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Google+ Badge Tuesday, December 31, 2013 Friday, December 27, 2013 This amazing replica was on display at the Codissia Fair held recently in Coimbatore: This vehicle featured a rear mounted horizontal engine with a vertical crankshaft and final transmission to the rear wheels by side chains all mounted on a tubular chassis.The 984 cc IC engine developed a then spectacular 0.9 HP giving a top speed of approx. 8 K mph amidst a veritable cacophony of sounds smells and vibrations. Today the Motorwagen may be considered primitive to the extreme but Benz's patent of 29 January 1886 was indeed "state of the art" The original car was donated to the Deutche's museum by Papa Benz in 1906. This one is a replica built in Yorkshire England a few years back. Attractively presented with black framing and iron work, varnished wood platform & wooden tool box, and a plethora of brass fittings this fabulous exhibition piece can also be made to run but with care. Wednesday, December 25, 2013 The farewell dinner on Day 2 ( 17th November 2013) was held at the Patna Golf Club.Patna Golf Club History: 1916 was a hallmark year in the history of Patna with the founding of the ‘South Bihar Gymkhana Club’ which was later rechristened as the Patna Golf Club. Sprawling over 165 acres this is the sole club for the golf lovers. The ‘South Bihar Gymkhana Club’ stretched from Government House in the west to Bihar Gymkhana Club in the south. The 1st secretary and president of the club were H.K Briscoe and W. Maude. Formerly, the club used to serve as the ground for playing golf and polo by the British Officers and the socialites. After the Second World War, the British lost interest in maintaining the club’s ground and polo’s popularity as a sport also diminished. In 1956, the District Judges J.G.Shearer and K.Banerji stepped in and decided to take necessary measures for the revival of the club’s golfing activities. The name of club was changed from the ‘South Bihar Gymkhana Club’ to ‘Patna Golf Club’ and consequently, the ground, solely began being used for golf. Through its glorious journey of 96 years of existence, Patna Golf Club has pioneered and encouraged the game of Golf amongst all ages and sections of society. The vast course serves as a training ground to the young budding golfers to achieve their dreams in the days to come. Many popularl golf tournaments such as Basant Utsav, Heat and Dust Golf Tournament etc, are hosted by the club annually. Due to all these endeavours the magnificent game of Golf has found an irreplaceable place in the state of Bihar. The farewell dinner commenced around 8.00 pm at night.It was as usual cocktails, snacks & dinner. There were also many speeches by participants and thanksgiving to the organizers. The reunion had been a wonderful event and by the time we reached the finale at The Patna Golf Club there was a tinge of sadness as the proceeding were coming to an end.The mood that prevailed at the farewell dinner is aptly demonstrated in the below video & pictures. Cheers. Adieu until 2015. And for the final session - We all Xavierian's 56-65 meet again a t the Golf Club. Vinay Sinha regaled the gathering with his melodious voice - he kept belting out the golden oldies from the 60's and 70's. Kavitha Shivaji, Luxmi Shil& Meena Jayanth look on in admiration. Tuesday, December 24, 2013 Thursday, December 19, 2013 Bali is an island and the smallest province of Indonesia. The island is home to most of Indonesia's Hindu Minority.According to the 2010 Census, 84.5% of Bali's population adhered to Balinese Hinduism. while most of the remainder followed Islam. Bali is also the largest tourist destination in the country and is renowned for its highly developed arts, including traditional and modern dance, sculpture, painting, leather,metal working and music. A tourist haven for decades, the province has seen a further surge in tourist numbers in recent years. This a popular dance form from Bali. This troupe of young girls is colorful costumes are enacting the Ramayana as part of the entertainment during a cruise we took during a visit to the Island of Bali. Wednesday, December 18, 2013 After the devastating famine of 1770 which killed nearly 10 million people in regions of Bengal & Bihar and modern day Bangladesh,Warren Hastings , then Governor General of India, ordered the construction of this beehive shaped structure (Gol Ghar) for the purpose of storing grains for the British Army. It was conceived and built by Captain John Garstin, an engineer with the East India Company and has a storage capacity of 140,000 tons, it construction was completed on 20 July 1786. Built in the native Stupa architecture, Gol Ghar has a foundation of 125m, and a height of 29 m. It is pillarless with a wall of thickness of 3.6 m at the base. One can climb atop the Golghar through the 145 steps of its spiral stairway around the monument. The spiral staircase was designed so as to facilitate the passage of the coolies, who had to carry grain-bags up one flight, deliver their load through a hole at the top, and descend the other stairs. The top of the Gol Ghar presents a wonderful panoramic view of the city and the Ganges flowing nearby. At time of its construction, it was the tallest building in Patna. Golghar has never been filled to its maximum capacity and there are no plans to do so. The reason for this is a flaw whereby the doors are designed to open inwards. Thus, if it is filled to its maximum capacity, then the doors will not open. Friday, December 13, 2013 The party at Chanakya on Day One ended pretty close to midnight and by the time most of us got to our homes/hotel rooms it was close to 1.00 am. So it was decided we deserved to sleep till late on Sunday morning have a leisurely break fast and then meet up at St.Xavier's School around 11.00 am. The entry into our school after a gap of 48 long years was nostalgic and my mind was filled with so many fond memories.We old boys were all wearing our blue striped school ties and we felt so proud of this. We took a tour of the school campus around the old school buildings, to the hand ball courts, the old auditorium, swimming pool, basketball & tennis courts. Alas some of the important landmarks like the huge tamarind tree and the shuffle boards had vanished.The aviary which used to house little birds and small pet animals had also been dismantled. The swimming pool was in a state of disuse and the tennis court in a poor state of maintenance. A new additional block has been constructed opposite to the old blocks basically with an idea of expanding and adding more students.The school had over the years also switched syllabus from Senior Cambridge to Matriculation. Also the exclusive boys school had now become co-ed. Once every one arrived we started the days proceedings with light refreshments - the traditional bun,butter,chops & chips accompanied by soft drinks and beer/vodka/gin etc. The camaraderie,fellowship and the bonhomie continued to overflow.We had a super entertainment session involving both men and ladies. Men were asked to pick up folded slips of paper from a basket and then they had to do what ever was written in the slips - stand one one leg for one minute, bleat, moo, meow, cluck, bark,dance,hum a tune till it was identified,sing a song,jump, skip,propose to a girl at a date.......The list went on. Surprisingly some of the men were a bit shy to perform and the women had a jolly good time.Next we had a musical session of Antakshari, Here the men scored heavily. Majority of the old Bollywood numbers were belted out by Vinay Sinha who is gifted with a wonderful melodious voice. Binny Kocchar too sportingly contributed to many songs.Then it was time for lunch. The Chinese menu of noodles,rice,sweet & sour vegetables,garlic chicken was delicious.The lunch concluded with mouth watering gajar ka halwa and yummy kulfi/ice cream. After lunch we walked through the polished corridors of the school, went into our old classrooms,trekked upstairs to see the dorm, barged in to the Principals Office........................... Amarendra & G.P.Singh posing in front of the school gate We enter St.Xaviers. I ( Ramanathan) am entering the portals of the school after 48 years. It was nostalgic and I was flooded with many fond memories. The main school block was unchanged - the Tamarind tree had disappeared & so were the shuffling boards. Relaxed and having a Teta a tete ! The ladies provided the entertainment - the men danced to their tunes.Some stood on one leg, others bleated like lambs and clucked like hens. Some were asked to hum tunes while others danced. In the end there was an entertaining Antakshari - where Vinay Sinha took the strangle hold belting out old tunes in quick succession. Enjoying the meal of Butter,Bread, Beans,Chops & Chips. There was plenty of Beer & Vodka also going around. The Stair case leading to the first floor - where the dorm was situated. The corridor with mirror finish polished marble floor on the ground floor. The classrooms & the furniture were virtually unchanged. This was a trip down the memory lane. The majestic main entrance doors with stained glass clicked from the inside. Ramanathan & Rai Shivaji Nath posing with the Vice Principal. The School Motto - The plaque was in the Principals room. The water taps and cement trough remained unchanged This awesome B & W was found hanging outside the Principals Office. The Rev.Father Murphy (our Principal during the 60's) shaking hands with the then Governor of Bihar Dr.Zakir Husain. Thursday, December 12, 2013 About 22 of us old boys(some accompanied by wives) from St.Xavier's High School Patna 1956-65 Batch had a happy reunion at Patna on 16-17 November 2013.Many of us were seeing each other after 48 years - but the recognition was immediate and the chemistry instantaneous.Basic structure and general looks of most of us hadn't changed - we were older, heavier,weaker, had paunches, grey hair, bald pates,some looked more mature,others sillier ........................... On 16th morning we had the inaugural meeting and lunch at the Bankipore Club - This club established in the year 1865 on the bank of River Ganges at Patna, Bihar.Originally known as "European Club" and used exclusively by Europeans.The club was renamed "Bankipore Club" as Bankipore denoted the civil station of Patna District. We started with registration of participants followed by a round of introductions.A 2 minutes silence was observed in memory of about 20 of our fellow classmates who were no longer in our midst on mother earth. A special cake had been ordered for the occasion which the ladies were accorded the privilege to blow the candle, cut the cake and distribute. Next was fellowship with a round of cocktails,juices & snacks followed by lunch.Post lunch we all gathered on the sprawling lawns facing the Ganges for a group photo session. After this we all drove off in a convey of cars to the Ganga Ghat for a river cruise. We had a wonderful two hour cruise and watched the beautiful sunset. It was Kartik Purnima and after dusk we saw the full moon in all her glory. We also had the good fortune to view the special Arti on the Ganga Ghat on the auspicious occasion of Kartik Purnima. After the cruise we all dispersed to our various homes & hotels only to reassemble at the Hotel Chanakya for cocktails and dinner which was being so graciously hosted bt Vinay Kocchar - a leading hotelier and successful businessman who also happens to be one amongst us old boys. Cocktails and snacks were served in the well stocked and brightly illuminated Takshila bar on the roof top and dinner was at open roofed terrace. The camaraderie and bonhomie was excellent. The men were turned out smartly and ladies dressed in gorgeous colorful attires. We all had a grand gala time. Here are some pics of the adventures of Day one: Shiladitya & Jitendra Sahai posing for the camera while Akhoury seems to be silently enjoying a joke The weather was lovely - there was a little nip in the air. Binod Yadav, Vinay Sinha, Amarendra & Abhai Choudhary enjoying their souffle & ice cream. To be continued.............................................................

Tracking of Noise Tolerance to Measure Hearing Aid Benefit. The benefits offered by noise reduction (NR) features on a hearing aid had been studied traditionally using test conditions that set the hearing aids into a stable state of performance. While adequate, this approach does not allow the differentiation of two NR algorithms that differ in their timing characteristics (i.e., activation and stabilization time). The current study investigated a new method of measuring noise tolerance (Tracking of Noise Tolerance [TNT]) as a means to differentiate hearing aid technologies. The study determined the within-session and between-session reliability of the procedure. The benefits provided by various hearing aid conditions (aided, two NR algorithms, and a directional microphone algorithm) were measured using this procedure. Performance on normal-hearing listeners was also measured for referencing. A single-blinded, repeated-measures design was used. Thirteen experienced hearing aid wearers with a bilaterally symmetrical (≤10 dB) mild-to-moderate sensorineural hearing loss participated in the study. In addition, seven normal-hearing listeners were tested in the unaided condition. Participants tracked the noise level that met the criterion of tolerable noise level (TNL) in the presence of an 85 dB SPL continuous discourse passage. The test conditions included an unaided condition and an aided condition with combinations of NR and microphone modes within the UNIQUE hearing aid (omnidirectional microphone, no NR; omnidirectional microphone, NR; directional microphone, no NR; and directional microphone, NR) and the DREAM hearing aid (omnidirectional microphone, no NR; omnidirectional microphone, NR). Each tracking trial lasted 2 min for each hearing aid condition. Normal-hearing listeners tracked in the unaided condition only. Nine of the 13 hearing-impaired listeners returned after 3 mo for retesting in the unaided and aided conditions with the UNIQUE hearing aid. The individual TNL was estimated for each participant for all test conditions. The TNT index was calculated as the difference between 85 dB SPL and the TNL. The TNT index varied from 2.2 dB in the omnidirectional microphone, no NR condition to -4.4 dB in the directional microphone, NR on condition. Normal-hearing listeners reported a TNT index of -5.7 dB using this procedure. The averaged improvement in TNT offered by the NR algorithm on the UNIQUE varied from 2.1 dB when used with a directional microphone to 3.0 dB when used with the omnidirectional microphone. The time course of the NR algorithm was different between the UNIQUE and the DREAM hearing aids, with the UNIQUE reaching a stable TNL sooner than the DREAM. The averaged improvement in TNT index from the UNIQUE directional microphone was 3.6 dB when NR was activated and 4.4 dB when NR was deactivated. Together, directional microphone and NR resulted in a total TNT improvement of 6.5 dB. The test-retest reliability of the procedure was high, with an intrasession 95% confidence interval (CI) of 2.2 dB and an intersession 95% CI of 4.2 dB. The effect of the NR and directional microphone algorithms was measured to be 2-3 and 3.6-4.4 dB, respectively, using the TNT procedure. Because of its tracking property and reliability, this procedure may hold promise in differentiating among some hearing aid features that also differ in their time course of action.

Am Nichole from France and i wouldn't have believed that i would someday share my survival from cancer with anyone because cancer almost ended my life. I bless that faithful day i went online in search of help and i found my helper Dr. George who helped me via his email to defeat cancer that had almost sucked life out of me with his cannabis oil which was as effective as he said it was. I will also like to use this medium to appreciate Dr.George contacthospital_eastern.george@yahoo.com for his care, support and of course his cannabis oil because i would have been history if not for you My greatest hero Dr. George. My name is Mrs. Kerry Daniel from Florida, It is with pleasure that i thank Dr. Morris for saving my dying husband with his cannabis oil. We already lost hope for a better life when the report came that my husband cannot go for more Chemo anymore. But after so many research online, I gained a lot about the cannabis oil that i bought from the Dr. Morris whose contact I got online on reading a testimony about his past works and glory, The medication was delivered to me within 24 hours by the UPS delivery service after procurement. My husband has completed his treatment, unquenchable joy to all as my husband is cured of his stage 4 lungs cancer within 90 days of treatment. Thanks to all, today i acknowledge the greatness of cannabis oil and to those that wish to purchase the medication contact:healthcareservice01@gmail.com for help. Cannabis Oil is the a medication for cancerous disease. Kerry Daniel. Historical Use: Hemp is the most universally useful plant we have at our disposal. The history of mankind's use of hemp can be traced way back in time to between about 5000 - 7000 BC. Remains of seed husks have been found at... Although I’ve been aware of the recent discussion of cannabis oil as a treatment for various serious diseases, I was still skeptical to consider it a viable solution for certain health disorders. After all, so many people these days are looking for a miracle pill to solve their health issues! Is this another way of buying into one-size-fits-all treatments without making necessary lifestyle changes? It was time I found out more. By Contributing Writer Raluca Schachter “After nine months of taking two different forms of cannabis oil, one, a cannabis capsule infused with organic coconut oil around 10:30am and high THC oil about an hour before bed, dad was given the life changing report, no... Paediatric cannabis therapy is saving children. Awareness is the most important thing at this moment. This young lady is finishing up her last bit of required chemotherapy (because she is a child, her parents had no choice) treatment, so take a moment to send her your love and healing vibes, and then read away. You […] If you're reading HIGH TIMES you are probably aware of all the ways ingesting marijuana can improve your life, so maybe just file this one away for a future argument with a spouse/boss/family member/lawmaker. It's a big year ahead in Colorado, Washington state, Uruguay, and for me here in Mississippi. As of today, Wednesday January 1st, retail stores and licensed pot growers commence legalized business transactions. Sharing your scoops to your social media accounts is a must to distribute your curated content. Not only will it drive traffic and leads through your content, but it will help show your expertise with your followers. Integrating your curated content to your website or blog will allow you to increase your website visitors’ engagement, boost SEO and acquire new visitors. By redirecting your social media traffic to your website, Scoop.it will also help you generate more qualified traffic and leads from your curation work. Distributing your curated content through a newsletter is a great way to nurture and engage your email subscribers will developing your traffic and visibility. Creating engaging newsletters with your curated content is really easy.

