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The Oracle Database Oracle Rdbms Computer Science Essay
Published: Last Edited:
Oracle is the most popular database in the world. It can be run on all the platforms say from a mainframe to a Macintosh. Oracle is more robust and complicated since it has great load balancing Architecture and allows you to control virtual memory and disk storage. Oracle is a better transaction system and everything is a transaction and not permanent until you COMMIT.
In Oracle RDBMS, DMCL (Device Media Control Language) layer provides mapping between physical data files and the logical storage areas. Oracle maps its physical data blocks to logical storage, which is called as "tablespace". Since Oracle runs on UNIX, blocksizes (pages) can range from 2K to 32K. To setup an Oracle server, one database with many "users/schemas" and tablespaces are needed which are shared by all the users.
Oracle is expensive than SQL server, as it is compatible and runs on every platform whereas SQL Server runs on Windows only. In Oracle RDMS, more memory tables like for e.g., 100 GB can be easily partitioned into range partitions at database level. Such partitioned tables and indexes give more benefits in case of performance and maintenance.
Oracle provides industry-leading security features within the database product, rendering it difficult to subvert security. Oracle database security stands on its own without requiring customers to license separate security products for essential, evaluated security features. Independent security evaluations validate proper implementation of security in the Oracle RDBMS. Customers are not obliged to purchase add-on products for key security features, nor pay for upgrades and support for such products. The Oracle database is one product family built on one code base. Oracle Corporation's database group is Oracle's security group. Customers enjoy the benefits of secure Oracle products from day one of General Availability. Oracle has more recovery options for corrupted database, redo log or datafile than MSSQL.
Microsoft SQL server
SQL Server is lean and easy to use with lots of one-size-fits-all applications. SQL Server has only a few dozen tuning knobs while Oracle has hundreds of parameters. This makes SQL Server less robust, but far easier to use. In MS-SQL, there is no transaction control and it has separate databases that do not share disk files.
In SQL server also, the Device Media Control Language (DMCL) layer provides mapping between physical data files and the logical storage areas. SQL Server named this logical storage as "page" and the unit of storage is called "file group". SQL Server uses "logins" to give you access to the SQL Server instance and each database has "users" that map to a login to get individual access to the tables and views etc.
SQL Server is compatible only with Windows, so it must use 8K blocksizes (8k "pages"). This means there is no way to specify larger extents to ensure contiguous space for large objects if required. Â
In MS-SQL, range partitioning of large tables and indexes is not possible and also the DBA has no "real" control over sorting and cache memory allocation. The memory allocation is decided only globally in the server properties memory folder, and that applies for all the memory.
In the past MS-SQL was cheaper but today it is also an expensive product. SQL Server offers integration with Microsoft Office and better security, developer productivity and business intelligence tools than Oracle Database at a lower TCO (total cost of ownership). SQL Server has lower total cost of administration than Oracle.
DB2 database can be run on multiple UNIX and Linux platforms and requires more Memory. It is robust and handles high volume workloads and uses a cluster-based, shared-disk architecture to offer easy scalability and high availability. DB2 has Self-Tuning Memory Manager, that free up IT staff from many administration tasks. As a result, IT staff can spend less time administering the system and more time focusing on other activities that benefit the business.
DB2 is actually three distinct products with three separate code bases: OS/390, AS/400 and Unix/NT/Linux. DB2 supports Oracle leads DB2 in transaction Benchmark testing. DB2 is a less secure database, more vulnerable to users or hackers subverting the security due to the security model that adds security after the fact. It is difficult to add layers of security after a product has been designed, coded and shipped. Higher up-front costs because of the additional products necessary to secure DB2. Customers must purchase a database that includes little out-of-the box security, then augment the purchase with other products. High long-term cost of ownership because customers must pay for the database product, security products and required services- plus upgrades and support services for all those products. Increased total cost of ownership.
This scenario also illustrates the divergent production goals of the two organizations, Tivoli and the DB2 groups. The DB2 groups build databases and Tivoli builds security. Without Tivoli, there is little DB2 security.
IBM forces customers to purchase the DB2 database, and then add on the appropriate Tivoli SecureWay products for the customer's requirements. Additionally, customers oftentimes pay for IBM Global Services to integrate security in DB2 for one operating system that supplies a particular security mechanism, DB2 for another that doesn't natively support that mechanism, and any SecureWay pieces they choose. The choices are so complex that IBM actually has services called "IBM's Secure Product Selection." |
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Christianity for young people!
What does Christianity have to offer a committed and energetic young person? What opportunities exist for someone who wants to make a difference?
Young people are often radical, idealistic and energetic. Most of the revolutions in recent decades have mainly been propelled with young people in the front line.
If there is a need to go to the barricades to fight for a cause or a principle, it’s usually the young people who do so. Our great writers also understood this when they called for people to make an effort and a commitment to human dignity and freedom. They didn’t appeal to those who were old and well established, but they wrote to the youth.
Large numbers of young people go around today with plans and a desire to do something for humanity. Solving the cancer enigma. Fighting for the environment. Battling hunger and poverty. Taking care of the weak in society. The list is long; for those who want to make a difference, there is no shortage of areas to get involved in. A few of them find a cause to advocate with a strong commitment that lasts a lifetime. Most people, however, are involved for a time, but quickly become disillusioned or consumed by the anxieties and responsibilities of adult life. As the years go by, idealism is often overcome by the pursuit of a career and the need for money and recognition.
A life force for today
The gospel about Jesus—His life, His death and His resurrection—opens unimagined perspectives for anyone with a fervent and wholehearted commitment to do something positive in the world! It invites you to a life of service for your fellow man, a life where every day means a chance to give of yourself. It invites you to be along in relieving need, to give the needy the help that will cause them to rejoice in gratitude for the whole of eternity. Can you imagine any more meaningful and rewarding life to be involved in?
Christianity does not consist of wise thoughts that must be learned and understood, or theories about salvation that must be memorized. Nor does it consist of outstanding human achievements and mysterious rituals. Christianity is not a life insurance against the day of judgment; it is a life force for today! Christianity is a life in which your personal development goes hand in hand with a growing commitment for others. It is a life of ever-deepening joy about being able to be an instrument of God’s care and mercy towards mankind.
This life is open to everyone
This life is not reserved for people with any special strength of character, education, cultural background or talent. It is open to everyone. However, there is an entrance gateway that must be passed—God wants your whole heart. He wants your thoughts, plans for the future, and your commitment. He doesn’t want to share these with anyone. However, if He receives these things, there is no limit to what He will accomplish in and through you.
Those who have taken this step soon find that they also have to look inwardly. As a human being you fall short, because sin soon turns up—even when you have a strong desire to be of help to others. This is when life really gets interesting! This is when you start to wage war against selfishness, pride, envy, and all other sins that are obstacles to your desire to help. God, who has received your whole heart, is watching carefully, and He guarantees the victory Himself.
Then it doesn’t take long until you start being permeated with joy. A deep gratitude begins to fill your heart, a love for the Savior that increases and develops the rest of your life. The urge to help other people also increases and becomes more heartfelt. Life becomes meaningful and interesting and provides a far greater satisfaction than you could ever experience by living out your own dreams or interests.
You don’t need to travel to distant countries to gain an outlet for this urge. On the contrary, it’s enough to look around at your immediate surroundings. Aren’t there plenty of tasks to address for someone with a burning commitment, one that would love to be of help?
Isn’t Christianity a message for young people who want to make a difference?
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AHRF Funded Research 2007
AHRF Awards Five $20,000 Research Grants For 2007
The American Hearing Research Foundation has selected five researchers to receive one-year, $20,000 grants for 2007. The recipients, from universities around the nation, will investigate hearing and hearing disorders. Research ranges from studying how good and poor readers process sound, to genetics involved in the development of the cochlea.
Otoferlin’s Role in Hearing
NeeliyathRamakrishnan, Ph.D., of Wayne State University, Detroit, Michigan, will study the role of a protein called otoferlin and its function in hearing with the help of his 2007 grant from the American Hearing Research Foundation.
Mutations in the gene that codes for otoferlin can cause severe or total deafness. When this mutation is present, the only symptom is deafness, there are no other known consequences.
Otoferlin contains regions that bind calcium. These calcium-binding regions make otoferlin’s structure very similar to that of another protein, synaptotagmin I, known to support signaling between neurons by forming part of a specialized cellular structure (synaptic complex) that releases chemical neurotransmitter during communication between nerves. Synaptotagmin I, although widespread, is not present in the sensory cells of hearing (hair cells).
Sound triggers a rise in hair-cell calcium that is thought to be sensed by otoferlin, which in turn modulates and facilitates fusion of synaptic vesicles containing neurotransmitter, leading to transmitter release and ultimately, the perception of sound. Dr. Ramakrishnan and associates will examine whether otoferlin binds known proteins of the synaptic complex and/or unknown proteins that may also be involved in hearing. Dr. Ramakrishnan will also investigate whether otoferlin takes the place of synaptotagmin in hair cells, and if otoferlin’s structural similarities to synaptotagmin give clues as to the function of otoferlin in hearing and its malfunction in deafness.
Additionally, the researchers will synthesize model proteins, in either normal or mutated form, so as to dissect their interactions at molecular level in the hair cell synaptic complex. Otoferlin, being a calcium sensor, may, for example, modulate the activity of voltage-gated calcium channels and proteins called SNAREs through direct protein-protein interactions. In this sense, otoferlin holds the key to synaptic transmission necessary for hearing.
Researcher to Investigate Reinnervation of Cochlear Hair Cells
Qiong Wang, M.D., Ph.D. of the University of Iowa, Iowa City is an AHRF grant recipient for 2007. Her research project, entitled “Reinnervation of Cochlear Inner Hair Cells by SGN Peripheral Processes in vitro,” will investigate how peripheral processes of neurons in the cochlea regenerate and reestablish functional connections with inner hair cells after noise-induced damage.
Synapses between hair cells and neurons in the cochlea are sensitive to sound vibrations entering the inner ear. Each hair cell is in contact with several neurons (called type I spiral ganglion neurons, or SGNs), which transmit the vibratory information to the brain, where it is interpreted as sound. Even brief exposure to noise can damage the terminal ends of SGNs (where they make contact with hair cells) and the synapses between SGNs and hair cells. The damage occurs when hair cells are overstimulated and release too much of a certain neurotransmitter, which causes the connection between the hair cells and the SGNs to break. When this happens, the SGN terminal ends shrink back, and some die off. The disconnection can lead to hearing loss. However, SGNs can regenerate and reestablish their connections with the inner hair cells. But researchers have found that the “system” does not return to absolute normal, although hearing is not immediately impaired. Exposure to excessive noise over time leads to accelerated hearing loss later in life. Dr. Wang will investigate what influences nerve regeneration after exposure to noise and how the reinnervation process may be lacking in some way. She especially interested in how the aberrant reinnervation could lead to accelerated hearing loss later in life.
Qiong Wang, MD. Ph.D, is a postdoctoral research scholar working in Dr. Steven Green’s lab in Department of Biological Sciences, University of Iowa in Iowa City. The AHRF has previously funded Dr. Green’s research.
Building an Ear From the Ground Up
Suzanne Mansour, Ph.D., an Associate Professor in the Department of Human Genetics at the University of Utah, Salt Lake City, received a grant from the AHRF for 2007 for her research project titled, “How to Build an Ear: Discovery of FGF-Regulated Hearing Loss Genes.”
To understand Dr. Mansour’s research, it is helpful to get an idea of how the ear forms during development.
The inner ear is a highly organized sensory organ with many specialized cell types that are responsible for both hearing and balance. Despite its complexity, all the cells that make up the inner ear are derived from a single patch of cells, referred to as the oticplacode, which is located on the surface of the embryonic head. Small signaling molecules, termed Fibroblast Growth Factors (FGFs), function as molecular triggers to activate genes which specify what the cells will develop into, for example tissues of the ear, or other sensory organs or skin.
Dr. Suzanne Mansour and her colleagues at the University of Utah have shown that FGF3 and FGF10 are key regulators of ear development. Knock-out mice that lack both of these factors fail to initiate ear development of any kind, suggesting that these trigger molecules play critical roles at the top of a genetic hierarchy to activate a constellation of “inner ear-specific” genes.
The protein products of these genes, many of which have not yet been discovered, are ultimately responsible for building the specific components of the ear. Once these inner ear genes are activated by FGF3 and FGF10, their protein products transform the thin layer of embryonic cells into a sphere, which then continues to undergo complex reorganization to form the elaborate cochlear and vestibular structures (which are responsible for balance). FGFs are also required during these later stages of inner ear development to coordinate cellular proliferation, specialization and tissue movements. With these myriad roles, it is not surprising that several human hearing loss syndromes are caused by mutations affecting FGF signaling.
By comparing the genetic profile of mice lacking FGF3/10 with normal mice, Dr. Mansour plans to pinpoint the genes that are regulated by FGF3/10. In turn, the genes that are identified will be studied with various functional methodologies to uncover their specific role in ear development. These studies will ultimately contribute to our understanding of the genetic “blueprint” for ‘building an ear.’ Moreover, it is anticipated that many of these genes may be implicated in congenital hearing or balance disorders and that their discovery may suggest potential therapeutic interventions.
Sound Processing and Reading: How are They Related?
Catherine Warrier, Ph.D., of the Roxelyn and Richard Pepper Department of Communication Sciences and Disorders department at Northwestern University in Evanston, Illinois, is one of the recipients of an AHRF grant for 2007. Dr. Warrier will be using the grant to investigate the function of the auditory cortex (the part of the brain that interprets sounds from the ear) in good- and poor-reading children.
Learning disabilities are estimated to affect approximately eight percent of school-aged children in the United States. Further studies have found that many of these children have a hard time discriminating certain speech sounds, suggesting that an auditory deficit may underlie their learning disability.
Most normal brains have an asymmetrical distribution of white matter in the auditory cortex, with more white matter found on the left side. This increased white matter is believed to be due to increased myelination of the neurons. Myelin is an insulating substance that is found wrapped around neurons. Greater insulation allows for faster transmission of electrical impulses along the nerve fibers, aiding in rapid acoustic processing. Poor readers tend to have a more symmetrical processing of rapid sounds than normal reading children. It is believed that white matter in the auditory cortex of poor-reading children is more symmetrically distributed than in normal reading children.
Dr. Warrier wants to determine whether this anatomical asymmetry is related to the strength of asymmetric acoustical processing in normal- and poor-reading children. She will study 22 children aged 8 to 13 with normal hearing (11 normal readers and 11 poor readers). She hopes to understand the extent to which the structure of the auditory cortex influences how children process sounds, and learn how this relates to reading ability.
Protein May Hold Key to Hair Cell Regeneration
Tzy-Wen Gong, Ph.D., of the University of Michigan, will investigate the role of a newly-identified gene, UBE3B in the potential regeneration of hair cells in mammals.
Birds and reptiles have the ability to regenerate and regrow hair cells, an ability that mammals lack.
Dr. Gong and her team have determined that the protein UBE3B codes for, called ubiquitin ligase, is dramatically increased in the regions of the chick chochlea that are damaged by noise. Ubiquitin ligase is an enzyme that in turn, works to destroy other proteins.
Gong has determined that in chicks, after ubiquitin ligase is released, and its target proteins are destroyed, this process somehow triggers cells in the damaged region of the choclea to differentiate into new hair cells, thus replacing those that are lost as a result of noise trauma.
Little is known about this process, and Dr. Gong hopes to investigate how the degradation of specific proteins triggers cell differentiation into hair cells in chick cochlea. She hopes that her research may yield new insights into hair cell regeneration in mammals, and ultimately, humans. |
Sam’s Story
Sam in his colonyMeet Sam. Sam had been living in an Annex Cat Rescue colony for a few years, where ACR volunteers fed and interacted with him daily. Because Sam was so friendly and showed signs of being open to human contact, ACR volunteers decided he would be a good candidate to be fostered and adopted. It can often be difficult to foster an adult feral cat that has been raised without human contact and some cats are not able to make this transition. The first step in determining this is to do an assessment.
An assessment determines if living indoors with humans is an option for a cat. Some adult cats born and raised in feral colonies cannot be domesticated and will never be happy living with humans. These cats are often neutered and released back into their colonies as part of a Trap Neuter Return (TNR) program in an effort to stabilize the number of feral cats in the community. One of the main things a person doing an assessment looks for is temperament; this is a good indication of whether a cat will become comfortable in a human home.
The assessment process usually takes a few weeks; socializing can take a few more weeks and usually continues in the foster home. ACR volunteers can assess cats within an assessment home, or remotely once a foster home is found. Mobile assessment is often a better option because there is less movement for the cat.
Sam getting the treatment he needed
Sam had been waiting for an assessment home when he was taken in by ACR volunteer, Marianne. A reality with most adult feral cats, and with Sam, is chronic disease. Efforts to feed and care for feral cats by ACR and other organizations often extend the life of feral colonies, and accelerated age can invite chronic disease for these cats. This is a reality that assessment and foster homes often must combat in the care and socialization process. Sam was brought into an assessment home with serious dental disease. Dental issues are very common with older cats and are often hard to spot while the cats are in feral colonies. Sam was still eating daily but was in a lot of pain and had to have most of his teeth extracted, in addition to dealing with vaccinations, worms and neutering. ACR takes on the cost of these expenses as part of the assessment process.
