the stark frequency is given by @xmath21 and the quantum - defect precession frequency ( hezel _ et al _ 1992 ) is given by @xmath22 where _ _ @xmath23__@xmath24 is the quantum defect , @xmath25 is the charge of the projectile and @xmath26 is the impact parameter . by setting @xmath27 equal to @xmath28 , we obtain a maximum impact parameter , @xmath29 . the electron orbit precession will be faster than the stark beating at larger impact parameters , so that transitions are increasingly less likely . to insure symmetry , we use the average @xmath27 of the initial and final levels . we use vf01 for @xmath11-changing collisions involving initial and final levels with @xmath30 , and like bss99 we use the impact parameter treatment of s62 for @xmath11-change from @xmath31 , @xmath32 , and @xmath33 levels . we use electron , proton and he@xmath34 colliders for all transitions , taking @xmath35 = 0.1 @xmath36 and @xmath37 = @xmath36 + @xmath35 . since s62 , which describes electron collisions , is based upon the method of virtual quanta ( see jackson 1999 ) , we can readily adapt it for the positive - ion collisions : the power spectrum of the time - dependent fields generated at the target atom by a passing charged projectile depends only on the projectile s charge magnitude , speed ( not kinetic energy or mass separately ) and impact parameter . the same considerations apply to ps64 and vf01 and have been implemented to allow for all three collider species . in calculating the necessary thermal averages we have assumed that the same temperature characterizes electrons , protons and he@xmath34 ions . figure [ vf_vs_ps ] compares emissivities we predicted using the vf01 and ps64 theories . the predicted emissivities typically change by about 1% for nebular densities by using the theory of vf01 rather than that of ps64 . the difference is much greater at high densities found , for example , in parts of quasars . in figure [ comp_w_bss ] we compare our results with those of bss99 for the case @xmath38 k and @xmath39 @xmath40 . the average difference for the 32 emission lines is 4.6% . the greatest difference is for @xmath414121 , for which our emissivity is 25% greater . in general , agreement worsens with increasing density ; at @xmath42 @xmath40 , the average and greatest differences are 1.6% and 6.4% , respectively , while at @xmath43 @xmath40 , we find differences of 7.0% and 35% . agreement also worsens with increasing temperature . table [ tab1 ] presents emissivities for all of the temperatures and densities considered by bss99 . we believe that these results are a significant improvement . the application of these results to specific astrophysical problems will be the subject of future papers . we thank g. w. f. drake for making available extensive tables of his calculations , d. vrinceanu and m. j. cavagnero for helpful discussions , and p. j. storey , whose constructive criticisms helped us to significantly improve our work . we also acknowledge support from nasa grant nag5 - 12020 and nsf grant ast 0307720 . benjamin , r. a. , skillman , e. d. , & smits , d. p. 1999 , apj 514 , 307 bray , i. , burgess , a. , fursa , d. v. , & tully , j. a. , 2000 , a&as 146 , 481 - 498 brocklehurst , m. 1972 , mnras 157 , 211 cunto , w. , mendoza , c. , ochsebein , f. , & zeippen , c. j. 1993 , a&a 275 , l5 drake , g. w. f. 1996 , in atomic , molecular , & optical physics handbook , ed . g. w. f. drake ( new york : aip press ) , 154 . ( actual oscillator strengths taken from tables received via private communication from drake . ) ferland , g. j. , korista , k. t. , verner , d. a. , ferguson , j. w. , kingdon , j. b. , & verner , e. m. 1998 , pasp 110 , 761 - 778 hezel , t. p. , burkhardt , c. e. , ciocca , m. , he , l - w . , & leventhal , j. j. 1992 , am . 60 , 329 hummer , d. g. & storey , p. j. 1998 , mnras 297 , 1073 jackson , j. d. 1999 , classical electrodynamics , 3rd edition ( new york : john wiley & sons ) kazansky , a. k. & ostrovsky , v. n. 1996 , jphysb : at . 29 , 3651 kono , a. & hattori , s. 1984 , physreva 29 , 2981 macadam , k. b. , rolfes , r. , & crosby , d. a. 1981 , physreva 24 , 1286 pagel , b. e. j. 1997 , nucleosynthesis and chemical evolution of galaxies , ( cambridge ; cambridge university press ) peimbert , a. , peimbert , m. , & luridiana , v. 2002 , apj 565 , 668 pengelly , r. m. , & seaton , m. j. 1964 , mnras 127 , 165 sawey , p. m. j. , & berrington , k. a. 1993 , adndt 55 , 81 seaton , m. j. 1958 , mnras 118 , 504 seaton , m. j. 1962 , proc . 79 , 1105 smits , d. p. 1991 , mnras 248 , 193 smits , d. p. 1996 , mnras 278 , 683 vrinceanu , d. & flannery , m. r. 2001 , physreva 63 , 032701 rlrrrrrrrrr 2945 & & 0.4142 & 0.4261 & 0.4567 & 0.2687 & 0.2816 & 0.2958 & 0.1648 & 0.1987 & 0.2112 + 3187 & & 0.8693 & 0.8950 & 0.9594 & 0.5617 & 0.6119 & 0.6507 & 0.3432 & 0.4584 & 0.4963 + 3614 & & 0.1115 & 0.1151 & 0.1241 & 0.0691 & 0.0717 & 0.0752 & 0.0397 & 0.0471 & 0.0496 + 3889 & & 2.2452 & 2.3261 & 2.5038 & 1.4116 & 1.6794 & 1.8348 & 0.8315 & 1.3332 & 1.4859 + 3965 & & 0.2280 & 0.2353 & 0.2532 & 0.1409 & 0.1471 & 0.1543 & 0.0807 & 0.0966 & 0.1020 + 4026 & & 0.5279 & 0.5427 & 0.5866 & 0.2917 & 0.3029 & 0.3175 & 0.1457 & 0.1782 & 0.1896 + 4121 & & 0.0341 & 0.0348 & 0.0363 & 0.0249 & 0.0300 & 0.0323 & 0.0184 & 0.0338 & 0.0379 + 4388 & & 0.1411 & 0.1453 & 0.1568 & 0.0772 & 0.0798 & 0.0834 & 0.0380 & 0.0445 & 0.0468 + 4438 & & 0.0145 & 0.0149 & 0.0157 & 0.0101 & 0.0111 & 0.0117 & 0.0070 & 0.0100 & 0.0107 + 4471 & & 1.1469 & 1.1781 & 1.2699 & 0.6124 & 0.6465 & 0.6806 & 0.3010 & 0.4077 & 0.4418 + 4713 & & 0.0904 & 0.0929 & 0.0977 & 0.0652 & 0.0833 & 0.0917 & 0.0478 & 0.0957 & 0.1087 + 4922 & & 0.3132 & 0.3222 & 0.3463 & 0.1655 & 0.1722 & 0.1801 & 0.0799 & 0.0973 & 0.1027 + 5016 & & 0.5849 & 0.6039 & 0.6498 & 0.3539 & 0.3808 & 0.4035 & 0.1996 & 0.2554 & 0.2735 + 5048 & & 0.0355 & 0.0366 & 0.0387 & 0.0244 & 0.0281 & 0.0301 & 0.0167 & 0.0253 & 0.0276 + 5876 & & 3.3613 & 3.4419 & 3.6889 & 1.6344 & 1.8724 & 2.0179 & 0.7887 & 1.4753 & 1.6649 + 6678 & & 0.9640 & 0.9872 & 1.0512 & 0.4629 & 0.4962 & 0.5223 & 0.2170 & 0.3082 & 0.3250 + 7065 & & 0.4273 & 0.4750 & 0.5303 & 0.2997 & 0.5897 & 0.7166 & 0.2154 & 0.6809 & 0.8096 + 7281 & & 0.1318 & 0.1387 & 0.1497 & 0.0886 & 0.1203 & 0.1357 & 0.0593 & 0.1086 & 0.1227 + 9464 & & 0.0229 & 0.0235 & 0.0252 & 0.0148 & 0.0155 & 0.0163 & 0.0091 & 0.0109 & 0.0116 + 10830 & & 4.9896 & 13.9601 & 21.4091 & 3.3152 & 18.8390 & 25.4507 & 2.3419 & 18.8421 & 23.6646 + 11970 & & 0.0532 & 0.0547 & 0.0591 & 0.0294 & 0.0305 & 0.0320 & 0.0146 & 0.0179 & 0.0191 + 12530 & & 0.0278 & 0.0286 & 0.0307 & 0.0179 & 0.0195 & 0.0208 & 0.0109 & 0.0146 & 0.0158 + 12780 & & 0.2010 & 0.2056 & 0.2196 & 0.0936 & 0.0972 & 0.1011 & 0.0410 & 0.0513 & 0.0546 + 12800 & & 0.0670 & 0.0686 & 0.0728 & 0.0311 & 0.0320 & 0.0330 & 0.0137 & 0.0169 & 0.0175 + 12970 & & 0.0178 & 0.0183 & 0.0198 & 0.0097 & 0.0101 & 0.0105 & 0.0048 & 0.0056 & 0.0059 + 15080 & & 0.0121 & 0.0125 & 0.0134 & 0.0074 & 0.0078 & 0.0082 & 0.0042 & 0.0051 & 0.0054 + 17000 & & 0.0811 & 0.0833 & 0.0898 & 0.0433 & 0.0457 & 0.0481 & 0.0212 & 0.0288 & 0.0312 + 18680 & & 0.5062 & 0.5126 & 0.5412 & 0.2184 & 0.2282 & 0.2367 & 0.0955 & 0.1261 & 0.1324 + 18700 & & 0.1687 & 0.1711 & 0.1793 & 0.0727 & 0.0748 & 0.0768 & 0.0321 & 0.0449 & 0.0445 + 19090 & & 0.0289 & 0.0297 & 0.0319 & 0.0152 & 0.0159 & 0.0166 & 0.0073 & 0.0089 & 0.0094 + 19550 & & 0.0162 & 0.0167 & 0.0179 & 0.0104 & 0.0114 & 0.0121 & 0.0064 & 0.0085 & 0.0092 + 21120 & & 0.0138 & 0.0141 & 0.0149 & 0.0099 & 0.0127 & 0.0139 & 0.0073 & 0.0146 & 0.0166 +

we calculate the he i case b recombination cascade spectrum using improved radiative and collisional data . we present new emissivities over a range of electron temperatures and densities . the differences between our results and the current standard are large enough to have a significant effect not only on the interpretation of observed spectra of a wide variety of objects but also on determinations of the primordial helium abundance .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Yemen Security and Humanity Act''. SEC. 2. FINDINGS. Congress finds the following: (1) Yemen, a country that has been plagued by violence and insurgency for many years, has been locked in a devastating civil war since 2015. (2) In April 2017, the World Food Programme announced that Yemen is on the brink of ``full-scale famine'' and classified approximately 7,000,000 Yemenis, including 2,200,000 children, as ``severely food insecure''. (3) Although many factors account for the famine conditions in Yemen, including years of government mismanagement, corruption, and natural disasters, the World Food Programme indicates that the impact of the conflict--including the destruction of public services, infrastructure, transport, and Yemen's economy--is having a significant impact on Yemen's food insecurity. (4) According to the United Nations International Children's Emergency Fund, a Yemeni child dies every ten minutes, on average, from malnutrition, diarrhea, or respiratory tract infections. (5) Disease, war, and desperate poverty in Yemen threaten United States core values and strategic priorities for combating global terror. (6) According to the January 2014 ``Worldwide Threat Assessment of the US Intelligence Community''-- (A) a ``[l]ack of adequate food will be a destabilizing factor in countries important to US national security that do not have the financial or technical abilities to solve their internal food security problems''; and (B) ``[f]ood and nutrition insecurity in weakly governed countries might also provide opportunities for insurgent groups to capitalize on poor conditions, exploit international food aid, and discredit governments for their inability to address basic needs''. (7) Yemen imports 90 percent of its food, a majority of which enters the country through the port of Hodeida, currently a Houthi-controlled city. (8) In response to the August 2015 bombing of the port of Hodeida, the United States Agency for International Development funded, in part, the replacement of port cranes destroyed in the bombing, though the replacements have not been delivered because of current conditions on the ground despite being essential to accelerate the rapid delivery of food from the port. (9) Relief organizations are concerned that the closure of the port of Hodeida for any reason could further exacerbate famine in Yemen because the majority of humanitarian aid enters the country through that port. SEC. 3. SENSE OF CONGRESS. It is the sense of Congress that-- (1) effectively addressing the famine conditions in Yemen is in the national security interests of the United States; (2) interventions supported by the United States to advance national security should also consider the impact of military engagement on humanitarian operations in such regions; and (3) bureaucratic procedures with respect to humanitarian aid must be urgently improved and expedited to allow for an expansion of the scale of the humanitarian operations providing such aid. SEC. 4. COORDINATION IN FAMINE-RISK AREAS. Section 5(a) of the Global Food Security Act of 2016 (22 U.S.C. 9304(a)) is amended-- (1) in paragraph (16), by striking ``and'' at the end; (2) in paragraph (17), by striking the period at the end and inserting ``; and''; and (3) by adding at the end the following: ``(18) facilitate coordination between the United States Agency for International Development, the United Nations Office for the Coordination of Humanitarian Affairs, and United States military personnel, with respect to famine-risk areas.''. SEC. 5. UNITED STATES SECURITY AND HUMANITARIAN SUPPORT STRATEGY FOR YEMEN. (a) In General.--Not later than 90 days after the date of the enactment of this Act, the Secretary of State and the Secretary of Defense, in coordination with the Administrator of the United States Agency for International Development, shall jointly submit to Congress a comprehensive report on United States security and humanitarian interests in Yemen, including each of the following: (1) The strategic objectives of the United States in Yemen, including humanitarian support to civilian populations under threat of famine, and the criteria for determining the success of such objectives. (2) A description of efforts to coordinate civilian and military efforts with respect to Yemen. (3) A description of the diplomatic strategy with respect to regional partners seeking to end the civil war in Yemen.

Yemen Security and Humanity Act This bill expresses the sense of Congress that: (1) addressing the famine conditions in Yemen is in U.S. national security interests, (2) U.S.-supported interventions to advance national security should consider the impact of military engagement on humanitarian operations, and (3) bureaucratic procedures with respect to humanitarian aid must be improved. The Global Food Security Act of 2016 is amended to include in the U.S. global comprehensive food security strategy, with respect to famine-risk areas, coordination among the U.S. Agency for International Development, the United Nations Office for the Coordination of Humanitarian Affairs, and the U.S. military. The Department of State and the Department of Defense shall jointly report to Congress regarding U.S. security and humanitarian interests in Yemen, including: (1) U.S. strategic objectives, including humanitarian support to famine-threatened civilian populations; (2) efforts to coordinate civilian and military efforts; and (3) the diplomatic strategy with respect to regional partners seeking to end Yemen's civil war.

KRASNODAR, September 16 (RIA Novosti) – A 36-year-old Russian woman has been detained on suspicion of murdering a 21-year-old woman for dancing with her boyfriend at a birthday party, investigators said Monday. The suspect became jealous when she saw her boyfriend dancing with a 21-year-old guest at a birthday party in a local cafe, a statement on the Krasnodar Territory investigative committee site said. She then “took a knife, approached the dancing woman and stabbed her twice,” the statement said. The 21-year-old was taken to hospital but later died from the injuries sustained, the statement said. If found guilty, the suspect faces up to 15 years in prison. ||||| ROSTOV-ON-DON, September 16 (RIA Novosti) – A “passionate argument” about 18th-century Enlightenment philosopher Immanuel Kant, renowned for his treatises on ethics, “deteriorated into a fistfight” between two men waiting in line for beer during an outdoor City Day event in the southern Russian metropolis of Rostov-on-Don, police said Monday. The argument ended when one of the debaters pulled out an air gun and shot the other in the head, local police said in a statement. The shooter then fled the scene but was later detained, police said. The other man’s wound was not critical, but he was hospitalized, the statement said, without disclosing any names. Local media said the men were in their late 20s. The attacker now faces up to a decade in prison for intentional infliction of serious bodily harm, police said. That sentence would give him time to more thoroughly study the works of Kant, who contemplated a universal law of morality. ||||| An argument in southern Russia over philosopher Immanuel Kant, the author of "Critique of Pure Reason," devolved into pure mayhem when one debater shot the other. The state news agency RIA Novosti on Monday cited police in the city of Rostov-on-Don as saying the argument took place in a small store and deteriorated into a fistfight. One participant pulled out a small nonlethal pistol and fired repeatedly. The victim was hospitalized with injuries that were not life-threatening. The weapon fired plastic bullets or blanks. Neither person was identified. It was not clear which of Kant's ideas may have triggered the violence.