Q: Using local imports in Pytest I have never really fully understood how packages are handled in Python and I'm having a problem with that right now. But googling doesn't seem to help as I find the topic really confusing. I have a project with this structure: project_name/ src/ main.py utils/ string_utils.py tests/ test_string_utils.py I am using Pytest for running unit testing and currently inside the "test_string_utils.py" file I have the following: from ..src.utils.string_utils import StringUtilsClass But I go to the folder "project_name" and try to run tests with any of this command I get errors: $ pytest tests/ ValueError: attempted relative import beyond top-level package I know about the -m argument for python, but it seems that running "pytest -m" has a completely different behavior. How can I solve this? Am I using the wrong folder architecture? I don't think what I'm building should be a pip package (which would simplify imports) A: did you try : from src.utils.string_utils import StringUtilsClass without .. before src? or from string_utils import StringUtilsClass

ZetaTalk: Minority Votes Note: written Jul 15, 1997. Humans used to arranging a place on court dockets often feel left out of activities ongoing at the Council of Worlds. Their votes are collected and then that’s the end of it, and they long to argue their case. On Earth, depending upon the human society, one can either bribe the judge, bribe or otherwise influence those who appoint or control the judge, selectively screen the jury, arrange to be represented by high priced and high powered attorneys, or endlessly petition. That the Council of Worlds does not have similar avenues open to them feels like a breach of rights! In fact, probably for the first time, they are experiencing a true democracy. They are the minority vote! Their viewpoint lost! Manipulating the outcome by trying to manipulate the courts is simply not democratic! The Council does not arbitrarily make pronouncements affecting the lives and futures of intelligent species. Except for the preconscious period, when genetic engineering is about to begin or is in process, the spirits incarnating into an intelligent species always determine the outcome. Neanderthal man determined that its line would die out to be replaced by another version of early man, for instance. They were polled as to their opinion on the eating disorder that was killing so many of them at a young age, and the alternatives were abundantly clear to those polled. Once the decision had been made, the feelings of any given Neanderthal man about to be sterilized, but not castrated, with a small snip to his groin mattered not. His was the minority vote!

The Pirates! Band of Misfits Synopsis In The Pirates! Band of Misfits, the luxuriantly bearded Pirate Captain is joined by a rag-tag crew. With seemingly blind to the impossible odds stacked against him, the Captain has one dream: to beat his bitter rivals Black Bellamy and Cutlass Liz to the much coveted Pirate Of The Year Award. It's a quest that takes our heroes from the... Production Details Synopsis In The Pirates! Band of Misfits, the luxuriantly bearded Pirate Captain is joined by a rag-tag crew. With seemingly blind to the impossible odds stacked against him, the Captain has one dream: to beat his bitter rivals Black Bellamy and Cutlass Liz to the much coveted Pirate Of The Year Award. It's a quest that takes our heroes from the shores of exotic Blood Island to the foggy streets of Victorian London. Along the way they do battle with the pirate-hating Queen Victoria and team up with a young Charles Darwin, but never lose sight of what a pirate loves best: adventure! The Pirates! Band of Misfits Let's face it, the world of Hollywood pirating — with its peglegs, eyepatches, shoulder parrots and bounty of other swashbuckling tropes — is pretty silly. Even a high seas adventure like Pirates of the Caribbean has the ridiculous Jack Sparrow to help it hobble along. Pushing the comedy can only work in pirate movie's favor, and Aardman Animation's Pirates! A Band of Misfits goes all out, seizing the absurdity with a flare only British sensibilities could conjure. The film is a treasure trove of design and technical wizardry, but for those less interested in the intricacies of stop motion animation, Pirates!'s simple story packs plenty of low-key laughs that viewers all ages can pick up. The Pirate Captain (Hugh Grant) is at wit's end. While he's enjoyed his time leading a ragtag group of wannabe pirates, including Albino Pirate (Anton Yelchin), Pirate with Gout (Brendan Gleeson), Surprisingly Curvaceous Pirate (Ashley Jensen) and his number two, Pirate with a Scarf (Martin Freeman), a lifestyle of eating ham and barely making ends meet is losing its luster. ALTWhen Pirate Captain shows up to the annual Pirate of the Year submission day, he's once again outdone by Black Bellamy (Jeremy Piven), who rides in on a whale full of gold. Driven by competition, Pirate Captain reassembles his crew, hits the open waters and begins a new wave of pillaging. It's all for naught, until the pirates cross paths with Charles Darwin (David Tennant), who identifies Pirate Captain's "parrot" as an extinct dodo bird. Suddenly, the pirates have a new (and lucrative) calling: science. There's an unexpected intelligence to Pirates!. The movie, based on a children's book of the same name, centers on Pirate Captain's mid-life crisis, delves into the world of 18th century science and pegs Queen Victoria (Imelda Staunton) as the mastermind bad guy behind the elimination of the pirate occupation. That gives the accompanying adults plenty to chew (and laugh) on, but director Peter Lord doesn't stray away from an ol' fashioned slapstick routine. There's a marvelous stray bathtub sequence halfway through the film, a wild ride through Charles Darwin's old tudor, that's a true spectacle. But even a simple gag involving baking soda and vinegar exploding sud bubbles is expertly crafted and executed by Lord. The stop motion technique never feels limited in Pirates!, even with a great deal of walking and talking scenes. Gideon Defoe's script is elevated by the vocal performances; Grant is perfectly cast as the faux-burly Pirate Captain, while Martin Freeman's perfected "timid skeptic" routine from The Office and Sherlock is once again on full display. The Aardman team continues to have a knack for gesturing, their puppets uniquely natural and human. Even with all the enormous pirate ships, detailed cityscapes and dazzling action, Pirates! is at its best when it focuses on the sillier, calmer moments. The tangibility of Pirates! A Band of Misfits comes through in its physical stop-motion animation techniques, but also its genuine heart. There's a rare reality to the storytelling, even at its most fantastical. While the film doesn't hit the same emotional chords as some of Pixar or Dreamworks' best, you would need an X-marked map to find a Hollywood cartoon as sweet and heartfelt. So don't walk the plank on this one — board, with kids in tow, immediately. MovieTickets.com is a worldwide leader in advance movie ticketing and a top destination for celebrity interviews, movie reviews and trailers. You can also access theater information, check movie showtimes, view video clips, and much more.

Assisted living is the ideal alternative for seniors that need help with activities of daily living, but do not require the high level of medical care typical of skilled nursing homes. Activities of daily living in Assisted Living include such things as meal preparation, housekeeping, laundry, medication... Many may not realize that there is a unique and special history about the services that Libby Bortz Assisted Living brings to Littleton and the Denver metro area. Libby Bortz Assisted Living was built in 1994. Libby Bortz is a collaborative success for the Littleton community, which cooperated with the Littleton... We are so proud of our wonderful community! Libby Bortz Assisted Living is nestled in charming downtown Littleton, Colorado – Browse our photos and take a tour of our wonderful property. If you have any questions call us! Explore the photographs below to learn more about Libby Bortz Assisted Living. We also... Libby Bortz Assisted Living is the result of the Littleton Housing Authority, people serving on their board and members in the Littleton community bringing together their experience to create an assisted living center for modest-income older adults. In the late 1980’s the community and the Littleton Housing... Libby Bortz Assisted Living opened in 1994 and today is a well-known affordable assisted living community serving the Denver metro area. We are located the in historic downtown Littleton area. Our residents and their families can enjoy many of the wonderful events, fine and casual dining and shopping experiences in... New and Exciting things are happening in 2018 with the Libby Bortz Assisted Living with the new Expanded Care & Services. Libby Bortz Assisted Living is pleased to announce that Expanded Care & Services are coming... New and Exciting things are happening in 2018! Coming Soon in 2018 – Libby Bortz will be offering more care and services to our residents at an additional cost. We have designated some of the apartments on 1st Floor West... THE HOLIDAY PARTY was a huge success! Thank you, Barbara Dawson for the great music. Refreshments were enjoyed and our singing raised the roof. Santa was greeted by residents with smiles from ear to ear. Again, a thank you to... Residents, staff and families enjoy the holidays at Libby Bortz Assisted Living. Be sure to review our newsletter and calendar for all the wonderful events. One of our special events is our traditional Candlelight Dinner for...

Mâliâraq Vebæk Mâliâraq Vebæk (20 April 1917 – 25 February 2012) was a Greenlandic teacher and writer. She is known as the first woman of Greenland to publish a novel. One of the first women to obtain a higher education in Greenland, she began her career as a teacher. After six years, she relocated to Denmark and worked on archaeological excavations and ethnographic surveys with her husband from 1946 to 1962. She began publishing stories, legends and folktales in the 1950s, both through print media and on radio. In 1981, after having participated in a survey on the intercultural issues for Greenlanders and Danes, published a novel inspired by the research. It won the Greenlandic Authors Association Award for 1982. Early life Marie Athalie Qituraq Kleist, known as Mâliâraq, was born on 20 April 1917 in Narsarmijit, Greenland to Bolette Marie Ingeborg (née Chemnitz) and Hans Hoseas Josva Kleist. There were eight children in her family and her father was a local priest who wrote popular hymns and served on the South Greenland County Council. Though school was stressed at home, their mother made sure that her daughters learned the traditional skills, like leather tanning and skinning, which were required of Greenlandic women at that time. When she was ten years old, she moved to Alluitsoq (formerly known as Lichtenau) to live with her grandparents, taking some of the financial strain off of her parents. Her grandfather, Jens Chemnitz, had been educated in Denmark and was one of the first priests to come to Greenland and was also known to have been one of the first Greenlanders to engage in raising sheep. In 1932, for the first time secondary schooling was offered for girls when a boarding school opened in Aasiaat (formerly known as Egedesminde). Kleist had to go to Qaqortoq to take a test, but upon passing the examination was admitted to study at Aasiaat. The program was a two-year curricula and for girls included in addition to academic studies, domestic science, childcare and practical skills they would need as wives. She finished her studies as valedictorian of her class, surpassing all the boys in their parallel courses. Because of her marks, the Committee for Greenlandic Education, a private organization which promoted further studies in Denmark to enable girls to learn various trades, offered Kleist a scholarship to continue her education. In September 1934, she arrived in Holte, where she lived with the pastor, Thorvald Povlsen, a family relative, for a year to improve her Danish. She enrolled in the Theodora Lang Seminars (da) in Silkeborg and attended through 1939. Though initially she had some trouble linguistically as the only Greenlandic speaker, she graduated, after passing her examination as a teacher. Career Returning to Greenland in 1939, Kleist began working as a teacher in Ilulissat. In the summer of 1939 she met Christen Leif Pagh Vebæk, an archaeologist and museum inspector for the National Museum of Denmark's prehistoric department. Because of the war she remained in Greenland, teaching in Aasiaat and later Paamiut, while Vebæk returned to Denmark and was unable to reunite with her until the conflict ended. On 4 August 1945, the couple were married in Qaqortoq and almost immediately moved to Denmark, where their daughters, Bolette (1946) and Astrid (1947) were born. In the early years of their marriage, while raising their children, Vebæk accompanied her husband on numerous archaeological expeditions to Greenland, including his explorations in 1946, 1948 to 1951, 1954, 1958 and 1962. She served as his interpreter and prepared ethnological surveys in Greenlandic to assist in the collection of information about the culture. Once the surveys were completed, she translated them for Danish analyzers. During these archaeological and ethnological expeditions, Vebæk began collecting songs, legends and folktales, which from the mid-1950s, she published in journals and newspapers in both Denmark and Greenland. She illustrated her articles with silhouettes of her own design. From 1958, she worked as a freelancer for the Greenlandic department of Copenhagen, which later shared the recordings with the radio station in Kuuk. She began reading traditional stories, but by 1959 was producing her own soundtracks, which would be recorded with other Greenlanders living in Denmark playing the various roles. There had been an influx of Greenlanders moving to Denmark in the decade from 1950 to 1960. At the beginning of 1970, she was asked to participate in a comprehensive study of the relationship of the two countries. She helped with the interviews and translated the work into Greenlandic. The result was published in Danish as Grønlændere i Danmark (Greenlanders in Denmark) in 1971–72 and two years later in Greenlandic as Kalâtdlit Danmarkime. During the survey, Vebæk became aware of the problems that interculturalism posed for women, specifically Greenlandic women who had married Danish men. These insights influenced her later writings focused on women, such as the suppression that their gender caused and conflicts between Danish and Greenlandic culture. In 1981, she published the first novel written by a Greenlandic woman, Búsime nâpínek (Meeting on the Bus), the tragedy of a chance meeting which turned into a friendship and tells the story of repression which leads to the main character Katrine's demise. Vebæk received the Greenlandic Authors Association award in 1982 and that same year, she translated the story into Danish, which was published as Historien om Katrine. The book gained a wide readership and was reprinted in 1993 and 1994, being subsequently translated into Russian and Sami. In 1992, Vebæk picked up the story of what happened to Katrine's daughter in Ukiut trettenit qaangiummata (Then, Thirteen Years Later). In 1990, she published a history of Greenlandic women using much of her ethnographic material collected earlier. The Danish title Navaranaaq og de andre was released as Navaranaaq Allallu in Greenlandic in 1996 and retold women's story from legendary times to the present. The previous year, she published a children's story, Sassuma Arnaanut pulaarneq (A Visit to the Mother of the Sea). Death and legacy Vebæk died on 25 February 2012 in Søborg and her funeral was held on 2 March 2012 at Gladsaxe Church. She is remembered not only for her own writings, but for her contributions to collect and preserve the folklore of Greenland. References Citations Bibliography Category:1917 births Category:2012 deaths Category:People from Kujalleq Category:Greenlandic women writers Category:20th-century women writers

Map originally found on reddit The map above shows what the borders of Europe, the Middle East and North Africa might look like if they were based on the dominant Y-DNA haplogroup rather than ethnicity and/or any other political considerations. Here’s some very basic information about each group: Haplogroup R1b: “It is the most frequently occurring paternal lineage in Western Europe, as well as some parts of Russia (e.g. the Bashkir minority) and Central Africa (e.g. Chad and Cameroon). It is also present at lower frequencies throughout Eastern Europe, Western Asia, as well as parts of North Africa and Central Asia.” Haplogroup R1a: “It is distributed in a large region in Eurasia, extending from Scandinavia, Central Europe and southern Siberia to South Asia.” Haplogroup N: “It has a wide geographic distribution throughout northern Eurasia, and it also has been observed occasionally in other areas, including Southeast Asia, the Pacific, Southwest Asia and Southern Europe.” Haplogroup I1: “The haplogroup reaches its peak frequencies in Sweden (52 percent of males in Västra Götaland County) and western Finland (more than 50 percent in Satakunta province).[6] In terms of national averages, I-M253 is found in 35–38 per cent of Swedish males, 32.8% of Danish males, about 31.5% of Norwegian males and about 28% of Finnish males.” Haplogroup I2: “The haplogroup reaches its maximum frequency in the Dinaric Alps in the Balkans, where the men are on record as being the tallest in the world, with a male average height of 185.6 cm (6 ft 1.1 in).” Haplogroup J1: “This haplogroup is found today in significant frequencies in many areas in or near the Middle East, and parts of the Caucasus, Sudan and Ethiopia. It is also found in high frequencies in parts of North Africa, Southern Europe, and amongst Jewish groups, especially those with Cohen surnames. It can also be found much less commonly, but still occasionally in significant amounts, throughout Europe and as far east as Central Asia and the Indian Subcontinent.” Haplogroup J2: “It is found in Western Asia, Central Asia, South Asia, Europe and North Africa, but it is usually associated with Northwest Asia. It is thought that J2 might have originated between the Caucasus Mountains, Mesopotamia and the Levant.” Haplogroup E: “Most members of haplogroup E-M96 belong to one of its identified subclades, and the E-M96(xE-P147, E-M75) is rare. E1a and E-M75 are found almost exclusively in Africa. By looking at the major subclade frequencies, five broad regions of Africa can be defined: East, Central, North, Southern and West. The division can be distinguished by the prevalence of E-V38 in East, Central, Southern and West Africa, E-M78 in East Africa and E-M81 in North Africa.” Haplogroup G: “At the level of national populations, G-M201 is most commonly found in Georgia; it is found at even higher levels among many other regional and minority populations in The Caucasus. G-M201 is also widely distributed at low frequencies, among ethnic groups of Europe, South Asia, Central Asia, and North Africa.” To learn more about DNA and Haplogroups have a look at the following books: Also if you’d like to get your DNA tested have a look at: If you found this map interesting please help by sharing it:

Artificial neural network to predict the natural convection from vertical and inclined arrays of horizontal cylinders The main focus of the present study is to utilize the artificial neural network (ANN) in predicting the natural convection from horizontal isothermal cylinders arranged in vertical and inclined arrays. The effects of the vertical separation spacing to the cylinder diameter ratio (Py/d), horizontal separation spacing to the cylinder diameter ratio (Px/d) and Rayleigh number (Ra) variation on the average heat transfer from the arrays are considered via this prediction. The training data for optimizing the ANN structure is based on available experimental data. The Levenberg-Marquardt back propagation algorithm is used for ANN training. The proposed ANN is developed using MATLAB functions. For the best ANN structure obtained in this investigation, the mean relative errors of 0.027% and 0.482% were reached for the training and test data, respectively. The results show that the predicted values are very close to the experimental ones.