Sam’s medical issues played a role in his socialization process; he was in a lot of pain before and after the surgery, and stopped eating altogether during the overwhelming process. As a result Sam did not make much progress until his medical issues were attended to and he was recovering. This is a common issue that assessment and foster homes must be open and compassionate about in order to achieve success with their cats.
Sam's bathroom set up
After Sam had recovered his progress remained slow until he was introduced to Marianne’s cat. “He instantly perked up,” Marianne tells us, once Sam met her small cat. Being around another cat gave Sam confidence and he began to come out of his shell. A large part of the assessment process is determining the best conditions for each individual cat to flourish. Some cats require solidarity, and some, like Sam, require other cats to be happy. For any foster home, however, it is often important to have a small, isolated room in which to begin the transition process. This allows the cat to get accustomed to its new home in a less overwhelming process, as Marianne did with Sam in her bathroom. Once the cat feels secure, other cats and humans can be introduced and eventually, the cat can explore the rest of the home.
Sam relaxing
Sam has been with Marianne since May — longer than average for an assessment home. He is currently waiting for a suitable foster home to become available so he can continue being socialized and eventually adopted. Sam has a gentle and shy nature, and loves being petted and brushed. He has learned that he does not need to be afraid of humans; however, his instincts sometimes take over when he becomes startled. This is a common obstacle with older feral cats and it can be a personality trait that never fades. The ideal home for Sam would be one with other cats for him to socialize with. Sam is very shy but loves attention and requires a gentle home, without small children because of his tendency to get startled. Marianne recommends a home with children 7 years and up. Contact ACR at 416-410-3835 if you think your home is an optimal foster home for Sam.
—Kathy Ribeiro
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Faster-Than-Light Neutrinos: Looks Like a Bad Cable Is To Blame
I am not sure how I missed this when it was first posted, but it seems that experimentalists have found a probable explanation for those neutrinos that were clocked traveling faster than light. According to Science‘s website, a bad connection in a fiber-optic cable that carries GPS signals to the system’s master clock most likely made the particles appear as if they were traveling faster than they really were. There also seems to be a problem with a specific oscillator in the system, but it is not clear how big the problem is. Also, it is thought that correcting the oscillator’s problem might actually end up shortening the time measured, which would mean that the particles actually traveled faster than the original measurement indicated. As the web article makes clear, however, the main focus is on the fiber-optic cable connection.
We’ll know better in May, when a new experiment will be run. Hopefully, the fiber-optic cable’s connection, the oscillator problem, and anything else that is discovered between now and then will be fixed. However, based on what I have read, I think the most likely conclusion is that the neutrinos did not travel faster than light. Of course, as I said before, that was the most likely conclusion to begin with. When it comes to physics, don’t bet against Einstein. You aren’t likely to win!
1. jlwile says:
Heisenberg bet against some of Einstein’s gut feelings about physics, like the whole “God doesn’t play dice” thing. I am not aware of any of Einstein’s actual theories against which Heisenberg bet.
1. josiah says:
Well, Quantum Physics does kind of stand against Einstein…
Besides, I don’t like the attitude that says you leave the work of a past master to stand as a monument to their Genius. That’s exactly how the “science” of the Dark ages worked, and the mistakes of centuries past were protected as Gospel. Then there was that sneaky little hope that such neutrinos might make my dream of owning a pet triceratops actually come true!
Even so, this is a very important fact, and a very important thing to remember. If you have an unexpected result, check!
1. jlwile says:
Josiah, you are right that quantum mechanics and relativity are inconsistent with one another.
I don’t think you understood my comment. I wasn’t saying it’s impossible for Einstein to be wrong. I just said that you shouldn’t bet against him. In other words, it’s not likely that he was wrong. That’s a far cry from the science of the Dark ages, which said that someone like Aristotle couldn’t be wrong.
2. josiah says:
Well, my comment was slightly tongue in cheek. 🙂
I agree that the evidence behind Einstein’s theory does make it seem pretty solid, I merely assert that things shouldn’t be believed just because Einstein said them.
3. WSH says:
Oh well, not this time…
Eventually, GR may indeed be proven wrong, or at least, insufficient. I would suspect that time travel would not be possible anyways due to the macro-scale absurdities it would cause.
1. jlwile says:
WSH, I agree that time travel is probably not possible. |
Open Access
BMC Biology20119:87
DOI: 10.1186/1741-7007-9-87
Received: 27 July 2011
Accepted: 28 December 2011
Published: 28 December 2011
The bacterial family Enterobacteriaceae gave rise to a variety of symbiotic forms, from the loosely associated commensals, often designated as secondary (S) symbionts, to obligate mutualists, called primary (P) symbionts. Determination of the evolutionary processes behind this phenomenon has long been hampered by the unreliability of phylogenetic reconstructions within this group of bacteria. The main reasons have been the absence of sufficient data, the highly derived nature of the symbiont genomes and lack of appropriate phylogenetic methods. Due to the extremely aberrant nature of their DNA, the symbiotic lineages within Enterobacteriaceae form long branches and tend to cluster as a monophyletic group. This state of phylogenetic uncertainty is now improving with an increasing number of complete bacterial genomes and development of new methods. In this study, we address the monophyly versus polyphyly of enterobacterial symbionts by exploring a multigene matrix within a complex phylogenetic framework.
We assembled the richest taxon sampling of Enterobacteriaceae to date (50 taxa, 69 orthologous genes with no missing data) and analyzed both nucleic and amino acid data sets using several probabilistic methods. We particularly focused on the long-branch attraction-reducing methods, such as a nucleotide and amino acid data recoding and exclusion (including our new approach and slow-fast analysis), taxa exclusion and usage of complex evolutionary models, such as nonhomogeneous model and models accounting for site-specific features of protein evolution (CAT and CAT+GTR). Our data strongly suggest independent origins of four symbiotic clusters; the first is formed by Hamiltonella and Regiella (S-symbionts) placed as a sister clade to Yersinia, the second comprises Arsenophonus and Riesia (S- and P-symbionts) as a sister clade to Proteus, the third Sodalis, Baumannia, Blochmannia and Wigglesworthia (S- and P-symbionts) as a sister or paraphyletic clade to the Pectobacterium and Dickeya clade and, finally, Buchnera species and Ishikawaella (P-symbionts) clustering with the Erwinia and Pantoea clade.
The results of this study confirm the efficiency of several artifact-reducing methods and strongly point towards the polyphyly of P-symbionts within Enterobacteriaceae. Interestingly, the model species of symbiotic bacteria research, Buchnera and Wigglesworthia, originated from closely related, but different, ancestors. The possible origins of intracellular symbiotic bacteria from gut-associated or pathogenic bacteria are suggested, as well as the role of facultative secondary symbionts as a source of bacteria that can gradually become obligate maternally transferred symbionts.
One of the most fundamental evolutionary questions concerning insect-bacteria symbiosis is the origin and phylogenetic relationships of various symbiotic lineages. This knowledge is necessary for understanding the dynamics and mechanisms of symbiosis establishment and maintenance within the host. For instance, close relationships between symbionts and pathogenic bacteria suggests a transition from pathogenicity to symbiosis; polyphyly of the symbionts within a single host group is evidence of their multiple independent origins and close relationships among symbionts of different biology indicate high ecological flexibility within a given symbiotic group [16]. These implications are particularly important within Enterobacteriaceae, the group containing a broad spectrum of symbiotic lineages and forms described from various groups of insects. Their biology varies from loosely associated facultative symbionts (often called Secondary (S) symbionts) to obligatory mutualists of a highly derived nature, called Primary (P) symbionts [79]. However, the concept of the P- and S-symbionts and the associated terminology are a major oversimplification and they become inadequate for the description of the ever increasing complexity of the symbiotic system within Enterobacteriaceae. This complexity is manifested by such phenomena as the presence of multiple symbionts in a single host [10], occurrence of intermediate symbiotic forms and the replacement of symbionts within a host [1114] or close phylogenetic relationships between typical S- and P-symbionts revealing their high ecological versatility [15]. A good example of such a complex system is provided by the occurrence of multiple obligate symbionts within Auchenorrhyncha [10], universally harboring Sulcia muelleri (Bacteroidetes) [16] with either Hodgkinia cicadicola (α-Proteobacteria) in cicadas, Zinderia insecticola (β-Proteobacteria) in spittlebugs or Baumannia cicadellinicola (γ-Proteobacteria) in sharpshooters. All of these latter symbionts are obligate and have been cospeciating with their hosts for millions of years [1721]. A close phylogenetic relationship between typical S- and P-symbionts has been so far demonstrated in two well defined and often studied groups, the enterobacterial genera Arsenophonus and Sodalis [5, 22, 23]. The general capability of S-symbionts to supplement the metabolic functions of P-symbionts or even replace them was demonstrated experimentally by replacement of Buchnera with Serratia in aphids [24].
It is obvious that all these fascinating processes can only be studied on a reliable phylogenetic background [9, 2528]. Unfortunately, under current conditions, the phylogeny within Enterobacteriaceae and the placement of various symbiotic lineages are very unstable. Particularly, the P-symbionts present an extremely difficult challenge to phylogenetic computation due to their strongly modified genomes [9]. There are several root problems that are responsible for this dissatisfactory state. Traditionally, 16S rDNA was frequently used as an exclusive molecular marker for the description of a new symbiont. Many lineages are thus represented only by this gene, which has been shown within Enterobacteriaceae to be inadequate for inferring a reliable phylogeny [29]. In addition, it is notoriously known that the phylogenetic information of symbiotic bacteria is often seriously distorted due to the conditions associated with the symbiotic lifestyle. The effect of strong bottlenecks accompanied by reduced purifying selection and the overall degeneration of symbiotic genomes have been thoroughly discussed in many studies [3033]. As a result of these degenerative processes, symbiotic lineages may experience parallel changes of their DNAs and these convergences produce the main source of phylogenetic artifacts. Among the most important features are biased nucleotide composition favoring adenine-thymine bases and rapid sequence evolution. While the compositional bias leads to the introduction of homoplasies at both nucleotide and amino acid levels, the accelerated evolution is a well known source of the long-branch attraction phenomenon [34, 35]. Due to these circumstances, symbionts almost always appear as long branches in phylogenetic trees and tend to cluster together [36].
Various methodological approaches have been tested to overcome these difficulties (Additional file 1). They are based mainly on the concatenation of a large number of genes through the whole genome [3739], the supertree and the consensus approach [37], exclusion of amino acids (FYMINK: phenylalanine, tyrosine, methionine, isoleucine, asparagine and lysine) most affected by nucleotide bias [37], modifications of sequence evolution models [11, 12, 36, 40] and use of the genome structure as a source of phylogenetic data [41]. Phylogenomic studies based on large concatenated sets frequently imply monophyly of the typical P-symbionts (Additional file 1). However, due to the limited number of available genomes, these studies are usually based on inadequate taxon sampling. For example, secondary symbionts and plant pathogens that were shown to break the P-symbiont monophyly in the analysis using a nonhomogeneous model [40] could not be included into these phylogenomic studies. It is important to note that P-symbionts are probably only distantly related to the Escherichia/Salmonella/Yersinia clade. Therefore, the monophyly of P-symbionts derived from such a phylogenomic dataset is logically inevitable, but does not carry any evolutionary information.
The non-monophyletic nature of P-symbionts has been recently suggested in several studies. Perhaps the most inspiring is a study based on a nonhomogeneous model that separates P-symbionts into two independent lineages [40]. As an alternative, a paraphyletic arrangement of these symbionts in respect to several free-living taxa has been revealed from gene-order analysis based on break-point and inversion distances [41]. Most recently, Williams et al. [42] performed a 'telescoping' multiprotein phylogenomic analysis of 104 γ-Proteobacterial genomes. The phylogeny of Enterobacteriaceae endosymbionts was difficult to resolve, although it appeared that there were independent origins of at least the Sodalis and Buchnera lineages.
Thus, there is now a spectrum of hypotheses on the phylogeny of insect symbionts, ranging from complete polyphyly with multiple independent origins to complete monophyly with one common origin. In this study, we take advantage of current progress in computational methods to investigate phylogenetic relationships among the symbiotic lineages. One of the promising recent methodological advances is the introduction of a site-heterogeneous non-parametric mixture CAT model that allows for site-specific features of protein evolution [43]. This model was shown to solve the long-branch attraction (LBA) artifacts and outperform the previous models [4447]. Similarly, the slow-fast method based on removal of the fastest evolving sites was shown to reduce phylogenetic artifacts [4854], as well as purine/pyrimidine (RY) data recoding [5558] or amino acid data recoding [59, 60]. We used these methods as the core of a complex approach and tried to investigate series of methods, models and parameters to detect common trends in changes of the topologies. To do this, we applied two parallel approaches, one based on the application of recently developed algorithms and the other on the removal or recoding of the positions most affected by rapid sequence evolution and/or compositional (AT) bias. In addition, we paid particular attention to the sampling and used as much of a complete set of both symbiotic and free-living lineages as possible. This approach is particularly important to avoid interpretation uncertainties due to the absence of phylogenetically important lineages.
The complete methodological design of this study and the resulting topologies are depicted in Figure 1. All matrices, alignments and phylogenetic trees are available in the TreeBASE database, as supplementary material, or on the webpage
Figure 1
Study design. General design of the study summarizing all analyses and results. Individual topologies show the gradient of acquired results; method names are written above and below the arrows. Notice an increasing number of independent origins of symbionts and decreasing number of phylogenetic artifacts along the continuum towards the 'derived' methods. 1+2: third codon positions excluded; AT/GC(BI/4-11): AT/GC datasets 4-11 analyzed by BI; BI: Bayesian inference; Dayhoff6/Dayhoff4/HP: amino acid recoded matrices; ML: maximum likelihood; nhPhyML: ML under nonhomogeneous model; MP: maximum parsimony; RY: purine/pyrimidine recoded matrix; SF: slow-fasted datasets.
Standard maximum likelihood and Bayesian inference
The single gene maximum likelihood (ML) analyses of both nucleic and amino acid data provided an array of mutually exclusive topologies. The majority consensus based on amino acid data (Additional file 2a) groups almost all symbionts into polytomy with only two pairs of sister symbiotic species being resolved (Buchnera and Blochmannia). Phylogenetic trees inferred by ML and Bayesian inference (BI) from the nucleic acid concatenated data using the General Time Reversible model with an estimated proportion of invariable sites (I) and heterogeneity of evolutionary rates modeled by the four substitution rate categories of the gamma (Γ) distribution with the gamma shape parameter (alpha) estimated from the data (GTR+I+Γ) were apparently affected by phylogenetic artifacts, as demonstrated by placement of Riesia and Wigglesworthia within the Buchnera cluster with high posterior probabilities in the BI tree (Figure 2) and the attraction of two outgroup species (Haemophilus and Pasteurella) in the ML tree with high bootstrap support (Additional file 2b). Similar topologies were also retrieved from the amino acid concatenate by ML and BI using the LG+I+Γ, WAG+I+Γ and GTR+I+Γ models (Figure 3). Nevertheless, in contrast to the nucleotide-derived results, the monophyly of the Buchnera clade was not disrupted and Hamiltonella and Regiella were unambiguously separated from the other symbionts and clustered with Yersinia.
Figure 2
MrBayes phylogram - 69 genes, nucleotide matrix. Phylogenetic tree inferred from the concatenated nucleotide matrix using BI under the GTR+I+Γ model. Asterisks designate nodes with posterior probabilities equal to 1.0, values next to species names represent GC content calculated from the 69-gene dataset, genomic GC content can be found in Additional file 4. BI: Bayesian inference.
Figure 3
MrBayes phylogram - 69 genes, amino acid matrix. Phylogram inferred from the concatenated amino acid matrix using BI under the WAG+I+Γ model. Values at nodes represent posterior probabilities (WAG+I+Γ model, GTR+I+Γ protein model) and bootstrap supports from ML analysis (LG+I+Γ model). Asterisks designate nodes with posterior probabilities or bootstrap supports equal to 1.0, dashes designate values lower than 0.5 or 50, values next to species names represent GC content calculated from the 69-gene dataset, genomic GC content can be found in Additional file 4. BI: Bayesian inference. ML: maximum likelihood.
PhyloBayes, non-homogenous PhyML and modified matrices
The phylogenetic trees acquired under the CAT+GTR PhyloBayes model from 14 and 55 concatenated genes (Figure 4 and Additional file 2p) split symbiotic bacteria into four and three independent lineages, respectively. First, Arsenophonus nasoniae is a sister species to Proteus mirabilis; second, Hamiltonella and Regiella form a sister clade to Yersinia pestis; third, the Sodalis, Baumannia, Blochmannia, Wigglesworthia, Riesia and Buchnera clade form a sister clade to Dickeya/Pectobacterium. The position of Ishikawaella differs between the two datasets. In the 14-gene dataset, Ishikawaella forms a sister clade to Pantoea (Figure 4) and in the 55-gene dataset, it is attracted to the P-symbiont cluster (Additional file 2p).
