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Q: SQL Server: why variable works outside IF I have trigger where on top of it I declare DECALRE @variable VARCHAR(100) = ' ' And then below it, I have this sample IF statement IF UPDATE ([data]) BEGIN SET @variable = 'Data change' END And then insert with this @variable on the end of the trigger. My problem is that even though [data] remains unchanged it inserts 'Data change' into DB instead of '' A: Documentation of UPDATE - Trigger Functions states clearly: UPDATE() returns TRUE regardless of whether an INSERT or UPDATE attempt is successful. Please check: UPDATE t SET id = 2 WHERE id = 1; /*if block is not executed */ -- 1 rows affected and(even though there is no real change on data column): UPDATE t SET id = 1, data = data WHERE id = 2; /*if block is executed */ -- Data change -- 1 rows affected db<>fiddle demo | High | [
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UPDATE: Subject is safely down off of the Kirkman Road overpass to the Florida Turnpike. Drivers and others in the vicinity: Please be patient - we are getting you moving. Special thanks to the truck drivers that assisted us out there! pic.twitter.com/F6x3e3ukSC | Low | [
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The labour market is crumbling as coronavirus containment efforts drive a sharp spike in job losses that could have lifted the unemployment rate as much as three percentage points over the last fortnight, to its highest since June 2014. The surge in new claims wipes out 77% of the 1.23 million new jobs created between the referendum of June 2016 and January 2020 while implying a severe increase in unemployment that's likely to lift the jobless rate by 2.7 percentage points to 6.6% for the three months to the end of March. There were 31.75mn people in full and part-time work during the three months to the end of June 2016 but 32.98mn were employed in the three months to the end of January 2020. "An increase in the unemployment rate of this magnitude is reasonable given the surge in Canadian and US jobless claims," says Joseph Capurso, a strategist at Commonwealth Bank of Australia. Official figures from the Office for National Statistics will not confirm the increase until May 19 as they are published with a 45-day lag of the period-end in question, although with preliminary claims data being released ahead of time economy-watchers now have all of the important moving parts required for them to track unemployment rate changes as often as the data are made available. Above: Changes in full and part-time employment for men and women in the UK ahead of the coronavirus shutdowns. Source: Office for National Statistics. There were 1.33mn people out of work but seeking it in January, which is the ONS definition of unemployment, and when combined with the total number of individuals in work this made for an unemployment rate of 3.9%. That jobless rate was close to its lowest since 1973 but it's gone sharply into reverse since the government took serious stock of the health threat posed by the coronavirus and effectively shuttered the economy to slow the virus' run on the population and, in process, prevent the health service from being overrun. "Going further by assuming that new claims stay at 440,000 a week in the first two weeks of April, then unemployment could rise by 2,237,000 and the [unemployment] rate would soar to 10.4%," warns Paul Dales, chief UK economist at Capital Economics. The government first asked people to avoid pubs, restaurants and cafes before instructing that those businesses all shut their doors until further notice. It's since required that citizens remain in their homes at all times except for in certain limited circumstances, unless of course they're 'key workers' - a potentially new class of citizen who's labour is fundamentally necessary for the continued servicing and operation of a skeleton crewed society. "It's too soon to assess the lockdown's efficacy, but overseas data suggest three months will be needed. The public supports the lockdown now, but fatigue and concern about the financial costs will grow," says Samuel Tombs, chief UK economist at Pantheon Macroeconomics. Above: Daily changes in the number of new coronavirus infections and related deaths in the UK. Source: UK Government. Chancellor Rishi Sunak has announced unprecedented measures to support companies and households through the shutdown that's billed by politicians and others as a China, if not prison-style 'lockdown'. Those measures include offers to pay up to 80% of wages to avoid seeing workers lose jobs, tax deferrals and cash grants for companies as well as uber cheap and government guaranteed loans for businesses deemed by state authorities to be 'viable'. "A further leap in new claims for Universal Credit suggests that the government support designed to keep people employed isn’t working," Dales says. "Our forecast that the unemployment rate will peak at 6% now looks too hopeful." Those measures could see the government splurging more than £100bn this year alon and such expenditure could easily lift the government deficit by high single digit perentages of GDP this year and next. Some economists see the 2020 deficit potentially coming in above 10% of GDP, which could have profound implications for a Pound Sterling that carries on its shoulders the developed world's largest current account deficit and requires continuous capital inflows from abroad to sustain its value. "The current account deficit declined to £5.6B in Q4, from £19.9B in Q3. As a share of GDP, it fell to 1.0%, from 3.6%," notes Pantheon's Tombs. Above: Changes in usage of various forms of transport in the UK. Should those investors deem the government's efforts to preserve what it can of the economy to be a fiscal expense too far, or more likely one that is perceived to pose such a risk that it necessitates an increased 'risk premium' for holders of British sovereign debt, then Pound Sterling would likely have to pay the tab. And the only way any currency could pay such a bill is through a depreciation that, with cash flows measured in foreign currency terms, lifts to a sufficient level the percentage value of the interest coupon paid by government bonds. In other words, a buyers' strike on the British Pound that lasts until it becomes cheap enough to sufficiently augment the returns of would-be debt investors could be in the pipeline. That's the only way those interest returns can be augmented in a world where the Bank of England (BoE) is crushing bonds yields to death through a £645 bn quantitative easing programme that's already seen it buy up more than 30% of all sovereign debt issued by the government. This is a substantial driver of some bearish year-end and 2021 analyst views on why the Pound might be found trading near to recent post-1985 lows long after the coronavirus crisis subsides. "A record-breaking public sector deficit may require additional external borrowing," warns Stephen Gallo of BMO Capital Markets. "The UK's floating exchange rate is an important buffer for the economy in these extraordinary times, and we have penciled in a move to 1.15 at the 9M part of the curve." There has been an increase in the number of companies considering laying off staff and freezing wages in order to safeguard working capital over coming months, according to the latest Lloyds Business Barometer. The UK furlough scheme for employees and its equivalent for the self-employed are costing HM Treasury one percent of annual economic output per month, newly released figures showed this week, explaining concerns about the budget deficit as well as nascent and forthcoming government efforts to wind it down. American welfare claims rose further last week despite a widespread view that the bottom of the coronavirus-splattered economic trough was seen in April and suggesting that U.S. unemployment climbed deep into the second quarter, but there was a silver lining in the small print as well as in downwardly-revised GDP figures. The UK economy suffered a 18.1% plunge in retail sales in the month of April, a record collapse but one that is hardly surprising given the scale of the economic shutdown enforced by the government in its effort to stop the spread of covid-19. This website carries advertisements for providers of leveraged trading products. Please be aware that YOUR CAPITAL IS AT RISK if you should choose to engage in their services. The news and information contained on this site is by no means investment advice. We intend to merely bring together and collate the latest views and news pertaining to the currency markets - subsequent decision making is done so independently of this website. All quoted exchange rates are indicative. We cannot guarantee 100% accuracy owing to the highly volatile and liquid nature of this market. | Mid | [
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Q: How to handle downloading in GeckoFX 60 I have Jason Shuler's solution (https://stackoverflow.com/a/38058475/10707700) running on GeckoFX 45.0.34, now I want to update my application to GeckoFX version 60.0.22, but the line: nsILocalFile objTarget = Xpcom.CreateInstance<nsILocalFile>("@mozilla.org/file/local;1"); fails, because the Gecko.nsILocalFile object does not exist, How do I update the previous line to work in GeckoFX version 60.0.22? A: use nsIFile instead of nsILocalFile for more information see this geckofx issue | Mid | [
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Adventures in Taipei, Taiwan Kinda overdue post on my mini Easter vacay to Taipei which consisted of 3 days of fooooood, sweating in 30 degrees heat, night markets (which I somehow have no photos of), wandering around lost and getting the best foot massage ever. Other half was equipped with a tour guide and was glued to it every waking moment, so thanks to that we ended up getting a lot done and visiting some great places. So Taiwan wasn't really one of my to-go places, but we ended up going there anyway. And then I got there and wondered why Taiwan was never on my bucket list because my 13-year old self was obsessed with all things Taiwanese. Meteor Garden, Devil Beside You, F4, Wu Chun and Mike He anyone? It was boiling hot, but not humid. I now appreciate anywhere more breathable and easier on the lungs than Hong Kong. I also appreciate anywhere with more space than Hong Kong. I forget how modern HK is sometimes; Taiwan has a slightly quaint and old-school feel. For anyone who's watched Meteor Garden, Taiwan still looks THE SAME. Fyi, MG was released 15 years ago and I was reliving it everywhere I walked. We ended up eating and finding a lot more sushi than I expected (but Taiwan was once part of Japan's colony after all). This sushi restaurant with a train track conveyor belt was a particularly cute find. Sushi train - choo choo | More sushi | Mini hotpot We also had sashimi at Addiction Aquatic Development - a wet/wholesale market. Everything is fresh and I guess not as expensive as fresh sashimi could be, so basically it's sashimi heaven. There's a table area where you can stand and eat as soon as you buy. It was super busy, but genuinely the fattest and best scallops everrrrr. Mouth is watering as I reminisce about this moment | Addiction Aquatic Development | Another spot for breakfast ft. a massive beef dumpling Taipei is dotted with Instagrammable cafés. Oyami Café was a random find before we left to go to the airport. The interior was decked out like a pretty countryside, shabby chic wedding complete with bride and horse near the entrance. (Although the bride looked slightly creepy, so no pictures) We also went to Taipei 101, the 4th tallest building in the world, and home to the fastest passenger elevator in the world too. And of course we had to visit the famous Din Tai Fung (3 Michelin Stars chain specialising in xiao long bao). I think this one is their flagship or first store? Queuing time was a ridiculous 90 minutes so we just had takeaway. There's so many different variations, but the original xiao long bao has to be the best. And yes, I would say it's probably the best I've had. | Mid | [
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1. Field of the Invention The present invention relates to a method of fabricating Cu.sub..alpha. (In.sub.x Ga.sub.1-x).sub..beta. (Se.sub.y S.sub.1-y).sub..gamma. film for solar cells. 2. Description of the Prior Art Solar cells in recent years have achieved a high maximum conversion efficiency of 17.7% by using films consisting of Cu.sub..alpha. (In.sub.x Ga.sub.1-x).sub..beta. (Se.sub.y S.sub.1-y).sub..gamma. (hereinafter also referred to as "CIGS"). However, when such films are grown under conditions in which there is an excessive supply of group III elements In and Ga, it is possible to fabricate single phase CIGS, but it has a high defect density and high resistance that degrade the properties of the resultant solar cell. On the other hand, while using an excess supply of Cu, a group I element, does provide large, good-quality crystals, it also results in the surface and boundary formation of the low resistance Cu--Se metal phase that makes devices prone to short circuit. In order to grow high-quality CIGS films for solar cells, a complicated method is currently used, comprising first using an excess supply of Cu to form large-grain, high-quality CIGS, and followed by a step of using excess Ga and In to thereby remove a Cu--Se phase on the surface. Moreover, since a high temperature of around 550.degree. C. is used to ensure the adequate reaction of each element, the method can only be used with substrates able to withstand such temperatures. An object of the present invention is to provide a method of fabricating CIGS film for solar cells in which the generation of point defects (divacancies) and twin-crystal stacking faults is suppressed to thereby fabricate high-quality film. Another object of the invention is to simplify the formation process by providing a method of fabricating high-quality CIGS films for solar cells in which the film is formed at a low temperature. | Mid | [
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Q: Why doesn't RelatedManager.add() accept an iterable as an argument? This question is about RelatedManager.add() which is used to add model object instances to a many-to-one or many-to-many relation. To illustrate my question, let's say I have the following two models: class Book(models.Model): title = models.CharField() class Author(models.Model): name = models.CharField() books = models.ManyToManyField(Book) Now, for each Author I have a list of Book objects that I want to add to the relation. At the moment, I'm doing it like this: book_objects = [ <Book: Harry Potter and the Philosopher's Stone>, <Book: Harry Potter and the Chamber of Secrets>, <Book: Harry Potter and the Prisoner of Azkaban> ] jk_rowling = Author.objects.get(name='J. K. Rowling') for book in book_objects: jk_rowling.books.add(book) jk_rowling.save() However, this is not very efficient as I have to deal with thousands of objects to be added to a relation of this kind and it takes ages. Rather, the Django documentation recommends to call add() with more than one model object as an argument. That is, I would have to do it like the following: jk_rowling.books.add(book1, book2, book3) But I cannot do this because I don't know the number of objects added to the relation beforehand. I don't understand why I can't do the following: jk_rowling.books.add(book_objects) Why doesn't add() accept an iterable as an argument? And how can I add a large amount of objects to a relation like this more efficiently than calling add() for each object separately? Thanks a lot! A: You can just expand your array as varargs: book_objects = [ <Book: Harry Potter and the Philosopher's Stone>, <Book: Harry Potter and the Chamber of Secrets>, <Book: Harry Potter and the Prisoner of Azkaban> ] jk_rowling = Author.objects.get(name='J. K. Rowling') jk_rowling.books.add(*book_objects) # <--------------- jk_rowling.save() | Mid | [
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<?xml version="1.0" encoding="UTF-8"?> <!-- This web.xml file is not required when using Servlet 3.0 container, see implementation details http://jersey.java.net/nonav/documentation/latest/jax-rs.html --> <web-app version="2.5" xmlns="http://java.sun.com/xml/ns/javaee" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://java.sun.com/xml/ns/javaee http://java.sun.com/xml/ns/javaee/web-app_2_5.xsd"> <servlet> <servlet-name>Jersey Web Application</servlet-name> <servlet-class>org.glassfish.jersey.servlet.ServletContainer</servlet-class> <init-param> <param-name>jersey.config.server.provider.packages</param-name> <param-value>com.waylau.rest</param-value> </init-param> <load-on-startup>1</load-on-startup> </servlet> <servlet-mapping> <servlet-name>Jersey Web Application</servlet-name> <url-pattern>/webapi/*</url-pattern> </servlet-mapping> </web-app> | Low | [
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Darvill Racing Test The ContiRoadAttack 2 CR After seeing the successes of a number of teams in 2013 running the ContiRoadAttack 2 CR including Phase One who claimed top spot in the European Classic Bike Series, the team at Darvill Racing decided to test out the high performance classic race tyre from Continental in a race at Jurby on the Isle of Man. Darvill Racing have regularly been using a classic tyre from another leading manufacturer, but when fitted to the torquey Kawasaki ZR-1 they decided that they needed something that offered both the increased performance and durability that was required for the bike. The ContiRoadAttack 2 CR features a number of our unique technologies including the fast warming Black Chili compound, as well as Traction Skin which minimises the need to scrub in the tyre once fitted. Our Continuous Compound Technology also allows us to create a Multi-Compound style tyre from a single piece of rubber, whilst also eliminating the feeling of step which riders experience when transitioning in and out of a corner. These technologies are also featured on the sport touring versions of the ContiRoadAttack 2 including the new EVO version. Team Principal Alex Aitchison was instantly impressed with the design of the ContiRoadAttack 2 CR when fitted to the bike, but the real test would come during the weekend of racing at Jurby running in the Andreas Racing Classics Championship. Rider Keith McKay reported that the conditions were damp and patchy, as well as being freezing cold during practice, with conditions drying a little later on in the day for the race but the temperature remaining cold. Keith made it two class wins from two on the day which was a fantastic start racing on an unfamiliar tyre, and afterwards he said of the performance: “The Conti RoadAttack CR compound tyres were also amazing, they didn’t give me a single “moment” all day in conditions that were challenging to say the least… we had a waved yellow for an incident *every* lap of practice and many, many fallers through the day” When sending us the race report Team Principal Alex summed up the thoughts of the Darvill Racing team saying: “We have been blown away by the performance of the Conti tyres, not only have they been fantastic in all conditions but they have hardly worn, we are very, VERY impressed!” Darvill Racing are also keen to try Continental on the teams electric and modern race bikes, and you can follow the teams progress and latest news via their website. | High | [
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Iron Hill Pro Men’s Criterium Part of the Benchmark Twilight Cycling Classic As the marquee event of the Benchmark Twilight Cycling Classic, the Iron Hill Pro Men’s Criterium is considered one of the most challenging courses in the pro criterium circuit. Top professional cyclists from all over the USA and beyond vie for thousands of dollars in prize money in downtown West Chester, PA. This demanding 65K race takes place on a 0.6-mile course encompassing 8 city blocks features four 90º turns and one short rise. The start and finish line is at Gay and High Streets. This family-friendly event features plenty of great racing action and activities for all: Brumbaugh Wealth Management Pro Women’s Criterium, Rothman Institute Amateur Criterium, West Chester Dental Arts Kid’s Race, Tolsdorf Trike Challenge, Kid’s Zone, Community Festival, Market Street Block Party and much more! | Mid | [
0.59860788863109,
32.25,
21.625
]
|
An award-winning Syrian journalist and former BBC reporter is finally able to share secrets about the war in Syria without fearing for her life. Zaina Erhaim, 33, is fundraising to translate her book Evil Wheels of Our War into English without the pressures of censorship that she faced in her home country. Ms Erhaim, who now lives back in the UK, said: “It really tells the story from a different perspective, feminist, journalist, woman perspective.” Working with Richmond-based Palewell Press which champions stories of human rights, refugees and environmentalists, the journalist has turned secrets previously not to be published into a book-length manuscript in Arabic. Born in Idlib in north western Syria and educated in Damascus, the journalist and activist was finishing her master’s degree at City, University of London in international journalism when the Syrian Civil war began in 2011. She worked with the BBC before returning to Syria in 2013 to pass on her expertise as a journalist. In September 2016, British authorities confiscated Ms Erhaim’s passport at the request of the government in Damascus, attempting to block her work as an activist. Palewell Press owner Camilla Reeve, 71, said: “She’s written a book which I think needs to be heard, it definitely needs to be out there.” The aim is to raise £20,000 to translate the work into English. Ms Erhaim expressed frustration at having to suppress journalistic instincts due to censorship. She said: “I wasn’t free enough for what I wanted to say, fearing for my life and my family’s, so being forced to suppress myself and self-censor was one of the most difficult things I had to do.” She remembered when a rebel battalion killed a gay man, something none of the local journalists deemed as newsworthy. She said: “I was dying because I couldn’t write anything about it and I had to suppress myself until finally writing it in the book the way I saw it, the way I heard it, the way I lived it. “This is my main trauma. I think my main struggle is being a journalist, having to suppress myself, to be able to keep working and to keep living where I was helping others. “Finally at the beginning of this year I started printing all these notes that I couldn’t publish before and I made a book out of it, so it’s also like my healing conclusion for what has happened.” She added: “I’m sure there is going to be plenty of bullying campaigns against me because I am speaking really about everyone, military leaders, activists. “One of the main goals is to document what’s happened so I put names, dates, locations, because those things are completely forgotten and I’m seeing how history is being manipulated while I am living it. “However I’m excited because those stories haven’t ever been told and I’m excited to see what kind of impact they might make. “I hope they will be able to see what is happening in different eyes, they will be able to care more.” Since leaving the BBC Ms Erhaim’s perceptions of achievement changed. “I felt it was really selfish at the BBC because I’m just reporting what is going on, putting my name on it, while in Syria I was helping other to do their own stories” she said. “My personal accomplishments have dropped, but my contribution to the media scene in Syria I think is essential and I’ve done what could. “In many cases I really felt like some of them became my kids, whenever they published a story.” She added: “Eventually when I see those articles written mainly by the women who had no experience of journalism at all and then they became journalists, I think that’s the greatest reward I would have aimed for.” Related Posts Author Diana Darke told an enraptured audience at Wimbledon BookFest last weekend that she will return to war-torn Syria to reclaim a house she bought in 2005. She purchased a grand but tumble-down property in the country’s capital, Damascus, and painstakingly renovated it with dedication and passion. Like many great… | Mid | [
0.649867374005305,
30.625,
16.5
]
|
Kinetic disposition of ethanol in the neonatal piglet and hemodynamic effects in the presence and absence of 4-methylpyrazole. The hemodynamic effects of acute ethanol intoxication and the kinetic disposition of ethanol are reported for the first time in neonatal piglets under nitrous oxide anesthesia. Two hours after a single dose of ethanol (1.4 g/kg), blood pressure decreased from 76 +/- 4 to 71 +/- 4 mm Hg (p less than 0.05) and heart rate increased from 194 +/- 10 to 227 +/- 8 beats/min (p less than 0.05; means +/- SE). By 5 hr, blood pressure dropped to 67.5 +/- 4 mm Hg and heart rate increased to 239 +/- 8 beats/min. In piglets pretreated with 4-methylpyrazole, an alcohol dehydrogenase inhibitor, there was a transient increase in blood pressure (p less than 0.05) and a decrease in heart rate (p less than 0.05) immediately after the end of the ethanol infusion. However, the hemodynamic alterations observed 2 hr after ethanol treatment alone were prevented with 4-methylpyrazole. These findings indicate that ethanol metabolites play a significant role in hemodynamic alterations observed after acute ethanol intoxication. The mean ethanol metabolic rate derived from plasma data was 94 +/- 9 mg/liter/hr. This corresponded to an apparent Km of 68 +/- 3 mg/liter and a Vm of 123 +/- 11 mg/liter/hr. The Vd was 0.966 +/- 0.031 liter/kg. The metabolic rate for ethanol, derived from plasma data, correlated with in vitro alcohol dehydrogenase activity at pH 7.4 and 25 and 37 degrees C. The optimum pH for hepatic alcohol dehydrogenase activity was 9.9. | High | [
0.689473684210526,
32.75,
14.75
]
|
1. Field of the Invention The present invention relates to a brushless rotary electric machine to be mounted in a vehicle as, for example, a brushless AC generator. 2. Description of the Related Art Conventionally, the following AC generator for an automobile is known. The AC generator includes a case, a stator, a shaft, a rotor, and a cooling fan. The case includes a pair of brackets, i.e., a first bracket and a second bracket, which are opposed to each other. The stator is fixed to the case. Two ends of the shaft are rotatably supported respectively by the first bracket and the second bracket through an intermediation of bearings. The rotor is provided to the shaft. The cooling fan is fixed to the shaft. The rotor includes a magnetic-pole core fixed to the shaft, a cylindrical exciting core fixed to the first bracket while being inserted into the magnetic-pole core, and an exiting coil obtained by winding a conductor around a minor-diameter portion of the exciting core (for example, see JP 57-16559 A (FIG. 1)). In the above-mentioned AC generator for the automobile, vent holes are formed through the rear bracket at positions so as to face a diode and a regulator. Therefore, cooling air generated by the rotation of the cooling fan passes through the diode and the regulator. After that, the cooling air reaches the exciting core and the exciting coil through the vent holes. Therefore, there are the following problems. A. After cooling the diode and the regulator, the cooling air cools the exciting core and the exiting coil. Therefore, the exciting core and the exciting coil are cooled with the warmed cooling air. Therefore, cooling performance for the exiting core and the exciting coil is low. B. There is no structure in an internal space after the cooling air passes through the vent holes, and hence the cooling air is disadvantageously diffused in the internal space. The exciting core and the exciting coil are cooled by the diffused cooling air, and hence the cooling performance for the exciting core and the exciting coil is low. | Mid | [
0.5469061876247501,
34.25,
28.375
]
|
// Copyright (c) 2012 The Chromium Authors. All rights reserved. // Use of this source code is governed by a BSD-style license that can be // found in the LICENSE file. #include "chrome/renderer/autofill/password_autofill_manager.h" #include "base/bind.h" #include "base/memory/scoped_ptr.h" #include "base/message_loop.h" #include "chrome/common/autofill_messages.h" #include "chrome/renderer/autofill/form_autofill_util.h" #include "content/public/renderer/render_view.h" #include "third_party/WebKit/Source/WebKit/chromium/public/WebAutofillClient.h" #include "third_party/WebKit/Source/WebKit/chromium/public/WebDocument.h" #include "third_party/WebKit/Source/WebKit/chromium/public/WebElement.h" #include "third_party/WebKit/Source/WebKit/chromium/public/WebFormElement.h" #include "third_party/WebKit/Source/WebKit/chromium/public/WebFrame.h" #include "third_party/WebKit/Source/WebKit/chromium/public/WebInputEvent.h" #include "third_party/WebKit/Source/WebKit/chromium/public/WebSecurityOrigin.h" #include "third_party/WebKit/Source/WebKit/chromium/public/WebView.h" #include "third_party/WebKit/Source/WebKit/chromium/public/platform/WebVector.h" #include "ui/base/keycodes/keyboard_codes.h" #include "webkit/forms/form_field.h" #include "webkit/forms/password_form.h" #include "webkit/forms/password_form_dom_manager.h" namespace { // The size above which we stop triggering autocomplete. static const size_t kMaximumTextSizeForAutocomplete = 1000; // Maps element names to the actual elements to simplify form filling. typedef std::map<string16, WebKit::WebInputElement> FormInputElementMap; // Utility struct for form lookup and autofill. When we parse the DOM to look up // a form, in addition to action and origin URL's we have to compare all // necessary form elements. To avoid having to look these up again when we want // to fill the form, the FindFormElements function stores the pointers // in a FormElements* result, referenced to ensure they are safe to use. struct FormElements { WebKit::WebFormElement form_element; FormInputElementMap input_elements; }; typedef std::vector<FormElements*> FormElementsList; // Helper to search the given form element for the specified input elements // in |data|, and add results to |result|. static bool FindFormInputElements(WebKit::WebFormElement* fe, const webkit::forms::FormData& data, FormElements* result) { // Loop through the list of elements we need to find on the form in order to // autofill it. If we don't find any one of them, abort processing this // form; it can't be the right one. for (size_t j = 0; j < data.fields.size(); j++) { WebKit::WebVector<WebKit::WebNode> temp_elements; fe->getNamedElements(data.fields[j].name, temp_elements); // Match the first input element, if any. // |getNamedElements| may return non-input elements where the names match, // so the results are filtered for input elements. // If more than one match is made, then we have ambiguity (due to misuse // of "name" attribute) so is it considered not found. bool found_input = false; for (size_t i = 0; i < temp_elements.size(); ++i) { if (temp_elements[i].to<WebKit::WebElement>().hasTagName("input")) { // Check for a non-unique match. if (found_input) { found_input = false; break; } // This element matched, add it to our temporary result. It's possible // there are multiple matches, but for purposes of identifying the form // one suffices and if some function needs to deal with multiple // matching elements it can get at them through the FormElement*. // Note: This assignment adds a reference to the InputElement. result->input_elements[data.fields[j].name] = temp_elements[i].to<WebKit::WebInputElement>(); found_input = true; } } // A required element was not found. This is not the right form. // Make sure no input elements from a partially matched form in this // iteration remain in the result set. // Note: clear will remove a reference from each InputElement. if (!found_input) { result->input_elements.clear(); return false; } } return true; } // Helper to locate form elements identified by |data|. void FindFormElements(WebKit::WebView* view, const webkit::forms::FormData& data, FormElementsList* results) { DCHECK(view); DCHECK(results); WebKit::WebFrame* main_frame = view->mainFrame(); if (!main_frame) return; GURL::Replacements rep; rep.ClearQuery(); rep.ClearRef(); // Loop through each frame. for (WebKit::WebFrame* f = main_frame; f; f = f->traverseNext(false)) { WebKit::WebDocument doc = f->document(); if (!doc.isHTMLDocument()) continue; GURL full_origin(doc.url()); if (data.origin != full_origin.ReplaceComponents(rep)) continue; WebKit::WebVector<WebKit::WebFormElement> forms; doc.forms(forms); for (size_t i = 0; i < forms.size(); ++i) { WebKit::WebFormElement fe = forms[i]; GURL full_action(f->document().completeURL(fe.action())); if (full_action.is_empty()) { // The default action URL is the form's origin. full_action = full_origin; } // Action URL must match. if (data.action != full_action.ReplaceComponents(rep)) continue; scoped_ptr<FormElements> curr_elements(new FormElements); if (!FindFormInputElements(&fe, data, curr_elements.get())) continue; // We found the right element. // Note: this assignment adds a reference to |fe|. curr_elements->form_element = fe; results->push_back(curr_elements.release()); } } } bool IsElementEditable(const WebKit::WebInputElement& element) { return element.isEnabled() && !element.isReadOnly(); } void FillForm(FormElements* fe, const webkit::forms::FormData& data) { if (!fe->form_element.autoComplete()) return; std::map<string16, string16> data_map; for (size_t i = 0; i < data.fields.size(); i++) data_map[data.fields[i].name] = data.fields[i].value; for (FormInputElementMap::iterator it = fe->input_elements.begin(); it != fe->input_elements.end(); ++it) { WebKit::WebInputElement element = it->second; // Don't fill a form that has pre-filled values distinct from the ones we // want to fill with. if (!element.value().isEmpty() && element.value() != data_map[it->first]) return; } for (FormInputElementMap::iterator it = fe->input_elements.begin(); it != fe->input_elements.end(); ++it) { WebKit::WebInputElement element = it->second; if (!IsElementEditable(element)) continue; // Don't fill uneditable fields. // TODO(tkent): Check maxlength and pattern. element.setValue(data_map[it->first]); element.setAutofilled(true); element.dispatchFormControlChangeEvent(); } } void SetElementAutofilled(WebKit::WebInputElement* element, bool autofilled) { if (element->isAutofilled() == autofilled) return; element->setAutofilled(autofilled); // Notify any changeEvent listeners. element->dispatchFormControlChangeEvent(); } bool DoUsernamesMatch(const string16& username1, const string16& username2, bool exact_match) { if (exact_match) return username1 == username2; return StartsWith(username1, username2, true); } } // namespace namespace autofill { //////////////////////////////////////////////////////////////////////////////// // PasswordAutofillManager, public: PasswordAutofillManager::PasswordAutofillManager( content::RenderView* render_view) : content::RenderViewObserver(render_view), disable_popup_(false), ALLOW_THIS_IN_INITIALIZER_LIST(weak_ptr_factory_(this)) { } PasswordAutofillManager::~PasswordAutofillManager() { } bool PasswordAutofillManager::TextFieldDidEndEditing( const WebKit::WebInputElement& element) { LoginToPasswordInfoMap::const_iterator iter = login_to_password_info_.find(element); if (iter == login_to_password_info_.end()) return false; const webkit::forms::PasswordFormFillData& fill_data = iter->second.fill_data; // If wait_for_username is false, we should have filled when the text changed. if (!fill_data.wait_for_username) return false; WebKit::WebInputElement password = iter->second.password_field; if (!IsElementEditable(password)) return false; WebKit::WebInputElement username = element; // We need a non-const. // Do not set selection when ending an editing session, otherwise it can // mess with focus. FillUserNameAndPassword(&username, &password, fill_data, true, false); return true; } bool PasswordAutofillManager::TextDidChangeInTextField( const WebKit::WebInputElement& element) { LoginToPasswordInfoMap::const_iterator iter = login_to_password_info_.find(element); if (iter == login_to_password_info_.end()) return false; // The input text is being changed, so any autofilled password is now // outdated. WebKit::WebInputElement username = element; // We need a non-const. WebKit::WebInputElement password = iter->second.password_field; SetElementAutofilled(&username, false); if (password.isAutofilled()) { password.setValue(string16()); SetElementAutofilled(&password, false); } // If wait_for_username is true we will fill when the username loses focus. if (iter->second.fill_data.wait_for_username) return false; if (!IsElementEditable(element) || !element.isText() || !element.autoComplete()) { return false; } // Don't inline autocomplete if the user is deleting, that would be confusing. // But refresh the popup. Note, since this is ours, return true to signal // no further processing is required. if (iter->second.backspace_pressed_last) { ShowSuggestionPopup(iter->second.fill_data, username); return true; } WebKit::WebString name = element.nameForAutofill(); if (name.isEmpty()) return false; // If the field has no name, then we won't have values. // Don't attempt to autofill with values that are too large. if (element.value().length() > kMaximumTextSizeForAutocomplete) return false; // We post a task for doing the autocomplete as the caret position is not set // properly at this point (http://bugs.webkit.org/show_bug.cgi?id=16976) and // we need it to determine whether or not to trigger autocomplete. MessageLoop::current()->PostTask( FROM_HERE, base::Bind(&PasswordAutofillManager::PerformInlineAutocomplete, weak_ptr_factory_.GetWeakPtr(), element, password, iter->second.fill_data)); return true; } bool PasswordAutofillManager::TextFieldHandlingKeyDown( const WebKit::WebInputElement& element, const WebKit::WebKeyboardEvent& event) { // If using the new Autofill UI that lives in the browser, it will handle // keypresses before this function. This is not currently an issue but if // the keys handled there or here change, this issue may appear. LoginToPasswordInfoMap::iterator iter = login_to_password_info_.find(element); if (iter == login_to_password_info_.end()) return false; int win_key_code = event.windowsKeyCode; iter->second.backspace_pressed_last = (win_key_code == ui::VKEY_BACK || win_key_code == ui::VKEY_DELETE); return true; } bool PasswordAutofillManager::DidAcceptAutofillSuggestion( const WebKit::WebNode& node, const WebKit::WebString& value) { WebKit::WebInputElement input; PasswordInfo password; if (!FindLoginInfo(node, &input, &password)) return false; // Set the incoming |value| in the text field and |FillUserNameAndPassword| // will do the rest. input.setValue(value); return FillUserNameAndPassword(&input, &password.password_field, password.fill_data, true, true); } bool PasswordAutofillManager::DidSelectAutofillSuggestion( const WebKit::WebNode& node) { WebKit::WebInputElement input; PasswordInfo password; return FindLoginInfo(node, &input, &password); } bool PasswordAutofillManager::DidClearAutofillSelection( const WebKit::WebNode& node) { WebKit::WebInputElement input; PasswordInfo password; return FindLoginInfo(node, &input, &password); } void PasswordAutofillManager::SendPasswordForms(WebKit::WebFrame* frame, bool only_visible) { // Make sure that this security origin is allowed to use password manager. WebKit::WebSecurityOrigin origin = frame->document().securityOrigin(); if (!origin.canAccessPasswordManager()) return; WebKit::WebVector<WebKit::WebFormElement> forms; frame->document().forms(forms); std::vector<webkit::forms::PasswordForm> password_forms; for (size_t i = 0; i < forms.size(); ++i) { const WebKit::WebFormElement& form = forms[i]; // Respect autocomplete=off. if (!form.autoComplete()) continue; // If requested, ignore non-rendered forms, e.g. those styled with // display:none. if (only_visible && !form.hasNonEmptyBoundingBox()) continue; scoped_ptr<webkit::forms::PasswordForm> password_form( webkit::forms::PasswordFormDomManager::CreatePasswordForm(form)); if (password_form.get()) password_forms.push_back(*password_form); } if (password_forms.empty() && !only_visible) { // We need to send the PasswordFormsRendered message regardless of whether // there are any forms visible, as this is also the code path that triggers // showing the infobar. return; } if (only_visible) { Send(new AutofillHostMsg_PasswordFormsRendered( routing_id(), password_forms)); } else { Send(new AutofillHostMsg_PasswordFormsParsed(routing_id(), password_forms)); } } bool PasswordAutofillManager::OnMessageReceived(const IPC::Message& message) { bool handled = true; IPC_BEGIN_MESSAGE_MAP(PasswordAutofillManager, message) IPC_MESSAGE_HANDLER(AutofillMsg_FillPasswordForm, OnFillPasswordForm) IPC_MESSAGE_UNHANDLED(handled = false) IPC_END_MESSAGE_MAP() return handled; } void PasswordAutofillManager::DidFinishDocumentLoad(WebKit::WebFrame* frame) { // The |frame| contents have been parsed, but not yet rendered. Let the // PasswordManager know that forms are loaded, even though we can't yet tell // whether they're visible. SendPasswordForms(frame, false); } void PasswordAutofillManager::DidFinishLoad(WebKit::WebFrame* frame) { // The |frame| contents have been rendered. Let the PasswordManager know // which of the loaded frames are actually visible to the user. This also // triggers the "Save password?" infobar if the user just submitted a password // form. SendPasswordForms(frame, true); } void PasswordAutofillManager::FrameDetached(WebKit::WebFrame* frame) { FrameClosing(frame); } void PasswordAutofillManager::FrameWillClose(WebKit::WebFrame* frame) { FrameClosing(frame); } //////////////////////////////////////////////////////////////////////////////// // PageClickListener implementation: bool PasswordAutofillManager::InputElementClicked( const WebKit::WebInputElement& element, bool was_focused, bool is_focused) { // TODO(jcivelli): http://crbug.com/51644 Implement behavior. return false; } bool PasswordAutofillManager::InputElementLostFocus() { return false; } void PasswordAutofillManager::OnFillPasswordForm( const webkit::forms::PasswordFormFillData& form_data, bool disable_popup) { disable_popup_ = disable_popup; FormElementsList forms; // We own the FormElements* in forms. FindFormElements(render_view()->GetWebView(), form_data.basic_data, &forms); FormElementsList::iterator iter; for (iter = forms.begin(); iter != forms.end(); ++iter) { scoped_ptr<FormElements> form_elements(*iter); // If wait_for_username is true, we don't want to initially fill the form // until the user types in a valid username. if (!form_data.wait_for_username) FillForm(form_elements.get(), form_data.basic_data); // Attach autocomplete listener to enable selecting alternate logins. // First, get pointers to username element. WebKit::WebInputElement username_element = form_elements->input_elements[form_data.basic_data.fields[0].name]; // Get pointer to password element. (We currently only support single // password forms). WebKit::WebInputElement password_element = form_elements->input_elements[form_data.basic_data.fields[1].name]; // We might have already filled this form if there are two <form> elements // with identical markup. if (login_to_password_info_.find(username_element) != login_to_password_info_.end()) continue; PasswordInfo password_info; password_info.fill_data = form_data; password_info.password_field = password_element; login_to_password_info_[username_element] = password_info; webkit::forms::FormData form; webkit::forms::FormField field; FindFormAndFieldForInputElement( username_element, &form, &field, REQUIRE_NONE); Send(new AutofillHostMsg_AddPasswordFormMapping( routing_id(), field, form_data)); } } //////////////////////////////////////////////////////////////////////////////// // PasswordAutofillManager, private: void PasswordAutofillManager::GetSuggestions( const webkit::forms::PasswordFormFillData& fill_data, const string16& input, std::vector<string16>* suggestions) { if (StartsWith(fill_data.basic_data.fields[0].value, input, false)) suggestions->push_back(fill_data.basic_data.fields[0].value); webkit::forms::PasswordFormFillData::LoginCollection::const_iterator iter; for (iter = fill_data.additional_logins.begin(); iter != fill_data.additional_logins.end(); ++iter) { if (StartsWith(iter->first, input, false)) suggestions->push_back(iter->first); } } bool PasswordAutofillManager::ShowSuggestionPopup( const webkit::forms::PasswordFormFillData& fill_data, const WebKit::WebInputElement& user_input) { WebKit::WebFrame* frame = user_input.document().frame(); if (!frame) return false; WebKit::WebView* webview = frame->view(); if (!webview) return false; std::vector<string16> suggestions; GetSuggestions(fill_data, user_input.value(), &suggestions); if (disable_popup_) { webkit::forms::FormData form; webkit::forms::FormField field; FindFormAndFieldForInputElement( user_input, &form, &field, REQUIRE_NONE); WebKit::WebInputElement selected_element = user_input; gfx::Rect bounding_box(selected_element.boundsInViewportSpace()); Send(new AutofillHostMsg_ShowPasswordSuggestions(routing_id(), field, bounding_box, suggestions)); return !suggestions.empty(); } if (suggestions.empty()) { webview->hidePopups(); return false; } std::vector<string16> labels(suggestions.size()); std::vector<string16> icons(suggestions.size()); std::vector<int> ids(suggestions.size(), WebKit::WebAutofillClient::MenuItemIDPasswordEntry); webview->applyAutofillSuggestions( user_input, suggestions, labels, icons, ids); return true; } bool PasswordAutofillManager::FillUserNameAndPassword( WebKit::WebInputElement* username_element, WebKit::WebInputElement* password_element, const webkit::forms::PasswordFormFillData& fill_data, bool exact_username_match, bool set_selection) { string16 current_username = username_element->value(); // username and password will contain the match found if any. string16 username; string16 password; // Look for any suitable matches to current field text. if (DoUsernamesMatch(fill_data.basic_data.fields[0].value, current_username, exact_username_match)) { username = fill_data.basic_data.fields[0].value; password = fill_data.basic_data.fields[1].value; } else { // Scan additional logins for a match. webkit::forms::PasswordFormFillData::LoginCollection::const_iterator iter; for (iter = fill_data.additional_logins.begin(); iter != fill_data.additional_logins.end(); ++iter) { if (DoUsernamesMatch(iter->first, current_username, exact_username_match)) { username = iter->first; password = iter->second; break; } } } if (password.empty()) return false; // No match was found. // Input matches the username, fill in required values. username_element->setValue(username); if (set_selection) { username_element->setSelectionRange(current_username.length(), username.length()); } SetElementAutofilled(username_element, true); if (IsElementEditable(*password_element)) password_element->setValue(password); SetElementAutofilled(password_element, true); return true; } void PasswordAutofillManager::PerformInlineAutocomplete( const WebKit::WebInputElement& username_input, const WebKit::WebInputElement& password_input, const webkit::forms::PasswordFormFillData& fill_data) { DCHECK(!fill_data.wait_for_username); // We need non-const versions of the username and password inputs. WebKit::WebInputElement username = username_input; WebKit::WebInputElement password = password_input; // Don't inline autocomplete if the caret is not at the end. // TODO(jcivelli): is there a better way to test the caret location? if (username.selectionStart() != username.selectionEnd() || username.selectionEnd() != static_cast<int>(username.value().length())) { return; } // Show the popup with the list of available usernames. ShowSuggestionPopup(fill_data, username); // Fill the user and password field with the most relevant match. FillUserNameAndPassword(&username, &password, fill_data, false, true); } void PasswordAutofillManager::FrameClosing(const WebKit::WebFrame* frame) { for (LoginToPasswordInfoMap::iterator iter = login_to_password_info_.begin(); iter != login_to_password_info_.end();) { if (iter->first.document().frame() == frame) login_to_password_info_.erase(iter++); else ++iter; } } bool PasswordAutofillManager::FindLoginInfo( const WebKit::WebNode& node, WebKit::WebInputElement* found_input, PasswordInfo* found_password) { if (!node.isElementNode()) return false; WebKit::WebElement element = node.toConst<WebKit::WebElement>(); if (!element.hasTagName("input")) return false; WebKit::WebInputElement input = element.to<WebKit::WebInputElement>(); LoginToPasswordInfoMap::iterator iter = login_to_password_info_.find(input); if (iter == login_to_password_info_.end()) return false; *found_input = input; *found_password = iter->second; return true; } } // namespace autofill | Mid | [
0.5657894736842101,
32.25,
24.75
]
|
Molecular docking prediction and in vitro studies elucidate anti-cancer activity of phytoestrogens. The study is aimed at evaluating the chemosensitization and apoptotic effect of aglycone rich extracts of dietary phytoestrogens (derived from soybean and flaxseed) on estrogen receptor positive, MCF-7 and estrogen receptor negative, MDA-MB-231 cells. The extracts show potent activity on both the cell lines, hence, in silico studies have been carried out to find the possible reason for their activity. MTT assay was carried to assess chemosensitization effect and activated caspase-3/7 activity was studied using flow-cytometry and western blotting. In silico studies were carried out using PharmMapper and the top hits were taken up for docking using the Schrödinger software. Top molecular targets were subjected to gene expression studies by qPCR and protein expression using Western blot analysis. This study reports the apoptotic activity and chemosensitization effect of the phytoestrogens. Molecular docking studies predict AKR1B1 (aldose reductase), HRAS (Harvey rat sarcoma) and GSTP1 (glutathione s-transferase pi) as potential molecular targets for genistein, daidzein and secoisolariciresinol, respectively. Gene and protein expression studies show down-regulation of AKR1BI, HRAS and GSTP1 by the extracts. The qPCR and western blot analysis results support the computational analyses, and hence genistein, daidzein and secoisolariciresinol may be considered as good candidates for future development into potent inhibitors of the respective protein targets through medicinal chemistry optimization. | High | [
0.71137026239067,
30.5,
12.375
]
|
It is a speech bubble square with rounded corners. Inside of it are 2 triangular mountains (one slightly larger and in the foreground) and a circular sun, somewhat like a stereotypical landscape photo. | Low | [
0.42790697674418604,
23,
30.75
]
|
Q: UIWindow endDisablingInterfaceAutorotationAnimated: error I'm receiving the following error when a user is in MFMailComposerViewController and presses the Home button: [UIWindow endDisablingInterfaceAutorotationAnimated:] called on > without matching -beginDisablingInterfaceAutorotation. Ignoring. I have looked around the forums and some other people have experienced this error in different circumstances, but there is no solution. I have set shouldAutorotate to this in all the View Controllers in the app: - (BOOL)shouldAutorotateToInterfaceOrientation: (UIInterfaceOrientation)interfaceOrientation { return interfaceOrientation == UIInterfaceOrientationPortraitUpsideDown || interfaceOrientation == UIInterfaceOrientationPortrait; } A: Check if you have redundant calls to dismiss keyboard, UIActionSheet and etc. I had the same problem and solved by changing my way to dismiss the keyboard. I found this below post to be the most helpful one Unknown error [UIWindow endDisablingInterfaceAutorotation] | Low | [
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Login with Your Social Media Accounts Yeddyurappa admits to meeting JD(S) MLA’s son, says audio was edited Karnataka BJP President admits voice in audio clip was his own, but says it was edited according to convenience Bengaluru: Karnataka BJP president, BS Yeddyurappa admitted that the voice in the audio clip that Chief Minister HD Kumaraswamy released was his own but claimed that the audio was edited as per convenience. He also admitted to meeting Sharanagouda. Yeddyurappa spoke to media at Hubbali airport and said that the met JD(S) MLA Naganagouda's son Sharanagouda at the inspection bungalow in Devdurg. In his statement however, Yeddyurappa reiterated that he would step down as an MLA if HD Kumaraswamy's allegations were proved true. Yeddyurappa's has made alterations to earlier statements regarding the audio clip just a few days after he claimed that the audio was fake and the allegations of him meeting Sharanagouda was untrue. Nevertheless, despite the change in statements the BJP has filed a complaint against the Kumaraswamy for defamation. On Feb 8, Karnataka Chief Minister HD Kumaraswamy had released an audio recording of an alleged conversation between BS Yeddyurappa and Sharanagouda Kandkur just hours before his budget speech. In the alleged conversation, Yeddyurappa was heard trying to woo Sharanagouda with an offer of crores in cash and a ministerial berth. In his conversation, he is heard saying that the speaker of the Assembly has also been bought on order to accept resignations of the ruling party MLAs. Many prominent names such as Prime Minister Modi, Amit Shah and officials of the court were also mentioned in the alleged conversation. BS Yeddyurappa dismissed the allegations and called it a dramatization with voiceovers. Though the Karnataka BJP leader did not however mention the purpose of meeting Sharanagouda, there’s enough in this controversy to keep the ‘Operation Lotus’ theory afloat. | Low | [
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Avatar Sequels To Start Production Next Fall James Cameron created a sensation when he released Avatar in December of 2009. Holding the top spot at the charts for seven weeks in a row, the film wound up making nearly $750 million domestically when it was first released, and it continues to be the only film other than Titanic to make over $2 billion at the global box office. Fans have waited patiently ever since for Cameron to get around to making the sequel, and were excited back in August when the director promised Avatar 2 for December 2016. But when does that mean cameras will start rolling? According to star Sam Worthington, the answer to that question is about one full year from now. Variety picked up on an interview that the actor did with an Australia radio station called NovaFM and revealed both when and how they will be shooting the sequels for Avatar. “We are going to start this time next year and we will do two, three and four,” he said. “In one shot, we’ll do them simultaneously. I’ll be grateful if it finishes.” He added, "I think Jim is building the ship to Pandora, to be honest." This, of course, won't be the first time that a major blockbuster franchise has filmed a bunch of movies at the same time. Peter Jackson decided that this method was the best way for him to make his Lord of the Rings trilogy - a series that went on to become an unquestionable success - and he did it again when it came time to start filming The Hobbit. What makes this such a challenging way to shoot is that the production needs to have all of the scripts in place before production begins, which means that Cameron and his writers have to have three full scripts ready to go. This would also go a long way in explaining why it's taken so long for these sequels to get going. Making three movies in one go could also suggest that all three will be playing out one big over-arching storyline while each of the individual movies have full narratives of their own. Hopefully this means that Cameron and screenwriters Josh Friedman (War of the Worlds), Rick Jaffa & Amanda Silver (Rise of the Planets of the Apes), and Shane Salerno (Savages) are putting more thought into the story than what we saw last time. They'll certainly have a ridiculous budget to work with thanks to the box office earnings of the first movie, so we'll just have to hope that they use it appropriately. | Mid | [
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The present invention relates to a valve for an opening of a pressure vessel. More particularly, it relates to a valve for such pressure vessel which has a housing and a resiliently deformable partition wall -- e.g. a diaphragm -- located in the housing and forming two compartments so that one of the compartments is filled with a liquid and has an opening in which latter the valve is mounted. Valves for pressure vessels have been proposed each having a movable body member that is urged into a closed position by the resiliently expanded partition wall and urged into an open position by a spring acting in a direction substantially opposite to the direction in which said partition wall acts. It has, however, been recognized that when the liquid enters an outflow passage defined or in part bounded by the body member, at great speed, it exerts a component force upon the body member which tends to prematurely urge the latter into the closed position. Taking this into consideration, means have been proposed for preventing premature movement of the body member into the closed position, including a stem formed in the portion of the body member located in the pressure vessel and a passage provided in said portion so that the liquid flows through the passage, reacts against an inner end of the stem and provides a force operatively reacting against a valve head and urging the body member into an open position. While it is true that the above construction reliably performs its functions of preventing premature closing of the valve, it is very complicated and expensive. | Low | [
0.5086705202312131,
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Role of unstable periodic orbits in phase and lag synchronization between coupled chaotic oscillators. An increase of the coupling strength in the system of two coupled Rössler oscillators leads from a nonsynchronized state through phase synchronization to the regime of lag synchronization. The role of unstable periodic orbits in these transitions is investigated. Changes in the structure of attracting sets are discussed. We demonstrate that the onset of phase synchronization is related to phase-lockings on the surfaces of unstable tori, whereas transition from phase to lag synchronization is preceded by a decrease in the number of unstable periodic orbits. | High | [
0.7278020378457061,
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INTRODUCTION {#s1} ============ Malignant mesothelioma (MMe) is an aggressive fatal cancer, predominantly of the pleura and peritoneum, primarily caused by occupational asbestos exposure \[[@R1]\]. Current approaches involving surgery, radiotherapy or chemotherapy have failed to bring a clear survival benefit to patients, with a median survival of less than 12 months from diagnosis \[[@R2]\]. Clearly, new therapeutic strategies are urgently needed to improve the survival rate and quality of life of these patients. The Hedgehog (Hh) pathway is a conserved signaling pathway responsible for the regulation of pattern specification during embryonic development \[[@R3]\]. It is also involved in the control of adult tissue homeostasis and stem cell maintenance \[[@R4]\]. For Hh signaling, the Hh protein acts as a ligand for the Patched1 (PTCH1) transmembrane receptor proteins \[[@R5]\]. PTCH1 interaction with transmembrane signal transducer Smoothened (SMO) under normal conditions inhibits SMO function \[[@R6]\]. Upon binding of Hh ligand to PTCH1, the inhibition of SMO by PTCH1 is alleviated, resulting in the activation of Gli transcription factors, capable of regulating expression of Hh target genes \[[@R7]\]. Several small molecule compounds with inhibitory effects on the Hh pathway have been reported. Notably, US FDA has approved GDC-0449, a SMO antagonist, for the treatment of patients with advanced stages of basal cell carcinoma \[[@R8]\]. Besides targeting SMO, the Hh ligand and Gli transcription factors appear highly amenable to inhibition by small molecule inhibitors. Of particular interest is GANT61, discovered in a cell-based screen for antagonists of Gli-mediated transcription \[[@R9]\]. GANT61 induces apoptosis in various human cancer cells including MMe \[[@R10]--[@R13]\] and suppresses the growth of prostate carcinoma \[[@R9]\] and neuroblastoma \[[@R14]\] xenografts in mice, suggesting that Gli proteins could be a therapeutic target in these cancers. The cytotoxic effect of GANT61 was previously attributed to the inhibition of Gli binding to DNA \[[@R9]\], thus preventing the transcription of Hh target genes such as Bcl-2 \[[@R10], [@R15]\], which are involved in cell proliferation and apoptosis. Recent studies showed that GANT61 induced autophagic death in hepatocellular carcinoma (HCC) cells through upregulation of Bnip3 \[[@R16]\]. However, it is unclear whether GANT61 have effects independent of Hh/Gli signaling. Reactive oxygen species (ROS) are traditionally viewed as toxic molecules that damage cellular DNA, proteins and lipids \[[@R17]\]. However recently, ROS have been shown to have important physiological signaling functions \[[@R18]\]. Generation of ROS in response to chemo- and radio-therapy has been reported to induce cell cycle arrest and/or cell death in various cancer models \[[@R19]\]. However, whether GANT61 induces ROS generation has not been reported. Therefore, we examined the role of ROS in mediating GANT61-induced apoptosis and determined if this occurred via Hh/Gli signaling. RESULTS {#s2} ======= GANT61 induces G1 cell cycle arrest and apoptosis in human MMe cells {#s2_1} -------------------------------------------------------------------- The antiproliferative activity of GANT61 was assessed in MMe cells. GANT61 inhibited cell proliferation in all MMe cell lines in a dose-dependent manner (Figure [1A](#F1){ref-type="fig"}). Among the cell lines tested, JU77 cells showed highest sensitivity to GANT61 treatment (IC~50~ = 4.02 μM) whereas NO36 cells appeared to be the most resistant (IC~50~ = 31.8 μM) (Figure [1A](#F1){ref-type="fig"}). As shown in Figure [1B](#F1){ref-type="fig"}, concomitant with growth inhibitory effect, GANT61 induced G1 cell cycle arrest as indicated by the increased percentage of LO68 cells in G1 cell cycle phase at 24 h compared to vehicle-treated cells. There was also an accumulation of cells in the sub-G1 fraction at 48--72 h compared to vehicle-treated cells, suggesting that apoptosis is involved (Figure [1C](#F1){ref-type="fig"}). To understand the cell death response to GANT61 in LO68 cells, cells were treated with GANT61 and phosphatidylserine externalization, a marker of early apoptosis, determined. GANT61 induced a parallel increase in apoptotic cell death in a dose- and time-dependent manner, as indicated by FACS analysis of annexin V-binding (Figure [1D](#F1){ref-type="fig"}). {#F1} GANT61 targets Gli transcription factors in MMe cells {#s2_2} ----------------------------------------------------- GANT61 reduced mRNA expression of *GLI1* and *GLI2* following treatment with 20 μM GANT61 for up to 72 h (Figure [2A](#F2){ref-type="fig"}) as well as the Gli downstream target gene *PTCH1* (Figure [2A](#F2){ref-type="fig"}). A similar downregulation of GLI1 and GLI2 proteins was observed after 24 h exposure to different concentrations of GANT61 (10--30 μM) (Figure [2B](#F2){ref-type="fig"}). The protein level of Bcl-2, a GLI1 downstream target gene \[[@R20]\], was also reduced after GANT61 treatment (Figure [2B](#F2){ref-type="fig"}). To confirm the specificity of inhibition of GLI1 and GLI2 by GANT61, we tested its efficacy in a Gli luciferase reporter assay. Consistent with previous findings, GANT61 inhibited the Gli reporter activity in LO68 cells (Figure [2C](#F2){ref-type="fig"}). These findings point to GANT61 being an inhibitor of GLI1 and GLI2 \[[@R9]\]. {#F2} GANT61 induces oxidative stress {#s2_3} ------------------------------- Previous studies showed that GANT61 can induce DNA damage in colon cancer cells \[[@R10]\]. We hypothesize that GANT61 triggers the production of reactive oxygen species (ROS), which in turn damages DNA. To test this hypothesis, cells were treated with GANT61 (10--20 μM) for 24 to 48 h and intracellular ROS levels were measured using the carboxy derivative of fluorescein, CH~2~DCFDA. As shown in Figure [3A](#F3){ref-type="fig"}, ROS levels increased significantly in LO68 cells treated with GANT61 in a dose- and time-dependent manner. GANT61 also triggered ROS generation in HCT116 and HT29 colon cancer cells, suggesting that the production of ROS could be a general effect of GANT61 exposure (Figure [3B](#F3){ref-type="fig"}). Moreover, pretreatment of LO68 cells with N-acetylcysteine (NAC) and reduced L-glutathione (GSH), two potent ROS scavengers, attenuated this accumulation of ROS (Figure [3C](#F3){ref-type="fig"}). As shown in Figure [3D](#F3){ref-type="fig"}, neutralization of ROS by NAC in GANT61-treated cells restored cell viability, suggesting that ROS is responsible for GANT61 cytotoxicity. Consistent with this data, annexin V/7AAD assays showed that NAC pretreatment rescued LO68 cells from GANT61-induced apoptosis (Figure [3E](#F3){ref-type="fig"}). {#F3} GANT61 downregulates GLI1, GLI2 and PTCH1 through ROS {#s2_4} ----------------------------------------------------- We next examined the effect of NAC on GANT61-mediated *GLI1*, *GLI2* and *PTCH1* expression. As shown in Figure [4A](#F4){ref-type="fig"}, the downregulation of *GLI1*, *GLI2* and *PTCH1* expression by GANT61, as determined by qRT-PCR, was abolished by pretreating cells with NAC. The blockade of ROS accumulation by NAC prevents reduction of *GLI1*, *GLI2* and *PTCH1* expression indicating the involvement of ROS in modulation of the Hh pathway. Stimulated by our novel finding that ROS could potentially impact on the Hh pathway, we next assessed the effect of exposing LO68 cells to menadione, a ROS generator, and hydrogen peroxide (H~2~O~2~), a mimic of oxidative stress, on the Hh pathway. FACS analysis of intracellular ROS production indicated that exposure of LO68 cells to menadione and H~2~O~2~ resulted in a significant increase in ROS production as measured by the fluorescent CH~2~DCFDA probe (Figure [4B and 4C](#F4){ref-type="fig"}). Furthermore, qRT-PCR analysis of gene expression in LO68 cells following treatment clearly indicated the ability of menadione and H~2~O~2~ to downregulate the expression of *GLI1*, a marker of Hh pathway activity (Figure [4D and 4E](#F4){ref-type="fig"}). Together, these findings suggest that ROS plays a critical role in the suppression of *GLI1*, *GLI2* and *PTCH1* expression by GANT61. {#F4} GANT61-induced ROS, apoptosis and cell cycle arrest are independent of Gli inhibition {#s2_5} ------------------------------------------------------------------------------------- Because GANT61 is an inhibitor of Gli transcription factors, we set out to determine whether GANT61-induced G1 cell cycle arrest, apoptosis and ROS production are dependent on Gli inhibition. First, we examined apoptosis and ROS production in LO68 cells following siRNA-mediated depletion of GLI1 and GLI2. qRT-PCR analyses demonstrated knockdowns of GLI1 and GLI2 mRNA in LO68 cells (Figure [5A](#F5){ref-type="fig"}). Surprisingly however, neither individual GLI1 or GLI2 knockdowns nor their combined depletion induced cell death as indicated by the small sub-G1 apoptotic population (\< 5% in sub-G1 phase in GLI1- and/or GLI2-depleted cells compared to \~5% cells in sub-G1 phase in LO68 cells transiently transfected with negative control (NC) siRNA), indicating that the pro-apoptotic activity of the drug is likely to be independent of Gli inhibition (Figure [5B](#F5){ref-type="fig"}). Similarly, the results from FACS analysis showed that the knockdowns of GLI1 and GLI2 by siRNA did not result in G1 cell cycle arrest (\~60% in G1 phase in GLI1- and/or GLI2-depleted cells compared to \~60% cells in G1 phase in LO68 cells transiently transfected with NC siRNA) (Figure [5C](#F5){ref-type="fig"}). Moreover, depletion of GLI1 and GLI2, individually or together using siRNAs did not result in ROS generation in LO68 cells (Figure [5D](#F5){ref-type="fig"}). Taken together, our data suggest that generation of ROS and induction of apoptosis and cell cycle arrest in response to GANT61 is independent of Hh/Gli signaling in LO68 cells. {#F5} GANT61-induced apoptosis and ROS production is dependent on mitochondria {#s2_6} ------------------------------------------------------------------------ The mitochondrion is a major site of ROS generation in mammalian cells \[[@R18]\]. To determine the site of ROS production in response to GANT61, LO68 cells were treated with GANT61 in the absence or presence of rotenone, a mitochondrial complex I inhibitor, and the effects on GANT61-induced ROS generation and apoptosis were assessed. GANT61-induced ROS production (Figure [6A](#F6){ref-type="fig"}) and apoptosis (Figure [6B](#F6){ref-type="fig"}) were significantly blocked by the addition of rotenone, indicating that the ROS produced in response to GANT61 was of mitochondrial origin. The addition of a mitochondria-targeted antioxidant, MitoTEMPO, also blocked the increase in apoptosis induced by GANT61 (Figure [6C](#F6){ref-type="fig"}). We further confirm the mitochondrial origin of ROS by measuring the levels of superoxide within mitochondria after exposure to GANT61 using the fluorescent probe mitoSOX red. As shown in Figure [6D](#F6){ref-type="fig"}, exposure to 20 μM GANT61 for 48 h induced an increase in intramitochondrial superoxide levels. In addition, this increase in intramitochondrial superoxide was attenuated by pretreating cells for 1 h with 20 mM NAC before co-treating with 20 μM GANT61 (Figure [6D](#F6){ref-type="fig"}). {#F6} Mitochondrial superoxide is essential for GANT61-induced apoptosis {#s2_7} ------------------------------------------------------------------ To genetically confirm involvement of mitochondrial superoxide in GANT61-induced apoptosis, we generated LO68 ρ^0^ cells, which lack mitochondrial DNA, by exposing cells to low concentration of ethidium bromide. Mitochondrial DNA depletion was verified in LO68 ρ^0^ cells by amplifying three mitochondria-encoded genes, *COX1*, *D-loop* and *ND6*, by PCR. In addition, *GADPH* was amplified to serve as a control for nuclear-encoded genes. As shown in Figure [7A](#F7){ref-type="fig"}, ethidium bromide treatment resulted in a marked reduction of PCR products for *COX1*, *D-loop* and *ND6*. There was no difference in the levels of *GAPDH* PCR product between LO68 and LO68 ρ^0^ cells, indicating that nuclear DNA was not depleted in the process of establishing LO68 ρ^0^ cells (Figure [7A](#F7){ref-type="fig"}). Next, LO68 and LO68 ρ^0^ cells were treated with GANT61 (10--20 μM) for 48 h before staining with mitoSOX red. In LO68 cells, exposure to GANT61 for 48 h resulted in an induction of mitochondrial superoxide formation. MitoSOX red oxidation was significantly reduced in LO68 ρ^0^ cells, indicating that a functional respiratory chain is required for the GANT61 induction of superoxide formation (Figure [7B](#F7){ref-type="fig"}). To determine whether functional mitochondrial respiratory chain is important for mediating GANT61-induced apoptosis, we compared apoptosis in LO68 and LO68 ρ^0^ cells exposed to GANT61 (10 and 20 μM) for 48 h. As shown in Figure [7C](#F7){ref-type="fig"}, GANT61 increased apoptosis in a dose-dependent manner in LO68 cells as assessed by annexin V staining. In contrast, GANT61 induced negligible apoptosis in LO68 ρ^0^ cells after exposure to GANT61. Furthermore, to exclude the possibility that LO68 ρ^0^ cells were resistant to apoptosis because of their loss of a functional mitochondrial respiratory chain, LO68 and LO68 ρ^0^ cells were treated with cisplatin (10 and 20 μM), a standard chemotherapeutic drug known to induce apoptosis in LO68 cells, for 48 h, and apoptosis was assessed by annexin V staining. As shown in Figure [7D](#F7){ref-type="fig"}, LO68 and LO68 ρ^0^ cells undergo apoptosis when treated with cisplatin. Also there was no statistical difference in the level of apoptosis between LO68 and LO68 ρ^0^ cells as demonstrated by annexin V assay (*p* \> 0.05). Taken together, these results suggest that GANT61-induced apoptosis is mediated by mitochondrial superoxide. {#F7} DISCUSSION {#s3} ========== Targeting the Hh pathway either through RNA-interference knockdown of GLI1 and GLI2 or using Gli inhibitors, has been shown to induce growth inhibition and cell death in mesothelioma cells and xenograft tumors *in vivo* \[[@R13], [@R21], [@R22]\]. A promising anticancer agent GANT61, with Gli inhibitory activity, displayed potent cytotoxic activity against diverse human cancer types including MMe \[[@R13]--[@R15], [@R23]--[@R25]\]. On the basis of computational docking and surface plasmon resonance data, GANT61 has been proposed to mediate its pro-apoptotic effect by binding directly to GLI1, which in turn inhibits GLI1 from binding to DNA \[[@R9], [@R26]\]. There is evidence that GANT61 appears to have a novel anticancer mechanism that differs from other Hh antagonists. Recent studies have reported that GANT61 triggers apoptosis via induction of DNA double strand breaks and activation of ATM-Chk2 DNA damage response in colon cancer cells \[[@R10], [@R27]\]. Using a panel of MMe cell lines, we have demonstrated that GANT61-induced anti-proliferative effects were related to the inhibition of cell growth, as confirmed by reduction of cell growth and induction of G1 cell cycle arrest. Our data also show that GANT61 induced apoptotic cell death in LO68 cells in a concentration- and time-dependent manner. We present data indicating that GANT61 specifically acts on the Hh-Gli pathway, as demonstrated by a reduction in the expression levels of downstream pathway effectors GLI1 and GLI2 and Gli target genes PTCH1 and Bcl-2. GANT61 also significantly decreased the Gli-luciferase reporter activity in a dose-dependent manner. These results are consistent with previous reports in HEK294 cells transiently overexpressing GLI1 and colon cancer cells with constitutively active Hh signaling \[[@R9], [@R15]\]. At this juncture, our data corroborate previous findings that GANT61 inhibits Hh signaling at the level of Gli transcription factors \[[@R9], [@R14], [@R15]\]. However, silencing GLI1 and GLI2, individually or together, were not sufficient to induce cell death in LO68 cells, strongly suggesting that GANT61-induced apoptosis was not associated with Gli inhibition. Our data is in contrast to previous siRNA experiments, where silencing of GLI1 resulted in increased apoptosis and reduced level of anti-apoptotic Bcl-2 in HCC, glioma and breast cancer cells \[[@R28]--[@R30]\]. Thus, it is possible that GANT61-induced apoptosis may be initiated by another factor other than Gli inhibition. An alternative explanation for Gli-independent induction of apoptosis by GANT61 is production of ROS. Previous reports have shown that certain chemotherapeutic drugs can induce caspase-independent apoptosis that is brought about by the production of ROS \[[@R31], [@R32]\]. The present studies showed that ROS were generated concomitantly with apoptosis in a dose- and time-dependent manner in LO68 cells upon treatment of cells with GANT61. Interestingly, similar to GANT61-induced apoptosis, Gli silencing by siRNA showed that although GLI1 and GLI2 were downregulated in LO68 cells, they did not appear to be involved in induction of ROS generation. Furthermore, the apoptogenic role of ROS production was supported by the ability of two general antioxidants, NAC and GSH, to rescue cells from GANT61-induced apoptosis. However, it is hard to determine the specific ROS species that are generated from GANT61 exposure in LO68 cells. It seems likely that the superoxide produced in the mitochondria might play an important role in the induction of apoptosis. Approximately 1--2% of electrons can "leak" to oxygen to form superoxide in a reaction mediated mainly by complex I and III of the mitochondrial respiratory chain \[[@R33]\]. To identify the source of ROS, rotenone, a complex I inhibitor, was able to reduce GANT61-induced ROS production and rescue LO68 cells from GANT61-induced apoptosis when it was added to cells prior to GANT61 exposure. This result implied that GANT61-induced ROS might come from mitochondria. Because the blockade of GANT61-induced apoptosis by rotenone was partial, there could also be other sites of ROS production. Another major site of ROS generation is plasma membrane NADPH oxidase \[[@R34]\]. Mitochondrial DNA-depleted ρ° cells lack a working respiratory chain and are not able to generate ATP and ROS within mitochondria \[[@R35], [@R36]\]. We thus hypothesized that the depletion of mitochondrial DNA in LO68 ρ° cells may interfere with ROS production and in turn apoptosis, after treatment with GANT61. Consistent with our hypothesis, LO68 ρ° cells showed resistance to GANT61, and lower mitochondrial superoxide levels were also observed after GANT61 treatment. The resistance of LO68 ρ° cells to GANT61 was not associated with a decreased susceptibility to apoptosis, as indicated by the equal sensitivity to cisplatin of wild-type and ρ° cells. Overall, our results are consistent with the hypothesis that susceptibility to GANT61 stems from exaggerated production of ROS from the mitochondrial respiratory chain. In conclusion, the present study not only demonstrates the therapeutic potential of GANT61 in MMe, but also demonstrates a novel mechanism for GANT61-induced G1 phase arrest and apoptosis in MMe cells. This is the first report of apoptosis induced by GANT61 via generation of mitochondrial ROS. Based on the findings in this paper, we propose a model showing the relationship of GANT61, ROS and mitochondria in the induction of growth suppression and apoptosis of MMe cells (Figure [8](#F8){ref-type="fig"}). Our results offer an initial proof-of-concept that mitochondrial ROS-mediated anticancer mechanisms may be exploited for therapeutic benefits in MMe. {#F8} MATERIAL AND METHODS {#s4} ==================== Cell lines and culture conditions {#s4_1} --------------------------------- The cell lines MSTO-211H, NCI-H28, HCT116 and HT29 were obtained from the American Type Culture Collection; JU77, LO68, NO36, ONE58 and STY51 were gifts from Professor Bruce W. Robinson \[[@R37]\]; GAY2911, OLD1612 and VGE were derived from pleural fluids or tumors of MMe patients. Cells were cultured in Dulbecco\'s modified Eagle\'s medium supplemented with 10% fetal bovine serum (Serana), 4 mM L-glutamine (Life Technologies), 100 units/ml penicillin (Life Technologies) and 100 μg/ml streptomycin (Life Technologies) in a humidified 37°C incubator with 5% CO~2~. TaqMan quantitative real-time PCR analysis (qRT-PCR) {#s4_2} ---------------------------------------------------- qRT-PCR was performed as described previously \[[@R38]\]. mRNA expression of genes was quantified using the following TaqMan gene expression arrays (Applied Biosystems): *GLI1* (hs01110766_m1), *GLI2* (hs01119974_m1), *PTCH1* (hs00181117_m1) and *PGK1* (4326318E-1006008). The levels of each gene were normalized to *PGK1* mRNA and presented as fold change with respect to untreated cells for each gene. Cell proliferation assay {#s4_3} ------------------------ Cell proliferation was determined using the methylene blue assay as previously described \[[@R39]\]. Briefly, cells were seeded in 96-well plates and treated the following day with GANT61 (0.2 -- 50 μM) (Tocris Bioscience) or dimethyl sulfoxide (DMSO) (Sigma Aldrich) as vehicle control. Following treatment, cells were fixed with 4% paraformaldehyde (Sigma Aldrich) for 10 min at 4°C followed by staining with 2% methylene blue/0.01M borate (pH 8.5) solution (Sigma Aldrich). Excess dye was then washed off using 0.01M borate buffer (pH 8.5) and the methylene blue dye from cells were extracted with 1:1 (v/v) ethanol and 0.I M hydrochloric acid and quantitated at 650 nm on a Wallac 1420 VICTOR2 multilabel plate reader (Perkin Elmer). Half maximal inhibitory concentrations (IC~50~) were determined using Graphpad Prism 4.03 software (Graphpad Software, Inc.). Cell cycle analysis by DNA content {#s4_5} ---------------------------------- Cells were treated with 20 μM GANT61 for 24--72 h then fixed with 70% ethanol at 4°C. Cells were stained with 50 μg/ml propidium iodide (Sigma Aldrich) in the presence of 100 μg/ml DNase-free RNase A (Life Technologies) for 30 min at room temperature. Stained cells were analyzed for DNA content using a FACSCalibur flow cytometer (BD Biosciences) and quantified using the FlowJo software (Tree Star, Inc.). Detection of apoptosis {#s4_6} ---------------------- Detection of apoptotic cells was performed with the PE Annexin V Apoptosis Detection kit (BD Biosciences) according to the manufacturer\'s protocol. Briefly, cells were harvested after drug treatment, washed twice with ice-cold phosphate buffered saline (PBS) and incubated with Annexin V PE conjugate and 7-aminoactinomycin D (7AAD) for 15 min in the dark. Stained cells were analyzed by flow cytometry and quantified using the FlowJo software. ROS detection {#s4_8} ------------- Intracellular ROS production was determined by loading cells with 20 μM 6-carboxy-2′,7′-dichlorodihydrofluorescein diacetate (CH~2~DCFDA) (Life Technologies) at 37°C for 45 min. Intramitochondrial superoxide production was determined by loading cells with 5 μM mitoSOX red mitochondrial superoxide indicator (Life Technologies) at 37°C for 45 min. Red and green fluorescence emissions were analyzed by flow cytometry using excitation/emission wavelengths of 488/530 nm and 488/585 nm for CH~2~DCFDA and mitoSOX red, respectively. RNA interference {#s4_11} ---------------- Cells were grown to 80% confluence and transfected with 100 nM GLI1 siRNA (Santa Cruz Biotechnology), GLI2 siRNA (Sigma Aldrich) or negative control siRNA (Santa Cruz Biotechnology) using Lipofectamine 2000 transfection reagent (Life Technologies) according to the manufacturer\'s instructions. Gli luciferase reporter assay {#s4_12} ----------------------------- Gli transcriptional activity was measured using a Cignal Gli Reporter (luc) kit (SABiosciences) according to manufacturer\'s instructions. Briefly, cells were seeded in 12-well plates 24 h before transfection. Cells were cotransfected with 500 ng of Gli luciferase reporter construct and a Renilla luciferase construct (40:1 ratio) using Lipofectamine 2000 transfection reagent, with a 9:1 ratio (v/w) of Lipofectamine 2000 to DNA. Cells were harvested using the Dual-Glo Luciferase assay system (Promega) 48 h after transfection according to the manufacturer\'s instruction. Luciferase activity was measured using a microplate reader. All reporter assays were normalized to Renilla luciferase activity. Western blot analysis {#s4_13} --------------------- Cells were harvested, lysed using CelLytic M mammalian cell lysis/extraction reagent (Sigma Aldrich), and the protein concentrations determined by NanoDrop 2000c Spectrophotometer (Thermo Scientific). Proteins (30 μg) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrotransferred onto nitrocellulose membrane (Millipore), which was then blocked with 5% nonfat milk or bovine serum albumin (Sigma Aldrich) in 0.1% Tris-buffered saline-Tween 20 for 1 h at room temperature. The membranes were incubated at 4°C overnight with the indicated primary antibodies. Antibodies recognizing GLI1, GLI2 and Bcl-2 were purchased from Cell Signaling Technology. As a protein loading control, membranes were probed with a mouse anti-β-actin monoclonal antibody (Santa Cruz Biotechnology). After repeated washing to remove unbound antibodies, the membranes were further incubated with horseradish peroxide-conjugated anti-rabbit or anti-mouse secondary antibodies (Cell Signaling Technology) for 1 h at room temperature. Chemiluminescent detection of antibody binding was performed using the Immobilon Western HRP Substrate (Millipore). Generation of LO68 θ^0^ cells {#s4_14} ----------------------------- LO68 ρ^0^ cells were generated by treating LO68 cells with 100 ng/ml ethidium bromide (Sigma Aldrich), 50 μg/ml uridine (Sigma Aldrich) and 1 mM sodium pyruvate (Life Technologies). PCR amplification {#s4_15} ----------------- Total DNA was isolated from cells using the PureLink Genomic DNA kit (Life Technologies), according to the manufacturer\'s instructions. PCR primers that amplify genes coding for cytochrome c oxidase subunit 1 (*COX1*), *D-loop*, NADH dehydrogenase 6 (*ND6*) and glyceraldehyde-3-phosphate dehydrogenase (*GADPH*) were obtained from published literature \[[@R40], [@R41]\]. PCR amplification was performed as described \[[@R41]\] and the PCR products were visualized on 1.5% agarose gels. Statistical analysis {#s4_16} -------------------- Statistical calculations were performed using Graphpad Prism 5 software (Graphpad Software, Inc.). Student\'s *t*-test was used to determine statistical differences between two groups. Statistical differences between multiple groups were calculated using one-way ANOVA analysis and Tukey\'s multiple comparison post-hoc test. *P* \< 0.05 was considered statistically significant. The authors wish to thank Winthrop Professor Bruce Robinson for MMe cells; Associate Professor Matthew Linden and Ms. Tracey Lee-Pullen (Centre for Microscopy, Characterisation and Analysis, University of Western Australia) for support with flow cytometry; Ms. Hui Min Cheah for help with illustration. This study was supported by grants from the National Health and Medical Research Council, Australia (Project ID number 572676) and the Mesothelioma Applied Research Foundation, USA (to SEM). CBL was supported by the University of Western Australia International Postgraduate Research Scholarship and Lung Institute of Western Australia PhD Top Up Scholarship. | Mid | [
