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The color wheel is a fundamental concept that is introduced in Grade 1 and then further discussed in later grades. So I am always interested in developing projects to help teach Color Theory. Now Color Theory can get quite complex but we'll start with the basics. For this project the kids make a color wheel that becomes the basis for a fun interactive painting. With a turn of the wheel........ ......and the gecko changes color. So let's get started and once you know the technique you can adapt this project in numerous ways. - tempera or watercolor paint - 2 sheets of watercolor paper - fine sharpie - template, (use mine or better yet come up with your own) - scissors, pencil, eraser - paper fastener - glue, tape - transparency (optional) Take one sheet of watercolor paper and trace out the largest circle you can. I used a plate. Cut it out and save your scraps. Mark in pencil the center of that wheel on both the cut circle and where it would lay on that other paper. Now hold the paper up to a bright window and make this center mark on the back as well. This helps out a lot later. If you are using the template or a pattern that you have made yourself, lay this on the marked out circle on the paper. It's hard to see in this photo so I'm leaving the wheel in place to show you. You want the gecko to be inside that circle and you also don't want to cover up the that center pencil mark. You'll have to fiddle with your image to get it in the right place. Trace out that pattern or just free draw in your image. Now you want to create your window so you need to cut away that image. Instead of fussing with exacto blades or tears from trying to make these difficult cuts I just get the kids to cut their paper in half thru the drawing. They then can easily cut out both sides of the drawing. We then turn the 2 sides over to the back, fit together and tape into place. Much easier and safer. Now let's start painting. Get the kids to paint in the primary colors leaving white space between them. Then start mixing the primaries together. It's best to mix these together on a separate palette or plate and then add onto your color wheel. Add a little water on the edges of each color so they mix a little rather than having such definite stripes. Now paint in your top sheet. If you are pressed for time with this project you can also just use black paper, draw in some background lines with white pencil crayon and then you can skip this painting step. Outline your painting if you want with sharpie or black pencil crayon. You can also outline the cut out section (older kids). Now I like to hide the paper fastener. In order to do this you need a scrap piece of wc paper. (remember those scraps from cutting out our wheel). Cut a circle, square, what ever will fit. You'll understand in a minute. Punch a hole through it with an awl, scissors, or knitting needle and put the fastener in hole. Now glue or tape this onto the back of your cutout sheet. (Prongs sticking up at you) You want it to be approximately where that center mark is that you marked out. You don't want any of the scrap paper showing thru the window so sometimes you have to cut it to fit. Now you could just stop at this point but if you want details on your gecko take a transparency sheet. Lay it on the back, you'll have to poke a hole to let the fastener get thru. Now you don't have to use a full sheet, I know transparencies can be quite expensive. You just want to cover up that cutout. Tape into place. Put Color wheel face down on fastener and fold back prongs, a little loose for easy turning. Now you can add details in sharpie right on to the transparency. Here is a smaller one I made that does not have the transparency. I added googly eyes. You can also make these in your journals and I hope to show you those next time with more color theory. Just a quick note to let you know that a link to this post will be placed on CraftCrave today [07 Jul 01:00am GMT]. Thanks, MariaReplyDelete This is why I love your site! My class with LOVE this! Thanks!ReplyDelete Absolutely love the idea!ReplyDelete hi, my name is andre and i love art very much.ReplyDelete i just visit your blog and find out that your color wheel technic is very nice. i do also have a blog. my blog is about crafts and handmade things that maybe you also like. please visit my blog and leave a comment. perhaphs we can exchange link if you don't mind? i guess it will be good.. Oh my, this is just AWESOME! Thanks for sharing!ReplyDelete What a cool project! You always have the best ideas! I'm in art teacher in Colorado and I always check your blog for great ideas, thanks!!ReplyDelete I teach a craft class in the Philippines and would love to use this idea for a craft if that is OK with you.. I'll link to you once I have photos up on my blog www.ilovecrafts-manila.blogspot.com. My girls love butterflies so I'll probably let the boys do your gecko and the girls do butterflies.ReplyDelete JUst wanted to let you know that I posted pictures of our version on our blog at www.ilovecrafts-manila.blogspot and credited you. Thanks for all the hard work you put into this blog. You have such great ideas!ReplyDelete What a creative lesson to teach the color wheel! Thanks for sharing!ReplyDelete Thank you for the idea! I am going to try this activity with my class and am excited to see the results!ReplyDelete I tried this with a 7yr old and 3yr old and got great results - they loved it! I cut out the lizard for them both, and the circle for the little one, they did the rest. My 7yr old taught the 3yr old how to to the color wheel.ReplyDelete I bought some transparencies that don't work with my printer,this will be a great way to use them. Love this projectReplyDelete What a great project! Print shops that do large laminating sheets aften have off-cuts that they will give you, or if your school library does large sheet laminating, they also might have them - save money and recycle too : )ReplyDelete

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When potassium chloride is dissolved in water, Potassium chloride is the solute. Potassium chloride is the solvent. Potassium chloride is the solution. A single displacement reaction can also be classified as An oxidation reduction reaction A precipitation reaction A decomposition reaction. A synthesis reaction 29) When Pottasium chloride is dissolved in water. Pottasium chloride is the solute. Water is the solvent and mixture of these two is solution. 30) A single displavement reaction can also be classified as a synthesis reaction. A reaction, where an element reacts with compound and replaces another element to give new compound is called as a single displacement reaction. An oxidation reaction may or may not involve displacement of an elemnet and hence it is not the answer. When two elements of compound reacts to give precipitate is called as a percipitation reaction. When compound decompses to give different elements of compounds is called as a decomposition reaction, and hence it is not the answer.

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Aircraft of the Isle of Wight: 1960-2000 Created | Updated Jan 28, 2002 In 1949, John Britten and Desmond Norman, out of the de Havilland aeronautical engineering apprentices training school, formed a partnership to build new aircraft. Their first plane, the BN-IF Finibee, made its first flight on 26th May 1951. It wasn't as successful as hoped, but it still survives and is in the Southampton Hall of Aviation. They then abandoned the idea of building planes, concentrating on converting training aircraft into crop spraying. They designed crop spraying equipment, creating the Micronair Rotary Atomiser. Following Saunders-Roe interest in hovercraft, they also formed a company called Cushioncraft, building hovercraft. This, in 1972, was taken over by British Hovercraft Corporation. Britten and Norman, based in Bembridge on the Isle of Wight, were still interested in building aircraft. When they noticed that there were no low-maintenance aircraft capable of using short, rugged aircraft on the market, Britten-Norman decided to make one of their own. So the BN-2 Islander was designed in 1963, and made its maiden flight in June 1965. A few days later it appeared at the Paris Air Show. The Islander is a twin-engined plane, with accommodation for 9 passengers, and soon became popular. By 1968 over 200 had been made for service in over 27 different countries. They are still being built today, with over 900 to the original design. In fact, the Islander has had the longest production run of any post-war British aircraft. Different variations were tried. The first, the BN-3 Nymph, was a smaller, single-engined version. Only two prototypes were made, and did not make it into production. On the 11th September 1970, the BN-2A Mk III made its maiden flight. It was a three-engined, 17 passenger version, and was soon named the Trislander. 81 Trislanders were built, and now an American version is being made by the International Aviation Corporation, known as the Tri-Commutair. Trislanders are the main aircraft operating to the Channel Islands, and many American airlines use several also. The Trislander was also the first, and so far only, three piston-powered passenger air transport. In 1971 the first Defender was built - a larger, military version of the Islander. Over 200 have been built so far. Other ideas were the BN-4, an even larger Islander capable of carrying 21 people, and the Mainlander, a three engined STOL prop-jet for up to 100 passengers, yet nothing came of either design. Sadly, though, John Britten died in July 1977. New models were designed in 1981, 1991 and 1994. By 1998 over 1,200 Islanders had been built, and they are still in production at Bembridge today Small Aircraft Companies Desmond Norman also formed another company, NDN Aircraft, in Sandown, Isle of Wight, in 1976. The NDN-1 Firecracker first flew in May 1977, but did not win a production order. In 1983 a turbine version made its maiden flight, and three were built. They too failed to make any impact. In 1981 the tandem-seated NDN-6 Fieldmaster was built and flown as a crop-sprayer, but oil-pollution clearance and firefighting versions, known as the Firemaster, were designed. Over five were built. NDN Aircraft changed its name to Norman Aeroplane Company, and in 1984 the NAC-1 Freelance was built, based on the BN-3 Nymph. Only a prototype was built. In 1976 Britten Aviation Technical Services was established at Sandown, and tried to develop a twin-engined pleasure aircraft called the Sheriff, but it failed. Wight Engineering at Shanklin built parts for the Edgley EA7 Optica surveillance Aircraft, which also wasn't a commercial success. In 1983 ARV Aviation started by Sandown Airport by Richard Noble1. They designed the Super Two, a small, light plane with a two-stroke engine. Thirty were sold in total before 1991. Other aircraft companies based at Sandown Airport include Solar Microlights, which builds small, single-person micro lights. Another, Airframes Assemblies, builds spare parts for historic aircraft, specialising in Spitfires. In 1985, British Hovercraft Corporation, which had been Saunders-Roe, was renamed Westland Aerospace. The East Cowes workplace concentrated less on building hovercraft, and started to build composite engine nacelles for the de Havilland Dash-8 and wings for the Short S330. Within 10 years, over 60% of the world's turboprop nacelle production took place at East Cowes, for aircraft such as the Dornier 328, British Aerospace Jetstream 41, the Saab 2000, the C130J Hercules in 1993, and in 1995 the Dash 8-400series. They also supply components for turbofan nacelles, such as for the French SNECMA CFM 56-5C2, the McDonnell Douglas MD-11, as well as building parts for the Boeing Globemaster, Boeing 747 and 737. As Westlands, they provide helicopter structures for the Westland EH101 Merlin as well as equipment for the Wessex, Sea King, Lynx and Puma, although most helicopter work is at Westland's Yeovil factory. They also make long-range fuel pods for the Boeing Chinook helicopter. In 1983, they were awarded the honour of constructing the Mast Torque Sensing System for the revolutionary Bell-Boeing V-22 Osprey tilt-rotor aircraft. In 1994, Westland Aerospace was taken over by Guest, Keene And Nettlefold, to form GKN Westland Aerospace. Since then the East Cowes workers have been working on the huge fan cowl doors for the Airbus A330, the tailcone for the Canadair CRJ-700 and in 1998 Lockheed Martin ordered nacelles for the C27J transport. The Isle of Wight, therefore, has had considerable success in its aircraft industry considering the size of its companies. It may not have produced many world-changing aeroplanes such as the Spitfire, Harrier or Concorde, but it has played a significant part in aircraft history, culminating in the SR.A1, the Princess and the launch of the Prospero satellite.Aircraft of the Isle of Wight: 1900-1919Aircraft of the Isle of Wight: 1920-1945Aircraft of the Isle of Wight: 1946-1960The Isle of Wight Space ProgrammeAircraft of The Isle of Wight: 1960-2000

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Obviously it is not the same to take a whole piece of fruit thinking that it can be replaced by a juice. Juice or whole fruit? Whole fruit produces a greater feeling of satiety therefore has an advantage in weight control,and is involved in glucose regulation. In addition the fruit presentsfiber, which is a factor of protection against obesity. Fruit juices contain less fiber than whole fruit, resulting in low fiber intake. Fiber is mainly located on the skin and pulp. If the fruit is taken in juice, the fiber is not used as much, let alone if you have a habit of straining it (the little fiber left is completely removed). It should also be noted that, to make an orange juice, for example, at least three oranges are needed. Eating three whole oranges in a row would cost a lot. Taking a juice,therefore, you take more calories and more sugar than recommended. For example, an orange can weigh about 200 grams which, peeled, become about 150 grams. To make a juice of about 200 milliliters we will need at least two or three oranges, depending on the variety. According to the World Health Organization (WHO), scientific studies confirm a likely link between fruit juice consumption and obesity. Therefore, it is advisable to reduce the consumption of fruit juices. Therefore, the juice is easier to drink and would be indicated for the little fruiters who have no problem with weight, but in general and for all the reasons exposed, whole fruit is recommended for the public. Care in your diet, will say a lot about you, take care, take care of them. #NaranjasAmparo

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Capital city of Punjab, Pakistan / From Wikipedia, the free encyclopedia Dear Wikiwand AI, let's keep it short by simply answering these key questions: Can you list the top facts and stats about Lahore? Summarize this article for a 10 years old Lahore (/ləˈhɔːr/ lə-HOR; Punjabi: لہور [ˈlɔ̀ːɾə̆]; Urdu: لاہور [laːˈɦɔːɾ] (listen)) is the second most populous city in Pakistan after Karachi and 26th most populous city in the world, with a population of over 13 million. It is the capital of the province of Punjab where it is the largest city. Lahore is one of Pakistan's major industrial and economic hubs, with an estimated GDP (PPP) of $84 billion as of 2019. It is the largest city as well as the historic capital and cultural centre of the wider Punjab region, and is one of Pakistan's most socially liberal, progressive, and cosmopolitan cities. It is situated in the northeast of the country, close to the international border with India. |Coordinates: 31°32′59″N 74°20′37″E| |• Type||Metropolitan corporation| |• Mayor||None (Vacant)| |• Deputy Mayors||9 Zonal Mayors| |• Commissioner||Muhammad Amir Jan| |• Deputy Commissioner||Rafia Haider (PAS)| |• Total||1,772 km2 (684 sq mi)| |Elevation||217 m (712 ft)| |• Rank||2nd (Pakistan)| |• Density||6,300/km2 (16,000/sq mi)| |Time zone||UTC+5 (PKT)| |GDP/PPP||$84 billion (2019)| |- Per capita||$7,550| Lahore's origins reach into antiquity. The city has been inhabited for at least two millennia, although it rose to prominence in the 10th century. Lahore was the capital of multiple empires throughout its history, including the Hindu Shahis, Ghaznavids, and Delhi Sultanate in the medieval era. Lahore reached the height of its splendor under the Mughal Empire between the late 16th and early 18th century and served as its capital city for many years. During this period, it was one of the largest cities in the medieval world. The city was captured by the forces of the Afsharid ruler Nader Shah in 1739. Although the Mughal authority was re-established, it fell into a period of decay while being contested among the Afghans and the Sikhs between 1748 and 1798. Lahore eventually became the capital of the Sikh Empire in the early 19th century, regaining some of its lost grandeur. Lahore was annexed to the British Raj in 1849 and became the capital of British Punjab. Lahore was central to the independence movements of both India and Pakistan, with the city being the site of both the declaration of Indian Independence and the resolution calling for the establishment of Pakistan. It experienced some of the worst riotings during the Partition period preceding Pakistan's independence. Following the success of the Pakistan Movement and the subsequent partition of British India in 1947, Lahore was declared the capital of Pakistan's Punjab province. Lahore exerts a strong cultural influence over Pakistan. A UNESCO City of Literature and major center for Pakistan's publishing industry, Lahore remains the foremost center of Pakistan's literary scene. The city is also a major centre of education in Pakistan, with some of Pakistan's leading universities based in the city. For many years, Lahore was home to Pakistan's film industry, Lollywood, though in recent years most filming has shifted to Karachi. Lahore is a major centre of Qawwali music. The city also hosts much of Pakistan's tourist industry, with major attractions including the Walled City, the famous Badshahi and Wazir Khan mosques, as well as several Sikh and Sufi shrines. Lahore is also home to the Lahore Fort and Shalimar Gardens, both of which are UNESCO World Heritage Sites.

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Hybrid cars have two motors, one electric and one internal combustion. While they’re generally more fuel efficient, do hybrid cars really save you money? A HYBRID VEHICLEis one that is powered by two different types of motor,one electric and one internal combustion – the kind we’reused to where a fuel ismixed with air in a confined space to produce a driving force (petrol or diesel as examples).There are several different variations on that theme: - petrol/electric – mainly powered by a petrol engine, but has a battery which powers an electric motor. The electric motor can drive the car by itself, or in concert with the petrol engine for extra power. The battery is recharged by harvesting energy as the car slows down, or by the petrol engine. Examples here are Toyota’s Prius and Camry; - diesel/electric – same, but uses a diesel engine. Typically only found on larger vehicles. Example is the Range Rover Sport hybrid; - plug-in hybrid – same again, but you can recharge the battery from an external power source. Examples are the Porsche Cayenne and Panamera hybrids; and - generator – a pure electric-drive car, but also have a small petrol (rarely diesel) engine that cannot drive the wheels, only recharge the battery. This simplifies the car somewhat. Example is the Holden Volt. While we’re on the subject, an EV is an Electric Vehicle, or one powered only by electricity, nothing else. Teslas are the most famous example here. What’s a hybrid like to drive? A good one is no different to a normal car, or only in such a small way as to be almost unnoticeable by the average driver/owner. There is no technical reason why the hybrid need be any slower than a conventional car, handle worse or significantly compromise on loadspace. However, because hybrids are naturally focused on fuel efficiency carmakers tend toprioritisefuel consumption over handling, for example fitting thin, low-rolling-resistance tyres that are not great for handling, and they don’t exactly go overboard on the power either. Interior packaging is very similar to normal cars, as while there is an electric motor that is small the conventional engine is often a bit smaller than would otherwise be the case. Batteries are hidden out of view too, so the day-to-day compromises are not noticeable for most users. But does a hybrid make sense if you look at the costs? The short answer is simple – “depends on your situation” as there’s always going to be outliers and unusual factors specific to every owner. However, what we can do here is look at some of the basics which readers can then modify for their own circumstances. At the moment, hybrids cost more to buy and “may” cost less to run – so from a financial perspective you need to work out how soon, if ever, that additional capital cost will be recouped by lower running costs. Exactly the same maths applies to choosing a diesel car over petrol – higher purchase price, lower fuel consumption. But hybrids may not always be more expensive. One of the leaders, Toyota, say that “in the future, Toyota sees Hybrid Synergy Drive technology extending across its full range of vehicles. In Australia, the range will continue to grow.” And it is interesting that the three hypercars of late, the Ferrari La Ferrari, Porsche 918 and McLaren P1 are all hybrids, not for efficiency but for performance. Given the ever more stringent emissions regulations, and the improving hybrid technology we can certainly expect to see more and more hybrids – there’s already around 15 on the Australian market, with more to come. Our visit to the Toyko Motor Show proved that every car manufacturer, without exception, is focusing on hybrids, electric vehicles and alternative power sources. With that sort of investment we can expect prices to lower, range and efficiency to improve, and hybrids to become the norm. Even off-roaders are embracing hybrid technology, not least because electric power offers superb low-speed control. All we then need is governments at all levels to wake up and provide incentives to clean cars such as lower registration, free or reduced parking, and lower tax. That’ll help make them more cost-effective, and despite what they say, consumers buy cars with their hip pockets. So to see what sort of savings could be generated we took a look at the Toyota Camry, which comes in four trim levels, three of which have hybrid options. The base stats are: |Altise||Atara S, SL||Altise||Atara S, SL| |Example driveaway cost||$ 28,990||$ 31,990||$ 32,990||$ 34,990| |Engine||2.5L 133kW / 231Nm||2.5L 135kW / 235Nm||2.5L 118kW / 213Nm + 105kW electric. Combined maximum 151kW| |Dimensions (mm)||4850mm l, 1520mm w, 1200mm h| |Weight (kg)||1460kg – 1505kg||1575kg||1610kg| |Co2 g / 100k||183||183||121||121| |Towing||1200kg braked / 500kg unbraked||300kg| The stats show the vehicles are very similar. As you’d expect, the hybrid weighs a bit more, and has a smaller petrol engine as there’s an electric to back it up. The hybrid is also marginally more aerodynamically efficient. It can’t tow as much as the normal car, really not much more than a box trailer. Empty. So what does this mean for your running costs? Here’s the analysis: |Altise||Atara S, SL||Altise||Atara S, SL| |Analysis||Buy price difference||–||–||$4,000||$3,000| |Fuel cost reduction per annum (1)||–||–||-$586||-$586| |Co2 reduction (kg)||–||–||-8.68||-8.68| |Years to pay off||–||–||6.8||5.1| According to the AustralianBureauofStatistics, 14,000km is the average mileage. We’ve added 15% to the combined fuel consumption figures to better reflect real-world use. As you can see, the hybrid will pay for itself in fuel, after about 5 to 7 years, based on that usage pattern. If you do a lot of freeway driving your savings won’t be as great, but more if you spend time in slow city traffic. And of course the greater your annual mileage, the greater the savings. There are more factors to consider than just the cost of fuel: - Capital costs. In this case, you’re spending an extra $3000 or $4000. On a loan, that means greater interest payments. Or if you bought cash, you could invest the money or use it on a home loan, or otherwise make it work for you. In a car, than money is just depreciating; - Resale. Hybrids typically don’t have a great resale value, and depreciation is a huge part of running costs; - Servicing. Will your hybrid be as cheap to service as a normal car, or as easy to fix? Servicing is not a big difference as the hybrid systems are simple and reliable, but hybrids add complexity to a car, and complexity is never cheap to fix. Servicing is often slightly higher for hybrids; - Tyres – hybrids are heavier which means tyres wear out quicker, but in reality the difference is negligble so need not be considered; - Brakes – hybrids are heavier, so go through brake consumables quicker, right? Wrong! Hybrids slow down by regeneration, so if anything they are easier on the brakes than a normal car. However, the difference is not huge and isn’t a major factor…the average driver does not replace their brakes every year, not even every three years; - Registration – hybrids do not yet attract any form of registration discount; - Parking – Australia hasn’t really got into offering discounts for hybrids just yet; and - Insurance – hybrids are pretty much the same to insure as a conventional car. The bottom line A hybrid only starts to make financial sense if you drive enough low-speed kilometers per year to offset the higher purchase price, and the larger the car, the greater the savings. For example, the Prius c costs around $26k on the road, and a Yaris can be had for under $20k. You are veryunlikelyto ever see a financial return on the Prius, but with the larger Camry and a less significant price difference it may work. But for many owners, the sums will never add up. A hybrid will never cost as little as a conventional car, simply because a hybrid has all of the complexity of a conventional car plus additional components, in the same way that diesel engines are more complex than petrols and therefore more expensive. The only way hybrids would become cheaper to buy is ifeconomiesof scale kicked in such that demand for hybrids was so great the cost difference was reduced or even eliminated, but that won’t happen until the overall cost of ownership is significantly lower – something that can only be achieved by government action to reduce hybrid running costs. We have a comprehensive roadtest of a Toyota Prius c and a fuel consumption comparison between the Prius cand a Hyundai i30 diesel automatic. We’ve also just tested the Range Rover Sport hybrid.

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- How do you add three numbers in Python? - How do you add numbers in a loop? - How do you print numbers from 1 to 100 in Python while loop? - How do you print 1 to 10 numbers in Python without loop? - How do you print a 1 to 10 loop in Python? - How do you improve code without using loops? - How do you print a number 10 times in python? How do you add three numbers in Python? “add 3 numbers in python” Code Answer’s - a = int(input(“Enter first number:”)) - b = int(input(“Enter second number:”)) - sum = a+b. How do you add numbers in a loop? Getting the sum using a for loop implies that you should: - Create an array of numbers, in the example int values. - Create a for statement, with an int variable from 0 up to the length of the array, incremented by one each time in the loop. - In the for statement add each of the array’s elements to an int sum. How do you print numbers from 1 to 100 in Python while loop? This python program display the prime numbers from 1 to 100. First, we used For Loop to iterate a loop between 1 and 100 values. Within the for loop, we used another For Loop to check whether the number is divisible or not. If true, count incremented, and break statement skip that number. How do you print 1 to 10 numbers in Python without loop? Python Program to Print Numbers in a Range (1,upper) Without Using any Loops - Define a recursive function. - Define a base case for that function that the number should be greater than zero. - If number is greater than 0, call the function again with the argument as the number minus 1. - Print the number. How do you print a 1 to 10 loop in Python? The for loop prints the number from 1 to 10 using the range() function here i is a temporary variable that is iterating over numbers from 1 to 10. It’s worth mentioning that similar to list indexing in range starts from 0 which means range( j ) will print sequence till ( j-1) hence the output doesn’t include 6. How do you improve code without using loops? Another way we can avoid using imperative loops is through recursion. Recursion is simple. Have a function call itself (which creates a loop) and design an exit condition out of that loop. How do you print a number 10 times in python? PROCEDURE DIVISION. PERFORM 10 TIMES DISPLAY “Hello” END-PERFORM STOP RUN. for (int i = 0; i < 10; ++i) cout << “Hello/n”; C#

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Researchers have found a brand new type of insulin-producing cell hiding in plain sight within the pancreas, and they offer new hope for better understanding - and one day even treating - type 1 diabetes. Type 1 diabetes occurs when a person's own immune system kills off most of their insulin-producing beta cells. And seeing as insulin is the hormone that regulates our blood sugar, type 1 diabetics are left reliant on injecting themselves with insulin regularly. While the condition can usually be managed effectively, in order to properly treat it, researchers would need to find a way to regenerate a patient's beta cells and prevent them from being attacked in future - something we're getting better at, but ultimately has eluded scientists so far. The discovery of these previously unnoticed cells in the pancreas - which the team are calling 'virgin beta cells' - could offer a new route for regrowing healthy, mature beta cells - and also provides insight into the basic mechanisms behind the disease. "We've seen phenomenal advances in the management of diabetes, but we cannot cure it," said lead researcher Mark Huising from the University of California, Davis. "If you want to cure the disease, you have to understand how it works in the normal situation." To get a better insight into exactly what happens in type 1 diabetes, the researchers studied both mice and human tissue. Huising and his team were looking at regions inside the pancreas known as the islets of Langerhans, which in healthy humans and mice are the regions that contain the beta cells that detect blood sugar levels around the body and produce insulin in response. Researchers also know that the islets contain cells called alpha cells, which produce glucagon, a hormone that raises blood sugar. These alpha cells, combined with the blood sugar-lowering beta cells, are how the body regulates blood sugar levels. But in patients with type 1 diabetes, two things go wrong: the beta cells are killed off by the body's own immune system, and then they fail to regenerate. In order to treat the disease, we need to find a way to overcome both of those problems. For decades, scientists have been trying to do this, and they had long assumed that there was one main way for beta cells to be produced - through other adult beta cells dividing. But after using new microscope techniques to study islet tissue in the lab, Huising and his team found a new type of cell scattered around the edges of the islets that no one had noticed before - and they looked a lot like immature beta cells, suggesting that maybe there was actually another way beta cells were being made. Further study revealed that these new virgin beta cells could make insulin, but they didn't have the receptors to detect glucose, so couldn't function as mature beta cells. But that wasn't all the researchers found. They also observed some mature beta cells in the islets transitioning into alpha cells - representing a completely unexpected alpha cell generation pathway. "There's much more plasticity in the system than was thought," said Huising. It's still very early days, and these new cells now need to be confirmed in live humans and animals - not just tissue in the lab. But the fact that we now have evidence that they exist opens up a whole avenue of research on type 1 diabetes and potential treatments. According to Huising, there are three main reasons to get excited about the result: firstly, it represents a new beta cell population in both humans and mice that we had no idea about before, and secondly, it also provides a potential new source of beta cells that could be used to treat diabetics. "Finally, understanding how these cells mature into functioning beta cells could help in developing stem cell therapies for diabetes," a press release explains. The research could also have benefits for type 2 diabetes, which occurs when beta cells become inactive and stop releasing or secreting insulin. The results have been published in Cell Metabolism.

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What is Kotlin? Kotlin is a general-purpose programming language that has a type interface. Kotlin works with Java, and about 60% of professional Android developers make use of Kotlin because it is a developer-friendly language. Using a modern language like Kotlin helps improve developers’ efficiency, productivity and ensures code safety. And as it is open-source, developers using Kotlin for Android app development can benefit from timely support from other developers in the community. Kotlin also has a clean and compact syntax that allows operator overloading and functional programming which can be used in developing Android apps as an alternative to Java. Strong evidence suggests that Kotlin is becoming an increasingly popular choice and hiring Kotlin android app developers will help you build android apps fast and in an easy manner. Access Africa's Best Talent Access Africa's Best Talent What is the role of Kotlin Developers in the market? The role of Kotlin developers varies from one company to another, and in most cases, it varies from one team or project to another. Here are some typical responsibilities of a Kotlin developer: - Writing understandable and efficient code for an Android app. - Comprehending the Product Requirements Document and converting the same into wireframes and later into code. - Ensure optimization and code reusability. - Collaborating with the QA team and the design team to build a full-fledged app. - Ensuring the Android apps designed are secure and performing maintenance checks whenever required. Hire Kotlin Android App Developers if you wish to build an interactive Android app that your users or customers would enjoy using. How will hiring Kotlin Developers benefit your business? Hiring Kotlin developers will impact your company’s growth indirectly. Here’s how: - Android app development is easier using Kotlin as it can make use of any existing library on the Java Virtual Machine. - Kotlin is easy to code, which means that apps can be developed in a fast manner and can also be deployed faster too. - Kotlin saves developers a lot of time and effort as it doesn’t take long to code. - As a general-purpose programming language, the documentation is plenty. So, developers do not require any third-party help to fix errors. - If your business is predominantly based on a web application and you want to transition to an Android app, you might want to Hire Kotlin Android App Developers to help you with this transition. How do I hire Kotlin Developers through the Gebeya Platform? If you or your company is looking to hire Top Kotlin Developers from Africa then Gebeya could come in handy. We recommend that you follow the structure enclosed below : - Search candidates on Gebeya. Ensure the candidate has all the essential requirements for the role. - Shortlist the candidates based on your requirements and needs. You can consider looking at their GitHub repositories if they have developed previous apps. - You can also get reviews and feedback on the type of projects they have worked on from colleagues and past employers. - Interview the candidates to understand their technical skills better and have a discussion more than an interview. - Onboard the candidates if they meet the requirements set by your company. We believe the above-mentioned structure will help you hire the best Kotlin Android App Developers while ensuring a smooth onboarding process for both the candidates and you as the employer.

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There’s one animal you want to avoid encountering: the saltwater crocodile. These massive reptiles can grow up to 23 feet long and weigh 2,200 pounds, making them more than capable of taking down a human. So, how can you tell if one of these creatures is lurking nearby? Here are a few things to look out for. How can you tell if a saltwater crocodile is nearby? 1. Pay attention to warning signs. If you see a sign that says “Warning: Crocodiles inhabiting this area,” take it seriously! That’s not the kind of animal you want to mess with. Crocodiles are large, predatory reptiles that can pose a severe threat to humans. They are found in tropical and subtropical regions worldwide, and their populations are increasing. In recent years, there have been several reports of crocodiles attacking people in their natural habitats. Some of these attacks have been fatal. If you’re planning to visit a crocodile-inhabited area, be sure to stay away from the water’s edge and be on the lookout for signs of crocodiles. If you see one, it’s best to leave the area immediately. 2. If you spot a crocodile on land, you’ll be able to tell by the tracks it leaves behind. Crocodiles have a distinctive gait that results in a V-shaped footprint up to 18 inches wide. So, if you see a set of footprints that fit this description, it’s a good bet that a crocodile is nearby. But, of course, you should always be cautious when approaching any wild animal, and crocodiles are no exception. These animals are dangerous and should not be approached without proper safety gear. If you’re not experienced in dealing with crocodiles, it’s best to leave them alone. 3. Saltwater crocodiles are the largest of all living reptiles, and they are notoriously aggressive predators. If you find yourself in their territory, it is essential to look for signs of their presence. One telltale sign is the sound of grunting or bellowing. These sounds are used to communicate with other crocodiles in the area, and they usually indicate that the crocodile is getting ready to attack. If you hear these sounds nearby, it is best to get away as quickly as possible. Remember, saltwater crocodiles can run up to 30 miles per hour, so you won’t be able to outrun them if they decide to attack. So the best thing you can do is to avoid their territory altogether. 4. When swimming in croc-infested waters, it’s essential to be aware of any water level changes or current changes. A crocodile lying in wait for prey will often cause the water level to drop slightly as it holds its breath. Conversely, you might also notice an increase in the water’s current if a croc swims nearby. If you see any changes in the water, swim to safety immediately. Crocodiles are fast and ferocious predators, and they will not hesitate to attack if they think you’re an easy meal. So stay alert, and don’t let your guard down for a moment when you’re in croc country. 5. Keep an eye out for floating logs . . . that aren’t logs. A saltwater crocodile floating motionless in the water can be nearly impossible to spot since its coloring allows it to blend perfectly with its surroundings. So if you see what looks like a log floating calmly in the water, be wary—it could be a crocodile waiting to attack. Saltwater crocodiles are terrifying predators, but fortunately, there are ways to avoid becoming their next meal. If you’re hiking or swimming in an area where these animals are known to live, keep an eye out for warning signs, tracks, strange noises, and changes in the water level or current. And if you see what looks like a log floating peacefully in the water? It’s probably best not to take any chances—get away from there as quickly as possible!

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The Ebola virus infection which left Guinea in Deember 2015 is back; since March 17 2016 five people have died from the disease prompting Liberia to close its borders with the country. Four of the five persons were members of the same family while the fifth was from a village about 200 kilometres away. Health officials in Guinea are currently tracking 816 persons who made contacts with the five dead people. Ebola first came to West Africa in Decenmber 2014, affected about 28000 people with about 11800 deaths; Guinea, Liberia and Sierra Leone were most hit during that pandemic. Health systems in West Africa like in all other developing regions of the world are extremely weak and ill placed tofight epidemics/pandemics

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Mission Blues Flying Now; Log a Sighting & Win a Prize! Informal reports from several locations suggest that the Mission Blue Butterfly is flying in the GGNRA right now. That means it’s the right time for Golden Gate National Parks Endangered Species Big Year participants to score points in the year-long competition to see and save the park’s endangered species. To give you an extra incentive, the Wild Equity Institute is offering a $25 Sports Basement gift certificate to the first person who logs a GGNP sighting of the Mission Blue on our website! Mission Blue Butterfly, © Margo Bors. The Mission Blue is a small, quarter-sized butterfly. Males are characterized by dark-bordered, silver blue to violet blue upper wings, while females have brown upper-wings with blue traces. The species flies from March until mid-June, but an adult Mission Blue Butterfly only lives for 6-10 days, so the time for observing any one individual is short. It uses one of three species of perennial lupines as a host plant: the silver lupine (Lupinus albifrons) the Lindley varied lupine (L. variicolor) and the summer lupine (L. formosus). Sometimes the butterfly makes it easy to spot: the species has the unique behavior of actually sitting on its lupine host for a while. The Mission Blue Butterfly exists within the GGNP at Fort Baker in Marin County, and Milagra Ridge in San Mateo County. Remember, always stay on trail in the park, and always comply with our ethical principles when participating in the Big Year. To log your sighting, you must have a wildequity.org account, sign-up to participate in the GGNP Endangered Species Big Year, and enter your sighting information at the wildequity.org Mission Blue Butterfly species profile. Leave a ReplyWant to join the discussion? Feel free to contribute!

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Nearly 200 nations agree deal to cut greenhouse gases to fight climate change Nearly 200 nations have agreed a legally binding deal to cut back on greenhouse gases used in refrigerators and air conditioners, a major step against climate change that prompted loud cheers when it was announced on Saturday, reports Reuters. The deal, which includes the world's two biggest economies, the United States and China, divides countries into three groups with different deadlines to reduce the use of factory-made hydrofluorocarbon (HFC) gases, which can be 10,000 times more powerful than carbon dioxide as greenhouse gases. "It’s a monumental step forward," U.S. Secretary of State John Kerry said as he left the talks in the Rwandan capital of Kigali late on Friday. Under the pact, developed nations, including much of Europe and the United States, commit to reducing their use of the gases incrementally, starting with a 10 percent cut by 2019 and reaching 85 percent by 2036. Many wealthier nations have already begun to reduce their use of HFCs. Two groups of developing countries will freeze their use of the gases by either 2024 or 2028, and then gradually reduce their use. India, Iran, Iraq, Pakistan and the Gulf countries will meet the later deadline. They refused the earlier date because they have fast-expanding middle classes who want air conditioning in their hot climates, and because India feared damaging its growing industries. The deal binding 197 nations crowns a wave of measures to help fight climate change this month. Last week, the 2015 Paris Agreement to curb climate-warming emissions passed its required threshold to enter into force after India, Canada and the European Parliament ratified it. But unlike the Paris agreement, the Kigali deal is legally binding, has very specific timetables and has an agreement by rich countries to help poor countries adapt their technology. A quick reduction of HFCs could be a major contribution to slowing climate change, avoiding perhaps 0.5 degrees Celsius of a projected rise in average temperatures by 2100, scientists say. Environmental groups had called for an ambitious agreement on cutting HFCs to limit the damage from the roughly 1.6 billion new air conditioning units expected to come on stream by 2050, reflecting increased demand from an expanding middle class in Asia, Latin America and Africa. Donors had already put $80 million in a fund to start implementing the agreement, said Gina McCarthy, administrator of the U.S. Environmental Protection Agency. But Sergey Vasiliev, the head of the Russian delegation, said Russia's estimates of the costs were higher and argued countries' contributions to a multilateral fund to help poor countries adapt their technology should be voluntary. The details of the funding will be finalized at a later meeting. - World's nations agree elephant ivory markets must close - Study: Global temperature reaches level not seen in 115,000 years thanks to climate change - European Parliament backs ratification of Paris climate deal - Moldova will have first mobile laboratory for tracking, prevention and control of anthrax - Moldova to sign cooperation agreement in labor, social protection and family field with Lithuania - Climate change experts fear 'bonfire of regulations' after Brexit

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Today, tooth decay is the most common childhood disease. The figures in Spain are devastating; in 2012, one in three children suffered from caries in at least one tooth. Furthermore, according to the results of the Spanish Observatory of Oral Health in Spain, 2015, carried out by the Council of DentistsIn fact, it is children under 7 years of age who are the least likely to visit the dentist. Caries is a disease that particularly affects children, and can even diminish their physical development and their ability to learn, which is why we must pay the necessary attention to it and put our children in the hands of the best professionals. See a dentist as soon as the first teeth appear. It is vital to see a paediatric dentist when the first teeth appear. So-called 'early childhood caries' is a disease that is more prevalent than is often believed, and may even be related to the baby's habits as an infant. The paediatric dentists are professionals whose training is specialised in the oral care of the very young. A single visit to the specialist during this first period can prevent a multitude of problems in the future. The use of soothers or bottles are issues that paediatric dentistry knows well and can advise us on. The dental clinic Velez & Lozano has qualified professionals with extensive experience in the care and prevention of children's oral health. By making at least one visit a year during the first years of life, the number of children's cavities decreases drastically. These professionals control and monitor the formation of the jaw, teeth, etc., and can prevent serious problems. Learning oral hygiene habits in a fun way. Introducing children to the brushing routine can be an arduous task if approached too seriously. If, on the other hand, we help children to see this part of the day as a game, we are likely to get a better response from them. Moreover, as the brushing technique will be with them all their lives, teaching them the right way can be key to their oral health as they grow into adulthood. The use of games and even songs that teach children the correct brushing techniques for each group of teeth will help them to remember the correct procedure in a fun way. It is also important to remember that the use of personalised toothbrushes can help them to become more comfortable with the activity of brushing. The toothbrushes used by the youngest children should be approved and of medium hardness, preferably electric from the age of 6 so that they can control the pressure they exert on their teeth and gums.

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Government shutdown is a natural part of a grand old bargaining process Despite the shrieking accusations and opportunistic grandstanding, this government shutdown could one day serve as a textbook example of political bargaining. Perhaps both parties are doing exactly what they need to do. This episode in American history just may be a fascinating demonstration of the legislative capacity of the democratic republic that is the United States of America. The “power of the purse” is a controversial topic these days. In the Federalist Papers, No. 58, James Madison noted that the House of Representatives was given this power as a “complete and effectual weapon … for obtaining a redress of every grievance …” Historically, however, using the power of the purse in such a dramatic and comprehensive way has not been fashionable. The intensity of the Republican ethic has prompted House members to vote against seemingly pedestrian funding measures in an attempt to block implementation of the Affordable Care Act. This usage of the power of the purse has now wrought a government shutdown. One reason why this approach is traditionally so uncommon is because constituents generally do not favor a government shutdown, and politicians respond to that. It’s a politically risky move. Now, many people are looking to place blame. Some blame the Republicans for taking a brazen approach to governance. Some blame the Democrats for taking a cocksure approach to negotiations. Many say both are blameworthy. However, if you’re interested in keeping your blood pressure at a manageable level, you may want to view this predicament from a new perspective: The government shutdown is due to natural causes. Both sides have acquired substantial amounts of political capital in the form of constituent support for their respective platforms. Now, that capital is being tested in an epic showdown. Who blinks first? The fact of the matter is that we do not live in a politically homogenous country. Even within each of the two parties, there are a variety of flavors. We’ve reached the final stages of a natural bargaining process framed by widely dissimilar interests. And while it’s unfortunate for government employees to be caught in this strategic crossfire, we should remember that both parties also have the power to restore normalcy on a whim. The House Republicans could pass a “clean” continuing resolution. The Senate Democrats could agree to pass the narrower funding proposals offered by the House Republicans. These facts indicate that neither side is actually too upset about the current government shutdown. Instead, they both view it as an opportunity to continue trying to out-bid the opposition using what’s left of their political capital from constituent support. The most important question now is, “Whose political capital will dissipate first?” The answer: It depends on how the dominos fall. Pennsylvania Republicans are already feeling the pressure, and have alluded to supporting a “clean” continuing resolution. However, the Republican Party at large may be willing to withstand the pressure of the shutdown to achieve certain results. Despite previously insisting on completely defunding “Obamacare,” the GOP could very likely settle for narrower concessions, many of which have already been proposed. If the Republicans can hold the line, various Democrats may succumb to pressure to entertain negotiations. It’s possible that both sides will eventually make concessions and meet somewhere in the middle. Despite the irritatingly drawn-out theatrics, this aggressive and animated bargaining procedure is the natural result of the abundance of political capital on both sides of the aisle. In a sense, we the people have brought this on ourselves. We the melting pot, we the motley crew. While both parties will continue to hurl hyperbolic insults and fan the flames of constituent emotion in the short-term, it’s worth remembering that in the long-term, both sides are taking a strategically rational approach on behalf of their interests. Ultimately, lack of homogeneity within either party could lead to negotiations and compromise. Is it ironic that our differing opinions could somehow lead us beyond this clash of differing opinions? Or is it simply American? Either way, in the name of civility, let’s keep (relatively) calm as we bargain on. Kevin Brett is a student at Temple University’s Beasley School of Law, where he was selected by a faculty committee for a highly competitive program in Washington, D.C., designed to study the intersection of law and public policy. As a Law and Public Policy Scholar, Kevin completed a white paper analysis of the Jumpstart Our Business Startups (JOBS) Act pertaining to entrepreneurship and securities law while interning with the U.S. Senate. WHYY is your source for fact-based, in-depth journalism and information. As a nonprofit organization, we rely on financial support from readers like you. Please give today.

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Mass-Engineering of Cells for Cancer Therapies What if you could cure cancer by re-engineering patients’ cells to better target and destroy their own tumors? “With the advent of powerful new cellular engineering technologies, this is no longer the stuff of science fiction,” notes a UC Riverside press release. A new microfluidic technology dubbed deterministic mechanoporation (DMP) can mass-produce, at low cost, engineered cells with holes that allow for delivering genes (see below). “This simple, but elegant nanomechanical poration approach provides significant advantages relative to existing gene delivery techniques,” said research leader Masaru Rao. “For example, since viral vectors make up a large fraction of the overall manufacturing cost of current cell therapies, their elimination through the use of DMP holds potential for considerable cost reduction.” “In fact, in our paper we show that DMP can engineer primary human T cells, the same kind of cells used in CAR-T therapies, with efficiencies that exceed a state-of-the-art electroporation tools by more than four-fold,” said Rao. Science fiction indeed, and an exciting future ahead. New Device Punches Holes in Cells for Gene Delivery Engineers at UC Riverside and City of Hope National Medical Center have invented a microfluidic device that addresses one of the most costly steps in the engineered cell therapy manufacturing process, namely gene delivery. Deterministic mechanoporation, or DMP, uses fluid flow to pull each cell in a large population onto its own tiny needle, as described in a research paper published in Nano Letters. The flow is then reversed to release the cells from the needles, leaving a singular and precisely defined pore within each cell that allows for gene delivery. Eliminating viral vectors can substantially reduce cost. Inhalable Nanoparticles for Lung Cancer Immunotherapy Scientists at Wake Forest Baptist Health have developed a new approach to treating lung cancer with inhaled nanoparticles. A proof of concept study published in Nature Communications describes a nanoparticle-immunotherapy system that delivered immunostimulants via inhalation to a mouse model of metastatic lung cancer. The results are encouraging, and the new inhalable immunotherapy appears to present several key advantages to previous methods. Protein Drives Growth of Pancreatic Cancer Scientists at Francis Crick Institute have identified a protein that drives growth of pancreatic cancer, and which could be a target for new treatments. A study published in Nature Cell Biology shows that a protein, called CD9, is present in pancreatic cancer stem cells. This protein could therefore be used as a marker to help locate these cells. The study further established that this protein is not just a marker of cancer stem cells, but also promotes their malignant behaviour, which could guide the development of new treatments that are targeted at the protein. Anthrax Virus Can Target Cancer While Ignoring Healthy Cells Researchers at Purdue University, supported by partners at Indiana University, MIT, and Harvard University, have found a way to combine the anthrax toxin with a growth factor to kill bladder cancer cells and tumors. The research results, published in International Journal of Cancer, are promising and suggest the possibility of new therapies able to kill cancer cells without harming normal cells. Injectable Flexible Electrodes for Nerve Stimulation University of Wisconsin-Madison biomedical engineers and their collaborators have made a significant advance that could dramatically reduce the cost of neuromodulation therapy, increase its reliability, and make it much less invasive. By electrically stimulating nerves, neuromodulation therapies can reduce epileptic seizures, soothe chronic pain, and treat depression and a host of other health conditions without the use of conventional drugs like opioids. The engineers have developed a new type of electrode dubbed "injectrode," described in a research paper published in Advanced Healthcare Materials, which can be injected as a liquid and then cure in the body. According to the engineers, this could eventually result in a new kind of neural interface system. CRISPR Can Provide Universal Electrochemical Biosensors Case Western Reserve University researchers have converted the CRISPR 'recognition induced enzymatic signal' to an electrical signal, which was then used to detect the biomarkers for viruses such as HPV or parvo, as described in a paper published in Angewandte Chemie International Edition. The researchers hope the end result could be a new 'universal biosensing' point-of-care medical device, similar to the existing commercial blood-glucose sensor, which rapidly and accurately detects viruses. Don't miss a beat! In our Pulse Newsletter, Thrivous curates the most important news on health science and human enhancement, so you can stay informed without wasting time on hype and trivia. It's part of the free Thrivous newsletter. Subscribe now to receive email about human enhancement, nootropics, and geroprotectors, as well as company news and deals. Read more articles at Thrivous, the human enhancement company. You can browse recent articles in Thrivous Views. See other Pulse Newsletter articles. Or check out an article below. L Theanine Benefits Cognition and Sleep L Theanine is an amino acid found naturally in the tea plant, also known as camellia sinensis. People commonly use ... Read the article → THC Additive May Cause Lung Injury from Vaping Vitamin E acetate, an additive sometimes used in combination with tetrahydrocannabinol (THC), may be to blame for recent cases of ... Read the article →

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Anthony Mournian’s portrait of Calvin Grier a master carbon printer, from starting a Carbon printing service, his art and his eBook “Calibration for Alternative Photographic Processes” where we learn to calibrate prints. In the timespan of well over a century and a half, the alternative photographic process called Carbon Transfer Printing has seen many changes. Like tributaries to a river, many individuals, including William Henry Fox Talbot, Alphonse Louis Poitevin, Louis Ducos du Hauron and Joseph Wilson Swan have contributed to the creation and evolution of this beautiful and permanent process. The process wound its way through many evolutions, but none as great as the modernization of the process in the 1970s by Charles Berger. Berger made a huge update to the process, incorporating a stable and less toxic-non-dichromate sensitizer, Image-setter negatives, a pin registration system, plus modern color separation techniques, allowing the process to reliably reproduce a photograph. Discovered by Alphonse Louis Poitevin in the 1850s, Carbon Printing on the one hand is probably the most durable and archival of all photographic processes. On the other hand, it is also one of the more daunting and complex processes, offering its rewards only to those with patience and fortitude, fine attention to detail, and a strong sense of self capable of dealing with frequent failure. In the same way, a large-format camera demands a step by step progression to set up and capture an image, Carbon Printing requires multiple steps, each of which must be performed with care and in a prescribed order. Daguerre’s groundbreaking Daguerreotype process gave superb detail, but the silver discolors with tarnish when not properly stored in a sealed display case and, without a negative, was not reproducible. Henry Fox-Talbot’s competing Calotype process used sensitized or “salted” paper for his “Pencil of Nature” images, but was subject to fade with continued exposure to stronger levels of light. Not long after, Sir John Herschel helped solve the fading problems with his discovery of hyposulphite of soda, or “Stop,” as a way of preventing further development of an image, and by doing so “fixing” the image. Poitevin‘s discovery of Carbon Printing shortly before the beginning of the Civil War in the floundering and divided United States of America solved the nagging problem of fade. The earliest stages of Carbon Printing involved coating pigmented gelatin directly on paper, which was sensitized with toxic Dichromate. The emulsion was hardened upon exposure to light through a negative, then the soft unhardened gelatin was washed away under hot water. Now there was a Direct Carbon Print, to be sure, but its tonal range was limited because of hardened gelatin being above the soft gelatin, which caused much of the tonal range to wash away during development. Calvin Grier’s hero in Carbon Printing history is Sir Joseph William Swan. Building upon Poitevin’s discovery, Swan’s ingenious concept was to create separate support with the pigmented gelatin called the “tissue”, then “transfer” the image to a “permanent paper support.” Now the soft gelatin was above the hardened gelatin and could be easily washed away during development, leaving a much more refined tonal range. This is called a “single transfer carbon print.” By adding the “transfer” step, Swan was able to easily make photographs with a much more refined tonal range. Swan patented the transfer process in 1864. Generally known as Carbon Printing because of its original use of Carbon, or lampblack as the pigment, the Carbon Printing process can use almost any color pigment, alone or in combination. In other words, a Carbon Print need not be black and white, and it need not be monochromatic. Piggybacking off the advancements from the end of the 20th century, enter Calvin Grier of Valencia, Spain. Grier, born in Minnesota, USA, had parents who encouraged, or at least allowed him to pursue his many and varied interests. When Grier was about twelve he discovered photography. He built himself a workspace in cramped quarters under a staircase and began to experiment with developing negatives. His interest in the process was intense, but it didn’t last be-cause music caught his young eye. He thought for a time he would become a concert musician in a symphony orchestra. Photography took a back seat for more than a decade while he studied music. As time passed Grier realized he wasn’t happy as a musician, and needed a change. About six years ago he decided to put aside music and to devote himself to commercial photography doing weddings and sports events. But did Calvin Grier really want to be a commercial photographer? Or was there a place for him within photography to which he could turn his talent for problem-solving while producing tangible products of his efforts? Commercial photography wasn’t as fulfilling as he had hoped and he realized, as with music, the problem was his need to create a tangible object with his hands. With a strong talent for problem-solving, a trait useful in photography as well as engineering, Grier likes to see a product of his own hand. Among other talents, Grier worked summers as a carpenter to help pay for school. He considered becoming a carpenter during 2014, then stumbled on the alternative photographic processes. For Grier it was the perfect combination: photography, problem-solving, and working with one’s hands. Grier decided to try the Alternative Process of Carbon Printing, but with a twist. From 2014 to 2016 he worked twelve hours a day learning the ins and outs of Carbon Printing. It’s a long way from a “single transfer” with a commonly used Inkjet negative resulting in a black and white photograph, to a triple transfer color print going beyond basic CMYK color separations while introducing tonal separations along with Imagesetter negatives. Calvin Grier decided to open a Carbon printing service, Wet Print. With capturing the image no longer his primary goal, Grier worked to become a master of printing the images for others. He put aside his commercial photography and opened Wet Print, a business devoted to the production of the highest quality Carbon Prints. The biggest hurdles he overcame in the two years of testing were getting smooth highlights, creating a system for making tonal separations, and learning how to accurately “calibrate” a print. As his skill in making “Wet Prints” advanced, his business developed. Since 2017 he has printed for photographers ranging from enthusiasts to Oscar winning cinematographers. The prints shown here are accompanied by short statements by the photographers who made the original images. Alongside his business of printing for others, Calvin Grier developed workshop courses. These are five to ten-day intensive workshops limited to four students at a time focusing on learning the fundamentals of Carbon Printing. In his studio in Valencia, Spain he has taught over 60 students from 25 countries. An excellent, logical, well-organized workshop is worth its weight in gold. Many of Calvin Grier’s students travel long distances for his training and advice. The goal is for each student to leave the workshop with a successful Carbon Print showcasing the photographer’s artistry, and sufficient knowledge to return home to continue Carbon Printing using Grier’s methods. The workshops for 2020 and 2021 are sold out, with waiting lists for future workshop dates. Calvin Grier’s latest E-book publication is “Calibration for Alternative Photographic Processes.” The course sequence takes the student through calibration in each step of the Carbon Printing process. Little of the actual carbon process is discussed because the goal is to make a process neutral E-book limited to calibration that can be applied to any of the alternative photographic processes that use a digital negative. What is Calibration? It’s the correction of printed values against a traceable reference standard. As used in his e-book, Calibration involves setting a density, creating tonal separations and linearizations, (the even distribution or separation of tones,) then combining those elements to create the best print possible, or one that is as close as possible to the desired result. In his introduction to “Calibration,” Calvin Grier says, “A well-calibrated workflow [allows] you to predictably print a digital interpretation of your photograph. An un-calibrated print might come out too light or with too much contrast compared to what you had hoped for. This results in frustration and high costs in having to remake negatives and the print. Good calibration will eliminate trial and error from your workflow.” There’s almost no information available on making alternative process prints in color, prints with tonal separations, or how to choose an appropriate density. Most publications for the alternative processes focus on linearization, but there’s much more to calibration. Calvin Grier walks the reader through all the steps needed to choose a correct density, to create and linearize tonal separations, and to use ICC profiles to create prints that look as expected. With proper calibration, there are no more prints that come out too dark, with banding, or with a color cast. Traditional monochromatic black and white carbon prints require a single analog/in- camera, Imagesetter or digital negative. Carbon Color Prints, however, require individual negatives or color separations for each of the CMYK, or Cyan, Magenta, Yellow, and Black. The color separation negatives are combined during the printing process in a specific order. Grier begins with Yellow, followed by Magenta, then Cyan, and finishes with Black. The CMYK negatives are overlaid one at a time in sequence and in perfect register to complete the color printing process. This introduces a complexity requiring a minimum of four negatives, (or three negatives in the case of a CMY print with no black, which is usually how analog color prints are made.) The levels of density in individual color separations, the number of negatives and number of separations increase rapidly. As each negative is added to the process, an additional printing “pass” is required. It doesn’t take long for the total number of “passes” to add up, and with it the requirement for exact registration of the negative, at the desired density and correct linearity. It’s easy to skip a step or to make a mistake in printing. A perfect Color Carbon Print requires perfection at each step. The result can be breathtaking, and rare. In a traditional single transfer Carbon Print, using an in-camera negative or a digital negative there are a number of steps, each of which must be accomplished correctly and in proper sequence. Misstep at any stage and the print is ruined. Calvin Grier says in a single transfer print there are ten steps. A monochromatic print takes him about an hour. For a triple transfer six layer color print there are closer to 120 steps using as many as ten Imagesetter negatives and color separations. Again, each and every step must be performed with precision in proper sequence. Any misstep along the tortuous path ruins the print. Sum total: it can take a week or more to make a color print such as Michael Strickland’s “Sierra Wave,” or Calvin Grier’s portrait of “Aida.” Grier says few people are willing to endure the level of frustration to reach the success rate for each step of 99.9%, in which case only about one in ten prints end up in the trash. At a 99% success rate for each step, over two-thirds of the prints are failures. For that reason, very few people print in color. Grier repeats with justification Ansel Adams’, “The negative is the score, the print is the performance.” You must know and understand the elements of the negative before you can put them together in the beauty of a nuanced and subtle final print ranging from the softest and most delicate high- lights of a print such as Grier’s “Peony,” to the deep shadows of Arun Patel’s “Haifoss Waterfall” In 2020 and 2021 Grier plans to devote a major portion of his time to research. He plans to do a number of stability and permanence tests with different pigments, gelatins, and papers. Also on the agenda are to research alternative ways to harden gelatin, and to do another round of testing of available materials for the process as well as start applying his calibration methods to other processes. With too little time to do it all, he would like to write more books on the Carbon process as well as color theory and to work on a portfolio of his own photography and prints. Calvin Grier is a master Carbon printer, an inspiring teacher and a clear, logical writer. If you want to learn more about calibrating your prints in any of the Alternative Processes, click here to read more about Calvin’s latest E-book, “Calibration for Alternative Photographic Processes”. Calibration for Alternative Photographic Processes A 4-part series on getting your alt. proc. prints right. Become an expert calibrator.

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New research unravels what was previously a mystery: how do taste buds change in people with obesity? Although the new study — now published in the journal PLOS Biology — was carried out in mice, the findings shed a clarifying light on a poorly understood phenomenon: the blunting of taste buds frequently noticed in people with obesity. Eating delicious food activates reward centers in the brain. Dopamine — the “sex, drugs, and rock ‘n’ roll” neurotransmitter — is released every time our taste buds come into contact with yummy flavors. Taste buds are nerve endings that comprise 50–100 different cells. It’s a fact that people with obesity tend to So, scientists at Cornell University in Ithaca, NY, led by Andrew Kaufman and Robin Dando, set out to explore the link between taste buds and obesity. For 8 weeks, Kaufman and team fed rodents either a regular diet (consisting of only 14 percent fat) or a high-fat diet (which consisted of 58 percent fat). After the study period, mice with obesity had fewer taste buds than the regular mice. In fact, the high-fat diet reduced the number of their taste buds by 25 percent. But why did this happen? The researchers also found that mice with obesity had higher levels of a pro-inflammatory cell called TNF-alpha, a class of pro-inflammatory cytokine. Kaufman and team also genetically engineered a mouse model that was incapable of producing these cytokines, and interestingly, the researchers found that these mice did not lose any taste buds — despite being fed a high-fat diet and developing obesity. Additionally, the scientists injected TNF-alpha into the tongues of normal-weight mice. This caused the rodents to lose taste buds as well, despite the fact that they did not have obesity. These findings “demonstrate that chronic low-grade inflammation brought on by obesity […] is likely the cause of taste dysfunction seen in obese populations — by upsetting this balance of renewal and cell death,” write the authors. In fact, the researchers noted that mice with obesity had a higher rate of taste bud cell death, while the rate at which new progenitor cells appeared in the tongue decreased. “These data together suggest that gross adiposity stemming from chronic exposure to a high-fat diet is associated with a low-grade inflammatory response causing a disruption in the balancing mechanisms of taste bud maintenance and renewal.” “These results may point to novel therapeutic strategies for alleviating taste dysfunction in obese populations.”

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is labeling enough for preserving the biodiversity of food? Published: 02-03-2014 - Last Edited: 08-11-2022 The problem of organic labeling requirements is based in food safety. Seeds of Corruption, written by Mary Zhou states; “No matter how short the duration of the Monsanto Protection Act, the fact that it was passed at all affirms Monsanto’s status as a GMO giant that needs to be held accountable for its actions. Congress’s ignorance combined with Monsanto’s increasing economic prowess should be fair warning to us as consumers- that we are no longer in control of what we consume.” Is labeling enough for preserving the biodiversity of food? Community gardens simply celebrate native food by establishing connections between the grower, the laborer, the cook, and the consumer. Once GMO seeds are planted the ecosystem adapts. Native seeds no longer contribute to diversity. This creates the need for native seed production by heirloom seed saving. New disease is a symptom of Genetically Modified Organisms (GMO) monoculture farming, or our inherited agricultural industry. GMO seeds have been engineered to produce specific results. Organic gardening with heirloom seeds is blossoming only through green industry exposure. Glass Corn is an example of some of the best from heirloom gardens. Save your seed projects use heirloom gardening techniques. Choices such as eat organic food, or one ingredient foods are not yet available everywhere. With genetically engineered seeds, the chemicals applied in the growing process are specific to only this seed, not the weeds, or close neighbors. The ignorance of seeds which have been engineered as food cannot remain. Commercial food production increases profits by larger and larger facilities that are sustained by vastly foreign mono-cultural crops to feed people in faraway places. How are we educating ourselves on the quality of food sources? Research how the food is traveling, and compare quality. The global threats of genetically modified organisms is extreme in India. Here, outraged farmers fight a flooded agricultural seed market, suicide. Several other countries including Switzerland, Ireland and France have adopted policy against these genetically engineered food sources. Stating the lack of research on health effects to humans, as well as deleterious effects on the ecosystems surrounding these mono-culture crops. Heirloom seeds change the monoculture of farming. Serious consideration needs to be given to transportation of food. Advocates of healthy lifestyles extend their consumer dollars by consuming products from local farmers. Policy advocates work to eliminate barriers that prevent farms from providing food to neighboring towns. Additionally, there is growing support for educational environments which promote heirloom garden seed propagating techniques. Educational centers treat all community members as learners because idigenous knowledge about native seeds may hold the answer to diseases that have developed since monoculture agriculture began. The local municipality benefits from exposure to quality food, social aid, and sustainable conservation projects. Consuming food grown locally, never should have escaped any country’s economic model. There is always a choice. Native seeds projects are inter-generational diverse, cross-cultural, community building events. Community gardens potentially host native seed education. Further collaboration with social aid organizations (churches, schools, military) will increase effective use of space in residential communities. Even greater is the potential of aquaponics, or living machines to further enhance communities that support farm to table gardens. Read next >> lifestyle tweaks to help conserve our oceans

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T Glauser. Hepatitis C. The Internet Journal of Health. 1999 Volume 1 Number 1. The first report of a blood-borne virus that caused hepatitis (inflammation or swelling of the liver) that was not either of the 2 well-known viruses, hepatitis A or hepatitis B, was published in 1975. The new virus proved very difficult to isolate by the means then currently available, but in 1988, the hepatitis C virus was finally identified. It was not until 1993 that a specific test was developed that could reliably and rapidly identify the virus. In the United States, approximately 1.4 % of the population has antibodies to hepatitis C, but this percentage is higher in developing countries. Hepatitis C is transmitted primarily through contaminated blood. Risk factors for contracting the virus include intravenous drug use (the most common source in the US), receiving a transfusion of infected blood (not a very common source in developed countries, where testing of donated blood for hepatitis C is now routine, but this source continues to be of concern in third-world countries), hemodialysis, and tattooing. There are now a number of very accurate tests available to diagnose hepatitis C, but testing is nonetheless a complicated process for 2 reasons. The first is that the blood levels of virus rise and fall over time. The second is that the hepatitis C virus exists as 6 different genotypes, more than 30 subtypes, and each of these mutates rapidly into what are called quasispecies. These factors make treatment difficult, too. People with acute (newly infected) hepatitis C tend to have mild infections. Most people have no symptoms at all, with only 25 % developing jaundice. Very few people with acute hepatitis have liver injury or failure. Unfortunately, 80% of people with acute hepatitis C do not fight off the virus and they go on to develop chronic hepatitis C. Chronic hepatitis C is associated with a number of complications, including fibrosis and cirrhosis of the liver and liver cancer. Nevertheless, a majority of those infected with hepatitis C virus live a normal life span without apparent liver disease. The diagnosis is often made when laboratory studies obtained during a routine physical examination are not normal. The decision to treat infected individuals is a complex one. Pretreatment factors that help conclude whom to treat include the amount of virus in the blood, the viral genotype, and the number of viral quasispecies. Another consideration is the amount of liver injury as measured by how much of a liver enzyme, ALT, has been leaked into the bloodstream, as well as the presence of cirrhosis or liver decompensation. This means that all patients have a liver biopsy before starting therapy. Other medical problems the patient has, their ability to adhere to treatment recommendations, and any previous treatment failures are also factors in whom to treat. Treatment has the potential to eradicate the virus because this virus does not incorporate itself into the human DNA. Treatment has proved difficult, however, because the virus replicates and mutates so quickly. Currently available therapies are inconvenient (they involve an injection three times a week, as well as daily pills), lengthy (12 months), and have side effects. Thus, only patients who show signs of liver injury and are willing to undergo this rigorous regimen are candidates for treatment. The treatment of hepatitis C is constantly being improved. In 1986, a pilot study reported that therapy with interferon a led to remission in a proportion of patients with non-A, non-B hepatitis and this was confirmed in a series of randomized clinical trials. From the results of these studies, a standard interferon a regimen was defined. Three forms of interferon a are currently approved in the US for the treatment of HCV infection, and a fourth interferon a is approved for this use in other countries. Side effects include initial flu-like symptoms, fatigue, bone marrow suppression, and neuropsychiatric disorders including depression and psychosis. Side effects are dose-dependent, and while dose reduction is helpful, can lead to withdrawal of therapy in 15% of patients. The standard interferon a regimen leads to normalization of liver function studies and a loss or decrease in the amount of hepatitis C RNA in the blood at end of treatment for 50% of patients, and a sustained response for one year or more in 25% of patients. This means that only one quarter of patients given this regimen have long-term remission or cure. Attempts to improve the sustained response rate have included increasing the dosage, the dose frequency, and the duration of treatment. Increased duration of therapy significantly increases the sustained response rate, but the long-term results of increased dosage and dose frequency have been disappointing. Other agents have been used for the treatment of hepatitis C infection, although none as successfully as interferon a . Amantadine and rimantadine are both oral drugs that are used to treat influenza A. Trials using these drugs have had some success in producing sustained responses in patients infected with hepatitis C virus. Ribavirin is an oral drug that has been effective against a range of viruses. Ribavirin used alone for the treatment of hepatitis C virus infection decreases the amount of ALT in the blood and improves the liver cell structure in 30% to 50% of patients, but does not affect serum hepatitis C virus levels: that is, it helps the symptoms but doesn’t cure the infection. The limited efficacy of using one drug alone led to studies assessing combination therapies. Multiple agents given simultaneously may block viral replication by acting at different target sites. Combinations of 2 and 3 different drugs have been studied. The most commonly used involves standard interferon a plus ribavirin. This leads to a sustained response in 42% of patients. Triple therapy using interferon a , ribavirin, and amantadine was recently studied in a small pilot study. Triple therapy led to a response in 70% of patients who had not responded to standard interferon a therapy, and was well tolerated. Other recent efforts to develop a more successful treatment for HCV have focused on altering the interferon a molecule by attaching one or more chains of polyethylene glycol (PEG) to it, forming a selectively protective barrier around the base molecule. This increases the amount of time the drug remains in the bloodstream, making it more effective. Modifying interferon with polyethylene glycol has recently shown great success in increasing the percentage of sustained responders with no change in safety.