Figure 4
PhyloBayes phylogram - 14 genes, amino acid matrix. Phylogram derived from concatenation of 14 genes (AceE, ArgS, AspS, EngA, GidA, GlyS, InfB, PheT, Pgi, Pnp, RpoB, RpoC, TrmE and YidC) using PhyloBayes under the CAT+GTR model. Asterisks designate nodes with posterior probabilities equal to 1.0, values next to species names represent GC content calculated from the 69-gene dataset, genomic GC content can be found in Additional file 4.
A topology with four independent symbiotic clades resulted from the trees derived from dayhoff6 and dayhoff4 recoded amino acid data sets analyzed by CAT and CAT+GTR models (Figure 5, Additional file 2r, q) and partially with the hp (hydrophobic-polar) recoded dataset (Additional file 2c) - which was on the other hand affected by the substantial loss of phylogenetic information. The first clade is Buchnera+Ishikawaella as a sister clade to the Erwinia/Pantoea clade, the second clade is Riesia+Arsenophonus as a sister clade to Proteus, the third clade is Hamiltonella+Regiella as a sister clade to Yersinia, and the last clade is composed of Sodalis, Baumannia, Blochmannia and Wigglesworthia.
Figure 5
PhyloBayes cladogram - 69 genes, Dayhoff6 amino acid recoded matrix. Cladogram inferred from amino acid matrix recoded with Dayhoff6 scheme using PhyloBayes with the CAT and CAT+GTR model. Because of the length of symbiotic branches, phylogram is presented only as a preview (original phylogram can be found in Additional trees on our website). Values at nodes represent posterior probabilities from CAT and CAT+GTR analyses, respectively (asterisks designate nodes with posterior probabilities equal to 1.0). Values next to species names represent GC content calculated from the 69-gene dataset, genomic GC content can be found in Additional file 4.
The analyses testing each symbiont independently, using a CAT+GTR model on the dayhoff6 recoded datasets, resulted in topologies supporting multiple origins of endosymbiosis (Additional file 2s). Arsenophonus clusters with Proteus; Hamiltonella clusters with Yersinia; Regiella clusters with Yersinia; and Sodalis, Blochmannia, Baumannia, Riesia and Wigglesworthia grouped into polytomy with the basal enterobacterial clades. Most importantly, the Buchnera clade clusters as a sister clade to the Erwinia clade and Ishikawaella is placed in polytomy with the Pantoea and Erwinia clade.
The non-homogenous (nh) PhyML nucleotide analyses with two different starting trees resulted in two different topologies (Figure 6 and Additional file 2d, e, f). When compared by the approximately unbiased (AU) test, the topology with four independent origins of symbiotic bacteria prevailed (P = 1) over the topology with monophyly of P-symbionts, which therefore corresponds to a local minimum due to a tree search failure (complete matrix: P = 2 × 10-67; matrix without the third positions: P = 9 × 10-87). The only incongruence in topologies based on the complete matrix (Additional file 2d) and the matrix without the third positions (Figure 6) was the placement of the Sodalis+Baumannia+Blochmannia+Wigglesworthia clade as a sister clade to the Edwardsiella or Dickeya/Pectobacterium clades.
Figure 6
Matrices obtained by removing positions according to the AT/GC contents produced trees covering the whole continuum illustrated in Figure 1. The most severe restrictions, that is, removal of all positions that contain both AT and GC categories or relaxing for up to three taxa (see BI trees in Additional file 2g, h, i, j), yielded topologies compatible with the results of the CAT model applied on the recoded amino acid data and of the nhPhyML analysis. Further relaxing the restriction rule led to a variety of trees along the Figure 1 continuum, with a less clear relation between the used parameter and the resulting topology (Additional file 3).
Compared to the ML analysis of all nucleotide positions, the analysis of first plus second positions reduced the obvious artifact of outgroup attraction (Additional file 2k). Nevertheless, it also sorted symbionts according to their branch length. Analysis of the RY recoded nucleotide matrix produced a tree compatible with the results of the CAT+GTR model (Additional file 2l). Analysis of the RY recoded nucleotide matrix without the third positions resulted in a topology with a Sodalis+Baumannia+Blochmannia cluster (as a sister to the Pectobacterium/Dickeya clade) separated from the rest of the P-symbionts, which clustered with the Erwinia/Pantoea clade (Additional file 2m). Slow-fast analyses with gradual reduction of saturated positions did not produce the polyphyly of P-symbionts (Additional file 3; only the first five trees presented, subsequent trees are identical to the fifth tree). However, this analysis shows an increasing effect of LBA artifacts associated with the increasing number of remaining saturated positions, especially Riesia attraction and swapping of symbiotic branches according to their length.
Performance of the methods: convergence towards non-monophyly
The results obtained in this study strongly indicate that the frequently retrieved monophyly of P-symbionts is an artifact caused by their highly modified genomes. None of the most widely used methods, that is, ML and BI with different models used on nucleic (GTR+I+Γ) and amino acid (GTR/LG/WAG+I+Γ) data, were capable of resolving deep phylogenetic relationships and correct placement of the symbiotic taxa. This conclusion is evidenced by obvious artifacts, such as the inclusion of Riesia into the P-symbiotic lineage or the even more conspicuous distorted placing of Wigglesworthia within the Buchnera cluster. The arrangement of such trees suggests that these methods sort the symbionts according to their branch lengths and/or AT contents and attach the whole symbiotic cluster to the longest branch available. While the difficulty with placement of the most aberrant taxa, such as Riesia, Wigglesworthia and Buchnera (Cinara cedri) was also observed when using the mixture model accounting for site specific characteristics of protein evolution (Figure 4; Additional files 2p and 5), these artifacts disappeared after amino acid data recoding followed by CAT and CAT+GTR model analysis and the application of a nonhomogeneous model.
Additional support for the non-monophyly view stems from the second, parallel approach based on the restricted matrices. While our newly developed method shares the basic principles with the slow-fast and recoding methods, such as the removal of the positions that are likely to distort the phylogenetic relationships due to their aberrant evolution, it differs in the criteria of their removal and thus produces different input data. It is therefore significant that this method led independently to the same picture, the non-monophyly of the P-symbionts with clustering identical to the above analyses: Ishikawaella+Buchnera and Sodalis+Baumannia+Blochmannia+Wigglesworthia. The removal of the heteropecillous sites was recently shown to have similar effectiveness as our new method [61], which further supports the results. Moreover, this topology was obtained even under the maximum parsimony (MP) criterion (Additional file 3), which is known to be extremely sensitive to LBA [34]. On the other hand, although slow-fast analysis is generally considered a powerful tool for resolving relationships among taxa with different rates of evolution, we show in our data that the mere exclusion of the fast evolving sites is not sufficient when using empirical models and should be followed by analysis using some of the complex models, such as the CAT-like models. In addition, since this method usually requires an a priori definition of monophyletic groups, it should be used and interpreted with caution. Similar to the slow-fast method, RY recoding and exclusion of third codon positions were not sufficient for resolving deep symbiont phylogeny. However, all these methods can remove at least some of the artifacts and provide insight for further analyses.
Summarizing the topologies obtained in this study (Figure 1), a convergence can be detected towards a particular non-monophyletic arrangement of P-symbionts, as revealed under the most 'derived' methods. This result strongly supports the view of multiple origins of insect endosymbionts, as first revealed by the nonhomogeneous model of sequence evolution [40], and is partially congruent with the analyses of gene order [41] and phylogenomics of Gammaproteobacteria [42]. It is also important to note that, apart from multiple symbiont clustering, the arrangement of the non-symbiotic taxa corresponds to most of the phylogenomic analyses using Escherichia/Salmonella/Yersinia taxon sampling [3739].
Biological significance of P-symbionts non-monophyly
Considering that most of the 'artifact-resistant' analyses point towards the non-monophyly of enterobacterial P-symbionts, the questions of how many symbiotic lineages are represented by the known symbiotic diversity and what are their closest free-living relatives now becomes of particular importance. It is not clear whether the split of the original P-symbiotic cluster into two lineages is definite or these two groups will be further divided after yet more sensitive methods and more complete data are available. At the moment there are still several clusters composed exclusively of derived symbiotic forms. In principle, three different processes may be responsible for the occurrence of such clusters: first, horizontal transmission of established symbiotic forms among host species; second, inadequate sampling with missing free-living relatives; or third, phylogenetic artifacts. All of these factors are likely to play a role in the current topological patterns. Being the main issues of this study, the role of methodological artifacts has been discussed above. Horizontal transmission, as the basis of non-artificial symbiotic clusters, is likely to take part at least in some cases. Perhaps the most convincing example is the Wolbachia cluster [62]: while within Enterobacteriaceae it may apply to Arsenophonus, Sodalis and possibly some other S-symbionts.
Recognition of the third cause, the incomplete sampling, and identification of the closest free-living relatives, now becomes a crucial step in future research. It is often assumed that symbionts originate from bacteria common to the environment typical for a given insect group. For example, cicadas spend most of their life cycle underground and feed primarily on plant roots. Consequently, their α-Proteobacterial symbiont Hodgkinia cicadicola originated within Rhizobiales [19]. A similar ecological background can be noticed in yet different hosts, the ixodid and argasid ticks. Several reports have shown that some of the tick-transmitted pathogens are related to their symbiotic fauna [6365]. Many of the insect taxa associated with symbiotic Enterobacteriaceae are phytophagous, and plant pathogens thus fit well into this hypothesis as hypothetical ancestors of various insect symbionts lineages. The presence of a type III secretion system, which is used in pathogenic bacteria for host cell invasion, in secondary symbionts [6669] and its remnant in the primary symbiont of Sitophilus spp. weevils [70] could further support the theory of pathogenic ancestors of insect symbionts. It can only be speculated that these bacteria first became S-symbiont type and were horizontally transferred to various other insect species. Within some of the infected species, facultative symbionts eventually became obligatory primary symbionts. An identical situation can be observed in symbiotic clades with numerous species, such as Wolbachia [71, 72], Sodalis [23, 73, 74] or Arsenophonus [5].
In our study, we gave particular attention to the sampling of free-living Enterobacteriaceae to provide as complete a background for the symbiotic lineages as possible under the current state of knowledge (that is, the availability of the genomic data). The most consistent picture derived from the presented analyses places the four main symbiotic clusters into the following positions. First, for the Buchnera cluster, its previously suggested relationship to Erwinia was confirmed. Erwinia, as a genus of mostly plant pathogenic bacteria, has been previously suggested to represent an ancestral organism, which upon ingestion by aphids at least 180 million years ago [75] turned into an intracellular symbiotic bacterium [76]. However, it is not known whether it was primarily pathogenic to aphids, similar to Erwinia aphidicola [77], or a gut associated symbiotic bacterium as in pentatomid stinkbugs [78], thrips [79, 80] or Tephritidae flies [8183]. Ishikawaella capsulata, an extracellular gut symbiont of plataspid stinkbugs [84], was the only symbiotic bacterium that clustered in our 'derived' analyses with the Buchnera clade. However, several single-gene studies indicate that this group contains some additional symbiotic lineages for which sequenced genome data is not currently available. These are, in particular, the extracellular symbionts of acanthosomatid stinkbugs [85], parastrachid stinkbugs [86], scutellerid stinkbugs [87, 88] and some of the symbionts in pentatomid stinkbugs [78].
The second clade, represented in our analysis by Sodalis+Baumannia+Blochmannia+Wigglesworthia, is likely to encompass many other P- and S-symbionts [8992]. The possible single origin of these symbionts has to be further tested, however the interspersion of both forms, together with basal position of Sodalis, seem to support a transition from a secondary to primary symbiotic lifestyle [15]. In our analysis, the whole clade was placed between pathogenic bacteria of plants and animals, the Edwardsiella and Pectobacterium/Dickeya clades, or as a sister to the latter group. Recently, another symbiotic bacterium (called BEV, Euscelidius variegatus host) was shown to be a sister species to Pectobacterium [93].
Two additional independent origins of insect symbionts are represented by the Arsenophonus/Riesia clade and Hamiltonella+Regiella. Both of these clades clustered in our analyses in the positions indicated by previous studies, that is, as related to Proteus and Yersinia, respectively [5, 67, 9397].
While the position of individual symbiotic lineages is remarkably consistent across our 'artifact-resistant' analyses and are well compatible with some of the previous studies, the topology can only provide a rough picture of the relationships within Enterobacteriaceae. To get a more precise and phylogenetically meaningful background for an evolutionary interpretation, the sample of free-living bacteria as a possible source of symbiotic lineages has to be much improved. An illuminating example is provided by the bacterium Biostraticola tofi, described from water biofilms. When analyzed using 16S rDNA, this bacterium seemed to be closely related to Sodalis [98]. Its position as a sister group to the Sodalis/Baumannia/Blochmannia/Wigglesworthia clade was also retrieved in our single-gene analysis (groEL, data not shown). If confirmed by more precise multigene approach, Biostraticola would represent the closest bacterium to the large symbiotic cluster.
The topologies obtained by several independent approaches strongly support the non-monophyletic view of enterobacterial P-symbionts. Particularly, they show that at least three independent origins led to highly specialized symbiotic forms, the first giving rise to Sodalis, Baumannia, Blochmannia and Wigglesworthia (S- and P-symbionts), the second to Buchnera and Ishikawella and the last to Riesia and Arsenophonus (S- and P-symbionts). This separation of symbiotic clusters poses an interesting question as to whether the presented disbandment of the P-symbiotic cluster is definite or if it will continue after yet more complete data are available and more realistic evolutionary models [99101] are applied. One obvious drawback of the current state is that many additional symbiotic lineages already known within Enterobacteriaceae cannot be at the moment included into serious phylogenetic analyses due to the lack of sufficient molecular data and will have to be revisited once complete genomic data are available. These bacteria include symbionts of mealybugs [89, 102], psyllids [90, 103], lice [2, 91], weevils [11, 12, 92], reed beetles [104, 105], true bugs [78, 8488, 106, 107] and symbionts of leeches [108, 109]. Similarly, the importance of free-living bacteria and variety of S-symbionts as possible ancestors of P-symbionts should not be underestimated when assembling datasets for phylogenetic analyses. The shift from polymerase chain reaction-based gene-centered sequencing towards high-throughput next-generation sequencing may soon provide sufficient data for more complete analyses of the Enterobacteriaceae phylogeny.
Matrices and multiple sequence alignments
The genes used in this study were extracted from 50 complete genome sequences of γ-Proteobacteria available in GenBank (Additional file 4), including 14 endosymbiotic Enterobacteriaceae. We did not include Carsonella ruddii [110] since this psyllid symbiotic bacterium does not appear to be a member of the Enterobacteriaceae clade [90, 111] and is only attracted there by the AT rich taxa. After removal of the AT rich lineages from the analysis, Carsonella ruddii clusters with the genus Pseudomonas [42]. Also, we did not include Serratia symbiotica [95] because its genome only became available after completion of our datasets. However, the phylogenetic position of this symbiotic bacterium within Serratia genus is robust and was confirmed in several studies [6, 14, 112].
To minimize the introduction of a false phylogenetic signal, we compared the genomes of all symbiotic bacteria and selected only single-copy genes present in all of the included symbiotic and free-living taxa. Such strict gene exclusion was also necessary regarding the usage of computationally demanding methods; it was one of our goals to produce a taxonomically representative data set of efficient size with no missing data. Altogether, 69 orthologous genes, mostly involved in translation, ribosomal structure and biogenesis (Additional file 4) were selected according to the Clusters of Orthologous Groups of proteins (COGs) [113, 114]. Single-gene nucleotide data sets were downloaded via their COG numbers from a freely available database (MicrobesOnline [115]).
All protein coding sequences were translated into amino acids in SeaView version 4 [116], aligned by the MAFFT version 6 L-INS-i algorithm [117] and toggled back to the nucleotide sequences. Ambiguously aligned positions (codons) were excluded by Gblocks v0.91b [118, 119] with the following parameters: minimum number of sequences for a conserved position: 26; minimum number of sequences for a flanking position: 43; maximum number of contiguous nonconserved positions: 8; minimum length of a block: 10; allowed gap positions: with half. The resulting trimmed alignments were checked and manually corrected in BioEdit v7.0.5 [120]. Alignments were concatenated in SeaView. The 69 gene concatenate resulted in an alignment of 63, 462 nucleic acid positions with 42, 481 parsimony-informative and 48, 527 variable sites and 21, 154 amino acid positions with 12, 735 parsimony-informative and 15, 986 variable sites.
Phylogenetic analyses
We used two different approaches to deal with the distortions caused by the highly modified nature of symbiotic genomes, which are the main source of the phylogenetic artifacts in phylogenetic analyses.
First, we applied complex models of molecular evolution. Using PhyloBayes 3.2f [121], we applied non-parametric site heterogeneous CAT and CAT+GTR models [43]. For all PhyloBayes analyses, we ran two chains with an automatic stopping option set to end the chain when all discrepancies were lower than 0.3 and all effective sizes were larger than 100. Under the CAT and CAT+GTR models, the four independent PhyloBayes runs were stuck in a local maximum (maxdiff = 1) even after 25, 000 and 10, 000 cycles, respectively, and we were not able to reach Markov Chain Monte Carlo (MCMC) convergence. Therefore, we present these trees only as supplementary material (although they mostly point toward multiple origins of symbiosis; Additional file 5) and we ran the CAT+GTR analyses with the reduced dataset based on 14 genes with the number of parsimony-informative amino acid positions higher than 300 (AceE, ArgS, AspS, EngA, GidA, GlyS, InfB, PheT, Pgi, Pnp, RpoB, RpoC, TrmE and YidC). To check for compatibility of these arbitrary selected 14 genes with the rest of the data, we also analyzed, in a separate analysis, the remaining 55-gene dataset under the CAT+GTR model. Using nhPhyML [122], we applied a nonhomogeneous nonstationary model of sequence evolution [123, 124], which can deal with artifacts caused by compositional heterogeneity [40, 125, 126]. We used two different starting trees (Additional file 2n) and ran the analyses with and without the third codon positions. The resulting trees were evaluated by an AU test in CONSEL [127].