– A spate of odd news today concerning attacks in Russia: one on a dance floor, three in a cemetery, and another over a philosopher. Two 20-something men in line for beers at a festival in southern Russia, got in a heated dispute about 18th-century philosopher Immanuel Kant. The feud "deteriorated into a fistfight," police said today, and one of the men eventually shot the other in the head with an air gun—multiple times, the AP notes. The victim survived; the attacker could be in prison for a decade, RIA Novosti adds. Police arrested a 36-year-old woman after she allegedly stabbed another woman at a birthday party; the 21-year-old victim was apparently dancing with the attacker's boyfriend, RIA Novosti reports. The alleged attacker "took a knife, approached the dancing woman, and stabbed her twice," investigators say. The victim died in the hospital. A guilty verdict could mean 15 years in prison for the suspect. A man has been convicted of killing his mother, brother, and father in a cemetery. They were reportedly living in the graveyard after he evicted them, and when his mother accused him of the eviction, he hit her. His brother stepped in, and the man ended up stabbing both of them—and killing his father, who'd seen the attack. The suspect has been sentenced to life in prison, RIA Novosti reports.

catharanthus roseus ( l. ) g. don ( formerly vinca rosea l. , apocynaceae ) is commonly known as the madagascar periwinkle . it is a perennial ever green herb , 30 - 100 cm tall originally native to the island of madagascar but now widely dispersed in the tropics ( 1 ) . the significance of this plant is its ability to synthesize a wide range of terpenoid indol alkaloids with medicinal values . these compounds have a broad application in the treatment of leukemia in children , and lymphocytic leukemia , wilkins s tumor , neuroblastoma and reticulum cell sarcoma , hodgkin s disease besides lymphosarcoma , choriocarcinoma ( 2 ) . except alkaloids , other natural compounds in c. roseus the genus agrobacterium is gram - negative soil bacterium and belongs to the family rhizobiaceae . agrobacterium rhizogenes is the best known species , it can infect plants and cause abnormal proliferation of plant cells at the site of infection which is manifested by the appearance of adventitious roots called hairy roots ( 4 ) . the transformation process depends on the presence of large size plasmid , 200 - 800 kilo base ( kb ) in the bacterium called root inducing ( ri ) plasmid ( 5 ) . these plasmids carry one or more dna fragments called transferred - dna ( t - dna ) . the t - dna contain many genes , these genes are the four rol ( root locus ) genes , rola , rolb , rolc and rold . to identify the contribution of each t - dna gene to the induction of hairy root disease ( 6 ) . it has been reported that a. rhizogenes rol genes enhance the biosynthesis of certain groups of secondary metabolites in transformed plant cells . of these genes , rolb is apparently the most powerful induce of secondary metabolism and rolb has the morphogenic effects similar to auxin - mediated effects ( 7 ) . oxidative stress occurs as the result of an imbalance between the internal production of free radicals and the antioxidant defense mechanisms of living organisms ( 8) . when the level of free radicals is increased and also when both the enzymatic systems and low molecular antioxidants are not sufficient to protect the organism , free radicals formed in excess induce cellular damage , which contribute to the development of diseases well as the spoilage of food products ( 9 ) . antioxidant enzymes such as catalase , glutamine peroxidase , and superoxide dismutase act to reduce the cellular level of free radicals . however , antioxidant supplementation is often necessary to limit the deleterious effects of the excess free radicals which have been formed . synthetic antioxidants such as butylated hydroxy toluene ( bht ) are being used in food industry to delay the oxidation of lipids . however , because of the tumorigenic potential and other side effects of chemical preservatives ( 10 , 11 ) , it is particularly important to replace them with herbs and natural antioxidants . thus , plant tissue culture is being considered for producing valuable metabolites in significant quantities ( 12 ) . among the natural products with antioxidant properties , phenolic compounds have been extensively studied . because these compounds neutralize free radicals and inhibit lipid oxidation such phenolic compounds are particularly useful in the preservation of food products and in the pharmaceutical industry . additionally , these phenolic compounds directly promote health and well - being through disease prevention ( 13 ) . gallic acid is a type of phenolic acid with chemical formula c6h2(oh)3cooh with antioxidant , anti - inflammatory , antifungal and antitumor properties ( 14 ) . previous studies have shown that aqueous extract of the root of c. roseus has good antioxidant properties ( 15 , 16 ) . however , because the root growth is limited , and that the root has pharmaceutical values , almost all roots are used in cultures to extract alkaloids . therefore , plant tissue engineering and tissue culture are necessary to increase the capacity of the plant to produce secondary metabolites in greater quantities . earlier studies indicated that the calli produced from the tissue culture of other plants can be a good source of useful secondary metabolites such as flavonoids ( 17 ) . the hairy root culture is as an important resource of valuable secondary metabolites owing to rapid growth , short doubling time , and the dependable synthesis of chemical compounds ( 18 ) . in the past two decades , considerable attention has been paid to the synthesis of these valuable hairy root compounds . the employment of cell suspension cultures from c. roseus has greatly expanded the production and enhanced the stability of secondary metabolites . in recent decades , this technique has extensively been used to produce more effective alkaloids and anti - cancer drugs from c. rosus ( 19 ) . continuing to research the anti - oxidation potential of these hairy roots can lead to other , more efficacious , applications of this transgenic product ( 20 ) . to the best of our knowledge , no other report was found on the antioxidant potential of plant hairy roots and callus , and also their phenolic content . the present study assessed the antioxidant properties of transgenic hairy roots and leaf callus of c. roseus by measuring the free radical scavenging activity , reducing power , the ability to inhibit lipid peroxidation , and the capacity to inhibit the formation of mda , and compared these results with those obtained for the root and leaf . plant material and process hairy roots and callus calture seeds from the roseus varieties of c. roseus were sterilized for 60 s with 70% ethanol and then for 15 min sodium hypochlorite ( 2 % available chlorine ) followed by three washing with sterile distilled water and cultivated in pots inside a greenhouse . a sample of the plant was identied and a voucher specimen ( 6559-the ) was deposited in the herbarium , at the college of pharmacy , tehran university of medicinal science , tehran , iran . explants were prepared from the young leaves ( 4 - 5 cm , 2 months old ) and used for hairy roots and callus induction ( temperature 25 - 30 c and air humidity about 80% ) . agrobacterium rhizogenes suspension preparation agrobacterium rhizogenes strain atcc 15834 was provided for transformation from the national research center for genetic engineering and biotechnology of iran that each cell of this bacteria harbors a ri plasmid that involved in the root induction process ; the root loci ( rol ) genes located in the tl region . the bacterial strain was cultivated in a new solid culture medium of lb ( 10 g l bactotrypton , 5 g l yeast extract , 10 g l sodium chloride plus agar 10 g l in the acidity of 7 , 50 mg l , rifampicin ) at 28 c . a colony of grown bacteria was added to 5 ml liquid lb medium at 28 c insert on 180 rpm for 24 h in the dark . one ml of culture suspension was added to 30 ml of the same medium and shaked for 24 h , and the concentration of bacteria was adjusted to 0.4 - 0.6 by spectrophotometer ( uv / vis t90 pg instrument ) at 600 nm wavelength ( 21 ) . induction and establishment of hairy roots culture leaves obtained from young leaves of a 2 months old were used explants , each explants was infected by injection of a. rhizogenes strain atcc 15834 suspension . in order to infect by injection , 5 l of bacteria suspension were injected in to the dorsal vein of each leaf via insulin syringes angled at one or two positions . the leaf explants were blotted after 30 min with a sterile filter paper ( to remove excess agrobacterium ) and transferred to petri dishes containing solid ms medium . petri dishes were kept in darkness at 26 c for 48 h , and the samples were transferred to the ms medium ( no hormone , 3 % sucrose , 500 mg l cefotaxime and 0.8 % agar ) . hairy roots appeared at the wound sites 10 - 15 days after infection , were allowed to grow about 2 cm , and were transferred to the solid ms medium supplemented with cefotaxime 500 mg l. after 4 subculture hairy roots on solid medium , the hairy roots were excised and immediately placed into 50 ml ms liquid medium containing 3% sucrose and 500 mg l cefotaxime in 250 ml erlenmeyer flasks on a 60 rpm shaker ( 22 ) . to ensure a sufficient amount of hairy roots , a subculture was created once every 2 weeks . after 3 months hairy roots kept and used for extraction . the presence of t - dna in the hairy roots was by polymerase chain reaction ( pcr ) and the rolb was used as a target for pcr analysis in c.roseus hairy roots . hairy roots were made bacteria free by transferring into a fresh medium containing cefotaime every 14 days . the hairy roots were checked for a. rhizogenes contamination by culturing hairy roots sample on lb medium . after the removal of bacteria , genomic dna was extracted via the ctab procedure from hairy roots as well as from roots and leaves of c. roseus ( 23 ) . each pcr reaction ( 20.0 l ) contained : standard pcr buffer 10x ( mgcl2 15 mm , kcl 500 mm , tris - hcl 100 mm , ph 8.3 ) 2.0 l , dntp mix ( 10 mm ) 0.5 l , forward primer ( 10 m ) 1.0 l , reverse primer ( 10 m ) 1.0 l , target dna ( 50ng l ) 1.0 l , tag dna polymerase 0.2 l . amplification conditions were : 35 thermal cycles , initial denaturizing at 94 c for 1 min , primer annealing at 57c for 1 min , and primer extension at 72c for 1 min . the sequences of the two primers used to amplify a fragment of the rolb gene were : 5-atggatcccaaattgctattccccacga-3 ' ( forward primer ) and 5'- ttaggcttctttcattcggtttactgcagc-3 ' ( reverse primer ) ( 24 ) . the amplied product was run on 1.2% ( w / v ) agarose gel at 100 v to separate the dna fragments . induction of callus culture plant leaves were sterilized for 60 s with 70 % ethanol and then for 15 min sodium hypochlorite ( 2 % available chlorine ) followed by three washing with sterile distilled water and cut into pieces of 0.4 - 0.6 cm and were used for preparing the explants . the explants were transferred to petri dishes containing ms medium and 2 , 4-dichlorophenoxyacetic acid ( 2 , 4-d ) under sterile conditions . the cultures were maintained under a photoperiod ( 16 h/8 h light/ dark ) at 26 2 c ( 25 ) . to ensure a sufficient amount of callus , to study the antioxidant composition , the plant material was dried in an oven at 40 c for 72 h and ground by a grinder ( ika , germany ) . briefly , a powder ( 200 mg ) of each sample was extracted by 20 ml of ethanol 80 % , while being stirred at the temperature of 40 c for 2 h. after this period , the mixture was filtered and the residue was remixed with the same solvent mixture ratio and the operation was repeated for 2 h. the filtered solutions of both stages were mixed together . the extracts were evaporated by using a rotary evaporator ( heidolph 4001 , germany ) at 40 c and were dried by a freeze dryer ( cherist 1 - 4 ld , uk ) . antioxidant composition total phenolic content ( tpc ) total phenolic compound content was determined by the folin - ciocalteu method ( 27 ) . in this way , 1 ml ethanol 80% was added to 10 mg dried extract powder of each samples and stirred . 200 l diluted folin reagent ( 1:10 ) was added to 40 l of this extract and the mixture was shaken . after 8 min , 600 l sodium carbonate 7.5 % was added . after mixing the solution after 90 min incubation at 23 c the absorbance of samples was measured using spectrophotometer at 760 nm by spectrophotometer ( uv / vis t90 pg instrument ltd ) . the total phenolic content was expressed as tannic acid equivalent in microgram per miligram of the extract using a standard curve generated with tannic acid ( merck , germany ) . total flavonoid content ( tfc ) total flavonoid content of the extracts was measured spectrophotometrically using aluminum chloride as described by zhishen et al . ( 1999 ) . in this way , 500 l ethanol extract ( 10 mg ml ) of different plant organs was added to 2 ml double distilled water . after 15 min , the absorption of samples was read using spectrophotometer at 510 nm ( 28 ) . the total flavonoid content was expressed as catechin equivalent in microgram per miligram of the extract using a standard curve generated with catechin ( sigma - aldrich , usa ) . gallic acid content ( gac ) the chromatographic analysis was carried out on a hplc system ( knauer , germany ) equipped with a k-1001 pump and a uv - vis detector ( k-2600 ) at 271 nm , column : c-18 ( 4.6250 mm , 5 particle size ) . an isocratic mobile phase of methanol : ethyl acetate : water ( 25:50:70 v / v ) with an elution volume of 0.7 ml min was selected . identification of gallic acid in samples was based on retention time in comparison with standard ( pure gallic acid ) . the solution of pure gallic acid ( merck , germany ) at various concentrations ( 1 - 5 g ml ) was injected into the hplc system and the calibration curve was established . the concentration of gallic acid in each sample was calculated from peak area according to calibration curve ( 29 ) . antioxidant activity free radical scavenging activity ( dpph assay ) the 1 , 1-diphenyl-2-picrylhydrazyl ( dpph ) free radical scavenging activity was assessed according to the method of brand - williams et al . the absorption using spectrophotometer was measured at 517 nm after 60 min ( 30 ) . the following equation was utilized to calculate the percentage of free radical scavenging : scavenging activity% = ( 1 - asample / a0 ) 100 . where asample is the absorbance in the presence of extract or positive control , while a0 is the absorbance in the absence of extract ( 31 ) . the half maximal inhibitory concentration ( ic50 ) was defined as the concentration of the sample , required for scavenging 50% of the dpph free radicals ( 32 ) . ferric reducing antioxidant power ( frap assay ) the reducing power of ethanol extract was measured according to the method of ferreira et al . 1 ml different amount of each ethanol extracts ( 6.25 to 400 g ml ) , 2.5 ml phosphate buffer 0.2 m ( ph = 6.6 ) , and 2.5 ml potassium ferro cyanide solution ( 10 mg ml ) were mixed together and incubated at 50 c for 20 min . 2.5 ml trichloroacetic acid ( merck , germany ) 10 % was added to the mixture and was centrifuged at 3000 rpm for 10 min . 2.5 ml the supernatant was mixed with 1 ml distilled water and 0.1 ml ferric chloride ( 1.0 mg ml ) , and then the absorbance was measured at 700 nm ( 33 ) . butylated hydroxytoluene ( sigma - aldrich , usa ) was used as positive control . reducing capacity of the samples was calculated by the following formula : relative reducing effect % = [ asample - amin / amax - amin ] 100 where , asample is the absorbance in the presence of extract or positive control , while amin is the minimum absorbance in the test and amax is the maximum absorbance ( 34 ) . lipid peroxidation inhibitory activity ( ftc assay ) the effect of ethanol extracts on lipid peroxidation was determined by the ferric thiocyanate ( ftc ) method ( 35 ) . different extracts ( 4 mg ) were mixed with 4 ml of absolute ethanol , 4.1 ml linoleic acid ( 2.51 % , v / v ) in absolute , 8 ml phosphate buffer ( 0.05 m , ph 7.0 ) and 3.9 ml distilled water . 0.1 ml this solution was then mixed with 9.7 ml ethanol 75 % and 0.1 ml ammonium thiocyanate ( 30 % w / v ) . three minutes after adding 0.1 ml ferrous chloride ( 20 mm ) , the absorbance was measured at 500 nm in a spectrophotometer ( uv / vis t90 pg instrument ltd ) . the inhibition of linoleic acid peroxidation by ethanol extracts was calculated as : inhibition% = 100 - [ ( absorbance increase of the sample / absorbance increase of the control ) 100 ] ( 36 ) . malondialdehyde inhibitory activity ( tbars assay ) the effect of ethanol extracts on the formation of mda was determined by the thiobarbituric acid reactive substances ( tbars ) assay ( 37 ) . 1 ml each extract on the final hour ( 120 h ) of the ftc assay was added to 1 ml aqueous thiobarbituric acid 0.67% . after boiling for 10 min , absorbance of the supernatant was measured at 532 nm in a spectrophotometer ( uv / vis t90 pg instrument ltd ) . the malondialdehyde scavenging activity was calculated according to the following equation : inhibition% = ( 1 - asample / a0 ) 100 where , asample is the absorbance in the presence of extract or positive control , while a0 is the absorbance in the absence of extract ( 38 ) . the data were analyzed by an analysis of variance ( p 0.01 ) and the means were compared by duncan s multiple range tests . the half maximal inhibitory concentration ( ic50 ) values were calculated from a linear regression analysis . hairy roots and callus induction the hairy roots were obtained after 10 - 15 days past transformation of c. roseus with a. rhizogenes strain atcc 15834 . the transformation efficiency was 3 % in co - cultivated explants ( leaf ) with bacteria suspension by injection method . pcr products amplified with rolb primers were detected in the hairy roots and positive control ( fragment with 500 bp ) . these results indicate that the rolb gene ( 500 bp ) , from the t - dna of the a. rhizogenes ri - plasmid , was integrated in to the genome of c. roseus hairy roots ( figure 2 ) . no band was formed in the wells , which corresponded to the control ( dna extracted from natural roots and leaves , bands 5 and 6 ) . leaf calli were induced after two weeks with frequency of induction 90 % and reached full growth after 45 days ( figure 3 ) . stages of hairy roots inoculation in c. roseus leaf and growth of these roots in ms culture medium a : plant young leaf , b : hairy root inoculation in leaf ( one month after inoculation ) , c , d and e : growing hairy roots in ms medium liquid ( six , seven and eight weeks , respectively , after inoculation stages of leaf explants preparation , inoculation and c. roseus callus growth in medium containing dichlorophenoxyacetic acid ( 2 , 4-d ) a : young leaves for preparation of explant , b : cutting leaf into 4 - 5 cm pieces c : two weeks after explant culture in culture medium , d : magnified image of an explant transforming into callus , e : formed callus , six weeks after culture in ms medium pcr analysis of c.roseus hairy roots for rolb transgenesis with a.rhizogenes atcc 15834 . molecular weight marker ( lanes 1 and 4 , 1 kb ) , transgenic hairy roots ( lanes 2 and 3 ) , genomic dna from normal root and leaf culture separately ( negative control , lanes 5 and 6 ) , plasmid genome ( positive control , lane 7 antioxidant composition the results showed the significant difference between of phenolic content for dried ethanol extract of root , leaf , hairy roots and callus ( figure 4 ) . phenolic content was higher in hairy root ( 99.38 4.38 ) than in root ( 78 2.79 ) , leaf ( 63.63 0.42 ) and callus ( 51.84 1.69 ) , equal to g of tannic acid per milligram of dried weight of extract according to the standard curve of y = 0.000492x + 0.04819 , r = 0.973 . according to the equation ( y = 0.00289x - 0.0076 , r = 0.989 ) , flavonoids content was higher in hairy root ( 50.1 0.35 ) than in root ( 32.02 0.91 ) , leaf ( 42.9 1.34 ) and callus ( 13.46 1.2 ) , equal to g of catechin per mg of dried weight of extract . gallic acid content was higher in hairy root ( 12.86 0.37 ) than in root ( 10.55 0.37 ) , leaf ( 8.52 0.19 ) and callus ( 7.28 0.19 ) , g gallic acid per mg of dried weight of extract according to the standard curve of y = 34385.7x + 845900 , r = 0.992 by hplc . the phenolic , flavonoid and gallic acid content of ethanol extracts of root , leaf , hairy root and callus of c. roseus . data show means of three replicates with standard error antioxidant activity free radical scavenging activity according to figure 5 , percentage of free radical scavenging at concentration of 6.25 to 400 g ml of ethanol extract samples compared to standard antioxidant showed that increased concentration of ethanol extracts led to increased inhibition of free radicals , and concentration of standard antioxidant in excess of 50 g ml had no significant effect on increasing inhibition of free radicals . the hairy roots extract showed the best performance in dpph free radical trapping activity compared with c. roseus root , leaf , and callus . the ethanol extracts of hairy root , root , leaf , and callus at the concentrations of 221.22 5.85 , 238.9 2.02 , 277.95 4.443 and 342.11 2.67 g ml , respectively , scavenged a half of dpph radicals in contrast to standard antioxidants ) 22.29 0.4 g ml ( . at equal concentrations , however , at higher concentrations , the extracts , particularly that of hairy root ( 400 g ml ) , scavenged free radicals as efficiently as the standard antioxidant ( bht ) . scavenging of dpph activity by ethanol extracts of root , leaf , hairy root and callus of c. roseus . bht used as antioxidant standard ferric reducing antioxidant power ( frap assay ) reducing power of ethanol extract samples at concentration of 6.25 to 400 g ml showed that increased concentration of extracts led to increased percentage of fe ( iii ) reduction ( figure 6 ) . the ethanol extracts of hairy root , root , leaf , and callus , at concentrations of 393.07 2.8 , 407.70 4.75 , 745.68 6.46 , and 961.71 25.1 g ml , respectively , were able to reduce half of the fe into fe ions in contrast to the standard antioxidant ( 114.33 1.18 g ml ) . reducing power activity by ethanol extracts of root , leaf , hairy roots and callus of c. roseus . bht used as antioxidant standard lipid peroxidation inhibitory activity ( ftc assay ) ftc assay measures the amount of produced at the initial stage of lipid oxidation . according to figure 7 , percentage of inhibition of linoleic acid peroxidation at final concentration ( 200 g ml ) of ethanol extract samples and standard antioxidant at 37 c showed that all extracts are capable of inhibiting linoleic acid peroxidation at maximal absorption of the control ( after 108 h ) , the extent of inhibition of linoleic acid peroxidation by extracts followed the orders : hairy roots > root > leaf > callus . after 12 h , hairy root extract and bht inhibited linoleic acid peroxidation 71.6 0.84 % and 77.14 0.17 % , respectively , whereas the extent of inhibition by these extracts after 108 h was 47.25 0.2 % and 52.65 0.17 % , respectively . after 12 h , ethanol extracts of root , leaf , and callus inhibited reaction by 67 % , 60 % , and 50 % respectively , and 108 h later , their inhibitory power reached 45 % , 40 % , and 25 % , respectively . inhibition of linoleic peroxidation by ethanol extracts of root , leaf , hairy root and callus of c. roseus . bht used as antioxidant standard malondialdehyde inhibitory activity ( tbars assay ) the results also revealed that the ethanol extracts potently inhibited formation of mda ( table 1 ) . the hairy root extract inhibited the formation of this toxic substance by 83 % , whereas the extent of inhibition by the standard antioxidant was 87 % ( table 1 ) . inhibition of malondialdehyde by ethanol extracts of root , leaf , hairy roots and callus of c. roseus . bht was used as antioxidant standard relationship between antioxidant composition and antioxidant activity a strong relationship was observed between phenolic , flavonoid and gallic acid contents and antioxidant power of the plant in inhibition of free radicals , reducing power and inhibition of mda formation . pearson coefficients were applied in determining the relationship between antioxidant composition ( phenolic , flavonoid and gallic acid contents ) and antioxidant capacity of the extracts based on reducing antioxidant power , dpph and mda inhibition ( table 2 ) . pearson s coefficients of determining the relationship between antioxidant composition and antioxidant activity of ethanol extracts of c. roseus significant at p 0.01 , significant at p 0.05 it infects the plant cell and leads to the formation of hairy roots ( 39 ) . several other studies have reported on hairy roots induced by this strain ( 40 , 41 ) . ( 2008 ) reported exit points of hairy roots which induced by a. rhizogenes strain atcc 15834 from the stem , hypocotyl and epicotyl of five host plant , were after 10 days ( 42 ) , which was confirmed in the present study . recently , hairy roots applied for production of secondary metabolit ( 18 ) . according to reports , rolb gene is able to increase biosynthesis of secondary metabolites ( 7 ) . thus , this gene is expected to stimulate synthesized secondary metabolites in transformed hairy roots . studies have , in fact shown that secondary metabolites are produced faster and more abundantly in hairy roots than in other normal parts of the plant . ( 2010 ) reported that the total alkaloid content was 1 % in a leaf , 23 % in root , and up to 9% in hairy roots ( 3 ) . some studies show that alkaloid synthesis routes are closely allied with the synthesis of phenolic compounds ( 43 ) . among these phenolic compounds , a higher level of gallic acid was found in hairy roots versus roots and leaves , which signals greater antioxidant properties . due to limitation in culture and increased demand for secondary metabolites , alternative natural sources were considered , such as hairy roots and callus culture , which was confirmed by bolda et al . ( 2011 ) , reporting that callus can be considered as a source of antioxidants ( 44 ) . shahidi and zhong ( 2005 ) reported that many secondary metabolites , such as phenolic compositions , contain antioxidant properties ( 45 ) , thus this study aimed to investigate and compare the antioxidant potential . this study aimed to investigate and compare the antioxidant potential of transgenic hairy roots from the leaves of c. roseus infected with a. rhizogenes strain atcc 15834 and leaves callus of this plant with natural root and leaves of this plant . mustafa and verporter ( 2007 ) reported that the plant contains considerable amounts of phenolic compounds as well as alkaloid ( 47 ) . a report by sroka and cisowski ( 2003 ) cites some phenolic acid compounds in the plant , such as gallic acid ( 48 ) . shahidi and zhong ( 2005 ) believe phenolic compositions are one of the best natural sources of antioxidants , which play an important role in protecting tissues against oxidizing free radicals of oxygen and other active strains ( 45 ) . dpph free radical inhibition method that relies on hydrogen - donating activity illustrates an important mechanism of antioxidant activity of phenolic compositions . although root and leaf were appropriately capable of inhibiting this radical , transformed roots had greater inhibition power . even though the present study is a new report on inhibition power of free radicals by hairy roots of this plant , previous reports on its root ( 15 ) , and leaf ( 16 ) confirm inhibition of free radicals and hydrogen - donating capability of ethanol extracts . transformed hairy roots of the plant at concentration of 400 g ml had similar performance to synthesized antioxidants . fe ( iii ) reducing is often used as an indicator of electron - donating activity , which is an important mechanism of phenolic antioxidant action ( 49 ) . amount of fe complex can be then be monitored by measuring the formation of perls prussian blue at 700 nm . although extracts in hydrogen donation activity in dpph free radical scavenging test were able to neutralize half radicals by hydrogen donation at lower concentrations ; hairy roots were capable of higher electron donation compared to other extracts . although the present study provides a new report on hydrogen donation power of extracts of this plant , weremczuk - jezyna et al . ( 2013 ) reported significantly stronger hydrogen donation activity than electron donation activity in hairy roots of dracocephalum moldavia , which agrees with the present study results ( 50 ) . asan uzosaglam and karacoca ( 2014 ) , reported high antioxidant capability of glycyrrhiza glabra l. , and extracts of root and aerial parts of this plant at concentrations 582.14 and 432.63 g ml respectively were able to convert half fe iii ions to fe ii ions ( 51 ) . yet , in the present study , extracts of hairy root and c.roseus root were stronger than g.glabra . lipid peroxidation is a free - radical - mediated chain of reactions that , once initiated , results in oxidative deterioration of polyunsaturated lipids . once formed , the unstable lipid peroxides , degrade rapidly into a variety of products . these reactions can be initiated or facilitated by toxic products , including endoperoxides and aldehydes . antioxidants donate one hydrogen atom to peroxperyl radicals , converting them into non - radical species ( 52 ) . in this study , ethanol extracts had similar function to synthesized antioxidant in inhibition of linoleic acid peroxidation , and extract of hairy roots prevented this process more than other extracts . the results showed reduced capability of extracts and synthesized antioxidant in inhibition of peroxide radicals with increasing time , which suggests accumulation of these radicals in reaction medium.his finding , agrees with mathew and emili abraham report ( 2006 ) on reducing trend of lipid peroxidation of cinnamomum verum leaf extract , and synthesized antioxidant with time in the present study , and also reported c.verum leaf extract 24 and 144 h after experiment was able to inhibit 80 % and 50 % , respectively of linoleic acid peroxidation process ( 53 ) , which is similar to performance of hairy root extract of this plant . the injury mediated by free radicals can be assessed by measuring the amounts of conjugated dienes , mda , and other products . extracts of plant material used in this study showed the ability inhibit the formation of mda . compared to other extracts , hairy roots of the plant inhibited greater percentage of mda , and showed a very similar performance to synthesized antioxidant . to our knowledge , this is the first report describing the ability of c. roseus extracts to inhibit the formation of mda . ( 2011 ) in a study of mda inhibition methanol extract of momodia charantia fruit reported that this extract inhibited 32.5 % of mda by the end of experiment ( 8 day ) ( 37 ) . phenolic compositions act like antioxidants because they donate hydrogen or electron to free radicals ( 54 ) . hydrogen or electron donation to free radicals and formation of a complex between the lipid radical and the antioxidant radical ( free radical acceptor ) are among the chemical mechanisms that empower antioxidants to inhibit free radicals ( 55 ) . this finding was confirmed in the present study by the strong relationship between phenolic compositions and antioxidant activity the results of the present study revealed that transformed hairy roots with c.roseus rolb gene had a considerable antioxidant power and antioxidant compositions compared to its root , leaf , and callus . the greater presence of phenolic compositions in transformed hairy roots can be attributed to rolb gene transfer to plant leaf . hairy roots hydrogen donation power in free radical scavenging and also electron donation power as greater reducing power compared to other extracts led to considerable power of hairy roots in inhibition of lipid peroxidation process and prevention of toxic mda formation . although plant callus can be considered as a source of antioxidant , it did not have a high phenolic content or antioxidant power due to its short life in vitro . therefore , from a pharmaceutical perspective , the extraction of their potent antioxidants from transformed hairy roots of the plant can be very beneficial in inhibiting free radicals and reducing the risk of degenerative diseases . transformed hairy roots of the plant can be a rich source of natural antioxidants .