Welcome to Being the Book!!! This item is also available in Digital Downloadable Format Click below to check Kindle Sale Prices or Click on Title to view full description Beebe, Steven A.; Mottet, Timothy P.; Roach, K. DavidTraining & Development: Communicating for SuccessPrentice Hall College Div 2012-01-18 0205006124 / 9780205006120 Paperback New Paperback Due to the popularity of this item, we recommend purchasing it from Amazon.com. Amazon will offer the fastest shipping price and best quality. Every Amazon purchase is 100% refundable through Amazon's A-Z policy. Due to the popularity of this item, we recommend purchasing it from Amazon.com. Amazon will offer the fastest shipping price and best quality. Every Amazon purchase is 100% refundable through Amazon's A-Z policy. Price: 35.96 USD Berk, Laura E.Infants and Children: Prenatal Through Middle ChildhoodPrentice Hall College Div 2010-12-31 0205006469 / 9780205006465 Paperback New Paperback Due to the popularity of this item, we recommend purchasing it from Amazon.com. Amazon will offer the fastest shipping price and best quality. Every Amazon purchase is 100% refundable through Amazon's A-Z policy. Due to the popularity of this item, we recommend purchasing it from Amazon.com. Amazon will offer the fastest shipping price and best quality. Every Amazon purchase is 100% refundable through Amazon's A-Z policy. Price: 50.00 USD Schiffman, Leon G.; Wisenblit, Joseph LConsumer BehaviorPrentice Hall College Div 2013-06-30 0132544369 / 9780132544368 Hardcover New Hardcover Due to the popularity of this item, we recommend purchasing it from Amazon.com. Amazon will offer the fastest shipping price and best quality. Every Amazon purchase is 100% refundable through Amazon's A-Z policy. Due to the popularity of this item, we recommend purchasing it from Amazon.com. Amazon will offer the fastest shipping price and best quality. Every Amazon purchase is 100% refundable through Amazon's A-Z policy. Price: 50.00 USD Shank, MatthewSports MarketingPrentice Hall College Div 2013-07-30 0132147629 / 9780132147620 Hardcover New Hardcover Due to the popularity of this item, we recommend purchasing it from Amazon.com. Amazon will offer the fastest shipping price and best quality. Every Amazon purchase is 100% refundable through Amazon's A-Z policy. Due to the popularity of this item, we recommend purchasing it from Amazon.com. Amazon will offer the fastest shipping price and best quality. Every Amazon purchase is 100% refundable through Amazon's A-Z policy. Price: 92.61 USD

Q: How do I change color of a particular word document using apache poi? Current output: Needed output: above are the snapshots of the .docx and below is the code sample code, I want to change the color of a after it is replaced by @. r.setColor("DC143C") doesn't work: for (XWPFParagraph p : docx.getParagraphs()) { List<XWPFRun> runs = p.getRuns(); if (runs != null) { for (XWPFRun r : runs) { String origText = r.getText(0); if (origText != null && origText.contains("a")) { origText = origText.replace("a", "@"); r.setText(origText, 0); } } } } A: If the need is to change the color of just one character then this character must be in its own run. This is because only runs can be styled. If you have a document containing text already then you must run through all already existing runs and possible split those runs into multiple ones. As the result each string part which shall be styled separately must be in its own run, also if it is only one character. Example: import java.io.*; import org.apache.poi.xwpf.usermodel.*; import java.awt.Desktop; import org.apache.poi.openxml4j.exceptions.InvalidFormatException; public class WordReadAndWrite { public static void main(String[] args) throws IOException, InvalidFormatException { XWPFDocument doc = new XWPFDocument(new FileInputStream("source.docx")); for (XWPFParagraph p : doc.getParagraphs()) { //go through all paragraphs int runNumber = 0; while (runNumber < p.getRuns().size()) { //go through all runs, we cannot use for each since we will possibly insert new runs XWPFRun r = p.getRuns().get(runNumber); String runText = r.getText(0); if (runText != null && runText.contains("a")) { //if we have a run with an "a" in it, then char[] runChars = runText.toCharArray(); StringBuffer sb = new StringBuffer(); for (int charNumber = 0; charNumber < runChars.length; charNumber++) { //go through all characters in that run if (runChars[charNumber] == 'a') { //if the charcter is an 'a' then r.setText(sb.toString(), 0); //set all characters, which are current buffered, as the text of the actual run r = p.insertNewRun(++runNumber); //insert new run for the '@' as the replacement for the 'a' r.setText("@", 0); r.setColor("DC143C"); r = p.insertNewRun(++runNumber); //insert new run for the next characters sb = new StringBuffer(); //empty buffer } else { sb.append(runChars[charNumber]); //buffer all characters which are not 'a's } } r.setText(sb.toString(), 0); //set all characters, which are current buffered, as the text of the actual run } runNumber++; } } doc.write(new FileOutputStream("result.docx")); doc.close(); System.out.println("Done"); Desktop.getDesktop().open(new File("result.docx")); } }

NOT RECOMMENDED FOR PUBLICATION File Name: 15a0200n.06 Nos. 13-5215/13-5217 FILED Mar 11, 2015 UNITED STATES COURT OF APPEALS DEBORAH S. HUNT, Clerk FOR THE SIXTH CIRCUIT UNITED STATES OF AMERICA, ) ) Plaintiff-Appellee, ) ) v. ) ) ON APPEAL FROM THE DWAYNE MICHAEL JOSEPH, JR., ) UNITED STATES DISTRICT ) COURT FOR THE WESTERN and ) DISTRICT OF KENTUCKY ) JAMES LAMONTE DUNBAR, ) ) Defendants-Appellants. ) ) OPINION BEFORE: MERRITT and WHITE, Circuit Judges; HOOD, District Judge HELENE N. WHITE, Circuit Judge. After a jury convicted them of conspiracy to distribute 50 grams or more of cocaine base, Appellants-Defendants Dwayne Joseph (Joseph) and James Dunbar (Dunbar) were sentenced to 120 months and 240 months in prison, respectively. They appeal, arguing that their sentences were improperly enhanced based on two facts not submitted to the jury and proven beyond a reasonable doubt: the quantity of drugs attributable to each of them and their past criminal convictions. For the reasons discussed below, we AFFIRM.  The Honorable Joseph M. Hood, United States District Judge for the Eastern District of Kentucky, sitting by designation. No. 13-5215 and 13-5217 U.S. v. Joseph and U.S. v. Dunbar FACTS In 2007, the Drug Enforcement Agency (DEA) received information that Donald and Demetrius Williams (Williams Brothers) were trafficking marijuana, cocaine, and crack cocaine in the Hopkinsville, Kentucky, area. The DEA’s investigation revealed Dunbar’s and Joseph’s involvement in the Williams Brothers’ operation. Agents made ten controlled purchases totaling 1.225 kilograms of cocaine base from drug dealers associated with the Williams Brothers, including two from Joseph. On June 9, 2009, a grand jury in Paducah, Kentucky, indicted Joseph, Dunbar, and nineteen other defendants on charges of conspiracy to distribute 50 grams or more of cocaine base in violation of 21 U.S.C. §§ 846 and 841(b)(1)(A). Dunbar and Joseph were arrested later that month and pleaded not guilty at their arraignments. On June 15, 2010, the Government filed an information and notice of intent to enhance both Dunbar’s and Joseph’s sentences pursuant to 21 U.S.C. § 851. Joseph’s enhancement was based on his May 9, 2001 felony drug conviction of trafficking in a controlled substance within 1000 yards of a school; Dunbar’s enhancement was based on his April 2, 2003 felony conviction for trafficking in controlled substances in the first degree and his February 8, 2006 felony conviction for trafficking in controlled substances within 1000 yards of a school. The trial, which involved only Joseph, Dunbar, and one other defendant, Rodney Moore (Moore),1 began in January 2011. The remaining defendants accepted plea agreements, many of which required them to testify against Joseph, Dunbar, and Moore. Demetrius Williams testified that he sold Joseph between 50 and 60 ounces (1.4175–1.700 kilograms) of crack cocaine, and Dunbar approximately 20 ounces (567 grams). Perry Rudd testified that he purchased 2.25 ounces of powder cocaine from Joseph. And, Ronnie Whaley testified that he sold Joseph a 1 Rodney Moore manufactured or “cooked” the crack cocaine. Demetrius Williams estimated that Moore cooked 20 kilos of crack over the course of the conspiracy. -2- No. 13-5215 and 13-5217 U.S. v. Joseph and U.S. v. Dunbar “brick,” or 36 ounces (1.020 kilograms), of powder cocaine. The jury found Dunbar and Joseph guilty of conspiracy to distribute 50 grams or more of cocaine base. Based on the evidence offered at trial, particularly the testimony of the co-defendants, the Presentence Investigation Report (PSR) attributed 20 ounces (567 grams) of crack cocaine to Dunbar, and 50 ounces (1.4175 kilograms) of crack cocaine and 36 ounces (1.02 kilograms) of powder cocaine to Joseph. The statute required a mandatory minimum term of 10 years. 21 U.S.C. § 841(b)(1). However, the 21 U.S.C. § 851 enhancements for Joseph’s and Dunbar’s prior convictions increased the minimum statutory sentence to 20 years’ imprisonment for Joseph and life imprisonment for Dunbar. Joseph’s base offense level, calculated pursuant to § 2D1.1(a)(5) of the United States Sentencing Commission Guidelines (Guidelines) was 34, with a criminal history category of III, resulting in a Guidelines range of 188 to 235 months’ imprisonment. However, the application of the enhanced penalties resulted in a mandatory minimum term of 240 months’ imprisonment as the advisory Guidelines sentence. Dunbar’s base offense level was 37, with a criminal history category of VI, resulting in a Guidelines range of 360 months’ to life imprisonment, with life imprisonment as the minimum enhanced advisory Guidelines sentence. Before his first sentencing hearing, Joseph filed objections to the 240-month statutory mandatory minimum, arguing that the Fair Sentencing Act of 2010 (FSA)—which increased the amount of cocaine base necessary to trigger the higher 21 U.S.C. § 841(b)(1) penalties—applied to his case and thus his mandatory minimum sentence should be calculated pursuant to § 841(b)(1)(B),2 not (b)(1)(A).3 He also objected to the amount of drugs attributed to him. 2 “Such person shall be sentenced to a term of imprisonment which may not be less than 5 years and not more than 40 years . . . If any person commits such a violation after a prior -3- No. 13-5215 and 13-5217 U.S. v. Joseph and U.S. v. Dunbar Dunbar argued that the FSA should apply to his case, objected to the amount of drugs for which he was held responsible, and asserted that the statutory mandatory minimum sentence of life imprisonment was a violation of the Eight Amendment. Joseph and Dunbar were sentenced to 240 months’ and life imprisonment, respectively. They appealed their sentences, arguing based on Dorsey v. United States, 132 S. Ct. 2321 (2012), that the more lenient penalties of the FSA apply to offenders whose crimes preceded the effective date of the Act, but who are sentenced after that date. This court vacated and remanded for resentencing. United States v. Moore, 495 F. App’x 680 (6th Cir. 2012). At Joseph’s resentencing, the parties agreed that his statutory minimum sentence was 10 years,4 and the Guidelines range, based on an offense level of 34 and a criminal history category of III, was 188 to 235 months’ imprisonment. Dunbar and the Government agreed that his statutory minimum sentence was 120 months’ imprisonment5 and his Guidelines range was 360 months’ to life imprisonment, based on an offense level of 37 and a criminal history category of VI. 6 Joseph and Dunbar requested and were given below-Guidelines sentences of 120 months’ and 240 months’ imprisonment, respectively. conviction for a felony drug offense has become final, such person shall be sentenced to a term of imprisonment which may not be less than 10 years and not more than life imprisonment . . .” 3 “Such person shall be sentenced to a term of imprisonment which may not be less than 10 years or more than life . . . If any person commits such a violation after a prior conviction for a felony drug offense has become final, such person shall be sentenced to a term of imprisonment which may not be less than 20 years and not more than life imprisonment . . . If any person commits a violation of this subparagraph . . . after two or more prior convictions for a felony drug offense have become final, such person shall be sentenced to a mandatory term of life imprisonment without release . . .” 4 Calculated pursuant to 21 U.S.C. § 841(b)(1)(B), the minimum takes into account Joseph’s one prior felony drug conviction. 5 Calculated pursuant to 21 U.S.C. § 841(b)(1)(B), the minimum takes into account Dunbar’s two prior felony drug convictions. 6 Dunbar was considered a career offender. -4- No. 13-5215 and 13-5217 U.S. v. Joseph and U.S. v. Dunbar DISCUSSION I. Attribution of Quantity of Drugs for Sentencing Purposes Joseph and Dunbar argue that despite being indicted and convicted by a jury for conspiring to distribute 50 grams or more of crack cocaine, at sentencing they were held responsible for 1.4175 kilograms and 567 grams of crack cocaine, respectively. This, they argue, is a violation of their Fifth and Sixth Amendment rights because it increased their potential sentences even though the quantities were not presented to a jury and proven beyond a reasonable doubt. The Government responds that sentencing enhancements based on the Guidelines, which is what is at issue here, can be determined by the sentencing court’s findings, so long as the enhanced sentence is still within the statutory range. This court “review[s] for clear error the district court’s factual findings on drug quantity attributable to a defendant for sentencing purposes.” United States v. Darwich, 337 F.3d 645, 663 (6th Cir. 2003) (citing United States v. Mahaffey, 53 F.3d 128, 131 (6th Cir.1995)). “A finding of fact will only be clearly erroneous when, although there may be some evidence to support the finding, ‘the reviewing court on the entire evidence is left with the definite and firm conviction that a mistake has been committed.’” United States v. Latouf, 132 F.3d 320, 331 (6th Cir. 1997) (quoting Anderson v. City of Bessemer, 470 U.S. 564, 573 (1985)). Dunbar and Joseph argue that we should review their constitutional claims de novo. Although Joseph challenged the constitutionality of the drug-quantity determination in his sentencing memorandum, the Government points out that Dunbar did not make a constitutional challenge in the district court, and argues for plain-error review. The result is the same regardless whether our review is de novo or for plain error. -5- No. 13-5215 and 13-5217 U.S. v. Joseph and U.S. v. Dunbar According to the Court, Any fact that, by law, increases the penalty for a crime is an ‘element’ that must be submitted to the jury and found beyond a reasonable doubt. Mandatory minimum sentences increase the penalty for a crime. It follows, then, that any fact that increases the mandatory minimum is an ‘element’ that must be submitted to the jury. Alleyne v. United States, 133 S. Ct. 2151, 2155 (2013) (internal citations omitted) (holding Defendant’s minimum sentence could not be increased for brandishing a firearm where, based on jury instructions, jury convicted Defendant of the lesser offense of carrying, rather than brandishing, the firearm). However, Joseph and Dunbar do not challenge their minimum statutory sentences, which correlated to the drug quantity actually found by the jury—50 grams or more—but, rather, challenge sentencing enhancements that increased the Guidelines range. “[T]he amount of drugs must be submitted to a jury and proved beyond a reasonable doubt when a drug amount calculation either threatens a penalty that would pierce the ceiling authorized by the statute, or threatens a penalty that would raise the floor authorized by the statute.” United States v. Hough, 276 F.3d 884, 890 (6th Cir. 2002) (internal citation omitted). Here, the court’s drug-quantity determinations did neither. Therefore, the district court was permitted to “rely on any competent evidence in the record,” id. at 891, to determine the drug quantity attributable to the Defendants for sentencing purposes “so long as [it] appreciate[d] that the guidelines are advisory, not binding,” United States v. Mickens, 453 F.3d 668, 673 (6th Cir. 2006). The amount of drugs attributed to each defendant was determined based on the testimony of co- defendants, which the district court found credible, as well as other evidence, including controlled transactions with government agents and confidential informants. Further, the district court demonstrated its appreciation of the non-binding nature of the Guidelines by imposing below-Guidelines sentences. -6- No. 13-5215 and 13-5217 U.S. v. Joseph and U.S. v. Dunbar II. Consideration of Past Convictions in Sentencing Joseph and Dunbar also argue that their Sixth Amendment rights were violated when the district court considered their prior criminal convictions to determine their sentencing enhancements based on 21 U.S.C. § 851 and the Guidelines. They maintain that this court should review this issue de novo because they are challenging the constitutionality of the sentence. The Government disagrees, arguing that Appellants forfeited this argument because neither previously objected to the § 851 notices and review should be for plain error. Again, the result is the same without regard to which standard of review we apply. The Government argues that Almendarez–Torres v. United States, 523 U.S. 224, 228–29 (1998)—which held that the Sixth Amendment does not require it to charge past convictions in the indictment and prove them to the jury beyond a reasonable doubt—is binding precedent. Dunbar and Joseph acknowledge Almendarez-Torres, but argue that it may soon be overturned. See, i.e., Joseph Br. at 18. Dunbar also questions Almendarez–Torres in light of Alleyne. Dunbar Br. at 24. This court has rejected similar arguments. [Appellant’s] contention that the holding in Almendarez–Torres has been whittled away, and that Almendarez–Torres has been overruled by implication, and is no longer good law, is unavailing. Although Almendarez–Torres may stand on shifting sands, the case presently remains good law and we must follow it until the Supreme Court expressly overrules it. United States v. Nagy, 760 F.3d 485, 488–89 (6th Cir. 2014) (internal quotation marks omitted) (citing United States v. Mack, 729 F.3d 594, 609 (6th Cir. 2013)); see also United States v. Pritchett, 749 F.3d 417, 434 (6th Cir. 2014) (“Alleyne did not disturb the holding in Almendarez– Torres”). -7- No. 13-5215 and 13-5217 U.S. v. Joseph and U.S. v. Dunbar Thus, the district court did not err in enhancing Joseph’s and Dunbar’s sentences based on a finding of past convictions without first submitting the factual question to a jury for determination beyond a reasonable doubt. CONCLUSION For these reasons, we AFFIRM the sentences imposed by the district court. -8- 