The second approach relies on the selective restriction of the data matrix. We used four previously established methods of data weighting and/or exclusion (see Background): RY data recoding, amino acid data recoding, exclusion of third codon positions and slow-fast analysis, and developed one additional method: since transition from G/C to A/T at many positions is a common homoplasy of symbiotic genomes, we removed from the matrix all positions containing both the G/C and A/T states. All substitutions considered in the subsequent analyses thus included exclusively transversions within the A/T or G/C categories. To analyze an effect of this restriction on the reduction of the data, we prepared 11 matrices with a partially relaxed rule (removing all positions with AT+GC, allowing for one taxon exception, two taxa exception, and so on, up until a 10 taxa exception). Since this method has never been tested, we analyzed the restricted matrices by the BI, ML (parameters as for standard analyses) and MP using PAUP* 4.0b10 with the tree bisection and reconnection algorithm [128]. Four other types of data weighting and/or exclusion were used to increase the phylogenetic signal to noise ratio and determine the robustness of our results. First, the third codon positions were removed in SeaView. Second, RY recoding was performed on all and first plus second positions. Third, saturated positions were excluded from the concatenated data sets by SlowFaster [129]. To assign substitutional rates to individual positions, unambiguously monophyletic groups were chosen on a polytomic tree (Additional file 2o), positions with the highest rates were gradually excluded and 21 restricted matrices were produced. These weighted data sets were analyzed by ML. Fourth, amino acid data recoding was performed in PhyloBayes with hp (A, C, F, G, I, L, M, V, W) (D, E, H, K, N, P, Q, R, S, T, Y), dayhoff4 (A, G, P, S, T) (D, E, N, Q) (H, K, R) (F, Y, W, I, L, M, V) (C = ?) and dayhoff6 (A, G, P, S, T) (D, E, N, Q) (H, K, R) (F, Y, W) (I, L, M, V) (C) recoding schemes. In addition, we have prepared 10 dayhoff6 recoded matrices to test individual symbiotic lineages without the presence of other symbionts. Amino acid recoded matrices were analyzed using the CAT and CAT+GTR models, which are more immune to phylogenetic artifacts than one-matrix models.
To allow for comparison of the results with previously published studies, as well as to separate the effect of newly used models and methods from changes due to the extended sampling, we also used standard procedures of phylogenetic inference, ML and BI. The following programs, algorithms and parameters were used in the ML and BI analyses. ML was applied to single-gene and concatenated alignments of both nucleotides and amino acids using PhyML v3.0 [130] with the subtree pruning and regrafting tree search algorithm. BI was performed in MrBayes 3.1.2 [131] with one to five million generations and tree sampling every 100 generations. Exploration of MCMC convergence and burn-in determination was performed in AWTY and Tracer v1.5 [132, 133]. Evolutionary substitution models for proteins were selected by ProtTest 2.4 [134] and for DNA by jModelTest 0.1.1 [135] according to the Akaike Information Criterion. For DNA sequences, the GTR+I+Γ model was used [136138]. Transition and transversion models [139] were used with I+Γ under ML for the first two AT/GC datasets. LG+I+Γ [140], WAG+I+Γ [141] and GTR+I+Γ models were used for amino acid data. A cross-validation method implemented in PhyloBayes [121, 142] was used to estimate the fit of CAT-like models. For both datasets, the 14 selected genes as well as the complete 69 genes set, the cross-validation was performed according to the PhyloBayes manual in 10 replicates each with 1, 100 cycles. The CAT-Poisson model had significantly better fit to the data than the GTR model (Δl 157.37 ± 56.9379 for the 14-gene matrix and Δl 3923.9 ± 1963.5 for the 69-gene matrix); of the CAT-like models, the CAT+GTR model was found to be significantly better than the CAT-Poisson model (Δl 536.71 ± 32.8341 for the 14-gene matrix and Δl 1633.4 ± 123.482 for the 69-gene matrix) in all 10 replicates.
This work was supported by the Grant Agency of Academy of Sciences of the Czech Republic (grant number P505/10/1401 to VH); the Student Grant Agency of the Faculty of Science, University of South Bohemia (grant number SGA2009002 to FH); and the Ministry of Education, Youth, and Sports of the Czech Republic (grant numbers LC06073 and MSM 60076605801 to VH). Access to the MetaCentrum computing facilities provided under the 'Projects of Large Infrastructure for Research, Development, and Innovations' program LM2010005 funded by the Ministry of Education, Youth, and Sports of the Czech Republic is highly appreciated.
Authors’ Affiliations
Faculty of Science, University of South Bohemia
Institute of Parasitology, Biology Centre of ASCR
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Glossary Terms
The 35mm equivalent focal length of a lens is sometimes given for cameras using other film formats, and often for digital cameras. This is to give some comparison of the angle of view of lenses between different cameras with different film frame or digital sensor sizes.
Typical 35mm-format lenses standard lenses are between (approximately) 40-55mm. Telephoto lenses being longer, and wide angle being shorter.
The equivalent is calculated by the dividing standard full-frame 35mm diagonal, of 43.27mm, by the diagonal of the camera's sensor/film frame diagonal, and multiplying the lens focal length by this ratio. Thus, for example, an APS camera with a typical lens of, say 25mm, using the full HDTV format (30.2 x 16.7 mm), has a frame diagonal of 34.51mm, so the lens' 35mm equivalent is 25*43.27/34.51 = 31mm.
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Xian City Wall
Xi’an is one of the few cities in China where old city walls are still visible.The city wall of Xi’an is an extension of the old Tang Dynasty structure, as a result of this wall building campaign. Xi’an’s city wall after its enlargement in the Ming Dynasty stands 12 meters high. It is 12-14 meters across the top, 15-18 meters thick at bottom and 13.7 kilometers in length. There is a rampart every 120 meters. The ramparts are towers that extend out from the main wall, the top of the rampart being at the same level as the top of the wall. The distance between two ramparts is just within the range of arrow shot from either side. This allowed soldiers to protect the entire wall without exposing themselves to the enemy. There are altogether 98 of them on the wall; each has a sentry building on top of it. The weapons in ancient times were primitive. The gates of the city wall were the only way to go into and out of town. Therefore, these gates were important and strategic points, that the feudal rulers racked their brains to try to defend.
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Limited Educational Instruction
It is crucial to the success of any school to employ dedicated teachers who are physically present to administer quality education to each student. Excessive absenteeism by the teaching staff can drastically hinder the learning environment and academic achievement of students when instructors are not routinely present to teach them. When teachers are absent, schools must rely on substitute teachers to provide instruction for the students. However, many substitute teachers may not be qualified to provide quality educational instruction. Substitute teachers are not always required to possess a teaching certification, and in some school districts they are able to teach with only a high school GED. The loss of quality instructional time for students can result in unlearned academic skills and objectives, and subsequent reduction in students' standardized test scores.
Poor Academic Progress
Successful schools cannot survive without physically present students. According to the "Excessive Absences Intervention" research study by author Linda L. Williams, excessive absenteeism by students may result in unlearned course material from fewer hours of instruction, and a disruption of class instruction for teachers who have to administer remediation for the absent student when he returns to school. Excessive absenteeism by students may additionally result in poor academic achievement because students are not receiving instruction on a consecutive basis. This problem also causes low standardized test scores because absent students are not present to learn key concepts and skills that are assessed on standardized exams.
Future Problems
Excessive student absenteeism can lead to an increasing disinterest in school and academics in general. According to author Jason A. Schoeneberger’s "Longitudinal Attendance Patterns" study, excessive absenteeism increases the chances of a student eventually dropping out of school, which can lead to long term consequences for these students, such as lower average incomes, higher incidences of unemployment, and a higher likelihood of incarceration. Schoeneberger asserts that students who drop out of school face a higher risk of poverty because of their inability to secure quality paying employment due to their lack of education and resources. Dropouts who lack education and resources are more likely to commit criminal activity leading to incarceration.
Decreased School Budget
Excessive absenteeism also places an extreme strain on the school's budget, and allocated finances in each school district. Average daily attendance, or ADA, is the average attendance rate of students in a school year. States utilize a school district's ADA to determine the allocated funding it will receive. Schools may encounter a decrease in funding due to a loss of full-time students. This limited budget due to excessive absences causes a lack of educational resources and materials for the all the students in the school. According to "USA Today," about one in three teachers misses more than 10 days of school each year in the public school system. Providing substitutes for all of these absent teachers costs schools, cumulatively, at least $4 billion a year. "USA Today" further reported that in some states nearly 50 percent of the teachers miss more than 10 days of school in a typical 180-day school year. |
Progress is possible for every golfer to achieve, but golfers have to understand the only way to improve is done by improving their alignments and application of force through impact.
It's unbelievable how many golfers throughout my years of teaching have told me that the club should lift the ball into the air by hitting from underneath the ball. This misconception is without a doubt one of the key elements to why this game is so difficult and why the average golfer gets worse the more he plays rather than better.
Understanding the the design of the golf club is a vital topic to gain any long term improvement. The golf club had 3 parts: a handle, a shaft and a club head. Understanding that the grip and shaft must always pass the ball before the club head will help you understand that the club head is trailing behind so subsequently being pulled through the impact interval. Secondly the golf shaft has to remain on plane throughout the swing otherwise inconsistency is all you will succeeded in establishing.
What I'm looking at in a golf swing?????
Well there are a few key things that I'm looking for in a golf swing when I look at it for the first time.
• 1) The shape of the golf swing as this will largely determine the quality of strike and influence the direction of the initial flight of the ball.
• 2) The sources of power within that swing, how the swing loads, stores and delivers that energy into the ball throughout the impact interval.
• 3) How the foundations affect the first 2 areas.
• 4) The concepts the golfer is trying to implement.
Remeber golf is a game of scoring-teaching students to produce lower scores is the ultimate goal.
Good impact alignments are necessary to play consistent golf.
To teach students that mechanics produce and feel reproduces.
Fundamentals are essential and will be the foundation of every lesson.
Until students can produce an uncompensated stroke with a basic motion a full swing will only add frustration.
The next lesson begins where the last lesson finished.
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The cloning.
The term of cloning came from a Greek word that meant “a
branch”, or “a bine”. It has to do chiefly with apprehension of plant cloning.
The cloning of plants by stems, bulbs or gemmas has been known for more than 4
thousand years.
Starting from 1970s, for plant
cloning the use of small groups of somatic cells and sometimes the use of a
single detached cell has been applied.
However, the process of cloning
animals has it’s own obstacles. At the time of the animals’ cells development,
the cells lose their ability to negotiate the genetic information that lies in
the nucleus.
Owing to the experiments on the
amphibia in 1950s, the possibility of cloning vertebrates was first shown.
These experiments let scientists see that the serial nucleus grafting and “in
vitro” cell cultivation in some degree increase the ability of genetic information
Early in the 90s, the problem of
cloning embryonic cells of mammals has been solved. The reconstructed
egalitarian of cattle at first are cultivated “in vivo” that is in the corded
oviduct of intermediate recipient. Then they are being washed out and
transplanted into uterus of the final recipient where their development
continues until the cub’s birth time.
In 1997, dr. Williut together
with joint authors published a sensational article about successful cloning
of a mammal. It was the first time the cloned animal (Dolly) was born as a
result of the bank mamma nucleus of fullgrown sheep use. This experiment had a
sugnificant defect. There was a very low coefficient of survival (about 0,36%).
However, it demonstrates the possibility of full value of obtaining a fullgrown
man clone.
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W. Virginia Factory Farm Seeks Right To Pollute
The factory farm and farm bureaus admit the chicken manure and other pollutants end up in protected creeks, rivers and streams but insist their pollution is an “agricultural stormwater discharge,” which is exempted from the Clean Water Act.
This exemption allows industrial animal factories to pollute America’s water but only when the pollution is caused by rain or snow that creates runoff from land areas where waste is applied as fertilizer as part of a permitted nutrient management plan.
In this case, the manure in question comes from an area near where the animals are warehoused and not an area where waste is applied to the land as fertilizer.
A win for the environment is important here if there’s any hope to clean up other industrial animal factories across the country that are producing massive amounts of manure and other pollutants every day that are ending up in the nation’s rivers and streams.
We already suffer a massive dead zone in the Gulf of Mexico in large part because of manure and waste from factory farms located all along the Mississippi basin. Parts of Chesapeake Bay are similarly wiped out due to massive volumes of waste and sewage products running off industrial animal factories located near rivers that drain into the bay.
We need to fix this.
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Source document:
SCHER (2010)
Summary & Details:
Media Consulta
1. Introduction
Fluoride is a naturally occurring element, abundant in the Earth’s crust. It is not essential for growth and development of humans or other organisms. Most fluorine occurs as insoluble fluorides, but there is some ionised fluoride in soil and groundwater.
There are large differences in the amount of fluoride found naturally in water supplies. Observation of large populations suggested that people drinking water high in fluoride have better dental health, and less tooth decay, than those consuming less fluoride as they drink. As a result, some countries have added fluoride to drinking water as a public health measure. This remains controversial. Some suggest that it is unnecessary, because most people receive enough fluoride from other sources. These now include fluoridated toothpastes and mouthwashes, which are widely used. In addition, there have been suggestions that adding fluoride to drinking water can produce adverse health effects, and that the environmental risks of the most common fluoridating agents have not been fully assessed.
Concentration of fluoride in groundwater in the EU is generally low, but there can be large variation in the levels in natural drinking water between and within countries. In Ireland, for example, levels vary between 0.01 parts per million (ppm), or mg/L and 5.8 ppm, in Finland between 0.1 and 3.0 mg/L and in Germany between 0.1 and 1.1 mg/L.
In Europe, Ireland and some regions in Spain and the UK currently add fluoride to drinking water, at levels ranging from 0.2 to 1.2 mg/L.
People’s exposure to fluoride varies a lot, depending on levels in water, what toothpaste they use, and other factors like use of mineral water and some kinds of tea. The existing collection of risk assessments suggests that there is quite a narrow gap between the fluoride intake recommended to safeguard teeth and the maximum recommended exposure.
In Europe, exposure assessments have been made by the European Food Safety Authority (EFSA). The Authority has set upper tolerable intake levels related to levels in natural mineral waters and other common sources of fluoride. The Commission Scientific Committee on Consumer Products has also set levels for fluoride in dental products.
As questions continue to be asked about water fluoridation in countries where it is added to the water supply, the Commission asked the Scientific Committee on Health and Environmental Risks (SCHER) for updated advice on the latest research findings.
This report reviews these findings and assesses the risks and benefits of fluoridation in the light of estimates of fluoride intake by different groups of people.
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Humans have been exploring this planet for almost 70,000 years. We have all been born out of, what is now Northern Ethiopia, and migrated all over the planet.
This picture shows the genetic heritage and migration of my own mother's DNA over the past 70 -100,000 years. She was a member of
Haplogroup K.
My Mother's Haplogroup Migration
This picture shows my father's migration. He and I am a member of DNA
Haplogroup Q:
My Father's Haplogroup Migration
This is ironic because, a) I was born in
England, and b) I just became a US citizen -- which cost me a lot of time and money. Yet my ancestors must have traversed the US some 50,000 years ago
I received these results as part of a series of
DNA tests that are relatively inexpensive to obtain.
I've always wondered why I was "pulled" to come from my birthplace in England to the US, but also have this innate affection for Greece.
Now I can see that my ancestors were in both places.
Bora Bora - Tahiti
All human beings have DNA that reveals the history and wanderings / migrations of their ancestors. Some went south to India and some went to Polynesia and Australia, others went to Northern Europe and Russia.
Earth This is how our planet was initially populated.
The Silk Route
We have continued of course to explore: (the "New World", Australia, the Silk Route, often conquering and destroying to bring home riches and worse. Hopefully we are beginning to grow up.
Now we are beginning to explore
Star Fruit
This will not happen immediately. Just as my own ancestors must have adapted (mutated) over centuries, to seek shelter, warmth and nutrition amidst changing climates and different types of foods, our own bodies will need to adapt to life in Space.
So we have several problems to overcome in Human Space exploration.
1. Getting anywhere -- building transport vehicles to take us places, and
2. Adapting to survive in extreme climates. In space, we are subject not just to extreme temperatures, but also to
solar radiation -- something we are largely protected from on Earth, and
3. Our bodies are not yet acclimated -- as a specie -- for long term space flight. In a weightless environment, we must exercise strenuously to avoid losing
bone density.
We are at the beginning.
Low Earth Orbit
We can get into Low Earth Orbit (LEO), but it's dangerous, and wildly expensive.
We have been to the moon, but we didn't stay there.
Other peoples are planning outposts and maybe in a few years from now, we will have figured out how to sustain ourselves safely in space.