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If your genome is public, so are you, researchers find Scouring information available to anyone with an Internet connection, a team of genetic sleuths deduced the names of dozens of supposedly anonymous people who had their DNA analyzed for scientific and medical research. Scouring information available to anyone with an Internet connection, a team of genetic sleuths deduced the names of dozens of supposedly anonymous people who had their DNA analyzed for scientific and medical research. The snooping feat, which took advantage of genealogy websites that let people compare their DNA to search for relatives, was in full compliance with federal privacy regulations. Experts said it underscored a stark reality about genetic privacy in the age of social media: Don’t count on it. “Nobody can promise privacy,” said Mildred Cho, who heads up Stanford University’s Center for Integration of Research on Genetics and Ethics, and wasn’t involved with the study. Whitehead Institute geneticist Yaniv Erlich and his team, who described their work Thursday in the journal Science, didn’t provide a complete recipe that would help others ferret out the identities of research volunteers. Nor did they divulge the names of the people they were able to unmask. Since the first draft of the human genome was published in 2000, scientists have scrutinized its 3 billion pairs of DNA letters to try to find variants that cause disease, to understand human physiology, and to unravel the evolutionary history of our species. Toward that end, academic efforts like the 1000 Genomes Project post complete genomes online for public use. The idea is that providing free access to the data will allow scientists to compare DNA from many people and help them discover connections between genes and traits, eventually leading to the development of personalized, targeted treatments for a wide range of disorders. Keeping genomic data private has been a concern all along. Worries that health insurers or employers might use information about genetic health risks to drop benefits or discriminate against workers inspired the 2008 Genetic Information Nondiscrimination Act, which provides protection against abuse. Last year, the Presidential Commission for the Study of Bioethical Issues recommended a variety of additional measures to further secure genetic data. Potentially complicating these efforts are the legions of amateur geneticists who want to learn their risk for diseases or gain clues about their ancestry. As sequencing costs have dropped, these enthusiasts have sent vials of saliva, swabs of cheek cells, circles of dried blood or other types of DNA samples to private sequencing companies. Often, they post their tests results online, for the world to see. Erlich has been interested in privacy since he worked as a professional hacker – breaking into corporate networks as a “vulnerability researcher” for a computer security company – to help support himself in college. He started planning the current research after hearing about a 15-year-old boy who had part of his genome sequenced in 2005 in order to find his biological father, a sperm donor. The boy compared a pattern of repeating DNA letters from his Y chromosome to the corresponding patterns of men who had posted their genetic data on a genealogy website. Finding several men whose pattern matched his led him to his father’s last name. He then used other clues to make contact. Y chromosomes correlate with surnames because both are passed directly from father to son. Erlich said he thought the boy’s approach was “brilliant,” and he wondered if his lab could do something similar with public genome data. He and his colleagues started by analyzing the repeat patterns of Y chromosomes in published studies of genomes whose owners were known. They used a free genealogy website to look for surname matches. In two of the cases, the Y chromosome data lined up with relatively common last names, so the results were of little use. But one of the samples – provided by sequencing pioneer J. Craig Venter – matched the surname “Venter.” From there, the team used a free Web directory and personal information that often accompanies genomes in public databases – age and state of residence – to zero in on the scientist. Then they moved on to 10 mystery genomes collected from Utah residents who participated in public sequencing projects. They found surname matches for five people, then used those names to look at obituaries, family trees on file with the genomic information and other information to link nearly 50 related men and women to their DNA. Analyzing census and genetic data, the team calculated they could find the correct surnames of white, middle- and upper-class men in the U.S. 12 percent of the time. Conducting a search using last name, year of birth and state of residence produced lists with about a dozen — a number small enough to investigate in more detail, Erlich said. The discoveries in the new study point to a new level of vulnerability for research subjects who wish to remain private, Cho and others said. To Laura Lyman Rodriguez, a policy specialist at the National Human Genome Research Institute in Bethesda, Md., the bottom line is that research subjects should be told that their genomic data could be breached. “It’s important to be clear,” said Lyman Rodriguez, who co-wrote a commentary that accompanied the report in Science. | Mid | [
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Inhibition of PAF-induced human platelet responses by newly synthesized ether phospholipids. A series of 10 analogues of platelet-activating factor (PAF) was evaluated for proaggregatory and inhibitory behaviour on human blood platelets in vitro. Most of the compounds did not activate platelets but inhibited the PAF-induced aggregation. The inhibition was concentration-dependent and selective for PAF. Platelet responses to ADP and collagen were not suppressed. Schild analysis of the aggregation data was consistent with a simple competitive antagonism. The pA2 of the most effective antagonist (1-O-hexadecyl-2-O-ethylglycero-3-phosphoric acid-6'-(1-chinuclidinium)-hexylester) was 5.96. There is also evidence for its ability to inhibit the high affinity binding of [3H]PAF to the platelet receptors. | High | [
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Damassine Damassine (eau de vie) is a liqueur produced by distillation of the damson plum, called Damassine in French. According to local tradition, the Crusaders or Bernard de Clairvaux brought seeds for the Damassinier plant back from the Orient (hence its name originating from Damascus “fr Damas”). The Romans might have already known the fruit, cited in the Duhamel de Monceau encyclopaedia. In the Jura area, the first citation dates back to a written reference regarding a “Grandfontaine” plantation in 1791. Fruit Damassine is a small red prune of “a thousand scents”. Of round to slightly oval shape, it weighs between 6 and 10 grams and measures approximately 26,5 x 23,5 and 22,5 mm in diameter. The colour of its skin is not uniform. Predominantly from pink to red, it can even be dark red on the sun-exposed side, whilst slightly yellow with reddish dots on its "shadowy" side. However, size and colour may vary from season to season, from tree to tree and even from one branch to the other. Its yellowish, slightly orange, juicy flesh does not adhere to the kernel. Its skin is thin, adhering lightly to the flesh. The fruit ripens around the first days of August. When fully ripe it falls from the tree naturally. This is the right time to collect the fruit, as picking it up or shaking it from the tree would result in a loss of flavour and scent. Eau de vie The aromas are very complex, composed of different kinds of ingredients. The scents of wild prune dominate, with herbal and almond touches. The latter can easily be explained by the fruit morphology (proportion of kernel and flesh). The herbal touches must come from the fact that it has to be gathered once falling onto the ground. The secondary scents and aromas are those of the other similar kernel fruits (cherries, Mirabelle), sweetness (honey, dried banana) and spices (coriander, cloves with a little touch of cinnamon). References See also Appellation d'origine protégée External links History of Damassine Terroir Jura Jura Information (in French) Patrimoine culinaire suisse Official Site of the Culinary Swiss Patrimony with infos on Damassine and another odd 400 produce/recipes Category:Fruit brandies | High | [
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How-To: Make a Circle Shelf I have been dying to get my hands on a circle shelf for my home, but all the ones I've come across have always been out of my price range. I wasn't even sure how to go about making my own but as it turns out, this tutorial by A New Bloom makes it totally do-able. And although it can't hold heavy duty things like books, it's perfect for displaying those special keepsakes. You can even knock this project out in a day making it the perfect thing to make this weekend! | Low | [
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import { DESCRIPTORS } from '../helpers/constants'; import { createIterable } from '../helpers/helpers'; import Symbol from 'core-js-pure/features/symbol'; import getIteratorMethod from 'core-js-pure/features/get-iterator-method'; import from from 'core-js-pure/features/array/from'; import defineProperty from 'core-js-pure/features/object/define-property'; QUnit.test('Array.from', assert => { assert.isFunction(from); assert.arity(from, 1); let types = { 'array-like': { length: '3', 0: '1', 1: '2', 2: '3', }, arguments: function () { return arguments; }('1', '2', '3'), array: ['1', '2', '3'], iterable: createIterable(['1', '2', '3']), string: '123', }; for (const type in types) { const data = types[type]; assert.arrayEqual(from(data), ['1', '2', '3'], `Works with ${ type }`); assert.arrayEqual(from(data, it => it ** 2), [1, 4, 9], `Works with ${ type } + mapFn`); } types = { 'array-like': { length: 1, 0: 1, }, arguments: function () { return arguments; }(1), array: [1], iterable: createIterable([1]), string: '1', }; for (const type in types) { const data = types[type]; const context = {}; assert.arrayEqual(from(data, function (value, key) { assert.same(this, context, `Works with ${ type }, correct callback context`); assert.same(value, type === 'string' ? '1' : 1, `Works with ${ type }, correct callback key`); assert.same(key, 0, `Works with ${ type }, correct callback value`); assert.same(arguments.length, 2, `Works with ${ type }, correct callback arguments number`); return 42; }, context), [42], `Works with ${ type }, correct result`); } const primitives = [false, true, 0]; for (const primitive of primitives) { assert.arrayEqual(from(primitive), [], `Works with ${ primitive }`); } assert.throws(() => from(null), TypeError, 'Throws on null'); assert.throws(() => from(undefined), TypeError, 'Throws on undefined'); assert.arrayEqual(from('𠮷𠮷𠮷'), ['𠮷', '𠮷', '𠮷'], 'Uses correct string iterator'); let done = true; from(createIterable([1, 2, 3], { return() { return done = false; }, }), () => false); assert.ok(done, '.return #default'); done = false; try { from(createIterable([1, 2, 3], { return() { return done = true; }, }), () => { throw new Error(); }); } catch { /* empty */ } assert.ok(done, '.return #throw'); class C { /* empty */ } let instance = from.call(C, createIterable([1, 2])); assert.ok(instance instanceof C, 'generic, iterable case, instanceof'); assert.arrayEqual(instance, [1, 2], 'generic, iterable case, elements'); instance = from.call(C, { 0: 1, 1: 2, length: 2, }); assert.ok(instance instanceof C, 'generic, array-like case, instanceof'); assert.arrayEqual(instance, [1, 2], 'generic, array-like case, elements'); let array = [1, 2, 3]; done = false; array['@@iterator'] = undefined; array[Symbol.iterator] = function () { done = true; return getIteratorMethod([]).call(this); }; assert.arrayEqual(from(array), [1, 2, 3], 'Array with custom iterator, elements'); assert.ok(done, 'call @@iterator in Array with custom iterator'); array = [1, 2, 3]; delete array[1]; assert.arrayEqual(from(array, String), ['1', 'undefined', '3'], 'Ignores holes'); assert.notThrows(() => from({ length: -1, 0: 1, }, () => { throw new Error(); }), 'Uses ToLength'); assert.arrayEqual(from([], undefined), [], 'Works with undefined as asecond argument'); assert.throws(() => from([], null), TypeError, 'Throws with null as second argument'); assert.throws(() => from([], 0), TypeError, 'Throws with 0 as second argument'); assert.throws(() => from([], ''), TypeError, 'Throws with "" as second argument'); assert.throws(() => from([], false), TypeError, 'Throws with false as second argument'); assert.throws(() => from([], {}), TypeError, 'Throws with {} as second argument'); if (DESCRIPTORS) { let called = false; defineProperty(C.prototype, 0, { set() { called = true; }, }); from.call(C, [1, 2, 3]); assert.ok(!called, 'Should not call prototype accessors'); } }); | Low | [
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576 F.Supp. 1423 (1983) 15 McKAY PLACE REALTY CORP., Dolly Barksdale, Sheldon Crutchfield, Chet Dash, Martin Carson and Adam Keller, Plaintiffs, v. AFL-CIO, 32B-32J, SERVICE EMPLOYEES INTERNATIONAL UNION, Gus Bevona, President, and Thomas Latimer, Contract Director of said Union, Joseph Simpson, Isaac Bornweld, Roosevelt Singleton and Dario Nunez, Defendants. No. 82 Civ. 1846. United States District Court, E.D. New York. December 23, 1983. *1424 Frederick Schwartz, New York City, for plaintiffs. Michael Geffner, Israelson, Manning & Raab, New York City, for defendants. MEMORANDUM AND ORDER GLASSER, District Judge: Plaintiff, 15 McKay Place Realty Corp., a New York corporation, and five individual plaintiffs[1] instituted this action against defendant AFL-CIO, Local 32B-32J, Service Employees International Union ("Union") and six individual defendants[2] in the Supreme Court for the State of New York, Kings County, on June 21, 1982, seeking relief from alleged violent illegal picketing and other tortious conduct of defendants. In June 1982,[3] defendants removed this action to this Court pursuant to 28 U.S.C. § 1446,[4] alleging original federal jurisdiction *1425 under the Labor Management Relations Act ("LMRA"), 29 U.S.C. §§ 141-197, and sections 8(a)(1), (3) and (5) of the National Labor Relations Act ("NLRA"), 29 U.S.C. §§ 151-168. Plaintiffs now move for an order remanding the case to the state court. For the reasons stated below, plaintiff's motion is granted. Facts Plaintiff, 15 McKay Place Realty Corp. ("Corporation") was the mortgagee of an apartment building located at 255 Eastern Parkway in Brooklyn. After the mortgagor, Eastern Parkway Corporation, defaulted, the Corporation purchased the building at a foreclosure sale on May 26, 1982. The prior owner of the building, through its agent, apparently had been party to a collective bargaining agreement with defendant Union under which the individual defendants performed services at that building. When it acquired ownership of the building, the plaintiff Corporation discharged the individual defendants. As to its potential contractual relationship with defendant Union, plaintiff Corporation alleges in the complaint: SIXTH: That said plaintiff corporation, at no time prior to May 26, 1982, owned said building, nor entered into any agreement with the former owner (mortgagor) to purchase the said building but came into possession and title of said building by being the successful bidder and purchaser of said building, at public auction, held pursuant to a duly constituted foreclosure sale. * * * * * * TENTH: .... that the defendants and all of them are not in privity with the plaintiff either by contract with the plaintiff and plaintiffs have had no transaction with the foreclosed mortgagor or previous owner of said apartment building. Shortly thereafter, the discharged employees began picketing in front of plaintiffs' building. Plaintiffs allege that defendants illegally congregated in large numbers, interfered with the tenants' and new employees' ingress and egress to the building, harassed the tenants and new employees, and otherwise variously caused damage to the premises and to an adjacent building owned by plaintiffs. Defendants contend, on the other hand, that the picketing defendants were engaged in activity which is protected under the LMRA. Plaintiffs seek injunctive relief. Procedural Background This case had a confusing procedural beginning. Prior to plaintiffs' institution of this suit in state court by filing and service of a complaint and order to show cause on June 21, 1982, defendant Union had filed charges against the Corporation with Region 29 of the National Labor Relations Board ("NLRB") on June 7, 1982. The hearing on the order to show cause was scheduled for June 25, 1982 and defendants filed their petition for removal with this Court on that date. On July 21, 1982, the NLRB filed a formal complaint against the plaintiff Corporation ("NLRB Complaint"). The NLRB Complaint designated January 10, 1983 as a hearing date on the charges contained therein. That hearing was since adjourned to January 16, 1984. Discussion Section 1441 of Title 28 governs the type of actions which may be removed from state to federal court. In the context of the instant case, the relevant part of Section 1441 reads: (b) Any civil action of which the district courts have original jurisdiction founded on a claim or right arising under the Constitution, treaties or laws of the United States shall be removable without regard to the citizenship or residence of the parties. Generally, a cause is removable only if a federal question appears on the face of the complaint. Gully v. First National Bank, 299 U.S. 109, 113, 57 S.Ct. 96, 98, 81 L.Ed. 70 (1966). In Gully, the Supreme Court held: *1426 To bring a case within the statute [28 U.S.C. § 1441], a right or immunity created by the Constitution or laws of the United States must be an element, and an essential one, of the plaintiff's cause of action .... The right or immunity must be such that it will be supported if the Constitution or laws of the United States are given one construction or another.... A genuine and present controversy, not merely a possible or conjectural one, must exist with reference thereto, ... and the controversy must be disclosed upon the face of the complaint, unaided by the answer or the petition for removal.... Indeed, the complaint itself will not avail as a basis of jurisdiction insofar as it goes beyond a statement of the plaintiff's cause of action and anticipates or replies to a probable defense. 299 U.S. at 112-13, 57 S.Ct. at 97-98. A federal court may, however, attempt to ascertain whether a plaintiff's claim is state or federal in nature if this is not obvious from the face of the complaint. 14 C. Wright, A. Miller & E. Cooper, Federal Practice and Procedure (1976), § 3722 at 561-62, 564, 566. A plaintiff is generally the master of his claim. The Fair v. Kohler Die & Specialty Co., 228 U.S. 22, 25, 33 S.Ct. 410, 411, 57 L.Ed. 716 (1913) and when his claim can be based upon either a state or federal ground, he "is normally free to ignore the federal question and pitch his claim on state ground." Hearst Corp. v. Shopping Center Network, Inc., 307 F.Supp. 551, 556 (S.D.N.Y.1969); see also 1A Moore's Federal Practice, ¶ 0.160, at 185 (2d ed. 1979). In such a case, the federal court may not look beyond the complaint in its attempt to ascertain the nature of plaintiff's claim. When, as here, the complaint is ambiguous as to the federal or state nature of the claim, a plaintiff may restrict himself to a state cause of action in a timely motion to remand. See Vitarroz Corp. v. Borden, Inc., 644 F.2d 960 (2d Cir.1981). However, "where Congress has explicitly said that the exclusive source of a plaintiff's right to relief is to be federal law, it would be unacceptable to permit that very plaintiff, by the artful manipulation of the terms of a complaint, to defeat a clearly enunciated congressional objective." Hearst Corp. v. Shopping Center Network, Inc., 307 F.Supp. at 556. When a plaintiff's purported state law claim has been preempted by federal law, federal jurisdiction will lie. Billy Jack for Her, Inc. v. New York Coat, Suit, Dress, Rainwear & Allied Workers' Union Local 1-35, 511 F.Supp. 1180, 1186 & n. 8 (S.D.N.Y.1981) ("Billy Jack I"). Furthermore, federal removal jurisdiction is derivative or dependent on state court jurisdiction. Id. at 1188. Therefore, should the federal district court determine that the case is subject to exclusive federal jurisdiction or that a body other than the state or federal court has exclusive jurisdiction, the district court must dismiss the case. Id.; see also id. at 1192-93. Finally, should a complaint filed in state court state a claim which is preempted by federal law as well as a pure state claim, the state claim may be removable in accordance with the doctrine of pendent jurisdiction or under 28 U.S.C. § 1441(c).[5]Billy Jack for Her, Inc. v. New York Coat, Suit, Dress, Rainwear & Allied Workers' Union Local 1-35, 515 F.Supp. 456, 458 (S.D.N.Y.1981) ("Billy Jack II"). See also United Mine Workers v. Gibbs, 383 U.S. 715, 725, 86 S.Ct. 1130, 1138, 16 L.Ed.2d 218 (1966). In their petition for removal, defendants allege original federal jurisdiction because (1) the Corporation is engaged in interstate commerce;[6] (2) plaintiffs seek to enjoin *1427 activity protected under Section 7 of the LMRA, 29 U.S.C. § 157,[7] which activity is (3) in response to violations by the Corporation of Sections 8(a)(1), (3) and (5) of the LMRA, 29 U.S.C. § 158.[8] Petition for Removal, ¶ 6. On the other hand, plaintiffs' motion to remand asserts that the Corporation is not engaged in interstate commerce, Schwartz Affidavit II at ¶ 9, and that the state court has primary jurisdiction to adjudicate plaintiff's claim under Kay-Fries, Inc. v. Martino, 73 A.D.2d 342, 426 N.Y. S.2d 304 (2d Dep't 1978), appeals dismissed, 50 N.Y.2d 1056, 410 N.E.2d 750, 431 N.Y.S.2d 817 (1980); 51 N.Y.2d 994, 417 N.E.2d 92, 435 N.Y.S.2d 979 (1980). In Kay-Fries v. Martino, supra, the appellate court reviewed the trial court's issuance of an injunction against a union for tortious conduct committed incident to a strike against the plaintiff employer. In this suit brought under Section 807 of the New York Labor Law,[9] the appellate division specifically held that the statutory requirement that findings of fact must be filed or recited in the record was not a jurisdictional prerequisite to the issuance of the injunction. 426 N.Y.S.2d at 308, 309. The Kay-Fries court cited a decision of the New York Court of Appeals which interpreted the predecessor of Section 807(1) as follows: *1428 The effect of that statute is to prevent courts from enjoining peaceful picketing. It was never intended to deprive the Supreme Court [of New York] of jurisdiction to enjoin dangerous, illegal acts which constituted disorderly conduct and breach of the peace. 426 N.Y.S.2d at 308, citing Busch Jewelry Co. v. United Retail Employees' Union Local 830, 281 N.Y. 150, 156, 22 N.E.2d 320, 322. Kay-Fries thus appears to provide a state law remedy for plaintiffs, barring preemption by federal law. As stated above, defendants urge that federal jurisdiction must lie because their alleged activity is protected under Section 7 of the LMRA, 29 U.S.C. § 157. See supra note 7. While defendants' contention here appears to be a defense which would preclude removal under Louisville & Nashville R.R. Co. v. Mottley, 211 U.S. 149, 29 S.Ct. 42, 53 L.Ed. 126 (1908), and Gully, supra, it is well settled that "[w]hen an activity is arguably subject to Section 7 or Section 8 of the Act, the States as well as the federal courts must defer to the exclusive competence of the National Labor Relations Board if the danger of state interference with national policy is to be averted." San Diego Building Trades Council v. Garmon, 359 U.S. 236, 244-45, 79 S.Ct. 773, 779-80, 3 L.Ed.2d 775 (1959). State courts may entertain tort claims in connection with picketing if the risk that such state adjudication would interfere with federal policy is minimal. Rodriguez v. Bar-S Food Co., 539 F.Supp. 710, 714-15 (D.Colo.1982), citing, e.g., Youngdahl v. Rainfair, Inc., 355 U.S. 131, 139-40, 78 S.Ct. 206, 211-12, 2 L.Ed.2d 151 (1957) (labor related violence and threats thereof could be enjoined by state court, although peaceful picketing could not). The view that a claim alleging violent picketing is not preempted by federal law and should be adjudicated by the state court has been pronounced elsewhere in this Circuit. Billy Jack II, 515 F.Supp. at 457-59. See also Palm Beach Co. v. Journeymen's & Production Allied Services of America & Canada International Union Local 157, 519 F.Supp. 705, 707 n. 3, 713 (S.D.N.Y. 1981). Where the record indicates that violence or threats of violence attendant to picketing are "so enmeshed" that the violence can only be prevented by enjoining all picketing, a state court may enjoin such activity. Acme Markets Inc. v. Retail Store Employees Union Local 692, 231 F.Supp. 566, 571 (D.Md.1964). However, if such enmeshment is not demonstrated, the state court enters the "pre-empted domain of the National Labor Relations Board" if it attempts to enjoin peaceful picketing. Youngdahl v. Rainfair, supra, 355 U.S. at 139, 78 S.Ct. at 211. See also Acme Markets, supra, 231 F.Supp. at 571; Norton v. United Mine Workers, 387 F.Supp. 50, 52-53 (W.D.Va.1974). In the instant case, plaintiffs allege that defendants' picketing was accompanied by (1) interference with the tenants' and new employees' ingress and egress to the building; (2) abusive language and threats directed toward those employees; (3) a cutting of electrical wires in the building; (4) emptying of the building's garbage onto the premises; and (5) feeding of 800 gallons of water into the oil tank of an adjacent building owned by the same stockholders as those of plaintiff Corporation. Complaint ¶¶ 7, 8. Although the allegations of violent acts and threats thereof do not rise to the severity or frequency of those alleged in Youngdahl, supra, this case is similar enough to warrant the applicability of Youngdahl and Billy Jack II. I therefore find that the Supreme Court for Kings County does have jurisdiction to enjoin any acts not attributable to peaceful picketing that it finds are being committed by defendants.[10] *1429 Conclusion For the reasons set forth above, plaintiffs' motion to remand this case to the Supreme Court for Kings County is granted. The defendants are directed to pay all costs and disbursements incurred by reason of these removal proceedings pursuant to 28 U.S.C. § 1446(d).[11] Case remanded. SO ORDERED. NOTES [1] The five individual plaintiffs are the present employees of plaintiff Corporation, who were employed on or after May 26, 1982. Petition for Removal, Exh. A ("Complaint") at ¶ 11. [2] Defendant Gus Bevona is the President of the defendant Union. Joseph Simpson, Isaac Bornweld, Roosevelt Singleton and Dario Nunez are members of the Union. Petition for Removal, ¶ 5. Thomas Latimer is employed by the Union as Contract Director. Id.; see National Labor Relations Board Charge Against Employer, Exh. B to Petition for Removal ("NLRB Complaint"). [3] The actual date of effective removal by defendants is unclear. Pursuant to 28 U.S.C. § 1446(e), removal is effective after the petition is filed with the state court and notice thereof is served on the opposing parties. See infra note 4. Defendants here claim that they effectuated removal in compliance with this section on June 25, 1982. Affidavit of Michael Geffner, ¶ 7 ("Geffner Affidavit"). If true, such removal would have stayed any action by the State Supreme Court, including its hearing on the order to show cause for injunctive relief returnable June 28, 1982. Plaintiffs state that removal was effectuated on June 28, 1982. They claim that on that date, the state court granted the order to show cause by default and that the Notice of Removal was served on plaintiffs later that same day. Affidavit in Support of Motion to Remand of Frederick Schwartz dated July 22, 1982, ¶¶ 2-3 ("Schwartz Affidavit II"); Reply Affidavit of Leon Port at ¶ 4 ("Port Affidavit"). Defendants have not submitted proof of service on plaintiffs or the state court; neither have plaintiffs submitted proof of the alleged default judgment in state court. Although the above allegations render the issuance or validity of the alleged state court injunction unclear, I do not find it necessary to consider this fact in deciding this motion. I note that attorney for plaintiffs, Frederick Schwartz, has submitted two very similar affidavits in support of the motion to remand. The affidavit cited above as Schwartz Affidavit II refers to the July 22, 1982 Affidavit; the earlier July 9, 1982 Affidavit will hereinafter be referred to as Schwartz Affidavit I. [4] Section 1446 of Title 28 governs the procedure for removal of civil or criminal actions from a state court to the United States District Court for the district within which the action is pending. Removal of a civil action requires the filing of a verified petition pursuant to 28 U.S.C. § 1446(a) and (b) and the posting of a surety bond under § 1446(d). Section 1446(e) further requires: Promptly after the filing of such petition for the removal of a civil action and bond the defendant or defendants shall give written notice thereof to all adverse parties and shall file a copy of the petition with the clerk of such State court, which shall effect the removal and the State court shall proceed no further unless and until the case is remanded. [5] 28 U.S.C. § 1441(c) provides: Whenever a separate and independent claim or cause of action, which would be removable if sued upon alone, is joined with one or more otherwise nonremovable claims or causes of action, the entire case may be removed and the district court may determine all issues therein, or, in its discretion, may remand all matters not otherwise within its original jurisdiction. [6] Defendants contend that plaintiff Corporation is engaged in interstate commerce in support of their argument that only the NLRB has jurisdiction to adjudicate the lawfulness of the Union's picketing activities. Defendants' Memorandum of Law at 4. The NLRB would indeed have jurisdiction if this action was concerned with activity that is arguably subject to Section 7 or 8 of the LMRA. See infra p. 1428. However, because this action seeks to enjoin violent picketing, see infra, it is unnecessary to determine the actual nature of the plaintiff Corporation's business. I note in passing, however, that the NLRB Complaint indicates a finding that the plaintiff Corporation is engaged in interstate commerce. NLRB Complaint at 4(a)(b). [7] Section 7 of the LMRA, 29 U.S.C. § 157, provides: Employees shall have the right to self-organization, to form, join, or assist labor organizations, to bargain collectively through representatives of their own choosing, and to engage in other concerted activities, for the purpose of collective bargaining or other mutual aid or protection, and shall also have the right to refrain from any or all of such activities except to the extent that such right may be affected by an agreement requiring membership in a labor organization as a condition of employment as authorized in section 158(a)(3) of this title. [8] Sections 8(a)(1), (3) and (5) of the NLRA, 29 U.S.C. § 158, provide: (a) It shall be an unfair labor practice for an employer (1) to interfere with, restrain, or coerce employees in the exercise of the rights guaranteed in section 157 of this title; * * * * * * (3) by discrimination in regard to hire or tenure of employment or any term or condition of employment to encourage or discourage membership in any labor organization; Provided, That nothing in this subchapter, or in any other statute of the United States, shall preclude an employer from making an agreement with a labor organization (not established, maintained, or assisted by any action defined in this subsection as an unfair labor practice) to require as a condition of employment membership therein on or after the thirtieth day following the beginning of such employment or the effective date of such agreement, whichever is the later, (i) if such labor organization is the representative of the employees as provided in section 159(a) of this title, in the appropriate collective-bargaining unit covered by such agreement when made, and (ii) unless following an election held as provided in section 159(e) of this title within one year preceding the effective date of such agreement, the Board shall have certified that at least a majority of the employees eligible to vote in such election have voted to rescind the authority of such labor organization to make such an agreement; Provided further, That no employer shall justify any discrimination against an employee for nonmembership in a labor organization (A) if he has reasonable grounds for believing that such membership was not available to the employee on the same terms and conditions generally applicable to other members, or (B) if he has reasonable grounds for believing that membership was denied or terminated for reasons other than the failure of the employee to tender the periodic dues and the initiation fees uniformly required as a condition of acquiring or retaining membership; * * * * * * (5) to refuse to bargain collectively with the representatives of his employees, subject to the provisions of section 159(a) of this title. [9] N.Y.Lab.L. § 807 (McKinney 1977) provides, in relevant part: 1. No court nor any judge or judges thereof shall have jurisdiction to issue any restraining order or a temporary or permanent injunction in any case involving or growing out of a labor dispute, as hereinafter defined, except after a hearing, and except after findings of all the following facts ... [10] Any attempts by plaintiffs to enjoin peaceful picketing by defendants are within the exclusive jurisdiction of the NLRB. See International Longshoremen's Association, Local 1416 v. Ariadne Shipping Co., 397 U.S. 195, 90 S.Ct. 872, 25 L.Ed.2d 218 (1970). Plaintiffs here urge that they were not bound to any kind of agreement with defendants because they did not succeed to the obligations of the mortgagor of 255 Eastern Parkway, see supra p. 1424, although plaintiffs concede: 8. ... the former employees were not discharged because they belong to the Union; they were discharged because the corporation, not a successor in interest, has their own employees and wanted them in the place of the former employees. The plaintiff corporation states that if it was the successor in interest and had privity of relationship with the former owner, the corporation would have honored the union contract.... * * * * * * 10. The union and its members would be protected by Section 7 of the Act if they were employees of the corporation or of its former owner, providing the present owner was a successor in interest by transfer, sale or assignment, which it is not. Schwartz Affidavit II (emphasis in original). The initial determination of successorship, however, lies not within plaintiff's own power, but within the NLRB's jurisdiction. See, e.g., NLRB v. Hudson River Aggregates, Inc., 639 F.2d 865, 869 (2d Cir.1981); Saks & Co. v. NLRB, 634 F.2d 681, 684 (2d Cir.1980). It is apparent from the NLRB Complaint, ¶ 9(g), (i), that the NLRB does consider the plaintiff Corporation to be a successor to Eastern Corp. and therefore duty bound to bargain with the incumbent defendant Union. See NLRB v. Burns Security Services, 406 U.S. 272, 281, 92 S.Ct. 1571, 1579, 32 L.Ed.2d 61 (1972) (successor employer must bargain with incumbent union but is not bound by substantive terms of prior collective bargaining agreement). Therefore, although the NLRB Complaint does not precisely deal with the instant case, it is clear that the Board would be the proper tribunal to adjudicate any dispute over peaceful picketing in the instant case. That is, if, after consideration by the state court on remand, it becomes necessary to plaintiff's claim to evaluate whether defendants' picketing is "arguably subject" to ¶ 7, such determination will be within the jurisdiction of the NLRB. If the Board's exclusive jurisdiction was required by the instant facts, this Court would be constrained to dismiss the case. Billy Jack I, 511 F.Supp. at 1188, 1192-93. [11] 28 U.S.C. § 1446(d) provides in part: Each petition for removal of a civil action ... shall be accompanied by a bond ... conditioned that the defendant or defendants will pay all costs and disbursements incurred by reason of the removal proceedings should it be determined that the case was not removable or was improperly removed. | Low | [
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Want to join us? News GREEK BLACK BELT SEMINAR See Our Events Page! EUROPEAN HAPKIDO ALLIANCE Traditional Korean Martial Arts EUROPEAN HAPKIDO ALLIANCETraditional Korean Martial Arts HOW TO CHOOSE AN INSTRUCTOR To effectively teach the skills of Hapkido requires many, many years of study, practice and dedication. One of the most important decisions one makes when starting out in the martial arts is choosing an instructor. The man regarded as the founder of modern Hapkido, Yong Sul Choi, had taught all of the techniques of the art to only a select few of his students before his death in 1986. However, in the Western World today there seems to be numerous people claiming to be "Masters" of Hapkido. In recent years, there seems to have appeared many martial arts schools claiming to teach Hapkido as part of another style. There appears to be many innocent and well-meaning instructors advertising themseves as "Masters" in Hapkido but in reality they are misguided and only have a limited knowledge of this complex art. So how do you find a genuine instructor? How does the unsuspecting public determine the qualifications of a prospective instructor? The techniques of Hapkido literally number in tens of thousands and most black belts who have reached 1st or 2nd Dan have probably learned only two or three hundred of these. We can now see that an instructor in another martial art, who has learned a few Hapkido techniques to complement his self-defence teachings, does not qualify for the title of Master. Within the European Hapkido Alliance, International Hapkido MooHakKwan and the Korea Hapkido Federation, the title of Master is only issued when the student reaches the rank of 5th Dan. This requires a minimum of 15 years regular training and teaching. Don't be fooled by photographs of an instructor taken with a high-ranked Master of Hapkido, such as Grandmaster Sung Soo Lee. Master Sam Plumb has had his photograph taken with dozens of Korean Masters and likewise, Master Lee has had his picture taken with thousands of students. A few photographs don't qualify the instructor as a Master. The instructors certificates should be signed and stamped by the recognized head of the organization. If the certificate does not come from an internationally recognized organization you must ask "Why?". Also there are some schools whose instructors are perhaps 2nd or 3rd Dan grade and they are conducting black belt gradings for their students. This simply does not happen within the KHF and EHA as instructors must be 5th Dan Master grade or above to conduct black belt gradings. Take time to choose an instructor and ask questions. If the instructor is willing and pleased to answer all your queries and show you his qualifications, the chances are he is genuine. | Mid | [
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Trump sacks Tillerson over policy disagreements Tillerson's imminent departure had been rumoured for several months following reports of friction with US President Donald Trump. But the tensions peaked last fall amid reports Tillerson had called... Trump ousts Tillerson, names Pompeo as secretary of state The US president says he is replacing Secretary of State Rex Tillerson with CIA Director Mike Pompeo, and has tapped Gina Haspel to head the intelligence... Venezuela opposition urges UN not to send observers to May vote Newly formed opposition coalition says fraudulent election is set by officials loyal to socialist President Nicolas Maduro, who accuses US of pressuring the UN... Conservative billionaire Pinera sworn in as president of Chile Sebastian Pinera – whose fortune has been estimated by Forbes at $2.7 billion – has promised to transform Chile into a developed economy in eight years. Chile's... Colombia's Santos, ELN rebels to restart talks The talks were suspended by Colombian President Juan Manuel Santos in January after a series of bombings by the National Liberation Army. Colombia's President Juan Manuel Santos speaks during... Colombia election: Farc's Timochenko pulls out of race Rodrigo Londoño - aka Timochenko - has also been pelted with eggs and tomatoes while out on the campaign trail The Farc former rebel group says its... 7 charged in Greece with belonging to violent neo-Nazi group ATHENS, Greece A Greek prosecutor has charged seven men with alleged membership in a violent neo-Nazi group linked to a series of arson attacks on... US President Donald Trump mocks low Oscars ratings https://youtu.be/U-QvgMWCf2Q President Donald Trump has mocked the low ratings this year's Academy Awards brought in – and gave a theory for why that is. "Problem is, we don't have... Fear as South Africa meat recall over listeria spreads The outbreak that claimed the lives of 180 people is the worst outbreak ever recorded globally. Several countries have banned imports of processed meat from South... 100 killed in Philippines since resumption of Duterte’s 'drugs war' More than 100 drug suspects have been killed since Philippine President Rodrigo Duterte’s call on police forces to rejoin his ‘war on drugs’ campaign, an... We are a group of professionals in all areas interested in transmitting empowering news to improve the globalized world. Orbi News is a means of information and citizen training that seeks to go far beyond the news. | Mid | [
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Q: Create custom notification in post insert in buddypress I want to add custom notification in the time of post creation. I have followed this url https://webdevstudios.com/2015/10/06/buddypress-adding-custom-notifications/ What i have done, I am adding custom notification in creation of project or bid post type. But it not working. Please check my code and let me what i have done wrong. // this is to add a fake component to BuddyPress. A registered component is needed to add notifications function custom_filter_notifications_get_registered_components( $component_names = array() ) { // Force $component_names to be an array if ( ! is_array( $component_names ) ) { $component_names = array(); } // Add 'custom' component to registered components array array_push( $component_names, 'projectadd' ); // Return component's with 'custom' appended return $component_names; } add_filter( 'bp_notifications_get_registered_components', 'custom_filter_notifications_get_registered_components' ); // this hooks to post creation and saves the post id function bp_custom_add_notification( $post_id, $post ) { if ( $post->post_type == 'project' || $post->post_type == 'bid' ) { $post = get_post( $post_id ); $author_id = $post->post_author; bp_notifications_add_notification( array( 'user_id' => $author_id, 'item_id' => $post_id, 'component_name' => 'projectadd', 'component_action' => 'projectadd_action', 'date_notified' => bp_core_current_time(), 'is_new' => 1, ) ); } } add_action( 'wp_insert_post', 'bp_custom_add_notification', 99, 2 ); // this gets the saved item id, compiles some data and then displays the notification function custom_format_buddypress_notifications( $content, $item_id, $secondary_item_id, $total_items, $format = 'string', $action, $component ) { // New custom notifications if ( 'projectadd_action' === $action ) { $post = get_post( $item_id ); $custom_title = $post->post_author . ' add the project ' . get_the_title( $item_id ); $custom_link = get_permalink( $post ); $custom_text = $post->post_author . ' add the project ' . get_the_title( $item_id ); // WordPress Toolbar if ( 'string' === $format ) { $return = apply_filters( 'projectadd_filter', '<a href="' . esc_url( $custom_link ) . '" title="' . esc_attr( $custom_title ) . '">' . esc_html( $custom_text ) . '</a>', $custom_text, $custom_link ); // Deprecated BuddyBar } else { $return = apply_filters( 'projectadd_filter', array( 'text' => $custom_text, 'link' => $custom_link ), $custom_link, (int) $total_items, $custom_text, $custom_title ); } return $return; } } add_filter( 'bp_notifications_get_notifications_for_user', 'custom_format_buddypress_notifications', 10, 7 ); A: You've changed the number and order of arguments from the example you linked. The two arguments you added are never used. Restore the arguments in the function to match the example and the the number in your add_filter to 5. function custom_format_buddypress_notifications( $content, $item_id, $secondary_item_id, $total_items, $format = 'string', $action, $component ) { ... } add_filter( 'bp_notifications_get_notifications_for_user', 'custom_format_buddypress_notifications', 10, 7 ); needs to be function custom_format_buddypress_notifications( $action, $item_id, $secondary_item_id, $total_items, $format = 'string' ) { ... } add_filter( 'bp_notifications_get_notifications_for_user', 'custom_format_buddypress_notifications', 10, 5 ); | Low | [
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Term access refers to a capability to obtain or make use of or take advantage of something. In communications, access typically refers to the right to obtain or make use of or take advantage of a communication resource. Such communication resource may be, for example, a physical or logical communication channel, or a service provided by a service provider. The roles and responsibilities in communications have conventionally been divided to subscribers, operators, network providers, service providers, and the like. However, due to the evolving new technologies, these conventional roles and responsibilities are undergoing a change. Conventionally, a subscriber has been defined as user of a telecommunication service, based on a contract with the service provider. Additionally, telecommunications companies have made agreements to apply roaming such that user terminals registered in their user registers may be used in both networks. People move and travel more and more, but due to this agreement-based operation models, the users of communication services have been encumbered to static configurations of operators and prices contractually agreed between them. Due to the rapid development, user terminals of today typically include more than one communication interface such that they are able to communicate over different access networks. This increases the potential for roaming significantly, because a particular communication need or a service could be implemented though various accesses networks and interfaces. However, it is very difficult and laborious to identify and go though the various access alternatives and quickly decide the best one for the current communication need. | Mid | [
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Pat Lam's side shot into an early 13-3 lead and produced an heroic backs-to-the-wall effort in trying to contain the reigning RaboDirect PRO12 champions. But having lost Ronan Loughney (70 minutes) and Kieran Marmion (76) to the sin-bin, Connacht's wilting scrum was unable to keep Leinster at bay and Matt O'Connor's men escaped with a fortunate win. The westerners - winless in Dublin since September 2002 - went 10 points up with scrum half Marmion poaching a 13th minute try and Dan Parks kicking the rest of the points. Ian Madigan's third successful penalty closed the gap to four points right on half-time, but Leinster had to bide their time against an aggressive Connacht defence. The scoreline remained at 13-9 until the dying minutes when Connacht's penalty count took its toll - 18 in all - and Leinster's forward power, aided by replacement tighthead Martin Moore, edged it for them. There were only two minutes on the clock when Parks drilled over a right-sided penalty from inside the 10-metre line. Connacht's solid start continued as they tackled tigerishly to chop down both Fergus McFadden and David Kearney, and Parks drove home a penalty from halfway for 6-0. The returning Madigan punished a scrum infringement from Jake Heenan to get Leinster on the scoreboard, splitting the posts with a confident strike from the right. Connacht failed to take advantage of a five-metre scrum after a Madigan kick was charged down by Craig Ronaldson, but Leinster then blundered on their own scrum ball to gift Marmion the opening try. The alert Connacht scrum half reached out to score after the visitors got the push on in the set piece, with Jamie Heaslip and Eoin Reddan both unable to control the loose ball and Noel Reid beaten to it on the line by Marmion. After Parks converted from close range, a promising Leinster attack was foiled by a Luke Fitzgerald knock-on and there was some concern for a prone Madigan, who was hit hard by Robbie Henshaw, before he got back on his feet. Slashing runs from Mata Fifita and McFadden saw both sides attack with vigour in an open, exciting first half, the hosts picking up the pace noticeably as Madigan landed his second penalty following a Henshaw offside. Leinster pressed for more approaching the interval and while Connacht defended heroically, they did leak a late penalty - Craig Clarke was pinged for not rolling away and Madigan mopped up with an important three points. Clarke, Heenan and Brett Wilkinson were all having big shifts for Connacht, who signalled their intent on the restart when turning down a kickable penalty. Lam's charges worked a lineout maul and Wilkinson went close before Kevin McLaughlin infringed near the whitewash, but Parks' poor penalty attempt came back off an upright and Leinster had a real let-off. Madigan was just short with his own penalty attempt from halfway, and with man-of-the-match George Naoupu getting on the ball Connacht doggedly held onto their slim advantage. Although handling errors from Gavin Duffy and Matt Healy invited Leinster forward, Connacht somehow survived a spell of scrum pressure near their line. The proceedings were decidedly stop-start entering the final quarter as a succession of penalties broke up play. Leinster's hopes were boosted when replacement prop Loughney was sin-binned with 10 minutes left. Leinster shunned a shot at the posts as they looked for their set piece to decide the game. Marmion duly saw yellow for interfering with Isaac Boss at the base of a scrum and a couple of collapses led to the vital penalty try which Madigan converted. | Mid | [
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The present invention relates to a system and method for test generation with dynamic constraints, and in particular, to a system and method for dynamically solving constraints by creating a set of instructions which provide a specific, random solution when executed. Design verification is the process of determining whether an integrated circuit, board, or system-level architecture, exactly implements the requirements defined by the specification of the architecture for that device. Design verification for a device under testing (DUT) may be performed on the actual device, or on a simulation model of the device. For the purposes of explanation only and without intending to be limiting in any way, the following discussion centers upon testing which is performed on simulation models of the device. As designs for different types of devices and device architectures become more complex, the likelihood of design errors increases. However, design verification also becomes more difficult and time consuming, as the simulation models of the design of the device also become more complex to prepare and to test. The problem of design verification is compounded by the lack of widely generalizable tools which are useful for the verification and testing of a wide variety of devices and device architectures. Typical background art verification methods have often been restricted to a particular device having a specific design, such that the steps of preparing and implementing such verification methods for the simulation model must be performed for each new device. The process of verifying a design through a simulation model of the device is aided by the availability of hardware description languages such as Verilog and VHDL. These languages are designed to describe hardware at higher levels of abstraction than gates or transistors. The resultant simulated model of the device can receive input stimuli in the form of test vectors, which are a string of binary digits applied to the input of a circuit. The simulated model then produces results, which are checked against the expected results for the particular design of the device. However, these languages are typically not designed for actual verification. Therefore, the verification engineer must write additional programming code in order to interface with the models described by these hardware description languages in order to perform design verification of the device. Examples of testing environments include static and dynamic testing environments. A static testing environment drives pre-computed test vectors into the simulation model of the DUT and/or examines the results after operation of the simulation model. In addition, if the static testing environment is used to examine the results which are output from the simulation model, then errors in the test are not detected until after the test is finished. As a result, the internal state of the device at the point of error may not be determinable, requiring the simulation to be operated again in order to determine such internal states. This procedure consumes simulation cycles, and can require the expenditure of considerable time, especially during long tests. A more useful and efficient type of testing is a dynamic testing environment. For this type of environment, a set of programming instructions is written to generate the test vectors in concurrence with the simulation of the model of the DUT and while potentially being controlled by the state feedback of the simulated device. This procedure enables directed random generation to be performed and to be sensitive to effects uncovered during the test itself on the state of the simulation model of the device. Thus, dynamic test generation clearly has many advantages for design verification. Within the area of testing environments, both static and dynamic testing environments can be implemented only with fixed-vector or pre-generation input. However, a more powerful and more sophisticated implementation uses test generation to produce the environment. One example of such a test generator is disclosed in U.S. patent application Ser. No. 09/020,792, filed on Feb. 6, 1998, incorporated by reference as if fully set forth herein. This test generation procedure interacts with, and sits as a higher level over, such hardware description languages as Verilog and VHDL. The test generation procedure is written in a hardware-oriented verification specific object-oriented programming language. This language is used to write various tests, which are then used to automatically create a device verification test by a test generator module. A wide variety of design environments can be tested and verified with this language. Thus, the disclosed procedure is generalizable, yet is also simple to program and to debug by the engineer. The disclosed language features a number of elements such as structs for more richly and efficiently describing the design of the device to be simulated by the model. Unfortunately, the disclosed language and resultant test generation environment does not include features for providing a good, random solution for dynamic constraints in a reasonable processing time, and also cannot react dynamically on the same scale as the time period which is actually required for simulation. Furthermore, such features are also not known in the background art, which handles such constraints with a non-random solution. Therefore, there is an unmet need for, and it would be highly useful to have, a system and method for solving dynamic constraints through a specific, random but correct solution, which would be created by executing a specific set of instructions. The system and method of the present invention tests the quality of a simulation model for the DUT (device under test) with dynamic constraint solving and test generation for the testing and verification process. The present invention provides such dynamic constraint solving through the creation of a sequence of instructions in a xe2x80x9cgenerator mini-languagexe2x80x9d (GML). These instructions are then executed in order to provide a correct random solution to a given set of dynamic constraints. The process of execution is preferably performed by a constraint resolution engine, optionally and more preferably implemented as software, which manages the requirements imposed by the constraints on the execution, while simultaneously enabling a random solution to the set of constraints to be provided. Such a constraint resolution engine may optionally be viewed as a type of state machine, in which individual elements of the state machine are more preferably represented by one or more dynamic graph(s). According to the present invention, there is provided a system for dynamically solving constraints for test generation for a DUT (device under test), comprising: (a) a data model for the DUT; (b) an abstract generation machine for solving the constraints by creating a plurality of static instructions; and (c) a test generator for performing test generation according to the plurality of static instructions and according to the data model. According to another embodiment of the present invention, there is provided a method for dynamically solving a plurality of dynamic constraints for test generation for a DUT (device under test), each constraint featuring at least one parameter, the steps of the method being performed by a data processor, the method comprising the steps of: (a) creating at least one dynamic graph for describing the plurality of dynamic constraints, each node of the at least one dynamic graph representing a constraint or a parameter, and each edge representing a relationship between constraints; (b) reducing a number of nodes for the at least one dynamic graph; and (c) determining a path for traveling through the at least one dynamic graph to create a plurality of instructions for solving the dynamic constraints. Hereinafter, the term xe2x80x9ccomputing platformxe2x80x9d refers to a particular computer hardware system or to a particular software operating system. Examples of such hardware systems include, but are not limited to, personal computers (PC), Macintosh(trademark) computers, mainframes, minicomputers and workstations. Examples of such software operating systems include, but are not limited to, UNIX, VMS, Linux, MacOS(trademark), DOS, FreeBSD, one of the Windows(trademark) operating systems by Microsoft Inc. (USA), including Windows NT(trademark), Windows95(trademark), Windows98(trademark) and Windows 2000(trademark). The method of the present invention could also be described as a plurality of instructions being performed by a virtual or actual data processor, such that the method of the present invention could be implemented as hardware, software, firmware or a combination thereof. For the present invention, a software application could be written in substantially any suitable programming language, which could easily be selected by one of ordinary skill in the art. The programming language chosen should be compatible with the computing platform according to which the software application is executed. Examples of suitable programming languages include, but are not limited to, C, C++ and Java. Hereinafter, the term xe2x80x9cnon-randomxe2x80x9d refers to a process, or an entity selected by the process, which is not random but which is not necessarily deterministic. | Mid | [
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Best Site to Buy Xbox Live Card The other great novelty is found in Longshot, the story mode that introduces the Madden saga for the first time and that, truth, it feels like ring finger. This is a way in the style of The Road to FIFA 17, which last year followed the steps of 2K in the introduction of this type of stories in their sports titles. In this case we live the story of Devin Wade, a young man from a small town in Texas who has had to go through difficult times and ends up entering a reality show in which he will have to prove that he has the necessary qualities to play in the NFL. We have such notable performances as the Oscar winner, Mahershala Ali, giving birth to Devin's father, or the historic quarterback and member of the Dan Marino Hall of Fame. In the playable, it can be said that this story mode is quite limited as it relies almost entirely on the narrative, and allows us to interact on few occasions. We will only take control in dialogue choices (in which we will be asked even for tactical aspects of the game) and in some other real playable moment, which in our view are scarce. Although it is true that history has liked and may from the study decided to do so to strengthen precisely that section, and not let it be diluted in the 5 hours that lasts. It should be noted that the game is not translated into Spanish and we think it convenient to discuss it in this section, as it is a much focused mode in the argument and can be a barrier for those who do not understand the language. Are you a video game fan? Which platform do you play? We will offer you more guide about video games and best site to buy xbox live card from. It’s American football turn, it’s Madden NFL 18 turn. MUT 18 review. Get free tips and guide of game play and best site to buy xbox live card. | Low | [