Transition metals potentiate paraquat toxicity. The involvement of transition metal ions in paraquat toxicity was studied in bacterial model system. We show that the addition of micromolar, or lower, concentrations of copper dramatically enhanced the rate of bacterial inactivation. In contrast, the addition of chelating agents totally eliminated the killing of E. coli. No inactivation was observed under anaerobic exposure to paraquat, both in the absence and presence of copper. However, in the presence of copper, the anaerobic addition of hydrogen peroxide resulted in complete restoration of inactivation as under aerobiosis. Paraquat either produces superoxide ions or directly reduces bound copper ions in a catalytic mode. The reduced cuprous complexes react with hydrogen peroxide to locally form hydroxyl radicals (OH.) which are probably responsible for the deleterious effects. This study indicates the involvement of a site-specific metal-mediated Haber-Weiss mechanism in paraquat toxicity. It is in agreement with earlier observations that copper unusually enhance biological damage induced by either superoxide or ascorbate.

Q: Error when returning character array from function, C++ I'm writing a sketch for the Arduino board and am using the following C++ code to do so. I'm trying to convert decimal numbers to binary by passing a decimal through the dec2bin function which is to return a character array that I will then print out. However, I'm getting the error: "Incompatible types of assignment of 'char' to 'char [0]'" at the function call to dec2bin and I'm receiving another error at the return inside of the dec2bin function that says: "Invalid conversion from 'char*' to 'char' [-fpermissive]" If anyone could please assist me with this it would be greatly appreciated. I need to use a character array here and not a string! Thank you! void loop() { // put your main code here, to run repeatedly: if (Serial.available() > 0){ char BinaryNum [0]; int Decimal = Serial.parseInt(); BinaryNum = dec2bin(Decimal); Serial.println (BinaryNum); } } char dec2bin (int Decimal){ int Remainder; // Remainder of Decimal%2 char Binary [0]; // Character array returned by dec2bin int x = 0; while (Decimal != 0 ){ Remainder = Decimal%2; Decimal = Decimal/2; Binary[x] = Remainder; Serial.println(Binary[x]); x+=1; } return Binary; } A: Danger Danger, you're returning a pointer to a local variable, Binary, that is on the stack, once the function returns it is out of scope and no longer valid. This will cause weirdness, it will work some times and then it will stop working, don't do it! See Can a local variable's memory be accessed outside its scope? You need to pass in the storage. eg. void loop() { // put your main code here, to run repeatedly: if (Serial.available() > 0){ char BinaryNum[33]; // allows for 32 bits plus null terminator int Decimal = Serial.parseInt(); dec2bin(Decimal, BinaryNum); Serial.println (BinaryNum); } } void dec2bin (int Decimal, char* Binary){ int Remainder; // Remainder of Decimal%2 int x = 0; while (Decimal != 0 ){ Remainder = Decimal%2; Decimal = Decimal/2; Binary[x] = Remainder; x+=1; } Binary[x] = '\0'; } On a "real" computer with an operating system there are many more memory management options than on a little arduino. You could allocation from the heap and use something fancy like an auto_ptr to manage it (see What is a smart pointer and when should I use one?). This just isn't possible on something as small as an arduino. You could however allocate it as a static. This isn't appropriate for a fancy computer because it is not re-entrant and thus not thread safe. Static allocation is done at program linking or startup and persistent across calls. void loop() { // put your main code here, to run repeatedly: if (Serial.available() > 0){ int Decimal = Serial.parseInt(); char* BinaryNum = dec2bin(Decimal); Serial.println (BinaryNum); } } void dec2bin (int Decimal) { static Binary[33]; // allows for 32 bits plus null terminator int Remainder; // Remainder of Decimal%2 int x = 0; while (Decimal != 0 ){ Remainder = Decimal%2; Decimal = Decimal/2; Binary[x] = Remainder; x+=1; } Binary[x] = '\0'; return Binary; }

Catch Up 9/6 1). With us having been gone for a week and Ryan, Ali, and Justin heading out across the pond for a week and a half, we wanted to spend as much time as possible with our friends before they left. The girls had so much fun playing together, running around (evidence of Emmie’s running is in her skinned knees!), and driving around (motor gang!). We had lunches and dinners with them, hung out in the burbs and in the city, and made a mess of Ali’s perfectly cleaned house. They and their extended family are such special people, and we are so glad to have them in our lives! Even if Emmie did had to be clingmonster when she first arrived at Ali’s parents’ house. Ah well, she warmed up ultimately. 2) Emmie has been undergoing a lot of really exciting mental development recently–I feel like she surprises me every day with a new action that I wasn’t expecting. Some examples: Trying to feed her play doggie by putting him facedown into her food (which she didn’t want to eat). Sending her crayons (which are triangular) down the slide/LEGO Elephant nose and saying “Wheeeeee.” Putting her little girl figure in the front seat and the horse in the back of her ice cream truck (which she can say) and playing with it. Saying more and more words without prompting — out of nowhere yesterday, she came up to me with her barn puzzle piece “baaaaaaahhhhnnn” and then when I pointed to the chicken piece she said “CHICK-en.” I was super surprised by this because those are probably our least mentioned/named pieces! Interacting with different stuffed animals in new ways. We can do “Head, Shoulders, Knees, and Toes”! Eating corn like a big girl! I should have taken a picture of her with the full cob from the day before (also better lighting then), but here is her working on a mini cobb. Lots of running. Generall fairly successful, but apparently not when she is around Ryan. See knees from above. 3) Lots of walking and going to Strides this week! I try to walk on the treadmill upstairs when Emmie naps and adjust so that I don’t do too much on days that I am also doing Strides. I missed these views while I was hurt! I’m back to doing up to 20 full pushups in one go. I took a few days off this past weekend just because I needed a break, but I’m back to doing my pushups at least. I need to add back in my dips and plank. But I’ve been feeling pretty tired, so I’m slothing a little. OH good news! I had Remicade last Friday and got full bloodwork done because I’m in a research study, and my labs looked GREAT! Whooooooooo 3 Comments Poor knees, Ouch! I love the girls in their matching cars, and Emmie watching RyRy getting ahead of her– RyRy looks like she’s ready for the Indy 500! A mini cob is just the right size for Ems, but where is the ketchup? Yay! Glad your blood work is good . It’s so great to have a little bestie for our littles. Squish loves the consistency of getting to see the same friends often. We’re planning a van camping/rock climbing weekend away. Fingers crossed it goes smoothly! My husband will be leading the group and setting things up so I will be on 3-year-old wrangling duty! She loves being outside and just with both of us in general on van trips so I think she’ll love it.Suchot recently posted…How to get cheap life insurance Aw I havent been able to do much blog reading lately and now I can’t believe how big she looks 🙁 Where did our babies go?! Sounds like you two had a lovely summer and she’s turning in to a full fledged toddler!Heather recently posted…A Heavy Joy Welcome to Suzlyfe ​ Suzlyfe is a Chicago-based healthy life, fitness, running, and food blog that aims to educate, connect, and inspire: educate readers in an accessible way about fitness, running, and wellness; connect readers to myself (Susie) and others with the same interests and passions; and inspire all to live a life beyond expectations.Email Me Though I am a RRCA Certified Running Coach and NASM Certified Personal Trainer with a chronic illness, a physician husband, and a lot of experience, and though I may seem like a know it all, please remember that all views expressed on my blog are mine along. Consult your physician before making any personal changes to your mental or physical health and wellness programs.

Applied Forensic Sciences Department The Applied Forensic Sciences Department includes an Undergraduate Bachelor of Sciences Degree program as well as a Graduate Certificate program and Master of Science in Anthropology program which have a primary focus on Forensic and Biological Anthropology. Both the undergraduate and graduate programs present state-of-the-art techniques in forensic sciences and forensic biological anthropology in the classroom, and provide a variety of practical, hands-on opportunities both in the field and in the laboratory. Undergraduate The development of the undergraduate Applied Forensic Sciences Program represents the first truly multidisciplinary major at Mercyhurst that incorporates the major natural sciences (biology, chemistry, physics) and mathematics within the core curriculum. The program includes three concentrations: High end statistical analysis and interpretation of the biological significance of those remains Graduate courses prepare students for the application of Forensic Anthropology to real life cases. Students play a major role in processing real forensic cases under the direction of department professors Dr. Symes, Dr. Dirkmaat, and Dr. Garvin. Graduate students are involved in all phases of the cases—from initial recovery and documentation in the field to processing, photographing and analyzing the remains in the laboratory.

Recently, besides a monochrome machine including a scanning optical system employing a single light source, a tandem color machine is also proposed. In the tandem color machine, for the purpose of realizing an increase of speed of scanning on the surfaces of photoconductive drums, plural light sources are provided in one laser unit. A method of increasing the number of laser beams for performing scanning once (a multi-beam method) is used. In the tandem color machine, a large-capacity cassette feeder (LCF) that can store a large volume of sheets is provided. The large-capacity cassette feeder feeds sheets to a sheet conveying path as required. If sheets are stacked in left and right independent cassettes in the large-capacity cassette feeder, in order to designate a stacking range of the sheets or in order to prevent the stacked sheets from extending beyond a predetermined stacking range, shutters are provided for each of the cassettes. However, power is required for the opening and closing of the shutters. Therefore, in the past, the number of electronic components such as solenoids used for the opening and closing of the shutters increases. It is possible to reduce the number of shutters in order to hold down the increase in the electronic components. However, if the number of shutters is reduced, the sheets extend beyond the stacking range.

It was a tie party in the fourth week of the 2016 European League Championship Series. For the first time in LCS history, all the matchups ended in a draw. Teams with varying degrees of success this season have scored a point each, and that includes Team ROCCAT and the Unicorns of Love, two teams with different fortunes early this season. Pierre "Steeelback" Medjaldi once wore UoL's colors, and following a stint in the North American Challenger Series, he was determined to return to the European LCS at any cost. "I tried out for some teams, and it went really well with the Unicorns, so I went there," he recalled. Editor's Picks East vs. West: Street Fighter V at CEO 2016 Best/Worst - The 2016 Summer LCS so far The 2016 top 10 esports draft 2 Related But four weeks into the LCS spring split, visa issues plagued the team as Danil "Diamondprox" Reshetnikov, the squad's jungler, had to leave the team. Diamondprox had laid the foundations for UoL's early surge in the 2016 spring split, and morale was at an all-time high. "[Diamondprox] was really good in the jungle. He knows almost everything [there is to know]. He explained everything to us, always," noted Steeelback. The ensuing situation in the jungle -- a revolving door of sorts -- caused motivation levels to drop despite the AD carry's efforts to revitalize the squad. "I tried to stay in the team," he said. "I tried to ask everyone to pool more effort, but we couldn't make it work. [UoL and I] then decided to part ways because I wasn't happy about the result. I don't think anyone was happy, but I didn't think that I could reach the World Championship with them." His decision to join Team ROCCAT, a squad that ranked ninth in the 2016 LCS spring split, may have seemed illogical as some would perceive such a move as a downgrade based on the difference in rankings between it and the Unicorns of Love (sixth in the spring split). But Steeelback specifically chose to join the organization, despite receiving offers from other teams in the league. "I really liked the players that remained -- Airwaks and Betsy. I thought they were really good," he pointed out. In a way, Team ROCCAT and the Unicorns of Love had a lot in common, especially when it came to frequent swaps within the roster. But he wanted to build a powerhouse from scratch and settle down, and ROCCAT presented itself as his best option. "I changed teams often, and I would like to go to a squad and build something as YellOwStaR did in Fnatic, or stay in a squad and try to shoot for the top," he justified. "It's really hard to do, and you need to be a captain. That's what I'm trying to learn." But, unlike the Unicorns of Love, Team ROCCAT stands within playoff contention -- and it has more to do with ROCCAT's recent acquisitions, and its ability to communicate as a team. Before week four, ROCCAT was one of the only two teams to secure a tie against G2 Esports, a squad that looks nearly unstoppable since the acquisition of Alfonso "Mithy" Aguirre Rodriguez and Jesper "Zven" Svenningsen. According to Steeelback, even though he and Airwaks contribute the most to the team's calls, he and his teammates all contribute to the overall shot-calling. That includes Raise, whose contribution contrasts with the minimalistic one of his shy top laner, Parang. "Raise talks a lot," he added. "He isn't afraid to talk. He shot-calls even though his English isn't that good at the moment." But so far, the squad's shot-calling has been hit-and-miss, and the primary issue seems to be its tendency to overcommit to calls. "For now, we throw games, and we struggle, but since we went 0-4 [in Week 3], I felt that we improved a whole lot," Steeelback said. "I felt we took bad fights. We didn't know when to back away. We always wanted, even when ahead, to be even farther ahead. So we ended up going too far and throwing the game." The squad's head coach, Fabian "GrabbZ" Lohmann, is assisting his players in their effort to prevent themselves from overcommitting and to take a more patient approach: warding, farming and controlling the map. He also has helped them refine their in-game communication. Steeelback noted, as an example, "After the game, he goes to a player and tells him, 'You should have told them that you were recalling,' or, 'You should have told them that we were team-fighting.'" Practice yields results, but it is a process. The 1-1 record against the Unicorns of Love stands as an example. A botched team fight in the first game allowed UoL to secure a landslide victory, and the AD carry indicated, "We took a fight when Airwaks was really low [health], but we didn't notice. So we still fought, and we all died." "I'd like us to stay the course," the French AD carry concluded. "Even if we lose some games, that we don't feel down, and that we keep it up because, in the end, it's the playoffs that matter. We want to be in the top six."