free radicals play an important role in pathological processes such as aging and developing cancer ; hence , natural products inhibit free radical production , and can play an important role in preventing diseases . we aimed to evaluate the scavenging activity of free radicals , reducing power , inhibition of lipid peroxidation and malondialdehyde ( mda ) formation , and the antioxidant composition of rolb - transformed hairy roots and leaf callus of catharanthus roseus . hairy roots of the catharanthus roseus were induced using agrobacterium rhizogenes strain atcc 15834 to transfer the rolb gene . polymerase chain reaction analysis was used to identify the presence of the gene in the transformed hairy roots . folin - ciocalteu reagent , aluminum chloride calorimetry and high performance liquid chromatography were used to determine the content of total phenolic , flavonoid and gallic acid , respectively . to this end , we assayed the free radicals scavenging activity by 1-diphenyl-2-picrylhydrazyl ( dpph ) , reducing power , inhibition of lipid peroxidation and inhibition of malondialdehyde production . the results showed that phenolic , flavonoid , and gallic acid contents in the ethanol extract of the hairy roots were signicantly higher ( p 0.01 ) than those naturally found in the extracts of root , leaf , and leaf callus of c. roseus . the hairy roots extract showed the lowest ic50 for the inhibition of dpph. furthermore , the ethanol extract showed the best reducing power and had the highest potential to inhibit lipid peroxidation and to form the mda . the transformed hairy roots can be considered a rich natural source of antioxidants .

SECTION 1. SHORT TITLE. This Act may be cited as the ``United States Agricultural Products Market Access Act of 1997''. SEC. 2. FINDINGS; PURPOSES. (a) Findings.--Congress makes the following findings: (1) The export of agricultural products is of vital importance to the economy of the United States. (2) In 1995, agriculture was the largest positive contributor to the United States merchandise trade balance with a trade surplus of $25,800,000,000. (3) The growth of United States agricultural exports should continue to be an important factor in improving the United States merchandise trade balance. (4) Increasing the volume of agricultural exports will increase farm income in the United States, thereby protecting family farms and contributing to the economic well-being of rural communities in the United States. (5) Although the United States efficiently produces high- quality agricultural products, United States producers cannot realize their full export potential because many foreign countries deny fair and equitable market access to United States agricultural products. (6) The Foreign Agricultural Service estimates that United States agricultural exports are reduced by $4,700,000,000 annually due to unjustifiable imposition of sanitary and phytosanitary measures that deny or limit market access to United States products. (7) The denial of fair and equitable market access for United States agricultural products impedes the ability of United States farmers to export their products, thereby harming the economic interests of the United States. (b) Purposes.--The purposes of this Act are-- (1) to reduce or eliminate foreign unfair trade practices and to remove constraints on fair and open trade in agricultural products; (2) to ensure fair and equitable market access for exports of United States agricultural products; and (3) to promote free and fair trade in agricultural products. SEC. 3. IDENTIFICATION OF COUNTRIES THAT DENY MARKET ACCESS. (a) Identification Required.--Chapter 8 of title I of the Trade Act of 1974 is amended by adding at the end the following: ``SEC. 183. IDENTIFICATION OF COUNTRIES THAT DENY MARKET ACCESS FOR AGRICULTURAL PRODUCTS. ``(a) In General.--Not later than the date that is 30 days after the date on which the annual report is required to be submitted to Congressional committees under section 181(b), the United States Trade Representative (hereafter in this section referred to as the `Trade Representative') shall identify-- ``(1) those foreign countries that-- ``(A) deny fair and equitable market access to United States agricultural products, or ``(B) apply standards for the importation of agricultural products from the United States that are not related to public health concerns or cannot be substantiated by reliable analytical methods; and ``(2) those foreign countries identified under paragraph (1) that are determined by the Trade Representative to be priority foreign countries. ``(b) Special Rules for Identifications.-- ``(1) Criteria.--In identifying priority foreign countries under subsection (a)(2), the Trade Representative shall only identify those foreign countries-- ``(A) that engage in or have the most onerous or egregious acts, policies, or practices that deny fair and equitable market access to United States agricultural products, ``(B) whose acts, policies, or practices described in subparagraph (A) have the greatest adverse impact (actual or potential) on the relevant United States products, and ``(C) that are not-- ``(i) entering into good faith negotiations, or ``(ii) making significant progress in bilateral or multilateral negotiations, to provide fair and equitable market access to United States agricultural products. ``(2) Consultation and consideration requirements.--In identifying priority foreign countries under subsection (a)(2), the Trade Representative shall-- ``(A) consult with the Secretary of Agriculture and other appropriate officers of the Federal Government, and ``(B) take into account information from such sources as may be available to the Trade Representative and such information as may be submitted to the Trade Representative by interested persons, including information contained in reports submitted under section 181(b) and petitions submitted under section 302. ``(3) Factual basis requirement.--The Trade Representative may identify a foreign country under subsection (a)(1) only if the Trade Representative finds that there is a factual basis for the denial of fair and equitable market access as a result of the violation of international law or agreement, or the existence of barriers, referred to in subsection (d). ``(4) Consideration of historical factors.--In identifying foreign countries under paragraphs (1) and (2) of subsection (a), the Trade Representative shall take into account-- ``(A) the history of agricultural trade relations with the foreign country, including any previous identification under subsection (a)(2), and ``(B) the history of efforts of the United States, and the response of the foreign country, to achieve fair and equitable market access for United States agricultural products. ``(c) Revocations and Additional Identifications.-- ``(1) Authority to act at any time.--If information available to the Trade Representative indicates that such action is appropriate, the Trade Representative may at any time-- ``(A) revoke the identification of any foreign country as a priority foreign country under this section, or ``(B) identify any foreign country as a priority foreign country under this section. ``(2) Revocation reports.--The Trade Representative shall include in the semiannual report submitted to the Congress under section 309(3) a detailed explanation of the reasons for the revocation under paragraph (1) of the identification of any foreign country as a priority foreign country under this section. ``(d) Definitions.--For purposes of this section, a foreign country denies fair and equitable market access if the foreign country effectively denies access to a market for a product through the use of laws, procedures, practices, or regulations which-- ``(1) violate provisions of international law or international agreements to which both the United States and the foreign country are parties, or ``(2) constitute discriminatory nontariff trade barriers. ``(e) Publication.--The Trade Representative shall publish in the Federal Register a list of foreign countries identified under subsection (a) and shall make such revisions to the list as may be required by reason of the action under subsection (c). ``(f) Annual Report.--The Trade Representative shall, not later than the date by which countries are identified under subsection (a), transmit to the Committee on Ways and Means and the Committee on Agriculture of the House of Representatives and the Committee on Finance and the Committee on Agriculture, Nutrition, and Forestry of the Senate, a report on the actions taken under this section during the 12 months preceding such report, and the reasons for such actions, including a description of progress made in achieving fair and equitable market access for United States agricultural products.''. (b) Clerical Amendment.--The table of contents for the Trade Act of 1974 is amended by inserting after the item relating to section 182 the following: ``Sec. 183. Identification of countries that deny market access for agricultural products.''. SEC. 4. INVESTIGATIONS. (a) Investigation Required.--Subparagraph (A) of section 302(b)(2) of the Trade Act of 1974 (19 U.S.C. 2412(b)(2)) is amended by inserting ``or 183(a)(2)'' after ``section 182(a)(2)'' in the matter preceding clause (i). (b) Conforming Amendment.--Subparagraph (D) of section 302(b)(2) of such Act is amended by inserting ``concerning intellectual property rights that is'' after ``any investigation''. SEC. 5. AUTHORIZED ACTIONS BY UNITED STATES TRADE REPRESENTATIVE. Section 301(c)(1) of the Trade Act of 1974 (19 U.S.C. 2411(c)(1)) is amended-- (1) by striking ``or'' at the end of subparagraph (C); (2) by striking the period at the end of subparagraph (D)(iii)(II) and inserting ``; or''; and (3) by adding at the end the following: ``(E) with respect to an investigation of a country identified under section 183(a)(1), to request that the Secretary of Agriculture (who, upon receipt of such a request, shall) direct the Food Safety and Inspection Service of the Department of Agriculture to review certifications for the facilities of such country that export meat and other agricultural products to the United States.''.

United States Agricultural Products Market Access Act of 1997 - Amends the Trade Act of 1974 to direct the United States Trade Representative (USTR) to identify those foreign countries that: (1) deny fair and equitable market access to U.S. agricultural products or apply standards for the importation of U.S. agricultural products that are not related to public health concerns or cannot be substantiated by reliable analytical methods; and (2) are determined by the USTR to be priority foreign countries. Limits the identification of priority foreign countries to those that engage in the most onerous or egregious acts which have the greatest adverse impact on the relevant U.S. products. Provides that if available information indicates that such action is appropriate, the USTR may at any time: (1) revoke the identification of any foreign country as a priority foreign country; or (2) identify any foreign country as a priority foreign country. Subjects priority foreign countries to investigation by means other than a petition. Authorizes the USTR, with respect to an investigation of a country identified as denying fair and equitable market access to U.S. agricultural products, to request the Secretary of Agriculture to direct the Food Safety and Inspection Service of the Department of Agriculture to review certifications for the facilities of such country that export meat and other agricultural products to the United States.