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Background {#Sec1} ========== The mouse and human genomes harbor similar types of TEs that have been discussed in many reviews, to which we refer the reader for more in depth and general information \[[@CR1]--[@CR9]\]. In general, both human and mouse contain ancient families of DNA transposons, none currently active, which comprise 1--3% of these genomes as well as many families or groups of retrotransposons, which have caused all the TE insertional mutations in these species. As in humans \[[@CR4]\], the mouse genome contains active retrotransposon families of long and short interspersed repeats (LINEs and SINEs) that can cause germ line mutations via new insertions but, in contrast to humans, the mouse also contains several groups of retrotranspositionally active endogenous retroviral elements (ERVs) that are responsible for most reported insertional mutations. ERVs/LTR retrotransposons {#Sec2} ------------------------- ERVs are the result of retroviral infections or retrotranspositions in the germline. The general structure of an ERV is analogous to that of an integrated provirus, with flanking long terminal repeats (LTRs) containing the transcriptional regulatory signals, specifically enhancer, promoter and polyadenylation motifs and often a splice donor site \[[@CR10], [@CR11]\]. Sequences of full-length ERVs can encode *gag, pol* and sometimes *env,* although groups of LTR retrotransposons with little or no retroviral homology also exist \[[@CR6]--[@CR9]\]. While not the subject of this review, ERV LTRs can often act as cellular enhancers or promoters, creating chimeric transcripts with genes, and have been implicated in other regulatory functions \[[@CR11]--[@CR13]\]. The mouse genome contains many different groups of ERVs and related LTR retrotransposons that together comprise \~ 10% of the sequenced genome \[[@CR1]\] and which have been characterized to varying extents \[[@CR6], [@CR9], [@CR14], [@CR15]\]. ERVs in mouse and other vertebrates are generally categorized into three classes. Class I ERVs are most related to the exogenous gamma-retroviral genus, Class II to beta- and alpha-retroviruses and Class III to spuma-retroviruses \[[@CR6], [@CR9]\]. The very large non-autonomous MaLR (mammalian apparent LTR retrotransposon) group is also considered Class III but has only very small traces of retroviral homology. Different mammals have distinct collections of ERVs and the mouse is unusual in having a much higher fraction of Class II elements compared to humans or other mammals \[[@CR1], [@CR6]\]. For all but very young groups, the majority of ERV loci exist only as solitary LTRs, the product of recombination between the 5′ and 3′ LTRs of integrated proviral forms \[[@CR16], [@CR17]\]. Moreover, for ERVs that have not undergone this recombination event, most have lost coding competence due to mutational degradation over time. Unlike human ERVs that are likely no longer capable of autonomous retrotransposition \[[@CR18], [@CR19]\], some mouse ERVs are retrotranspositionally active and are significant ongoing genomic mutagens in inbred strains, causing 10--12% of all published germ line mutations via new integration events \[[@CR1], [@CR20]\]. The large Intracisternal A-particle (IAP) ERV group is responsible for close to half the reported mutations due to new ERV insertions, with the Early Transposon (ETn)/MusD ERV group also contributing substantially \[[@CR20]\](Fig. [1](#Fig1){ref-type="fig"}a). These groups and other mutation-causing ERVs will be discussed in more detail in the subsequent relevant sections. The majority of mutagenic ERV insertions occur in introns and disrupt normal transcript processing (e.g. splicing and polyadenylation) to varying degrees, a mechanism well recognized since the 1990s \[[@CR21]--[@CR25]\] and discussed further below.Fig. 1Distribution of mouse mutations caused by TE insertions. **a** Numbers of published mutations caused by different TE types. **b** Strain bias for IAP and ETn/MusD insertional mutations. **c** Upper panel -- proportion of LINE1 insertional mutations that are full length or near full length. Lower panel shows high proportion of B2 SINEs among insertional mutations Long interspersed repeats (LINEs) {#Sec3} --------------------------------- LINE-1s (L1s) are autonomous non-LTR elements that have accumulated to as many as 500,000 copies in both mouse and human genomes using a copy-and-paste mechanism of amplification \[[@CR1]--[@CR3], [@CR26]\]. Full length L1s are 6--7 kb and contain two open reading frames (ORFs) encoding ORF1p and ORF2p, with the latter having endonuclease and reverse transcriptase activity \[[@CR27]--[@CR30]\]. The number of potentially active L1s (i.e. full-length elements containing intact ORFs) varies significantly between human and mouse. Bioinformatics analyses of the reference genomes have documented 2811 mouse and 146 human L1s that are fully structurally intact \[[@CR31]\]. Functional studies have estimated numbers of active L1s to be \~ 3000 for mouse \[[@CR32]\] and 80--100 for human \[[@CR33]\]. In contrast to the human genome that has had a single subfamily of LINEs active at any given evolutionary time, the mouse genome contains three concurrently active L1 subfamilies (T(F), A, and G(F)) \[[@CR32], [@CR34]\] that are insertionally polymorphic among strains \[[@CR17], [@CR35]\]. One of the distinguishing features of these subfamilies is the differing 5′ monomer tandem repeats which, when combined with a downstream non-monomeric sequence, form their 5′ UTRs \[[@CR36]\]. The 5′ UTR also contains the L1 pol II promoter, which occurs downstream of the transcriptional start site \[[@CR37], [@CR38]\], an arrangement common to non-LTR retrotransposons \[[@CR39]\], allowing the promoter to be retained in the L1 mRNA. Mouse and human L1s contain promoters, splice and polyadenylation signals in both sense and antisense directions that are utilized during L1 and host gene transcription, also sometimes leading to the formation of chimeric mRNAs \[[@CR40]--[@CR44]\]. As with ERVs \[[@CR20], [@CR45]\], such cis-acting sequences are a likely reason for the negative impact of some intronic L1 insertions on gene expression \[[@CR43]\]. De novo L1 inserts can vary in size from just a few bases to those containing a full-length L1 sequence \[[@CR26]\], with the vast majority of such inserts being 5′-truncated to varying extents. Although the exact mechanisms underlying this truncation phenomenon remain unclear, there is a positive correlation between the frequency of retrotransposition and insert length \[[@CR46]\], and cellular DNA repair interference with L1 integration may play a role \[[@CR47], [@CR48]\]. Sporadically, new germ line L1 insertions cause mutations when they land in or near a gene in human \[[@CR4]\] or mouse (discussed below), and somatic insertions can also occur, although few of the latter have been shown to exert a significant biological effect \[[@CR49]--[@CR51]\]. Mutagenic L1 inserts can potentially disrupt normal gene function or expression by interfering with it directly or by introducing deletions or complex genomic rearrangements that are sometimes associated with the integration process \[[@CR3], [@CR52]\]. In addition to introducing de novo insertions containing L1 sequences, L1 can mobilize flanking genomic sequences as well. This occurs as a result of their incorporation into the nascent L1 mRNA generated by either inaccurate/upstream transcriptional initiation (5′ transduction) or inefficient transcriptional termination at the L1 3′ polyadenylation site resulting in readthrough and 3′ transduction \[[@CR3], [@CR53], [@CR54]\]. Recent analysis of endogenous L1 expression in human cell lines determined that only about a third of expressed L1 loci generate such readthrough transcripts \[[@CR55]\] but a similar analysis has not been performed for mouse. The uniqueness of these transduced sequences are often useful in identifying the source L1 element responsible for a newly retrotransposed copy \[[@CR56]\]. Short interspersed repeats (SINEs) {#Sec4} ---------------------------------- SINE elements are non-autonomous retrotransposons, as they do not encode proteins involved in their amplification. As with human Alu SINE sequences \[[@CR57]\], mouse SINEs have been shown to be retrotransposed by mouse L1 \[[@CR58]\]. Only one of the two L1 proteins (ORF2p) is sufficient to drive Alu SINE mobilization in tissue culture \[[@CR57]\], although ORF1p enhances the process \[[@CR59]\]. Both mouse and human L1s can efficiently mobilize their non-orthologous SINEs, suggesting that such a symbiotic relationship has evolved multiple times \[[@CR58]--[@CR62]\]. There are several SINE classes in the mouse genome that together comprise \~ 8% of the genome \[[@CR1]\]. Among these are B1, B2, B4/RSINE, ID, and MIR. New mutagenic insertions have been documented for B1 and B2 (see below), indicating that at least some copies are still potentially active. B1 (like human Alu) is derived from 7SL RNA, and B2 is derived from tRNA \[[@CR3]\]. B1 and B2 SINEs are both present at very high genomic copy numbers: \~ 560,000 for B1 and \~ 350,000 for B2 \[[@CR1]\]. Like mouse L1s and ERVs, these mouse SINEs are insertionally polymorphic in inbred strains \[[@CR17], [@CR63], [@CR64]\]. Cataloging TE-induced mouse mutations {#Sec5} ------------------------------------- We assembled lists of mutations caused by TEs by perusing the literature and by querying the Mouse Genome Informatics (MGI) database of mutant alleles \[[@CR65]\]. In October 2018 we obtained lists from MGI of all spontaneous mutant alleles that listed "viral", "transposon" or "insertion" as the cause and extracted all relevant cases through manual curation. To avoid ascertainment bias, we excluded cases where investigators were specifically screening for effects of insertionally polymorphic TEs \[[@CR35], [@CR66], [@CR67]\]. While such cases can show effects on gene expression, observable phenotypes due to these insertionally polymorphic TE insertions were not reported in the aforementioned studies. In addition, we excluded cases where the insertion event likely occurred in cultured ES cells used to produce transgenic mice. Nearly all arose spontaneously but two cases of mutations occurring during a chemical mutagenesis experiment, but likely not caused by the chemical mutagen, were also included. This search resulted in a total of 115 TE insertion mutations. Ninety-four of these were caused by insertions of ERVs/LTR retroelements and 21 were L1 or L1-mediated (Fig. [1](#Fig1){ref-type="fig"}). In the case of the ERV mutations, the tables shown here are updates of previously published lists \[[@CR1], [@CR20], [@CR68]\]. IAP insertion mutations {#Sec6} ----------------------- The group of ERVs responsible for the most reported mutations are the IAP elements. IAP sequences are Class II elements and are highly abundant in the mouse \[[@CR6], [@CR69]\]. Different estimates for IAP copy number exist in the literature but a recent analysis of all sequences annotated "IAP" by Repeatmasker \[[@CR70]\] found \~ 3000 solitary LTRs and \~ 2800 full-length or partial full-length elements in the reference C57BL/6 genome \[[@CR71]\]. Of the latter, \~ 1000 have 5′ and 3′ LTRs that are 100% identical, indicative of a very young age, and most of these belong to the IAPLTR1 or 1a subtypes \[[@CR71]\]. As expected for such a young ERV group, IAP elements are highly insertionally polymorphic among inbred mouse strains \[[@CR17], [@CR66], [@CR67], [@CR72]\]. Although \~ 200 IAP sequences (IAPE elements) contain an *env* gene \[[@CR73]\], most do not. Loss of *env* and other specific genetic modifications facilitated adoption of an intracellular retrotranspositional life cycle by IAPs \[[@CR74]\] resulting in their accumulation to high copy numbers as genomic "super spreaders" \[[@CR75]\]. Besides the lack of *env*, there are a few common partly deleted proviral forms \[[@CR69]\] with the most notable being the 1Δ1 subtype, which has a 1.9 kb deletion removing part of *gag* and *pol,* resulting in an ORF encoding a novel gag-pol fusion protein. Although retrotransposition of 1Δ1 proviruses is non-autonomous, requiring gag and pol proteins in *trans* from other IAPs \[[@CR76]\], this subtype is responsible for the great majority of new IAP insertion mutations \[[@CR20]\]. Interestingly, it has been shown that the gag-pol fusion protein functions in *cis* to facilitate retrotransposition \[[@CR77]\]. Together with a generally higher level of 1Δ1 transcripts compared to full length IAP mRNAs (see below), this *cis* effect could explain why most new insertions are of the 1Δ1 subtype. Although transgenic experiments have shown expression of an IAP LTR only in the male germ line \[[@CR78]\], endogenous IAP transcription is also detectable in embryogenesis as early as the two cell stage and appears highest in the morula and blastocyst stages \[[@CR79]\]. Moreover, at least some IAP elements can be transcribed in normal somatic tissues, particularly in the thymus, where a specific subtype of IAP LTR shows transcriptional activity \[[@CR80], [@CR81]\]. Notably, the levels of 1Δ1 5.4 kb IAP transcripts are comparable or often more abundant than full-length IAP transcripts in different tissues or cell types \[[@CR69], [@CR80], [@CR82]\], although the former are present in lower copy numbers \[[@CR69], [@CR71], [@CR83]\]. The molecular mechanisms underlying the generally higher transcript levels of 1Δ1 elements are unknown but one possibility is that these elements are more likely to escape the general epigenetic transcriptional repression of IAPs by DNA methylation and repressive histone modifications \[[@CR84]--[@CR87]\]. Table [1](#Tab1){ref-type="table"} lists mouse germ line mutations caused by insertions of IAPs. Somatic insertions of IAP elements can also occur and cause oncogene or cytokine gene activation in mouse plasmocytomas, myelomas and lymphomas \[[@CR88]--[@CR90]\], likely due to the fact that some IAP LTRs are transcriptionally active in lymphoid tissues \[[@CR80], [@CR81]\]. Most of the germ line insertions occur in gene introns and disrupt transcript processing, notably splicing and polyadenylation (Table [1](#Tab1){ref-type="table"}) \[[@CR20]\]. However, several IAP-induced mutations involve ectopic gene transcription promoted by an upstream or intronic inserted LTR that is regulated by DNA methylation \[[@CR20], [@CR91]\]. In these cases, the IAP is oriented in the opposite transcriptional direction with respect to the gene and it is an antisense promoter within the LTR that is responsible for the ectopic gene transcription. For a number of such cases, including the most well studied A^vy^ allele of *agouti* \[[@CR92]\], variable establishment of epigenetic repressive marks on the IAP LTR result in variable expressivity of the mutant (IAP) allele in genetically identical mice and have been termed metastable epialleles \[[@CR91], [@CR93]\]. Interestingly, a recent genome-wide screen for other IAP metastable epialleles in C57BL/6 mice identified \~ 100 such loci, with an enrichment of flanking CTCF binding sites as the primary distinguishing feature \[[@CR94]\].Table 1IAP insertions^a^MutationMGI ID^b^Strain of originYear mutation aroseLocation & Orientation^c^Mutational mechanism(s) or effectsReferences^*a*^ *A* ^*hvy*^1855945C3H/HeJ\~ 1994Exon 1C,-^c^IAP forms 5′-end of transcript^d^, Regulation by methylation\[[@CR181]\]^*a*^ *A* ^*iapy*^1856403C57BL/6J xC3H male1992Intron, −IAP forms 5′-end of transcript^d^, Regulation by methylation\[[@CR182]\]*A* ^*iy*^1855933C3H/HeJ1964Intron 1, −IAP forms 5′-end of transcript^d^, transcript contains internal IAP sequence\[[@CR183]\]^*a*^ *A* ^*vy*^1855930C3H/HeJ1960Exon 1A, −IAP forms 5′-end of transcript^d^, Regulation by methylation\[[@CR92], [@CR183]\]*Adamts13* ^*s*^3579136unknown, present in several strains?Intron 23, +IAP causes premature polyadenylation and protein truncation. Reduced enzyme activity but no obvious phenotype\[[@CR184], [@CR185]\]*Ap3d1* ^*mh-2J*^1856084C3H/HeJBefore 1988Intron 21, +Transcript contains internal IAP sequence, Truncated protein\[[@CR186]\]*Atcay* ^*ji-hes*^1856898C3H/HeJ-Tyr^c-a^1987Intron 1, +Transcript contains internal IAP sequence\[[@CR187]\]*Atp2b2* ^*jog*^3664103DSO, derived from C3H/He-Pw hybrid2000Intron,+Reduced mRNA levels, likely by terminating at poly(A) in IAP, also cryptic splicing suggested\[[@CR188]\]*Atrn* ^*mg*^1856081C3H -- Swiss stock cross1950Intron 26, −Transcript contains internal IAP sequence, Truncated protein, Likely termination in IAP\[[@CR189]\]*Atrn* ^*mg-L*^2156486C3H/HeJ1981Intron 27, +Transcript contains internal IAP sequence, Reduced protein levels, Likely termination in IAP\[[@CR189]\]^*a*^ *Axin1* ^*Fu*^1856035Bussey stockBefore 1931Intron 6, −IAP forms 5′-end of transcript^d^, Regulation by methylation, and transcript contains internal IAP sequence, Truncated protein\[[@CR190], [@CR191]\]^*a*^ *Axin1* ^*Fu-kb*^1856037unknownmid 1970s?Exon 7, −IAP forms 5′-end of transcript^d^, transcript contains internal IAP sequence, Internally deleted protein\[[@CR190]\]*Clcc1* ^*m1J*^5618134C3H/HeSnJAfter 1947Intron 2, +Transcripts contains internal IAP sequence, Reduced normal mRNA levels\[[@CR192]\]*Cryge* ^*No3*^3713105C3H/HeH × 102/E1 F1Late 1990sExon 3, +Reduced mRNA levels, Transcript contains internal IAP sequence, Truncated protein\[[@CR193]\]*Dab1* ^*scm*^1856801Dc/Le (Dc arose in an obese stock outcrossed to BALB/c x C3H/He hybrid. One cross to C3H/HeJ, then inbred.)1991Intron, −Transcript contains internal IAP sequence, Truncated protein\[[@CR194], [@CR195]\]*Dnmt3C* ^*IAP*^NC3HeB/FeJ\ From chemical induction exp.\~ 2014Last intron, −IAP provides alternate splice acceptor site, resulting in exclusion of Dnmt3C last exon, chimeric Dnmt3C-IAP mRNA\[[@CR97]\]*Eya1* ^*bor*^1857803C3HeB/FeJ1984Intron 7, +Transcript contains internal IAP sequence, Reduced mRNA levels\[[@CR25]\]*Gata3* ^*jal*^3027100C3H/HeJ1990sIntron 3, −Unknown\[[@CR196]\]*Gpr179* ^*nob5*^5431477C3HAfter 1951Intron 1, +Drastically reduces gene expression\[[@CR197], [@CR198]\]*Gria4* ^*spkw1*^3580141 (QTL)C3H/HeJ1950--2002Intron 15, +Full-length protein expression is significantly reduced\[[@CR199]\]*Gusb* ^*mps-2J*^2152564C3H/HeOuJmid 1990s?Intron 8, +,Reduced mRNA size and level, No enzyme activity detected\[[@CR200]\]*Hps3* ^*coa-6J*^1861609C3H/HeJ1999?Exon 10, −Transcript contains internal IAP sequence\[[@CR201]\]*Hps1* ^*ep*^1856712C3HeB/FeJ19573′-coding exon, −Transcript contains internal IAP sequence, Protein contains IAP-encoded amino acids\[[@CR202]\]*Hps6* ^*ru-6J*^1856410C3H/HeJ1995Unknown, +Kidney: loss of expression, Brain: transcript contains IAP sequence\[[@CR203]\]*Kcnq1* ^*vtg-2J*^2389447C3H/HeJCrl-Il2^tm1Hor^\~ 2000Exon 2, −IAP fusion transcript likely promoted by antisense LTR. IAP provides 5′ end of 31 bp fused in frame to the gene.\[[@CR204]\]*LamB3* ^*IAP*^2179716C3H (C3Hf/R1 male bred separately from JAX for decades)\~ 1990Intron/exon junction (5′), −Transcript contains internal IAP sequence, No mRNA or protein expression\[[@CR205]\]*Mc1r* ^*mpc59H*^5791971C3H.Pde6b2010Exon,?Disruption of single exon gene\[[@CR206]\]*Mgrn1* ^*md*^1856070C3H/HeJ\~ 1960Intron 11, +Reduced mRNA levels, aberrantly sized transcripts\[[@CR207], [@CR208]\]*Mgrn1* ^*md-2J*^1856072C3H/HeJ1978--1993Exon 12, +Reduced mRNA levels, aberrantly sized transcripts\[[@CR207], [@CR208]\]*Mgrn1* ^*md-5J*^1856519C3H/HeJ1978--1993Intron 2, +Not characterized\[[@CR207], [@CR208]\]*Oprm1* ^*IAP*^NCXBK recomb. Inbred of B6 & BalbBefore 1984Exon 4,?Decreased mRNA levels, increase in length of 3'UTR. Modifies response to opioids\[[@CR209]\]*Pcnx2* ^*C3H/HeJ*^6161760C3H/HeJAfter 1950Intron 19, +Modifier of *Gria4* mutation, reduces Pcnx2 expression\[[@CR83]\]*Pitpna* ^*vb*^1856642DBA/2JEarly 1960sIntron 4, +Transcript contains internal IAP sequence, Reduced mRNA & protein\[[@CR210]\]*Pla2g6* ^*m1J*^4412026C3H/HeJmid 2000sIntron 1,?Reduces normal gene transcripts by \~ 90%\[[@CR211]\]*Plcd3* ^*mNab*^NC3H mix\~ 2005Intron 2, −Causes truncated protein, LTR may act as antisense promoter?\[[@CR212]\]*Pofut1* ^*cax*^3719000C3H/HeJmid 2000sIntron 4,Reduced mRNA and protein levels\[[@CR213]\]*Reln* ^*rl-Alb2*^1857345C3H/HeJ\ From chemical ind. Exp.\~ 1990Exon 36, −Exon skipping, Reduced mRNA levels\[[@CR214]\]*Slc35d3* ^*IAP*^3802578C3H/HeSn-Rab27a^ash^/JRos1980s--1990sExon 1, −IAP fusion transcript likely promoted by antisense LTR. IAP provides 5′ end of 18 bp fused in frame to the gene.\[[@CR215]\]*Spta1* ^*sph-Dem*^2388936CcS3/Dem recomb. Con. strain from BALB/cHeA and STS/A1991Intron 10/exon 11 junction, +Exon skipping, Reduced protein expression, Reduced α−/β-spectrin dimer and tetramer stability\[[@CR216]\]*Tal1* ^*Hpt*^1859843C57BL/6J x C3HeB/FeJLe-a/a)F1.1979Intron 4, +Promotes overexpression of exons 4 and 5, fusion transcripts found.\[[@CR217]\]*Tnfrsf13c* ^*Bcmd1*^2389403 (QTL)A/WySnJBefore 1991Exon 3, +Fusion transcripts, Loss of function mutation\[[@CR218]\]*Tyr* ^*cm1OR*^2153728C3Hf/R11988Upstream, −IAP does not form 5′-end of transcript, Reduced mRNA expression\[[@CR219]\]*Usp14* ^*ax-J*^1855959CBA or kreisler stockEarly 1950sIntron 5, +Transcript contains internal IAP sequence, Reduced mRNA levels,\ Truncated protein\[[@CR220]\]*Wnt9b* ^*clf1*^1856821A1920sDownstream, +Produces transcript antisense to *Wnt9b.*\[[@CR221], [@CR222]\]*Zfp69* ^*IAP*^NUnknown,\ present in C57BL/6, NZO,\ other strains?Intron 3 of Zfp69, +IAP causes premature polyadenylation and alternate splicing. Loss of functional *Zfp69* in strains carrying the IAP is protective against diabetes.\[[@CR223]\]*9630033F20Rik*NC3H/HeDiSnJ\~ 1985?Exon 5, −Deletion of exon 5, decreased gene expression. Occurs in "lew" mice with point mutation in *Vamp1* thought to be cause. IAP may contribute.\[[@CR224], [@CR225]\]^a^Variable phenotype or expression (metastable epiallele)^b^ID number in Mouse Genome Informatics (MGI) database, "N" indicates not present in MGI^c^- = antisense, + = sense,? = orientation unknown^d^Ectopic expression of IAP-driven transcript IAP activity in C3H mice {#Sec7} ------------------------ Because high numbers of IAP mutations in C3H mice and high IAP insertional polymorphisms among C3H substrains have been noted before \[[@CR20], [@CR83]\], we investigated the strain of origin for all TE-induced mutations. For IAPs, the strain of origin could not be ascertained for three of the 46 cases but, of the remaining 43, a remarkable 84% (36 cases) occurred in a C3H strain or hybrid involving C3H (Table [1](#Tab1){ref-type="table"}, Fig. [1](#Fig1){ref-type="fig"}b). This marked skew is not seen for mutations caused by any other retroelements, indicating that ascertainment bias cannot explain the high frequency of IAP-caused mutations in C3H mice. While the date of the mutation is difficult to determine in some cases, IAP retrotranspositions in C3H mice have spanned several decades, with the earliest reported cases in the 1950s and the latest in 2014 (Table [1](#Tab1){ref-type="table"}). This indicates that the unusual IAP activity has been a characteristic of C3H strains for at least 60 years. Indeed, Frankel et al. have shown that at least 26 1Δ1 IAP insertions present in C3H/HeJ are absent from the highly related C3HeB/FeJ substrain \[[@CR83]\], again indicative of ongoing activity of IAPs, particularly the 1Δ1 subtype, in this strain. Although reasons for the numerous IAP insertional mutations in C3H strains are unknown, it is noteworthy that normal spleen, bone marrow and thymus from C3H/He mice have much higher levels of IAP transcripts compared to C57BL/6 and STS/A mice \[[@CR95]\], suggesting that transcriptional deregulation may be involved. As well, IAPs are transcriptionally upregulated in radiation-induced acute myeloid leukemia in C3H/He mice, resulting in new insertions in the leukemic cells, most of which are of the 1Δ1 subtype \[[@CR95], [@CR96]\]. These observations, coupled with the fact that most new mutations in C3H mice involve the 1Δ1 subtype suggests that this IAP subtype is accumulating in the C3H genome at a faster rate than full length elements. Two recent reports illustrate the prudence of considering IAP induced mutations whenever working with C3H mice (Fig. [2](#Fig2){ref-type="fig"}). In the first case, Frankel et al. found that an IAP insertion in the *Pcnx2* gene in C3H/HeJ mice (*Pcnx2*^*C3H/HeJ*^) reduces expression of this gene, which in turn mitigates the effect of an IAP insertion in *Gria4* (*Gria4*^*spkw1*^) which causes seizures \[[@CR83]\]. Hence one IAP insertion modifies the effect of another (Fig. [2](#Fig2){ref-type="fig"}a). In another intriguing example, Barau et al. conducted a screen in C3HeB/FeJ mice using *N*-ethyl-*N*-nitrosourea (ENU) mutagenesis to identify genes involved in retrotransposon silencing in the germ line \[[@CR97]\]. They identified several lines with the same mutation, indicating it was not induced by ENU but rather was spontaneous. This mutation was an IAP element inserted in an intron of a gene, annotated as a non-functional pseudogene, that formed as a tandem duplication of *Dnmt3B*. Barau et al. showed that this gene, now termed *Dnmt3C*, is indeed a functional DNA methyltransferase responsible for methylating promoters of young retroelements, including L1 elements and IAPs, in the male germ line \[[@CR97]\]. Therefore, an IAP insertion facilitated the discovery of a gene involved in its own silencing (Fig. [2](#Fig2){ref-type="fig"}b).Fig. 2Effects of IAP insertions in C3H mice. **a** An IAP insertion in *Gria4* in C3H/HeJ causes seizures associated with spike-wave discharges but seizure episodes are much more frequent when the allele is crossed into another strain. The modifying effect in C3H/HeJ is due to another IAP insertion in *Pcnx2*, which reduces the detrimental effect of the *Gria4* mutation. **b** A new IAP insertion in the previously unknown *Dnmt3c* gene was detected in a C3HeB/FeJ colony during a screen for genes involved in retrotransposon silencing in the male germ line. See text for references. Black boxes are gene exons and green arrows and lines represent IAP LTRs and internal sequences. Numbers of exons/introns and distances are not to scale C3H mouse history {#Sec8} ----------------- The C3H strain was derived by Leonard Strong from a 1920 cross of a Bagg albino female (ancestors to the BALB/c strain) and a male from Little's strain of "dilute browns" (ancestors to the DBA strain) \[[@CR98]\]. One of the original female progeny of this mating developed spontaneous mammary tumors and this trait was selected for or against by subsequent inbreeding to develop the C3H strain (highly susceptible to mammary tumors) and the CBA strain (highly resistant). Mouse mammary tumor virus (MMTV), the transmissible agent responsible for the early onset mammary tumors in C3H \[[@CR99], [@CR100]\], was later purged from most C3H related strains by pup fostering or re-derivation. In particular, the most widely used C3H substrain C3H/HeJ was re-derived to be MMTV-free at the Jackson Laboratory (JAX) in 1999 and all C3H substrains carried at JAX have been free of MMTV since that time. Because IAP mutations have continued to occur in C3H/HeJ mice after removal of MMTV (Table [1](#Tab1){ref-type="table"}), it is unlikely that activities of the two retroviral entities are directly related. Various substrains of C3H, including the commonly used C3H/HeJ, were derived in the late 1940s and early 1950s \[[@CR101]\]. Interestingly, there is some evidence that C3H/HeJ has a higher spontaneous mutation rate than most other strains. A multi-year study conducted at JAX from 1963 to 1969 examined over 7 million mice derived from 28 inbred strains for spontaneous observable and heritable mutations \[[@CR102]\]. C3H/HeJ had marginally the highest overall rate of mutations but not remarkably so \[[@CR102]\]. However, this study also documented mutational cases of "irregular inheritance" where the trait was heritable but showed very poor penetrance. Of the 35 examples of such cases, 16 (46%) arose in C3H/HeJ, even though this strain accounted for only 9.7% of the 7 million mice in the study \[[@CR102]\]. It is tempting to speculate that at least some of these unusual cases may involve a new IAP insertion behaving as a metastable epiallele \[[@CR91], [@CR93]\]. ETn/MusD insertion mutations {#Sec9} ---------------------------- After IAPs, the ETn/MusD group is responsible for the next highest number of germ line mutations, with 31 cases (Fig. [1](#Fig1){ref-type="fig"}, Table [2](#Tab2){ref-type="table"}). ETn elements were first described as repetitive sequences expressed highly in early embryogenesis \[[@CR103]\]. Subsequent expression analyses showed that ETns are transcribed in two windows of embryonic development. First during E3.5--7.5 in the inner cell mass and epiblast and second between E8.5--11.5 in various tissues including the neural tube, olfactory/nasal processes and limb buds \[[@CR103]--[@CR105]\]. Although ETns have LTRs, they have no coding capacity and, hence, their mode of retrotransposition was initially a mystery. Based on traces of retroviral homology in canonical ETns, we identified an ERV group, termed MusD, which is the likely progenitor of ETn \[[@CR106], [@CR107]\] and Ribet et al. demonstrated that coding competent MusD elements provide the machinery necessary for ETn elements to retrotranspose \[[@CR108]\]. A subsequent phylogenetic analysis of the large betaretrovirus genus classified MusD as belonging to the Class II ERV-β7 group \[[@CR14]\]. One analysis of copy numbers of ETn and MusD in C57BL/6 found \~ 240 ETn elements, \~ 100 MusDs and \~ 550 solitary LTRs \[[@CR107]\], and they are highly insertionally polymorphic \[[@CR17], [@CR66], [@CR109]\]. As for IAP elements, loss of the *env* gene and other genetic modifications likely resulted in genomic amplification of MusD (and ETn) elements as intracellular retrotransposons \[[@CR110]\]. In another similarity to IAPs, most germ line mutations caused by ETn/MusD are due to insertions of the non-autonomous ETn (Table [2](#Tab2){ref-type="table"}), in particular a specific subtype ETnII-β \[[@CR20]\]. Of the 31 cases, only three are documented to be MusD while the rest are ETn (Table [2](#Tab2){ref-type="table"}). The reasons for this are not clear but ETn transcripts are much more abundant than MusD transcripts in embryos and ES cells \[[@CR107], [@CR111]\] and there is evidence that MusD is subject to greater levels of epigenetic suppression \[[@CR111], [@CR112]\].Table 2ETn/MusD insertionsMutationMGI ID^a^Strain of originLocation & Orientation^\#^Mutational mechanisms or effectsReferences*Adcy1* ^*brl*^1857405ICRIntron 14, +^\#^Transcripts contain ETn sequence, Transcripts terminate within the ETn\[[@CR226], [@CR227]\]*Bloc1s5* ^*mu*^1856106Stock-tIntron 3, +Transcripts contain internal ETn sequence\[[@CR228]\]*Cacna1f* ^*nob2*^3605845AXB6/PgnJExon 2, +Premature termination and alternative splicing within ETn\[[@CR229], [@CR230]\]*Cacng2* ^*stg*^1856548A/JIntron 2, +Transcripts contain ETn sequence, Probable termination within ETn\[[@CR231], [@CR232]\]*Cacng2* ^*stg-wag*^1856386MRL/MpJ-Fas^lpr^/JIntron 1, +Transcripts contain ETn sequence, Probable termination within ETn\[[@CR231], [@CR232]\]*Cacng2* ^*stg-3J*^2155891BALB/cJIntron 2, +Transcripts contain internal ETn sequence\[[@CR231], [@CR232]\]*Clcn1* ^*adr*^1856316A2GIntron 12, +Transcripts contain ETn sequence, Termination within ETn\[[@CR233]\]*Dsg4* ^*hage*^3766998Recom. inbred of MRL/lpr x BXSBIntron 8, +Aberrant splicing in ETn causes in frame additional exon of 63 amino acids\[[@CR234]\]*Dysf* ^*prmd*^3055150A/JIntron 4,+ETn fixed in A/J strain. Aberrant splicing, No detectable dysferlin protein\[[@CR235]\]*Edar* ^*Dl-slk*^1856017Stock Tyrp1^b^ Dock7^m^ Rb(4.6)2BnrunknownTranscripts contain ETn sequence, Termination within ETn\[[@CR236]\]*Eml1* ^*heco*^5560734NOR-ICRIntron 22, +Aberrant splicing and premature termination, transcripts contain ETn sequence\[[@CR237], [@CR238]\]*Etn3* ^*Ppd*^3665247CD-11.6 kb 3′ of *Dusp9* gene, −Upregulates *Dusp9* in ES cells, causes phenotype in Polypodia mutant\[[@CR120]\]*Fas* ^*lpr*^1856334MRL/MpIntron 2, +Transcripts contain ETn sequence, Termination within ETn\[[@CR21], [@CR239], [@CR240]\]*Fbxw4* ^*Dac*^1857833SM/Ckc10 kb 5′ of exon 1, −No evident difference in size or abundance of transcript, **MusD\*** insertion\[[@CR121]--[@CR123]\]*Fbxw4* ^*Dac-2J*^1857834MRL/MpJIntron 5, +Small amounts of normal transcript, **MusD\*** insertion disrupts a conserved motif in intron\[[@CR121]--[@CR123]\]*Fig4* ^*plt1*^3716838'mixed' (129/Ola, C57BL/6J, C3H & SJL)Intron 18, +Abnormal splicing from exon18 to SA site of EtnII, very low abundance of transcript\[[@CR241]\]*Fign* ^*fi*^1856870Random bredIntron 2, +Transcripts contain ETn sequence, Probable termination within ETn\[[@CR242]\]*Foxn1* ^*nu-Bc*^1856110SELH/BcIntron, −Transcripts contain internal ETn sequence\[[@CR113]\]*Gli3* ^*pdn*^1856282Jcl:ICRIntron 3, +5 alternatively spliced transcripts contain ETn sequence, three terminate within ETn, two terminate as wild-type\[[@CR243]\]*Hk1* ^*dea*^2151848A/JIntron 4, +Probable aberrant splicing of ETn sequences into mRNA, Decreased hexokinase activity\[[@CR244]\]*Hsf4* ^*ldis1*^3056560RIIIS/JIntron 9, +ETn alters splicing resulting in a chimeric truncated protein, and causes at least 100 fold up-regulation of the transcript\[[@CR245]\]*Lep* ^*ob-2J*^1858048SM/Ckc-Fbxw4^Dac^Intron 1, +Transcripts contain ETn sequence, Probable termination within ETn, Loss of leptin expression.\[[@CR23]\]*Mip* ^*Cat-Fr*^1857104A/JIntron 3, +Transcripts contain ETn sequence, Termination within ETn, LTR sequence translated to protein domain\[[@CR246], [@CR247]\]*Rubie* ^*SWR-J*^5568608SWR/JIntron 1, +Aberrant splicing and premature polyadenylation of the long non-coding RNA transcript Rubie which is proposed to regulate Bmp4 expression\[[@CR248]\]*Sgk3* ^*fz-ica*^3032837SwissIntron 6, +Aberrant splicing, transcript contains ETn sequence\[[@CR249], [@CR250]\]*Sil1* ^*wz*^3055918Recomb. inbred CXB5/ByJIntron 7, +Aberrant splicing and premature termination. Transcript contains ETn sequence\[[@CR251]\]*Slc6a5* ^*m1J*^5086232NOD.Cg-Emv30^b^ Prkdc^scid^/DvsIntron 5, +**MusD\*** insertion, Inclusion of 183 bp of MusD sequence in mRNA, complete loss of protein\[[@CR252]\]*Ttc7* ^*fsn*^1856879A/JIntron 14, +Transcripts contain internal ETn sequence\[[@CR253]\]*T* ^*Wis*^1857760A/Jsplice donor of exon 7, −8 alternatively spliced transcripts, 4 contain ETn sequence, 1 terminates within ETn, 7 terminate as wild-type, 5 have exon skipping\[[@CR254], [@CR255]\]*Tyr* ^*c-Bc3*^1856303SELH/BcExon 1, −Transcripts probably contain ETn sequence, Probable termination in ETn\[[@CR113]\]*Zhx2* ^*BALB/cJ*^3623885BALB/cJIntron 1, +Transcripts contain ETn sequence, Termination within ETn\[[@CR256], [@CR257]\]^a^ID number in Mouse Genome Informatics (MGI) database, "N" indicates not present in MGI^\#^- = antisense, + = sense,? = orientation unknown\*MusD insertions are bolded. All others are ETns ETn/MusD mutations do not show an extreme strain bias as observed for IAP insertions. However, eight mutations have occurred in "A" strain mice (Fig. [1](#Fig1){ref-type="fig"}b), such as A/J, and two in the seldom used strain SELH/Bc (Table [2](#Tab2){ref-type="table"}) which has a high incidence of exencephaly \[[@CR113], [@CR114]\]. Interestingly, genomic copy number estimates in different mouse strains revealed that, while there are no detectable differences in MusD numbers, A/J, SELH/Bc and CD-1 mice have two to three times more ETnII-β elements compared to C57BL/6 \[[@CR107]\]. Transcript levels of MusD and ETnII-β in day 7.5 embryos are also higher in SELH/Bc and CD-1 compared to C57BL/6 \[[@CR107]\]. Nearly all of the ETn mutagenic insertions occur in gene introns, in the same transcriptional direction as the gene, and disrupt normal transcript processing through utilization of canonical or cryptic signals within the ETn, notably a specific strong splice acceptor site in the LTR, coupled with either a downstream splice donor or polyadenylation signal \[[@CR20], [@CR45]\]. This extreme orientation bias for mutagenic insertions is also observed for the intronic IAP insertions that do not involve IAP promoter activity (Table [1](#Tab1){ref-type="table"}). Such an orientation skew for detrimental insertions is indeed expected, given that fixed/older ERVs have an antisense bias in genes \[[@CR115], [@CR116]\], presumably reflecting the fact that such insertions are less likely to be potentially deleterious and selected against. In an attempt to mechanistically understand these orientation biases, we modeled splicing events involving intronic ERVs (using computationally predicted splice and polyadenylation motifs) and surprisingly found similar predicted frequencies of alternate splicing caused by sense or antisense ERVs \[[@CR45]\]. However, actual splicing patterns of human mRNAs with intronic ERVs suggests that suppression of splicing within antisense-oriented ERVs occurs, possibly via steric hindrance due to annealing of sense-oriented ERV mRNAs \[[@CR45]\]. This scenario would be analogous to gene therapy approaches where oligonucleotides that anneal to and suppress the use of mutagenic splice sites are used to redirect splicing and restore gene function \[[@CR117]\]. Although unproven, such a mechanism could contribute to the general antisense bias for neutral/fixed ERV insertions and the opposite bias for mutagenic insertions. Unlike for IAPs, there are no documented cases of ETn promoters causing a phenotype by driving ectopic gene expression (Table [2](#Tab2){ref-type="table"}). This is likely due at least in part to the fact that ETn/MusD LTRs are normally only transcriptionally active in embryogenesis, responding to embryonic transcription factors \[[@CR118], [@CR119]\], so their promoter/enhancer activity would be silent in somatic tissues where most observable but non-lethal phenotypes manifest themselves. There is, however, at least one case where enhancer effects of an ETn insertion are likely responsible for a mutant phenotype. In this example, an ETn insertion downstream of the *Dusp9* gene upregulates this gene and also causes malformations in *Polypodia* mice, although a direct link between *Dusp9* deregulation and malformations has not been shown \[[@CR120]\]. There is an intriguing but complex story involving two of the three documented MusD insertions \[[@CR121]--[@CR123]\]. Both of these cause the *dactylaplasia (Dac)* embryonic limb malformation phenotype by insertions within (*Fbxw4*^*Dac-2J*^) or upstream (*Fbxw4*^*Dac*^) of the *Fbxw4* gene. Both are full length MusD elements that share 99.6% identity and have occurred in different mouse strains. In the former case (*Fbxw4*^*Dac-2J*^), the intronic, sense oriented MusD severely reduces the amount of normal *Fbxw4* transcripts, likely via typical transcript processing disruption or via physical disruption of a conserved, and hence potentially regulatory, \~ 1.5 kb region within the intron \[[@CR123]\], although neither mechanism has been formally demonstrated. In the other *Dac* mutation (*Fbxw4*^*Dac*^, also termed *Dac*^*1J*^) the MusD is inserted 10 kb upstream of the *Fbxw4* gene in antisense orientation. However, no effects on the size or abundance of *Fbxw4* transcripts are evident in mice carrying this insertion, so the mechanism by which it causes dactylaplasia remains unclear \[[@CR121]--[@CR123]\]. Interestingly, the *Dac* phenotype is modified by an unlinked polymorphic locus *mdac (*modifier of dactylaplasia) \[[@CR124]\]. In strains homozygous for the *mdac* allele (eg. BALB/c and A/J), the dactylaplasia phenotype is observed if the mice carry either *dac* mutation. However, in strains carrying the other allele *Mdac* (eg. CBA, C3H or C57BL), the phenotypic effects of the *dac* mutations are not observed \[[@CR122], [@CR124]\]. Although the identity of *mdac* is still unknown, it could be a gene involved in epigenetic regulation of MusD. In *mdac/mdac* mice, the 5′ LTR of the *Dac*^*1J*^ MusD element is unmethylated and enriched in active histone marks whereas this LTR is heavily methylated and enriched in repressive histone marks in mice carrying the *Mdac* allele \[[@CR122]\]. Moreover, ectopic MusD transcript expression is observed in embryos and limb buds of *dactylaplasia mdac/mdac* mice, but not in wildtype *mdac/mdac* mice, suggesting that the increased MusD expression is due to transcription of the *Dac*^*1J*^ MusD element itself, rather than general upregulation of MusDs in the genome \[[@CR122]\]. The *mdac* locus has been mapped to a 9.4 Mb region between markers D13Mit310 and D13Mit113 on chromosome 13 \[[@CR122], [@CR124]\]. Interestingly, this region includes a cluster of KRAB-ZFP (zinc finger protein) transcription factor genes. KRAB-ZFP genes are found in multiple clusters in the genome, are rapidly evolving and highly polymorphic in mice \[[@CR125], [@CR126]\] and some are involved in epigenetic silencing of ERVs \[[@CR126]\]. Hence, it is tempting to speculate that the identity of *mdac* is such a gene. MLV insertion mutations {#Sec10} ----------------------- The murine leukemia virus (MLV or MuLV) group is the most well characterized ERV group in the mouse and has caused seven documented spontaneous mutations (Fig. [1](#Fig1){ref-type="fig"}a,Table [3](#Tab3){ref-type="table"}). MLV is also likely responsible for retrotransposing the non-autonomous VL30 ERV involved in the *non-agouti* mutation that will be discussed in the next section. MLVs are Class I elements, belonging to the gamma retrovirus genus, entered the mouse genome less that 1.5 million years ago and still contains infectious members \[[@CR127]\]. MLV loci are highly insertionally polymorphic among strains \[[@CR128], [@CR129]\] with copy numbers of \~ 20 for xenotropic MLV and \~ 40 for polytropic MLV \[[@CR9]\]. Ecotropic copies, i.e. those able to infect only mouse cells (and not those of other species) based on env protein recognition of a cellular receptor, are present in very few copies in various strains \[[@CR127]\]. New germ line insertions appear to occur primarily through oocyte reinfection, rather than intracellular retrotransposition \[[@CR130]\], which has likely kept MLV copy numbers low. Ever since it was first reported that exogenous MLV can integrate into the germ line \[[@CR131]\], MLV and MLV-based vectors have been widely used for many applications including insertional mutagenesis screens, gene therapy and oncogene discovery \[[@CR132]--[@CR134]\].Table 3MLV InsertionsMutationMGI ID^a^Strain of originERV location, orientation^b^Mutational mechanisms or effectsReferences*Abcb1a* ^*mds*^3044239CF-1Solitary MLV LTR, Intron 22, −Transcripts contain viral sequence, Exon skipping, Disruption of gene function.\[[@CR258], [@CR259]\]*Aifm1* ^*Hq*^1861097CF-1Intron 1, +80% decrease in transcript and protein levels, Aberrant splicing\[[@CR260]\]*Hr* ^*hr*^1856057HRS/JIntron 6, +Transcripts contain viral sequence, Probable termination within LTR\[[@CR24], [@CR137]\]*Lamc2* ^*jeb*^3609880129X1/SvJSolitary MLV LTR, intron 18, +Aberrant splicing and premature termination, low level of normal transcripts\[[@CR261]\]*Lmf1* ^*cld*^1856820*M. m. musculus*Intron 7,?Transcripts contain ERV sequence, Termination within ERV\[[@CR262]\]*Myo5a* ^*d*^1856004Fancy miceIntron, +Shortened and abnormally spliced transcripts that vary among tissues\[[@CR135]\]*Pde6b* ^*rd1*^1856373unknownIntron 1, −Associated with nonsense mutation in gene but effect of ERV is unclear\[[@CR263]\]^a^ID number in Mouse Genome Informatics (MGI) database^b^- = antisense, + = sense,? = orientation unknown All of the MLV mutation-causing insertions occur in gene introns and affect normal gene transcript processing to varying degrees (Table [3](#Tab3){ref-type="table"}). The very first ERV-induced mutation to be described, over 35 years ago, was an MLV insertion causing the *dilute* coat color mutation (*Myo5a*^*d*^) in DBA/2J mice \[[@CR135]\]. This mutation can revert due to homologous recombination between the 5′ and 3′ LTR of the full length provirus, leaving a solitary LTR at the locus \[[@CR136]\]. Phenotypic reversion by this mechanism also occurs for the hairless mutation (*Hr*^*hr*^), another of the first documented cases caused by an MLV insertion \[[@CR137]\]. Insertional mutations by other class II ERVs {#Sec11} -------------------------------------------- In addition to the ERVs discussed above, members of five other ERV groups have caused mouse mutations (Table [4](#Tab4){ref-type="table"}). Like the IAP and ETn/MusD groups, two of the groups, ERV-β2 and ERV-β4, belong to Class II or the betaretrovirus genus as defined by *pol* homology \[[@CR14]\]. Both of these groups are heterogeneous and relatively low in copy number. The ERV-β2 group includes mouse mammary tumor virus (MMTV) but the ERVs responsible for the four cases of mutations belong to a different ERV-β2 cluster which has internal sequences annotated in Repbase \[[@CR138]\] primarily as "ETnERV3" with LTRs annotated as "RLTR13A" \[[@CR14]\]. The full ERV was not sequenced for the *Nox3*^*het*^ mutation but we presume it to be an ERV-β2 since the limited LTR sequence provided matched RLTR13A or RLTR13B \[[@CR139]\]. For the other three ERV-β2 cases in Table [4](#Tab4){ref-type="table"}, their full sequences have been published and they are 96--99% identical to each other with the major differences being internal deletions in the *Agtpbp1*^*pcd-2J*^ and *Prph2*^*Rd2*^ elements with respect to the longer *Etn2*^*Sd*^ ERV insertion (D. Mager, unpublished observations).Table 4Other ERV InsertionsMutationMGI ID^a^Strain of OriginERV, Location, Orientation^b^Mutational mechanisms or effectsReferences*Agtpbp1* ^*pcd-2J*^1856536SM/JERV-β2/ETnERV3, Intron 13, +Greatly reduced full length gene transcripts\[[@CR264]\]*Etn2* ^*Sd*^1857746Danforth's posterior duplication stockERVβ-2/ETnERV3, 12 kb upstream, +Overexpression of Ptf1a and two neighboring genes, acts as an enhancer\[[@CR140]--[@CR142]\]*Nox3* ^*het*^1856606GL/LePresumed ERVβ-2/ETnERV3, Intron 12, +Transcripts show aberrant splicing from *Nox3* into retroviral element\[[@CR139], [@CR265]\]*Prph2* ^*Rd2*^1856523O20/AERVβ-2/ETnERV3, Exon 2, −Transcripts contain entire ERV, coding sequence disruption\[[@CR266], [@CR267]\]*Ednrb* ^*s*^1856148Fancy miceERVβ-4, Intron 1, +Aberrant splicing and premature polyadenylation\[[@CR268]\]*a*1855937Fancy miceVL30, Intron 1, −; ERVβ-4 within VL30, +Smaller gene mRNA and levels 8 fold lower than in wild-type.\ Aberrant splicing and premature termination within the ERVβ-4\[[@CR22], [@CR143]\]*Dock7* ^*m*^1856946JAX Dilute BrownMERV-L, Exon 18, +Frameshift and premature termination\[[@CR269], [@CR270]\]*Fgf5* ^*go-moja*^6147688ICRPartial MTA MaLR, Intron 2, −498 bp insertion is combined with 9.3 kb deletion of exon 3 and flanking sequence, no detectable transcripts\[[@CR158]\]*Grm1* ^*crv4*^3664783BALB/c/PasMERV-L solitary LTR, intron 4, +Aberrant splicing and premature termination, transcripts contain LTR sequence\[[@CR271]\]*Npc1* ^*m1N*^1857409BALB/cPartial MERV-L, Exon 9824 bp partial and rearranged MERV-L combined with 703 bp deletion. Transcripts contain MERV-L sequence, decreased expression, premature truncation\[[@CR159]\]^a^ID number in Mouse Genome Informatics (MGI) database^b^- = antisense, + = sense,? = orientation unknown The above cases highlight the continual difficulties and confusion with ERV annotation. As an example, the ERV insertion causing the allele termed "*Etn2*^*Sd*^", where the ERV likely acts as an enhancer, was reported to be an "ETn" element \[[@CR140]--[@CR142]\]. However, as discussed above, this is misleading since "ETnERV3" is a separate entity compared to the more well-known ETn/MusD group, an important distinction but likely generally overlooked. Interestingly, when the reference C57Bl/6 genome was analyzed in 2004, less than 15 ERV loci falling into the ERV-β2 group were found and none were fully coding competent \[[@CR14]\]. Moreover, all of the ERV-β2s discussed above also lack full open reading frames. Nonetheless, the presence of these elements at sites of new mutations in other strains suggests such strains have or had coding-competent members to provide proteins in *trans,* allowing retrotransposition of defective elements. The strains in which the ERV-β2 mutations arose (Table [4](#Tab4){ref-type="table"}) do not share close relationships so the origin of any active autonomous copies is unknown. The ERV-β4 group \[[@CR14]\] has been involved in two known mutations and both occurred in old "fancy mice" (Table [4](#Tab4){ref-type="table"}). One of these mutations (*Ednrb*^*s*^) was caused by insertion of a 5 kb non-coding competent element whose internal sequence is classified as "ERV-β4_1B-I (internal)" in Repbase \[[@CR138]\] but half of the sequence in the middle of the element actually lacks homology to retroviruses (unpublished observations). Fifteen to 20 sequences closely related to the *Ednrb*^*s*^ element exist in the C57BL/6 reference genome and, since they contain LTRs and parts of the 5′ and 3′ internal sequences highly similar to the ERV-β4 element discussed below, it is likely that this small non-autonomous group has amplified using retroviral proteins provided by coding competent ERV-β4 elements. The other mutation case involving an ERV-β4 is complex. The *a* (*non-agouti*) allele of the *agouti* gene is one of many *agouti* alleles affecting coat color \[[@CR143]\], including four caused by IAP insertions (Table [1](#Tab1){ref-type="table"}). The *a* allele is fixed in the reference strain C57BL/6 and is responsible for its black coat color. Molecular characterization of *non-agouti* in the early 1990s revealed that it was caused by a 5.5 kb VL30 ERV insertion in the first intron of the *agouti* gene with another reported \~ 5.5 kb segment flanked by 526 bp direct repeats found within the VL30 \[[@CR22], [@CR143]\]. Our perusal of the fully sequenced reference C57BL/6 genome shows that the sequence within the VL30 is \~ 9.3 kb. The mutation is reported to be caused by a VL30, which belongs to a well-studied medium repetitive non-autonomous Class I ERV group that is co-packaged with MLV, allowing its retrotransposition \[[@CR144], [@CR145]\]. Although VL30 is insertionally polymorphic among inbred strains \[[@CR17]\], this is the only reported VL30-caused mutation. The nature of the insertion within the VL30 was not known at the time of analysis, but the C57BL/6 sequence shows it to be an ERV-β4 (coordinates of the full \~ 14.7 kb VL30/ERV-β4 insertion are chr2:155014951--155,029,651, GRCm38/mm10). Hence two ERV insertion events contributed to the *non-agouti* mutation, a VL30 insertion followed by insertion of an ERV-β4 within it (Fig. [3](#Fig3){ref-type="fig"}). The *non-agouti a* allele reverts at a high frequency to "black and tan" (*a*^*t*^) or white-bellied agouti (*A*^*w*^) \[[@CR22], [@CR143]\]. Molecular analyses by Bulman et al. showed that the *a*^*t*^ allele contains the VL30 element with a single ERV-β4 LTR and the *A*^*w*^ allele contain just one VL30 LTR \[[@CR22]\](Fig. [3](#Fig3){ref-type="fig"}). Therefore, normal *agouti* gene expression can be partly restored by homologous recombination between the LTRs of the VL30 or the ERV-β4, as has also been observed for MLV mutations (discussed above). Notably, the ERV-β4 element involved in the *non-agouti a* allele is the only fully coding competent ERV-β4 copy in the C57BL/6 genome \[[@CR14]\].Fig. 3Three alleles of the *agouti* gene involving ERV insertions. The *a (non-agouti)* mutant allele is fixed in the reference strain C57BL/6. It involves a VL30 ERV and an ERV-β4 inserted within it. Partial phenotypic reversion of *non-agouti* occurs frequently. The *a*^*t*^ (black and tan) allele results from recombination between the LTRs of the ERV-β4. The *A*^*w*^ (white-bellied agouti) allele results from recombination between the VL30 LTRs. See text for references. Gene structure in black is shown to very rough scale. Green arrows and lines are the LTRs and internal VL30 sequences. Purple arrows and line depict the ERV-β4 Insertions by MERV-L/MaLR elements {#Sec12} ---------------------------------- The Class III MERV-L LTR retrotransposon group has also caused a few mutations (lower part of Table [4](#Tab4){ref-type="table"}). MERV-L is a large, recently amplified group in the mouse with coding competent members but lacking an *env* gene \[[@CR146]--[@CR148]\]. These retrotransposons are highly expressed in the 2-cell embryo \[[@CR79], [@CR149]\], create viral-like particles \[[@CR150]\] and \~ 700 full length or near full length elements exist in the reference C57BL/6 genome \[[@CR148]\]. Therefore, the fact that there are only three reported germ line mutations caused by MERV-L insertions is somewhat paradoxical. Despite the high transcript level and particle formation by MERV-L at the two cell stage, it appears that any fully retrotranspositionally competent members are very rare or effectively blocked from completing retrotransposition by host defense mechanisms. Indeed, MERV-L elements amplified in two major bursts in mouse evolution, approximately 2 and 10 million years ago \[[@CR147]\] and it is possible that host genetic adaptations as a result of a host-virus "arms race" \[[@CR151]\] have effectively repressed further MERV-L expansion. Interestingly, MERV-L and associated MT MaLR LTRs have been co-opted to drive expression of genes and other transcripts involved in early embryogenesis and zygotic genome activation \[[@CR79], [@CR152]--[@CR154]\] and there is evidence that MERV-L expression is important for embryonic development \[[@CR155]\]. Insertion of a partial MTA MaLR element, belonging to a large young group of non-autonomous retrotransposons related to MERV-L \[[@CR15], [@CR156]\], and also highly expressed in early embryogenesis \[[@CR153], [@CR157]\], has contributed to a mutation in the *Fgf5* gene \[[@CR158]\]. However, this case and the MERV-L insertion causing the *Npc1*^*m1N*^ mutation \[[@CR159]\] are both partial elements and are coupled with genomic deletions, so the order of events resulting in these mutations is unclear. It is noteworthy that two of the four cases associated with Class III MERV-L/MaLR mutagenic insertions involve rearrangements of the ERV itself as well as genomic deletions. Interestingly, MaLR elements are associated with formation of independent hypervariable minisatellite sequence arrays in both human and mouse \[[@CR160], [@CR161]\], suggesting that these elements may foster genomic recombination and rearrangements. LINE1 insertion mutations {#Sec13} ------------------------- Our literature and MGI database search resulted in a list of 12 germ line mutations caused by L1 insertions (Table [5](#Tab5){ref-type="table"}, Fig. [1](#Fig1){ref-type="fig"}). Of the 11 where the length and/or sequence of the insertion was published, five are full length (or nearly full length) and six are partial elements, with the shortest being only 81 bp. All five full length insertions belong to the L1MdTf family, subtypes I or II, which are among the youngest L1 subfamilies, each with over 1000 full length elements in C57BL/6 \[[@CR34]\]. (Note that some revisions and updates to L1 subfamily classification and nomenclature have occurred \[[@CR34]\]). In two cases, the source L1 element could be identified due to inclusion of flanking transduced sequence at the new insertion site. In the *Nr2e3rd*^*7*^ mutant allele, the L1 insertion includes 28 bp of 5′ transduced sequence, allowing the source element to be traced to the L1 at chr4:21650298--21,656,544 (GRCm38/mm10) \[[@CR162]\]. The other case (*Lama2*^*dy-Pas*^) is interesting in that it involves an IAP LTR and an L1 \[[@CR163]\]. While not reported as an L1 3′ transduction event in the original paper \[[@CR163]\], our perusal of the inserted sequence (Genbank accession AJ277888) revealed that the L1 has transduced the IAP LTR, with the inserted sequence polyadenylated within the 5′ LTR (Fig. [4](#Fig4){ref-type="fig"}a). The source L1 has a 3.7 kb partly deleted IAP element inserted within it, so that \~ 700 bp of the 3′ end of the L1 occurs on the other side of the IAP (coordinates of the source L1/IAP are chr13:4065522--4,076,041, GRCm38/mm10). Another L1 insertion (*Pde6c*^*cpfl1*^), which occurred in a recombinant inbred strain established from a C57Bl/6 and BALB/c intercross, has the classical molecular structure of a 3′ transduction event \[[@CR164]\]. However, there is no L1 element in either the sequenced C57BL/6 or BALB/c genomes at the original location of the transduced sequence (unpublished observations), which occurs in an intron of the *Diaph2* gene \[[@CR164]\]. Therefore, the simplest explanation is that an L1 inserted in the *Diaph2* gene in the particular mouse colony being used and then retrotransposed again, creating the *Pde6c*^*cpfl1*^ allele.Table 5L1 InsertionsMutationMGI ID^a^Strain of originL1 length, location and orientation^b^Mutational mechanisms or effectsReferences*Atp7a* ^*Mo-ca*^2387450unknown81 bp L1, exon 10, −Aberrant splicing causing in-frame loss of 10 amino acids\[[@CR272]\]*Dab1* ^*yot*^1857750Chimera of 129 and C57BL/6Rearranged partial L1MdTf, intronPartial gene deletion and atypical 962 bp L1 insertion\[[@CR273]\]*Frem1* ^*heb*^1856897AKR/JUnknown length L1, exon 17, +Transcript and protein truncation\[[@CR274]\]*Glrb* ^*spa*^1856363Random-bred stockFull length L1MdTf_I intron 6, −Reduced expression of normal transcript and exon skipping\[[@CR275]--[@CR277]\]*Lama2* ^*dy-Pas*^6220701Non-inbred AgoutiNearly full length L1MdTf_II and 3′ transduction, intron 34, +Transcript contains internal IAP sequence, Truncated protein.\ L1-mediated retrotransposition event involving an L1 and 3′ transduced IAP LTR\[[@CR163]\]*Lyst* ^*bg*^1855968C3H/Rl X 101/R1 (from radiation exp.)1.1 kb 5′ truncated L1, intron, +Two alternatively spliced transcripts containing L1 sequence results in two truncated forms of the protein\[[@CR278], [@CR279]\]*Mitf* ^*mi-bw*^1856089C3HFull length L1MdTf_II, intron 3, +Decreased expression and exon skipping of two isoforms and abolished expression of the third isoform\[[@CR280]\]*Nr2e3* ^*rd7*^185918077-2C2a-special- JAXFull length L1MdTf_I with 28 bp 5′ transduction, exon 5, −Accumulation of incompletely spliced transcripts.\[[@CR162]\]*Pde6c* ^*cpfl1*^2657247Recom. Inbred CXB1/ByJ1.5 kb insertion of truncated L1 & likely 3′ transduction, Intron 4, −Aberrant splicing within inserted sequence causes inclusion of extra 116 bp exon and frame shift.\[[@CR164]\]*Reln* ^*rl-Orl*^1856416BALB/cFull length L1MdTf_I exon 59, +220 bp deletion in mRNA due to skipping of exon containing L1\[[@CR281]\]*Scn8a* ^*med*^1856078PCT180 bp 5′ truncated L1, Exon 2, −Skipping of exon containing L1, loss of functional protein\[[@CR282]\]*Ttn* ^*mdm*^1856953C57BL/6J2.4 kb L1, exon 3, +779 bp gene deletion and L1 insertion causes exon loss or chimeric transcripts\[[@CR283]\]^a^ID number in Mouse Genome Informatics (MGI) database^b^- = antisense, + = sense,? = orientation unknownFig. 4**a** Transduction of IAP LTR by an L1. A full length L1MdTf element interrupted by an IAP ERV exists in intron 3 of the *Akr1c14* gene on chromosome 13. This L1 is the source element responsible for the *Lama2*^*dy-Pas*^ mutation, with the newly inserted sequence polyadenylated in the IAP LTR. Thick orange lines are L1 genomic sequences and thin orange lines represent L1 RNA. The IAP LTRs and internal sequences are in green. Genes and number of exons are not to scale. **b** B2 insertion causing gene upregulation. The *TNF*^*BPSM1*^ mutation is a B2 insertion (in yellow) in the 3′ UTR of *Tnf*, causing *Tnf* upregulation due to polyadenylation within the B2 which removes the negative regulatory ARE (AU rich element) from the *Tnf* mRNA. Mice with this mutation have heart disease and arthritis due to overexpression of TNF. B2 is yellow and thicker black boxes are coding sequences L1 insertions have occurred in a variety of genetic backgrounds, with no evident strain bias. The mutational effects of these insertions are as expected, with intronic L1s affecting splicing and exonic cases physically disrupting the coding sequence. Interestingly of the 12 L1 cases, half occur in gene exons and half in introns (Table [5](#Tab5){ref-type="table"}), which is more skewed toward exons compared to the ERV insertions discussed above (Tables [1](#Tab1){ref-type="table"}-[4](#Tab4){ref-type="table"}). It is a reasonable assumption that truncated (and hence shorter) L1 insertions might be less likely to affect transcript processing if inserted in an intron. (See also discussion of SINE insertions below). Indeed, the two shortest L1 insertions of 81 and 180 bp both occur in exons (Table [5](#Tab5){ref-type="table"}). However, two of the five full length L1s, which are similar to size to ERVs, also occur in exons. SINE and other LINE1-mediated insertion mutations {#Sec14} ------------------------------------------------- Members of two mouse SINE families, B1 and B2, have caused documented mutations (Table [6](#Tab6){ref-type="table"}). Also included in this Table is a presumed L1-mediated insertion of *Cenpw* cDNA into an exon of *Poc1a* \[[@CR165]\]. It is noteworthy that, although higher numbers of B1 elements have accumulated during mouse evolution \[[@CR1]\], seven of the eight mutation-causing SINE insertions are B2 with no evident strain bias (Table [6](#Tab6){ref-type="table"}, Fig. [1](#Fig1){ref-type="fig"}c). In accord with the preponderance of B2- over B1-caused mutations, retrotransposition assays in vitro showed a higher retrotransposition rate for B2 compared to B1, although the assays were conducted in human cells \[[@CR58]\]. It is possible that B2 is currently the more active family in inbred strains, contains some members more efficient at utilizing the L1 retrotransposition machinery and/or are more transcriptionally active in the germ line. Interestingly, Dewannieux et al. \[[@CR58]\] found that most B1 elements have a nucleotide mutation compared to Alu elements and 7SL RNA (from which both B1 and Alu were derived) and noted that this highly conserved nucleotide is critical for 7SL RNA interaction with SRP9/14 proteins \[[@CR166]\]. As has been shown for Alu elements \[[@CR167]\], this interaction is expected to enhance L1-mediated retrotransposition of B1. Indeed, replacement of this nucleotide in several tested B1 elements resulted in a much higher retrotransposition rate in culture \[[@CR58]\]. Therefore, B1 elements harboring this mutation have become the most prevalent in the genome despite the fact that the mutation lowered their ability to retrotranspose. Although the evolutionary trajectory resulting in B1 prevalence is unknown, it has been suggested that, during mouse evolution, such B1 elements have been selectively retained to minimize harm to the host \[[@CR58]\].Table 6SINEs and other L1-mediated insertionsMutationMGI ID^a^Strain of originInsertion type, location, and orientation^b^Mutational mechanisms or effectsReferences*Atcay* ^*ji*^1856574Bagg albinoB1, exon 4, +B1 insertion causes protein truncation and rare exon skipping\[[@CR187], [@CR284]\]*Comt* ^*B2i*^4819952Strain variant, likely origin in Lathrop stockB2, 3′ UTR, +Premature polyadenylation leads to shortened 3'UTR and increased protein expression. Associated with behavioral difference.\[[@CR170], [@CR171]\]*Gsdma3* ^*Dfl*^2385837BALB/cB2, exon 7, +B2 causes premature termination, transcript includes B2 sequence\[[@CR285]\]*Ndufs4* ^*fky*^4942335Male Dnmt3L +/− x female transgenic RIP-mOVA C57BL/6B2, exon 3, +B2 insertion causes exon skipping and premature termination\[[@CR286]\]*Nrcam* ^*m1J*^5444298B6.129P2-Cnr2tm1Dgen/JB2, exon 26, −Aberrant splicing and premature termination\[[@CR287]\]*Poc1a* ^*cha*^2135614DBA.B6-A^hvy^/a x DBA/2JGene cDNA, exon 8, −L1 mediated insertion of *Cenpw* cDNA in exon 8. Exon 8 is skipped, reading frame preserved\[[@CR165]\]*Ptpn6* ^*me-B2*^4947257BALB/cB2, exon 6, +Replacement of exon 6 sequence with B2 sequence, reading frame preserved\[[@CR288]\]*Slc27a4* ^*wrfr*^2445864(129X1/SvJ x 129S1/Sv)F1B2, exon 3, −Coding sequence disruption, no mRNA or protein detected\[[@CR289]\]*Tnf* ^*Bpsm1*^5795894C57BL/6B2, 3'UTR, +Premature polyadenylation leads to shortened 3'UTR and gene overexpression\[[@CR172]\]^a^ID number in Mouse Genome Informatics (MGI) database^b^- = antisense, + = sense,? = orientation unknown Unlike the ERV mutation-causing insertions, where most cases occur in introns (Tables [1](#Tab1){ref-type="table"}-[4](#Tab4){ref-type="table"}), all such mouse SINE insertions have occurred in exons (Table [6](#Tab6){ref-type="table"}), which represent a much smaller genomic space. The marked bias toward exonic insertions also occurs for disease-causing Alus \[[@CR4]\]. This could simply be due to the fact that SINEs are shorter and therefore new insertions are much less likely to significantly disrupt gene expression if inserted into an intron. Indeed, although SINEs, particularly Alus, can cause alternative splicing and exonization \[[@CR168]\], both human and mouse SINEs are relatively enriched in introns \[[@CR169]\] and show less evidence of selection against intronic insertions compared to ERVs or L1s \[[@CR68]\]. As is the case for mutation-causing human Alu insertions \[[@CR4]\], most of the mouse SINE insertions directly disrupt the gene's coding sequence, causing exon skipping, protein ablation, truncations or amino acid replacements (Table [6](#Tab6){ref-type="table"}). However, in the *Comt*^*B2i*^ allele, which is a strain variant present in C57BL/6 and a few other strains \[[@CR170], [@CR171]\] and in the *Tnf*^*Bpsm1*^ mutation \[[@CR172]\], a B2 element inserted into the 3′ UTR causes gene upregulation, which underlies the phenotype. This effect is due to a shortened 3′ UTR caused by premature polyadenylation within the B2 and a resultant replacement or disruption of negative regulatory motifs within the UTR, which has been directly shown for *Tnf*^*Bpsm1*^ \[[@CR172]\] (Fig. [4](#Fig4){ref-type="fig"}b). Concluding remarks {#Sec15} ================== This review has provided a comprehensive catalog and discussion of mouse mutations caused by insertions of ERVs, LINEs and SINEs. It is clear that, among these TE types, ERV insertion mutations are the most prevalent (Fig. [1](#Fig1){ref-type="fig"}a). Through an accounting of all independent spontaneous mutant alleles in mouse, it was previously estimated that ERV insertions comprise 10--12% of all published spontaneous mutations \[[@CR1], [@CR20]\]. Another previous report estimated that L1 insertions account for 2--3% of mouse mutations \[[@CR173]\], suggesting a relative ratio of ERV to L1 insertion mutations of 4 to 6. Our updated numbers (94 ERV cases and 12 L1 cases) reveal a somewhat higher ratio of approximately eight. If the nine SINE insertion cases reported here are included, the ratio of ERV to "L1-mediated" insertion mutations is \~ 4.5. Since both human and mouse have active L1s, we can attempt to compare relative L1 recent "activity" based solely on the number of documented mutations due to L1 insertions. Both bioinformatics and functional studies \[[@CR31]--[@CR33]\] suggest that the typical inbred mouse genome harbors roughly 20--30 times more retrotranspositionally competent L1s compared to human (\~ 3000 versus \~ 100--150). All else being equal, one might then expect the frequency of L1 insertional mutations to be 20--30 times higher in mouse. Recent reviews on retrotransposons in human disease report 22 cases of L1 insertions causing heritable mutations/diseases \[[@CR4], [@CR174]\]. To put these numbers in context, it should be remembered that many more mutations have been described in human compared to mouse. The Human Gene Mutation Database \[[@CR175]\], lists \~ 240,000 entries as of January 2019. In contrast, the MGI database \[[@CR65]\], lists only \~ 2100 spontaneous mutant alleles as of the same date, and many of these are non-independent entries or revertant cases. While comparing such overall numbers is fraught with caveats, they are however still useful to illustrate the point that the mouse "mutational space" is vastly understudied compared to human. Hence, the relatively low number of 12 mouse L1 mutations (when compared to the number of human L1 mutations) is not unexpected but rather simply appears low when viewed against the high numbers of ERV mutations. Indeed this number is approximately in line with expectations when compared to human, given the much higher number of active L1s but much lower numbers of all characterized mutations in mouse. In considering L1-mediated insertion mutations as a fraction of all mutations, the numbers reported here suggest a frequency of 3--5% in mouse, building on the previous L1 estimate of 2--3% \[[@CR173]\] and including the SINE cases. There have been various estimates for the frequency of L1-mediated mutations in human, with an early estimate of 1 in 600 (0.16%) reported by Kazazian \[[@CR176]\]. A more recent study of the spectrum of mutations in a single gene found that TE insertions caused 0.4% of all mutations in *NF-1* \[[@CR177]\], although it is unclear if this figure can be extrapolated to all genes. In any case, these estimates suggest that the contribution of L1 activity to overall mutational burden is at least 10 fold higher in mouse. Concerning mouse ERVs, there are several distinct ERV groups currently able to retrotranspose at least in some strains, including the low copy number and poorly characterized ERV-β2 and ERV-β4 groups \[[@CR14]\], previously not known to be active. Unpublished transcriptome analysis indicates that expression of both these groups is readily detectable in early embryonic stages (Julie Brind'Amour and Matt Lorincz, personal communication) but little else is known about them. The fact that new insertions have been found for such low copy number ERV groups indicates they are still mutagenic in some strains and worthy of further investigation. Another point worth emphasizing is that, although IAP ERVs are young and have accumulated to high copy numbers in inbred strains, they perhaps do not deserve the often used designation as the currently "most active" group of mouse ERVs. This is likely true only in C3H mice and, if this strain is removed from consideration, a modest seven IAP-caused mutations can be documented to have occurred in strains unrelated to C3H (Table [1](#Tab1){ref-type="table"},\\ Fig. [1](#Fig1){ref-type="fig"}b). This number of mutations places IAP recent "activity" more on a par with the low copy number MLV and ERV-β2 groups and suggests that the genomic expansion of IAPs in most strains has largely ceased, likely due to host defense mechanisms \[[@CR86], [@CR151], [@CR178]--[@CR180]\] gaining the upper hand. Exclusive of the C3H strain, the ETn/MusD group accounts for the most mutagenic ERV insertions. One possible reason for the high IAP-induced mutations in C3H mice could be a slight relaxation of repression in the germ line, so it would seem prudent for investigators to consider including this strain in studies to investigate the regulation of IAPs. This extreme strain bias for IAP activity also illustrates the difficulty in attempting to compare de novo TE insertion mutation rates in the "outbred" human population with those in the artificial environment of inbred mice. Nonetheless, the primary difference between human and mouse in terms of TE-induced insertional mutations is clearly the lack of ongoing ERV activity in modern humans. Dac : Dactylaplasia ERV : Endogenous retrovirus ETn : Early transposon IAP : Intracisternal A type particle JAX : The Jackson Laboratory L1 : LINE-1 family LINE : Long interspersed element LTR : Long terminal repeat MaLR : Mammalian apparent LTR retrotransposon MLV : Murine leukemia virus ORF : Open reading frame SINE : Short interspersed element TE : Transposable element We thank Rita Rebollo for help with figures and for making suggestions on this review. We also thank Diana Juriloff for advice on mouse history and Jonathan Stoye for reading the MLV section. We apologize to authors if we failed to mention relevant work. Funding {#FPar1} ======= Relevant work in the Mager lab is currently funded by the Natural Sciences and Engineering Council of Canada. V. Belancio is funded by NIH grants R21AG055387 and R01AG057597 and the Brown Foundation. Availability of data and materials {#FPar2} ================================== This is a review article. Data sharing not applicable to this article as no datasets were generated or analyzed during the current study. LG and DLM compiled data and VLP and DLM wrote the manuscript. All authors read and approved the final manuscript. Ethics approval and consent to participate {#FPar3} ========================================== Not applicable. This is a review article on mouse. Consent for publication {#FPar4} ======================= Not applicable Competing interests {#FPar5} =================== The authors declare that they have no competing interests. Publisher's Note {#FPar6} ================ Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. | Mid | [
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Q: In C#, can you find what proxy server your computer is using? I've noticed some programs (such as IE and Firefox) can automatically detect a network proxy server to use for Internet traffic. Is it possible to do the same in C#? Are there APIs for this? Thanks! A: You're probably looking for WebRequest.DefaultWebProxy or possibly WebRequest.GetSystemWebProxy. This should be able to pick up whatever IE detects. Also, other SO questions indicate that HttpWebRequest will go through your system proxy by default. | High | [
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parser grammar RexxParser; options { tokenVocab=RexxLexer; } file : program_ EOF ; program_ : ncl? instruction_list? ; ncl : null_clause+ ; null_clause : delim+ label_list? | label_list | include_statement ; delim : SEMICOL | EOL ; label_list : ( label COLON delim* )+ ; label : VAR_SYMBOL | CONST_SYMBOL | NUMBER ; include_statement : STMT_INCLUDE ; instruction_list : instruction+ ; instruction : group_ | single_instruction ncl? ; single_instruction : assignment | keyword_instruction | command_ ; assignment : ( VAR_SYMBOL | SPECIAL_VAR | CONST_SYMBOL ) EQ expression ; keyword_instruction : address_ | arg_ | call_ | drop_ | exit_ | interpret_ | iterate_ | leave_ | nop_ | numeric_ | options_ | parse_ | procedure_ | pull_ | push_ | queue_ | return_ | say_ | signal_ | trace_ | upper_ ; command_ : expression ; group_ : do_ | if_ | select_ ; do_ : KWD_DO do_rep? do_cond? ncl instruction_list? KWD_END var_symbol? ncl? ; do_rep : assignment do_cnt? | KWD_FOREVER | expression ; do_cnt : dot dob? dof? | dot dof? dob? | dob dot? dof? | dob dof? dot? | dof dot? dob? | dof dob? dot? ; dot : KWD_TO expression ; dob : KWD_BY expression ; dof : KWD_FOR expression ; do_cond : KWD_WHILE expression | KWD_UNTIL expression ; if_ : KWD_IF expression delim* then_ (delim+ else_)? ; then_ : KWD_THEN ncl? instruction ; else_ : KWD_ELSE ncl? instruction ; select_ : KWD_SELECT delim+ select_body KWD_END ncl? ; select_body : when_+ otherwise_? ; when_ : KWD_WHEN expression delim* then_ ; otherwise_ : KWD_OTHERWISE delim* instruction_list? ; /* Note: The next part concentrates on the instructions. It leaves unspecified the various forms of symbol, template and expression. */ address_ : KWD_ADDRESS ( taken_constant expression? | valueexp )? ; taken_constant : symbol | STRING ; valueexp : KWD_VALUE expression ; arg_ : KWD_ARG template_list? ; call_ : KWD_CALL ( callon_spec | function_name call_parms? ) ; callon_spec : KWD_ON callable_condition ( KWD_NAME function_name )? | KWD_OFF callable_condition ; callable_condition : KWD_ERROR | KWD_FAILURE | KWD_HALT ; call_parms : BR_O expression_list? BR_C | expression_list ; expression_list : COMMA* expression ( COMMA+ expression )* ; drop_ : KWD_DROP variable_list ; variable_list : ( vref | var_symbol )+ ; vref : BR_O var_symbol BR_C ; var_symbol : VAR_SYMBOL | SPECIAL_VAR ; exit_ : KWD_EXIT expression? ; interpret_ : KWD_INTERPRET expression ; iterate_ : KWD_ITERATE var_symbol? ; leave_ : KWD_LEAVE var_symbol? ; nop_ : KWD_NOP ; numeric_ : KWD_NUMERIC ( numeric_digits | numeric_form | numeric_fuzz ) ; numeric_digits : KWD_DIGITS expression? ; numeric_form : KWD_FORM ( KWD_ENGINEERING | KWD_SCIENTIFIC | valueexp | expression )? ; numeric_fuzz : KWD_FUZZ expression? ; options_ : KWD_OPTIONS expression ; parse_ : KWD_PARSE KWD_UPPER? parse_type template_list? ; parse_type : parse_key | parse_value | parse_var ; parse_key : KWD_ARG | KWD_EXTERNAL | KWD_NUMERIC | KWD_PULL | KWD_SOURCE | KWD_VERSION ; parse_value : KWD_VALUE expression? KWD_WITH ; parse_var : KWD_VAR var_symbol ; procedure_ : KWD_PROCEDURE ( KWD_EXPOSE variable_list )? ; pull_ : KWD_PULL template_list? ; push_ : KWD_PUSH expression? ; queue_ : KWD_QUEUE expression? ; return_ : KWD_RETURN expression? ; say_ : KWD_SAY expression? ; signal_ : KWD_SIGNAL ( signal_spec | valueexp | taken_constant ) ; signal_spec : KWD_ON condition ( KWD_NAME function_name )? | KWD_OFF condition ; condition : callable_condition | KWD_NOVALUE | KWD_SYNTAX ; trace_ : KWD_TRACE ( taken_constant | valueexp | expression | KWD_ERROR | KWD_FAILURE | KWD_OFF ) ; upper_ : KWD_UPPER var_symbol+ ; // if stem -> error (cannot do 'upper j.') /* Note: The next section describes templates. */ template_list : COMMA* template_ ( COMMA+ template_ )* ; template_ : ( trigger_ | target_ )+ ; target_ : VAR_SYMBOL | SPECIAL_VAR | STOP ; trigger_ : pattern_ | positional_ ; pattern_ : STRING | vref ; positional_ : absolute_positional | relative_positional ; absolute_positional : NUMBER | EQ position_ ; position_ : NUMBER | vref ; relative_positional : (PLUS | MINUS) position_ ; // Note: The final part specifies the various forms of symbol, and expression. symbol : var_symbol | CONST_SYMBOL | NUMBER ; expression : and_expression ( or_operator and_expression )* ; or_operator : OR | XOR ; and_expression : comparison ( AND comparison )* ; comparison : concatenation ( comparison_operator concatenation )* ; comparison_operator : normal_compare | strict_compare ; normal_compare : EQ | CMP_NEq | CMP_LM | CMP_ML | CMP_M | CMP_L | CMP_MEq | CMP_LEq | CMP_NM | CMP_NL ; strict_compare : CMPS_Eq | CMPS_Neq | CMPS_M | CMPS_L | CMPS_MEq | CMPS_LEq | CMPS_NM | CMPS_NL ; concatenation : addition ( CONCAT? addition )* ; addition : multiplication ( additive_operator multiplication )* ; additive_operator : PLUS | MINUS ; multiplication : power_expression ( multiplicative_operator power_expression )* ; multiplicative_operator : MUL | DIV | QUOTINENT | REMAINDER ; power_expression : prefix_expression ( POW prefix_expression )* ; prefix_expression : ( PLUS | MINUS | NOT )* term ; term : function_ | BR_O expression BR_C | symbol | STRING ; function_ : function_name function_parameters ; function_name : KWD_ADDRESS | KWD_ARG | KWD_DIGITS | KWD_FORM | KWD_FUZZ | KWD_TRACE | KWD_VALUE | taken_constant ; function_parameters : BR_O expression_list? BR_C ; | Mid | [
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# # Example pipeline configuration for matlab based image filter # # ================================================================ process input :: frame_list_input # Input file containing new-line separated paths to sequential image # files. :image_list_file input_image_list.txt :frame_time .03 :image_reader:type ocv # ================================================================ process filter :: image_filter :filter:type matlab :filter:matlab:program_file example_filter/example_matlab_filter.m # Specify initial config for the detector # The following line is presented to the matlab script as "a=1;" :filter:matlab:config:a_var 1 :filter:matlab:config:border 2 :filter:matlab:config:saving false # ================================================================ process disp :: image_viewer :annotate_image true :pause_time 1.0 :footer NOAA images :header header-header # ================================================================ # global pipeline config # config _pipeline:_edge :capacity 2 # ================================================================ # connections connect from input.timestamp to disp.timestamp connect from input.image to filter.image connect from filter.image to disp.image | Mid | [
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Q: Obtaining 15 V from a single lithium polymer cell I want to get 15V output from a 1 cell lithium polymer battery which has a voltage range of 3v-4v. I am thinking about using a 34063 to accomplish this. But will this work over a 1v range or do I need a different ic? edit: I want to get around 250mA A: The 1V range from 3-4V isn't the problem. The IC regulates by comparing the output voltage with an internal reference voltage, so as long as the input stays within spec (some unpublished minimum voltage to a max of 50V) and below your desired Vout (this isn't a buck/boost converter), you should be fine. It's the minimum voltage requirements are worrying. Your desired operation from a single coin cell is really a special application, and, as Madmanguruman said, it looks like this IC was made for much less imaginative applications - boosting a 5V supply. Since your users might be tempted to stick in an alkaline battery or a dead battery, why not use something that's designed to work with a lower voltages? Linear Technology's LT1308 switcher will work down to 1V, and has a switch current of up to 3A, so you should be able to get 15V at 250mA out of it. (Disclaimer: I like Linear products; I go to their site first to look up stuff like this. I didn't compare with other manufacturers, but you should.) | High | [