1. Introduction {#sec1-pharmaceutics-12-00422} =============== Electroporation is a physical method for exogenous molecule delivery through the plasma membrane that is used to increase the plasma membrane permeability by applying short (ns--ms) but strong electric pulses \[[@B1-pharmaceutics-12-00422]\]. The permeability is increased due to the electric-field-induced transmembrane voltage, resulting in the formation of transient hydrophilic pores in the cell membrane \[[@B2-pharmaceutics-12-00422]\]. Pore formation starts when transmembrane voltage exceeds an electroporation threshold ranging between 0.2 and 1 V \[[@B3-pharmaceutics-12-00422],[@B4-pharmaceutics-12-00422]\]. During the prolonged application of the over-threshold electric field, the electropore density and/or size increases \[[@B5-pharmaceutics-12-00422]\]. However, when the external electric field is switched off, the electric-field-induced transmembrane potential dissipates, initiating the process of pore resealing \[[@B6-pharmaceutics-12-00422]\]. The presence of electropores---either reversible or irreversible---enables bidirectional transport across the cell membrane \[[@B7-pharmaceutics-12-00422]\]. Such increased permeability can be used for the effective delivery of small charged molecules (e.g., fluorescent dyes \[[@B8-pharmaceutics-12-00422]\] or membrane-impermeable chemotherapeutic drugs \[[@B9-pharmaceutics-12-00422]\]) to the cells. The combined application of electroporation and chemotherapeutic agents is termed electrochemotherapy and is a successful method with clinically proven efficiency in treating different tumours \[[@B10-pharmaceutics-12-00422]\]. In the recent years, intracellular calcium ion (Ca^2+^) delivery via electroporation has been suggested as an alternative to electrochemotherapy with bleomycin or cisplatin \[[@B11-pharmaceutics-12-00422]\]. A recent clinical trial has shown that calcium electroporation has comparable efficiency as electrochemotherapy and is feasible and effective in patients with cutaneous metastases \[[@B12-pharmaceutics-12-00422]\]. Ca^2+^ ions are universal signal mediators that regulate many cellular functions \[[@B13-pharmaceutics-12-00422]\]. At physiological conditions, the concentration of Ca^2+^ ions in the cytoplasm ranges between 10^−8^--10^−7^ M and between 10^−3^--10^−2^ M in the extracellular environment. Calcium homeostasis is maintained by the interplay between multiple types of energy-dependent pumps and passive directional transporters located in plasma membranes and organelles \[[@B14-pharmaceutics-12-00422]\]. Calcium ion distribution between extra- and intra-cellular compartments plays a crucial role in cellular response to various external stress conditions, and they are also involved in certain types of cell death, for instance, intracellular Ca^2+^ overload initiated necrotic and apoptotic processes \[[@B11-pharmaceutics-12-00422],[@B15-pharmaceutics-12-00422]\]. Calcium is also known for its role in the resealing of an injured membrane \[[@B16-pharmaceutics-12-00422]\]. There are several ways that Ca^2+^ ions are involved in membrane resealing, further delineating the importance of maintaining membrane integrity \[[@B17-pharmaceutics-12-00422]\]. Therefore, in this study, we aimed to investigate the impact of different CaCl~2~ concentrations on the electrotransfer of small charged molecules. For this purpose, Chinese hamster ovary (CHO) cells were electroporated in media with different CaCl~2~ concentrations using either microsecond or nanosecond electroporation. Microsecond electroporation is the "classic" mode of electroporation and utilizes electric pulses of µs--ms duration. In contrast, the nanosecond duration pulses have their duration below 1 µs, and much higher pulse strengths. Due to the short duration, they can generate transmembrane potential on intracellular membranes instead or in addition to the plasma membrane \[[@B18-pharmaceutics-12-00422],[@B19-pharmaceutics-12-00422]\] and are lucrative for medical applications because, unlike microsecond duration pulses, they do not induce muscle twitching \[[@B20-pharmaceutics-12-00422]\]. Propidium iodide (PI), YO-PRO-1 and ethidium bromide (EtBr) were used as fluorescent probes to investigate the uptake of small charged molecules after electroporation. The obtained results show that CaCl~2~ presence in the electroporation media prior electric field application impedes the uptake of small charged fluorescent molecules through the plasma membrane. 2. Materials and Methods {#sec2-pharmaceutics-12-00422} ======================== 2.1. Cell Line {#sec2dot1-pharmaceutics-12-00422} -------------- Chinese Hamster Ovary (CHO) cells (European Collection of Authenticated Cell Cultures, 85050302) were used for in vitro experiments. CHO cells were cultivated in Dulbecco's Modified Eagle Medium (DMEM) (Sigma, Darmnstadt, Germany) supplemented with 10% Foetal Bovine Serum (FBS) (Sigma), 1% [l]{.smallcaps}-glutamine (Sigma) and 1% penicillin-streptomycin solution (Sigma). The cells were grown in monolayers in 10 cm Petri dishes (Techno Plastic Products (TPP) (Trasadingen, Switzerland) and incubated at 37 °C in 5% CO~2~ atmosphere. To maintain the culture, cells were passed every 2--3 days and 24 h before the experiments. 2.2. Cell Electroporation {#sec2dot2-pharmaceutics-12-00422} ------------------------- After harvesting, cells were washed and diluted in electroporation medium (10 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) (Lonza, Basel, Switzerland), 250 mM sucrose (Sigma), 1 mM MgCl~2~ (Sigma) in sterile water) that was supplemented with different CaCl~2~ (Sigma) concentrations (0, 0.0001, 0.001, 0.01, 0.1, 0.25, 0.5, and 1 mM). The HEPES buffer with 0 mM CaCl~2~ was used as the experimental control. Cell suspensions were prepared at a concentration of 1.8 × 10^6^ cells/mL, using buffers with different CaCl~2~ concentrations. For each experimental point, 6.5 × 10^4^ cells (36 μL) were used. Cuvette electrodes with a 1-mm gap between electrodes were used for cell electroporation. For small molecule electrotransfer experiments, the cell solution was supplemented with 4 μL propidium iodide (PI) (Sigma, Darmnstadt, Germany) at the final concentration of 40 µM, 4 µL ethidium bromide (EtBr) (Carl Roth, Karlsruhe, Germany) at the final concentration of 40 µM or 4 µL YO-PRO-1 (Thermo Fisher Scientific, Dublin, Ireland) at the final concentration of 4 µM. For the experiments to test the medium conductivity effect on the efficiency of PI electrotransfer CaCl~2~ was replaced by MgCl~2~. For the experiments investigating pore resealing dynamics, PI was present in the electroporation medium during electroporation only for positive controls and was introduced into the solution at 15, 30, 60, 120, 360, 480 or 600 s after electroporation. As the PI can only enter the cells with compromised plasma membrane integrity, the percentage of PI positive cells in these experiments reflect the percentage of cells that did not reseal after electroporation. For micro-electroporation, CHO cells were electroporated using 1 square HV pulse (800--1800 V/cm pulse strength, 100 μs pulse duration) using BTX T820 electroporator (Harvard Apparatus, Holliston, MA, USA) For nano-electroporation, cells were electroporated using 10 square HV pulses (10,000--18,000 V/cm pulse strength, 200 ns pulse duration, 1 Hz repetition frequency) using high voltage pulse generator (VGTU, Vilnius, Lithuania). After 15 min incubation at 37 °C in 5% CO~2~ atmosphere, cell permeabilization was evaluated using flow cytometry (BD Accuri C6, BD Biosciences, Franklin Lakes, NJ, USA). A total of 10^4^ cells per sample at 66 µL/min flow rate and 22 µm core size were collected. The cells were excited with 488 nm laser and fluorescence was collected using 585/40- and 533/30-nm bandpass filters. The flow cytometry gating strategy to collect the cells after various conditions and for all three molecules used are depicted in [Figure 1](#pharmaceutics-12-00422-f001){ref-type="fig"}. 2.3. Visualization of Electroporation {#sec2dot3-pharmaceutics-12-00422} ------------------------------------- For the visualization of PI electrotransfer experiments, 22 × 22 mm glass cover slips (Carl Roth, Karlsruhe, Germany) were immersed into 70% ethanol for 15 min. Then, the coverslips were removed from the ethanol and placed into the 4-cm Petri dishes and airdried for 15 min. Then, 40 µL of cell suspension (1.8 million per mL) was placed on the middle of the coverslip in the Petri dish. After an additional 5-min incubation (for the cells to settle down on the surface) and a gentle 2-mL addition of DMEM (supplemented with 10% FBS, 1% [l]{.smallcaps}-glutamine and 1% penicillin-streptomycin solution), the Petri dishes with cells were placed in the incubator (37 °C and 5% of CO~2~). After 5 h of incubation, the coverslips with cells attached (5 h incubation) was taken from the petri dishes and placed on the laboratory made electrodes (copper foil mounted on the objective glass) with a 2-mm gap. Electroporation medium (HEPES buffer supplemented with different concentrations of CaCl~2~ (0, 0.25, 0.5, 1 mM) and supplemented with PI (40 µM final concentration) was added between the gap of electrodes prior to the coverslip being mounted on the top of the electrodes. The cells were electroporated using 1 HV pulse (1400 V/cm or 1800 V/cm pulse strength, 100 μs pulse duration) delivered by a BTX T820 pulse generator. A Motic AE31 fluorescent microscope mounted with a MoticamPro 285B camera was used for cell imaging. For PI fluorescence imaging, a filter cube (D560/40X excitation, dichroic 595DCLP mirror, D630/60 emission) was used. Motic Images Advanced 3.2 software was used to obtain the images. At all conditions, phase contrast images were taken prior to the application of electric fields. For the fluorescence imaging time lapse was switched on before electroporation. Single HV pulse was delivered at time '0 s'. Then, additional fluorescent images were taken at every second for 300 s. Open source image processing software ImageJ (Version 1.52p, National Institute of Health, Bethesda, MD, USA) was used to calculate corrected total cell fluorescence (CTCF) \[[@B21-pharmaceutics-12-00422]\]. The phase contrast image was used to determine the area of the cell, in which the changes of the propidium iodide fluorescence were measured over time. CTCF was calculated by multiplying the cell area (the area in phase contrast image delineated by single cell) with its average fluorescence. The changes in CTCF allowed to monitor the dynamics of PI entry. The CTCF mean values in a corresponding figure were made from the observation of at least 20 different cell images. 2.4. Model for Computation {#sec2dot4-pharmaceutics-12-00422} -------------------------- The model is mathematically defined in Equations (1), (2) and (3) \[[@B22-pharmaceutics-12-00422]\]. $$\Delta\Phi_{m}\left( t \right) = fERcos\theta~\left\lbrack {1 - e^{\lbrack{- \frac{t}{\tau}}\rbrack}} \right\rbrack$$ where Δ*Φ* is transmembrane voltage, *f* is the shape factor, *R* is the cell radius, *θ* is the angle measured from the centre of the cell with respect to the direction of the field, *t* is the time elapsed since the onset of the field, and *τ* is the time constant of membrane charging. $$f = \frac{3\lambda_{ο}\left\lbrack {3dR^{2}\lambda_{i} + \left\lbrack {3d^{2}R - d^{3}} \right\rbrack\left\lbrack {\lambda_{m} - \lambda_{i}} \right\rbrack} \right\rbrack}{2R^{3}\left( {\lambda_{m} + 2\lambda_{ο}} \right)\left( {\lambda_{m} + \frac{1}{2}\lambda_{i}} \right) - 2{(R - d)}^{3}\left( {\lambda_{ο} - \lambda_{m}} \right)\left( {\lambda_{i} - \lambda_{m}} \right)}$$ where *λ~o~*, *λ~m~* and *λ~i~* are the conductivities of the external, membrane and cytoplasm, respectively, *R* is the radius of the cell and *d* is the thickness of the membrane. $$\tau = \frac{Rc_{m}}{\frac{2\lambda_{ο}\lambda_{i}}{2\lambda_{ο} + \lambda_{i}} + \frac{R}{d}\lambda_{m}}$$ where *τ* is the membrane charging time, *R* is the radius of the cell, *C~m~* is the capacitance of the membrane, *λ~o~*, *λ~m~* and *λ~i~* are the conductivities of the external, membrane and cytoplasm, respectively, and *d* is the thickness of the membrane. In all the situations, the transmembrane potential change at cell poles (cos(0°) = 1) was calculated. The thickness of the membrane d was 3 × 10^−9^ m, as described in \[[@B23-pharmaceutics-12-00422]\], the cytoplasm conductivity *λ~i~* was 0.5 S/m, as described in \[[@B24-pharmaceutics-12-00422]\], membrane conductivity *λ~m~* was 3 × 10^−7^ S/m as described in \[[@B22-pharmaceutics-12-00422]\] and membrane capacitance *C~m~* was 10^−2^·F·m^−2^ as described in \[[@B22-pharmaceutics-12-00422]\]. The average cell radius *R* was experimentally evaluated by calculating the radii of \>100 cells in microscopy pictures using open-source image processing program ImageJ. The *R* value determined this way was 9.7 µm. The specific conductivity values of the extracellular media with different CaCl~2~ concentrations were measured and the results are presented in [Table 1](#pharmaceutics-12-00422-t001){ref-type="table"}. 2.5. MTT Assay {#sec2dot5-pharmaceutics-12-00422} -------------- 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) (Carl Roth, Karlsruhe, Germany) assay was performed to evaluate long term cell response after cell electroporation in the presence of CaCl~2~. MTT is used as a colorimetric cell viability assay, which relates the enzymatic activity of the cell with its viability. The colorimetric assay is based on ability of NAD(P)H-dependent cellular oxidoreductase enzymes to reduce the yellow tetrazolium dye MTT to its insoluble purple formazan. After cell treatment with electric pulses in electroporation medium, supplemented with different CaCl~2~ concentrations (0, 0.25, 0.5, 1 mM), 9000 cells in 200 µL of growing media were plated in each well of 96-well microplates (Plastibrand; Wertheim, Germany) and incubated at 37 °C in 5% CO~2~ atmosphere. After 24 h of incubation, 20 µL of growing medium was removed from the wells and 20 µL of MTT salt at concentration of 0.5 mg/mL was added and incubated for additional 2 h. Afterwards, the medium was taken out from the wells and the wells were washed twice with 100 µL of Phosphate-Buffered Saline (PBS) (Carl Roth, Karlsruhe, Germany) Formazan formed in the cells was dissolved by using 100 µL of DMSO (Sigma). A multiwell scanning spectrophotometer (spectro star nano BMG Labtech, Ortenberg, Germany) was used to measure the absorbance of the samples in microplate. Optical density was estimated at 570 nm. All experimental points were normalised to the control (untreated cells). 2.6. Flow Cytometry Assay (FCA) {#sec2dot6-pharmaceutics-12-00422} ------------------------------- The flow cytometer (BD Accuri C6, BD Biosciences, Franklin Lakes, NJ, USA) modality to determine the number of cells in a specific volume was employed in the study to estimate exact number of cells in a specific sample at 15 min time points after the cell treatment with electric pulses in electroporation medium, supplemented with different CaCl~2~ concentrations. A flow cytometer value of obtained cell speed was obtained when 10,000 cells from the sample were measured. A mean of measured cells in control samples was normalised to a 100%. Other samples were normalised according to the control (untreated cells). 2.7. Statistical Analysis {#sec2dot7-pharmaceutics-12-00422} ------------------------- Experiments for each individual experimental point were repeated 3 times on at least two separate days. The results are presented as mean ± standard mean error (SEM). For visualization, 20 cells per field of view were used to calculate the average CTCF. To test significance, one-way ANOVA with a Bonferroni post-hoc test was used for all experiments. The assumption for normality distribution was verified with Shapiro--Wilk normality test by setting the p value for rejection to 0.05. The statistical analysis was performed using Sigma Plot 12.5 software. The percentages were transformed using logit transformation before the ANOVA analysis. 3. Results {#sec3-pharmaceutics-12-00422} ========== The first set of experiments was designed to evaluate whether the addition of CaCl~2~ to the electroporation medium can have any influence on the PI electrotransfer efficiency after microsecond range electroporation. The dependence of PI positive cell percentage on the CaCl~2~ concentration in the electroporation medium is summarized in [Figure 2](#pharmaceutics-12-00422-f002){ref-type="fig"}A, and the total fluorescence of PI positive cells is shown in [Figure 2](#pharmaceutics-12-00422-f002){ref-type="fig"}B. These results show that CaCl~2~ reduce the efficiency of PI electrotransfer. Even the lowest CaCl~2~ concentration used (0.25 mM) has significantly reduced both the amount of PI positive cells and their total fluorescence. For example, using 1600 V/cm electric pulse strength in a medium without added calcium, PI positive cell percentage is around 69%. However, 1600 V/cm electric pulse in the electroporation medium with 0.25 mM CaCl~2~ yields only \~28% of PI positive cells. The increase in CaCl~2~ concentration from 0.25 to 0.5 and 1 mM did not further decrease the amount of PI positive cells or their total fluorescence. The total cell fluorescence depicted in [Figure 2](#pharmaceutics-12-00422-f002){ref-type="fig"}B shows similar trends. Irrespectively of the electric pulse strength, the total fluorescence of PI positive cells that were electroporated with CaCl~2~ (0.25, 0.5, 1 mM) is \~2 times lower than that of the cells electroporated in the control medium (0 mM CaCl~2~). It should also be noted that, after increasing the electric pulse strength from 1600 to 1800 V/cm, the percentage of PI positive cells increases more sharply than the total fluorescence of the cells. Our results indicate that PI entry into the cells electroporated with microsecond electroporation parameters is significantly diminished when CaCl~2~ is added to the electroporation medium prior to the application of electric field. The next set of experiments was performed in order to determine whether the same effect is visible when nanosecond electroporation was used. The obtained results are presented in [Figure 3](#pharmaceutics-12-00422-f003){ref-type="fig"} (A---percentage of PI positive cells, B---total fluorescence of PI positive cells). The effect of the CaCl~2~ concentration on the PI electrotransfer efficiency after nanosecond electroporation can be most clearly seen at 14,000--15,000 V/cm of electric field strength. At these conditions, there are no significant differences in PI positive cell percentage when the cells were electroporated in the media with 0.25 and 0.5 mM CaCl~2~ concentrations. Cells electroporated in either of these media resulted in significantly lower amount of PI positive cells (\~25%) when comparing to the cells electroporated in control medium (0 mM CaCl~2~, \~77%). A further increase in CaCl~2~ concentration to 1 mM leads to the percentage of PI positive cells (\~45%) that is significantly increased from the one observed with 0.25 and 0.5 mM CaCl~2~ concentrations, but significantly lower than the one observed in the control (0 mM CaCl~2~). Therefore, it can be summarized that CaCl~2~ reduces the efficiency of PI electrotransfer using both microsecond ([Figure 2](#pharmaceutics-12-00422-f002){ref-type="fig"}) and nanosecond ([Figure 3](#pharmaceutics-12-00422-f003){ref-type="fig"}) pulses. However, using nanosecond electric pulses, this reduction is lower when a higher concentration of calcium is used, showing the likelihood of a secondary effect of CaCl~2~ on nanosecond electroporation. Interestingly, the effect of CaCl~2~ is the same with all CaCl~2~ concentrations used for microsecond duration pulses and the same with 0.25- and 0.5-mM CaCl~2~ concentrations for nanosecond duration pulses. This shows that the calcium induced reduction in PI electrotransfer efficiency might be based on external CaCl~2~ concentration threshold that is below 0.25 mM. Alternatively, this effect might be dependent on the concentration but has already reached a plateau at 0.25 mM. To elucidate this, we electroporated the cells with 1 × 1400 V/cm strength and 100 µs duration electric pulse or 10 × 1.4 kV/cm strength and 200 ns electric