This section deals with human exploration of Space. |
Title: Health behaviour in a social and temporal context
Author: Schooling, Catherine Mary
ISNI: 0000 0001 3556 6627
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2001
Availability of Full Text:
Access through EThOS:
Access through Institution:
Smoking, alcohol consumption, diet and exercise are sources of risk for many chronic diseases and the need to change unhealthy behaviours is now a key aspect of health promotion policies. Interventions to change adult behaviours have been unsuccessful despite, or perhaps because of, rather dramatic secular changes. Health behaviour is usually understood in terms of three different motivating forces for action, which can be categorised as individual utility, social structure and agency (i.e. engagement in a specific social and temporal context). The first two of these have been relatively well studied. The role of individual utility has been explored using a variety of expectancy-value models that relate individual psychological attributes (attitudes, beliefs and suchlike) to health behaviour. The role of social structure has been explored by studying how behaviour varies with economic circumstances (such as income or tenure) and social relationships (such as family and neighbourhood). Less well studied has been the role of agency. This thesis develops Giddens's concept of self-identity and Simmel's ideas on fashion, to provide an operationalisation of agency. The concept of image is used to link the individual's presentation of self and the appearance of an activity, in terms of underlying attributes such as conformity, gender-identity, sociability and asceticism. Considerations of image provide a potential explanation as to why some people might be more attracted to one activity than another. The concept of status seeking is used to explore why some people are motivated to follow new trends more quickly than others. This operationalisation of the role of agency in health behaviour is tested by exploring the relationship between all these potential motivating forces (individual utility, social structure and agency) and the initiation of and change in 4 specific health behaviours (smoking, drinking, diet and exercise), using data from the 1946 national birth cohort. The 1946 cohort provides a unique opportunity to explore these relationships because it provides the historical specificity necessary to delineate the changing public image of these health behaviours. It covers a period (1946-1989) during which advice about and the public image of the 4 health behaviours changed considerably, and it has data on the cohort's health habits and self images. Results indicate that people's views of themselves in relation to public images do indeed relate to these 4 health behaviours along with the other motivating forces. Understanding how all these motivating forces operate offers the possibility of predicting future behaviour and designing strategies to promote healthy choices.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: DOI: Not available
Keywords: Chronic disease; Unhealthy behaviour; Promotion Psychology Sociology Human services Medicine |
Computer fonts today
Since the appearance of the printing press in the 15th century, people have realized how important is the shape and size of characters that will be printed. Printing machine made a real revolution in the dissemination of knowledge and the reproduction of the written work. For the first time in history it was possible to amplify a literary work in several hundred copies without rewriting. In the centuries before the advent of printing, people are hand-copied books and literary works. For this reason the books were very expensive and rare. A library with 200 titles was considered as a very rich library. Then appeared Johannes Gutenberg who invented the model of cast letters in the prepared printing presses. This invention in the beginning was only used for reproduction of religious literature. A few decades later appeared Martin Luther and the Protestant movement that advocated for translating the Bible into vernacular languages. With the help of the press, Bible could read the every resident of Germany and England. There has been a democratization and enlightenment of millions of people. In some areas before that time, literacy rate was at a very low level of 1-3%. After the appearance of the press, in England, for example, the literacy rate has increased 6 times.
History of fonts and typography
Let’s go back to the beginning of the story and the story of fonts. The science that deals with individual font sets is called typography. Designers involved in the development of new typefaces are called type designers. One of the basic concepts of the font family and refers to a group of fonts that share similarities in design. The first groups of fonts were created shortly after the making of the first printing press. According to some sources, it was in the beginning of the 16th century. Great strides in developing of new font families was made in 1728. That year, William Caslon issued his famous book Cyclopaedia. It has printed dozens of new typefaces and made the first systematized overview of the new species. Until the advent of digital publishing, the terms font and typeface had clearly separated meaning. However, after the advent of computers and digital fonts, everything has become more complicated with new generations. As an example, we can state that at the time of classic printing the word means specific font size. In contrast, in electronic form can be scalable font that can include dozens of sizes.
Computer fonts
There are many definitions of computer font. According to the generally accepted rules, it is a set of character glyphs and other symbols, which are contained in the electronic file. It should be noted that the computer font is scalable symbol set, which can be printed in all available sizes. There are three basic forms in which a computer fonts are available.
1. Outline (some call them fonts and vector). For a description of each symbol are used mathematical formulas. We can list several subspecies vector fonts: TrueType, OpenType, Type1 and Type3 and many others.
2. Bitmap fonts use the technology matrix to describe the appearance of the dots of each symbol. Within this group are the following font formats: BDF, PCF, SNF, FON, AFM, BMF, sf and many others.
3. Stroke With this type of use and additional information specific to the front lines defined to describe fonts. Stroke subtypes were Metafont, Digitype, Stylized Stroke Fonts …
Currently, there are over 10,000 types of fonts. Every day, this number increases by several more. Of course, there are those who use several basic fonts, but for true lovers of typography on the web, it is possible to find a real treasure.
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SBS or Vaccine-Induced Encephalitis? 2004 Update
by Harold E Buttram, MD and Alan R. Yurko
The shaken baby syndrome theory, as it stands today, assumes that findings of brain and/or retinal hemorrhages in the absence of known major accidental trauma are diagnostic of shaken baby syndrome (SBS), sometimes also referred to as non-accidental injury. For reasons that will be reviewed in this article, this theory is being increasingly challenged in the scientific literature.
Although there are many variations of SBS, in our experiences a common pattern is emerging in which there is an abrupt and unexpected onset of apnea (respiratory collapse) in a delayed onset following immunizations. A parent or caretaker may understandably panic in such a situation. Most being untrained in resuscitation techniques, they may slap or shake the infant as an emergency measure. Later admitting this to the police, they may then be accused of child abuse or, upon death of the infant, murder. We believe this line of thinking is superficial. The real question is what caused the apnea that preceded the shaking.
A counter-science to SBS is developing and has now advanced to the point where there are grounds for claiming that many SBS accusations and convictions are the result of misdiagnosis for the following reasons:
1. The current theory of shaken baby syndrome—that shaking alone without impact can cause brain hemorrhages—is an assumption not supported by scientific evidence. In addition, in court cases where brain damage was assumed to be the result of impact, it has been very unusual in our experiences to find significant bruises or other marks of trauma upon the infant’s first arrival at a hospital emergency room—marks one would expect to find if there had been impacts severe enough to cause brain hemorrhage.
2. Due to gross deficiencies in scientific infrastructure in safety testing of childhood immunizations, it is a near certainty that many adverse vaccine reactions are taking place unrecognized as such. Some of these reactions may mimic findings now thought to be diagnostic of SBS.
3. Many or most cases of SBS involve medically fragile infants from a variety of causes (to be reviewed below).
4. Based on the limited science we do have on vaccine reactions, it is probable that immunizations in fragile infants may at times provoke a smoldering inflammatory encephalopathy with initiation of brain edema (swelling), which often culminates in apnea. Brain hypoxia (lack of oxygen) following the collapse then causes an acceleration of the brain edema. Locked into the skull as it is, the swelling brain may reach a point where it acts as its own tourniquet, cutting off venous outflow. Brain and/or retinal hemorrhages may then take place secondary to a very rapid increase in central venous pressure.
The rationale for these conclusions will be reviewed in the following:
Controversies Surrounding Shaken Baby Syndrome (SBS)
Shaken baby syndrome, as reviewed in the Journal of the Royal Society of Medicine and other journals [1-3], describes a combination of subdural hematoma, retinal hemorrhage, and diffuse axonal (nerve) injury (DAI) as the complex of diagnostic criteria. In some cases, the presence of rib or other fractures is also taken as a sign of abuse. The basic issue is whether or not in some instances in which a father, mother, or caretaker has been accused of causing the death or injury of an infant by SBS, the true cause was a catastrophic vaccine reaction.
Of special interest in this regard is an unpublished series of dozens of cases of accusations or convictions of SBS, largely collected by jury counselor Toni Blake of San Diego, California (private communication, 2002). Also pertinent are many cases in our personal experiences. All these cases have the following suggestive features:
• All occurred in fragile infants born from complicated pregnancies. Problems included prematurity, low birth weight, drug/alcohol problems, diabetic mother, or other maternal complications.
• All were 6 months age or less.
• In each instance there was a pattern of timing at 2, 4, or 6 months, with onset of signs/symptoms of deterioration in most instances following within 12 or 13 days of vaccines, although in some instances this time period (referred to as a “latent period”) was more prolonged.
• All had subdural hematomas.
• Some had multiple fractures.
When Toni Blake was first contacted, in the year 2000, she reported that she had 25 of these cases, but in a communication in 2002, she said that the series had become much larger.
As will be reviewed in a later section, gross deficiencies in the scientific safety infrastructure of vaccines have been revealed in the past several years, so that, as a matter of opinion, it is a virtual certainty that many unrecognized vaccine reactions are taking place. Among these may be complications now being (mis)diagnosed as shaken baby syndrome.
Medical-Legal Issues
As reviewed in an amicus brief filed in several court cases and signed by dozens of experts around the world, provided through the courtesy of Toni Blake [4], the following beliefs have become prevalent in courts dealing with SBS: (1) shaking alone in an otherwise healthy child can cause a subdural hematoma; (2) non-traumatic new bleeding in an existing subdural hematoma will always present only minor symptoms; (3) a child suffering from an ultimately fatal brain injury will not experience any lucid interval; (4) short-distance falls by children are never fatal; and (5) retinal hemorrhage occurs only in shaken babies. For the sake of brevity, only beliefs (1), (2), and (5) will be considered here.
Belief #1: Shaking alone in an otherwise healthy child can cause a subdural hematoma. Dr. Buttram has a number of publications which have led us to the opinion that shaken baby syndrome is based on assumptions unsupported by scientific evidence. Foremost among these is an article by Mark Donohoe (2003, American Journal of Forensic Medicine and Pathology) in which he stated that half of the articles about SBS were published before 1999, and half after 1999. Given that 1998/1999 is regarded as a turning point in acceptance of the tenets and practice of evidence-based medicine, it seemed reasonable to the author to assess the quality of evidence before 1999 and to compare it with the quality of evidence on the same subject since that time.
Quality of evidence was placed in four broad categories, with level I or level II indicating compelling evidence from consistent findings in two or more well-constructed, controlled trials or population-based epidemiologic studies. In contrast, level IV evidence represented consensus statements of the expert panel according to clinical experience and limited scientific data. Following a review of articles on SBS published before 1999, Donohoe found that the majority of evidence showed a level of IV, “opinions that shed no new light upon SBS and did not add to knowledge about SBS.” None were found that exceeded a level III.[5]
In the fall issue of The Warrior, Journal of the Trial Lawyers College, 2003, Attorney Elaine Whitfield Sharp wrote a comprehensive article reviewing the history of SBS.[6] Beginning in 1966 and 1968 Ayub K. Ommaya, MD, a Pakistani-born and Oxford-educated neurosurgeon, set out to determine the amount of force it takes to cause certain types of brain injuries and hemorrhages from rear-end car crashes. In experiments with rhesus monkeys (experiments now mercifully prohibited), Ommaya used the monkeys to mimic car accidents by accelerating them on chairs fixed to a track and decelerating them without impact to their heads. Ommaya’s experiments showed that it took between 35,000 to 40,000 radians per second (squared) of angular or rotational acceleration to cause brain hemorrhages in the monkeys.
Transposing the size of monkey brains to that of human brains, Ommaya calculated that the amount of force required to cause brain hemorrhages in humans would be 6,000 to 7,000 radians. According to the review by Sharp, other notable names in the field of SBS transposed Ommaya’s findings to the field of SBS.
It was not until 1987 that a specialist in biomechanics and a group of neurosurgeons set out to prove that subdural hemorrhages in babies were not caused by shaking but by impact. The biomechanics specialist was Lawrence E. Thibault who, with team members made a surrogate baby model and attached an accelerometer to its neck. First they asked some burly football players to shake the model as hard as they could. The most force they were able to generate was a mean of 1,138 radians, far below the 6,000 to 7,000 radians required to cause human brain hemorrhages.[7]
Other publications since that time tend to confirm rather than contradict these findings, one example being a report by Prange, Coats, Duhaime, and Margulies which concluded that “there are no data showing that the maximum change in angular velocity….during shaking and inflicted impact against unencased foam is sufficient to cause subdural hemorrhages or primary traumatic axonal (nerve) injury in an infant.”[8]
Belief #2: Nontraumatic new bleeding in an existing subdural hematoma will always present only minor symptoms. There are a number of publications reporting on instances in which rebleeding took place in chronic hematomas with minimal trauma.[9-12] In an article by Hymel et al, (2002) the authors reviewed the pathophysiology of subdural hematomas and the mechanisms by which chronic subdural hematomas may rebleed spontaneously or with minimal trauma.[13] In addition, the authors provided a table extending nearly four pages of possible differential diagnosis for subdural hematomas.
Perhaps the most convincing evidence that brain hematomas, whatever their location, may lead to spontaneous and significant rebleeding comes from the work of Kawakami et al in which 19 patients with chronic subdural hematomas had venous blood taken at the same time as surgical aspiration from subdural hematomas. Both the blood and surgical aspirates were then tested for coagulation factors. The venous blood tests were found to be normal, but blood from the chronic hematomas was found to have markedly prolonged coagulation markers (prothrombin and partial thromboplastin times), marked reduction of clotting factors (prothrombin, fibrinogen, and clotting factor V), and increased indications of clot disintegration (increased fibrin and fibrinogen degradation products).[14] In other words, each brain hemorrhage was generating its own coagulation process, thus consuming clotting factors. As clotting factors were depleted, conditions for potential spread of the bleeding were created.
Belief #5: Retinal hemorrhages occur only in shaken babies. Proponents of the SBS theory have been allowed to testify that retinal hemorrhages are pathognomic (diagnostic) of SBS in spite of foundational objections. To the contrary, relevant scientific literature reveals that retinal hemorrhages are found with a myriad of pathologies, including cardio-pulmonary resuscitation, scurvy, pre-existing brain hemorrhages, strangulation (drowning) cases, Hepatitis B vaccine, cerebral edema (swelling) from any cause, any situation associated with a sudden increase in intracranial pressure, and in persons with coagulation disorders.[15-19, 59-62] The amicus brief for SBS provides 36 references in support of this contention, only a representative few of which are given here—others will be provided on request.
Deficiencies in Scientific Safety Infrastructure in Childhood Vaccines
ASince 1999 there have been ongoing hearings in the U.S. Congress concerning growing concerns about vaccine safety. These hearings have dealt primarily with a possible link between the MMR vaccine and the growing epidemic of childhood autism in the USA. From these hearings there is now an emerging a background pattern of deficiencies in basic science in vaccine testing. Autoimmune reactions, for example, may be delayed for months or even years, and simply go unrecognized.
Since misdiagnosed SBS is merely one phase of potential vaccine reactions, it is a virtual certainty that many adverse vaccine reactions are taking place unrecognized due to this pattern of deficiencies in safety testing and scientific infrastructure of vaccines.
In cases of misdiagnosed SBS, Dr. Buttram has seen two reactions that occurred within the same day, most within 12 to 13 days, but also some delayed for 2 or 3 months. The causal relation was apparent in that the families noticed subtle but distinct and persistent changes in behavior of the infants (such as fussiness, fever, and high-pitched screaming) which persisted until sudden and unexpected respiratory collapse.
Based on these hearings, scientific evidence does not support the safety of immunizations. Particularly unfortunate is that there are no long-term (months or years) safety studies on any childhood vaccine in use today. In addition there have been no systematic before-and-after studies on the effects of vaccines on the immune, hematologic, brain, and neurologic systems of babies—studies which should be considered indispensable for any ongoing medical intervention. Nor has adequate consideration been given to the additive or synergistic adverse effects of multiple simultaneous vaccines, even though in cases of chemical toxicity 2 chemicals together may be 10 times as toxic than either separately, or 3 chemicals 100 times more toxic.[20-21]
As one example of the deficiencies in basic science among the vaccines, in 1994 the Institute of Medicine, a federal government advisory board, published a comprehensive review addressing the safety (or lack of it) of the Hepatitis B vaccine. When the committee investigated five possible and plausible adverse effects, they were unable to come to a conclusion on four of them, because they found that relevant safety research had not been done. Furthermore, they found that serious “gaps and limitations” existed in both the knowledge and infrastructure needed to study vaccine adverse events.
Among the 76 types of potential adverse reactions reviewed by IOM, the basic science evidence was inadequate to assess definitive vaccine causality for 50 (66%). The IOM also noted that “if research…(is) not improved, future reviews of vaccine safety will be similarly handicapped.”[22]
Following are three examples of before-and-after studies provided as examples of studies that are not being done in a systematic fashion, but should be:
Vaccines and Immune Paralysis
As reported in the New England Journal of Medicine in 1984 [23], 11 healthy adults had tests involving subpopulations of T-lymphocytes (white blood cells which mediate immune function) before and after routine tetanus booster immunizations. The results showed a significant though temporary drop in T-helper lymphocytes. Special concern rests in the fact that in 4 of the subjects the T-helper lymphocytes dropped to levels found in active AIDS patients. If this was the result of a single vaccine in healthy adults, it is sobering to think of the immune consequences of the multiple vaccines given to infants with their immature and vulnerable immunity. This study should have served as a pilot for ongoing vaccine safety studies, but as far as can be determined from surveys of the medical literature, it has never been repeated.