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Friday, October 31, 2008 Not really my flat, but rather the People's Flat, this being a council block in Ted Knight's Lambeth Socialist Paradise. I was sharing with one chap who went on to feature aomg the Liberal Democrats' least successful general election candidates before joining the diplomatic corps and a housing officer. Laibach were very jolly and not at all sinister. The comically-misnamed Socialist Workers Party didn't appreciate their totalitarian imagery, which can only be called a virtuoso lack of self-awareness, and its claque booed them offstage at their gig. We still exchange Christmas cards. 2. I was the only sixth-former at Ysgol Y Gader secondary school, Dolgellau, not to be made a prefect. I thought The Man knew I was down with the kids, and would let them shelter in the classrooms during the constant rain. Reigning School Bully 1976-1980 Paul Humphreys told me it was because the teachers thought I was "a twat". Paul was literally in a position to know, as he spent considerable time and effort on impregnating successive gym mistresses and any girls who looked like they might become gym mistresses. Paul never bullied me, on the grounds that we were cousins. As far as I can tell this was not true, but I kept the information to myself. We still exchange Christmas cards. 3. I was engaged to marry a Belarussian ballet dancer. During an enjoyable career cul-de-sac as a ballet impressario in 1991 I proposed to a charming lady from Minsk, the idea being that if the Soviets suddenly turned nasty and reversed perestroika we could whisk her away on the wings of my British passport. The Soviet Union collapsed quietly and she, having visited our Tulse Hill flat, decided to stay in the irradiated swamp that is Belarus. It was good while it lasted. 4. I have a double. Some fellow with the same name as mine lazily stalked me around Britain from about 1983. It wasn't all bad: he won the University of Wales Russian-to-Welsh translation prize, and I garnered the credit due to our identical names and interests. The real me came third. Various people would denounce me as an imposter, having sworn that they had met the real Boyo. He's gone quiet since the early '90s, and I still wonder who he was and why. And whether he was real and I'm the fake. Like writing poetry in Esperanto, this has been a real hit with the ladies. 6. I am Wales's foreign correspondent. The role of explaining Kosovo, Iraq and the Isle of Man to Welsh-speaking news junkies via Radio Cymru and S4C is passed from one Cambrian hack to another in an arcane ceremony each St Trisant's Day. Like the transmission of the Torah from Moses to the rabbis via the Prophets and the Men of the Great Assembly, this is a hallowed affair. I received the ceremonial dictionary, nasal-hair clippers and pack of mints from "Bedroom" Jones, who himself had been handed them by Sioba Siencyn. The highlight of my tenure was calling on the people of Wales to hoist the banner of Glyndŵr in support of our Chechen mountain brethren in a Radio Cymru interview that turned out to be going out live. No one in Carmarthenshire seemed to mind, and I got a street named after me in Duba-Yurt, so fair play. I'm meant to pass this tag on, but can't be fagged. Just write droll stuff about yourself and let us all rejoice in the anarchy of it all. Thursday, October 30, 2008 Boyo: So, The K-Man, when Barack Obama turns out to be yet another American president and not the Messiah Son of David (for whom we wait although he tarries), what will you do with your "Obama 2008" baseball cap? Wednesday, October 29, 2008 Believe me, that was not the worst of my schoolboy Esperanto poems. Another, called "La Numenio", included the horrific line: "fluĝis sub la stelajn lampojn". Sweet Lethe has washed away all other traces. Esperanters have been dragging their Frankenstein idiom around this and other web blogs ever since I made a passing reference to Incubus, the only major goat-themed film shot in something approaching that language. If Marcel Proust managed, through bad luck and indolence, to end up in Hell, each crumb of his madeleine would dredge up memories of shambling terror such as I have endured and will now inflict upon the rest of you. I had drowned all recollections of Esperanto through a combination of alcohol, drugs and acquiring a life. But the selective candour with which Wales commends itself to the nations demands that I retrace the steps of shame that brought me into its bucktoothed penumbra. As a 14-year-old Welsh nationalist I had drawn the melancholy conclusion that other peoples were never going to learn my vowel-shunning native tongue, meaning that I would have to learn every other language or use English. Then my German teacher introduced me to Esperanto. You would think that someone whose livelihood depends on persuading 1970s British youth to learn a genuine, difficult language generally associated with beastly behaviour and lumpy women would want to keep Esperanto a secret. But then my German teacher was not only Dutch, but a Quaker. Quakers, of course, have turned lack of self-interest into a religion. The Dutch, however, are aggressive landgrabbers who conceal their plans to colonise the North Sea bed by pretending to be irritating, hash-mashed peaceniks. If people learn German they will realise that the Hun, for all his faults, is willing to buy a round of drinks and has something approaching a national cuisine. The Dutch will then be exposed as grubby polder-dodgers and get schlepped back to the marshes from which they never fully emerged. So Mevrouw Niederlage inducted me into the Zamenhof Cult. She herself had joined the Esperanters while being brainwashed at a volunteer work camp in Communist Czechoslovakia. Stalin had stamped out all Esperantovian tendencies in the 1930s, understanding that the colossal struggle with the Nazis meant there was room for only one kind of internationalism. But by the 1950s the Soviets realised that feckless Western youngsters could be lulled into fellow-travelling through an appeal to their idealism and dislike of all things American - apart from the music, singers, films, actors, clothes, food and Marshall Aid. Luckily for the cause of freedom, the Communists thought the best way of bundling bourgeois youth into Bolshevism was by sticking them in a logging camp with a bunch of thyroid-deficient Slovaks, no soap and singsongs in Esper-bloody-ranto. The only teens who enjoyed this were Communists from the Rhondda, for whom near-starvation in the singing Tatras was like a fond memory of holidays in Snowdownia. And the Quakers, of course. For me, as a louche Cambrian Gaullist, Esperanto appealed as an easy way to conjugate with French girls rather than their verbs. I learned it fast and convinced my Byronic self that young women swoon over speeches about the Battle of Morfa Rhuddlan, detailed accounts of my political programme and, of course, poems written just for them. In a language only Belgian peace-studies teachers can understand. My first and last school exchange was educational in showing me that French girls liked cigarettes, singing English pop songs, discos, mopeds and non-spoddish boys several years their senior. Among their major turn-offs were all things Welsh, poetry, and total bollocks like Esperanto. I've stuck by being Welsh over the years, and just can't shake off poetry, but Teach Yourself Esperanto went straight down the Red Cross Shop once the bus got back from Guérande. So, if your teenage son starts saying things like "Verb declensions are pointless, but the accusative case and noun-adjective agreement are a must", this is what you do: Slip into his bedroom when he's out, and check under the sports bag in his cupboard. There you may find grainy mimeographs adorned with Lovecraftian symbols like "Ĉ" and "ĝ" and group photographs of squirrely people in windcheaters. These are the fetishes of the Esperanto Cult. Replace them, along with any pamphlets on the Baha'i faith, vegetarianism and the United Nations, with some decent porn, a hairdresser's appointment and Top Gear magazine. Thenget him laid by one of your divorced ladyfriends fast. He will thank you for it in years to come, and most likely immediately. Tuesday, October 28, 2008 All day random people (parents; the still, small voice of calm, etc) have been throwing stones through my window wrapped in paper. Moreover, they've been ringing me up and saying "Boyo, you work in the media, what do you think about the BBC/Jonathan Ross/Russell Brand/Andew Sachs ansaphone/granddaughter scandal?" All BBC staff go on a "don't lie or be a bastard/don't say ffyc" course, run by an independent consultancy recently set up by Jonty. This is not good enough. I advocate the No Good Boyo Damage Limitation Plan: Emasculate. Denigrate. Escalate. Applying these precepts would produce not the lukewarm brew the BBC has served up today, but rather a cracked mug of brick-red steaming bulldog defiance. I donate this draft letter to the Governor-General of the BBC, Sir Lew Grade. He can use it gratis. If it works, I ask only a commission and the wiping clean of my personnel file. From the Governor-General of the BBC, My Fellow Britons,I am flying in my private Zeppelin high above this Great Britain of ours. A catsuited minion - probably Oriental, certainly female - has brought to my attention various complaints about a broadcast on the Light Programme by the jesters Ross and Brand. Their capers have long amused you, so I must admit to some annoyance at your red-nostrilled mewlings. Where is your patriotism? Having fun at innocent people's expense is an essential component of our national character, judging by the tele-visual programmes before which you eat your meagre suppers. Has something changed since we slipped anchor at Ravello (that, and so much else)? I taught Churchill all he knew, including his favourite slogan "Action Now". And so I am obliged by the yoke of history not merely to reply but also to respond: The radio programme of Ross & Brand is immediately to be transmitted live on BBC1 from 1800 hours until further notice. It is to be broadcast through the emergency services public address system in all market towns where sales of The Daily Mail outstrip those of Razzle. The programme itself is to be renamed "You Bleedin' Kant". Agaton Sax and his family will have a programme of their own, on which they will be welcome to accuse Mssrs Ross and Brand of regular church attendance, admiration for musicals such as"Miss Saigon", and use of hair-buffing products. I am the Queen of the Divan. Yours, lighting a suspiciously moist Cohiba with more of your licence fees, Saturday, October 25, 2008 The BBC spends a fortune sending lipless Canadian women around the dustier parts of the world to report the wrongdoings of bourgeois imperialists like us. And yet the most popular story on its website is usually about some leathery pervert in Sudan who married a goat. TV in Crete has found the golden section of goat coverage. It runs none of the salacious stuff that the BBC struts, nor does it openly advocate traditional Greek goat worship - simply solid updates on who's grazing what, how the latest bells sound and stuff about creepy horizontal pupils. When on holiday there I felt fully informed and yet not patronised. William Shatner was ever the pioneer, not least in the field of goat promotion. His literally seminal film Incubus stars a goat who plays the Devil. The whole business is acted in the international language Esperanto on the endearing premise that the goat and his relatives in the audience might understand it. Sadly the film cursed its cast with murder, suicide and French subtitles. The goat's career went nowhere, while that dog in the Beethoven films lived in a Conran kennel and dated an Avon lady. Let us recall for a moment how William Shatner has trailed many a blaze: He launched the US civil rights movement with the film The Intruder, and kept it going in the dark days after the assassination of Martin Luther King by kissing Lt Uhura on Star Trek; He denounced science fiction as "pants" on Saturday Night Live despite the great personal risk to himself from thwarted mummy's boys and, possibly, alien beings; and He proved that Pulp's Common People didn't depend entirely on having Sadie Frost wander around Asda in the video, while at the same time giving Joe Jackson a break from his job at the Ramada Inn, Reading ("Your bossa favourites in a bontempi tempo"). When Shatner spoke on these matters, the world listened. Then he addressed the dignity of Man, the need to date girls and read proper books, and generally to rock out. Now he calls on us to confront the pathetic fallacy. Animals, unlike people, do not smoke pipes or operate heavy machinery. They wander around rutting and having long naps, finding food where they may. These roles may be reversed in Wales and some parts of Bulgaria, but the truth remains that our activities bore most beasts. God put animals on this Earthly disc to be eaten by me or filmed by various Attenboroughs, not to indulge the Neronic excess of Nubians or upstage terrorists. Let us follow Shatner's example and accord animals the respect they are due. The BBC could take the first steps by screening Incubus, perhaps with an introduction by the late Welsh naturalist Johnny Morris, and scheduling a run of Chania Kydon TV's "Η Ώρα της αίγας" goat-focused chatshow and cookery programme. NB This web blog is openminded in every sense, but does not tolerate crude national stereotyping. Anyone who posts comments about sheep and lonely Carmarthenshire hill-farmers will have his car painted green and his house burnt down. "Slezynka plunged deep down the orphanage wellTo smother her shame wrought by Szekler lords fell.But "crack!" went her bones on a rocky outcrop -The Szeklers had stolen the water as well. "Poor Slezynka knew that to stifle her sobAnd drown out her heart like a leper boy's bellShe would weep booming tears that droplet by dropFilled the well and her lungs from bottom to top." The audience at Zhakhiv Cultural Agitational Facility No.17 in the Name of Bragg was struck dumb and, in a few happy cases, deaf, by "Szkeklers Shamed Slezynka", the latest in a long series of poems about violated orphans of the monarchy era read by the author herself, Symona "Shmonka" Cheshetsya - Deputy Minister of Peasantry and retired People's Popular Folk Bard (1952). Agent Kafka and I applauded as freely as our NAKRO-issued civilian suits allowed. These garments came in two sizes - too large and too small - and were fashioned from the clothes cut off the pulped bodies of CIA infiltrators at the Comrade Samantha Smith Memorial Execution Ground and Timber Mill. As no bourgeois spy ring had bothered with Ruthenia since the notorious Yankee Incursion of 1947, this left the Ruthenokex State Textile and Haberdashery Trust with a small selection of brown shorts, green arms patches and a whistle (minus nutritious pea) from which to kit us out. According to the History of the Workers' Democratic and (United) Socialist Party of Ruthenia (Medium Course), CIA agents masquarading as a group of so-called Hungarian Boy Scouts had crossed the border in 1947 using the cover of an invitation from the Ruthenian Scouting Association. They were immediately intercepted by a detail of the Internal Retentive Border Coordination Guards. Their private possessions were redistributed along collectivist principles among various individual commanders, and the alleged scouts themselves were given the fraternal opportunity to dance with Bodjo the Largely-Tamed Bear - a gift from the Moldavian Socialist League for Animal Cruelty - while the Guards put on a reciprocal display of virtuoso slyvovytz drinking. The Guards then retired to consume a festive meal of mamalygha and papanasz, leaving Bodjo to forage for himself among the Scouts. Provocative questions from the wholly-compromised Hungarian "government" led to an urgent NAKRO investigation of the incident. This concluded that the Border Guards had acted correctly in disarming the insurgent unit of "American-trained paramilitary dwarves", and rewarded Bodjo with the title of Progressive Woodland Ranger, a peasant ration book (grade IX) and several conjugal visits to the infirmary at Political Prison No.49 in Szeumas-on-Myłn - at least once at an inmate's request. NAKRO later arranged a visit for the leaders of the Ruthenian Scouting Association to the scene of the incident, where the Internal Retentive Border Coordination Guards and Ranger Bodjo were happy to re-enact the events of that day with them.For Kafka and myself, this meant that the clothes allowed me to raise my right hand to an almost horizontal position, while Kafka struck his with knee-length lapels. We squinted at full attention as the crowd shuffled in the pews and pulpits of what had once been The Cathedral of The Interrupted Ascencion, and prepared for the main event of the evening - the Battle of the Bands. Socialist Ruthenia had fought a stern rearguard action against the advance of music throughout the postwar period, prompted by Comrade General Secretary Yütz's displeasure at a performance of Symphony No 5 in G# Minor ("The Bastard") by People's Popular Composer Uzz Kalnis. Massed timpani had hammered out the Morse Code for "Starve The Comprador Latifundistas!" a few metres from the General Secretary's box, while a chorus of Fishwives for Peace chanted "Fist Up, Fist Up, Comrade Yütz!" during the 20-minute ondes Martenot improvisation in the scherzone. The Central Committee's decision was swift. Kalnis was called up for a "lap of honour" second stint of military service, this time in the 8th Experimental Submarine Parachute-Launching Brigade, despite his advanced years and inability to breath underwater. The new principles were cascaded more broadly across the portfolio of the Ministry of Applied Culture. All music had to accord with the 1949 Yütz Theses: It must accord with the Will of the People, as expressed through the mood of the General Secretary. It must be played on instruments whittled, ground or stolen by workers, peasants and ill-nourished soldiers, and at a distance of not less than one county from all members present and future of the Præsidium of the Central Executive Committee of the Acting Organs of the Workers' Democratic and (United) Socialist Party of Ruthenia. It must not exceed five minutes in length (considerable debate followed as to whether this referred to individual pieces of music or all music composed in the People's Democratic and Popular Republic. Much of this debate was conducted in prison). All public performances in the capital must feature young Gypsy women in bodices a size too small. For 30 years music in Ruthenia consisted of crones tapping out Lehár waltzes on sacks of flour as gravy-streaked college girls jumped up and down in oily lingerie liberated from ex-Queen Sylja's bath house. Then came Beatlemania, and the country was flooded with six reels-to-reel of songs by what turned out to be The Scaffold. By 1981, the authorities felt they had to intervene - especially as Lily the Pink was taken to be an attack on Comrade First (General-)Secretary Novak's wife Liljljanja and her allegedly Polish tendencies. The Ministry of Cultural Reassignation therefore empowered itself to create two singing ensembles in order to stem the "rising tide of subjective melody and crypto-Francoist rhythm" ("Sotsjalystychna Muzsyqa", editorial, 4 March 1983). These two "bands", as they came to be known ,were recruited by the People's Self-Defence Army Penal Battalion from a group of conscripts found trying to mount an accordion in the backyard of a distillery. They were joined by four prostitutes and a drummer who, on medical examination, proved to be a barbary ape donated to Zhakhiv Zoo by the government of Algeria. The ape was shaved carefully and emerged as the leading songwriter of Kava Break, the marginally faster of the two groups. The other band, Izotop, played up to its fondly-imagined "bad boy" image with single-entendre song-titles like "(Swing From) My Girder Of Love" and "(Politically-Engaged Miners) Slide Down My Shaft". They alternated as winners of the annual Battle of the Bands, filmed live and shown five months later by Ruthenian State Television on lignite-powered sets in many interrogation centres of the less mountainous parts of the republic's maritime territory. This pattern was briefly interrupted in 1987, when the Party decided to show solidarity with the Progressive Palestinian People by adding the category "Least Zionist Ensemble" to the competition criteria. That year's winners, Izotop, pointed out that this objectively made Kava Break the Most Zionist band in the country and therefore liable for re-education and confiscation of their possessions. NAKRO and at least two other security organs, one of them subsequently believed to be Izotop dressed in Bulgarian marching-band uniforms, turned up, turned over and turned in Kava Break. They got 15 years hard labour: five for lack of Semitic awareness, five for not understanding the charges, and five for each year they had failed to reveal their Zionism.The ape got off with a suspended sentence after convincing the judges that he was a member of Neturei Karta. He then joined Izotop, making it Ruthenia's first super-group. Izotop enjoyed its three-year run as default winner before successfully petitioning the Supreme Higher Party Council of Organs (Verxvysszstrankradorh) to pardon Kava Break on the condition that the freed musicians should undertake Izotop's solidarity tour of South Yemen. Izotop generously relinquished the ape as well - rumour had it because lead singer Lev Basar resented his sidelocks and college-girl following. Kava Break scored a commanding musical and ideological comeback with the ape's drum-led single "Golda Meir Stole My House" [translator's note: the song later enjoyed a copyright-free afterlife as a remixed trance track on the Tel Aviv dance scene.] Now, the two bands mounted the stage to compete once again for Ruthenia's highest popular music award - the continued waiver of their military service. In keeping with the the Party's drive to economise on power, time and individualism, both bands performed their latest hits simultaneously and on the same instruments. This policy was dubbed "Creative Lamarckism" and promoted the adaptation of a citizen's limbs to the eventual ideal of Socialist multitasking in gunfire, forgery and the seduction of West German Embassy clerks. As the bands tussled over their dulcimers, Kafka nodded towards the bar as vigorously as his crumbling garments would permit. We crabbed our way through the throng, with Kafka rather undermining our cover by brandishing his Laika pistol and NAKRO club card at anyone who stood between him and 500 grammes of slyvovytz. "What do you think of this competitive element in popular music, Agent Kafka?" I inquired as he crunched the cap off another bottle with his eye socket. "I mean, surely it's an inherently capitalistapproach to what ought to be a collaborative effort?" He downed the spirits thoughtfully, pausing to belch a blue flame of satisfaction around his Karbin filtertip, and said: "I void myself on them, on their music, on the nuns that bore them, and on the Slovak who comforts the pig that sired them. And then on that pig, too. But most of all, Zhatko, I crack open my codpiece and..." His words were drowned by the bitonal, overamplified version of the banned royalist anthem "Hey Ruteni, masluy mi sztifli!"(O Ruthenians, Oil My Boots!") being blasted out of the sound system. Kava Break and Izotop gestured in vain that they were not playing their lyres, hornpipes and gamelans as the local militia and music-lovers seized the opportunity and backing vocalists and stormed over the footlights, truncheons and skinning belts aloft. Banners strung across the stage proclaimed that all concerned would Put The Resolutions of the XIIIth Congress of the Workers' Democratic and (United) Socialist Party of Ruthenia Into Life. They suddenly fizzed and sparked into life, leaving behind the stench of sulphur and these letters stencilled into the proscenium - ZHIJE NAXAJLO! - Naxajlo Lives! "He focked us," Kafka concluded. Not for the first time, Agent Kafka was understating the matter. As gouts of slyvovytz-scented khaki ichor erupted from our every accessible orifice, we turned to the barman. He was gone. Sunday, October 05, 2008 University types and Guardian commentators have, with typical bourgeois boorishness, robbed the stevedore and Thuringian infantryman of their sole remaining pleasure - anti-Semitism. Whereas they were once damned for running department stores and undermining the Ludendorff Offensive, Jews are now accused of controlling the British Liberal Democratic Party and their own country, not to mention the world. Nonsense, of course. A Jewish world would be neater, better-fed and more musical than this lot, although there's only a certain amount of Diet Coke one can take. Middle class extremists are obsessed with political influence. They skip over the boring stuff Marx wrote about the economy and go straight to Lenin's cut-out-and-keep guide to taking over useless countries. All they think they need is a newspaper and the willingness to get up early in the morning. It is all the more surprising, then, that they've failed to condemn the one nation that has spent a millennium systematically wrecking political parties. I speak of us Welsh, and here is the charge sheet. 1. The British Liberal Party. In 1906 the Liberals all but wiped out the Tories, leaving the latter in the hands of porcelain pansy Arthur Balfour and Canadian mute Bonar Law with only Ulstermen for comfort. The Liberals invented pensions, built Dreadnoughts and bullied their betters in the House of Lords. They led us in defence of gallant Belgium. Their leader was a Classicist. Then they dropped Asquith in favour of David Lloyd George, who strapped the Liberals onto the scabby flanks of the Conservative Party and spurred his gullible colleagues on into electoral oblivion. The Liberals showed some signs of revival during the Second World War under their Scottish leader Archibald Sinclair, but Montgomery's Clement Davies took over just to time to drag them back to six MPs representing escaped convicts on exposed moors. Another Scot, Jo Grimond, began their rehabilitation, and the Liberals perked up considerably under the vulpine dandy Jeremy Thorpe - and who wouldn't? But the leader was lost when he found himself accused alongside a pair of Welsh businessmen, John Le Mesurier and George Deakin, of conspiracy to murder. The plucky Libs rallied again to the Braveheart banner of Scotsman David Steel (can you see the pattern here, people?), only to have it dragged through the bog-snorkelling ditch of despond by Taffmesiter Dr David "Llywellyn" Owen and his Alliance of Evil. The Liberal Democrats have not been doing badly of late, but that's largely because we've transferred our Silurian attentions to the major parties. Watch out for adopted Welsh Lembit Öpik, though. He's bidding to be President of the party, and owes us one after the way he treated the lovely Siân Lloyd. 2. The Conservative Party. This has been a tougher nut to crack. The Tories are often called the Stupid Party by people who win far fewer elections than they do, but if there's one thing a Tory can spot it's a Welsh in his midst. For this reason we have had to use guile. Selwyn Lloyd did what he could to wreck both the Eden and Macmillan governments from within, but Supermac gave him the Supersack in 1962. In revenge we activated Mandy Rice-Davies, and the Profumo Affair pretty much did for the Tories. We can't claim credit for the shark-toothed disaster that was Edward Heath, and dropped the ball badly over Mrs Thatcher. It took over ten years to get her in our triangulation of fire from North West Clwyd MP Sir Anthony Meyer, Portalbot baronet Sir Geoffrey Howe and Welsh Guardsman Michael Heseltine. Since then we've found the odd easy lob - Ffion Hague, Michael Howard - has kept the Tories hors de combat. Once again, however, we face a Scottish challenger in the form of Young Cameron, and are working fast to get Monmouthshire MP and prize buffoon David "Top Cat" Davies into a position where he can cause real damage. 3. The Labour Party. Long insulated by its thick layer of Scots, Labour suffered few direct hits in its early decades: It got over Aberavon MP Ramsay MacDonald. Colonial Secretary Jimmy Thomas failed to detonate until well after the 1929-1931 Labour Government had fallen. Aneurin Bevan backfired on us too. Indeed, it wasn't until the 1980s that we got into our stride against Labour. Sacrificing the pawn of a Welsh parliament in the 1979 referendum was a stunning start to a campaign that involved planting Ebbw Vale MP Michael Foot and Neil "Bloody" Kinnock as party leaders in succession. Labour's subsequent loss of the 1992 election to Kaspar Hauser impersonator John Major remains our finest hour. Labour under neo-Scotsman Tony Blair proved impervious to our efforts. He identified and neutralised our sleeper, Prestatyn-born John Prescott, early on, and took the premature explosion of Martyr Ron Davies in his stride. As for Gordon Brown, we're genuinely baffled. Our best genealogists have found no Welsh blood in his ancestry. For the time being we're happy to leave him to it, while we concentrate on: 4. Plaid Cymru. That's right. Not since the doomed Social Democratic Party (Roy Jenkins, David Owen, Welsh-in-law Shirley Williams, anyone?) has any political group been so farshtopt mit Walizers. Spoilt for choice, we've unleashed some of our finest saboteurs on our own national party. Dafydd Elis Thomas, Ieuan Wyn Jones and Helen Mary Jones should be enough to teach party chairmen the Lloyd George Rule - They've Got Three Names: You're Out of the Game. Evelyn Waugh once wrote "We can trace almost all the disasters of English history to the influence of Wales". And England is still making lots of history for us to trample over with our loping, lupine tread. Bear in mind too that "Waugh" as a surname is cognate with "Welsh". Do I have to draw you a map? Wednesday, October 01, 2008 Fellow-sufferers Gyppo Byard and Gadjo Dilo have recounted the horrors that mothers-in-law can always surprise you with, and I'm sure they have far more in store. I will recall the first meeting with my own mother-in-law, Bela, at a later date. Here I present the true story of Mikhas', quondam editor of Belarus magazine. I spent a delightful couple of years prior to the collapse of the Soviet Union shuttling between London and Minsk in a quest to make money out of Belarus. "Guid tank country" was my Caledonian colleague "Shuggy" MacLeod's laconic account of that country, a radioactive swamp dotted with dazed peasants who bumble about in ill-fitting clothes and gas-fuelled buses waiting for the Russians to come back and make them miss the Poles all over again. I frittered away the funds of my then employers while enjoying the company of ballerinas, models, artists and war veterans. Among the many random people whose homes I cuckooed in at uncertain hours of the evening was Mikhas'. Soviet-era Belarus was as much of an enigma wrapped up in a waste of time as it is now. My then boss still gasps at the Belarusian Tourism Board's plan to market not their own malarial parade-ground but rather 1980s Cambodia as a holiday destination, with flights via Minsk's impenetrable airport. "Sun, sea and genocide?!?" he had yelled at the officials as I translated. "So, but perhaps not the last element," responded a turtle-faced berry-picker in a cardboard suit. One evening we had dinner at home with Mikhas'. His wife Lyuda was an official interpreter, and between them they made up the entire Belarusian pro-Gorbachev camp. Most other intellectuals did nothing to counter one historian's remark that the entire Belarusian national movement in 1920 could have fitted on one modest sofa. The only change since that was that the latest generation of patriots could barely stay upright on any item of furniture for long enough to make their point. Mikhas' edited Belarus, a magazine doomed from the start by being published in Belarusian - the cheeriest but least-spoken tongue in the whole country. It's difficult not to love a language that calls the railways "chyhunka", birds "ptushki" and your good lady wife a "zhonka". The magazine was twice cursed by trying to promote the Third Way of Soviet reform in a country that either liked being kicked in the head while being lectured about The (Second) Great Patriotic War or else wanted to be an independent mini-Poland and top of the European Rickets League. Mikhas' had just come back from a conference in Moscow, during which he had been received at the Kremlin by President Gorbachev himself. The Heir to Lenin was clearly a micro-manager, as he had found time to assure Mikhas' that his 60 unread monthly pages of articles about bison grass and how all the famous Poles were really just shy Belarusians was the key to promoting prudent financial management, local democracy and general sobriety on the western borders of the Unbreakable Union of Free Republics. Our host was recounting this to our general bemusement when his mother-in-law walked in. She had been ferrying bowls of cabbage from the stove for half-an-hour with the eerie glide that old ladies perfect. Mikhas' decided she ought not to miss out on his good news, and declared "Did you hear that, Mama? I met the president yesterday!" "That's very nice, Misha," she replied, bearing a tureen of spent offalback into the kitchen. "But then I danced with the Tsar." We spent a good 10 minutes watching Mikhas's crest fall before the good lady rejoined us with a tray of traditional gunpowder nuts and turpentine schapps. She sat down and told us the story. "I was a debutante in Mogilev in 1916, and we were all excited that the Tsar was coming to our New Year Ball. His military train had been based nearby for much of the War. He arrived, as promised, and I nearly fainted when he cut in and asked me to dance. I remember that his eyes were pale blue, watery and kind, and his beard smelled very strongly of tobacco." He said nothing. At the end of the dance he bowed with a smile, and walked off." Into history. Within weeks the February Revolution had cost Tsar Nicholas his throne, and in little over a year he and his family were murdered by their Bolshevik captors. Mikhas's mother-in-law had kept her genteel origins quiet, and somehow survived civil war, Stalin, starvation and Hitler. Mikhas' may have felt upstaged, but her readiness to tell the story that evening was a tribute to the efforts that he and other Gorbachevians had made to let some light into the dank cellar of Soviet society. | Low | [
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Support WGBH Awaiting Probation Indictments On Beacon Hill BOSTON — This week in Massachusetts politics, lawmakers anxiously await possible criminal indictments, House Speaker Robert DeLeo discusses his legislative priorities in a speech to the House chamber and Attorney General Martha Coakley debates the federal health care law in Washington, D.C. State lawmakers are on pins and needles waiting to see who will be indicted in the Probation Department’s patronage scandal. Beacon Hill has been buzzing for weeks with rumors that as many as 15 indictments are about to drop from the U.S. Attorney’s office. Prosecutors have been investigating whether state lawmakers boosted the Probation Department’s budget with the understanding its commissioner would give jobs to their families and friends. No criminal charges have been handed down so far, but indictments could be imminent. In this tense atmosphere, DeLeo will take the floor on Wednesday to outline his legislative agenda for 2012. He’s expected to focus on the budget, criminal sentencing, and health care costs. Then later in the day, the Governor’s Council, which vets judicial nominees, will meet for the first time since the sudden death last week of longtime councilor Kelly Timilty, who died on Jan. 31 after a brief illness. She was 49. Timilty was a frequent supporter of Gov. Deval Patrick’s judicial nominees. Now the House and the Senate, which are both controlled by Democrats, have the power to appoint her successor. On Feb. 9, Coakley travels to Washington, D.C., to square off against Virginia AG Ken Cuccinelli on the constitutionality of President Obama’s health care law. Cucinelli was the nation’s first attorney general to sue over the 2010 law; Coakley plans to defend it. The U.S. Supreme Court is set to consider the law in March. | Low | [
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Athletics at the 2006 Asian Games – Men's 10,000 metres The men's 10000 metres competition at the 2006 Asian Games in Doha, Qatar was held on 9 December 2006 at the Khalifa International Stadium. Schedule All times are Arabia Standard Time (UTC+03:00) Records Results References Results Category:Athletics at the 2006 Asian Games 2006 | Mid | [
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Sununu Blasts Obama for ‘Demonizing’ Rich Former New Hampshire Gov. John Sununu on Tuesday blasted President Obama for “demonizing” success in a recent speech. “Can you imagine anybody trying to demonize the successful result of the American Dream? Or when he says ‘rich,’ he says it with a snarl,” he said on CNBC’s “The Kudlow Report.” “And so you’ve got young people out there thinking that if they succeed and they get rich, they’ve done something evil.” The former White House chief of staff under President George H.W. Bush, Sununu ramped up the rhetoric against Obama, a former U.S. senator from Illinois. “This is a guy who was raised in Chicago, where the way of doing business is to take care of your friends, and that’s what he’s been doing,” he said. “And that’s why he thinks government creates business, because he gives a federal taxpayer grant to people like Solyndra when the companies are owned by his bundlers and his backers, his financial backers.” Solyndra, a manufacturer of solar panels, received more than $500 million in government support before filing for bankruptcy. Sununu also called the Mitt Romney campaign’s response to Obama’s “you didn’t build it” speech a gift, one that provided ammunition to the Republican presidential hopeful’s camp. Last week, Obama said in a speech that government investment helped spur innovation and growth, crediting it for such projects as the Hoover Dam and the Golden Gate Bridge. “If you were successful, somebody along the line gave you some help. There was a great teacher somewhere in your life. Somebody helped to create this unbelievable American system that we have that allowed you to thrive. Somebody invested in roads and bridges,” Obama said. “If you’ve got a business, you didn’t build that. Somebody else made that happen. The Internet didn’t get invented on its own. Government research created the Internet so that all the companies could make money off the Internet.” Sununu said it was a perfect opportunity for Romney, likening it to a scene in the Mel Gibson movie “Braveheart,” in which the title character commands his troops to “hold, hold, hold” before launching a counterattack on a much larger military force. “When you get a gift like that from someone makes a gaffe that big that defines how little the president knows about the economy, even while they were hold-hold-holding, they had to come out and lay it on,” he said. CORRECTION: A previous version of this story incorrectly said Obama's speech was this week. | Low | [
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Elijah Wood seems to be having the longest, darkest tea time of the soul imaginable in the trailer for Dirk Gently’s Holistic Detective Agency, released at Comic-Con. The setup, as the trailer frames it, as much in common with Fight Club as with Douglas Adams’ Dirk Gently novels: Wood plays a character named Todd, who has the dullest, most humiliating life imaginable, working as a bellboy at a place with the same dress code as Barton Fink’s Hotel Earle. That all changes when Dirk Gently (Samuel Barnett) shows up, forcibly pointing out the misery Todd’s been putting up with and plunging him into a new life of danger and adventure. Todd bucks against the eccentric detective wreaking havoc in his life, telling him, “I am not your Watson, asshole!” but once you invite Tyler Durden into your head, good luck turning back the clock. The show, produced by Max Landis, looks competent and funny: Barnett’s blithe delivery is great, and Wood’s always had a talent for misery. Setting the show in the United States (while keeping Gently British) seems like a surprisingly good idea: making Gently play off against non-Brits makes the Douglas Adams’ cleverness in lines like “no private detective looks like a private detective—that’s one of the first rules of private detection” a lot funnier. Plus: Bloc Party! The show premieres on BBC America on Oct. 22. | Mid | [
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REPORT: City board fires West Point police chief The West Point Board of Mayor and Selectmen voted to terminate West Point’s Chief of Police Steve Bingham during the board’s executive session held on Tuesday night. Mayor Scott Ross said the vote was split, 4 to 1, the Daily Times Leader reported. Ross said the job termination will take effect in about 10 days, adding that no replacement for the position has been discussed at this time. Bingham said he would not comment further on the board’s decision. There have been no reasons given by board members, the mayor or Bingham as to why the police chief was fired from his position. | Low | [
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Sejarah berdiri PT Tanjung Power Indonesia Lowongan Kerja Terbaru 2016 Tanjung Power Indonesia untuk beberapa posisi dengan kualifikasi sebagai berikut: 1. Site Manager - Tanjung Power Indonesia Job Responsibilities: Establishment and management of Site Team, provide guidance and leadership for Site Team, as well as to coordinate with EPC contractors site management to ensure the construction of the power plant is done according to PPA requirements, contract, schedule, specification and to ensure the safety of the overall project. Establish the power plant projects construction planning as according to the contract schedule and specification to ensure all construction activities are well organized and completed as according to PPA, contract schedule, budget, specification as well as adhering to HSE principles and best industrial practices. Lead the project execution on site by optimally utilizing the available resources so the execution of the project meets the contract quality, budget, and schedule requirements. Oversee and control the EPC contractors performance and work execution to ensure works are completed in estimated time and budget, in accordance with industrial standards and applicable specifications. Oversee and control EPC contractors technical documentation to ensure works are carried out providing the required quality, reliability and durability of the plant as well as complete technical trace ability. Oversee and control EPC contractors HSE awareness and culture to ensure the establishment and implementation of a clean and safe construction site (zero accident and zero incidents). Determine alternative steps to be taken in the occurrence of technical and non-technical issues during the construction of the power plant, while adhering to contract requirements, to ensure the construction project is done as according to the schedule. Ensure the project execution, in terms of materials and work methods meet the required technical specifications to ensure the quality of the project works. Job Requirements: Minimum Bachelor Degree majoring in Engineering Minimum 10 years of experience in construction project activities as Site Manager (coal fired power plant, oil & gas) 2. QAQC Inspector - Tanjung Power Indonesia Responsible for all QAQC inspection for all of the power plants construction works to ensure that all works are done according to contract and specification. To collect and analyze all non-conformance reports for all the power plant construction works, ensuring that all NCRs are done through a single channel and thus to ensure all NCRs are well controlled. To ensure all works that do not comply with contract specifications and standards are documented and monitored. To follow up on all works that do not comply to specification and standards and to process the necessary documentations for works that have been corrected and meet quality specifications and standards. To monitor and control all from contractors and subcontractors to ensure contractor and subcontractors work quality is according to contract spec and standards. Job Requirements: Minimum Diploma Degree (D3) graduate majoring in Engineering Min. 3 years of experience as QAQC Material Inspector on Construction works from power plant/ oil & gas/ heavy industry Good communication and interpersonal skills Good command in English both verbal and written Willing to be on contractual basis during the project Willing to be located at Tanjung - Tabalong, South Kalimantan 3. Civil Inspector - Tanjung Power Indonesia Job Responsibilities: Responsible for monitoring and control EPC Contractor performance and progress on the construction of the power plant civil works in order to ensure the construction is done according to appreciate specifications, design, schedule and safety requirements. Monitor EPC contractors performance on the construction of the power plants civil works to ensure that construction is done as according to design Identity civil design issues during the construction of the power plants civil works and to recommend and coordinate action plans to ensure corrective action is taken. Monitor and report EPC contractors construction progress for the power plants civil works to ensure construction is done on schedule and to recommended corrective actions for any civil engineering issues. Identify potential cost-effective equipment modification that has the potential to improve performance, reliability, and safety. Control and monitor the implementation of instructions and procedures regarding the construction of the power plants civil works to ensure construction is done as according to the agreed design, quality, and safety Monitor and control EPC contractor activities regarding the construction of civil works for the power plant and to monitor the progress and performance of the EPC contractor to ensure that the power plants civil works is constructed on schedule and on spec. Control HSE performance of EPC contractor to ensure the power plants civil constructed in safe manners. Have 3-5 years experience in civil engineering, construction or maintenance preferably in coal fired power plant projects. Have Government Certification on Civil Engineering Have good competencies on construction methods and system analysis. Good command in English both verbal and written Willing to be on contractual basis during the project Willing to be located at Tanjung - Tabalong, South Kalimantan 4. Mechanical Inspector - Tanjung Power Indonesia Job Responsibilities: Responsible for monitoring and coordinating subcontractor performance on the construction of the power plant projects mechanical works to ensure that all construction is done as according to specification, design, and schedule. Monitor subcontractors performance on the power plants mechanical works to ensure that construction is done as according to design. Identify mechanical design issues during the engineering and construction of the power plant and to recommended and coordinate action plans to ensure corrective action is taken. Monitor and report subcontractors construction progress to the power plants mechanical works to ensure engineering and construction are done on schedule and to recommended corrective actions for any mechanical engineering issues. Identify potential cost-effective equipment modification that has the potential to improve performance, reliability, and safety. Coordinate and monitor the implementation of instructions regarding the engineering and construction of the power plants mechanical works from the Mechanical Team Leader and Mechanical Engineering Manager to ensure construction is done as according to the agreed design. Coordinate subcontractor activities regarding the construction of mechanical works for the power plant and to monitor the progress and performance of the subcontractors to ensure that the power plants mechanical works are constructed on schedule and on spec. 5. Electrical Inspector - Tanjung Power Indonesia Job Responsibilities: Responsible for monitoring and coordinating subcontractor performance on the construction of the power plant projects electrical facilities and other common electrical facilities to ensure that construction is done as according to specification, design, and schedule as well as to support the electrical engineering construction for auxiliary power. Monitor subcontractors performance on the construction of the power plants Electrical facilities to ensure that construction is done according to design and provide back up for voltage facilities management if needed. Identify instrumentation and electrical design issues during the construction of the power plants Electrical facilities and to recommend and coordinate action plans to ensure corrective action is taken. Monitor and report subcontractors construction progress for the power plants Electrical facilities to ensure construction is done on the schedule and to recommend corrective actions for any instrumentation, control, and electrical engineering issues. Identify potential cost-effective equipment modification that has the potential to improve performance, reliability and safety. Coordinate and monitor the implementation of instructions regarding the construction of the power plants Electrical facilities from Electrical team leader and C&I and E Engineering Manager to ensure construction is done as according to the agreed design. Coordinate subcontractor activities regarding the construction of Electrical facilities for the power plant and to monitor the progress and performance of the subcontractors to ensure that the power plants Electrical facilities is constructed on schedule and on spec. | Mid | [
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4 men charged with slavery offenses in Britain Authorities says four men have been charged with slavery offenses for holding a group of men in squalid conditions at a caravan site north of London. Prosecutors said the men, who were all from the same family, were charged Monday with conspiracy to hold others in servitude and requiring them to perform forced labor. They were arrested Sunday during a raid on the caravan site in Leighton Buzzard, north of London. A pregnant woman was also arrested but was released Monday on bail. Police found 24 men, mostly of English and eastern European backgrounds, in poor health and in cramped and dirty conditions at the site. Officers said they believed some of the men had been working in a state of "virtual slavery" for up to 15 years. | Low | [
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Q: Store and retrieve files from outside the WAR in google app engine? Well I am pretty happy working at home with a local Apache Tomcat and serving the static files with help of FileServlet, also I am following a instruction as said in this answer that: You should not store the files in the webcontent. This will fail when the WAR is not expanded and even when it is, all files will get lost whenever you redeploy the WAR. But now I am using Google App Engine for my application, where I cannot configure the server, also it usesjetty which is new for me. All the things in my web application gets uploaded to server through eclipse but I cannot upload a folder outside to WAR. Now how can I apply such static file serving here using a Servlet, should I use Google Blobstore? , or just simply a database that can be Google Cloud SQL or there is any other way out? Thanks, Asif A: You don't need a FileServlet to serve static content. Instead, declare the files that intend to be static, and App Engine will manage serving them. If for some reason you need to read a file programatically, then declare it to be a resource. See https://developers.google.com/appengine/docs/java/config/appconfig#Static_Files_and_Resource_Files | High | [
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Horoscope for April 21 2018 Horoscope for Saturday 21st April 2018 Today is the last day the Moon will be in gentle Cancer. It's a great day to spend with those who mean the most to you. Today is all about togetherness and warm emotions. Everyone is feeling the need to get together and do good for other people. It' s a great time for charitable acts and giving back to the greater community. Discover what lies ahead for your sign, below! Today Horoscope for Aries: You could find yourself feeling a bit confused about a certain matter, Aries. You've thought it over for a while now, and you can't seem to form an opinion or conviction. Life can be a mystery at times, and we are not meant to have all of the answers or make the right decision all of the time. The best you can do is act based on your instincts. They won't lead you astray. Today Horoscope for Taurus: Taurus, sometimes you have to ask yourself if something is truly worth the struggle. You have been tirelessly pursuing a certain goal, but it has completely consumed your life and hasn't left room for very much else. How important is this matter to you, really? Is it worth making such a great sacrifice? The answer will bring you some relief. Today Horoscope for Gemini: Geminis could find themselves looking forward to an event today. Something big is on the horizon and it's all you can think about right now. Every once in a while an event comes along and it is truly life-changing. You may find that you are forever changed and influenced by what is about to transpire. Enjoy the moment. Today Horoscope for Cancer: Sometimes it pays to stay away from gossip, Cancer. It seems some people close to you are really on a roll, telling tall tales and speculating about another person who is a bit of an outsider. Sure, you could sit by passively and not engage. But wouldn't it feel better to try to put a stop to this senseless talk? It's always good to defend those who can't defend themselves. Today Horoscope for Leo: Leos are feeling the urge to expand their mind. Mercury is in your 9th House of Mental Exploration, and you're ready for a new perspective and a new view of the world. Surround yourself with inspiring people who are busy doing deep, meaningful work. We only get one life on this Earth-we may as well make it the very best it can be! Today Horoscope for Virgo: Sometimes you can take yourself so seriously, Virgo! While everyone knows they can rely on you in a pinch, you have all but forgotten your silly and humorous side. Try to see the lighter side of matters whenever possible today. Crack a joke or two, and maybe let a few mistakes or misgivings slide by without note. People just may have a good response to the new, carefree you! Today Horoscope for Libra: Libra, you may be feeling a bit discouraged today. Something recently didn't go according to your plan and you are trying to work through this disappointment. First, consider how silly the notion of a "plan" is in the first place. You're essentially trying to control the uncontrollable and placing unreasonable expectations on life for it to work out exactly as you see fit. Wouldn't it be great to let go of the reigns and live a little? Today Horoscope for Scorpio: There's nothing you won't do for the people you love, Scorpio. Recently you have been deeply moved by a loved one's circumstances and you are out to make things a little easier for them. Think of ways you can subtly give back to them without bruising their pride too much. Sometimes just knowing they have someone there in the trenches with them is all they need to carry on. Today Horoscope for Sagittarius: Sagittarians could find themselves yearning for some personal space today. You have been in close quarters with a certain person for quite some time now and it seems as if you are about to go mad! There's little you hate more than being confined and constricted. Do what you can to find a little open space and breathing room-both literally and figuratively. Today Horoscope for Capricorn: Capricorn, you still have a lot of work to do. You may find yourself mid-way through a project and lack motivation today. Sure, you could sit around and think about how unfortunate you are, how uninspired you are, and how much you need a break. Or you could pull yourself up by your bootstraps and do what needs to be done. Sitting around feeling sorry for yourself won't get the job done! Today Horoscope for Aquarius: You may want to try out a new health and wellness practice today, Aquarius. The Moon is in our 6th House of Service and Health, prompting you to think of new and innovative ways to care for yourself. Think of how refreshing a morning yoga class could be, or how relaxing and restoring an evening walk may feel. If you think of the positive feelings associated with each action they are far more appealing! Today Horoscope for Pisces: Someone could be meddling in your business today, Pisces. You are a very private person, and you pride yourself on handling your personal affairs without a lot of pomp and fanfare. Well, someone has taken an interest in your life and they seem to have all kinds of ideas about what you should and shouldn't do. Smile, nod, act interested-and then do whatever you want! | Low | [
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Q: Force someone to do what you want [to] [do] 1) Don't force your friends to do what you want to do. 2) Don't force your friends to do what you want to. 3) Don't force your friends to do what you want. I think 1) is 'Don't force your friends to do something. You want to do something.' And 3) is 'Don't force your friends to do something. You want something.' But generally, forcing is kind of acts so I think 1) is the most grammatical sentence. But now I have still a few questions. 2) Don't force your friends to do what you want to. - > Is it grammatically correct? 2) If it is possible, what is the difference between 1) to 3)? A: 1) and 2) are the same. The word "do" is elided but understood at the end of 2). They mean, "You want to do something. Don't force your friends to do that same something." Suppose you want to see the movie Fast and Furious 7. If you're a good person, you won't force your friends to go with you. 3) means, "You want something done. Don't force your friends to do that something. Suppose you need money, and you think robbing a bank would be a good way to get it. If you're a good person, you won't force your friends to rob a bank for you. Whether you're willing to go with them or not. | Low | [
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Q: jQuery loop through object and look for title but skip others I have been teaching myself JS and Jquery and I still struggle with how to effectively use $ to loop through an object and extract the info I want. I have a table that has a flag icon and a title describing that I want to put at end of the row. However, there are sometimes other icons that I must ignore. So I look for "flag" in url and if it exist I set innerHTML of 2nd to last cell to 'title'. As you can see below I have had to create a decrement VAR y to keep from skipping to next row with "title" if I encounter non flag icon. I want this row to be appended with "title" which is the location: <td>11:44pm</td><td><a href="/stats/visitors?site_id=66351439&date=2011-04-27&country=the+united+states"></a></td><td> <a class="custom" title="Comcast Cable" href="/stats/visitors?site_id=66351439&date=2011-04-27&ip_address=75.70.103.23">Comcast Cable</a></td><td><a href="/stats/visitors-actions?site_id=66351439&date=2011-04-27&session_id=228613269">1 action</a></td><td>10s</td><td width="100%"> </td><td></td> To look like this: <td>11:44pm</td><td><a href="/stats/visitors?site_id=66351439&date=2011-04-27&country=the+united+states"></a></td><td> <a class="custom" title="Comcast Cable" href="/stats/visitors?site_id=66351439&date=2011-04-27&ip_address=75.70.103.23">Comcast Cable</a></td><td><a href="/stats/visitors-actions?site_id=66351439&date=2011-04-27&session_id=228613269">1 action</a></td><td>10s</td><td width="100%">Aurora, CO, USA</td><td></td> So my question - What is a better way to do this whole procedure. Here is a link to the jsfiddle - http://jsfiddle.net/ukJxH/78/ - at 3:47 you can see a non flag icon. var x = $('.tableborder tr img'); y = 1; for (i = 0; i < x.length; i++) { var flagg = x[i].src; var pattn = /flag/gi; var loca = x[i].title; if (flagg.match(pattn) == "flag") { //$('td:nth-child(6)')[i + 14 + y].innerHTML = loca; $('#main :nth-child(i) td:nth-child(6)')[i].innerHTML = loc } else { y = y - 1; } } A: I'm sorry but I'm not sure I understand your question too well. However, the following selector will give you all the flags in the table $('.tableborder tr img[src*="flag"]').each(function(){ $(this) .closest('td') .nextAll('td:last') .html('Title from image : ' + $(this).attr('title')); }); This should give you a chance to traverse the DOM and get at what you need Live demo : http://jsfiddle.net/jomanlk/ukJxH/87/ | Mid | [
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Q: Performing mathematical operations on a pandas dataframe The column looks like Mod_month Mod_year Reg_Year Reg_Month 10 2016 2016 10 1 2018 2016 12 2 2017 2017 2 I want to perform some mathmatical operations on coloumns of a dataframe to calculate difference between dates. I've tried using: df['difference']=df[df['mod_month']-df['last_month']+df['mod_month']*12-df['last_year']] Which returns the Error: KeyError: '[-1896 -2015 -1993 ... -1955 -1877 -1981] not in index' Which I think is due to null values, I also tried using coerce = 'True', which returns invalid syntax. I have seen other posts, but none of them has the error that I have, therefore any help would be appreciated. A: I think need remove df[], because it is syntax of boolean indexing or selecting by subset of columns: df['difference'] = df['mod_month'] - df['last_month'] + df['mod_month'] * 12 - df['last_year'] | Mid | [
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SCOOTALOO: *repeats loud enough so the rest of the frightened victims could follow along with the plan* Clear! Fly! Fall! Complete! BOTH: One.. two.. THREE! A collective shout reverberated around the room, as every filly that could actually fly took off. The suited ponies gasped and fell back, unsure of where to go. There was too much confusion. A few of the faster thinking ones took off as well, tasers at the ready, aiming... | Low | [
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A method and system for media navigation. A descriptor hierarchy may be accessed. The descriptor hierarchy may include at least one category list. One or more media descriptors may be accessed for a plurality of media items. The plurality of media items may be accessible from a plurality of sources....http://www.google.com/patents/US7908273?utm_source=gb-gplus-sharePatent US7908273 - Method and system for media navigation A method and system for media navigation. A descriptor hierarchy may be accessed. The descriptor hierarchy may include at least one category list. One or more media descriptors may be accessed for a plurality of media items. The plurality of media items may be accessible from a plurality of sources. The one or more media descriptors may be mapped to the at least one category list. The navigation may be processed through a user interface to enable selection of the plurality of media items from the plurality of sources. Images(27) Claims(28) 1. A method of facilitating navigation of a media library including a plurality of media objects, the method comprising: accessing a local database provided on a client device, the local database comprising an entity hierarchy of a plurality of semantic entities and a plurality of media descriptors, wherein one or more of the plurality of semantic entities is associated with one or more media descriptors; processing the plurality of media objects using at least one processor of a machine to identify one or more of the media descriptors associated with each media object; identifying an entity in the entity hierarchy corresponding to the one or more media descriptors associated with the media object; applying inheritance to the plurality of semantic entities so that at least some of the plurality of semantic entities not having directly associated media descriptors are associated with media descriptors associated with one or more other entity; and storing the association between the media objects and the one or more media descriptors associated with the media objects through the applied inheritance to allow a user to subsequently navigate using the media descriptors to select a media object or a group of media objects on the client device. 2. The method of claim 1, wherein applying inheritance to the plurality of semantic entities further comprises: when a child entity in the entity hierarchy does not have the directly associated media descriptor, applying cascading down inheritance to the plurality of semantic entities wherein the child entity inherits a media descriptor associated with a parent entity. 3. The method of claim 1, wherein applying inheritance to the plurality of semantic entities further comprises: when a parent entity in the entity hierarchy does not have the directly associated media descriptor, applying cascading up inheritance to the plurality of semantic entities wherein the parent entity inherits a media descriptor associated with a child entity. 4. The method of claim 1, further comprising associating a flag with a media object, the flag identifying media object is to receive special handling during navigation. 5. The method of claim 1, wherein applying inheritance to the plurality of semantic entities further comprises: creating a mapping between at least two entities of the plurality of semantic entities of the same entity type to provide for an additional association between the at least two entities; and wherein storing the association between the media objects and the plurality of semantic entities further comprises storing the mapping between the at least two entities. 6. A method of creating an information architecture for media objects for facilitating navigation of a media library including the media objects, the method comprising: creating, using a processor of a machine, a semantic descriptor hierarchy from at least one descriptor system, the at least one descriptor system including a plurality of semantic descriptors and a master descriptor code list, the master descriptor code list including a plurality of master descriptor codes associated with the media objects; creating a descriptor relation table, the descriptor relation table relating at least some of the master descriptor codes with other master descriptor codes in the master descriptor code list in accordance with a weighting; and deploying the semantic descriptor hierarchy and the descriptor relation table in a client as the information architecture to allow a user to subsequently navigate the media library to select a media object or a group of media objects on the client, wherein a semantic descriptor not having an associated master descriptor code inherits a master descriptor code from another semantic descriptor in the semantic descriptor hierarchy. 7. The method of claim 6, wherein creating the semantic descriptor hierarchy from the at least one descriptor system comprises: selecting a plurality of category lists from a plurality of available category lists of the at least one descriptor system, the category lists providing the plurality of semantic descriptors; and using the selected category lists as the semantic descriptor hierarchy. 8. The method of claim 7, wherein creating the semantic descriptor hierarchy from the at least one descriptor system further comprises: 13. The method of claim 6, wherein the at least one descriptor system includes at least one of an original descriptor system or a translated version of the original descriptor system with labels in a different language. 14. The method of claim 6, wherein the client is a media player device. 15. The method of claim 1, wherein the entities comprise a media channel, a media stream, a station, a program, a slot, a playlist, a web page, a recording artist, a composer, a composition, a movement, a performance, a recording, a recording mix track, a track segment, a track, a release, an edition, an album, an album series, a graphic image, a photograph, a video segment, a video, a video still image, a TV episode, a TV series, a film, a podcast, an event, a location, and/or a venue. 16. The method of claim 1, wherein the media descriptors comprise at least one of identification codes and a textual label. 18. The method of claim 1, wherein processing a plurality of media objects using at least one processor comprises: extracting a digital fingerprint from a media object to obtain an identifier; and associating the one or more of the media descriptors with the media object using the identifier. 19. Apparatus comprising: memory to store instructions; and at least one processor to execute the instructions to perform operations comprising: accessing a local database provided on a client device, the local database comprising an entity hierarchy of a plurality of semantic entities and a plurality of media descriptors, wherein one or more of the plurality of semantic entities is associated with one or more media descriptors; processing a plurality of media objects to identify one or more of the media descriptors associated with each media object; identifying an entity in the entity hierarchy corresponding to the one or more media descriptors associated with the media object; applying inheritance to the plurality of semantic entities so that at least some of the plurality of semantic entities not having directly associated media descriptors are associated with media descriptors associated with one or more other entities; and storing the association between the media objects and the one or more media descriptors associated with the media objects through the applied inheritance to allow a user to subsequently navigate a media library using the media descriptors to select a media object or a group of media objects on the apparatus. 20. Apparatus comprising: memory to store instructions; and at least one processor to execute the instructions to perform operations to create an information architecture for media objects in a media library, the operations comprising: creating, using a processor of a machine, a semantic descriptor hierarchy from at least one descriptor system, the at least one descriptor system including a plurality of semantic descriptors and a master descriptor code list, the master descriptor code list including a plurality of master descriptor codes associated with the media objects; creating a descriptor relation table, the descriptor relation table relating at least some of the master descriptor codes with other master descriptor codes in the master descriptor code list in accordance with a weighting; and deploying the semantic descriptor hierarchy and the descriptor relation table in a client as the information architecture to allow a user to subsequently navigate the media library to select a media object or a group of media objects on the apparatus, wherein a semantic descriptor not having an associated master descriptor code inherits a master descriptor code from another semantic descriptor in the semantic descriptor hierarchy. 21. The method of claim 1, wherein one or more entities have associated information for display in a user interface element for display on a display device to allow the user to subsequently navigate the media library. 22. The method of claim 2, wherein the parent entity is associated with a recording artist and has an associated genre media descriptor and the child entity is associated with an album by the recording artist but does not have a directly associated genre media descriptor, the method comprising the child entity inheriting the genre media descriptor of the parent entity. 23. The method of claim 2, wherein the parent entity is associated with an album and has an associated genre media descriptor and the child entity is associated with a recording on the album but does not have a directly associated genre media descriptor, the method comprising the child entity inheriting the genre media descriptor of the parent entity. 24. The method of claim 3, wherein the child entity is associated with an album and has an associated genre media descriptor and the parent entity is associated with a recording artist of the album but does not have a directly associated genre media descriptor, the method comprising the parent entity inheriting the genre media descriptor of the child entity. 25. The method of claim 3, wherein the child entity is associated with a recording and has an associated genre media descriptor and the parent entity is associated with an album but does not have a directly associated genre media descriptor, the method comprising the parent entity inheriting the genre media descriptor of the child entity. 26. The method of claim 4, wherein the flag is used as a display filter option. 