According to court documents, Bagley lost control of a Range Rover she was driving in the desert 17 miles east of Battle Mountain, Nev., on Dec. 27, 2011, when she hit a big sagebrush, causing the vehicle to flip upside down. Her husband was thrown from the vehicle and suffered severe injuries. The 55-year-old was taken to Battle Mountain General Hospital, where he died Jan. 6, 2012. The couple's Shetland sheepdog, which was in the vehicle and ran after the crash, survived 53 days in the desert before being found. In her suit, Bagley claims she was negligent for failing to maintain a proper lookout and to keep her vehicle under proper control. Third District Judge Paul Maughan dismissed the case in January 2014. But last week, the appeals court reinstated the suit, saying in a 3-0 ruling that Utah statutes do not bar Bagley from seeking damages from herself. Mark Rose and Reid Tateoka, the attorneys representing the widow in her capacity as personal representative, said Bagley sued to meet her legal responsibility to act to benefit the estate, not herself. By law, creditors will have to be paid before Bagley, as her husband's sole heir, could get any money from the estate. "She can't, by law, look out for herself," Tateoka said Tuesday. "She has to look out for the estate." Lawyers representing driver Bagley in the wrongful-death suit point out that in similar scenarios in other states, courts have held that allowing those at fault to recover damages would be unjust. "Further, if this suit is allowed to continue, a jury would be asked to determine whether Barbara Bagley's fault caused Barbara Bagley's own harm," attorneys Peter Christensen and Kathryn Tunacik Smith said in a motion to dismiss the suit. "The jury would be asked to determine how much money will fairly compensate Barbara Bagley for the harm she caused herself. The jury will be highly confused — it cannot order a person to compensate herself." In its decision, the appeals court focused on the phrase "of another" in two statutes. The wrongful-death law says heirs or personal representatives can sue when the death of a person is caused "by the wrongful act or neglect of another," and the survival action law also allows for similar lawsuits. Driver Bagley's attorneys argued that the phrase "of another" means heirs or personal representatives cannot sue themselves if they caused the injury or death. The appeals court disagreed and said the phrase "of another" means someone other than the injured or deceased person — and that allows Bagley, as personal representative, to sue herself. Christensen said Tuesday that no decision has been made yet on whether to appeal to the Utah Supreme Court. — The Associated Press contributed to this story. [email protected] Twitter: @PamelaMansonSLC ||||| An unusual lawsuit in Utah is raising eyebrows among some legal and financial experts: A woman is suing herself in a wrongful death case. Earlier this week, the Utah Court of Appeals ruled that Barbara Bagley could indeed begin legal proceedings against herself. Bagley wants to charge herself with negligence in a 2011 car accident that killed her husband. She was driving the vehicle in the Nevada desert at the time when she hit a sagebrush and flipped the Range Rover over. Her husband was thrown from the car and later died from his injuries. Bagley claims she was negligent for not keeping control of her vehicle and for "failing to maintain a proper lookout" while driving. A state Third District judge dismissed the lawsuit last year, but it was reinstated last week in a unanimous ruling by the Utah Court of Appeals. Bagley's attorneys say she is advancing this lawsuit for the benefit of her husband's estate because creditors will have to be paid before the widow can receive any money as her husband's only heir. But other lawyers are looking to once again dismiss the suit, saying if it is allowed to continue, a jury would then be called upon to figure out if Bagley's negligence caused her own trauma. "The jury would be asked to determine how much money will fairly compensate Barbara Bagley for the harm she caused herself," attorneys Peter Christensen and Kathryn Tunacik said in their motion. "The jury will be highly confused -- it cannot order a person to compensate herself." John Holcomb, professor in the Department of Business Ethics and Legal Studies at the University of Denver's Daniels College of Business, told CBS MoneyWatch the lawsuit is "quirky and also clever." Bagley, he noted, plays multiple roles in this legal drama. She may be the two plaintiffs in the case, as heir and representative of the estate, but she's also the defendant. "Bagley as the two plaintiffs is really trying to get Bagley's insurance carrier to pay for Bagley's negligence," Holcomb said. "You can see why several states would see such a suit as unjust, as a victory would allow the plaintiff to be rewarded for her own negligence. That raises an ethical question of unjust reward and lack of deservedness." He also observed that the Utah Court of Appeals issued a unanimous decision for the lawsuit to proceed, basing its opinion on state law. But that doesn't necessarily resolve the bizarre legal wrangling the case presents. "Yes, the creditors will have first call on any money in the estate," Holcomb continued, "but they would in any case, so any damages paid would probably mainly benefit Bagley as heir, depending on debts owed by the deceased." "Had there been a disinterested or less interested party appointed as representative of the estate, and that party had brought suit," he said, "there would be fewer questions raised about an unjust lawsuit and one not based purely on the enrichment of Bagley."

– This part makes sense: A woman in Utah named Barbara Bagley is suing the driver who caused a car crash that killed her husband. This part is screwy: Bagley herself is that same driver. As the Salt Lake Tribune explains, Bagley is playing dual roles here in the bizarre lawsuit—as the representative of her husband's estate, she is going after the person responsible for his death, which just happens to be herself. Utah's Court of Appeals allowed the suit to proceed earlier this month. The case stems from a one-vehicle accident in 2011 in which Bagley lost control of her vehicle while driving in the desert. Her husband was fatally injured when it flipped, and Barbara Bagley is now accusing Barbara Bagley of "failing to maintain a proper lookout while driving," reports CBS News. The attorneys for Bagley the driver ("whose interests in the case are represented by her insurance carrier," the Trib notes) argued unsuccessfully that the case should be dismissed. "The jury would be asked to determine how much money will fairly compensate Barbara Bagley for the harm she caused herself," they wrote. "The jury will be highly confused—it cannot order a person to compensate herself." The story has one bright spot: The couple's dog also was in the car, and it ran into the desert after the accident—only to be reunited with Barbara Bagley nearly two months later.

galaxies are not expected to form a poisson sampling of the distribution of matter in the universe . indeed , it has been known for some time that different populations of galaxies demonstrate different clustering strengths @xcite , showing that they can not all have a simple relationship linking their distribution with that of the matter . this galaxy bias severely limits our ability to extract cosmological data from galaxy surveys @xcite . the large - scale shape of the linear matter power spectrum is dependent on @xmath1 because of the change in the evolution of the jeans scale after matter - radiation equality @xcite . however , changes in the general shape of the power spectrum , such as that caused by this physical process , are hard to separate from galaxy bias , which also imprints a signature that changes smoothly with scale . galaxy bias can also affect mode - coupling in the power spectrum by changing the non - linear scale , which can lead to small changes in the baryon acoustic oscillation positions @xcite . such effects are beyond the scope of our work , and we concentrate here on the broad changes to the shape of the galaxy power spectrum . the simplest model of galaxy bias is local , linear , deterministic bias , @xmath2 where @xmath3 is the galaxy overdensity field , and @xmath4 is the linear mass overdensity field . in this model , the bias @xmath5 is constant in space , but can change for different galaxy populations . a more generic model may also include a stochastic element which enters the description as an additional term , @xmath6 . or the bias could be non - local , where it depends on a smoothed version of the density field . in this paper , we will only be concerned with the relation between the galaxy and mass power spectra , and therefore define a practical measure of galaxy bias @xmath7 such a model can incorporate some of the complexities discussed above , but is local in @xmath8-space , so can not include any mode coupling terms , which are expected to be present . as we move to large scales , the galaxy bias is expected to tend towards a constant value . the simplest model for this is the peak - background split model @xcite . here galaxy formation depends on the local density field . large scale density modes can alter the local galaxy number density by pushing pieces of the density field above a critical threshold . on large scales we expect a linear relationship between the large scale mode amplitudes and the change in number density , so the shape of the galaxy and mass power spectra are the same . interestingly , such a linear relationship is broken if the density field has a non - gaussian component @xcite . on small scales we expect galaxy clustering to be different from that of the mass , as pairs of galaxies inside single collapsed structures become important @xcite . although large - scale bias is seen as a nuisance when extracting cosmological information from galaxy power spectra , it does provide constraints on possible galaxy formation models . @xcite proposed bivariate lognormal models of relative bias motivated by observations of galaxy distributions . the data were found to support a small ( everywhere @xmath95% ) , but significant , amount of stochasticity and non - linearity in these models on all scales , implying that galaxy formation is not solely a function of local density ; these effects must be understood in order to properly utilise the next generation of galaxy surveys . a related work , @xcite , also supported these findings . in order to use the power spectrum to extract cosmological information , we need to investigate the transition between scale - independent and scale - dependent galaxy bias . this transition is known to be a function of the galaxy population chosen . comparing work in @xcite and @xcite , which used the same techniques , and the analysis of @xcite , shows that there are deviations between the shapes of the 2dfgrs and sdss galaxy power spectra . if this results from galaxy bias and the fact that the 2dfgrs selected galaxies in a blue band whilst the sdss selected galaxies in a red band , then we should expect that similar changes show up in red and blue galaxies drawn from a single survey . using the sdss , @xcite showed that at @xmath10 , the shape of the power spectrum is a strong function of the @xmath11-band luminosity . in this paper we extend this work by splitting in galaxy colour and luminosity , and by fitting models to the resulting power spectra , in order to see if the sdss contains sufficient galaxies to fully explain the trend observed between sdss and 2dfgrs galaxies . previous work examining the observed dependence of the large scale bias on luminosity was carried out by @xcite who proposed the phenomenological model @xmath12 , @xcite extended this to better fit the available data by including an extra parameter in the form @xmath13 . @xcite reexamined both these models for samples split by galaxy colour . @xcite also examined the colour dependence of relative bias . @xcite presented colour dependent and luminosity dependent measurements of the projected correlation function of sdss galaxies . in all cases subsets of the data existed where some aspect of the bias model in question was shown to be a function of colour or luminosity . we first describe the sdss catalogues we use in section [ sec : cats ] , and how we model the radial selection function of our subsamples using luminosity function fits in section [ sec : sel_func ] . section [ sec : calc_spectra ] describes our calculation of power spectra and uncertainties , and the bias models to be fitted are presented in section [ sec : bias ] . results of fitting the bias models are given in section [ sec : results ] . in section [ sec : bias_lum ] we present simple models for the luminosity dependence of our bias parameters and the results of fitting these to our data . conclusions and discussion are presented in section [ sec : conclusions ] . we use galaxy catalogues selected from the sloan digital sky survey dr5 main galaxy sample . the sloan digital sky survey ( sdss ; @xcite ) , which was recently completed , used a 2.5 m telescope @xcite to obtain @xmath14 square degrees of imaging data in five passbands @xmath15 , @xmath16 , @xmath11 , @xmath17 and @xmath18 @xcite . the main galaxy sample @xcite consists of galaxies with petrosian @xmath11-band magnitude @xmath19 . this gives approximately @xmath20 galaxies per square degree , with a median redshift @xmath21 ; in this paper we use the dr5 sample @xcite . we exclude a small subset of the data taken during initial survey operation , for which the apparent magnitude limit fluctuated . this gives @xmath22 galaxies with @xmath23 and redshift @xmath24 ; the lower redshift cut strongly reduces the contribution from mis - classified stars . this is the catalogue used in @xcite , and further details can be found here . where specified , we have k - corrected the galaxy luminosities using the methodology outlined in @xcite . we also use the same @xmath25 shifted @xmath11-band filter to define our luminosities ( as discussed in @xcite ) , which we refer to as m@xmath26 throughout this paper . absolute magnitudes and @xmath8-corrections were calculated assuming @xmath27 , @xmath28 and @xmath29 , and we have applied the recommended ab corrections to the observed sdss magnitude system @xcite . .description of the subcatalogues analysed in this paper . the limits of the absolute magnitude bins are given , with the weighted mean and standard deviation . we also give the galaxy count for each bin . [ cols="^,^,^,^ " , ] , but now for model power spectra calculated assuming the @xmath30-model for galaxy bias . [ fig : pk_pmodel ] ] the model and data power spectra are compared in figs . [ fig : pk_qmodel ] & [ fig : pk_pmodel ] . these data are divided by our fiducial model convolved with the appropriate window function . comparisons are shown for the red galaxies in the left hand panels and blue galaxies on the right , with the rows of panels showing different absolute magnitude bins with the brightest at the top and faintest at the bottom . the offset visible between the data and model in the lower left panel is due to the high best - fit large - scale bias in the best - fit solution ( eq . [ eqn : linearmagbias ] , fit parameters given in table [ table : param_fits ] ) . such effects arise because the data are correlated , and the maximum likelihood solution does not match the @xmath31-by - eye expectation . + + in this section we try to fit a simple model for the luminosity dependence of the parameters in the bias models given in eqns . [ eqn : scalebias_eqn1 ] & [ eqn : scalebias_eqn2 ] . the asymptotic large - scale bias @xmath32 is known to be a function of galaxy luminosity @xcite , and galaxy colour @xcite . here , we extend the form of the model introduced by @xcite in order to cope with the more complicated behaviour seen when we also split galaxies by colour . we assume the three parameter model @xmath33 for relative biases where @xmath34 , we would have that @xmath35 , so the model would only have two free parameters . this model reduces to the form of @xcite in the case of @xmath36 . in addition , we parametrise @xmath37 and @xmath38 where @xmath39 , @xmath40 , @xmath41 and @xmath42 are parameters that we can fit to the data . we therefore have 5 free parameters in our fit to the data in addition to choice of whether to use the p or @xmath43-model . we have fitted these parameters by performing a simultaneous maximum likelihood search using all 12 power spectra , and allowing for covariances between band powers in each , and between different power spectra . i.e. we do not simply fit the recovered data values in fig . [ fig : bias_param_vs_mag ] , but instead perform a new fit to the data . the resulting bias models are compared with the results calculated when we allowed @xmath32 , @xmath43 and @xmath30 to match each catalogue individually in fig . [ fig : bias_param_vs_mag ] . as can be seen , this simple model does very well in matching the luminosity - dependent trends observed . , but now showing models with parameters calculated from a simple fit to the luminosity dependent trends observed in fig . [ fig : bias_param_vs_mag ] . [ fig : pk_qmodel_bm ] ] the resulting best - fit parameters allow us to define the following models for redshift - space galaxy power spectra . using the @xmath43-model , for red galaxies , @xmath44 and for blue galaxies , @xmath45 these model power spectra are compared with those observed in fig . [ fig : pk_qmodel_bm ] , where good agreement is seen . , but now showing models with parameters calculated from our simple fit to the luminosity dependent trends observed in fig . [ fig : bias_param_vs_mag ] . [ fig : pk_pmodel_bm ] ] using the @xmath30-model , for red galaxies , @xmath46 and for blue galaxies , @xmath47 where , as previously noted in the text , @xmath48 . these model power spectra are compared with those observed in fig . [ fig : pk_pmodel_bm ] where , as in fig . [ fig : pk_qmodel_bm ] , good agreement is seen . the @xmath49 values of the best - fit models including the @xmath30-model of bias are good , with @xmath50 given @xmath51 degrees - of - freedom for the red galaxies and @xmath52 for the blue galaxies given the same number of degrees of freedom for the blue galaxies . for the @xmath43-model , the corresponding numbers are @xmath53 , and @xmath54 . these numbers depend strongly on the covariance model adopted and , as a consequence , we do not analyse these further other than to note that the fits seem to give reasonable numbers . we have quantified the bias of red and blue galaxies as a function of luminosity on scales @xmath55 . we find clear differences in the large - scale asymptotic bias between blue and red galaxies , similar to that found by @xcite and @xcite , and shown in fig . [ fig : bias_param_vs_mag ] . at large scales red galaxies have are more biased than blue galaxies for all luminosities . the bias of blue galaxies is a strong , monotonically increasing function of luminosity , with more luminous galaxies being the most biased . for red galaxies , the picture is more complicated , with an increase in the bias of faint red galaxies ( @xcite find a similar result but stress the scale dependence of the observation ) . this trend is significant at the @xmath56 level.we find a stronger bias for luminous blue galaxies , compared with that of @xcite . the reason for this is unknown , although it is worth noting that our catalogue is larger than that used by @xcite , as they used additional cuts , constructing volume limited subsamples , compared with our sample selection procedure ( see section [ sec : cats ] ) . we performed a simple test of the dependence of this difference on observed scale , repeating our analysis for scales @xmath57 which approximates the @xcite measurement scale of @xmath58 , the discrepancy in the bias of the brightest blue galaxies was not removed . however , the change of scales brought the best fit red galaxy linear bias model into better agreement with the @xcite faint , red galaxies ; the model is poorly constrained at the faint end due to the lack of unique data points in that range . it is worth noting that , due to different colour cut criteria , the brightest absolute magnitude bins in @xcite are inherently more red than ours , this might lead one to expect larger bias measurements for those bins , the opposite of the observed trend . the bright blue sample contains the smallest numbers of galaxies , so the errors on the relative bias should be the largest of any sample . however , our expected errors are insufficient to fully explain the discrepancy , and there remains no obvious reason for this difference . the work on constant bias models has been extended by considering how the turn - off from constant large - scale bias depends on galaxy colour and luminosity . we have compared two models for this turn - off : the @xmath30-model and @xmath43-model given in eqns . [ eqn : scalebias_eqn1 ] & [ eqn : scalebias_eqn2 ] respectively . we find that there is little to choose between the two in terms of how well they can fit the current data , and both provide adequate fits to the power spectrum trends observed as a function of galaxy luminosity and colour at the current level of data precision . although there is no observational motivation , @xcite argued that the @xmath30-model has a physical motivation , and therefore offers a more attractive model of bias . we use the values of @xmath30 and @xmath43 obtained for these two models to quantify the degree of divergence from a constant bias model . note that these parameters change both the position and amplitude of the turn - off . we find that the best - fit values of @xmath30 and @xmath43 , shown in fig . [ fig : bias_param_vs_mag ] , are a strong function of luminosity for blue galaxies . red galaxies show far weaker evolution with luminosity , and are consistent with the hypothesis of no change in the scale at which the bias can no longer be described as a constant , to current data precision . interestingly , this trend in the turn - off from apparent scale - independent behaviour does not match that of the amplitude of the large - scale bias . if amplitude and turn - off scale were linked , we might have expected the @xmath43 and @xmath30 parameters to match for red galaxies of high or low luminosity , where the constant bias component matches , but be different for intermediate luminosity galaxies . we do not observe such a trend , suggesting that there might not be a simple link between the amplitude of bias and the scale at which the 1-halo term becomes important . it is clear that the simple @xmath30 and @xmath43-models will become insufficient to model the observational data , both on very small scales , and as the data improve . they are , after all , simply motivated to fit observed trends , and do not encompass all of the physics involved . one alternative and more complex prescription for bias prediction is that presented in @xcite which can predict @xmath59 given a set of cosmological parameters and a hod model , the parameters of which have been determined from the observed , projected correlation function ( the correlation function provides additional information to that of the power spectrum as they are sensitive to different scales ) . however , the potential limits of simple , phenomenological models , such as the @xmath30 and @xmath43-models , does not stop us being able to use them to investigate trends in the data , as we have done in this paper . the current data clearly show that , on relatively large scales ( our small scale limit of @xmath60 approximately corresponds to @xmath61 ) , blue and red galaxies have very different bias properties . it is the blue galaxies that are faint in the @xmath11-band whose relative clustering on different scales most closely resembles that of the mass , and the luminous blue galaxies the least . this supports the hypothesis that the shapes of the 2dfgrs and sdss main galaxy power spectra of @xcite and @xcite differ because the average galaxy bias of each sample differs , caused by different sample selections . the clustering of the 2dfgrs galaxies , on average , would be expected to be a better tracer of the linear clustering signal out to smaller scales than the sdss galaxies . this highlights the importance of sample selection for future galaxy surveys , and the importance of understanding galaxy bias for extracting cosmological information from power spectrum shapes from such surveys . red and blue galaxies show very different trends in their large - scale bias and the scale - dependent smaller - scale bias as a function of luminosity . it is clear that galaxies need to be split into sub - populations by more than just the luminosity in a single band in order to properly understand and model bias . jc would like to thank steven peter bamford and bjoern malte schaefer for helpful and insightful discussions . we thank molly swanson for providing her data for comparison with ours in fig . [ fig : relativebias ] , and for helpful discussions . we thank the referee for helpful comments . jc is funded by a stfc phd studentship . wjp is supported by stfc , the leverhulme trust and the european research council .