Vaccines and Seizure Disorders
For the second example, in 1955 AL Low of Chicago published a study in which he performed electroencephalograms (EEGs) on 83 children before and after pertussis immunization.[24] In two of the children he found that the EEGs became abnormal following the immunizations without other signs or symptoms of abnormal reactions. In his report he commented:
“This study suggests that mild but possibly significant cerebral reactions may occur in addition to the reported very severe neurological changes.”
Vaccines Provoking Patterns of Sickness
As reported in Mediators of Inflammation (2003), a study was undertaken to analyze the immune responses of live attenuated rubella vaccine in eighteen school girls ages 11 to 13 years by collecting blood before immunization and again at 7 and at 30 days after immunization to test whether or not there would be immune suppression.[25] Subclasses of lymphocytes (a class of white blood cells that mediates immune function) were tested before and after vaccine. Also, plasma samples were tested for cytokines (cellular messengers) including interleukins (IL). IL 4 and 10, tumor necrosis factor, and gamma-interferon (all pro-inflammatory) were measured. It was found that certain lymphocyte subsets were decreased and that IL 10 and tumor necrosis factor were markedly increased following vaccines. The study concluded: “Our data indicate that the vaccination with live attenuated rubella vaccine results in moderate but sustained immune disturbance. The signs of immunosuppresion, including defective lymphocyte response to mitogens and cytokine production, may persist for at least one month after vaccination.”
Increased Hazards of Vaccines in Premature Infants [26]
The authors of many well-documented studies have concluded that the risk and benefit of vaccination in preterm infants should be evaluated prior to administering the vaccines. They also emphasized that preterm infants who have received vaccines should be monitored. The following are descriptions of several selected studies conducted in the USA and other countries to illustrate these points.
• Case histories of 45 preterm babies who were vaccinated with DPT/Hib (diphtheria, tetanus toxoids, and pertussis (Haemophilus influenzae type B conjugate) in the neonatal intensive care unit of the Royal Gwent Hospital, Newport, UK between January 1993 and December 1998 were studied retrospectively (2001).[27] Apparent adverse events were noted in 17 of 45 (37.8%) babies; 9 (20%) had major events, i.e. apnea, bradycardia or desaturations, and 8 (17.8% had minor events; i.e. increased oxygen requirements, temperature instability, poor handling and feed intolerance. Age at 70 days or less was significantly associated with increased risk (p<0.01). Of 27 babies vaccinated at 70 days or less, 9 (33.3%) developed major events compared with none when vaccinated over 70 days. The authors concluded that vaccine-related cardiorespiratory events are relatively common in preterm babies. Problems were much more common if vaccine is administered at or before 70 days. Babies should therefore be monitored post-vaccination.
• After observing the occurrence of apnea (a respiratory pause of 20 seconds or longer, usually associated with bradycardia, heart rate less than 80 beats/min) in two preterm infants following immunization with DTP and HibC, Sanchez et al (1997) conducted a prospective surveillance of 97 preterm infants (50 girls and 47 boys) younger than 37 weeks of gestation who were immunized with DTP (94 also received HibC at the same time) in the neonatal intensive care unit in Texas USA [sic - in article] to assess the frequency of adverse reactions, and in particular the occurrence of apnea. For each infant data were recorded for a 3-day period before and after receipt of the immunizations.[28]
Their study showed that apneic episodes occurred in 34 infants (34%) after immunizations. Twelve infants (12%) experienced a recurrence of apnea, and 11 (11%) had at least a 50% increase in the number of apneic and bradycardia episodes in the 72 hours after immunization. This occurred primarily among smaller preterm infants who were immunized at a lower weight (p=0.01, who had experienced more severe apnea of prematurity (p=0.01), and who had chronic lung disease (p=0.03). Some of these infants required new medical intervention for the increased apneic/bradycardiac episodes.[23]
• Bothan et al (1997) conducted a prospective study of 98 preterm infants (53 males and 45 females) of gestational age 24-31 weeks who were immunizated at approximately 2 months postnatal age with diphtheria-tetanus whole-cell pertussis vaccine (DTPw) in the neonatal intensive care unit (NICU) at King George V Hospital in Sydney, Australia.[29] Half the infants also received Haemophilus influenzae type b conjugate vaccine (Hib) simultaneously. All infants were monitored for apnea and bradycardia in the 24 hour periods pre- and postimmunization.
Their study showed only one infant had apnea and/or bradycardia pre-immunization compared with 17 post-immunization. For 12 infants these events were brief, self-limiting and not associated with desaturations (oxygen saturation <90%). However, for five infants (30%) these events were associated with oxygen desaturation, and two of these infants required supplemental oxygen. When considering immunization for preterm infants, the benefits of early immunization must be balanced against the risk of apnea and bradycardia.
• Slack et al, (1999) from the United Kingdom stated that four premature infants developed apneas severe enough to warrant resuscitation after immunization with diptheria-tetanus-pertussis (DTP) and Haemophilus influenzae B (Hib).[30] One required intubation and ventilation. They also reported that, although apneas after immunization are recognized, they are not well documented. They concluded that it is time for further research to elucidate the best time to immunize such infants.
• Botham et al (1994) conducted a prospective study to document respiratory and cardiac events in 97 preterm infants who were immunized with DTP.[31] The mean gestational age at birth was 28.1 weeks (range 24 to 34) and the mean age at immunization was 80.6 days (range 44-257). They found that nineteen (20%) infants developed apnea or bradycardia within 24 hours of immunization. The infants who developed apnea and/or bradycardia had a younger gestational age at birth than those who did not (p=0.03), were artificially ventilated for longer (p=0.01), and were more likely to have a diagnosis of chronic lung disease (p=0.006). Two infants who developed concurrent upper respiratory tract infections required additional oxygen, and one of them was treated with oral theophylline. The researchers stated that cardiorespiratory function should be monitored after immunization in very preterm infants who had prolonged ventilatory support and/or chronic lung disease.
In Nelson Textbook of Pediatrics, 16th Edition, there are precautions in the use of potentially toxic medications in premature infants because of diminished renal clearances for almost all substances excreted in the urine.[32] The text also cautions about drugs that are detoxified in or conjugated by the liver in premature infants.
As will be found in current editions of the Physicians’ Desk Reference, potentially toxic and/or sensitizing substances routinely found in childhood vaccines include aluminum phosphate, mercury (still present in some vaccines), formaldehyde, phenols, alcohols, mineral oils, antibiotics, animal serums, animal DNA, and aborted fetal tissue. In addition, the Hepatitis B vaccine, which is cloned in yeast cells, runs the risk of causing sensitivity reactions in children who may be sensitive to yeast.
Diphtheria-Pertussis-Tetanus (DPT) Vaccines and Infant Apnea in Sudden Infant Death Syndrome (SIDS)
RAccording to a report by WC Torch of Reno, Nevada in 1986, over 150 DPT-postvaccinal deaths had been reported in the literature by 37 authors in 12 countries.[66] The report is not particularly well written, but we include it here because of its historical importance. Although the technical details are ambiguous in some places, it is one of the very few published articles in the literature which dares to say that vaccines can and do kill babies:
Although 90% of the deaths occurred within one week of DPT, the remainder occurred as long as 20 months, following protracted reactions. About one-half were sudden-infant-death-like (SIDS) or anaphylactic; about one-half followed neurotoxic or systemic symptoms (dyspnea, seizures, shock, irritability, lethargy, apathy, coma, decerebrate-decorticate rigidity, spasticity, hypotonia, paralysis, or apnea). In deaths within 3 hours of DPT, the brain was normal; in deaths between 6 and 72 hours, varying degrees of brain edema, vascular congestion, petechiae or (brain) hemorrhage, monocytic infiltrates, and neuronal degeneration were seen. In some later deaths, demyelination, gliosis, or atrophy were seen. The author and others maintained a causal relationship between DPT vaccine and yet-to-be determined SIDS fraction.
Vaccines, Vitamin C Depletion and Shaken Baby Syndrome [33]
TIn the next 25 years or so, when there is greater knowledge about the adverse reactions and aftermath from current childhood vaccine programs, physicians and scientists, as well as the lay public, may look back on these programs with embarrassment if not worse. This is not to say that vaccines do not have a proper role in preventive health, which they do, but not with neglect in safety considerations.
The rationale for these statements is based largely on the work of Dr. Archivedes Kalokerinos, who worked as a medical officer among the Australian aborigines in the “outback” in the 1960s and 1970s. Troubled by very high infant mortality, in some areas approaching 50%, he began to investigate possible causes. Having noticed signs of scurvy in some of the infants, and observing that the children often died following immunizations, especially if they had colds or minor respiratory infections, the thought occurred to him that there might be a connection between vitamin C deficiency and deaths following vaccines.
With improved nutrition; routine oral vitamin C supplementation; avoidance of immunizations during illnesses, even minor ones, such as a runny nose; and large doses of injectable vitamin C during crises, infant mortality was virtually abolished. Although Kalokerinos and his research partner, Glen Dettman, PhD, who was originally sent to prove Kalokerinos wrong, were awarded the Australian Medal of Merit in 1978 for their work, it has never been acknowledged by mainstream medicine. What is worse, it has never been subjected to systematic, meaningful scientific studies.
In contrast to classical scurvy of earlier times in the days of wooden sailing ships, when scurvy was characterized by a total lack of vitamin C, what we may be seeing today is something quite different. As described by Dr. Kalokerinos [34] and C. Alan Clemetson, MD [35], subclinical scurvy is a condition in which apparently healthy infants with marginally low but adequate levels of vitamin C in unstressed conditions may be suddenly thrown into states of critical vitamin C depletion by combinations of stresses from common infections and toxins, including the toxins found in vaccines.
As one example of marginal vitamin C deficiency on the modern scene, in a study of people attending an HMO (Health Maintenance Organization clinic) in Tempe, Arizona in 1998, 30% were found to be depleted, with plasma vitamin C levels between 0.2 and 0.5 mgs/100 ml; and 6% to be deficient, with levels below 0.2%.[36] In regards to infants, it is true that infant formulas have been mandated to include vitamin C at levels providing the required 30 mgs per day. However, this is a maintenance level and makes no allowances for additional stresses which may bring about manifold increases in need for vitamin C. Common colds, for instance, have been shown to reduce vitamin C levels up to 50%.[37]
No one knows the effects of vaccines on vitamin C levels in infants, because before-and-after studies of this type have never been done, but vitamin C is known to neutralize the toxins of diphtheria, [38-41] tetanus, [42] typhoid endotoxin, [43] and four varieties of gas gangrene.[44] As will be described below, in the process of neutralizing these toxins, vitamin C is necessarily depleted.
If the reader will consult with these references, which were extracted from an article by Clemetson [45], it will be found that most of these studies are quite old and some published in foreign languages. To us that is the pity of it, as our own scientific & medical system has never recognized their importance or followed through with further investigations.
Returning to the importance of vitamin C in relation to vaccines, one of the prime roles of vitamin C in the body is its action as an antioxidant in donating electrons to quench free-radical and inflammatory damage from toxins and/or infections, with our consideration here being vaccine toxins. In the process of donating electrons, vitamin C necessarily becomes depleted. Once the level is reduced to the point that it can no longer protect the brain, which is unduly susceptible to toxic and infectious damage, it (the brain) may become subject to free-radical damage.
By definition, a free radical consists of a molecular fragment with one or more unpaired electrons in its outer orbital ring, causing it to be highly oxidative, unstable, and to react instantaneously with other substances in its vicinity. Within a few millionths of a second, free radicals can react with and damage nearby molecules and cell membranes with a chain reaction effect.[46-47] When uncontrolled, such as may occur during exposure to harmful ionizing radiation, these reactions can be very destructive to the body.
Vitamin C is critically important in protecting against free-radical proliferation because, in donating electrons, it neutralizes the unpaired electrons in the free-radical molecular fragments. Of all the organs of the body, the brain appears to be most vulnerable to this type of damage because of its relatively high fat content. For these reasons, the combination of ill-advised vaccines given to fragile infants with highly immature detoxification organs (liver and kidneys) and immature immune function, or, as often takes place, in the presence of viral or bacterial infections, may be an invitation to disaster, with the brain being potentially subjected to a firestorm of free-radical damage and inflammation.
Once this pattern has been set in motion, there may be a variable latent period with gradual progression of inflammatory brain edema (swelling). The breathing center, located at the base of the brain, appears to be uniquely vulnerable to the process, resulting in respiratory paralysis and collapse. In other instances there may be seizures. Among the cases of SBS that we have reviewed, this pattern has occurred too frequently to be coincidental.
In his autobiography, Dr. Kalokerinos describes the mechanisms involved in the production of brain edema, with retinal and brain hemorrhages in much the same fashion:[34]
1. Endotoxin (endogenous and/or from vaccines) damages the endothelial linings of the brain’s blood vessels.
2. Endotoxin then ‘leaks’ through to the surrounding brain tissue. This includes the retina that is an extension of the brain.
3. The brain tissue is damaged.
4. The blood supply to the portions of the brain involved is reduced.
5. Insufficient oxygen, glucose, and vitamin C follows.
6. Parts of the brain are ‘rich’ in ‘bound’ (controlled) iron. This is released.
7. Violent free radical reactions result, and these cannot be controlled because of a lack of immediately available vitamin C and other antioxidants.
8. So further, and rapid, brain tissue damage results, with more free radical reactions.
9. Hemorrhages occur in the area/areas involved.
10. After a variable period (depending on a host of factors) some of the red blood cells in the hemorrhages break down and release their stores of iron and copper.
11. This results in a further cascade of free radical reactions and tissue destruction.
12. Cerebral edema (brain swelling) occurs.
By way of historical comparison, in Vienna in the 1840s, long before recognition of the importance of sanitation and the role of microbes in causing disease, a doctor named Ignaz Semmelweis was assigned to an obstetrical post at a birthing center which was notorious for its high maternal mortality rates. Based on simple observation, Semmelweis deduced that doctors and nurses were carrying infections from one patient to another and subsequently required that they wash their hands between patients. As a result, the mortality rate among maternity patients under his care was reduced from nearly 30% in other wings of the hospital to less than 2% for patients under his care or supervision.
Was Semmelweis honored at the time by his peers for this discovery? No, instead he was dismissed from the hospital staff because his procedures did not conform with the medical thinking of the time. In the cases of Drs. Archivedes Kalokerinos and C. Alan Clemetson, could history be repeating itself?
In reviewing many medical-legal cases involving accusations of SBS over the last four years, we have yet to see a case in which hospital emergency room doctors have included tests for vitamin C as part of the diagnostic evaluation. We know from references 38-44 that vitamin C detoxifies bacterial endotoxins and that it would inevitably be reduced in a baby’s system as a result, very likely to critically low levels. There are good reasons for believing that this is one of the primary missing links in many of these cases.
Plasma Vitamin C / Histamine Levels, and Capillary Fragility
In 1980, C. Alan Clemetson reported that the whole-blood histamine levels of human subjects are inversely proportional to their plasma vitamin C levels [48], in that 34 percent of people who had subnormal but not deficient ascorbic acid levels were found to have significantly increased blood histamine concentrations. The 2 percent of subjects who were markedly vitamin C depleted (<0.2 mg/100 ml) had a four-to-five-fold increase in their blood histamine concentrations. Frank scurvy does not occur until blood histamine is increased more than tenfold. Nevertheless, the blood histamine concentration returns to normal very rapidly following the oral administration of ascorbic acid.
Indications that elevated blood histamine is the true cause of capillary fragility in scurvy comes from electron-microscopic studies by Gore et al in guinea pigs with scurvy, in which widening of the intercellular junction gaps were demonstrated in the vascular endothelium.[49] Moreover, Majno and Palade have observed similar widening of the endothelial junction gaps and leakage of tracer particles through endothelial gaps in rats following the injection of histamine.[50] Consequently it seems that histaminemia is the crucial factor causing bleeding in scurvy and may be responsible for the fragility of the bridging veins and venules between the brain and the dura mater, as well as the retinal petechiae.
In our opinion, Clemetson’s work in elucidating the inverse relationship between vitamin C and blood histamine levels, with elevated histamine being the primary cause of capillary fragility, is of critical importance in shaken baby syndrome, such that there should be mandatory requirements for obtaining blood plasma levels of vitamin C and whole blood histamine in hospital emergency rooms before bringing charges of shaken baby syndrome.
Rib Fractures
Fairly often in SBS cases there are findings of multiple skeletal fractures along with brain and/or retinal hemorrhages. This is not surprising since a majority are “fragile” infants with immature, delayed, or impaired development organ and tissues systems. Attention here will be limited to rib fractures which appear to be the most common of the fractures.