27. The method of claim 4, wherein the flag is used to handle duplicate items, the flag identifying duplicates based at least on a fingerprint, duplicates based on a Table Of Contents (TOC), duplicates based on a filename, duplicates based on a track name, and/or duplicates based on file hash. 28. The method of claim 4, wherein the flag indicates that an entity is a various artist compilation, a soundtrack, a holiday related theme, an interview, and/or a bootleg recording. Description CROSS-REFERENCE TO A RELATED APPLICATION This application claims the benefit of U.S. Provisional Patent Application entitled “Method and System to Navigate Media from Multiple Sources”, Ser. No. 60/781,609, Filed 9 Mar. 2006, the entire contents of which is herein incorporated by reference. FIELD This application relates to media navigation, and more specifically to systems and methods for navigating media from a plurality of sources. BACKGROUND The growth in popularity of digital media has brought increased benefits and accompanying new challenges. While developments have continued to improve the digitization, compression, and distribution of digital media, it has become difficult to easily and effectively navigating through such media. Accessing media from a variety of sources of potentially different types for navigation increases the difficultly of navigation, as each of the sources may include a large number of media items including songs, videos, pictures, and/or text in a variety of formats and with varying attributes. The sheer volume of digital media available, along with significant diversity in metadata systems, navigational structures, and localized approaches, makes it difficult for any single device or application user interface to meet the needs of all users for accessing the digital media. In general, descriptive metadata ordinarily associated with the digital media may be unavailable, inaccurate, incomplete and/or internally inconsistent. When available, the metadata is often only available via textual tags that indicate only a single level of description (e.g., rock genre), and the level of granularity used in that single level may vary greatly even within a single defined vocabulary for the metadata. Often the level of granularity available is either too detailed or too coarse to meet the needs of a given user interface requirement. Additionally, for a given media object there may be multiple values available for a given descriptor type, and/or multiple values of the same type from multiple sources that may cause additional problems when attempting to navigate the digital media. While the scope and diversity of digital media available to users has increased, the user interface constraints of limited screen size and resolution in some devices have remained effectively fixed. Although increases in resolution have been gained, the screen size being used to access some digital media has decreased as the devices have become more portable. Portable devices may include constraints that the length of lists and the length of the terms used in such lists remain short and simple. At the same time, the application logic driving media applications such as automatic playlist engines, recommendation engines, user profiling and personalization functions, and community services benefits from increasingly detailed and granular descriptive data. Systems that attempt to utilize the same set of descriptors for both user interface display and application logic may be unable to meet both needs effectively at once, while using two completely separate systems risk discontinuity and user confusion. In addition, different users may use different media navigation structures, labeling and related content when accessing content from different geographic regions, in different languages, from various types of devices and applications, from different user types, and/or according to personal media preferences. Existing navigation structures may not enable developers to easily select, configure and deliver appropriate navigational elements to each user group or individual user, especially in the case of an embedded device. Traditionally, access to media available from such alternatives has been organized in a source or service paradigm. If a user desired to hear jazz music, they would either pre-select just a single device or source to browse, such as a local HDD, or drill in and out of the navigation UI for each device/source separately to view available jazz content. Existing media navigation solutions have been more or less static in terms of not being able to respond dynamically to changes in a user's media collection or other explicit or implicit, temporary or long-term personal preferences. Likewise, there has been only limited capability for media navigation options to respond dynamically to real-time or periodic changes in other global and personal contextual data sources including those related to time, location, motion, orientation, personal presence, object presence. BRIEF DESCRIPTION OF DRAWINGS Embodiments are illustrated by way of example and not limitation in the figures of the accompanying drawings, in which like references indicate similar elements and in which: FIGS. 1A & 1B are block diagrams of example navigation systems; FIG. 2 is a block diagram of an example configuration system; FIG. 3 is a block diagram of an example navigation template; FIG. 4 is a block diagram of an example information architecture; FIG. 5 is a flowchart illustrating a method for pre-processing the configuration system of FIG. 2 in accordance with an example embodiment; FIG. 6 is a flowchart illustrating a method for creating a reference media database in accordance with an example embodiment; FIG. 7 is a flowchart illustrating a method for creating an information architecture in accordance with an example embodiment; FIG. 8 is a flowchart illustrating a method for creating a descriptor system that may be deployed in the navigation systems of FIGS. 1A & 1B in accordance with an example embodiment; FIG. 9 is a flowchart illustrating a method for defining a navigation package in accordance with an example embodiment; FIG. 10 is a flowchart illustrating a method for dynamically generating a navigation template in accordance with an example embodiment; FIG. 11 is a flowchart illustrating a method for coding descriptor codes in media objects in accordance with an example embodiment; FIG. 12 is a flowchart illustrating a method for preloading a client in accordance with an example embodiment; FIG. 13 is a flowchart illustrating a method for loading an information architecture in accordance with an example embodiment; FIG. 14 is a flowchart illustrating a method for coding media items in accordance with an example embodiment; FIG. 15 is a flowchart illustrating a method for loading content from a plurality of sources in accordance with an example embodiment; FIG. 16 is a flowchart illustrating a method for content recognition in accordance with an example embodiment; FIG. 17 is a flowchart illustrating a method for mapping content IDs in accordance with an example embodiment; FIG. 18 is a flowchart illustrating a method for receiving master descriptor codes and content IDs for content in accordance with an example embodiment; FIG. 19 is a flowchart illustrating a method for utilizing a navigation package in a client in accordance with an example embodiment; FIG. 20 is a flowchart illustrating a method for creating a navigational view in accordance with an example embodiment; FIG. 21 is a flowchart illustrating a method for updating navigational views in accordance with an example embodiment; FIG. 22 is a flowchart illustrating a method for presenting a navigation view on a client in accordance with an example embodiment; FIG. 23 is a flowchart illustrating a method for altering navigation on a client in accordance with an example embodiment; FIG. 24 illustrates a diagrammatic representation of machine in the example form of a computer system within which a set of instructions, for causing the machine to perform any one or more of the methodologies discussed herein, may be executed; and FIG. 25 illustrates a block diagram of an example end-user system in which the client of FIGS. 1A & 1B may be deployed. DETAILED DESCRIPTION Example methods and systems for media navigation are described. In the following description, for purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of example embodiments. It will be evident, however, to one skilled in the art that the present invention may be practiced without these specific details. A navigation system is described that may provide consistent, simple, effective, and efficient access to a vast scope of digital media, regardless of application, display device or user interface (UI) paradigm. The navigation system may be deployed to enable end-users to perform customization and re-classification of their media collections without impacting the integrity of an underlying portion of the navigation system. Example embodiments of the navigation system may be used to navigate digital content (e.g., digital audio) and may thus be deployed in a portable media device (e.g., MP3 player, iPOD, or audio any other portable audio player), in vehicle audio systems, home stereo systems, computers or the like. The navigation system may enable the efficient configuration and dynamic updating of diverse navigational structures across a plurality of devices and applications, while maintaining the integrity of the underlying metadata. A configuration module of the navigation system may automatically pre-generate and load into a client (e.g., provided on a media player) appropriate alternative normalized media navigation structures. The structures may be used to create an indexed application media database and navigational elements to present one or more views of media items of diverse and multiple sources, types and metadata. The views may be switched on demand, personalized, dynamically adapted and updated without altering the underlying global granular source media identifiers, descriptor codes and/or labeling data. An example system may be built upon a foundation of navigation structures that may include lists, ordering data, hierarchies, trees, weighted relations, mappings, links, and other information architecture elements, as well as entity grouping, labeling, filters and related navigational content. The navigation structures may incorporate a set of semantic entities and descriptors designed to be understandable and appropriate and may be automatically optimized. Thus, for example, a user of a media device (e.g., a portable media player or vehicle audio system) may be customized or optimized for one or more particular users or user location(s). The navigation system may include a mapping of global internal granular annotation codes to a variety of alternative category lists and navigational content used for user interface purposes. The category lists may be fluidly mixed and matched to generate a wide variety of hierarchies and navigation trees while maintaining the integrity of the parent-child mapping between each list and without any change in the global granular annotation codes. In a pre-processing phase, a configuration module may be utilized to automatically select from a pre-defined super-set of options, pre-generate and load into a specific connected or unconnected client at time of manufacture or initial start-up an appropriate set of alternative normalized media navigation structures. The options chosen may be determined based on a combination of device, application, region, language, user type, manufacturer/publisher, and/or end-user account IDs which are provided as parameters to the configuration module. A client application may then utilize the navigational structures to create an indexed application media database, typically in conjunction with media recognition technology. The index may compile media items sourced from diverse and multiple types, services and providers. Additionally, the media items may be accessed from diverse and multiple devices, connectivity and transport. The media items may furthermore contain identifiers and metadata of diverse types, completeness, consistency and accuracy without materially impacting the performance of the system. The client application may utilize the navigational structures to generate default and alternative user interface elements such as browse trees, faceted navigation, and relational lists, and/or to drive aspects of application logic such as auto-playlisting, search, personalization, recommendation, internet community, media retail and on-demand subscription services, and the like. In an example embodiment, the user interface elements present, uniquely for each user on a client, simple, unified (descriptor-based and other) views. Via an application programming interface (API) provided on the media player, the views and structures may be altered on demand, personalized, dynamically adapted (based on personalized and/or contextual input) and updated remotely from a set of master databases via a network service and/or from a local database. The alternate views may be applied on a global (e.g., a country or several countries), region (e.g., regions within a country), application (e.g., an online catalog or store . . . ), device (e.g., portable media player, vehicle media player, etc.), and/or user-account level. All such changes at the presentation information architecture layer may be achieved without altering the underlying master granular media identifiers, descriptor codes, labeling data, and file tags. The master media, information architecture, contextual data, and user profile databases may be refined and appended based on feedback from the clients and thus be modified based on user input. The navigation system may be used to power various applications running on any device rendering media including a search, a recommendation, playlisting, internet community facilitation, stores, on-demand subscription services, and the like. FIG. 1A illustrates an example navigation system 100. As mentioned above, the system 10 may be deployed on any device that renders media (e.g., a portable media player, a vehicle media player such as a vehicle audio systems, etc.). The navigation system 100 may include a client 102 in the form of an application or a device. The client 102 may receive architecture information (e.g., selected category lists 122) from a plurality of descriptor systems 104.1-104.n that may be used to enable the client 102 to navigate content from a plurality of media sources 106.1-106.n (e.g., a radio station, a flash drive, an MP3 player . . . ) and/or a media service 108 (e.g., provided on a media player or by an online catalog) by use of a client application 110. The client application 110 may provide navigational access to content through a user interface 112. The user interface 112 may provide navigational information and other information to an end-user through a display device (e.g., on a device) or an application. Navigation templates 114 may access one or more descriptor hierarchies 116 available to the client 102 through the user interface 112 to provide one or more navigation views. Master descriptor code list 124 associated with content may be used to enable navigational access to the content (e.g., audio, video, or the like) by mapping it to selected descriptor category lists 122 that are contained within the descriptor hierarchies 116. The descriptor codes may describe an attribute an entity of a media item. The selected category lists 122 may be selected from the plurality of available category lists 132 contained within a plurality of the descriptor systems 104.1-104.n. In an example embodiment, the master descriptor code list 123 of the client may not include all master descriptor codes of the master descriptor code list 124 of a descriptor system 104.1. A descriptor system 104.1 includes a master descriptor code list 124 from which master descriptor code list 124 may be selected. The master descriptor code list 124 may include a list of a plurality of available master descriptor codes and associated names for a particular type of media descriptor. For example, the master descriptor code list 124 for a genre media descriptor may include coded identification of a greatest amount of granularity desired for genre. By way of example, the master descriptor code list 124 for genre may include, e.g., more than fifteen hundred different genres). For example, the master descriptor code list 124 may be a detailed genre list used for coding media items such as artists, albums, and recordings. The master descriptor code list 124 for a particular type of descriptor may optionally be given a unique identifier that may be used for identification. In an example embodiment, by linking the master descriptor code that is associated with the media items 134 to the corresponding master descriptor code in the master descriptor code list 124, the media item may be associated with the descriptor categories by mapping the media item to the master descriptor code. The most granular descriptor category list of the available category lists 132 may be referred to as the master descriptor category list. The master descriptor codes are mapped directly into the master descriptor category list, which may contain an equal or smaller number of categories than there are codes in the master descriptor code list 124. By maintaining the master descriptor category list separately from the other descriptor category lists, maintenance of the descriptor system 104.1 may be simplified. The mapping from the master descriptor code list 124 to each of the other descriptor category lists may not need to be directly updated as the mapping from the master descriptor category list to each of the other descriptor category lists may remain unchanged. The plurality of available category lists 132 (e.g., the descriptor category list) may include a number of levels of category lists as part of each descriptor system. Each category list may include a differing number of category codes and associated labels from the other category lists in the descriptor system. For example a category list at a first level may include five category codes and associated labels and at a second level may include twenty category codes and associated labels. The most granular level of the plurality of available category lists 132 may be referred to as a master descriptor category list. Each descriptor category code in each descriptor category list in each descriptor system may be mapped to its parent descriptor category code in the next less granular descriptor category List. A number of child category codes may be mapped to each parent category code. The mapping may have an indirect effect of mapping each master descriptor code to its appropriate parent category in every category list via the master descriptor category list, and mapping every category code to its appropriate parent and child category code in every non-adjacent category list. The mappings from the master descriptor codes to the descriptor category codes may also be stored directly. Each descriptor code may be a unique identifier. To enable data annotation by end-users, artists, venue/label/content/broadcast partners, internal experts or others using the more simplified category lists, rather than the highly granular master descriptor lists, mapping may be used. A one to one “downward” mapping 130 may be created and stored for each descriptor category. As the descriptor categories may generally be of more aggregate nature than many of the master descriptor codes, the descriptor categories may typically be mapped to the more aggregated master descriptor codes to ensure than only the level of information actually known is encoded. The user interface presented to the submitter may only display the applicable hierarchy of category lists, from which they select the annotation labels. Once selected, the item may be annotated with the mapped master descriptor code. For example, a venue operator may “publish” the music genres that are primarily associated with the venue, but do so by selecting from a simplified list of fifteen meta-genres. A descriptor system 104.1 may be created for each desired viewpoint. The viewpoints of the descriptor system 104.1 may be defined by a combination of regional, genre preference, psychographic, demographic and/or other factors that combine to define a preferred perception of the applicable descriptor types. Examples of viewpoints of descriptor systems 104.1 include North American Default, Japanese Classical Aficionado. South American, Youth, and Southern European Traditional. To provide for a more useful user interface 112, different descriptor systems 104.1-104.n may group the same master descriptor code list 124 into substantially different category arrangements. The grouping may enable the ability to substantially change the areas of category focus in different implementations while utilizing the same master descriptor codes. For example, a European genre descriptor system might include the genre “Chanson” in its shorter, more highly aggregated genre category lists, as a European end-user may desire quick access to music of this type, whereas for a North American genre descriptor system, the genre category might only be exposed at the lower levels, if at all, with content coded with “Chanson” master descriptor codes instead being included along with music from other related master genre codes in a genre category of “World”. A recognition module 125 may be further included in the client to recognize media items 134.1, 134.2. The recognition module 125 may optionally use a local database 127 and/or a remote database 129 to perform look and/or obtain metadata for the media items 134.1, 134.2. An example embodiment of a method for recognizing the media items 134.1, 134.2 that may be performed at the recognition module 125 is described in greater detail below. FIG. 1B illustrates another example of a navigation system 131 in which a client may be deployed. The navigation system 131 may include a client 135 that may have access to media objects 138.1 from one or more media sources 133 and media objects 138.2 from one or more media services 136. The media objects 138.1 may be associated with entity types 140.1, while the media objects 138.2 may be associated with the entity types 140.2. The media objects 138.1, 138.2 may be accessed through an indexing module 144 by a local information architecture 142. The media objects 138.1, 138.2 may be recognized by use of a recognition module 146. The recognition module 146 may use a local media object lookup database 148 to identify the media objects 138.1, 138.2 to assemble a local metadata database 150 of metadata for the media objects 138.1, 138.2. The recognition module 118 may also, instead of or in addition to the local lookup, perform a remote lookup by contacting a recognition service 170. The recognition service 170 may use a master media object lookup database 172 to identify the media objects 138.1, 138.2 and a master media metadata database 174 to obtain metadata for the media objects 138.1, 138.2. The local information architecture 142 may be used by a navigation system application 160 to configure various navigational views as described in greater detail below. The navigation system application 160 may configure the navigational views according to a personalization module and/or a contextualization module. Hierarchies 152 and navigation trees 154 may be generated from the local information architecture 142 and used to provide the navigational views. The hierarchies 152 and the navigation trees 154 may optionally be stored and available for later retrieval. A navigation API 162 may be used to provide access to the navigation system application 160. One or more contextual data feeds and/or sensors may be used to provide contextual data through the navigation API 162 to the navigation system application 160. Personalized data may also be received from a master user profile database 194 by use of a personalization service 192. A navigational update module 156 may be used to update the local information architecture 142. The navigation update module 156 may optionally use one or more IDs 158 which may identify a build ID, a device ID, an application ID, a customer ID, a region ID, a taste profile ID, a user type ID, a client ID, and/or a user ID to receive the appropriate updates for the local information architecture 142 as deployed. A navigation service 176 may provide updated information to the navigation update module 156. The navigation service 176 may obtain information used for navigation (e.g., navigational content) from one or more descriptor systems 178 and navigational content from a master navigation content object store 180, utilizing a navigational content metadata database 182. The navigational content may be provided to aid in navigation and may include, by way of example, audio clips, media packaging images, text, genre icons, genre mini-clips, genre descriptions, origin icons, origin descriptors, channel icons, phonetic data, and the like. One or more navigation templates 184 may be accessed by the navigation service 176. The navigation templates 184 may enable differing navigational views into one or more descriptor hierarchies 152 available to the client 135 through the user interface 168. One or more navigation templates 184 may be accessed by the navigation service 176. The navigation templates 184 may enable differing navigational views into one or more descriptor hierarchies 152 available to the client 102 through the user interface 138. Descriptor codes associated with content in the local metadata database 150 may be used to enable navigational access to the content by mapping content to selected category lists that are contained within the descriptor hierarchies 152. The selected category lists may be selected from the plurality of available category lists contained within a plurality of the descriptor systems 178. The plurality of available category lists may include a number of levels of category lists. Each category list may include a differing number of category codes and associated labels. For example, a category list at a first level may include five category codes and associated labels and at a second level may include twenty category codes and associated labels. FIG. 2 illustrates an example configuration system 200. The configuration system 200 may be used to create one or more hierarchies 116 from the descriptor systems 104.1-104.n for use in the navigation system 100 (see FIG. 1). The configuration system 200 includes a configuration application 202 in which a configuration module 216 may communicate with one or more master media sources 204 and a reference media database 206. The configuration application 202 may utilize one or more master descriptor code lists 124.1-124.n for content (e.g., media items) available through the master media sources 204. A master code descriptor list 124.1 of the master descriptor code lists 124.1-124.n may be provided to a plurality of descriptor systems 208, 210, 212. The configuration application 202 may also create a descriptor hierarchy 214 from an original descriptor system 208 or an alternate viewpoint descriptor system 210. From each of these, an alternate label and/or a translated language descriptor system 212 may also be created. The original descriptor system 208 includes the master descriptor code list 124 (see FIG. 1), third party descriptor label mappings, third party descriptor ID mappings, master category lists 126, other category lists, system mapping tables 228, and ordering value data 230. The third party label and identifier mapping tables may associate third party labels (e.g. genre label “R&R”) or IDs (e.g. ID3 Genre tag #96) with the appropriate master descriptor code. 3rd party mapping tables associate descriptor term labels and descriptor term unique identifiers utilized externally to the most appropriate master descriptor code for each applicable descriptor type. If more than one 3rd party system uses an identical descriptor label, this one label may be mapped to the single “best-fit” master descriptor code, or alternatively, the system may store a 3rd party organization ID with each instance of a descriptor label, such that it is possible to support alternate mapping form 3rd party descriptor to master descriptor code, depending on the source, as indicated by the 3rd party entity identifier. In the case of mapping 3rd party descriptor unique identifiers, it is always necessary to include the 3rd party organization ID. External descriptor labels do not have to be associated with a specific entity; they may represent colloquial expressions. The ordering value data 230 may optionally be associated with the category lists 126 of the descriptor systems 208, 210, 212. The ordering values for each of the categories indicate an order in which the labels of a category list may be presented in the user interface 112 (see FIG. 1). For example, the ordering values may be based on judgmental similarity, judgmental importance, judgmental chronological, and the like. The labeled hierarchy 210 may be assembled from a specific descriptor system 208 with specific labels associated with each category ID. The labeled hierarchy 210 includes the master descriptor code list 124, labeled category lists 224, the system mapping tables 228, and the ordering value data 230. The alternate master category lists 224 may include one or more alternate labels for the category lists contained in the master category lists 126. For example, the alternate labels may include nicknames, short names, and the like. The translated hierarchy 212 is a version of a labeled hierarchy 210 with translated labels (e.g., in Spanish, Japanese, and English). The localized language descriptor system. The translated hierarchy 212 includes the master descriptor code list 124, translated labeled category lists 226, the system mapping tables 228, and the ordering value data 230. The category list ordering data 234 may enable one or more alternate orderings of the category lists of the descriptor hierarchy 214. The third party mapping tables 236 (e.g., tables provided by a third party content provider) may associate descriptor terms and unique identifiers used by third parties to the master descriptor codes contained in the master descriptor code list 124. For example, a third party descriptor term may be mapped to a master descriptor code to which it is most similar. Thus discrepancies in terminology used may be accommodated. The descriptor relational tables 238 relate master descriptor codes with other master descriptor codes in the master descriptor code list 124. The relations may be defined by a correlation value or a weighting for each relationship. The entity hierarchies 240 define the parent/child relationship between at least some of the entity types. An example of an entity item hierarchy is as follows: Series <-> Album <-> Edition <-> Release <-> SKU <-> Disc <-> Track <-> Recording <-> Movement <-> Composition. FIG. 3 illustrates an example navigation template 300. The navigation template 300 may be used by a navigation service to select the appropriate elements to be included in a navigation package. The client may utilize these elements to assemble navigation views for navigating content from one or more media sources 106.1 -106.n and/or the media library 108 (see FIG. 1). The navigation template 300 may include a template ID 302, a region 304, one or more application parameters 306, one or more device parameters 308, a user type 310, one or more third party IDs 312, and/or one or more navigation trees 314. The region 304 may define the regional viewpoint that is used to select the appropriate descriptor systems and other navigational elements such that they can be assembled into a user interface that conforms to the cultural expectations of a specific regional user base. For example, the selection of the region may include the United States, Germany, Brazil, Japan, Korea, the Middle East, China, global, Eurasia, America, and/or Asia, U.S. East Coast, New England States, Chicago, and the like. Other regions may also be available for selection. The region 304 may define the regional viewpoint that is used to select the appropriate descriptor systems and other navigational elements such that they can be assembled into a user interface that conforms to the cultural expectations of a specific regional user base. For example, the selection of the region may include the United States, Germany, Brazil, Japan, Korea, the Middle East, China, global, Eurasia, America, and/or Asia, U.S. East Coast, New England States, Chicago, and the like. Other regions may also be available for selection The one or more application parameters 306 indicate the application type (e.g. media player, a web site, a playlist generator, a collection manager, or other application) in which the navigation package may be deployed. For example, the application parameters 306 may cause alternate category labels to be made selected such as short names, standard names, or extended names. The one or more device parameters 308 specify the device in which the navigation package may be deployed. For example, the device parameters 308 may indicate whether the device is a PC, a home media server, a vehicle stereo, a portable media player, a mobile phone, a digital media adapter, a connected CD/DVD/flash player, a remote control, and the like. The user type 310 may identify a type of user that may use the deployment of the navigation template 300 in the client 102. For example, the user type may identify a user of the navigation template 300 as a basic user, a simple user, a standard user, an advanced user, or a professional user. Other user types may also be used. The one or more third party IDs 312 may identify third parties associated with a deployment of the navigation template 300. The third party IDs may be associated with third party customers and/or partners that have IDs (e.g., unique IDs) that define their navigational preferences for the end-user, as well as IDs of third parties whose labels or IDs may need to be mapped via the appropriate third party mapping tables. The one or more navigation trees 314 may be a sequence of category lists taken from selected category lists 122 and/or entity types to be available for constructing elements of the user interface 112 based on the selection of the application parameters 306, the device parameters 308, the user type 310, and/or the other third party IDs 312. The navigation trees 314 may also include an ordering of items in a category list. The list ordering definition may include a judgmental unique ordering, alphabetical, dynamic item count, a dynamic popularity, or the like. FIG. 4 illustrates example information architecture 400. The information architecture may be deployed in the client 102 (see FIG. 1) and/or in other applications and devices. The information architecture 400 may include one or more descriptor hierarchies 116, one or more navigation trees 314, one or more other category lists 406, default mappings 408, one or more descriptor relation tables 238, and/or navigational content 120 (see FIGS. 1-3). The other category lists 406 may selected from one or more descriptor hierarchies 116 not included in the information architecture 400. The default mappings 408 may be used in the information architecture 400 to enable mapping of legacy descriptors IDs (e.g., from a provide or a third party) and/or to perform third party descriptor label mapping. Other configurations of the information architecture 400 including different elements may also be deployed in the client 102. FIG. 5 illustrates a method for pre-processing content to enable deployment of the information architecture 400 (see FIG. 4) in the client 102 (see FIG. 1) for navigation of the content in accordance with an example embodiment. The reference media database 206 may be created at block 502. Upon creation, the reference media database 206 may include the plurality of master descriptor code lists 124.1-124.n. An example embodiment of creating the reference media database 206 is described in greater detail below. Information architecture 400 (see FIG. 4) may be created at block 504. An example embodiment of creating the information architecture 400 is described in greater detail below. A navigation template 300 (see FIG. 3) may be defined at block 506. An example embodiment of defining a navigation template is described in greater detail below. FIG. 6 illustrates a method 600 for creating a reference media database 206 (see FIG. 2) according to an example embodiment. In an example embodiment, the method 600 may be performed at block 502 (see FIG. 5). The reference media database 206 created through the operations of the method 600 may be used in the configuration system 200; however it may also be used in other systems. Media descriptors may be associated with a plurality of entities at block 602. The plurality of entities may be from a single media source 106.1 (e.g., from a single content provider or fixed disk), the plurality of media sources 106.1-106.n, and/or the media library 108 (see FIG. 1). For example, the entities may include a channel, a stream, a station, a program, a slot, a playlist, a web page, a recording artist, a composer, a composition, a movement, a performance, a recording, a recording mix track, a track segment, a track, a release, an edition, an album, an album series, a graphic image, a photograph, a video segment, a video, a video still image, a TV episode, a TV series, a film, a podcast, an event, a location, and/or a venue. Other entities may also be used. The media descriptors may use an identification (ID) code to identify a characteristic of an entity with which it is associated. For example, the ID code used with the media descriptors may include a genre ID code, an origin ID code, a recording era ID code, a composition era ID code, an artist type ID code, a tempo ID code, a mood ID code, a situation ID code, a work type ID code, a topic ID code, a personal historical contextual IDs, a community historical contextual ID code, a timbre ID code, and the like. Other ID codes may also be used with the media descriptors to identify characteristics of entities. Each of a particular type of ID code may be associated with a single master descriptor code list 124. For example, the genre ID codes may be on a genre master descriptor code list where each genre ID code is associated with a genre label, and the mood ID codes may be on a mood master descriptor code list where each mood ID code is associated with a mood label. A particular entity may be associated with a plurality of media descriptors. One or a plurality of media descriptors with a same type of code (e.g., a genre ID code) may be associated with an entity. The media descriptors may optionally be given a ranking and/or weighting to indicate their relevance among other media descriptors. For example, an album may be associated with a primary media descriptor of blues and a secondary media descriptor of rock, where the primary media descriptor is ranked higher than the secondary media descriptor. A determination of which media descriptors to associate with an entity may optionally be based on information received from one or more data sources. For example, the data sources may include content information received from providers (e.g., label data feeds and/or content registries), expert editorial information, individual community submissions, collaborative community submissions, digital signal processing (DSP) analysis, statistical analysis, and the like. One or more flags may optionally be associated with one or more entities of the plurality of entities at block 604. The flags may be used to identify a certain type (e.g., a special type) of entity that may receive special handling during navigation. For example, a flag may be used to indicate that an entity is a various artist compilation, a soundtrack, a holiday related theme (e.g., Christmas), an interview, and/or a bootleg recording. Other types of flags may also be used to identify other certain types of entities that may receive special handling during navigation. Inheritance may be applied to the plurality of entities at block 606. Applying inheritance to the plurality of entities may enable access for at least some of the plurality of entities to selected media descriptors associated with one or more other entities. Inheritance may optionally be used to reduce an amount of media descriptors associated with a plurality of entities based on the relationship among the entities. The use of inheritance may provide greater efficiency and/or scalability of the reference media database 206. By way of an example, a set of media descriptors may be associated with a recoding artist. For an album of the recording artist where the media descriptors differ from the set of media descriptors associated with the recording artist, a set of media descriptors may be associated for the album. When the individual recordings of the artist differ from that of an album on which the recordings were recorded, a set of media descriptors may be associated with the individual recordings. If one or more individual segments of a recording differ from a parent recording, a set of media descriptor may be associated with the individual segments. Inheritance may be applied to entities in a cascading down manner (e.g., cascading down inheritance) to provide for inheritance from a parent and/or in a cascading up manner (e.g., cascading up inheritance) to provide for inheritance from a child. Inheritance may be applied in a cascading down manner when a child entity does not have directly associated media descriptors. The child entity may then inherit the media descriptors associated with a parent entity. For example, if a genre ID code is associated with a recording artist and an album does not have an associated genre ID code, the album may inherit the genre ID code of the recording artist. If a recording on the album does not have an associated genre ID code, the recording may inherit the genre ID code of the album. Inheritance may be applied in a cascading up manner when a parent entity does not have directly associated media descriptors. The parent entity may then inherit the media descriptors associated with a child entity. For example, if a genre ID code is associated with one or more recordings and an album containing the recordings does not have associated genre ID code, the album may inherit the genre ID code associated with the most common genre ID code from its recordings. If an artist who recorded a plurality of recordings has not been associated with a genre ID code, the artist may inherit the most common genre ID code associated with albums associated with the artist. An additional mapping may be created for the reference media database 206 at block 608 to provide for an additional association among at least two entities of the plurality of entities. For example, an alternate artist billing may be mapped to a primary artist ID code and/or an individual artist ID code may be mapped to a collaboration artist ID code. Other additional mappings may also be created. The reference media database 206 may optionally be stored at block 610. The reference database 206 may include the association of the media descriptors with a plurality of entities, the association of a flag with the selected entities of the plurality of entities, applied inheritance to the plurality of entities, and/or the additional mapping among at least two entities of the plurality of entities. FIG. 7 illustrates a method 700 for creating an information architecture 400 (see FIG. 4) that may be deployed in a client 102 (see FIG. 1) according to an example embodiment. In an example embodiment, the method 700 may be performed at block 504 (see FIG. 5). A descriptor hierarchy 116 (see FIG. 1) may be created at block 704. The descriptor hierarchy 116 may be created by selecting from a plurality of available category lists 132 of a corresponding descriptor type and mappings from the upward mapping 128 and/or downward mapping 130 associated with the selected category lists 232. The descriptor system 104 thereby may act as having a superset of available category lists 132 from which the selected category lists 232 of the descriptor hierarchy 116 are selected.122. A descriptor hierarchy 116 (see FIG. 1) may be created at block 704. The descriptor hierarchy 116 may be created by selecting from a plurality of available category lists 132 of a corresponding descriptor type and mappings from the upward mapping 128 and/or downward mapping 130 associated with the selected category lists 232. The descriptor system 114 thereby may act as having a superset of available category lists 132 from which the selected category lists 232 of the descriptor hierarchy 116 are selected. 122. A plurality of descriptor hierarchies 116 may be created for a particular descriptor type from one or more descriptor systems 104.1-104.n (e.g., an original descriptor system 208, an alternate language descriptor system 210, and/or a localized language descriptor system 212). Two or more of the multiple descriptor hierarchies 116 may be linked together (e.g., through pointers) to facilitate version selection during viewing. The category list ordering data 234 may be created at block 706. The category list ordering data 234 may enable one or more alternate orderings of the selected category lists 122 of the descriptor hierarchy 214. Third party mapping tables 236 may optionally be created at block 708. The third party mapping tables 236 may associate descriptor terms used by third parties to the master descriptor codes contained in the master descriptor code list 124. Descriptor relation tables 238 may be created at block 710. In an example embodiment, the descriptor relation tables 238 may be created at a macro and micro level. At a macro level, a macro level correlate list may define correlation levels for the items on a single category list. At a micro level, correlation levels may be defined between master descriptor codes. The micro level may then be mapped to the macro level to create the descriptor relation tables 238. The entity hierarchies 240 may be created at block 712. The information architecture 400 created during the operations at blocks 702-712 may optionally be deployed in the client 102 at block 714. FIG. 8 illustrates a method 800 for creating a descriptor system 104 that may be deployed in the navigation system 100 (see FIG. 1) or another system according to an example embodiment. The created descriptor system 104 may be accessed during the operations at block 702 (see FIG. 7). A master descriptor code list 124 (see FIG. 1) may be generated at block 802. A media descriptor for which the master descriptor code list 124 may be generated may include, but is not limited to a genre media descriptor, an origin media descriptor, a recording era media descriptor, a composition era media descriptor, a time cycle media descriptor, an artist type media descriptor, a tempo media descriptor, a mood media descriptor, a situation media descriptor, or a topic media descriptor. A descriptor system 104 may be generated from the master descriptor code list 124 at block 804. The descriptor system 104 is generated to include a plurality of available category lists 132. The available category lists 132 of the descriptor system 104 may be generated to include summarized versions of the master descriptor code list 124 with decreasing or increasing granularity. The summarized versions of the master descriptor code list 124 may include a lesser number of list entries. The amount of list entries in a category list of the descriptor system 104 and the number of category lists in the descriptor system 104 may be selected to provide flexibility when selecting a number of category lists for deployment as a hierarchy 116 as described in greater detail below. Each category list may optionally be provided with a unique identifier. A plurality of descriptor systems 104.1-104.n may optionally be created for a particular descriptor type, where each descriptor system 104 of the particular descriptor type may have a different number of category lists and each category list may include a different number of list entries. For example, a plurality of descriptor systems 104.1-104.n may be created for different region focuses (e.g., a global descriptor system, a US descriptor system, a Japan descriptor system, etc.), different genre focuses (e.g., general descriptor system, classical descriptor system, internal descriptor system, etc.), different mood focuses (e.g., smooth, excited, reflective, etc.) or the like. Master descriptor codes may be mapped to a master category list 222 of the descriptor system 104 at block 806. The master category list 222 may be the category list of the descriptor system with the highest granularity (e.g., number of list entries). When the master category list 222 of a descriptor system is not a master list, more than one descriptor code may be mapped into a category code of a same list entry. The category lists of the descriptor system 104 may be mapped to one another at block 808. The category codes of the category lists may be mapped to a category code of a parent category list (e.g., a less granular category list) in the descriptor system. The category codes of a parent category list may include one or more mappings from a category code of a child category list. An alternate label version of the descriptor system 104 (e.g., the alternate language descriptor system 210) may be created at block 810. The alternate language descriptor system 210 may include the same category lists of the original descriptor system on which the alternate version is based, but contain the alternate master category lists 224 with an alternate language label substituted for some or all of the category names of the master category lists 222. The alternate language labels may include abbreviated names, short names, extended names, and the like. Multiple alternate language label versions of an original descriptor system 208 may be created. A localized label version of the descriptor system 104 (e.g., the localized language descriptor system 212) may be created at block 812. The localized language descriptor system 212 may include a different label based on localization. For example, a localized label version of the descriptor system 104 may be in Japanese, Korean, German, French, and/or other different languages. A localized label version may be created for an original descriptor system 208 and/or the alternate language descriptor system 210. Ordering value data may optionally be associated with the category lists of a descriptor system at block 814. The information may then be deployed as a descriptor system 104 at block 816. FIG. 9 illustrates a method 900 for defining a navigation package that may be deployed in a client 102 (see FIG. 1) according to an example embodiment. A determination of a template selection for inclusion in a navigation package may be made at decision block 902. The determination may be made from explicit input, presence, data received from a geolocation service, dynamically, or the like. The template selection may be for a selection of a pre-built template at block 904, a dynamically generated template at block 906, or a manually configured template at block 908. The pre-built template that may be selected at block 904 may be a navigation profile based on a common use case. The pre-built template may identify included descriptor hierarchies 116 and other information architecture elements that are associated with the template. The pre-built template may include a unique identifier to enable selection among other available templates. Examples of pre-built templates include pre-built templates for a basic user in the European market that plays classical music in a car using a media player, and a pre-built template for an advanced user in the Japanese market that plays music on a personal computer using a media player. Other pre-built templates may also be available for selection. The dynamically generated template that may be selected at block 906 may be a template dynamically generated as needed based on use case parameters. The template may be dynamically generated by input regions and/or markets for deployment, taste/demographics/psychographic profiles(s), application and/or device type, user type, and/or customer/partner preferences. An example embodiment of dynamically generating a template is described in greater detail below. The manually defined template that may be selected at block 908 may be manually defined based on a use case. For example, the manual selection may include: A number of levels (e.g., category lists) from the descriptor system 104 for a descriptor hierarchy 116, Which category lists are used at each level of the descriptor hierarchy 116; Default and/or alternate languages, Label alternate terms, Label formatting alternatives (e.g., short names, full names, etc.), Text term mappings to master codes and other mappings, Navigational content 120, and/or Navigation trees 314. Upon completion of the selection at block 904, block 906, or block 908, a determination may be made at decision block 910 whether to make another template selection for the navigation package. If a determination is made to make another template selection, the method 900 may return to decision block 902. If a determination is made not to make another selection at decision block 910, the method 900 may proceed to block 912. Descriptor hierarchies 116, mappings and navigational content 120 corresponding to the selected templates may be associated with the navigation package at block 912. Other lists may be associated with the navigation package at block 914. The other lists may include category lists not contained within the descriptor hierarchies 116. FIG. 10 illustrates a method 1000 for dynamically generating a navigation template 300 (see FIG. 3) for use in a navigation path according to an example embodiment. In an example embodiment, the method 1000 may be used to dynamically generate a template during the operations performed at block 906 (see FIG. 9). A region for deployment may be selected at block 1002. The selection of the region may be used in determining which descriptor systems 104.1-104.3 will be used by the navigation template 300 and the default and/or alternate language labels that will be used to label the descriptor hierarchy 116. The selection of the region may also be used in determining which navigational content parameters may be used. For example, the navigational content parameters may include basic, audio, graphic, voice, or advanced settings. The selection of the region may be used in determining which text terms may be use in a mapping set. For example, slang terms, regional dialect terms, professional terms, and the like may be used as text terms in the mapping set. Personal profile parameters may be selected at block 1004. The personal profiles may include a taste profile, based on age, based on sex, based on historical information, explicit input, and the like. The taste profile may be a classical view, an electronica view, a boomer view, a generation X view, and the like. The selection of the personal profile may be used in determining which taste profile variation may be selected. For example, the taste profile variation may be used in determining which view of the descriptor system 104 may be made. The selection of the personal profile may also be used in determining alternate label terms selected for labelling of the descriptor hierarchy 116. For example, the alternate labelling may include slang labels, regional dialect labels, informal labels, old school labels, and the like. The selection of the personal profile may be used to determine which navigational content parameters and the related content parameters. For example, the related content parameters may include basic, audio, graphic, voice, or advanced settings. The selection of the personal profile may also be used determining the text terms for a mapping set. Application parameters 306 (see FIG. 3) may be selected at block 1006. The selection of the application parameters may be used in determining a number of levels (e.g., a number of category lists) to include in a hierarchy system and label formatting parameters. Device parameters 308 (see FIG. 3) may be selected at block 1008. The selection of the device parameters may be used in determining a number of levels (e.g., a number of category lists) to include in a hierarchy system, the length of category lists used at each level of the category list, and label formatting parameters. For example, the category list at each level may be twenty for a single level, ten and seventy-five for two levels, twenty-five, two hundred and fifty, and eight hundred for three levels, and five for each of four levels. The selection of the device parameters may also be used in determining the related content parameters. A user type 310 (see FIG. 3) may be selected at block 1010. The selection of the user type may be used in determining the length of category lists used at each level of the category list. Third party IDs 312 (see FIG. 3) may optionally be selected at block 1012. The selection of one or more third party IDs 312 may be used in determining which partner mapping selection may be used. An identifier may be associated with a navigation tree 314 at block 1014. The navigation tree 314 may include a sequence of category lists that may be taken from selected hierarchies and/or entity types to be available for constructing UI elements based on the selection of application parameters, device parameters, user type, and/or other unique IDs. Upon completion of the selections from the operations of blocks 1002-1012, a navigation template may be definable based on the selections that were made. A unique identifier may optionally be associated with one or more navigation trees at block 1014. A template ID 302 (see FIG. 3) may be generated at block 1016. The identifier (e.g., a unique identifier) may be generated and stored based on the combination of the selected attributes of the navigation template 300. Unique IDs for the component attributes and the navigational profiles that drive the component attributes may also be associated with the identifier of the navigation template 300. In an example embodiment, current updated version of corresponding descriptor hierarchies 116, the mappings 236 and the navigational content 120 may be retrieved based on the parameters in the navigation template. Other lists may also be retrieved for the use case. Upon completion of the method 1000, a navigation package including default hierarchies 214, alternate hierarchies 214, mapping tables and navigational content 120 appropriate for the use case may be available for deployment. FIG. 11 illustrates a method 1100 for coding descriptor codes in media objects according to an example embodiment. The media objects may be media available from the media sources 106.1-106.n and/or the media library 108 (see FIG. 1). A determination may be made at decision block 1102 whether to code a media object (e.g., a media item). If a determination is made to code the media object, the media object may be embedded during production at block 1104 and/or during encoding at block 1106. Identifiers and/or master descriptor codes may be embedded (e.g., as metadata containers) in media objects during production (e.g., during product and/or post-production) at block 1104. The embedded data may optionally be encrypted or otherwise obfuscated. The master descriptor codes may be associated with one or multiple entities of the media object. Unique identifiers and/or master descriptor codes may be associated with media objects during encoding (e.g., during encoding and/or other processing step as part of distribution) at block 1106. Examples of identifiers that may be embedded during the operations at block 1104 or associated at block 1106 include DDEX, GRID, MI3P ID, UPC, EAN, ISRC, ISWC, DOI ID, commercial IDs, public IDs (e.g., FreeDB), proprietary recording ID, proprietary album ID, or a proprietary composition ID. Other unique identifiers may also be embedded and/or associated. If a determination is made not to code the media object at decision block 1102 or upon completion of the operations at block 1104 and/or block 1106, the method 1100 may proceed to decision block 1108. At decision block 1108, a determination may be made code another media object. If a determination is made to embed another media object, the method 1100 may return to decision block 1102. If a determination is made not to embed another media item at decision block 1108, the media objects may be delivered at block 1110. The media objects may be delivered with any metadata that has been embedded or associated. The delivery methods for providing the metadata with the media objects may include as part of a media object's exposed predefined tag field, in a proprietary tag field, as a watermark, as MPEG-7 data, as MPV or HiMAT Tag, in an FM sideband (e.g. RDS), in a satellite radio data channel, in a digital radio data channel, or in an Internet radio data stream (e.g. MPEG ancillary data). Other delivery methods may also be used. FIG. 12 illustrates a method 1200 for preloading a client 102 (see FIG. 1) according to an example embodiment. A media collection may be pre-loaded on the client 102 at block 1202. The media collection may be pre-loaded prior to use by an end-user. The media collection may be the same for all of a number of units, a finite set of target libraries geared for a specific genre, regional, lifestyle, or other interest, or may be personalized based on a personal profile of an end-user. The media collection may include audio files, video files, image files, and the like. Customer related content and information architecture elements may be ingested by the client 102 at block 1204. Related content may be pre-loaded (e.g., prior to use by an end-user) on the client 102 at block 1206. The related content may include the navigational content 120 and/or other content. The other content may include album cover art, artist photos, concert posters, text artist factoids, lyrics, channel/station logos, and the like. The information architecture 400 (see FIG. 4) may be pre-loaded at block 1208. The information architecture may be made locally accessible and subject to customization based on the template ID 302 (see FIG. 3). The template ID 302 may be stored on the client 102 for future use. The preloaded information architecture 400 may include genre hierarchies, era hierarchies, origin hierarchies, navigation trees 404, mappings 236, ordering data, and station/channel directories. FIG. 13 illustrates a method 1300 for loading an information architecture 400 (see FIG. 4) according to an example embodiment. A request may be received for a navigation package including an information architecture 400 at block 1302. The request may also be made by obtaining a device ID, generating a default template ID using the device ID, and/or issuing a request for a navigation package from the default template ID. Other methods for requesting the navigation package may also be used. Predefined descriptor hierarchies 116 may be accessed at block 1304. A default descriptor hierarchy 116 and optionally alternate descriptor hierarchies 116 may be accessed for use in the information architecture 400. The descriptor hierarchies 116 may optionally be accessed based on the template ID 302. The alternate hierarchies 116 may be accessed from one or more different descriptor systems 104.1-104.n. By way of example, the predefined descriptor hierarchies 116 that may be accessed include one predefined and one or several alternate genre hierarchies, a predefined and alternate origin hierarchies, a predefined and alternate artist type hierarchies, a predefined and alternate recording era hierarchies, a predefined and alternate composition era hierarchies, a predefined and alternate composition mood hierarchies, a predefined and alternate temp or rhythm hierarchies, a predefined and alternate composition theme/topic hierarchies, and the like. Predefined navigation trees 314 may be accessed at block 1306. A default and optionally alternate navigation trees may be accessed for use in the information architecture 400. The navigation trees 314 may be accessed from one or more descriptor systems 104.1-104.n. The navigation trees may optionally be accessed based on the template ID 302. By way of example, the navigation trees 314 may include genre/era/track, genre/mood/tempo/recording, artist/mood/year/track, and genre/album/mood/track. Other navigation trees 314 may also be used. Other category lists 406 may be accessed at block 1308. The other category lists 406 may be used to generate alternate navigation trees 314, descriptor hierarchies 116, faceted navigation, or other local navigation options that have not been pre-defined. In an example embodiment, a descriptor system 104 may be retrieved to provide increased flexibility. By way of example, the other category lists 406 may include a selected genre category list from a genre descriptor system, a selected origin category list from an origin descriptor system, a selected artist type category list from an artist type descriptor system, a selected recording era category list from a recording era descriptor system, a selected composition era category list from a composition era descriptor system, a selected mood category list from a mood descriptor system, a tempo category list from a tempo descriptor system, a selected theme/topic category list from a theme/topic descriptor system, and the like. The selected category lists may be supported by the client. The default mappings 408 may be accessed at block 1310. The descriptor relational tables 238 may be accessed at block 1312. A filter may optionally be applied to the descriptor relational tables 238 that are accessed to obtain relational data for relationships with weightings above a threshold level. Navigational content 120 may be accessed at block 1314. The default navigational content may be accessed using a navigational content ID. The accessed material may then be loaded in the client 102 as the information architecture 400 at block 1316. FIG. 14 illustrates a method 1400 for coding media items according to an example embodiment. The media items 134 may be coded when a media collection is initially provided and/or during a media collection update on the client 102. Media items may be provided at block 1402. The media items may be loaded and/or transmitted into the client 102. An example embodiment of providing media items is described in greater detail below. The provided media items may be identified (e.g., through recognition) at block 1404. An example embodiment of recognizing the provided media items is described in greater detail below. The media items may be mapped to entities at block 1406. An example embodiment of mapping media items to entities is described in greater detail below. Codes and content IDs may be received for the entities at block 1408. An example embodiment of receiving codes and content IDS is described in greater detail below. Indices may be created at block 1402. The index may be into a unified data system. The index may physically reside on the client, on another client in a local network, on a remote server, or distributed across more than one client. The indices may be created dynamically based on a client ID a user ID, and/or a combination of one or more parameters indicating a type of indexing that is relevant for a particular user. The indices may optionally indicate which one or more users are associated with a media collection. FIG. 15 illustrates a method 1500 for loading content from a plurality of sources according to an example embodiment. A determination may be made at decision block 1502 whether to load content from a service/directory or from a device. The content may include media objects in a variety of forms including audio, video, image, text, and spoken word audio. For example, the formats of the media objects may include WAV, MP3, AAC, WMA, OggVorbis, FLAC, analog audio or video, MPEG2, WMV, QUICKTIME, JPEG, GIF, plaintext, MICROSOFT WORD, and the like. The content may be loaded from a variety of media including, by way of example, optical media such as audio CD, CD-R, CD-RW, DVD, DVD-R, HD-DVD, Blu-Ray, hard disk drive (HDD) and other magnetic media, solid state media including SD, MEMORY STICK, and flash memory, stream, and other IP or data transport. The content may reside locally or be available through a tether using connections such as LAN, WAN, Wifi, WiMax, cellular networks, or the like. The media objects may be taken from a variety of objects including an intra-media item segment, a media item (e.g., audio, video, photo, image text, etc.), a program, a channel, a collection, or a playlist. If a determination is made to load from a service/directory, one or more media items may be loaded from the service/directory at block 1504. The service/directory may include local content, AM/FM/HD radio, satellite radio, Internet on-demand and streaming radio, web page, satellite and cable TV, IPTV, RSS and other web data feeds, and other web services. If a determination is made to load from a device, one or more media items may be loaded from the device at block 1506. The devices may include, by way of example, a PC, a home media server, an auto stereo, a portable media player, a mobile phone, a PDA, a digital media adapter, a connected CD/DVD/Flash player/changer, a remote control, a connected TV, a connected DVD, in-flight entertainment, or a location based system (e.g., at a club, restaurant, or retail). Other devices may also be used. Upon completion of the operations at block 1504 and/or 1506, a determination may be made at decision block 1508 as to whether additional media items may be loaded. If additional media items may be loaded, the method 1500 may return to decision block 1502. If no additional media items may be loaded at decision block 1508, the method 1500 may terminate. FIG. 16 illustrates a method 1600 for content recognition according to an example embodiment. In an example embodiment, the method 1600 may be performed at the block 1404 (see FIG. 14). A determination may be made at decision block 1602 as to how identifier recognition may be performed on content. Identifier recognition may be performed by extracting the identifiers from the content at block 1604, recognizing the content using one or more techniques at block 1606, performing a lookup using a mapping table at block 1608, and/or utilizing an embedded or associated identifier with the content at block 1610. An example of a digital fingerprint technique that may be used during the operations at block 1606 to identify digital content is robust hashing. For example in mono audio, a single signal may be sampled. If the audio is stereo, either hash signals may be extracted for the left and the right channels separately, or the left and the right channel are added prior to hash signal extraction. A short piece or segment of audio (e.g., of the order of seconds), may be used to perform the analysis. As audio can be seen as an endless stream of audio-samples, audio signals of an audio track may be divided into time intervals or frames to calculate a hash word for every frame. However, any known technique that may used to identify content from a segment or portion of content (e.g., the actual audio content or video content) may be also used. Thus, in an example embodiment, the content may be identified independent of any watermark, tag or other identifier but rather from the actual content data (actual video data or actual audio data). The embedded and/or associated identifiers that may be used in performing a lookup using a mapping table at block 1608 may include a UPC, an ISRC, an ISWC, a GRID/MI3P/DDEX, a third party ID, a SKU number, a watermark, HiMAT, MPV, and the like. Upon completion of the operations at block 1604, block 1606, 1608, and/or 1610, a determination may be made at decision block 1612 whether to perform text analysis recognition. If a determination is made to perform text analysis recognition, a text match of entity names may be performed at block 1614 and/or mapping tables may be utilized at block 1616. The text match of entity names to a more normalized entity ID at block 1614 may include artist name, album name, alternate spellings, abbreviations, misspellings, and the like. The mapping tables may be utilized at block 1616 to map available textual descriptors from an available entity (e.g., album, artist, or track) to a normalized descriptor ID. The available textual descriptors may include a genre name text, a mood name text, a situation name text, and the like. If text analysis recognition is not to be performed or upon completion of the operations at block 1614 and/or block 1616, the most granular descriptive data may be accessed at block 1618. The most granular descriptive data may be embedded in a media item and/or may be retrieved from the database of descriptors associated with the identifier. The most authoritative descriptive data may be accessed at block 1620. The most authoritative descriptive data may be embedded in a media item and/or may be retrieved from the database of descriptors associated with the identifier. Higher level descriptors may optionally be created at block 1622. The higher level descriptors may be created by extracting features, and classifying and creating one or more mid-level or high-level descriptors. A taste profile may optionally be generated at block 1624. The taste profile may be generated by summarizing the media collection and using the summary to generate the taste profile (e.g., a preference of a user of the client 102). FIG. 17 illustrates a method 1700 for mapping content IDs according to an example embodiment. In an example embodiment, the method 1700 may be performed at block 1406 (see FIG. 14). Media identifiers may be mapped to entities at block 1702. The media identifiers may optionally be mapped to normalized, semantically meaningfully core entities. The media identifiers that may be mapped include, but are not limited to, a lyric ID, a composition ID, a recording ID, a track ID, a disc ID, a release ID, an edition ID, an album ID, a series ID, a recording artist ID, a composer ID, a playlist ID, a film/TV episode ID, a photo ID, or a text work ID. Parent and child entities may be mapped at block 1704. The mapping may be a local map to hierarchically-related semantically meaningful entities. Example of mappings between parent and child entities may include mapping between a composition ID, a recording ID, and a track ID; a lyric ID, a recording ID, and a track ID; a lyric ID, a composition ID, and a track ID; a lyric ID, a composition ID, and a recording ID; a track ID, a release ID, an edition ID, an album ID, and a series ID; a track ID, a disc ID, an edition ID, an album ID, and a series ID; a track ID, a disc ID, a release ID, an album ID, and a series ID; a track ID, a disc ID, a release ID, an edition ID, and a series ID; and a track ID, a disc ID, a release ID, an edition ID, and an album ID. Other mappings may also be used. Relationally related entities may be mapped at block 1706. For example, segments may be mapped. An example of a map for relationally related entities includes a map between disc ID, release ID, edition ID, album ID, and series ID. FIG. 18 illustrates a method 1800 for receiving master descriptor codes and content IDS for content according to an example embodiment. In an example embodiment, the method 1800 may be performed at block 1408 (see FIG. 14). Descriptor codes may be received for the entities of the content at block 1802. The retrieved descriptor codes may be for granular ordered or weighted factual and descriptive codes. The descriptor codes may be received from one or a plurality of sources locally and/or over a network. Unrecognized descriptor IDs may be optionally mapped at block 1804. The mapping may translate the unrecognized descriptor code into a normalized descriptor code. Examples of maps that may be used to map the descriptor IDs include a genre map, an origin map, a recording era map, a composition era map, a mood map, a tempo map, and a situation map. Descriptor IDs may optionally be mapped to entities without descriptor IDs at block 1806. For example, when a descriptor has not been mapped to parent and child entities via cascading prior to retrieval, a local mapping to an entities without a direct descriptor ID may be performed after retrieval of a parent or child descriptor ID. Alternative billings and collaboration artist IDs may be received at block 1806. Mappings of alternative billing IDs to primary artist IDs and mappings of collaborations to component individual contributors may be received. Navigational and related content IDs may be received at block 1808. Navigational and related content IDs may include, by way of example, cover art, an artist photo, an artist bio, an album review, a track review, a label logo, a track audio preview, a track audio, a palette, or phonetic data. Related content may be received at block 1810. Related content may be received by using a related content ID to request delivery of /or unlocking of related content from local and/or remote sources (e.g., a store) FIG. 19 illustrates a method 1900 for utilizing a navigation package in a client 102 (see FIG. 1) according to an example embodiment. One or more default navigation views may be generated at block 1902. One or more alternate navigation views may be generated at block 1904. One or more personalized navigation views may be generated at block 1906. One or more contextually relevant views may be generated at block 1908. An example embodiment for creating the views that may be generating during the operations of the method 1900 is described in greater detail below. FIG. 20 illustrates a method 2000 for creating a navigational view according to an example embodiment. In an example embodiment, the method 2000 may be performed at block 1902, block 1904, block 1906, and/or block 1908. A single descriptor type hierarchy 116 may be created at block 2002. Default templates may be used to organize media items into one or more single descriptor type hierarchies that may optionally be normalized (e.g., normalized single descriptor type hierarchy). Options for the single descriptor type hierarchy may include a number of levels, an average number of categories under each note at each level, and/or the entity type contained in the lowest level categories (e.g., track, artist, album, or composition). Example of single descriptor type hierarchies 116 include meta-genre /genre/sub-genre:track, meta-mood/mood/sub-mood:track, meta-origin /origin/sub-origin:track, meta-era/era/sub-era:track, meta-type/type/sub-type: track, meta-tempo/tempo/sub-tempo:track, meta-theme/theme/sub-theme:track, meta-situation/situation/sub-situation:track, and meta-work type/work type/sub-work type:track. Each of the single descriptor hierarchies may optionally be identified with a unique identifier. Hierarchical views may be created using normalized metadata at block 2004. The normalized metadata from recognition may be used to organize media items into summarized, normalized single-entity hierarchical views. The hierarchical views may be a single level or multiple levels. For example, a main artist may be displayed at a top level and an alternate billing level may be displayed when applicable. By way of example, the hierarchical views may include recording artist:track, composer:track, album:track, recording:track, and composition:track. Hierarchical views may be created using existing metadata and/or entity hierarchies from templates at block 2006. The existing metadata and/or entity hierarchies from the navigation templates 300 may be used to organize media items into summarized, normalized single-entity hierarchical views. For example the views may include artist/album:track or composer/composition:recording. Other views may also be created. Navigation trees 314 may be created at block 2008. The default navigation template 300 may be used to organize media items into one or more navigation trees 314. The navigation trees 314 may optionally be normalized and may include a unique identifier for subsequent identification. A particular navigation tree 314 may be defined by a number of levels of the tree, the container (e.g., a descriptor category or entity type) used at each level of the tree, and a number of categories for each category level of the tree (e.g. which category list is used for the levels using category lists), the entity type or types that are ultimately organized by the categories of the tree at the lowest level or alternatively the navigation tree may consistent only of levels of descriptors. The particular navigation tree 314 may be further defined by the mappings from the master descriptor list to the category lists and the mappings from each category list to the other category lists. Examples of navigation trees 314 may include genre/era:track, genre/mood/tempo:recording, artist/mood/year:track, genre/year:news article, genre/origin, and the like. FIG. 21 illustrates a method 2100 for updating navigational views according to an example embodiment. In an example embodiment, the navigational views generating during the method 2000 (see FIG. 20) may be update. A determination may be made at decision block 2102 whether a parameter was received. If a determination is made that the parameter was received, the parameter may be processed to enable control at block 2104. The parameter may be received to allow for control over a category list and entity item ordering at each level. For example, the ordering options of the API input may include alpha-numerical, date/time, number of sub-categories, number of items in container, editorial semantic relationship B (e.g., similarity clustering), editorial semantic relationship B (e.g., liner sequence closest fit), editorial: importance or quality, popularity (e.g., may be static or dynamically generated), custom, and the like. If a determination is made that the parameter was not received at decision block 2102, the method 2100 may proceed to decision block 2106. At decision block 2106, a determination may be made as to whether a display selection has been received. If a determination is made that the display selection has been received, the display selection may be processed at block 2108. The display selection may specify (e.g., through an API of the client 102) whether to display metadata as is being from a media item or alternatively display a higher-level category item label from a selected hierarchy category list for a descriptor/category field. The display selection may optionally be used to override parameters inherited from a global profile for a device or application. If a determination is made that the display selection has not been received at decision block 2106, the method 2100 may proceed to decision block 2110. A determination may be made at decision block 2110 whether to perform a conversion. If a determination is made to perform a conversion (e.g., based on instructions received through the API), the conversion may be preformed at block 2112. The conversion may be to convert text into alternate forms of presentation (e.g., TLS) for a name/label field. If a determination is made not to perform the conversion at decision block 2110, the method 2100 may proceed to block 2114. The unified library of media items may be navigated at block 2114. The unified library may include the media items 134 available from the plurality of media sources 106.1-106.n. The unified library may be navigated from the client 102 and optionally another client on the network. At decision block 2116, a determination may be made whether to modify the navigation. If a determination is made to modify the navigation, the method 2100 may return to decision block 2102. If a determination is made not modify the navigation at decision block 2116, the method 210 may proceed to decision block 2118. A determination may be made at decision block 2118 whether to further navigate the unified library of media items. If a determination is made to further navigate the unified library, the method 2100 may return to block 2114. If a determination is made not to further navigate the unified library, the method 2100 may terminate. FIG. 22 illustrates a method 2200 for presenting a navigation view on a client 102 (see FIG. 1) according to an example embodiment. The method 2200 may be used to enable multiple descriptor hierarchies 116 to be available in a single client (e.g., a device and/or application). The multiple hierarchies 116 may be built from the same master descriptor code. For example, both a gender-oriented and group-type oriented view of artist type master descriptor codes and both a recording-era oriented and a classical composition oriented view of era master descriptor codes may be presented. Global settings may be defined per client 102 at block 2202 and per navigation tree at block 2204. Settings may also be defined per navigation tree level at block 2206. Examples of settings that may be defined during the operation of the method 2200 is as follows: Select Descriptor Value(s) associated