it has been known for a long time that the clustering of galaxies changes as a function of galaxy type . this galaxy bias acts as a hindrance to the extraction of cosmological information from the galaxy power spectrum or correlation function . theoretical arguments show that a change in the amplitude of the clustering between galaxies and mass on large - scales is unavoidable , but cosmological information can be easily extracted from the shape of the power spectrum or correlation function if this bias is independent of scale . scale - dependent bias is generally small on large scales , @xmath0 , but on smaller scales can affect the recovery of @xmath1 from the measured shape of the clustering signal , and have a small effect on the baryon acoustic oscillations . in this paper we investigate the transition from scale - independent to scale - dependent galaxy bias as a function of galaxy population . we use the sloan digital sky survey dr5 sample to fit various models , which attempt to parametrise the turn - off from scale - independent behaviour . for blue galaxies , we find that the strength of the turn - off is strongly dependent on galaxy luminosity , with stronger scale - dependent bias on larger scales for more luminous galaxies . for red galaxies , the scale - dependence is a weaker function of luminosity . such trends need to be modelled in order to optimally extract the information available in future surveys , and can help with the design of such surveys . [ firstpage ]

turbulent convection is ubiquitous in nature and in many engineering applications . rayleigh - bnard convection ( rbc ) in which fluid confined between two plates is heated from below and cooled on the top is an idealized yet an important paradigm to understand convective turbulence . the dynamics of rbc is governed by the two non - dimensional parameters : the rayleigh number @xmath3 and the prandtl number @xmath4 , where @xmath5 is the vertical height of the container , @xmath6 is the acceleration due to gravity , @xmath7 is the temperature difference between the bottom and top plates , and @xmath8 , @xmath9 , and @xmath10 are the thermal heat expansion coefficient , thermal diffusivity , and kinematic viscosity , respectively , of the fluid . @xcite performed experiments on water ( @xmath11 ) and silicon oil ( @xmath12 ) and observed coherent roll structures , also known as `` large scale circulation '' ( lsc ) , in the turbulent regime . subsequently , @xcite ascertained the existence of lsc in helium ( @xmath13-@xmath14 ) contained in a cylindrical container . they proposed that coherent large scale structures exist statistically only above a certain rayleigh number ( @xmath15 ) . they also observed a low frequency peak in the power spectrum of the temperature field . @xcite studied the onset of large - scale coherent mean flow in rbc using shadowgraph and particle image velocimetry techniques and showed that lsc is a result of the organization of plume motion . @xcite performed rbc experiments on mercury ( @xmath16 ) and placed several thermistors along the azimuth of the cylinder . they deduced the presence of global circulation from the dipolar temperature distribution measured by the probes . the temperature fluctuations ( after subtracting the mean ) switched sign randomly in their experiment . since the warmer fluid ascends from one side , and the cooler fluid descends from the other side of the apparatus , @xcite deduced that the vertical velocity would also exhibit random `` reversals '' in phase with the temperature fluctuations . this feature of convection has been studied extensively using theoretical , experimental , and computational tools ( see reviews by * ? ? ? * ; * ? ? ? * ) . in this paper we perform computational investigation of the reversal dynamics of lsc in a cylindrical geometry . @xcite computed the first fourier mode of the measured temperature field . they observed that the amplitude of the first fourier mode never vanishes , but the phase of the fourier mode is highly variable . a phase change of @xmath17 corresponds to the reversal of the flow . @xcite also observed a low - frequency peak in the energy spectrum that corresponds to the circulation frequency of the large - scale flow inside the cylinder . et al._@xcite performed an experiment with mercury contained in cylindrical container for aspect ratios @xmath18 , @xmath19 , and @xmath20 and found that the low frequency peak is absent for aspect ratio @xmath18 . @xcite , and @xcite reported reversals in their convection experiments on helium . @xcite and @xcite performed similar experiments on water ( @xmath21 ) and measured the temperature field in the bulk using probes placed at @xmath22th , @xmath18 and @xmath23th height of the cylinder . they observed that the plane containing lsc exhibits diffusive and sometimes quick significant drift in the azimuthal direction with the angular change ( @xmath24 ) ranging from small values to @xmath17 , i.e. , @xmath25 . this is called the `` reorientation '' of lsc . the reorientation of the flow can occur in two ways : ( a ) through rotation of the circulation plane without any major reduction of the circulation strength ; ( b ) through `` cessation '' of the circulation , followed by a restart in a randomly chosen new direction . @xcite also computed the amplitude of the first fourier mode , and found it to be nonzero for rotation - led reorientations and close to zero during cessation - led reorientations . @xcite measured azimuthal motion of the lsc using particle image velocimetry and studied reversals of lsc . they observed `` double cessation '' in their experiments . in a similar set of experiments , @xcite , @xcite , and @xcite observed strong dependence of the azimuthal reorientations on the aspect ratio of the cylinder . @xcite performed rbc experiments on water and computed temperature correlation functions . they reported a transition from random chaotic states to a correlated turbulent states at around @xmath26 . however , @xcite report strongly correlated large scale flow beyond @xmath27 for helium gas ( @xmath28 ) . various models have been proposed to understand the dynamical behaviour of the lsc . @xcite and @xcite proposed a stochastic model in which the reversal of lsc was explained as noise induced switching between two meta - stable states . @xcite attempted to explain the irregular cessation and subsequent reversal of the lsc using the force and thermal balance on a single plume modelled by coupled nonlinear equations related to the lorenz equations . @xcite and @xcite proposed a stochastic model with the strength and the azimuthal orientation of the lsc being determined by two stochastic ordinary differential equations ; this model appears to explain the experimental observations of cessation and reorientation . villermaux@xcite proposed a model to explain the low frequency oscillations in the temperature signal in the bulk . his model assumes that the modes of the boundary layers interact through the slow moving large scale circulation . there are only a small number of computational studies on the reorientation or reversal of lsc . @xcite simulated convection in air ( @xmath28 ) in a cylinder with an aspect ratio of @xmath18 and observed a single roll breaking into two counter rotating rolls stacks vertically . benzi & verzicco@xcite performed a simulation of the fluid at @xmath29 with white noise added to the heat equation and studied the statistical behaviour of the observed reversals . @xcite studied rbc for infinite prandtl number in a 2d box and observed reversals of lsc for very high @xmath30 ( @xmath31 ) . there are others 2d numerical experiments in a box that report that the reversals of the lsc is due to cessations ( see * ? ? ? * ; * ? ? ? * ) or due to the chaotic movement of rolls perpendicular to the roll axis ( see * ? ? ? in this paper we study the dynamics of reversals of convective structures using direct numerical simulation ( dns ) of turbulent rbc for @xmath28 in a cylinder of aspect ratio one . we apply conducting boundary conditions on the top and bottom plates and adiabatic boundary conditions on the lateral walls of the container . no - slip boundary condition is applied on all the surfaces of the container . our simulations indicate a lsc in the container . furthermore , we observe rotation - led and cessation - led reorientations of lsc similar to those observed in experiments . we compute the amplitudes and phases of the fourier modes of the vertical velocity measured near the lateral wall in the mid plane , and establish that the dynamics of the lsc can be captured quite well by the low wavenumber fourier modes . the outline of the paper is as follows . we present our numerical method in section @xmath20 . the results pertaining to observation of lsc and their reorientations are presented in section @xmath32 . we conclude our results in section @xmath33 . we numerically simulate the convective flow in a cylinder . the boussinesq approximation is assumed for the buoyancy in the fluid . the relevant non - dimesionalized dynamical equations for the fluid are @xmath34 where @xmath35 is the velocity field , @xmath36 is the temperature field , @xmath37 is the deviation of pressure from the conduction state , @xmath38 is the rayleigh number , @xmath4 is the prandtl number , and @xmath39 is the buoyancy direction . here @xmath10 and @xmath9 are the kinematic viscosity and thermal diffusivity respectively , @xmath5 is the vertical height of the container , and @xmath7 is the temperature difference between the bottom and top plates . for the non - dimensionalization we have used @xmath5 as the length scale , @xmath40 ( free fall velocity ) as the velocity scale , and @xmath7 as the temperature scale . consequently , @xmath41 is the time scale of our simulation . the aspect ratio of the container is taken to be one . we confine our study to @xmath28 which is a typical prandtl number for air . the above non - dimensionalized equations ( [ eq : u]-[eq : incompressible ] ) are solved numerically for a cylindrical geometry using a finite - difference scheme . the convective parts of the equations are discretized in cylindrical coordinates using tam and webb s fourth order central explicit scheme with enhanced spectral resolution ( see * ? ? ? the diffusive part is discretized using the second - order central - difference scheme . for the time advancement , we use the second - order adam - bashforth scheme for the nonlinear terms , and the crank - nicholson scheme for the diffusive terms . we perform simulations for rayleigh numbers @xmath29 , @xmath42 , @xmath43 , and @xmath1 . comparison with experimental results show that these rayleigh numbers are near the threshold of strong turbulence regimes ( see * ? ? ? * ) . .@xmath44 , @xmath45 , and @xmath46 are the number of grids along the radial , azimuthal , and vertical directions of the cylindrical container ; @xmath47 and @xmath48 are the minimum and maximum mean - grid sizes ; @xmath49 ; @xmath50 is the kolmogorov length scale calculated using the expression @xmath51 ; @xmath52 is the number of points inside the thermal boundary layer ; @xmath53(comp ) is the nusselt number obtained from the simulation ; @xmath54 ( @xmath55 ) and @xmath56 ( @xmath57 ) are the numerically calculated viscous and thermal dissipation rates respectively ; @xmath58 ( @xmath59 ) and @xmath60 ( @xmath61 ) are the analytical values of viscous and thermal dissipation rates respectively . the last two columns show @xmath62 and @xmath63 . [ cols="^,^,^,^,^,^,^,^,^,^,^ " , ] in the next section we will study the properties of the temperature and velocity time series , and relate them to the earlier experimental results on reversals of lsc . the time series measured by the probes of fig . [ schematic_profile](a ) carries signature of the lsc that will be described below . later in the section we will relate the reversals of the vertical velocity field with the reorientation of the lsc . in figs . [ schematic_profile](b ) and [ schematic_profile](c ) we display the temperature profiles for @xmath64 for a vertical plane ( @xmath65 ) and the middle horizontal plane ( @xmath66 ) respectively . as a supplementary material , we also provide two short movies depicting the flow behaviour for the above two sections . these figures and movies clearly indicate the presence of convective structures in the flow . vs. delay time @xmath67 ( in units of large eddy turnover time ) for a probe at @xmath68 , @xmath69 , and @xmath66 : ( a)@xmath70 on a ( @xmath71 ) grid , ( b)@xmath72 on a ( @xmath73 ) grid , ( c)@xmath64 on a ( @xmath74 ) grid , and ( d)@xmath75 on a ( @xmath74 ) grid . the insets show oscillations on eddy turnover time scale . ] in figs . [ fig : autocorr](a , b , c , d ) we plot the normalized autocorrelation @xmath76 at @xmath77 for @xmath78 , and @xmath1 respectively . here @xmath79 ( @xmath80 is the mean temperature ) and @xmath81 , and time is measured in the units of eddy turnover time . the autocorrelation functions indicate two time - scales in the system . variations at the shorter time - scale , shown in the insets , are due to the statistical return of the convective flow after one eddy turnover time or less ( see table [ num_details ] ) . for @xmath70 and @xmath82 , the oscillations are somewhat irregular . however for @xmath83 and @xmath84 , the oscillations in the insets are quite regular , and the oscillation time period of the auto - correlation function is around one eddy turnover time . this is also evident from the plot of the cross - correlation function of temperature between two azimuthally opposite probes placed at @xmath69 and @xmath85 , @xmath68 , and @xmath66 ( see fig . [ fig : cross_cor_ra2e7 ] ) . the cross - correlation function also shows oscillations with approximately one eddy turnover time as the time period , in general agreement with the observations of @xcite , @xcite , @xcite , and @xcite . the above correlations are related to the peak in the power spectrum at frequency corresponding to @xmath86 . the peak in the spectrum however tends to be overshadowed by noise . consequently the correlation function appears to be a good tool to analyze these oscillations . note that the autocorrelation studies tend to become strongly periodic when lsc direction is locked , e.g. , by a small tilt of the cylinder @xcite . on a ( @xmath74 ) grid , the cross - correlation function between the temperature measured at two azimuthally opposite probes at @xmath69 and @xmath85 in the mid plane at @xmath68 . the inset shows oscillations on eddy turnover time scale . ] in addition to the above , we observe variations in the above auto - correlation and cross - correlation functions at much larger time - scales . for @xmath70 ( see fig . [ fig : autocorr](a ) ) , there is a significant decrease in correlations till @xmath87 , after which correlations rise again to reach a maximum value at @xmath88 . these variations possibly correspond to the reorientations of the lsc . similar features are observed for @xmath89 ( see fig . [ fig : autocorr](b ) ) . for @xmath83 and @xmath90 , the auto - correlation functions decrease with time ( see figs . [ fig : autocorr](c , d ) ) . incidentally , the cross - correlation function for @xmath83 shows minima at @xmath91 and then at @xmath92 , and a maximum at @xmath93 , which possibly indicates reversals of the flow at @xmath93 , and reoccurrence at @xmath94 . we could not perform longer statistics since the computer simulations of rbc flows for large rayleigh numbers are computationally very expensive . the auto - correlation and cross - correlation function studies are inconclusive due to averaging , yet , the above observations indicate with some certainty that the lsc exist in rbc . the reversal time could not be deduced from the present correlation functions . the presence of lsc becomes more apparent when we will study the time series of the velocity and temperature fields , a topic of next subsection . the time series of the vertical velocity field for @xmath95 , @xmath96 recorded by the probes at @xmath97 @xmath98 , @xmath68 , and @xmath66 are shown in figs . [ timeseries_r6e5 ] , [ timeseries_r8e6 ] , and [ timeseries_r2e7 ] respectively . here time is measured in the units of the free fall time ( @xmath99 ) . the figures clearly show that vertical velocity at probes @xmath100 and @xmath101 are clearly anti - correlated . these observations indicate the presence of a large scale convective structure ( see figs . [ schematic_profile](b , c ) ) . as shown in figs . [ timeseries_r6e5]-[timeseries_r2e7 ] the local mean value ( in time ) of the vertical velocity changes sign , and this feature is called `` reversal '' of lsc in literature . in the following discussions we will show that the above mentioned reversals are connected to the `` reorientations '' of lsc . to quantify the reorientations , we fourier transform the vertical velocity field measured at @xmath68 and @xmath66 . note that these probes are near the lateral wall in the mid plane . the velocity signal at a given probe can be expressed in terms of its fourier transform as @xmath102 where @xmath97(@xmath103 ) , and @xmath104 is the phase of the @xmath105-th fourier mode . note that the reality condition @xmath106 is used to derive eq . ( [ eq : fourier ] ) . in our simulations we observe that the first fourier mode ( @xmath107 ) dominates over the other modes except possibly during the reversals . note that @xcite , and @xcite have analyzed the properties of @xmath108 and @xmath109 only using their experimental data . in later part of our discussion we will compute the amplitudes of the fourier modes using the vertical velocity fields measured by probes at @xmath66 and @xmath68 . for quantitative analysis , @xcite and @xcite proposed that the phase of the first fourier mode @xmath110 can be used as an approximate measure for the orientation of the plane of lsc . using this criteria , they defined reorientation of the lsc " as a sudden and significant rotation of the above plane . they used two selection criteria for the reorientation of lsc : ( a ) the magnitude of angular change in orientation ( @xmath111 ) should be greater @xmath112 ; ( b ) the azimuthal rotation rate ( @xmath113 ) should be greater than @xmath114 , where @xmath115 is the eddy turn over time . we follow the same criteria for the selection of reorientation events in our simulation . in figs . [ timeseries_r6e5]-[timeseries_r2e7 ] we plot the phase of the first fourier mode ( @xmath110 ) , which is a measure of the plane of lsc . note that the discontinuities from @xmath116 degree to @xmath117 degree in the @xmath110 diagrams are not reorientations ; they simply indicate jitters near 180 degree . in all the time series of the vertical velocity and the phase of the first fourier mode , we observe that the mean value of the vertical velocity changes sign but not necessarily simultaneously for all the probes . for example in fig . [ timeseries_r6e5 ] , the vertical velocity @xmath118 measured by all the probes reverse sign near @xmath119 ( the right boxed region of fig . [ timeseries_r6e5 ] ) . this reorientation