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When Hazard Larken was born from 1750 to 1777, his father, Capt David Larkin, was 47 and his mother, Mary Knowles, was 46. He died from 1755 to 1856, at the age of 106. English: from a medieval personal name, a diminutive of Lar-, Lor-, both pet forms of Lawrence , formed with the addition of the Middle English suffix -kin. Irish: shortened Anglicized form of Gaelic Ó Lorcáin ‘descendant of Lorcán’, a personal name from a diminutive of lorc ‘fierce, cruel’. This Gaelic name was often regarded as an equivalent of English Lawrence . Possible Related Names As a nonprofit, we offer free help to those looking to learn the details of their family story.

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In our district, sixth grade is the end of a significant time period as student prepare to move to middle school. Recalling major events spanning from kindergarten through sixth grade... The rest of this content is restricted to Choice Literacy members. Join us today for instant access and member-only features: Get full access to all Choice Literacy article content Get full access to all Choice Literacy video content Receive members-only product discounts for online courses, DVDs, books and more

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Not a member? Sign Up! Enter Username or Email to reset. Managing autism spectrum disorder (ASD) may be more challenging now that kids are supposed to stay home to be safe from COVID-19. Without the usual intervention of developmental pediatricians or specialists involved in a child with autism’s program, parents and caregivers are left to manage the situation themselves. Findings from initial studies show that advanced medical imaging is a powerful tool for detecting early signs of autism. This tool also helps in investigating brain structural changes in children with ASD. Using brain imaging data, medical professionals can gather insights on brain activity and how it responds to various environmental factors. Children with autism may have difficulty adjusting to changes in the environment, lifestyle, and routine, leading to stress and anxiety. Thus, setting routines and having clear expectations can help your child understand what’s going on around them and help them cope during these trying times. Here are some valuable tips for managing autism during the COVID-19 quarantine. Setting a routine is helpful for anyone in the family, especially for children with ASD. The predictability of routines helps your children understand what behavior is expected of them. Changes in routine can be overwhelming for kids on the autism spectrum. Try sticking to their daily schedules, such as regular wake-up time and bedtime, screen time, meal and snack times, and household chores. This practice will provide your children with cues for different parts of the day and help maintain their daily living activities. At the end of each day or activity, allow your children to check off their completed tasks. Help your kids take control by giving them an opportunity to make a couple of choices every once in a while. For example, you can ask what activity your child would like to do next, or let them choose what to eat for lunch. Also, it is helpful to incorporate new routines to include schoolwork and physical activities. You can use your children’s school schedule as a guide. Don’t forget to add breaks in between activities. Including a transition helps your kids prepare for “school” mode and “out-of-school” mode. [Related: 6 Ways to Support Children with Autism During the Pandemic] Once you have organized a routine, create visual schedules so your kids know what to expect. Concrete, visual cues and to-do lists are beneficial tools that prepare your children mentally for the day or tasks ahead of them. You can be as creative as you want and work with what you have in your home. Create child-friendly visual schedules with pictures, drawings, and Post-it notes. Put them in an easily accessible area, like your children’s room or workspace. Developing a clear structure and set routine helps reduce your children’s anxiety. It often takes a while for kids to get used to these activities, so it’s essential to stay patient, guiding them through the schedule several times each day. According to the National Autistic Society, social stories can help people with ASD learn appropriate behaviors and develop a greater social understanding. Social stories are brief descriptions of a specific situation, event, or activity, including details of what to expect in that situation and why. Children on the autism spectrum need extra support to understand what’s going on around them and what’s expected of them. Using written or visual cues may help your children navigate unfamiliar situations and adapt to new routines. Through social stories, you can also teach and explain to your kids what COVID-19 is. It will help them understand the following: During this time, helpful therapies and interventions outside the home might be paused or discontinued. You can contact your child’s school or other therapists to determine which treatments are available to continue at home. If you are working at home and caring for your children during quarantine, try creating different activity zones. Allocating certain areas to specific activities may help separate your personal time and time with your kids from work time. For instance, you can designate parts of your living space for academic activities, eating, and recreation. Getting up and doing different things in different places encourages physical movement, even if you’re staying home. Technology may also be necessary as most resources are currently accessed via computers, tablets, and phones. Set clear limits on screen time for your children. You can use visual schedules to help your kids understand when they can use gadgets and to help them determine if it’s for educational or recreational purposes. Children on the autism spectrum may express their anxiety or fear by throwing tantrums and displaying challenging behaviors. Find calming or coping strategies as a proper outlet for your child’s emotions. Take note of the activities that help your child calm down. It may be through deep breathing, exercise, listening to music, writing, reading, or drawing. Schedule time for coping strategies throughout the day and include reminders in the kids’ visual routines. To build a stronger relationship with your child, talk to them regularly and ask them to express anything on their minds. Allow them to communicate their needs and wants intentionally. Offering emotional support will help ease their fears and anxieties. Try to schedule breaks for yourself during the day. Taking a breather is just as important for parents to relax their minds. Self-care is vital to our mental, emotional, and physical health. It is key to a good relationship with oneself and the people around us. Don’t forget to make self-care a priority, even in the most simple ways. Find some time for yourself to relax each day, take deep breaths, talk to a friend, or prepare nutritious and filling snacks. Allot time to engage with your children and plan some activities they can do alone. If possible, you can ask someone to watch over them while you take a break. Are you interested in the Medi-Cal Peer Support Specialist Certification Training? New Classes begin October 24. Space is limited.

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Want to earn continuing education credit for this article? Learn more. When you have a headache, do you really care what type you have. All you know is that it hurts and you want relief. If you really want relief though, it may be worth the time and effort to take the time and find out just what is causing it and what the best remedy may be. What helps to ease the pain of one headache could actually make another one worse. Relief for headaches also differs from one person to another, so knowing yourself and your habits will also help to reduce the frequency of, or get rid of completely, those nasty headaches. The International Headache Society has created a kind of dictionary of headaches, which includes approximately 200 types of headache disorders. For example, a migraine is broken down into six varieties, with each one of those broken down further into several causes or types. There can be a migraine without aura, a migraine with aura, a retinal migraine and so on. To make things a bit easier for the consumer, they have taken those 200 or so headaches and classified them into three broad types: Primary, Secondary and Cranial Neuralgia/Primary Facial Pain/Other. In the United States, the National Institute of Neurological Disorders and Stroke (part of the National Institutes of Health) have simplified it even further into Primary and Secondary headaches, bringing together the neuralgia and facial headaches into one or the other. Primary Headache Pain Primary headache disorders consist of four main groups: migraine, tension, trigeminal autonomic cephalgia and miscellaneous. They occur independently and are not caused by any other medical condition. They come about because of various events occurring in blood vessels, nerves and muscles, but not because of disease or injury. The most familiar primary headaches are migraine, cluster and tension. Secondary Headache Pain Secondary headaches are actually symptoms of some other underlying disorder or disease. These disorders can press or push on nerve endings causing pain. Secondary headaches can be caused by such ailments as high blood pressure, head injury, stroke, tumors, nerve disorders and even psychiatric problems. Cranial Neuralgia/Primary Facial Pain/Other The third category, Cranial Neuralgia/Primary Facial Pain/Other, is a category recognized by the International Headache Society but not the National Institutes of Health. The National Institutes of Health puts these types of headaches mostly in the Primary Headaches category. The causes of these headaches are often unknown and affect the trigeminal nerve (CN-V) or other nerves which affect the face and head including the glossopharyngeal nerve (CN-XII). The headache pain can also be caused by a cold temperature stimulus (eating icy cold foods or being in extremely cold weather). Neuraligia is nerve pain occurring without stimulation of nociceptor (pain receptor) cells. It is, instead, produced by changes in neurological structure or function. Massage for Headaches Massage therapy in and of itself is not a cure for headaches. It can, however, help to reduce their occurrence, their frequency and their intensity. Determining what type of headache a person has is the first step in deciding what massage techniques can be used. This needs to be diagnosed by a doctor. The client who says he or she had been having migraines for years, may actually have deep sinus headaches or trigeminal nerve pain. Many individuals who experience regular headaches do not tell the doctor about them and self medicate based on what they have read or what friends tell them. Symptoms can often be similar among sufferers of varying types of headaches. Always make sure the client has a definitive diagnosis before proceeding with massage designed to alleviate headache pain. Three Types of Headaches Massage May Help Ease - Tension Headaches – It is estimated that tension headaches are experienced by as many as 90 percent of the population. A person will usually feel it on both sides of the head as a kind of pressing or tight sensation. There is no one cause, though it can be aggravated by stress – and massage therapy is well-known for relieving stress. Whether it be Shiatsu or Swedish massage, just about any slow movement techniques can help to reduce stress. Stay away from deep tissue or invigorating strokes. - Migraines – Migraines are the second most reported primary headache. Approximately 12 percent of the U.S. population experience them, and they are the 19th most debilitating disease worldwide. About 18 percent of adult women experience them, compared to only about 6 percent of men. A migraine can last just a few hours or as long as three days, and can range from moderate to severe. If a person tells you he or she has a migraine and are out and about, functioning fairly well – the individual most likely does not have a true migraine. A migraine will usually incapacitate anyone who has one. Someone with a true migraine will most likely not want a massage at the time it is happening, but having a regular therapeutic massage may help reduce the frequency, duration and intensity of them over a period of time. A light touch Swedish massage once a week would be ideal, but even every other week or once a month can help. Cranial-sacral work, various Asian techniques and polarity therapy has also been found to help. - Secondary headaches include a wise range of causes. Because the reasons are so varied, no one type of massage can be recommended. For these headaches, some basic knowledge of pathology is needed as well as a thorough understanding of contraindications and more than just a nodding acquaintance with pharmacology. A secondary headache can be caused by injury – such as head trauma. It can also be caused by infection, high fevers, dental problems, alcohol or drug withdrawal, caffeine (caffeine can be a cause or cure for headaches – if you drink a lot of coffee or caffeinated beverages, suddenly stopping can cause a headache whose cure is to drink more of them!), concussions, overuse or misuse of prescription medication, strokes, cerebral aneurisms and sinus infections – just to name a few. To determine which type of massage might be beneficial, look first to the root cause. A massage technique that may help a sinus headache may be contraindicated for someone with a headache cause by a concussion. If a client comes to you complaining of persistent headaches, remember to do a thorough intake. You may even want to include a special section on your intake form for headaches. It will give you an indication of the cause as well as the technique that is safe to use and offer the greatest benefit. If the client says he or she has a certain type of headache, such as migraine, make sure you get an accurate diagnosis from a qualified physician. If the cause is unknown and severe, or the client is experiencing pain on one side along with any numbness, slurring of speech, sudden vision problems or other signs of possible stroke – call 911. Earn continuing education credit for this article contained in our Headaches, Facial Pain & Massage series. Click here to enroll. Massage for Headaches & Neck Pain Advanced Anatomy & Pathology Shiatsu Amma Therapy Swedish Massage for Professionals

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Many people with anxiety disorders understand that their thoughts are irrational, but they still can’t stop them.Anxiety disorders are often linked to depression. It’s important that both conditions are treated simultaneously. People with anxiety disorders — social anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder — or phobias spend most of their lives in an agitated state. After a while, that can take a huge emotional toll, and depression often sets in. There’s no conclusive explanation as to why anxiety and depression so often co-exist, according to the Anxiety and Depression Association of America, but you can find relief from both with the right treatment. Why Anxiety Leads to Depression Anxiety disorders are much more than just nervousness and worrying. They can cause terrifying fear about things that other people wouldn’t give a second thought to. “It’s a cycle,” says Sally R. Connolly, LCSW, a therapist at Couples Counseling of Louisville in Kentucky. “When you get anxious, you tend to have this pervasive thinking about some worry or some problem and you feel bad about it. Then you feel like you’ve failed, and you move to depression.” The two conditions have a complicated relationship: - The incidence of developing depression in addition to an anxiety disorder is high — almost half of all people with major depression also suffer from severe and persistent anxiety, Connolly notes. - “People who are depressed often feel anxious and worried, so one can trigger the other,” she says. “Anxiety often comes before depression.” - There may be a biological predisposition to both depression and other anxiety disorders. - People who have post-traumatic stress disorder (PTSD), an anxiety disorder, are particularly likely to also develop depression, according to the National Institute of Mental Health (NIMH). “Especially with anxiety, more so than depression, there often is some family history, and so therefore we think that there may be some genetic predisposition to this,” Connolly explains. “Some people are just worriers and pass it down.” Symptoms of Anxiety and Depression These are signs that a person may suffer from both anxiety disorder and depression: - Constant, irrational fear and worry - Physical symptoms like rapid heartbeat, fatigue, headaches, hot flashes, sweating, abdominal pain, and difficulty breathing - Changes in eating, either too much or too little - Difficulty with memory, decision making, and concentration - Constant feelings of sadness or worthlessness - Loss of interest in hobbies and activities - Feeling tired and cranky - Inability to relax - Panic attacks The Road to Recovery Both anxiety and depression should be treated together. Effective treatment strategies include: - Cognitive-behavioral therapy (CBT), which is often used to treat anxiety disorder with depression. CBT can teach people to manage their fears, anxieties, and depressive symptoms by figuring out what’s really causing them; people also learn how to take control of their emotions. - Antidepressant medications, which may be prescribed to help treat both conditions. These drugs are often used in conjunction with CBT. Selective serotonin reuptake inhibitors (SSRIs) are newer, commonly used antidepressants that offer fewer side effects than older antidepressants, according to the NIMH. - Exercise, which can also help both depression and anxiety disorders. Exercisereleases chemicals in the body that make you feel good, and it can help you relax. Taking just a 10-minute walk may alleviate symptoms for several hours, the Anxiety and Depression Association of America states. - Relaxation techniques, which include practicing meditation and mindfulness. Both can ease symptoms of both anxiety and depression and improve your quality of life, according to a large research review published in the March 2014 issue of JAMA Internal Medicine. - Organizations offering mental health services, which can include a hospital or support group in your community. Check out the National Institute of Mental Health or the Anxiety and Depression Association of America for more resources. Warning Signs You Shouldn’t Ignore Loved ones of those struggling with anxiety and depression should be on the lookout for these warning signs of a mental health crisis: - Poor daily self-care, such as refusing to perform personal hygiene habits, get out of bed, or eat - Sudden and extreme changes in mood - Becoming violent, threatening, or aggressive - Abusing substances - Appearing confused or having hallucinations - Talking about suicide or about not having a reason to live Treatment for anxiety disorders and depression needs to be administered and managed by a psychiatrist, Connolly says. “It’s really crucial for people with both [anxiety and depression] to have a good assessment to rule out bipolar disorder,” she says. Bipolar disorder, a condition in which emotions can swing from very low to very high levels of mania and depression, is treated much differently than anxiety disorder with depression. No one has to suffer from anxiety disorder or depression, and certainly not both. People with anxiety disorder should speak with a psychiatrist, therapist, or other healthcare professional about their symptoms, and start treatment before depression has a chance to set in. Read more about Foods You shall Eat Every Day to Beat Depression Source: Everydayhealth.com, Google.com

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ART, IMAGES, AND THE GLOBALIZATION OF CULTURES FROM THE PRINTED ERA TO THE INTERNET The VISUAL CONTAGIONS project studies the global circulation of images in the print era over a century, from the 1890s to the advent of the Internet. It describes and analyzes how certain images have circulated more than others - in reproductions, copies, pastiches, imitations -, through which channels and according to which chronology they have spread. The ambition is to understand what makes an image successful, but also to identify how the circulation of images has contributed to the globalization of cultures, and whether or not it reveals the symbolic domination of certain countries and cultures over others according to the times. Visual Contagions is a project in Digital Humanities: computational methods are applied to objects and questions in the humanities. Visual Contagions is a project in Digital Humanities: computational methods are applied to objects and questions in the humanities (here, art history and cultural history), along with more traditional methods. The team uses quantitative analysis, geographical and chronological visualization, digital analysis of texts, as well as computer vision - algorithmic description of content, style or period of images, automatic pattern recognition. These methods make it possible to approach and compare large corpora, on a global scale and over a long period of time. The results of the numerical study are then confronted with the historical interpretation of the images.

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What Happens If Timing Chain Is Off By One Tooth? Timing chains are among the most important components of the intricate engine mechanism. Its primary function involves transferring power from the crankshaft onto the camshafts or camshafts. In addition, the timing chain is used to coordinate (time) the openings and closings of valves according to the pistons’ location. The primary symptom of a timer chain missing the tooth is a loud rattling and a severe engine shake. If you spot this sign, you must switch off the engine. You should also have it repaired to avoid totalizing the engine. This blog will look at the signs of a timing chain breaking off its teeth and the reasons and solutions for this issue. How To Tell If The Timing Is Off On An Engine? Timing is a crucial element in internal combustion engines. It ensures that the engine’s valves are closed and open precisely at the appropriate time and that the spark plug ignites the mixture of fuel and air at the perfect time. If the timing isn’t right, it could result in low engine performance, lower efficiency of fuel, and even cause damage to the engine. Here’s a thorough guide on how to detect when the timing is not working in an engine: What Is Engine Timing? Engine timing is when the mixture of fuel and air is ignited in the combustion chamber, and the valves open and close. In a four-stroke engine, timing is achieved by the rotation of the crankshaft as well as the use of the timing belt or chain. The timing belt/chain links the crankshaft and the camshaft, which regulates the closing and opening of valves. How To Check Timing The process of checking the timing of an engine isn’t too difficult, but it will require specialized tools and understanding. Here’s a step-by-step guide for how to test the timing of an engine: Step 1: Locate The Timing Marks The first step in determining the engine’s timing would be identifying those markings. They are typically located on the crankshaft as well as the camshaft pulleys. The marks show the proper position of the pulleys concerning one another. Step 2: Remove The Timing Belt/Cover You’ll have to take off the cover or timing belt to determine the timing. This will allow you to see the marks for timing on your pulleys. Step 3: Set The Engine To Top Dead Center (TDC) The engine must be adjusted to Top Dead Center (TDC) to verify the timing. This is where your piston sits at the highest point of the stroke. To achieve this, you’ll need to turn the crankshaft until you see that the TDC marker on the pulley aligns and coincides with the time mark of the engine. Step 4: Check The Camshaft Timing Once your engine is TDC, You can check the timing of the camshaft. The timing of the camshaft should be set to ensure that the exhaust and intake valves remain in the proper place. Marks usually indicate this on the pulley of the camshaft. Step 5: Check The Ignition Timing The timing of the ignition is the last step in determining the timing. This is accomplished by connecting a timing lamp to the spark plug of the engine’s wires. The timing light will inform you how your spark plug has started to fire due to the direction in which the crankshaft is. If the timing is incorrect, you must alter the timings by losing the crankshaft pulley or camshaft and then rotating it until it is in the right position. How Do You Know If Your Timing Belt Broke While Driving? First, how do you know the moment your timing belt is broken? It’s simple: your vehicle cannot function without an engine-specific timing belt. If the belt is damaged while you’re driving, the car will soon fail, and the engine will be severely damaged. Therefore, it is important to watch out for the signs and symptoms of a worn-out timing belt, so you can intervene before it’s too late. This could be a loud click coming from your engine, sounding like a squealing, or your engine cannot start even once. These are some of the frequent warning signs to watch out for. If you are aware of any of these, make sure you immediately take your vehicle for an inspection by a repair expert. If the belt begins its wear, there may be a distinct ticking sound. The sound can have different meanings. In any case, your engine could get into trouble if you aren’t examining it promptly. The engine is not starting. When you put in the ignition key and the timing belt is damaged, you’ll hear the starter ringing, but without a belt that drives the crankshaft, your engine will not be able to begin. The engine is not running properly. The timing belt regulates the valves and cylinders within your engine. If it cannot align a tooth in the unlikely event, it could create one valve to close or open too in the early hours. This could cause the engine to operate poorly and will trigger the check engine light. If this happens, make sure you check your car immediately. Many possible causes cause misfires. All of them could be a sign of significant problems for your engine. Fixes For Timing Chain Off A Tooth? If a timing chain slips off one tooth, it could create many engine issues. Timing chains are responsible for synchronizing the camshaft and the crankshaft to ensure the proper timing of the engine components. When it falls off one tooth, it could cause issues like diminished engine performance, unresponsiveness, or, in extreme cases, engine damage. There are various ways to fix the timing chain slipping off teeth. Finding The Cause Identifying the issue is the first step to fixing an unbalanced timing chain slipping off the tooth. It is done by visually examining the timer chain to determine whether it’s still in its place and is properly aligned. If the timing chain appears misaligned, the tooth will likely slip off. In some instances, the timing chain might be stretched and require replacing. Check Timing Marks One of the most efficient methods to determine if there is an issue with the timing chain is to examine the marks of timing. These marks are situated on the crankshaft and camshaft gears, indicating the correct alignment of the chain. By examining those marks for timing, you will be able to identify if the timing chain is slipping off one tooth. Adjust Timing Chain Tension If the timing chain is slipping off a tooth, it could be due to a lack of tension in the timing chain. In this instance, adjusting the tension on the timing chain may suffice to solve the issue. Modern engines are equipped with an automatic tensioner; however, certain older engines might necessitate manual adjustment. Adjusting the tension of the timing chain is done by loosening tensioners and then tightening them to ensure that the tension is correct for the timing chain. Replace Timing Chain Guides The guides for the timing chain helps keep the chain’s timing in its place and aligned properly. However, if they wear out or are damaged, they cannot hold the chain’s timing in place, which could lead to a slip-off. In this scenario, the timing chain guides are required to be replaced. Replace Timing Chain If the timing chain is damaged or stretched, the chain may have a replacement. This is a much more complex procedure than simply adjusting the tension of the timing chain and replacing guides; however, it could be necessary when the chain has sustained damage. When replacing the timing chain, it is essential to ensure that it’s aligned with the timing marks and has the right tension. Realign Camshaft And Crankshaft When the chain loses a tooth, it could cause the camshaft or crankshaft to misalign. In this situation, it is required to align the camshaft and the crankshaft to ensure they are in sync. This can be accomplished by using an alignment tool that aligns the crankshaft and camshaft gears according to the correct timing marks. How To Tighten The Timing Chain? To Increase The Tension On The Timing Chain, You Will Have To - The timing chain cover must be removed. - Turn the crankshaft to ensure that your pulley’s timing marking lines up with the dead-center mark at the top of the engine. - Attach a wrench to the bolt holding the tensioner to the bolt, and then turn it counterclockwise until you feel resistance. This releases tension in the tension chain. - Utilizing a different wrench, remove the lock nut, which holds the screw that adjusts. - Adjust the screw counterclockwise until there’s resistance. This will pull the loose part of the chain in line with the sprocket of the camshaft. - The locknut should be tightened to lock the adjuster screw. Then, turn the crankshaft for two full turns clockwise until it lines with the marking on the pulley to an external edge that is on the sprockets on the camshaft. - The crankshaft should be rotated counterclockwise until it aligns with the dead-center top mark. This will ensure there isn’t any slack in the timing chain after you tighten it. - Clean any tools or objects from the area around the engine, then put on the new one and tightening of the cover on the timing chain with the torque wrench. How To Replace Timing Chain? If you are looking for a replacement for your timing chain, Follow these steps: Remove the Timing Cover To access the chain of timing, you’ll first remove the cover for the timing. This can be accomplished using a socket wrench or the ratchet. After you’ve removed the bolts holding the timing cover and removed the cover, remove it carefully and place it in a safe place. Remove the Old Timing Chain After you’ve removed the cover for the timing, you’ll be visible in the previous timing chain. You’ll need pliers or an adjustable wrench to take it off. Remove this old timer chain from the engine, and dispose of it. Install the New Timing Chain Once you’ve removed your old timing chain, then you are now able to begin installing your new chain. Begin by connecting the new chain through the crankshaft sprocket. Make sure you feed this the same way as your previous timing chain. After you have routed the new timing chain to the crankshaft shaft, attach it to the camshaft’s sprocket. Adjust the Tensioner After you have put in the timing chain, you’ll be able to alter the tensioner. The tensioner is accountable for maintaining the correct tension in the timing chain. To alter the tensioner’s settings, use an adjustable or socket wrench to rotate it clockwise until there’s resistance. This relieves tension from the chain. Tighten The Timing Chain After you’ve adjusted the tensioner, use an abrasive or socket wrench to loosen the bolts holding the timing chain. Ensure you do not over-tighten the bolts since this could cause damage to the engine. After you tighten the bolts, begin your vehicle and check whether the timing chain is repaired. If the issue is due to a worn-out timing chain, you’ll require replacing it. It is done by removing the old chain from the engine. Once you’ve removed your old chain, install an entirely new chain. Be sure to put it in the same manner as the original one. If the issue is due to the lost timing chain, You will have to adjust it. To do this, you’ll have to remove the timing cover and turn the crankshaft until the timing mark on the pulley is aligned with the dead-center top mark on the engine. Once you’ve done this after that, you will need a hammer or socket wrench to move the bolt that holds the tensioner into place clockwise until you feel resistance. This will loosen tension from your timing chain. Then, you can use a second or socket wrench to remove the locknut, which holds the adjuster screw, before turning the adjuster screw counterclockwise until you feel resistance. Adhere to the manufacturer’s instructions when replacing or altering your chain timing. Inadequately following the manufacturer’s instructions can destroy your engine. If you’re uncomfortable handling your car, you should take it to a professional mechanic. What happens if timing is out by one tooth? The valve timing will get out of sync if the belt is unintentionally moved during replacement by a single tooth. The inlet and exit valves will thus open and close at the incorrect times. This is a surefire reason why an engine won’t operate well. How do you know if your timing chain has skipped a tooth? Unusual rattling noises when the engine is started or when the brakes are applied are a frequent sign that a timing chain in a car is damaged. As the engine is running, the timing chain that is stretched or loose shakes and rattles as it rotates. What happens if your timing belt is a tooth off? Your engine’s valves and cylinders are timed by the timing belt. In the unlikely event that it skips a tooth, one or more of the cylinders may open or close prematurely. As a result, the engine will run badly and the check engine light will come on. What happens if timing is a little off? The ignition timing of an automobile is changed in accordance with any engine modifications. If not, your engine might have a number of issues with poor ignition timing, including banging, difficulty starting, increased fuel consumption, overheating, and decreased power. Will a broken timing chain destroy my engine? An engine with a broken timing chain will either not start or fail while being driven. The engine won’t start if the belt is already damaged since there won’t be adequate compression. The pistons will sustain damage by coming into touch with the valves if it breaks or leaps while being driven. The actual valves will flex, perhaps ruining the engine. What damage can a loose timing chain cause? Also, if the timing chain breaks free, you should brace yourself for major and expensive issues. The pistons will sustain damage by coming into touch with the valves, the valves will flex, and the engine might potentially be destroyed if the timing chain snaps or jumps while you are driving.

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The drive from Paoli, Pennsylvania, to Hudson, Ohio, is mostly along the Pennsylvania Turnpike and it is not particularly enjoyable. For most of the distance, the Pennsylvania Turnpike is only two lanes wide, and it carries a lot of truck traffic and a lot of automobile traffic. If you’re driving alone, you don’t have much time to look at the scenery because you’re concentrating on the winding roads and the traffic. This is too bad, because the scenery is worth looking at. The Turnpike winds up and down and back and forth to get across the Allegheny Mountains, and there are four tunnels, the last of which is almost a mile long — it’s a major engineering feat. This is one of several routes through the Alleghenies that date back to the nineteenth century when various interests were competing to connect eastern Pennsylvania with the west. After the American Revolution ended, Americans started pushing west through Pennsylvania, but “in these early years, terrible roads were the norm; they were rudimentary, often badly built, poorly graded, and seldom maintained.” (Robert Kapsch, Over the Alleghenies: Early Canals and Railroads of Pennsylvania [Morgantown, W.V.: West Virginia Univ. Press, 2013], p. 13). By 1824, the Commonwealth of Pennsylvania was making plans for building a canal from Philadelphia to Pittsburg, in order to make travel across the mountains easier. One early plan called for a canal “40 feet wide at the top, 24 feet wide at the bottom, and four feet deep” to get through and across the mountains; “to accomplish the most difficult portion, a canal over the Alleghenies, … the commissioners proposed a tunnel [over] 4 miles long” (Kapsch, pp. 52-52). As amazing as it sounds, canals were built through this rugged terrain; these canals mostly followed rivers, but there were sections of canals to be dug, locks to be built on the rivers, aqueducts and tunnels that had to be constructed — and most of the work had to be done by hand, in those early days. Hearing about the early canals and railroads makes the construction of the Pennsylvania Turnpike seem less impressive. Imagine getting a canal boat through the mountains — after thinking about that, the winding grades that require semi-trailers to grind upwards in low gear with flashers on are not at all impressive. Aside from the scenery — which I did not have time to look at — aside from the scenery, the Pennsylvania Turnpike is not a pleasant highway to drive: enough traffic to be annoying, too many poor drivers, service areas that range from cheerless to grim. But it was worth the drive because I got to visit with cousins and an uncle in Pennsylvania, and tomorrow I will visit with cousins and an uncle in Ohio. Sometimes the point of the journey is not the journey, but the destination. Posted several days late, due to lack of good Internet access.

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Environmental Health and Safety Available for 90 days after enrollment Approximate Course Run Time Continuing Education Units E-learning content is available on demand! The Resource Conservation and Recovery Act (RCRA), is an amendment to the Solid Waste Disposal Act, which was enacted in 1976, to address the huge volumes of municipal and industrial solid waste generated nationwide. This training course will start with a history of RCRA and thoroughly review key provisions, management, common violations and current requirements of RCRA, and how this regulation sets the basic framework of hazardous waste management, throughout the United States. - Lesson One: History and Overview of RCRA - Lesson Two: RCRA Provisions, Programs and Key Elements - Lesson Three: Transportation, Treatment, Storage and Disposal - Lesson Four: Common Waste violations and Enforcement - Lesson Five: Reporting and Recordkeeping Interested in hosting this training on your own Learning Management system, specifically for your employees or are you interested in a reselling agreement? Or are you interested in customizing this course for your organization? Contact our custom solutions training team at [email protected] for more information and to set this training up for your organization. Coming in 2022 Be on the look out for newly released training. - CAA 101: Introduction to the Clean Air Act (CAA) - CAA 102: Clean Air Act Permitting - CAA 103: Title V Permitting - CWA 104: Construction Stormwater Management - Environmental Law 103: What to Expect from an Environmental Inspection - TSCA 101: Introduction to the Toxic Substance Control Act - Sustainability 101: Sustainability and Circular Economy - Hazardous Communication and Global Harmonization - And more.

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A 32-year-old female asked: Is palilalia more often related to tourette's or autism spectrum? my child has asd and multiple motor tics started palilalia 6+ months ago. 2 doctor answers • 5 doctors weighed in A Verified Doctoranswered 42 years experience Statistics unavailab: Palilalia can occur in both. Reports would implicate tourette's as most common, but it has been reported in autism and asperger's. Formal comparative incidence studies appear to be unavailable at this time. Perhaps one of my colleagues in research will comment further. 4.8k viewsReviewed >2 years ago Dr. Carlos Barriosanswered Child Psychiatry 25 years experience Much more tourette's: Also given that for tourette's vocal tics are central to the diagnosis along with motor tics. Vocal tics including palilalia, are not the case for the autism spectrum. By the way, echolalia is more common in the autism spectrum. And remember, the cornerstone for autism spectrum is social awkwardness and this is not a requirement for tourette's. Take care. 3.8k viewsAnswered >2 years ago Last updated Aug 12, 2014 People also asked Connect with a U.S. board-certified doctor by text or video anytime, anywhere. 24/7 visits - just $44! 50% off with $15/month membership Content on HealthTap (including answers) should not be used for medical advice, diagnosis, or treatment, and interactions on HealthTap do not create a doctor-patient relationship. Never disregard or delay professional medical advice in person because of anything on HealthTap. Call your doctor or 911 if you think you may have a medical emergency.

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The state network infrastructure is only one piece of the bandwidth puzzle. We continue to hear sporadic reports that internet provider capacity is strained. This makes sense. In many households, two or more members are telecommuting simultaneously. Often, children are doing distance learning, internet gaming, live streaming, or video downloads. This is an immense amount of traffic to support. Here are a few other tips to help prioritize home network use: - If household members are watching video like Netflix, consider downloading shows and movies during off-peak hours for later viewing, rather than streaming. Most services (Netflix, Amazon, and Vudu) offer this capability when streaming to a computer. - For those who have unlimited bandwidth on their phone plans, we suggest using your phone for streaming. Check with your internet provider. - Data caps are one of the biggest culprits of slow internet speeds. A data cap means you can use a certain amount of data every month—anything from a couple hundred megabytes to hundreds of gigabytes. If you exceed your data limit, your ISP will seriously restrict your internet speeds. And you'll notice. If you don't know whether or not you have a data cap, check your bill. It should be outlined in the fine print. If you keep exceeding your data cap every month, talk to your provider about a plan with a higher data limit. - Reset your router every month or so to give the device a break and refresh your internet connection by turning it off then on again. - This is a quick one—is your router in some remote corner of your house? If so, move it closer to where your computer is located. It will work better for you.

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Renewable energy and technologies may play a vital role in meeting countrywide energy requirements. However , it will need the government to produce and apply effective procedures. Deployment of renewable solutions can be achieved through a collaborative effort among governments, businesses, and nongovernmental organizations. The aim of such a technique is to solve the environment change and energy poverty strains. It entails technical, societal, and institutional adjustments. To triumph over these obstacles, governments should arranged ambitious focuses on at the community, national, and international amounts. This can be achieved through specific alternative support procedures that encourage expenditure and development of needed infrastructures. These guidelines should be based upon clear standard goals and targets. www.gwelectricco.com/2022/03/28/best-data-room-software-suppliers-for-corporation-tax-management/ They should become anchored in a strong a finance framework that may withstand monetary and energy crisis. This may include duty reductions and subsidies to help reduce upfront investment commitments. Guidelines should also always be designed to motivate broad ownership of alternative energy projects. This will improve the competitiveness of alternative energy production. In addition, it will help encourage innovation and design creativity. Investing in renewables requires a thorough understanding of its costs and benefits. This can be facilitated by incorporating external costs into energy prices. This will reveal the true costs and benefits of deploying renewables, which is often used being a basis with respect to improving economical competitiveness. Employing fiscal offers will help inspire innovation inside the design of alternative energy technologies. These offers should also solve stakeholder concerns and encourage extensive ownership of renewable energy assignments.

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Allowed image types are jpeg,png,gif Max file size is 20MB Seawatching, several species rarely observed from mainland France can be found. Especially by wind from the North-West in specific pelagic species. Cap Gris-Nez is the migration bottleneck of the Straits of Dover. It allows the observation of a number of seabirds, often difficult to observe from the coast. It is a strategic site for a migration survey of seabirds, both in spring and autumn. Seawatching is usually drawing in birders between the end of August and early November. During that time of the year, several species rarely observed from mainland France can be found: Sabine's Gull, Great Skua, Pomarine Skua, Arctic Skua (Parasitic Jaeger) and Long-tailed Skua (which is regularly seen), Sooty Shearwater, Manx Shearwater, Balearic Shearwater and Red Phalarope. During spring, the site is less reknowned for seabirds. A regular survey during mid March to mid May, however, has revealed the interest of the site for seawatching during spring. If the migration survey is mainly focusing on seabirds, the high cliffs are also suitable to watch migration over land (passerines, raptors), both for migrants following the coast, as well as for those leaving or arriving from Britain. Big Parking place on top of Cape Griz Nez. Special place in spring and autumn with winddirection from North-West. By strong wind the birds pass underneath you.

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The theme of nature is only discreetly present in Buddhist literature, and its most expressive modulations are to be found in poetic texts, of which Danièle Masset offers here a transversal reading, limited to the Indo-Tibetan domain. This reading is based on the exploration of a corpus covering more than two millennia, from the stanzas of the Pali canon to the songs of Tibetan masters such as Milarepa. The nature staged in this set is seen in the mirror of religious and literary conventions, but it also constitutes a mirror of the world and of doctrine. It inspires many images faithfully transmitted over time. The study of these metamorphoses is an opportunity to highlight the deep continuity that unites the Indian and Tibetan traditions, but also to discover, or rediscover, a relationship with nature that is no longer ours, a complicity whose we have lost the secret. Excerpt from the intro: “The theme of nature is not one that imposed itself immediately on Westerners who have chosen to study Buddhist literature: other religious, historical or philosophical subjects have held their attention more. In this they espoused the point of view of the Buddhists themselves, followers of a doctrine in which this theme has nothing central. What is more, the notion of nature has no exact equivalent in ancient Indian thought, at least when it is approached as we will do here in its most concrete sense, not as a "set of characteristics defining a being or an object" ("nature of fire", "human nature"), but as a "set of beings and things constituting the terrestrial universe (1)", among which man can be understood or not, depending on whether or not it is posited as exterior to this set. On this point, some of the texts that will be discussed in this book are at the antipodes of modern Western thought, where man is defined as a being of culture more or less dissociated from a nature that he can then transform into an object. study or as an object of love, by cultivating a "feeling of nature" which has nothing universal about it, and which attests to the nostalgia for a unity whose secret has been lost over time, and in a cultural context specific to Western societies (2). » In partnership with the Institute of Buddhist Studies (https://bouddhismes.net/)

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Bacterial canker, caused by Pseudomonas syringae pvs. syringae (PSS) and morsprunorum, is an important disease of sweet cherry, tart cherry, apricot, and other stone fruit. Symptoms include blossom blast and spur dieback, leaf and fruit lesions, cankers with associated gummosis of woody tissue, loss of scaffold limbs, and overall decreased fruit yields. This disease is most problematic in sweet cherries, and epidemics often occur in conjunction with cold, frost-prone weather in the spring. Of the two bacterial canker pathogens, PSS is the most virulent. PSS is the predominant pathogen on sweet cherry in Michigan and represented approximately 62% of the pathogenic Pseudomonas isolates we recovered in a recent two-year survey of Michigan orchards. The most important factor regarding bacterial canker is that the PSS pathogen is an opportunistic pathogen. This means that trees must be weakened or predisposed to infection for disease to occur. There are four main factors that can predispose trees to PSS infection: • reduced soil fertility, with nitrogen levels most critical • nematodes in the soil • low soil pH • frost injury Researchers in California, led by Dr. Bruce Kirkpatrick, have shown that canker lengths on inoculated peach trees receiving supplemental nitrogen fertilization were significantly reduced compared with nonfertilized trees. Regarding nematodes, populations of the lesion nematode in Michigan soils and the pin nematode in California soils are associated with an increased incidence of bacterial canker. Trees planted on nematode-free fumigated sites typically are more resilient to bacterial canker. The nematodes may predispose trees to infection by altering tissue nitrogen levels. When soil pH falls below 5.5, this benefits the PSS pathogen, and this may also involve alterations in nutrient uptake. These first three predisposing factors affect the general health of trees and, in combination with PSS infection, lead to the overall decline of orchard blocks. The fourth factor, frost injury, can result in a much more active phase of canker infection due to the association of the PSS bacterium with frost-injured tissues as discussed under “Ice formation” below. Risk to cherries Sweet cherry trees infected with bacterial canker are at high risk of being killed by this disease due to the endophytic nature of the infection and systemic movement of the pathogen in woody tissue. In young trees, this can mean death of the tree and, in older trees, loss of scaffold limbs. Endophytic PSS populations can be established in a number of ways. One method is through leaf scar infection in autumn at leaf drop, which results in internal migration and colonization of dormant buds. Bacterial populations are typically high on symptomless leaves in autumn, and conditions at leaf drop (wind and driving rain) favor dissemination of bacteria to leaf scars. Colonized buds can remain apparently healthy over the winter or can be killed by the pathogen, leading to the dead bud symptom which is typically associated with canker formation. In either case, colonized buds provide pathogen inoculum for the next season. PSS can only infect trees through wounds or natural openings; however, this can include pruning wounds and other natural wounds such as cracks in bark. From a disease standpoint, the timing of pruning is best when the pathogen is inactive, either when trees are dormant or in midsummer. Systemic invasion of shoots following blossom infection can also occur. In the spring, PSS populations that overwintered in dormant buds provide the primary inoculum for epiphytic blossom colonization. Cold, wet weather then favors increases in PSS populations on blossoms; these populations are a particular problem because frost injury to blossoms causes wounds that provide an easy entry for the pathogen. Unfortunately, PSS cells also contribute to frost injury because most PSS strains are ice nucleation active. Ice nucleation activity is a trait whereby PSS cells can catalyze ice formation at temperatures only slightly below freezing. Pure water can supercool significantly below 32°F without freezing. The presence of ice-nucleation–active PSS cells, however, enables ice to form at temperatures of approximately 28°F or below. Once ice is formed, it rapidly propagates through sensitive tissue such as blossoms. The severity of frost damage plays a critical role in the occurrence of subsequent bacterial canker infection. Ice formation initiated by PSS is dependent upon temperature and the number of cells present. At 28°F, approximately one in 1,000,000 PSS cells freeze. At 27°F, one in 10,000 cells freeze, and at 25°F and below, one in 10 cells freeze. Sweet cherry blossoms in Michigan typically harbor relatively large PSS populations on the order of 200 to 80,000 cells per individual blossom. Thus, these populations are large enough that orchard exposure to temperatures of 27°F or below during bloom can result in large-scale damage. Luckily, frost events below 27°F are rare and so frost damage is usually sporadic and typically results in the killing of small numbers of flowers without associated PSS infection. However, on May 22, 2002, a hard radiational frost occurred in northwest and west central Michigan with sustained temperatures of 26°F over an 11-hour duration. This freeze event and resulting injury was followed by widespread wood invasion, canker formation, and death of trees. Few control options Thus, when these type of freeze events happen, they can be devastating. A major limiting factor is our ability to effectively reduce populations on blossoms. The only bactericide registered for bacterial canker management is copper, which is of limited use because sweet cherry trees are susceptible to copper phytotoxicity following bud break in the spring. Copper sprays have been traditionally applied during leaf drop in an attempt to reduce leaf scar infection, and as dormant sprays prior to bud break in an attempt to reduce pathogen populations either on the surface of cankers or emerging from dormant buds. Relatively high rates of copper (2 pounds metallic copper per acre) can be used at these timings. If the trees have broken dormancy and are in the prebloom stage (bud swell through white bud), copper rates should be reduced to 25% of the dormant rate, but we have found that knockdown of PSS populations only lasts for a few days. The development of copper resistance in PSS can be a factor, but we have found that currently this is not a serious problem in Michigan. Bacterial canker may be the most difficult tree fruit disease to manage due to the lack of effective chemical controls and the susceptibility of many important varieties. Improving tree health may reduce long-term decline from this disease. Leave A Comment

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https://www.goodfruit.com/update-on-bacterial-canker-of-stone-fruit/

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When we observe the universe through the naked eye, we think there is a non-unmoving universe. The immense activities in the universe started to be noticed only after the invention of the telescope. In a very long period of history, people thought the world was not moving and that the sun rotated round the world. Then, in the process that started with Copernic, Kepler and Galileo, they discovered that the sun rotated round the sun, which remained fixed. This discovery, which is regarded as a revolution, was very important but it had not yet been discovered that the sun moved on its own orbit. Then, thanks to the advanced telescopes and the development of science, it was understood that the world rotated round the sun, which also moved. The sun moved at a speed faster than 720.000 km an hour with the planets around it toward the star Vega on an orbit called the Solar Apex. This fact, which was discovered only in the last century, was stated by the Quran 1400 years ago: “And the Sun runs his course for a period determined for him: that is the decree of (Him) the Exalted in Might, the All-Knowing” (Yasin: 38) “It is not permitted to the Sun to catch up the Moon, nor can the Night outstrip the Day: each (just) swims along in (its own) orbit (according to Law)” (Yasin: 40) “It is He Who created the Night and the Day, and the sun and the moon: all (the celestial bodies) swim along each in its rounded course” (al-Anbiya: 33) As we can see it, the Quran stated 1400 years ago that the sun and the stars moved; this proves that the Quran is the word of Allah. The Quran attracts attention to another scientific discovery about the movements of the sun through another verse. The following is stated in verse 5 of the chapter of as-Saffat: “The Lord of the heavens and the earth and what is between them, and Lord of the easts.” It is understood from the phrase “the Lord of the easts” that the sun had more than one rising point; it attracts attention to the fact that “the east”, which we know as the rising “place” of the sun, needs to be thought as “places”, that is, more than one “east”. Yes, the sun rises every morning and sets every evening. However, these risings and settings take place in a different part of the universe each time. That is, the stars and the planets that float in the sea of the sky do not pass from the same route again; they move on their orbits. The sun, which rises in a place, sets in another place at the same time since the world is round. The night follows the day and the day follows the night. Then, the rising places of the sun, not the rising place, is in question. The morning time is different for every point of the globe. Every place waits for the sun to rise at a different hour, minute and second. We watch the sun rise from different places of space. The sun is the same sun, the world is the same world but the place in space is different… Now, let us ask some questions about these two miracles of the Quran: 1- Can the fact that the sun and the stars moved – something stated by the Quran 1400 years ago – was approved by scientists be interpreted as anything but as “the Quran is the word of Allah, who created the skies, determined routes there and made the sun and stars move on that routes”? 2- Is it possible for a person who lived 1400 years ago and who could not read and write to discover a fact that was rejected by a lot of scientists who lived before the last century and that was discovered only in the last century, which was a century of science and technology? 3- Why should Hz. Muhammad (pbuh) make these claims and risk his credibility by opposing the people of that century in a period when almost all of the knowledge about the sky was wrong and superstitious and when people did not have anything like that on the agenda? All of these questions can only be answered by the fact that the Quran is the book of Allah. If it is accepted that the Quran is the word of a human being, hundreds of questions will arise. In that case, no scientific fact stated by the Quran can be explained. The only answer to this question that can persuade the heart and the mind is as follows: The Quran is the pre-eternal book of Allah and His address to humanity. Hz. Muhammad (PBUH) is Allah’s Messenger and beloved slave. We believe in it.

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Most of the “recyclable” plastic we all use ends up in the landfill. Its a logistics and economics problem. There needs to be a better way to handle this massive waste stream. A company called CRDC Global may have a viable solution. Plastics play a wide range of crucial roles in modern society, but they also represent a major waste disposal challenge. Particularly when it comes to consumer packaged goods (CPG) the practical reality is that only a small fraction of the plastic is actually recycled, and a great deal ends up going to landfills or to even more undesirable “end of life” scenarios such as incineration or release into the environment. The problem was exacerbated in 2018 when China stopped accepting this waste for hand sorting. There are many positive strategies being implemented to deal with this waste crisis including better collection in the developing world, decomposable alternative materials, and fully sorted collection of plastics at the business-level. There is also a new technology based on hyperspectral imaging which can differentiate the various clear or plastics based on how they “look” at light wavelengths outside of the visible range. There is another innovative alternative that is gaining momentum because it addresses the sorting challenge and also provides a positive value proposition. CRDC Global has developed a way to turn mixed plastic waste into a synthetic lightweight aggregate, a substitute for the sand used in making concrete and asphalt. This option benefits from a geographic alignment between where plastic waste is generated and where most construction is underway – major population centers. From a business perspective this is a push/pull scenario – the CPG industry needs a plastic waste solution, and the construction industry needs an alternative to sand. If you look on the bottom or side of “recyclable” plastic containers there is a number between 1 and 7. In terms of recycling, only “1s” and “2s” (PET and HDPE) are practical candidates for recycling into new containers and there is an almost zero tolerance for any mixing of types or contamination with labels or organic matter. Plastics marked “3” to “6” are of minimal value for re-use and “7” stands for “other” and has essentially no value. CRDC has developed a process that can take a mixed load including all these plastic categories and turn it into a new plastic resin. The process is the “brainchild” of CEO Donald Thomson. Ross Gibby, COO, creatively named its output “RESIN8.” The process is as follows: the mixed plastics are chopped, shredded and granulated into small flakes which can include a reasonable degree of organic contamination (e.g. the residue left in a bottle of ketchup or a peanut butter container). At that stage some naturally occurring minerals are added – similar to those that are used for “liming” of agricultural soils. That mixture is melted and extruded as a foam which hardens to something akin to a plastic lava rock. It is finally ground into granules the size and gradation of fine sand. That material can then be added to cement at a ration of 2% to 25% to make concrete for anything from pre-formed blocks to poured structures or surfaces. High quality sand is a scarce resource in many regions, and it is very expensive to transport. A local alternative is a very attractive concept for the construction industry as long as it is functionally and visually equivalent. The RESIN8 concrete checks all those boxes. Not only that, concrete made with RESIN8 has several advantages compared to conventional concrete. It is lighter weight; it provides higher thermal insulation, and it absorbs more noise. It is just as strong and long-lasting. At the end of its useful life, concrete made with RESIN8 can be recycled to be used as aggregate in new concrete. CRDC Global started with seed capital and through loans from the Alliance To End Plastic Waste and its CEO Donald Thomson is motivated by his desire to leave a better world for his grandchildren. They have now shifted to a mix of family office and institutional investors. They have set up 6 small scale facilities during a proof of concept stage, and currently have three large scale facilities running in Pennsylvania, Costa Rica and South Africa. Their vision is to have 20 sites operating within 3 years each producing around 20 thousand tons of synthetic aggregate sand substitute every year. The company has a global action plan and its board includes individuals from around the globe who meet via Zoom. 27 different countries have expressed interest in starting to use the technology. There is also on-going research about the process at universities in the United States, Costa Rica, South Africa, the UK and Australia. CRDC Global is cooperating with a major cleanup project in Alaska which has a huge problem with plastic waste, mostly from Asia, crossing the ocean and ending up on that state’s 33 thousand miles of coastline. There is an excellent video presentation about this GoAK project. There are several models for how this can work. Existing trash hauling players can divert either all their plastic or plastics 3-7 to a CRDC site. They have also worked with a direct consumer connection they called “The Bag That Builds”, often through presentations at schools through which they find motivated children and “soccer moms” and dads who like the idea of helping with the problem. The slogan they teach potential helpers is that most plastic will end up meeting one of three fates– “burnt, buried or built” with the later being a much better outcome. These voluntary participants are supplied with a supply of labeled green bags which these consumers can bring it to collection points - either by bagging all plastics together or better yet separating out easily identifiable 1s and 2s for one bag and another with any other kind of plastic everything. In the later scenario CRDC is able to generate income through true recycling of the 1s and 2s to help pay for the overall collection system. Consumers are easily trained to accurately identify things that are made of plastic, and in the process, they get a feeling for just how much plastic they need/use. The CRDC process can use things other than CPG containers, in fact the entire post consumer thermoplastic waste stream. Even the foil/plastic used as a wrapper for something like a granola bar can be handled within this system. “Compostable” plastics or fully biodegradable ones will likely be eliminated during the high heat step but can also be part of RESIN8 if they persist. If this approach is greatly expanded, it could provide a better end of life alternative for the majority of plastics because there is so much potential demand from the construction side.