It is well understood in the medical literature that there are a variety of conditions in which multiple fractures can take place spontaneously or with minimal trauma, including scurvy, rickets, osteogenesis imperfecta, and birth trauma. Standard texts point out that subperiosteal hemorrhages (bleeding beneath the fibrous covering of bone) is the most common type of hemorrhage in scurvy and may be indistinguishable from fractures in their healing phases. Three references are provided showing a coincidental relationship of posterior rib fractures with birth trauma.[51-53] In addition, temporary brittle bone disease (TBBD) is a condition wherein spontaneous fracture occurs during the neonatal period, as described by Miller and Hangartner, associated with decreased fetal movement.[54-55]
Based on personal experiences, it is unusual to find thorough evaluations of these infants to rule out alternate causes of fractures. But in most infants there are even more compelling reasons for excluding parental or caretaker trauma: (1) in a majority of cases there are no bruises or external marks of trauma in association with the fractures; (2) in instances of multiple rib fractures, there are no findings of internal thoracic trauma; (3) there are negligible indications of pain in these infants when handled or moved.
Taking each of these in turn:
The literature provides evidence that surface injury should be present if multiple fractures are from child abuse. First, when a child incurs a fracture caused by physical abuse, there is a probability that the traumatic event will also cause a bruise. Mathew et al determined the frequency of bruising in children with fractures.[56] The frequency was 8% at time of presentation and 28% during the first week of trauma. Using this information the probability of trauma to an infant who is followed by health care providers during the first few weeks of life during which there are no findings of bruises can be calculated. If there are multiple fractures, then each fracture is an independent event for showing bruising, and the likelihood that a series of fractures could have taken place without showing bruising is quite small.
Next, Garcia et al found that in infants who have normal-strength ribs and incurred multiple rib fractures from trauma (either from child abuse or motor vehicle accidents), there was always internal thoracic injury or other internal injury when 4 or more rib fractures were involved.[57]
In regards to the pain issue, traumatic rib fractures are very painful at any age. Multiple rib fractures from trauma should be quite painful to the infant and immediately apparent to the handler. This situation has rarely arisen in cases we have reviewed. Further insights into the nature of spontaneous fractures of metabolic origin, possibly explaining why they would be relatively pain-free, was provided in an article by Hiller, entitled “Battered or Not – a Reappraisal of Metaphyseal Fragility” [58], in which the author cited studies showing a proneness for epiphyseal slippages at the ends of long bones in rickets and scurvy.
Slippages would either be posterior at the vertebral-costal junctions (junctions of the ribs with the spine) or anterior at the costo-sternal junctions (junctions of ribs with the sternum). In long bones of arms and legs these “slippages” would take place at the proximal or distal ends. Although these slippages result in subsequent callus formations, which radiologists would read as healing fractures, they are not the same. This may be the reason they are usually less painful.
Summary and Conclusions
As previously reviewed, experience has shown that there is a common pattern in many shaken baby syndrome cases with sudden and unexpected onset of apnea (cessation of breathing) in a delayed fashion following immunizations. Untrained parents or caretakers may shake the baby in sheer panic to restore breathing and later be accused of child abuse or murder when, on the baby’s hospitalization, tests and exams show the presence of brain and/or retinal hemorrhages.
The hypothesis proposed here is that, in many cases, a smoldering hemorrhagic encephalitis with gradual development of brain edema is triggered by vaccines ultimately affecting and paralyzing the respiratory center at base of the brain, this in turn causing sudden onset of apnea. Once this takes place the resultant hypoxia (lack of oxygen) causes an acceleration of the brain edema. Since the brain has little room for expansion inside of the skull, the swelling may reach a point where the brain becomes its own tourniquet by cutting off the easily collapsible venous outflow from the brain. As a result there is a rapid increase in central venous pressure in the brain, which then becomes the source and cause of brain and retinal hemorrhages.[59-62]
This concept is supported by publications of Jennian Geddes, neuropathologist at Royal London Hospital, and colleagues who have shown that the abrupt onset of apnea in many supposed SBS cases is the result of injuries to the respiratory center not necessarily involving either violence or impact.[63-64] Although Geddes et al did not take into account a possible role of vaccines in the process, they did specify that brain swelling rapidly ensues as a result of hypoxia following respiratory collapse and that the brain and retinal hemorrhages were secondary to the brain edema.
A reasonably full spectrum of animal models already exists for vaccine-induced hemorrhagic encephalitis, which is reviewed elsewhere.[65] The time is long overdue for vaccine safety testing at a human level, establishing a valid and objective scientific infrastructure in this area. Let the chips fall where they may.
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[3] Weston IT, "The pathology of child abuse", In: Heifer RE, Kempe CH, Editors, The Battered Child, University of Chicago Press, 1968, 77-100.
[4] The amicus brief was prepared by Toni Blake, attorney and jury counselor of San Diego, and coworkers for presentation in court in cases dealing with the shaken baby syndrome (private communication).
[5] Donohoe M, Evidence-based medicine and shaken baby syndrome, Part I: Literature review, 1996-1998, Am J Forensic Med Path, September, 2003; 24(3):239-242.
[6] Sharp EW, "The Elephant on the Moon", The Warrior, Fall, 2003:28-39.
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[8] Prange MT, Coats BS, Duhaime AC, Margulies SS, Anthropomorphic simulations of falls, shakes, and inflicted impacts in infants, J Neurosurgery, 2003; 99:143-150.
[9] Piatt, JH, A pitfall in the diagnosis of child abuse: external hydrocephalus, subdural hematoma, and retinal hemorrhages, Neurosurg Focus, 1999; 7(4): Article 4.
[10] Parent AD, Pediatric chronic subdural hematoma: A retrospective comparative analysis, Pediatr Neurosurg, 1992; 18:266-271.
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[12] Kim KA, Wang MY, Griffith PM et al, Analysis of pediatric head injury from falls, Neurosurg Focus, 2000; 8:1-8.
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[16] Weedn VW, Mansour AH, Nichols NM, retinal hemorrhages following cardiopulmonary resuscitation, Am J Foren Med Pathol, 1990; 11:79-82
[17] Hess A, Scurvy, Past and Present, JP Lippincott Co, Philadelphia and London, 1920.
[18] Devin F, Roques G, Disdier P, Rodor F et al, Occlusion of central retinal vein after Hepatitis B vaccination, Lancet, 1996; 147:1626.
[19] Nelson, L. Disorders of the Eye, In: Textbook of Pediatrics, Behrman R, Kliegman R, Arvin A, Fifteenth Edition, WB Saunders Co, Philadelphia, 1996, pages 1437-1438.
[20] Arnold SF et al, Synergistic activation of estrogen receptor with combinations of environmental chemicals, Science, 1996; 272:1489-1492.
[21] Abou-Donia AB et al, Neurotoxicity resulting from exposure to pyridostigmine bromide, DEET, and Permitrin; implications of Gulf War chemical exposures, J Tox & Environ Health, 1996; 48:35-36.
[22] Stratton KR, Howe CJ, Johnston RB Jr, Editors, Adverse Events Associated with Childhood Vaccines; Evidence Bearing on Causality, Institute of Medicine, National Academy Press, Washington DC, 1994:211-236.
[23] Eibl M et al, Abnormal T-lymphocyte subpopulations in healthy subjects after tetanus booster immunization, (letter), NEJM, 1984; 310(3):198-199.
[24] Low AL, electroencephalographic studies following Pertussis immunization, J Pediatrics, 1955; 47:35-39.
[25] Pukhalsky AL, Shmarina GV, Bliacher MS et al, Cytokine profile after rubella vaccine inoculation: evidence of the immunosuppressive effect of vaccination, Mediators of Inflamm, August, 2003; 12(4):203-207.
[26] The references under this subject were provided through the courtesy of Mohammed Ali Al-Bayati, PhD, DABT, DABVT, Toxicologist and Pathologist, Toxi-Health International, 150 Bloom Drive, Dixon, California 95620.
[27] Sen S, Cloete Y, Hassan K, Buss P, Adverse events following vaccination in premature infants, Acta Paediatr, 2001, 33(5):418-421.
[28] Sanchez PJ, laptook AR, fisher L et al, Apnea after immunization of preterm infants, J Pediatr, 1997; 130(5):746-751.
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[31] Botham SJ, Isaacs D, Incidence of apnoea and bradycardia in preterm infants following triple antigen immunization, J Paediatr Child Health, 1994; 30(6): 533-535.
[32] Nelson Textbook of Pediatrics, 16th Edition; Behrman, Kliegman, & Jenson Editors, WB Saunders Co., Philadelphia, 2000, Page 483.
[33] The material under this title has been extracted from my article by the same name published on the website,, edited by Nicholas Regush in September, 2003.
[34] Kalokerinos, A, Medical Pioneer of the 20th Century, an Autobiography, Dr. Archivedes Kalokerinos, Biology Therapies Publishing, Braeside, Melbourne, Victoria, Australia, Fax 011-61-39587-1720, Publ.2000.
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[37] Hume R, Weyers E, Changes in the leucocyte ascorbic acid concentration during the common cold, Scot Med J, 1973; 18:3.
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[40] Harde E, Acide ascorbique (vitamin C) et intoxications, CR Acad Sci, 1934; 119:618-620.
[41] Parrot JL, Richet, Accroissement de la sensabilite a histamine chez le cobaye sournis a un regime scorbutogene, CR Soc Biol, 1945; 139: 1072-1075.
[42] Dey PK, Efficiency of vitamin C in counteracting tetanus toxin toxicity, Naturwissenchaften, 1966; 53:310.
[43] Fukada T, Koyama T, Prevention by ascorbic acid of liver glycogen depletion in endotoxin intoxication, Nature (London), 1963; 200:1327.
[44] Buller Souto A, Lima C, Activity of L-ascorbic acid on the toxins of gas gangrene, Vol 12, Sao Paulo, Brasil: Memorias do instituto Butantan, 1939:265-295.
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[46] Chemical Sensitivity, Volume I (volume one of four volumes), William J Rea, MD, Lewis Publishers, Boca Raton, 1992, (pages 122-124 discuss the role of pollutants in creating free radicals).
[47] Casarett & Doull’s Toxicology, the Basic Science of Poisons, Curtis D. Klaassen, McGraw-Hill, New York, 2001, pages 40-42.
[48] Clemetson CAB, Histamine and ascorbic acid in human blood, J Nutrition, 1980, 110:662-668.
[49] Gore I, Fujinami T, Shirahama T, Endothelial changes produced by ascorbic acid deficiency in guinea-pigs, Arch Pathol, 1965; 80:371-376.
[50] Majno G, Palade GE, Studies on inflammation. 1. The effect of histamine and serotonin on vascular permeability. An electron microscopic study. J Biophys Biochem Cytol, 1961; 11:571-605.
[51] Harlman RW Jr, Radiological case of the month: Rib fractures produced by birth trauma, Arch Pediatr Adolesc Med, 1997; 151(9):947-948.
[52] Rizzolo PJ, Coleman PR, Neonatal rib fracture: Birth trauma or child abuse? J Family Practice, 1989; 29(5):561-563.
[53] Cumming WA, Neonatal skeletal fractures, birth trauma or child abuse? J Canadian Assoc Radiol, 1979; 30(1):30-33.
[54] Miller ME, temporary brittle bone disese: a real entity? Seminars in Perinatology, 1999; 23: 174-182.
[55] Miller ME, Hangartner TN, Temporary brittle bone disease: Association with decreased fetal movement and osteopenia, Calcific Tissue International, 1999; 64:137-143.
[56] Mathew MO, Ramamohan N, Bennet GC, Importance of bruising associated with paediatric fractures: prospective observational study, Brit Med J, 1998; 317: 1117-1118.
[57] Garcia et al, Rib fractures in children: A marker for severe trauma, J Trauma, 1990; 30:695-700.
[58] Hiller HG, Battered or not – a reappraisal of metaphyseal fragility, Am J Roent Rad Therap & Nucl Med, 1972; 114(2):241-246.
[59] Smith DC, Kearns TP, Sayre GP, Pre-retinal and optic nerve sheath hemorrhage: pathologic and experimental aspects in subarachnoid hemorrhage, Trans Am Acad Ophthalmol Otolaryngol, 1957; 61:201-211.
[61] Vanderlinden G, Chisholm L, Vitreous hemorrhages and sudden increased intracranial pressure, J Neurosurgery, 1974; 41:167-176.
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[63] Geddes JF, Hackshaw AK, Vowles GH et al, neuropathology of inflicted head injury in children, 1. Patterns of brain damage, Brain, July, 2001; 124(7):1290-1298.
[64] Geddes JF, Tasker RC, Hackshaw CD et al, Dural haemorrhage in nontraumatic infant deaths: does it explain the bleeding in ‘shaken baby syndrome’? Neuropathol & Applied Neurobiol, 2003;29:14-22.
[65] Buttram H, Shaken baby syndrome or vaccine-induced encephalitis? Townsend Letter for Doctors & Patients, October, 2003:72-78.
[66] Torch WC, Characteristics of diphtheria-pertussis-tetanus postvaccinal deaths and DPT-caused sudden infant death syndrome (SIDS): a review, Neurology, (Supp 1); April, 1986.
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Gone Outdoors
How to Lure a Turtle
by Tanya Robertson
Turtles are naturally attracted to places offering hospitable environments for their species. Many homeowners manage to attract common turtles, such as the painted turtle or the red-eared slider to their backyards by providing the turtles with a sufficient aquatic wetland. In order to lure and keep the turtles happy, you'll need to provide a pond, adequate food sources, ample shade, and places for the turtles to bask in the sun. Natural shelters are also helpful to protect the turtles from unwanted predators.
Build a pond, if you don't already have one. It's best to hire a professional to do this for you. At a minimum, a pond intended to attract and sustain turtles should be 10 feet in diameter. The depth of the pond should be varied with some shallow places less than 3 feet, and deeper spots of at least 10 feet. The incline up to the shore should be gradual and the land around the pond should be soft, to allow the turtles to dig.
Install a water filtration pump, or a waterfall into the pond. The professional you hired to construct the pond can often do this for you. The water in the pond will need to be kept moving, so it doesn't become stagnate.
Place a floating driftwood log into the pond. The turtles will use this for sun basking and to protect themselves from land predators. The log should be at least 2 feet in length.
Introduce non-aggressive water plants into the pond. Try to use plants native to your local area. Common water plants that turtles enjoy are cattails, pickerel rush, and marginal grasses. Avoid aggressive plants -- such as water bamboo and duckweed -- that will consume your pond. Turtles have a particular fondness for eating lilies and lily pads.
Landscape the areas around the pond to provide both sun and shade. Plant trees and other vegetation to produce more shade. Cut back trees and other vegetation to produce more sun.
Add feeder fish to the pond. Guppies and minnows tend to be the most common and can be purchased from any pet store. To start, add about a dozen or two feeder fish for an average pond with a 10 foot diameter. If your pond is larger, add more feeder fish accordingly. Other food sources, such as water bugs and snails will be attracted to the pond naturally.
Wait for local turtles to seek out this new wetland. It could takes days, months, or even years, depending on where you live and how close you are to their natural environment. If your pond fails to lure turtles on its own, you can always relocate turtles to the pond yourself.
Items you will need
• Pond
• Filtration pump or waterfall
• Floating driftwood log
• Variety of native water plants
• Feeder fish
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dan graham
Peter Doroshenko: Over the last twenty-five years you have examined architecture and urban planning in both your art work and critical writing. How is New York City changing as an urban center?
Dan Graham: New York is slowly becoming suburbanized. Besides the large city-operated parks, I have been fascinated over the years by the corporate make-overs of open public spaces, such as the botanical garden inside the Chemical Bank headquarters on Park Avenue or the IBM Building atrium on Madison Avenue and 57th Street. This was the very beginning of the suburbanization of New York. The gardens and atriums these corporations built, as part of larger complexes, were an attempt to have a controlled, semipublic green space, to keep people in the city.
Doroshenko: Are there any successful corporate arcadias?
Graham: The Ford Foundation Building designed by Kevin Roche and the building's landscaped atrium garden designed by Dan Kiley is the best example of an ecologically balance public space. It is a very classical modernist space, but very ahead of its time, since all of the plants use rain collected from the roof and condensed stream collected in a cistern. Each office has a sliding door onto the atrium and it creates a sense of common purpose.
Doroshenko: Once homogeneous, the suburbs have taken landscape architecture further along than New York has. Is this the missing component in the large city projects?
Graham: New York has less space to work with, but more could be done with what we have. Landscape architects need to do more with future building projects and the existing city parks. I still question the success of corporate public spaces and the city's funds that are diverted from public safety and cultural programs to build them.
Doroshenko: Don't developers get incentives to create public spaces in their planning and construction of new buildings?
Graham: In the late 1960s, the city passed zoning laws to allow incentives for covered public spaces or atriums. If a public space or certain amenities were to be added to a construction project by the developer, it would increase the total floor area of the building.
Doroshenko: Aren't there various community boards and organizations that screen most of the new building projects?
Graham: I believe all New Yorkers should look to sister cities in Europe to examine the next steps of urban planning. The Europeans are very concerned with public spaces and the suburbs are not an issue.
Doroshenko: But on the newly revamped Avenue Champ-Elysée in Paris, there has been an outbreak of mini-malls.
Graham: It's pure capitalism, happening on only one street in the city, set up to attract the visiting Long Island, New Jersey and Connecticut tourist shoppers.
Doroshenko: Having exhibited your work mainly abroad over the years, do you think there is anything specifically American in your work?
Graham: My work is more influenced by the time and site for which it was made, rather than a geographical place of its making.
Doroshenko: Do you feel there is a right or wrong way to understand your recent works?
Graham: Yes. The newest projects deal with architecture, urban space and power.