is `` complete reversal '' of lsc , and it corresponds to the change in @xmath110 by around @xmath17 , i.e. , @xmath120 . near @xmath121 ( the left boxed region of fig . [ timeseries_r6e5 ] ) however @xmath118 changes sign for all the probes except at @xmath122 and @xmath17 . this kind of reorientation will be termed as a `` partial reversal '' , and it corresponds to @xmath123 . near @xmath121 , @xmath124 . the time series shown in figs . [ timeseries_r6e5]-[timeseries_r2e7 ] exhibit several partial and complete reversals . for example , we observe complete reversals for @xmath125 and @xmath126 in the boxed regions shown in the figures . a careful analysis of the fourier modes reveals that the complete and partial reversals are intimately related to the change in orientations of the convective structures by @xmath127 . we take the real space @xmath118 data before and after the reversals for the three cases marked with arrows in the @xmath110 time series of figs . [ timeseries_r6e5 ] and [ timeseries_r2e7 ] . in figs . [ profile_r6e5](a , c , e ) we illustrate the azimuthal profile of vertical velocity at @xmath66 and @xmath68 before and after the reorientations as blue and red curves respectively . we calculate @xmath127 , the change in the phase of the first fourier mode , during the reorientations of the structures . if the convective structure rotates by an angle @xmath127 during a reorientation , then , according to eq . ( [ eq : fourier ] ) , we can cancel the effects of this reorientation by subtracting @xmath128 from the phases of all the positive @xmath105 modes , and by adding @xmath129 to all the negative @xmath105 modes of the data recorded after the reorientation ( note that the @xmath130 mode is left unaltered ) . we perform the above exercise on the fourier modes of the data sets recorded after the specified reversals or reorientations . subsequently we compute the velocity field from the modified fourier coefficients . the modified velocity field , shown as green curves in figs . [ profile_r6e5](b , d , f ) , matches quite well with the corresponding velocity profiles before the reorientations . thus we show that the convective structures essentially rotate by @xmath127 during the reorientations . and @xmath68 before ( blue curve ) and after the reorientation ( red curve ) : ( a ) @xmath64 at @xmath131 and 750 ; ( c)@xmath132 at @xmath133 and 2850 ; ( e ) @xmath29 at @xmath134 and 4050 . during the reorientations the phase of the first fourier mode changes by @xmath135 , @xmath136 and @xmath116 degrees respectively . for the reoriented time series we subtract @xmath127 from the positive @xmath105 modes , and add @xmath127 to the negative @xmath105 modes , and construct a modified velocity profile ( green curve ) . as seen in the subfigures ( b ) , ( d ) , and ( f ) , the reconstructed velocity profiles match quite well with the profiles before the reorientation . ] the above features of our simulations are in general agreement with the experimental results by @xcite , @xcite , @xcite , and @xcite . note that the numbers of reorientations in the convection experiments are much larger than those observed in numerical simulations . in the next subsections we analyze the detailed dynamics of the reorientation of the lsc using numerical data . careful analysis of the phases and amplitudes of the fourier modes provide important clues about the dynamics of the reorientations of lsc and the reversals of the vertical velocity . the amplitudes of the fourier modes vary significantly over time . we observe that during some of the reversals or reorientations , the amplitude of the first fourier mode almost vanishes ; these reorientations are termed as `` cessation led '' . in the other reorientations that are termed as `` rotation led '' the fourier modes continue to fluctuate around their mean values . these kinds of reversals were reported by @xcite , @xcite , and @xcite based on their rbc experiment . in the present paper we probe the dynamics of reversals using numerical simulations . ) ( in units of @xmath137 ) , amplitude of the first fourier mode ( @xmath138 ) , and amplitude of the second fourier mode ( @xmath139 ) during the rotation - led reversals . ( a ) , ( b ) , ( c ) , and ( d ) show the time series of @xmath110 , @xmath140 , @xmath139 , and @xmath141 respectively for @xmath29 on a ( @xmath71 ) grid in which the reversal takes place near @xmath142 . ( e ) , ( f ) , ( g ) , and ( h ) show the time series of @xmath110 , @xmath140 , @xmath139 , and @xmath141 respectively for @xmath64 on a ( @xmath74 ) grid with a reorientation event near @xmath143 . ] in fig . [ amp_ph_fullrev ] we plot the phases and amplitudes of the first two fourier modes during two rotation - led reorientations . for @xmath29 fig . [ amp_ph_fullrev](a ) exhibits the time series of the phase ( @xmath144 , i.e. , in units of @xmath137 ) . figs . [ amp_ph_fullrev](b , c ) show the amplitudes of the first and second fourier modes ( @xmath138 , @xmath145 ) respectively , while fig . [ amp_ph_fullrev](d ) shows their ratio @xmath146 . as shown in the figures , @xmath110 changes by approximately @xmath17 near @xmath147 , but @xmath138 and @xmath145 continue to fluctuate around their average values . however , @xmath138 always dominates over @xmath145 , as evident from the plot of @xmath146 shown in fig . [ amp_ph_fullrev](d ) . figures [ amp_ph_fullrev](e , f , g , h ) exhibit similar features for @xmath64 . note however that @xmath138 tends to have a small dip during the reorientation , but @xmath148 is much smaller compared to the cessation - led reversals to be described later . note that both the above events lead to complete reversals " since @xmath120 . , @xmath138 , @xmath145 , and @xmath146 indicating cessation - led reorientation near @xmath149 for @xmath72 ( @xmath73 ) . the strength of @xmath138 decreases significantly , while @xmath146 increases during this event . ] in the other set of reversals or reorientations , we observe that the amplitude of the first fourier mode ( @xmath138 ) tends to vanish during the event . these set of reversals were termed as `` cessation led '' by @xcite , @xcite , and @xcite . we illustrate the cessation - led reversals using the following examples . figures [ cess_rev_ra8e6](a ) and [ cess_rev_ra8e6](b ) exhibit the time series plots of @xmath110 and @xmath138 respectively for @xmath72 . during the cessation at @xmath149 , @xmath150 and @xmath138 tends to zero . the amplitude of the second fourier mode @xmath145 however increases slightly above its average value during this event ( see fig . [ cess_rev_ra8e6](c ) ) . the fluctuations in @xmath138 and @xmath145 however tend to hide the above features . therefore we use @xmath151 to amplify the decrease in @xmath138 and increase in @xmath145 to be able to identify the cessation - led reversals clearly . in [ cess_rev_ra8e6](d ) we plot @xmath151 that exhibits a sharp peak during the event . this is an example of cessation - led complete reversal since @xmath150 . figure [ cess_partial_ra6e5 ] shows the corresponding quantities for another set of cessation - led reorientations for @xmath70 . as evident from the time series , near @xmath152 , @xmath153 . later at @xmath154 , @xmath155 . these two reorientations of fig . [ cess_partial_ra6e5 ] are partial ones , and the lsc comes back to its original configuration after the two reorientations ( @xmath156 ) . during both these events @xmath157 has a sharp peak . , @xmath138 , @xmath145 , and @xmath146 indicating cessation - led partial reorientations near @xmath158 and @xmath159 for @xmath29 ( @xmath71 grid ) . for both the events @xmath127 are approximately @xmath160 . ] in our simulations we also observe reorientations involving `` double cessations '' , first observed by @xcite in their experiments . during these events , the phase @xmath110 changes in two stages in quick succession , first by @xmath161 and then second by @xmath162 . therefore the net @xmath163 . during double cessation , @xmath138 vanishes on two occasions separated by a small time gap ( within an eddy turnover time ) . @xmath145 tends to increase during these times , hence @xmath157 exhibits two peaks within a short time interval . two independent double cessation events have been illustrated in fig . [ amp_ph_cessation1_r6e5](a ) and fig . [ amp_ph_cessation2_r6e5](a ) ( for @xmath164 ) . in fig . [ amp_ph_cessation1_r6e5](a ) we observe the first cessation at @xmath165 followed by the second cessation at @xmath166 , and @xmath167 . in fig . [ amp_ph_cessation2_r6e5](a ) the first cessation occurs at @xmath168 followed by the second cessation at @xmath169 with @xmath170 . since the net change in the phase @xmath110 is approximately zero , the final configuration of lsc is similar to its original configuration . note that one eddy turn time for the corresponding run is approximately 26 free fall time ( see table 2 ) . hence the two double cessations occur within @xmath171 and @xmath172 eddy turnover time respectively , which is consistent with the experimental result of @xcite . , @xmath138 , @xmath145 , and @xmath146 indicating double cessation for @xmath29 ( @xmath71 grid ) . first cessation occurs at @xmath173 and second one occurs at @xmath174 . during both the events @xmath138 becomes weak and @xmath145 dominates . ( d ) shows the two spikes in @xmath146 during the events . ] , @xmath138 , @xmath145 , and @xmath146 indicating double cessation for @xmath29 ( @xmath71 grid ) . first cessation at @xmath175 is followed by the second at @xmath176 . during both the events @xmath138 becomes weak and @xmath145 dominates . ( d ) shows the two spikes in @xmath146 during the events . ] time series plot of @xmath110 , @xmath138 , @xmath145 , and @xmath146 depicting events similar to double cessations ( @xmath71 grid ) . @xmath177 near @xmath178 , while @xmath179 near @xmath180 . during both the events @xmath181 but the ratio @xmath146 increases significantly . ] for @xmath182 we observe two events that are similar to the above mentioned double cessation events ( see fig . [ amp_ph_cess_r6e5](a , b , c , d ) ) . near @xmath183 , @xmath110 changes twice , @xmath184 and @xmath185 with net @xmath186 . these two events however occur very close to each other , and we observe only one peak peak for @xmath157 , rather than any double peaks indicative of double cessation . another cessation - led reorientation occurs near @xmath187 that resembles the above double - cessation event except one major difference . here @xmath188 and @xmath185 , hence lsc reorients by a net angle after the event . note that for the double cessation reported by @xcite @xmath189 and the net change in @xmath110 is zero . in our numerical simulations we find such events . in addition we also observe a double cessation where @xmath190 , and the lsc reorients by a finite angle after the event . ) of lsc during reorientations . criteria of @xcite and @xcite have been used for identifying reorientations of lsc . ] figure [ rotation_reorientation ] illustrates the distribution of @xmath127 of lsc observed in our numerical simulations . we observe three complete reorientations ( @xmath120 ) among which two are rotation - led while one of them is cessation - led . the number of observed partial reorientations are rather large ( total 19 ) . among the partial reorientation events , 15 of them are rotation - led , while 4 of them are cessation - led . we also observe 4 double cessations among whom three of them have @xmath186 while the fourth one has @xmath191 . the above observations indicate that cessation - led events are rarer compared to the rotation - led ones , an observation consistent with those of @xcite and @xcite . the number of reorientations observed in our simulations are far fewer compared to those observed in the experiments of @xcite , @xcite , @xcite , and @xcite . consequently we are unable to perform statistics of reorientations similar to those by @xcite and @xcite . in our numerical simulations we observe that the higher fourier modes play interesting role during reorientations . these kind of investigations were missing in earlier experimental works . we find that during the cessation - led reorientations @xmath145 tends to become significant when the @xmath138 tends to vanish . this feature is evident from the significant increase in the magnitude of @xmath146 during the cessation - led reorientations . @xcite and @xcite interpret such events as cessation of the circulation , followed by a restart in a randomly chosen new direction . our simulation results are consistent with the above interpretation , yet another scenario is also possible . during the cessation , the circulation structure corresponding to @xmath192 ( dipolar in a horizontal plane ) becomes very weak , and the quadrupole structure corresponding to @xmath193 becomes dominant . after the cessation , the quadrupole structure disappears and dipolar structure reappears with a shift in the azimuthal direction . these features have been illustrated in fig . [ snap_cess_r6e5 ] in which we show the horizontal profile of temperature in @xmath66 plane before , during , and after two cessation - led reorientations for @xmath29 . figures [ snap_cess_r6e5](a , b , c ) represent the temperature snapshots near a double cessation event ( near @xmath194 of fig . [ amp_ph_cessation1_r6e5 ] ) . the system starts from @xmath192 dominant state with approximate profile as @xmath195 ) of fig . [ snap_cess_r6e5](a ) . during the cessation , the system profile appears as fig . [ snap_cess_r6e5](b ) which has @xmath193 as the most prominent fourier mode with profile as @xmath196 . after the double cessation , the system return to @xmath192 dominant structure as evident from fig . [ snap_cess_r6e5](c ) . similar features are observed for another cessation - led reorientation near @xmath197 for @xmath29 shown in figs . [ snap_cess_r6e5](d , e , f ) . note that in the rotation - led reorientations , the dipolar structure continues to be dominant during the reorientation itself . in this section we present some of the complex dynamics of the reorientations of lsc . the reversals of the vertical velocity have been shown to be intimately related to the reorientations of lsc . we observe rotation - led and cessation - led reorientations , which were first reported by @xcite and @xcite , and observed later in other experiments @xcite . in our simulations we also find double cessation , previously observed by @xcite . a new feature of our simulation is a double cessation in which the orientation of the lsc after the event is different from the original orientation . in our analysis we study higher fourier modes , notably @xmath193 , which was missing in earlier work on reversals . we propose a new interpretation of the cessation - led reorientations , and argue that the lsc transforms from dipolar ( @xmath192 dominant ) to quadrupolar ( @xmath193 dominant ) , and then back to dipolar ( @xmath192 dominant ) structure during this event . in summary , we numerically compute turbulent convective flows for a cylindrical geometry and study the characteristics of the lsc , in particular those related to flow reversals . the first fourier mode along the azimuthal direction is the most dominant mode ; the phase of this mode ( @xmath110 ) is used as a measure of the orientation of lsc . our numerical results and earlier experimental results indicate that the lsc occasionally reorients itself by rotating along the azimuthal direction by an arbitrary angle . when the reorientation angle is around @xmath17 , the vertical velocity at _ all _ probes change sign signaling complete reversal of the flow . a partial reversal is observed when the reorientation angle is less than @xmath17 . we therefore argue that the primary cause of the flow reversal is the azimuthal reorientation of the lsc . in our numerical simulations we observe two kinds of reorientations : ( a ) rotation - led , and ( b ) cessation - led , earlier observed by @xcite , @xcite , and @xcite . the rotation - led reversals involve rotation of the lsc without appreciable reduction in circulation strength , i.e. , the amplitude of @xmath138 remains finite . in the cessation - led reversals , @xmath181 , which is interpreted by @xcite and @xcite as cessation of circulation followed by a restart in a randomly chosen new direction . during this event , our numerical simulations reveal that the ratio of the amplitude of the second fourier mode and the first fourier mode , i.e. , @xmath146 , increases significantly , and then it comes back to its original level . these properties of the fourier modes reveal that during the cessation , the lsc transforms from a dipolar - like structure to a quadrupolar - like structure , and then back to a dipolar - like structure . these features appear to have certain similarities with the reversals of magnetic field in dynamo @xcite . the role of higher fourier modes for reversals and reorientations of lsc have been highlighted in our simulations for the first time . we also observe double cessation in our simulations . @xcite had observed in their experiments that the lsc returns to its original orientation ( approximately ) after a double cessation . we however find in our numerical simulations that the change of the orientations of lsc during some double cessations are zero , while in some others , the changes are nonzero . our numerical simulations reproduced many features ( rotation - led reorientations " , `` cessation - led reorientations '' , `` double cessation '' , etc . ) observed in convection experiments by @xcite , @xcite , @xcite , @xcite , and @xcite for rayleigh numbers greater than those in our simulations . several researchers have argued that the reorientations , including reversals , of lsc occur only under strong turbulence regimes ( say @xmath198 ) . we however observe that the nature of convective flows and reorientations are very similar for the range of rayleigh numbers studied by us ( @xmath29 to @xmath75 ) . the lowest rayleigh number @xmath164 is probably in the weak turbulence regime where the lsc is not well organized , and @xmath199 is in the lower end of strong turbulence regime . we could not carry out simulations for even larger rayleigh numbers due to very expensive computational requirements for these runs . however we believe that reversals in high rayleigh number regimes are highly likely to be similar to those presented in the simulations . * acknowledgements : * we thank krishna kumar , stphan fauve , pankaj wahi , supriyo paul , and pinaki pal for very useful discussions and comments . we also thank the reviewers of this paper who provided many useful comments , interesting ideas and suggestions that have contributed significantly to the improvement of the paper . this work was supported by a research grant by the department of science and technology , india as swarnajayanti fellowship to mkv . xi h. d. & xia k. q. , ( 2008b ) azimuthal motion , reorientation , cessation , and reversal of the large - scale circulation in turbulent thermal convection : a comparative study in aspect ratio one and one - half geometries . e _ * 78 * , 036326 .