with Specific Entity Level to be Included Select Most Granular Entities to Be included IV. Entity Item Categorization Options API Input Display Entity Item only under Primary Category that is coded to it or display under all Categories that are coded to it Display Category and Entity Item if Applicable Descriptor is Coded to Which Entity Item Level(s) Parameters Input to the API Allow for the Control Over Whether Category Display V. Category Display Options API Input (yes/no) Display “All Other/General” Child Categories Display child Category When only a single Child Category Exists Move child Category Label\to Parent level when only a single Child Category Display Child Category only under Primary Parent, or display under all Parents Skip Identical Categories at Adjacent Levels Display Empty Categories VI. Category Name Display API Input Language Use Short Terms Use Alternate Labels VII. Entity List Grouping API options In Artist List, Group Artists appearing on Various Recording Artist compilations under single Category In Artist List, do not list Artists appearing on Various Recording Artist compilations separately In Composer List, Group Composers appearing on Various Composer compilations under single Category In Composer List, do not list Composers appearing on Various Composer compilations separately In Artist List, Group Artists with only a single track under single Category In Artist List, Alternate Billings of Artist Name all Under Main Artist Name In Artist List, List all Alternate Billings of Artist Name Separately In Artist List, List all Alternate Billings of Artist Name Separately, and under Main Artist For Collaborations, List only the Collaboration Name For Collaborations, List the Collaboration name and the Primary Artist Name For collaborations, List the Collaboration Name, Primary Artist Name and Secondary Artist Name In Album List, group single-artist Collection/Anthology compilations under a single category VIII. Item Name Profanity Filter Options API Input Remove Item from Item List Display with Flagged word(s) obscured Display with all but first letter of flagged word(s) obscured Display all Flagged words, but flag No special Treatment IX. Entity List Duplicate Item Handling Flag duplicates based on Fingerprint Flag duplicates based on TOC Flag duplicates based on Filename Flag duplicates based on Track Name+Artist Name\ Flag duplicates based on Track Name+Artist Name+Album Name Flag duplicates based on File Hash For each duplicate: Display both, but flag Display only one X. Item Name List Display Options API Input Display Short Names Display First, Last Display First, Last Display “Name, The” Display “The Name” XI. Detail Item Display Only Display Movement Name in Track Field for TLS Classical Display Composer Name Last in Track for TLS Classical Do not Display Soloist in Artist Field for TLS Classical Display Short Names Display First, Last Display First, Last Display “Name, The” Display “The Name” Parameters Input to the API Allow for the Control Over Category List Ordering at the Levels XII. Category Name Ordering Options API Input (options may be selected for a sort number (e.g., first and second sort) and ascending/descending) Alpha-Numerical Date/Time Number of Sub-Categories Number of Items in Container Duration of Items in Container Editorial Semantic Relationship B: (e.g. similarity clustering) Editorial Semantic Relationship B: (e.g. Linear sequence closest fit) Editorial: Importance or Quality Popularity (may be dynamically generated) Custom—Developer Custom—End-User Order based on other descriptor of Category Parameters Input to the API Allow for the Control Over Entity Item Ordering at Each Level XIII. Item Ordering Options API Input (options may be selected for a sort number (e.g., first and second sort) and ascending/descending) Alpha-Numerical (based on as-displayed, First Last Option, Preceding Article Option) Flags (e.g. Release Type: Album, Single, Collection) Chronological Popularity (Can be dynamically generated) Custom Order based on other descriptor/attribute of Entity XIV. Navigational content Items to Display API Input—Navigational content items can be dynamic by being updated in real-time or by periodic updates upon connection with a server (yes/no) Album Cover Art Artist Photo Genre Icon Era Icon Origin Icon/Flag Venue Logo Time Cycle Icon Mood Icon Custom Tempo Icon Instrument Icon Situation Icon Theme Icon Video Still Moving Thumbnail Thumbnail Sequence Descriptor/Entity Type Icon Audio Description of Category, Entity Item Custom FIG. 23 illustrates a method 2300 for altering navigation on a client 102 (see FIG. 1) according to an example embodiment. A determination may be made at decision block 2302 whether to use personalized navigation. If a determination is made to use personalized navigation, personalized navigation may be used at block 2304. Navigation may be personalized by providing tools for user tagging and to adapt tagging menus based on a profile. End-users may be able to personalize by manually overriding category names, entity item names, and category groupings. Navigation may also be personalized by dynamic configuration of hierarchies 116 based on collection and/or user profile. An end-user may also manually select and/or construct a hierarchy 114 to be used for navigation. Content may be flagged and/or tagged by the user at the client 102 level and/or file level. Preferences may be stored remotely to be retrieved by a difference client (e.g., application or device) of the user and/or may be transferred directly from one client to another via a wired or wireless connection. If a determination is made not to use personalized navigation at decision block 2302, the method 2300 may proceed to decision block 2306. At decision block 2306, a determination may be whether to use dynamic personalization. If a determination is made to use dynamic personalization, dynamic personalization may be used at block 2308. Assembled personal profile data may be accessed automatically to provide dynamic personalized navigation. An implicit profile may be overridden with any explicit input provided by the user. Sources used for dynamic personalization may include explicit input, an index of user media collection including counts of media items per entities and per categories, or an activity log that logs user activity to track activity across a current device or multiple devices of a user to an activity and consists of plays, clicks, time engages, and/or other factors. The output of the dynamic personalization may be a combined profile. The profile may indicate a relative level of interest/importance of category or entity item to the end-user and may be stored remotely and/or locally. An alternative navigational tree 314 may be dynamically constructed based on profile input. A determination may be made as to how many levels to step up or down for sub-sections of the list in order to re-tune. An example of the alternative navigation tree 314 dynamically constructed is as follows: A standard view may present a U.S. default 25-Item Genre Category List at Top level; A customized 25-item list view may be presented instead by looking at the next higher level in the hierarchy specified by the template (e.g., a 6-item list). The profile may indicate that “rock” is the user's most preferred genre of those listed at the higher level. The new 25-Item list may then be generated as follows: First, the remaining categories (e.g., 5 categories) from the higher list (e.g., 6 items) are used to cover all music other than Rock. This leaves twenty rock categories to be populated. These are taken by identifying the 19 most preferred categories from the rock section of the next lower level in the hierarchy (which, say, includes 30 Rock Categories), each of which is listed. The main category labelled “more rock” may contain all of the remaining rock categories from the next lower level. The next level down under the “More Rock” category may either show the remaining 9 rock categories from the next lower level, or just show a single list of all sub-categories that would normally be displayed at that level. Composite graphical, audio, video or textual navigational icons may be dynamically selected for personalization based on current contents of the container. If a determination is made not to use personalized navigation at decision block 2306, the method 2300 may proceed to decision block 2310. A determination may be made at decision block 2310 whether to use contextual adaptation. If a determination is made to use contextual adaptation, contextual adaptation may be used at block 2312. Contextual adaptation may use real-time global textual adaptation and/or real-time personal contextual adaptation. The data may be accessible by a client 102 either locally or remotely. If a determination is made not to use contextual adaptation at decision block 2310, the method 2300 may proceed to decision block 2314. At decision block 2314, a determination may be whether to restore navigation. If a determination is made to restore navigation, navigation may be restored at block 2316. If a determination is made not to restore navigation at decision block 2314, the method 2300 may proceed to decision block 2318. A determination may be made at decision block 2318 whether to make further modifications. If a determination is made to make further modifications, the method 2300 may return to decision block 2302. If a determination is made not to make further modification, the method 2300 may terminate. FIG. 24 shows a diagrammatic representation of machine in the example form of a computer system 2400 within which a set of instructions for causing the machine to perform any one or more of the methodologies discussed herein may be executed. In alternative embodiments, the machine operates as a standalone device or may be connected (e.g., networked) to other machines. In a networked deployment, the machine may operate in the capacity of a server or a client machine in server-client network environment, or as a peer machine in a peer-to-peer (or distributed) network environment. The machine may be a personal computer (PC), a tablet PC, a set-top box (STB), a media player (e.g., portable audio player, vehicle audio player, or any media rendering device), a Personal Digital Assistant (PDA), a cellular telephone, a web appliance, or any machine capable of executing a set of instructions (sequential or otherwise) that specify actions to be taken by that machine. Further, while only a single machine is illustrated, the term “machine” shall also be taken to include any collection of machines that individually or jointly execute a set (or multiple sets) of instructions to perform any one or more of the methodologies discussed herein. The example computer system 2400 includes a processor 2412 (e.g., a central processing unit (CPU), a graphics processing unit (GPU), digital signal processor (DSP) or any combination thereof), a main memory 2404 and a static memory 2406, which communicate with each other via a bus 2408. The computer system 2400 may further include a video display unit 2410 (e.g., a liquid crystal display (LCD) or a cathode ray tube (CRT)). The computer system 2400 also includes an alphanumeric input device 2413 (e.g., a keyboard), a user interface (UI) navigation device 2414 (e.g., a mouse), a disk drive unit 2416, a signal generation device 2418 (e.g., a speaker) and a network interface device 2420. The disk drive unit 2416 includes a machine-readable medium 2422 on which is stored one or more sets of instructions and data structures (e.g., software 2424) embodying or utilized by any one or more of the methodologies or functions described herein. The software 2424 may also reside, completely or at least partially, within the main memory 2404 and/or within the processor 2412 during execution thereof by the computer system 2400, the main memory 2404 and the processor 2412 also constituting machine-readable media. The software 2424 may further be transmitted or received over a network 2426 via the network interface device 2420 utilizing any one of a number of well-known transfer protocols (e.g., FTP). While the machine-readable medium 2422 is shown in an example embodiment to be a single medium, the term “machine-readable medium” should be taken to include a single medium or multiple media (e.g., a centralized or distributed database, and/or associated caches and servers) that store the one or more sets of instructions. The term “machine-readable medium” shall also be taken to include any medium that is capable of storing, encoding or carrying a set of instructions for execution by the machine and that cause the machine to perform any one or more of the methodologies of the present invention, or that is capable of storing, encoding or carrying data structures utilized by or associated with such a set of instructions. The term “machine-readable medium” shall accordingly be taken to include, but not be limited to, solid-state memories, optical and magnetic media, and carrier wave signals. FIG. 25 illustrates an example end-use system in which the client 102, 132 may be deployed. The end-use system 2500 may include a device processor 2502 in which a client 2504 may be deployed on device storage 2506. The device may include a car radio, an MP3 player, a home stereo, a computing system, ant the like. The client 2504 may include the functionality of the client 102 and/or the client 135 (see FIGS. 1A and 1B). The device storage 2506 may be a fixed disk drive, flash memory, and the like. The device processor 2502 may receive content from a plurality of sources 2508.1-2508.6. The plurality of sources as illustrated include a mobile phone/PDA 2508.1, a CD/DVD/BLURAY/HD/DVD 2508, a media player 2058.3, local and/or remote storage 2508.4, a radio station 2508.5, internet access/streaming content 2508.6. However other sources of content may also be used. The content may be made navigable by an end-user through user of a user interface 2516 coupled to a display 2518, an audio output 2520, and a user input 2514 (e.g., for voice and/or text). The information obtain by the device processor 2502 may be stored locally on the device storage 2506 and/or remotely on a system database 2512 by use of a system server 2512. Although an embodiment of the present invention has been described with reference to specific example embodiments, it will be evident that various modifications and changes may be made to these embodiments without departing from the broader spirit and scope of the invention. Accordingly, the specification and drawings are to be regarded in an illustrative rather than a restrictive sense. The accompanying drawings that form a part hereof, show by way of illustration, and not of limitation, specific embodiments in which the subject matter may be practiced. The embodiments illustrated are described in sufficient detail to enable those skilled in the art to practice the teachings disclosed herein. Other embodiments may be utilized and derived therefrom, such that structural and logical substitutions and changes may be made without departing from the scope of this disclosure. This Detailed Description, therefore, is not to be taken in a limiting sense, and the scope of various embodiments is defined only by the appended claims, along with the full range of equivalents to which such claims are entitled. Such embodiments of the inventive subject matter may be referred to herein, individually and/or collectively, by the term “invention” merely for convenience and without intending to voluntarily limit the scope of this application to any single invention or inventive concept if more than one is in fact disclosed. Thus, although specific embodiments have been illustrated and described herein, it should be appreciated that any arrangement calculated to achieve the same purpose may be substituted for the specific embodiments shown. This disclosure is intended to cover any and all adaptations or variations of various embodiments. Combinations of the above embodiments, and other embodiments not specifically described herein, will be apparent to those of skill in the art upon reviewing the above description. The Abstract of the Disclosure is provided to comply with 37 C.F.R. §1.72(b), requiring an abstract that will allow the reader to quickly ascertain the nature of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. In addition, in the foregoing Detailed Description, it can be seen that various features are grouped together in a single embodiment for the purpose of streamlining the disclosure. This method of disclosure is not to be interpreted as reflecting an intention that the claimed embodiments require more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive subject matter lies in less than all features of a single disclosed embodiment. Thus the following claims are hereby incorporated into the Detailed Description, with each claim standing on its own as a separate embodiment. Thimbleby, H. , et al., "Ethics and Consumer Electronics", Proceedings of the 4th ETHICOMP International Conference on the Social and Ethical Impacts of Information and Communication Technologies, (1999),9 pgs. | High | [
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Serum ferritin and lactate dehydrogenase in a case of hemophagocytic lymphohistiocytosis. A 40-day-old baby girl presented with intermittent fever, lymphadenopathy, massive hepatosplenomegaly, progressive pancytopenia and features of disseminated intravascular coagulopathy. A bone marrow aspiration was performed and showed florid histiocytic proliferation with marked hemophagocytosis. Based on the diagnostic guideline for Hemophagocytic Lymphohistiocytosis proposed by the Familial Hemophagocytic Lymphohistiocytosis Study Group of Histiocyte Society, this patient has fulfilled most of the criteria. We have also found that serum ferritin and lactate dehydrogenase to be very high in this patient. It remains uncertain whether the disorder is reactive or neoplastic. | High | [
0.662125340599455,
30.375,
15.5
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Annuities and Structured Settlements You’re unlikely to reach retirement age without somebody asking you about annuities. They want to know whether you considered buying one, and if they work for an insurance agency, they’re likely to try to sell you on the benefits of a lifetime income that annuities can provide. So, what exactly are annuities? Annuities are an insurance policies that behave like investments. Annuities offer a hedge against something bad happening to your money, like a huge loss in a stock market collapse. Instead of personally managing your money and assuming risks inherent in stocks and mutual funds, you buy an annuity that guarantees a steady monthly income for decades or even a lifetime. Annuities are contracts between investors and insurers designed to meet long-term retirement goals for investors. Money can either be invested in a lump sum or through a series of payments. In exchange for the investment, the insurer agrees to make periodic payments to the investor beginning at a specified date. Just like a life insurance policy, which guarantees a lump-sum payment to your heirs, an annuity is a contract with an insurance company that pays you, slowly in most cases, while you’re alive, and often provides a payment to a beneficiary when you die. Annuities come with large initial costs. Many purchasers put a substantial part of their retirement savings into an annuity, giving them comfort that no matter what happens, they’ll always have an income. In addition, the amount you invest grows tax deferred until it is withdrawn. Types of Annuities Retirement annuities, properly called deferred annuities, come in three varieties, fixed, indexed and variable. All are tax deferred and will pay your beneficiary a specified minimum amount when you die. Periodic payments are made to you for a fixed period or a lifetime, and payments can continue after your death to your spouse. Variations of Annuities: Fixed Annuities. Returns are based on a fixed interest rate that you agree to when you purchase the annuity. The insurance company will also make regular payments of a certain amount on each dollar your invested. Indexed Annuities. These base your payouts on the performance of a financial index like the S&P 500 with the stipulation that you will never receive less than a minimum payment amount each month. If the index performs strongly, your return could be greater than the investment, but if it’s weak, you will never receive less than the specified amount. Variable Annuities. These use investments such as mutual funds to determine your return. The rate of return on your investment, and the amount of periodic payments you receive, depends on the performance of the funds you choose. Variable annuities typically pay a death benefit to someone you designate. That person can receive all the money remaining in the account or an agreed upon guaranteed minimum. Annuities come with two payout plans. Immediate annuities begin paying immediately after you purchase them. These products are often sold to retirees who want to convert savings into guaranteed income streams. The other variety is deferred-income. This model allows you to buy an annuity now to receive payouts in the future. If you are in your 50s and don’t envision needed annuity income until you’re 70, this model lets you build value before payouts begin. You should also remember that unlike savings in government regulated banks, annuities are insurance products that aren’t insured. If you are uncertain about the condition of the company issuing the annuity, you probably ought to rethink making the investment since a corporate failure could eat your retirement savings. History of Annuities The concept of annuities dates to ancient Rome, but the first record of annuities in America comes from the Colonial period. In 1759, a company formed to provide a secure retirement for aging Presbyterian ministers and their families. In 1812, the Pennsylvania Company for Insurance on Lives and Granting Annuities received a charter to sell annuities to the public. The current era of annuities began in 1952 when the educators’ retirement fund, TIAA-CREF, first offered a group variable deferred annuity. Annuities today are mostly used to provide for an individual’s retirement, usually on a tax-deferred basis. Americans bought more than $117 billion in annuities in 2016, according to LIMRA Secure Retirement Institute, and the nation held nearly $2.3 trillion worth of polices. Structured Settlements and Annuities Structured settlements are linked to annuities because they’re considered an effective way to deliver money to people who need it but also need the discipline of a monthly or yearly payout. Congress in 1982 passed the Periodic Payment Settlement Tax Act, which established structured settlements to provide long-term financial security to accident victims and their families. The idea was to replace lump-sum payments awarded to personal injury claimants with periodic payments. The government’s aim was to decrease the number of personal injury award recipients who went through their funds too quickly and were subsequently forced to rely on public assistance. In addition to personal-injury claimants, structured settlements are frequently set up for those who win big liability and damage judgments, for lottery winners and for lawyers and law firms who are owed large sums in fees. Because annuities can be designed to offer timed payouts, guarantees on principal, as well as investment gains, and were already being offered by insurance companies, they quickly became the preferred vehicle to implement structured settlements. To encourage their use, the new law made any interest or capital gains earned on the annuity within a structured settlement tax free. Pros and Cons of Annuities The primary reason to own an annuity is security. In addition to ensuring a continuing stream of income during one’s retirement, many annuities are guaranteed for a minimum rate of return, meaning that not only can their principal be protected against loss; their earnings can be, as well. In some cases, by annuitizing the contract, the owner of an annuity can even receive a life-long stream of income, far more than his or her original investment. Annuities also offer predictability. Fixed annuities – ones tied to an unwavering interest rate – are especially attractive to investors who want to know how much money they will have years, or even decades into the future. They generally offer rates superior to money market accounts or certificates of deposit (CDs), and come with similar built-in protections and guarantees. Conversely, variable annuities – ones tied to rising and falling rates – offer the possibility of returns equal to those achieved via stocks or mutual funds, but with greater flexibility, more protections against loss, and certain tax advantages. Other things to consider: Annuities come with fees, often high ones. The broker who sells you an annuity usually receives a commission, and the company that manages the annuity charges an annual maintenance fee. If the annuity is invested in mutual funds, the funds’ fees become part of the cost. Since annuities are insurance products, their structure reflects the risk the insurer assumes. For instance, the value of a variable annuity invested in mutual funds varies with the value of the funds, which can go down. If the annuity guarantees a minimum periodic payout, the annuity costs will reflect the risk the insurer takes, and that risk is a premium built into the cost of the annuity. Some annuities also lock in your gains after a certain take, which also adds to the risk the issuer incurs. Again, that risk means extra fees built into the annuity. The biggest con for annuities is that you must be 59 and a half to with draw the gains from an annuity and not have to take a 10% early withdrawal penalty. There also will be a surrender charge if you try to withdraw early. The charge goes own over time, but if you need the money now, you will pay a penalty. Another negative for owning an annuity is that many of them charge higher annual fees, especially on variable annuities than those charged on managed mutual funds or stocks. Also, the current interest rates are so low that inflation could easily go up faster than the return on interest you would receive with an annuity. There are negative tax implications associated with annuities. Gains on annuities are taxed as ordinary income, meaning you could pay twice as much in taxes on it as you would from the capital gains on stocks or mutual fund investments. Another tax penalty comes if you pass along annuity benefits to your survivors after your death. They will have to pay taxes on it as ordinary income. Questions You Should Ask If you’re considering an annuity to cover retirement costs, ask yourself questions. Remember there are other ways to pay for retirement, including withdrawals from independent retirement accounts and 401(k) plans. You should consider the alternatives and get solid advice, perhaps from a certified financial planner. If you are leaning toward an annuity, consider: Are you willing to accept the risk that your value could decrease if you invest in a variable annuity? Do you understand all the fees and expenses connected with the annuity? Do you plan to keep a variable annuity long enough to avoid surrender charges if you decide you want to redeploy your money? Are there elements of a variable annuity, such as long-term care insurance, that might be purchased less expensively elsewhere? Have you talked to a tax or financial adviser about the tax consequences of an annuity? Structured Settlements Using Annuities To pay the financial obligations owed to an injured party, a defendant – or more usually, his or her casualty insurance carrier – will purchase one or more annuities from a life insurance company, or delegate its periodic payment obligations to a third party, which in turn would purchase a qualified funding asset – either an annuity or a government bond. About $5.5 billion in structured settlements were issued in 2015, according to LIMRA Secure Retirement Institute. The payments are then structured, or scheduled. An insurance company agrees to pay the injured individual a predetermined amount of cash for a fixed length of time or for the duration of the life of the claimant, depending on the terms of the settlement agreement. Structured settlements are governed by both federal and state laws and must be closed under court order. The process is highly regulated by the courts. Some states also require the hiring of an attorney as a precondition to acquiring a structured settlement annuity. Pros and Cons of Structured Settlements The biggest advantages to structured settlements are predictable, secure income for the owner and the fact the total amount of money you receive will be greater than what you would get from a one-time lump sum payment. If you receive a structured settlement as part of a personal injury settlement, the payments are not subject to taxes. Structured settlements offer advantages to both sides in a personal injury case when damages are awarded. Most important to the plaintiffs is their built-in protection against having settlement funds dissipate too quickly based on bad financial decisions. An injured person who has long-term special needs or loss of income due to an accident will often benefit greatly from having monthly payments to meet daily expenses, as well as periodic lump sum payments with which to purchase medical equipment, modified vehicles, etc. Minors can benefit from a structured settlement in that their futures can be financially insured to point. Their structured settlements can provide certain payments during childhood, additional disbursements to pay for college, etc. Defendants enjoy structured settlements because they free them from any future liability claims made by the injured party. Settlements can be purchased at a discount, as the plaintiffs will be earning tax-free gains on the capital used to purchase them. The cons of structured settlements are the lack of flexibility; the low annual return and the fact that payments could cease if you die. There are some parts of a structured settlement that can be taxed. How to Sell a Structured Settlement Sometimes those who receive structured settlements wish to claim their cash awards sooner than a payment schedule allows. This typically follows a significant change in someone’s life situation. Financial situations can change, and more money than an incremental monthly income is needed: to pay medical bills, to buy a house, to pay off debts, to fund a college education, etc. In these situations, someone with a structured settlement agreement can negotiate to sell the rights to their future settlement payments. They can sell these rights in whole or in part, although a judge must agree to the terms and the sale before the sale can happen. Finding a buyer for your future settlement payments could be as easy as visiting review sites online and view the comments by others in your situation. Prospective buyers should have some or all of these characteristics: Offer full explanation of the fees and exactly how much you will receive for the annuity A staff of lawyers available to help make the sales process a smooth one Helpful customer service representatives able to explain the process and answer any questions Offer fair rates and cash advances Prepare paperwork and allow time for you to review it before signing Allow you to use your own attorney to review contract Individuals do not negotiate with the owner of the structured settlement (usually an insurance company) but do so with a third party willing to buy all or part of the remaining settlement, known as the funder. The structured settlement rights holder must provide a legitimate need for the money and calculate the requested payout amount so that the best interests of the seller and any dependents are recognized and upheld. When selling a structured settlement, it’s important to find a reputable funder, who bids on your structured settlement. Locating a funder is only part of task. To sell your structured settlement you must prove that you have a legitimate need for the settlement money in a lump payment and calculate what that payment might be. In most cases, it requires judicial approval. The need can’t be something frivolous or discretionary. Generally, the desire to buy a new car or a diamond ring won’t win approval, but a cash out agreement might be acceptable to cover an unexpected medical expense, job loss or some other urgent financial demand. In most cases, structured settlement holders only sell part of their annuity. Typically, the funder will ask for a discount rate of between 6% and 29% of the settlement’s value. There are other costs, including surrender charges of as much as 10%, and if you sell the annuity before you reach the age of 59 ½ you will pay federal tax penalties. Before selling a structured settlement, policy holders should weigh the financial losses they might incur against the need they have for an immediate payout. Check on line to learn if the broker has customer complaints, and check that the broker is listed with the Better Business Bureau. Determine that the funder has never defaulted on a settlement purchase, has been in the business at least three years, is registered to do business in all 50 states and is based in the United States. The funder should also have a policy of offering the best price and be prepared to complete the transaction within two months. Steps for Selling a Structured Settlement When you decide you want a cash payout from a structured settlement, estimate how much money you’ll need. Typically, this will only be a portion of the settlement’s value. Then, Research funders to find several reputable ones. Contact the funders and ask for quotes on potential payout and costs. Choose a funder and complete required paperwork. Work with funder to set a court date to seek judicial approval. Arrange for the payout to be deposited in your bank account. Qualifications of a Trustworthy Buyer The sale of an annuity or structured settlement can be stressful if you’re not familiar the financial product and its value so don’t rush into it. There are plenty of companies that specialize in buying these products. Most of them can easily be found on the internet or buy consulting your financial adviser. Sever companies may be interested in buying your product so don’t jump at the first offer. Some of the qualifications buyers should meet for you to negotiate with them include: Suggest the seller be represented by attorney or accountant Encourage the seller to compare with other buyers Make sure you’re given time to read and understand paperwork No high-pressure sales tactics Have their own staff of attorneys available to facilitate the sale Have verified customer reviews on their websites Offer discount rate State and federal laws protect the sellers because this hasn’t always been a fair process. The most important thing for sellers to remember is that you must prove to a state judge must you’re your reason for selling is in your best interest and those of your dependents. Once you’ve done that, let a few companies make offers for your annuity or structured settlement and determine if any of the deals meet your needs. Author Staff Writer Bill Fay is a journalism veteran with a nearly four-decade career in reporting and writing for daily newspapers, magazines and public officials. His focus at Debt.org is on frugal living, veterans' finances, retirement and tax advice. Bill can be reached at [email protected]. In debt? We can help! Amount Type Contact How much do you owe? What can we help you with today? Credit Cards Zip Code Student Loans My loans are Bankruptcy Credit Monitoring First Name Last Name Phone Email I agree to the Privacy Policy and I agree to be contacted at the phone number I provided as a best contact number, including on a mobile device, using an auto-dialer and/or text message, or by email for the purpose of communicating regarding an evaluation of credit or debt relief services. Wireless carrier fees may apply. My consent does not require purchase. | Mid | [
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The 1.45 A resolution structure of the cryptogein-cholesterol complex: a close-up view of a sterol carrier protein (SCP) active site. Cryptogein is a small 10 kDa elicitor produced by the phytoparasitic oomycete Phytophthora cryptogea. The protein also displays a sterol carrier activity. The native protein crystallizes in space group P4(1)22, with unit-cell parameters a = b = 46.51, c = 134.9 A (diffraction limit: 2.1 A). Its complex with cholesterol crystallizes in space group C222(1), with unit-cell parameters a = 30.96, b = 94.8, c = 65.3 A and a resolution enhanced to 1.45 A. The large inner non-specific hydrophobic cavity is able to accommodate a large variety of 3-beta-hydroxy sterols. Cryptogein probably acts as a sterol shuttle helping the pathogen to grow and complete its life cycle. | Mid | [
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/* jQuery News Ticker is free software: you can redistribute it and/or modify it under the terms of the GNU General Public License as published by the Free Software Foundation, version 2 of the License. jQuery News Ticker is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU General Public License for more details. You should have received a copy of the GNU General Public License along with jQuery News Ticker. If not, see . */ (function($){ $.fn.ticker = function(options) { // Extend our default options with those provided. // Note that the first arg to extend is an empty object - // this is to keep from overriding our "defaults" object. var opts = $.extend({}, $.fn.ticker.defaults, options); // check that the passed element is actually in the DOM if ($(this).length == 0) { if (window.console && window.console.log) { window.console.log('Element does not exist in DOM!'); } else { alert('Element does not exist in DOM!'); } return false; } /* Get the id of the UL to get our news content from */ var newsID = '#' + $(this).attr('id'); /* Get the tag type - we will check this later to makde sure it is a UL tag */ var tagType = $(this).get(0).tagName; return this.each(function() { // get a unique id for this ticker var uniqID = getUniqID(); /* Internal vars */ var settings = { position: 0, time: 0, distance: 0, newsArr: {}, play: true, paused: false, contentLoaded: false, dom: { contentID: '#ticker-content-' + uniqID, titleID: '#ticker-title-' + uniqID, titleElem: '#ticker-title-' + uniqID + ' SPAN', tickerID : '#ticker-' + uniqID, wrapperID: '#ticker-wrapper-' + uniqID, revealID: '#ticker-swipe-' + uniqID, revealElem: '#ticker-swipe-' + uniqID + ' SPAN', controlsID: '#ticker-controls-' + uniqID, prevID: '#prev-' + uniqID, nextID: '#next-' + uniqID, playPauseID: '#play-pause-' + uniqID } }; // if we are not using a UL, display an error message and stop any further execution if (tagType != 'UL' && tagType != 'OL' && opts.htmlFeed === true) { debugError('Cannot use type of element for this plugin - must of type | Low | [
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Category Archives: Articles We are taught from our early years, in our introduction to commerce that prices are prices. Whether you walk into a clothing store, a supermarket, a gas station, or a coffee shop, the posted prices are typically non-negotiable. Generally speaking, attempting to haggle in cases such as these won’t get you too far. This is… Once you have obtained your CCNA, it is now time to set your sights a bit higher. Of course, this means beginning to prepare for the CCNP exams. You should also put some thought into the best order to take the CCNP exams. The CCNP exams are not necessarily more difficult than the CCNA exam.… A child’s early years constitute a period of rapid intellectual, social, and emotional development. Integrating music and movement into children’s education at this point in their lives is well-established as a great way to maximise this golden ‘window of opportunity’. But how does music and movement actually work to benefit a child’s early development, and… When all seems dull and lost, the world brings in a touch of hope. Under the snowy façade lies an unborn life ready to burst through the barriers. The world will now be a happier place with daffodils and crocus flowers aiming at imprinting a smile on that face. The green, the blue, the yellow,… A Small Form Factor (SFP) transceiver is a compact hot swappable module that is used in computing for both telecommunication and data communications applications. The increase in the high-speed data transmission due to the demands of the people have led to the fast rise in demand for the SFP modules. SFP transceivers can be used… With the introduction to Cobb Tuning making a comeback to producing hard parts, their anticipated release of a bypass valve is welcomed. Many of us have been waiting for a valve that is easy to adjust, sounds great and works 100% without any surging on the turbo compressor. Question: So what exactly is a BPV… 1. State a Benefit to Your Customer in Your Opening Statement If any of us had a dollar for every time some one from a mortgage company called to try to get us to refinance our mortgage we would have a lot of money. Normally I just say that I am not interested and politely… Over time your fire pit may begin to show some wear and tear from the elements. A great way to refurbish an old pit and get it looking like new again is to remove the fire bowl (area where the fire burns) and make some simple repairs. Typically, there are two common areas that tend… What do person, place, product, and process (the 4 P’s) have in common? According to creativity researchers, these are the four generally accepted facets to creativity. Additionally these facets are interrelated, which makes creativity complicated to understand and to cultivate, especially in organizations. Understanding its multiple aspects, however, is a critical first step in bringing… Are you quietly fumbling in the dark with your sex life? Although raw sex is a physical act, the sensual experience of making love together can be greatly enhanced by engaging all your senses. Every one of your five senses contributes to your mood to some degree. By setting the scene for your romantic or… Radiant Barrier Insulation is a reflective insulation made mostly out of aluminum. There are lots of different types radiant barrier out there and they all have their specific applications. I know mostly about radiant barrier that is used to retrofit existing homes, specifically adding the insulation to the attic. There are some radiant barrier types… The Wagner 915 is a very good carpet cleaner. It also excels at removing wallpaper and performs all sorts of other cleaning functions as well. Most of these involve cleaning hard surfaces like tiles and wood. Carpets cannot be put into the washing machine and hung out to dry, but they do get very dirty.… Application of epoxy floor coatings is big business for many reasons. The first is that concrete is the most used commodity on earth. Concrete is a critical part of every structure worldwide but with problems such as moisture, bacterian and mold growth. With new high performance, decorative epoxy and polyurea systems there is no need… Hot water demand systems are specialized circulating systems for use when there is not already a hot water return line. They are systems designed to pump your hot water from your water heater to your fixtures fast without running water down the drain. Your cold water line connects to the inlet of the water heater.… If you’ve never worked out with a kettlebell, you are missing out on one of the most effective fitness tools of all time. With a cheap and compact instrument such as this, you can build the kind of body that drives women crazy. Kettlebell conditioning is one of the best ways to become much stronger… | Low | [
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Q: Error 1215, cannot add foreign key constraint create database blood_bank; use blood_bank; create table Employee( Emp_id integer not null, Emp_name char(20) not null, phone integer, address char(20), constraint primary key(Emp_id) ); create table WorkInStorage( Emp_id integer not null, since date not null, emp_salary integer, constraint primary key(Emp_id), constraint foreign key(Emp_id) references Employee(Emp_id) on delete cascade ); create table Reports_To( supervisor_id integer not null, subordinate_id integer not null, constraint primary key (supervisor_id,subordinate_id), constraint foreign key(subordinate_id) references Employee(Emp_id), constraint foreign key(supervisor_id) references Employee(Emp_id) ); create table Nurse( nurse_salary integer , Emp_id integer not null, constraint primary key(Emp_id), constraint foreign key(Emp_id) references Employee(Emp_id) on delete cascade ); create table Receptionist( Receptionist_salaray integer, Emp_id integer not null, constraint primary key(Emp_id), constraint foreign key(Emp_id) references Employee(Emp_id) on delete cascade ); create table donor( donor_id integer not null, donor_address char(20), birthdate date, donor_name char(20), donor_gender char(5), donor_phone integer, Emp_id integer not null, blood_id integer not null, constraint primary key(donor_id), constraint foreign key(Emp_id)references Nurse(Emp_id) on delete cascade , constraint foreign key(Emp_id)references Receptionist(Emp_id) on delete cascade , constraint foreign key(blood_id)references Blood(blood_id)on delete cascade ); create table Checks( isQualified boolean not null, donor_id integer, donor_address char(20), birthdate date, donor_name char(20), donor_gender boolean, donor_phone integer, Emp_id integer not null, constraint primary key(donor_id), constraint foreign key(Emp_id) references Nurse(Emp_id) ); When I try to execute this query it says it cannot ad foreign key in the donor table. create table donor( donor_id integer not null, donor_address char(20), birthdate date, donor_name char(20), donor_gender char(5), donor_phone integer, Emp_id integer not null, blood_id integer not null, constraint primary key(donor_id), constraint foreign key(Emp_id)references Nurse(Emp_id) on delete cascade , constraint foreign key(Emp_id)references Receptionist(Emp_id) on delete cascade , constraint foreign key(blood_id)references Blood(blood_id)on delete cascade ) Error Code: 1215. Cannot add foreign key constraint A: If you are asking to run that script where the db did not exist, then you are getting the Error 1215 because your table blood does not exist. For a test to prove that, if I execute create table blood ( blood_id int auto_increment primary key ); And then attempt the creation of table donor, it works. | Low | [
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CALMODULIN AND CALMODULIN-BINDING PROTEINS IN PLANTS. Calmodulin is a small Ca2+-binding protein that acts to transduce second messenger signals into a wide array of cellular responses. Plant calmodulins share many structural and functional features with their homologs from animals and yeast, but the expression of multiple protein isoforms appears to be a distinctive feature of higher plants. Calmodulin acts by binding to short peptide sequences within target proteins, thereby inducing structural changes, which alters their activities in response to changes in intracellular Ca2+ concentration. The spectrum of plant calmodulin-binding proteins shares some overlap with that found in animals, but a growing number of calmodulin-regulated proteins in plants appear to be unique. Ca2+-binding and enzymatic activation properties of calmodulin are discussed emphasizing the functional linkages between these processes and the diverse pathways that are dependent on Ca2+ signaling. | High | [
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using System.Threading.Tasks; namespace GraphQL.Instrumentation { public delegate Task<object> FieldMiddlewareDelegate(IResolveFieldContext context); } | Low | [
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Not all of the concept designs for Big Hero 6's superhero costume designs were as bright and colorful as what we saw in the final film. In fact, some of the suggestions from the design team were heavy on the black and earth tones—and one put Honey Lemon in cat ears. These are some of the designs that Big Hero 6 character designer Shiyoon Kim tossed into the mix. While they don't fit with the final visual tone of the movie, they're still a lot of fun to look at, especially when it comes to the many iterations of Honey Lemon. Kim posted these to his Tumblr, where he also has tons of other Big Hero 6 character art, including some of his particularly frightening alternate designs for Yokai. some superhero suits that never made the cut but were fun to design [Shiyoon Kim] | Mid | [
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Around 300 away fans from Serbia came in Razgrad for match against Ludogoretz. Grobari were supported by CSKA Sofia hooligans group – Varna Firm. In last season Partizan met again Ludogoretz, then in the away sector was another CSKA group – Animals. They are friends with Alcatraz. Strict access regime to join stadium in Razgrad for Grobari. Photo report: Varna … Before match from Champions League qualifications hooligans from Feyenoord attacked busses with away fans. Around 2500 Carsi made corteo in the city. 2 hours before match Photos from stadium, tickets sold out few days ago. Dutches are singing “Allah, Allah your mother is a wh*re!” Feyenoord fans are trying to attack the away sector. Incidents after the match Celtic fans were attacked before last night’s Champions League qualifier against Legia Warsaw. At least two incidents are understood to have taken place at a bar in the Polish capital, with at least one Hoops supporter injured. In same day before match Celtic’s supporters lost 2 banners. On the photo are 2 flags Celtic and one St. Patrick’s (This small … | Low | [
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// Copyright 2014 The Go Authors. All rights reserved. // Use of this source code is governed by a BSD-style // license that can be found in the LICENSE file. package icmp import ( "encoding/binary" "net" "reflect" "runtime" "testing" "golang.org/x/net/internal/socket" "golang.org/x/net/ipv4" ) type ipv4HeaderTest struct { wireHeaderFromKernel [ipv4.HeaderLen]byte wireHeaderFromTradBSDKernel [ipv4.HeaderLen]byte Header *ipv4.Header } var ipv4HeaderLittleEndianTest = ipv4HeaderTest{ // TODO(mikio): Add platform dependent wire header formats when // we support new platforms. wireHeaderFromKernel: [ipv4.HeaderLen]byte{ 0x45, 0x01, 0xbe, 0xef, 0xca, 0xfe, 0x45, 0xdc, 0xff, 0x01, 0xde, 0xad, 172, 16, 254, 254, 192, 168, 0, 1, }, wireHeaderFromTradBSDKernel: [ipv4.HeaderLen]byte{ 0x45, 0x01, 0xef, 0xbe, 0xca, 0xfe, 0x45, 0xdc, 0xff, 0x01, 0xde, 0xad, 172, 16, 254, 254, 192, 168, 0, 1, }, Header: &ipv4.Header{ Version: ipv4.Version, Len: ipv4.HeaderLen, TOS: 1, TotalLen: 0xbeef, ID: 0xcafe, Flags: ipv4.DontFragment, FragOff: 1500, TTL: 255, Protocol: 1, Checksum: 0xdead, Src: net.IPv4(172, 16, 254, 254), Dst: net.IPv4(192, 168, 0, 1), }, } func TestParseIPv4Header(t *testing.T) { tt := &ipv4HeaderLittleEndianTest if socket.NativeEndian != binary.LittleEndian { t.Skip("no test for non-little endian machine yet") } var wh []byte switch runtime.GOOS { case "darwin": wh = tt.wireHeaderFromTradBSDKernel[:] case "freebsd": if freebsdVersion >= 1000000 { wh = tt.wireHeaderFromKernel[:] } else { wh = tt.wireHeaderFromTradBSDKernel[:] } default: wh = tt.wireHeaderFromKernel[:] } h, err := ParseIPv4Header(wh) if err != nil { t.Fatal(err) } if !reflect.DeepEqual(h, tt.Header) { t.Fatalf("got %#v; want %#v", h, tt.Header) } } | Mid | [
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Portland payday loan company Texas Car Title and Payday Loan Services, Inc - Title Advance America is here to help you with Payday Loans, Cash Advances, Title Loans, and Installment Loans. Apply online now or visit any of our 2,000 locations. Payday loans in the United States - Wikipedia We've made getting a car title loan in Portland as simple as possible—no one in the state’s as fast as us at getting you cash. Portland Car Title Loans. Oregon Car Title Loans - USA Car Title Loans National Payday offers payday loans and cash advances completely online. Let us know on our easy payday loan application that you'd like us to deposit the funds in your account the same day and you'll get approved in just a few minutes! Credit Central: Installment Loans, Financial Services Come visit us at United Finance Company today to get your consumer finance loan, bill consolidation, or other personal loan with fast cash. | Low | [
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Tuesday, October 31, 2006 It's been a lousy few days. Five tournaments, five losses, and down another $20 at a Razz ring game. The only bright spot was $12 I walked away from a $0.50/$1 limit hold em game. No real bad beats, either -- just me being too aggressive and getting caught in a race. Even this one (see the screen shot), I should have won, but I really had no business calling an all in preflop -- even from a maniac like this guy was, and even though I got a good read on him -- just a few hands into the tournament when holding The Hellmuth. Thursday, October 26, 2006 I bought a Bag of Crap from Woot.com on Friday the 13th, and it arrived today, one day ahead of schedule. People across the country started receiving theirs last Saturday, and the anticipation of it was really the best part. I was pretty sure I was getting the same camera bag (cool) and thumb drive locks (lame) that everyone else was getting. The real question was what my good bonus crap would be. Almost everyone else seemed to get something else good, and some cheap Chinese toy. The box was labeled "Kensington Standard Keyboard - 10 Pack", and I know that a lot of people had received these. I was hoping I got one, too, because I'd like to be able to use it with my laptop instead of my smaller laptop keyboard. No luck -- it's got a PS2 connection, not USB. Bah. But my daughter wanted a new keyboard,,,, because her comma key has a habit of repeating. What else? My Chinese toy crap was a 5-pack of "color-your-own" velvet stickers, with 45 tiny stickers per sheet. Groovy. But wait! I got a bonus crap: an alternator tester. Discontinued, but Google shows that it was $2.99 at Harbor Freight. Bill's claimed it :-) Wednesday, October 25, 2006 Over the last two nights, I've been playing at the $1.50 + $0.25 sit-n-go tournaments, NLHE and HORSE. Five tournaments, two wins and an in-the-money: Last night, NLHE, I get knocked out in 12th place out of 18, after losing a third of my stack after flopping two pair, then losing a race to a small all-in stack, then losing the rest of my stack with bottom pair. Simultaneously, I win a HORSE tournament, 1st out of 18 (+$9.60), winning with a better two pair than my opponent in seven stud (my worst of the five HORSE games) Then, I place 4th out of 18 in another NLHE (+$2.70, net +$0.95), taking down some big pots along the way with: AQo (two pair, QQ22A); AJo (scaring out my solo opponent with an aggressive post-flop bluff bet, when the board was three clubs); AQo again (buying the blinds); and ATo (buying the blinds) But then I went too aggressive in the big blind with K4o, when the board came 999/J/4, then lost the rest of my stack with pocket deuces (never leuces!) against pocket kings on a paired flop (344). Tonight, I placed 6th out of 18 in HORSE, overvaluing my pair of kings in a four handed seven stud check-o-rama. Then I won a NLHE tourney, 1st out of 18 (+$10.80), in a long 58 minute marathon (yeah, turbo SNGs seem really long after 45 minutes), scoring a huge heads-up pot near the end with 87o and a board of J8K/7/A, then finishing it off with pocket aces against A9, and a board of 7JJ/4/J. Monday, October 23, 2006 Before I toss my notes from my grand tournament weekend, I figured they might be useful to someone. This is probably already outdated, but for what it's worth, here's a list of poker tournaments in the south sound scheduled for weekends in October 2006. All prices include buy-in and fee (usually $5), and are NLHE, unless otherwise noted. Most information is compiled from the Western Gambling Journal. [A] month before a major election, the Republicans have allied themselves with a scattering of voters who are upset by online gambling and have outraged the millions who love it. [T]he outraged millions are disproportionately ... Republicans and Reagan Democrats. In the short term, this law all by itself could add a few more Democratic Congressional seats in the fall elections. We are talking about a lot of people (an estimated 23 million Americans gamble online) who are angry enough to vote on the basis of this one issue, and they blame Republicans. In the long term, something more ominous is at work. If a free society is to work, the vast majority of citizens must reflexively obey the law not because they fear punishment, but because they accept that the rule of law makes society possible. ...Thus society is weakened every time a law is passed that large numbers of reasonable, responsible citizens think is stupid. Such laws invite good citizens to choose knowingly to break the law, confident that they are doing nothing morally wrong. [T]he federal government once again has acted in a way that will fail to achieve its objective while alienating large numbers of citizens who see themselves as having done nothing wrong. The libertarian part of me is heartened by this, hoping that a new political coalition will start to return government to its proper functions. But the civic-minded part of me is apprehensive. Reflexive loyalty to the rule of law is an indispensable cultural asset. The more honest citizens who take for granted that they are breaking the law, the more their loyalty to the law, and to the government that creates it, is eroded. FWIW, 888.com (Pacific Poker) e-mailed me this weekend; they're pulling out of the US. Rumor is that Neteller's going to pull out in nine months, but I haven't confirmed that yet. (Edit: Confirmed; Neteller will comply with the act.) Sunday, October 15, 2006 I don't know what makes it so easy to end up in the money here, but it is. Play tighter than Hellmuth's top ten hands, let go when you miss the flop, don't worry about being blinded out, and you're in. I probably won only three hands all night, and ended up in fifth place, winning $40. Add $20 for blackjack match play, subtract the $25 buy-in, and that's a net of +$35 for the day, and +$121 for the entire weekend. My knockout hand was the Hellmuthian 77. Perhaps I could have waited one more round, but the final five were playing uncharacteristically tight. A8 called me, and hit an 8 on the turn. Saturday, October 14, 2006 I arrived just after 7:00 to sign up for the 8:00 tournament, and the 30 spots were already filled; there was already a waiting list. I was second on the list. As an idea of how tight this tournament was: 1) it started at 7:00; 2) I didn't get a seat as the second alternate until after 7:30, and 3) I didn't hear them seat any alternates after me. I played until about 9:15, and the three tables were still at 8 people each. I took advantage of the tight play a couple of times, building my initial 4000 chip stack to almost 7000, but had two bad beats which brought me down to about 2000 (the player to my right, with pocket fours both times, called my AQ and AK, hitting a 4 on the flop both times). Then, on the small blind, I made a donkey move, trying to win a battle-of-the-blinds with K7o, raising the big blind, who called, then bet, and I pushed all in to scare him off, and he called, winning with A4 (yes, his four paired. Fours were mean to me tonight.) My remaining 300 in chips weren't enough to live past the blinds. Net: -$40 I could stay up and hit Happy Days' 2:00 AM tourney, but I think I'm pokered out for the night. And I've got to see about a Horse in Renton tomorrow morning. With an hour to spare before the tournament started, I had lunch at the buffet. Outstanding food. All the clams you can eat. Definitely somewhere to stop for lunch again next time I'm in the area. I hop into the tournament at 5:00, and play for 1:45. The top five spots pay, and I'm eliminated in seventh place. With 3000 in chips left, and blinds at 1000 and 2000, I'm dealt TT in middle position. I push my three chips all in, get a caller, he shows Q7, and hits a Q on the flop. Bah. And after playing for 1:45, I'm not going to make it to Happy Days' 7:00 tourney tonight. I'm sensing a pattern tonight. Medium pair, all in, getting beat by a higher pair. Time to stop doing that. I returned to Happy Days for the 2 AM tournament, and was essentially knocked out after the first orbit. On the button, I was dealt KK, with blinds at 100/200. Several players called, and I raised to 600. Big blind raised to 1200, everyone else folded, and I pushed all in, hoping to scare him off. He thought for quite a while, then called, turning over AQ. He hit his ace on the flop, leaving me with 200 in chips. I waited until I was UTG, put my 200 in, tripled up to 600, and then got stuck on the big blind when the blinds went up to 200/400. My all-in in the dark didn't turn out so well, when I ended up with 63o and not pairing. IGHN. (Edit: originally titled "Four for four: respect my authoritah!") After yesterday's rant about how I seem to suck at low limit brick and mortar ring games, I spent a few minutes talking to my wife about it. As I described it to her, I think I discovered what the problem is: I play very tight, and very aggressive, and in online play, and in tournaments, that aggression is rewarded -- I frequently take down pots unopposed. In low limit ring games, where true donkeys will call with almost anything, aggression is very rarely rewarded with an uncontested pot. Somebody's gonna go to the river, and somebody's gonna hit two pair. The only solutions I see: tournament play only. I don't know that playing higher stakes would make a difference, and I really doubt that I could play as aggressively at the higher level; it's too intimidating. So, with the wife and kid on a trip this weekend to Ocean Shores, I'm spending the weekend playing as many tournaments as possible. It's started out well -- at tonight's 7:00 Happy Days tournament, I placed third, netting $156 (plus $10 in blackjack match play, plus another $10 in non-match play BJ waiting for the tourney to start.) I've placed in the money every time in the last four Happy Days tournaments, and have won four of the seven brick and mortar tournaments I've entered this year. I tried something new tonight, which allowed me to finish in third place instead of fifth, which is a big chunk of change: when it gets down to the final table, don't worry about getting blinded out. Almost everyone has a small stack compared to the blinds, and you're going to lose a couple of players every orbit. Let the other players knock each other out. Even if your on the big blind of 10000, and your stack has only 10000 left, there's no need to call with a less than premium hand. You've got another orbit left in you -- let some other people get knocked out, and you'll end up in the bigger money. Thursday, October 12, 2006 I had a free hour tonight, so I set down at the $3/$6 table at Happy Days with $100. 90 minutes later, I go home with nothing. I'm trying to figure out why I do so badly at live tables with really bad players. In my last three Happy Days ring games, I've ended -$100, +$26, and -$94. When I played the $1/$2 games in Los Angeles last winter, I had four losing sessions for a total loss of $150. When I have the best hand, I know I've got it, and I raise the pot. This generally has the intended effect -- scaring all but one or two other players out. With few exceptions, though, they limp along, and hit their winning card on the river. Case in point: two big hands tonight. I was fairly card dead, and only played past the flop on three hands all night. One hand, I had AT, and the flop came A74. Five players called $3 to me on the small blind, and I raised it to $6. They all called. The turn was another rag. I bet six. All but one guy -- who seemed like he was on crack -- folded. He called. The river's a Q. I bet 6. He called. He turns over pocket queens. Did I make the pot too big? I don't think so, since he only had two outs. But this is how it frequently goes when I finally get into a hand. Similarly, I have K♥Q♦ in late position, and hit a Qxx flop with two diamonds. I raise, get a caller, and the turn is another diamond. I bet to see if I'm behind, and crack man just calls. I think I'm still good, and when the river's a fourth diamond, I push my last $4 all in. He calls, and shows A♦4♣. Bah. I'd hate to play so tight that all I do is play sets, flush draws, and open ended straight draws after the flop. Folding TPTK makes no sense, but when six players see the flop with six really random hands, I think I might always be behind two pair every time. Sunday, October 08, 2006 I arrive at Happy Days at about 12:30 this morning, get on the $3/$6 waitlist, watch Pai Gow for a few minutes, and soon get a seat at the table. The players here seemed much more reasonable than last week -- loose, but not insanely loose. No spectacular plays, but after an hour, I was up $26. With the $25 tournament buy in, and a match play win and loss at blackjack (net +$10, minus $1 tip), I'm ahead $10 for the night, regardless of how I do in the tournament. Hand 1, blinds are 100/200, and we've got 5000 stacks, I'm dealt AJo in early position, I raise to 500 pre-flop, and have two callers from late position. The flop is J-rag-rag, so I bet 500. One folder, and the button raises to 1500. I'd played against him in the ring game, and he was a very aggressive player who played some marginal hands. I put him on JTs, or AK. I push all in. He thinks, knows from my previous ring game play that I'm a tight, tight aggressive player, and makes the correct decision to fold. Thus my lucky streak began. Over the next 2½ hours, I won the hands I was supposed to win, even in near-race situations: My pocket kings won twice. I knocked out an AA player with 6♥ 8♥ when he let me limp in on the big blind, and the flop came ♥♥♥. My AQ beat KQ. My AJ beat KJ after the flop, belonging to the guy who folded to me on hand one. When I called his all-in, he said, "OK, show me your AJ." I was happy to oblige. My QQ beat 99. I split a pot when the board made a straight with our matched kickers. At the final table, a good solid player, pondering whether to call my semi-bluff raise (I paired an ace on the board with something like A4), told me "You're the one person I don't want to face in a situation like this," and folded. That's a huge compliment. thx; good fold. Finally, in fifth place with a medium sized stack, blinds of 5000/10000, I've got 63o on the big blind, and get to see the flop for free: A63. Small blind puts in 10000, and I put him all in for 25000 more. I've got 20000 left. He says, "did you pair the ace?" "Nope," I tell him, and he calls, showing pocket sevens. My two pair are in a comfortable lead, but an ace falls on the river, forfeiting my threes, giving him two pair, aces-over-sevens, beating my two pair, aces-over-sixes. The next hand, dealt A5 in the small blind with 15000 left, it's checked around to my, and I try to buy the big blind with an all in raise. He calls, pairs the board, and I go home in fifth place. Perhaps I should have stuck around another orbit; maybe someone else would have gone out before I did. For my 2½ hours of play, I cash out for $70. On my way to collect my winnings from the brush, a player at the $4/$6 table asks how I'm doing; I tell him I got knocked out in fifth, having my two pair get beat. "I'd counted on you winning the whole thing," he said. Another great compliment. That's cashing three times in the last three times I've entered the tournament. I'm shocked, really. +$80 for the night. After dropping $100 at the $3/$6 tables at Happy Days last weekend, I was looking for somewhere else to play last night. I'd seen an ad in the Western Gambling News two months ago for the Torch Lite casino, which is in Lakewood on Pacific Highway near the new fire station. It was vacant. This wasn't very surprising, since I had never heard about them, other than their one ad, and from the outside, it wasn't clear that there actually was a card room. Heading further north, to 84th Street, I stopped by Chips Casino, which doesn't offer poker, but the new Palace Casino next door does: $3/$6, $4/$8, $8/$16, and Omaha. The waiting list for $3/$6 was at least 15 people. I put my name on the list, sat around for a while, and when the list wasn't moving, went across the freeway to Silver Dollar. After fighting for years to stay in business, the owners of Tacoma’s three remaining minicasinos have quietly closed their doors following the defeat of last month’s ballot initiative aimed at overturning a city-imposed casino ban. Michael Purdy, former general manager of two Silver Dollar casinos and the leader of a group that brought legal action against the city, said Friday that a few of the approximately 285 employees at the two locations found jobs at other Silver Dollar casinos in Washington. The rest, like him, are looking for work. Although he’s disappointed by the outcome of the election, Purdy said he accepts the decision of the voters. Purdy said his group, called the Associated Casino Employees for Survival, agreed with casino ownership that if voters rejected the initiative, they should shut down. “It’s not worth beating a dead horse,” he said, even if it wasn’t an overwhelming “no” vote and a low election turnout. Initiative 1 received 15,372 no votes, or 53 percent, and 13,661 yes votes, or 47 percent. I guess the Washington State Brick and Mortar Casino Protection Act of 2006 didn't help them at all. Sigh. Up Pearl Steet, into Ruston, stopping at the Point Defiance Casino. Two tables: $4/$8 and Omaha, close to full, but with immediate seating. I'm still chicken to play live $4/$8, so I left there, drove out of Ruston through the tunnel, out past where Luciano's used to be, and while I briefly considered heading north into Fife to check out Freddy's club, it was about midnight, and I knew Happy Days would be starting the signup for their 2:00 a.m. tournament fairly soon. Home freak home, I guess. Monday, October 02, 2006 Well, as I feared, Congress -- led by the party of smaller government (?!?) -- has attached an anti-internet gambling measure to an unstoppable port security bill. President Bush will be signing it shortly. Neteller is mentioned in a few of the articles I've read, and I'm getting the feeling that its days of servicing the US are numbered. Maybe I'm paranoid, but I think it's time to cash out until the dust settles. I've cleaned out my Party Poker account, leaving $25 that I'm willing to lose. I've cleaned out my Neteller acocunt, leaving nothing. I've still got money in my PokerStars account, but will probably empty that tonight. It's a run on an uninsured bank, Wonderful Life style! Hopefully, I'm near the front of the line. It'll be fascinating to see what springs up to take its place. I wouldn't be surprised if some foreign bank begins allows US citizens to create offshore bank accounts, and access them through an ATM. It's probably happened already, and I'm just not aware of it yet. Sunday, October 01, 2006 I went to Happy Days to play in their midnight tournament again last night, but they had just changed the schedule: noon, 7 p.m., and 2 a.m. No more midnight tournament. Instead, I sat down at the $3/$6 table, and was absolutely card dead. By playing tight agressive, you could make a killing at these tables, with six people seeing almost every flop, and half the hands ending with a three person showdown. In my 75 minutes at the table, I only saw two hands where there wasn't a showdwn. Wild. Unfortunately, I only received three hands worth playing. My pocket nines didn't improve by the river; on the small blind, my pocket jacks got beat the by pocket aces on the button; and my AK hit a king on the flop, but lost to K8 when an 8 came on the river. Add in five orbits where my big blind was either garbage (fold on the flop) or was mediocre (fold to a pre-flop raise), and I ended up not winning a single hand. Bah. | Low | [
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CIAC BOYS' LACROSSE GAMEDAY CAPSULES Published 12:00 am, Friday, June 7, 2013 CIAC Class L Championship No. 4 Fairfield Prep (17-3) vs. No. 3 Staples (16-4) ?When: Today, 1:30 p.m. ?Where: McMahon High School, Norwalk ?What to look for: Fairfield Prep is the defending Class L state champion. The No. 1 team in the Register Top 10 Poll, the Jesuits arrived in the title game after a come-from-behind 12-9 victory against Ridgefield in the semifinals. Prep is has a myriad of weapons led by senior attack Kevin Brown, who is coming off a five-goal game against the Tigers. Attacker Tim Edmonds, midfielders Austin Sims, David White and Sean Henry add depth to a smart and talented offense. Defensively, Prep is just as strong, highlighted by Connor Henry in between the pipes. Staples earned its way to the title game after a huge 6-5 victory over Greenwich in the quarterfinals and then a 4-2 win over No. 2 Simsbury. Defense has been the No. 3 ranked Wreckers' strength all season. Senior captain Quinn Mendelson, along with Lancer Lonergan, Jack Greenwald and junior goalie Cole Gendels, are the face of an aggressive and formidable defensive line. Seniors Joey Zelkowitz and Colin Bannon are two of the top offensive threats in the state. ?Championship appearances: Prep will be playing in its eighth straight Class L title game. Staples' is making its first Class L appearance. The last time the Wreckers played for a title was in 1999 at the Division II level. ?You should know: The two schools are just six miles apart. The last time they faced each other was in the quarterfinals last season, with Prep winning 13-4. In 2010, Prep defeated the Wreckers in the semifinals, 9-8. CIAC CLASS M championship No. 2 BARLOW (20-1) vs. No. 17 WILTON (12-9) ?When: Today, 11 a.m. ?Where: McMahon High School, Norwalk ?What to look for: Defense is the Falcons' strength and a good indication of that is Barlow's come-from-behind 5-4 win in OT over New Canaan in the semifinals. The defense is led by goalie Cooper Brown and midfielders Ian Zangrillo and Billy Wilson and defender Alex Gallaer. The offense is led by attackmen Liam Rooney and Zach Pompei and midfielder Conn Curry. The Warriors' strength is also on defense led by goalie Connor Johnson and defenders Henry Lee, Michael LaSala and Nick Wells. Among the top scorers for the Warriors are Thomas Hayes, Brendan Devane and Ryan Brameier. ?Championship appearances: Barlow won the Class S title last season and moved up to Class M. Barlow makes its fifth state championship appearance with a Division II title in 2002 in addition to the S title. Wilton makes its ninth state championship appearance with four Division I titles (1995, 1998-99, 2004) and a Class M title in 2011. ?You should know: The Falcons are on a 10-game winning streak including a victory in the South-West Conference Division I tournament championship game. Class S State Championship No. 13 St. Joseph (12-8) vs. No. 15 Weston (13-9) ?When: Today, 6 p.m. ?Where: McMahon High School, Norwalk ?What to look for: Defense is the name of the game here. Both teams arrived in the title game via a stifling effort limiting their opponent's offensive attacks. St. Joseph is the younger team that beat No. 1 Stonington 9-6 in the semifinals. Sophomore keeper Mike Braddick, along with defenders Jorge Yoguez, Kurtis Murde and Zak Psaras make a tough match for opposing teams. Ryan Corcoran of Stratford leads the offense for the Cadets as a smart player who can change a game at a moment's notice. Weston's road to the title game started in the qualifying round on May 24. Since then, the Trojans have been on a mission, outscoring opponents 47-25. Weston uses an effective zone defense, coupled with great ball possession play. In the Trojans' 10-5 semifinal win over Morgan, Weston showcased its offensive weapons as Austin Drimal scored four times, Troy Flynn added two and Sean Fumai chipped in with one and added three assists. Grant Limone is the Trojans' goalie. ?Championship appearances: Weston has won state titles in 2007 and 2010. St. Joes won its last Class S title in 2011, beating Barlow 6-5. ?You should know: These two teams met for the Class S title in 2010. Weston won 7-6. | Mid | [
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Q: SQL like wrapper for Windows Registry? The per key handling of updating the registry seems a bit poor when dealing with large volumes of data. Are there any libraries that would treat all keys as tables and allow INSERTS, UPDATES, or SELECTS in a more programmatic fasion? A: If you want do do scripting windows powershell has some quite nifty registry access. It handles the registry as if it were a filesystem. | Mid | [
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Alternative Titles: ワンド オブ フォーチュン2 FD～君に捧げるエピローグ～ Company: Otomate Release Date: 22.11.12 Official Site: LULU <3 Platform: PSP Genre: AVG, Otome, MORE LULU <3 End to WOF Plot Summary: I JUST FINISHED MA FINALS and guess what I did? I went home, all ready to sleep from the horrible consecutive all nighters pulled, but for some reason, I ended up sitting down for 2 hours and typing a 9000 word…review. This. It seems like I am a masochist after all…Anyway this is the final wof game and it’s a shitton of fanservice of Lulu growing up, growing…down and just Lulu being super adorable <3 Continue reading → | Mid | [