pulses repeated at 1 Hz frequency with an expanded range of CaCl~2~ concentrations (0.0001--1.0 mM). The results of these experiments are presented in [Figure 4](#pharmaceutics-12-00422-f004){ref-type="fig"}. We see a gradual decline in the number of PI positive cells ([Figure 4](#pharmaceutics-12-00422-f004){ref-type="fig"}A) and total fluorescence ([Figure 4](#pharmaceutics-12-00422-f004){ref-type="fig"}B) with microsecond-duration electric pulses as they were well approximated by the exponential function (*R*^2^ = 0.95 and *R*^2^ = 0.86, respectively). However, the approximations failed for the results of PI electrotransfer that were obtained using nanosecond-duration electric pulses ([Figure 4](#pharmaceutics-12-00422-f004){ref-type="fig"}C,D). This indicates gradual continuous PI positive cell dependence on CaCl~2~ concentration for microsecond electroporation and a concentration threshold effect for nanosecond electroporation. The threshold for nanosecond electroporation was determined to be between 0.1 and 0.25 mM CaCl~2~ concentration, as indicated by the results of PI positive cells ([Figure 4](#pharmaceutics-12-00422-f004){ref-type="fig"}C) and total cell fluorescence ([Figure 4](#pharmaceutics-12-00422-f004){ref-type="fig"}D). The next step in our investigations was to assess if CaCl~2~ induced reduction in electrotransfer efficiency is caused by a specific feature of propidium iodide or is it applicable to electrotransfer of other small charged molecules as well. To assess this, we electroporated the cells with 1 × 1400 V/cm strength and a 100-µs duration electric pulse or 10 × 1.4 kV/cm strength and 200-ns electric pulses repeated at 1 Hz of frequency electric pulses in media containing 0, 0.25 or 1 mM CaCl~2~ concentration in the presence of three different small charged molecules: propidium iodide (molecular weight 668.36 g/mol, formal charge +2), YO-PRO-1 (molecular weight 629.32, formal charge +2) and ethidium bromide (EtBr, molecular weight 394.29 g/mol, formal charge +1). The results of these experiments are presented in [Figure 5](#pharmaceutics-12-00422-f005){ref-type="fig"}A (microsecond pulses) and [Figure 5](#pharmaceutics-12-00422-f005){ref-type="fig"}B (nanosecond pulses). It can be seen that, after microsecond duration electric pulses, the electrotransfer efficiency ([Figure 5](#pharmaceutics-12-00422-f005){ref-type="fig"}A) decreases for all three molecules tested. The highest drop in both the electrotransfer efficiency is observed with EtBr. However, a different situation is observed with nanosecond electric pulses ([Figure 5](#pharmaceutics-12-00422-f005){ref-type="fig"}B). It can be seen that while the decrease in electrotransfer efficiency ([Figure 5](#pharmaceutics-12-00422-f005){ref-type="fig"}B) is observed with YO-PRO-1 and PI, the electrotransfer efficiency increases when EtBr is used. In order to obtain a deeper understanding of the phenomenon of the CaCl~2~-mediated inhibition of PI electrotransfer, we visualized the dynamics of PI electrotransfer into the cells after microsecond pulse treatment using electroporation media with different CaCl~2~ concentrations (0, 0.25, 0.5, 1 mM). The results of PI electrotransfer dynamics after electroporation are shown in [Figure 6](#pharmaceutics-12-00422-f006){ref-type="fig"}. These results show that PI electrotransfer into the cells with CaCl~2~ present in electroporation media is disturbed from the first seconds after electroporation when comparing to cells without CaCl~2~ using both 1400 ([Figure 6](#pharmaceutics-12-00422-f006){ref-type="fig"}A,C) and 1800 V/cm ([Figure 6](#pharmaceutics-12-00422-f006){ref-type="fig"}B,D) electric field strengths. It can be seen that PI electrotransfer is significantly lower with all electric parameters and all CaCl~2~ concentrations tested in comparison to PI electrotransfer to cells in media without CaCl~2~. However, using a 1800-V/cm pulse strength, the results show that the medium with 0.25 mM CaCl~2~ yields a significantly higher PI entry in comparison to media with 0.5 or 1 mM CaCl~2~. The representative pictures of cells electroporated at 1400 ([Figure 6](#pharmaceutics-12-00422-f006){ref-type="fig"}C) and 1800 V/cm ([Figure 6](#pharmaceutics-12-00422-f006){ref-type="fig"}D) in the media with different CaCl~2~ concentrations visually illustrate the data presented in [Figure 6](#pharmaceutics-12-00422-f006){ref-type="fig"}A,B, providing visual proof that the fluorescence of the cells decreases with increasing CaCl~2~ concentration. One of the possible ways in which the calcium ions could exert its effect on the electroporation is the increased rate of membrane resealing, leading to diminished molecular transport across the membrane. To test this theory, we decided to investigate the dependence of pore resealing dynamics on the presence of extracellular CaCl~2~ concentration by monitoring the percentage of PI positive cells when PI is added after the application of electric pulses. The results of these experiments are presented in [Figure 7](#pharmaceutics-12-00422-f007){ref-type="fig"}. A single HV pulse with 1400 V/cm ([Figure 7](#pharmaceutics-12-00422-f007){ref-type="fig"}A) or 2800 V/cm ([Figure 7](#pharmaceutics-12-00422-f007){ref-type="fig"}B) strength and 100 µs duration was used. The results after electroporation with 1400 V/cm strength electric pulses showed that PI transfer to the cells is reduced immediately after application of electric fields in the presence of extracellular Ca^2+^ ions. Therefore, it can be assumed that these conditions either cause immediate membrane resealing (pore closure and/or membrane repair) or impede the pore formation. However, this is not the case when electric pulses with double (2800 V/cm) electric field strength are used. In these conditions, a clear dependence of the duration of the membrane resealing on the concentration of extracellular Ca^2+^ is observed. Indeed, it can be seen that 0.25 mM of extracellular CaCl~2~ was enough to significantly diminish the membrane resealing duration. However, it is interesting to note that while we see the calcium-induced decrease in PI electrotransfer, there is a significant difference in the trend of PI electrotransfer between the cells electroporated with micro- and nano-second duration pulses. After a certain threshold in CaCl~2~ concentration, the PI electrotransfer efficiency increases again using nanosecond duration electric pulses, while no such effect is observed using microsecond duration pulses ([Figure 2](#pharmaceutics-12-00422-f002){ref-type="fig"} and [Figure 3](#pharmaceutics-12-00422-f003){ref-type="fig"}). For a better understanding of this inversion, we have utilized the widely accepted model of transmembrane voltage induction by electric field \[[@B22-pharmaceutics-12-00422]\]. The model neglects possible cell deformation during prolonged electric field application \[[@B24-pharmaceutics-12-00422],[@B25-pharmaceutics-12-00422]\]. The results of the modelling ([Figure 8](#pharmaceutics-12-00422-f008){ref-type="fig"}) show that the specific conductivity of the extracellular medium does not significantly change the generated transmembrane potential when microsecond duration pulses were used. However, a dramatic transmembrane potential change is observed when the simulations were performed using nanosecond duration pulses. The modelling results showing the transmembrane potential distribution on the whole surface of the cell are presented in [Figure 8](#pharmaceutics-12-00422-f008){ref-type="fig"}A and the peak transmembrane potential at the electrode-facing poles (cos*θ* = 0) is presented in [Figure 8](#pharmaceutics-12-00422-f008){ref-type="fig"}B (microsecond duration pulses) and [Figure 8](#pharmaceutics-12-00422-f008){ref-type="fig"}C (nanosecond duration pulses). It is clearly observed that, using nanosecond duration pulses, the peak of transmembrane potential increases approximately twice in all parameters used when extracellular the CaCl~2~ concentration changes from 0 to 1 mM. Moreover, one can suggest that the observed effects are related with changes in medium conductivity. To test this possibility, we performed corresponding experiments with medium conductivities ranging from 0.016--0.16 S/m, where CaCl~2~ in the medium was replaced by MgCl~2~. The results showed that medium conductivity, in this range, has no effect on PI electrotransfer efficiency [Figure 9](#pharmaceutics-12-00422-f009){ref-type="fig"}. It is also possible that Ca^2+^ can induce cell death in a very short time range after cell electroporation, and the observed decrease in PI positive cells could be because of the disintegration of those cells. However, cell count by flow cytometry assay (FCA), as described in \[[@B26-pharmaceutics-12-00422]\], shows no cell disintegration in the range of CaCl~2~ concentrations used ([Figure 10](#pharmaceutics-12-00422-f010){ref-type="fig"}). In addition, MTT assay performed 24 h after cell treatment with 1 HV pulse (1400 V/cm, 100 µs) demonstrates no additional cell death at 0.25 and 0.5 mM compared to that at 0 mM CaCl~2~ ([Figure 10](#pharmaceutics-12-00422-f010){ref-type="fig"}). 4. Discussion {#sec4-pharmaceutics-12-00422} ============= In the current research, CHO cells were electro-permeabilized in the presence of different extracellular CaCl~2~ concentration in order to investigate the effect of Ca^2+^ on the electrotransfer efficiency of small charged molecules. The presented results clearly demonstrate that the electrotransfer efficiency of PI is impeded when calcium is present in electroporation medium. This process is dependent on the concentration of calcium ions, although a plateau is apparent at relatively low calcium concentrations. Notably, the phenomenon is observed after electroporation with both microsecond duration and nanosecond duration pulses with some differences. To eliminate possibility that this effect is not specific to PI only, for example, due to a calcium-mediated decrease in PI fluorescence or calcium-mediated inhibition of PI and DNA binding, we performed similar experiment with two other small hydrophilic molecules, namely EtBr and YO-PRO-1. After microsecond electroporation, the reduction in the electrotransfer efficiency is observed with all three different molecules---PI, EtBr and YO-PRO-1---investigated in this study. However, after nanosecond electroporation, both the electrotransfer efficiency and the total fluorescence of the cells markedly decreased for PI and YO-PRO-1 but increased for EtBr. This is likely related to the size and the charge of the molecules. PI and YO-PRO-1 both have similar molecular weights and +2 formal charge. In contrast, EtBr has \~1/3 lower molecular weight and +1 formal charge, which likely changed its behaviour after nanosecond electroporation. In order to understand the observed differences, we performed the simulation of transmembrane voltage generated upon delivery of microsecond and nanosecond duration pulses. Simulation showed that with an increase in CaCl~2~ concentration, a higher transmembrane voltage was induced when nanosecond, but not microsecond, pulses were used. Most probably, this is related with the increase in electroporation medium conductivity (see [Table 1](#pharmaceutics-12-00422-t001){ref-type="table"}) and consequently the decrease in membrane charging time. Indeed, since the cell membrane charging time is below 5 µs \[[@B24-pharmaceutics-12-00422]\], the delivery of ten 200-ns pulses at 1 Hz of frequency might result in incomplete membrane charging. Therefore, although calcium ions decrease the efficiency of small molecule electrotransfer, this decrease can be compensated by increase in transmembrane voltage generated upon the delivery of nanosecond pulses. According to simulation, increases in CaCl~2~ concentration do not have any effect on the generation of transmembrane voltage when microsecond pulses are used. Therefore, the observed effect with microsecond pulses is attributed solely to calcium ions. Calcium ions play multiply roles in cell physiology; however, when analysing the role of CaCl~2~ in the decrease in efficiency of small charged molecules, electrotransfer pore formation and annihilation must be considered. The cell after electroporation faces a critical threat to its viability in the form of uncontrolled transport of essential ions and organic molecules through the electric field affected membrane. Therefore, defense mechanisms that rapidly repair plasma membrane lesions have to be employed in order to maintain cell viability after membrane permeabilization. The plasma membrane repair requires membrane replacements, fusion events and cytoskeleton reorganization \[[@B27-pharmaceutics-12-00422]\]. It can be segmented into passive and active membrane repair, both of which are triggered by Ca^2+^ ion influx at the injury site due to a thousand-fold gradient of calcium that exists across the plasma membrane \[[@B28-pharmaceutics-12-00422]\]. It has been shown that Ca^2+^ ions interact with phospholipid heads, leading to phospholipid bridging via hydrophobic bonding \[[@B29-pharmaceutics-12-00422]\]. The phospholipid bridging initiates the aggregation of the phospholipids, which provides a significantly higher chance for the fusion of the vesicles, thus allowing phospholipids in damaged cell membrane areas to fuse. This way, there is a greater chance for a damaged cell membrane to reseal. Another Ca^2+^-ion-induced phenomenon that was observed in previously published experiments with liposomes is the reduction in the fluidity of the membrane induced by Ca^2+^ interaction with the phospholipid heads \[[@B30-pharmaceutics-12-00422],[@B31-pharmaceutics-12-00422]\]. The membrane fluidity term describes a relative diffusion motion of molecules within membranes \[[@B32-pharmaceutics-12-00422]\]. Some studies had been investigating the relationship between the membrane fluidity and the electroporation \[[@B33-pharmaceutics-12-00422],[@B34-pharmaceutics-12-00422]\]. In these, the membrane fluidity was changed by regulating the cholesterol percentage in the membrane \[[@B35-pharmaceutics-12-00422],[@B36-pharmaceutics-12-00422]\]. The studies have indicated that the electroporation threshold is dependent on the membrane fluidity \[[@B33-pharmaceutics-12-00422],[@B34-pharmaceutics-12-00422]\]. Indeed, the transmembrane potential threshold for electroporation has an inverse correlation with the fluidity of the lipid bilayer \[[@B37-pharmaceutics-12-00422]\]. Therefore, if calcium ions are present in the extracellular medium, then the fluidity of the membrane is decreased, increasing the transmembrane potential threshold required for electroporation in turn. This assumption also goes in agreement with the published simulations addressing the dependence of electropore formation on Ca^2+^ ions \[[@B38-pharmaceutics-12-00422]\]. Here, we show that higher applied electric pulse strength is needed in order to obtain the similar amount of PI positive cells in Ca^2+^-containing medium in comparison to the medium without added Ca^2+^, which is consistent with this hypothesis. Moreover, it has also been demonstrated that phospholipid aggregates induced by Ca^2+^ ion bridging increase the phospholipid aggregate repulsiveness to water molecules \[[@B39-pharmaceutics-12-00422]\]. The change in phospholipid--water interactions becomes relevant when using hydrophilic pore formation model to explain electroporation. According to this model, pores do not immediately close after the electric-field-induced transmembrane potential dissipates \[[@B22-pharmaceutics-12-00422]\]. Instead, after the electric field is switched off, the size of the pores rapidly diminishes to \~0.4--2.3 nm \[[@B22-pharmaceutics-12-00422],[@B40-pharmaceutics-12-00422]\]. Taking the reduced pore size and the model of the phospholipid head lined interior of the pore into the account, the repulsion to water by the Ca^2+^ ion bridging of phospholipid aggregates can make a great impact on the transfer of hydrophilic molecules. Additionally, extracellular calcium, intracellular vesicles and calcium-dependant exocytosis are involved in the active membrane repair \[[@B41-pharmaceutics-12-00422]\]. Specifically, calcium and cytoplasmic vesicles have been identified as a part of repair/resealing machinery \[[@B21-pharmaceutics-12-00422]\]. This repair machinery is initiated via annexins, a family of Ca^2+^ regulated proteins \[[@B42-pharmaceutics-12-00422],[@B43-pharmaceutics-12-00422]\]. However, the exact mechanism of the annexin role in the repair of membrane damage is not yet clearly understood. Nevertheless, it has been shown that annexins 1 and 2 interact with dysferlin, a protein involved in membrane resealing after dramatic damage \[[@B44-pharmaceutics-12-00422],[@B45-pharmaceutics-12-00422]\]. The calcium-triggered assembly of 2D arrays of annexin 5 has been also observed to play a key role in cell membrane repair \[[@B46-pharmaceutics-12-00422]\]. One could also suggest that Ca^2+^ influx can close non-specific ion channels that permit dye uptake. Indeed, it has been shown that Ca^2+^ overload in the cell desensitizes many cation channels \[[@B47-pharmaceutics-12-00422],[@B48-pharmaceutics-12-00422],[@B49-pharmaceutics-12-00422]\]. Nevertheless, these channels do not permit the transmembrane diffusion of dyes like propidium iodide. On the other hand, connexin hemichannels allow for the exchange of small molecules between the cytoplasm and the extracellular space \[[@B50-pharmaceutics-12-00422]\]. This opens the possibility that Ca^2+^ can regulate PI uptake through these hemichannels. Nevertheless, studies on gating of various connexin hemichannels show that these hemichannels open under low extracellular calcium concentrations \[[@B51-pharmaceutics-12-00422],[@B52-pharmaceutics-12-00422]\], i.e., in conditions that are opposite to the ones described above. 5. Conclusions {#sec5-pharmaceutics-12-00422} ============== In conclusion, we report that extracellular calcium induces a negative effect on the small charged molecule electrotransfer into the cells due to electroporation. This effect was demonstrated by using conventional microsecond duration pulse electroporation. All used concentrations of extracellular CaCl~2~ had the negative effect small charged molecule electrotransfer. However, the effect was diminished when CaCl~2~ concentration increased from 0.25 to 1 mM using nanosecond duration pulse electroporation. This can be explained by mathematical modelling, which proves that, with nanosecond electric pulses, the increase in specific conductivity due to the higher concentration of CaCl~2~ results in significantly higher transmembrane potential generated on the cell. However, no change in the transmembrane potential generated on cells in media with different CaCl~2~ concentrations is observed when microsecond electric pulses are used. These results underline the differences between micro- and nano-second pulses used for electrotransfer of small charged molecules in the presence of CaCl~2~. D.N., P.R. and S.S. conceived and designed the experiments; D.N., M.M. and P.R. performed the experiments; D.N., P.R., V.N., R.S., S.S. analysed the data; D.N., P.R., M.J. wrote the paper, S.S. reviewed and edited the paper. All authors have read and agreed to the published version of the manuscript. This research is funded by the European Social Fund according to the activity 'Improvement of researchers' qualification by implementing world-class R&D projects' of Measure No. 09.3.3-LMT-K-712-01-0188. The authors declare no conflict of interest. {#pharmaceutics-12-00422-f001} {#pharmaceutics-12-00422-f002} {#pharmaceutics-12-00422-f003} {#pharmaceutics-12-00422-f004} {#pharmaceutics-12-00422-f005} {#pharmaceutics-12-00422-f006} {#pharmaceutics-12-00422-f007} {#pharmaceutics-12-00422-f008} {#pharmaceutics-12-00422-f009} {#pharmaceutics-12-00422-f010} pharmaceutics-12-00422-t001_Table 1 ###### The measured specific conductivity of used electroporation media containing different concentrations of CaCl~2~. Measurements were done using conductometer (Mettler Toledo S230). CaCl~2~ Concentration in the Medium Specific Conductivity ------------------------------------- ----------------------- 0 mM 0.016 S/m 0.25 mM 0.021 S/m 0.5 mM 0.026 S/m 1 mM 0.035 S/m [^1]: These authors contributed equally to this work.