we present a numerical study of the reversals and reorientations of the large scale circulation ( lsc ) of convective fluid in a cylindrical container of aspect ratio one . we take prandtl number to be 0.7 and rayleigh numbers in the range from @xmath0 to @xmath1 . it is observed that the reversals of the lsc are induced by its reorientation along the azimuthal direction , which are quantified using the phases of the first fourier mode of the vertical velocity measured near the lateral surface in the mid plane . during a `` complete reversal '' , the above phase changes by around @xmath2 leading to reversals of the vertical velocity at all the probes . on the contrary , the vertical velocity reverses only at some of the probes during a `` partial reversal '' with phase change other than @xmath2 . numerically we observe rotation - led and cessation - led reorientations , in agreement with earlier experimental results . the ratio of the amplitude of the second fourier mode and the first fourier mode rises sharply during the cessation - led reorientations . this observation is consistent with the quadrupolar dominant temperature profile observed during the cessations . we also observe reorientations involving double cessation . [ firstpage ] rayleigh - bnard convection , convective turbulence , direct numerical simulation .

attempts to construct a quantum model of gravity starting from the geometrical description of classical case in general relativity may be characterized as very poor in its possible consequences . the classical limit has not any clear physical mechanism of formation of the metric , and it is similar to the newtonian version where the law of gravity is postulated . there are a few facts which may be considered as contradicting to the mainstream in this field of physics : the pioneer anomaly @xcite , the discovery of quantum states of ultra - cold neutrons in the earth s gravitational field with very low energies of levels @xcite ; perhaps , we should include in the list the problem of dark matter in galaxies . many people are searching for dark energy , an existence of which has been claimed on a basis of the standard cosmological model ; but the initial cause for this conclusion may be put in our list , too . i would like to review here some results of my work in a non - geometrical approach to quantum gravity , which is based on the assumptions that : 1 ) gravitons are super - strong interacting particles and 2 ) the low - temperature graviton background exists . this model of low - energy quantum gravity has many interesting consequences , and the one may pave the alternative way to the future theory . to be shorter , i use here notations of my cited works . it was shown by the author @xcite that screening the background of super - strong interacting gravitons creates for any pair of bodies both attractive and repulsive forces due to pressure of gravitons . for single gravitons , these forces are approximately equal . if single gravitons are pairing , an attractive force due to pressure of such graviton pairs is twice exceeding a corresponding repulsive force if graviton pairs are destructed by collisions with a body . in such the model , the newton constant may be computed . the attractive force @xmath0 due to pressure of single gravitons in this model is equal to : @xmath1 where the constant @xmath2 is : @xmath3 with @xmath4 by @xmath5 @xmath6 that is of three order greater than the newton constant , @xmath7 if single gravitons are elastically scattered , they create a repulsive force @xmath8 which is equal to @xmath9 but for black holes which absorb any particles and do not re - emit them , we will have @xmath10 it means that such the objects would attract other bodies with a force which is proportional to @xmath2 but not to @xmath11 i.e. einstein s equivalence principle would be violated for them . in a case of graviton pairing , a force of attraction of two bodies @xmath12 due to pressure of graviton pairs will be equal to : @xmath13 where @xmath14 the difference @xmath15 between attractive and repulsive forces is twice smaller : @xmath16 where the constant @xmath17 is : @xmath18 if one assumes that @xmath19 then it gives for the new constant @xmath20 : @xmath21 the inverse square law takes place in the model if the condition of big distances is fulfilled : @xmath22 @xcite . it leads to the necessity of some `` atomic structure '' of matter for working the described quantum mechanism ; it is a unique demand for known models of gravity . recently , it was shown in @xcite that asymptotic freedom appears at very short distances in this model . in this range , the screened portion of gravitons tends to the fixed value of @xmath23 , that leads to the very small limit acceleration of the order of @xmath24 of any screened micro - particle . = 6.0 cm the ratio @xmath25 describes the screened portion of gravitons for a big distance @xmath26 . for small @xmath26 , let us consider fig . 1 , where @xmath27 , @xmath28 is the screening area . it is necessary to replace the ratio @xmath29 by the following one : @xmath30 to find the net force of gravitation @xmath15 at a small distance @xmath26 , we should replace the factor @xmath31 in eq . ( 31 ) of @xcite with the more exact factor @xmath32 . then we get : @xmath33 where @xmath34 is an energy of particle 1 , and @xmath35 is the function of @xmath26 : @xmath36 where @xmath37 . by @xmath38 , this function s limit for any @xmath39 is : @xmath40 . for comparison , graphs of the function @xmath35 are shown in fig . 2 for = 6.0 cm the following different energies : @xmath41 and @xmath42 . the functions have the same limit by @xmath38 , but the most interesting thing is their different transition to this limit when @xmath26 decreases . the range of transition for a proton is between @xmath43 meter , while for an electron it is between @xmath44 meter . the property of asymptotic freedom leads to the important consequence : a black hole mass threshold should exist @xcite . due to forehead collisions with gravitons , an energy of any photon should decrease when it passes through the sea of gravitons . from another side , none - forehead collisions of photons with gravitons of the background will lead to an additional relaxation of a photon flux , caused by transmission of a momentum transversal component to some photons . it will lead to an additional dimming of any remote objects , and may be connected with supernova dimming . average energy losses of a photon with an energy @xmath45 on a way @xmath46 will be equal to : @xmath47 where @xmath48 . in this model , @xmath49 where @xmath50 is an average graviton energy . as a result , we have : @xmath51 where @xmath52 is an initial value of energy . both redshifts and the additional relaxation of any photonic flux due to non - forehead collisions of gravitons with photons lead in the model to the following luminosity distance @xmath53 @xmath54 where @xmath55 , with the factor @xmath56 for soft radiation . it is easy to find a value of the factor @xmath57 in another marginal case - for a very hard radiation . due to very small ratios of graviton to photon momenta , photon deflection angles will be small , but collisions will be frequent because the cross - section of interaction is a bilinear function of graviton and photon energies in this model . it means that in this limit case @xmath58 for an arbitrary source spectrum , a value of the factor @xmath57 should be still computed . it is clear that @xmath59 and in a general case it should depend on a rest - frame spectrum and on a redshift . it is important that the hubble diagram in the model is a multivalued function of a redshift : for a given @xmath60 @xmath57 may have different values @xcite . using only the luminosity distance and a geometrical one as functions of a redshift in this model , theoretical predictions for galaxy / quasar number counts may be found @xcite . for example , galaxy number counts as a function of a redshift @xmath61 may be characterized with the function @xmath62 for which we have in this model : @xmath63 a graph of this function is shown in fig . 3 ; the typical error bar and data point are added here from paper @xcite by loh and spillar . there is not a visible contradiction with observations . _ there is not any free parameter in the model to fit this curve ; _ it is a very rigid case . = 6.0 cm to compute the average time delay of photons , it is necessary to find a number of collisions on a small way @xmath64 and to evaluate a delay due to one act of interaction . let us consider at first the background of single gravitons . given the expression for @xmath65 in the model , we can write for the number of collisions with gravitons having an energy @xmath66 : @xmath67 where @xmath68 is described by the plank formula . in the forehead collision , a photon loses the momentum @xmath69 and obtains the energy @xmath70 ; it means that for a virtual photon we will have : @xmath71 the uncertainty of energy for a virtual photon @xmath72 . if we evaluate the lifetime of a virtual photon on a basis of the uncertainties relation : @xmath73 , we get @xmath74 . in the time @xmath75 , the time delay @xmath76 will be equal to : @xmath77 the full time delay due to gravitons with an energy @xmath70 is : @xmath78 . taking into account all frequencies , we find the full time delay on the way @xmath64 : @xmath79 the full time delay on the way @xmath64 will be maximal for @xmath80 and it is easy to evaluate the one : @xmath81 on the way @xmath26 the time delay is : @xmath82 in this model : @xmath83 ; let us introduce a constant : @xmath84 , then @xmath85 we see that for @xmath86 the maximal time delay is equal to @xmath87 , i.e. the one is negligible . if we take into account graviton pairing , the estimate of delay becomes smaller . if we consider another possibility of lifetime estimation , for example , @xmath88 , where @xmath89 is the proper lifetime of a virtual photon ( it should be considered as a new parameter of the model ) , taking into account that now : @xmath90 we shall get in the same manner ( my paper about the time delay is now in progress ) : @xmath91 where @xmath52 is an initial photon energy , @xmath92 is a new constant : @xmath93 . in this case , the time delay of photons with different initial energies @xmath94 and @xmath95 will be proportional to the difference @xmath96 , and more energetic photons should arrive later , also as in the first case . it is still necessary to calculate the dispersion of the delay . to find @xmath97 , we must compare the computed value of time delay with future observations . recently , an analysis of time - resolved emissions from the gamma - ray burst grb 081126 @xcite showed that the optical peak occurred @xmath98 _ later _ than the second gamma peak ; perhaps , it means that this delay is connected with the mechanism of burst . the observed pioneer anomaly @xcite has the following main features : 1 ) in the range 5 - 15 au from the sun it is observed an anomalous sunward acceleration with the rising modulus which gets its maximum value ; 2 ) for greater distances , this maximum sunward acceleration remains almost constant for both pioneers ; 3 ) it is observed an unmodeled annual periodic term in residuals for pioneer 10 @xcite which is obviously connected with the motion of the earth . in a frame of this model , a universal character of gravitational interaction should lead to energy losses of any massive body due to forehead collisions with gravitons , so the body acceleration @xmath99 by a non - zero velocity @xmath100 is equal to : @xmath101 for small velocities : @xmath102 if the hubble constant @xmath65 is equal to its theoretical estimate in this approach @xmath103 a modulus of the acceleration will be equal to @xmath104 that is of the same order of magnitude as a value of the observed additional acceleration @xmath105 for nasa probes . the acceleration @xmath106 is directed against a body velocity in the frame of reference in which the graviton background is isotropic . this acceleration will have different directions by motion of a body on a closed orbit . the observed value of anomalous acceleration of pioneer 10 should represent the vector difference of the two accelerations @xcite : an acceleration of pioneer 10 relative to the graviton background , and an acceleration of the earth relative to the background . perhaps , namely the last one is displayed as an annual periodic term in the residuals of pioneer 10 @xcite . an observed value of the projection of the probe s acceleration on the sunward direction @xmath107 should depend on accelerations of the probe , the earth and the sun relative to the graviton background . if the sun moves relative to the background slowly enough , then anomalous accelerations of the earth and the probe would be directed almost against their velocities in the heliocentric frame , and in this case : @xmath108 , where @xmath109 is an angle between a radius - vector of the probe and its velocity in the frame . by the very elongate orbits of the both pioneers , it would explain the second ( and main ) peculiarity . for example , for pioneer 10 at the distance 67 au from the sun one has @xmath110 , i.e. @xmath111 if for big distances from the sun we use the conservation laws of energy and angular momentum in the field _ of the sun only _ , then in the range 6.7 - 67 au a value of @xmath112 changes from 0.942 to 0.994 , i.e. approximately on 5 per cent only . due to this fact , a projection of the probe s acceleration on the sunward direction would be almost constant @xcite . as toth and turyshev report @xcite , they intend to carry out an analysis of newly recovered data received from pioneers , with these data are now available for pioneer 11 for distances 1.01 - 41.7 au . if the serious problem of taking into account the solar radiation pressure at small distances is precisely solved ( modeled ) @xcite , then this range will be very lucky to confront the expression @xmath108 of the considered model with observations for small distances when pioneer 11 executed its planetary encounters with jupiter and saturn . in this period , a value of @xmath112 was changed in the non - trivial manner . for example , when the spacecraft went to saturn , @xmath112 was _ negative _ during some time . if this model is true , the anomaly in this small period should have _ the opposite sign_. it would be the best of all to compare the two functions of the probe s proper time : the projection of anomalous acceleration of pioneer 11 and @xmath112 for it . these functions should be very similar to each other if my conjecture is true . at present , a new mission to test the anomaly is planned @xcite . it is seen from this consideration that it would be desirable to have a closed orbit for this future probe , or the one with two elongate branches where the probe moves off the sun and towards it . this deceleration of massive bodies by the graviton background may lead to an additional _ relative _ acceleration of bodies in a closed system . for example , when a galaxy moves through the background , a deceleration of its center will be constant , but for orbiting it stars the same deceleration will change its sign . the kinetic energy of stars should increase with time in the rest frame of the center . perhaps , namely the fact obeys successes of mond by m. milgrom in explanation of flat rotation curves of galaxies @xcite ( and its failure for clusters of galaxies ) . in mond , when a body acceleration gets the threshold value of @xmath113 one introduces by hand the growth of interaction ; but namely this value characterizes the pioneer anomaly in this model . i hope that this model may help us to see and to realize some fresh ideas in the very old area . the coincidence of the magnitude of the anomalous deceleration of pioneer 10/11 with the product value of @xmath114 , and an appearance of the same quantity in the mond can not be due to a chance . many consequences of the model have an impact on our understanding of cosmological problems , and these very close ties between micro and macro cosmoses are very exiting . references anderson , j.d . _ 1998 , _ 81 , _ 2858 . anderson , j.d . d65 , _ 082004 ; [ gr - qc/0104064 v4 ] . nesvizhevsky , v.v . nature _ 2002 , _ 415 , _ 297 . ivanov , m.a . [ gr - qc/0207006 ] . ivanov , m.a . in the book `` focus on quantum gravity research '' , ed . moore , nova science , ny - 2006 - pp . 89 - 120 ; [ hep - th/0506189 ] , [ http://ivanovma.narod.ru/nova04.pdf ] . ivanov , m.a . _ j. grav . phys . _ , 2008 , v.2 , no.2 , pp . 26 - 31 ; [ arxiv:0801.1973v1 [ hep - th ] ] . ivanov , m.a . [ arxiv:0901.0510v1 [ physics.gen-ph ] ] . ivanov , m.a . gravitational asymptotic freedom and matter filling of black holes . contribution to pirt-09 , moscow , 6 - 9 july 2009 . ivanov , m.a . [ astro - ph/0609518v4 ] . ivanov , m.a . [ astro - ph/0606223 ] . loh , e.d . and spillar , e.j . _ apj _ 1986 , _ 307 , _ l1 . klotz , a. et al . 697 ( 2009 ) l18 ; [ arxiv:0904.4786v1 [ astro-ph.co ] ] . turyshev , s.g . [ gr - qc/9903024 v2 ] . ivanov , m.a . [ arxiv:0711.0450v2 [ physics.gen-ph ] ] . toth , v.t . and turyshev , s.g . [ arxiv:0710.2656v1 [ gr - qc ] ] . anderson , j.d . and nieto , m.m . _ contemp . _ 2007 , _ 48 _ , no . 1 . 41 - 54 ; [ arxiv:0709.3866v1 [ gr - qc ] ] . dittus , h. et al . [ gr - qc/0506139 ] . milgrom , m. [ astro - ph/9810302 ] .

some results of author s work in a non - geometrical approach to quantum gravity are reviewed here , among them : a quantum mechanism of classical gravity giving a possibility to compute the newton constant ; asymptotic freedom at short distances ; interaction of photons with the graviton background leading to the important cosmological consequences ; the time delay of photons due to interactions with gravitons ; deceleration of massive bodies in the graviton background which may be connected with the pioneer anomaly and with the problem of dark matter .

solar eruptive events , including flares , filament eruptions , and coronal mass ejections ( cmes ) are due to magnetic reconnection or loss of equilibrium in the solar corona ( see , e.g. , a recent review by webb & howard 2012 ) . from time sequence magnetograph observations , irreversible and rapid changes of surface magnetic fields associated with a large number of major flares have been observed ( e.g. , wang 1992 , 2006 ; kosovichev & zharkova 2001 ; wang et al . 1994 , 2002 , 2004a , b ; liu et al . 2005 ; sudol & harvey 2005 ; petrie & sudol 2010 ; burtseva & petrie 2013 ) . wang & liu ( 2010 ) synthesizes earlier studies and presented analysis of new events , and found a trend of increase of horizontal field at the polarity inversion line ( pil ) associated with almost all the flares studied by the authors . the results agree with our previous finding of rapid changes of sunspot structure associated with flares ( liu et al . 2005 ; deng et al . 2005 ) , where the spot feature near the flaring pil darkens while part of peripheral penumbra decays . recently , the helioseismic and magnetic imager ( hmi ) on board the solar dynamics observatory ( sdo ) is providing state - of - the - art observations under seeing - free condition , which help advance the study of magnetic field changes associated with flares ( e.g. , liu et al . 2012 ; wang et al . 2012a , b ; petrie 2012 ) . all these photospheric magnetic field changes are interpreted due to either the change of field line orientation or the appearance of newly formed magnetic loops near the surface . in both cases , the changes are more prominent in the horizontal rather than the vertical component . from the viewpoint of the theory of the flare phenomenon , hudson et al . ( 2008 ) and fisher et al . ( 2012 ) pointed out that the coronal energy release and magnetic restructuring may cause back reaction to the solar surface and interior . the authors found that after a flare , the photospheric magnetic field may become more horizontal at the pil . the authors used the simple principle of energy and momentum conservation , and specifically predicted that flares can be accompanied by rapid and irreversible changes of photospheric magnetic field . melrose ( 1997 , 2012 ) also provided an explanation for the enhancement of magnetic shear at the flaring pil , using the concept of reconnection between two current - carrying flux systems . such a magnetic share increase at the pil is often observed ( wang et al . , 2012a , b ) . the work of melrose and those of hudson and fisher , may have physics linkage : there are two current systems , one moves upward as part of an eruption and the other moves toward the surface . these might be linked to the tether - cutting reconnection model for sigmoids ( moore et al . 2001 , 2006 ) . it is noticeable that even with the sdo / hmi observations , the resolution of data is no better than 1 . therefore , the detailed evolution of sunspot structure may not be well observed . the high - resolution ( 0@xmath01 ) observation with the 1.6 m new solar telescope ( nst ; goode et al . 2010 ; cao et al . , 2010 ) at big bear solar observatory ( bbso ) thus provides a unique opportunity to understand the fine - scale structure change of sunspots associated with flares . compared with most of the previous observations mainly for x - class flares , nst images also allows such a study related to weaker flares . in this letter , we provide a detailed analysis of rapid formation of a @xmath1 sunspot associated with the c7.4 flare on 2012 july 2 from the noaa ar 11525 . we describe the multiwavelength observations and results in section [ result ] , and summarize and discuss our major findings in section [ summary ] . more dynamic detail can be seen in the accompanying animations in the online journal . noaa ar 11525 produced numerous c - class and m - class flares during its disk passage from 2012 june 29 to july 12 . figure [ f1](f ) displays a hmi vertical field covering the entire active region . multiple pils and the possible interaction between emerging flux systems could be the primary reasons of the high flare productivity . we concentrate our analysis on a small field - of - view ( fov ) ( 27 @xmath2 27 ) as marked by the black box in ( f ) , in order to scrutinize the flare - related changes of sunspot structure . this fov includes a main flaring pil , and is within the larger 70 @xmath2 70 fov of nst diffraction - limited observation . nst best covers the c7.4 flare on july 2 , which started at 18:45 ut , peaked at 18:56 ut , and ended at 19:02 ut in goes 18 flux . the related nst observations are at three wavelengths , the h@xmath3 line center , [email protected] offband , and the tio band at 7057 which is a good proxy for the photospheric continuum . the cadence of h@xmath3 blue - wing images is 6 s , while that of h@xmath3 line center and tio images is 15 s. all the observations were taken with the bbso s 76 element adaptive optics , which is able to correct most of the atmospheric seeing at these wavelengths . speckle reconstruction using 100 frames ( obtained within 3 s ) is subsequently applied in order to obtain diffraction - limited image sequences ( i.e. , around 0@xmath01 at h@xmath3 and tio ) . figures [ f1](a ) and ( b ) are the h@xmath3 line center and offband images at the flare peak time , showing the double flare ribbons and the erupting material ( pointed to by arrows ) . in fact , this flare is most probably preceded by the eruption of a filament lying along the pil from @xmath518:33:50 onward ( see the time - lapse movie ) . a complete study of the erupting filament will be presented elsewhere . figures [ f1](c ) and ( d ) compare preflare and postflare tio images , with the preceding spots p1p3 and the following spot f1 labeled . it can be distinctly seen that after the flare , there is a newly formed penumbra ( pointed to by the arrow ) that directly connects p1 and f1 ( see further discussion below ) . contours of hmi line - of - sight ( los ) magnetic field is also over - plotted on the pre - flare tio image in figure [ f1](e ) to clearly exhibit the polarity of each spot . bbso did not have magnetograph observations on that day . to shed light on the 3d magnetic field structure , we resorted to the nonlinear force - free field extrapolation ( nlfff ) , using hmi vector magnetograms as the boundary condition . this extrapolation model uses the `` weighted optimization '' method as discussed by wiegelmann ( 2004 ) . the photospheric boundary is pre - processed to simulate the force - free condition ( wiegelmann et al . the calculation was performed to a volume of @xmath5171 @xmath2 171 @xmath2 171 mm@xmath6 . selected nlfff lines are superimposed on figures [ f1](e ) and ( f ) , demonstrating a possible sheared flux rope lying along the pil ( red ) and the overlying arcade field ( blue ) . these are nicely consistent with the above observation of the erupting filament and flare ribbons . in the standard flare picture , filament eruption can stretch open the overlying fields , which then reconnect and produce flare ribbons at their footpoints . we present in figure [ f2 ] the time sequence of tio images right across the flare ( panels ( a)(g ) ) and a corresponding hmi vector magnetic field map ( panel ( h ) ) . it is evident that there exists strongly sheared fields along the pil between the positive , ridge - like p2 and negative f1 spots , and that before the flare , a sheared penumbra lies between p2 and f1 ( figure [ f2](a ) ) . with the occurrence of the flare , a significant new section of penumbra then rapidly forms and is obviously seen to directly connect the main positive spot p1 with the negative f1 ( figures [ f2](e)(g ) ) and hence link part of the flare ribbons ( cf . figures [ f1](b ) and ( d ) ) . we note that some penumbral fibrils may apparently join positive spots p1 and p2 . this is most probably because that the inclined penumbral field stemming from p1 could have a dip near the region of p2 but then curves up again to reach f1 ( e.g. , figure 8 of wang , deng , & liu 2012 ) . in the sense that the main spots p1 and f1 with opposite magnetic polarity now share a common penumbra , the flare effectively creates a new @xmath1 sunspot . in order to further demonstrate the rapidness of the flare - related penumbral formation , we show in figures [ f3](a ) and ( b ) the temporal evolution of the mean tio intensity within the red boxed region in figure [ f2 ] along with that of the corresponding horizontal magnetic field , in comparison with the goes 18 flux ( the red line ) . it is remarkable that the tio intensity begins to sharply drop with the onset of the flare at 18:45 ut and reaches a nearly 20% lower level around 19:30 ut . at the meantime , the horizontal field starts to gradually increase from @xmath518 ut but exhibits a highest increase rate ( see the cyan line in ( b ) ) simultaneously with the flare peak . similar to our previous studies ( e.g. , liu et al . 2005 ; wang et al . 2012b ) , we believe that the rapid intensity darkening and horizontal field enhancement are resulted from the 3d magnetic field reconstruction due to the flare . the long - term gradual strengthening of the horizontal field , however , may be related to the overall evolution of the active region , i.e. , the converging motion between p1/p2 and f1 as discussed below . the spatial - temporal relationship of the formation of the new penumbra can be best seen in figure 4 , in which we show the time slice image along the slit as marked in figure [ f2](a ) . before the flare , obvious convective pattern is present in the upper region ( @xmath51019 ) with a time scale of 1020 minutes and a spatial scale of about 12 , which are typical scales of granulation . after the flare , such a pattern is replaced by a typical penumbral structure with alternating dark and bright fibrils . it is also convincing that the transition from granulation to penumbrae is rapid and occurs right after the flare peak ( the over - plotted solid line ) . since long - term evolution of magnetic field can provide hints for understanding the triggering of flares , we also examine in figure [ f3](c ) the time profiles of magnetic flux within the cyan box in figure [ f2](h ) that encompasses the main flaring pil . we realize the difficulty in separating the short - term change in the smaller scale from the long - term change in the larger scale . nevertheless , with the help of the accompanied magnetograph movie , there is some indication of magnetic cancellation in this region beginning from @xmath518 ut , which reduces the positive flux with the highest cancellation rate ( see the cyan line ) co - temporal with the peak of the flare . the cancellation could be caused by the collision between p2 and the eastward motion of the emerging negative f1 field . however , it is also possible that such a reduction of positive flux is partially due to its southward migration . the evolution of negative field can not be used to identify the flux cancellation , as f1 is part of another larger scale flux emergence . the sharp increase of negative flux ( see the green line ) around the flare peak time is then due to the emerging flux moving into the calculation box . all these may be resulted from the interplay between the long - term and short - term magnetic restructuring , for which we presently can not draw a definite conclusion . it is worth emphasizing two facts in our plots . first , a rapid change is only observed in the tio intensity observed with nst . in contrast , all the hmi magnetic quantities have a more gradual change with an onset time even before the flare , although the sharp increase of the change rate is apparently associated with the flare . this could be attributed to the very different image scales of the two sets of observations and the long - term evolution of the entire active region in a large scale . second , there is another peak in the field change rate around 21:15 ut , while we can not find any goes x - ray signature around this time . after carefully examining the nst h@xmath3 data , we noted a sub - flare peaked at 21:16 ut , which has a similar morphology as the c7.4 flare . we speculate that the magnetic field as well as intensity changes are associated with this sub - flare . taking advantage of the 0@xmath01 spatial resolution and 15 s cadence images of the nst , we observed in detail the rapid formation of a sunspot penumbra across the pil closely associated with the 2012 july 2 c7.4 flare . the penumbral formation is unambiguously evidenced by the transformation from patterns of typical granulation to penumbral fibrils , and is accompanied with rapid tio intensity darkening and horizontal field enhancement . the formation of this penumbra produces a larger scale @xmath1 sunspot . such a fine - scale study is only possible with observations at sufficiently high resolution . based on the observational results , we propose the following interpretation . there could exist a low - lying flux rope right above the initially sheared pil , which can be supported by sheared arcade fields . some evidence of magnetic cancellation at this pil and the filament eruption preceding the flare are consistent with the formation and eruption of the flux rope ( e.g. , green , kliem , and wallace 2010 ) . as the flux rope moves upward , the closing of the opened overlying fields are then pushed back toward the surface as a result of the downward momentum ( fisher et al . this leads to the formation of the new penumbra and the @xmath1-spot configuration . several supporting evidences for this scenario are as follows . ( 1 ) sheared fields exist around the original pil before the vertical fields cancel across it . ( 2 ) nlfff extrapolation clearly shows both the flux rope and the overlying arcade fields . ( 3 ) rising of the flux rope is visible in the h@xmath3 movie , and part of the bundle is apparent in the h@xmath3 blue - wing image in figure [ f1](b ) . ( 4 ) as shown in h@xmath3 images ( figures [ f1](a ) and ( b ) ) , the flare ribbons are not located beside the compact flaring pil , but lie further apart in the main sunspots p1 and f1 that are finally connected by the newly formed penumbra . we also note that there are four homologous flares occurred during this period ( 1722 ut ) . each flare may have a partial contribution to the flux rope eruption but the c7.4 flare plays a major role . the penumbral formation is also only associated with this flare . we emphasize that only high - resolution observing sequence would allow such a detailed examination of sunspot structure change . the size of the new penumbra is only about 5 . without these new nst observations , we might only conclude on the feature darkening near the flaring pil as what have been described in our previous observations ( e.g. , liu et al . the formation of new penumbra also signifies the downward push of fields due to lorentz force change , as implied by the more horizontal field lines after flares ( hudson et al . 2008 ; fisher et al . as soon as some horizontal fields subside close to the surface , the penumbra can be formed . the opposite process was also observed before ( wang , deng & liu 2012 ) , in which the peripheral sunspot penumbra may disappear suddenly after flares , so that convection in the granule scale appears immediately as the fields turn from horizontal to vertical state . in both cases , penumbra may be quite a thin layer of structure , as discussed by wang , deng & liu ( 2012 ) . although the study of larger scale flare activity is out of the scope of this letter , it is worth mentioning that the present flare involves additional brightenings in other areas in the active region . in fact , by looking at figure [ f1](f ) , we find a magnetic field configuration favorable for circular - ribbon flares ( e.g. , pariat et al . that is , positive field surrounds the central negative field , and the negative field also exhibits obvious motion . indeed , during this flare , euv images taken by the atmospheric imaging assembly ( aia ) show a semi - continuous circular ribbon in the outer positive field together with the more compact ribbon in the central negative field region . the two ribbons in figure [ f1 ] as seen by nst represent part of the outer ribbon and most of the inner flare core . this circular flare picture is supported by the outward ejecting jets as clearly seen in the aia movies . flares having a circular ribbon have rarely been reported , although it is expected in the fan - spine magnetic topology involving reconnection at a 3d coronal null point ( masson et al . 2009 ; reid et al . 2012 ; wang & liu 2012 ) . it is speculated that the eruption of flux rope may have been triggered by the outer null - point reconnection ( e.g. , jiang et al . 2013 ) , which cause homologous jets as observed by aia . we are grateful to the referee for the valuable comments to improve the paper . we thank the bbso staff for obtaining the outstanding nst observations , and the sdo / hmi team for the magnetic field data . we are indebted to dr . yurchyshyn for pre - processing and transferring the nst data . this work is supported by nsf grants ags 1153226 and ags 1153424 , and nasa grants nnx13ag13 g and nnx13af76 g .