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HYPOTHESIS AND THEORY article Sec. Exercise Physiology Volume 10 - 2019 | https://doi.org/10.3389/fphys.2019.01412 The Performance Gap in Sport Can Help Determine Which Movements Were Most Essential to Human Evolution - Columbia University, New York, NY, United States Men outperform women in sports that require muscular strength and endurance, but the magnitude of this performance gap (PG) does not appear to be constant; that is, the PG between men and women is greater in some sports than it is in others. Here, we examine the size of this gap within the realm of track and field by comparing the top 50 world-record performances of men to the top 50 records set by women in a number of long-distance running, medium-distance running, short-distance running, and jumping events. While women do not perform at the level of men in any track and field event, the magnitude of the PG trends up or down depending on the type of event. Jumping events exhibit a larger gap between the sexes than do running events, and short-distance running events show a smaller disparity between the sexes than do medium- or long-distance running events. This difference suggests that general sexual dimorphism does not explain why female performance is relatively closer to male performance at some track and field events than others. We hypothesize that this trend can be explained by the presence of sex-blind musculoskeletal adaptations (SBMA’s), which accumulate over generations to reduce the size of the PG in certain movements. We conclude that the selection trend favoring in humans should be explored further to determine whether the PG in sport can indeed be used to determine movements to which the human body is adapted. Movement is key to an organism’s reproductive success; better quality of movement allows an individual to escape predators and acquire food, heightening its reproductive fitness (Kuhn et al., 2016; Marck et al., 2016). Hominids in particular are capable of a variety of actions, including both arboreal (Venkataraman et al., 2012) and terrestrial movement (Crompton et al., 2010; Roberts et al., 2016), and the notable ability of humans to successfully navigate different environments has led to the remarkable spread of Homo sapiens all around the world (Petraglia et al., 2010; Rito et al., 2013). The human body is capable of climbing, short- and long-distance running, swimming, jumping, and many more movements, all of which can be assessed experimentally between individuals as sport. Sport, specifically track and field, has existed for thousands of years. Recent advancements in exercise science and nutrition have allowed new track and field world records to be consistently achieved throughout the 20th century, but in recent years, the rate of new records has slowed (Matrahazi and Hymans, 2015; Marck et al., 2017). This stagnation of world records suggests that humans are approaching the apex of our species’ ability to perform, which makes current track and field world records a good gauge for the overall capacity of the human body at these established events. And while the rate of new world records has slowed in recent years, a notable performance gap (PG) remains between top-performing men and top-performing women across all track and field events. Men have a physiological makeup that does indeed advantage them over women in strength- and endurance-based competition (Sandbakk et al., 2018). In addition to a lower body-fat percentage, men have a greater percentage of muscle mass, denser bones, higher testosterone levels, and a longer stride length than women do (Smith and Smith, 2002; Nieves et al., 2004). While women have closed much of the PG throughout the 20th century due to changing cultural norms (Thibault et al., 2010), it appears that the PG has reached an asymptote since the 1980’s (Millard-Stafford et al., 2018). Though men tend to outperform women overall, the magnitude of the PG narrows or widens depending on the sport. Swimming, track and field, and speed skating tend to show a relatively small PG, whereas the gap is considerably larger in weightlifting competition (Thibault et al., 2010). Even within the sport of track and field, the PG demonstrably expands or contracts depending on the event (Matrahazi and Hymans, 2015). If the general physiological advantages men have over women in sport are the sole contributors to superior male ability in track and field events, we would not expect the PG to be significantly different across different events. That the magnitude of the athletic gap appears to be event-dependent instead suggests that sexual dimorphism is not the only factor contributing to the PG. Absent confounding factors, a smaller athletic gap in a particular event indicates either that female physiology is relatively better-suited to the event, or that there exist sex-blind musculoskeletal adaptations (SBMA’s) shared by men and women which partially negate the general physiological advantage men have over women. The purpose of this investigation was to determine how the gap that exists between the top 50 records set by males and the top 50 records set by females expands or contracts across different track and field events. These results will be further analyzed through an evolutionary lens. The goal of this analysis will be to determine whether the magnitude of the PG corresponds to established movements considered essential to human evolution, which in turn could determine whether the PG in sport can be used as evidence that SBMA’s exist in humans. Materials and Methods Sex Equity Score by Event The sex equity score (SES) data set was collected online from the website of the International Association of Athletics Federations (IAAF, 2018) (Supplementary Data Sheet 1). The top 50 world-record overall performances (independent of athlete) and the top 50 world-record performances by athlete as of May 1, 2018 were taken for both men and for women. The SES, which is the ratio of the mean of the top men’s world records (MTSm) and the mean of the top women’s records (MTSw) in the same track and field event, is calculated differently for chronometric and non-chronometric events, as follows. The initial result is multiplied by 100 to better illustrate inter-event differences. The SES was calculated 12 times for each event. The first six calculations compared the MTSm to the MTSw for world-record performances independent of athlete. The MTSm for all 50 male performances was compared to the MTSw for all 50 female performances for the first SES calculation. Then, the top 50 performances for both men and women were broken into five quintiles: performances 1–10, 11–20, 21–30, 31–40, and 41–50. The SES was calculated laterally for each group, so that the MTSm of the top 10 male performances (the first male quintile) was compared to the MTSw of the top 10 female performances (the first female quintile). Next, the MTSm of male performances 11–20 was compared to the MTSw of female performances 11–20; this calculation was repeated for all five quintiles. This procedure was repeated for the next six SES calculations, except these calculations compared the MTSm to the MTSw for world-record performances by athlete so that no athlete is represented more than once. The purpose of calculating SESs for both top overall performances and top performances by athlete was twofold. First, this removed athlete outliers, who recorded multiple top-50 world records. Second, this allowed for more data to be included in the SES analysis. These data are reported in Table 1 as the mean SES for world-record performances overall, world-record performances by athlete, and as an aggregate of both categories. Sex Equity Score by Event Category After determining the 12 SES’s for each event, the 14 events were sorted into four event categories (EC’s): long-distance running, medium-distance running, short-distance running, and jumping. The three long-distance running events were the marathon, the half-marathon, and the 10-kilometer run (10 km). The four medium-distance events were the 5-kilometer run (5 km), the 3000-meter race (3000 m), the 1500-meter race (1500 m), and the 800-meter race (800 m). The four short-distance running events were the 400-meter dash (400 m), the 200-meter dash (200 m), the 100-meter dash (100 m), and the 60-meter dash (60 m). The three jumping events were the high jump (HJ), long jump (LJ), and triple jump (TJ). All records were taken for outdoor events except for the 60 m, which is an exclusively indoor event, and the 3000 m. This sorting led to 36 SES data points for the long-distance running EC, 48 data points for the medium-distance running EC, 48 data points for the short-distance running EC, and 36 data points for the jumping EC. To determine significance across EC’s, the aggregate SES for each EC (N = 36 for long-distance running and jumping; N = 48 for medium- and short-distance running) was compared to the aggregate SES of every other EC to determine whether there were significant SES differences between EC’s. Our purpose was to test whether or not the mean changes depending on the EC. We then ran ANOVA between EC’s, as it is summarized in Table 2, where we report the corresponding p-values. Significance was set at P < 0.01. Participation Disparity and Sex Equity Score Data provided by the 2018–2019 High School Athletics Participation Survey were used to determine the degree to which the Participation Disparity (PD) between male and female athletes across different sports might act as a confounding factor and affect the SES (The National Federation of State High School Associations, 2019). The PD was calculated as a ratio of the total number of female high school athletes to the total number of male high school athletes in the same sport. This ratio was subtracted from 1 and the result multiplied by 100 to better illustrate the PD, so that a higher PD was correlated with a greater disparity between the number of male and female participants. The PD was calculated twice in total, once for cross-country high school athletes and once for outdoor track and field high school athletes. The SES was also computed for two high school running events, the 2018 high school cross-country (HS XC) 5 km championships and the 2019 high school outdoor track (HS OT) 100-meter dash championships, using the earlier SES formula for chronometric events. The data regarding the and were collected online from the Foot Locker Cross-Country Championships and the New Balance Outdoor Nationals, respectively (Foot Locker Cross-Country Championships, 2018; New Balance Nationals Outdoor, 2019). These data were of lower quality than the data offered by the IAAF. Only 40 timed results in total were available from the 2018 boys’ HS XC championships, and 39 timed results were available from the 2018 girls’ HS XC championships. Only 41 timed results were available from the 2018 boys’ HS OT 100-meter dash preliminary finals, and 31 timed results were available from the 2018 girls’ HS OT 100-meter dash preliminary finals. The 100-meter dash preliminary finals results were used because only the top eight athletes from the preliminaries were permitted to compete in the finals; collecting data from the finals would have limited the quality of the data even further. Because the data were limited, the SES was calculated only four times for each high school event, the first event being the HS XC 5 km and the second being the HS OT 100 m. The boys’ and girls’ results were first equalized so that the total number of male results were equal to the total number of female results in each event. This left 39 results for each sex for the HS XC 5 km and 31 results for each sex for the HS OT 100 m. The first SES calculation for each event compared the MTSm to the MTSw for all of the results listed in each sport. Then the results were split into terciles, so that the MTSm of the top tercile of male scores was compared to the MTSw of the top tercile of female scores; this was repeated for all three terciles. This process yielded four total SES calculations for each of the two high school events. By Individual Event Results of the SES for each event are displayed in Table 1, and all 12 SES data points are illustrated as a boxplot in Figure 1. Because the SES measures how close women are to men at a given athletic event, it is inversely correlated with the magnitude of that event’s PG so that a higher SES aligns with a more equitable sport. The aggregate SES by event ranged from a low of 84.42 ± 0.48 for the LJ to a high of 92.10 ± 0.13 for the 60-meter dash. The three lowest aggregate SES’s all belonged to jumping events, whereas the four highest SES’s all belonged to short-distance running events. Figure 1. Sex equity scores by event. For each event, N = 12 data points were used to calculate values. Values are presented as the median (central horizontal line), mean (X), first and third quartiles (box), and minimum/maximum values (whiskers), with outliers as individual points outside of the whiskers. Between Event Categories The real SES data for all EC’s is displayed in Table 2. The aggregate SES by EC was lowest for jumping, at 84.77 ± 0.57. Medium-distance running was next, at 88.59 ± 0.29. Long-distance running followed, at 88.80 ± 0.49. Finally, the highest SES was 90.74 ± 1.00 for short-distance running. This is illustrated in Figure 2. On the basis of this data, one can strongly conclude the average SES is significantly different for running events versus jumping events, at P < 0.01. Within the running events, there seem to be discrepancies: when pairwise compared, one can only fail to reject the null hypothesis that the means are uniform in the case of long versus medium distance. While there was no statistical difference in SES between long- and medium- distance EC’s, the difference between each of those events and the short-distance EC was statistically significant, at P < 0.01. This suggests that short-distance events exhibit a smaller PG between the sexes as opposed to events of long and medium distances. Figure 2. Sex equity scores by event category. For long distance and jumping N = 36, for medium distance and short distance N = 48. Values are presented as the median (central horizontal line), mean (X), first and third quartiles (box), and minimum/maximum values (whiskers), with outliers as individual points outside of the whiskers. Participation disparity data are shown in Table 3. The PD was 18.55 for HS XC and 19.34 for HS OT. The PD is useful in the context of the SES as a way to try and control for a confounding factor, so the SES for each of these high school sports is also displayed in Table 3. To better illustrate SES differences between these short- and medium-distance events, both for high school and adult athletes, the high school SES’s and the corresponding IAAF SES’s for the 5 km and the 100 m are displayed in Figure 3. Table 3. Participation disparity (PD) in high school cross-country versus high school outdoor track and field. Figure 3. Sex equity scores for adult and high school athletes in two events: the 5 k and the 100 m. The symbol “∗” indicates significantly different values between events when comparing events within the same population pool, “Adult” or “High School” (P < 0.01). While some studies have explored the PG in different sports, (Thibault et al., 2010; Millard-Stafford et al., 2018; Sandbakk et al., 2018) this is the first to compare the top 50 world records in different track and field events between men and women to measure the gap that exists in these events. There was a clear difference in male versus female performance in all of these events, but the magnitude of this athletic gap ranged from 84.42 ± 0.48 for the LJ up to 92.10 ± 0.13 for the 60-meter dash. Short-distance running had a smaller PG, measured as a greater SES, than either of the other running distances, whereas jumping had a larger gap in performance than any type of running. This study supports the idea that the PG might be used to measure the evolutionary necessity of different movements. This would be a key finding, as anthropologists and evolutionary biologists often debate the movements to which the human body and earlier hominids adapted. Our reasoning is that adaptations which increase the quality of movement of an organism, and thus the organism’s reproductive fitness, are especially selected for regardless of the organism’s sex. As a result, SBMA’s are more likely to increase the quality of movement in an organism’s offspring than are sex-dependent adaptations. Over time, these SBMA’s accumulate to advantage evolutionarily critical movements, resulting in a smaller gap in athletic ability between males and females at these and similar movements. Whether it is due to a greater degree of neuromuscular control, more efficient muscular recruiting patterns, or some combination of other physiological factors, it appears that the human body is better equipped across sex lines for a movement like short-distance running versus a movement like jumping. The significant differences in SES across track and field EC’s suggest that humans have accrued SBMA’s which favor short-distance running over medium- and long-distance running, and every sort of running over jumping. Early humans needed to be able to quickly escape from rapidly approaching predators, similar to how modern apes in the wild are noted to have been killed by larger animals (Boesch, 1991; Tsukahara, 1993), a selective pressure that favored individuals who were good sprinters. This also could explain the SES trend within short-distance events, which was found to be inversely correlated with distance. The highest SES was 92.10 ± 0.13 for the 60 m, and the SES decreased as distance increased, down to 91.13 ± 0.17 for the 100 m, 90.19 ± 0.26 for the 200 m, and 89.53 ± 0.20 for the 400 m. The downward trend suggests that when escaping a predator, an early human’s ability to accelerate quickly, within as little as 60 m, may have determined its survival. Long- and medium-distance running each had a smaller SES than short-distance running (88.80 ± 0.49 and 88.59 ± 0.29, respectively, compared to 90.74 ± 1.00), which would suggest that early humans’ survival and overall fitness depended more on sprinting than on longer running. The ability to run long distances was a useful trait (Bramble and Lieberman, 2004), as it allowed early bipedal hominids to travel great distances in pursuit of food or more favorable living conditions (Liebenberg, 2006). Still, an early human’s ability to sprint would have determined its survival in an encounter with a larger predator. As such, the ability to run long distances at a greater speed was a less selected-for trait, and as a result the modern human musculature is less adapted to running longer distances than it is to a single quick sprint. Jumping, on the other hand, was considerably less useful to terrestrial hominids than any kind of running, which is reflected in the low SES’s for all jumping events. The aggregate SES for the jumping EC was significantly lower than that of any running EC, P < 0.01, which suggests that humans have accrued a greater number of SBMA’s in service of running rather than jumping. The contrast between short-distance running and jumping in our results is of particular note. Short-distance and jumping events alike involve quick bursts of speed and anaerobic energy expenditure (Kasabalis et al., 2005; Saraslanidis et al., 2009); during the LJ, for instance, athletes tend to sprint approximately 40 m to increase their speed before leaping (Long Jump, 2016). The major difference between an event like the LJ and the 60-meter dash, then, is the jump at the end, and this variable is enough to cause a significant drop in the SES between the two events. This suggests that the duration of a movement does not correlate with how equitable that movement is between the sexes, otherwise the SES of jumping events would be greater, perhaps even in line with the SES of short-distance running, to reflect the brief duration of a jumping event. Instead, it is another factor – the presence of SBMA’s – that shrinks the PG. The SES has the potential to complement existing analytical tools, like surface electromyography, to determine movements to which the human body is adapted. Surface electromyography has been used to compare activity levels of muscles across different movements, which has led some researchers to conclude that jumping, which has a higher median amplitude of lower-body muscle contraction than sprinting or endurance running, reflects a type of movement to which H. sapiens may have adapted (Carrier et al., 2015). The results of our study, however, contradict that conclusion. Although jumping may have a greater median muscle activation than running, it is running that exhibits a smaller PG, suggesting that a greater number of SBMA’s have accumulated in the human body in service of running rather than jumping. Additionally, running can be sustained for a longer duration than jumping, which could explain how jumping, though it shows a greater relative median peak muscle amplitude than running, involves less overall muscle recruitment over an extended period of time. Far from merely contradicting the use of surface electromyography, the PG can be used alongside it to determine the evolution of the genus Homo. Gluteus maximus activity, for instance, is higher in endurance running than it is in walking (Lieberman et al., 2006), and the muscle is even more active in sprinting than it is in endurance running (Bartlett et al., 2013). A large gluteus maximus that developed to facilitate sprinting is therefore an example of a SBMA, which could explain the significantly smaller PG in short-distance events versus long-distance events and the higher levels of gluteus maximus engagement during sprinting versus endurance running or walking. This shows how the SES could serve as a tool alongside existing analyses, such as measurements of muscle activation, to better understand the evolution of the human musculoskeletal system. Some confounding variables regarding the SES should be addressed here. The first is the potential for a difference in PD across events to affect our results. The greater the PD in overall male to female participation, the more likely it is that the PG increases for that event. Hypothetically, if 1,000 men competed in fictional Event A while only 500 women did the same, versus if 1,000 men and 1,000 women competed in fictional Event B, we would expect Event A to have a lower SES than Event B, because the top 50 female scores would be drawn from half the population size in Event A versus Event B. If women are more inclined to participate in certain sports (like running) rather than others (like jumping), the SES would be inflated in the events with more female participants. Research documenting a general disparity between general male and female participation rates in athletics does exist (Deaner et al., 2012; Drake et al., 2015), but the literature does not specifically suggest that a participation gap exists between different track and field events. To control for this, we examined the PD as it related to two running events: the 5 km and the 100 m. These two events were compared because they fell into different EC’s – medium-distance running for the 5 km and short-distance running for the 100 m – and thus would be expected to possess significantly different SES’s. Because there was no available IAAF data on participation rates amongst world-record athletes, we used high school athletics statistics to measure the PD between male and female athletes in two sports: HS XC and HS OT. The PD for HS XC was calculated as 18.55, whereas the PD for HS OT was calculated as 19.34, meaning there was a greater PD for HS OT events like the 100 m versus for HS XC events like the 5 km. Figure 3 illustrates that, while high school running events appear to have smaller SES’s than adult events, the SES difference between the adult 100 m and the adult 5 km (2.41 ± 0.44) is relatively similar to the SES difference between the high school 100 m and the high school 5 km (2.70 ± 1.27). If a greater proportion of males compete in any given event, the PG between the male performance and female performance should widen, too. This does not appear to be the case for high school running events. The PD is greater for HS OT versus HS XC, yet the 100 m, a HS OT event, has a greater SES – indicating a smaller PG – than the 5 km, a HS XC event. Though HS OT has a greater PD than HS XC, its PG is smaller between men and women, as evidenced by the SES of 90.19 ± 0.21 for the high school 100 m versus the SES of 87.49 ± 1.06 for the high school 5 km. The PG is smaller in this short-distance running event even though the PD is greater, which indicates that the proportion of male to female participants is not likely to be as impactful as the type of track and field event on the magnitude of the PG. While these data provide substantial evidence that the PD is greater in HS OT than HS XC, the data from the 2018–2019 High School Athletics Participation Survey lumps all HS OT participants together, rather than just athletes who participate in the 100 m, so there is still room for error in the calculation of this PD. However, the differences in event performances by sex between events appear to remain stable when looking at track and field competition across all levels. At the 2018 National Collegiate Athletic Association (NCAA) Division I track and field championships, for instance, the PG between the top-scoring woman and the top-scoring man followed the same general pattern as that of all-time track and field records calculated in this paper. It should be noted that in the case of the NCAA championships, only the top results are listed for men and women, which leaves more room for error when computing the magnitude of the PG for its events. The NCAA PG is 92.01 for the 100-meter dash (vs. 91.13 ± 0.17 all time), 88.87 for the 10-kilometer run (vs. 88.37 ± 0.29), and 83.62 for the TJ (vs. 84.52 ± 0.38) (NCAA Division I Championships, 2018). More research should be done on equally sized samples of male and female populations, including, for instance, untrained individuals to confirm that the magnitude of the PG between men and women remains stable for these track and field events. The main issue with the PG as a tool to measure evolutionary movement is that in some cases, the magnitude of the gap appears to be notably unrelated to the evolutionary history of H. sapiens. Swimming, for instance, has a PG similar to – and in some cases smaller than – some running events (Millard-Stafford et al., 2018), even though swimming lacks the evolutionary record that running does in humans (Bramble and Lieberman, 2004; Castillo and Lieberman, 2018). This is in part due to the difference in fat distribution between men and women; females hold more subcutaneous fat in their lower body, which aids in buoyancy and therefore improves their swimming capacity (Blaak, 2001; Karastergiou et al., 2012). This differing subcutaneous fat distribution reduces the magnitude of the PG for swimming, even though running has been more evidently useful for humans on an evolutionary level. However, the world records kept for swimming are sparser than those kept by the IAAF for track and field, so the swimming data may be particularly affected by outliers. Still, the SES alone should not be used to measure how evolutionary a movement might be; the PG needs to be examined alongside other components of the evolutionary record to determine whether a smaller disparity between the sexes is truly due to SBMA’s or whether the gap is caused by a factor unrelated to evolution. The SES is a new approach to the evaluation of movement that could help clarify the movements essential to the evolution of the human musculoskeletal system. By applying it to 14 track and field events, we see that running has a significantly smaller disparity between the sexes than jumping does. Furthermore, within running events, short-distance running exhibits a significantly smaller PG than do medium- or long-distance running. The magnitude of this PG could be explained by the importance of SBMA’s in early humans. Because SBMA’s are more efficient at improving the quality of movement across generations than sex-specific adaptations, the result is a smaller gap between male and female performance in the track and field events most similar to movements early humans engaged in as a result of some selective pressure. While more research on the PG in sport is needed, it has the potential to evaluate movements to which the human musculoskeletal system adapted, which in turn can help clarify the evolutionary history of H. sapiens and inform exercise scientists as to which movements the human body is best-suited. Data Availability Statement All datasets generated for this study are included in the article/Supplementary Material. CC is the sole author of this manuscript, and the hypothesis described here is entirely his own. Self-funded with my own hard-earned cash. 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U.S.A. 110, 1237–1242. doi: 10.1073/pnas.1208717110 Keywords: performance gap, sex-blind, musculoskeletal, adaptations, track and field, sex equity score Citation: Carroll C (2019) The Performance Gap in Sport Can Help Determine Which Movements Were Most Essential to Human Evolution. Front. Physiol. 10:1412. doi: 10.3389/fphys.2019.01412 Received: 31 May 2019; Accepted: 31 October 2019; Published: 19 November 2019. Edited by:Pascal Edouard, Centre Hospitalier Universitaire de Saint-Étienne (CHU), France Reviewed by:Juliana Antero, Institut National du Sport, de l’Expertise et de la Performance, France Guillaume Saulière, Institut National du Sport, de l’Expertise et de la Performance, France Copyright © 2019 Carroll. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Collin Carroll, [email protected]

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Many Indonesians are worried about the damage that hoaxes and disinformation are causing to social cohesion in the country. Concerns first emerged during the 2014 presidential election and reached a fever pitch following the polarised 2017 Jakarta gubernatorial election. But these elections were just a practice run for the main event. Many observers expect a deluge of hoaxes in the months leading up to the 2019 presidential election. Hoaxes are powerful, but dangerous, political tools. Politicians who rely on hoaxes are like factories that dispose of their toxic waste into the public water supply. They only care about profit, not the damage they cause. The Ministry of Communication and Information has already begun making preparations. In the new year, it began operating a “negative content crawling machine”, worth Rp 194 billion (A$18.3 million), which will target pornographic content and hoaxes. Some 58 staff will work 24 hours a day to track problematic content, split over three shifts. This is typical of many responses to the problem of hoax news. They deal with the problem superficially, on a case-by-case basis, and fail to get to the bottom of the issue. Combing through social media to censor hoax news is like trying to use an ointment to cure cancer – it won’t do anything to treat the underlying problem. Many of the so-called “fake news” stories that have emerged in recent times could be considered “secondary hoaxes”, made possible by the existence of a larger, more potent “primary hoax”. In the history of the Indonesian republic, it is difficult to find a more powerful or destructive hoax than the story of the 30 September Movement (G30S/PKI). The story of G30S/PKI was devastating in the extent of lies told, and the number of victims it affected. This was a hoax that was produced and disseminated by the state on a massive scale for more than three generations, since 1966. Civil society organisations and private firms were complicit in its spread. There are two common misconceptions about hoaxes. First, although the word “hoax” is a relatively new term in the Indonesian lexicon, it would be wrong to assume that hoaxes have only become a problem over the past few years, with the rise of social media. Second, hoax news cannot be resolved or debunked simply by providing accurate information as an alternative, especially when nothing is done about the primary hoax. Hoaxes that have targeted President Joko “Jokowi” Widodo and environmental activist Heri Budiawan demonstrate these problems. Since running for president in 2014, Jokowi has often been the target of hoax news and smears. During the 2014 campaign he was accused of being a Christian of Chinese descent, and he and his family have repeatedly been accused of having connections to communism. These allegations are rubbish and can easily be refuted. When these political attacks rely on potent myths about communism, however, they can’t be ignored. But any response appears incapable of countering propaganda that has been absorbed by the population for three generations. Even the most accurate facts are incapable of neutralising phobia about communism. Instead of repeatedly rejecting the accusations, on occasions, Jokowi has tried a different strategy. He has said that he would “clobber” the Indonesian Communist Party (PKI) if it rose again. Perhaps by making such statements Jokowi is trying to appear firm or powerful. But for anyone who understands the roots of the problem, Jokowi’s statement simply reinforces the propaganda that he was trying to refute. He ended up reproducing the myth about the “danger of PKI”, a hoax that stems from the primary hoax about G30S/PKI. No statements, slurs, or compliments have a natural power to damage or elevate an individual’s reputation. Such power must be constructed, cultivated, reproduced and maintained in public. This is true of all stories: be that about the “miracle” of camel urine for health or the dangers of the PKI. The G30S/PKI hoax spread so widely because it was tightly protected by armed military officials and the thugs who were trained by them. After being reproduced for more than a generation, the G30S/PKI hoax has become established, and has entered the national imagination and everyday language. Thugs and weapons are no longer needed to safeguard the myth from the threat of counter-narratives. The G30S/PKI hoax is now accepted as fact. It has been widely accepted as if the PKI is a serious threat to the nation. As if communism is identical with atheism and is the enemy of religion. As if in 1965, the PKI rebelled against the state. As if members of the Indonesian Women’s Movement (Gerwani) that was affiliated with the PKI had an orgy at Lubang Buaya and mutilated the bodies of the kidnapped generals. The primary hoax about G30S/PKI has provided fertile ground on which various kinds of other nonsensical hoaxes can flourish. Accusations that someone is “PKI” only carry political weight if the primary hoax is still accepted as unquestionable fact. It is enough to accuse someone of being PKI without needing an explanation of what is so bad about being affiliated with the party. In this way, hoaxes can become like superstitions or beliefs. They are feared, without being understood, and cannot be countered by facts. As long as the G30S/PKI hoax remains a superstition, accusations of PKI can be easily thrown by anyone, at anyone. The second demonstrative case involves environmental activist Heri Budiawan, also known as Budi Pego, from Banyuwangi. In early January, prosecutors at the Banyuwangi District Court accused Budi Pego of spreading communism, or Marxism-Leninism, and demanded that he be sent to prison for seven years. This was only the most recent of thousands, maybe even tens of thousands, of similar cases. It won’t be the last either, unless something is done about the primary hoax. The case against Budi Pego was based on suspicions that he made a banner that included a hammer and sickle and used it in a demonstration against a goldmine in Tumpang Pitu Mountain, Banyuwangi, in April 2017. But prosecutors have been unable to produce the banner in court, leading to several observers questioning the validity of their indictment. It would be a shame if criticism of the indictment stops here. A more reasonable question would be: What is the problem with such a banner if it exists in the first place? To equate preparing and publicly displaying a banner with a hammer and sickle with spreading communist teachings is just as silly as suggesting that corruption can be reduced if more anti-corruption banners are displayed in public. One could go further. What is wrong with an ideology or discipline, including communism, being studied critically and openly? Studying communism does not necessarily mean that a person will become a communist. And even if they did, what would be the problem? The question is not whether Jokowi, Budi Pego, or anyone else is a communist sympathiser. Rather, we should be asking: what is the problem with communism? What really happened in 1965? What type of myths did the state perpetuate and maintain across three generations? What was the goal, and what have been the social costs for the Indonesian nation? What is the difference between believing that drinking camel urine is beneficial to health and listening to stories about the danger of the rise of the PKI in the twenty-first century? This article was originally published as “Dari Kencing Onta Sampai PKI” on mojok.co. It has been translated by Tim Mann and reviewed by the author.

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Kids stuck on screens all day? Give their eyes a rest with these Interesting Screen-free Activities for Kids, suitable for kids of all ages! With the pandemic continuing in our country and elsewhere, we’ve grown accustomed to this new life of masks, sanitizers and of course, online learning. Our kids are probably among the most affected due to the pandemic restrictions, and it’s not easy for them. From learning to communicating with grandparents, a large part of their lives have moved online. And when they go to screens for entertainment too, parents begin to worry. Problems with Excessive Screen Time This worry is not unfounded. It is not recommended for kids to have unlimited screen time, as it can have many adverse effects on their physical and emotional well being. Here is a quick look at some of them: - Excessive screen time has been linked to childhood obesity as children spend increased hours without any activity - Screens emit blue light which affects the release of melatonin, which in turn disrupts sleep patterns - Too much time in front of a screen has also shown to increase chronic neck and back problems in kids - Overdoing it on screen time also leads to behavioral problems, as well as depression and anxiety - Younger children are more seriously affected by too much screen time, as it affects their language and social skills, along with causing decreased attention spans Due to this, the American Academy of Pediatrics recommends screen time for children as follows: - Under 2 years – No screen time - 2-5 years – Less than an hour a day, under adult supervision - 6-18 years – Preferably 2 hours or less However, with the pandemic, it has become difficult to stick to these guidelines, especially since online classes often take up quite a chunk of this screen time. Older kids may also need to use screens for school work and projects even when there are no classes. According to the American Academy of Child and Adolescent Psychiatry, kids ages eight to 12 spend an average of four to six hours a day in front of screens, and teenagers end up having as much as nine hours of screen time a day. All this excess screen time is taking its toll on children’s eye health. According to the Wall Street Journal, experts are seeing an increase in eye problems in young children, particularly myopia and eye strain. When children spend extended periods in front of screens, the shape of the eye changes to adjust to a close range focus, leading to myopia. Decreased outdoor time and exposure to sunlight are other factors causing eye problems in the pandemic. As parents, this can be concerning, since with the current situation, we’re still unsure about when offline classes will resume. Since our children are stuck with online learning for the foreseeable future, we need to make a conscious effort to ensure their eyes stay healthy. The Indian Academy of Pediatrics suggests balancing screen time with other activities that ensure overall development without affecting sleep and physical activity. Here are some ways to do it: - Have a proper daily routine in place, with specified times for screens, physical activity, sleep, meals and entertainment - As far as possible, have all meals together at the table, with all screens and devices switched off - Avoid screen time at least 3-4 hours before bedtime - Try to have some ‘unplugged’ time during weekends where the family does something together without involving screens - Opt for phone calls to communicate with friends and grandparents instead of video calls Along with these, you need to find entertainment options that don’t involve screens, and in today’s world that can be quite a challenge! That’s why we’ve rounded up 25 of the most interesting and practical screen-free activities for kids that they can do by themselves or with a parent’s help. You’re sure to find something here for every age group. 20 Interesting Screen-free Activities for Kids There seriously can’t be a better screen-free activity for kids than reading! A study by the National Literacy Trust in America found that children today read less than any previous generation, and devices are partly to blame. Get your child some books suitable for his age and interests. Start with smaller books so they don’t get overwhelmed. Make it more interesting by setting up a small reading corner with a comfortable chair and a small basket or box to store books. Let them start with 15 minute sessions every day, and they will gradually increase the time themselves as they get more interested. 2. Play Board Games When we were young, playing board games was a usual activity, but with the increased popularity of video games and computer games, board games aren’t as common. However, the pandemic has brought about a renewed interest, especially in classics like Monopoly, Connect 4, Pictionary and Scrabble. There are also some new ones like Hungry Hippos, Tumblin’ Monkeys and Dr. Eureka. Board games are great fun for the whole family and keep everyone occupied for a good while. 3. Write a Letter Everyone laments the lost art of letter writing, as emails, instant messages and now emojis have taken over the world of communication. Let kids revive this art by writing a letter to their school friends or grandparents or cousins. It can be a simple letter about their day, something new they tried, a movie they watched, or it can even be a complaint about Mom to Grandma! Encourage them to use drawings, colors and stickers to perk up their letter. Nothing can compare to the charm of a handwritten letter, and when they get letters back from their loved ones, they will realize how delightful the experience is. 4. Try STEM Activities STEM refers to Science, Technology, Engineering, and Math. STEM education encourages children to question, seek answers and experiment to find solutions. STEM has become an integral part of modern education as science and technology advances at a rapid pace. Online classes may cause kids to miss out on a lot practical experiences, so have them participate in some STEM activities at home. Even young children can perform simple experiments like testing density, building structures, sprouting a seed, playing with magnets and many more. Let older kids maintain a science journal where they can track and record their experiments and findings. The pandemic has seen an increase in anxiety – in adults as well as children. The uncertainty of our lives, as well as fear of getting ill affects kids more than adults, especially since they often have incomplete information and bigger fears. Journaling is one of the best ways to relieve this anxiety and to get some clarity in their thoughts. Writing in a journal everyday can be a little overwhelming for beginners, so start with a gratitude journal. Write down 3-5 things they are grateful for that day. Gradually, they can start writing about experiences and feelings. Some children may prefer sketching or doodling instead of writing – let them do whatever makes them feel comfortable. 6. Try Cooking and Baking Cooking is a life skill that everyone should have – boys and girls. Rather than waiting for them to grow up and learn it on their own, it’s far easier to teach them right from an early age. Even young children can find some way to help in the kitchen, like measuring, stirring, pouring, washing dishes and setting the table. Older children can start to prepare simple meals like sandwiches, and pre-teens and teenagers can learn basic knife skills and how to operate the stove. Who knows, they might even discover a career path! Get children interested by making their favorite dishes. Young children often enjoy the process of baking and watching liquid batter turn into fluffy cupcakes and cakes. 7. Draw and Color There is a reason there has been an upsurge in demand for adult coloring books – they are known to relieve stress and improve attention, at a very low cost! This is also why drawing and coloring are great for kids, and it helps them give vent to emotions they can’t articulate through speaking or writing. All you need are blank sheets – you can even use the backs of documents you no longer need. Coloring pages are easily available to download and print for free. If a blank page is too overwhelming for a child, you can give them prompts, like to draw something from a dream, or a picture of a gift they’d like for their next birthday. 8. Get involved in Gardening As soon as lockdown began, many of us took to gardening, and studies from across the world show that this has become more than a panic hobby. Many people have expanded their gardens and are growing their own herbs and vegetables. Gardening is a very relaxing activity, and it also has many benefits for children. It is an opportunity to connect with nature, even when living in a city high rise. It teaches patience, nurturing, and the importance of small everyday tasks. If this is a new world for you, start with something very low maintenance, like a money plant or mint and then try growing your own microgreens. 9. Play with Puzzles Puzzles are something that appeal to people of all ages, and especially to kids who love a bit of a challenge. There are many kinds of puzzles out there, ranging from crossword, sudoku and word searches to actual jigsaw puzzles, Rubik’s cube, magnetic puzzles and many more. There are some really intricate puzzles available today, and you can choose one based on a complexity level your child is comfortable with. Many of the word puzzles are available for free online, and you just need to print them out. There are many proven benefits of dance for children, and it solves many problems in one go! It gets kids moving, it relieves stress, it increases appreciation of the arts, and it’s immensely enjoyable. You don’t need to join a formal dance program – all you need is some open space and a few upbeat tunes. Kids can dance on their own, with their siblings or with their parents. Let them choose any song they like and simply move their body however they like. 11. Start a Project This is an idea for slightly older kids who have a little more patience to see the project through. You can choose any project – it can be a small skit that the kids are putting up on their own. It can be constructing a doll house or play kitchen out of cardboard boxes, or it could be repainting or repairing something in the house. Pre-teens can try something more advanced, like an electronic project, for which you can find ready made kits. Go through all the steps, like planning it out in detail, gathering all the supplies, and reviewing the project at every stage. Not only will this teach them valuable life skills they’ll need in their adult life, it also encourages them to stick with something and see it to completion. 12. Play Active Games The lockdown has restricted the movement of kids outdoors, and this can be more stressful if you live in an apartment or don’t have a front yard of your own. This can naturally cut down on kids’ natural activity, so you need to find ways for kids to stay active indoors. You can get some simple indoor activity toys and games that make this more fun. It can be something as simple as a hula hoop or a bowling set – as long as it gets kids to move, it works! 13. Build a Fort Most young children enjoy playing with pillows and making their own buildings with them. Take it a step further and build a little fort. If you have enough pillows and cushions, you can use them. Or you could put a bedsheet on a table so that it hangs down the sides and you have an instant play house. You can also make an obstacle course with makeshift tunnels and hurdles – it will keep little kids active and busy for hours. 14. Make DIY Toys Who says you need to spend loads of money to be entertained? You can easily make your own simple toys with things you have lying around the home, and kids will enjoy playing with things they made themselves. Cardboard boxes are incredibly versatile and you can make all sorts of things out of them. You can also recycle old containers and ladles to create a pretend play kitchen. Old clothes and costume jewelry are perfect for a dress-up corner. A pipe cleaner easily turns into a bubble wand, and you need nothing but a light for shadow play! 15. Try a Room Makeover One problem most parents across the world have is with getting their kids to clean their rooms. It starts out with not putting toys back into the box when they’re toddlers, and ends up with teen rooms that look like a cyclone hit them! Avoid this in the future by getting kids interested in how their rooms look right from a young age. Go through magazines or use your imagination to come up with a room makeover plan and set about executing it. Even just rearranging the furniture or changing out the cushion covers can make big difference. You can then mix and match decor items from other rooms to create a space they’ll be more invested in. 16. Make Recycled Crafts Kids have powerful imaginations, and they’re at a stage in their lives when everything seems possible. Make use of this by encouraging them to find new uses for old items. Empty containers, plastic bottles, newspapers, bottle caps – all these things we throw into the trash can be upcycled or recycled into something else. You can of course, find ideas online, but since this is supposed to be a screen-free activity, let the kids rack their brains and think about how they can turn trash into treasure. 17. Celebrate a Festival We live in a huge world with 195 countries spread across six continents, and each one has their own unique culture. Even in a single country, you’ll find many different styles of clothing, cuisines, music and languages. Just take India for example! Unfortunately we can’t travel during the pandemic but you’re sure to find a festival every couple of weeks, and it’s a great opportunity to learn about a particular region. Set up a calendar with festivals you’d like to celebrate, and go all the way. Make decorations, try out a regional dish, try to dress up like the locals of that place and learn a few celebratory phrases in that language. It’s an exciting project that’ll also increase kids’ appreciation for cultures different from theirs. 18. Try a Creative Challenge A wonderful way to keep kids occupied for an entire month is to opt for a creative challenges. You’ll find many ideas online, like a 30-day photo challenge or a 30-day doodle challenge. Find one that suits your child’s interests and then mark each day on the calendar as you complete the day’s task. Make sure the challenge is something very simple – like click a photograph a day – or it’ll be cumbersome to keep up for an entire month. Look for activities that don’t require screens; for instance, go with a digital camera instead of a phone for a photo challenge. 19. Learn a New Skill Since the kids are at home with you all day, it’s a great opportunity to teach them something you know. It could be anything, from making the perfect sponge cake to embroidery, it just needs to be age appropriate. Avoid assigning activities according to gender; keep it open so anyone can learn anything. Spend a little time every day teaching this new skill and it’ll turn into a lovely memory for both you and your child in the years to come. 20. Go Outside No, we’re not asking you to break lockdown rules and travel; we’re talking about taking a small walk in your neighborhood with your kids. Simply walk down the street and encourage your child to observe. How many floors a building has, the color of the flowers on a tree, the writing on the signs. This will relieve your child from the stress of being indoors all day, and will help her get some sunshine and fresh air. If you take pets along with you, it can also turn into some good exercise. At the end of the day, don’t stress yourself out too much. In a situation like this, it’s understood that kids will spend a little extra time on their screens. It’ll work better if you don’t constantly nag your child about screen time and instead, build the screen-free activities into his day in an organic manner. Remember, you don’t have to plan every single second of your child’s day. Leave plenty of white space between activities so your child’s brain has time to take a break from all the stimulation. Boredom is also important for children as it helps to develop their imagination and problem solving skills. Don’t forget to be a good role model too, by putting aside your device and spending more time on books, games and physical activity. After all, we need to practice what we preach! Leave a Reply

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Bladder Stones in Rabbits Dr. Deb Reed Bladder stones develop when calcium crystals in the urine combine with each other and oxalate and other particles in the urine, including protein, mucous, and bacteria. Symptoms range from blood in the urine, straining to urinate, frequent urination, and sometimes just acting uncomfortably. Diagnosis is by bladder x-rays and urinalysis and culture. Treating the infection and correcting any dietary or general healthy conditions is important. You would think it would be a simple fix – surgically remove the stone(s) and treat the infection, reduce calcium in the diet – but it’s actually much more complicated. Studies show that most bladder stones recur, sometimes within 1-2 months of surgery, even with the best preventative care. Dietary changes lower calcium, medications such as potassium citrate, increasing water consumption by feeding fresh greens which are rinsed well and fed with the water on them, and even diuretics in some cases are used to slow the growth of the existing stone and reformation of new stones postsurgery. Dietary changes include feeding primarily timothy hay or grass hay, along with a very small amount of Oxbow rabbit pellets (⅛ for rabbits under 3.5 lbs and ¼ for rabbits over 3.5 lbs), and 1-2 cups of fresh greens per day. Good greens are cilantro, celery leaves, dark leaf lettuce, endive. Bad greens are kale, parsley, broccoli leaves, and collard greens. There is a full list of calcium content of vegetables listed on rabbit.org put together by Dr. Harkness. Abdominal surgery and bladder surgery in rabbits has more risks than with dogs and cats, due to their sensitivity to surgery’s stress and its effects on recovery. A stressed rabbit will develop problems such as poor appetite, decreased motility and functioning of their gastrointestinal tract (GI stasis), leading to complications. The healthy bacteria in the GI tract that are needed for digesting the plant foods can be affected by the antibiotics needed to treat the infection in the urine. Metoclopramide to promote healthy GI motility, along with good pain control with Metacam, and supplemental feeding with Critical Care Herbivore are helpful, but do not prevent all complications. Rabbits are also known to pull out the sutures, and they don’t accept wearing a protective cone such as used with dogs and cats. Consequently, if the bladder stone is small and treatment for the bladder infection, along with other medications results in a happy rabbit, we can often go years without surgery. If on the other hand, the rabbit is not doing well and/or the stone becomes very large, then surgery is recommended – at this point we are concerned about quality of life and getting the stone out is worth the other surgical risks mentioned earlier. Each rabbit is an individual patient in our eyes and requires a plan tailored to their needs and health.

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Do you truly want to know how to prosper after dropping out of high school? However, you’re not alone. Many individuals are looking for the same answers. Dropping out of school is abandoning your studies before they are completed. However, this does not imply that you should abandon your life. After all, everyone’s life is unique. Each of us has our own set of goals and obstacles. And there are as many different pathways to achievement as there are people on this earth. Nobody is the same as the other. To have a good voyage, you don’t have to follow the herd. Facts about High School Dropouts According to the Pew Research Center, the high school dropout rate in the United States reached a new low in 2016. Only 6% of participants between the ages of 18 and 24 have left the program. As a consequence, the highest-ever high school graduation percentage of 84.1 percent was achieved. State-by-state, however, high school dropout rates might vary significantly. According to KIDS COUNT, for example, in 2017: - In America, between 2% and 7% of 16- to 19-year-olds were not in school and had not completed high school. Connecticut and Virginia had the lowest rates. New Mexico had the highest rate. - Between 4% and 14% of those aged 25 to 34 did not complete high school. Hawaii, North Dakota, and the District of Columbia were among the states with the lowest rates. Mississippi had the highest percentage. As a result, high school dropout rates aren’t rising. Fewer and fewer high school students appear to be choosing to drop out. In addition, the number of schools classified as “dropout factories” is dropping. According to America’s Promise Alliance, the number of big high schools with 67 percent or more graduation rates has decreased by around 40 percent between 2002 and 2016. Why High School Students Drop Out Every dropout has their reasons for dropping out of school. However, such justifications are frequently based on common experiences shared by many other students. In a poll of American high school dropouts conducted by the Bill and Melinda Gates Foundation, over half of them listed dull and useless coursework as the primary reasons for dropping out. Other elements that frequently come into play are: - Not feeling backed up, challenged, or inspired - Being unable to do studies, particularly after missing multiple days of courses - Having to look for work to assist a single parent or younger siblings - Having to look after an ill or handicapped family member - Taking up the role of a parent - Do you have a lot of social anxiety? - Disrespectful feelings - I have a tremendous desire for greater adventure. - Believing that one’s time might be better spent elsewhere Is it True That Successful High School Dropouts Exist? In truth, some of the world’s most successful people never finished high school. And for every renowned dropout, there is a slew of other dropouts who are quietly leading successful and meaningful lives. The following are some of the most well-known high school dropouts: - Richard Branson, the Virgin Group’s wealthy CEO - Tumblr’s multimillionaire creator, David Karp - Filmmakers like Quentin Tarantino and Peter Jackson have won awards for their work. - Robert De Niro, Uma Thurman, and Catherine Zeta-Jones are some of the most well-known performers in Hollywood. - 50 Cent, Jay-Z, and Billy Joel are some of the most well-known musicians in the world. - Several other millionaires from the business, sports, and entertainment realms were also there. Check to See Whether You May Legally Drop Out Every state in the United States requires students to attend school. It is illegal for a youngster not to attend school. You must be homeschooled in line with your state’s rules if you do not attend a public, private, or parochial school. So, when may you drop out of school without your parents’ permission? Depending on the state, all pupils are obligated to attend school until they are 16, 17, 18, or 19 years old (if they do not graduate first). Make a List of Your Future Objectives How to Quit Your Job It’s always beneficial to be able to see where you’re aiming to go. So write it down. You’ll be less likely to make a decision that puts one or more of your dreams on hold. You’ll also have a better notion of where to concentrate your efforts and which tasks are worthwhile. Examine Every Possibility This phase is crucial in determining what to pursue after graduating from high school. After you’ve written out your objectives, spend some time researching what you’ll need and how you’ll achieve them. Will you need a college diploma or a certain type of vocational accreditation, for example, to qualify for the job you want? If this is the case, you may need to look for schools and unique programs that may help high school dropouts develop the college and job preparedness skills they need to succeed. Obtain a GED or Other Form of a High School Equivalency Diploma GED certification is typically a good choice for dropouts who do not have a high school diploma. General Educational Development (GED) is an acronym for General Educational Development. The GED Testing Service has a trademark license for it. You can receive a certificate that is frequently accepted at the same level as a standard high school diploma by completing a series of examinations that examine your fundamental understanding of math, science, reading, writing, and social studies. As a final thought, some people think that high school is slowing them down from achieving their goals. Usually is because they can’t focus on the skills they are good at. Still, dropping out is a huge decision, which you shouldn’t make lightly. So, plan you strategy and if you are really up for it, go for it and make your dreams come true.

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7az sa3eed. I know what you are thinking:"Why are there numbers mixed in with letters?!". Well, the answer is simple. There are some sounds in the Arabic language that are not represented by letters. For example "7ah". This sound has no equivalent in the English alphabet and therefore we use the number 7 to represent the sound. And by the way the number 7 actually looks quite similar to how you would write the letter using Arabic script. Numbers and letters July 16, 2009 November 22, 2010 now I understand. And 'am enjoying the lesson. May 9, 2011 Hi Amira, what sound does 3 represent? May 10, 2011 Ahlan Stephanie The number 3 represents the Arabic letter ع or 'ayn. You can see a list of the alphabet and their sounds here: http://members.rocketlanguages.com/arabic/language-and-culture/1-9-i-like/738#writing I hope that helps! - Amira

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This Google Map shows the sites of Jewish communities in Latvia and other sites of use to Jewish genealogists and ancestral tourists visiting Latvia. Surviving synagogue buildings are marked on the map with Stars of David. Most of these are no longer functioning and have been put to temporal uses. A few known sites of destroyed synagogues are also marked in the same way. Surviving and former Jewish cemeteries are marked with regular pins. Many of the older and smaller cemeteries are now overgrown or wooded with few surviving legible gravestones. Some mass graves from the Holocaust are also marked in this way although most now have a commemorative stone. Holocaust monuments and memorial sites, including Nazi concentration camps, are shown with black memorial pins. It should be noted that not all of the sites actually have a physical memorial marking them. The balance of pins (for those places with no specifically sited synagogue, cemetery or memorial) are simply dropped on to the approximate centre of the town or village (shtetl) which had a Jewish community. Places are listed alphabetically under their current Latvian names. Alternative place names (for instance German, or Russian or Yiddish in transliteration) are given in the text. If you do not know the modern place name, you can search under the old name and the correct place will be returned in your results – for example, search for Goldingen and you will be shown Kuldīga; search for Hasenpoth and you will be offered Aizpute. Switching the base map from road map to satellite view or vice versa may assist researchers in understanding particular sites or reaching them if undertaking ancestral research on location in Latvia.

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A third character to explore in The Scarlet Letter is the minister, Arthur Dimsdale. Many sources narrow in symbolically on the idea that Dimsdale is ‘dim.’ Dim as in stupid, when he fails to recognise the evil in Chillingsworth. Dim as in weak, as his physical health declines. Dim as in muted light, when he is hiding himself in the dark of his denial of Hester and Pearl. However, there is far more to explore here. Dale means ‘valley.’ I live in a valley, and I love the sense of comfort and security the hills provide. One feels hidden away, not everyone can see you when you’re in a valley. Being in a valley cuts off light though. The sun isn’t visible until it has climbed over the hills, and it leaves earlier dropping behind them. This gives valley dwellers a shorter day. Being down in the valley also limits our perspective. We see what we see of our own little area, we don’t get a sense of the larger world unless we climb up to the top of the mountains. Isolation tends to produce navel gazers, and this certainly applies to Dimsdale. He has no sense of a wider world of possibility open to him. Finally, Arthur is an old Welsh name means ‘bear.’ There are lots of bears where I live as well, so I know something of their characteristics and I see Arthur reflected in this name choice as well. A bear is a powerful creature which has the ability to get whatever it wants, but it can be defeated until it becomes a dancing bear- moving to the tune of trainer who has weakened it, until it has no idea of its power anymore. A bear looks distinguished and capable to some, but the bear itself often seems slow and stupid, going about motions without a lot of consideration to more creative solutions (return to the same places to feed on easy garbage, for example, instead of fleeing to the safety of the wilderness where freedom means more effort). Bears also hibernate. They fill themselves and climb into their dens and ignore the world, stuck in their own dreams until awakened by the hunger for more. However, this is the time when bears are their most vulnerable, for a hunter can pick them off as they groggily head out the door. Yes, Nathaniel Hawthorne made a very appropriate name choice for Arthur Dimsdale! (c) Shawn Bird. Students, to avoid plagarism, cite this article as follows: Bird, Shawn. “Arthur Dimsdale: can’t see his power.” https://shawnbird.com/2011/02/20/arthur-dimsdal…-see-his-power/ Collected (insert the date you copied the information) inspirational kids October 10, 2012 Tags: characters, Grace Awakening Myth, J-Roy, mixed martial arts, Roy, ucl I’ve already told you that I occasionally use the names of my students (with their permission, of course) in my stories. The characters are not representations of their namesakes; they have their own adventures, conflicts, and personalities which are completely distinct. Still, sometimes the fictional and real have the odd thing in common. For example, in Grace Awakening Myth there’s a character called J-Roy. You learned the other day that J-Roy dances, is athletic, and looks great in a unitard. The real J-Roy is also pretty tough. Look who’s a head-liner in a local mixed martial arts fight? Uh huh. Ben desperately needs all the help he can get. I wonder if J. Roy will give him fighting lessons? 😉

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Episode 6 in Science @ESA vodcast series. Rebecca Barnes explains how astronomers measure positions and motions of the stars. Using Hipparcos data as an example Rebecca shows how vital astrometric data is for our understanding of fundamental science in the fields of astronomy, astrophysics, cosmology and fundamental physics (for example, Solar System studies, detection of exoplanets, stellar structure and evolution, evolution and structure of our Galaxy, distribution of dark matter, testing general relativity theory, timekeeping, development of celestial reference frame) . The video introduces Gaia mission and its scientific goals, explains how Gaia will carry out measurements, and looks at the handling of the vast amount of data gathered by the satellite. Download the script of the vodcast. Download "Episode 6: Charting the Galaxy - from Hipparcos to Gaia" from ESA's website. (Courtesy of ESA) Page last updated: 02 June 2014

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Dallas Asphalt Shingle Roofing Asphalt Shingles are designed for use as multilayered, water shedding roof components that rely on the slope of a roof decking to effectively shed off water. They were first manufactured in Michigan in 1903. By the 1950’s the three-tab design was the most popular. This shingle was a thick-butt asphalt and felt with a weight of approx. 235lbs. per roofing square. Their reinforcements and shapes categorize asphalt roofing Shingles. Asphalt shingles that use organic reinforcing mats are referred to as “organic-reinforced asphalt shingles”, and those that use glass-fiber reinforcing are designated as “glass-fiber reinforced asphalt shingles.” There are basically just two styles of asphalt roofing shingles today, which are, three tab strip shingle, and Laminated strip shingles sometimes-called “dimensional” or “architectural” roofing shingles. Asphalt Roofing Shingle History During the 70’s most roofing manufacturers began to replace the organic core of the shingles to fiberglass felt. This fiberglass mat core is far superior in performance than the organic “i.e. paper” felt shingles of the past. Fiberglas roofing shingles do not absorb moisture so maintain their stability. They also do not mildew, mold up, or rot. Fiberglass roofing shingles are incombustible, so they are considered a “Class A” fire rated shingle. - Strip Shingles: These roofing shingles are in a strip form and generally longer in width than height. Common dimensions for standard shingles are 12”x36”. For metric shingles, the common dimensions are about 13”x39-3/8 “. Products referred to as “three-tab” and laminated shingles all are categorized as strip shingles. Strip shingles are “self-sealing”; that is they contain adhesive seal strips that bond to overlaying or underlying course of shingles for wind resistance. - Laminated Strip Shingles: Sometimes called “dimensional” or “architectural” roofing shingles, these shingles have additional material laminated to strips to create random thicknesses, thereby giving the shingles a more dimensional appearance. Laminated shingles are “self-sealing”; that is they contain adhesive seal strips that bond to overlaying or underlying course of shingles for wind resistance. Dimensions and weighs vary depending on the manufacturer. Laminated shingles can also take the form of full double laminates, cu-out laminates and triple laminates. - Installation Considerations: The bundles of roofing shingles are typically set up on the roof utilizing a crane or shingle conveyor. Shingle bundles are then mixed on the roof to provide a color blend. During a “tear off” of the old roofing layers, precautions are made to protect the building and property below. All old shingles and some roofing components are removed, nails pulled, roof decking securely fastened and rotten decking replaced. All propriety components are then applied including chimney and wall flashing as well as valley, pipe, skylight and venting. - Cost Considerations: the costs or any Dallas roofing job will vary depending on these following conditions. - The slope of the roof. - The type of roof decking. - The design of the roof planes, (simple or complicated). • Style of roof “i.e. gable, hip, mansard”. - Solid or spaced sheathing. - Type of roofing shingle applied. - Single story or multi-story building. - New, Recover, or Tear off. - Access to working conditions.

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VLAN Interfaces are required in network scenarios where you have different VLANs and need Inter-VLAN switching on Layer3 (Routing capable) switches. Every VLAN that needs to be routed should have a VLAN interface. Let’s say we have VLAN 10 which hosts the subnet 192.168.10.0 subnet, VLAN hosts 192.168.20.0 subnet and VLAN 30 hosts 192.168.30.0 subnet. For Inter-VLAN routing to work, we need to have a VLAN interface setup for each of these VLANs and configured with an IP address from the same subnet which will be the default Gateway for that subnet. Lets say, 192.168.10.254,192.168.20.254.192.168.30.254 are the IP addresses for VLAN Interfaces of VLAn 10,20,30 respectively. Assuming the VLANs are configured already, let’s proceed to get the VLAN interfaces created. Enable Routing on the Switch ciscoswitch# conf t ciscoswitch(config)# ip routing Add VLAN Interface ciscoswitch(config)# interface vlan10 ciscoswitch(config-if)# no shut ciscoswitch(config-if)# ip address 192.168.10.0 255.255.255.0 This configures a VLAN interface for VLAN 10. Default Route on Switch Add a default route on the Switch. This will forward all traffic from the different VLANs to the default router. ciscoswitch(config)#ip route 0.0.0.0 0.0.0.0 192.168.100.1 Interface to the Router If the switch cannot reach the default router through a VLAN then an interface that connects to the router which does these routing needs to configured as a routed interface and assigned with an IP address that is in the same subnet as that of the Default router. ciscoswitch(config)# interface gi0/1 ciscoswitch(config-if)# no shut ciscoswitch(config-if)# no switchport ciscoswitch(config-if)# ip address 192.168.100.2 255.255.255.0 This makes the interface as a routed interface and assigns an IP address in the same subnet as the default router. If you're new here, you may want to subscribe to my RSS feed. Thanks for visiting! it is very good. 10 Q! Thank you for hints Is quite ohk bt wat do u config ip route of an exit interface Never thought it was possible in cisco’s iOS but I was definitely proven wrong because of this. Though it’s weird upon checking my IP address at IP Elk after this, it didn’t displayed correctly. I need to fix it probably. Thanks for this insightful post!

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Gardening is a hobby that increasingly is becoming popular among young people. However, those who live in the cities have a disadvantage: many do not have enough space in their backyard or not have a backyard at all to grow their own produce. Fortunately, there are a number of fruits and vegetables that city-dwellers can plant inside their own apartment. Most of them would still need regular exposure to sunlight, and you have to plan for insect control so that your produce, and your home, will not be infested with pests. When you are ready, here are some fruits and vegetables you can grow in the comforts of your home. Tomatoes are a staple for many cuisines. You can add them into salads, turn them into a sauce for your pasta, and transform them into soups. Tomatoes are also surprisingly easy to grow, even for beginners, and they can survive inside your apartment. Your plant would need at least 10 hours of daylight every day to make sure that it would yield fruits. You also would need to water it regularly so that the fruits do not split. When the flowers have bloomed, tap the stem lightly to induce pollination. Scallions are probably some of the most common vegetables grown indoors. It is easy to care for: unlike tomatoes, they do not need as much sunlight to thrive. You can leave the plant in your kitchen under partial shade and it will still Moreover, you do not need to start by planting and germinating seeds. As soon as you have cut off the green part of the scallion, save the root. Leave it in a jar with water. You only have to wait a few weeks to produce a full-grown plant. You can also transfer your scallion to the soil in a clay pot. Surprisingly, you can grow carrots just about anywhere and tolerates most conditions. It needs exposure to full sunlight but will also survive in partial shade. You can also grow it in a container which means it, too, can be an indoor plant. However, you would need a longer container to provide your carrots with room to grow. You may want to grow the smaller variety which is easier to care for and does not need a long time to mature. If you love herbs, this is the project for you. You can grow a variety of herbs easily on your windowsill. You will have access to fresh herbs all-year-round. Herbs still require a lot of sunlight (a minimum of six hours a day) that is why you should keep them near a window. Otherwise, your plant will become leggy. It might also lose its flavor. It should always be watered regularly. Do not let the soil dry out. However, be careful not to overwater it either. A good rule to follow is if the topsoil is dry, but the lower layer is still damp, that is when you should water the plant. Avocados have become a staple to breakfast food around the world. If like many millennials, you like to eat your toast with avocados, you probably have a lot of avocado pits in your home. ; The pit you often discard can be regrown into an avocado plant. Once you remove the pit, wash it under the tap and remove any extra flesh. Place several toothpicks into the pit and suspend it on top of a glass of warm water. The pit should not be completely submerged underwater. Only about an inch of the pit should be touching the water. Place the pit under bright light and change the water frequently. You will notice that roots and, eventually, stems and leaves will sprout from the pit. Once the roots have filled much of the glass, transfer it into a pot. Caring for an avocado plant is tougher than growing tomatoes or herbs. You also will not get an avocado fruit in years — if you even get one at all. Indoor gardening is a fun and rewarding hobby. If you really spend time caring for your plants, they will repay you with clean air and fresh produce.

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What are routing attacks? Routing table poisoning means the unwanted or malicious change in routing table of the router. This is done by editing the routing information update packets which are advertised by routers. This attack can cause severe damage in the network by entering wrong routing table entries in the routing table. What are the different types of network attacks? Common Types of Networking Attacks - Computer Virus. Computer viruses are one of the most common network security attacks that can cause sizeable damage to your data. - Computer Worm. - DoS (Denial of Service) and DDoS Attacks. What are the five main types of network attack? What are the Common Types of Network Attacks? - Unauthorized access. Unauthorized access refers to attackers accessing a network without receiving permission. - Distributed Denial of Service (DDoS) attacks. - Man in the middle attacks. - Code and SQL injection attacks. - Privilege escalation. - Insider threats. What are the main types of Internet security attacks? 7 Types of Cyber Security Threats - Malware. Malware is malicious software such as spyware, ransomware, viruses and worms. - Denial of Service. - Man in the Middle. - SQL Injection. - Password Attacks. What are active and passive attacks? In an active attack, an attacker tries to modify the content of the messages. In a passive attack, an attacker observes the messages and copies them. What are wireless attacks? A wireless attack is a malicious action against wireless system information or wireless networks; examples can be denial of service attacks, penetration, and sabotage. What are three types of access attacks? The four types of access attacks are password attacks, trust exploitation, port redirection, and man-in-the-middle attacks. What are router attacks and how do they work? These low-level attacks are often designed to hijack the router for nefarious tasks including DDoS attacks or malicious cryptomining – but more sophisticated hacking operations are increasingly targeting routers as a means of gaining access to networks and data sent and received across them. What is router poisoning and how to prevent it? Routing poisoning can cause extremely harmful damage to networks and servers as a result of the incorrect data being added to the routing table. Another of the most common router attacks is something called a hit and run attack and they are designed as one off attack on a specific network or router. What is a hit and run attack on router? Hit and run attacks. Another of the most common router attacks is something called a hit and run attack and they are designed as one off attack on a specific network or router. Hot and run attacks are often referred to as ‘test hacks’ and also occur when malicious data is injected into router through code. Can router attacks be prevented? Unfortunately, router attacks cannot be 100 percent prevented, but there are a few things that you can be doing to prevent one of the most common router attacks from occurring on your system and network. Large organisations are vulnerable to widespread attacks, with come being malicious and some carried out simply to prove a point.

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26: Based on your answers in Exercises 24 and 25, sketch a phase portrait of the dynamical system Phase portrait of a dynamical system is: Transition matrix may refer to: The matrix associated with a change of basis for a vector space. Stochastic matrix, a square matrix used to describe the transitions of a Markov chain. State-transition matrix, a matrix whose product with the state vector at an initial time gives state vector at that time. As we clearly now that, Hence, the final answer is: 25: Consider a positive transition matrix meaning that a, b, c, and d are positive numbers such that a + c = b + d = 1. (The matrix in Exercise 24 has this form.) Verify that are eigenvectors of A. What are the associated eigenvalues? Is the absolute value of these eigenvalues more or less than 1? Sketch a phase portrait. 94% of StudySmarter users get better grades.Sign up for free

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Jump to navigation Jump to search |Skill and improvement| Main / Skills / Nature / Gardening / Rose trellis Some climbing roses growing up a sturdy wooden trellis. A decorative trellis created out of a rose sprout. It can be harvested when rose bushes are in season, using the Gardening skill and a sickle. Creation and Improvement - The sprout's quality determines the chance to create a trellis, but a minimum of at least 10 gardening skill is required to start a trellis in all cases. - Improves using carpentry items/tools but uses the gardening skill for actual improvement and creation. - The final shaft attached will determine the trellis' wood type. - Trellis quality does not affect harvest or any aspect of the growing function. A quality level of 10 allows for securing, and higher quality provides better decay resistance off-deed, as is typical with most items. - It must be planted/secured in order to actually begin growth and reach eventual harvestability. - A maximum of 4 trellises of any type can be secured and utilized on any one tile. - It can be harvested when rose bushes are in season, using the gardening skill and a sickle. - Rose sprouts can be picked from a rose trellis. - They cannot be loaded - They can be moved and picked up. - May be given a name which can be seen on the tooltip. - Trellises age & grow slower than bushes. - Shriveled trellises will regrow to young over time. - Aside from obvious outward beauty, shininess, and posterity, rarity, unfortunately, has no effect on trellises.

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Vol. 10 Issue 3, Fall 2005 By Ginger Walker Loudoun County provides a unique wintering environment for migrating birds. While our area certainly isn’t a tropical haven, it doesn’t experience the harsh winter weather of New England or the Midwest, either. As a result, Loudoun residents can anticipate migrant visitors each winter as well as enjoy some “summer” birds year-round. Northern states lose their bluebirds and robins in winter, while our populations of these birds can actually increase during the winter months. Catbirds will fly south, but mockingbirds will stay. Grackles will leave, but starlings will remain. House wrens will go, but Carolina wrens will stay and may even visit a birdfeeder if you offer peanuts or suet. We can look forward to the arrival of wintering finch and sparrow species in October and early November. Pine siskins (plain, brown-streaked finches with bright gold wing bars) and purple finches (recognized by the male’s bright red-wine coloring and the female’s distinctive white eyebrow) may join your house finches and goldfinches at a thistle feeder. Sparrow species prefer to eat millet seeds scattered on the ground. In this family you’re likely to see the white-crowned sparrow and the white-throated sparrow. However, the most populous migrating member of the sparrow family is the beloved “snowbird,” or dark-eyed junco, which returns to our area in October and typically remains until late March. The species known as the dark-eyed junco is actually made up of five different sub-species: slate-colored, Oregon, pink-sided, dark-headed, and white-winged. In the past these five sub-species were considered separate until it was discovered that Oregon and slate-colored juncos were crossing the Rocky Mountains and interbreeding with each other. The juncos we’ll see in our area are the slate-colored sub-species. At the feeder, these small birds in their dapper black ostensibly appear docile. However, wintering juncos have one of the strictest hierarchy structures among flock birds. Each flock has a dominant male. Fights break out between birds when the dominant male is challenged. The “zipping” sound and flashing white tail feathers are signs of alarm among juncos. In the flock, the older males dominate younger birds as well as the females, which are easily identified by their rusty color. The farther north the flock, the higher the number of males as females and first-year birds are pushed south by aggressive males. Simply tossing some millet or other small seeds on the ground in mid October will help attract juncos. These birds return to the same wintering area each year. If you feed juncos consistently every year, then you’re likely to have repeat visitors choose your yard as their winter home. Dense evergreens provide an ideal roosting habitat for juncos. Feeding juncos year after year is a special delight precisely because they are only present during the winter months. These sparrow relatives are not as skittish as other feeder birds, allowing us the chance to closely observe how a community of birds interacts. While the autumn months can’t offer a birdwatcher the thrills of spring, the arrival of winter migrants brings quiet pleasures that are as unique to the season as the smell of the first frost and the sound of dry leaves rustling in the October wind.

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Experiencing Mental Health Concerns Due To Punishment? Work With A Therapist Online. Psychological punishment can refer to a variety of actions meant to psychologically affect others so that they will engage in desired behavior. Although punishment may have been used extensively in the past, positive reinforcement is often more highly recommended today. If you are experiencing mental health concerns due to experiences with psychological punishment, you may wish to consider online therapy. The Law Of Effect Dr. Burrhus Frederic Skinner, or B.F. Skinner, was a psychologist who thought classical conditioning may have been too simple to explain human behavior accurately. Therefore, he decided to use the causes of action and consequences to determine why we do what we do. Skinner based his operant conditioning on Dr. Edward Thorndike'sLaw of Effect. The Law of Effect theory was that satisfying responses can cause an individual's actions to be repeated, and unwelcome responses can cause these actions to occur less frequently. For example, if you did something nice for someone else, and they praised you for it, you might be more likely to do it again. Dr. Skinner found three different operant responses that often follow certain behaviors. These include: - Neutral responses, which are those that do not decrease or increase the probability of the behavior happening again. - Reinforcement, which is a response that increases the chances of a certain behavior happening again. - Punishments, which are responses that weaken the behavior and lessen the chance that it will happen again. Psychological Punishment Definition Psychological punishment can include ignoring, yelling, intimidating, or nagging someone to do or not do something. Other forms of psychological punishment that can be traumatic include physical and verbal abuse, swearing, and violent anger. These forms of psychological punishment are often effective because the person on the receiving end can be filled with fear, shame, or guilt. These methods of punishment should never be used as they may not teach the individual anything but fear and violence and are likely to have negative impacts. If you are experiencing any abuse or violence at home or elsewhere, you can call the National Domestic Violence Hotline at 1.800.799.SAFE (7233) for advice and assistance. Positive Punishment Versus Negative Punishment Positive punishment is a type of punishment that produces a stimulus that can cause a behavior or activity to stop. For example, let's say your child runs into the street, and you yell at them. When your child is no longer in the street, you stop yelling at them. This can increase the chance that your child will stay out of the street in the future because they will likely associate being in the street with being yelled at. Even pain can be considered apositive punishment. When you do something that causes pain and then stop doing it, and the pain also stops, you may refrain from doing it again because of the pain it caused. An example of this could be touching a hot stove or curling iron. Although it may hurt, the pain can serve a purpose by reminding you to be careful around hot objects so that you don't get hurt again. Negative punishment is when the person doing the punishing removes a stimulus that the subject considers a privilege. For example, if you arrive at work an hour late, your boss may not pay you for that hour, or if you do not do your work properly, you may not get the promotion you want. The punishment can increase the chance that you come in on time and do your work properly because of your desire for pay and a promotion. Positive And Negative Reinforcement There are two other forms of operant conditioning: positive and negative reinforcement. These are similar to the punishment theory but reversed. They can be used to reinforce a behavior rather than discourage a behavior. - Positive Reinforcement: Positive reinforcement consists of giving an individual something they like or want so that they are influenced to repeat the desired behavior. For example, if your partner cleaned the kitchen and made dinner, you could verbally express your appreciation or take care of their least favorite chore. This may influence them to repeat the behavior of cleaning the kitchen and making dinner in the future. - Negative Reinforcement: This consists of stopping something negative or unpleasant to encourage the individual to repeat the positive behavior. For example, you might stop an employee's supervision when shown that they can be trusted to do their job correctly. They may be more likely to do their job correctly in order to avoid supervision. Is Psychological Punishment A Healthy And Effective Practice? You may wonder whether we should use punishment as a learning tool for our children or peers. Is it wise to attempt to enforce our desires on others by punishing them? Punishment may have been the preferred teaching tool at home and school in the past. However, in the United States, punishment may be more frequently frowned upon today. Some experts believe that punishment and negative consequences can encourage bad behavior rather than reinforce good behavior. There has been quite a bit of research showing that positive reinforcement can be more effective than negative reinforcement or punishment. Many parents and schools may now be turning to methods like positive parenting, which can encourage good behavior while promoting children’s inherent worth and self-esteem. is often remembered long after it takes place. While remembering a spanking for misbehaving at school may stop a child from misbehaving again, it may also lead to aggression because the child may think being aggressive is an effective way of handling challenging situations. Punishment may also lead to fear of the punisher, which can mean that obedience becomes the result of fear, rather than the child simply wanting to behave well. Even though you may believe that it could be good for your child to be afraid of the consequences of "being bad" at school, it may not be helpful if they are afraid of their teacher or going to school in general. This could cause your child not to want to go to school or to be frightened of authority figures such as teachers and police officers. Some types of punishment are typically not useful in any context, such as becoming violent or abusive. Studies have shown that children who have been subject to abuse or violence can be more likely to be abusive as adults. Approximately one-third of those neglected or abused as a child may abuse or neglect their children. In addition, survivors of abuse can be more likely to have mental health disorders such as depression, post-traumatic stress disorder (PTSD), and anxiety disorders. Survivors can also be moresusceptible to addiction disorders. Still, it can be important to note that many abused and neglected children can grow up to become excellent parents who may never abuse or mistreat their children. Experiencing Mental Health Concerns Due To Punishment? Work With A Therapist Online. Online Therapy May Help You Cope With Mental Health Concerns From Punishment If you’re living with mental health concerns stemming from psychological punishment, you may wish to seek therapy so that you can work with a mental health professional to learn coping skills and gain insight into the way the punishment affected you. Traditional therapy may not be your preferred method of getting help, and if that’s the case for you, you may be interested in online therapy. With online therapy, you still get to connect with a licensed professional, but you can do so without leaving the house. Often, psychological punishment can negatively impact self-esteem. According to this study, online therapy can be effective in increasing self-compassion and happiness, as well as decreasing difficulties with emotion, depression, and stress. When a person takes action to affect another psychologically in order to get them to behave in a certain way, that can be considered psychological punishment. This type of punishment was frequently used in the past, but today, it may be considered more effective to use positive reinforcement to encourage desired behavior. Psychological punishment can sometimes lead to negative impacts on mental health. If you’ve experienced this personally, please know that help is available, and online therapy may provide the support and guidance you deserve. Why is punishment good psychology? › A punishment in psychology is a consequence which reduces or aims to reduce the likelihood of a targeted and undesirable behavior from happening again. Punishment is a part of operant conditioning, or the use of rewards to encourage certain behaviors and use of negative consequences to discourage unwanted behaviors.What is punishment as used in psychology? › Punishment is a term used in operant conditioning psychology to refer to any change that occurs after a behavior that reduces the likelihood that that behavior will occur again in the future.How can punishment be used effectively in psychology? › Punishment has also been used to psychologically manipulate individuals to gain control over victims. It has also been used in scenarios where an abuser may try punishment in order to traumatically bond their victim with them. Stuttering therapy has also seen the use of punishment with effective results.How do you use punishment correctly? › - The punishment has to be relative intense. The subject should feel it as a punishment) - It has to be giving promptly. ... - It should be given consistent. ... - The punishment should not be associated with any kind of positive enforcement. ... - It should not lead to escaping or avoidance behavior. Research shows that spanking, slapping and other forms of physical punishment don't work well to correct a child's behavior. The same holds true for yelling at or shaming a child. Beyond being ineffective, harsh physical and verbal punishments can also damage a child's long-term physical and mental health.Why should punishment not be used? › Punishment creates more negative behavior, and it shifts a child's focus to avoiding punishment, often by getting more skilled at not getting caught, rather than making choices based on morals, respect, or love.What is the best purpose of punishment? › There are five main underlying justifications of criminal punishment considered briefly here: retribution; incapacitation; deterrence; rehabilitation and reparation.Why do we use punishment? › The utilization of punishment is justified in terms of deterrence, retribution, or incapacitation. The deterrence position maintains that if the offender is punished, not only the offender by also those who see his example are deterred from further offenses.What are some of the problems with punishment psychology? › Punishment elicits aggression towards the punishing agents and others. Not only is there little evidence to show the effectiveness of punishment, but often it makes behavior worse. Skinner found pigeons and rats get more aggressive after being punished, and current research shows similar findings with children.Is punishment the best way to modify behavior? › Punishment does not need be extreme. It is simply a stimulus that is used to discourage or decrease an undesirable behavior. Although punishment does not replace the negative behavior like reinforcement does, it is still a resourceful technique. When can punishment works best? › Positive punishment can be effective when it immediately follows the unwanted behavior. It works best when applied consistently.How can punishment be positive and negative? › Positive punishment involves adding an aversive consequence after an undesired behavior is emitted to decrease future responses. Negative punishment includes taking away a certain reinforcing item after the undesired behavior happens in order to decrease future responses.What are the 4 dangers or the use of punishment? › Corporal punishment is linked to a range of negative outcomes for children across countries and cultures, including physical and mental ill-health, impaired cognitive and socio-emotional development, poor educational outcomes, increased aggression and perpetration of violence.Is punishment justified or not? › Consequentialist accounts contend that punishment is justified as a means to securing some valuable end—typically crime reduction, by deterring, incapacitating, or reforming offenders. Retributivism, by contrast, holds that punishment is an intrinsically appropriate (because deserved) response to criminal wrongdoing.Is punishment ever justified? › If punishment is justified according to its beneficial consequences in maximising well-being or satisfaction by deterring crime and mitigating social insecurity, scapegoating acts of victimisation against non-offenders can be justified in the same way.Does punishment help anyone improve? › In psychology, punishment is always effective in changing behavior, even when children don't feel punished. Not only is it possible for children's behavior to be punished without punishing children, it is possible for their behavior to be punished while at the same time being nice to them.Why punishment is not good for students? › It results in more negative behaviour Lots of students misbehave because they want attention. Punishing students gives them the attention that they want. The more you punish your students the more likely it is you'll see the same behaviour in the future. The more you use a punishment, the less effective it becomes. Retribution is the most ancient justification for punishment. This theory insists that a person deserves punishment as he has done a wrongful deed. Also, this theory signifies that no person shall be arrested unless that person has broken the law.Why is positive punishment? › Positive punishment is adding something to the mix that will result in an unpleasant consequence. The goal is to decrease the likelihood that the unwanted behavior will happen again in the future. This approach may be effective in certain circumstance, but it's only one part of the equation.What is an example of positive punishment in psychology? › Positive punishment involves adding an aversive stimulus after an unwanted behavior to discourage a person from repeating the behavior. Spanking and chores are examples of this. On the other hand, negative punishment involves the removal of something desirable. Why is effective punishment important? › Encourages Good Choices Kids need to learn problem-solving skills, impulse control, and self-regulation skills from appropriate training. It is important to distinguish the difference between consequences and punishments. When kids are disciplined with appropriate consequences they learn from their mistakes.