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Lawsuit Filed to Stop Voter Photo ID Law A lawsuit has been filed to stop Missouri’s new Voter Photo ID requirement from becoming law on August 28th. Attorney Don Downing has filed the suit in Cole County Circuit Court on behalf of several plaintiffs who say that while a non-drivers license photo identification is free, the documents required to get one of those cost voters. That, he says, constitutes a violation of voting rights. Downing says the current requirement allows people to identify themselves with their voter registration cards or even a utility bill when going to vote. He considers this adequate. Downing says even the Governor, a backer of voter photo ID, had to admit that there was no problem with people fraudulently voting in the last two elections in the state under the old requirements of identification. Downing calls the new requirement a solution in search of a problem. Downing’s lawsuit has the backing of the state Democratic Party. | Mid | [
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John Dickerson is a political junkie, peppering his conversations with references to previous election cycles and stats from contests in decades past. | AP Photo Inside CBS host John Dickerson's debate prep The network plans a debate focused on foreign policy and Wall Street. The day before the New Hampshire primary, CBS anchor John Dickerson walked into an American Foreign Legion post in Manchester to observe a Ted Cruz event. The host of one of the big Sunday talk shows and the moderator of Saturday’s Republican debate went nearly unnoticed, slipping in among reporters with little fanfare. It seems that few people noticed him, or if they did, they didn’t care. The CBS team is keen to keep the focus tonight off its “Face the Nation” host too. "My goal is to be a window; you see the candidate, I’m just making it easier for people to see what the candidates believe and think,” Dickerson said in an interview in his barely-unpacked offices in the week before the first primaries. "We want to illuminate things so people feel like they have some control over this thing that’s happening on their behalf. They’re out there talking and trying to work out answers and we’re trying to facilitate that for people in the audience." In the corner of Dickerson’s barely moved-into office at CBS’ Washington bureau, brown butcher paper hangs on the wall. It's where Dickerson has mapped out the questions he'll ask at the debate in a big spiderweb-like flow chart of topics, questions and comments. Over days and weeks, the chart expanded until Dickerson ripped the paper off, folded it up and took it with him to planning meetings with the rest of the CBS debate team. “It’s like outlining but less linear,” Dickerson said of the butcher paper method, something he said he “always wanted” in an office. “We’ve got about 150 questions planned. I have had questions I’ve wanted to ask for 10 years,” he added. Part of Dickerson’s preparation for the debate has included dozens of interviews with policy experts, his weekly interviews with the candidates as host of “Face the Nation”, the Slate podcast "Whistlestop", and reporting from the trail. Dickerson is also a political junkie, peppering his conversations with references to previous election cycles and stats from contests in decades past. The 1980 presidential debates serve as an examples of a debate that illuminated real differences between the candidates and famed NBC News anchor John Chancellor, a moderator he admires. "When he unfurled the brown paper and tacked it up on the wall in Des Moines (before a Democratic debate) I thought it was a joke. Then I went and took a closer look and I realized this man is slightly obsessed but it became actually a road map for what we were going to do," said CBS News Executive Editor Steve Capus. "He’s a great collaborative player." Dickerson, as he prepped for the debate, said he would have never guessed the anger and restiveness in the country would translate into Donald Trump rising to front-runner status in the Republican primary. "That he would be able to survive all the things he’s survived, that he would totally change the posture of a party that ended the last presidential campaign by talking about the need for immigration reform and his number one issue would be the opposite message that came out of the Republican Party autopsy is one of the wonderful thing about politics -- that it’s a total surprise," Dickerson said. "That’s what makes races so much fun to cover -- they're a surrpise and people get to make the choice and not us." Dickerson said that in his dozen interviews with Trump, the New York billionaire answers some questions more bluntly and candidly than other politicians. The questions facing the candidates on Saturday will likely focus on foreign policy and Wall Street than spats between the candidates, the network said. "While we're doing the debate prep, we kept an eye on Wall Street, an eye on Syria and what the Russians were saying that was going on in Aleppo, and we kept our eye on what the candidates were saying on the campaign trail. There are four timely areas of discussion and I know that we’ll be doing that into Saturday," Capus said. "I think in our last debate we were still sitting in a conference room about 25 minutes before the debate, putting the final touches on the questions." Other questions, such as whether Sen. Ted Cruz is eligible to run for president, an issue Trump resurfaced this week, are less likely to be raised by the moderators. "If it’s something one candidate is shooting at another about, you have to worry, are you doing the candidate’s work for them? Is this going to tell us something?" Dickerson said. Capus emphasized that CBS is not looking for flashy cage matches to capture big TV moments. "We want to keep focusing forward," he said. "We know that the candidates are going to go after each other. I think that other news organizations get in trouble when they feel like they’ve got to generate food fights between the candidates." | High | [
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Q: App loading stages and memory leak hunting I'm still fighting with memory leak. Using improved MemoryDiagnosticsHelper, i added possibility to make datastamps to see immediate memory cunsumption. Problem starts at full app: i have a pivot with 3 items, 2 of them containing list of 10-20 objects (with possibility to jump to item details). Memory diagnostic shows, that it consumes about 50Mb of memory. After jumping to detail page and returning to pivot, memory consumption easily grows to 70Mb. At first, i moved list to separate app. Without style, it takes 15 Mbs. I didnt check yet, but i assume, 2 lists in pivot would take about 20Mbs, because dlls are already loaded. So, i decided to go deeper into app loading stage. At the InitializePhoneApplication(), it takes 7 Mb. At the CompleteInitializePhoneApplication(), it takes 8.5 Mb with empty ViewModelLocator, or 10.5 Mb with all viewmodels. Quite large, but i have 30-40 dataservices and 40-50 viewmodels. So let it be, i'd feel myself pretty ok, if it would not grow anymore. At the first page's OnNavigatedTo(), it takes almost the same, kinda 10.7 Mb with all VMs, that's ok. ??? No profit. Seriously, what happens next? I cant see, what exactly is going on next, but MemoryDiagnosticsHelper says, that memory consumption jumps to 30 Mbs. Why? All dlls and VMs are already loaded. I'm just loading a very empty page, totally white. Profiler (running in release mode, of course), is also helpless. It just shows growth in memory consumption, but it happens in non-managed memory. It annoys alot, really. Ok, lets make question more clean. What happens next, when app is initialized (passed initialization, and viewmodel loaded and attached, and page passed OnNavigatedTo())? EDIT 1: in the night, i got and idea, that the only weak part in my app (at least, that master-detail pages) is MVVMLight's EventToCommand. Almost first article in google is http://atomaras.wordpress.com/2012/04/23/solving-mvvmlights-eventtocommand-memory-leak-wp7/ Anybody knows, if it is alreasy fixed? I checked MvvmLight's blog, and looking like Laurent is working on installer for now. That pushes me to idea, that this leak should be already solved, isnt it? EDIT 2: i see 2 solutions for leaking problem: either to use fix from the link above, or call commands from the codebehind. Or use another MVVM lib. A: References. I expected them to be loaded smoothier, during first stages of app init. Also, now it is clear, why profiler said that there's not that much managed code in the memory. | Mid | [
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70 years before The Avengers regularly broke box-office records for The Marvel Cinematic Universe, Universal Studios had its own cultural juggernaut with the Universal Monsters. Bela Lugosi and Boris Karloff became immortal in 1931 as the titular and the oft-mistakenly-titular Dracula and Frankenstein respectively. Their individual box-office success made monster movies a cultural mainstay and paved the way for Universal Studios to expand their roster to include The Mummy, The Invisible Man and The Wolf Man. This is exactly the model Marvel Studios followed when building to The Avengers. Start with the most straightforward character available and use him as the foundation. Dracula and Iron Man, both ambitious gambles that paid huge dividends. Step two is trickier because it involves investing in an unreliable green monster. Universal struck gold with Frankenstein but Marvel hit an early sophomore slump with The Incredible Hulk. If you don’t count Marvel going back to the well with Iron Man 2, then step three is pluck a supernaturally powerful cinema icon out of the myths of a foreign nation like The Mummy and Thor. Once you complete the team with Captain America: The First Avenger and The Wolf Man you’ve got yourself the makings of a team up film. Frankenstein Meets the Wolf Man is technically the first Universal Monster team-up film, and you might think Monster Squad is the best monster team-up movie, but House of Frankenstein is where the shared universe expands and begins to direct the course fo the preceding films in the franchise. This is a crazy movie when viewed in the context of the shared universe. Taking place years after the events in Frankenstein Meets the Wolf Man, House of Frankenstein begins with Dracula, the Wolf Man and the Monster all more dead than usual and it’s up to Boris Karloff to bring them all back to life. That’s not a typo. Boris Karloff, the man made legend for his portrayal of Dr. Frankenstein’s monster, does not play the monster in House of Frankenstein. Karloff plays Doctor Niemann, an escaped inmate listed as simply ‘Mad Doctor’ on the English movie posters. Niemann’s imprisoned with his hunchback assistant Daniel for experimenting with replacing a dog’s brain with a human brain. Niemann wants revenge for the 15 years he spent behind bars and lucks into assuming control over a traveling circus which just so happens to have the skeleton of Dracula as its main attraction. Yeah, it’s really Dracula’s skeleton, stuck in his coffin with a stake through his heart surrounded by the dirt of his homeland. Niemann knows that removing the stake will reanimate the vampire Lord and makes haste to do so. Undead once more, Dracula agrees to assist Niemann in killing his enemies. Oh but this is not Bella Lugosi reprising his famous role as Count Dracula, no the vampire is played here for the first time by John Carradine. His resurrection is short lived as the searing rays of sunlight disintegrates the Count to so much dust, forever mixing with the soil of a land not his own. At this point, Daniel the hunchback wants to be a handsome man with a good body. With the unwavering confidence of the man who both brought back and rekilled Dracula, Niemann decides sets a course to Frankenstein’s castle or… house… where he expects to find secret documents to aide him in replicating the process which animated the monster in the first place. Well, what do you know, they succeed. In a mysteriously glacial cave beneath the castle, Niemann and Daniel find the bodies of the Wolf Man and the Monster entombed in nice clear blocks of ice (not unlike Captain America) waiting to be defrosted. It occurs to the Mad Doctor that these two creatures might know the location of the missing secret documents. That’s enough incentive for these two maniacs to start a huge bonfire in the rubble of a destroyed castle in the hopes of awakening two literal monsters without regard for their own safety… or you know… the safety of the missing secret documents. The succeed in freeing both monsters and convince Larry Talbot, the Wolf Man played by Lon Chaney Jr., to assist them in their cause. He’s incentivized in no small part by the addition of a beautiful young gypsy woman to the team. Actually he doesn’t seem to care about her at all, but like all Lon Cheney Jr.’s characters from the Inner Sanctum Mysteries, Larry Talbot is irresistible to women. This time I can’t blame her, she’s a young woman in the prime of her life and she’s suddenly surrounded by three eligible bachelors. One is a psychotic mad scientist, his hunchback assistant and a tall doughy man who turns into a murderous lycanthrope every full moon. We’d all make the same choice. The Monster’s in shambles compared to the Wolf Man and it becomes Neimann’s goal to get him back in working order. Oh, you might be wondering who’s playing the Monster since Karloff is playing Niemann the Mad Doctor. Well it’s probably not Lon Chaney Jr. who’s already reprising his role as the Wolf Man, even tho he did play the Monster in Ghost of Frankenstein. Gasp, could it be? Bella Lugosi played the Monster in Frankenstein Meets the Wolf Man, if he isn’t playing Dracula then he’s at least playing the Monster… right? Wrong. He’s not in this movie! Look at the poster! He’s not listed. Some nobody named Glenn Strange played the Monster in this feature. Yeah, I know what a bummer. I looked him up and it looks like he had a meager career only appearing in 239 episodes of Gunsmoke. That’s like, almost a third. He’s the Scott Baio of Gunsmoke. Anyway, Lugosi isn’t in this picture. Which is a shame. You couldn’t have The Avengers without Robert Downey Jr. I mean, presumably we will have that the next time there’s an Avengers film, barring some sort of lame cameo or if Bobby wants to buy his dad a new island. Back to the plot. Unbeknownst to Daniel, who’s furious that Neimann’s changed his mind and is no longer planning to put his brain into Talbot’s body, Larry is preparing to transform once again into the murderous Wolf Man under the light of the full moon. Daniel, furious that he’ll never use Larry’s good looks to win the affection of Rita the gypsy girl, goes rouge and attempts to murder Karloff with his bare hands in the laboratory. This invigorates and enrages the Monster who breaks his shackles and throws Daniel to his death through a castle window. Meanwhile a mob of torch wielding villagers approach the ruins of a castle that’s brought nothing but death and destruction to their lands. As the mob nears, the light of the moon beams into Talbot’s room transforming him into the wolf man yet again. But he’s in luck, Rita has crafted a silver bullet to end his torturous existence once and for all (he comes back in later films). She succeeds but not before the mindless Wolf Man kills her in turn. The Monster flees the mob’s torches with Niemann in tow, eventually running the two of them from one lethal end to another. House of Frankenstein, the The Avengers of its day, ends with Frankenstein’s Monster dragging an objecting Karloff, his surrogate father (who feels more like a brother ya know?), to his death in an enormous pit of quicksand. And then the movie just ends. Karloff has his head just above water when the film fades to an end slate. That’s just how they did it back then. House of Frankenstein is far more watchable than many of its preceding monster films like Dracula’s Daughter or Son of Dracula. It’s easy to see the care taken in the set design, cinematography and story development in House of Frankenstein. It’s not a script that’ll change your life but it’s impressive to see how Universal handled incorporating these otherwise mostly independent characters into a relatively coherent plot. Even if Dracula was shoehorned in. It’s a fun movie, check it out. I’m left pondering the irony that despite setting the pace for shared universe film franchises like Marvel with their Universal Monsters, Universal Studios couldn’t replicate Marvel’s success when reanimating their monsters for 21st century audiences. Tom Cruise’s The Mummy seemed to kill all hopes of a Dark Universe but then again, Blumhouse’s The Invisible Man might be successful enough to save this newest iteration of the franchise. I certainly don’t know or claim to know, but If it was me, I wouldn’t have started a new franchise with the box-office equivalent of The Incredible Hulk. | Mid | [
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How to Build Your Company's Sustainability Cred How to Build Your Company's Sustainability Cred It's pretty well accepted now that sustainability is not the key purchase criteria for most customers. Few are going to buy a product or service because it's greener than a competitor's or made by more equitably treated employees if it costs more or doesn't perform as well. Of course, there are product and service "eco-niches" supported by customers who will buy green despite poorer performance and price. But, with competitors continually strengthening the value of what they provide while increasingly making their offerings more sustainably, eco-niches will come and go But here's the flip side: Sustainability is a key consideration in attracting and retaining employees. And, it has become an increasingly important factor to shareholders of companies that have significant sustainability risks So what's the solution? Should you make your operations more sustainable, building your green-cred with employees and shareholders while passing on developing poor returning, eco-niche products and services? Perhaps, but that's a bar many will hurdle soon, if they haven't already in your industry. E&Y's recent survey found that 65 percent of executives planned to invest to "develop new products and services" in response to climate change. A more compelling approach is to grow your revenue with new products and services by leveraging sustainability taking one or more of the paths I've described below. None of these will put you in a position of trying to sell products to customers based on how green they are or responsibly they are made. All will strengthen the credible link between your company and sustainability that your employees and shareholders care about. This path is ideal for B2B businesses that sell equipment to reduce their customers' operating costs by cutting their use of resources and environmental impact in the process. GE has built a $7 billion business selling wind turbines this way. Diversey, a multi-billion dollar leader in industrial cleaning products and services, has introduced innovations that allow it to clean beverage plants and lower operating costs by using 30 percent less water and 60 percent less energy. P&G does the same thing on the consumer side, reducing customer energy costs with cold water washing machine detergents. Key to success taking this innovation path is to understand your customers' sustainability challenges well enough to develop solutions that help address them in a way that either lowers their costs and or improves their performance. "Innovating for" is clearly the busiest path for top line sustainability innovation and growth now. And with good reason -- there are tremendous efficiency improvement opportunities available. But, if your product or service has little opportunity to change a customer's sustainability, following this path will not yield the opportunity to benefit them or advantage you. Many associate environmental and socially responsible solutions with higher operating, capital or product costs. While investments are usually required to commercialize any innovation, sustainability solutions can take enormous costs out of company operations and processes and can provide improved product or service performance benefits. These can lead to discontinuous changes in the cost-performance relationship that will allow new products to grab greater share of existing markets or open new markets. New, less toxic and environmentally harmful household cleaners, for example, are taking share from traditional ones because they improve personal health. Sales of long-lasting LED lights are growing because the cost savings achieved from not having to regularly replace light bulbs in hard to reach locations outweighs the high purchase cost of these LEDs. This benefit is made possible because designers used their understanding of how sustainable materials and technology could greatly extend bulb life. Market demand drove $5 billion Eastman Chemical Company to develop its Tritan copolyester, a hard plastic for food and beverage container applications that had higher heat resistance than other solutions used at the time. Consumers wanted to be able to run their reusable plastic water bottles, baby food containers and other houseware items in the dishwasher and have them be resistant to odors, tastes and stains. Several years in development, Eastman introduced Tritan in 2007 to meet these performance requirements with a solution that was free of bisphenol A (or BPA). At the time of Tritan's introduction, BPA had just begun to receive more scrutiny for potential health issues but the research was not yet clear and no consensus had been reached amongst consumer and government agencies. In the next couple of years as companies including Thermos, CamelBak, and Evenflo adopted the Tritan innovation for its performance benefits, the testing on BPA made its risks better understood and states banned its use in kids' products. Eastman's "Innovate in Sustainability" got the jump on competitors developing BPA free solutions coming later from an "Innovate for Sustainability" path Key to "Innovating in" is the ability to build and combine deep knowledge of market needs with a well-considered understanding for the cost and performance trade-offs that exist with more sustainable product and process solutions. 3. Innovate with Sustainability: Develop or acquire innovations working with outside parties -- suppliers, researchers, licensors, startups and other corporations. As with any relatively new area of innovation, companies should look to collaborate with a wide range of external sources to accomplish their "Innovate for" and "Innovate in Sustainability" goals. Venture and corporate investment in cleantech continues high and quite promising, largely for sustainable energy and other resource solutions. GE, which built its $7 billion wind turbine business after acquiring it for $200M in 2002 from Enron, is now investing another $200M through a different type of "Innovate with Sustainability" initiative: an open-to-all idea generation contest. Its "ecomagination Challenge" is soliciting ideas for smart grid innovations from businesses, entrepreneurs and students through an online submission process. It will award $50,000 to $100,000 prizes to the best ideas and consider an equity investment or cooperative development agreement with the winners. Between outright acquisition of innovations and open innovation contests to find new ideas, companies driving for top line sustainability innovation are reaching out to suppliers to develop potential solutions. As an example, Coca-Cola, PepsiCo and Nestle are working to source bio-plastics for their beverage containers. Bottles made from these plant-based materials hold the promise of fully degrading in compost piles after only a few months. Those dedicated to growing their revenue through sustainability innovation must realize what competencies and technologies they lack to develop "Innovate for" or "Innovate in Sustainability" products and services. If they don't have the ability in-house, and most companies don't have the full range of what is needed, they must find others to "Innovate with" to remain competitive. These three paths to top-line sustainability innovation can focus your plans and action. Increasingly, all three will be needed to successfully leverage sustainability for innovation and revenue growth. | Mid | [
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# vi:filetype= use lib 'lib'; use Test::Nginx::Socket; #repeat_each(2); plan tests => repeat_each() * 4 * blocks(); $ENV{TEST_NGINX_MEMCACHED_PORT} ||= 11211; #master_on(); no_shuffle(); run_tests(); __DATA__ === TEST 1: flush all --- config location /flush { set $memc_cmd 'flush_all'; memc_pass 127.0.0.1:$TEST_NGINX_MEMCACHED_PORT; } --- response_headers Content-Type: text/plain Content-Length: 4 --- request GET /flush --- response_body eval: "OK\r\n" === TEST 2: basic fetch (cache miss), and no store due to max-age=0 --- config location /foo { default_type text/css; srcache_fetch GET /memc $uri; srcache_store PUT /memc $uri; content_by_lua ' ngx.header.cache_control = "public; max-age=0" ngx.say("hello") '; } location /memc { internal; set $memc_key $query_string; set $memc_exptime 300; memc_pass 127.0.0.1:$TEST_NGINX_MEMCACHED_PORT; } --- request GET /foo --- response_headers Content-Type: text/css Content-Length: --- response_body hello === TEST 3: basic fetch (cache miss because not stored before) --- config location /foo { default_type text/css; srcache_fetch GET /memc $uri; srcache_store PUT /memc $uri; echo world; } location /memc { internal; set $memc_key $query_string; set $memc_exptime 300; memc_pass 127.0.0.1:$TEST_NGINX_MEMCACHED_PORT; } --- request GET /foo --- response_headers Content-Type: text/css Content-Length: --- response_body world === TEST 4: flush all --- config location /flush { set $memc_cmd 'flush_all'; memc_pass 127.0.0.1:$TEST_NGINX_MEMCACHED_PORT; } --- response_headers Content-Type: text/plain Content-Length: 4 --- request GET /flush --- response_body eval: "OK\r\n" === TEST 5: basic fetch (cache miss), and no store due to max-age=0, and srcache_response_cache_control on --- config location /foo { default_type text/css; srcache_fetch GET /memc $uri; srcache_store PUT /memc $uri; srcache_response_cache_control on; content_by_lua ' ngx.header["Cache-Control"] = "public; max-age=0" ngx.say("hello") '; } location /memc { internal; set $memc_key $query_string; set $memc_exptime 300; memc_pass 127.0.0.1:$TEST_NGINX_MEMCACHED_PORT; } --- request GET /foo --- response_headers Content-Type: text/css Content-Length: --- response_body hello === TEST 6: basic fetch (cache miss because not stored before) --- config location /foo { default_type text/css; srcache_fetch GET /memc $uri; srcache_store PUT /memc $uri; echo world; } location /memc { internal; set $memc_key $query_string; set $memc_exptime 300; memc_pass 127.0.0.1:$TEST_NGINX_MEMCACHED_PORT; } --- request GET /foo --- response_headers Content-Type: text/css Content-Length: --- response_body world === TEST 7: flush all --- config location /flush { set $memc_cmd 'flush_all'; memc_pass 127.0.0.1:$TEST_NGINX_MEMCACHED_PORT; } --- response_headers Content-Type: text/plain Content-Length: 4 --- request GET /flush --- response_body eval: "OK\r\n" === TEST 8: basic fetch (cache miss), and store due to max-age=0, and srcache_response_cache_control off --- config location /foo { default_type text/css; srcache_fetch GET /memc $uri; srcache_store PUT /memc $uri; srcache_response_cache_control off; content_by_lua ' ngx.header["Cache-Control"] = "public; max-age=0" ngx.say("hello") '; } location /memc { internal; set $memc_key $query_string; set $memc_exptime 300; memc_pass 127.0.0.1:$TEST_NGINX_MEMCACHED_PORT; } --- request GET /foo --- response_headers Content-Type: text/css Content-Length: --- response_body hello === TEST 9: basic fetch (cache miss because not stored before) --- config location /foo { default_type text/css; srcache_fetch GET /memc $uri; srcache_store PUT /memc $uri; echo world; } location /memc { internal; set $memc_key $query_string; set $memc_exptime 300; memc_pass 127.0.0.1:$TEST_NGINX_MEMCACHED_PORT; } --- request GET /foo --- response_headers Content-Type: text/css Content-Length: 6 --- response_body hello === TEST 10: flush all --- config location /flush { set $memc_cmd 'flush_all'; memc_pass 127.0.0.1:$TEST_NGINX_MEMCACHED_PORT; } --- response_headers Content-Type: text/plain Content-Length: 4 --- request GET /flush --- response_body eval: "OK\r\n" === TEST 11: basic fetch (cache miss), and store due to max-age=<not 0> --- config location /foo { default_type text/css; srcache_fetch GET /memc $uri; srcache_store PUT /memc $uri; content_by_lua ' ngx.header["Cache-Control"] = "public; max-age=7"; ngx.say("hello") '; } location /memc { internal; set $memc_key $query_string; set $memc_exptime 300; memc_pass 127.0.0.1:$TEST_NGINX_MEMCACHED_PORT; } --- request GET /foo --- response_headers Content-Type: text/css Content-Length: --- response_body hello === TEST 12: basic fetch (cache miss because not stored before) --- config location /foo { default_type text/css; srcache_fetch GET /memc $uri; srcache_store PUT /memc $uri; echo world; } location /memc { internal; set $memc_key $query_string; set $memc_exptime 300; memc_pass 127.0.0.1:$TEST_NGINX_MEMCACHED_PORT; } --- request GET /foo --- response_headers Content-Type: text/css Content-Length: 6 --- response_body hello | Mid | [
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'Offline beer' glass stops drinkers using their phones YOU all have that friend who can't stop checking their phone, whether they're out having drinks with friends or sitting down to a nice dinner. The reason I know this is because that friend is me. I have serious FOMO (Fear Of Missing Out). The need to constantly have my finger on the pulse has ruined my social life. My friends hate hanging out with me and my husband thinks I'm having a secret love-affair online. But now, there might finally be a device that can save me from myself. It doesn't have any buttons. Or a touchscreen. In fact it's totally manual. It's a beer glass. And unless I want to spill my beer everywhere I have to use my phone as a coaster. It's called the "Offline Beer Glass" and it was designed by Brazilian ad agency Fischer & Friends to discourage anti-social behaviour. The glass basically looks like it has been given a thick heel, which unless is balanced out with a second platform, will fall and spill beer all over the place. The phone slides in underneath it, allowing it to sit normally on a table. The beer glass was unveiled at Salve Jorge bar in Brazil's biggest city, Sao Paulo to help drinkers put down their mobile phones and start enjoying their festivities. Watch the video above to see how the glass works. The good people at Jorge Bar haven't said what happens when people drink too much and knock their glasses over, spilling beer all over their phones. Hope Salve Jorge has a good insurance policy. They're going to need it! | Low | [
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1. Introduction {#sec0005} =============== With diffusion tensor imaging (DTI) the morphology of brain tissue, and especially the white matter fiber bundles, can be investigated in vivo ([@bib0155]), offering new possibilities for the evaluation of brain disorders and preoperative counseling. The optic radiation (OR) is a collection of white matter fiber bundles which carries visual information from the thalamus to the visual cortex ([@bib0210]). Numerous studies ([@bib0295], [@bib0225], [@bib0020], [@bib0280], [@bib0010], [@bib0090]) have accomplished to reconstruct the OR with DTI, by tracking pathways between the lateral geniculate nucleus (LGN) and the primary visual cortex. In the curved region of the OR, configurations with multiple fiber orientations appear, such as crossings, because white matter tracts of the temporal stem intermingle with the fibers of the Meyer\'s loop ([@bib0120]). Therefore, it is especially challenging to reconstruct the Meyer\'s loop, which is the most vulnerable bundle of the OR in case of surgical treatment of epilepsy in which part of the temporal lobe is removed ([@bib0090]). However, a limitation of DTI is that it can extract only a single fiber direction from the diffusion MRI data. With the advent of multi-fiber diffusion models it has become possible to describe regions of crossing fibers such as the highly curved Meyer\'s loop. Tractography based on constrained spherical deconvolution (CSD) ([@bib0240], [@bib0035]) has been shown to have good fiber detection rates ([@bib0270]) and has been applied in several studies to reconstruct the OR ([@bib0140], [@bib0150]). Furthermore, probabilistic tractography is considered superior in comparison to deterministic tractography for resolving the problem of crossing fibers in the Meyer\'s loop ([@bib0130]). The probabilistic tracking results between the LGN and the visual cortex for a healthy volunteer are illustrated in [Fig. 1](#fig0005){ref-type="fig"}. The tracking results are shown in a composite image along with other brain structures such as the ventricular system.Fig. 1Left: An example of the reconstruction result of the OR using probabilistic tractography from an axial view. As inserts, close-ups are shown of the anterior tips of the reconstructions of the OR from a coronal view. Right: The tracking results are shown for the same volunteer in a composite image along with other brain structures such as the ventricular system. The ML-TP distance measurement is indicated.Fig. 1 However, a common occurrence in tractograms obtained from probabilistic tractography are spurious (deviating) streamlines. Spurious streamlines are by definition not well-aligned with neighboring streamlines and may hinder the measurement of the distance between the temporal pole to the tip of the Meyer\'s loop (ML-TP distance). An accurate measurement of the ML-TP distance is required for estimating the potential damage to the OR after temporal lobe resection (TLR). Methods have been proposed for the identification and removal of spurious streamlines, for example based on outlier detection ([@bib0290], [@bib0150], [@bib0115]), based on the prediction of diffusion measurements by whole-brain connectomics ([@bib0185]), or based on the uncertainty in the main eigenvector of the diffusion tensor ([@bib0175]). Most of these methods for reducing spurious streamlines are based on density estimation in $\mathbb{R}^{3}$. In contrast, in the current study fiber-to-bundle coherence (FBC) tractometry measures are employed that are based on density estimation in the space of positions and orientations $\mathbb{R}^{3} \times S^{2}$. The stability metrics introduced in this study are based on the FBC measures. These metrics provide a reliable OR reconstruction that is robust under stochastic realizations of probabilistic tractography. To achieve a reliable reconstruction of the full extent of the Meyer\'s loop, an appropriate selection of streamlines is required such that spurious streamlines are removed while preserving streamlines that are anatomically more likely to exist. For this purpose the FBC parameter *ϵ* is estimated based on the measured variability in ML-TP distance. Here we respect an a-priori constraint on the maximal ML-TP distance variability for a test--retest procedure on streamline tracking and determine the corresponding minimal threshold *ϵ*~selected~ on the FBC measures. This threshold removes a minimal amount of spurious streamlines while allowing for a stable estimation of the ML-TP distance. In the current study the validity of the distance measurements is evaluated based on pre- and post-operative comparisons of the reconstructed OR of patients who underwent a TLR. It is investigated whether it is feasible to assess pre-operatively for each individual patient the potential damage to the OR as an adverse event of the planned TLR. The deviation between the prediction of the damage to the OR and the measured damage in a post-operative image is compared, giving an indication of the overall error in distance measurement. The main contributions of this paper are:•Quantification of spurious streamlines. We provide FBC measures that quantify how well-aligned a streamline is with respect to neighboring streamlines.•Stability metrics for the standardized removal of spurious streamlines near the anterior tip of the Meyer\'s loop.•Robust estimation of the variability in ML-TP distance by a test--retest evaluation.•Demonstration of the importance of the FBC measures by retrospective prediction of the damage to the OR based on pre- and post-operative reconstructions of the OR of epilepsy surgery candidates. 2. Materials and methods {#sec0010} ======================== 2.1. Subjects {#sec0015} ------------- Eight healthy volunteers without any history of neurological or psychiatric disorders were included in our study. All volunteers were male and in the age range of 21--25 years. Furthermore, three patients were included who were candidates for temporal lobe epilepsy surgery. For each patient a standard pre- and post-operative T1-weighted anatomical 3D-MRI was acquired. Patient 1 (46/F) was diagnosed with a right mesiotemporal sclerosis and had a right TLR, including an amygdalohippocampectomy. Patient 2 (23/F) was diagnosed with a left mesiotemporal sclerosis and had an extended resection of the left temporal pole. Lastly, Patient 3 (38/M) was diagnosed with a cavernoma located in the basal, anterior part of the left temporal lobe and had an extended lesionectomy. All patients had pre- and post-operative perimetry carried out by consultant ophthalmologists. The study was approved by the Medical Ethical Committee of Kempenhaeghe, and informed written consent was obtained from all subjects. 2.2. Data acquisition {#sec0020} --------------------- Data was acquired on a 3.0 T magnetic resonance (MR) scanner, using an eight-element SENSE head coil (Achieva, Philips Health Care, Best, The Netherlands). A T1-weighted scan was obtained for anatomical reference using a Turbo Field Echo (TFE) sequence with timing parameters for echo time (TE = 3.7 ms) and repetition time (TR = 8.1 ms). A total of 160 slices were scanned with an acquisition matrix of 224 × 224 with isotropic voxels of 1 × 1 ×1 mm, leading to a field of view of 224 × 224 × 160 mm. Diffusion-weighted imaging (DWI) was performed using the Single-Shot Spin-Echo Echo-Planar Imaging (SE-EPI) sequence. Diffusion sensitizing gradients were applied, according to the DTI protocol, in 32 directions with a *b*-value of 1000 s/mm^2^ in addition to an image without diffusion weighting. A total of 60 slices were scanned with an acquisition matrix of 112 × 112 with isotropic voxels of 2 × 2 ×2 mm, leading to a field of view of 224 × 224 × 120 mm. A SENSE factor of 2 and a halfscan factor of 0.678 were used. Acquisition time was about 8 min for the DWI scan and 5 min for the T1-weighted scan. The maximal total study time including survey images was 20 min. 2.3. Data preprocessing {#sec0025} ----------------------- The preprocessing of the T1-weighted scan and DWI data is outlined in [Fig. 2](#fig0010){ref-type="fig"} (top-left box). All data preprocessing is performed using a pipeline created with NiPype ([@bib0075]), which allows for large-scale batch processing and provides interfaces to neuroimaging packages (FSL, MRtrix). The T1-weighted scan was first aligned to the AC-PC axis by affine coregistration (12 degrees-of-freedom) to the MNI152 template using the FMRIB Software Library v5.0 (FSL) ([@bib0095]). Secondly, affine coregistration, considered suitable for within-subject image registration, was applied between the DWI volumes to correct for motion. Eddy current induced distortions were corrected within the Philips Achieva scanning software and did not require further post-processing. The DWI b=0 volume was subsequently affinely coregistered to the axis-aligned T1-weighted scan using normalized mutual information, and the resulting transformation was applied to the other DWI volumes. The DWI volumes were resampled using linear interpolation. After coregistration, the diffusion orientations were reoriented using the corresponding transformation matrices ([@bib0125]).Fig. 2A schematic overview of the analysis procedures followed to reconstruct the optic radiation (OR) and to acquire a robust estimate of the Meyer\'s Loop to Temporal Pole (ML-TP) distance. The stages in which data are processed are indicated by the dashed boxes. The red dashed boxes indicate the new contributions of the study. The various software packages are color-coded. The inputs of the pipeline are a diffusion-weighted imaging (DWI) dataset and an anatomical T1-weighted MRI image. Outputs of the pipeline are shown with double-headed arrows. Abbreviations: FOD, fiber orientation density; CSD, constrained spherical deconvolution; ROI, region of interest; FBC, fiber to bundle coherence; RFBC, relative FBC. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)Fig. 2 2.4. Probabilistic tractography {#sec0030} ------------------------------- Probabilistic tractography of the OR (outlined in [Fig. 2](#fig0010){ref-type="fig"}, top-middle box) is based on the Fiber Orientation Density (FOD) function, first described by [@bib0035]. With probabilistic tractography, streamlines are generated between two regions of interest (ROIs): the LGN, located in the thalamus, and the primary visual cortex (see [Fig. 1](#fig0005){ref-type="fig"}). The LGN was defined manually on the axial T1-weighted image using anatomical references (lateral and caudal to the pulvinar of the thalamus) ([@bib0065]) using a sphere of 4 mm radius, corresponding to a volume of 268 mm^3^. The ipsilateral primary visual cortex was manually delineated on the axial and coronal T1-weighted image. The primary visual cortex ROI\'s used in this study have an average volume of 1844 mm^3^. The FOD function describes the probability of finding a fiber at a certain position and orientation ([@bib0255]). In the current study the FOD function is estimated using CSD, which is implemented in the MRtrix software package ([@bib0245]). During tracking, the local fiber orientation is estimated by random sampling of the FOD function. In the MRtrix software package, rejection sampling is used to sample the FOD function in a range of directions restricted by a curvature constraint imposed on the streamlines. Streamlines are iteratively grown until no FOD function peak can be identified with an amplitude of 10% of the maximum amplitude of the FOD function ([@bib0100], [@bib0245]). In MRtrix tracking, 20,000 streamlines are generated, which provides a good balance between computation time and reconstruction ability. A step size of 0.2 mm and a radius of curvature of 1 mm were used. These settings are reasonable for our application of reconstructing the OR and are recommended by [@bib0245]. The FOD function was fitted with six spherical harmonic coefficients, which is suitable for the DTI scanning protocol used in this study. Anatomical constraints are applied when reconstructing the OR in order to prevent the need for manual pruning of streamlines and to reduce a subjective bias. Firstly, streamlines are restricted within the ipsilateral hemisphere. Secondly, fibers of the OR are expected to pass over the temporal horn of the ventricular system ([@bib0220]). The ventricular system is manually delineated using ITK-SNAP image segmentation software ([@bib0300]). Streamlines that cross through the area superior-laterally to the temporal horn are retained. Thirdly, an exclusion ROI is created manually of the fornix to remove streamlines that cross this region, which is in close proximity to the LGN and Meyer\'s loop. Furthermore, in order to remove long anatomically implausible streamlines, the maximum length of the streamlines is set to 114 mm based on a fiber-dissection study of the OR by [@bib0180]. 2.5. Quantification of spurious streamlines {#sec0035} ------------------------------------------- The stability metrics to identify spurious streamlines are outlined in [Fig. 2](#fig0010){ref-type="fig"}, top-right box. These metrics are used to provide a reconstruction of the OR that is robust against the presence of spurious streamlines, which occur especially near the anterior tip of the Meyer\'s loop as shown in [Fig. 1](#fig0005){ref-type="fig"} (left). The application of these metrics is important to obtain a stable measurement of the ML-TP distance as indicated in [Fig. 1](#fig0005){ref-type="fig"} (right). The *Fiber-to-Bundle Coherence FBC* measure, providing the basis of the stability metrics, is a quantitative measure of streamline alignment and is used for removing spurious streamlines. Spurious streamlines are (partially) poorly aligned with surrounding streamlines in the streamline bundle, which is illustrated schematically in [Fig. 3](#fig0015){ref-type="fig"} (top right). In order to compute the FBC, streamlines are lifted to 5D curves by including the local orientation of the tangent to the streamline. A lifted streamline *γ*~*i*~ can be written as$$\gamma_{i} = \left\{ {(\mathbf{\text{y}}_{i}^{k},\mathbf{\text{n}}_{i}^{k}) \in \mathbb{R}^{3} \times S^{2}\text{ \,\,}|\text{ \,\,}k = 1,\ldots,N_{i}} \right\},$$where **y** and **n** are the position and orientation of a streamline element, *N*~*i*~ is the number of points in the streamline and *i* denotes the index within the streamline bundle $\Gamma = \cup_{i = 1}^{N}\{\gamma_{i}\}$. To include a notion of alignment between neighboring streamline tangents, we embed the lifted streamlines into the differentiable manifold of the rigid-body motion Lie group SE(3). Within this differential structure, a measure is defined that quantifies the alignment of any two lifted streamline points with respect to each other in the space of positions and orientations $\mathbb{R}^{3} \times S^{2}$ ([@bib0160], [@bib0025], [@bib0045]). In order to compute this measure, kernel density estimation is applied using a (hypo-elliptic) Brownian motion kernel (see [Fig. 3](#fig0015){ref-type="fig"}, top left). The kernels used in the kernel density estimation have a probabilistic interpretation: they are the limiting distribution of random walkers in $\mathbb{R}^{3} \times S^{2}$ that randomly move forward or backward, randomly change their orientation, but cannot move sideways ([@bib0040], [@bib0190]). The FBC measure results from evaluating the kernel density estimator along each element of all lifted streamlines, shown in [Fig. 3](#fig0015){ref-type="fig"} (top right) where the FBC is color-coded for each streamline.Fig. 3Top: The *fiber-to-bundle coherence* FBC measure is determined via kernel density estimation. A Brownian motion kernel is used (shown left), which is defined on the space of positions and orientations. The streamlines are color-coded according to their FBC measure, scaled from high (blue) to low (white). Bottom: The RFBC is computed using a sliding window of size *α* and produces a single value for each streamline. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)Fig. 3 A spurious streamline can be identified by a low FBC that occurs anywhere along its path. For this purpose, a scalar measure for the entire streamline is introduced, called the relative FBC (RFBC), which computes the minimum average FBC in a sliding window along the streamline *γ*~*i*~ ∈ Γ relative to the bundle Γ. The RFBC for a streamline *γ*~*i*~ is calculated according to$${RFBC}^{\alpha}(\gamma_{i},\Gamma) = \frac{{AFBC}^{\alpha}(\gamma_{i},\Gamma)}{{AFBC}(\Gamma)}.$$The numerator AFBC^*α*^(*γ*~*i*~, Γ) gives the minimum average FBC of any segment of length *α* along the streamline *γ*~*i*~. The denominator *AFBC*(Γ) is used for normalization and is the average FBC of all the streamlines in the bundle, computed over the entire length of each streamline. The segment length *α* was determined empirically as 2 mm (corresponding to 10 streamline points when using a stepsize of 0.2 mm), which is considered small enough to characterize local deviations of the streamline but contains enough streamline points for stable quantification of local FBC. For a formal definition of the numerator and denominator in Eq. [(2)](#eq0010){ref-type="disp-formula"}, see Eqs. (A.5) and (A.6) in [Appendix A](#sec0095){ref-type="sec"}, respectively. Further details regarding the implementation of FBC measures, which includes several optimization steps such as pre-computed lookup tables for the Brownian motion kernels, are available in [Appendix B](#sec0100){ref-type="sec"}. 2.6. Standardized parameter selection {#sec0040} ------------------------------------- To control the removal of spurious streamlines the threshold parameter *ϵ* is introduced, which is defined as the lower bound criterion on RFBC that retains a streamline. More precisely, every streamline *γ*~*i*~ that meets the condition RFBC^*α*^(*γ*~*i*~, Γ) ≥ *ϵ* is retained. However, a careful selection of this threshold is required in order to prevent an underestimation of the full extent of the Meyer\'s loop. A method is introduced for the standardized selection of the minimal threshold *ϵ*~selected~ through test--retest evaluation of the variability in ML-TP distance. To this end, probabilistic tractography of the OR is performed multiple times, followed by the computation of the RFBC measure in each repetition. Subsequently, a parameter sweep is performed in which *ϵ* is varied between 0 ≤ *ϵ* ≤ *ϵ*~max~ where *ϵ*~max~ corresponds to the state where all streamlines are removed from Γ. During every step of the parameter sweep, the ML-TP distance is calculated for all test--retest repetitions by computing the Hausdorff distance ([@bib0195]) between the temporal pole and the OR. Using these distance measurements, the mean and the standard deviation (variability) of the ML-TP distance are determined for each value of *ϵ*. The procedure is illustrated for a healthy subject in [Fig. 4](#fig0020){ref-type="fig"}, showing the mean and standard deviation of the ML-TP distance for increasing values of *ϵ*. Initially, a high variability is seen at *ϵ* = 0, indicating the presence of spurious streamlines near the anterior tip of the Meyer\'s loop. At *ϵ* = 0.075 most spurious streamlines are removed and a variability in the order of several millimeters is seen. The variability rises and falls during 0.1 ≤ *ϵ* ≤ 0.3. A stable region is obtained at *ϵ* ≈ 0.3, however at this point too many streamlines have been discarded according to the condition RFBC^*α*^(*γ*~*i*~, Γ) ≥ *ϵ* and thereby the ML-TP distance will be overestimated. In order to estimate the minimal threshold *ϵ*~selected~, in which the ML-TP distance is neither under- nor overestimated, a maximum is set for the variability of 2 mm. This maximum is based on the maximal accuracy of 2--5 mm that may be achieved during resective surgery. In the selection procedure, *ϵ* is set at the first occurrence of low variability, i.e.$$\epsilon_{selected} = \min\{\epsilon > 0\text{ \,\,}|\text{ \,\,}\sigma(\epsilon) \leq 2{mm},\sigma^{\prime}(\epsilon) = 0,\sigma^{\prime\prime}(\epsilon) > 0\}$$where *σ*(*ϵ*) denotes the standard deviation in ML-TP for the chosen *ϵ*. After crossing the 2 mm threshold on variability, *ϵ*~selected~ is placed on the local minimum of *σ*(*ϵ*). Using this procedure, in the example shown in [Fig. 4](#fig0020){ref-type="fig"} the ML-TP is estimated for *ϵ* = 0.075 at 36 mm. This ML-TP distance is within the range of 22--37 mm as reported by [@bib0055], who performed a dissection study on 25 human cadavers.Fig. 4Boxplot showing the mean and standard deviation of the estimated ML-TP distances for test--retest evaluation of the reconstruction of the OR for an example healthy volunteer. A sweep from low to high *ϵ* is performed to evaluate the effect of removing streamlines on the stability of the estimated ML-TP distance.Fig. 4 For the patients studied, the distance measurement outcomes are compared to the predicted damage of the OR after surgery, as outlined in [Fig. 2](#fig0010){ref-type="fig"} (bottom row, red dashed box). The resection area is manually delineated in the post-operative T1-weighted image using ITK-SNAP ([@bib0300]). The resection length is measured from the temporal pole, at the anterior tip of the middle sphenoid fossa, up to the posterior margin of the resection. The predicted damage is determined by the distance between the pre-operative ML-TP distance and the resection length. The difference between the predicted damage and the observed damage, given by the distance between pre- and post-operative ML-TP distances, is named the margin of error. The margin of error indicates the maximal error in distance measurements, which includes both the variability in probabilistic tractography and unaccounted sources of error such as brain shift or distortions. 2.7. Open source software {#sec0045} ------------------------- The methodology for the robust reconstruction of the OR (outlined in [Fig. 2](#fig0010){ref-type="fig"}) is available as an open source software package. The NiPype based pipeline for the basic processing of DW-MRI data, tractography, and FBC measures is available at <https://github.com/stephanmeesters/DWI-preprocessing>. An open source implementation of the FBC measures for the reduction of spurious streamlines described in [Appendix A](#sec0095){ref-type="sec"}, [Appendix B](#sec0100){ref-type="sec"} is available in the DIPY (Diffusion Imaging in Python) framework ([@bib0070]) or as a C++ stand-alone application at <https://github.com/stephanmeesters/spuriousfibers>. Visualization was performed in the open source vIST/e tool (Eindhoven University of Technology, Imaging Science & Technology Group, <http://sourceforge.net/projects/viste/>). 3. Results {#sec0050} ========== 3.1. Robust estimation of ML-TP distance {#sec0055} ---------------------------------------- The effect of the removal of spurious streamlines on the ML-TP distance measurement using the FBC measures is demonstrated for eight healthy volunteers. For each volunteer the mean ML-TP distance and its standard deviation are listed in [Table 1](#tbl0005){ref-type="table"} for the left and right hemisphere, together with its corresponding test--retest variability. The additional value of the FBC measures for a robust ML-TP distance measurement is further evaluated for three patients who underwent a TLR.Table 1Listed are the ML-TP distances estimated for the left and right hemispheres of the healthy volunteers studied (*N* = 8) and the corresponding selected values for the FBC thresholding parameter *ϵ*.Table 1VolunteerML-TP distance*ϵ*Left (mm)Right (mm)Left (--)Right (--)136.4 ± 1.532.1 ± 1.30.0750.15230.0 ± 0.627.8 ± 1.00.130.14333.4 ± 1.523.5 ± 0.90.20.35434.9 ± 1.731.4 ± 0.20.450.1536.8 ± 1.432.2 ± 1.00.0750.33628.3 ± 0.325.8 ± 0.60.0250.28732.3 ± 0.423.4 ± 1.10.150.05822.5 ± 0.530.7 ± 1.00.1250.18 The parameter estimation based on test--retest evaluation is illustrated in [Fig. 5](#fig0025){ref-type="fig"} for the reconstructed OR of the left hemisphere for the eight healthy volunteers studied, showing for a range of parameter *ϵ* (0--0.6) the standard deviation (left) and the mean (right) of the estimated ML-TP distance. The test--retest evaluation was performed with 10 repeated tractograms of the OR, which was empirically determined to be a good balance between group size and computation time. For all volunteers evaluated, a high standard deviation of the ML-TP distance (over 2 mm) was observed at low values of *ϵ* (0.0--0.05), which indicates the presence of spurious streamlines with a very low RFBC. The corresponding mean ML-TP distance reflects large jumps for an increase of the value of *ϵ* from 0 to 0.05, showing an average increase for the eight healthy volunteers of 8 mm. For each healthy volunteer the *ϵ*~selected~ is selected according to Eq. [(3)](#eq0015){ref-type="disp-formula"}. The *ϵ*~selected~ corresponds to a mean ML-TP distance that is depicted by the arrows in [Fig. 5](#fig0025){ref-type="fig"} (right) for the eight healthy volunteers studied. After the initial high variability of the ML-TP distance, a stable region occurred for all healthy volunteers in which the standard deviation was below 2 mm. The healthy volunteers 1, 5 and 4 indicated regions of instability for relatively high values of *ϵ*. This can be attributed to gaps within the reconstructed OR with a lower number of streamlines compared to the main streamline bundle. Lastly, it can be observed that for volunteer 4 the selected *ϵ* is large compared to the other healthy volunteers. However, for this volunteer the mean ML-TP distance is stable from *ϵ* = 0.15 onward and therefore does not reflect an overestimation of the ML-TP distance.Fig. 5Shown is the parameter estimation for the reconstructed left OR of the eight healthy volunteers studied. Left: The standard deviation of the ML-TP distance is shown as a function of *ϵ*. For each healthy volunteer a suitable choice of *ϵ* is made at the point where the standard deviation first drops below the threshold of 2 mm and reaches a local minimum, shown by the black dotted line. Right: The estimated mean ML-TP distance is shown as a function of *ϵ*. The *ϵ*~selected~ for each volunteer is indicated by an upwards pointed arrow, indicated along with the values of the associated estimate of the ML-TP distance.Fig. 5 On the group level the ML-TP distances listed in [Table 1](#tbl0005){ref-type="table"} are on average 31.7 ± 4.7 mm for the left hemisphere and 28.4 ± 3.8 mm for the right hemisphere. The mean variability in probabilistic tractography on the individual level for the group of healthy volunteers is 1.0 mm and 0.9 mm for the left and right hemispheres, respectively. Large deviations in ML-TP distance were observed between the left and right hemispheres, especially, for volunteers 3, 7 and 8. 3.2. Pre- and post-operative comparisons {#sec0060} ---------------------------------------- The importance of the robust ML-TP distance measurement is illustrated for three patients who underwent resective epilepsy surgery. [Fig. 6](#fig0030){ref-type="fig"} displays the pre-operative (first and last columns) and post-operative reconstructions (second and third columns) of the OR and indicates for both hemispheres the estimated ML-TP distances (first and second column). Given is also the resection length (third column) and the pre-operative reconstruction of the OR along with the predicted damage, indicated by the red colored streamlines (fourth column). The pre- and post-operative distance measurements and the corresponding values of *ϵ* are listed for both the left and right hemisphere in [Table 2](#tbl0010){ref-type="table"}. Furthermore, the predicted damage is listed in [Table 2](#tbl0010){ref-type="table"} and reflects the distance between the pre-operative ML-TP distance and the resection length. Finally, the margin of error is indicated, defined as the difference between the predicted damage and the observed damage.Fig. 6Tractography and distance measurement results for the three patients included in the study. The first and second columns show the reconstructions of the OR before and after surgery, respectively. For each reconstruction the ML-TP distance and associated variability are displayed. The third and fourth columns show a 3D view of the reconstruction of the OR in the affected hemisphere after and before surgery, respectively. The resection area is displayed in red and the predicted damage is indicated by color-coded red streamlines. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)Fig. 6Table 2The results listed for the pre- and post-operative comparison of the reconstruction of the OR for both hemispheres of the three epilepsy surgery candidates included in our study. Distance measurements of the anterior extent of the OR to the temporal pole (ML-TP) are displayed along with the variability in probabilistic tractography for the corresponding *ϵ*~selected~. Furthermore, the resection lengths, predicted and observed damages, and the measured margins of error are listed for the affected hemispheres.Table 2Patient/hemisphereML-TP distance*ϵ*Resection length (mm)Predicted damage (mm)Observed damage (mm)Margin of error (mm)Pre-op (mm)Post-op (mm)Pre-op (--)/Post-op (--)*Patient 1*Left30.2 ± 0.428.5 ± 1.00.10/0.20--------Right30.1 ± 0.642.1 ± 2.00.48/0.1841.010.9 ± 0.612.0 ± 2.64.3
*Patient 2*Left28.7 ± 0.448.2 ± 1.60.13/0.445.016.3 ± 0.419.5 ± 2.05.6Right32.0 ± 0.730.5 ± 0.50.13/0.2--------
*Patient 3*Left35.3 ± 0.736.2 ± 0.90.10/0.1821.00.00.01.6Right29.2 ± 0.930.1 ± 1.20.22/0.18-------- The tractography results indicate that for patients 1 and 2 the OR is damaged, likely resulting in a disrupted Meyer\'s loop for both patients. The perimetry results of these patients indicated a visual field deficit (VFD) of 60 degrees for patient 2, which was smaller than the VFD measured for patient 1 at 90 degrees despite the larger resection of patient 2 (see [Table 2](#tbl0010){ref-type="table"}). Note, that for patient 3, for whom there was no damage to the OR, the reconstruction of the OR is well reproducible for both hemispheres, with a difference of maximally 3.0 mm including the variability in ML-TP distance. The difference between the predicted damage and the observed damage was small for these patients, indicating an maximum error of the predicted damage of the OR of 5.6 mm or less. The reproducibility of the reconstruction results obtained following the procedures as here described is further confirmed by the unaffected hemispheres of each individual patient, which show a similar anterior extent for both pre- and post-operative reconstructions of the OR. The ML-TP distance of the OR reconstructed for the OR of the non-pathologic hemisphere showed deviations for the two different scans of maximally 3.1 mm, 2.7 mm and 3.0 mm for Patient 1, Patient 2 and Patient 3, respectively, including the variability measure. The overall mean ML-TP distance pre-operatively is 31.4 ± 3.5 mm for the left hemisphere and 30.4 ± 1.4 mm for the right hemisphere. The mean variability in probabilistic tractography is 0.5 mm and 0.7 mm for the left and right hemispheres, respectively. 4. Discussion {#sec0065} ============= Stability metrics were introduced for a robust estimation of the distance between the tip of the Meyer\'s loop and temporal pole. Standardized removal of spurious fibers was achieved, firstly by quantification of spurious streamlines using the FBC measures, and secondly by a procedure for the automatic selection of the minimal threshold *ϵ*~selected~ on the FBC measures. The results presented indicate that a reliable localization of the tip of the Meyer\'s loop is possible and that it is feasible to predict the damage to the OR as result of a TLR performed to render patients seizure free. 4.1. Procedures for the reconstruction of the OR {#sec0070} ------------------------------------------------ For the estimation of the FOD function, CSD was applied on diffusion data obtained with the prevalent DTI acquisition scheme, thus allowing for a broad clinical applicability. In the current study, the DTI acquisition scheme (*b* = 1000, 32 directions) has a relatively low number of directions of diffusion. Since the tip of the Meyer\'s loop has a high curvature, its reconstruction could especially benefit from the HARDI acquisition scheme ([@bib0250]), which measures a larger number of directions of diffusion such as 64 or 128 directions. However, unlike DTI, HARDI is not commonly applied within a medical MRI diagnosis. Instead, the DTI data may be improved by applying contextual enhancement ([@bib0230], [@bib0190]), such as the one available in the DIPY framework (<http://dipy.org>). Additionally, in order to improve the image quality of the diffusion measurements it may be beneficial to apply denoising. This may, for example, be achieved by a recently proposed denoising approach based on non-local principal component analysis (PCA) ([@bib0145]). The MRtrix software package was employed for the estimation of the FOD function and for performing probabilistic tractography. As an alternative to the rejection sampling method that is implemented in MRtrix for sampling the FOD during tracking, the importance sampling method as introduced in [@bib0060] could be used. In contrast to the hard constraints used in rejection sampling, the importance sampling method provides a soft constraint on the space of positions and orientations, which is in line with the mathematical framework introduced in this paper (see [Appendix A](#sec0095){ref-type="sec"}). The seed regions of the LGN and visual cortex are highly influential for the tractography results ([@bib0135]). It may be possible to improve the fiber orientation estimation at the white matter to gray matter interface, such as near the LGN and visual cortex ROIs, by applying the recently introduced informed constrained spherical deconvolution (iCSD) ([@bib0205]). iCSD improves the FOD by modifying the response function to account for non-white matter partial volume effects, which may improve the reconstruction of the OR. In the current study, the LGN was identified manually and could possibly be improved by using a semi-automatic method such as presented by [@bib0275]. Another approach proposed by [@bib0005] is to place different ROIs around the LGN and within the sagittal stratum, or by seeding from the optic chiasm ([@bib0110]). A recent study suggested using seeding around the Meyer\'s loop with an a-priori fiber orientation ([@bib0015]). 4.2. Application of the stability metrics {#sec0075} ----------------------------------------- The FBC measures are used for the quantification of spurious streamlines. These FBC measures are based on the estimation of streamline density in the space of positions and orientations $\mathbb{R}^{3} \times S^{2}$. An advantage of the FBC method is that it is generally applicable, regardless of the type of diffusion model and the tracking algorithm being used, since it depends only on the outcome of tractography. A possible limitation of the FBC measures are the number of streamlines that can be processed, since for densely populated regions of streamlines the method is computationally expensive. However, through the use of several optimization steps such as pre-computed lookup tables for the Brownian motion kernel, multi-threaded processing, subsampling of streamlines, and the exclusion of far-away streamline points, the computation times maintain manageable. Details are available in [Appendix B](#sec0100){ref-type="sec"}. In order to remove spurious fibers while preventing an underestimation of the full extent of the Meyer\'s loop, a procedure for estimating *ϵ*~selected~ was introduced based on the test--retest evaluation of the variability in ML-TP distance. Using this methodology, a robust measurement of the ML-TP distance was achieved in the left and right hemispheres of eight healthy volunteers. The variability in the reconstruction results of the OR stems mostly from data acquisition (e.g. SNR, partial volume effects, and patient motion) ([@bib0260]). Therefore, *ϵ*~selected~ may vary between pre- and post-operative scans in the non-affected hemisphere (see Table [2](#tbl0010){ref-type="table"}). The mean ML-TP distances for both brain hemispheres, measured to be 30.0 ± 4.5 mm for the healthy volunteer group and 30.9 ± 2.4 mm for the patient group (pre-operatively), are within the range of the ML-TP distance reported on by [@bib0055] and outcomes from other OR reconstruction methodologies. For example, ConTrack ([@bib0215]) showing 28 ± 3.0 mm, Streamlines Tracer technique (STT) showing 37 ± 2.5 mm ([@bib0285]) and 44 ± 4.9 mm ([@bib0165]), Probability Index of Connectivity (PICo) showing 36.2 ± 0.7 mm ([@bib0030]), tractography on Human Connective Project (HCP) multi-shell data showing 30.7 ± 4.0 mm ([@bib0110]), and MAGNET showing 36.0 ± 3.8 mm ([@bib0015]). It appeared, furthermore, that the mean ML-TP for both the healthy volunteers and the patients was larger in the left hemisphere compared to the right hemisphere, which is not consistent with a recent study by [@bib0090] that indicated a significantly higher ML-TP in the right hemisphere. A possible limitation of the parameter estimation procedure is that its application is tailored towards OR tractography. Unlike the FBC measures, which can be used for any tractogram, the parameter estimation procedure may not be generally applicable for other fiber bundles since a distance measurement between well-defined landmarks is required. However, a possible approach for generalized parameter selection is to fit the streamline bundle on a manifold such as used by BundleMAP ([@bib0115]) and optimize *ϵ*~selected~ by minimizing the spread on the manifold. 4.3. Towards damage prediction for epilepsy surgery {#sec0080} --------------------------------------------------- The methodology for the estimation of the ML-TP distance is applied for the surgical candidates, firstly to assess the validity of the distance measurements, and secondly to indicate its additional value for resective epilepsy surgery. An indication of the validity of distance measurements was given by the margin of error, which was the largest for patient 2 amounting to 5.6 mm. The margin of error observed for the three patients can be lowered, e.g. by correcting for brain shifts that occur due to resection and CSF loss ([@bib0265]) and by correcting for distortions present in MR echo-planar imaging ([@bib0105], [@bib0085]). The measurement of the ML-TP distance may be further complicated due to a shifted location of the temporal pole, or even its complete absence. However, the reproducibility of the pre- and post-operative reconstructions of the OR in the non-pathological hemisphere indicates that the effects of brain shift and imaging distortions may be limited. Small deviations in the ML-TP distance were seen (see [Table 2](#tbl0010){ref-type="table"}), which suggests a good reproducibility, albeit for a limited number of patients. In the standardized estimation procedure of *ϵ*~selected~ the maximal variability was set at 2 mm, both for the OR reconstructions of the healthy volunteers and the patients, which is based on the maximal surgical accuracy that can be achieved during standard or tailored anterior temporal lobectomy before the leakage of cerebrospinal fluid (CSF). A surgical accuracy below 2 mm has been reported ([@bib0235]) if a stereotactic frame is used or robotic assistance is involved. After the leakage of CSF however, cortical displacement up to 24 mm may be seen ([@bib0080]), while other sources of inaccuracy are likely present such as echo-planar imaging distortion, partial volume effects, and image noise. However, despite these inaccuracies the pre- and post-operative comparison of the OR reconstructions indicates that the procedures developed in this study are a valid tool to assess the robustness of the distance measurements. It appeared that the robust estimation of the ML-TP distance enabled to predict the damage of the OR after surgery, which was concordant with the actual damage for the three patients studied. Based on the damage prediction the margin of error was estimated, giving an indication of the overall error in distance measurement. The perimetry results of two of the patients studied indicated damage of either the left or right visual field, corresponding to a disruption of the Meyer\'s loop. A relatively small VFD was indicated for patient 2 despite the large temporal lobe resection. This result may be indicative of the large inter-patient variability in OR anatomy and function, but may also be the result of the non-standardized procedures for visual field testing in-between hospitals. It is recommended to evaluate the developed methodology further in a clinical trial including a sizable group of patients who are candidate for a TLR in order to be able to assess what the relation is between a VFD and the damage to the OR after a TLR. 5. Conclusion {#sec0085} ============= It was shown for a group of healthy volunteers included in this study that standardized removal of spurious streamlines provides a reliable estimation of the distance from the tip of the Meyer\'s loop to the temporal pole that is stable under the stochastic realizations of probabilistic tractography. Pre- and post-operative comparisons of the reconstructed OR indicated, furthermore, (1) the validity of a robust ML-TP distance measurement to predict the damage to the OR as result of resective surgery, and (2) the high reproducibility of the reconstructions of the non-pathological hemisphere. In conclusion, the developed methodology based on diffusion-weighted MRI tractography is a step towards applying optic radiation tractography for pre-operative planning of resective surgery and for providing insight in the possible adverse events related to this type of surgery. Conflicts of interest {#sec0090} ===================== The authors declare that the research was conducted in absence of any commercial or financial relationships that could be construed as a possible conflict of interest. Appendix A. Mathematical background {#sec0095} =================================== The fiber-to-bundle coherence (FBC) measures are based on kernel density estimation in the non-flat 5D position-orientation domain. First of all, each equidistantly sampled streamline $\gamma_{i} = \left\{ {\gamma_{i}^{k}\text{ \,\,}|\text{ \,\,}k = 1,\ldots,N_{i}} \right\}$ with $\gamma_{i}^{k} = (\mathbf{\text{y}}_{i}^{k},\mathbf{\text{n}}_{i}^{k}) \in \mathbb{R}^{3} \times S^{2}$ are represented by delta distributions $\delta_{(\mathbf{\text{y}}_{i}^{j},\mathbf{\text{n}}_{i}^{j})}$. Here, *N*~*i*~ denotes the number of streamline points of streamline *γ*~*i*~ and $\mathbf{\text{y}}_{i}^{k}$ and $\mathbf{\text{n}}_{i}^{k}$ denote the position and tangent orientation of the streamline point $\gamma_{i}^{k}$, respectively. The full lifted output of the tractography is given by$$F_{\Gamma}(\mathbf{\text{y}},\mathbf{\text{n}}) = \frac{1}{N_{tot}}\sum\limits_{\sigma = 1}^{2}\sum\limits_{i = 1}^{N_{tot}}\sum\limits_{j = 1}^{N_{i}}\delta_{(\mathbf{\text{y}}_{i}^{j},{( - 1)}^{\sigma}\mathbf{\text{n}}_{i}^{j})}(\mathbf{\text{y}},\mathbf{\text{n}}),$$where $\Gamma = \cup_{i = 1}^{N_{tot}}\{\gamma_{i}\}$ denotes the streamline bundle and *N*~tot~ indicates the number of streamlines in the bundle Γ. The summation over *σ* is used to include antipodal symmetry (where we identify $\mathbf{\text{n}}_{i}^{j} \sim - \mathbf{\text{n}}_{i}^{j}$) of each tangent orientation $\mathbf{\text{n}}_{i}^{j}$. The kernel density estimator is defined by Fokker-Planck diffusion equations, which describe Brownian motion on $\mathbb{R}^{3} \rtimes S^{2}$ ([@bib0170], [@bib0040], [@bib0050]). The following evolution process is used where *F* = *F*~Γ~ serves as the initial condition,$$\left\{ \begin{array}{l} {\partial_{t}W_{F}(\mathbf{\text{y}},\mathbf{\text{n}},t) = (D_{spat}{(\mathbf{\text{n}} \cdot \nabla_{\mathbf{\text{y}}})}^{2} + D_{ang}\Delta_{S^{2}})W_{F}(\mathbf{\text{y}},\mathbf{\text{n}},t),} \\ {W_{F}(\mathbf{\text{y}},\mathbf{\text{n}},0) = F(\mathbf{\text{y}},\mathbf{\text{n}}).} \\ \end{array} \right)$$Here, *t* ≥ 0 is the evolution time, *D*~spat~ \> 0 is the coefficient for spatial smoothing strictly in the direction of **n**. *D*~ang~ is the coefficient for angular smoothing ($\Delta_{S^{2}}$ is the Laplace-Beltrami operator on the sphere *S*^2^). In this evolution process, *W*~*F*~(**y**, **n**, *t*) represents the transition density of a moving particle with position **y** and orientation **n** at the time *t* ≥ 0, given that it started with initial distribution *F*(**y**, **n**) at *t* = 0. Then, the Local FBC (LFBC) is the result of evaluating the Brownian motion kernel *p*~*t*~ (see [Fig. 3](#fig0015){ref-type="fig"}, left) along each element of the lifted streamline$$\begin{array}{l} {{LFBC}(\mathbf{\text{y}},\mathbf{\text{n}},\Gamma) = (p_{t}*_{\mathbb{R}^{3} \times S^{2}}F){\left( \cdot \right) = \int_{\mathbb{R}^{3}}\int_{S^{2}}p_{t}(R_{\mathbf{\text{n}}^{\prime}}^{T}(\mathbf{\text{y}} - \mathbf{\text{y}}^{\prime}),R_{\mathbf{\text{n}}^{\prime}}^{T}\mathbf{\text{n}})F(\mathbf{\text{y}}^{\prime},\mathbf{\text{n}}^{\prime})d\sigma(\mathbf{\text{n}}^{\prime})d\mathbf{\text{y}}^{\prime}.}} \\ \\ \end{array}$$Here, *p*~*t*~(**y**, **n**) denotes the Green\'s function of the evolution process in Eq. [(A.2)](#eq0025){ref-type="disp-formula"}, which equals the probability density of finding a random oriented particle at position **y**, with orientation **n**, at time *t* ∈ *R*^+^ given that it started at position **0** and orientation **e~z~** ∈ *S*^2^ at time 0. Likewise, $p_{t}(R_{\mathbf{\text{n}}^{\prime}}^{T}(\mathbf{\text{y}} - \mathbf{\text{y}}^{\prime}),R_{\mathbf{\text{n}}^{\prime}}^{T}\mathbf{\text{n}})$ is the probability density of finding a random oriented particle at position **y** and orientation **n** given that it started at position **y**′ and orientation **n**′ at *t* = 0. Here, *dσ* is the usual measure on the sphere *S*^2^. As a result, by superposition in [(A.3)](#eq0030){ref-type="disp-formula"}, LFBC(**y**, **n**, Γ) denotes the probability density of finding a random oriented particle at **y** and pointing at orientation **n** at time *t* \> 0 given that it started at some point of the bundle Γ at *t* = 0. For exact formulas for the kernel *p*~*t*~(**y**, **n**), and the Gaussian approximations that we used for our computations, see [@bib0190]. A whole streamline measure, the relative FBC (RFBC), is calculated by the minimum of the moving average LFBC along the streamline *γ*~*i*~$${RFBC}^{\alpha}(\gamma_{i},\Gamma) = \frac{{AFBC}^{\alpha}(\gamma_{i},\Gamma)}{{AFBC}(\Gamma)},$$where AFBC^*α*^(*γ*~*i*~, Γ) indicates the minimal average LFBC over a small segment of the streamline with length *α*, given by$${AFBC}^{\alpha}(\gamma_{i},\Gamma) = \min_{a \in \lbrack 0,l_{i} - a\rbrack}\frac{1}{\alpha}\int_{a}^{a + \alpha}{LFBC}(\gamma_{i}(s),\Gamma){ds},$$and AFBC(Γ) is the average FBC of the entire streamline bundle Γ$${AFBC}(\Gamma) = \frac{1}{N}\sum\limits_{i = 1}^{N}{FBC}(\gamma_{i},\Gamma),$$where$${FBC}(\gamma_{i},\Gamma) = \frac{1}{l_{i}}\int_{0}^{l_{i}}{LFBC}(\gamma_{i}(s),\Gamma){ds}.$$Here, *l*~*i*~ is the total length of the spatially projected curve **x**~*i*~(·) of fiber *γ*~*i*~ = (**x**~*i*~, **n**~*i*~). Further details of the computation of FBC can be found in [@bib0190]. Appendix B. Computational optimization {#sec0100} ====================================== The FBC measures are implemented inside DIPY ([@bib0070]) using the high-speed Cython (C++ in Python) language. The kernel density estimation is executed with multithreading via the OpenMP library, which especially for cluster computing provides a significant speedup. To further accelerate the kernel density estimation, lookup-tables are computed containing rotated versions of the kernel *p*~*t*~ rotated over a discrete set of orientations ([@bib0200]). The rotated versions are equally distributed over a sphere to ensure rotationally invariant processing. To be able to use the lookup table during kernel density estimation, each (continuous) streamline tangent orientation is matched with the closest (discrete) orientation on the sphere. For efficient implementation of orientation matching, a KD-tree is used, which is a multi-dimensional (*K* = 3) binary space partitioning, to minimize the number of angular distance computations. We would like to thank Bart ter Haar Romeny for contributing to the research collaboration between the Academic Center for Epileptology, Kempenhaeghe & MUMC+ and the Eindhoven University of Technology. Furthermore, we thank Jan Verwoerd (Philips Healthcare Benelux) for contributions to the MRI scanning protocols, Jorg Portegies for the help in developing the FBC measures, and Remco Berting for assistance during MRI scanning. The patients were evaluated and discussed presurgically in the local presurgical workgroup of *Kempenhaeghe and Maastricht UMC+ (AWEC)* and in the national Dutch epilepsy surgery workgroup (LWEC). The research leading to these results has received funding from the European Research Council under the European Community\'s Seventh Framework Programme (FP7/2007-2014)/ERC grant agreement no. 335555. | Mid | [