rapid , irreversible changes of magnetic topology and sunspot structure associated with flares have been systematically observed in recent years . the most striking features include the increase of horizontal field at the polarity inversion line ( pil ) and the co - spatial penumbral darkening . a likely explanation of the above phenomenon is the back reaction to the coronal restructuring after eruptions : a coronal mass ejection carries the upward momentum while the downward momentum compresses the field lines near the pil . previous studies could only use low resolution ( above 1 ) magnetograms and white - light images . therefore , the changes are mostly observed for x - class flares . taking advantage of the 0@xmath01 spatial resolution and 15 s temporal cadence of the new solar telescope at big bear solar observatory , we report in detail the rapid formation of sunspot penumbra at the pil associated with the c7.4 flare on 2012 july 2 . it is unambiguously shown that the solar granulation pattern evolves to alternating dark and bright fibril structure , the typical pattern of penumbra . interestingly , the appearance of such a penumbra creates a new @xmath1 sunspot . the penumbral formation is also accompanied by the enhancement of horizontal field observed using vector magnetograms from the helioseismic and magnetic imager . we explain our observations as due to the eruption of a flux rope following magnetic cancellation at the pil . subsequently the re - closed arcade fields are pushed down towards the surface to form the new penumbra . nlfff extrapolation clearly shows both the flux rope close to the surface and the overlying fields .

hyperglycaemia is frequently seen following renal transplantation , due to the effects of immunosuppressant regimens , particularly glucocorticoids , on glucose metabolism , and the presence of preexisting diabetes . there is limited evidence for a specific postoperative blood glucose ( bg ) range following surgery other than coronary artery bypass grafting . in the absence of specific data , standard perioperative targets of 510 however , these perioperative glucose targets may not be appropriate in patients with end stage renal failure , which is a catabolic and insulin resistant state . specifically , appropriate glycaemic targets during the transplant admission are not clear . during the transplant admission , there is evidence of harm from both hypoglycaemia and hyperglycaemia ; how these relationships are modified by pretransplant diabetes status is not clear . understanding any impact of glycaemia on outcomes may provide support to determine appropriate glucose targets . the aim of this study was to determine perioperative and one - year outcomes after renal transplantation and whether these outcomes are affected by preexisting dm ( dm ) or posttransplant diabetes mellitus ( ptdm ) or , alternatively , by glycaemia during the transplant admission . we performed a retrospective review of all patients who underwent kidney transplantation at a single tertiary referral centre for all local renal transplants from january 2009 until june 2014 . eligible patients were adults with at least one year of follow - up data available . all patients undergoing renal transplantation had point of care capillary blood glucose monitoring performed preprandially and before bed for the first 72 hours after renal transplant . given the pattern of hyperglycaemia usually seen with glucocorticoids with relatively unaffected fasting bg with peak bg seen in afternoon or evening , fasting bg and peak bg for days 13 after transplant were collected . dm : listed as a pretransplant comorbidityptdm : any of the following present : management instituted based on hyperglycaemia and required beyond the first 3 months after transplant , hyperglycaemia documented according to current ada criteria , or if defined by the treating physician on follow - upacute rejection ( ar ) : biopsy - proven rejection ( banff criteria)cardiovascular ( cv ) complication : composite of acute myocardial infarction , cerebrovascular accident , or peripheral vascular disease requiring interventioninfection : positive culture or treatment with antibiotics instituted dm : listed as a pretransplant comorbidity ptdm : any of the following present : management instituted based on hyperglycaemia and required beyond the first 3 months after transplant , hyperglycaemia documented according to current ada criteria , or if defined by the treating physician on follow - up acute rejection ( ar ) : biopsy - proven rejection ( banff criteria ) cardiovascular ( cv ) complication : composite of acute myocardial infarction , cerebrovascular accident , or peripheral vascular disease requiring intervention infection : positive culture or treatment with antibiotics instituted statistics was performed by spss v22 . anova was performed for continuous variables . for other variables , the chi - square test or t - test was used as appropriate . given that this was a retrospective study and all results are exploratory correlation testing was determined by pearson 's or spearman 's coefficients as appropriate . where binary logistic regression was performed , stepwise analysis was performed , known risk factors for delayed graft function as covariates . in total , 148 patients were analysed : 29 patients ( 19.6% ) had preexisting dm and 27 patients ( 18.2% ) developed ptdm . of those with preexisting dm , 93.1% had type 2 dm and the remaining 6.9% had type 1 dm . standard immunosuppression was initial basiliximab and methylprednisolone as well as ongoing prednisolone , mycophenolate , and either tacrolimus ( 79% ) or cyclosporin ( 22% ) based on the treating clinician 's decision , in line with the recommendations at the time of transplantation . patients assessed by the treating clinician to be at higher risk of rejection were treated with additional rabbit antithymocyte globulin ( 62% ) at induction . there were no differences in type of immunosuppression regimens between the 3 groups ( no dm , dm , and ptdm ) . the cumulative glucocorticoid dose in the first week was not different across the 3 groups ( 853 mg in no dm , 888 mg in dm , and 914 mg in ptdm ) ; however , on day 7 after transplant , the mean prednisone dose was higher in those who developed ptdm ( 74 mg versus no dm , 30 mg , p < 0.05 ) . dose of prednisone at latter time points was not collected . dm patients were older , more obese , and more likely to have had a prior vascular event . they were also more likely to be treated with a statin or any antihypertensive medication . mean hba1c was 54 10 mmol / mol ( 7.1 1.4% ) prior to transplant , which was higher than those without dm ( 36 3 mmol / mol [ 5.4 0.5% ] , p < 0.001 ) . of those who developed ptdm , 14 ( 52% ) were diagnosed during the initial transplant admission and the remainder 1 to 6 months after the transplant . ptdm patients had higher triglyceride levels at baseline compared to those without dm ( 2.6 mmol / l versus 1.7 mmol / l , p < 0.01 ) . fasting glucose levels taken on admission for transplant were higher in dm patients compared to those without dm ( 6.8 1.8 mmol / l versus 5.1 0.9 mmol / l , p < 0.05 ) ( table 2 ) . fasting and peak bg on days 1 , 2 , and 3 following transplant were significantly different across the 3 groups . mmol / l ) only occurred on 5 occasions days 13 postoperatively and so was not analysed further . following transplantation , dm patients had a longer hospital stay ( 16.9 9.7 versus 13 5.6 days , p < 0.01 ) , had more infective complications during that admission ( 34.5% versus 13% , p < 0.01 ) , and were more likely to return to dialysis ( 48.3% versus 19.6% , p < 0.01 ) as compared to those with no dm ( table 3 ) . there was no difference in the rate of acute rejection ( ar ) in patients with dm as compared to those without dm ( 13.8% versus 7.6% , p = ns ) . ptdm patients had increased rates of returning to dialysis ( 51.9% versus 19.6% , p < 0.01 ) and ar ( 25.9% versus 7.6% , p < 0.05 ) but no differences in their length of stay or infective complications compared to those without dm ( table 3 ) . any relationship between risk of infection and prior glycaemic control could not be assessed as < 50% of the whole cohort had an hba1c result available from the year prior to transplant . in dm patients , there was a nonsignificant increase in the hba1c in those who had an infective complication compared to those without ( 60 9 mmol / mol [ 7.6 1.2% ] versus 53 12 mmol / mol [ 7.0 1.4% ] , p = 0.25 ) . although hba1c is less reliable in this cohort and this is underpowered , there is a suggestion of a trend towards worse glycaemic control in those with infective complications . there was no correlation with fasting bg taken at admission for transplantation nor with fasting bg or peak bg on day 1 , 2 , or 3 after transplant and occurrence of infection . there was no relationship between return to dialysis and fasting glucose just prior to transplantation . for the whole cohort , return to dialysis during transplant admission correlated with fasting and peak bg on day 2 and 3 postoperatively . binary logistic regression was performed using a stepwise analysis . when adjusted for type of donor ( deceased versus live ) and hla mismatching ( both known factors for delayed graft function and return to dialysis ) , of the fasting and peak bg on days 13 , only fasting bg on day 3 remained significant ( or 1.63 , 95% ci 1.112.39 , p = 0.013 ) . there was no relationship between days 13 fasting or peak bg and ar during transplant admission . in those who developed ptdm as compared to those without diabetes , days 1 , 2 , and 3 fasting and peak bg were significantly higher ( table 2 ) . at follow - up , glycaemia remained significantly higher in those with diabetes . at 12 months , mean hba1c for dm patients was 61 14 mmol / mol ( 7.7 1.8% ; dm versus no dm , p < 0.01 ) , 48 5 mmol / mol ( 6.5 0.7% ) for patients with ptdm ( versus no dm , p < 0.05 ) , and 38 4 mmol / mol ( 5.6 0.6% ) for those patients without dm ( table 4 ) . there were no differences in serum lipids except for lower total cholesterol in the dm patients compared to those without dm ( 4.5 versus 5.1 mmol / l , p < 0.05 ) which could be accounted for by lipid treatment . at 12 months after transplant , patients with dm had more cardiovascular complications ( 20.7% versus 4.3% , p < 0.05 ) compared to those without diabetes ( table 4 ) . in those with dm , cardiovascular events were associated with age and smoking status but not with hba1c , prior history of a vascular event , bmi , or pretransplant lipids . graft loss censored for death ( return to dialysis or death ) at one year was not significantly different between the 3 groups and did not correlate with days 13 bg . at 12 months , there were no differences in any of the measured outcomes in those with ptdm compared to those without dm . this retrospective study has shown that patients with dm and ptdm have worse perioperative outcomes after renal transplantation compared to those without dm . these patients have increased rates of return to dialysis after transplant , and this need was related to bg control during transplant admission . dm was associated with increased risk of infection during transplant admission , although this risk was unrelated to glycaemia . bg levels were highest in those with dm ; those who developed ptdm also had bg levels significantly higher than those without dm . at 12 months , the only difference in outcomes was an increased number of cardiovascular events in those with dm . our results confirm that dm is a risk factor for dgf [ 8 , 9 ] and suggest that pretransplant hyperglycaemia contributes to pathogenesis of dgf , possibly due to increased ischaemic - reperfusion injury . in our analysis , we controlled for known risk factors for dgf ( such as type of donor and hla mismatching ) and found that fasting bg on day 3 remained significant . this suggests that hyperglycaemia immediately after transplant may also represent a potentially modifiable risk factor for dgf . we were unable to collect data on other known risk factors , such as donor age and cold ischemia time . a single trial of tight bg control after transplant ( with intensive intravenous insulin to target bg 3.95.5 mmol / l ) did not show a benefit but may have been confounded by high rate of hypoglycaemia which was associated with an increase in acute rejection [ 4 , 10 ] . alternatively , as only day 3 fbg remained significant after adjustment for covariates , hyperglycaemia may reflect reduced glycosuria as a consequence of dgf . the glycaemic impact of renal handing of glucose by the transplanted kidney is unknown . given the relationship between hyperglycaemia and infection risk in other inpatient groups we hypothesised a relationship between peak bg and risk of infection , as mean bg is not likely to adequately reflect the degree of hyperglycaemia secondary to glucocorticoids . we found that postoperative daily fasting or peak bg was unrelated to infection arising during transplant admission , which is in keeping with prior studies which did not show a relationship between mean bg during transplant admission and infection by 30 days or by 12 months . the increased risk of infection seen only in those with dm may relate to other factors such as prior glycaemic control , the chronic inflammatory milieu of dm , or obesity . our results are consistent with other groups that hyperglycaemia is common during the transplant admission and that inpatient hyperglycaemia is a predictor for development of ptdm . pretransplant fasting glucose and hba1c were elevated in those who developed ptdm , suggesting that ptdm is driven by both transplant - specific and transplant - independent factors and that adequate pretransplant screening , combined with posttransplant hyperglycaemia , may predict those who develop ptdm . pretransplant hba1c was limited to < 50% of patients , limiting its usefulness in identifying any meaningful relationship between longer term glycaemic variability and outcomes . future studies to investigate the diagnostic utility of combining pretransplant glycaemic control and posttransplant glycaemia are warranted . although tight glycaemic control after transplant may not be useful for preventing infection , a single trial has shown that modest glycaemic control using isophane insulin was able to reduce the risk of ptdm in kidney recipients . the increased risk of ar seen in patients who developed ptdm is also consistent with prior findings . we found no relationship between perioperative glycaemia and ar , supporting the supremacy of preventing rejection rather than modifying diabetogenic immunosuppressant regimens as the primary strategy to prevent ptdm . although ptdm has been associated with poorer outcomes in early studies , our results at 12 months are consistent with more recent findings that outcomes of those with ptdm are similar to those without diabetes [ 19 , 20 ] , although this is limited by short follow - up and small numbers . cardiovascular events were more frequent following transplant in those with dm compared to those without dm and ptdm . this was despite greater use of antihypertensive therapy and statin therapy at time of transplantation and equivalent lipid targets , suggesting a limitation to cardiovascular risk prediction by traditional factors . although this is a retrospective study and is not powered for cardiovascular outcomes , this result does highlight the need for future studies to better address the question of the ideal glycaemic target , both for inpatients and in the longer term , given the coexistence of both established microvascular disease and high risk for macrovascular disease . ptdm patients did not have increased cardiovascular disease at one year , suggesting that that cardiovascular risk factor management should be in keeping with those with ckd . we included a number of criteria for ptdm as formal screening for ptdm with an oral glucose tolerance test was not routine in our institution . we therefore included patients in whom treatment for hyperglycaemia was instituted or a physician diagnosis of ptdm recorded , on the basis that elevated glucose levels had been measured elsewhere , in order to maximise the number of diagnosed patients , although there could be selection bias . glycaemic management and other cardiovascular risk factor management were individualised , which may have also affected outcomes that could not be quantified . bg measurements were performed by point of care reading , which can be affected by a number of posttransplant factors . however , our study strengths include frequent bg testing in all patients during the transplant admission , specifically with separate analysis of fasting and peak bg and not just mean bg , allowing for more detailed examination of the effect of inpatient hyperglycaemia . our study is a detailed examination of outcomes after renal transplantation and has shown that these outcomes vary according to the presence of preexisting or posttransplant diabetes and transplant admission glycaemia . perioperative glycaemic control is associated with return to dialysis and may represent a modifiable risk . further studies to identify the effect of intervention and appropriate glucose targets in this cohort are warranted .

background . optimal glycaemic targets following transplantation are unknown . understanding the impact of dm and posttransplant diabetes mellitus ( ptdm ) may improve patient and graft survival in transplant recipients . aim . to determine the perioperative and one - year outcomes after renal transplantation and whether these outcomes are affected by preexisting dm , ptdm , or glycaemia during transplant admission . method . adult recipients of renal transplants from a single centre over 5.5 years were retrospectively reviewed . measured outcomes during transplant admission included glycaemia and complications ( infective complications , acute rejection , and return to dialysis ) and , at 12 months , glycaemic control and complications ( cardiovascular complication , graft failure ) . results . of 148 patients analysed , 29 ( 19.6% ) had dm and 27 ( 18.2% ) developed ptdm . following transplantation , glucose levels were higher in patients with dm and ptdm . dm patients had a longer hospital stay , had more infections , and were more likely return to dialysis . ptdm patients had increased rates of acute rejection and return to dialysis . at 1 year after transplant , there were more cardiovascular complications in dm patients compared to those without dm . conclusions . compared to patients without dm , patients with dm or ptdm are more likely to suffer from complications perioperatively and at 12 months . perioperative glycaemia is associated with graft function and may be a modifiable risk .