The objectives of these projects are to: 1) develop equipment for use by investigators in Viral Oncology, 2) develop narrated, slide presentations for use by intra- and extra-mural members of oncogenic virus research on the hazards of laboratory procedures and equipment, 3) develop a training workshop for "Certification of Biological Safety Cabinets", 4) prepare monographs and safety notes on current hazards that occur within the laboratory, 5) assist in the development of standards for production and procurement of Class II biological safety cabinets, 6) provide consultation services on biohazards to Viral Oncology intra-and extra-mural personnel.

The present invention relates generally to memory devices and, more particularly, to a memory bar for use in expanding the capacity of, for example, a high density multichip module (MCM). For the past several years, substantial attention has been directed to the field of memory modules including, for example, single inline memory modules (SIMMs) and dual inline memory modules (DIMMs). Such modules are useful, for example, in expanding the memory of a personal computer or other computing system, and the market for such modules is extremely competitive. In short, there is intense pressure within the memory module market to provide modules with increased capacity for less cost. In view of the competitiveness of the memory module market, it is believed that those skilled in the art would find systems and methods for expanding the capacity of memory modules to be quite useful.

Puresyn, Inc. has developed purification processes for recombinant adeno-associated virus gene therapy vectors utilizing its proprietary chromatographic resin, PolyFlo. In Phase I, two tandem chromatography processes were developed: heparin affinity and PolyFlo and tandem PolyFlo in two different modes. Each process resulted in product of high purity and recovery that exceeds gradient centrifugation processes. We demonstrated each process removes significant amounts of host and viral contaminants. We are seeking Phase II funding to concentrate on AAV production to include large-scale purification up to 5 x 10e14 particles per run without compromising purity, yield or biological activity. We will refine and expand our current processes to assure they are applicable to AAV serotypes 1, 2 and 5. We will also address the significant problem of AAV aggregation. Finally, we will conduct an in vivo mouse study to determine the correlation between purity, biological activity and safety through the evaluation of immune and histopathological responses to the vector. Results of this research will have immediate impact for those engaged in the use of recombinant AAV vectors for gene delivery because it will allow the large-scale development of AAV vectors, It will have positive commercialization implications for PoIyFlo and Puresyn, Inc. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

Gjon Gjon (definite form: Gjoni) is an Albanian male given name, clan, surname and onomastic element. As given name Etymology and history Gjon as a given name is a form of the English name John. It is the name of the apostle Saint John in Albanian (). Most saint names in Albanian come from Latin; John is from the Latin Iohannes, the Latin form of the Greek Ioannes (), derived from the Hebrew name Yohanan (), meaning "God is gracious". Both theologists and linguists are unsure about the relationship of the name Gjon to Gjin—the Catholic clergy considers the two to be the same saint, but the Christians of the Central Albanian Shpati region (who are Orthodox) revere Gjin and Gjon as separate saints, while linguists are unsure about the etymology of Gjin and whether or not it shares its origin with Gjon. In the Middle Ages the name Gjon was very widespread in all Albanian regions. Until lately it was also prevalent among Arvanites in Greece The name Gjon is also mentioned in the afterword of Gjon Buzuku's 1555 book, Meshari, where the author introduces himself to the reader as "Unë, dom Gjoni, biri i Bdek Buzukut" ("I, don Gjoni, son of Bdek Buzuku"). People with the given name Gjon Gjon Françesku Albani (1720–1803), Italian cardinal of Albanian descent Gjon Buzuku (1499–1577), Albanian writer Gjon Delhusa (born 1953), Hungarian singer Gjon Gazulli (1400–1465), Albanian scholar and diplomat Gjon Kastrioti II (1456–1502), Albanian nobleman Gjon Kastrioti (died 1437), Albanian nobleman Gjon Markagjoni (1888–1966), Albanian clan leader Gjon Mili (1904–1984), Albanian photographer Gjon Muzaka, medieval Albanian noble of the Muzaka family and writer of his famous memoir Gjon Ndoja (born 1991), Albanian basketball player Gjon Progoni (died 1208), Albanian nobleman Gjon Simoni (1936–1999), Albanian musician Gjon Zenebishi (died 1418), Albanian nobleman As surname Gjoni or Gjonaj is a common Albanian last name, from the given name Gjon. The names Joni and Jonima also have the same source, and the latter (under the modern Albanian form Gjonima) being the surname of members of the Jonima family. The Serbian language family name Đonović is derived from the first name Gjon which means that it is of Albanian origin. History The clan of Gjoni was first recorded in 1306. Originally Christian, it is shared between Albanian Christians and Muslims. People with the surname Gjoni Simon Gjoni, Composer Dhimitër Gjoni, Nobleman Xhelil Gjoni, Politician Sadri Gjoni, Soccer player Ilir Gjoni, Politician Vladislav Gjoni, Nobleman Ingrid Gjoni, Singer Vilson Gjoni, Soccer player Sara Gjoni, Miss Albania Eron Gjoni, Programmer, 1st Amendment activist As toponym Gjon, due to historic naming of places after the saint, became an element in Albanian toponyms, contributing to the formation of placenames such Shijon, Shinjan, Gjonm and Gjorm, the difference between the latter two demonstrating Tosk rhoticism. See also Jonima family Gjonaj Gjin References Sources https://web.archive.org/web/20120211183414/http://www.albanianhistory.net/texts15/AH1470.html Category:Albanian masculine given names Category:Albanian-language surnames

These are the display colors in RGB. The game is actually displaying extended ASCII characters in OpenGL, so you can modify the colors.