Doroshenko: Power?
Graham: The way corporations are changing the urban landscape of New York and the continued suburbanization of high traffic pedestrian locations.
Doroshenko: So, does the suburbanization of New York continue with the construction of shopping malls such as Pier 17, Trump Tower and Winter Garden over the last ten years?
Graham: Originally, the mall concept was tied into luxury housing, offering suburban convenience in the city. The first mall was South Street Sea Port and later the addition of Pier 17. This project was built as a fake market space, an early 1980s concept of historical restoration. Buildings were rehabed and then leased out to national retail chains and upscale restaurants. It proved to be a financial disaster because our historical curiosity with this fabricated past came to an end. The problem with the South Street area is that it was set up as a major tourist attraction and the community in and around the development suffered in the long run — overcrowding, lack of services and higher real estate costs. What people living in that area want is less tourism and more of a real neighborhood. The same could be said for the other mall projects.
Doroshenko: Whether it's a small strip mall on 7th Avenue or a gigantic multilevel mall at Herald Square, they seem to be changing the urban landscape. Even the airports are mimicking the mall idea.
Graham: Well, La Guardia, Kennedy and Newark airports were originally designed and built as having separate pavilions and were much more isolated than they are now. I would hate to travel through Denver or Pittsburgh and deal with their new mall stylized airports.
Doroshenko: Today, almost all the airports contain several, big name, fast food restaurants, a few specialty shops and a small subway system.
Graham: Subway? What New York really needs is an express subway or rapid transit train to and from the airports, similar to the RATP/SNCF in Paris or BART in San Francisco. A transportation system that will go longer distances, supplementing the local subways and trains. The only way one can get to and from any of the airports in New York is by either taxi or limousine.
Doroshenko: Aren't limousines and car services a bit expensive as transportation systems?
Graham: They were a luxury at first, in the 1970s and 1980s, but now they are very competitive and inexpensive. Using this kind of transportation is only good to the airports and nowhere else — taking a limousine from the airport back to Manhattan is very pricey.
Doroshenko: A situation where it's fun to leave New York, but it's not fun to come back.
Graham: Exactly! But it's great fun to take a ferry. It would make sense to implement a more extensive ferry system, besides the ferries that now go to Hoboken and Jersey City. An express ferry to La Guardia or Long Island City would make sense.
Doroshenko: I don't understand why Manhattan built a new Robert Venturi designed ferry terminal downtown, but Staten Island did not get an upgrade on its present facility?
Graham: You would think both sides would be equally important for the Port Authority, since only Staten Island residents use the ferry. It's all comes down to money, Manhattan has the financial resources and Staten Island doesn't.
Doroshenko: At the same time, Manhattan is not an automobile city — the tunnels and bridges are always congested with traffic. What makes it so unique is the ability to walk everywhere.
Graham: New York is the only city in the United States where you can walk everywhere and to everything. I don't know of another city where walking is not only a recreation, but a possibility. Since the city is so vertical, it is also very much about walking on various layers, separated only by a set of stairs or an elevator.
Doroshenko: In your walks around the city, have you ever come across successful public art projects?
Graham: The two strongest works that come to mind are Richard Artschwager's "Chase Lounge," in Battery Park City and Dennis Adams's "Bus Shelter I" which was temporarily installed for a few months near Broadway and 66th Street. Unlike Claes Oldenburg, whose works are Disneyland fantasies, Richard Artschwager's installation plays with the concept of typical suburban patio furniture and the suburban planning of the Battery Park City area. The Dennis Adams bus shelter had a certain derivation from my work with pavilions, but his installation had a site situation and a pictorial content. Both installations are or were used by many people, either as a rest stop after walking a distance or waiting for a bus.
Doroshenko: Wasn't Battery Park City the first time artists were invited to participate in the planning of a large permanent public park project in the City — either in collaboration with an architect or on their own?
Graham: Yes, but the finished projects were very disappointing, most of the works were very ineffective. The landscape architect who worked with some of the artists was the most imaginative, making a walk through the park more enjoyable.
Doroshenko: Wouldn't it be nice to find easy access to a restroom after walking a few hours?
Graham: There is great irony to this problem — restaurants are happy to serve you water, but they don't want you to use the restroom. I love New York, but San Francisco is more of an innovation leader when it comes to the public's needs; they have had the French-manufactured public restrooms for a few years now, maybe because San Francisco is a very compact city and a large tourist destination. I really don't know what the holdup is on getting public restrooms onto our streets, maybe some politician should make it a campaign issue.
Doroshenko: In which part of the city would they be installed first?
Graham: Probably around City Hall. Being a typical New Yorker, I would like to see more done for the City's neighborhoods. I still have a residence in Chinatown and a studio on the border of Chinatown and Little Italy. These are real ethnic communities that make the City an interesting and enjoyable place to live.
Doroshenko: Are these neighborhoods changing?
Graham: They are slowly becoming ethnic ghettos. When I first moved to Chinatown, there was an interesting mix of Chinese, Jews, Italians and artists living together. But, after the huge Hong Kong investment and immigration into the community in the 1970s and early 1980s, the population balance changed and now, for the most part, only Chinese remain.
Doroshenko: Keeping a diverse ethnic balance in a community may be impossible.
Graham: I keep believing it can happen, but many times it has to do with economics. In the early 1980s, many Koreans began to open up gourmet grocery stores and small businesses in SoHo. It was great to see them there among the various boutiques and art galleries.
Unfortunately, many had to relocate after only a few years because of the rising costs of real estate.
Doroshenko: This sounds like a story that many artists have experienced.
Graham: Well, it seems that every time artists invest their time and money in a neighborhood, it only becomes a matter of time before the trendy boutiques and restaurants follow — the East Village and Tribeca are good examples.
Doroshenko: Today, the demolition of older buildings and the construction of new ones in such areas as the East Village and Tribeca is rare, most are converted to other uses.
Graham: In the early 1970s, when the city had its first major financial crisis and almost went bankrupt, the real estate market collapsed and many New Yorkers turned to the concept of urban recycling. The idea of putting a cultural institution inside a decaying building brought out a lot of civic pride — the pride of making something out of nothing. Artists such as Gordon Matta-Clark who destroyed condemned buildings as art — putting more holes where there were holes before — were championed by the art world. A negative rather than a positive aesthetic became popularized. The city needs to have that same spirit again — people co-opting space, taking over dilapidated spaces and creating their own situations.
Doroshenko: Similar to your Rooftop Urban Park at the Dia Center for the Arts?
Graham: Yes. When I was first approached by former director, Heiner Friedrich, in 1987 to do a project for Dia at its West 22nd Street building, I instantly became interested in using the roof which no one had conceived of using before. My idea was to construct a park that would be related to the surroundings of Battery Park City, the Hudson River and the New Jersey landscape. It was to be an extension of the history of Battery Park, a sandy landfill that was later used in the summer of 1985 for an art event called Art at the Beach.
Doroshenko: So, you started planning and working on this project before the Dia moved into the building?
Graham: Yes, but I had to convince the architect, Richard Gluckman, who was hired to renovate the entire building, not to alter the roof.
Doroshenko: I read somewhere that you worked with other architects on this project.
Graham: It was a collaboration with architects Mojdeh Baratloo and Clifton Balch.
Doroshenko: Other than the glass pavilion, no other structures were added to the roof?
Graham: No. I wanted the park to feel open, and yet have all the amenities of the IBM Building atrium or the Winter Garden atrium in The World Financial Center.
Doroshenko: Such as the coffee lounge in the converted utility shed?
Graham: Yes. And a video viewing room, plus a performance space in and around the pavilion. I was interested in the possibilities of servicing different audiences in the Chelsea neighborhood as the alternative space The Kitchen once did. My project became emblematic with the way Dia operated and their own content was grafted onto my original programs. Both have grown together over the years.
Doroshenko: Most of Dia's projects and exhibitions on West 22nd Street are temporary and replaced after a certain amount of time. What is the fate of Rooftop Urban Park?
Graham: The staff is in the process of purchasing the work for the Dia permanent collection. It would be wonderful if the project could become a permanent part of the building's architectural context.
Doroshenko: A known destination for artists and architects?
Graham: The most interesting spaces in art centers are the restaurants, coffee bars and book shops — romantic spaces where people could relax.
Doroshenko: A place people meet each other? A pickup spot?
Graham: The lobby and restaurant of The Museum of Modern Art are the best places for people watching. I always see people flirting in these locations and I wanted to carry a bit of that spirit into my project.
Doroshenko: Dia's roof also has one of the best views in New York.
Graham: What I didn't realize was that my work was going to become an Eiffel Tower for young artists.
Doroshenko: Every century needs its own Gustave Eiffel.
Graham: Which fulfills the fantasy I have always had: artist as architect.
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Sociology of Mental Illness
A mental illness is a disorder that causes mild to severe abnormalities in thinking, cognitive functions and behavior patterns of the affected people. If these disturbances are too severe, they may impair a person’s ability to cope with life’s ordinary demands and routines.
Mental illnesses are still stigmatized in contemporary society, in spite of a general increase in awareness about such diseases as depression and anxiety. Even the very term “mental illness” has a negative connotation to it as opposed to “physical illnesses”. The widespread perception is that mental illnesses are somehow “worse” and patients afflicted with it “unpredictable” and “dangerous”. While such labels are applicable to a small fraction of patients, a majority of them are “normal” individuals by common standards. Their disorders and disturbances only affect their concentration, cognition and efficiency. Yet, they get ostracized for their condition. The mainstream media plays a significant role in spreading such misconceptions among the citizenry. As a matter of statistic, crime rates among the mentally disturbed are quite similar to that of the control group (Angermeyer, 2004). Yet, the media portrays them as people prone to violent and antisocial behavior. For example,
“Mental illness also has not received the sensitive media coverage that other illnesses have been given. We are surrounded by stereotypes, popular movies talk about killers who are “psychos” and news coverage of mental illness only when it related to violence. We also often hear the causal use of terms like “lunatic” or “crazy,” along with jokes about the mentally ill. These representations and the use of discriminatory language distort the public’s view and reinforce inaccuracies about mental illness.” (Schulze, 2003)
It is not an even keel with all types of afflictions. Some of them like schizophrenia are subject to more ridicule and stigma than say depression. People affected with this condition are portrayed as “psychos”, “whackos”, “nut balls”, etc. While disorders like depression don’t attract such treatment as a result of widespread awareness about anti-depressants within the mainstream media (Kelly, 2007).
There are other negative consequences to such stigma. For one thing, many people shy away from getting proper treatment for their conditions on fear of being ridiculed and disparaged. They also develop unreasonable fears of abandonment by their family and friends once the illness comes to light (Kelly, 2007).
When someone is a little different than the normal stereotype, they immediately become prone to stigmatization. There are a whole range of negative stereotypes that is not approved of or respected in society. For example, sexual orientation, skin color, ethnic accents, etc. are all subject to ridicule and disregard. This discrimination becomes more hostile and takes unreasonable proportions when it comes to mental illnesses. People who are at the receiving end of such discrimination lose their sense of objectivity and start doing things to make them acceptable. Their personal beliefs and values take a backseat as “people pleasing” becomes their primary cause. In some conservative social settings many legends, myths and falsehoods are passed on from one generation to the other through study of classical texts, etc. Although the people studying them understand the dubiousness of the negative conceptions, they still fall victim to indoctrination. So, at a subconscious level they still hold prejudices and hostilities toward stereotypes that are deemed unacceptable in civil societies. Due to inaccuracies and misunderstandings, people have been led to believe that an individual with a mental illness has a weak character or is inevitably dangerous (Jamison, 2006). For example,
“Some people also believe that those with mental illness are less competent, unable to work, should be institutionalized or will never get better. As a result of such stigma, mental illnesses remain the butt of jokes in popular culture. Negative portrayals of people with mental illnesses fuel fear and mistrust and reinforce distorted perceptions, leading to even more stigma.” (Murray, 2006)
Since mental illnesses are “invisible”, in that their symptoms are psychological as opposed to physiological, makes them all the more suspicious and mysterious. No wonder then that some corners of the world still maintain traditions and practices that deal with mental illnesses through mysticism and black magic (Jamison, 2006).
Most of us have an idea of what it is to suffer from a mental illness, but most of our perceptions and understandings have been distorted through traditionally held social beliefs and attitudes. In this regard, the advertiser supported popular media, as a reflection of society, has done almost nothing to change this distorted view of mental illnesses. Even today, characters in soap operas and movies who are shown as aggressive, dangerous and unpredictable have their abnormality attributed to a mental illnesses (Weiss, 2006).
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How to Improve it
WHY crunches neck
How to find the root of the number of
How to find the root of a number
Find the root of it is easy.
Enough to have a calculator handy, mobile or kompyuter.No and then there are nuances.
The easiest way to find the root of the number if the handthere is a calculator. It is desirable to engineer? one in which there is a button with the sign of the root: ???. Typically, to extract the root itself is enough to dial the number, and then press the button: ???.
In most modern mobile telephonesIt has an application? calculator? with the root function. The procedure for determining the number of roots with a telephone calculator is similar to the above.
Find the square root of 2.
Turn on the calculator (if it is turned off), andconsistently push the button with the image and the square root of two (? 2? ???). Press the key? = ?, It is usually not necessary. The result is a number of type 1.4142 (number of characters and? Roundness? Depends on the bit and calculator settings).
Note: when trying to find the root of a negative number calculator usually displays an error message.
If you have access to your computer, find the root of a number is very simple.
1. You can use the app? Calculator ?, existing on almost any computer. For Windows XP, this program can be run as follows:
?Start? - ?All programs? - Standard? - Calculator ?.
View is better to install? Normal ?. By the way, unlike a real calculator button to extract the root is labeled as? Sqrt ?, instead of ???.
If you get to the calculator in this way can not, then you can start the standard calculator? Manually ?:
?Start? - Run? -? Calc ?.
2. To find the root of the number, you can also use some of the programs installed on your computer. In addition, many programs have their own built-in calculator.
For example, you can do the following steps for MS Excel applications:
Start MS Excel.
Write in any cell number from which you want to extract the root.
Put the cell pointer to a different location
Push the button on the function (fx)
Select the function? ROOT?
The argument function specify the number of cell
Push? OK? or? the enter?
The advantage of this method is that it is now enough to enter the cell with any number of value as a function of the cell response appears immediately.
There are several other, more exoticway to find the root of a number. For example,? Area ?, using a slide rule or Bradis tables. However, these methods are not discussed in this article, due to their complexity and practically useless.
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Short answer to the challenge... The Egg of Columbus
(But read on for the rest of the story!)
This search challenge was harder than I thought… but for an interesting reason. I'll take the blame here-the question ("English 4-word idiomatic expression for something thought to be impossible, but shown to be trivial") is not exactly a cleanly defined, clearly answerable kind of question!
As a consequence, people found all KINDS of answers that I hadn't thought about.
Forest for the trees
Cutting the Gordian knot
Thinking outside the box
Keep it simple stupid
Hiding in plain sight
To square the circle
Elephant in the room
Needle in a haystack
And even some unusual ones:
Riddle of the Sphinx
L'spirit de esclair
Alas, while many are close, they're not exactly right. "Cutting the Gordian knot" has the right sense of a sudden rapid solution to an unsolvable problem.
Thing is, I hadn't thought of that phrase as a possible solution. So kudos to those of you who made all of these suggestions. I'd put "Cutting the Gordian knot" as a correct answer, with "Forest for the trees" and "thinking outside the box" as decent half-credit answers. (They don't saying anything about the solution, just the path to the clever solution.)
Out of the roughly 20,000 who read this problem, only 3 found the answer I planned: JacobM, Johns1111 and Amarek all found what I'd INTENDED which is such problem/solutions are called "The Egg of Columbus"—as in the sentence "That's a real 'Egg of Columbus' type problem.'
In the comments, Johns1111 points out that in German this would be "das Ei des Kolumbus," which is a transliteration of "The Egg of Columbus," and, in my opinion, quite correct. Congrats also to Amarek for also finding the same solution.
Image of Columbus breaking the egg by William Hogarth (Wikipedia).
Search lessons: (1) First, as should be obvious, finding idioms is hard. People who searched in idiom dictionaries were on to something. That's a great strategy for searching out this kind of information. I tried a couple before giving up, hoping to stumble across it (which is what happened).
My big tip about long searches is pretty simple: Keep track of what you've searched for and found. That's especially true for long search processes that take weeks. I just kept an open text file with my "search notes" in it. It really prevented me from duplicating my searches and let me systematically eliminate possibilities.
Search on! (But systematically...)
Wednesday Search Challenge (Feb 29, 2012) Answer: Impossible, yet simple? | SearchReSearch
Title image by simlik (Shutterstock) |
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📚 DCLM-pro
DCLM-pro is refined from DCLM using the ProX refining framework. It contains about >500B high quality tokens, ready for general language model pre-training.
License
DCLM-pro is based on DCLM, which is made available under an cc-by-4.0 license.
Citation
@article{zhou2024programming,
title={Programming Every Example: Lifting Pre-training Data Quality like Experts at Scale},
author={Zhou, Fan and Wang, Zengzhi and Liu, Qian and Li, Junlong and Liu, Pengfei},
journal={arXiv preprint arXiv:2409.17115},
year={2024}
}
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