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Tackling TraffickingJan 01, 2021 ● By Allie Spletter January is National Slavery & Human Trafficking Prevention Month and January 11 is National Human Trafficking Awareness Day. In light of this day, the hope is to be diligently aware of a very real problem in which more people than we know are involved. Regardless of personal, political or religious beliefs, human trafficking is a topic that has had more light shed on it recently, and we can only hope that the light can remain as bright as possible to continually raise awareness. According to the United Nations Office of Drugs and Crime, human trafficking is the recruitment, transportation, transfer, harboring or receipt of persons through threat or use of force, coercion, abduction, fraud, deception, abuse of power or vulnerability, or giving payments or benefits to a person in control of the victim for exploitation, which includes exploiting the prostitution of others, sexual exploitation, forced labor, slavery or similar practices and the removal of organs. There are many types of trafficking that include forced labor, bonded labor/debt labor, child slavery, domestic servitude and sex slavery or trafficking. Addison-based Traffick911’s mission is to free youth from sex trafficking. Of sex trafficking, specifically, Lindsey Speed, executive director of Traffick911 explains further, “Trafficking can look many different ways, but at its core, trafficking is the exploitation of vulnerability. Sex trafficking typically involves a sex buyer (the demand), a victim (primarily women and girls) and a trafficker (providing the supply). Traffickers often take advantage of a girl’s vulnerability, such as an unstable home life, and lure them into a ‘better life.’ Once lured, the trafficker asserts psychological control over the victim, buyers purchase sex from the victim and the trafficker takes the profit. Sex trafficking is right here in our North Texas communities – often happening at hotels, motels, apartment complexes or Illegal Massage Businesses (IMBs) – because there are men in our communities who believe it is ok to objectify and commodify women and girls.” Globally, the most common form of human trafficking is sexual exploitation and the victims of such exploitation are largely women and girls. Surprisingly, in 30 percent of countries that provided information to the United Nations, women make up the largest proportions of traffickers. The second most common form of global human trafficking is forced labor and though trafficking seemingly implies people moving across continents, most exploitation takes place close to home. The United Nations’ data shows that intra-regional and domestic trafficking are the major forms of trafficking in persons. Texas ranks second in the country behind California for trafficking frequency, with more than 300,000 annual victims statewide, approximately 79,000 youth and minor victims of sex trafficking in Texas. In Dallas, it’s estimated that 400 teens are sold for sex every night as part of a $99 million illegal industry. Program Director Letetia Smith of Treasured Vessels Foundation, a Frisco-based foundation that provides safe communities that restore survivors of sexual exploitation to achieve their true potential adds, “We think that it happens overseas and not in our back yards and that it doesn’t happen in Frisco, Dallas, Plano, McKinney. That’s probably the biggest misconception. We want people to know that it is happening in your backyard. The other misconception is that kids are kidnapped. There’s a one percent chance of that happening, but a lot of it happens in a variety of different ways, such as online and even families trafficking their own kids. I want the community to know that it is happening in your neighborhood.” Ms. Speed says that there isn’t necessarily one demographic that’s targeted for trafficking. “Since trafficking is basically the exploitation of any vulnerability, that means anyone could be trafficked. However, people with the most vulnerabilities are most likely to be targeted through psychological manipulation or the promise of a relationship. This means kids are vulnerable in their very essence, but they are especially vulnerable to the manipulation tactics of predators if they don’t have stable, loving relationships in their homes, if they experience abuse or neglect from people they trust, or if they are affected by poverty or other instability in their childhood. Statistically, victims of trafficking tend to be women and girls disproportionately of color.” Factors that increase vulnerability include a history of physical, sexual, or verbal abuse, homelessness, poverty, chaotic home life and substance abuse. While Frisco is a largely affluent area, residents must remain diligent in educating themselves as there are many misconceptions and preconceived notions regarding human trafficking that hinder our understanding and the reality of the issue. Ms. Speed wants citizens to know that “if you have a steady income and stable people in your life caring for you, you more than likely will not be targeted by a trafficker. Traffickers are smart and they know how to prey upon young people who are already invisible. While it’s true that anyone can be a target for trafficking, it’s a grievous misconception to believe that women being kidnapped and smuggled across borders is the most common trafficking situation in the U.S.” Ms. Speed continues, “Of the 1,700 victims Traffick911 has served, the vast majority were coming from an impoverished community, running away from neglect or abuse, or fleeing the foster care system. Most have experienced deep relational brokenness in their own families or homes, making them more vulnerable to the manipulation tactics of traffickers. Many were sold for sex mere miles from the homes where they grew up. However, young people who have unsupervised access to the Internet can be vulnerable (no matter their socioeconomic status) as predators often seek to build a relationship with youth online. We have served teenagers who were groomed via social media, only to find out their ‘friend’ on the other side of the screen is someone other than whom they claim to be. To effectively work toward a solution, you have to understand the social dynamics of your own community, be aware trafficking happens in every city and invest in organizations who are utilizing research and specialized training to serve victims and arrest perpetrators.” While many might think that human trafficking would seemingly be easy to spot or literally see, Ms. Speed wants citizens to know that it can be difficult to spot because victims are walking around in plain sight and certainly may not ask for help, or even look like they need help. “We try to be mindful of sharing with the public a certain list of signs because it’s not that black and white. Instead, we like to equip professionals such as teachers, social workers and medical professionals with tools and in-depth training because someone is more likely to identify a victim once they’ve built trust and/or have an established relationship to understand the complexities of what may be going on,” she concludes. Unfortunately, there isn’t any one specific thing we can do to put a hard stop to human trafficking but, according to Ms. Speed, knowledge is power. We can educate ourselves and others given that, like any social issue, trafficking is much more complicated than most forms of media make it out to be. “For example, trafficking very rarely happens in the form of a kidnapping,” Ms. Speed admits. “For every kidnapping case you hear on the news, there are many more cases of coercion or fraud by someone the victim knows. The difficult thing is that because traffickers groom and manipulate their victims, youth who are being exploited most likely will not ask for help,” she explains. Ms. Speed believes sharing the truth about the issues is vital as well. Additionally, we must not share sensational stories. Ms. Speed encourages residents to ensure that the source of the story is reputable, that a victim’s abuse isn’t being exploited for drama or personal gain and that the story is advocating for the voices and dignity of survivors before sharing. Lastly, we can invest in vetted organizations that are doing the work on the ground. While community members and area residents can work hard to educate themselves and raise awareness, there are incredible programs right here in North Texas that are dedicated to education, awareness and serving those rescued from human trafficking. Traffick911’s mission lies in freeing youth from sex trafficking through trust-based relationships and through the utilization of a 24/7 crisis response team, advocates and community volunteer mentors who walk along with child sex trafficking victims with multi-disciplinary team partners. “We believe our communities are most likely to see trafficked youth heal from trauma and reclaim their lives when they are given the tools and stability to build healthy and safe relationships,” states Ms. Speed. The Treasured Vessels Foundation (TVF) provides safe places for victims of human trafficking to be restored to their full potential by way of a residential living facility in North Texas and operates as a clinically therapeutic aftercare program for survivors of domestic sex trafficking. “Our residential program consists of life skills, financial literacy, leadership development, education and S.T.E.M. (Science Technology Engineering Math),” Ms. Smith explains. “We also offer in-house counseling service for our residents to continue their healing.” It’s not easy to talk about, and it’s even harder to grasp that it’s happening so close to home, but the reality of human trafficking both globally and right here in North Texas is that it’s happening and it’s happening more than we think. While there isn’t a magic-wand-waving solution to make it disappear, we can help. We can make a difference. We can be educated. We can remain aware. When it comes to addressing the issue, Ms. Smith sums it up perfectly: “Trafficking is an issue at the community level. Therefore, the solution has to come from a community level. The extent to which individuals understand the issues and take informed action is the extent to which the existence of trafficking will be challenged.” To find out more information on how to volunteer or give back, please visit traffick911.com and/or tresuredvesslesfoundation.org.

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Pepper originates from the Malabar Coast in southwest India. It is a vine belonging to the Piperaceae botanical family and is now found in many countries in the tropical belt. Real pepper comes from the tropical Piper Negrum lianas from which white, black, red or green pepper is obtained, and Piper Longum, the long pepper. Others are in the form of a berry with a tail. Fake peppers have all the pungency of real peppers. Some are sweeter or fruitier. They are in fact derived from another plant, quite different from the Piper. Organic whole black pepper from the Bolaven plateau * Organic whole green pepper from the Bolaven Plateau* Organic red pepper from the Bolaven plateau * Cocoa red pepper Wild red Voatsiperifery peppercorns from Madagascar Whole red pepper from Mondulkiri Red peppercorns from Phu Quoc Red Kampot PGI peppercorns Dark Red peppercorns from Kampot Long red pepper from Kampot Whole red pepper from the Bolaven plateau Smoked black pepper What is a pepper? Piper Nigrum King of the spices Pepper (Piper Nigrum) originates from the Malabar Coast, in the south-west of India. It is a vine which belongs to the Piperaceae botanical family. Today it is found in many tropical belt countries. Whether it is green, black, white or red, it is the same fruit. Pepper grows in clusters. Green pepper is a fruit picked before maturity. It is subtly spicy, delicately hot and very fresh. We rarely see it in our markets. It is typically found dehydrated or brined. The grains yellow as they ripen. They are generally picked at this stage of maturity. When dried in the sun, they wrinkle and turn brown, becoming black pepper. At full maturity, the fruit turns a shimmering red colour. It is then soaked in rainwater basins and its skin is removed. After a long period of drying in the sun, white pepper is obtained. Red pepper (mature fruits) shouldn't be confused with "pink pepper ", incorrectly named because it does not belong to the Piperaceae family. Another language mistake - "grey pepper". It doesn't exist! It is actually a mixture of poor quality white and black pepper powders. It isn't of great interest to us. Rules and usage tips Never buy pepper as a powder. Its aromas are subtle and disappear quickly when it is milled. Avoid aggressive cooking as it makes it bitter and burnt. Preferably use a pepper mill on your dishes when serving. It looks elegant and the odours are intoxicating. The regular use of different peppers will convince you of their diversity. The use of these peppers will not fundamentally change your cooking, but it will customise your dishes by bringing them a touch of exoticism and taking you on a journey. Why use several peppers? In our kitchens today we use several different olive oils or vinegars because they are different, so then why should we always use the same pepper?

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Lundberg Family Farms The Lundbergs have been growing rice ecologically since 1937, when Albert Lundeberg began farming in the Sacramento Valley in Northern California. Albert had lived through the Dustbowl and had seen, first hand, the long-term effects of poor soil management. Witnessing the ramifications of short-sighted farming techniques led Albert to believe that, on his farm, he should only employ methods that respect the soil, wildlife, air and water. In turn, he passed these methods on to his four sons who have continued to experiment and seek out new and innovative ways to farm ecologically. The Lundberg Family Farm works in partnership with nature to produce the highest quality rice possible. Unlike conventional rice farms, the Lundberg Family Farm never burns their rice fields after harvest. The straw is converted back into soil and they plant different types of crops to improve the soil fertility and tilth. These crops grow over the winter and enrich the soil with nitrogen. On conventional farms, the rice straw is burned, often with harmful chemicals, as it can cause diseases such as stem rot or it can "sour" the field. The Lundbergs chop the straw and roll it into the field with huge rubber rollers. The elements, along with the help of various waterfowl (ducks, geese, cranes) help to decompose the straw. Every few years the fields are left fallow to let the soil to replenish itself. The organic brown rice on the Lundberg's farm is also allowed to mature longer than conventional rice. This gives the rice a fuller, more complete flavour. Conventional white rice can be harvested earlier as younger rice is wetter, which means it is less likely to break or crack during milling.

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The Basics of HoneypotsA honeypot is essentially a "fake" system that looks like a real one. The basic idea is that a hacker will deploy their attack against the fake honeypot rather than real systems. If this happens, the company which has deployed the honeypot can gain insight into the types of tools, tactics, and procedures that are used by the hacker and maybe even gain advanced warning of an attack on their real systems. Beyond this basic description, honeypots vary widely. In fact, a honeypot is more of a general technique than a specific tool. As complex networks get harder to secure, honeypots are being deployed that simulate a vast range of systems, from blogging platforms to SaaS cloud services. In general, however, there are two major types of honeypot: research and production honeypots. Research deployments are used to gather information about potential attacks and are used by cybersecurity professionals to gather information about the types of attacks that are occurring in the wild. Production honeypots, by contrast, are those deployed by individual companies to give them advanced warning of an imminent attack and to test specific systems for security vulnerabilities. Different Types of HoneypotThe types of systems in use by the average business today are incredibly varied, and as such, the types of honeypot they can deploy are also varied. An important high-level distinction is between honeypots that seek to replicate full-scale systems and which contain confidential information and lower-level deployments that only aim to mimic a particular part of a system. Large, complex honeypots are generally referred to as "pure"; they contain everything that a real system would, albeit whilst also being full of sensors to detect unauthorized access. "Low-interaction" technologies, by contrast, will typically only run a handful of services and contain no sensitive information. This latter type serves more as a "tripwire" than a research tool, giving a company advance warning that they are being targeted. Within these broad categories, honeypots can make use of a vast range of different web technologies. There are, for instance, malware honeypots that are designed to mimic USB storage devices. Since malware often spreads by infecting USB storage devices, this type of honeypot can be used to trick the malware into infecting the emulated device, where it can be contained and studied. Email marketers and bloggers often turn to spam honeypots which are designed to emulate email relays. If a hacker is tricked into thinking that this honeypot is a real relay, they will try to use it to send a flood of spam. The honeypot can be used to detect this attack, and then block the real attack from occurring. For beginners, the process of creating your blog typically includes deciding whether or not to go with one of the three main content management systems (WordPress, Joomla, Drupal). For any of these platforms, putting a honeypot to work combating spam is as easy as installing a plugin. Check with each site to see their current recommendations. Newbie bloggers should understand how critical it is to get control of spam comments fast because you can get buried by them and disillusioned with the whole project in a hurry. Other types of honeypots work with specific languages and systems. SQL injection can be detected via a fake SQL database, for instance; honeypot technologies can even be built that emulate entire user systems and "invite" hackers to attack them. The Benefits of HoneypotsHoneypots are an integral part of most contemporary cybersecurity systems, and as such, the many advantages of using them are shared with other forms of threat detection and protection. Large companies can use them to test for vulnerabilities, harden their backup systems, or detect ongoing attacks. Smaller firms use them to improve website security, protect personal data, and build a reputation for taking cybersecurity seriously. Beyond these general advantages, honeypots confer a level of detailed threat analysis that is impossible using more general cybersecurity analysis software. They act as a powerful tool for disrupting and defeating attacks that are already in progress since an attacker can get stuck trying to work out if a honeypot it real. Honeypots are also useful for detecting new types of threats. Since they do not rely on known attack signatures, they can often provide zero-day warning of potential security vulnerabilities. Unlike intrusion detection systems, a user does not need to be acting suspiciously in order to trigger a warning that a system has been compromised. The very fact that someone is poking around in a honeypot is enough to identify them as a threat. Finally, honeypots are also useful for testing managerial responses to cyberattacks. Since they can be used to emulate entire corporate systems, they can be used as part of penetration tests without the risk of compromising "real" data. This allows companies to run full-scale simulations of cyberattacks and assess whether they have the expertise and systems necessary to respond to them. Final ThoughtsBecause honeypots come in all shapes and sizes, they are rapidly becoming a major tool in the fight against cybercrime. Though the honeypot technique has long been associated with large-scale corporate networks, today it is possible for small companies (and even individual users) to deploy them on their systems. As such, honeypots are now an integral part of broader cybersecurity systems and are likely to stay "fashionable" for many years to come.

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In spite of the fact that exhaustion is normal among various sclerosis patients (85%), assessment is troublesome because of the subjectivity and fluctuation of the grumbling however it is critical that weakness is viewed in a serious way and its administration is thought about cautiously. Tragically weariness obstructs work, family, and public activity and is progressively perceived as a critical side effect for individuals with MS. The compelling administration of weariness significantly affects the patient’s working, capacities, and personal satisfaction. There has for some time been a conviction that downturn adds to weariness in different sclerosis (MS) albeit supporting information are negligible, best case scenario. Various techniques for estimating exhaustion in numerous sclerosis have been created including the Fatigue Descriptive Scale (FDS) created by Iriarte J, Katsamakis G, de Castro P. furthermore, the Fatigue Severity Scale (FSS) which was intended to separate exhaustion from clinical gloom, since both offer a portion of similar side effects. A Common Symptom Exhaustion is, maybe, the most widely recognized side effect of various sclerosis, with most of individuals with MS encountering it sooner or later over the sickness. Weariness Management can be generally accomplished with Occupational treatment, to work on each day errands, Physical treatment, to find more energy-effective methods of day to day undertakings, Relaxation preparing, Heat the executives and Medication (for example Amantadine and Modafinil). Medicines can be grouped in two primary subtypes: pharmacological and non pharmacological. Modaheal 200 Drug medicines for weakness in various sclerosis incorporate Amantadine, Modafinil, Pemoline, and Methylphenidate. As well as treating weakness in various sclerosis, Artvigil 150mg (Modafinil) is likewise used to treat Alzheimer’s sickness, despondency, a lack of ability to concentrate consistently jumble, myotonicdystrophy, schizophrenia and cocaine dependence. A preliminary of ibuprofen treatment for weakness might be a sensible initial phase in medicine the board. Headache medicine appears to have shown comparable outcomes to Symmetrel (Amantadine) albeit the portions required could cause gastrointestinal draining in certain individuals In a new study of nervous system specialists it was found that most preferred research coordinated toward figuring out the reason for weariness in numerous sclerosis, while 33% said examination ought to be centered around the improvement of new meds. Nonetheless, in accordance with the hypothesis that MS could be altogether impacted, in the event that not caused, by natural factors, for example, diseases there has been some progress in diminishing weariness in various sclerosis with medicines planned explicitly to decrease Candida movement. This loans further help for the proposed connection between MS related weakness and Candida action. Albeit various procedures have been contrived for decreasing weariness, treatment suggestions depend on a restricted measure of logical proof. Late advances in the comprehension of the pathophysiology of different sclerosis (MS) are giving fruitful ground to the improvement of novel treatment draws near. Rest aggravations are normal in individuals with MS, because of fits, misery or nervousness, torment, the regular need to pee around evening time (nocturia) or due to symptoms of prescriptions (corticosteroids like Solu-Medrol are famous for causing rest unsettling influences). While exhaustion is solely an emotional encounter, contingent upon the patient’s capacity to comprehend and report this side effect, there are viable techniques for recognizing the presence of weariness, deciding its seriousness, and separating it from related or contributing problems like sorrow, agony, and rest problems. A significant part of the actual weariness can be credited to upset rest designs brought about by urinary direness or nighttime fits (myoclonus). There may likewise have occasional leg developments, which is when legs kick automatically during rest. Another condition influencing rest is rest apnea, which is additionally normal among everyone. Exercise can bring on some issues for individuals with different sclerosis in light of the fact that the subsequent overheating can exacerbate neurological side effects. Mental weariness can change among gentle and seriously handicapping and is normally exacerbated by work out, expanded materially or surrounding temperature (Uhthoff’s side effect). Mental weariness is frequently connected with actual exhaustion and all you maintain that should do after actual activity is to implode on a bed and rest. It means quite a bit to stay aware of what practice one is fit for to keep the muscles from decaying and to keep the nerve pathways as functional as could really be expected. Anything that the exercise strategy, practice appears to assist MS patients with diminishing weariness side effects, Bourdette said. “This is valid whether the customary activity is yoga, swimming, utilizing an exercise bike or some other actual work,” Regular routines are progressively really overbearing and with the intricacy of weariness in MS, you should expect that a multi-procedure approach will be expected to have an effect on dealing with your exhaustion. Visit Here: Clicktowrite

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Sciatica is simply a pain that runs from the lower back down the leg, often into the foot and toes. It is brought on by an irritation of the sciatic nerve triggered by a compression. Some people struggling with sciatica also may experience a burning, tickling or prickly sensation, usually on one side of the body. The type and level of pain a person experiences depends upon the site of the nerve compression. In certain cases the pain can be very moderate, while in others it can be debilitating and extreme. The majority of people will recover from an episode of sciatica within a few weeks, the pain can sometime worsen over time or persist for much longer. Everything depends on the underlying root cause. Sciatica and also Nerve Destruction. Even though it is rare, in some instances sciatica can lead to irreversible nerve damage. The irritation of the nerve that induces the sciatica pain generally is reversible. Symptoms of a more dangerous medical issue include bladder or bowl incontinence, growing weakness, or the loss of sensation in the leg. Where Exactly the Sciatic Nerve is Found: Sciatic nerves are the longest in the body. They stretch out from the lower back completely down to the toes. Sciatic nerves leave the spine between two vertebrae in the lower back and travel behind the hip joint down the buttock and along the back of each leg into the foot. Sciatica is triggered by the irritation of one or both of these nerves. Usually, a herniated disc applies pressure on the sciatic nerve root. In many cases, people suffering from sciatica have leg pain, which makes them mistakenly think that the sciatica is caused by some sort of problem within the leg. Other root causes of sciatica can include spinal tumors, , trauma, spinal stenosis, or injury. Anyone Can Have Sciatica. People think that sciatica is something that just effects people who have an inactive lifestyle. And while it’s correct that sedentary people are more susceptible to get sciatica, it in reality can affect active people also, especially if they participate in activities that involve twisting the back or carrying heavy weights frequently. Sciatica will typically resolve itself within a few weeks. Treatment options include exercise, physical therapy and corticosteroid injections. For some patients, however, the pain can last much longer, so individualized treatment plans are suggested. Sciatica Therapy Solutions. Another more natural sciatica treatment option is , non-surgical spinal decompression treatment. By gently decompressing the involved spinal disks pressure on the sciatic nerve can be relieved and the pain from sciatica can disappear. Call South Charlotte Disc Center at (704) 583-6129 to Schedule A Complimentary Consultation!

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Common Gaslighting Phrases The term “gaslighting” refers to the manipulation of someone, by psychological means, into questioning their own reality, perception, or sanity. The term originated from the 1938 play (and 1944 film adaptation) Gaslight, where the protagonist’s husband slowly manipulates her into believing she’s going mad. Gaslighting usually takes place in relationships and social interactions where there is a power imbalance. A person experiencing gaslighting may become confused, withdrawn, or anxious and they may not realize the behavior is abusive. Here are some common gaslighting phrases: “You need help.” “You’re just crazy.” “It was just a joke.” “You’re just insecure/jealous.” “You’re too sensitive.” “You’re just being paranoid.” “You’re imagining things.” “That never happened.” “You’re just overthinking it.” People experiencing gaslighting often find it challenging to trust themselves. Gaslighting is abusive, it can wreak havoc on the mind, and it’s damaging to relationships.

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History of Wine an alcoholic drink made from fermented grape juice. "he opened a bottle of red wine" vin de table, vin ordinaire, vin du pays; informalplonk, vino, the grape · The earliest wine archaeobotanical evidence was found in Georgia, and date back 8,000 years to approximately 6,000 B.C. · The earliest historical evidence of wine dates back 9,000 years to 7,000 B.C. China. Grapes were also wined with rice and other fruits. · The spread of wine culture westwards is credited to the Phoenicians some 2,750 years in the past. The main vessel of transportation was the clay amphora. · The use of wine in religion was significant in ancient mythology and religion. 3100 BC till 30 BC, wine symbolized blood in ancient Egypt. · Ancient Romans planted vineyards in almost every settlement they’ve established. · Up until the Iron Age 900 B.C. there were no wooden barrels for wine transportation. · 77 AD The Roman Pliny the Elder writes “vino veritas” or “In wine there is truth” in Naturalis Historia. The Romans were also the first to talk about how "terroir", the concept of where and how you plant the vines will affect the wine. They were also among the first to use sulfur as a wine preservative some 2000 years ago. · In 380 AD Rome adopts Christianity; wine symbolized “the Eucharist”. * 1000 AD Château de Goulaine is built. Possibly the oldest operating winery. * 1629 AD Spanish missionaries introduced vitis vinifera to America. * 1500 AD wines that may have been sealed and stored in stoneware jugs re-fermented causing them to have spritz. These creamy or “Crémant” style led to the creation of French sparkling wine and British cider. · * 1600 AD the most highly desired wines of the day are sweet white wines such as Sauternes of Bordeaux, Riesling of Germany and Tokaji from Hungary. Enlightenment to Modern History · *1600AD glass wine bottles were first popularized in Portugal in an attempt to age Port wines, inspired by records of amphorae. Unfortunately, bottles stood upright and the corks would dry out and lose their seal. · 1650 AD Somewhere in Bordeaux, Cabernet Franc and Sauvignon Blanc naturally cross to create Cabernet Sauvignon. · 1737 AD the first demarcated wine region of the world is Tokaj in the foothills of the Zemplén Mountains of Hungary. · 1740 AD bottles were redesigned to be laid on their side, creating the ability to age wines long term. · 1855 AD the demarcated Bordeaux wine region was established. · 1862 AD Louis Pasteur discovers oxygen’s harmful effects on wine causing the industry to adapt to wine bottles. · 1900 AD 70% of vineyards in France were killed by the Phylloxera, and to a lesser extent in the rest of Europe. · * 1950 AD French wines, in particular "Bordeaux" are popularized in the United States. AD the first bag-in-a-box wines are introduced. · 2010 AD Cabernet Sauvignon is the world’s most planted wine grape. · 2013 AD China becomes the world’s largest consumer of dry red wines in the world. Lebanese Wine History · Wine has been produced in the region since its discovery 6000 BC · Jesus turned water into wine in a marriage in Cana, a southern village in Lebanon · Wine culture survived ottoman occupation in Christian territories · Pre-French colonization Lebanon had only two types of wine, cooked sweet wine and cooked dry wine (Faqsh) 1839 AD Moussa Riachi founded Riachi Winery & Distillery. · 1920’s the French bring with them the Phylloxera to Lebanon, killing off most of the indigenous grape varieties · 1923 – 1943 the French export French wine culture and French winemaking processes to Lebanon · 1940-2000 Riachi produced wine for several brands, most notably Touma, Kefraya, Asrar, Cave St. Jean, etc. · 1975 – 2000 most of the old family wineries of Lebanon close down · 1980 – 2000 wine mass marketing takes off · 2000 – Present more than 50 new wineries open · 2005 Michael Karam published his fist book “Wines of Lebanon” · 2007 The first exhibition dedicated to wine “Vinifest” was launched. · 2010 – National wine production at 7 million bottles per year · 2017 – National wine production at 10 million bottles per year What are the different types of wine? er Wine can be classified according to color, sweetness, and winemaking style (sometimes called regional style).The main wine colors are red, white, and rose. - Red wines are made from red grapes where the juice and skin are fermented together. - Red wines that have a lot of tannins are called full bodied and those that don't are light bodied. - Full bodied reds are usually darker than light bodied ones. - Red wines can be either sweet or dry - Red wines can be drank fresh if they are light bodies - Dry red wines have a maximum aging potential of 25 years, and that depends on the tannins content. - Their color gets lighter tending to brick red as they age. - Average drinking temperature ranges from 14 C to 21 C. - Red wines can be aged in oak barrels. - Red wines are made from red grapes where the grapes are pressed or bled and the juice is fermented without the skin. - Rose wines that have more of tannins are called full bodied and those that don't are light bodied. - Bled or ( Saignée ) rose wines are usually darker and more full bodies since they've had a longer contact time with the skin. - Full bodied rose are usually darker than light bodied ones. - Rose wines can be either sweet or dry depending on sugar content. - Rose wines can get darker as they age - Dry rose wines have a maximum aging potential of 7 years, and that depends on the tannins content. - Their color gets darker as they age. - White wines are made from white grapes where the grapes are pressed and the juice is fermented without the skin. - White wines are more acidic than red wines, and that's where they get their freshness from. - Some white wines are made from red grapes, where the grapes are pressed using a technique that removes the juice with minimal color effect from the skin. - Full bodied white wines are usually darker and less acidic than light bodied ones. - White wines can be either sweet or dry depending on sugar content. - White wines can get darker as they age - Dry white wines have a maximum aging potential of 15 years, and that depends on the tannins content. - Some white wines can be aged in oak. - Their color gets darker as they age. - Sweet wines are wines that have sugar content after fermentation if done. - There are several techniques used to produce sweet wine. - Sweet wines can be made from white grapes and red grapes. - Late harvest sweet wines are made from grapes that are harvested past their due and have higher sugar content. - Straw wines are made by drying the grapes after their are harvested. - Fortified wines have sugar and spirit added to them after fermentation is complete. - Cooked sweet wines have the juice cooked pre-fermentation. - Sweet wines have the longest aging potential, which can reach up to 100 years, and that depends on the tannins, sweetness, and alcohol content. - Some sweet wines can be aged in oak. - Their color gets darker as they age. - Lebanese wines are wines that are made in Lebanon. - Lebanon produces red, white, rose, sweet, and faqsh wine. - Sweet wines are usually cooked wines, where the grape must is boiled pre-fermentation. - Faqsh wine is the traditional dry wine of Lebanon. It is cooked pre-fermentation, however when it comes to a simmer, it is removed off the heat and fresh grapes are crushed on their surface, in order for wild yeast to activate the fermentation. - Red Lebanese wines are known for their intense black fruits flavor due to the warm climate of the Bekaa valley. - Obaidi is the dominant white grape that is used for white wine and also for the production of arak. - White wines are fresh and zesty, especially those that are coming from high altitude vineyards. How wine is made? The above illustration summarizes how most dry and still white, red, and rose wines are made. Both white and rose have the juice fermented without the skin. Both can either have the grapes pressed directly after they are crushed or macerated for a few hours with the skin before they pressed. The juice undergoes alcoholic fermentation at a cool temperature with an average of 17 C. The majority of white and rose wines don't undergo malolactic fermentation and are usually fined quickly with minimal aging and bottled to preserve freshness and acidity. Sparkling wines have a similar fermentation method, but usually at the end of the alcoholic fermentation a small percentage of sugar is added into the wine and then bottled, the wine referments in the bottle producing a bit more alcohol and CO2 gas, which is where the bubbles come from. As for red wines, the grapes are crushed and alcoholic fermentation usually occurs with the grape skin in contact with the juice. Alcoholic fermentation in red wines is called primary fermentation and usually occurs between 21 C and 32 C. After the alcoholic fermentation occurs, red wine usually undergoes a secondary fermentation called malolactic fermentation (MLF) after the wine is pressed, which converts the malic acid into lactic acid. This usually makes red wines more silky and savory. Then full-bodied red wines are usually aged in oak and light bodied wines are fined and bottled. Some wines also undergo bottle aging at the winery (also called cellaring) before they are released into the market. · Always use stemware glassware to drink wine · Never put ice in your wine · Always hold the glass by the stem or base · When opening the bottle, do it quietly · When clinking: clink glasses bell to bell (it reduces breakage) and look your clinking-buddy in the eye. · When Pouring wine, hold the bottle at the base · Always fill your glass less than halfway · Pour wine for others before pouring to yourself · Avoid Flavor Interference: avoid strong flavors like gum, coffee, smoking, or other strong flavors when tasting wine. As a guest · Everyone’s palette is different. By making negative comments, you might be ruining another groups’ experience at the tasting. · Try Everything: Try different varietals. It’s the only way to really get a feel for what you like and don’t like. If you constantly stick with the same few varietals, you will never know what flavors you are missing out on. · Spitting is okay when wine tasting. When you taste multiple bottles, you have a choice to overindulge and get overwhelmed by the flavors or to use a spittoon or cup. · Ask your host questions about the wine he or she is offering you As a host · Uncork quietly · Equal Portions: Try to keep the keep the portioning equivalent among all guests, unless instructed otherwise by the guest · Pouring Technique: Hold the bottle by the base · The person who checks/tastes the bottle first, has his glass poured last · Offer Seconds: Always offer seconds to your guests before you pour for yourself. If you are serving a few different varietals, be sure you are pacing the serving so that everyone gets to try everything. · Know Your Varieties: Although you may not be an expert, you can share how you came to serve this particular bottle. You may even want to have a list of what you’re serving, in case a guest wants to find it for themselves. Photo credit: Winefolly: Wine Tasting Wine tasting involves most of your 5 senses, it's an immersive experience that helps you drown out the noise from the world around you and lets you focus on the wine that's in your hands. The steps are as follows: Step 1: Look In this step you look down at the wine to identify the color, which can indicate the age and body. Then you swirl and look at the legs which indicated the alcohol content, it's scientific name is called the Gibbs-Marangoni effect, simply put, its when alcohol evaporates from the wine. So when more legs/tears form faster, it means that the wine has higher alcohol content. Step 2: Sniff This step helps you identify the aromas that are present in the wine. In general wine aromas are classified into primary, secondary, and tertiary aromas. The primary aromas are usually fruit aromas and reflect the varietal/grape expression. The secondary aromas reflect the terroir and winemaking process, and the tertiary aromas are aging aromas that develop as the wine matures. Even though most tertiary aromas are desirable, like wood notes, earthiness, etc. also some of them are wine defects, like acetic, moldy, chemically, etc. Step 3: Taste Tasting involves both the tongue and the nose, since the majority of taste is also smell. In other words, you can only taste salt, sweet, bitter, sour, and savory/umami without getting your nose involved. That's why you might have noticed a lot of wine geeks doing all sorts of weird things with their mouth as they taste the wine. However, to keep it simple, take a sip, swirl it in your mouth, then inhale from your mouth and exhale from your nose after you swallow, and marvel at what you've just tasted. The role of air and smell Moreover, it can also be aerated in the mouth, which boosts the dispersion of the wine on the tongue and release the odor while inhaling. For an optimal sensory experience, inhalation should be done with both the mouth and the nose at the same time. · Body or heaviness. If the food is rich and heavy, choose a full-bodied wine that won't be overwhelmed. If the food is light and delicate, go with a light, delicate wine. · Acidity. If you have an acidic food, maybe with a lemon sauce, choose an acidic wine. · A light-bodied wine like a fruity white wine may taste like water when paired with a steak or roast. · The iodine in fish and the strong tannin in some red wines can combine to produce an unpleasant metallic taste. · Light acidic white wines including champagne with varying degrees of dryness are generally good aperitifs that go well with appetizers. · The goal of pairing wine with food is to have the two reach a pleasing balance, without one overwhelming or clashing with the other. · Contrast is usually good, especially when it’s a balancing act. Sweet red wine goes perfectly well with blue cheese and chocolate truffles. Wine aromas are the odors expressed by the wine. Aromas fall into 12 odor groups which are: · Even though most animal notes are negative or reducing, there are some that are positive. · Negative – defect : horse sweat – wet dog – fish – sweat · Positive: Leather – tender meat · However, if positive notes are over powering, they can be indicative of wine defect. 2. Aromatic Herbs · Most herbal notes are positive, however there are some that are negative · Negative – defect: Turpentine – camphor (waxy) · Positive: Thyme – mint – rosemary – basil · Ethereal odors are odors similar to chemicals, and usually are negative and reducing. · Negative – defect : paint – soap – iodine – ethanol – acetone – solvent – wax – Acetic – iron – sulfur · Floral notes are odors that resemble flowers and are almost always positive. · Positive: Rose – lily – iris – violet – elder – citrus blossom – Melissa – peach flowers – dill 5. Dried Fruit – Jam · Dried fruit notes are aromas that are also found in jam and cooked fruits. · Positive: dates – blackberry jam – strawberry jam – dried figs – peanuts – almonds · Such notes are almost always positive, pleasant aromas and flavors that are sometimes mistaken for sweetness in dry wines · Positive: plum – wild berries – strawberry – peach – apple – banana – melon – coconut – guava – passion fruit – cherry – mandarin – papaya – grapefruit · Such notes are also desirable in wines, they add complexity and character. The main flavoring agent is the wood barrel that is used in the aging process. · Positive Notes: oak – cedar – sandal wood – bark – chestnut – walnut · Mineral or earthy notes are desirable when they are faint, however they can become reductive odors when they become too strong and mask other aromas in the wine. · Negative – defect : chalk – iodine – silica – pencil · Positive: amber – river stone – mineral – wet clay – wet forest · Such notes usually accompany wood notes; however some grape varieties that aren’t aged in oak can have some spice expressions, such as Syrah and Malbec. They are generally positive, but can become negative if they mask the other wine aromas. · Negative – defect : graphite – garlic – cumin – onion – green pepper – bell pepper · Positive: nutmeg – ginger – cardamom – tea – tobacco leaf – licorice root – cinnamon 10. Toasted – Empyreumatic · Such notes also usually accompany wood notes. They are generallym positive, but can become negative if they mask the other wine aromas. · Negative – defect : gun powder – burning rubber – cigarette smoke – tar – rubber – burnt plastic · Positive: roasting – coffee – chocolate – caramel – toast – frankincense – wood smoke – cocoa – toasted almonds 11. Vegetal – Herbal · Notes resembling vegetables and legumes, sometimes unripe fruits and zest. When subtle, they are generally desired in white and rose wines; they can complement some fruity reds, but will become a defect when they mask other aromas. · Negative – defect : raddish – geranium – cooked asparagus – cooked cabbage - artichoke · Positive: cut grass – celery – green coffee – fern – cucumber – hummus 12. Wide – Different – Miscellaneous · Since smell is a subjective olfactory perception, people might pick up much more aromas that are not encompassed by the categories below, which can lie on either end of the sensation spectrum. · Negative – defect: celluloid – oxidized notes – ink – oyster – gasoline – ash – medicine – plastic – etc. · Positive: candy – ginger bread – honey – cookie – croissant – praline – beeswax – yeast – brown sugar – gum – macaroon – volcanic soil – etc. Now that you have a decent idea about wine, I am confident that you will enjoy wine more. Also, the only way to become better at wine tasting it to enjoy more wines, more often. Also if you'd like to book a live masterclass with me, with food and wine pairing, you can reach out to me on [email protected]

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Arriving at a diagnosis of bladder cancer may involve one or more of these steps: - Urine tests to detect blood, cancer cells and other signs of disease. A 24-hour urine collection can measure volume of urine output, an indicator of kidney function. - Bladder wash during which a solution is delivered through a catheter (tube) to the bladder to loosen cells on the bladder’s inner lining. The solution is removed, and a sample is examined under a microscope. - Blood tests to assess kidney and liver function - Cystoscopy to see inside the bladder and identify any tumor - Imaging Scans to determine if a cancer has spread - Transurethral Resection of Bladder Tumor (TURBT) to obtain a biopsy, confirm a cancer diagnosis, and determine the stage and grade of a cancer It matters – getting the right diagnosis If you seek a second opinion at Roswell Park, our bladder cancer team will review your tests, scans and pathology. In about 10% of cases we review, the diagnosis is changed, impacting your treatment options and decisions. Getting an accurate diagnosis of your bladder cancer – including your cancer’s type, grade, shape, stage and whether it’s invasive or noninvasive – is essential to determining your treatment options and the way forward. At Roswell Park, our team of urologists, pathologists and radiologists, are uniquely experienced and specialize in performing and interpreting the tests, scans and procedures necessary for an accurate bladder cancer diagnosis. What is a cystoscopy? If you have symptoms of bladder cancer that cannot be attributed to another cause, such as an infection, your next step will be to undergo a simple procedure called flexible cystoscopy to allow your doctor to see the inside of your bladder. You may need a cystoscopy if: - You have visible blood in your urine (urine may be rusty, pink or red) - A urine test showed microscopic blood in your urine (not visible to your eyes) - You have symptoms such as urinary frequency or urgency In this procedure, a tube called a cystoscope (fitted with a tiny light and camera) is passed through the urethra and into your bladder, allowing your doctor to visualize the inside of your bladder and detect any tumors. This 15- to 30-minute procedure can be done in your doctor’s office and does not require anesthesia. A numbing gel is inserted into the urethra to prevent any discomfort. During this test, the doctor can collect cells from your bladder’s lining to examine, diagnose and even treat various bladder conditions, and perform a bladder wash. What does the doctor look for during cystoscopy? Your doctor will look for any abnormalities in the urethra and lining of your entire bladder, such as: Imaging scans — has my cancer spread? If your flexible cystoscopy revealed bladder cancer, your medical team will need to determine whether or not the cancer has spread beyond your bladder, using one or more of the following imaging tests: - Computerized Tomography (CT) - Intravenous pyelography (IVP) - Magnetic Resonance Imaging (MRI) - Positron Emission Tomography (PET) - Bone Scan Although these scans can provide your medical team with a picture of your body’s structure and function and direct your medical team to an area of concern, scans cannot tell what is going on with your cells. A biopsy or tissue sample is needed to allow a pathologist to examine the cells and determine definitely whether it is cancer and which type. What is Transurethral Resection of Bladder Tumor (TURBT)? If your cystoscopy or imaging scans found a suspicious mass, tumor or any irregularity such as a lesion, your next step is to obtain a biopsy or tissue sample through a surgical procedure called Transurethral Resection of Bladder Tumor (TURBT). During a TURBT procedure, the surgeon inserts a tool called a resectoscope through the urethra to reach the inside of your bladder and remove a piece of tumor tissue, or the entire tumor from your bladder.

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By Lucinda Glover, with contributions from Michael Woods, London School of Economics Australia has a regionally administered, universal public health insurance program (Medicare) that is financed through general tax revenue and a government levy. Enrollment is automatic for citizens, who receive free public hospital care and substantial coverage for physician services, pharmaceuticals, and certain other services. New Zealand citizens, permanent residents, and people from countries with reciprocal benefits are eligible to enroll in Medicare. Approximately half of Australians buy private supplementary insurance to pay for private hospital care, dental services, and other services. The federal government pays a rebate toward this premium and also charges a tax penalty on higher-income households that do not purchase private insurance. How does universal health coverage work? It took 10 years of political tension to establish Australia’s universal public health insurance program, known as Medicare. A universal health care bill was initially introduced in Parliament in 1973 but failed three times to pass through the Senate. Because of these failed attempts, a new parliamentary election was called, a procedure known as double dissolution, to resolve the deadlock. The new Parliament passed the health care legislation in 1974, establishing free public hospital care and subsidized private care. However, following a change in government in 1975, access to free health care services was limited to retired persons who met stringent means tests. After another change of government in 1984, the current Medicare system was established. Medicare provides free public hospital care and substantial coverage for physician services and pharmaceuticals for Australian citizens, residents with permanent visas, and New Zealand citizens following their enrollment in the program and confirmation of identity.1 Restricted access is provided to citizens of certain other countries through formal agreements.2 Other visitors to Australia, as well as undocumented immigrants, do not have access to Medicare and are treated as private-pay patients, including those needing emergency services. Role of government: Three levels of government are collectively responsible for providing universal health care: The federal government provides funding and indirect support for inpatient and outpatient care through the Medicare Benefits Scheme (MBS) and for outpatient prescription medicine through the Pharmaceutical Benefits Scheme (PBS). The federal government is also responsible for regulating private health insurance, pharmaceuticals, and therapeutic goods; however, it has a limited role in direct service delivery. States own and manage service delivery for public hospitals, ambulances, public dental care, community health (primary and preventive care), and mental health care. They contribute their own funding in addition to that provided by federal government. States are also responsible for regulating private hospitals, the location of pharmacies, and the health care workforce. Local governments play a role in the delivery of community health and preventive health programs, such as immunizations and the regulation of food standards.3 At the federal level, intergovernmental collaboration and decision-making occur through the Council of Australian Governments (COAG), with representation from the prime minister and the first ministers of each state. The COAG focuses on the highest-priority issues, such as major funding discussions and the interchange of roles and responsibilities among governments. The COAG Health Council is responsible for more detailed policy issues and is supported by the Australian Health Minister’s Advisory Council. The federal Department of Health oversees national policies and programs, including the MBS and PBS. Payments through these schemes are administered by the Department of Human Services. Other federal agencies involved in health care include the following: - The Pharmaceutical Benefits Advisory Committee provides advice to the Minister for Health on the cost-effectiveness of new pharmaceuticals (but not routinely on delisting). - The Australian Digital Health Agency is responsible for matters relating to electronic health data, and the Australian Institute of Health and Welfare and the Australian Bureau of Statistics (ABS) also provide health data. - The Therapeutic Goods Administration oversees supply, imports, exports, manufacturing, medical devices, pharmaceutical safety, and advertisement. - The Australian Health Practitioner Regulation Agency ensures registration and accreditation of the workforce in partnership with national boards. - The Australian Prudential Regulation Authority regulates private health insurance, and the Australian Competition and Consumer Commission promotes competition among private health insurers. The state governments operate their own departments of health and have delegated the management of hospitals to Local Hospital Networks. These hospital networks are responsible for working collaboratively with federally funded Primary Health Networks, which were established in 2015 to improve the efficiency, effectiveness, and coordination of care. Primary Health Networks have boards comprising medical professionals and community advisory committees. Role of public health insurance: Total health expenditures in 2015–2016 represented 10.3 percent of the GDP, an increase of 3.6 percent from 2014–2015. Two-thirds of these expenditures (67%) were funded by the government.4 Medicare is funded through the national tax system, in part by a government levy, which raised an estimated AUD 114.6 billion (USD 80.14 billion)5 in 2015–2016.6 Since 2014, a share of the money raised from this levy also supports the National Disability Insurance Scheme. Role of private health insurance: Private health insurance is readily available and offers coverage for out-of-pocket fees and private providers, greater choice of providers (particularly in hospitals), faster access to nonemergency services, and rebates for selected services. Private health insurance may include coverage for hospital care, general treatment, or ambulance services. General treatment coverage provides insurance for dental, physiotherapy, chiropractic, podiatry, home nursing, and optometry services. Coverage may be capped by dollar amount or by number of services. For hospital services, patients can opt to be treated as a public patient (with full fee coverage) or as a private patient (with 75% fee coverage). Government policies encourage enrollment in private health insurance through a tax rebate (8.5%–33.9%, depending on age and income) and an income-based penalty payment (1%–1.5%) for not having private insurance. This penalty, known as the Medicare Levy surcharge, applies only to singles with incomes above $90,000 and families with incomes above $180,000.7 The Lifetime Health Coverage program provides a lower health insurance premium for life. However, there is a 2 percent increase in the base premium for each year after age 30. Consequently, sign-up is highest among those 30 and under, with a trend to opt out starting at age 50. Nearly half of the Australian population (46%) had private hospital coverage and nearly 55 percent had private general treatment coverage in 2016.8 However, coverage varies by socioeconomic status: Private health insurance covers just one in five (22%) of the most disadvantaged 20 percent of the population, but more than 57 percent of the most advantaged population quintile. This disparity is due, in part, to the Medicare Levy surcharge applied to higher-income earners.9 Insurers are a mix of for-profit and nonprofit providers. In 2015–2016, private health insurance expenditures represented 8.8 percent of all health spending.10 Services covered: The federal government defines and funds MBS benefits, which cover hospital care and medical services, including mental health and maternity care. MBS also provides for limited optometry and children’s dental care. Pharmaceutical subsidies are provided by the government through the PBS. To be listed, pharmaceuticals need to be approved for cost-effectiveness by the Pharmaceutical Benefits Advisory Committee. The federal government also funds cancer screening and immunization programs that are provided free to targeted population groups. States are responsible for the delivery of free public hospital services, preventive care, chronic disease management, and supplementary mental health care not covered by Medicare. States also provide means-tested access to medical equipment such as wheelchairs. Home care for the elderly and hospice care coverage are funded separately by Medicare (see “Long-term care and social supports,” below). Cost-sharing and out-of-pocket spending: Out-of-pocket payments accounted for 16.5 percent of total health expenditures in 2016–2017. The largest share (68%) was for primary care, of which one-third (37%) was for medications, followed by hospital care (11%).11 Under Medicare, there are no deductibles or out-of-pocket costs for public patients receiving public hospital services. Cost-sharing for outpatient care varies. The federal government sets Medical Benefits Schedule (MBS) fees for general practitioner (GP) and specialty visits; it pays GPs 100 percent of the fee and specialists 85 percent. Patients pay the remaining 15 percent of specialist fees, as well as any surcharges. GPs and specialists can choose to charge above the MBS fees, although there is a maximum patient out-of-pocket fee of AUD 83.40 (USD 57.00) per service. About 86 percent of GP visits were provided without an additional charge to patients in 2016–2017.12 Patients who were charged paid an average of AUD 31 (USD 22). Out-of-pocket outpatient pharmaceutical expenditures are capped under the PBS (see table). Consumers pay the full price of medicines not listed on the PBS. Pharmaceuticals provided to inpatients in public hospitals are generally free. Safety nets: In addition to providing free public hospital care and capped drug costs, Australia has three safety nets to help with other out-of-pocket costs: - The Original Medicare Safety Net covers the MBS fee for all out-of-hospital Medicare services above an annual out-of-pocket threshold of AUD 461 (USD 322). If there are charges above the fee, the individual is responsible for them. - The Extended Medicare Safety Net covers 80 percent of out-of-pocket, out-of-hospital costs (these include costs above the MBS fee) over an annual threshold of AUD 668 (USD 467) for those with government-issued concession cards (e.g., low-income people, seniors, caregivers) and AUD 2,093 (USD 1,464) for others. A maximum out-of-pocket fee per out-of-hospital service (known as the Greatest Permissible Gap) is set at AUD 83.40 (USD 57.00); this fee may be covered by private health insurance for those with coverage.13 War veterans, the widowed, and their dependents may be eligible for further discounts. How is the delivery system organized and how are providers paid? Physician education and workforce: Physicians are trained primarily at public (but also private) universities, with their fees subsidized through the tax system. Annual tuition fees are approximately AUD 65,000 (USD 45,454), with the student contribution capped at AUD 10,754 (USD 7,520) per annum for Australian citizens.15 The federal government provides primary care doctors with financial incentives to practice in rural and remote areas. There is no cap on the number of physicians in Australia, and workforce shortages are addressed through internationally trained providers. Primary care: In 2015, there were 34,367 GPs, 49,060 practitioners registered as both generalists and specialists, and 8,386 providers registered as specialists.16 GPs are typically self-employed, with about four physicians per practice on average.17 In 2013–2014, GPs earned an average of AUD 3,024 (USD 2,115) per week, around half (56%) of what specialists earned.18 The schedule of MBS service fees is set by the federal health minister. Registration with a GP is not required, and patients choose their primary care doctor. GPs operate as gatekeepers; a referral to a specialist is needed for a patient to receive the MBS subsidy for specialist services. GPs are paid primarily on a fee-for-service basis through the MBS model, although they can also receive funding from a performance-based initiative called the Practice Incentives Program. The Practice Incentives Program accounts for 5.5 percent of federal expenditures on GPs.19 The federal government also encourages multidisciplinary care coordination by funding large multidisciplinary GP clinics, known as Super Clinics, and through the establishment of Primary Health Networks, which support more efficient, effective, and coordinated primary care. In 2015, there were 11,040 nurses or midwives working in a general practice setting.20 Their role has been expanding with the addition of a practice nurse payment in the Practice Incentives Program. Nurses in general practice settings provide chronic disease management and care coordination, preventive health education, and oversight of patient follow-up and reminder systems. Outpatient specialist care: Specialists deliver outpatient care in private practice (8,001 specialists in 2015) or in public hospitals (3,745).21 Patients are able to choose which specialist they see but must be referred by their GP to receive MBS subsidies. Specialists are paid on a fee-for-service basis. They receive federal subsidies for 85 percent of the MBS fee and set their patients’ out-of-pocket fees independently. Many specialists split their time between private and public practice. Administrative mechanisms for direct patient payments to providers: Many practices have the technology to process claims electronically so that reimbursements from public and private payers are instantaneous, and patients pay only their copayment (if the provider charges above the MBS fee). If the technology is not in place, patients pay the full fee and seek reimbursement from Medicare and/or their private insurer. After-hours care: GPs are required to ensure that after-hours care is available to patients, but are not required to provide care directly. They must demonstrate that processes are in place for patients to obtain information about after-hours care and that patients can contact them in an emergency. After-hours walk-in services are available and may be provided in a primary care setting or within hospitals. Because there is free access to emergency departments, some patients may use these facilities for after-hours primary care. The government also provides funds to Primary Health Networks to support and coordinate after-hours services, and there is an after-hours advice and support line. Hospitals: In 2016–2017, there were 695 public hospitals (673 acute, 22 psychiatric), with a total of nearly 60,300 beds. Hospital beds have increased by an annual average of 1.5 percent, maintaining a consistent supply of 2.5 beds per 10,000 population. In the same period, there were 630 private hospitals (341 day hospitals and 289 others) with 33,100 beds.22 Private hospitals are a mix of for-profit and nonprofit. Public hospitals receive a majority of funding (92%) from the federal government and state governments, with the remainder coming from private patients and their insurers. Most of the public hospital funding (66% of total recurrent expenditures) goes toward the salaries of employed physicians. Private hospitals receive most of their funding from private health insurers and patients (68%), with 32 percent coming from government.23 Public hospitals are organized into Local Hospital Networks, of which there were 136 in 2016–2017. These vary in size, depending on the population they serve and the extent to which linking services and specialties on a regional basis is beneficial. In major urban areas, a number of Local Hospital Networks comprise just one hospital. State governments fund their public hospitals largely on an activity basis, using diagnosis-related groups. Federal funding for public hospitals includes a base amount plus money for growth (for further details, see “How are costs contained?”). Small rural hospitals are funded through block grants.24 Pharmaceuticals used in hospitals are subsidized by the federal government through the PBS. Mental health care: Mental health services are a responsibility shared by the federal and state governments as articulated through a rolling series of five-year National Mental Health Plans, with the current plan running until 2022. In addition, federal and state health ministers agreed to the Fifth National Mental Health and Suicide Prevention Plan in August 2017. Mental health care is provided in many settings, including GPs and specialist care, community-based care, hospitals (both inpatient and outpatient, public and private), and residential care. GPs provide general mental health care and may devise treatment plans of their own or refer patients to specialists. Specialist care and pharmaceuticals are subsidized through the MBS and PBS. State governments fund and deliver acute mental health and psychiatric care in hospitals, community-based services, and specialized residential care. Public hospital–based care is free to public patients. In addition, nonprofit organizations, such as LifeLine, BeyondBlue, and HeadSpace, provide important services ranging from suicide prevention to primary preventive care for both adults and youth. Australia spent AUD 9.0 billion on mental health–related services in 2015–2016. Most of this expenditure goes toward services delivered by state governments ($5.4 billion), with AUD 2.4 billion being for public hospital services and $2.0 billion for community health services. The Australian government subsidizes additional mental health services through the MBS (AUD 1.2 billion) and the PBS (AUD 511 million). Specialized mental health services in private hospitals cost AUD 493 million in 2015–2016.25 Long-term care and social supports: Three out of four people receiving long-term care receive residential aged care (nursing home care). Three-quarters of older Australians receive informal care and 60 percent receive formal care. In 2015, 11 percent of Australians were informal caregivers, and 32 percent of these caregivers were the primary caregiver, or carer. In 2011–2012, the federal government provided AUD 3.18 billion (USD 2.22 billion) under the income-tested Carer Payment program for caregivers who are providing constant care and are unable to be otherwise employed. The government also contributes AUD 1.75 billion (USD 1.22 billion) to a separate caregiver program, called the Carer Allowance, that provides a supplement for daily care to primary carers, regardless of their income. In addition, the federal government provides an annual Carer Supplement of AUD 480 million (USD 336 million) to help with the cost of caring. Recipients of the Carer Allowance who care for a child under the age of 16 receive an annual Child Disability Assistance Payment of AUD 1,000 (USD 699). There are also a number of respite programs providing further support for caregivers.26 Home care for the elderly is provided through the Commonwealth Home Support Program in all states except Western Australia. Subsidies are income-tested and may require copayments from recipients. Services can include assistance with housework, basic care, physical activity, and nursing, among others. The program began in July 2015 and combines home and community care, respite care for caregivers, day therapy, and assistance with care and housing.27 The Western Australian government has its own initiative, the Home and Community Care Program, which is delivered with funding support from federal government. Residential aged care be private nonprofit, for-profit, or run by state or local governments. Federally subsidized nursing home accommodations are available. The Australian government supports both permanent and respite residential care. Eligibility is determined through a needs assessment, and permanent care and accommodation costs are means-tested.28 Hospice care is provided by states through complementary programs funded by the Commonwealth. In 2013, the federal government, in partnership with states, implemented the pilot phase of the National Disability Insurance Scheme. Full implementation is planned by 2020, at which point around 460,000 Australians are expected to receive support.29 The scheme provides more flexible funding support for long-term care (not means-tested), to allow greater tailoring of services. The main component of the NDIS is individualized packages of support to eligible people with disabilities. What are the major strategies to ensure quality of care? The overarching strategy for ensuring quality of care is captured in the National Healthcare Agreement of the COAG (2012). The agreement sets out the common objective of Australian governments in providing health care — a sustainable system with improved outcomes for all — and the performance indicators and benchmarks on which progress is assessed. It also sets out national-priority policy directions, programs, and areas for reform, such as addressing major chronic diseases and their risk factors. Indicators and benchmarks in the agreement address issues of quality from primary to tertiary care and include disease-specific targets of high priority, as well as general benchmarks. The Australian Commission on Safety and Quality in Health Care (ACSQHC) is the main body responsible for safety and quality improvement in health care. The ACSQH has developed service standards that have been endorsed by health ministers. These include standards for conducting patient surveys, which must be met by hospitals and day surgery centers to ensure accreditation. The Australian Bureau of Statistics, the national government statistical body, also undertakes an annual patient experience survey. The Australian Council on Healthcare Standards is the (nongovernment) agency authorized to accredit provider institutions. States license and register private hospitals and the health workforce, legislate on the operation of public hospitals, and work collaboratively through the National Registration and Accreditation Scheme to facilitate workforce mobility across jurisdictions while maintaining patient protections. States also ensure that the workforce maintains minimum hours and standards of continuing education to maintain accreditation. The Royal Australian College of General Practitioners has responsibility for accrediting GPs. To be eligible for government subsidies, aged-care services must be accredited by the government-owned Aged Care Standards and Accreditation Agency. Beginning in January 2019, the new Aged Care Quality and Safety Commission will be responsible for regulation, compliance, and complaints for aged care. There are a number of disease and device registries. Government-funded registries are housed in universities and nongovernmental organizations, as well as within state governments. The ACSQH has developed a national framework to support consistent registries. The National Health Performance Authority reports on the comparable performance of Local Hospital Networks, public and private hospitals, and other key health service providers, but not nursing homes or home care agencies. The reporting framework, agreed to by the Council of Australian Governments, includes measures of equity, effectiveness, and efficiency. The federal government has regulatory oversight of quarantine, blood supply, pharmaceuticals, and therapeutic goods and appliances.30 In addition, there are a number of national bodies that promote quality and safety of care through evidence-based clinical guidelines and best-practice advice. They include the National Health and Medical Research Council and Cancer Australia. What is being done to reduce disparities? The most prominent disparities in health outcomes are between the Aboriginal and Torres Strait Islander population and the rest of Australia’s population; these are widely acknowledged as unacceptable. In 2008, the COAG agreed to set a target for closing the gap in life expectancy by 2031. This is a government and nongovernment effort, with the nongovernment component supported through the Australian Human Rights Commission. Progress toward this target is not on track, with the gap currently at 10.6 years for males and 9.5 for females. From 2005–2007 to 2010–2012, there was a very small reduction in the gap of 0.8 years for males and 0.1 years for females.31 Disparities between major urban centers and rural and remote regions, and across socioeconomic groups, are also major challenges. The federal government provides financial incentives to encourage GPs and other health workers to work in rural and remote areas, where it can be very difficult to attract a sufficient number of practitioners. This challenge is also addressed, to an extent, through the use of telemedicine. What is being done to promote delivery system integration and care coordination? Approaches to improving integration and care coordination include the Practice Incentives Program, which provides a financial incentive to providers for the development of care plans for patients with certain conditions, such as asthma, diabetes, and mental health needs. In addition, the Primary Health Networks were established in July 2015 with the objective of improving coordinated care, as well as the efficiency and effectiveness of care for those at risk of poor health outcomes. These networks are funded through grants from the federal government and will work directly with primary care providers, health care specialists, and Local Hospital Networks. Care also may be coordinated by Aboriginal health and community health services. What is the status of electronic health records? The Australian Digital Health Agency, established in July 2016, has national responsibility for the country’s digital health strategy. An interoperable national e-health program based on personally controlled unique identifiers is now in operation. More than 6 million patients (one-quarter of Australians) and 13.4 million providers are currently registered. As of February 2019, all Australians have a My Health Record created for them unless they have opted out of the system, although individuals can choose to delete their record at any time.32 The record supports prescription information, medical notes, referrals, and diagnostic imaging reports. Patients can view their own medical information and control who can see it, as well as add information about allergies, adverse reactions, and their health care wishes in the event that they become unable to communicate. How are costs contained? The major drivers of cost growth are the MBS and PBS. The federal government regularly considers opportunities to reduce spending growth in the MBS through its annual budget process. To influence PBS costs, the government makes determinations about which pharmaceuticals to list on the scheme and negotiates the price with suppliers. It also provides funds to pharmacies to dispense medicines subsidized through the PBS and to support professional programs and the wholesale supply of medicines. This arrangement is implemented through the current Community Pharmacy Agreements, which are renegotiated every five years. The Sixth Community Pharmacy Agreement, which began in July 2015, supports AUD 6.6 billion (USD 4.6 billion) in savings through supply chain efficiencies.33 Hospital budgets are set by the Local Hospital Networks. Hospitals are funded on the basis of what is determined to be an efficient price for delivering services, as determined by the Independent Hospital Pricing Authority. Through 2020, the Commonwealth will fund 45 percent of the efficient growth in these services, capped at 6.5 percent of total growth.34 States are required to cover the remaining cost of services, providing an incentive to keep costs at the efficient price or lower. Beyond these measures, health costs are controlled mainly through capacity constraints, such as workforce supply. What major innovations and reforms have recently been introduced? The Australian government has introduced a number of reforms to care for older people aimed at improving financial sustainability, quality, and consumer choices. The independent Aged Care Quality and Safety Commission, established in early 2019, will bring together previously disparate functions of quality assurance, complaints, and regulation of the aged care sector. The government has also started conducting unannounced audits of aged-care (or nursing) homes for reaccreditation. The Australian government is also investing more funding to help people remain in their own homes as they age. One example is the Community Visitor scheme, which supports the 70 percent of elderly people who receive aged care at home and experience loneliness. In its 2018 budget, the federal government allocated AUD 102.5 million (USD 71.7 million) to services for older Australians, with AUD 82.5 million (USD 57.7 million) for residents of aged-care facilities and AUD 20.0 million (USD 14.0 million) for those in the community at risk of isolation. The 2018 budget also included AUD 72.6 million (USD 50.8 million) for suicide prevention and follow-up care for the adult population and AUD 110 million (USD 77 million) for child and youth health care. In 2017, the Australian government launched Head to Health, a one-stop electronic resource to direct people experiencing mental health issues to services and resources, supporting them in taking control of their health by reaching out to high-quality, reputable providers. The website was developed in partnership with people and families who have experienced a mental health issue, as well as those who provide care. The author gratefully acknowledges the contributions of LSE research assistant Michael Woods.