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My name is Jessica and I was recently been diagnosed with FM. My problems started a little over 2 years ago at the very end of my second pregnancy. After my daughter was born I always felt like I had the flu. It has progressively gotten worse and I was diagnosed about 2 months ago with FM after a very long wait to finally get in with a Rehumatologist. Whats worse is it just seems to be gettign worse, and worse, and worse with no end in sight. I hurt everywhere and it is a pain that is really hard to put into words. Sometimes it burns but more often it is a horrible ache that feels like it goes all the way to my bones. It is just so horrible, I am only 31, I have 2 young children and I feel like I am 90. I can't do things with them that I wish I could. I am thankful for good days and I try to do as much with them as I can. I just can't believe this is my life now. I cried when I found this board because I read stories from all of you and things jump out at me that sound just like me. It is a relief to find people who get it. I was taking Voltaren but it caused my BP to spike so I had to stop taking it and today my Dr. is going to start me on Cymbalta. I'm a little bit afraid of it but I am honestly willing to try anything. I have been able to find one trigger, EDTA. I have taken that out fo my diet and it does seem to make a difference I'm just very thankful to have found this board and a few people that understand. My husband tries but he just doesn't get it. Thanks for letting me vent! The following 2 users give hugs of support to: jessann80jroseliver (09-29-2012), tanasmom (09-28-2012) Welcome to te board! Unfortunetly we all know why you're going through... It's far from the way we've planne to live our lives. Unfortunetly we have to learn to live differently. I had probs for 11 yrs before fibro pain set in. After I had my last child recovery was really hard. I'd lived with fatigue for so long but it was at its worst... Then pain set in & got worst. Unfortunetly it's been 3 yrs now & only gotten worst & continues to. I'm going to get a lip biopsy done to test for Sjogrens since its the most accurate & makes sense to me. I don't doubt the fibro, just know something else is going on & that's why it keeps getting worst. I've always been against meds now I rely on them so much, especially tramadol... I tried cymbolta & 100% against it... I wanted to talk to you about it before you start the med... I don't think it should be on the market... It did help with my pain but my husband says I was kinda a zombie. What I really noticed is that it made the fatigue worst... I talke to my dr & decided to weine off slowely... I ended up being sooo sick & the pain & fatigue was unbearable. Imagine the worst fibro pain, migrain like headache, lethargic then so nauseous & vomiting... For a whole week! I should have went to the hospital for dehydration. I couldn't keep anything down, not even a sip. I've had flares like this but they only last a day K I think the pains from goin of cymbolta was even worst. It really wa a nightmare! After that I talked to another person on here that went through the same thing but went to the hospital 3x because of it. I did some reading & found that its been very common with cymbolta withdraws... Even wiening really slowely... I've been on nuerontin & Lyrica also. They also made fatigue worst for me but others like them. I'm on savella which I've liked the best... It makes me sweat really bad sometimes & really easy which I've never been one to sweat... Anyhow, please research cymbolta before trying it... Some people manage med free. I have a friend that takes Vicodin & 9 IB Profren daily & works for her. I have a cousin that takes only Alieve & it's enough for her... I take savella & tramadol. i also take a miscle relaxer called flexeril for pain & sleep. it helps me allot but ive been trying not to take it. will prob have to start again though. im looking at possibly a more "natural" way... Not everyone is the same. You just have to figure out what works best for you. I know exactly how you feel. I was diagnosed a couple of months ago and when the doctor said "lifelong condition" I felt like he punched me in the stomach. He also said that the chances of complete pain relief is slim. I walked out of there feeling completely defeated and depressed. I even had some really scary thoughts for a while. I couldn't stand the thought of having this pain another minute much less the rest of my life. Since then, I am feeling a little more positive. I've talked to a few people that have it that say that it's just a matter of learning your limitations and avoiding triggers and finding the things that work best for you. Right now I am just trying to learn as much as I can about Fibro so that I can learn to manage it. It's frustrating though cause I want immediate results and this is going to take time to figure out. From what I hear, what works for one person may not work for someone else. It's been trial and error for me. But at least I feel there might be a light at the end of the tunnel though. I talked to a girl that was in a wheelchair at one point from the pain but now she is managing her life without meds and she looks great. It gave me alot of hope. I feel for you. I put this same kind of post on here several weeks ago so I know what you are feeling. I'm taking Tramadol, Flexeril, Naprosyn and Provigil. My symptoms have improved slightly. The Tramadol takes the edge off the pain, the Provigil makes it possible for me to get out of bed cause my fatigue is awful, and the flexeril relaxes my muscles at night so they aren't cramping and spasming. I still feel like crap but at least I can get out of bed and take my kids to school. I have small kids also. The guilt of not being the mother I want to be is horrible. My husband doesn't get it either. I think he tries to understand sometimes...but then other times he comes home and sits on his butt and waits to be served dinner when I am in pain. It makes me so mad. But I try to remember that he just has no idea what it is like. Now I am starting to learn to tell him when I can't do something. I am learning to say No and I am learning to delegate too. It's hard cause I used to do it all before. I think it's just going to take time to adjust to the changes that have to be made. I have to prioritize now and find my limits and the meds that work best. Finding the right doctor is hard too. The Rheumatologist that diagnosed me has stopped taking Fibro patients because it is too frustrating for him. He said that there is no magic pill and that 25% of getting better is up to the doctor but 75% is up to the patient. I totally get what he means now. Meds only make it possible for me to get up out of bed and make the changes and adjust my lifestyle. I've started walking every day. It was hard at first but it is helping. I hope that you can use all the info on this board to get some relief. This board has been a lifesaver for me. It helps to have people who understand and who can offer advice and support. I'm glad you are here. The women on this board are amazing and they get me through the tough spots for sure. Good Luck to you on your recovery and don't give up hope for a better tomorrow. Hi There, jessica, how much sugar do you have in your diet? This might be in the form of fruit juice or white breads/crackers etc? Have a read of the note I put up about sugar and inflammation. Honestly, since I gave up eating sugar my life has completely changed pain wise. In the past I used to dread catching a cold because it would always turn into a major lung infection and last year I had pnuemonia. This year I got a cold and was over it in 4 days. I know I sound like an evangilist (sorry) but it's worth a try if you haven't already! Don't give up! Just wanted to say welcome to the board and you should find a lot of support here I too am newly diagnosed and started having most of my problems right after my last child. I have a 1, 2, and 3 year old. I totally understand about not being able to be the mom you want to be. When I have really bad days sometimes we will stay in our jammies, snack on fruits and crackers and veggies and whatever we find in the fridge. We will spend the day in the living room where I can lay on the couch or the recliner and put together puzzles, read books, color and watch movies. I don't worry about the house or anything and they LOVE the attention from mommy. I have a very understanding husband who doesn't mind bringing home dinner or making us something simple when he gets home. He will help clean up the messes we make with all the playing because he knows it will drive me crazy. No, it's not the way I planned for things to be when I dreamed of having kids. But that is ok with me. I feel like I am doing the best I can with what I have and that is all we can do. I'm sorry you are having such a hard time right now. I hope you get some relief soon. hi jessica, welcome. i am one of the oldies here. please know you will get the hang of this and it will get easier to cope with. it takes time. even tho it is for life it changes over time. you adapt, you stop being afraid and life takes on a new way of being. the one super smart thing i did do was find a shrink and ask for new coping skills to be taught to me so i can be happy and somewhat productive the rest of my life. it worked. i have gotten so good at it every time one of my doc's looks for the big C i just laugh. i never made a plan for my life and how i wanted it to go. maybe that helps me be more open to the changes, who knows? giggle. glad you decided to join us. you will get tons of ideas to try. give them a try if they are safe for you. each body is unique and responds differently. peace, bluelakelady ps. take a deep long healing breath. __________________ when faced with something you cannot control peace lies in self education and adaptation to the situation. Thank you all so much for your responses! I did do some more research into the Cymbalta and with all I read I have emailed my doctor and told him I don't really want to try that Rx yet. I would rather see if something less scary will work first. I am also trying to eat a preservative free diet this week and just see if that makes a difference for me. I know that the EDTA makes me feel bad very quickly so I thought maybe there were other preservatives that were triggers for me. Today has been a much better day for me which has given me a more positive attitude. Funny how when you feel better it is easier to be happier | Low | [
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You don’t need to worry anymore as there is a government scheme which many of the UK public are unaware of more people each day are using this scheme to have up to 75% off their debts legally written off and having their interestest rates and charges are frozen along with protection from their creditors. HOW TO GET STARTED Click your age to begin your FREE Review Check These findings show the need for better advice to be available to UK residents. It’s safe to say that a lot of people will not be aware of the government legislation that is available to them and this is because debt, in general, is a very taboo subject and its rare people open up about their finances to there family and friends and this is the reason so few people know about this scheme. You can find out if you qualify for the scheme for free here and its completely private and confidential and takes less then 30 seconds. Why you must check if you qualify to have 75% of your debt written off If you qualify for the government legislation and are able to have up to 75% off your debt written off you will also benefit from being able to consolidate your debts into one small monthly affordable payment. Alongside side this once you’ve been acceptedinto the plan it’s also guaranteed that all your interest rates and charges are frozen. The plan also provides you with full protection from your creditors so you won’t have to worry about being contacted by your creditors ever again. Imagine the feeling of waking up in the morning knowing you have an end date for when you will be debt free. | Low | [
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Wednesday, January 10, 2007 You just may start hearing incredible buzz soon about the Kevin Spacey Moon for the Misbegotten being the must-see event of the season. Not that the prospects aren't good, and the London reception was encouraging. But as Mr. Riedel reports, there just may be some other reason behind all that. The acclaimed actor is demanding such a hefty paycheck, some people involved in the show worry that there won't be anything left for the backers. Spacey, who's bringing the show to New York from his theater company in London, is said to be angling for a guaranteed weekly salary of $25,000, plus 10 percent of the weekly gross receipts over $350,000.... The problem for his backers is that "Moon"-which is being produced for $2.5 million - is scheduled to run only 10 weeks at the Brooks Atkinson Theatre. Factor in all the other production costs, and the show has to sell a lot of seats - many at premium prices of $250 or more - just to break even, production sources say. "It's insane," says one. "You can't pay him that kind of money for only 10 weeks." "There is no room for error," adds a veteran producer, who's not involved in the show. "It has to be the hottest thing in town." Good luck, guys. Well I suppose if Long Day's Journey could be such a surprise summertime hit a few years ago (not to mention Spacey's 1999 Iceman Cometh) then their recoup chances aren't totally hopeless. But, as Riedel reminds us, didn't Cherry Jones and Gabriel Byrne just do this play? And Moon is a much more "difficult" play than Journey, which always gets misunderstood as an All-American Family Drama. Yet another test coming up of just how serious the B'way audience is willing to get these days. | Low | [
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/* * \brief Window layouter * \author Norman Feske * \date 2015-12-31 */ /* * Copyright (C) 2015-2018 Genode Labs GmbH * * This file is part of the Genode OS framework, which is distributed * under the terms of the GNU Affero General Public License version 3. */ #ifndef _OPERATIONS_H_ #define _OPERATIONS_H_ /* Genode includes */ #include <util/interface.h> /* local includes */ #include "window.h" namespace Window_layouter { struct Operations; } struct Window_layouter::Operations : Interface { virtual void close(Window_id) = 0; virtual void toggle_fullscreen(Window_id) = 0; virtual void focus(Window_id) = 0; virtual void to_front(Window_id) = 0; virtual void drag(Window_id, Window::Element, Point clicked, Point curr) = 0; virtual void finalize_drag(Window_id, Window::Element, Point clicked, Point final) = 0; virtual void screen(Target::Name const &) = 0; }; #endif /* _OPERATIONS_H_ */ | Mid | [
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Broken ring solitons in Bessel optical lattices. We address the existence of ring solitons broken by several nodes in a defocusing saturable nonlinear medium with an imprinted Bessel optical lattice. Such a multipolelike soliton is composed of two or more arc patterns with opposite phase between the adjacent components. The width of existence domain is determined only by the saturation degree of medium. The maximum number of soliton components depends on the radius of the lattice ring, where they reside. Those novel solitons can be trapped entirely on any ring of the Bessel lattice provided that the lattice is modulated deep enough. This study offers a smooth transition from the multipole soliton to necklace soliton. | High | [
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N Korea cancels talks with South Korea and warns US North Korea has cancelled Wednesday's high-level talks with South Korea because of anger over its joint military exercises with the US.North Korea has cancelled Wednesday's high-level talks with South Korea because of anger over its joint military exercises with the US. The North's official KCNA news agency said the exercises were a "provocation" and a rehearsal for an invasion.It also warned the US over the fate of the historic summit between Kim Jong-un and US President Donald Trump that is scheduled for 12 June in Singapore.In March, Mr Trump stunned the world by accepting an invitation to meet Mr Kim."We will both try to make it a very special moment for World Peace!" the US leader later tweeted.The US state department said it was continuing to prepare for the Trump-Kim summit and that it was not aware of any changes in the North Korean position.The political gamble of the 21st CenturyHow does North Korea's Kim Jong-un travel?North Korea crisis in 300 wordsWhat exactly has North Korea cancelled?In short, the scheduled talks with South Korea were a follow-up to a rare summit that was held on 27 April.They were agreed earlier this week and were set to take place at Panmunjom, a military compound in the demilitarised zone between the two countries that is often referred to as the "truce town".Representatives had planned to discuss further details of the agreements they had made at the historic summit.This covers things like ridding the peninsula of nuclear weapons and turning the armistice that ended the Korean War in 1953 into a peace treaty.Other points the leaders agreed in a joint statement were:An end to "hostile activities" between the two nationsChanging the demilitarised zone (DMZ) that divides the country into a "peace zone" by ceasing propaganda broadcastsAn arms reduction in the region pending the easing of military tensionTo push for four-way talks involving the US and ChinaWhy is it so unhappy?Joint military drills between the US and South Korea have often angered the North.In the past, they have threatened an "all-out offensive" in response to the exercises and condemned them as pouring "gasoline on fire".The latest drills - known as Max Thunder - involve some 100 warplanes, including an unspecified number of B-52 bombers and F-15K jets.The North has described them as a "provocation" and preparation for a future invasion, which is something they have said before.But the US and South Korea have always insisted the drills are purely for defence purposes, and based out of a mutual defence agreement they signed in 1953.They also say the exercises are necessary to strengthen their readiness in case of an external attack.So what's happening with the Trump-Kim talks?It depends who you ask.North Korea fired a warning shot at the US when it announced it was cancelling Wednesday's talks with the South."The United States will also have to undertake careful deliberations about the fate of the planned North Korea-US summit in light of this provocative military ruckus jointly conducted with the South Korean authorities," the KCNA report said.The BBC's South Korea correspondent Laura Bicker says the wording of the statement showed North Korea was casting doubt over talks, rather than saying they were about to be cancelled.Will historic Koreas summit lead to peace?The Koreas - the basics explainedBut the US was quick to resist any suggestion that the summit was now in doubt."We will continue to plan the meeting," a state department spokeswoman told reporters soon after the news of the cancelled talks broke.She added that the US had received "no notification" of a change in the North's position. | Low | [
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Q: Windows Phone 7 open new email How can I open new email programatically in Windows Phone 7? I found only solution with using WebBrowser control and using it Navigate method with "mailto" syntax. Is any better approach? A: EmailComposeTask is another option. | Mid | [
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Welcome to Flash Express Delivery, Inc. For over 30 years we have specialized in same day delivery throughout the Greater Houston Area from envelopes to heavy haul freight. We also offer regional Hot Shot and Heavy Haul service. We offer service 24 hours a day, 7 days a week. Our phones are always answered by a staff member, even after hours. No answering services, or machines! We have a large fleet of drivers that are uniformed, bonded and insured. Each driver is individually trained on each aspect of the delivery business, thus insuring that you are given the most professional and personalized service anywhere. Our order entry, dispatch, and billing are completely computerized. You can feel secure in knowing that each customer service representative has the authority and the knowledge to promptly and professionally handle your request with accuracy, thus giving you the special attention you deserve. We put your needs first, no matter how special they may be.. and that makes us the most dependable and diversified company in the industry. 24-Hour Around the Clock Service Local / Nationwide Radio Dispatched Methods of Payment Service Types 1 Hour = Direct Hot Shot 90 Min = Call in by 3:30 PM 2 1/2 Hour = Call in by 2:30 PM 4 1/2 Hour = Call in by 1:30 PM Equipment Full Size Truck Pipe Racks Stake Beds Gooseneck Trailers (up to 40ft) Flat Beds (48x102) Drop Decks Flash Express Delivery, Inc. is a proud member of the following associations: | Mid | [
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Q: If $\,x-\frac 1 x=k, \, k$ being any integer,then $\,\,x^5-\frac {1}{x^5}=?$ I am stuck with the following problem which one of friends gave me : If $\,x-\frac 1 x=k, \, k$ being any integer,then $\,\,x^5-\frac {1}{x^5}=?$ The options are $\,\,k^5+4k^3+4k, \,k^5+5k^3+6k,\,k^5+5k^3+5k,\,k^5+5k^3+4k $. We see that $x-\frac 1 x=k \implies x=\frac{k \pm \sqrt{k^2+4}}{2}$. Now putting this value to $\,\,x^5-\frac {1}{x^2}$ makes the calculation complicated. Can anyone help? Thanks and regards to all. EDIT: The problem contained a typo and thanks to @noam for pointing that out. Now using binomial expansion of $x^5-\frac{1}{x^5}$, we see that option 3 is the correct choice. A: Let $a=x,b=\frac 1x$ and hence $$a^5-b^5=(a-b)(a^4+a^3b+a^2b^2+ab^3+b^4)$$ where $a-b=k,a^2+b^2=k^2+2,\,a^4+b^4=k^4+4k^2+2$. Now putting this values in the expression ,we get $a^5-b^5=k^5+5k^3+5k$. | High | [
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5 Best Cardio Exercises for Daily Routine With a hectic work schedule, it gets very difficult to focus on yourself and maintain your body’s fitness. Even in your leisure time, you would rather prefer relaxing than working out. However, exercising should be an integral part of your daily routine as it keeps your body active. Share this: At-home cardio workouts are the perfect way to keep your body fat in check and maintain a healthy routine. Here are some of the best ways to incorporate cardio workouts into your daily routine: Jumping It may not seem like much of a workout, but you can burn a high number of calories if you exercise on a trampoline at home. Not only does it give visible results, it is an extremely fun sport as well. You can follow certain cardio exercises like high knee and butt kicks while jumping or focus on your upper body by doing jumping jacks on the trampoline. It is pretty challenging and makes a world of a difference. Running This is the standard, yet very effective, exercise to burn calories. Running at a moderate pace or walking has been very helpful for people to lose weight. Age does not matter since it is not a very highly intensive working out technique, so it is recommended for the elderly to incorporate jogging into their routine to keep their bodies active and healthy. Jumping Rope Jumping rope or skipping is a very good way to burn fat and maintain a healthy exercise routine. Jumping rope not only burns the extra calories, but it also helps in enhancing the body stamina while increasing foot speed. Almost all sportsmen and sportswomen incorporate skipping into their routine since it builds body strength and speed. Cycling Indoor cycling can be a bit boring since the workout is a lot more intense and requires proper focus but it does pay off when it comes to burning off the excess calories. However, outdoor cycling is a bit more liberating for the soul while getting your body worked up. An early morning cycling trek helps in relaxing your mind and gives you the opportunity to soak in nature which is necessary after longs days of confinement within the office under work pressure. Swimming The best way to incorporate a total body cardio workout in your daily routine is swimming. Swimming forces the body to put in a lot of effort in order to stay afloat while using full body muscles to move forward inside the water. Just by trying to tread on the water you will be burning calories successfully. If you are new to swimming, then the best way to do it is in intervals. These are some of the best ways to have a workout activity within your daily routine to ensure a healthy lifestyle and a better outlook towards a fit body. Without the necessary dose of exercise that your body needs, it becomes lethargic, you lose your stamina and your muscles become weak. Published by Corey Daniel John and Corey are happily married couple with 2 kids. They enjoy outdoor activities together and healthy eating. Their love for trampolines is eternal and they believe that they are both fun and a healthy exercise. They ritually write on trampolinesco.com. View more posts | High | [
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Starting a New Skincare Routine: How Long It Takes to See Results In the last few decades, there have been significant evolutions in skincare technology. When it comes to clinical skincare, the industry has made huge leaps in terms of the problems they’re able to solve and the results they’re able to deliver. It’s really quite amazing! But regardless of how far skincare has come, there are some things that can’t be changed—like time. Convincing skincare consumers to stay the course and stick to their regimen is a challenge that many skincare experts still face. After all, skincare is an investment—and it’s reasonable for people to feel frustrated when they feel like they’re not getting a return on that investment. But the fact of the matter is, powerful skincare takes time to work. When you apply a serum, a neck cream, or a dark spot corrector, you’re essentially telling your cells what to do. And they need time—and constant encouragement—to do that. So in order to better understand why this is the case, let’s dive in to the aging process, the role skincare plays in mitigating the effects of aging, and why patience is key to navigating any new skincare routine. What happens when we age Remember your first growth spurt? Much of your formative years are spent growing, a constructive process in which your organs, tissues, and cells build. These building blocks are key to your development as you enter adulthood. Then, things start to change. Lifestyle choices start to catch up with you. Lots of time spent in the sun, late nights, a lack of exercise, a poor diet—things that didn’t have much of an effect on you during your childhood and early adulthood—start to become more consequential now. You start to notice signs of aging on your face—large pores, dullness, a loss of radiance, wrinkles and fine lines, dark spots. Well, aging is not a constructive process. It’s a decay process. It’s not as though your body is building a wrinkle, saggy neck, or dark spot; instead, what you’re experiencing is an erosion of certain structures of your skin. Your body runs out of building blocks and becomes less effective at resisting the wear and tear of life. Collagen production is a great example of this. Think of collagen—a protein essential to our skin’s strength and elasticity—as a natural building block. As we age, our body naturally slows down collagen production, causing our skin to weaken and lose elasticity. Why clinical skincare works to slow down the aging process Clinical skincare helps to provide the building blocks that you otherwise would lose naturally over time. It gives your cells the tools and support they need to help manage the deconstructive process of aging. Think of the key functional ingredients of clinical skincare as messengers that tell your body what to do. They encourage your body to get to work rebuilding. How long it takes to see skincare results Powerful skincare takes time to work. If you’re thinking about giving up on a new serum or under-eye cream because you haven’t seen any results after a week, think again. When starting any new skincare routine, wait 8 weeks to see results. If this seems like an unrealistic time frame for you, it may help to take a deeper look at the different types of skincare and the functional processes behind them, because some skincare products are more superficial than others. Cosmetic Effects: Let’s start with cosmetics. When you apply a BB Cream or a tinted moisturizer, you may instantly feel radiant, toned, and glowing. But a lot of that effect is purely optical, as is the nature of cosmetics. So while you may look better instantly, you’re not immediately addressing the underlying mechanisms of why your skin is the way it is. Moisture Repair: Similarly, some products, like those focused on moisturization, have an instant effect that doesn’t last particularly long. These are the products that contain plant-based oils, omegas, or glycerin—like a hand cream. The hand cream functions through nonbiological pathways, covering the skin, filling in cracks, and allowing moisture to build up on the skin without evaporating away. It’s not as though your skin is suddenly producing more moisture, it’s more of an artificial process that helps keep everything intact. Underlying Mechanisms: Now, if you want to get at more underlying mechanisms, you’re going to need to give it time. Our cells are pretty phenomenal in terms of what they can build, but they don’t work very quickly. On top of that, they need a consistent feedback loop of regular care and nourishment. So, when you apply a product with a key functional ingredient, you’re essentially sending your body a signal. It starts to build. But then that signal turns off—and you have to resend the signal by applying the product again. It takes time and consistency. That’s why most clinical skincare needs to be applied daily (to maintain the feedback loop) and needs time to show results (so that the building blocks are actually able to get to work). What to do when your routine still isn’t working If you’re not seeing results after 8 weeks, don’t assume that the ingredient doesn’t work for you. There are too many factors at play here—how much of the ingredient is actually in the formula, how stabilized the formula is, what other complementary ingredients are also in the formula. Instead, consider trying out a different product. Here are some tips to help with that: Turn to more scientific brands. Brands that do research and clinical testing offer the results of that research to consumers—and that data is important. Look for brands that validate their claims with numbers. If a brand claims that their products “smooth wrinkles,” do they say how much? By half a percent? By 20 percent? The more a skincare brand is able to validate their claims, the better. Talk to family members about their skincare routine and what products they use. Your genetics are a huge influencer in terms of how you age. What works for a parent or sibling will likely work for you as well. Talk to friends with similar complexions and lifestyles. If your best friend is similar to you in terms of diet, exercise, lifestyle choices, and complexion, then you two will likely harmonize over what products to use. Remember, patience is key. Take a methodical approach to your skincare—apply your products daily, focus on self-care, and be kind to your body. You’ll start to see results before you know it. | Mid | [
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An overall art discussion concerning the problems in relation to and the need for low calorie bulking agents is to be found in CRC Critical Reviews in Food Science and Nutrition, May 1979, pages 401-413, Low Calorie Bulking Agents, by J. J. Beereboom et al. In this discussion it is stated that low calorie food of good quality can only be made with bulking agents having physical properties permitting replacement of the bulk and functional properties of the usual fat or carbohydrate, and also that two types of bulking agents for carbyhydrates are needed: (1) a soluble material that can replace sucrose and other simple carbohydrates in food, and (2) an insoluble material capable of replacing flour or starch. This invention is concerned with the soluble material type of bulking agent. Among the known (low calorie) bulking agents of this kind Neosugar and Polydextrose are believed to be those most used commercially, and, thus, are presumed to be those considered by the art heretofore as the best in regard to properties which should be exhibited by bulking agents of the soluble type. They are not, however, ideal. Neosugar (No. GB 2.072.679, and the Journal of Nutrition, Volume 114, No. 9, Sept. 1984, pp. 1574-1581), is sweet which is not necessarily an advantage as it is often wanted to achieve a controlled level of sweetness e.g. by means of an artificial sweetener, and further, Neosugar would exhibit an inferior stability at low pH values, if used in acidic drinks such as Coca Cola.TM. and the like. Neosugar is a sweenener comprising oligosaccharides having from 1 to 4 molecules of fructose bound to sucrose. Polydextrose (U.S. Pat. No. 3,766,165, Food Technology, July 1981, 35 (7), 44049 (1981)), on the other hand, has a satisfactory stability at low pH values in acid drinks, but it exhibits an acid bitter taste which is difficult to mask. Other bulking agents have been sugested to the art. For example, U.S. Pat. No. 4,459,316 describes sweetening foods with non-caloric di- or trisaccharides having L-hexose component However, the L-hexoses ordinarily do not exist in nature and cannot be assimilated by the human organizm, but are also expensive. WO 82/03329 describes glucose polymers and a method for production thereof. Thus, a need exists for an improved low calorie bulking agent that can replace sucrose and other soluble, low molecular weight carbohydrates in food. The bulking agent should exhibit the following combination of desirable properties: a) satisfactory taste, i.e. an almost neutral taste and at any rate not an acid, bitter taste; and b) satisfactory stability at low pH values. | High | [
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Q: PayPal payment integration for REACT NATIVE with latest lib android + ios Can any body provide a swipe solution with latest react-native PayPal library ? I have spent a week but not getting a proper solution. There are many old and incomplete solution on net but not a proper and complete solution for new developers. Resources : https://www.npmjs.com/package/react-native-paypal https://github.com/MattFoley/react-native-paypal https://github.com/sharafat/sample-code-php A: Unfortunately, there isn't a single repo that is up to date and maintains by the community as far as I know. That's why your options are limited. Utilize PayPal APIs PayPal has various APIs for different use cases that you can pick up without worrying about the SDK itself. They give you lots of those functionalities, sure it might not be smooth as the SDK itself, but it can solve your problem, nicely. In case you are developing for both mobile and the web, you can use your APIs for both of them. Becuase they do not depend on the specific platform. Solution My solution for this is pretty straightforward. Do not use the PayPal SDK if you don't want to mess with Native functionality and not exactly sure why you need it. PayPal has a various set of APIs that you can use on your server side or client side without touching the native code. Here I give you a simple scenario that using ExpressCheckout APIs and handle on the server side. For all below steps, you can use PHP, Node or any other server-side languages. I only briefly tell you the steps and the rest are on you! 1. Create an access token for your transaction. Follow below link for details. https://developer.paypal.com/docs/integration/direct/make-your-first-call 2. Create a payment transaction. You need to pass your payment details such as currency and total amount. In this step, you can pass your 'return_url' and cancel_url too. Make sure to attach your order id or order code to both of them, so you can track the orders when either of them triggered and change your order status accordingly. https://developer.paypal.com/docs/integration/direct/express-checkout/integration-jsv4/advanced-payments-api/create-express-checkout-payments/ 3. Send the payment URL to React Native and load it by WebView. In this Step, you can use the WebView component in React Native and load the PayPal URL inside. Later for checking whether the payment is done, you can either use a throttling function or use other alternatives such as WebSocket. The goal here is to know whether the transaction is done or canceled. When the payment is done. get rid of the WebView and redirect the user to thank you page and any other things you need to do after the user payment is done. There might be more elegant ways to do this, but I believe for simple scenarios (or even more!) this is sufficient. A: As Danial suggested above, if you do not want your app do be dependant on third party react native libraries then try integrating paypal with a WebView wrapper. Here is how I did it Integrating Paypal in your react native app | High | [
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RECOMMENDED FOR FULL-TEXT PUBLICATION Pursuant to Sixth Circuit Rule 206 File Name: 08a0177p.06 UNITED STATES COURT OF APPEALS FOR THE SIXTH CIRCUIT _________________ X Petitioner-Appellant, - ROY B. JACKSON, - - - No. 07-1247 v. , > KENNETH T. MCKEE, Warden, - Respondent-Appellee. - N Appeal from the United States District Court for the Eastern District of Michigan at Ann Arbor. No. 05-60131—John Corbett O’Meara, District Judge. Argued: May 1, 2008 Decided and Filed: May 12, 2008 Before: BATCHELDER, SUTTON, and FRIEDMAN, Circuit Judges.* _________________ COUNSEL ARGUED: Marla R. McCowan, STATE APPELLATE DEFENDER OFFICE, Detroit, Michigan, for Appellant. Brian O. Neill, MICHIGAN DEPARTMENT OF ATTORNEY GENERAL, Lansing, Michigan, for Appellee. ON BRIEF: Marla R. McCowan, Michael L. Mittlestat, STATE APPELLATE DEFENDER OFFICE, Detroit, Michigan, for Appellant. Brad H. Beaver, OFFICE OF THE MICHIGAN ATTORNEY GENERAL, Lansing, Michigan, for Appellee. _________________ OPINION _________________ SUTTON, Circuit Judge. A state court jury convicted Roy Jackson of felony murder, armed robbery and carrying a firearm during the commission of a felony. The Michigan Court of Appeals affirmed the felony-murder and firearm convictions and reversed the armed-robbery conviction. In reaching these conclusions, the state court denied Jackson’s claims that his confession was involuntary, that his Miranda waiver was not knowing or intelligent and that the admission of non- testimonial hearsay statements violated the Confrontation Clause. Because the state court decisions were neither contrary to, nor an unreasonable application of, Supreme Court precedent, we affirm the district court’s denial of Jackson’s habeas petition. * The Honorable Daniel M. Friedman, Senior Circuit Judge of the United States Court of Appeals for the Federal Circuit, sitting by designation. 1 No. 07-1247 Jackson v. McKee Page 2 I. On December 11, 2000, a group of men robbed a Dollar Value store in Detroit, Michigan, and shot and killed the store’s owner, Hani Zebib. After an initial investigation, the police contacted Jackson and asked him to come to the police station to answer questions about the incident—which Jackson did at 8:00 a.m., January 6, 2001. At 10:30 a.m. that morning, Detroit Police Investigator Barbara Simon advised Jackson of his Miranda rights, which Jackson waived, and began interrogating him. During the two-hour interrogation, Jackson denied any involvement in the crimes. The officers nonetheless arrested Jackson and moved him to the homicide department for holding. At 3:00 p.m., Simon again interrogated Jackson, and Jackson again denied committing the crimes. After the second round of questioning, officers returned Jackson to his holding cell in the homicide department, where he sat in isolation for the rest of the day. The next day, officers interviewed Tykee Ross. As part of the interrogation, the officers gave Ross a polygraph examination, and Ross eventually signed a statement implicating Jackson in the robbery and murder. After Ross fingered Jackson in the crimes, the officers interrogated Jackson again. At 7:30 p.m., Sergeant Maria Cox-Borkowski again advised Jackson of his Miranda rights, which he again waived, and proceeded to interrogate him. During the hour-long interrogation, Jackson continued to deny any involvement in the crimes, after which the officers asked Jackson to take a polygraph test. At 9:55 p.m., Investigator Andrew Sims advised Jackson of his rights, and, at 11:55 p.m., Sims began the test. The polygraph ended at 12:10 a.m. that night, with Jackson still denying any involvement in the crimes. After the polygraph, Sims continued to interrogate Jackson, and, twenty to thirty minutes later, Jackson changed his story, confessing to the robbery and the murder. At 2:15 a.m. later that night, Simon again met with Jackson and advised him of his rights once more. Jackson told her that he understood his rights and, at 2:40 a.m., he signed a waiver of his Miranda rights. He then signed a statement admitting that he shot Zebib while robbing the store with Ross and Demel Dukes. Jackson concluded the statement by saying, “I’m sorry for what happened. I didn’t mean for anyone to be shot and killed. I’m so very sorry.” JA 107. The State charged Jackson, Ross and Dukes with armed robbery, felony murder and possession of a firearm during the commission of a felony. The three defendants were tried jointly but before two separate juries—one for Jackson, the other for Ross and Dukes—and the juries convicted all three defendants of felony murder, Mich. Comp. Laws § 750.316, and armed robbery, id. § 750.529, and Jackson’s jury also convicted him of possessing a firearm during the commission of a felony, id. § 750.227b. The court sentenced Jackson to life imprisonment without the possibility of parole on the murder count, a concurrent term of 18–30 years on the robbery count and a consecutive term of two years on the felony-firearm count. Jackson appealed to the Michigan Court of Appeals. The Michigan Court of Appeals reversed Jackson’s armed-robbery conviction, but it affirmed his felony- murder and firearm convictions. The Michigan Supreme Court denied leave to appeal. Jackson filed a habeas petition in federal court, challenging (1) the state court’s conclusion that his confession was voluntary, (2) its conclusion that his Miranda waiver was knowing and intelligent and (3) the state court’s admission of hearsay statements at trial. The district court denied Jackson’s petition but granted a certificate of appealability on each issue. No. 07-1247 Jackson v. McKee Page 3 II. This case, the parties agree, is covered by the Anti-Terrorism and Effective Death Penalty Act of 1996. 28 U.S.C. § 2254. To prevail on any of his three requests for habeas relief, as a result, Jackson must show not only that the state courts erred in ruling on his constitutional claim but also that their decision was contrary to, or an unreasonable application of, Supreme Court precedent. See id. § 2254(d). A. Jackson first argues that the state court’s admission of his confession at his criminal trial violated due process because he made it involuntarily. See Miranda v. Arizona, 384 U.S. 436, 462 (1966). “[C]ertain interrogation techniques,” it is true, “are so offensive to a civilized system of justice that they must be condemned under the Due Process clause.” Miller v. Fenton, 474 U.S. 104, 109 (1985). Accordingly, when a criminal defendant can show that “coercive police activity” caused him to make an involuntary confession, due process prohibits the government from relying on the statement. Colorado v. Connelly, 479 U.S. 157, 167 (1986); see also Reck v. Pate, 367 U.S. 433, 440 (1961) (holding that an interrogation violates due process if the suspect’s will is overborne at the time he confessed). Whether an interrogation rises to the level of coercion turns on a spectrum of factors: the age, education and intelligence of the suspect; whether the suspect was advised of his Miranda rights; the length of the questioning; and the use of physical punishment or the deprivation of food, sleep or other creature comforts. Schneckloth v. Bustamonte, 412 U.S. 218, 226 (1973). Consistent with these factors, the Michigan courts reasonably determined that Jackson’s interrogation was not coercive. Jackson voluntarily reported to the police station and agreed to be questioned. Before asking any questions, the officers advised Jackson of his Miranda rights, which he waived no fewer than four times during the interrogations. And when Jackson ultimately confessed, he added a statement of remorse, saying he was “sorry for what happened,” JA 107—suggesting that it was his conscience, not the police, that overbore his prior efforts to disclaim any responsibility for the robbery and murder. Other contextual clues point in the same direction. Jackson told the officers that he could read and write and that he understood the rights he was waiving. At no point during the questioning did Jackson indicate that he did not understand his rights. He never said he was tired, confused or uncomfortable. And he confirmed in his written confession that he was not “deprived of food, water or use of the restroom.” JA 567. Nor was Jackson unfamiliar with the criminal justice system. He had six juvenile indictments filed against him prior to this arrest. He was not ill, injured or under the influence of drugs or alcohol. He never asked for an attorney. He never asked the agents to stop questioning him. And he acknowledges that he was not threatened, harmed or promised anything to compel his confession. All things considered, this is not the “rare” case in which a suspect “can make a colorable argument that a self-incriminating statement was ‘compelled’ despite the fact that the law enforcement officers adhered to the dictates of Miranda.” Berkemer v. McCarty, 468 U.S. 420, 433 n.20 (1984). Jackson, in short, has not shown that the prophylactic Miranda warnings were not prophylactic enough. Jackson counters with the following facts: the interval between his first interrogation and his last one was 40 hours; he signed his written confession in the early morning hours at the end of these serial interrogations; and he could read at only a third-grade level. The officers’ questioning, however, never exceeded two and a half hours at a time; Jackson never said he did not understand the Miranda warnings, even after receiving them multiple times; and he never expressed any lack of understanding regarding the confession he was signing. No. 07-1247 Jackson v. McKee Page 4 These circumstances do not rise to the level of the kinds of involuntary-confession fact patterns that the Supreme Court has condemned; still less do they show that the Michigan courts unreasonably applied these precedents—most of which did not even involve Miranda warnings, as here. See, e.g., Mincey v. Arizona, 437 U.S. 385, 398–402 (1978) (holding that a confession was involuntary where officers questioned the defendant over his objection for four hours while he was incapacitated and sedated in an intensive-care unit); Greenwald v. Wisconsin, 390 U.S. 519, 520–21 (1968) (holding that a confession was involuntary where officers questioned the defendant for more than 18 hours while depriving him of food, sleep and medication); Beecher v. Alabama, 389 U.S. 35, 38 (1967) (holding that a confession was involuntary where officers, already having wounded the defendant, ordered him at gunpoint to confess or be killed); Davis v. North Carolina, 384 U.S. 737, 745–47 (1966) (holding that a confession was involuntary where officers interrogated the defendant over 16 days and held him incommunicado in a closed cell without windows and with limited food); Reck, 367 U.S. at 441–42 (holding that a confession was involuntary where the officers held the defendant for four days with inadequate food and medical attention); Culombe v. Connecticut, 367 U.S. 568, 626 (1961) (holding that a confession was involuntary where officers held the defendant and subjected him to five days of “systematic” and continuous questioning); Payne v. Arkansas, 356 U.S. 560, 566–67 (1958) (holding that a confession was involuntary where officers held the defendant incommunicado for three days with little food and threatened to expose him to mob violence if he did not confess). Ashcraft v. Tennessee, 322 U.S. 143 (1944), does not give Jackson’s argument traction. It involved an interrogation in which the suspect was questioned for 36 consecutive hours and denied sleep and rest. Id. at 153–54. Yet Jackson was never interrogated for more than two and a half hours at a time and he was never prevented from sleeping or resting. There also was a considerable gap in time—24 hours—between his confession and the prior interrogation. Cf. Culombe, 367 U.S. at 626–27 (“[In] cases in which we have sustained convictions resting on confessions made after prolonged detention, questioning . . . had been discontinued during a considerable period prior to confession, so . . . we did not find . . . that police interrogators had overborne the accused.”). Haley v. Ohio, 332 U.S. 596 (1948), does not change matters. Police arrested a 15-year-old male in his home, took him to the police station and questioned him from midnight to 5:00 a.m., when he confessed. Id. at 598. The Court ruled that the “age of petitioner, the hours when he was grilled, the duration of his quizzing, the fact that he had no friend or counsel to advise him, the callous attitude of the police towards his rights combine to convince us that this was a confession wrung from a child by means which the law should not sanction.” Id. at 600–01. Jackson, by contrast, was older (17 years old); he was questioned intermittently, not continuously; he was told repeatedly of his rights to counsel and to remain silent; and no evidence shows that the officers took a “callous attitude” toward his rights. Id. More to the point, the question is not whether a state court could plausibly extend Haley to this fact pattern, a point we need not decide; the question is whether the Michigan courts acted unreasonably in declining to extend this pre-Miranda precedent here. They did not. B. Jackson next argues that his Miranda waiver was not knowing or intelligent. To be effective, a Miranda waiver must be “made with a full awareness both of the nature of the right being abandoned and the consequences of the decision to abandon it.” Moran v. Burbine, 475 U.S. 412, 421 (1986). That does not mean, however, that the police must supply a suspect with enough “information to help him calibrate his self-interest in deciding whether to speak or stand by his rights,” as such additional information goes only to “the wisdom of a Miranda waiver, not its essentially voluntary and knowing nature.” Colorado v. Spring, 479 U.S. 564, 576–77 (1987). No. 07-1247 Jackson v. McKee Page 5 The circumstances surrounding Jackson’s waiver confirm that the state court reasonably applied Supreme Court precedent in determining that Jackson was aware of the nature of the right he was waiving and the consequences of his decision to waive it. Over the course of Jackson’s interrogation, officers advised him of his Miranda rights at least four times. The officers read his rights to him, asked him to read his rights and asked him to repeat his rights as he understood them. Jackson waived his rights both orally and in writing. Jackson stated that he understood his rights, and at no point did Jackson indicate that he did not want to waive them. When Jackson confessed, he remained lucid, coherent and remorseful. He confessed first in an oral statement, then he reduced that statement to writing. In his written statement, Jackson described the crime: It was December 11, 2000. It was about four o’clock p.m. It was me, Tykee and Demel. We all went up to the Dollar Store to rob the store. I don’t remember if anyone was in the store buying anything. I went in the store first and Tykee and Demel came in behind me. I had the gun. The man was behind the counter. I told him to open up the cash register. The man just looked at me. I fired one shot up in the air. The man opened up the cash register and Demel went behind the counter and got the money out of the cash register. I told the man not to move. I saw that the man was backing up some. He kept on moving. I told him again don’t move. He moved and that’s when I shot him. After that we all ran out of the store. After we ran out of the store we all went over to a vacant house on Cherrylawn. After we got to the vacant house Demel had the money. Demel gave me my part of the money and he gave Tykee his part of the money. After that we all left out of the vacant house. JA 564–65. After offering this description of the crime, Jackson responded in writing to questions from Officer Simon, providing additional details about the crime and explaining that he robbed the store “[b]ecause it was close to Christmas[,] and [he] wanted to buy [his] baby something.” JA 567. Dr. Edith Montgomery, the State’s expert witness, agreed that Jackson’s waiver was knowing and intelligent. During a pre-trial evaluation, Montgomery read each Miranda right to Jackson and asked him to explain what each of them meant. Jackson explained his rights as he understood them: “I ain’t got to talk,” JA 72; “if I go to court anything I said can be used against me,” id.; “I ain’t got to say nothing until an attorney gets there,” id.; and “[t]hey will pay for me an attorney,” id. Jackson responds that, because he required special-education classes and because he reads at only a third-grade level, his waiver could not have been knowing and intelligent. But those facts alone do not undermine a waiver—and no authority says they do. While the evidence showed that Jackson had difficulty reading, it also showed that he had average problem-solving skills and intelligence. Jackson waived his rights not only after reading them, moreover, but also after having them read to him and after accurately explaining to the officers what he understood his rights to be. And only one of the waivers of his Miranda rights was in writing; he gave the other three waivers orally. Because “there is nothing cognitively complex about the advice that one has a right to remain silent and not to talk to the police,” Finley v. Rogers, 116 F. App’x 630, 638 (6th Cir. Nov. 18, 2004); see also Clark v. Mitchell, 425 F.3d 270, 283–84 (6th Cir. 2005), because Jackson had average problem-solving skills and intelligence and because his considerable prior experience with the criminal justice system gave him reason to know the consequences of waiving these rights, the state court did not unreasonably apply Supreme Court precedent in holding that his waiver was knowing and intelligent. Jackson points out that his expert, Dr. Michael Abramsky, testified that Jackson’s mental deficiencies would have made it impossible for him competently to waive his rights. One answer No. 07-1247 Jackson v. McKee Page 6 is this: Dr. Montgomery testified that Jackson’s performance in his evaluations suggested he was not putting forth full effort and may have exaggerated his deficiencies. Another answer is this: the parties presented competing accounts of Jackson’s capabilities, and the state court, after weighing the evidence, determined that Jackson’s waiver was knowing and intelligent. Because Jackson presents no Supreme Court precedent that calls the state court’s determination into question and because the evidence reasonably supports that determination, AEDPA requires us to reject this argument. C. Jackson next argues that the trial court’s admission of non-testimonial hearsay statements violated his Sixth (and Fourteenth) Amendment rights under the Confrontation Clause. “In all criminal prosecutions,” that provision says, “the accused shall enjoy the right . . . to be confronted with the witnesses against him.” U.S. Const. amend. VI. Because the state court reasonably applied Supreme Court precedent in denying this claim, we must reject this argument as well. At trial, the State introduced testimony from Ramone Neal implicating Jackson in the robbery and murder. One afternoon, Neal testified, he ran into Ross and asked him for a ride. Ross refused, telling him that he had to “hurry up and go somewhere . . . we just did a robbery at the Dollar Store” and Jackson “just shot the man in the stomach.” JA 396–97. Jackson, Ross told Neal, was “nothing to f*** with.” JA 420. Conceding then (as he does now) that these statements were non-testimonial, see Davis v. Washington, 547 U.S. 813, 822 (2006), Jackson objected to the testimony on Confrontation Clause grounds. When Jackson raised this objection, Supreme Court precedent said that non-testimonial hearsay statements implicated a defendant’s confrontation rights. See Ohio v. Roberts, 448 U.S. 56, 66 (1980). Under Roberts, Ross’ non-testimonial hearsay statements could be admitted, consistent with Jackson’s Confrontation Clause rights, only if Ross was unavailable to testify and if the statements bore an “adequate indicia of reliability.” Id. (internal quotation marks omitted). A statement possesses an “adequate indicia of reliability” either if it is a “firmly rooted” hearsay exception or if it offers other “particularized guarantees of trustworthiness.” Id. The wrinkle is that, since Jackson’s trial, the Supreme Court has changed course, see Crawford v. Washington, 541 U.S. 36, 61–62 (2004), overruling Roberts and recognizing that non- testimonial hearsay does not implicate the Confrontation Clause, see Davis, 547 U.S. at 823–26. All of which prompts this question: what happens under AEDPA-constrained habeas review when a state court decision on direct review may amount to an unreasonable application of Supreme Court precedent but that precedent is overruled before a federal court entertains the habeas petition? Jackson argues that, because he can satisfy the requirements of 28 U.S.C. § 2254(d)(1)—by showing that the court’s decision “involved an unreasonable application of[] clearly established Federal law, as determined by the Supreme Court of the United States”—habeas relief is appropriate. The State counters that § 2254(d)(1) is a necessary, but not a sufficient, condition for habeas relief. Even if he could meet the “unreasonable application” requirement set forth in § 2254(d)(1), Jackson needs more. Section 2254(a) independently limits habeas relief to situations where a person “is in custody in violation of the Constitution or laws or treaties of the United States”—and that would not appear to be true here because Jackson is not currently being held in violation of the Constitution. See Flamer v. Delaware, 68 F.3d 710, 725 n.14 (3d Cir. 1995) (“Teague[’s] [non-retroactivity rule] only applies to a change in the law that favors criminal defendants.”); cf. Danforth v. Minnesota, 128 S. Ct. 1029, 1047 (2008) (“It would be quite wrong to assume . . . that the question whether constitutional violations occurred in trials conducted before a certain date depends on how much time was required to complete the appellate process.”); Lockhart v. Fretwell, 506 U.S. 364, 373 (1993) (“[T]he State will benefit from our Teague decision No. 07-1247 Jackson v. McKee Page 7 in some federal habeas cases, while the habeas petitioner will not. This result is not . . . a ‘windfall’ for the State, but instead is a perfectly logical limitation of Teague to the circumstances which gave rise to it.”). Jackson, at any rate, loses either way. Under today’s precedent, Jackson loses because Davis makes clear that the Confrontation Clause does not prevent the admission of non-testimonial hearsay. Under yesterday’s precedent, Jackson loses because the state court reasonably applied the Roberts test. Ross’ statements, the state court concluded, offered “particularized guarantees of trustworthiness,” Roberts, 448 U.S. at 66, and thus did not violate Jackson’s Confrontation Clause rights. In support of its decision, the court noted that (1) Ross’ statements to Neal were voluntary, (2) they were spontaneously made, (3) they were contemporaneous with the crimes, (4) they were made from one friend to another and (5) they did not reflect an attempt to downplay Ross’ own involvement but indeed implicated him in the crimes. See Williamson v. United States, 512 U.S. 594, 605 (1994) (noting, under the Roberts test, that “the very fact that a statement is genuinely self- inculpatory . . . is itself one of the ‘particularized guarantees of trustworthiness’ that makes a statement admissible under the Confrontation Clause”). In view of the “considerable leeway” Roberts once granted trial courts to determine whether non-testimonial hearsay statements comply with the Confrontation Clause, Idaho v. Wright, 497 U.S. 805, 822 (1990), we can safely say that the state court reasonably applied then-existing Supreme Court precedent in determining that Ross’ statements offered the particularized guarantees of trustworthiness Roberts requires. III. For these reasons, we affirm. | Low | [
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Background ========== Resistance to radiotherapy may be a significant factor in the development of local recurrence following surgical resection and radiotherapy. In addition, if patients with radioresistant breast cancers can be identified, harmful side effects from exposure to unnecessary ionizing radiation could be prevented. We aimed to develop a novel *in vitro*model of radio-resistance using a breast cancer cell line and to subsequently identify molecular biomarkers that may be associated with the radioresistant phenotype. Antibody microarrays offer a complementary approach for proteomic analysis in conjunction with standard screening methods such as two-dimensional gel electrophoresis/mass spectrometry. We have previously utilised the Panorama Cell Signalling Antibody Microarray Kit (Sigma-Aldrich, Poole, UK) consisting of 224 antibodies \[[@B1]\]. In the present study we assessed a novel high-density 725-antibody microarray to screen for proteins associated with radioresistance. Methods ======= We established a novel breast cancer cell subline that was significantly resistant to radiotherapy when compared with the parental cells (T47D). The radioresistant subline was created by irradiating cells in fractionated doses of 2 Gy up to a total dose of 40 Gy. Sufficient time was allowed for the cells to recover between subsequent irradiations. A dose--response curve was assessed at the end of treatment to demonstrate a statistically significant increase in radioresistance for the novel cell subline when compared with parental cells. The radioresistant/parental cell pair was analysed using the Panorama Antibody Microarray XPRESS Profiler725 Kit (Sigma-Aldrich). The microarray comprised 725 different antibodies on nitrocellulose-coated microscope slides. The antibodies were selected from a wide variety of pathways, including apoptotic and cell signalling pathways. Results ======= Utilising a Cy3/Cy5 labelling strategy, the antibody microarray approach yielded a number of possible targets for further study. These include zyxin, growth factor independence 1 and lysine-specific demethylase 1, which were differentially expressed between the radioresistant subline and parental cells. Immunoblotting has confirmed the identities and differential expression of some candidate protein targets. Conclusion ========== The use of a novel high-density antibody microarray has successfully identified a number of protein targets that may be associated with a radioresistant phenotype. These proteins require further study to validate the results. High-density antibody microarrays potentially offer a powerful new proteomic technique to allow the global analysis of many proteins simultaneously. These could be invaluable in the identification of candidate biomarkers that may be involved in radioresistance and may reveal novel therapeutic targets in breast cancer. | High | [
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Interleukin-6 production by macrophages from BALB/c mice with a chronic infection of lactic dehydrogenase virus. The production of interleukin-6 (IL-6), which is known as a B cell differentiation factor, by peritoneal macrophages from mice with a chronic lactic dehydrogenase virus (LDV) infection was compared with that from uninfected mice. The same amounts of IL-6 were detected in the culture supernatant of macrophages from LDV-infected mice as those from uninfected mice. Furthermore IL-6 production of macrophages from LDV-infected and uninfected mice was not affected by the addition of indomethacin. These results suggested that many immunological alterations seen in LDV-infected mice may not be due to, at least in part, altered IL-6 production ability of macrophages and the IL-6 production may not be affected by cyclooxygenase-derived products. | Mid | [
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Cybersyn was a project of the socialist government of Salvador Allende (1970-1973) and British cybernetic visionary Stafford Beer; its goal was to control the Chilean economy in real-time using computers and "cybernetic principles." The military regime that overthrew Allende dropped the project and probably for this reason when the project is periodically rediscovered it is often written about in a romantic tone as a revolutionary "socialist internet," decades ahead of its time that was "destroyed" by the military because it was "too egalitarian" or because they didn't understand it. Although some sources at the time said the Chilean economy was "run by computer," the project was in reality a bit of a joke especially in retrospect, albeit a rather expensive one, and about the only thing about it that worked were the ordinary Western Union telex machines spread around the country. The two computers supposedly used to run the Chilean economy were IBM 360s (or machines on that order). These machines were no doubt very impressive to politicians and visionaries eager to use their technological might to control an economy (see picture at right.) Today, our perspective will perhaps be somewhat different when we realize that these behemoths were far less powerful than an iPhone. Run an economy with an iPhone? Sorry, there is no app for that. Indeed, you don't have to read far between the lines of Andy "socialist internet" Beckett's account to get a flavor of what was really going on: Beer's original band of disciples had been diluted by other, less idealistic scientists. There was constant friction between the two groups. Meanwhile, Beer himself started to focus on other schemes: using painters and folk singers to publicise the principles of high-tech socialism; testing his son's electrical public-opinion meters, which never actually saw service; and even organising anchovy-fishing expeditions to earn the government some desperately needed foreign currency. (Note the classic, 'the visionary failed because others lacked idealism' story. Meanwhile the visionary is off on an anchovy-fishing expedition.) Recently, Jeremiah Axelrod and Greg Borenstein have put together an excellent video essay (fyi, 25 minutes) which gets to the heart (perhaps head would be a better word) of Cybersyn by focusing on the legendary "control room," which they delightfully call the "inverted panopticon." It is no accident, say Axelrod and Borenstein, that the control room looks like the bridge of the Starship Enterprise because the whole purpose of the room was to exude a science-fiction fantasy of omniscience and omnipotence. The fantasy naturally appealed to Allende who had the control room moved to the presidential palace just days before the coup. The control room is like the bridge of the Starship Enterprise in another respect–both are stage sets. Nothing about the room is real, even the computer displays on the wall are simply hand drawn slides projected from the other side with Kodak carousels. Ironically, when rumors of the project began to circulate, the illusion of omniscience and omnipotence that Beer had created, the same illusion that so appealed to Allende and that had funded Beer's visions and experiments, this illusion caused fear that an all-knowing big brother was on the way–and such fear may even have encouraged the coup. After the coup, rather than destroying the project because of its "egalitarian" nature, the military regime was more likely to have been disillusioned and disappointed to discover project Cybersyn's impotence. Hat tip to Boing Boing. | Low | [
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Opting to go ahead with a campaign rally on the very same day that America was reeling from a shooting in a Pittsburgh synagogue that caused the deaths of 11 people, and tone-deafly joking at a separate convention that perhaps he should cancel because he was in the middle of a “bad hair day”, Trump – as he known to – did himself few favours. But after telling reporters the shooting could have been avoided had there been an armed guard in the synagogue, reporters watched on as the commander-in-chief strolled up the stairs with an umbrella in hand to board Air Force One, before something that could really only happen under this presidency occurred. After arriving at the door of the plane and seeing that the umbrella wouldn’t fit, Trump barely attempted to close it, before simply leaving it behind for someone else to deal with – you know, like a very normal person would. Used it until he didn’t need it anymore so he tossed it. #WakeUpAmerica | Low | [
0.47261663286004,
29.125,
32.5
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This invention relates to single-substrate optical discs, such as single-substrate audio or video DVDs. Optical discs having pits and lands that form an optical track structure on one surface are known as single-substrate optical discs, while double-substrate optical discs, in which two single-substrate discs are bonded to each other back to back, are known as dual-substrate optical discs. When a dual-substrate disc is manufactured, the clamp area is characterized by the aggregate thickness of the two bonded substrates. (“Clamp area” is the area of a DVD that is covered or engaged by the clamp mechanism of the reproducing apparatus during play-back of the DVD. The word “area” is frequently used herein to refer to what is actually a three-dimensional portion or region of an optical disc. Thus the clamp area of a disc is not just a two-dimensional surface area, but also the thickness of the disc in that two-dimensional area. A certain volume, quantity, or amount of plastic material is therefore required to make the “clamp area” of a disc.) In an apparatus for reproducing the information recorded on an audio or video DVD, the clamp that grips the disc must be designed specifically for the thickness of the clamp area of that type of disc. The clamp area of a commercially available 80 mm DVD is usually located within the annular region having an outer radius of about 33 mm and an inner radius (defining the central aperture) of 22 mm. A typical reproducing apparatus in commercial use today is designed for double-substrate optical audio or video DVDs. The thickness of the clamp area in such double-substrate discs is typically about 1.2 mm, which is composed of the thicknesses of the two bonded substrates, about 0.6 mm each. In order to satisfy the specifications of the clamp designed for use with double-substrate discs, the thickness of the clamp area in a single-substrate optical disc must be made substantially the same as that of a double-substrate disc. For example, if the thickness of the clamp area in a single-substrate DVD is increased to about 1.2 mm, it becomes possible to play a single-substrate 0.6 mm-thick DVD on a player designed for use with bonded 1.2 mm-thick DVDs. A conventional way of accomplishing this object is by manufacturing an optical disc 10 (FIG. 1) having two regions 20 and 30 of different thicknesses. The first region 20 is a cylindrical region of annular cross section constituting the central portion of the optical disc 10, and the second region 30 is the remaining outer annular region of the disc. The thickness of first region 20 is greater than the thickness of second region 30. Such discs can be created by molding a hub with extra material in the clamp area of the disc, as described in International Application WO 98/10418. If additional material with a thickness of about 0.6 mm is molded onto a substrate 30 with the thickness of about 0.6 mm, the total thickness of region 20 will reach about 1.2 mm. This design makes it possible for a reproducing apparatus designed to play double-substrate DVDs to play single-substrate DVDs as well. The prior art solution, however, has a variety of disadvantages. For example, when a disc is manufactured according to the design described above, the large amount of material used in forming the hub may cause the hub to shrink radially and vertically, pulling in material from other regions of the disc, including information-carrying regions. This warping phenomenon may negatively affect the tilt, stress, birefringence and electrical properties of the disc. Attempts at reducing this phenomenon, such as increasing cool-down time in the mold for each disc, reduce the efficiency of the disc manufacturing process. | Mid | [
0.5618448637316561,
33.5,
26.125
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Tripleplay IPTV and Digital Signage to be used at Football’s European Championship Final London, UK/Montpellier, France, 17/5/2016:Tripleplay’s IPTV and Digital Signage solution will be utilised by both the Stade de France and Stade Bollaert-Delelis during this summer’s European Championships in France. RC Len’s Stade Bollaert-Delelis has Tripleplay’s IPTV and Digital Signage in place and will host three group games, with Albania-Switzerland, England-Wales and one second round game being competed at the recently renovated 38,223 seat stadium in the North East of France. France’s most iconic stadium, the Stade de France, originally built for the 1998 world cup, will host seven games throughout the tournament, including the opening match between France and Romania and the final, to be played on the 10th July. In total the Stade de France has around 450 screens of Tripleplay IPTV and Digital Signage. Both arena have implemented Tripleplay’s market leading IPTV and Digital Signage solutions, joining fellow sporting teams in France including Stade Toulousain and La Rochelles and globally iconic venues including the Daytona International Speedway, Twickenham Stadium, Wimbledon Tennis and Cape Town Stadium. | High | [
0.6702849389416551,
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