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» You should spend about 20 minutes on this task. The table below shows the monthly expenditure of an average Australian family in 1991 and 2001. Summarise the information by selecting and reporting the main features, and make comparisons where relevant. » Write at least 150 words. Sample Answer 1 The table data compare the monthly expenses of an average family in Australia for the years 1991 and 2001. Overall, monthly expenditure by an average Australian family had not increased that much in 10 years, from 1991 to 2001, and expenses on electricity, water, housing, and non-essential goods and services somewhat increased while the expenses on clothing and transport decreased over time. As is presented in the table, the average expenditure of an Australian family per month was AUD 675 in 1991, while this reached to AUD 715 after 10 years. This shows that the average spending of an average Australian family had not increased significantly. In 1991, the expenditure on non-essential goods and services was $250, the highest among the given categories. This reached to $270 in 2001, which was also the highest amount among the given expense categories in 2001. The expenses on food & housing were $155 and $95 consecutively in 1991, which increased by only 5 dollars after 10 years. Interestingly the monthly amount spent on clothing and transport decreased over the decade and reached $20 and $45 in 2001. The expenses on food, housing and electricity & water increased and the highest increase was for electricity and water. Sample Answer 2 The table given compares the average spending of an Australian family every month between 1991 and 2001. The initial impression of the table is that the total average expenditure in 2001 was higher than in 1991. It is also critical to note that the statistics provided illustrate a downward trend in Transport and Clothing categories over the period given. On top of the list across the years were non-essential goods and services, which accounted for over one-third of the total spending in both 1991 and 2001, at 250 AUD and 270 AUD respectively, indicating relatively small additions in its expenses. Food, ranking second among the items, experienced a slight increase between the two surveyed years, with a difference of 5 AUD (155 AUD to 160 AUD). Similar trends can be observed regarding Housing, accounting for 100 AUD in 2001, which was also just 5 AUD more than ten years prior. However, there was a substantial rise of 45 AUD in the average electricity and water spending. In contrast, the amount spent on Transport considerably dropped from 70 AUD to 45 AUD. Finally, the least expanding category was Clothing, which took up to 30 AUD in 1991 and dropped by one-third after the decade. Sample Answer 3 The table shows changes in the spending patterns of an average Australian household between 1991 and 2001. In general, Australian household spending was higher in 2001 than in 1991, but the difference was insignificant (AUD 715 per month and AUD $675 per month, respectively). The monthly spending on electricity and water saw a dramatic increase over the 10 years from $75 to $120. Yet in terms of the expenditure on non-essential goods and services, the rising trend was less obvious, with a minor increase of $20. At the same time, the amount of money spent on food and housing rose only slightly from $155 to $160 and $95 to $100 respectively. However, there was a decrease in expenditure on the other two items. Australians spent one-third less on clothing, which fell from $30 to $20. Similarly, expenditure on transport dropped from $70 in 1991 to $45 in 2001. Food and “other goods and services” were the two biggest expenditure items. Altogether, they accounted for more than half of the total household spending. By comparison, Australians spent little on dressing up. Leave a Reply

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Da-Lite Screen Co., Inc. BIM-objekt BIMobject Da-Lite Screen Co., Inc. BIM-objekt BIMobject - Silentium västerås - Serviceminded or service minded - Hoglunds butcher - Suicidal test - Anisette cookies - Sara lönn arkelstorp - Övervaka misstänks telefon Industrial Revolution inventions 1. Inventions of the Industrial Revolution Choose 5-6 Inventions to take notes on in your spiral. Write what the invention is, who invented it, when, and why it was important to history. 2. Often thought of as beginning in Britain in the 18th century, the Industrial Revolution (c.1750-1850) is characterised by its many brilliant figures and innovations.. It was a time epitomised by the wide scale introduction of machinery, the transformation of cities and significant technological developments. Eleanor Coade (1733–1821) · 3. Henrietta Vansittart (1833–1883) · 4. Anna Maria Garthwaite Follow the Author · Similar authors to follow · The Industrial Revolution: Age of Invention (Discovery Education: Discoveries and Inventions) Paperback – July 15 , Students will learn how the Industrial Revolution impacted transportation, manufacturing, and communication. The power of power - Hydro Energy's history - Hydro.com Top 10 Industrial Revolution Inventions 1: Ways to Mine Iron. Building the infrastructure to support the Industrial Revolution wasn't easy. The demand for 2: Spinning Jenny. Important inventions of the industrial revolution - Storyboard That Eli Whitney is another name synonymous with inventions of the Industrial Revolution. He invented the cotton engine, gin for short, in 1794. Prior to its introduction into the textile industry, The Industrial Revolution -- an innovative period between the mid-18th and 19th centuries -- pushed people from a predominantly agricultural existence into a more urban lifestyle. Without all the new inventions of this era, many of the basic goods and services we use today wouldn't exist. The Second Industrial Revolution, which lasted from the late 1800s to the early 1900s, saw a surge of new technology and inventions that led to dramatic changes in the economy and how people lived The Industrial Revolution was a time of rapid social and technological change that shaped world. The industrial age was famous for its manifold inventions. Inventions of the Industrial Revolution 1800-1920 Timeline created by cvz9031. Service elektriker jobb stockholm The Industrial Revolution lasted from approximately 1860-1914. Discover a few of the many Industrial Revolution inventions that changed the world, made history and continue to impact the modern world. Ola wong manifest på sikt om mats börjesson gu Industriella revolutionen - Skolbibliotek Uddevalla Jan 1, 1800. Battery Count Alessandro Volta invents the battery. Most of the inventors you’ll learn about in this interactive tutorial come from the Second Industrial Revolution--often known as the “Technological Revolution,” a time when American inventors created a host of new devices across a range of industries that increased efficiency and production, enhanced safety, furthered communication, and made the day-to-day lives of Americans a little easier. step training center Exploring Africa in the Nordic Press. David Livingstone, Henry 1846 History of Inventions Industrial Revolution. New! första årtionden som en revolution, och i så fall kanske det handlar om en revolution Brahe, and the Murder Behind One of History's Greatest Scientific Discoveries. Greer: The long descent: A use's guide to the end of the industrial age. The first industrial revolution, which REALLY was a revolution, and, among others thanks to invention of steam machines, the usage of water and steam power and Inventions of the Industrial Revolution Newcomen’s Steam Engine:. Newcomen’s steam engine was invented by Thomas Newcomen in England in 1712. SOU 2006:080 Patent och innovationer för tillväxt och välfärd In actuality, the spinning jenny is a multi-spindle spinning frame and was a great invention in the Industrial Revolution. However James Watt The most beautiful pieces from Meyer's Konversations Lexikon 1897: - Machines, apparatus, discoveries, inventions from the 19th century. - Beautiful samples of Da-Lite was founded with the invention of the Silver Screen during the second Industrial Revolution. It was a time when art and culture Svensk översättning av 'industrial revolution' - engelskt-svenskt lexikon med canals were invented in Britain before the Industrial Revolution, goods used to go "What was the greatest invention of the industrial revolution? Hans Rosling makes the case for the washing machine. With newly designed graphics from mid-1700s to the present. black mambaIndustrial Revolution 1760-1840 · Cotton Gin - Eli Whitney, inventor of the cotton gin that automated separating cotton av K Nyberg · 2010 — tion in Scandinavia. Craft Skills in the Industrial Revolution (Hamburg, New York 1987); S. Maxine Berg, "From Imitation to Invention: Creating Commodities in.

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At Woodgrange Infant School we believe that it is important for young children to meet Maths ideas through direct experience and relate them to their everyday life experiences. Children learn more quickly through handling objects and talking about concepts before they are asked to represent or record ideas. The programmes of study and the Early Years Foundation Stage Curriculum form the content of the school curriculum for mathematics and the activities that the children undertake are planned from these. Maths in the Early Years Foundation Stage All children in the EYFS follow a broad-based curriculum and have a wide range of opportunities to explore mathematical concepts; both planned and self-initiated inside and outdoors. Children also take part in whole class and group activities designed to develop mathematical language and concepts. Resources are used imaginatively and creatively to stimulate curiosity and excitement about the world around them. Children learn about numbers and about shape, space and measures, including money Assessments are observation based and inform planning to build on prior knowledge and understanding. Helping your child learn Maths at home Maths in Key Stage 1 Children have a daily maths lesson. Over the year they learn about: Numbers and place value- the position and value of digits Calculations- addition, subtraction, multiplication and division, including with money Fractions- halves and quarters Measurement of length, weight, capacity, time Shapes- properties and movement- such as quarter turns and for Year 2 simple statistics- interpreting graphs and tables Each term children are given opportunities that include: - practical activities - consolidation and practice of fundamental skills and routines - learning through mathematical games - individual, group and whole class discussions and activities - problem solving - mathematical investigations - using computers where appropriate Mathematics is used, applied and developed through activities in other areas of the curriculum where appropriate e.g. the use, recording and analysis of measurement skills in Science and Design technology. How do we assess maths? We use a wide range of strategies to inform us about progress including: – Observing children working – Talking to and questioning children in groups, as a class or individually – Marking recorded work and discussing with the children – Reviewing recorded independent work These assessment strategies inform learning and progress in the short term- the next few lessons and groups will be adjusted in response to this information. Three times a year children’s work is assessed against the objectives for the year group as set out in the National Curriculum. Progress is tracked and evaluated to: - identify pupils in need of either support or extension - identify areas of difficulty or areas of strength in terms of teaching or curricular provision - set new targets for learning which are shared with pupils This evidence contributes to the overall picture of achievement for each child. IMPORTANT FOR PARENTS At this stage children need to focus on calculating practically with objects and recording as either pictures or simple number sentences such as 6 + 5= 11 or 5 x 4= 20. We do not introduce more formal written calculations at Woodgrange. This is something they meet much later on. Children can get confused if they are asked to borrow etc before they fully understand what this means. Please speak to your class teacher for more advice. For more ideas and information please see these leaflets: Maths games to build fluency KS1 Helping your child with their maths learning in Key Stage 1

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30 000 a year is how much an hour? This is a question is being asked a lot. And it’s a good question! We all want to know how much we should be earning, and whether we’re being paid fairly. Whether you’re just starting out in your career or looking for a new job, it’s important to know what to expect when it comes to pay. So, what’s the average salary in the US? And how does your salary compare? Read our article to find out now! 30 000 a Year Is How Much an Hour? 30 000 a year is how much an hour? Assuming you work 40 hours per week, that means you’re making $14.42 an hour. But of course, not everyone works just 40 hours a week. Some people work more, and some people work less. And if you’re paid hourly, your earnings can fluctuate month to month or week to week depending on how many hours you work. Still, let’s say you work a fairly standard 40 hours a week. In that case, $30,000 a year is the equivalent of making $14.42 hourly rate. That’s not a bad wage! But it’s not an amazing wage, either. If you’re paid hourly, you can probably find jobs that pay more than $14.42 per hour. So, 30 000 a year is how much an hour? Around $14.42. 30,000 a Year Is How Much Biweekly? 30,000 a year is how much biweekly? This is a question that many people ask when they are considering their budget and financial planning. The answer, of course, depends on your salary and other factors. But in general, if you are making 30,000 a year, then your biweekly pay would be about $1,154 This can help you plan for your expenses and budget accordingly. Remember that your take-home pay may be different depending on your tax bracket and other deductions, so be sure to factor those in as well. 30,000 a Year Is How Much Per Week? The answer to this question can vary depending on a few different factors, but we have some tips that can help you calculate your own answer. First, it is important to consider your income. If you are earning a salary, your weekly paycheck will be based on your annual salary divided by 52 (because there are 52 weeks in a year). This means that if you make $30,000 per year, your weekly paycheck will be $576.92. However, if you are paid hourly, your weekly paycheck will be based on the number of hours you work multiplied by your hourly wage. 30,000 a Year – How Much Is It After Taxes? The amount of taxes you pay depends on your tax bracket and state you live in. The tax bracket you fall into depends on your taxable income. Assuming you are paid hourly, your gross pay would be $30,000 per year. After taxes, your pay would be reduced to around $24,854 per year, or $2,071 per month (example for a New York). These are calculations for a single filer with no dependents. Your take-home pay would be further reduced if you had deductions for health insurance, retirement savings, or other items. For example, if you contributed $100 per month to a 401(k) plan, your take-home pay would be reduced to $1,971 per month. 30k a Year. Is It More or Less Than a Minimum Wage? It actually depends on the state you live in, but generally 30 000 a year is more than a minimum wage. This salary allows for a comfortable lifestyle, although it may not be enough to live extravagantly. It is possible to save money and live well on this salary, but it may require some careful budgeting. Those earning 30k a year should make sure to take advantage of any opportunities to save, such as discounts and promotions. 30000 a Year. Can You Afford a Good Life? The simple answer is yes, you can afford a good life on $30000 a year. However, it will require sacrifices and lifestyle changes. You may need to downsize your home, move to a less expensive area, or get by with fewer material possessions. You’ll also need to be mindful of your spending and make sure you’re not wasting money on things you don’t really need. It also depends on the location. The cost of living in New York City is much higher than the cost of living in a small town. So, if you’re looking to save money, it might be worth considering a move to a less expensive area. But with some effort, you can definitely have a good life on $30000 a year. Who Earns 30,000 Per Year? Examples of Professions There are many occupations and professions that pay an annual salary of $30,000 or less. Some examples include: - social workers, - administrative assistants, - customer service representatives, - retail salespeople, - restaurant servers, - child care workers. While some of these occupations may not be as glamorous as others, they all provide important services to society. And, most importantly, they all offer the potential for career growth and advancement. With hard work and dedication, anyone can earn a good living, regardless of their starting salary. Now you know the answer to a question: 30 000 a year is how much an hour? What do you think about this salary? - None Found

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My first introduction to the importance of sugar here on the Big Island came in a sermon from Father Bob. He reminded us that 18 years before, the people all along the Hāmākua Coast were invited to step outside their homes to see something. The mood was not joyful, as when a parade passes by, nor grief-filled like the viewing of a hearse. He said the best word to describe it was melancholy; it was the passing of an era. As people lined the highway, tears in their eyes, they watched an 18 wheeler drive by. The truck let out a long sorrowful sound. It was the last truck of sugar cane to drive the Hāmākua Coast. The controlled life of the plantation, where the owners provided workers with housing, utilities and medical services, was over. The sugar industry was dead. The early camps in the mid-1800s were no more than barracks for single men, immigrants segregated by place of origin. Later their picture brides showed up, and real home life began in small plantation houses, with babies born and raised. Many of the people in the church listening to Father Bob’s sermon had lived in the camps. Some still live there. They remembered. It would be hard to overestimate the importance of sugar in these islands. While sugar was already here when Captain Cook arrived, the first plantation wasn’t built until 1835. By 1890, sugar comprised $12.6 million of Hawaii’s $13 million in exports, mostly to the US. The islands didn’t have sufficient population to supply the many laborers needed for the work, so plantation owners brought people here from China, Japan, Korea, the Philippines, Portugal, and Puerto Rico. Hawaii became a global village. Saturday, we honored the 20 year anniversary of the closing of the last sugar mill on the Big Island just makai (downhill) from Honoka‘a. It was the first Plantation Days Festival. True to Big Island festivals, we commemorated with food, dance, and celebrations of the rich cultural diversity we now enjoy. The Japanese welcomed all to join their bon dance (“the original line dance, just done in a circle,” quipped the MC). Women from the Portuguese Club proudly wore native dress and the Portuguese band played ukuleles, befitting the group that brought these instruments to the islands. Hawaiians danced the hula. It’s always fun to see the keiki dance, but nothing beats the beauty and subtle fluid motions of their teachers, some of whom have been dancing for 40 or 60 years. I must have been in the Honoka‘a Theatre seeing films of the plantation days when the other ethnic groups performed. It was a wonderful commemoration of that last harvest day for those who had been there. But it was also important for those of us who are newcomers, a chance to learn and feel history. Watching a Hāmākua Sugar Company training video for cane truck drivers, I learned that each truck carried 100,000 pounds of sugar cane to the mill, which sounds like a lot. But the sugar mills ran around the clock and required 1.5 million pounds of cane each hour to prevent a mill shutdown from having no cane available. These trucks arrived every three minutes, 24/7 in all weather. Back at the outdoor stage, the locals talked story about washing their cars and then driving behind a cane truck and having dirt clods and cane flying off in every direction, dirtying their cars again. And the old kupuna recalled few roads and fewer cars; they caught the sugar mill train to school every day. They talked story about seeing cane-burning clouds coming close to their houses and the rush to get the laundry off the line before the ash descended on everything. This burning process quick-flashed off the small sharp blades that cut workers, while the stalk remained intact. So much to learn. As with all festivals here, we enjoyed great street food. The Hāmākua Youth Center, my favorite non-profit in town, offered coconuts and sugar cane. The Japanese, Portuguese, Filipinos, Puerto Ricans and others offered their favorite items like Portuguese hot dogs, kalua pork and cabbage, pickled onions, poke bowls and pastelles. And all along the street, booths offered traditional plate lunches, each group offering their own twist. The Japanese served it with rice, three-cabbage tsukemono (Japanese pickles), nishime (Japanese stew) and Okinawan pork. It only struck me later how many of the foods included pork and then I made the connection; pork would have been one meat readily available years ago in the form of wild pig hunting. As I reflect on the Plantation Days Festival and what I absorbed there, a thought begins to simmer about what makes Hawaii different from other melting pots. When the plantation owners brought in different ethnicities and separated them into different camps, the workers did their best to recreate their life from back home, many deciding to settle here permanently. This firmly planted pockets of those cultures all over the islands. Later they started intermarrying. A local film on five generations of the Shigimatsu family revealed that it took four generations for family members to marry non-Japanese. Other ethnicities intermarried much sooner. Very few locals are pure anything anymore. One woman I met listed eight ethnicities that comprise her children’s heritage. Yet, unlike other melting pots, these locals still remember and celebrate all of them. The result is the wonderful mix of cultures that came together for this festival, with most people honoring more than one heritage. This is what makes Hawai‘i a global village: celebrating our differences together. For more on the Big Island’s ethnic diversity see Traditions and Family Values. For more information on plantation life, see YourIslandRoutes.com, and in particular, these articles by Melody Lassalle: Processing Sugar Cane in Hawaii Circa 1860, Male Workers on Hawaiian Sugar Plantations, Female Workers on Hawaiian Sugar Plantations, Hawaiian Sugar Plantation Occupations, and Sugar Plantation Work Days and Wages. If you like my blog, you’ll enjoy my book, Manifesting Paradise, available on Amazon. Receive my posts automatically by filling in your email address in the “follow” box at the top of the right column. And please join my mailing list. I missed it because I was at the Mai Tai Festival in Kona. Mahalo for providing me with some of the details of what happened. It sounds like a great event, and I will see you at the Peace Festival. I am really enjoying your book, Manifesting Paradise. I love this post, Diane. Your writing just gets better. Happens here all the time…wash your car and get stuck behind a manure wagon! That’s what you get for living in the country! Love it !! Almost made me wish I was home (NOT). xoxo Pingback: A safe cocoon – Honoka‘a | Manifesting Paradise

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When it comes to building construction, insulation is a crucial component that cannot be overlooked. Insulation serves as a barrier between the interior and exterior of a building, helping to regulate temperature and prevent heat loss. Not only does insulation play a vital role in maintaining a comfortable indoor environment, but it also helps to reduce energy costs and increase the overall efficiency of a building. In this article, we will explore the various types of insulation, their benefits, and why they are essential in building construction. Types of Insulation There are various types home insulation contractors near me available, each with its unique properties and benefits. The most common types include fiberglass, cellulose, spray foam, and rigid board insulation. Fiberglass insulation is made of tiny glass fibers woven together to form a dense, flexible material. It is often used in attics, walls, and crawl spaces, and is known for its affordability and ease of installation. Cellulose insulation is made from recycled paper and is known for its environmentally friendly properties. It is also fire-resistant and provides excellent soundproofing. Cellulose insulation is often used in walls, attics, and crawl spaces. Spray foam insulation is a type of insulation that is sprayed as a liquid and then expands to form a solid, seamless barrier. It is often used in hard-to-reach areas, such as corners and around pipes, and provides excellent insulation properties and air sealing capabilities. Rigid board insulation is made of rigid foam boards that are cut to size and installed in walls, roofs, and floors. It is often used in commercial and industrial construction, as it provides high insulation values and is easy to install. Benefits of Insulation Insulation provides a number of benefits, including: - Energy savings: Insulation helps to reduce energy costs by preventing heat loss and reducing the need for heating and cooling. This results in lower energy bills and a more efficient building. - Improved indoor comfort: Insulation helps to regulate temperature, providing a more comfortable indoor environment. This is especially important in extreme temperatures, when proper insulation can prevent indoor temperature fluctuations. - Increased durability: Insulation helps to protect a building from moisture and air infiltration, which can cause damage over time. By preventing moisture and air infiltration, insulation increases the overall durability of a building. - Environmental protection: Insulation helps to reduce greenhouse gas emissions by reducing the need for heating and cooling. This results in a smaller carbon footprint and a more sustainable environment. Why Insulation is Essential in Building Construction Insulation is essential in building construction for a number of reasons, including: - Energy efficiency: Insulation helps to improve the overall energy efficiency of a building, reducing energy costs and increasing sustainability. - Comfort: Insulation helps to regulate temperature, providing a more comfortable indoor environment. - Durability: Insulation helps to protect a building from moisture and air infiltration, increasing its overall durability. - Environmental responsibility: Insulation helps to reduce greenhouse gas emissions, promoting a more sustainable environment. The Importance of Metal Roofing in Building Construction Metal roofing is a popular choice in building construction due to its durability, versatility, and energy-efficient qualities. It is long-lasting, resistant to extreme weather conditions, and fire-proof, making it an ideal solution for protecting buildings and the people inside. Additionally, metal roofing reflects sunlight, helping to reduce cooling costs, and can be made from recycled materials, making it an environmentally friendly option. The ability to customize metal roofing to suit the specific needs and aesthetics of a building makes it an ideal choice for construction projects. Insulation is a crucial component of building construction that should not be overlooked. Whether you are building a new home or retrofitting an existing one, insulation is essential for maintaining energy efficiency, indoor comfort, and overall building durability.

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Dogs experience a full range of basic emotions, with sadness being one of them. Your lovely dog, which is usually a ball of energy, seems sullen; the dog is eating, and it is not sick; however, it is just not responding to you normally. If you notice that your dog is sad, it is good to figure out what is making them sad before it affects their overall health. Your dog may only be adjusting to a new environment, or they are bored. While sadness is a normal thing for both humans and dogs to experience, too much of it is detrimental. There are multiple reasons that can cause sadness in dogs, and we will cover each of them below. You will also find helpful information on recognizing sadness in dogs and tips to alleviate your dog’s sadness for the long term. Why Your Dog Is Sad Many of us think that dogs do not get sad because most of the time, they help us get over our bad days. Their constant love shines through to makes us smile, and that is why we need to find what is making them sad and sort it fast! What is making your dog sad could be; - They Are Stressed Or Depressed Life is not all a bed of roses for dogs either; there are points where they get stressed or sadden by events happening around them. When a dog is stressed or depressed, they withdraw and do not engage much with people. Losing their owner or someone they were close to can make dogs sad. Switching homes suddenly to new owners is another reason dogs get sad, especially if they were very attached to the previous owners. One can try to engage the dog to play or take a walk to ease the stress. - New Environment A change of scenery or environment can present a sort of culture shock to your dog. For instance, you move from the quiet suburbs to the noisy city, and your dog is not used to it. The change of environment may sadden the dog because they miss their old home. In this case, just give your dog some time to adjust. - New Diet Your dog’s diet has the power to affect its mood. Suppose the food you feed your dog is low in protein, its chances of developing lethargy and depression increase. Dogs, just like humans, are affected by what is going on in the gut; hence, a high protein diet can help fight this—the better the food, the healthier the dog. Sometimes, your dog’s withdrawal is due to the onset of an illness. One to three days before visible symptoms start appearing; your dog may be sullen or mostly sleepy. It is crucial to observe your dog for other symptoms to have information that can help the vet diagnose the illness. - Displaying Submissiveness Our pets are smart; they usually have a clue when the owner is not happy about something they did. Once you reprimand them, you find that they try to avoid you for a few hours until they are sure you are not mad anymore. In this case, you find that they are more withdrawn and may choose to sit somewhere you cannot see them. Dogs have memory, and when someone mistreats them, it is hard to forget their face. Dogs that get mistreated for a long while tend to be quieter and reserved around people because of fear. When you adopt a dog from the shelter, you might run into this issue as some shelters don’t have good management. - The Season When winter rolls around, it comes with its set of troubles for dogs. Apart from the low temperatures, you find that some dogs also get into low spirits; it is like the weather is making them sad. This is because they cannot go anywhere or do anything outdoors; therefore, boredom reigns sovereign. - Feeling Excluded A new pet in the house is a source of excitement more especially if you have kids around. If your dog has been enjoying attention for years and suddenly a new pet comes, it will sulk for a while. This is because everyone’s attention focuses on the new pet, which leaves the dog feeling excluded. How to Recognize Sadness in Dogs As a pet owner, knowing how to tell when your pet is sad is essential because you want to differentiate sickness from sadness. Common signs of sadness in dogs include: - A reduced appetite; your dog is eating but not as much as usual. - The dog avoids human contact. - Development of compulsive behavior such as continuously licking its paws. - They sleep more than average. Dealing With Sadness in Dogs Now that you know that your dog is sad, what do you do about it? Ask the Professionals It is good to see the vet beforehand to rule out any diseases. If your dog is not cheering up after a few days, then maybe it is something bigger that needs medical attention. When you get to the doctor, and the pooch is not sick, seek a behavioral expert’s advice. The behavioral expert can shed light on why the dog is not responding the way you want them to even though you have identified the source of the issue. No matter how busy life gets, taking your dog for walks or playing is important for their overall wealth. Regular exercise helps boost neurotransmitters like dopamine, serotonin, and endorphins that make the dog feel better. If you do not have the time, you can get your local dog walker to do it. You cannot go outside much during winter, but there are ways to exercise indoors, such as engaging in a tug of war, teaching new tricks, or walking up and down the stairs. Do not let your dog lay idle if you want them to operate at their best at all times. The diet you expose your dog to will affect its general health; instead of feeding your dog food rich in carbohydrates and low protein, select foods rich in protein. You can throw in some veggies, carbohydrates, and fruits, but the main ingredient needs to be a good protein source like beef, chicken, or turkey. If the dog is sad due to a recent loss or traumatizing incident, be more empathetic. Spend more time with your dog by going for walks or playing or training. The extra attention can help direct the dog’s thoughts to happier events. Avoid Frequent Punishments Some dog breeds are naturally naughty, like a labrador or a border collie, but too much punishment can cause a dog to be sad and fearful. Instead of using punishment to rectify bad behavior, use positive reinforcement training. The plan is to reward the dog when it responds to you positively while being sad. This will be a good distraction for the dog as it will chase the sadness away with every reward it gets. Watching your dog be sad is not a comfortable feeling because you want them to be bubbly and cheerful. Whenever you realize your dog is sad all of a sudden, contemplate on what might have happened within that period. This is an excellent way to narrow down the cause of sadness and attend to it. Don’t worry; your dog will not be sad for a long time. If you employ the tips featured above, we are sure your pooch will be back to its full glory in no time.

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Landscaping for Wildlife Why are people interested in landscaping for wildlife? The following report includes some fascinating information you can use. Everyone is responsible for the environment. Individuals can help by making one’s home friendly to wildlife and animals either big or small. Plants draw different kinds of wildlife, different species of birds, butterflies and chipmunks to name a few. You must choose what kind of animals you want to attract to your home. The first thing that the person must realize is that there are four basic things that are needed for wildlife to exist. Trees provide saps or seeds as a source of food for birds. For other creatures that frequent the area, you can accommodate them by having feeders installed in the garden or yard. To know the right type of food to place in the feeder, you should research what the animals eat. All creatures need water to survive. A pond or fountain in the garden can provide sustenance for those who frequent your garden. Just be sure that the water is clean and safe at all times for the animals to drink. Knowledge can give you a real advantage. To make sure you’re fully informed about landscaping for wildlife, keep reading. Animals need a good place to serve as a shelter, nesting and breeding ground. You can make a bird house or purchase one. They are available in many shapes and forms which are good for birds and bats. Once this has been made or purchased, it can be installed in the backyard. Trees planted in the garden can also serve as shelter and housing for creatures that live near your home. A good example is an evergreen tree that serves as protection against predators. Studies have shown that the use of plants that are not natural to the area destroys plants that are native. Since the creatures that you want around all year are native to the surroundings, it is advisable to use plants that these animals are accustomed to. That way, different creatures will be able to co-exist. By focusing on these four factors, you will be able to enjoy the diverse wildlife not just visiting but already living in your area. After the planning and construction phase of the project has been done, you will be able to enjoy the various species of birds, squirrels and other creatures that are native to your geographical area. Those who only know one or two facts about landscaping for wildlife can be confused by misleading information. The best way to help those who are misled is to gently correct them with the truths you’re learning here.

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WHAT ARE STAINLESS STEELS By stainless steels we mean steels resistant to corrosion and having a broad range of mechanical and physical properties linked to their chemical composition. According to EN 10088-1 norms, stainless steels are steels containing at least 10.5 % chromium and maximum 1% carbon. For stainless steels used to reinforce concrete the maximum carbon content allowed is 0.07 %: their high resistance to corrosion stems from the formation of a thin and colourless oxide film (mainly Cr 203) bonded to the steel surface and that makes the material virtually inert to the surrounding aggressive environment. Within the stainless steel family at least four main steels categories exist, on the basis of their crystalline structure (microstructure): - Austenitic stainless steels - Austenitic-ferritic (or duplex) stainless steels - Martensitic stainless steels - Ferritic stainless steels To the iron -carbon alloy (standard steel) , apart from Chromium, other elements such as nickel, molybdenum and titanium are sometimes added. Such elements greatly influence the microstructure, the mechanical properties and the corrosion resistance. Corrosion resistance in particular is increased through carbon content reduction and an increase in the other elements added to the alloy. The first two categories ( austenitic and austenitic – ferritic) are of particular interest for the production of stainless steel rebars. Those categories are often classified according to AISI American norms (American Iron and Steel Institute), Euronorm commercial grades are now commonly used.

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Water is a human necessity, but it is also a systemic and unpriced global challenge with significant economic and societal risks. It is the primary medium through which the effects of climate change will be felt globally through drought, flooding or sea level rise. According to the UN, by 2025, 1.8 billion people are expected to be living in countries or regions with absolute water scarcity and two-thirds of the world population could be under water stress conditions. Corporate water disclosures have long lagged those of carbon and climate, although there are signs that this is beginning to improve, as businesses focus more on water risk and corporate water withdrawals begin to slow down. However, disclosure around water quality issues continues to lag. For example, fewer than 5% of companies polled by the Carbon Disclosure Project (CDP) in 2020 were able to provide evidence of any progress against water pollution targets. This matters, as the annual cost to human health in Europe alone from one group of chemicals alone — per-and polyfluoroalkyl substances (PFAS) commonly known as “forever chemicals,” that are increasingly being found in drinking water — is estimated to be up to €84 billion every year. Water and watersheds also provide critical ecosystems services. Wetlands are major carbon sinks, storing more carbon than most terrestrial ecosystems. We are losing wetlands three times faster than natural forests, with up to 87% of global wetlands lost since 1700 and an 84% decline in freshwater species population sizes since 1970, compared to a 68% decline across all species. Measuring water impact Given this context, Impax has joined forces with Swedish public pension fund Sjunde AP‑fonden (AP7) for a project to investigate how best to assess, measure and report on water impact. The report, which will be published later this year, focuses on the companies providing the solutions and technologies that are critical to solving current and future water challenges. In our report we aim to provide “real-life water impact” insights by assessing the current methods to measure water impact, the gaps and challenges that these methodologies present, and suggest what data is needed to provide decision-useful information for investors. Our research will shape our future water impact reporting to our clients and inform our engagement with our investee companies. The cost of inaction The stakes are certainly high. CDP estimates that the potential financial impact of water risk inaction is more than $300 billion, while the capital required to mitigate the risks is $55 billion. This means that the cost of inaction would be five times higher than the cost of action. Will Sarni of Water Foundry has developed an excellent framework for understanding and visualizing a business-focused water strategy, in which he describes building blocks of water management, stewardship and innovation, with increasing value add and impact at each step. This model is helpful given the context that the most important water innovations and solutions for solving water risks, entail water savings, efficiency and reuse, as well as water treatment, nature-solutions and pollution control. These enable reductions in absolute water withdrawals and improvements in water quality and resilience. OECD projections of global financing needs for water infrastructure range from $6.7 trillion by 2030 to $22.6 trillion by 2050. Classifying water solutions Impax has invested in water solutions for more than two decades, focusing on the following areas: - Water infrastructure – water savings and efficiency - Water treatment – water purification, treatment, testing and recycling - Water utilities – water treatment and distribution services It is a broad and evolving investment universe: Water solution investments span diverse end-markets from consumer to industrials sectors globally, as all economic activities require water. The evolving landscape of water solutions In a rapidly evolving space, data is possibly the fastest moving area. As an example, an interesting recent development was the acquisition of water data company Innovyze by software specialist Autodesk in February 2021. This will allow data modeling and predictive analyses for cost-effective and sustainably designed water distribution networks, water and wastewater treatment plants, and flood protection systems for 3,000 water utility and engineering consultancy customers. This highlights the increasing role of data and software in water solutions. Data is of course crucial to understanding risk and impact. Impax has measured the positive water outputs of our investee water solution companies for six years in our annual Impact Report and have focused on three metrics: water saved, water treated and water provided. Following the project with AP7, we will be enhancing our water impact reporting this year to include water withdrawals and positive water outputs of companies. We are also investigating the opportunity to assess local water contexts to determine “net water impact” more precisely. We look forward to publishing our full research, which will enable us to better assess and measure both the systemic risk and the opportunities that water present. Water is inextricably linked to climate change. It is high time that corporates’ water disclosure caught up with that of carbon.

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Podcast: Play in new window | Download (Duration: 22:16 — 31.0MB) Subscribe: Google Podcasts | Android | RSS | More The history of pasta, ancient and modern, is littered with myths about the origins of manufacturing techniques, of cooking, of recipes, of names, of antecedents. Supporting most of these is a sort of truthiness whereby what matters most is not evidence or facts but – appropriately for us – gut feeling. Combine that with the echo chamber of the internet, and an idea can become true by virtue of repetition. So it is, by and large, for the idea that Arabs were responsible for inventing dried pasta and for introducing it to Sicily, from where it spread to the rest of the peninsula and beyond. You can find versions of this story almost everywhere you look for the history of dried pasta. Anthony Buccini’s gut feeling, however, was that this story was not true. His expertise in historical linguistics and sociolinguistics tells him that the linguistic evidence for an Arab origin gets the whole story backwards; rather, one of the principal elements in the spread of dried pasta through Italy and beyond was the commercial expansion of Genoa. The stuff itself was being made in southern Italy, the Genoese took the word and the stuff to the north and to Catalonia, and it was the Catalonians who took them to the Maghreb and the Arabs. So what did the Arabs do? They wrote it down in their cookbooks. And a bit more besides. - The 2nd Perugia Food Conference Of Places and Tastes: Terroir, Locality, and the Negotiation of Gastro-cultural Boundaries took place from 5–8 June 2014. It was organized by the Food Studies Program of the Umbra Institute. - World Pasta Day falls on 25th October. Enough time to prepare something special? - Banner photograph taken by Su-Lin in Vancouver. Used with permission.

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A WWII era bomb exploded in the United Kingdom’s town of Great Yarmouth. The 250kg bomb exploded unexpectedly, the police said. Army specialists and the police department were working to diffuse the bomb when it was first discovered on Tuesday. The unexploded bomb was discovered by a contractor working near the River Yare located in the English county of Norfolk. The bomb site was covered with sand barriers around the bomb to reduce the risk of detonation to nearby people. The bomb was around 1 meter long and weighed around 250kg. People living nearby were evacuated to safer places as the army tried to cordon the area to about 400 meters. The specialist tried to defuse the bomb by cutting it to let the explosives burn slowly. The police reported that luckily no one was injured. The bomb could have caused more damage if it was not for the army and police specialists to reduce its impact by cutting it. Although a number of car windows were broken including some damage to the flood wall.

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Some of the major components of biodiversity are as follows: i. Ecosystem Diversity ii. Species Diversity iii. Genetic Diversity. Man, Homo sapiens, is the product of bio-diversification. Biodiversity is intimately related to the function and stability of communities and ecosystems. It is of vital importance to humankind from many points of view. It is of economic importance, as it provides the basic material for food, clothing, medicines, housing and major industries such as tourism. It plays a vital role in the pollination of our fruit and cereal crops. It is of scientific importance for protecting and maintaining soils, regulating climate and ensuring photosynthesis. It has intangible values also as shown by the way in which nature inspires painters, poets, and musicians. Many people feel that the variety of living things adds to the quality of life. Biodiversity refers to the variety and variability among living organisms and ecological compliances in which they occur. Major components in biodiversity are ecosystem diversity, species diversity and genetic diversity. i. Ecosystem Diversity: It relates to variety of habitats, biotic communities and ecological processes in the biosphere, and is considered as complex level of diversity. ii. Species Diversity: It is the most common level of diversity, and comprises the number of different species at a place. iii. Genetic Diversity: Refers to total genetic information contained in the genes of individuals of plants, animals and microorganisms. Genetic diversity is comparatively less obvious level of diversity as it represents variations within species. Species diversity is a most common form of diversity as it refers to two different groups of organisms or species. Ecosystem diversity is a complex one and it refers to assemblages of the various forms of diversity in two different ecosystems. No comments yet.

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Early months of the COVID-19 pandemic brought an 18% increase nationwide in substance use overdoses compared with the same months in 2019. A year after the initial outbreak, substance use has continued to increase due to pandemic-related stress including financial instability, job loss, homelessness, and isolation. The Centers for Disease Control and Prevention (CDC) found 13% of Americans reported starting or increasing substance use to cope with stress or emotions related to COVID-19. A WalletHub study examining national drug abuse, rehab, and arrest data scored Missouri with the overall worst drug problem. The study considered 22 metrics and focused on three main data categories: drug use and addiction, law enforcement issues, and drug health issues and rehab. In these areas, Missouri scored 18th in drug use and addiction, 1st in law enforcement issues, and 16th in lack of health support and rehab opportunities. The Pitch KC has a breakdown of the study here. Along with substance use concerns, Missouri has seen a rise in symptoms of anxiety and depressive order in adults. In October 2020, 38.6% of adults in Missouri reported these symptoms compared to 37.7% of adults nationally. These Missouri adults (27.3%) also reported needing counseling or therapy but not receiving it within the last month, compared to the U.S. average (22.5%). As Americans nationwide are desperately searching for mental health services and emotional relief, providers are becoming overwhelmed and are struggling to keep up with demand. The rise of substance use and the opioid epidemic, as well as increased reports of mental health symptoms, are national health concerns. However, these sensitive topics carry stigmas which can interfere with the motivation to seek or receive treatment. Individuals struggling with substance use disorder (SUD) and addiction face negative judgements regarding their circumstance, behavior, or appearance. However, these factors are often a product of or influenced by their struggle with substances. SUD and addiction also cooccur with mental health issues; if someone needs treatment for one, they will likely require treatment for the other. For people who use substances or face mental health issues, harsh judgements or assumptions from family, peers, providers, and others can cause shame and distrust and may prevent someone from seeking help or continuing treatment. Understanding substance use and addiction as a disease, rather than a personal failure, is necessary to breaking down stigmas surrounding substance use in health care. The Toll Substance Use Takes I lost my oldest sister to complications from opioid use seven years ago. Because of the stigma surrounding drug use in our rural hometown and the strains put on our family due to her addiction, I have only just begun to grapple with my grief surrounding her loss. Throughout her hospitalization, hospice stay, and even for years after her death I held animosity towards her for the harm she caused me and our family. I was furious with her for hurting herself and putting our family in danger. I was angry at her for stealing, lying, sneaking around, and taking advantage of our parents’ generosity. I was disheartened by her lack of presence in her children’s lives and disappointed by her seemingly unwillingness to meet her full potential. She had recently returned to school to become a surgical technician; I had never felt prouder of her and more hopeful for her recovery until I discovered a bag of syringes she snuck home from work to use recreationally. My mother, a far more compassionate and spiritual woman, took a different route processing her grief. Throughout my sister’s addiction, our mom played the role of authoritarian, refusing to enable my sister nearly to a restrictive and cold fault. Her desperation to intervene and save my sister meant drawing firm boundaries and learning to say no. She feared every late phone call we received, anxious it would be the call letting us know about an overdose, and refused to play a part in allowing that to happen. Cutting off access to certain resources seemed like an act of love, such as refusing to send money believing it would be spent on drugs and only worsen the problem. To my sister, though, that money was a necessity, even if it was for another dose – especially one to stop painful withdrawal symptoms from settling in. During my sister’s final weeks and after her death, our mother transformed from a confused, frustrated, heartbroken parent to an empowering advocate for addicts and their support systems. She immersed herself in Nar-Anon meetings and programs, the support group counterpart to Narcotics Anonymous (NA) for family and loved ones, and eventually climbed the volunteer ranks to become the head of her local Kansas chapter. Through her advocacy work helping families understand the nature of addiction as a disease and navigate how to show compassion for addicts without perpetuating the problem, I learned how to let go of the anger towards my sister. In one of many back-and-forth trips to the hospice room, I walked in on my mother speaking to my sister in one of her last lucid moments. My mom softly whispered a gentle mantra reminding her that the addict self is not the same as the self and that while one physical body may be perishing, the disease and all its problems would with it. The spiritual being within my sister, the true self, full of personality and light and free of addiction or guilt, would continue in another form. Though spirituality differs between everyone, the recognition of a stark difference between the addict identity and the true identity of a loved one is vital to understanding addiction, breaking down stigma, and supporting those struggling with substance use in their journey to recovery. The Danger of Stigmas The combination of pandemic-related stress, increased substance use, and worsened mental health issues can be fatal. According to the American Psychological Association, those with substance use disorder (SUD) are more likely to develop COVID-19 and experience worse outcomes including higher risk of hospitalization and mortality. The American Medical Association reports SUD as deadly with more than 40 states seeing increases in opioid-related mortality in December 2020. Because these issues co-occur, treatment and recovery must prioritize whole-person care. Stigmas surrounding substance use and mental health often alienate or shame individuals who are struggling rather than motivate them to seek help. Intense negative feelings like shame and guilt often increase the urge to self-medicate as a coping mechanism, furthering the cycle of substance dependence. While navigating relationships of any kind with someone who is struggling with these issues may bring negative interactions and emotions, it’s important to remember that they are also a victim. Part of stigma reduction for those serving as support systems is to seek outlets for these difficult feelings and help navigate changes in relationship dynamics. As someone who has lost a family member to substance use, I constantly questioned why someone would continue to put themselves and others through the pain of addiction and its consequences and eventually assumed it to be personal. Unlearning the stigmas I knew surrounding substance use and addiction, particularly opioid use in my experience, was necessary to my own grieving and healing process as well as eventually assisting others in their recovery. In my experience speaking at outpatient recovery clinics, including First Step in Lawrence, Kansas where my sister was treated, the most common feedback I heard was the lack of support and understanding among family and friends. Addicts often felt ashamed to ask for help because they were raised to be strong enough to never need it, or were taught that substance use, even to a severe extent, was normal and to not be in control was a personal failure to be ashamed of. On weekly visitor nights, families and loved ones would attend meetings to celebrate the addicts’ progress and learn more about addiction and mental health’s toll on an addict as well as their support system. Education and support groups work in tandem to break down how addiction develops, how mental health intersects, how relationships and behaviors change, and how to overcome these challenges to develop new, healthier habits and behaviors. How Does Addiction Develop? According to the Substance Abuse and Mental Health Services Administration (SAMHSA), SUD occurs when recurrent use of alcohol and/or drugs causes clinically significant impairment, including health problems, disability, and failure to meet major responsibilities at work, school, or home. SUD often coexists with mental health issues which can worsen health symptoms and cause challenges in recovery. The Mayo clinic underscores that substance addiction is a disease affecting the brain, and that an addict may continue using a substance despite the harm it causes. Substance use can start with experimental or recreational use in social situations, such as vaping among youth or binge drinking and taking party drugs among young adults in college. Peer pressure or social culture, especially among teens and young adults, contribute to developing SUD. Opioids are often abused after someone obtains them through a prescription, usually for a relative or themselves. People who experience a serious injury and receive opioid painkillers are prone to becoming addicted after prolonged use leads to increased tolerance. Over time, more use means a higher tolerance and increased usage to gain the same effect or any effect at all. Because of this, opioid painkillers have a higher risk and cause addiction more quickly than some other substances. As someone develops SUD, their symptoms make it clear: maintaining the high is the priority. When an addict abruptly stops using a substance, they may become severely ill, lose consciousness, experience seizures, among other withdrawal symptoms. To avoid this, the disease wires the body and brain to prioritize the substance. An addict experiences intense urges and cravings for the feeling of being high or drunk, prioritizes maintaining the substance even if it is unaffordable, and fails to meet social and work obligations because of substance use. People with SUD continue to use despite physical, psychological, or financial issues and may even act out of character such as steal or do other risky activities to obtain the substance. Someone has severe SUD if they fail attempts to stop using and experience withdrawal symptoms when they do. People experiencing problems with substance use may miss school or work or show a drop in their performance and appearance. Physical health problems, besides withdrawal symptoms, include lack of energy or motivation, significant weight loss or gain, red eyes, bruises especially along veins, and poor dental hygiene. Changes in behavior are especially common, including being secretive about their location or belongings, drastic changes in relationships, and money issues including requests for money without explanation, stealing money, or stealing items to pawn. A full list of symptoms and signs of substance use is available here. Everyone Plays a Role in Recovery I vividly remember the night my sister stumbled into our childhood home, speech slurred more than usual. She always looked a bit disheveled, like her makeup had been slept in for a night or two, but her skin was gray and her eyes were glazed far worse than usual. As she tripped into the doorway and out of her shoes, she muttered over and over how cold she was, begging me in barely-English to grab her some socks, eventually melting to the kitchen floor where she began to seize and eventually became unresponsive. Terrified, I hollered for my parents to come. As she was rushed to the hospital, I tearfully scribbled a letter begging her to get clean so I never had to fear losing her again. When I discovered her still using opioids months after an ambitious promise to make good on my request, and especially after continuing to steal from and lie to our family, any fear of losing her became anger and resentment toward her decision to inflict pain. The mistrust created a strain in our relationship that was too difficult to mend before I lost her. Substance use disrupts the dynamic of a support system and can turn anyone into a villain. One of the most dangerous stigmas surrounding addicts, especially due to the behavioral changes, is that they are inherently bad and do these things intentionally. It is crucial to understand that those struggling with SUD are suffering from a disease they cannot overpower, and more importantly, that they cannot change until they are ready. No amount of shaming or guilting an addict about their actions will motivate them to pursue recovery. No one chooses to be an addict, no one wants to be an addict, and anyone can become an addict. Addiction is born from several factors and circumstances and is perpetuated by necessary increased use over time, social pressures, and emotional triggers. It’s no surprise we are seeing increased rates of substance use during a pandemic where so many people are struggling at various intersections of financial instability, emotional stress, and lack of support. Harmful stigmas surrounding addiction prevent people from seeking care, trusting providers, and feeling supported. Addicts often internalize stigmas and blame themselves for their addiction-driven actions and may need help working through these feelings to better understand their disease. The more they feel supported by trustworthy people, the more likely they are to find the motivation to continue seeking recovery. Honest but judgment-free conversations about risks of addiction are necessary while navigating opioid use to work towards preventing substance abuse. Support systems as a whole – providers, family, friends, therapists – have a responsibility to educate themselves about substance use and its consequences to better the chances of intervention, prevention, and reduction of SUD. Recovery Is Not One Size Fits All Substance use recovery often takes a multifaceted approach that combines various methods including guided support programs, such as the 12-step program used in Alcoholics Anonymous (AA) and Narcotics Anonymous (NA), and peer support, such as group counseling meetings, with lifestyle changes. Changes may include healthier eating habits, increased exercise, introduction of new hobbies to replace habits related to substance use, new social environments to replace ones that may have triggers (such as bars), and therapy or other mindfulness work. In some cases, Medication Assisted Treatment (MAT) is necessary. The Health Care Collaborative (HCC) of Rural Missouri and its Live Well Community Health Centers offers a grant-funded Rural Community Opioid Response Program (RCORP) with peer counselors who work locally with support groups including NA, AA, Celebration Recovery, and more. Kayla Schmidt, risk management coordinator for HCC and supervisor of RCORP, said that the peer counselors have the firsthand experience to best help those who are struggling. “I will never be able to understand someone’s story like they do,” she said. “They’re able to get patients resources they need because they’ve walked in their shoes.” Listen to our interview with Kayla Schmidt about the RCORP grant and learn more about the RCORP program. For individuals struggling with substance use or for more information, contact HCC at 660.259.2440 and ask to be transferred to an RCORP peer counselor. Peer counselors can also be contacted directly for support or more information about group counseling; Will Jordan (660.251.3793) oversees NA group meetings and Tamara Lane (660.251.8016) oversees the women’s small group for Celebration Recovery. For immediate or emergency support regarding substance use and mental health, call the SAMHSA 24/7 hotline at 1.800.662.HELP (4357). Recovery is possible. Though I lost my oldest sister to opioid addiction, I watched another sister recover from the same disease to live a happy, healthy, fulfilled life. Through support groups, recovery programs, NA sponsorship, and consistent personal lifestyle changes, I have watched her become a self-sufficient entrepreneur, a loving wife to a supportive partner, and a radiant mother to a healthy baby boy. My oldest sister’s death nearly tore our family apart at times but through understanding her disease and journey and by advocating for others, it has also brought us back together even stronger. Once I and the rest of my family educated ourselves about addiction, found our own support for the frustrations, pain, and mistrust we felt, and showed compassion for the addicts in our lives, recovery became much easier – for everyone.

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As the physiology of synapses began to be explored in the 1950s, it became clear that electrical communication between neurons could not always be explained by chemical transmission. Instead, careful studies pointed to a direct intercellular pathway of current flow and to the anatomical structure that was (eventually) called the gap junction. The mechanism of intercellular current flow was simple compared with chemical transmission, but the consequences of electrical signaling in excitable tissues were not. With the recognition that channels were a means of passive ion movement across membranes, the character and behavior of gap junction channels came under scrutiny. It became evident that these gated channels mediated intercellular transfer of small molecules as well as atomic ions, thereby mediating chemical, as well as electrical, signaling. Members of the responsible protein family in vertebrates—connexins—were cloned and their channels studied by many of the increasingly biophysical techniques that were being applied to other channels. As described here, much of the evolution of the field, from electrical coupling to channel structure–function, has appeared in the pages of the Journal of General Physiology. The mission of the Journal of General Physiology (JGP), as thoughtfully reviewed in previous articles in this series, is to publish research that explores the “basic biological, chemical, or physical mechanisms of broad physiological significance.” Essential to this definition is the meaning of “physiological.” The Physiological Society website cites the Oxford dictionary definition of physiology as “the science of the functions of living organisms and their parts.” This is a forgivable paraphrase of the definition in the actual Oxford English Dictionary (OED), which is “the branch of science that deals with the normal functioning of living organisms and their systems and organs.” Additional insight may be gained by noting the earlier definition of physiology, designated by the OED as obsolete, as “natural philosophy, natural science.” The OED provides a chronological set of examples of published uses of the term in this “obsolete” sense. The most recent is from an article in Science in 1881 that critically examined the research on Torpedo electric organs to inform the contemporaneous controversy between Volta’s “physical” electricity and so-called Galvanic “natural electricity,” arising from living organisms. In that example, the quoted use of “physiology” is: “In order to obtain a thorough comprehension of the electric organs and their action, it is necessary to have recourse to a third science, experimental physiology, to unite anatomy with natural philosophy, and thus make the result of one answer for the other” (Lanza, 1881).1 The quoted sentence makes an essential point regarding the underpinning of JGP. Natural philosophy is the philosophical study of nature—in other words, theory and conceptualization—and “anatomy” can be updated to refer to the physical manifestations of nature, or in the context of the time, aspects of nature that can be seen and/or measured. Thus, the “third science,” physiology, seeks to unite and demand resolution between physical reality and theory. In this light, the special mission of JGP is to explore the basics of both the theory and the reality of living organisms and to demand that they coincide, or at least not contradict. By this definition, physiology and JGP are never purely descriptive of either theory or biology. This article emphasizes the contributions of JGP to understanding the physiology of gap junctions, the signaling they mediate, and the molecular structures responsible in vertebrates (connexin channels). Obviously, much seminal work in these areas was published in other journals. In many instances, a key finding was initially published elsewhere and afterward explored in a more detailed, analytic, and physiologically relevant manner in JGP. This article refers to first reports of seminal findings published in other journals but will focus mainly on the contributions and development of the field in the pages of JGP. As such, it is easy to fail to mention, intentionally or not, key contributions published in other journals, for which I apologize in advance. Particularly for the earlier work, verbatim quotations of key points from the articles are included to convey the perspective of the time. The trajectory of the study of what are now known as “gap junctions” and “connexin channels” in JGP, like that of other topics, evolved in ways unlikely to have been predicted from the early work. The early studies of electrical coupling were inseparable from early studies of neuronal activity and synaptic function, and often were performed by the same investigators. Of necessity, this is a somewhat selective review; broader reviews of gap junction biophysics, physiology, biochemistry, cell biology, and relation to human pathology are available elsewhere (physiology, biophysics, cell biology: Harris, 2001; Bennett and Zukin, 2004; Bukauskas and Verselis, 2004; Harris and Contreras, 2014; Solan and Lampe, 2014; Miller and Pereda, 2017; Bargiello et al., 2018; connexins and disease: García et al., 2016; Belousov et al., 2017; Delmar et al., 2018; Laird and Lampe, 2018; Srinivas et al., 2018). Scholarly works on the role of electrical coupling in the philosophy of nature, particularly as applied to the nervous system, provide insight and perspective (Bennett, 1985, 1997, 2000, 2002). A review of JGP publications in this area reveals three major categories of investigation: (1) gap junctions as mediators of intercellular electrical signaling; (2) gap junctions and connexin channels as mediators of molecular permeability and signaling; and (3) the structure–function of connexin channel gating, modulation, and permeability. Early studies of electrical signaling and intercellular molecular transfer involve invertebrates as well as vertebrates. These are considered together, without distinction, in the sections dealing with the physiology of intercellular signaling, since the key physiological properties are similar. However, in discussion of structure–function aspects, the focus is on channels formed by connexin protein, which is the only protein that forms gap junctions in vertebrates. Connexins are not found in invertebrates, in which gap junctions are formed by innexin proteins, which have no sequence similarity to connexins, and therefore the specifics of structure–function of gating and permeability necessarily differ. Pre-JGP molecular and electrical coupling Direct intercellular current flow was first explicitly proposed by Engelmann in the 1870s on the basis of patterns of excitation in heart tissue following targeted lesions (Engelmann, 1875, 1877). The author stated, “All facts are irresistible to the idea that the excitation process proceeds directly from cell to cell, without mediation of special anatomical elements;” and “muscle cells are by contact physiologically held conductively connected with each other.” These initial observations of intercellular electrical coupling apparently went unnoticed, as neither article is found in the Web of Science citation databases. The 1875 article stresses that the tissue is not an actual syncytium, but only a functional one when healthy; based on the observed patterns of cell death after tissue injury, the article stated, “In consideration of life and death in the collective animal organism one can summarize a fundamental relationship in brief: Cells live together but die individually.” The first experimental evidence for a direct intercellular pathway permeable to molecules came in 1925 as a minor part of the habilitation dissertation of Martha Schmidtmann at the University of Leipzig that investigated differences in intracellular pH in cells and organs using neutral red and bromophenol blue as colorimetric pH reporters (Schmidtmann, 1925). Placement of these dyes inside one cell in an epithelium was followed by rapid spread to other cells. The author noted, “While we are accustomed to regard the cell as a self-contained unit from the histological point of view, the experiment shows us that for certain physiological functions such a separation of the cells does not exist…" and "this rapid distribution of staining over larger cell complexes raises some concern about the cell membrane being an ever-present envelope surrounding the cell on all sides.” This paper also reports that the efficacy of dye coupling (“Farbstoffübergang”) was different in different issues. This first report of dye coupling seems to have been ignored as well. The first firm experimental evidence for direct intercellular current flow was obtained in the early 1950s in studies of action potential propagation in ox heart (Curtis and Travis, 1951). The authors stated, “All the facts presented here indicate clearly that there is a functional protoplasmic continuity between adjacent Purkinje cells, both longitudinally and transversely. One can only conclude then that the cell membrane which appears microscopically to separate adjacent cells is merely a vestige of a true cell membrane.” However, presciently, they went on to say, “A functional protoplasmic continuity need not mean a free exchange of all substances between cells, but merely a relatively low electrical resistance of the membranes at the point of contact between cells.” The next year, Weidmann (1952) showed that the electrical length constant of Purkinje fibers was greater than that of the individual fibers, demonstrating electrical continuity between them. In 1957, Furshpan and Potter (1957) published in Nature what they later referred to as a “preliminary account” of a rectifying intercellular electrical connection at the giant motor synapse of the crayfish. Though indeed a brief report, it made clear that the synaptic signaling they found could not be adequately explained by chemical transmission. In 1958, Watanabe (1958) published what is believed to be the first rigorously demonstrated instance of direct (nonrectifying) electrotonic coupling between neurons. This paper explored the basis of a slow oscillatory potential in the lobster cardiac ganglion that leads to periodic bursting. A series of elegant studies showed clear cell-to-cell propagation of depolarizing and hyperpolarizing potentials between the “large/follower” cells (Fig. 1). The experiments included multiple controls to eliminate possibilities other than intercellular spread of electrical current. “The foregoing results indicate that the potential change observed in the second cell is an electrotonic spread from the first cell,” the authors wrote. “This conclusion suggests the presence of protoplasmic connection among the large cells of the present ganglion.” This work foreshadows one of the themes of electrotonic coupling in neuronal circuits, which is that it can act as a low-pass filter of electrical events (in this paper, the junctions passed slowly changing currents with fidelity but only occasionally were able to transmit fast events such as action potentials), a property largely a function of the time constant of the cell receiving the current. In this system, the slow potentials in the coupled cells arise from coincident chemical synaptic inputs from “small/pacemaker” cells. The author considered whether the pacemaker cells were also electrically coupled to the follower cells. He could not prove this, but provided indirect evidence for it (this coupling would be demonstrated by Watanabe and Bullock 2 years later in JGP; below). The coupling between the follower cells was further explored in a subsequent paper that implemented the first use of voltage-clamp to study electrical coupling (Hagiwara et al., 1959). The frequency dependence of the coupling between the cells was explicitly measured and accurately modeled. The coupling resistance was framed in cellular terms: “The observed protoplasmic resistance of the [intercellular] route corresponds to a fiber diameter of 1–3 µm when the intercellular route is assumed to be a single fiber which runs a linear course between the cells and has a specific resistance of 100 Ω-cm.” This paper also presented, for the first time, I believe, the equation for coupling coefficient (V2/V1, where V1 is the voltage in the “presynaptic” cell and V2 the voltage in the cell coupled to it), expressed as a function of the junctional resistance (Ri), the resistance and capacitance of the nonjunctional membrane of the coupled cell (Rm and Cm, respectively), and time (t) (Fig. 2). This formulation made explicit and quantitative that the degree of coupling depends on the electrical properties of the coupled cell, in addition to the resistance of the coupling pathway itself, and that coupling may be modulated by changes in either parameter. This paper was submitted to the Journal of Neurophysiology in September of 1958 but was not published until a year later, in the September 1959 issue. In the interim, two papers were published extensively characterizing rectifying electrical coupling and its effects on action potential transmission. The lesser known was that of Arvanitaki and Chalazonitis (1959) showing rectifying coupling between neighboring somata in the pleurobranchial ganglion of Aplysia. This report followed up their earlier observation in the same system that showed, by paired intracellular recordings, that spontaneous activity in one neuronal soma led to simultaneous depolarizations or action potentials in a neighboring one (Chalazonitis and Arvanitaki-Chalazonitis, 1958). The 1959 paper performed extensive analyses of the transmission of potentials and in particular the effects of different “presynaptic” stimuli on initiation of action potentials in the coupled cell, and the “synergique” versus “antergique” effects of different spiking patterns in the coupled cells. Particular note was made that the delay between the prejunctional spike and the postjunctional activity was not assignable to a delay in the process of transmission itself, but rather to the delay in the growth of the postsynaptic response (i.e., the charging of the postsynaptic membrane). No threshold for electrical transmission was found. A role for electrical coupling in synchronization of electrical activity in pathological conditions such as epilepsy was suggested. Interestingly, the paper makes a distinction between a “synaptic” connection explicitly analogous to that described by Furshpan and Potter (1957) and a “simple ephapse,” here apparently referring to transmission caused by close membrane apposition only. As in the earlier Furshpan and Potter report, action potentials propagated in one direction only, but hyperpolarizations could transmit in the opposite direction. The more widely known Furshpan and Potter paper (Furshpan and Potter, 1959) came out at virtually the same time, with a detailed characterization of electrotonic coupling at the giant motor synapse of the crayfish, clearly showing rectifying intercellular current spread, in which current flowed in one direction across the intercellular junction and not the other. In addition to evoking puzzlement (e.g., “How does one make an instantaneous current rectifier from cellular materials?”), this paper showed that electrical coupling might be mediated by something other than simple holes in membranes, or rather, that the holes could have interesting properties. None of this work was published in JGP. That would soon change, but first… Matching function to structure Understanding intercellular communication by gap junctions co-evolved in both the physiological and anatomical/cell biological worlds; the gap junction is defined by anatomy, and the ionic and molecular coupling it mediates is a physiological phenomenon. As a result, much of the work to identify the junctional structures that mediate electrical coupling was published in the Journal of Cell Biology (JCB), a sister journal of JGP at Rockefeller University Press. These structural and biochemical studies, and some functional studies, were published in JCB over the same period that JGP was publishing the fundamental studies of electrotonic coupling. Identification of the structures that became known as gap junctions as sites of electrical coupling enabled their purification and biochemical analysis (also largely published in JCB) and eventually to cloning of connexins. As noted above, by the mid-nineteenth century, it was widely accepted that the heart was an electrical syncytium as an explanation for the rapid spread of excitation throughout the tissue, well beyond where nerve fibers could be seen. Light microscopy showed intercalated disk structures, which were presumed to contain a region in which the apposed cell membranes were not intact, allowing intercellular flow of current. Perhaps the first correlation between intercellular current flow and morphology in neurons was in the giant nerve fibers of the crayfish and earthworm. It was known that excitation flowed rapidly and apparently unimpeded down the fibers, but in 1924 and 1926, it was firmly established that the axons were segmental in structure, with clear membranous septa interrupting what had been considered continuous cytoplasm (Johnson, 1924; Stough, 1926). These studies demonstrated the separateness of the segments bounded by septa, showing that degeneration after injury did cross not segmental boundaries, taken as evidence against fusion of adjacent segments. The lipidic nature of the septa was inferred from osmic acid staining. The giant fibers were initially viewed as being able to conduct action potentials in only one direction, but later work by Bullock (1945) showed that in fact the electrical communication across the septa was not rectifying, making two insightful observations about their functional properties: “…recent speculation that many of the apparently fundamental physiological properties of synapses, properties common used in the definition of this entity, are really not inherent in the nature of the junction,” and “the physiological evidence is quite definite that these fibers, which appear to be chains of compound axons separated by macrosynapses, are unpolarized, not only experimentally but in normal functioning. Furthermore, there must be no significant synaptic delay…” (Bullock, 1945). These observations laid the groundwork for first detailed studies of electrotonic coupling in this system (by Dewey and colleagues) and their function (Brink and colleagues), discussed later below. Identification of the structural substrate of electrical and/or dye coupling between cells was made possible by EM, which provided the resolution and sample preparation techniques required to identify and distinguish among different types of intercellular junctions. The first reports got some things right and some things wrong. In a brief report in 1954, followed by a more extensive report in 1958 (Sjöstrand and Andersson, 1954; Sjöstrand et al., 1958), Sjöstrand and colleagues showed in EM studies that the plasma membranes were intact at the intercalated disk: “The plasma membrane at the cell junction appears structurally organized in a similar way as the plasma membrane covering the rest of the cell surface.” Also, “cardiac muscle tissue is subdivided into units representing cell territories without any anastomoses” (Sjöstrand and Andersson, 1954; Sjöstrand et al., 1958). Moreover, they found a space of constant width separating the membranes (70 Å in some animals and 150 Å in others). The only specializations noted were densely osmiophilic zones, likely desmosomes. It was noted that there were filamentous lines crossing the intermembrane space in these so-called S-regions. To reconcile these findings with syncytial spread of excitation, two proposals were made: “A rather free, unsupported speculation is that the S-regions would represent areas with a lower ohmic resistance and would form paths with a greater safety factor for conduction across the cell junction.” An alternative was that, based on a report of metabolic enzymes (succinic hydrolase and alkaline phosphatase) localized at the disk (Bourne, 1953), “considerable metabolic activity…might act as boosters of the contraction wave.” The clear absence of fused plasma membranes in this electrically coupled system was not noted in several subsequent papers on the subject. A few years later, Dewey and Barr (1962) focused on what they termed the “nexus,” defined as a region of membrane fusion between electrically coupled smooth muscle cells, as the site of electrical coupling. EM images were interpreted to show “a true fusion of the outer lamellae of adjacent cell membranes…[which]…implies a lack of extracellular fluid between the cells.” Such structures were proposed to allow a “direct electrical connection between cell interiors without intervening extracellular space.” The mechanism by which membrane fusion would lead to a low resistance current pathway was not addressed. Soon afterward, Bennett et al. (1963) combined electrophysiology with EM of teleost electromotor neurons to similarly point to regions of membrane fusion as sites of coupling. In 1963, structures referred to as “synaptic disks” composed of closely packed, hexagonally arranged hexameric and/or pentameric polygons (periodic spacing of 90 Å) were resolved at goldfish Mauthner cell synaptic regions (Robertson, 1963). These structures were obviously distinct from chemical synapses. It was unclear whether the membranes had fused, but the author wrote that “the evidence is against complete fusion.” In retrospect, these were clear gap junctions, with the first images of what we now know are the component intercellular channels. The hexagonal packing, the hexagonal nature of the particles, and the interparticle spacing turned out to be exactly correct. The first paper in JGP to include EM analysis of gap junctions was an extensive correlative ultrastructural and electrophysiological study of the nexus in frog atrial muscle by Barr et al. (1965). This study used a modified sucrose gap technique (Stämpfli, 1954) to show that propagation between the cells was entirely electrically mediated. In this method, a wide region of nonconducting extracellular medium was imposed along the muscle, blocking action potential propagation across that segment. Action potentials propagated across that segment only when a shunt resistor was placed across it, showing that transmission across the nexal membranes was purely electrical.2 EM of the muscle located the cellular site and structure of the electrical coupling at the nexus. Hyperosmotic solutions caused the nexal membranes to pull apart and the electrical coupling to disappear. The site of the coupling was regarded as a place where “the opposing cell membranes are fused along their outer lamellae.” This article provided an informative overview of the attempts to correlate structure and function of coupling up until that time. The pivotal conundrum regarding the structure mediating electrical coupling was nicely expressed by Dewey (1965) as two alternatives: “electrical transmission across an intercellular gap” or “electrotonic coupling between…cells across a region of contact between cells.” As was soon discovered, it was both—there is an intercellular gap, and the proteins in the two membranes are in contact with each other. The same authors (Barr et al., 1968) later contributed an analogous study of coupling and its structural basis in smooth muscle that doubled down on the fusion of the outer lamellae on the basis that in permanganate-fixed EM material, the width of the nexal junction was less than the sum of the two component plasma membranes. A strong case for specialized EM-identified junctions mediating electrotonic coupling between neurons in a variety of vertebrates was made in 1966 by Pappas and Bennett (1966). These are referred to as “electrotonic junctions” rather than “nexi,” but they are similarly described as sites of fusion of the apposing plasma membranes.3 It was acknowledged that “the nature of the membrane modification that leads to decreased resistivity remains to be determined.” Based on flux of fluorescein across the septa of the crayfish giant axon, the authors suggested that the minimum diameter of the low-resistance pathway between cells was just under ∼10 Å and that the maximum diameter could not be much greater. This turned out to be accurate. Using a different approach in the same year, Weidmann (1966), in an article with a mathematical Appendix by A.F. Hodgkin, came very close to resolving the issue by showing that intracellular radiolabeled K+ diffused freely in the longitudinal direction between heart cells across intercalated disks. Explicit proof that the pathway was the disk was lacking, but the disks were identified as the only regions of contact between the cells that could provide a low-resistance intercellular pathway. In the description of membrane appositions, the paper refrained from referring to them as fused. Much was resolved the next year by Revel and Karnovsky (1967) in detailed EM studies of mouse heart and liver. This work cleanly distinguished the junctions thought to mediate electrotonic transmission from other types of “occluding” junctions (e.g., tight junctions and fused membrane structures). Instead of the membranes being fused at these junctions, they are seen be separated by a ∼20-Å “gap.” The hexagonal packing of hexagonal particles reported by Robertson (1963) was seen, with the same center-to-center spacing. Strikingly, in lanthanum-stained material, “in the center of each particle there appeared to be an electron-dense core 10 Å or less in diameter…it would appear that each subunit is a hollow prism some 50 Å tall.” This may be the first image and physical description of the pore of any membrane channel. The paper ends, “A hexagonal pattern [of particle packing] such as described here may prove to be characteristic of some, but not necessarily all, junctions involved in electrical interconnection between cells.” The term “gap junction” first appears in an abstract by the same authors in the same year (Revel et al., 1967). The definitive structure and characterization of gap junctions were presented by Brightman and Reese (1969) in vertebrate brain and Goodenough and Revel (1970) in mouse liver. These papers provided high-resolution EM images of gap junctions and insightful analysis using various sample preparation and staining techniques. Goodenough and Revel (1970) used the freeze-cleave technique to show the collections of particles (i.e., channels) and corresponding “pits” in the two leaflets of junctional membranes. It summarized the literature correlating observations of electrical coupling with gap junctions: “There is evidence that the gap junction is the site of electrotonic coupling between cells.” These papers were cited in subsequent work that visualized faint Procion Yellow fluorescence within the junctional regions of the crayfish septate axon after extracellular application of the dye (Payton et al., 1969a). This, together with EM images of lanthanum-stained material that showed a network of hexagonal arrays within the septa, inspired the authors to propose that cell-to-cell channels existed through the center of the hexagons, and that the hexagons themselves were closed tubular structures continuous with extracellular space (i.e., filled with lanthanum). An innovative drawing was made of this scheme (Fig. 3). In retrospect, the hexagonal structures are themselves the channels, and the lanthanum stain surrounds them rather than fills them. In any case, this appears to be the first diagram of the fine structure of junctional channels. Exploration of electrical coupling In reviewing the early work on electrical coupling in JGP, as for other aspects of physiology, one is struck by the extent to which investigators explored explanations and contingencies to explain the observed phenomena that one would dismiss out of hand today, but at the time were no less unreasonable than the inferences or conclusions to which they eventually came. These explorations are not discussed here, but make interesting reading. The debut of direct electrical coupling in JGP came in a “Note Added in Proof” in 1959 (Bennett et al., 1959). The paper to which it was appended had pretty much concluded that direct electrical coupling between cells was the most reasonable explanation for the observed and manipulated patterns of excitability among a set of teleost neurons. The note stated, “Recent experiments (Bennett, unpublished) disclose that both hyperpolarization and depolarization of one SMC [supramedullary neuron] may cause polarization in adjacent cells. This potential is of the same sign, but much reduced and slowed, as would be expected from electrotonic conduction. These observations suggest the existence of electrical connections between cells which might be responsible for the synchronization of SMC.”4 The bulk of the work in JGP in the immediately following years grappled with what this direct current pathway meant for spread of excitability and circuit behavior and how it was used to achieve and modulate electrical signal processing. JGP provided a robust forum of exploration of these properties for several decades. The first paper in JGP to explicitly study electrical coupling set this in motion, describing for the first time how electrical coupling was used in generating desired “circuit-level” neuronal behavior (Watanabe and Bullock, 1960). This paper built directly on the previous work by Watanabe (1958) and Hagiwara et al. (1959) on the relation between pacemaker and follower cells in the lobster cardiac ganglion. It documented and characterized the electrotonic coupling between these two cell types suggested in the previous work and showed how this coupling permitted the slow oscillatory voltage changes in the follower cells to be conducted “antidromically” back to the pacemaker cells, where they modulated the firing pattern. The effect of this reciprocal signaling (chemical transmission from pacemaker to follower, and electrical transmission in the reverse direction) was to effectively synchronize and stabilize the pacemaker firing pattern. It also provided a way for follower cells to modulate their own input from pacemaking cells. A key point was that the voltages of the action potentials of the follower cells did not propagate back to the pacemaker cells because of the low-pass filter characteristic of the electrotonic junctions (and because the follower cell somata were electrically inexcitable). Thus the interactions between follower cells and pacemaker cells ensured stable and oscillatory inputs while preventing the action potentials in the follower cells from affecting those inputs. This was the first demonstration that “subthreshold cross-talk” between neurons, not mediated by extracellular field effects, could modulate neural activity. Such subthreshold modulatory influences had been proposed, but not demonstrated, by Gerard (1941) and Bullock (1958). The results are summed up: “Some kind of direct, low resistance pathway for electrotonic spread, discriminating against spikes because of their brevity, is inferred, providing a basis for subthreshold interaction which is specific and not by way of a field effect.” Perhaps reflecting the collegial nature of scientific publishing at the time, this paper also contained a “Note Added in Proof” referring not only to the previous paper by Bennett et al. (1959) but also to even more recent work published in abstract form (Bennett, 1960), thereby recognizing the work of colleagues who had gotten a key result into print a bit earlier, though in abbreviated form. This was followed by a paper in JGP the next year (Watanabe and Grundfest, 1961) studying septal junctions in crayfish giant axons. In this work, extensive electrophysiological studies examined electrotonic spread across the septa and its consequences for spike transmission across them. The paper elaborated several features of the physiology of electrotonic coupling, including differences between transmission of action potentials and of current steps, an apparent synaptic delay, and the effects of polarization across the septa on these properties. The paper extensively tested and validated an equivalent circuit for the system. In a reflection of the historical context of electrotonic coupling, transmission across the septa in this paper was termed “ephaptic.” The term “ephapse” was first used to describe electrical interactions between neurons mediated by close proximity or contact of the cells, but without the morphology or properties of a chemical synapse (Arvanitaki, 1942).5 It was invented to describe electrical interaction between adjacent axons, first shown by Ewald Hering in 1882 (Hering, 1882), and later by Jasper and Monnier (1938) and Katz and Schmitt (1940).6 At the time, the idea of intercellular current flow between cells was most readily understood as arising from close apposition of low-resistance membranes without any specialized structures. In such a configuration, current flowing out through the membrane on one side of the ephapse divides between extracellular leak, via whatever space there is between the membranes, and entry into the closely apposed, low-resistance membrane of the neighboring cell. Some fraction of the current leaving one cell would enter the other, the fraction depending on the relative resistances of the “leak” and “apposed cell” pathways. Efficient coupling required only that the leak resistance be much greater than the resistance of the path across the apposed membrane and any interposed space. In this view, transmission across fused low-resistance membranes would be highly efficient, as there would be no leak. At the time, the potential difficulty posed by membrane conductivity requiring discrete protein channels, and how these channels would function in fused membranes, were below the radar. Initially, ephaptic transmission included transmission across “fused” membranes as well as across a narrow intercellular gap, but usage soon became limited to the latter case. In current usage, the ephaptic transmission includes both the effects of current leaving one cell and passing through extracellular space, however narrow, on its way into the other cell, as well as explicit extracellular field effects. Neither occurs at gap junctions, but at the time, in the absence of evidence for specialized structures, electrotonic transmission was considered to be ephaptic in nature. Ephaptic transmission can of course mediate electrical coupling, and can occur on its own or in conjunction with gap junction–mediated electrotonic coupling (see Veeraraghavan et al. ). Another instance of coupling was explored in JGP by Watanabe and Takeda (1963), who demonstrated high-fidelity electrotonic coupling between the axons of the heart ganglion of the mantis shrimp. Action potentials in one axon always produced action potentials in other axons. They stated, “…the electrical connections among neurons have developed to the extent that the independence of the individual neurons is almost abolished.” These studies localized the site of coupling as axonal–axonal, rather than involving the somata. In 1966, Ito and Hori (1966) published a study in JGP showing strong electrical coupling between blastomeres of amphibian embryos, starting at the first cleavage, and continuing through the morula stage. They showed that “the resistance of the junctional membrane…formed at the former planes of cleavage, is small in relation to that of the cell surface in contact with the exterior.” The ratio of these resistances accounted for the electrical coupling, because the greater portion of injected current would pass from cell to cell rather than exit to the outside of the embryo (the paper demonstrated that the enveloping chorionic membrane did not contribute significant resistance). In recognizing the limits of the study, the authors concisely articulated a key feature of electrotonic coupling, the importance of the ratio of resistances of junctional and nonjunctional membranes: “The difference in the pattern of electrical coupling, as revealed by the method of measuring voltage attenuation, can reflect differences (a) in resistivity of the junctional membranes; (b) in resistance of the nonjunctional membrane surfaces; and (c) differences in shunting by the intercellular medium.” They could not distinguish among these factors and were implicitly agnostic about whether the current pathway between cells involved flux across a (narrow) extracellular junctional space. Shortly afterward, Tanaka and Sasaki (1966) presented a mathematical model of 2-D cardiac muscle and compared its predictions for how potentials were distributed longitudinally, transversely, and within muscle cell fibers to experimental measurements. It had long been known that potentials spread throughout cardiac tissue, but quantitative analysis of the electrical properties, and the contribution of the junctions between the cells (intercalated disks) to this process, had been unresolved. A model with predictive value was generated. To make the measurements needed to validate the model, the authors made substantial technical innovations.7 The model and experimental data were presented in sequential sections headed “Theory” and “Evidence,” in what now appears a quaint distinction. Theory and evidence were in agreement, and additionally, “the resistance per unit area of intercalated disc can be calculated to be approximately 500 to 2,000 times lower than that of the fiber membrane.” In 1966 a seminal paper was published (not in JGP) by Bennett (1966). In addition to providing a comprehensive review of the findings on electrical coupling up to that time, the analysis and principles in the paper essentially defined the physiology of gap junctions and electrotonic coupling. It fully analyzed the equivalent circuits represented by two coupled cells for steady-state and transient presynaptic voltages. For the former, building on the earlier work by Watanabe and Grundfest (1961) in JGP, it presented a rigorous method by which one could analyze electrophysiological data to assess coupling resistance independently of changes in nonjunctional resistances. It described what became known as the “π-t” transform of the equivalent circuit that enabled real-time unambiguous assessment of junctional resistance during current-clamp. This method was used extensively to assess junctional conductance until the application of voltage-clamp techniques in an initial report in 1979 and full reports published in JGP in 1981 (below). The kinetic analysis revealed several nonintuitive insights about the potential for diversity and plasticity of electrical signal transmission. Solutions were derived for presynaptic potentials the shape of action potentials and for various time constants of the postsynaptic cell, with and without the contribution of junctional membrane capacitance. Among the observations were that for electrical synapses there could be significant “synaptic delay,” delay of postsynaptic time to peak, differences in magnitude of peak, and altered relaxation of the postsynaptic voltage, depending on the time course of the presynaptic potential relative to the time constant of the postsynaptic cell and the coupling coefficient (which, as noted above, is a function of both the junctional resistance and the resistance of the postsynaptic cell). In other words, observing the character of the postsynaptic potentials did not allow one to conclude a priori that the transmission was chemical versus electrical. The paper analyzed the effects of a “leaky” junction (essentially an ephapse) and considered whether the junctional membrane can be excitable, how changes in membrane voltage can alter transmission of action potentials, spatial and temporal summation, and how they relate to initiation of a postsynaptic action potential.8 There is also discussion of the various ways that unidirectional coupling might be generated. With the exception of an instantaneously rectifying junction (e.g., Furshpan and Potter, 1959), the analysis presumed that the junctional membrane is “electrically inexcitable in the most rigorous sense” and that the coupling resistance is linear, at least during the time frames of action potentials and typical current injections. Yet, the door is left open for other possibilities: “...it should be emphasized that symmetry is not the same as linearity. The actual potentials produced across junctions when impulses are present on only one side are usually considerably larger and briefer than can be tested experimentally.…Thus, linearity remains unproved in a significant time and voltage range, and either increased or decreased resistance might well occur.” This statement was prescient. Early electrical coupling studies in JGP In 1963, Roger Eckert explored electrical coupling between giant segmental ganglion cells of the leech, with particular attention to the effects of different degrees of coupling on transmission of action potentials and subthreshold potentials (Eckert, 1963). Other early characterizations and analyses of electrical coupling in JGP include those of Bennett in guinea pig smooth muscle (Bennett, 1967) and Kriebel in tunicate heart (Kriebel, 1967, 1968). Shortly after the first report of propagating electrical events in epithelia (Mackie, 1965), active conduction through epithelia was explored in JGP (Mackie and Passano, 1968), although the mechanism of intercellular propagation was not attributed to gap junctions until some years later. The subsequent work on gap junction coupling in excitable epithelia reported in JGP almost exclusively concerned hydrozoan coelenterates (Mackie, 1976; Josephson and Schwab, 1979). Reuss and Finn (1974) performed a detailed study of intercellular and transepithelial current flow pathways in toad urinary bladder epithelium. The epithelial cells were found to be highly coupled, and the resistance of the paracellular pathway to be determined by the tight junctions. Brink and Barr (1977) conducted a detailed and quantitative analysis of the junctional resistance of the septa in the median giant axon of the earthworm and presented a mathematical model of the axon. The conductance of the septal membrane was found to be three orders of magnitude greater than that of the nonjunctional membrane. Based on an estimated unitary conductance (∼100 pS) and morphometry of the septa and channel spacing, the authors calculated a septal conductance much lower than the septal conductance they measured. They suggested that frictional forces in the pore could account for the difference. In a first “pharmacological” test of junctional conductance, the authors applied TEA to the inside of the axons to see whether the intercellular channels were K+ channels (they found no effect). Electrical coupling in physiological function in JGP Each section below describes a role (or proposed role) of electrical coupling in a physiological process and makes a point or two about the properties of gap junctions (in parentheses in the heading). Invertebrate “swallowing” (modulation of electrical coupling by chemical synapses) The physiology of electrical coupling and how it interacts with chemical synapses was explored by Levitan et al. (1970). In the buccal ganglion of the opisthobranch mollusk Navanax inermis (a smaller and prettier cousin of Aplysia californica), the low-pass filter characteristic of electrical coupling was demonstrated using sinusoidal current stimuli and by showing that action potentials were more attenuated than postsynaptic potentials or direct current inputs. Of greater interest was demonstration that large cells that were not connected by chemical synapses were electrically coupled to each other, and also to “interneurons” that provided inhibitory feedback to them via chemical synapses. The effect of the former ensured that the large cells fired synchronously only when receiving simultaneous strong inputs, and the latter provided a delayed inhibitory input to terminate the burst. This coordination of chemical and electrotonic influences was proposed to underlie the rapid, brief pharyngeal expansion that allows the animal to swallow prey whole. The circuitry and the effects of electrotonic coupling in this paper provided the basis for a paradigmatic exemplar of dynamic modulation of electrotonic coupling via chemical synapses (Spira and Bennett, 1972; Spira et al., 1980). Modulation of electrical coupling by chemical synaptic activity is a key component of feeding behavior in Navanax. Efficacy of coupling between motor neurons is controlled by chemical synaptic activity (inhibitory postsynaptic potentials with reversal potential near the resting potential) that increases nonjunctional conductance without significant effect on membrane potential, thereby shunting to extracellular space current that would otherwise cross the gap junctions. Activity of these chemical synapses determines whether the cells tend to fire synchronously or independently. An analogous mechanism is thought to operate in the inferior olive (Llinás et al., 1974) and elsewhere in the central nervous system (Connors, 2017). Cardiac function (sometimes only a few are needed; interplay between action potentials) Aside from the early work by Tanaka and Sasaki (1966), JGP published surprisingly few studies on the role of electrical coupling in cardiac conduction, given its prominent role in that process. In 1970, Freygang and Trautwein (1970) performed an extensive analysis of the frequency-dependent impedance of strands of Purkinje fibers and its role in signal transmission. Much of the quantitative analysis was correct, but the proposed capacitative component to longitudinal conduction was later disproven (Levis, 1981; Levis et al., 1983). See also Lieberman et al. (1975). In 1975, Dehaan and Fozzard (1975) showed that heart cells grown as spherical aggregates were strongly electrically coupled and virtually isopotential, enabling study of their action potentials without the complications caused by the geometrical complexities of the cells in situ. The isopotentiality of the cells in the aggregates, imparted by the gap junctions, enabled the aggregates to be voltage clamped by Nathan and DeHaan (1979) to analyze the currents underlying the action potentials. The voltage control was assessed to have a 12% error in the first several milliseconds of a voltage step pulse and good control thereafter, which precluded detailed study of the role of voltage activated Na+ currents but allowed analysis of slower currents. This system was used by Clapham et al. (1980) to study the development of electrical coupling between aggregates of cardiac cells and its role in the propagation of action potentials between the aggregates. This may be the first assessment of the time course of development of coupling between cardiac cells. The study detailed correlations among electrical coupling, junctional conductance, and latency of action potentials between the two aggregates. The result: “The simple linear relationship between Rc [coupling resistance] and L [latency of action potentials], with no changes in action potential parameters as coupling progressed, suggests that the junctional resistance had a dominant effect in causing action potential delays across the junction in this preparation.” Of particular interest was the finding that a very low degree of coupling was sufficient to synchronize the beats between the aggregates. Synchronization began when the junctional resistance dropped below 20 times that of the input resistance of the aggregate (corresponding to a coupling coefficient less than 0.1). Using a reasonably accurate estimate of the unitary conductance of a gap junction channel (100 pS) and an estimate of the number of cells in initial contact between the aggregates, it was calculated that only five junctional channels per contacting cell would be sufficient to permit synchrony between two 160-µm-diameter aggregates. Relevant to the dominant paradigm at the time regarding cardiac conduction defects, the authors made the point that although "...the mechanisms that underlie conduction disturbances [to date] have generally been sought in terms of altered excitability or membrane parameters,…we have shown…changes in action potential delay resulting purely from alterations in junctional resistance.” In 1994, Rohr and Salzberg (1994) explored, using optical recording of membrane voltages, the propagation of action potentials in cultured neonatal rat heart cells across patterned transitions of different character. The idea was to recapitulate the essentials of impulse propagation across a transition from a narrow to a larger region of tissue (i.e., to a larger current sink), as would occur at the Purkinje fiber-to-ventricle junction and other sites in the heart. Multisite optical recording allowed detailed analysis of the shapes of the propagated action potentials on both sides of the transition, and of the potentials seen after the transition when propagation failed. Though electrical coupling was not directly assessed, its effects were evident in the observed physiology. Key findings were that (a) as the region of increased capacitative load was approached, the upstroke of the incoming action potential flattened out as current that would have maintained its rise flowed into the region of greater membrane area through the junctions, and (b) if an action potential was then initiated on the other side of the transition, current from it flowed back toward the incoming action potential to enhance its (compromised) upstroke; there was “bidirectional electrotonic interaction between the segments separated by the narrowing of the strand.” In more mechanistic terms, “the spatiotemporal evolution of the first phase of the upstroke of successfully propagating impulses is entirely determined by the electrotonic interaction between the activated proximal cell strand and the as yet still well-polarized large distal cell area (i.e.,…imposes a polarizing clamp on the transmembrane potential of the region upstream). Conversely, the second phase,…present only during successful propagation, could be explained by the delayed release of this ‘clamp’ during distal activation, which caused a secondary depolarization, supported by the electrotonic interaction in the upstream direction.” This paper demonstrated the reciprocal effects of gap junction coupling on the shapes and magnitudes of potentials and excitability upstream and downstream of a “source-sink” discontinuity caused by tissue geometry or damage. An interesting and unique investigation of how changes in gap junction coupling affect propagation of cardiac action potentials was published by Verheijck et al. (1998) in which a digital “coupling clamp” provided the intercellular coupling currents to spontaneously active isolated sinoatrial (SA) node cells located and impaled in separate electrophysiology rigs. The digital system monitored the voltage difference between the cells in real time and, for each experimenter-determined “junctional” conductance, calculated the junctional current that would pass between the cells, and deliver it, with opposite sign, to each cell. Various parameters of the action potentials were assessed as functions of the junctional conductance, including their shapes, magnitudes, kinetics, activation delay, and interbeat intervals. A notable finding was that 1:1 action potential synchronization could occur at very low coupling conductances, corresponding to two to three gap junction channels. This was in line with estimates derived from SA cells coupled by real gap junctions. Below this level of junctional conductance, there was clear evidence of “subthreshold” depolarizations that tended to have a phase-resetting effect on firing. This produced a mutual entrainment of excitability, which increased with increasing junctional conductance until synchrony was attained. It was noted that when frequency entrainment was achieved, the action potentials in the cells could still have somewhat different waveforms. This was caused by current flow between the cells during the diastolic interval—the time between the most negative value of the membrane potential and on the upstroke of the next action potential. During this time, coupling current leaves the cell with the decreasing potential, compromising its own depolarization, and increasing the depolarization of the other cell, distorting the voltage waveforms in both cells (analogous to the findings above in Rohr and Salzberg ). As junctional conductance is increased, the efficiency of the transfer and coordination of the waveforms increases; both frequency and waveform were identical when junctional conductance was an order of magnitude greater than the minimum required for action potential synchronization. The summative finds were that “at low Gc [coupling conductance] mutual pacemaker synchronization results mainly from the phase-resetting effects of the action potential of one cell on the depolarization phase of the other. At high Gc, the tonic, diastolic interaction prevails [due to the increased efficiency of current flow between the cells].” This study reasonably presumed that the junctional conductance was ohmic and did not change during the voltage transients. Through the work of Veenstra and colleagues, we know that this is not the case (Lin et al., 2003, 2005; Lin and Veenstra, 2004). It was shown for two cardiac connexins (Cx43 and Cx40) that there can be substantial reductions in junctional conductance during cardiac action potentials, because of the voltage sensitivity of the connexins involved. Cx45 is the dominant connexin expressed in the human SA node, and it is more voltage sensitive than Cx43. It remains to be seen whether in the SA node the junctional conductance decreases during action potentials, and the effect that would have on spike propagation. Invertebrate vision (first indication of voltage sensitivity of coupling) JGP has a strong record of publications in invertebrate visual physiology and especially on the photoreceptors of Limulus polyphemus. The first report in JGP of electrical coupling in a visual system was an abstract presented at the 1967 Society of General Physiologists meeting on Sensory Processes in Woods Hole, Massachusetts (Shaw, 1967). In 1972, Nolte and Brown (1972) published a study on the Limulus median ocellus. They showed that this primitive eye contained two types of photoreceptors, one sensitive to green light and the other to UV light. The latter were found to be electrically coupled to each other and to a second-order neuron. The study focused on the differences between these photoreceptors and their functional organization relative to the Limulus lateral eye. No particular inferences were drawn regarding the role of the coupling in visual processing. However, this work demonstrated that the UV-sensitive photoreceptors, like those of the retinular cells of the Limulus lateral eye, responded to strong hyperpolarization with an active process termed a “hyperpolarizing response.” With maintained constant hyperpolarizing current, the cell became more hyperpolarized, while in parallel the voltage in the cells coupled to it decreased. This uncoupling phenomenon had been observed and explored extensively in the Limulus lateral eye and attributed to a hyperpolarization-driven decrease in junctional conductance and the consequent increase in input resistance of the stimulated cell (Smith et al., 1965; Smith and Baumann, 1969). This “hyperpolarizing response” is the earliest example of a voltage-dependent junctional conductance, and this article in 1972 its first mention in JGP. More about this later. Taste (capacitance and coupling) The physiology of taste has also been prominent in JGP. Electrotonic coupling was examined in the taste buds of the mudpuppy Necturus maculosus (West and Bernard, 1978). In this initial report, the coupling was described as unsurprising and there was little speculation on its functional effect. Years later, Bigiani and Roper published two papers that used voltage clamp to explore electrotonic coupling in taste receptor cells in N. maculosus, using coordinate changes in membrane capacitance and input resistance to assess the degree of coupling (Bigiani and Roper, 1993, 1995). This method of assessing coupling among groups of cells had been worked out by Santos-Sacchi (1991) a few years earlier. The electrical measurements were complemented by dye-coupling studies using Lucifer yellow and validated by treating the tissue with 1-octanol, which decreases gap junction coupling. The measurements were incorporated into a model of the coupling network used to estimate junctional resistance. It was noted that, in this system, membrane capacitance was a more sensitive reporter of junctional coupling than was input conductance or degree of detectible dye coupling. It was speculated that the coupling favored synchronous activity and integration of subthreshold receptor potentials. Modeling suggested that the median level of junctional resistance fell on the steep part of the curve relating it to degree of coupling, so that relatively small changes in junctional resistance would have large effects on the intercellular spread of potentials. Parturition (hormonal regulation of gap junctions) Sims et al. (1982) performed a rigorous and comprehensive study of the basis of development of synchronous activity of uterine smooth muscle at the end of pregnancy. During most of gestation, uterine smooth muscle, although reasonably well coupled, does not exhibit notable synchronous activity. As birth approaches, the activity becomes highly synchronous to facilitate delivery. This study performed detailed electrophysiological studies (assessing membrane potential, length constant, and internal resistance) and longitudinal frequency-dependent impedance studies of rat uterine muscle before, during, and after delivery, in addition to EM. The authors were able to separate out changes in junctional, myoplasmic, and membrane resistances. The results showed that the myoplasmic resistance remained constant throughout, but that the junctional resistance decreased ∼60% leading up to delivery, along with a ∼50% increase in nonjunctional membrane resistance (each of these changes enhances coupling). The changes reversed after delivery. The decreased junctional resistance correlated with a dramatic up-regulation in morphological gap junctions and the expected changes in length constant. The authors were somewhat skeptical about whether gap junctions were the sole mechanism for electrical coupling, largely because of negative EM findings in some coupled tissues. However, they were convinced of the role of gap junctions in this particular instance, stating: “Whether gap junctions are necessary for cell coupling is a subject of debate, but available evidence including results described in this investigation suggests that the junctions are sufficient for coupling.…These data support, but do not prove, our hypothesis that gap junction formation causes an improvement in electrical coupling in parturient myometrium.” Exocrine gland function (amplifying the effects of chemical synapses) The role of electrical coupling in activation of an invertebrate salivary gland was explored by Senseman et al. (1983) using multisite optical recordings. The innervation of the salivary gland in the snail Helisoma trivolvis is such that action potentials are stimulated in only some cells in the gland, and in a variable manner. Electrical coupling within the gland had been demonstrated by others (Kater et al., 1978), but this study examined the interplay between chemical synaptic input and electrotonic coupling in the spread of excitation. By analyzing the spread of activity at multiple positions after stimulation, it was evident that action potential initiation in distal gland regions was propagated via electrotonic transmission rather than by direct chemical stimulation. The electrotonic transmission was essential for the gland to be fully activated; in only one of more than 100 trials did full activation not involve electrotonic transmission. Vertebrate vision (diverse modulatory influences and functional properties) By the mid-1980s, it was known that the central visual receptive fields of bipolar cells in teleost and amphibian retinas were much larger than could be accounted for by their dendritic field diameters and direct synaptic connections to photoreceptors. In 1986, Kujiraoka and Saito (1986) showed in Proceedings of the National Academy of Sciences (PNAS) that carp bipolar cells were electrically coupled to each other. In 1988, they expanded on this work in JGP, showing that this coupling enabled spatial summation of the inputs to the cells and that this contributed to the enhanced central visual field (Saito and Kujiraoka, 1988). They further showed that bipolar cells separated by as much as 130 µm could be electrically coupled, and that the coupling was only within each category of bipolar cells (ON and OFF cells) and not between them. Of note, the electrically coupled cells were not dye-coupled using Lucifer yellow. In the paper it was speculated that this was because of a detection issue (e.g., low number of junctional channels), but we know now that impermeability to larger dyes such as Lucifer yellow is characteristic of the particular connexin expressed in these cells (Cx35 or its murine orthologue Cx36). Kamermans et al. (1989a,b) conducted extensive studies to understand the determinants of the lateral feedback from horizontal cells back to the red- and the green-sensitive cones from which they receive their synaptic input. As for the bipolar cells above, it was known that electrical coupling among cone-driven horizontal cells was responsible for their receptive fields being larger than their dendritic fields. Furthermore, it was known that the coupling resistance between them could be modified by background illumination and various neurotransmitters. This study sought to characterize the changes in receptive field of the horizontal cells that occurred as functions of wavelength, spot size, intensity, and light and dark adaptation and identify the responsible mechanisms. The conclusion from the study and modeling was that the synaptic inputs from the cones modulated the electrical coupling among the horizontal cells by decreasing the membrane resistance, thereby decreasing the electrical coupling. This and other aspects of the circuitry explained the findings. This modulation of coupling by chemical synapse activity is functionally similar to that described above, under “swallowing.” Turning to rod-driven horizontal cells, Qian and Ripps (1992) investigated whether the receptive fields of cone-driven horizontal cells were modulated by background light and transmitters in the same way as were rod-driven horizontal cells, using the all-rod retinas of the skate. They found that indeed the rod-driven horizontal cells were coupled, but that the coupling and receptive fields were strikingly unaffected by background illumination or exposure to the wide variety of transmitters and pharmacological agents to which the coupling of cone-driven horizontal cells in retinas of a variety of other species were highly sensitive. The basis for this difference is still unknown, but the results show that modulatory sensitivities of gap junctions, and their functional effects, may differ, even within the same tissue. Lens circulation (circulation of water and ions) Much of what is known about the physiology of lens comes from the studies of Mathias and collaborators published in JGP. In 1991, they showed that the cells of the lens were extensively coupled, but that the character and modulatory sensitivities of the coupling differed with depth within the tissue (Mathias et al., 1991). Progressing from the periphery to the deeper layers, lens cells have somewhat lower junctional conductance and become insensitive to decreases in pH. The intracellular pH of the deeper cells was more acidic than that of the peripheral cells. Because ion transport out of the lens, including that of H+, occurs exclusively at the surface, it was proposed that the only way for H+ to be transported out of the deeper cells is via a circulating current that brings it to the surface cells through gap junctions. Like most gap junctions, those of the surface cells are inhibited by acidification, but for the H+ to circulate to the surface there must be a concentration gradient of H+, which required that the inner cells have a lower pH. For the system to work, the gap junctions of the inner cells must be relatively insensitive to pH, which was observed. It was postulated that the elimination of their pH sensitivity was caused by a modification of the gap junctions, with aging and/or position. The basis of these differences was presented in 2001, after identification of the two connexins involved and study of the lenses of corresponding knockout animals (Baldo et al., 2001). In the peripheral layers, coupling was partially reduced by knockout of either Cx46 or Cx50, suggesting that both connexins contribute to the coupling in that region. In the Cx50 knockout, the junctions in the deeper layers were pH insensitive, as in wild type, suggesting that Cx50 did not contribute to pH insensitivity in that region. It was inferred that Cx50 imparted pH sensitivity to the peripheral layers and Cx46 imparted pH insensitivity to the deeper layers. Knockout of either connexin caused cataracts of different types. In spite of the clear and satisfying results of this study, there was a conundrum: When exogenously expressed in oocytes, Cx46 junctions are sensitive to pH (White et al., 1994b), in contrast to the pH insensitivity of Cx46 in the deeper layers of the lens. We now know that at the transition between the peripheral and deeper layers, the C termini of both connexins are cleaved by calpain (Kistler and Bullivant, 1987; Lin et al., 1997). It was proposed that deletion of this domain of Cx46, thought to mediate the pH sensitivity, might render the channels pH insensitive. It was later shown that truncation of Cx46 did not actually eliminate the sensitivity but shifted the pKa 0.2 units in the acidic direction, from 6.8 to 6.6 (Eckert, 2002). Truncation of Cx50 dramatically down-regulates its channel activity (DeRosa et al., 2006), consistent with its minimal contribution to coupling in the deep layers of the lens. In 2004, the notion of a circulation system in the lens, which allowed metabolic products generated in the deeper layers to exit the tissue, was explored in the context of Ca2+ regulation (Gao et al., 2004). It was suspected that elevated Ca2+ levels facilitated development of cataracts via activation of a Ca2+-dependent protease that cleaved crystallins, which then aggregated. As for H+ and other ions, transport out of the lens is mediated only by transporters in the cells at the surface, so a circulatory system would be essential. Using wild-type, Cx46 knockout, and Cx46-for-Cx50 knock-in lenses, intracellular Ca2+ was assessed using FURA2 at calibrated depths, and the Ca2+ levels and gradients were correlated with previously published studies of gap junction coupling conductances for the wild-type and knock-in mice. The findings supported the role of connexin coupling on the circulation of Ca2+ that established its proper homeostasis in the lens. Because of the knock-in lenses having greater coupling conductances than wild-type, the Ca2+ levels increased less steeply with depth than in wild-type. The Cx46 knockout lenses had dramatically increased Ca2+ at all levels. The increased coupling in the knock-in provided support for the idea that in wild-type lenses, the Cx50 was essentially nonfunctional in the deeper layers, a consequence of its C-terminal cleavage. The role of connexins in lens physiology was elevated to a greater level of sophistication in work that explored the basis of volume flow in the lens circulatory system (Gao et al., 2011). This paper addressed a fundamental mechanism by which stratified epithelia can transport fluid. The ionic circulatory system described above was suspected to drive fluid movement as well as ion movement, and there was some supportive evidence. Previous work had established that the ionic circulation from the interior to the surface (driven by Na+/K+ ATPase at the surface) involved movement through gap junctions. If the water and the ions moved together, then the outward movement must be driven by hydrostatic rather than osmotic pressure. The experiments asked whether there is a such a pressure and whether the outward fluid flow is through gap junctions. An intracellular microelectrode-based manometer was devised, and hydrostatic pressure was measured as a function of depth from the surface in wild-type lenses and lenses from a heterozygous Cx46 knockout and the Cx46-for-Cx50 knock-in. There was indeed substantial hydrostatic pressure at the center of the lenses, which declined toward the surface. In the mutant lenses, the pressure profiles changed in accordance with the levels of coupling conductance—with greater conductance, the pressure was less, and with less conductance, the pressure was greater. Reduction of the Na+/K+ pumping capacity at the surface dropped the pressure, showing that the energy reflected by the hydrostatic pressure was ultimately provided by the Na+ circulation. On the basis of size and charge criteria, there is every reason to think that water can permeate gap junction channels and no reason to think otherwise (all-atom molecular dynamics simulations of connexin pores show freely mobile water; see Luo et al. ). In fact, early modeling of the effects of steady-state junctional currents on ion accumulation could not reproduce experimental results without incorporating water flux through the junctional channels as well (Brink et al., 1988). Overall, the demonstration that the transport properties and organization of a tissue can generate hydrostatic pressure that drives intercellular water flux through gap junctions is a fundamental insight with potential application to any fluid-transporting tissue. This gap junction–mediated circulation of water and ions, its modulation, and the role of cataract formation continue to be explored and their importance extended (Gao et al., 2015, 2018). Swimming (different strokes) Synaptic analysis, dye coupling, electrophysiology, and physiological stimulation in vertebrate skeletal muscle were integrated to show how electrical coupling was used (and not used) to generate swimming behavior in zebrafish larvae (Luna and Brehm, 2006). Luna and Brehm initially characterized the differences in electrotonic coupling in fast and slow muscle by application of sinusoidal stimuli over a range of frequencies, complemented by dye-coupling studies. They found a low degree of coupling in fast muscle and much greater coupling in slow muscle, and they defined the low-pass filtering characteristics of each. Building on this information, they were able to kinetically distinguish primary synaptic PSPs from electrotonically transmitted events in each type of muscle. To control for possible error in voltage clamp resulting from the coupling in the slow muscles, they compared the time courses of the clamped currents with those of extracellular field potentials. They confirmed that what they had identified as electrotonically transmitted transients were specifically eliminated by a gap junction inhibitor, and that they did not generate detectible extracellular field potentials. Further studies defined the size of coupled networks in both muscle types. To understand how the electrotonic spread of PSP-generated currents played out in swimming, they used a mutant strain of zebrafish (relaxed) in which muscle contraction did not occur, but in which neuronal patterns of fictive swimming could be induced by photic stimulation. The synaptic and electrotonic activity in the muscle was characterized with and without the gap junction inhibitor. Control studies with formamide-paralyzed WT larvae were also performed. Detailed analysis showed that the highly coupled low-pass filter property of the coupling in slow muscle (1) allowed effective but slowed transmission of potentials from PSPs, allowing temporal integration of depolarizations/contractions with a segment, and (2) imparted a fixed delay in transmission between segments to define the rostral-caudal wave of depolarizations/contractions that produces undulatory swimming. This is a rigorous and insightful example of how exploration of the temporal and spatial dynamics of electrical coupling can inform the mechanism of a physiological behavior. Pre-cloning physiology of gap junctions This section summarizes the early work, mostly in JGP, (1) revealing that junctional coupling is a modifiable cellular property, and (2) providing indications of what could move between coupled cells through the junctions. It includes studies of invertebrate junctions, which are formed by innexin, not connexin, proteins. Although the specifics of modulation and permeability differ, these fundamental properties overlap. Initial work addressed changes in coupling in response to manipulations of the extracellular and intracellular milieu, using the salivary gland of Chironomus thummi (Loewenstein et al., 1967). It was found that extracellular Ca2+ chelators, pH 10, trypsin, or hypertonic media caused rapid uncoupling, with only the effect of high pH being reversible. Iontophoretic injection of Ca2+ also uncoupled the cells. Injury of a cell in the presence of millimolar Ca2+ caused the input resistance of the cell coupled to it to rise (suggesting an “uncoupling” action of the junctional membrane thus exposed to high Ca2+), but this did not occur in nominally Ca2+-free medium. The latter two studies suggested that the junctional membrane conductance was reduced by high Ca2+ levels. In much of this work, it was difficult to discern whether the changes in coupling were caused by direct effects of the manipulations on the junctional membrane or were downstream of cellular responses to the manipulations. Exploration of regulation of Chironomus gap junctions by cytosolic Ca2+ was pursued in other journals, using aequorin imaging combined with focal Ca2+ injections (Rose and Loewenstein, 1975, 1976). In what may be the first “biophysical” study of electrical coupling, Payton et al. (1969b) examined the temperature dependence of junctional conductance in the crayfish septate giant axon. Low-chloride solutions had been shown to reversibly uncouple the cells and separate the septal membranes. This led to the somewhat dubious conjecture that the cell movements that pulled septal membranes apart might be eliminated by cooling. The effects of cooling and rate of temperature change on the relevant conductances, as well as septate membrane separation, were examined (the motivating low-chloride experiments seem to have been forgotten). With cooling over a 15°C range, junctional resistance increased with average Q10 of 3.1, whereas the nonjunctional resistance increased with Q10 close to that of aqueous diffusion. These changes were readily reversible, showed little hysteresis, and were not accompanied by any detectible separation of the septal membranes as assessed by EM. The authors speculated that cooling changed a feature of the septal membrane structure not visible by EM, causing it to revert to the high-resistance state of nonjunctional membrane. There was no comment on the implications of a Q10 in the range of 3.0. The junctions are described as “tight junctions,” but a “Note Added in Proof” confirmed that they were gap junctions as described by Revel and Karnovsky (1967) and Brightman and Reese (1969).9 The temperature dependence of junctional conductance has not been significantly pursued. A 1980 abstract showed a low Q10 for the conductance between blastomeres in the absence of junctional voltage but a substantial Q10 for voltage-dependent transitions (Harris et al., 1980). A study at the single-channel level using embryonic cardiac cells showed multiple unitary conductance levels (substates) with occupancies with different temperature dependencies (Chen and DeHaan, 1993). Turin and Warner (1977) were the first to show regulation of gap junctions by pH, using Xenopus laevis blastomeres. Electrical coupling was shown to be a reversible function of intracellular pH (pHi), assessed by an intracellular pH electrode. Injection of Ca2+ up to micromolar levels had no effect. It was suggested that in the earlier studies increased Ca2+ levels may have been accompanied by a drop in pHi, as had been seen in other cellular systems. This initial report was followed by more detailed studies of pH regulation and the relative influence of Ca2+, sometimes coming to different conclusions in different systems (Rose and Rick, 1978; Turin and Warner, 1980; Spray et al., 1981b, 1982). After these early studies, study of regulation of junctional coupling by cytosolic pH and Ca2+ moved largely to other journals and focused on specific tissues and connexins. In 1990, it was addressed in JGP by White et al. (1990) in ventricular myocytes, with an answer that might have been anticipated: both pH and Ca2+ can be involved. Using electrophysiology of paired myocytes, Fura-2 imaging, and manipulations of intracellular pH and Ca2+, the results showed that decreases in pHi or increases in intracellular Ca2+ alone did not reduce junctional conductance. There must be at least normal intracellular Ca2+ levels for decreases in pHi to reduce the conductance, and there must be acidic pHi for increases in intracellular Ca2+ to do so; thus, Ca2+ and H+ act synergistically. However, the relations are such that in a normal extracellular milieu, a drop in pHi will decrease junctional conductance, but increased intracellular Ca2+ in the absence of decreased pHi will not. As noted above, the first suggestion of voltage sensitivity of junctional conductance was reported in 1965 by Smith et al. (1965) in the ommatidium of the Limulus lateral eye. This paper showed that with hyperpolarizing current pulses delivered to a retinular cell, its input resistance increased as the electrotonic coupling to the eccentric cell decreased. Both changes are most simply explained by an increase in junctional resistance. The phenomenon was more fully analyzed by Smith and Baumann (1969), who showed that the same phenomenon occurred symmetrically between retinular cells: “...the coupling is a function of the potential difference across the junction, and uncoupling by appropriate adjustment of the junctional potential difference is quite reversible.” The same regenerative hyperpolarization in stimulated retinular cells was studied by Wasserman (1968), but without looking at the coupling. Instead, he focused on the observation that “steady current holds the cell in one of two stable states, depending on current strength.” Brief stimuli of opposite polarity could trigger a cell into either state, defined by a stable difference in membrane potential. As a result of not examining changes in coupling, the mechanism for the increased resistance is mistakenly attributed to nonjunctional voltage dependencies. The bistability of membrane potential of a cell coupled to neighbors by a voltage-dependent junctional conductance was recapitulated, by experiment and computation, in later studies based on the kinetics of junctional voltage dependence (Harris et al., 1983). These early indications of voltage-dependent junctional conductance went unnoticed until ∼10 yr later when the phenomenon was rediscovered by Spray et al. (1979) (Fig. 4, upper panels). Using current clamp, they showed that Ambystoma mexicanum, X. laevis, and Rana pipiens blastomeres uncoupled during hyperpolarizing or depolarizing current pulses, essentially reproducing the traces shown by Smith and Baumann (1969). The electrical uncoupling correlated with loss of Lucifer yellow spread between the cells. Two coupled cells were individually voltage clamped so that junctional currents could be directly observed and analyzed as functions of junctional voltage. This report included the first direct measurements of junctional currents and set the stage for study of junctional conductance using the electrophysiological tools being applied to other membrane conductances. The first full characterization of voltage-dependent junctional currents was in back-to-back papers in JGP (Fig. 4, lower panels; Harris et al., 1981; Spray et al., 1981a). These papers showed that nearly all of the junctional conductance was steeply voltage dependent, with a small voltage-insensitive component. The conductance was insensitive to the voltage across each plasma membrane, responding only to differences in voltage across the junctional membrane. The relaxations were voltage dependent and apparently first order. The steady-state and kinetic effects were analyzed using the Boltzmann distribution and standard rate theory, drawing explicitly on the analysis applied to excitability-inducing material10 (EIM) conductances in bilayers published in JGP by Ehrenstein and colleagues (Ehrenstein et al., 1970, 1974; Ehrenstein and Lecar, 1977). For each polarity of voltage, the relations among voltage, time constant, and steady-state conductance were well modeled by a reversible two-state reaction scheme. The data suggested that each oppositely oriented hemichannel contained a gating mechanism sensitive to one polarity of junctional voltage. The operation of the two voltage-sensitive gates in series seemed to be contingent on one another, perhaps via modulation of the voltage profile within the pore, whereby a “closed” gate reduces the portion of the junctional voltage that drops across the sensor of the other gate. These studies established the vocabulary and basis for the analysis and description of junctional voltage dependence that are still in use, although often in more complex form. To account for non-ephaptic electrical coupling, it was presumed that the junctions were highly permeable to small, mobile intracellular ions. Movement of molecules directly between cells was apparently not investigated after the work of Schmidtmann in the 1920s until Kanno and Loewenstein (1964) showed that Drosophila melanogaster epithelial cell junctions mediated intercellular diffusion of fluorescein. This initial report was followed by a more detailed study in JCB (Loewenstein and Kanno, 1964). The observation that the “impalability” of cultured chick heart cells (the ability to survive being impaled by a microelectrode) correlated with degree of electrical coupling inspired DeHaan and Gottlieb (1968) to make a prescient speculation in JGP: that electrical coupling allowed cells to replace the ions lost during impalement by diffusion through the intercellular coupling pathway from its neighbors. The paper stated that “those neighboring cells might serve as a source of current and of intracellular ions which would tend to maintain the resting potential of the impaled cell.” They continued, “The adjoining cells might also serve as a source of other substances which could hasten membrane repair or synthesis.” This is an assertion of what would later be called “metabolic cooperation” mediated by gap junctions, and may be the first suggestion in print, inferred from experiment, that gap junctions may have roles other than intercellular spread of electrical potential. As noted above, Pappas and Bennett (1966) showed that fluorescein freely traversed the septate junctions of the crayfish giant axon. However, there was concern that fluorescein might also cross nonjunctional membranes, so studies were performed using Procion Yellow, which is slightly larger, known to not cross cell membranes, and could be imaged by EM after tissue fixation (Payton et al., 1969a). Using the septate giant axon of crayfish, junctional transfer of Procion Yellow was seen, and control studies confirmed absence of its permeation of nonjunctional membrane. A footnote refers to studies showing that sucrose permeates the junctions, but this work apparently remained unpublished except in abstract form (Bennett and Dunham, 1970). It would be the first report of a specific biological molecule permeating an electrotonic junction. In 1972, Gilula et al. (1972) demonstrated that gap junctions enabled intercellular transfer of biological molecules and that this transfer could have functional effects. The phenomenon of “metabolic cooperation” had been described previously as dependent on cell contact, but this paper firmly established that, in the cells studied, it occurred only when cells were coupled electrically and morphologically by gap junctions. Donor cells with functional hypoxanthine-guanine phosphoribosyl transferase (HGPRT), which converts hypoxanthine to inosine monophosphate, were co-cultured with each of two types of HGPRT-negative cells, one of which was able to form electrical and morphological gap junctions with the donor cells and one that was unable to do so, in the presence of radiolabeled hypoxanthine. Only the former showed radiolabeling of its nuclei when cultured with the donor cells. Neither of the HGPRT-negative cells were radiolabeled when cultured without the donor cells. This was definitive evidence that gap junctions could mediate both electrical coupling and metabolic cooperation. As part of the Brink and Barr (1977) study of the septa of the earthworm giant axon, they showed that fluorescein and TEA permeated the junctions. The evidence for TEA permeation was that it significantly lengthened action potential durations on the noninjected side, thereby showing a functional effect on the K+ channels of the axon. That fluorescein and TEA have opposite charge suggested that the junctional pathway was not highly charge selective, even among large permeants. This work was expanded the next year in a combined freeze-cleave EM and quantitative dye-flux study of fluorescein derivatives of increasing size across the septal junctions (Brink and Dewey, 1978). The septal permeability decreased linearly with molecular weight over the range of 333 D (fluorescein) to 652 D (tetrabromofluorescein). Extensive controls and modeling were used to deal with cytosolic binding and potential technical and analytical confounders. The limiting dimensions of the probes ranged from 9 to 13 Å. Based on the “channel” surface area seen in freeze-cleave images, the specific resistance of junctional channels was calculated to be 50-fold greater than cytoplasm. The only negatively charged dye was aminofluorescein, which was less permeable than the cationic dyes, suggesting some degree of charge selectivity. It’s a channel For much of the 1960s, the existence of membrane channels, probably composed of protein, was largely theoretical but nevertheless widely accepted.11 By the early 1980s, it was dogma that ionic permeability of membranes was conferred by proteins that formed “aqueous” pathways through which ions could move from one side to the other. No channel proteins had been yet cloned, but single-channel recordings from cells had been obtained in 1976 by Neher and Sakmann (1976); as noted above, single-channel recordings had been seen in planar bilayers since 1969. As understanding of mechanisms of membrane permeability evolved, it was recognized that the pathway for current flow between cells was most likely a channel of some sort. This raised the question of what sort of channels they were. Were they similar to those thought to mediate action potentials, only spanning two membranes instead of one? They would have to be permeable to molecules at least the size of fluorescein, unlike other known channels. Furthermore, could they be “gated”? In spite of skepticism about just how channel-like the intercellular pathway was, it was exciting to think that the concepts, and analytic and technical tools then being applied to voltage-dependent ion channels could be used to explore the structure–function and biophysics of junctional channels and perhaps their single-membrane subunits (hemichannels). The uneasy relationship to the concepts and mechanisms of so-called “real” ion channels has continued to the present day. The dual voltage clamp studies demonstrating that junctional conductance was gated by voltage provided empirical evidence that “real” channels were involved (Harris et al., 1981; Spray et al., 1981a). The first recordings of single junctional channels were obtained by the dual voltage clamp technique in 1985 by Neyton and Trautmann (1985), from pairs of isolated lacrimal gland cells. The authors noted high unitary conductance, a near absence of charge electivity, a plethora of conductance states, and a remarkable slowness of transitions among them (tens of milliseconds). These would be hallmarks of connexin channel behavior. This paper was followed shortly by a more detailed biophysical characterization of single junctional channel behavior in coupled chick ventricle cells (Fig. 5; Veenstra and DeHaan, 1986). The first recordings of single junctional channels published in JGP were part of a detailed comparison of macroscopic junctional voltage-dependent currents with the underlying single junctional channel behavior (Chanson et al., 1993). This was achieved using pairs of neonatal rat Schwann cells in primary culture, some of which had sufficiently low coupling that single channels could be resolved by the dual voltage clamp technique, without use of pharmacological agents or blockers. Fortunately, even though the cells likely expressed more than one connexin, most of the junctional channels appeared to be of a single type (i.e., had a single unitary conductance). The analysis of macroscopic voltage-dependent junctional behavior essentially reproduced that of Spray et al. (1981a) and Harris et al. (1981), finding similar overall behavior with some differences in specific parameters, but the paper went on to characterize the voltage-dependent steady-state and kinetic features of the single channels. Overall, there was a good match, and a qualitative validation that the first-order kinetics seen in macroscopic currents were reflected at the single-channel level. That such a characterization could be made using a native tissue expressing multiple connexins was an impressive achievement. Exploration of the properties of junctional channels was greatly advanced by the cloning of connexin proteins and their expression in heterologous systems such as Xenopus oocytes and mammalian cells that lack endogenous connexins. There are ∼20 redundant human connexin isoforms, each with specific tissue and developmental distributions. The cloning of a full-length connexin was first achieved by Paul (1986). This was followed the next year by the first recording of junctional currents from a cloned connexin (Dahl et al., 1987). In 1990, Eghbali et al. (1990) made the first single-channel recordings of junctional channels formed by an identified, cloned connexin. Concurrent with electrophysiological studies of junctional channels came interest in the physiology of hemichannels, the hexameric single-membrane subunits of the junctional channel. Because they span only one membrane, they were more amenable to the techniques being applied to other channels. Also, the work on voltage sensitivity, in particular, suggested that each hemichannel contained its own gating mechanisms. There were several reports, starting in 1984, that material from isolated gap junctions formed channels in planar bilayers. Identifying the channel activity as arising from hemichannels was difficult because of the high sensitivity of bilayers to contaminants and the absence of specific pharmacological activators or inhibitors. Characterization typically relied on correlation with properties loosely inferred from cellular work on junctional channels. In reconstitution studies, permeability to molecules rather than atomic ions was used as an identifier in 1992 (Harris et al., 1992). The first use of a cloned connexin in bilayers was in 1995 (Buehler et al., 1995), and the first application of immunoaffinity purification of connexin to bilayer work was in 1996 (Rhee et al., 1996). It must be said that planar bilayer studies of connexin channels have not (yet) fulfilled their initial promise. Meanwhile, evidence for hemichannel activity in nonjunctional plasma membranes was obtained by Paul et al. (1991) in the oocyte expression system. Expression of Cx46 caused oocytes to lyse, which could be osmotically inhibited. The oocytes took up Lucifer yellow but not BSA from the extracellular medium. The cells had low resting potentials, and voltage clamp to potentials more positive than −10 mV induced large, slowly activating currents. Interestingly, expression of a different connexin (Cx43) did not cause any of these changes, suggesting that different connexins had different abilities to form open hemichannels under the conditions of these experiments. At about the same time, DeVries and Schwartz (1992) provided compelling evidence for functional hemichannels in horizontal cells of the catfish—a first demonstration of naturally occurring functional hemichannels. The currents were activated by reduced extracellular Ca2+ and strong depolarization, hallmarks of hemichannel activation. This work was the first to indicate that normal extracellular Ca2+ levels contribute to keeping undocked hemichannels closed. The steady-state and temporal responses to voltage were carefully characterized and found to correlate well with those of junctional currents in the same cells. Although the channels were not biochemically identified, this paper likely reported the first single-channel recordings of a connexin hemichannel in a cell membrane. The first report of hemichannel unitary currents from a cloned connexin was in 1996 (Trexler et al., 1996). The first study of a cloned connexin in JGP was also the first study of hemichannel currents in JGP (Ebihara and Steiner, 1993). This paper defined the fundamental properties of hemichannels and how to study them. Using Cx46 expressed in oocytes, hemichannel activity was activated by long depolarizations above −20 mV. Reducing extracellular Ca2+ from 0.5 mM to nominally Ca2+-free shifted the steady-state voltage–activation curve ∼40 mV to the left, without change in slope. It also accelerated activation and deactivation kinetics and increased the maximal current. This was the first quantitative investigation of the effects of both Ca2+ and voltage in regulation of hemichannel activity. Molecular structure and function These advances in the study of junctional channels and hemichannels made possible exploration of their detailed structure–function. As for other channels, these studies were initially lumped into two general categories: permeation and gating. For most channels, until recently, these were considered distinct processes. However, for connexin channels, there is inherent overlap between these two aspects of channel function, because voltage sensing and permeation occur in the same physical space, the lumen of the pore. That is, alterations of structural and/or electrostatic aspects of the pore are likely to affect permeation characteristics, voltage sensing, and even the gating structures themselves, and conversely, any change within the pore caused by gating is likely to affect both voltage sensing and the character of any permeation that remains (e.g., charge selectivity; Harris and Contreras, 2014). Therefore, genetic manipulations targeted to investigate one process are very likely to affect other processes, directly or indirectly. More than other channels, the connexin channel appears to operate as a single highly coupled allosteric unit. Nevertheless, the discussion below will attempt to deal with pore and gating issues separately, until that becomes untenable. Each member of the connexin protein family forms channels with distinct permeability properties and gating sensitivities. For example, the unitary conductance of junctional channels ranges from ∼6 to ∼300 pS, depending on the isoform. This alone makes clear that the pores are very different. Because the defining feature of this channel family is formation of wide, intercellular (or plasma membrane) channels, rather than a specific ion selectivity or activation by a specific ligand, one should not presume that the determinants of permeability or even gating are the same across the different family members. The inability to rigorously generalize across connexins has been a frustration for investigators inside and outside the field. The presentation below will emphasize “coarse-grained” rather than “atomistic” themes and understandings, as developed in JGP. Ionic conductance and its consequences In 1997, Veenstra and colleagues published a rigorous and comprehensive analysis of ionic selectivity of two cardiac connexins, Cx40 and Cx43 (Beblo and Veenstra, 1997; Wang and Veenstra, 1997). Pairs of transfected N2A cells were dual whole-cell voltage-clamped through patch pipettes filled with various electrolyte solutions. Single-channel slope conductances were measured for symmetric solutions of different salts, normalized by aqueous mobility. Relative permeabilities were determined from reversal potential measurements in asymmetric solutions. For Cx43, the K+:Cl− permeability ratio was ∼8:1. The relative permeabilities among cations was well fitted using the Levitt continuum theory for multi-ion pores (Levitt, 1975, 1991a,b) for a limiting pore radius of ∼6.3 Å. The selectivity corresponded to Eisenman sequence II or I (Eisenman, 1962; Eisenman and Horn, 1983). For Cx40, the K+:Cl− permeability ratio was ∼7:1, the corresponding limiting pore radius ∼6.6 Å, and the selectivity corresponding to Eisenman sequence I. In an extensive discussion of the finding that the anion conductance and permeability sequences differed greatly from the aqueous mobility sequences, it was suggested that the anion permeability is modulated by cation interaction with anionic sites within the pore, similar to a mechanism proposed by Franciolini and Nonner in JGP (Franciolini and Nonner, 1987, 1994). The larger point made by these papers, beyond the specifics of ion/charge selectivity of these particular connexins, was that the conceptual framework typically applied to narrow pores to account for selectivity, permeability, and conductance cannot be applied to these wide multi-ion occupancy pores. Interactions among mobile ions of both signs with each other and the electrostatic environment within the pore are likely to be dominant. Such effects also imply that the energies involved in permeation of connexin channels are likely to be much lower than those involved in ion-specific channels in which there is substantial dehydration of ions and the consequent involvement of large energies in the permeation process, as recently explored in Luo et al. (2016). As noted above, one of the earliest demonstrations of electrotonic coupling was one of the most difficult to understand. Furshpan and Potter showed that current rectified dramatically and instantaneously at the giant motor synapse of the crayfish (Furshpan and Potter, 1957, 1959), whereas almost all other instances of coupling described over the next decade were clearly nonrectifying. In 1969, Auerbach and Bennett (1969) described in JGP a rectifying electrotonic synapse in a vertebrate, the giant fiber-to-motor neuron synapse of the hatchetfish. The rectification of the junctional current was such that transmission from the giant fiber to the motor neuron was facilitated and transmission in the opposite direction was inhibited. The rectification was essentially instantaneous and largely attributable to an (unknown) electrical feature of the junctional conductance pathway itself, and not to differences in input resistance or membrane properties of the coupled cells. In 1983, Giaume and Korn (1983) showed that rectification at the crayfish giant motor synapse (the Furshpan and Potter synapse) could be reduced and eventually eliminated by hyperpolarizing the postsynaptic fiber, thereby demonstrating a voltage dependence of the junctional resistance. Given the near-instantaneous nature of the change in junctional resistance with voltage, it was suggested that these gap junctions “have either the voltage-dependence typical of many aqueous channels, the electron transfer properties of solid-state elements, or both.” Later the same year, Margiotta and Walcott (1983) showed quantitatively that the steady-state rectification at this synapse could be well described by very rapid voltage-dependent gating. This junction was studied by voltage-clamp by Jaslove and Brink (1986). They were able to resolve kinetics of the junctional conductance changes by cooling the preparation, observing a 7.5-ms relaxation at 9.4°C for voltage jumps steps between −85 and +85 mV, and a Q10 of ∼11. The kinetics were not observable at room temperature. The next year, a voltage clamp study by Giaume et al. (1987) extensively explored and modeled the conductance changes as exclusive functions of the junctional voltage. Kinetics could not be resolved at room temperature, even with clamp resolution of 0.8 ms. A major conclusion, supported by the previous studies, was that there was an inherent asymmetry of the effect of voltage at this junction, in spite of there being no indication of asymmetry in its observable structure. The striking asymmetry of behavior and vastly more rapid kinetics of the junctional conductance changes in this system were in stark contrast to the much slower and symmetric kinetics in other systems. Expression of specific cloned connexins permitted exploration of the basis of the rectification. In 1991, Barrio et al. (1991) found that the instantaneous junctional conductance between an oocyte expressing Cx26 and an oocyte expressing Cx32 (a “heterotypic” junctional configuration) was highly rectifying. In 1995, the basis for this was provided in recordings of single Cx26:Cx32 heterotypic junctional channels; the main state unitary conductance of these channels rectified. Over a junctional voltage range from −100 to +100 mV, the unitary conductance increased linearly from ∼20 to ∼80 pS (a slope of 32 pS/100 mV; Bukauskas et al., 1995). The mechanism was unknown, but it was suggested, based on unpublished experiments, that differences in ion selectivity of the two component hemichannels might be involved. This, and more, was established in an experimental and modeling paper in JGP that provided a mechanistic explanation for instantaneously rectifying junctional conductances (Oh et al., 1999). The experiments to tease out the mechanism from differences in function of two connexins in heterotypic and homotypic configurations, and the contributions of different parts of each connexin protein to unitary conductances and current–voltage (I-V) relations, were complex. Based on many mutations and domain swaps, it was concluded that Cx26 and Cx32 hemichannels have opposite voltage sensitivities (discussed below). Previous work by this group showed that this difference was a function of differences of charged residues near the N-terminal end of the first transmembrane helix (TM1), at the cytoplasmic end of the pore, and residues at the extracellular border of TM1 (at the beginning of the first extracellular loop, EL1; Fig. 6). It was also known that Cx26 was somewhat cation selective and Cx32 somewhat anion selective. Experiments showed that changing the amino acids at the same positions that controlled the voltage sensitivity also altered the single channel I-V rectification, and mutations/swaps elsewhere did not. With these results in hand, pore charge distribution profiles were generated that reproduced the I-V relations and anion/cation selectivities of homotypic Cx26 and Cx32 channels using the electrodiffusion model of Chen and Eisenberg, which provided a 1-D numerical solution of the Poisson-Nernst-Planck (PNP) equations (Chen and Eisenberg, 1993; Chen et al., 1997). The charge profiles for each hemichannel were concatenated to generate a profile to correspond to a heterotypic Cx26:Cx32 channel. The resulting calculated I-V showed rectification that qualitatively reproduced the rectification of the single-channel currents. The rectifying conductance of Cx26:Cx32 junctional channels thus appears to be due to the different charge distributions in each half of the channel. An essential insight: The experimental manipulations that altered the charge distributions that defined ionic flux were the same ones that control voltage sensing. Therefore, voltage gating and permeation were unlikely to be separable phenomena, as both were functions of the electrostatic environment in the pore. Later the same year, Suchyna et al. (1999) investigated the same phenomenon in the same Cx26:Cx32 heterotypic channels and applied a similar analytic method. In their implementation of the PNP electrodiffusion approach, the different ionic selectivities in the two hemichannels were represented computationally by asymmetric Donnan potentials at the entrances of the pores rather than by asymmetric positions of fixed charge within the pore. This approximation also reproduced the single-channel rectification seen experimentally, although not to the same degree. This explanation for the profound rectification of unitary currents in this heterotypic junctional channel provided insight regarding the more modest rectification of unitary conductances of some hemichannels in symmetric solutions. Hemichannel rectification was seen in Cx46 by Trexler et al. (1996) and Pfahnl and Dahl (1998) and later in Cx30, Cx45, and Cx50 by Valiunas and Weingart (2000). One may infer that the rectification in these hemichannels also arises from asymmetric distributions of charge that affect flux of atomic ions. A corollary is that the primary energetic determinant of ionic flux in these wide pores is not a centrally located energy barrier. Molecular permeability through connexin channels was initially used more as a diagnostic feature of coupling than a means to explore the properties of the pathway. Every time a new connexin was cloned and expressed, its permeability to dyes (usually Lucifer yellow) was documented. This provided a rough estimate of the limiting pore width (∼12 Å), taken to infer that cytoplasmic molecules of that dimension or smaller ought to be permeant as well. As noted above, evidence for purine permeation of gap junctions was provided by Gilula et al. (1972). Use of fluorescent tracers of different size and charge led to inferences about relative pore width and charge preference for different connexin channels (reviewed in Harris and Locke, 2009). The relatively few studies of molecular permeability of connexin channels published in JGP have focused on implications for pore structure–function and permeation by biological molecules. In 2002, Valiunas (2002) presented a detailed quantitative analysis of Cx45 hemichannels expressed in connexin-deficient mammalian cells, including studies of dye uptake and leakage of Lucifer yellow and propidium. The dye flux was correlated with magnitude of hemichannel currents and compared with junctional flux. Quantitative analysis of the flux of propidium was compromised by its binding to DNA, but it was clear that although highly anionic Lucifer yellow and highly cationic propidium both permeate Cx45 hemichannels, Lucifer yellow was the more permeable. The flux rates of Lucifer yellow through hemichannels was estimated from its concentration and estimation of the number of open channels from measured macroscopic and unitary conductances. Normalized to concentrations, the Lucifer yellow junctional permeability was 16-fold less than that of hemichannels, a greater reduction than expected for a doubling of pore length alone. Possible reasons were extensively discussed and illustrated the factors that could come into play, from alteration of the limiting pore diameter with hemichannel docking, to flux coupling, to altered occupancy of substates. Regarding molecular permeability, it is the ability of endogenous signaling molecules to permeate connexin channels that is of biological importance. In this context, it becomes important to know (1) the degree to which a specific type of connexin channel can distinguish among biological permeants, and (2) the different selectivities among biological permeants exhibited by different connexin channels. Early non-JGP studies demonstrated surprising degrees of both types of selectivity among biological permeants for connexin channels (Bevans et al., 1998; Goldberg et al., 1999, 2002; Hernandez et al., 2007). Using a cyclic nucleotide modulated channel (SpIH), in JGP, Kanaporis et al. (2008) obtained relative and absolute per-channel permeabilities of cAMP through junctional channels formed by each of three different connexins (Cx26, Cx40, and Cx43). SpIH tail currents reported real-time junctional flux of cAMP from a donor cell containing a known concentration of cAMP. During cAMP flux, junctional conductance was monitored by dual voltage clamp. As one would imagine, this experiment is difficult and prone to confounding factors and cellular behaviors. The data showed that the cAMP per-channel permeability of Cx43 junctional channels was 3.2-fold greater than that of Cx26 junctional channels and 5.2-fold greater than that of Cx40 junctional channels. The per-channel fluxes were normalized to cation flux and compared with previous work on flux of Lucifer yellow. The bottom line: Different connexin channels have different permeabilities to biological signaling molecules. The Na+/K+ permeability ratios were essentially the same for all three connexins, in spite of a range of unitary conductances from 55 to 125 pS. The Cl−/K+ permeability ratio for the lowest conductance channel (Cx43; 55 pS) and the highest conductance channel (Cx40; 125 pS) also were about the same (0.13), whereas that of the intermediate conductance channel (Cx26; 110 pS) was significantly greater (0.38). The permeabilities to the molecules differ, as one may expect, but do not correlate with unitary conductance; the channel with the lowest unitary conductance had the highest permeabilities to cAMP and Lucifer yellow. Lack of correlation among unitary conductance, molecular permeability, and charge selectivity had been reported previously (Veenstra et al., 1995), extended here to a biological signaling molecule. Speculation as to the responsible underlying mechanisms included different combinations of effective channel lengths and limiting widths. The continuum theory of Levitt (Levitt, 1975, 1991a,b) previously used by Veenstra and colleagues (Beblo and Veenstra, 1997; Wang and Veenstra, 1997), applied to the data in this paper produced different estimates of pore diameter for the same connexin when based on the Lucifer yellow or the cAMP permeabilities. These estimates also differed from the pore diameters based on monovalent cation data. This theory essentially scales the ratio of the diffusion constant of a permeant within the pore to that in cytoplasm as a function of the relation between the minimal radius of the permeant to the radius of the pore. That it results in different calculated pore widths for the same channels based on data for atomic ions (K+), a fluorescent dye (Lucifer yellow), and a biological signaling molecule (cAMP) says that other factors are involved in the permeation process. Although its inapplicability seems like a trivial point in retrospect, the notion that the junctional pore was a featureless right-cylinder had been the default idea in the minds of many, mostly a product of the idea that junctional channels were just holes that let anything through below a certain size. The data showing there was little correlation among unitary conductance, size of permeable molecules, charge selectivity, and limiting width forced an end to this simplistic notion. The pore width emerging from the Levitt formulation based on the cAMP permeability numbers was narrower than that based on the much larger molecule Lucifer yellow. This raised the possibility that the smaller, biological permeant interacted more strongly with the pore (i.e., decreasing its effective “diffusion constant” within the pore) than did the nonbiological tracer molecule. Rephrased, one must be cautious about inferring permeability of biological molecules from that of nonbiological molecules; in this case, cAMP permeability revealed something about the pore that Lucifer yellow did not. It is clear that each connexin has its own preferences and selectivities among biological molecular permeants, and they are not explained by simple considerations of permeant size and charge (reviewed in Harris, 2007). Although the specific mechanisms by which connexin channels select among molecular permeants are as yet unknown, the forces that come into play in the relatively low-energy interactions of molecules, with many degrees of freedom (configurational, orientational), within the connexin pore have been explored computationally (Fig. 7; Luo et al., 2016). In addition to its biological importance, the permeability of connexin channels to small cytoplasmic molecules creates a problem for application of a commonly used experimental strategy. In 2015, Tong et al. (2015) discovered that the MTS-based accessibility scanning technique was compromised by the permeability of connexin hemichannels to cellular glutathione. While performing a pore accessibility scan on a connexin expressed in oocytes, they noticed that the effect of 2-sulfonatoethyl methanethiosulfonate sodium salt (MTSES) modification of pore-lining engineered cysteines slowly reversed. This is usually interpreted to indicate an effect of the MTS reagent unrelated to cysteine modification. In this case, however, it turned out that the reversal was a result of oocyte glutathione gaining access to the MTS-modified residue via the hemichannel pore itself and reducing the MTS-thiol linkage. Thiol modifications made with linkages that could not be reversed by reductants were stable. The same year, a study in JGP explored the effects of pathogenic point mutants of a connexin on unitary conductance and dye permeability (Santa Cruz et al., 2015). The intriguing results illustrate the difficulty of facile explanations for the determinants of connexin pore properties. Cx40 is primarily found in the atrial myocardium. Junctional channels composed of three point mutants of Cx40 that are associated with atrial fibrillation but retain function were assessed by dual voltage clamp and dye permeation studies. Mutant A96S (in TM2) had unchanged unitary conductance and single-channel permeability to (anionic) Lucifer yellow but enhanced permeability to (cationic) ethidium. Mutant M163V (at the TM3/EL2 border) also had unchanged unitary conductance but greater permeability to both Lucifer yellow and ethidium. The third mutant (G38D), the only one in the pore-lining helix, had a significantly greater unitary conductance, greater permeability to Lucifer yellow, and essentially no permeability to ethidium. Each of these effects, while informative regarding the effects of each pathological mutation on unitary conductance and charge selectivity, are instructive in the inability to account for the effects in simple terms based on the location or character of the mutation. What lines the pore? The first studies to directly identify pore-lining segments of connexin channels were performed by Dahl and colleagues (Zhou et al., 1997; Pfahnl and Dahl, 1998, 1999; Hu and Dahl, 1999). Using cysteine-scanning accessibility mutagenesis (SCAM; Akabas et al., 1992) with extracellular application of a relatively large thiol reagent (maleimido-butyryl-biocytin; MBB), Zhou et al. showed modification at two positions deep in TM1 in two hemichannels (positions 33 and 34 in a Cx32 chimera and the corresponding positions in Cx46). The findings were inconclusive for positions in TM3, which had been predicted to be pore lining because it was the only overtly amphipathic transmembrane domain. Pfahnl and Dahl showed that position 35 was also accessible. Hu and Dahl generated chimeric channels in which TM1 was exchanged between the same two connexins as above. Several pore properties, including unitary conductance, were transferred, strongly suggesting that TM1 was a major contributor to the pore. As hinted above in the discussion of rectification, mutations near the N-terminus and at the beginning of EL1 affect voltage dependence of junctional channels. Because early studies indicated that the voltage being sensed was that in the pore, it seemed reasonable that the voltage-sensing moieties were exposed to the pore lumen, and therefore could also affect permeation. The involvement of EL1 in charge selectivity was explored in Cx46 hemichannels by Trexler et al. (2000). In the key experiment, the EL1 of Cx46, a cation-preferring high-conductance channel, was replaced by that of Cx32, an anion-preferring, lower-conductance channel. This substitution changed the channel from cation to anion preferring, reduced the conductance, and changed the single-channel I-V relation from inwardly rectifying to outwardly rectifying. In the native Cx46 channel, high-ionic-strength solutions applied to the extracellular face of the channel, but not to the intracellular face, reduced its cation selectivity, also suggesting that a determinant of the charge selectivity was near the extracellular end of the pore. Many other chimeric channels were made, with functional ones giving results consistent with the EL1 domain being a key determinant of charge selectivity and permeability. The rectification was reproduced by the 1-D PNP equations, as previously used by Oh et al. (1999) in studies of single-channel rectification. The paper that firmly identified TM1 (with the N-terminal [NT] domain at one end and EL1 at the other) as the primary pore-lining segment was published in JGP by Kronengold et al. (2003). Cysteine-scanning mutagenesis was performed on Cx46 in excised patches, using MTS reagents of different charge. Modification was seen with application from either side of the pore at positions at the N-terminal end of EL1 (i.e., closest to TM1), which altered single-channel rectification in opposite directions for oppositely charged modifying reagents. In addition, accessibility was seen at residues in TM1 about halfway through the membrane-spanning region from the extracellular side. Intriguingly, stepwise reductions in channel conductance were seen, suggesting sequential modification of cysteines in several of the subunits of the hexameric channel. No evidence of modification was seen when scanning TM3, which had earlier been suggested to be prelining on the basis of its amphipathicity and more recently by SCAM studies on junctional channels (Skerrett et al., 2002). Confirming evidence for the direct contribution of TM1 to the pore, particularly its C-terminal half, came from expanded chimeric and mutagenesis studies from Dahl and colleagues (Hu et al., 2006). This study also showed that replacing the leucine at position 35 in the middle of TM1 with the smaller glycine residue greatly increased unitary conductance. Structural proof that TM1 was the primary pore-lining segment came with the x-ray structure of Cx26 in 2009, confirmed by a second set of structures in 2016 (Maeda et al., 2009; Bennett et al., 2016). The 2009 x-ray structure of Cx26 (Maeda et al., 2009) provided the basis for a computational and experimental study in JGP that pulled together various themes to produce a validated structural model (Kwon et al., 2011). The crystal structure was lacking two cytosolic domains (the intracellular loop [CL] and the C-terminal tail [CT] as well as the N-terminal methionine [Met1]). These were added and the structure energy minimized, but Monte Carlo Brownian dynamics (grand canonical Monte Carlo/Brownian dynamics [GCMC/BD]) simulations showed that the pore was essentially nonconductive, mainly because of the position of Met1 deep within the pore. The system, including explicit water, ions, and lipid membrane, was equilibrated by MD. GCMC/BD of the equilibrated structure showed ion permeability, largely as result of widening of the pore in the region of Met1, but a strongly anion-selective channel and inward current rectification, unlike the native channel. Previous mass spectrometry (MS) studies had indicated a number of posttranslational modifications, some of which were charge-changing (Locke et al., 2009). Tandem MS/MS showed that Met1 was acetylated (an irreversible cotranslational modification that eliminates the charge of the terminal amine), consistent with known sequence determinants of this modification. Neutralizing the charge of the Met1 terminal amine to mimic the effect of acetylation produced I-V relations and charge selectivity that closely matched that of the native channel. Other charge changes corresponding to lysine acetylations (which are reversible) suggested by single MS caused minor modifications to selectivity and rectification, supported by variability in these parameters in channel recordings. Lessons from this include the importance of using MD-equilibrated structures, incorporating known cotranslational modifications (and perhaps posttranslational modifications) and explicit experimental validation, in generating meaningful models. This model was later used to explore mechanisms of gating (below) and the energetics of permeation of a molecular permeant and impermeant through the Cx26 hemichannel (Luo et al., 2016). Gating of connexin channels started out simple but became complex. Initial studies showed regulation by voltage, Ca2+ and pH. Soon it became clear that there were two separable varieties of voltage sensitivity in each hemichannel, which seemed to involve different parts of the protein. Then gating by Ca2+ appeared to involve the same or nearby parts of the protein, and one of the voltage-sensitive processes. The locations of the physical gates are uncertain, and what operates them unclear. Much of this complexity follows from the fact, mentioned above, that almost everything happens in the pore. These processes might be best viewed as different aspects of a single mechanistically integrated molecular machine (the fable of the elephant and blind men comes to mind). The initial observations of voltage gating and the influence of Ca2+ on hemichannel gating were discussed above. Below we start with the initial characterizations of modulation by pH followed by structure–function studies in which the various mechanisms become increasingly intertwined. Trexler et al. (1999) published in JGP a study of the gating of Cx46 channels by pH at the single-channel level, in what remains one of the most detailed and informative analyses of this process. It was also the first report of unitary hemichannel currents in JGP. This paper unequivocally showed that Cx46 junctional channels and hemichannels in excised patches were readily, directly, and reversibly closed by acidic pH acting at the cytoplasmic end of the pore (with pK 6.4). This action did not require Ca2+ or any other cellular components. The state dependence of low pH effects was examined using fast perfusion. Low pH was found to act from the cytoplasmic side whether the channels were open or closed by voltage. The effect of low pH was voltage dependent, but in a direction opposite to that which would enhance H+ flux into the pore. One of the more remarkable features was that the single-channel closing transitions induced by low pH were slow (10–100 ms) and appeared to involve transitions among numerous, short-lived subconductance levels. This kind of transition had been seen previously in a specific type of voltage-induced transition (see “loop-gating” below), suggesting action on a common mechanism. Work on another connexin (Cx43) had shown that an intact CL domain, and a specific histidine, were involved in pH sensing (Ek et al., 1994; Morley et al., 1996). However, in Cx46, pH sensing was unaffected by deletion of most of the CL or mutation of the histidine. There is clear diversity in the pH-sensing mechanisms in different connexins. A different kind of pH regulation of hemichannels and junctional channels was described by Locke et al. (2011) for a different connexin, Cx26. It had been shown that the apparent pH sensitivity of liposome-reconstituted Cx26-containing channels was a function of the pKas of the Good buffers (e.g., HEPES, MES) used to buffer the pH, and not the pH itself (Bevans and Harris, 1999). That is, the pH–activity relation shifted with the pKa of the buffer, and the inhibition of channel activity correlated with the concentration of the protonated form of the buffer. The same effect was seen for taurine, a cellular aminosulfonate, which is nearly fully protonated at intracellular pH. When non-aminosulfonate pH buffers were used, the channels showed no pH sensitivity. The structural basis of this regulation was explored by additions to the CT domain, NMR and ELISA binding assays of the relevant peptides, and channel permeability assays. An addition to the CT eliminated sensitivity to taurine in reconstituted channels and cells, suggesting CT involvement. However, NMR studies showed no interaction between taurine and the CT, suggesting that the CT interacted with another domain in this process, the CL being the most likely. ELISA studies of interaction between the CT peptide and segments of the CL showed that the CT interacted only with the segment of the CL closest to TM3, that low pH enhanced this interaction, and that taurine could disrupt it. NMR studies showed that taurine interacted with the target CL peptide at several of the same sites at which the CT peptide interacted, providing a basis for its disruption of the CL–CT interaction. Several scenarios could explain the findings, but the simplest is that in this connexin, a CL–CT interaction keeps the channel open, low pH enhances this interaction, and protonated aminosulfonates disrupt it, leading to channel closure. Thus the “pH sensitivity” is really a balance between a pH-driven interdomain association, which keeps the channel open, and the protonated aminosulfonate-driven disruption of that association, which closes the channel. In this context, it is interesting to note that other cytosolic aminosulfonates have the same effect as taurine (e.g., l-cysteic acid, l-homocysteic acid, and hypotaurine) and that other cytosolic compounds, which lack the sulfonate moiety, competitively antagonize the effect of taurine on these channels (β-alanine, glycine, and γ-aminobutyric acid; Tao and Harris, 2004). Voltage dependence (i.e., the usual source of confusion) Perhaps the most confusing and skepticism-inducing aspect of connexin channel function is the character of voltage gating. It is unlike voltage gating in any other channel, even at its simplest level—there is no S4 equivalent, yet the conductance–voltage (G-V) curve can be as steep as that of voltage-gated Na+ channels, and the kinetics are at least an order of magnitude slower than for other voltage-gated channels. The basics were described in two non-JGP articles. In 1994, Verselis et al. (1994) obtained two major insights about voltage gating of connexin hemichannels, deduced from the behavior of junctional channels: (a) some connexins form hemichannels that close in response to depolarization and others form hemichannels that close in response to hyperpolarization, and (b) the polarity to which a hemichannel responds is determined, and can even be reversed, by the presence or absence of charged residues at position 2 (one in from the N-terminal residue) and at the border of TM1 and EL1. These insights were derived from analysis of G-V relations of junctional channels formed by different combinations of wild-type and mutant hemichannels (point mutants and chimeras). Specifically, this paper showed that Cx26 hemichannels, when part of junctional channels, close in response to a positive junctional voltage and Cx32 hemichannels close in response to negative junctional voltage. If Cx26 and Cx32 hemichannels are paired, the junctional conductance is sensitive to only one polarity of voltage, since one hemichannel sees a positive voltage and the other a negative voltage but the hemichannels are oppositely oriented. Similarly, if a mutation that reverses the polarity of voltage sensing is made in either connexin, and it is paired with a wild-type hemichannel of the same connexin, the junctional channel will also close with only one polarity of voltage. That the polarity of voltage sensing is determined at two locations separated by a transmembrane domain was surprising. A straightforward inference is that these positions must be within the junctional voltage field. This leads to the structural inference that the NT domain folds into the pore so that its initial segment can directly sense voltage. Later work showed that charge changes at positions 1 to 10 but no further could reverse the polarity to which a hemichannel responds, supporting the idea that the end region of the NT is in the voltage field and therefore inside the pore (Purnick et al., 2000). Because charge changes in the NT can reverse the polarity of voltage to which a hemichannel responds, it is thought that the sensor moves in the same direction in each case to effect closure. This characterization of hemichannel voltage sensitivity was correct but incomplete, as revealed by Trexler et al. (1996) in a study of single hemichannel voltage-dependent gating. This study of on-cell and excised patches showed that as voltage is ramped from large negative voltages to large positive voltages, the channels transition from mostly closed, to mostly open, to “closed” to a substate. That is, single Cx46 hemichannels gate in response to both large positive and large negative voltages. This single-channel behavior matched the changes in macroscopic hemichannel currents. Closing at negative voltages accounts for the need to depolarize undocked hemichannels to open them. Closing to a substate at positive voltages provides an explanation for why, in junctional channels at large voltages, the conductance does not go to zero. To reinforce this point, others had shown in studies analogous to those of Verselis et al. (1994) above, that, like Cx26, Cx46 hemichannels in a junctional configuration gate in response to positive junctional voltage (White et al., 1994a), demonstrating that hemichannels have the same sensitivities to voltage when undocked and when part of junctional channels. Empirically, then, each hemichannel has two voltage-sensitive gating mechanisms, one fully closing the channel at negative voltages, and the other closing the channel to a substate at positive or negative voltages (the former in Cx26 and Cx46, and the latter in Cx32). A second defining characteristic of these two responses to voltage was the nature of the gating transitions seen in single-channel records. The transitions into and out of the substate were rapid. However, transitions into and out of the fully closed state were slow (in this study lasting 10–20 ms) and appeared to involve multiple unstable intermediate states. Thus the two responses to voltage could be distinguished by both the conductance state to which the channels close and by the kinetics of the transitions. The fast transitions to the substate, since they corresponded to the characterizations of junctional voltage sensitivity, are referred to as “Vj-gating” or “fast gating.” The multi-stepped slower transitions to and from the fully closed state resembled transitions seen when two hemichannels initially dock to each other and open, a process inferred to involve the extracellular loops that mediate the docking interaction (Bukauskas and Weingart, 1994). For this reason, these transitions are called “loop-gating” or “slow gating.” All these terms remain in use (this article will use the Vj- and loop-gating terms). Subsequent work showed that loop-gating always closes at negative voltages, whereas Vj-gating can close to positive or negative voltages depending on the connexin (as in the Cx26 and Cx32 examples above) and that the polarity to which Vj-gating responds can be switched by mutation without affecting loop-gating. One may ask, why at large voltages in junctional channels, when one of the two hemichannels is at a negative voltage, the channels are still conductive—shouldn’t the loop-gate of that hemichannel close the channel? A possible answer was provided by the notion, suggested by Harris et al. (1981) as a mechanism for “contingent gating” of hemichannels, that because voltage is sensed within the pore, the “closing” of one gate (e.g., to generate a substate) would alter the voltage field within the pore so that a greater portion of the field drops across that gate, reducing the portion of the field that drops across an “open” gate in the apposed hemichannel. In this scenario, in Cx46 when a Vj-gate closes to a substate, the loop-gate in the apposed hemichannel then sees a voltage insufficiently negative to induce its closure. Detailed modeling of this type of interaction has shown its essential empirical validity (Paulauskas et al., 2009), but other explanations are possible, such as the docking of hemichannels specifically destabilizing the loop-gate closed state. In 2000, Oh et al. (2000) applied and tested these ideas on Cx32 at the junctional and single hemichannel levels and explored the behavior of heteromeric channels formed of wild-type Cx32 and a Cx32 mutant in which the Vj-gating polarity was reversed. This was done on the background of a chimeric channel in which the EL1 of Cx32 was replaced by that of Cx43 (Cx32*43E1), which readily forms active undocked hemichannels as well as junctional channels while retaining the voltage-gating properties of wild-type Cx32 (first shown by Pfahnl et al. ). Coexpressing this chimera with its N2D mutation variant (which reverses the Vj-gating polarity) yielded hemichannels that gated to substates at both voltage polarities. The frequency of gating to the reversed polarity caused by the N2D mutant correlated with the degree of its expression. In other words, it seemed that each connexin monomer within the hemichannel could sense and respond to voltage (i.e., adopt a conformation leading to a substate) separately from the other monomers. Though there may be interactions among the subunits in response to voltage, these findings disfavor a concerted gating model in which all six monomers need to be activated to close the channel to a Vj-gated substate. In 2002, Bukauskas et al. (2002) published a detailed analysis of the properties of the substate to which Vj-gating closes the channel, which also yielded additional insights about the mechanism of Vj-gating. These studies used Cx43 junctional channels in which gating to the Vj substate by one of the hemichannels was blocked by a C-terminal addition, enabling clean recording of the currents through the substate induced by Vj-gate of the other hemichannel. The conductance of the substate rectified with larger conductances at negative potentials (∼30 pS at −70 mV and ∼18 pS at +35 mV; the main state conductance is ∼115 pS). Ion substitution studies showed that the rectification was accompanied by a substantial increase in anion selectivity (the main state of Cx43 being essentially nonselective between cations and anions). Furthermore, anionic and cationic dyes that readily permeate the main state did not permeate the substate. These changes in single channel I-V and selectivity were consistent with Vj-gating narrowing the pore and introducing a positive charge at the cytoplasmic end. This was computationally reproduced by application of the 1-D PNP equations, as in Oh et al. (1999) and Trexler et al. (2000) above. It was noted that in Cx43 negative voltage induces Vj-gating, which was accounted for by movement of a positively charged moiety in the NT into the pore (compare Oh et al. ), which also shows rectification of the Cx32 Vj-gating substate). This led to the inference that the positive charge mediating gating is the same positive charge that causes the single-channel rectification and anion selectivity. The suggestion is that a key part of the Vj-gating voltage sensor is also the Vj-gating gate, in the sense that it moves into the pore lumen. This is an example of gating and permeability being mechanistically interrelated in connexin channels. Bukauskas et al. (2002) above had speculated on the physiological importance of a voltage-induced narrowing but not closure of the pore, noting that the dyes that were excluded from the substate were about the size of biological signaling molecules. The paper ended with the statement, “Consequently, the Vj-gating mechanism can serve as a selectivity filter that preserves electrical cell–cell communication but can limit the communication of metabolic or biological signaling molecules.” In fact, 6 d before this article appeared online, this precise point was demonstrated by Qu and Dahl (2002) in PNAS. Using different connexins, they showed that Vj-gating could dramatically restrict intercellular movement of dyes and cAMP while having little effect on electrical coupling. Loop-gating and Ca2+ Loop-gating is defined as the mechanism by which negative voltages drive hemichannels toward a fully closed state. Extracellular Ca2+ shifts the loop-gating steady-state G-V relation to the right, empirically having the effect of stabilizing the closed state. The absence of a significant change in slope suggests that the effect of Ca2+ is not on the voltage sensitive process itself, but on the energy difference between the open and voltage-closed states (an effect of Ca2+ on surface charge would tend to shift the relations in the opposite direction, and would be the same for all divalent cations, which it is not). In highly schematic terms, this could be achieved by Ca2+ either binding to a closed state and lowering its energy, and/or binding to the open state and raising its energy. The biological and biomedical importance of loop-gating is that normal extracellular Ca2+ ensures, in the context of a normal resting potential, that undocked hemichannels remain closed. Mutational changes in loop-gating that reduce the apparent affinity for Ca2+ result in aberrantly open hemichannels, with pathological consequences. Therefore, understanding the mechanisms of loop-gating, what acts on it, and the effects of Ca2+ are of compelling biophysical and biomedical importance. The path toward this understanding has not been smooth and the ultimate goal has not yet been reached, though substantial progress has been made. The first study of the mechanism of Ca2+ effects on hemichannels was that of Pfahnl and Dahl (1999). Using Cx46 in whole-cell and excised patch configurations, they showed that the effect of Ca2+ was strongly voltage dependent and consistent with Ca2+ having its effect by entering the pore, more readily from the extracellular side. A Hill plot had slope greater than 2, suggesting that several Ca2+ ions were required. The paper concluded, “If calcium were to act on its own specific gate, that gate would need to interact strongly with the voltage gate to account for the strict interrelation of calcium and voltage effects on channel function.… Thus voltage and calcium may act on the same gating structure or on two separate structures that interact with one another.” In 2003, a mechanism for Ca2+ effects was proposed that involved sequential binding at two sites, one that exerts voltage-dependent pore block and one that stabilizes the channel once blocked (Ebihara et al., 2003). This study also used Cx46, with Mg2+ as a surrogate for Ca2+ in most experiments, to avoid contamination by Ca2+-activated conductances in the oocyte. Confirmatory studies were performed using Ca2+, which gave similar results, but with greater apparent affinities than Mg2+. Surprisingly, it was reported that in divalent-free solutions there was no voltage dependence of these channels. In this scheme, the voltage dependence arises from movement of Mg2+/Ca2+ through the field to its blocking sites. A similar mechanism was proposed in JGP for Ca2+ effects on Cx37 hemichannels (Puljung et al., 2004). As above, the voltage dependence was proposed to arise from the effect of voltage to drive Ca2+ into the pore to reach binding sites near the cytoplasmic end, where block occurred. Also as above, it was reported that removal of divalent cations resulted in an essentially linear G-V curve across negative and positive voltages, with little evidence of voltage-dependent gating. In this scenario, the channel has no intrinsic voltage-dependent gating processes, only open pore block that requires the Ca2+ to traverse the full membrane voltage. In this model, there was no second, stabilizing Ca2+ binding site, but kinetic considerations required that upon relief of block (depolarizing voltages) there is an accumulation of Ca2+ at the extracellular entrance of the pore. Voltage-dependent divalent block was an intriguing idea, but the hemichannel behavior in these papers is difficult to reconcile with other work. The low Ca2+ concentration at which no voltage dependence seen was ∼20 µM, well above that in cytoplasm, yet Cx37 junctional channels have strong voltage dependence. Cx37 hemichannels exposed to much lower Ca2+ concentrations show voltage-sensitive gating at both positive and negative voltages (Derouette et al., 2009). A possible explanation is that the above studies were of macroscopic hemichannel currents, which can become large enough in low Ca2+ to produce series resistance effects on the voltage clamp that can make the hemichannels appear insensitive to voltage. The relation between loop-gating and divalent cations was largely resolved by Verselis and Srinivas (2008) in JGP, in single-hemichannel studies of Cx46. Vj-gating in Cx46 occurs at positive voltages only, so loop-gating could be studied cleanly at negative voltages. The bottom line from this detailed work is that loop-gating is an intrinsic property of the hemichannel, occurring in the absence of divalent cations. Divalent cations were proposed to stabilize the loop-gate closed state, shifting the G-V relation to the right, as originally reported by Ebihara and Steiner (1993), as well as the Po–V relation. Effects at the macroscopic and single-channel levels showed that without divalent ions, the closures caused by loop-gating are short lived and unstable, seemingly to rapidly transit among substates and a closed state. The effect of divalent cations is to promote relatively long-lived closed states. In these effects, Ca2+ is ∼10-fold more effective than Mg2+. The divalent cations were effective only from the extracellular side of the pore. The relation between loop-gating and Ca2+ has been further explored recently by others (Pinto et al., 2017). Modulators of loop gating Several reagents are widely used to inhibit the activity of connexin channels. Most are not specific for connexin channels and are nonselective among connexin channels, and their modes of action are unclear. Articles in JGP have largely steered clear of relying on these agents. When it comes to the pharmacology of connexin channels, two studies have explored connexin isoform–specific modulators of loop-gating. In 2006, Srinivas et al. (2006) unexpectedly discovered that monovalent cations compete with the action of Ca2+ to close hemichannels, and in only one of two closely related connexins. As mentioned above, Cx46 and Cx50 are the two major connexins in the lens and have a high degree of sequence homology. Replacement of extracellular Na+ with K+ dramatically blocked the ability of Ca2+ to keep Cx50 (but not Cx46) hemichannels closed. Specifically, monovalent cations, with potency Cs+ > Rb+, K+ >> Li+, Na+, greatly increased Cx50 hemichannel currents, and this was Ca2+-dependent; the effects decreased as Ca2+ was lowered. The potentiation of the currents was not attributable to changes in unitary conductance, permeability, or voltage-gating properties. Ca2+ regulation of Cx50 seems to be uniquely sensitive to monovalent cations. Studies with chimeric channels showed that this sensitivity was determined by the amino-terminal half of the protein. Beyond this, the molecular basis of this effect is unknown, although it makes the most sense for the monovalent ions to be acting extracellularly (perhaps on EL1) but not within the permeation pathway. A potential biological relevance is that modest changes in extracellular K+ could alter the sensitivity of Cx50 hemichannels, specifically, to regulation by Ca2+. Quinine and its derivatives were found to robustly inhibit the activity of Cx36 and Cx50 channels, and have far less effect on channels composed of Cx26, Cx32, Cx40, Cx43, or Cx46 (the closest analogue of Cx50; Srinivas et al., 2001). In 2012, their detailed mechanism was studied in JGP by Rubinos et al. (2012) using macroscopic currents and excised patch single-channel recordings). The compound tested was a quaternary derivative of quinine (N-benzylquininium; BQ+). BQ+ inhibited Cx50 junctional and hemichannel activity. In excised patches, it inhibited channel opening from either side of the channel without a corresponding effect on unitary conductance. The inhibition was voltage dependent from each side in a manner consistent with entry into the pore. BQ+ also decreased mean open time as a function of concentration. Although these effects are expected of simple open-pore block from either side of the channel, the transitions between the open and closed/blocked states were indistinguishable from the characteristic slow (20–50 ms) and noisy transitions of the loop-gating mechanism that occurred in the absence of BQ+. Moreover, the mean closed times also increased with BQ+ concentration, inconsistent with simple open pore block. These data can be explained by BQ+ acting within the pore toward the cytoplasmic end to exert a relative stabilization of the (loop-gated) closed state. Rubinos et al. (2012) showed that the channel is intrinsically voltage dependent, but suggested that one BQ+ enters the pore to close it via loop-gating and a second stabilizes the closed state (a Hill plot suggested that more than one BQ+ was involved). An intriguing aspect is that BQ+ appears to affect the loop-gating mechanism from within the pore, but electrically much closer to the cytoplasmic end. Replacement of the NT of Cx50 with that of Cx46 essentially eliminated inhibition by BQ+, strongly suggesting that its effects on loop-gating involve the physical cytoplasmic end of the pore. The actions of BQ+ suggest that the loop-gating process likely involves the whole channel, or at least that it cannot be localized to one end or the other. The first studies to provide insight into the structural changes associated with loop-gating were those of Pfahnl and Dahl (1998, 1999). These studies, using Cx46 and the large thiol-reactive reagent MBB on whole-cell and excised patches, showed that position 35 in TM1 was accessible from both sides of the channel when it was open but was inaccessible from the extracellular side when the channel was closed by negative voltages (which close only the loop-gate in Cx46) or by extracellular Ca2+. It was concluded that the physical gate of the loop-gating mechanism was extracellular to position 35. Also, this was evidence that the loop-gate caused a local change in the pore, not a global pore narrowing. 2009 saw the first explorations of what was happening at the extracellular end of the pore during loop-gating of hemichannels, in two complementary papers on two different connexins, the first published in JCB and the second in JGP (Tang et al., 2009; Verselis et al., 2009). These studies used Cx50 and the chimeric channel Cx32*43E1 (used previously in studies of Vj-gating, above), probed by state-dependent cysteine modification and formation of metal binding sites. There were some minor differences in the two studies, but the big picture is that loop-gating involves movement of residues at the border of the TM1 and EL1 domains (Fig. 8). Specifically, in Cx46, cysteine substitutions at positions 43 and 46 (and to a lesser extent 51) resulted in closed channels stabilized by Cd2+ under conditions that favored the loop-gate closed state. Cysteine substitutions at positions 40 or 41, shown by SCAM not to be exposed to the pore, had no effect on loop-gating. A straightforward interpretation is that loop-gating causes the pore to narrow at least at positions 43 and 46, and perhaps 51. For the Cx32 chimera, cysteine substitutions at positions 38 and 45 (but not positions 37, 39, 40, or 43) were accessible to 2-aminoethyl methanethiosulfonate hydrobromide (MTSEA)-biotin from either end of the pore when the channels were open, indicating that the former set were exposed to the lumen and the latter set were not. Stepwise reductions in unitary conductance were seen for positions 38 and 45 (as in the Kronengold et al. studies on pore-lining residues in Cx46), suggesting sequential modification of intrapore cysteines in different subunits. However, with loop-gate closing, cysteines at positions 40 and/or 43 could be linked by dibromobimane, suggesting that they became accessible to the lumen, at close proximity, with loop-gating closure. This suggested that loop-gating involved a rotation of this portion of the TM1/EL1 structure, placing positions 40 and 43 into the pore. This was supported by studies showing that cysteine substitutions at 43 were able to bind Cd2+ with high affinity and form disulfide linkages with loop-gating. Under the same conditions, cysteine at position 40 could bind Cd2+, but at lower affinity. Small and reversible effects were seen for Cd2+ at positions 38 and 45, suggesting little change with loop-gating, and cysteines at positions 37 and 39 were not modified under any of the conditions. These two studies identified the TM1/EL1 region as involved in the dynamics of loop-gating. While Tang et al. (2009) was in press, the first x-ray crystal structure of a connexin was published (Maeda et al., 2009). In an Appendix to Tang et al. (2009), the findings of both papers were discussed in the context of the new structural information. Drawing on the structure showing a bend at the TM1/EL1 transition at about position 43, and an apparent loss of α-helicity in the following segment (positions 43–48 and perhaps extending to 51, soon to be called the “parahelix”), it was suggested that rather than a rotation, loop-gating could involve a relaxation of the TM1/EL1 bend, which could constrict the extracellular entrance of the channel pore and alter the helical periodicity of the TM1/EL1 segment sufficiently to put positions 40 and 43 into the pore. In 2012, an MD study characterized the fluctuations (in the open state) of the parahelix, its interactions, and the TM1/EL1 bend (Kwon et al., 2012). This work showed that the parahelix was part of an intersubunit electrostatic network whose dynamic changes correlated with changes in the configuration of the parahelix. Fluctuations in the network and parahelix affected the stability of the TM1/EL1 bend angle. It was suggested that the electrostatic network was the voltage sensor for loop-gating, and that voltage-driven changes in the network determined the configuration of the parahelix (proposed as the physical gate) and also drove changes elsewhere in the protein, including the TM1/EL1 bend angle. The implications of changes in the TM1/EL1 bend angle during loop-gating motivated studies to examine changes at the extreme intracellular and extracellular ends of the pore (Kwon et al., 2013). State-dependent formation of Cd2+-thiolate metal bridges was used to probe changes with loop-gating in the Cx32 chimeric channel. Cysteine substitutions were made at positions 108 and 109 in the CL, which were seen in MD-equilibrated structures to be at the cytoplasmic entrance to the pore, outside the membrane-spanning domains. In these mutants, Cd2+ stabilized the loop-closed state but had no effect on the open channels. The effect of Cd2+ on the 109C mutant could be lessened if the channel was first exposed to MTSEA. From the coordination distances, it was estimated that loop-gating narrowed the pore diameter at these positions from ∼15 to ∼10 Å, which would be insufficient to occlude the pore. Notably, Cd2+ had no effect in response to Vj-gating. Similar studies were performed with cysteine substitution at position 56 in EL1, shown in the MD simulations to be at the furthest extracellular pore-facing position. No effects of Cd2+ were seen under conditions of loop-gating or Vj-gating. It was a negative result but suggested that this portion of the protein either does not narrow with loop-gating or does not narrow sufficiently for Cd2+ coordination. Taken together with the previous work showing that loop-gating caused narrowing in the region of positions 43 up to position 47 and possibly to position 51 (these position numbers are approximate because of slight numbering differences in the two connexins), it was proposed that loop-gating narrowed but did not occlude the cytoplasmic pore entrance as a result of a straightening of the TM1/EL1 bend angle. Putting (most of) it together In 2013, two papers from different groups were published back to back in JGP, each addressing the fundamentals of how Ca2+ interacted with the Cx26 hemichannel to favor the closed state (Lopez et al., 2013; Sanchez et al., 2013). Both studies targeted mutations at D50, which cause syndromic deafness in humans, as a starting point. Mutations at this site in the parahelix reduce the ability of extracellular Ca2+ to keep the hemichannels closed, which is no doubt the proximate cause of the human pathology. In these papers, similar, but different, experimental strategies were used to investigate how and why mutations at this position compromised Ca2+ sensitivity. The big picture emerging from these studies was largely consistent, though there were specific areas of disagreement. Both studies found that a negative charge at position 50 was required for full sensitivity to Ca2+. Both studies suggested that D50 was not necessarily part of the binding site for Ca2+, but was intimately involved in its effects. Both studies suggested that Ca2+ interaction with the channel resulted in disruption of specific electrostatic interactions involving D50, and that these disruptions destabilized the open state—but that the specific disrupted interactions were different (D50–K61 for Lopez et al. and D50–Q48 for Sanchez et al.). The different conclusions on this score were based on different sets of mutations, different ways of dealing with the optimal but nonfunctional mutants, and double mutant cycle analyses using different parameters of the effects of the mutations. Later work by Lopez et al. (2014) indicated a D50–Q48 interaction that stabilized the open state, but it was relatively insensitive to Ca2+. Each study had unique aspects and conclusions. The kinetic data in Lopez et al. (2013) suggested that Ca2+ not only interacts with open channels to destabilize the open state, but also interacts with closed channels to stabilize the closed state. Activity of the channels was determined from peak tail currents following a depolarizing step to a single voltage maintained long enough for activation to reach steady state, and the mutant cycle analysis was performed on directly observable apparent Ca2+ affinities and rate constants. In Sanchez et al. (2013), the effects of cysteine substitution at position 48 indicated that the EL1 region was remarkably flexible, and that this could factor into control of several aspects of channel function. This work included studies of single channels as well as macroscopic currents, which showed that the transitions being affected were indeed loop-gating transitions, and also that D50 was pore lining. It also characterized the Ca2+ sensitivity of the mutants as a function of voltage. Both papers noted that further studies were needed to fully explain all the observations. Nevertheless, these papers make the essential point that Ca2+ induces a change or reorganization of interactions in the parahelix region to favor the loop-gate closed state of the channel. In early 2016, Yeager and colleagues (Bennett et al., 2016) published x-ray crystal structures of Cx26 junctional channels in the presence and absence of bound Ca2+, with resolution that matched or exceeded that of the previous structure (Maeda et al., 2009), which did not have Ca2+ bound. These structures were largely consistent with the 2009 structure, but showed that the bound Ca2+ did not induce a major structural change in the pore. There was a modest main chain rearrangement, in which the backbone between residues W44 and Q48 (the parahelix, again) shifted an average of 0.8 Å toward the pore center; the biggest changes with Ca2+ coordination were side-chain reorientations. The Ca2+ was coordinated by the carboxylate of E47 and the carbonyl oxygen of G45 of one subunit, and the carboxylate of E42 in the adjacent subunit. The carboxylates of the glutamate residues act as bidentate ligands. The resulting hemispheric coordination of the Ca2+ leaves it exposed to the aqueous channel. Electrostatic and MD computations showed that the effect of this was to dramatically alter the electrostatic environment within the pore such that cations were effectively excluded, creating an electrostatic rather than steric barrier. Unsurprisingly, these structures answered several questions and generated several more: The site of Ca2+ coordination is within the parahelix region, at the TM1/EL1 border, the same region that previous studies indicated was intimately involved in loop gating and Ca2+ regulation. The structure solved was that of a junctional channel (two docked hemichannels), whereas nearly all the work on loop-gating and Ca2+ regulation was on hemichannels. One does not know whether or how docking of hemichannels may affect Ca2+ coordination or its consequences; definitive answers require analogous structural solutions of undocked hemichannels, which are no doubt being pursued. It should be mentioned, however, that MD simulations of the hemichannel portion of the Maeda et al. (2009) structure (thought to be of a docked hemichannel) showed almost no change in the structure or configurations of the extracellular loops (Kwon et al., 2011). In further examination of the effects of Ca2+, Lopez et al. (2016) published work in PNAS that explored the parahelix electrostatic network idea presented in Kwon et al. (2012) in the context of Ca2+ regulation of loop-gating. In an MD simulation, several Ca2+ ions were placed near the extracellular end of the channel, and the system was allowed to run for 50 ns. Even in this short simulation, interaction of the channel with two Ca2+ ions resulted in a number of rearrangements in the electrostatic network involving the parahelix and surrounding regions. These changes involved several subunits and extended deeper into the pore than the sites of Ca2+ coordination. The simulations suggested specific sites at which mutations might affect the process, which were experimentally tested. Some of the mutations produced kinetic changes and others eliminated Ca2+ dependence. Together, the results suggested that the effect of Ca2+ on hemichannel closing is via relative destabilization of the open state involving disruption of (likely electrostatic) interactions of specific residues. The data suggest that the electrostatic interactions of residues D50 and E47 in Cx26, and the corresponding residues D51 and E48 in Cx46, are major contributors to the stability of the closed state induced by interaction with Ca2+. Further studies were performed to assess whether the site of Ca2+ coordination was the physical gate. It was found that MTSES and Cd2+ had extracellular access to residue 45, when the Ca2+-activated gate was closed and ionic conduction eliminated. This suggests that the physical loop-gate is below position 45, and is not at the level of Ca2+ binding. In the loop-gating narrative thus far, one would be forgiven for thinking that Ca2+ regulation is nicely confined to the parahelix and nearby regions. However, it has been known for some time that several point mutations in the NT domain, at the other end of the channel, produce aberrant hemichannel activity. One of these mutations, N14K, was studied in detail by Sanchez et al. (2016) in JGP. This mutation essentially eliminated the voltage sensitivity of loop-gating at low Ca2+ with no effect on Vj-gating (or on unitary conductance). The results were interpreted to indicate that the mutation causes relative destabilization of the loop-gate closed state. Curiously, the channels remained normally sensitive to regulation by Ca2+. Based on the crystal structures, an interaction between N14K and a specific residue at the TM2/CL border (H100) was assessed. The double mutant N14K + H100A restored the voltage sensitivity of loop-gating. This suggested that the effects of the N14K mutation to eliminate the voltage sensitivity of loop-gating (at low Ca2+) and/or destabilize the loop-gate closed state were mediated by an interdomain interaction involving N14K and H100. The main import of this study is that it shows that loop-gating can be modulated by changes at the cytoplasmic end of the channel, and may involve NT–CL interactions. The former point is consistent with the study of Kwon et al. (2013) above suggesting that loop-gating narrows at the cytoplasmic end of the pore, and with the study of Rubinos et al. (2012) indicating that BQ+ affected loop-gating at a site near the cytoplasmic entrance. In a recent paper, García et al. (2018) studied the mutation G12R in Cx26, a different NT gain-of-function mutation. This mutation essentially eliminated gating at large positive voltages, which is mediated by the Vj-gating process in this channel. Loop-gating retained normal sensitivity to Ca2+ but accelerated the deactivation kinetics in Ca2+ and rendered them insensitive to Ca2+ (they normally increase as Ca2+ is reduced). Based on MD simulations of the mutant channel, an interaction between G12R and R99 at the TM2/CL border (adjacent to H100 studied in Sanchez et al. ) was investigated. The double mutant G12R + R99K did not appear to affect channel function, but the double mutant G12R + R99A recovered the wild-type single channel and macroscopic gating behavior at positive voltages. Curiously, the R99A mutation by itself appeared to increase gating at large positive voltages (it is unclear if this was Vj-gating). The inference drawn from the data is that interaction between G12R and R99 (perhaps via guanidinium group stacking) keeps the NT away from the mouth of the pore, thereby disabling Vj-gating. It is unclear why the R99K mutation would not disrupt that interaction. An effect on the deactivation kinetics of loop-gating was not evident for the G12R + R99 mutants, which suggests that the effects of G12R on Vj-gating and loop-gating kinetics are separable. This paper supports that position 12 is involved in Vj-gating and can affect the Ca2+ sensitivity of closing of the loop-gate, and suggests that NT–CL interactions can play a role in the former. In G12R, the full closures in single-channel records at positive voltages do not have the kinetic hallmarks of loop-gating transitions, which take place over tens of milliseconds; the transitions are rapid, characteristic of Vj-gating, but not to a substate. Charge changes in the NT up to position 10 have been shown to reverse the polarity of Vj-gating in Cx32 (Purnick et al., 2000); if the G12R mutation did so, it could explain the apparent absence of Vj-gating at large positive potentials. Because both Vj-gating and loop-gating operate on the same open state, a mutation that lowers the energy of the open state would shift the G-V relations of both loop-gating and Vj-gating to the right, but not necessarily to the same degree, because the dominant energy barrier to each closed state is likely different. The voltage dependence of loop-gating was not examined directly; such a rightward shift could contribute to the reduced macroscopic conductance of G12R relative to wild type at moderate positive potentials. In any case, the G12R mutation may affect several aspects of channel function, and its effects at large positive voltages may involve interaction with the CL, but how or why it exerts its other effects remain to be elucidated. The integrated structural and energetic complexities presented by this channel inspire both creativity and caution. Back to the future This article began with the basics of electrical coupling and what it might mean for signaling, mostly among neurons. I would like to end it with an article in JGP that shows just how far we have come in that regard. This is the work of Feliksas Bukauskas and colleagues (Maciunas et al., 2016). It pulls together all that has been learned about voltage-gated behavior in junctional channels and applies it to a 2-D network of coupled cells whose excitability is explicitly described by the Hodgkin–Huxley equations. The spread of excitation is interrogated for the effects of different patterns of intrinsic activity and junctional channels of different types. The modeling of the junctional channels includes the single-channel behavior of two loop-gates that fully close the channel and two Vj-gates that close the channel to a substate, in series in each junctional channel, the effects of each gate’s activity on the voltage sensed by the others, and the observed rectification of single hemichannel currents. This model was developed and validated over several iterations of increasing complexity and has continued to be refined in subsequent publications (Snipas et al., 2016, 2017). For all phenomena studied, the effects of greater or lesser degrees of junctional voltage dependence were examined, using Cx45 parameters for the former and Cx36 parameters for the latter, as well as different sites of coupling (somata–somata vs. dendro–dendritic). It was found that with action potential bursting there can be accumulating decreases in junctional conductance because of the voltage dependence of the junctions, which can have a multitude of specific effects on patterns of activity. The process by which phase-shifting effects caused by coupling can lead to firing synchrony when cells in the network have different intrinsic patterns of firing was examined. Determinants of action potential synchrony were analyzed for how they were affected by junctional conductance, size of firing clusters, intrinsic firing rates, etc. It was found that even a slight and local rectification of junctional channel I-V in the network could cause strong unidirectional action potential transmission, and eventually lead to reverberation of firing. The conditions for generation of reverberating action potentials were described, as were conditions for its initiation and termination. This paper provides quantitative validation and understanding of phenomena seen in early studies of electrical coupling, particularly regarding action potential propagation, phase shifting, development of synchrony, and the low levels of initial coupling needed for these effects (compare Watanabe and Bullock, 1960; Eckert, 1963; Bennett, 1966; Clapham et al., 1980; Rohr and Salzberg, 1994; Verheijck et al., 1998; Lin et al., 2005). An extensive discussion relates the findings to what is known about diverse coupled neuronal systems, drawing on the experimental work performed by the senior author and others over several decades. This paper reflects an integration of physiological and modeling insights derived from extensive work in experiment and theory, and insistence that each answer to the other, as stated at the beginning of this review. The physiology of electrical coupling of excitable cells has been quantitatively analyzed and extensively studied. The fundamental process is well understood, and the functional and dynamic roles of this coupling in various systems remain active areas of inquiry. At this point in time, understanding of the molecular and energetic mechanisms of gating, molecular permeation, and modulation of connexin channels is still incomplete. One hopes that with the application of increasingly sophisticated biophysical, structural, and computational approaches, further and unique insights will be gained. No doubt the answers for these unusual wide pores will be both intriguing and informative. By rights this article should be dedicated exclusively to my mentor Michael Bennett, but I am sure he will not mind sharing this appreciation with the late Feliksas Bukauskas. Mike had a seminal role in the development of the field, from its early days to the present, as it evolved across many disciplinary lines on its way from the ephapse to molecular thermodynamics. He provided to the field an expectation of high standards and thorough reasoning that could stand up to informed challenge. He attracted to the Dominic Purpura Department of Neuroscience at Albert Einstein College of Medicine many of the key contributors to the field (and to JGP), including David Spray, Vytas Verselis, Ted Bargiello, and Feliks Bukauskas. Mike has an exceedingly informed, deep, and broad biological perspective. He insists on quantitative rigor, but more strikingly, insightful qualitative rigor in exploring the natural world. Feliks, simply put, was one of the good guys. He was an extraordinary, creative, and productive scientist, in the best Old World tradition. Unfortunately, these qualities tend to be undervalued in today’s increasingly corporatist university culture. Feliks was unfailingly thoughtful and considerate, without an ounce of self promotion. He is greatly missed by all who knew him. See photo: Mike Bennett (left) and Feliks Bukauskas (right). Left photo from Pereda et al. (2013), reprinted with permission from Neuron. Right photo reproduced with permission of the Bukauskas family. This article has benefited from decades-long relationships with colleagues inside and outside the connexin field, of which there are too many to name. I am grateful for those relationships, which include many of the people mentioned in this article, particularly those investigators who shaped the field in the “early years,” when the gap junction world was new and connexins were undiscovered. These include (aside from Mike Bennett and the others at Einstein), in roughly chronological order, Ted Bullock, who taught my first neurophysiology class, Susumu Hagiwara, Roger Eckert, Harry Grundfest, Mahlon Kriebel, Joel Brown, Jean-Paul Revel, Dan Goodenough, Brian Salzberg, Bernie Gilula, Peter Brink, Bob DeHaan, Harry Fozzard, Rick Mathias, and Brian Payton (whom I never met, but with whom I had an entertaining email correspondence a few years ago). In reading the older literature, I was struck by how different scientific writing was then compared to now. It was more like narrative storytelling than the impersonal, nearly telegraphic exposition that dominates today. The former enabled the reader to be carried along in the thought processes of investigators as they puzzled their way through a problem. This window into the process of discovery and the development of insight was integral to the scientific discourse. One wonders if as a result, today’s younger scientific readers are missing something important about how to approach the surprising and the unknown. The writing of this article was partially supported by National Institutes of Health grant R01GM101950. The author declares no competing financial interests. Olaf S. Andersen served as editor. One may find it interesting to note that the author of this sentence, and the insightful article about electric fish that contains it, was not a scientist, but a female journalist soon to be a successful novelist, writing what was called “realistic fiction,” with titles such as “A Righteous Apostate,” “Basil Morton's Transgression,” and “A Modern Marriage.” The technique of replacing a damaged/nonconductive segment by an electrically conductive pathway was first published in JGP by Osterhout and Hill (1930), using the alga Nitella. The two terms “electrotonic synapse/junction” and “electrical synapse” do not denote a distinction. In early years, the former was promoted by Bennett in opposition to the term “ephapse” used by his postdoctoral mentor Grundfest and to make explicit that the transmission occurred by passive spread of potential across the junction (Bennett, 2002). A revealing narrative of how these observations came about is in Bennett (2000). “It [‘ephapse’] would therefore differ from the word ‘synapse’ whose meaning is narrower and designates surfaces of contact…anatomically differentiated and functionally specialized for the transmission of the liminal excitations from one element to the following in an irreciprocal direction.” The Katz and Schmitt (1940) article pointed out that such interactions “are entirely consistent with the ‘local circuit’ theory of nervous conduction as proposed by Hermann and Cremer, and recently confirmed by Hodgkin and others.” A key technical innovation required to make the measurements was use of “a pencil type coaxial superfine microelectrode,” consisting of two coaxial glass microelectrodes, one inside the other, in which the internal electrode could be advanced in front of the other so that resistance between the two tips separated by known distances could be recorded (Tomita and Kaneko, 1965). Consideration of the latter may have inspired an intriguing and unique analysis of the relations among shape, time course, and magnitude of potentials on action potential initiation (Bennett et al., 1970). It may interest some readers to know that the corresponding author of this paper, and of another paper the same year cited previously (Payton et al., 1969a), Brian Payton, went on to become well known in certain circles as a cultural twin of the Monty Python brand of satire, as applied to physiology. His most well-known production is the film “Proprioceptive Receptor Potentials of Oscillatory Form” (https://www.youtube.com/watch?v=NWvF4-1wztM), a collaboration with John Nicholls, as was “Goodbye Mr. Ipecac.” He was also responsible for the instructional film “An Artificial Lung and Thorax Model or the Smoking Condom” and a number of exciting and memorable “demonstrations” of key concepts in medical physiology for the benefit of students at the Medical School of Memorial University of Newfoundland. EIM was a bacterial protein shown in the early 1960s to impart a voltage-dependent macroscopic conductance to planar bilayers (Mueller et al., 1962). In 1969, JGP published stepwise increasing conductances produced by EIM in bilayers, providing clear evidence it was a channel and not a carrier (Bean et al., 1969). It remains unidentified but is probably a porin. At the time, it was actively debated—in the pages of JGP—whether the action potential was produced by a single type of channel with voltage-driven changes in selectivity (Mullins, 1959, 1960, 1968a,b; Sjodin and Mullins, 1967; Narahashi and Moore, 1968) and/or whether the voltage changes of the action potential resulted from a voltage-driven ion-exchange process within a fundamentally nonselective but charged membrane (Tasaki and Hagiwara, 1957; Tasaki, 1963; Tasaki et al., 1965, 1967).

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MAEd - Course Descriptions EDUC 510 – Current Issues in Curriculum, Instruction, & Assessment (3) Course focuses on important Issues in designing, implementing, and managing school curricula. Candidates learn to collaborate with colleagues and stakeholders to design standards-based curricula reflecting best practices in culturally diverse and differentiated classrooms. Teaching/learning models that promote critical and creative thinking and metacognition are employed to help candidates become reflective practitioners. EDUC 511 – Practicum in Curriculum, Instruction, & Assessment (1) A first field experience course to observe and interact in educational environments that complement the MAEd summer course sequence. EDUC 520 – Foundations of the Teaching Profession (3) Course invites candidates to explore the historical, philosophical, cultural, and educational and social context of schools in our diverse society, culminating in the development of a personal philosophy of education. Candidates focus on interdisciplinary perspectives on educational and social issues to guide reflective, professional practice. EDUC 530: Cognition and Child and Adolescent Development (3) Course examines psychological theories and research findings dealing with child and adolescent development and learning. Special emphasis is placed upon the ways in which theoretical and empirical findings in educational, developmental, and cognitive psychology contribute to enhancing teaching and learning. EDUC 535 – Characteristics of & Adaptations for Exceptional Student Populations (3) Addresses academic and social learning needs of exceptional student populations in secondary level classrooms and appropriate interventions to meet these needs. This course prepares secondary education teachers to develop differentiated instruction for the individual learning needs of students in secondary and PreK-12 classrooms who have disabilities, who are at-risk for school failure, or who are gifted/talented learners, as well as students who are culturally and linguistically diverse. EDUC 540 – Classroom and Behavior Management (3) Provides behavior management content and skills that create positive classroom behavioral supports through strategies, effective teacher behaviors, and student assessments and interventions. Candidates develop an evidence-based, classroom management philosophy. Field experiences provide authentic classroom ontexts for candidates to reflect on implementation of evidence-based, practical management skills related to their philosophy. EDUC 550 – Content Reading and Writing Across the Curriculum (3) Candidates will engage in the study of processes related to reading and learning from content area texts and related media, and the instructional practices and tools which best enable content learners to become efficient, independent learners. Candidates will develop an understanding of the roles of reading, writing, speaking, and listening across content disciplines. Reading assessment and instructional strategies for students who have reading difficulties, including dyslexia, will be explored. EDUC 610 – Methods, Media, & Materials for Secondary Education (3) An intensive classroom and field-based course designed to provide students with opportunities to develop and apply skills and knowledge about teaching and learning. Guided by University faculty and a public-school mentor, candidates learn appropriate methodologies for teaching diverse learners. Following initial course meetings, candidates will be placed in appropriate sections of this course based on their content area. EDUC 611 – Internship in Secondary Education (1) Semester-long course designed to provide prospective secondary and PK-12 teachers with opportunities to experience and reflect on the practices of teaching their content area in school and community settings. [Fall semester; middle school placement 6-12, elementary for preK-12] EDUC 620 – Research Methods in Education (3) Candidates examine and learn the methods and techniques employed in education research. Emphasis is placed on understanding the research literature, which forms the basis of professional education. Course includes considerable study of qualitative methods, and emphasizes selected statistical methods used as tools in research, data analysis, and the field of educational tests and measurement. EDUC 621 - Collaboration with Communities, Families, and School Personnel (2) Course designed to develop specific professional skills to facilitate effective communication and collaboration with families, school personnel, and representatives of community agencies who are involved in the development, implementation, and monitoring of appropriate programs for school-age learners. Offered in January Term. EDUC 625 – Creating a Culture of Evidence-based Learning (2) Candidates will develop competence in constructing and employing valid and reliable assessments of student achievement at the classroom level; candidates will develop and implement an impact study during the supervised teaching semester that utilizes the strategies of action-based research. EDUC 690 – Internship in Supervised Teaching (8) A 10-12 week intensive, student teaching field experience in partner professional-development schools. Interns apply methods, strategies, and technological tools to engage culturally diverse students in a responsive and effective manner. Corequisite: EDUC 691– Internship Seminar. EDUC 691 – Internship Seminar (2) Course provides student teachers with opportunities to refine teaching and learning through analysis, reflection, and discussion of their own behavior as teachers and the behaviors of teachers, students, and other school personnel. Corequisite EDUC 690 –Internship in Supervised Teaching.

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Are you anxious about the stunted growth of classic tropical Tomatoes? You may have crashed to provide favorable conditions for them. Let me provide you with a few tips to speed up Tomato growth. Table of Contents Show - How to Speed up Tomato Plant Growth with Tips? - From Editorial Team How to Speed up Tomato Plant Growth with Tips? Tomatoes favor a warm and humid environment, with humidity between 65 and 75%. On top of that, here are some other great tips that support Tomato’s growth speed. 1. Heat the Soil For the seeds of tropical plants like Tomatoes, the seed germination rate is higher in warm soils. However, the warmth of the soil entirely depends on the weather and the soil type. Seeds of Tomatoes germinate well in soil temperature of 65-85ºF, so check the soil with a Soil Thermometer before sowing. In case of seeds are sown in wet or cold soil, the chance of rotting seeds would be high. You can heat the soil by various below-mentioned methods: - Cover the soil with polythene or mulch fabric to keep it warm during winter. During summer, remove the covering to provide direct sunlight to the soil. - You can use Cloches two to three weeks before sowing. They are used for covering the soil to trap the temperature within the soil. - Mulch prevents the soil water from evaporation and keeps the soil warm. Moreover, mulching keeps the soil warm during winter and cool during the summer. 2. Temperature & Sunlight Make sure you choose the sunniest part of your house to place the tomato plant. Direct sunlight is always the best choice, rather than placing it in the shade. Keeping your tomato plant on your house’s south side makes a big difference. Terraces, where there are no shade interferences, are also good options. Tomatoes favor a temperature between 15 and 32°C for fruitful growth. 3. Spacing and Root Depth Low spacing brings about improper distribution of nutrients and water among the plants. Moreover, inappropriate spacing leads to stunted growth, reduced yield, and diminished overall plant performance. The perfect spacing for Tomatoes would be between 24 and 36 inches. Also, adequate spacing between plants is a remedy for outspreading microbial diseases. Seeds are sown 8-12 inches deep to support healthy root growths. On top of that, mix the soil with organic perlite to improve soil aeration. 4. Nutrient Requirements Usually, Tomatoes thrive well in soil rich in micronutrients counting Phosphorus, Potassium, and Calcium. These nutrients play a significant role in plants’ growth, increased root growth, enlarged stem strength, and improved crop quality. It would be best to fetch optimum nutrients to the soil, but excessive is also not good. In case of deficiency, it can be detected through an indication of yellow leaves of the plant. The most common lacking nutrient is nitrogen. However, too much nitrogen can again cause ample green growth at the cost of fruits and flowers. Moreover, supply your plants with Nitrogen fertilizers. Apply a balanced ratio of NPK in the ratio of 10:10:10. Also, they must be fertilized immediately after planting and just before fruiting. Not the garbage, but the waste composts extracted from eggshells, onion skins, potato skins, banana peel, etc., help transport the nutrient properly. 5. Transplant Shock Transplant shock is a concern many of us do not pay much attention to. Instead, we get excited about bringing a plant to our house and directly cultivating it without adjusting them to the sudden temperature change. The changing environment can differ in the amount of light, air, and heat. Hence, this gives shock the plants. Try to acclimatize them firstly to the outdoor atmosphere to speed up Tomato growth. How to do it? - Firstly, try to keep the plant outside for a few hours every day and then bring it back. Keep doing this for a week. - Keep the plant away from harsh wind, rain, and direct sunlight while shifting outside. - Finally, you can transplant it into your garden or outdoor pot once it is hardened. This eliminates the shudder effect on the plant. 6. Watering Frequency DO NOT Overwater Don’t overdo your plant with excessive kindness! Overwatering is the most common issue for slowing the growth of Tomato plants. It usually instigates in heavy clay soil, which does not drain well, leading to Root Rot. Sandy or loamy soil is suitable for planting Tomatoes as it drains quickly. Too much watering generates moisture in the soil for a long time, leaving no space for air and suffocating the plant to breathe. Also, it gets difficult for the plant to absorb the required nutrients and water. This ultimately stops the plants’ growth. Be Careful: Even though the soil is moist, the plant may still look underwater sometimes. You can use your fingers to feel the soil a few inches in depth. Henceforth, watering the plant is recommended if it feels dry. DO NOT Underwater Tomato plants need plenty of optimum water to grow. Nevertheless, it should be the right amount. Too much or too little watering at any stage of plant growth leads to slow development. The plants are deep-rooted, with 2 feet or more inside the ground. As a result, they prefer receiving enough water to soak thoroughly into the ground and roots. You will be able to see some indications in case of underwater: The dryness of the soil causes floppy and yellow leaves, but if water is on time, it revives back rapidly again. How do you water your plant to speed up Tomato growth? - Water 1-2 inches of water per week in the Tomato plants. - Smear the water directly into the soil around the base of the plant with a garden pipe. - Water the plants in the morning if you are using an overhead sprinkler. This helps to lessen foliar disease problems. 7. Fast-growing Varieties Several varieties of Tomatoes speed up the Tomato growth to different maturity extensions. The most common type of Tomato is “Fourth of July Tomatoes.” As much as the name defines, it ripens within the fourth of July. They are easy to plant and grow. Early girl Tomatoes produce fruit and flowers until they are destroyed by external factors or frost. They are inexhaustible, reliable, and harvested within 50-62 days after transplantation. It is an excellent early yield, the same as its name. These varieties continue ripening even after the harvest. Whereas heirloom Tomatoes take a bit longer than 65-75 days to rip, beefsteak Tomatoes take much longer. 8. Pests and Pathogens The prevailing obstacles during the plant’s growth drag the time of receiving our fully ripe Tomatoes. Fungal diseases are caused due to the bottom leaves of the plant. The reason behind the infestation of pests and pathogens on these leaves is their presence near the ground. Likewise, soilborne pathogens and pests directly get to them. These lowermost leaves are old and receive little sunlight exposure and airflow. Tomatoes’ most prevalent pests and pathogens are Verticillium, Fusarium, Alternaria, Aphids, and Spider mites. Compost tea is also effective in managing the fungal disease of the plant. You can spray it weekly to speed up the Tomato growth. 9. Pruning of Tomatoes You can find small leaves in between the branches of Tomato plants. They will be popping up unnecessarily, absorbing the plant’s and fruit’s nutrients. These side vines suck up the energy of the whole plant, leading to small Tomatoes rather than big plump ones. Though the vines can bear fruit later on, the compromise will be on Quantity over Quality. Pruning is significant for bigger, redder, early-ripening Tomatoes. However, you should not do too much trimming. It leads to less sweet Tomatoes ripening. This is so because the leaves are photosynthesizing in generating sugar, giving flavors to your fruits. 10. Trellising the Tomatoes Trellis supports your Tomato plant by promoting good air circulation, strengthening the stems, and preventing the outspread of diseases. It works perfectly for garden Tomatoes by providing more sunlight, ensuring that the trellis does not disturb the sunlight exposure to other plants. Additionally, a 4 feet tall Tomato trellis gives the best result. Tomato plants can get infected by pests and pathogens when coming in contact with the ground, so trellises prevent them from the problem. Moreover, you can use various methods to trellis Tomato. - Place a Tomato cage of about 4 feet high immediately after pruning. It prevents pests and other herbivores. - Trellis Net would be the best option to cover the entire field if you have a huge Tomato field. - The stake would be an excellent option to trellis individual Tomato plants. 11. Grow in Containers You can plant your Tomato plant in containers and place it anywhere. Add a layer of mulch immediately after planting to prevent the escape of moisture from the soil. Growing in containers speeds up Tomato growth by preventing leaching out the nutrients from the soil. Moreover, the growth of weeds can be prevented in containers, which implies the nutrient intake by Tomatoes alone. Water directly in the soil since moisture invites fungi on the aerial plant parts. Consider the video given below to know tricks to speed up Tomato growth. From Editorial Team Despite proper care and nourishment, it isn’t delightful when our Tomatoes grow slowly. However, Tomato propagation is undemanding; just take cuttings from the high-yielding and fast-growing varieties, and the new plant will retain all characteristics of the mother plant. On top of that, Tomatoes don’t like the wetness of their leaves, so avoid overwatering them. Prolonged wetness will invite fungal infection on them.

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On-grid solar systems are the most popular solar setup in the country, and for good reason. Here’s how a typical home is powered by the system over the course of a day, beginning at night when everyone is asleep. Evening: There’s no solar, so the home’s energy needs are powered by electricity imported by the grid. However, little energy is used besides power required for the refrigerator, chest freezer, phone chargers, and maybe the heating or cooling system of the house. Morning: As the family wakes up and prepares for their day, energy use spikes with demand for the hot water heater for showers, hair dryers, the microwave, and other kitchen appliances. While solar does kick in, the sun is not strong yet so grid import continues to meet the demand. Midday: The sun is high in the sky and the solar energy system reaches maximum output. However, energy usage is still low since the residents are out working or at school, so the excess energy generated is exported to the grid. This will result in a credit for the homeowner on their electricity bill. In states that permit net metering, the homeowner can sell this excess energy at the same rate at which they bought it. Late Afternoon: The solar system continues to export energy to the grid. Early Evening: After sunset, there is no additional solar energy generated, and usage is up as the family returns home to make dinner, watch TV, etc. Import from the grid rises to meet this increased demand. However, the energy imported from the grid is offset by the excess energy produced during the day. With a properly designed system, on-grid solar energy can achieve a 100 percent offset of the home’s power requirements, resulting in a zero net usage charge. Ready to go solar? Call Ion Solar Pros today at 866-582-0000.

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Garden resources and information including hardiness zone maps, waste disposal sites, pesticide information, local food, and much more. Calculators – soil, mulch, compost Caretaking – maybe your can’t purchase your own piece of land quite yet. Check for properties that need caretakers. Compost –Find a composting facility – check my class info for classes on composting Edibles Native to the Americas Emergency Preparedness – We can only survive so long without food and water. Food and water are becoming more of a concern with toxins in the environment, natural disasters, transportation issues, etc. This resource has a list for information and finding emergency preparedness events in your area. Extension Service – Find your county Cooperative Extension Service- pest and plant identification, soil testing, pruning instruction, fact sheets Find Locally Grown Food – Community Gardens, Farmer’s Markets, Pick Your Own, CSAs Frost Dates – find out your last average frost date Gardening in Unconventional Ways and Places Gardens To Visit – botanical gardens, garden tours, etc Hardiness Zones/Frost Free/Climate Zones/Drought Monitor – find your climate zone, etc Hazardous Waste Disposal Sites – where to dispose of hazardous waste Heirloom and Open-Pollinated Seeds – Sources Herbs – herb information including Cooking, Growing, Associations, Blogs, Magazines Organic Lawn Care – how to care for your lawn with an emphasis on organic lawn care Organically and Sustainably Grown Flowers - find flowers and florists Pesticides and Herbicides – information and alternatives Square Foot Gardening or Square Foot Gardening Foundation official site Things to Do in Utah – parks, field trips, events, and more Wildlife Rehabilitators – if you found an injured wild bird or other injured wildlife this is who to call Work on an Organic Farm – World Wide Opportunities on Organic Farms – WWOOF – part of a worldwide effort to link visitors with organic farmers, promote an educational exchange, and build a global community conscious of ecological farming practices. Yardsharing – Don’t have a yard or want to share your yard with someone else? Learn about organic gardening, edible landscaping, composting, herb growing, organic lawn care, wild edible plants and more through my coaching and classes.

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Can medical cannabis help patients relieve symptoms of oral ulcers? Find out below. What are ulcers? Ulcers are open sores that can occur on internal and external parts of the body. They can be mild or severe. An ulcer is a type of crater-like wound and can develop outside or inside the body. Ulcers develop when tissue erodes, which has a variety of causes, but luckily there are successful treatment options. Ulcer symptoms can include pain, nausea, heartburn, or itching, depending on the affected area. Treatment may consist of acid reducers, antibiotics, antiviral drugs, lifestyle changes, and in extreme cases, surgery. What are oral ulcers? Oral or Mouth ulcers are small lesions that develop in your Mouth. The sores may be painful and swollen. Treatment for mouth ulcers may include: - topical corticosteroids - anti-inflammatory medications - antibiotic mouthwash - avoiding certain foods - pain relievers The causes of mouth ulcers include: - trauma to the Mouth - cuts or burns from eating - a food allergy - hormonal changes - an iron or vitamin B12 deficiency - a weakened immune system - Crohn’s disease or celiac disease - oral cancer Other Types of Ulcers There are seven primary types of ulcers: arterial, diabetic foot, esophageal, genital, Mouth, peptic, and venous. Let’s learn about their causes, symptoms, and treatments. The causes of arterial ulcers include: - high blood pressure - Minor injuries that heal slowly - kidney failure Arterial ulcers develop on the lower legs, feet, or toes and are generally brown, black, yellow, or gray. These ulcers don’t bleed but are very painful. If high blood pressure causes an arterial ulcer, you may need to make lifestyle and diet changes. Your doctor may prescribe oral antibiotics if the wound shows signs of an infection, such as swelling or discharge. The leading causes of diabetic foot ulcers include: - inadequate foot care - Peripheral vascular disease - high or low blood sugar levels A diabetic foot ulcer will appear as an open wound, commonly on the bottom of your foot. The injury may look like this: - odor filled drainage - tissue discoloration - continuous pain Doctors typically prescribe antibiotics to treat diabetic foot ulcers. They may also need surgery to address restricted blood flow to the area or remove any calluses and dead or infected tissue. The most common cause of esophageal ulcers is acid reflux. This condition occurs when stomach acid backs up into the esophagus and wears away the lining of the esophagus. The symptoms of esophageal ulcers include: - difficulty swallowing - chest pain - excessive saliva If you have an ulcer caused by GERD, your doctor will prescribe PPIs or H2 blockers that reduce the amount of acid the stomach produces. If an infection causes your ulcer, a doctor may prescribe antibiotics or antiviral medications. Making lifestyle changes, such as quitting smoking and drinking fewer acid-rich liquids, may benefit esophageal ulcers. The leading cause of genital ulcers are sexually transmitted infections (STIs), including: - herpes simplex virus Another rare cause of genital ulcers is Behçet’s inflammatory syndrome. The symptoms of genital ulcers will vary depending on which STI caused them, but they can cause illness, fever, and itching. Doctors may prescribe antiviral medications, antibiotics, or pain relievers. There are two main types of peptic ulcers. - Gastric ulcers-stomach - Duodenal ulcers-upper part of the small intestine There are two leading causes of peptic ulcers. - Bacterial infection: Infection that can cause inflammation and damage your stomach linings. - Nonsteroidal anti-inflammatory drugs (NSAIDs): NSAIDs, including aspirin and ibuprofen, are typically used to treat pain. Some common symptoms of peptic ulcers include: - stomach pain Peptic ulcers can bleed, which can be severe. If an ulcer is bleeding rapidly, symptoms can include the following: - black, sticky stool - bloody stool - bloody vomit Treatments for peptic ulcers include: - Proton pump inhibitors (PPIs): PPIs block acid production in your stomach, allowing the ulcers to heal. - Antibiotics: If H. pylori caused your ulcer, you need antibiotics to eliminate the infection. - NSAID cessation: If NSAID causes the ulcer, talk with your doctor about alternative pain medications. Two conditions that affect your veins cause venous ulcers. - Chronic venous insufficiency: The leg veins are not effectively sending blood to the heart - Venous hypertension: There is increased pressure in the veins Venous ulcers are irregular, shallow open wounds on the legs that form over the ankle and lower leg bones. Symptoms of venous ulcers include: - brown discharge - itchy skin - varicose veins - spider veins Treatment for venous ulcers includes: - Compression therapy involves using hosiery or bandages to apply gentle pressure to the leg, promoting better blood flow. - Wound care: Keeping the wound clean and avoiding infection is essential to promote healing Can Medical Marijuana Help? The cannabinoids found in the cannabis plant can activate the endocannabinoid system in the human body and may help many chronic issues, including oral ulcers. Cannabis activates CB1 receptors in the central nervous system and CB2 receptors in organs, muscles, and tissues. Cannabinoids can directly influence our ability to maintain homeostasis. A recent study followed thirty patients with Crohn’s and recorded their disease severity before and after cannabis use. Crohn’s is a known cause of oral ulcers. Researchers found that many users could decrease inflammation medications, including steroids. Approximately three-fourths of participants said they experienced reduced symptoms. Another study discusses the cannabis plant’s potential for helping to relieve digestive inflammation by activating the endocannabinoid system, a fat-based system of self-made neurotransmitters. When CB2 receptors line the intestinal tissue, a P-glycoprotein transmitter will help decrease the body’s inflammatory and autoimmune responses. Recent studies on the endocannabinoid system suggest that many patients with oral ulcers may have clinical endocannabinoid deficiency (CED). An ongoing theory is that these deficiencies could come from genetics, injuries, and diseases. Research on obese mice has proven a connection between the microbiome, gut, and brain. The microbiome of the small intestine, large intestine, and brain health are crucial for oral ulcer patients. The obese mice given doses of THC had improved microflora in the gut compared to mice who received the placebo, which could help with the autoimmune responses within the body. MMJ Patients with Oral Ulcers may see the following benefits: - Pain management improvement - Decreased anxiety and depression - Appetite Increase and regulation - Reduced need for regular steroid use Medical marijuana is commonly found to possess significant anti-inflammatory and antioxidant properties, which can help with chronic pain management reasonably quickly. Cannabinoid receptors bind to the brain and peripheral nerve cells and help regulate how you see and feel the pain to reduce symptoms. Medical cannabis, therefore, as opposed to other drugs, appears to be an excellent alternative to treat and manage pain due to inflammation. Recent studies from medicine and health sciences professionals suggest that certain cannabis products may effectively treat an overactive immune system. It can connect with the cannabinoid receptors of the body to combat the proinflammatory t-cell responses needed. It has been used to treat rare skin conditions, Crohn’s disease, neuropathic pain, particularly autoimmune disease, inflammatory bowel disease, acute psychosocial stress, and many other conditions. Maintaining homeostasis in the body will make you less likely to develop future oral ulcers. We recommend discussing MMJ options for oral ulcers with your doctor if you are looking for a new treatment plan. Last Updated: February 21, 2023 Get Your Medical Card Connect with a licensed physician online in minutes Table of Contents How to Make Edibles Are you looking to learn how to make your own delicious edibles? Look no further! Learn the basics of making edibles, from ingredients and recipes to tips on dosage and storage. Does Weed Make You Lose Weight? We all know someone who seems to be able to eat whatever they want and not gain a pound. But could their secret be marijuana? How Long Does Marijuana Stay in Your System Wondering how long marijuana stays in your system? Find out here! Discover the duration of marijuana’s effects and learn how you can rid your body of the substance more quickly.

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late 1800s-early 1900s Wood, organic materials (including resin and soil), plant fiber, and glass beads Overall: 22.4 x 10.7 x 12.4 cm (8 13/16 x 4 3/16 x 4 7/8 in.) Gift of Mr. and Mrs. Alvin N. Haas 1974.212 The substances contained in its cloth-covered cranial cavity indicate that this half-figure belongs to the broad category of charms or “power objects” that the Luba call mankishi. It was used by a ritual expert and functioned in a variety of rituals dealing with healing, protection, divination, or jurisdiction. Often such power figures were carved by the ritual experts rather than by professional artists. The information about this object, including provenance, may not be currently accurate. If you notice a mistake or have additional information about this object, please email [email protected]. To request more information about this object, study images, or bibliography, contact the Ingalls Library Reference Desk. All images and data available through Open Access can be downloaded for free. For images not available through Open Access, a detail image, or any image with a color bar, request a digital file from Image Services.

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The Irish Question In the debate around proposals to change to self-identification under the GRA, people often refer to the other countries where this has been adopted “with no problems”. In particular, Ireland is cited as a good example. However, there seems to be a misunderstanding about the way Irish equality law works and a lack of knowledge of the legal exceptions and caveats which mean Ireland does not, in fact or practice, have a simple self-declaratory system. To claim it does misrepresents the situation there. The law was changed in 2015 and was due for an audit this Summer. No audit of its impact has yet been published. The Irish law is outlined here and must be considered in its interplay with other different Irish statutes. The Irish Gender Recognition Act allows self-ID but is reliant on a quasi-judicial exercise of ministerial competence – in other words, a gatekeeper. This is an administrative process which includes: - – mechanisms to require information and overturn administrative decisions; - – an exclusion for married people, with or without spousal consent; - – the exercising of discretions which allow, for example, housing of prisoners in the estate relating to their sex. ‘Gender’ is protected by the prohibition of discrimination in the Irish Equal Status Act. The Irish Equal Status Act entitles equal treatment regardless of ‘gender’, which in Irish law means whether you are a man, a woman or a transgender person, in the circumstances of: - buying or selling goods that are available to the public or a section of the pub - using or providing services that are available to the public or a section of the public; - providing or using accommodation; - attending or managing a pre-school, school, college or other educational establishment. - People can be treated differently in relation to cosmetic services that involve physical contact – for instance, hairdressing, body waxing, and so on; - People can also be treated differently if there is a risk that you could be embarrassed because of a lack of privacy; - People can be treated differently at sporting events if the differences are reasonably necessary and relevant and, in relation to educational establishments, having regard to the nature of the facilities or events. - Insurance companies may differently decide how much to charge people for annuities, pensions, insurance policies and so on, based on different risk assessments, if the differences are based on proper research and statistics (although EU law proscribes the limit of this exemption in so far as men and women must be treated the same). - People can be treated differently if it’s necessary for a drama or entertainment production. - A person making a will or a gift is entitled to choose whoever they want to benefit. - Services may promote or favour the special interests of one person or group over another. - Goods and services which can be reasonably considered as being suitable only for the special needs of certain people may be provided. - In shared accommodation people may be treated differently in relation to personal privacy where lack of privacy might cause embarrassment. - When the accommodation is provided by a person in their private home, if for example a home-owner took in a lodger. - When housing is provided by or on behalf of the Minister for Justice and Equality. - When the accommodation is reserved for a particular category of people. - Single sex schools are allowed. - Institutions providing religious training to ministers of a particular religion may admit students of only one ‘gender’. - Third-level or adult education institutions may treat students differently by way of traditional university sponsorships, scholarships, bursaries, and so on. - Clubs may be established for a particular group of people. - Any person can be refused goods, services or accommodation if an experienced provider believes that there would be a substantial risk of criminal behaviour or disorderly conduct by that person, including abusing the service and causing trouble by being abusive or aggressive. - A person may be treated differently because of a doctor’s clinical judgement in relation to the person’s medical condition. A person may be differently in circumstances where they are not capable of entering into a contract or giving informed consent. Please make sure you have completed your response in the GRA Consultation. Our guidance is here 8th October 2018 We believe that it is important to share a range of viewpoints on women’s rights and advancement from different perspectives. WPUK does not necessarily agree or endorse all the views that we share.

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Effect of Dead Space on Gain and Noise of Double-Carrier-Multiplication Avalanche Photodiodes Institute of Electrical and Electronics Engineers IEEE Transactions on Electron Devices The effect of dead space on the statistics of the gain in a double-carrier-multiplication avalanche photodiode (APD) is determined using a recurrence method. The dead space is the minimum distance that a newly generated carrier must travel in order to acquire sufficient energy to become capable of causing an impact ionization. Recurrence equations are derived for the first moment, the second moment, and the probability distribution function of two random variables that are related, in a deterministic way, to the random gain of the APD. These equations are solved numerically to produce the mean gain and the excess noise factor. The presence of dead space reduces both the mean gain and the excess noise factor of the device. This may have a beneficial effect on the performance of the detector when used in optical receivers with photon noise and circuit noise. Hayat, Majeed M.; Saleh, B.E.A; and Teich, Malvin Carl, "Effect of Dead Space on Gain and Noise of Double-Carrier-Multiplication Avalanche Photodiodes" (1992). Civil and Environmental Engineering Faculty Research and Publications. 321. IEEE Transactions on Electron Devices, Vol. 39, No. 3 (March 1992): 546-552. DOI. Majeed M. Hayat was affiliated with University of Wisconsin, Madison at the time of publication.

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NASA’s 38-year-old dead satellite has returned to Earth without incident. The Defense Department has confirmed that the Earth Radiation Budget Satellite (ERBS) reentered the atmosphere off the Alaskan coast at 11:04PM Eastern on January 8th. There are no reports of damage or injuries, according to the Associated Press. That isn’t surprising when NASA said there was a 1-in-9,400 chance of someone getting hurt, but it’s notable when officials said there was a possibility of some parts surviving the plunge. ERBS had a storied life. It travelled to aboard Space Shuttle Challenger in 1984, and pioneering woman astronaut Sally Ride placed it in orbit using the robotic Canadarm. Crewmate Kathryn Sullivan performed the first spacewalk by an American woman during that mission. The satellite was only expected to collect ozone data for two years, but was only retired in 2005 — over two decades later. The vehicle helped scientists understand how Earth absorbs and radiates solar energy.

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Stodmarsh Update: “There is no prospect of the nutrients disappearing in the next 5-year period” “For the foresseable future, it looks like nutrient neutrality is here to stay. There is no prospect of the nutrients disappearing in the next 5-year period” Stodmarsh is a series of lakes; which is an Internationally designated wetland in unfavourable condition. Some of the lakes are suffering from poor water quality. Nutrient pollution (Nitrates & Phosphates) in the Stour catchment area in Kent are having an adverse effect on Stodmarsh causing eutrophication and algae blooms, which are harming the delicate Stodmarsh ecosystems. Stodmarsh is protected under the The Conservation of Habitats and Species Regulations 2017 Natural England first flagged this issue in July 2020 and ever since it has meant that Local Planning Authorities must carefully consider the impacts of any new developments across six districts which effect the habitat sites at Stodmarsh, and whether those impacts may have an adverse effect on the integrity of the habitat site which requires mitigation. At present, circa 30,000 homes are affected by the nitrate and phosphate issue at Stodmarsh The impact of the nutrient issue caused by too much nitrate and phosphate in the water has meant that some local planning authorities – Ashford, Dover, Canterbury, Folkestone & Hythe, Maidstone & Swale, are struggling to meet their housing land supply targets. Put simply it means some developments ; which are in the districts mentioned, but outside the Stodmarsh catchment area, are able to get planning persmission through appeals. However, those within the catchment area, its a different matter and it is impacting on some council’s local plans and housing numbers. On 6 September 22, Southern Water and Natural England officers met with the Chief Planners of Ashford, Canterbury, Dover, Folkestone and Hythe, Maidstone and officers from Kent County Council to discuss Stodmarsh Nutrient Neutrality. This follows Natural England advice on nutrient neutrality which stymies district councils issuing new planning applications. This is significantly impacting construction sector profits, as the number of houses being built is much lower than anticipated. Through Southern Water’s treatment of water, phosphorus and nitrogen are added to the river. There are other sources (outside Southern Water’s control) which also add nitrogen and phosphorous to the river (e.g., nitrate run-off from the soil due to agricultural use of fertilisers, and groundwater inflow). However, Southern Water’s treatment works are the main contributor of phosphorus to the water (the firm is probably responsible for circa 90% of the phosphorus introduce to the catchment). The requirement on Southern Water is only to reduce their portion according to their ‘fair share’. As they are not the sole contributor, Southern Water do not have to reduce theirs until the level of nutrients becomes sustainable, rather they only must reduce their portion of the total level of what would be sustainable. One issue is that the water company is only expected to use something known as ‘Best Available Technology’ or ‘Technical Achievable Limit’. This means that they cannot spend on expensive innovative technology, as ultimately all these costs are funded by the bill payers. There is a limit on what they can do. Unsurprisingly Southern Water has found for phosphorus, they cannot achieve their fair share of what the acceptable limit for phosphorus is just through using best available technology. They can achieve it, but only by going beyond best available technology, and the costs will be much higher. Southern Water estimate that the scale of investment needed to reach technical achievable limits with best available technology is circa £180m in the next 5 year Annual Maintenance Programme period – 2025/30. For nitrogen, Southern Water contribute a much smaller portion. Southern Water unsurprisingly cannot achieve their fair share of the nitrogen in any way, even if they go beyond using best available technology. Consequently, for the foreseeable future, it looks like nutrient neutrality is here to stay. There is no prospect of the nutrients disappearing in the next 5-year period. In short Stodmarsh will continue to have nitrates and phosphates pumped into an internationally recognised wetland, supposedly protected by the Habitats Regulations. The other issue covered in the workshop of 6th September was the broad strategy. Large sites are going to have to have treatment works on site probably discharging to a wetland. For most large sites, this should be enough to achieve nutrient neutrality. Smaller sites will not be able to do this, as they will not be able to meet the space requirements, and bespoke treatment works only function at a certain scale. It is not practical or economical, so for smaller sites, the strategy is exploring off-site provision. The main role of KCC as the catchment facilitator is to co-ordinate that piece of work. KCC is looking at various options, the principal option is probably wetlands; there are other options though, such as retrofitting existing housing with low-flow technology that is in the control of the district and borough (social housing). There are also some land-use changes that can help, such as converting agricultural land into woodlands or parklands. Also, Natural England provided more updates on the funding which the Government announced in March & July. Natural England said that the competitive funding will not be close to that sum needed; it will be a much smaller pot. Natural England did say that the catchments will be prioritised based on the need, and the Stour is probably one of the highest because of the scale of developments affected (at present, circa 30,000 homes are affected by this issue). Dover has recently announced that it is no longer required to achieve nutrient neutrality. Kent County Council is checking this with Natural England. Dover District Council has completed a study looking at the Dambridge treatment works (in Wingham), which discharges into one of the tributaries that goes into the downstream catchment for Stodmarsh. Dover District Council has demonstrated that the nutrients introduced there have an insignificant effect at Stodmarsh, which means anything connected to Dambridge no longer needs to reach nutrient neutrality. Kent County Council is waiting for Natural England to formally say what implications this will have for the rest of the downstream catchment. It is not clear yet if nutrient neutrality issues have completely gone away for this area, or not. However, the upstream area would still be affected by the issue. Local councils are working together on producing a catchment strategy and consultants have been appointed to lead on this; together they’ll be working out the off-site requirement for mitigation based on the principle that larger sites will have on-site treatment works; hoping to receive more information about the competitive bidding process from Natural England so the councils can start putting a collective bid together; work will continue to progress looking at off-site wetland mitigation; and will look at other offsetting opportunities. Once off-site mitigation is set-up, a credit mechanism will have to be established, to give developers a way of accessing and buying the credits, so they can evidence as part of their planning application that they have offset their nutrients. So there you have it, Southern Water pleading poverty, while continuing to pollute the environment (which sounds familiar) circa 30,000 homes being held up making a bad situation worse, rents being driven up, and Stodmarsh left to wallow in eutrophication and algae blooms for at least the next five years. The Shepway Vox Team Not owned by Hedgefunds or Barons The South East is already over populated but councils and developers want to encourage more people in – at the expense of locals. Build more homes north and west of London, with building in the South East being for local demand. This is good news unless your name is Quinn or Monk ‘This is good news unless your name is Quinn or Monk’. So you don’t live in a house, built by someone, then. So many NIMBY’s occupying housing want to stop others having the same life.

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Overview of Vedic Literature The Vedic literature starts with the discovery that Veda (= ultimate knowing) can be localized in our own consciousness and presents programs and methods for maximum inner growth: Upanga’s, Upaveda’s and Smriti’s. The wisdom of Yoga and Ayurveda are famous parts of these scriptures and are presented by Narada Kush in consultations, workshops and trainings. The centre of the Vedic literature is set up by the four Veda’s: Rig Veda, Sama Veda, Yajur Veda and Atharva Veda. These Veda’s contain the Vedic hymns which are in fact scientific formulae with complete and ultimate knowledge about existence, creation and human consciousness. They are divided in Mantra’s (knowledge) and Brahmana’s (organizing power). After becoming familiar with the ultimate reality of the Veda’s, it is the time to study the Vedanga’s, Itihasa’s and Purana’s. These scriptures offer unlimited possibilities to continue with the study and analysis of the Veda’s. A very important part of the Vedanga’s is called Jyotish or Vedic Astrology, which profound knowledge is globally taught by Narada Kush. Itihasa’s (Ramayana and Mahabharata) and Purana’s consist of a huge number of stories and legends of ancient heroes or deities and describe civilizations in days long past. The purpose of these expressive stories, with always a very profound contents, is to inspire people from all times to follow the path of Dharma (universal law) and to live a life in full enlightenment. |Nyaya||Ayurveda||18 Smritis||Mantras||Shiksha||Ramayana||18 Puranas| |Vaisheshika||(Upaveda of Rigveda)||–||Rig Veda||Kalpa||Mahabharata||–| |Samkhya||Gandharva Veda||–||Sama Veda||(Bhagavad Gita)||–||–| |Yoga||(Upaveda of Samaveda)||–||Yajur Veda||Nirukta||–||–| |Karma Mimamsa||Dhanurveda||–||Atharva Veda||Chanddas||–||–| |Vedanta||(Upaveda of Yajurveda)||–||Brahmanas||Jyotisch||–||–| |–||Sthapatya Veda||–||Upanishads||(Vedic Astrology)||–||–| |–||(Upaveda of Atharvaveda)||–||Aranyakas||–||–||–| Source: Maharishi Vedic Science The Three Sisters The ancient Vedic scriptures reveal the knowledge of life in a very holistic way. In the Vedic literature we find three practical applications for transforming life which are very interesting: Yoga, Ayurveda and Vedic Astrology. They are like three sisters, connected by an underlying field which we call the Self or in Sanskrit Atma. All three have the same source and the same destination. It is almost impossible to study all the parts of the Vedic Science, but when we want to make it practical, we apply Yoga, Ayurveda and Vedic Astrology in our lives. Actually all three support us to make life more comfortable, more growth-oriented and more enjoyable. We become the master of our destiny not allowing life to take it over. Compare it with a boat on the river. We can try to go against the stream and row and row, we get tired, we complain life is so hard and we get exhausted. Or we can go the other way, just co-creating with the flow of the river in the direction of the ocean. Life is not meant to make us struggle or to suffer all the time, it is meant for us to enjoy and to become more happy and wise. The three sisters make a complete package of life in a beautiful and enjoyable way. In Narada Kush’s workshops we will study and experience how we can implement these ancient Vedic tools in our daily lives.

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The era of Big Coal in the United States is on the ropes. Over the last decade we have steadily reduced our reliance on this dirty fuel, both because of its impacts on public health and our global climate, and because coal has been eclipsed by cheaper, cleaner energy options. But despite the gains we have made, the coal industry remains a political powerhouse that isn’t going down without a fight: Peabody Energy, Arch Coal, and the other mega-producers have now set their sights on the Asian market, where pollution and climate concerns have taken a backseat to a rabid demand for cheap energy. In an irony lost on no one, the cheapest and fastest route from the western coal fields of the Powder River Basin goes straight through the Pacific Northwest —– a region that is probably the most environmentally conscious in the country. People in the Pacific Northwest know how important a clean environment is to their economy and quality of life, whether that means healthy salmon runs or clean air and water. Sportsmen, Tribes, and citizens everywhere know they face a choice between those values and the opportunity to become a stopover for one of the world’s dirtiest industries: To date, Big Coal has proposed at least six export terminals in Washington and Oregon. If all of them are built we could see 150 million tons or more of coal moved by rail, barge, and tanker every year through those states. Until recently, coal exports weren’t even on the list of people's concerns for the Columbia River, Puget Sound, and the other rich but fragile fisheries in Washington and Oregon. Decades of overfishing, pollution and impassible dams took their toll, but progress has been made in recent years as cities and towns prioritize smart development, fish habitat is being restored, Columbia River dams are allowing more juvenile fish to pass and the Northwest’s remaining coal plants are being shut down. Fishing remains a multi-billion dollar industry in the region, so when evidence surfaced that the world’s dirtiest industry was planning an all-out blitz, residents began to take notice and speak out. In The True Cost of Coal, we examine the likely impacts these projects would have on the communities and ecosystems in their path, with a focus on the danger posed to fisheries and the people who depend upon them for their livelihoods, recreation, and cultures. We also peel back the curtain on the companies behind the rush to export, and the lessons are clear: Big Coal has razed, dynamited, and excavated immense swaths of once-pristine areas like the Appalachian Mountains and the Powder River Basin, leaving behind a toxic legacy of pollution and shattered communities. Not only is the mining process a fundamentally destructive one, but, as a whole, the coal industry has earned a reputation for unscrupulous—and often illegal—behavior. As if the point needed any emphasis, they have already gotten off on the wrong foot in the Northwest, deceiving regulators about the scope and size of their latest export plans. It is the wrong industry, at the wrong place, at the wrong time. We have an opportunity to say “NO!” to coal, but it will take a united effort by citizens, states, and the federal government. So far the first two groups have stepped up to the plate, with a growing coalition of diverse Northwestern voices opposing the plans: the health community, conservationists, tribes, fishermen, faith leaders, elected officials and many others. All agree that these proposals contradict deeply held regional values, and come with too high a price. As such, this report is a call to action for Americans to stand up against Big Coal to protect our natural resource legacy and public health. But the local and regional voices may not be sufficient to push back against the multi-billion dollar expansion plans that Peabody Energy, Arch Coal, and others are determined to push forward. Given the broad impact that increased coal shipments will have, not only on the local communities and the region’s critical natural resources, but also on the global climate, national scrutiny and oversight is essential. And national leadership to pursue an alternate energy path for our country is urgent. We lack crucial data on these issues, and National Wildlife Federation recommends a series of policy steps to ensure that we know the full extent of these proposals’ impacts on our environment and public health. A full list of recommendations can be found at the end of this report. The coal industry’s threat to fish and communities in the Pacific Northwest. Take the Clean Earth Challenge and help make the planet a happier, healthier place.Learn More Promoting more-inclusive outdoor experiences for allRead More A groundbreaking bipartisan bill aims to address the looming wildlife crisis before it's too late, while creating sorely needed jobs.Read More More than one-third of U.S. fish and wildlife species are at risk of extinction in the coming decades. We're on the ground in seven regions across the country, collaborating with 52 state and territory affiliates to reverse the crisis and ensure wildlife thrive.

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In what is only the fifth case of bubonic plague in humans in the state of Idaho, the diagnosis of a child with the disease is sparking concerns. The unidentified child, who lives in Elmore County, is recovering from the bacterial infection. According to WCVB 5, an ABC affiliate, Central District Health Department epidemiologists say it is not known whether the child was exposed to plague in Idaho or during a recent trip to the state of Oregon. Since 1940, only five human cases of plague have been reported in the Gem State (Idaho). The last two reported cases occurred in 1991 and 1992, with both patients fully recovering. But the plague was common in Madagascar toward the end of last year. That outbreak was the worst in Madagascar in 50 years. Between August 1, 2017, and October 30, 2017, there were a total of 1801 probable and suspected cases of plague, including 127 deaths, as reported by the Ministry of Health of Madagascar to World Health Organization. The plague, also known as the “Black Death,” is infamous for killing millions of people in Europe during the Middle Ages. Of course, now, modern medicine has given rise to antibiotics, which are effective in treating plague. However, without prompt treatment, the disease can cause serious illness or death. The United States is also facing an anti-biotics resistance in those who have taken the drugs often in the past. It is inevitable that each drug will lose its ability to kill disease-causing bacteria over time, says Marc Sprenger, the Director of the World Health Organization’s secretariat for antimicrobial resistance. This is because bacteria, through natural selection and genetic adaptation, become resistant to antibiotics. Essentially, bacteria, like most living things, evolve for survival. The best way to prepare for any superbug (a bacteria that is resistant to antibiotics) is to prevent the human body from contracting an infection and therefore, from rejecting antibiotic medications.–Ready Nutrition Epidemiologists say this particular case serves as a reminder that the plague is still dangerous and infectious to both humans and their pets, but the disease should not discourage recreationists from enjoying Idaho’s outdoors. People can greatly reduce their risk of becoming infected with plague by taking simple precautions, including avoiding contact with wild rodents, their fleas, and rodent carcasses. Do not feed rodents in picnic or campground areas and never handle sick or dead rodents. So basically, don’t play with dead things. But you should also consider trying to keep your pets from roaming and hunting ground squirrels or other rodents in affected desert areas and talk to your veterinarian about using an appropriate flea control product on pets as not all products are safe for cats, dogs or children. Sick pets should be immediately examined promptly by a veterinarian, especially if they may have had contact with sick or dead rodents and live in close proximity to humans. See your doctor if you have any unexplained illness involving a sudden and severe fever after being in a plague-endemic area. Clean up areas near your home where rodents can live, such as woodpiles, and put hay, wood, and compost piles as far away as possible and don’t leave any pet food or water where rodents or other wild animals can access them. Signs and symptoms of the bacterial infection often creep up within just a few hours after infection and include a bloody cough, difficulty breathing, high fever, nausea, vomiting, headache, and weakness. If it is not treated quickly, pneumonic plague is almost always fatal. The Bubonic plagues in history coincided with the changes in climate brought on by solar cycles. Sunspot activities go on an eleven year cycle but there are also longer cycles which are marked by grand solar maximums and minimums. We are currently at the start of a grand solar minimum (gsm) where sunspots are at their lowest point in numbers. The gsm is marked by colder- than-normal temperatures and intense rains. This causes famines which in turn drives animals indoors. With the animals comes the plagues. Weird weather phenomena such as freak snowstorms and early freezes where they shouldn’t occur are starting to show up. This is contrary to global climate change so the MSM aren’t reporting it. As always, the climatologists are arguing about how serious the problem will get. The gsm are related to the mini ice ages in history. I can see a “sheeple” who runs on Demon-rat talking points sponsored by George Soros! What caused the great, wide spread epidemic that swept Europe centuries ago??? Global Warming??? What causes plague today is illegals coming here with NO health check before allowing them to come in and suck the welfare system dry! Wake the hell up!! I think that climate change is allegorically true, like other myths. The ptb seem to be substituting key words but signaling their intentions, over public channels, imhblo. Like, if you spoke in nicknames and hints and people were supposed to catch your drift. It is probably from one of these sweet, peace loving muslims or some other garden variety foreign trash invading this damn place. Perhaps a “setup”. Europeans alive today probably carry genes that helped their ancestors survive. During the Middle Ages, infected fleas were on rats aboard trade ships coming from China to Europe. Plant lavender in your yard. Lavender repels ticks and fleas. Add lavender oil to coconut, apricot, grape seed, or any other oil or lotion. Put lavender under you pillow. It is a sleep aide. Add lavender to your life and forget about this horrible plague. Open Border Policy is treason. We have traitors in government. We have enemies with enormous power because of their ability to control the purse. IMHO change must begin with economic independence from the system. Buy silver and gold coins. Trade with them. Slowly but surely returning “power to the people”. (Excuse me for borrowing a Communist slogan.) and be sure to keep your dogs from chasing squirrels. HA MOFOING HA ! I like dogs and pets in general also, but they are too much trouble to care for properly in todays economic reality. Just as an FYI there is nothing special about this plague story. The plague, along with Hantavirus shows up in a number of western states every year. True. A wet spring in the southwest a few years ago increased the food supply that rodents eat. The rodent population exploded. The plague or the Hantavirus appeared. About half dozen people became infected. Some were infected when they entered small shacks that were not ventilated. William Talaber, what we need is “We the People” to place our bodies between Mexico and the U.S. The damn system in this country is broke! No politician in D.C. or state government gives a rats behind about the people they’re supposed to represent. The system is broke,and it needs to be torn down,people need to be hung and new people put in who represent US. Black Death? Could you be more dramatic? I live in Elmore Co. Idaho & no one is in a panic. Plague happens in the deserts of the US every year & is easily treated. This is straight up fear mongering. Shame on you. Most of us are subconsciously accepting a Medieval, s-hole country as the new normal, so should re-learn, either, how to deal with these diseases in the old fashioned or modern way. Practical people (if any are in these comments) should acknowledge, if they are being exposed, and take practical measures. Fight, flight, or freeze.

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PT | UNIVERSIDADE FEDERAL DO RIO GRANDE DO SUL FACULDADE DE CIÊNCIAS ECONÔMICAS PROGRAMA DE PÓS-GRADUAÇÃO EM DESENVOLVIMENTO RURAL FABIANA THOMÉ DA CRUZ PRODUTORES, CONSUMIDORES E VALORIZAÇÃO DE PRODUTOS TRADICIONAIS: UM ESTUDO SOBRE QUALIDADE DE ALIMENTOS A P The debate on the valorisation of traditional and artisanal food has been receiving increased attention recently. While there is growing consumer demand for natural, artisanal and unique foods, simultaneously, there is a significant discussion about the criteria used to assess these products which, given their singularity, can compromise their features if they are evaluated according to the same criteria which regulate industrial food production This research was conducted taking into account this context. For the development of this study, Serrano Cheese was taken as the object of research; this is a handmade traditional cheese made from raw milk and produced in Campos de Cima da Serra, a region located in the northeast area of Rio Grande do Sul, the southernmost state of Brazil. Empirical data were obtained from ethnographic research which prioritised information especially from producers and consumers but also from technicians and cheese sellers. The data analysis provided elements to discuss the relationship between producers’ lifestyles and cheese production; and to capture the practices, meanings and logics associated with the production and with the equipment, the tools and the raw milk employed in the production of the cheese. Regarding the consumption of Serrano Cheese, the study discusses the risk perceptions of local inhabitants in relation to the product, and the channels through which the cheeses are sold, usually based on the reputation of the producers and on close relationships. Changes in progress in the region, to varying degrees, have been resulting in alterations in the production methods, which can even affect the maintenance of those characteristics which make Serrano Cheese unique. By evidencing the significance of the knowledge legitimation employed in traditional food production, this study aims to contribute towards the enhancement and protection of this sort of production, which in turn is associated not only with the income maintenance but also with the safeguarding of the production methods and the lifestyle of producer families. Keywords: Traditional knowledge. Raw milk cheese. Risk perceptions. Intangible cultural heritage. Peasantry. Consumption.

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We’re usually aware of how much a balanced and healthy diet affects our overall well being. But do we really understand the extent of its impact? Would you believe us if we told you that the right foods can truly help your dry eye disease? Well, believe it or not, it really can. Dry eye disease is essentially inflammation in your eye. In other words, what we need to do is to decrease the state of alert and inflammatory process of the eye. We use all kinds of tools to do this in-clinic, as well as through the consumption of Omega 3 supplements. Of course, in order for these treatments and supplements to have their optimal effect- we must first begin by decreasing the overall inflammation in our body. The easiest way to do this, where we have most control, is through choosing the right foods to eat. Let’s explore these power foods that help reduce inflammation! VITAMIN ESSENTIALS GUIDE 101: VITAMINS A, E & C What are each of these vitamins for? How can they do wonders for our bodies? Which foods are packed with them? Vitamin A: the eye’s best friend Vitamin A is best known for providing essential nutrients for the eyes. Your retina needs vitamin A to help turn light rays into perceivable images. Also, without vitamin A, our eyes don’t have the moisture they need to prevent dry eyes. Vitamin A superfoods: sweet potatoes (200% of our daily dose of vitamin A), carrots, apricots and oranges. Vitamin C: powerhouse antioxidant Vitamin C helps repair and grow new tissue cells that were damaged by foods we ate, unhealthy habits (smoking), and environmental factors. This vitamin is obviously critical to our eye health. Vitamin C superfoods: cantaloupe, kiwis, citrus fruits (oranges, lemons, grapefruit), broccoli, brussel sprouts, green & red peppers, spinach & leafy greens. Vitamin E: keeping cells healthy Vitamin E is a fat-soluble antioxidant which protects our bodies’ cells. Foods which have vitamin E are good for tear function. Vitamin E superfoods: fish rich in omega 3 fatty acids (salmon, tuna, halibut, sardines, trout), avocados, almonds, sunflower seeds. FUN RECIPES TO HELP YOUR DRY EYE Maintaining good health and caring for your dry eye can be creative and fun! Here are a few healthy, delicious & easy treats that will help nurture your precious eyes: Can Fake Eyelashes Cause Dry Eye? Our natural eyelashes are very helpful in protecting the eyes, but do fake eyelashes increase your risk for dry eye? Common causes of dry eye are prolonged contact lens wear, dry air, and even simply getting older. But eyelashes aren’t always a common topic when discussing dry eye. LUMIFY Eye Drops for Red Eyes LUMIFY drops safely reduce redness temporarily in the eye due to minor eye irritations such as environmental allergies and dryness. The results are within a few seconds and last up to 8 hours... Diet for Dry Eye Dry eye disease (DED) is a pretty common eye problem—approximately 30% of Canadians experience symptoms associated with dry eyes. Symptoms can include burning or scratchiness, blurred vision, and redness...

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Pregnancy, under any circumstances, can be simultaneously exciting and terrifying. That’s even more true during a pandemic. With the rollout of the COVID-19 vaccine availability expanded recently to include Americans as young as 12, many pregnant women and their loved ones may still be uncertain about whether the vaccine is safe for them and the unborn child. Initial clinical trials did not include pregnant women, so initially there were more questions than answers. However, the director of the Centers for Disease Control and Prevention (CDC) recently recommended that pregnant people get the vaccine, citing new studies of the safety and efficacy of the Pfizer-BioNTech and Moderna vaccines. That new research shows that the vaccines appear to be safe for pregnant women vaccinated in their third trimesters – either for the parent or the child. The study showed that there were no discernable changes in the rates of pre-term births or miscarriages for vaccinated mothers-to-be. While pregnant women reported more frequent instances of pain at the injection site, they were less likely to report other common vaccine side effects like headaches, muscle pain, chills, or fevers. The study did not include the Johnson & Johnson vaccine, which was authorized for use in the U.S. after the Pfizer and Moderna vaccines. We recently shared the news that there is evidence babies born to vaccinated mothers may benefit by being born with antibodies to COVID-19, which could help protect them in the early days, weeks, and months of their lives when they are most vulnerable. Of course, choosing to get vaccinated while pregnant is a personal decision – one that should be made after reviewing available information and discussing the potential benefits and considerations with medical professionals. At The Surrogacy Law Center, we help protect the legal rights of intended parents and their children. Contact us to learn more!

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"Third Pole" Water Imbalances Examined Downstream Supply-Demand Challenges Predicted 26 Jun 2022 by The Water Diplomat A new study has identified a water imbalance in the Himalayas. The Hindu Kush–Karakoram–Himalayan system, or the “Third Pole” is a reservoir of fresh water that serves nearly 2 billion people downstream. The Tibetan Plateau in the Himalayas, often dubbed the Asian Water Tower, stores the largest amount of frozen water on the planet after the North and South poles. An international team of scientists has now identified imbalances caused by an increase in temperatures over the last 4 decades. Since 1980, the region has been warming at a rate of 0.42C per decade, a rate which is twice the global average. Despite an increase in annual precipitation, since 2000, the glacier mass has decreased by 340 Gt (gigatons). The faster rate of melting ice has caused levels in water basins to change. In basins with no output connections water levels have increased. On the contrary, in basins that are connected to rivers that supply downstream populations, water levels have decreased. Professor Tandong Yao, the lead researcher of the study whose findings were published in ”Nature Reviews - Earth & Environment”, said: “Such imbalance is expected to pose a great challenge to the supply-demand balancing of water resources in downstream regions.” While global warming is expected to exacerbate these imbalances, the researchers suggest that some water bodies like the Yellow and the Yangtze Rivers will see their levels rise as others such as the Indus and Amu Darya River basins will see hem decrease. More accurate predictions of these impacts, however, depend on further, more detailed studies with improved water level monitoring tools. 9 Jan 2022 KATHMANDU, Nepal Glacier melt in "third pole" will adversely affect livelihoods of an estimated 1.65 billion people living downstream. Faster change is likely to result in greater landscape instabi... 9 Feb 2021 New Delhi, India 26 have died and as many as 200 are missing after a glacier collapse in northern India on 8 February, causing deadly flooding in the state of Uttarakhand.On the morning of 7 Februa...

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Native Americans Are Not All the Same: An Exploration of Indigenous Diversity The largely incorrect and well-established perceptions regarding Native Americans as all residing in the exact social, traditional, economic, and religious boundaries have been detrimental to realizing the breadth of diversity exhibited between the various tribal communities throughout America. The Origins of the American Indian Movement and the Wounded Knee Occupation: A History of Liberation and Defiance While there are still many unresolved issues surrounding American Indians to this day, including new social and economic ailments to address, the American Indian Movement provided an opportunity for American Indians of all tribes to come together under one unified movement. Overlooked: Private Sector Economies in Indian Country as an Extension of Tribal Sovereignty Support of the private sector throughout Indian Country is conventionally viewed as secondary to that of the public sector, with encouragement of native entrepreneurism by many tribal governments faring even worse. The Fragility of Indian Gaming Amidst the COVID-19 Pandemic With the rapid spread of the COVID-19 virus around the world, American Indian communities in the United States have been hit especially hard due to the collateral effects of the illness upon their social, political, and economic outlets. Confronting the Historical Offenses of the Doctrine of Discovery in ‘Unsettling Truths’ Authors Mark Charles and Soong-Chan Rah’s Unsettling Truths: The Ongoing, Dehumanizing Legacy of the Doctrine of Discovery, offers an essential examination of the historical journey of how the Doctrine of Discovery played, and continues to play, a crucial part in shaping the American psyche and the collective comprehension of its past as a country. The Wealthy Elite and Indigenous Land Rights Clash in ‘Conscience Point’ Focusing on the Shinnecock Indian Nation and their continuous battle with the governmental bodies and public inhabitants of Hamptons, New York, Conscience Point explores the dangerous clashes that occur when centuries of Indigenous philosophy conflicts with unrestrained greed, exploitation, and cultural disregard. Connecting 573 Indigenous Communities and More in One App TeePee is a digital directory where every Native American tribe in the United States is available at your fingertips. You can easily access information on the currently federally recognized tribal communities, tribes, bands, nations, pueblos, rancherias, and Native villages located in the United States. Examining Business in Indian Country in ‘American Indian Business: Principles and Practices’ The topic of Indigenous business practices and principles is a subject far from that of the mainstream Western peripheral, and American Indian Business works to both acknowledge its place in the broader business spectrum as well as highlight its particularities. Steps to Combating Colonialism in the Tribal Workplace When does such Westernized thought processes find themselves emerging within Native mindsets, particularly in the workplace? Also, does the detached nature of an individual further add to the colonized perception of their own community’s value? Tommy Orange’s Debut Novel There, There A glimpse at the urban Native experience unearthed for the masses. Journalism, Politics, and the Dakota Access Pipeline: A Conversation with Dr. Ellen Moore American Indian Republic had the opportunity to sit down with Dr. Moore to discuss the process of writing her latest book titled Journalism, Politics, and the Dakota Access Pipeline: Standing Rock and the Framing of Injustice. The Medicine of LGBTQIA2 Visibility and Inclusiveness As I continued to navigate this communal silence, I recognized my unquestionable duty to step forward as a queer Indigenous woman and make myself available as a resource to others.

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An earthquake is the result of a sudden release of energy in the Earth's crust (ground) that creates seismic waves (shaking). Although Iowa isn’t known for having earthquakes, the New Madrid, Missouri seismic zone, is located within 400 miles of the campus and a seismic wave and potential damage could occur here. If you are inside a building - Stay indoors and seek shelter under sturdy tables, desks, or inside doorways. - Do not use elevators. - Stay away from windows, wall hangings, suspended objects, and tall unsecured furniture (bookcases, cabinets, or appliances) If you’re outside - Stay in the open, away from buildings, trees, and power lines. Don’t go near anything where there is a danger of falling debris. After the seismic waves (shaking stops) - Be prepared for aftershocks. Earthquakes sometimes occur in a series of tremors, which could last for a period of several days. Aftershocks, or even a series of aftershocks, are common after earthquakes and may last for a few seconds to perhaps as long as 5 minutes or more. - Attempt to safely evacuate the building. For additional information on evacuations, see Evacuation/Rescue Plan For Persons With Disabilities. - If you are trapped inside a building, try calling for help by yelling, banging on building materials around you, or by using a telephone or cell phone (if service is available). - Be alert for gas and water leaks, broken electrical wiring, downed electrical lines, or ruptured sewer lines. Whenever possible, turn the utility off at its source. - Don’t re-enter damaged buildings. Aftershocks could cause more damage or knock them down. Emergency units will respond and make decisions regarding the control and abatement of the incident. These units will issue an “all clear” for safe building re-entry, when appropriate. The emergency unit or agency in control will decide when to turn control of the scene back over to the appropriate University entity. Depending on the nature and degree of the incident, other supporting agencies and University resource units may be brought in for services or assistance.

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THE future of cities LAUNCHES ON world cities day 2021 on the occasion of world cities day 2021 on october 31st, the faculty of architecture at the university of hong kong (HKU) launched a series of short films to promote discussion on the big issues facing our urban environments in the post-covid era. ‘the future of cities’ comprises 12 three-minute videos, each of which questions what will happen as our cities continue to get bigger and denser, and as we become a city-dwelling race. each short focuses on a different theme linked to research currently or recently undertaken in HKUrbanlabs at HKU faculty of architecture. featured topics include the urban/rural divide, informal spaces in cities, aging urban populations, pandemic resilience, smart-city technologies, urban system optimization, urban greening and farming, urban externalities, social inequality, city boundaries, and settlement patterns of the future. video and images courtesy of faculty of architecture, the university of hong kong the films tackle both the good products of living together in cities (GDP, wages, inventions) and the bad products (crime, traffic congestion, some diseases). the series examines smart city technology, asking if it will allow us to better control the bad to enjoy unlimited good in the world’s growing agglomerations? the future of cities also looks at the new public health threats facing dense urban environments, asking how will we design and control cities of the future to become more pandemic resilient? will they be wired up to monitor real-time microbial health? will city densities, design, circulation systems, and even locations, dramatically change as a result of the twin existential threats of pandemics and extreme climate events? ‘had the city’s long-standing association with deadly infectious diseases not been reversed by antibiotics, it is unlikely that otherwise civilised societies would have put up for a century with the privations of being squeezed body-to-body in metro systems of the most advanced cities of the world,’ notes professor chris webster, dean of the faculty of architecture and director of HKUrbanlabs. ‘will the pandemic signal the end to this last remaining vestige of 19th century daily urban life, ushering in, in the nick of time, decentralized working, shopping and playing, supported by personalized road and air autonomous urban transportation modes?’ professor webster adds that the films are influenced by the location of hong kong. ‘as one of 11 cities in the greater bay area (GBA) of the pearl river delta – an ultra-dense polycentric city region connected by high speed transport corridors – we are at the epicenter of the world’s greatest ever urbanization experiment. unofficial population figures make GBA the first 100 million strong city region. what can we learn from it?’ discover more about the future of cities short film series on the HKU website here.

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█ CARYN E. NEUMANN The SR-71, a black, high-altitude airborne reconnaissance platform that flew at trisonic speed, gave the United States the ability to photograph military sites in hostile countries as well as the opportunity to confirm interpretations of satellite photographs from 1968 until 1990. Photographs taken from SR-71s helped end the siege of Khe Sanh in Vietnam in 1968, preserved the Strategic Arms Limitation Treaty (SALT) with the Soviet Union by monitoring troop movements in Cuba in 1979, and confirmed that Iran had acquired Silk Worm missiles from China for possible use against oil tankers in the Straits of Hormuz in 1987. While of obvious military value, each SR-71 burned enormous amounts of fuel, and required a large amount of staff support. For reasons of economy, the Department of Defense terminated the program and the last SR-71 flew in 1990. The SR-71, planned in the early 1960s as a weapon in the Cold War, gave the U.S. the ability to survey more than 100,000 square miles of Earth's surface in an hour's time. The 29 aircraft in service flew above 80,000 feet, higher than any other platform, and traveled at Mach 3.17–3.30 covering 30 miles every minute. The SR-71 could survey up to a quarter of a million square miles of territory in one sortie. High-strength lightweight titanium alloy covered 90% of the aircraft with 20% of the skin consisting of radar-transparent plastic. For missions, the platforms were fitted with either a high-resolution horizon-to-horizon optical bar camera or a radar package which generated film of the ground in all weather conditions. The SR-71 contained no armament. The first operational flight of the SR-71 took place on March 21, 1968, and brought information crucial to the American war effort in Vietnam. Photos taken by the crew revealed the location of heavy artillery emplacements around Khe Sanh, an American garrison in Vietnam under siege by the North Vietnamese. By providing data that had previously eluded sensors on other aircraft, the SR-71 allowed the American command to direct B-52 bombers to the enemy site and helped to end an event which had riveted the attention of the public. In 1979, when a satellite revealed a large Soviet force in Cuba, an SR-71 flew continuing surveillance over the island to monitor the situation and ensure Senate ratification of SALT. A 1987 mission to Iran gathered extensive information about masses of military equipment in the Persian Gulf, including the presence of Silk Worms, land-based anti-ship missiles from China that the Iranians apparently intended to use to threaten merchant tankers in the Straits of Hormuz. The U.S. Navy received warning of the missiles and diplomats brought pressure on Iran to remove them. On 80 occasions in the 1980s when satellites broke down or were unable to see through the atmosphere, SR-71s provided reconnaissance imagery of vital areas in the Middle East. The SR-71 penetrated hostile territory with comparatively little vulnerability to attack unlike other reconnaissance platforms like the U-2 spy plane. The workhorse U-2, however, operated for considerably less money and generally received reconnaissance assignments while the SR-71s remained in their hangars. The Department of Defense made the decision to terminate the program on November 22, 1989. Secretary of Defense Richard Cheney in June 1990 ordered that three SR-71 aircraft be placed into long-term storage for possible use in a future conflict. The SR-71s did not see service in the Gulf War, however, and most of their aircrews and skilled maintenance force are now unavailable because of the passage of time. As satellite technology involves less human risk and grows and more precise and cost-effective, it is uncertain that the United States will justify the cost of deploying SR-71 intelligence-gathering machines in the future. █ FURTHER READING: Crickmore, Paul F. Lockheed SR-71: The Secret Missions Exposed. London: Osprey, 1988. Thornborough, Anthony M. Sky Spies: Three Decades of Airborne Reconnaissance. London: Arms and Armour Press, 1993.

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