Background {#Sec1} ========== Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional (3-D) deformity of the spine, with a prevalence of 1.5--3% within the general population, that normally develops in the beginning of the growth spurt of previously healthy adolescents \[[@CR1], [@CR2]\]. For diagnosis, monitoring of progression, and clinical decision-making, periodical radiographic follow-up is traditionally performed using posterior-anterior and lateral upright radiographs. The Scoliosis Research Society defines scoliosis as a lateral curvature of the spine of more than 10° in the coronal plane on upright radiographs, also emphasizing the importance of radiography \[[@CR3]\]. In addition, supine or prone magnetic resonance imaging (MRI) and computed tomography (CT) are frequently used to obtain more in-depth information about neuroaxis and bony architecture abnormalities. Some imaging involves ionizing radiation, and the radiation doses are cumulative, resulting in 9 to 10 times more radiation exposure and a 17 times higher incidence of cancer in the AIS cohort as compared to the general population \[[@CR4], [@CR5]\]. The importance of the 3-D character of the scoliotic deformity has long been recognized, and the upright X-ray, the gold standard, is not able to accurately represent the true 3-D deformity \[[@CR6]--[@CR9]\]. CT scanning can obtain accurate 3-D information of bony structures but relies on radiation and is not obtained upright \[[@CR10]\]. An important step in attempts to visualize this 3-D character has been the development of low-dose upright imaging modalities that allow for 3-D reconstruction such as the EOS apparatus. Alternatively, MRI utilizes no harmful radiation but is considered inferior in visualizing the bone and is usually also not obtained upright. This study was designed to compare the morphology of the scoliotic spine on conventional radiographs in the upright position to those on MRI and CT obtained in supine and prone positions, respectively. Methods {#Sec2} ======= Study population {#Sec3} ---------------- A subsequent series of AIS patients of ten or more years of age scheduled for scoliosis surgery in one of our centers between 2011 and 2014 and had complete standard pre-operative work-up were included in this study. Complete work-up consisted of posterior-anterior and lateral upright radiographs of the spine, supine bending X-rays, T2-weighted MRI (3.0-T MR scanner (Achieva TX; Philips Healthcare, Best, The Netherlands)) of the spinal cord for exclusion of neural axis abnormalities obtained in a supine position, and high-resolution CT (64 Slice Multi-detector CT scanner, GE Healthcare, Chalfont, St. Giles, UK, slice thickness 0.625 mm), obtained in a prone position. The CT scans were made for navigation purposes according to protocol in one of our institutions, in a position mimicking the position at surgery as closely as possible. Children with other spinal pathology than AIS, early onset scoliosis, previous spinal surgery, neurological symptoms or neural axis abnormalities, syndromes associated with disorders of growth, or atypical left convex thoracic curves or right convex (thoraco)lumbar curves were excluded to obtain an as homogeneous a population as possible. Moreover, cases that had undergone the different imaging methods with an interval of more than 6 months in between imaging were also excluded. Curve characteristics (curve type according to the Lenke classification, Cobb end vertebrae, and apical levels) were determined on the conventional radiographs \[[@CR11], [@CR12]\]. Outcome parameters {#Sec4} ------------------ The conventional radiographs were analyzed for main thoracic and (thoraco)lumbar Cobb angle, apical rotation (using Perdriolle's method \[[@CR13]\]), thoracic kyphosis (TK; superior endplate T4--inferior endplate T12), and lumbar lordosis (LL; superior endplate L1--sacral plate), using our picture archiving and communications system (PACS) workstation (Carestream solution working station, Carestream Health, Version 11.0, Rochester, NY, USA). On the MRI and CT images, the main thoracic and (thoraco)lumbar Cobb angle, TK, and LL were measured using the same technique as for the conventional radiographs, by using multiplanar reconstruction technique through the midsection of each vertebral body for the MRI and the digital reconstructed radiograph (DRR) for the CT scan (Fig. [1](#Fig1){ref-type="fig"}). The same levels were used for each patient on the three different imaging methods. Cobb end vertebrae were selected on the radiographs and applied to the other imaging modalities \[[@CR14]\]. For measurement of apical rotation on the MRI and CT scans, complete 3-D reconstructions were acquired using semi-automatic analysis software (ScoliosisAnalysis 4.1, Imaging Division, Utrecht, The Netherlands) and a previously validated imaging method \[[@CR15]\]. The observer selected the upper and lower endplates of the vertebral body. Then, the observer used the sagittal and coronal orientation of the endplates to correct for coronal and sagittal tilt. Thus, each vertebral level was manually positioned in the true transverse plane as accurately as possible. Subsequently, for each endplate, its longitudinal axis was calculated automatically after manual segmentation of the vertebral body and spinal canal. The rotation was defined as the rotation of this axis minus the rotation of the neutral sacral plate (Fig. [2](#Fig2){ref-type="fig"}).Fig. 1On the MRI and CT images, the main thoracic and (thoraco)lumbar Cobb angle, thoracic kyphosis, and lumbar lordosis were measured using the same technique as for the conventional radiographs on the image where the curve and endplates were best visible by using the multiplanar reconstruction (MPR, **a**) for the MRI and the digitally reconstructed radiograph (**b**) for the CT scan. **c** The conventional X-ray Fig. 2The orientation of the upper and lower endplates of each individual vertebra of the computed tomography scans was determined by using the semi-automatic software, correcting for coronal and sagittal (**a** and **b**) tilt, to reconstruct the true transverse sections. The observer drew a contour around the vertebral body (*yellow line* in **c**) and spinal canal (*blue line* in **c**). The software calculated a center of gravity of the vertebral body (*yellow dot* in **c**) and spinal canal (*blue dot* in **c**). For each endplate, its longitudinal axis was calculated as the line between those two points (*purple line* in **c**). The rotation of this axis minus the rotation of the neutral sacral plate represents the rotation of the endplate Intra- and interobserver reliability for measurement of apical rotation using this method was tested in a previous study; intraclass correlation coefficients were 0.92 (95% confidence interval, 0.82--0.97) and 0.89 (0.74--0.95) on the 3-D scans \[[@CR9]\]. In this study, the intra- and interobserver reliability analysis of the rest of the outcome parameters (Cobb angles, TK, and LL on all the three modalities and the vertebral rotation on the X-rays) was studied. Two observers independently analyzed a randomly selected subset of ten X-rays, CT scans, and MRI scans of the subjects. Statistical analysis {#Sec5} -------------------- Statistical analyses were performed using SPSS 22.0 for Windows (SPSS Inc., Chicago, IL, USA). Descriptive statistics were computed providing means, ranges, and standard deviations. Potential outliers were identified. The agreement between the three positions was tested according to the Bland-Altman plot; first, the one-sample *t* test showed if there was a significant difference between the measurements; second, if there was no significant difference, the regression analysis showed if there was agreement between the measurements \[[@CR16]\]. The two-way mixed intraclass correlation coefficient (ICC) was used to evaluate the correlation between the parameters in different body positions. The intra- and interobserver reliability were obtained as intraclass correlation coefficients. The statistical significance level was set at 0.05 for all analyses. Results {#Sec6} ======= Population {#Sec7} ---------- A total of 142 subjects underwent surgery for AIS during the study period. Eighty subjects had to be excluded for several reasons, as shown in Table [1](#Tab1){ref-type="table"}. Ultimately, 62 AIS patients with full documentation were left for the purpose of this study. On average, the subjects were 15.6 ± 2.5 years of age, 56 (90%) were girls, and most of the curves were classified as type Lenke 1 of these moderate to severe AIS patients (thoracic Cobb angle 37°--110°, lumbar Cobb angle 18°--82°; Table [1](#Tab1){ref-type="table"}).Table 1Demographics are shown for all included AIS patients and controls. Also, the excluded patients are shownDemographic parameter*n* = 62 Age at radiograph (years)Range10--23Mean ± sd15.6 ± 2.5 Girls, *n* (%)56 (90.3%) Right convexity of main thoracic curve, *n* (%)Right convex62 (100%) Interval CT--radiograph (days)Range−7 to 130Mean ± sd2.98 ± 17.2 Interval radiograph--MRI (days)Range−46 to 181Mean ± sd81.3 ± 51.4 Interval CT--MRI (days)Range−26 to 181Mean ± sd84.2 ± 47.1Lenke curve type I26 II12 III6 IV4 V5 VI9Exclusion criterian Scan interval \>6 months38 No MRI available14 No CT scan available10 Incomplete radiologic work-up1 Associated congenital or neuromuscular pathologies12 Left convex main thoracic curve4 Prior spinal surgery1*sd* standard deviation Coronal parameters {#Sec8} ------------------ In the coronal plane, the main thoracic Cobb angle was on average 68° ± 15°, 54° ± 15°, and 57° ± 14° on the upright radiographs, prone CT, and supine MRI, respectively, and differed significantly between all the three positions (*P* \< 0.001; Table [2](#Tab2){ref-type="table"}). The average (thoraco)lumbar Cobb angle on the conventional upright radiograph was 44° ± 17° as compared to those on the prone CT (33° ± 15°) and supine MRI (35° ± 16°) (*P* ≤ 0.018, between the three positions). Although the upright angles were larger, the Cobb angles correlated very well between the three positions (ICC: thoracic 0.97 and lumbar 0.96; Table [3](#Tab3){ref-type="table"}; Fig. [3](#Fig3){ref-type="fig"}). Significant linear correlations were found, indicating that with increasing Cobb angle, differences between the body positions increased simultaneously. The conversion equations that resulted from the correlation analyses of the different parameters between the upright X-ray, prone CT scan, and supine MRI could be used for conversion purposes (Table [4](#Tab4){ref-type="table"}).Table 2Differences (mean ± standard deviation) between upright (X), prone (CT), and supine (MRI) positions for Cobb angle, thoracic kyphosis, lumbar lordosis, and apical vertebral rotation in the thoracic as well as lumbar curves. According to the Bland-Altman plot, the *P* value showed if there is agreement by using the *t* test. If this test showed no significant different (*P* \> 0.05), a regression analysis was performed to see is if there is agreement, written in bracketsUprightProneSupine*P* valueX vs. CTX vs. MRICT vs. MRIThoracic Cobb (°)68.2 ± 15.453.9 ± 14.856.7 ± 13.5\<0.001\<0.001\<0.001 Kyphosis (°)25.8 ± 11.422.4 ± 11.617.3 ± 9.80.004\<0.001\<0.001 Vertebral rotation (°)21.6 ± 11.719.9 ± 8.916.3 ± 10.80.161 (0.007)0.0010.002Lumbar Cobb (°)44.3 ± 16.833.1 ± 15.035.2 ± 15.9\<0.001\<0.0010.018 Lordosis (°)48.8 ± 12.045.4 ± 10.843.7 ± 12.40.006\<0.0010.341 (0.620)^a^ Vertebral rotation (°)10.7 ± 12.87.5 ± 11.46.2 ± 13.70.428 (\<0.001)0.663 (0.129)^a^0.679 (0.006)^a^Agreement according to the Bland-Altman plot Table 3Two-way mixed intraclass correlation coefficient (ICC) and 95% confidence interval (CI) between upright, prone, and supine positionsICC (95% CI)*P* valueThoracic Cobb angle0.967 (0.950--0.979)\<0.001Lumbar Cobb angle0.964 (0.945--0.977)\<0.001Thoracic kyphosis0.873 (0.806--0.919)\<0.001Lumbar lordosis0.854 (0.777--0.907)\<0.001Thoracic apical rotation0.815 (0.718--0.882)\<0.001Lumbar apical rotation0.900 (0.848--0.937)\<0.001 Fig. 3In these scatterplots, the relation between thoracic Cobb angle in the upright, prone (*red trend line*), and supine (*blue trend line*) positions is shown. Although the upright Cobb angle was significantly larger, significant linear correlations were found (ICC 0.967; *P* \< 0.001), indicating that with increasing Cobb angle, differences between the body positions increased simultaneously Table 4For translational purposes, the conversion equations that resulted from the linear correlation analyses of the different parameters between the upright X-ray, prone CT scan, and supine MRI are provided for the thoracic (Th) and lumbar (L) Cobb anglesCobb angleUpright X-rayProne CT scanSupine MRICobb angleUpright X-ray--Th: CT (°) = −6.2 + 0.88 \* X-ray (°)\ L: CT (°) = −2.7 + 0.81 \* X-ray (°)Th: MRI (°) = 2.9 + 0.79 \* X-ray (°)\ L: MRI (°) = −2.1 + 0.85 \* X-ray (°)Prone CTTh: X-ray (°) = 16.6 + 0.96 \* CT (°)\ L: X-ray (°) = 11.1 + 1.00 \* CT (°)--Th: MRI (°) = 11.0 + 0.85 \* CT (°)\ L: MRI (°) = 4.9 + 0.92 \* CT (°)Supine MRITh: X-ray (°) = 10.8 + 1.01 \* MRI (°)\ L: X-ray (°) = 9.5 + 0.98 \* MRI (°)Th: CT (°) = −2.8 + 1.00 \* MRI (°)\ L: CT (°) = 2.6 + 0.86 \* MRI (°)-- Axial rotation {#Sec9} -------------- Parallel to the coronal Cobb angles, in both the thoracic curve and the (thoraco)lumbar curve, the mean apical vertebral rotation was larger in the upright position (Table [2](#Tab2){ref-type="table"}). Significant correlations, however, were observed between the apical rotation as measured using the Perdriolle method on upright radiographs and the rotation on the prone CT and supine MRI (ICC: thoracic 0.82 and lumbar 0.90; Tables [3](#Tab3){ref-type="table"} and [4](#Tab4){ref-type="table"}). Sagittal parameters {#Sec10} ------------------- Also in the sagittal plane, the TK in the upright position (26° ± 11°) was significantly larger as compared to that in the prone (22° ± 12°) and supine (17° ± 10°; *P* ≤ 0.004) positions. The upright LL (49° ± 12°) was significantly higher as compared to the prone LL (45° ± 11°) and supine LL (44° ± 12°; *P ≤* 0.006). According to the Bland-Altman method, there was agreement between the LL in the supine and prone positions. The TK and the LL correlated well between all the positions (ICC 0.87 and 0.85; Tables [3](#Tab3){ref-type="table"} and [4](#Tab4){ref-type="table"}). Reliability {#Sec11} ----------- The ICCs for intra- and interobserver reliabilities of the Cobb angles, TK, LL, and vertebral rotation on the three modalities were all excellent (\>0.93 and \>0.74, respectively; Table [5](#Tab5){ref-type="table"}).Table 5Intra- and interobserver reliability analysis and 95% confidence intervalX-rayCT scanMRI scanIntraInterIntraInterIntraInterThoracic Cobb0.993 (0.971--0.998)0.972 (0.888--0.993)0.997 (0.988--0.999)0.995 (0.980--0.999)0.995 (0.982--0.999)0.974 (0.896--0.994)Lumbar Cobb0.999 (0.996--1.00)0.995 (0.980--0.999)0.999 (0.996--1.00)0.995 (0.981--0.999)0.997 (0.990--0.999)0.986 (0.945--0.997)Thoracic kyphosis0.989 (0.954--0.997)0.922 (0.610--0.984)0.931 (0.722--0.983)0.864 (0.454--0.966)0.992 (0.967--0.998)0.940 (0.759--0.985)Lumbar lordosis0.986 (0.944--0.997)0.989 (0.956--0.997)0.995 (0.980--0.999)0.973 (0.890--0.993)0.995 (0.981--0.999)0.971 (0.884--0.993)Thoracic rotation0.979 (0.915--0.995)0.977 (0.906--0.994)^aa^0.939 (0.756--0.985)0.744 (0.409--0.964)Lumbar rotation0.975 (0.899--0.994)0.996 (0.985--0.999)^aa^0.906 (0.620--0.977)0.885 (0.539--0.972)^a^Intra- and interobserver reliability for the rotation on 3-D scans; this method was tested previously (ICC 0.92 and 0.89) \[[@CR9]\] Discussion {#Sec12} ========== X-rays for scoliosis are, by convention, obtained in an upright position, allowing gravity to have its influence on the morphology of the spine. The drawbacks of this X-ray imaging in analyzing the deformity as well as planning treatment are becoming increasingly clear: the deformity has a complex 3-D nature that is hardly appreciated on plain films, and radiation exposure, even with modern day equipment, is becoming a serious concern. Although the use of ultrasound for diagnosis and follow-up of spinal deformities has been explored and seems promising, this technique gives little detail of the anatomy and needs further evaluation \[[@CR17]--[@CR19]\]. Additional imaging studies are frequently obtained in scoliosis; CT scanning is still considered the gold standard for providing accurate and detailed information on bony anatomy (for instance, in cases where congenital malformations are suspected) and can give accurate 3-D reconstructions of complex deformities \[[@CR10]\]. However, CT carries even more radiation exposure and is performed non-weight bearing \[[@CR10]\]. MRI is safe, provides accurate information on the spinal cord and other soft tissues, but is also (usually) performed in a non-weight-bearing manner, and is known to show less detail of bony structures. Therefore, it is important to define where these techniques overlap, in order to reduce costs and radiation exposure. Previous studies have already described the differences in morphology of the spine in AIS between different imaging methods and between different body positions \[[@CR20]--[@CR26]\]. This study is, however, to the best of our knowledge, the first to look into the relationship between the three different positions in all three planes of the body to visualize the scoliotic spine. In this study, we observed that there is underestimation of the deformation of the spine in the supine and prone positions as compared to that in the upright position, which is overall more pronounced in the thoracic curves as compared to the (thoraco)lumbar curves. The lying positions underestimated the thoracic and (thoraco)lumbar Cobb angles for 12°--14° and 9°--11°, respectively; the TK and LL for 3°--9° and 3°--5°, respectively; and the thoracic and lumbar apical vertebral rotations for 2°--5° and 3°--5°, respectively. Therefore, the parameters on supine and prone scans could not directly be compared to the upright radiographs. However, good and excellent linear correlations were observed for the morphological parameters in the coronal (ICC ≥0.964), sagittal (ICC ≥0.854), and axial (ICC ≥0.815) planes between X-ray, CT, and MRI. This implies that reliable conversion of the parameters between the different positions is possible. A limitation of this study is the population that only includes relatively severe curves. From our results, the reliability of conversion of parameters between different positions for patients with mild AIS curves cannot be derived. Shi et al. described the correlation of the coronal Cobb angle between upright and supine positions in mild, moderate, and severe AIS patients and concluded that the correlation coefficients were more reliable in the severe group, probably due to the reduced curve flexibility in the severe group \[[@CR26], [@CR27]\]. As we demonstrated before, evaluation of the true sagittal plane in scoliosis on plain X-rays is notoriously unreliable and differs greatly from the true sagittal plane as may be analyzed more accurately on both CT and MRI \[[@CR28]\]. Conclusions {#Sec13} =========== There is a good to excellent correlation of the morphology of the scoliotic spine in all three planes between standard upright X-ray, MRI, and CT scan in these moderate to severe AIS patients. Apparently, at least part of the information obtained by these different modalities overlaps. Findings of this study suggest that severity of scoliotic deformity in AIS patients can be largely represented by different imaging modalities despite the differences in body position. Future longitudinal studies to demonstrate the practical implications of these findings are planned. 3-D : Three-dimensional AIS : Adolescent idiopathic scoliosis CI : Confidence interval CT : Computed tomography DRR : Digital reconstructed radiograph ICC : Intraclass correlation coefficient LL : Lumbar lordosis MRI : Magnetic resonance imaging PACS : Picture archiving and communications system sd : Standard deviation TK : Thoracic kyphosis None. Funding {#FPar1} ======= Rob C. Brink received funding from the Alexandre Suerman, MD/Ph.D. program, and René M. Castelein from a Medtronic research grant and a K2M research grant. Availability of data and materials {#FPar2} ================================== The data are shared in the "[Results](#Sec6){ref-type="sec"}" section. The X-rays and scans of the subjects will not be shared. Software: ScoliosisAnalysis 4.1 for Windows (Imaging Division, Utrecht, The Netherlands) SPSS 22.0 for Windows (SPSS Inc., Chicago, IL, USA). Authors' contributions {#FPar3} ====================== RCB handled the conception and design, acquisition of the data, analysis and interpretation of the data, drafting of the manuscript, statistical analysis, and obtaining funding. DC handled the acquisition of the data, analysis and interpretation of the data, drafting of the manuscript, and supervision. TPCS handled the conception and design, acquisition of the data, analysis and interpretation of the data, critical revision of the manuscript for important intellectual content, statistical analysis, and supervision. KLV handled the acquisition of the data, analysis and interpretation of the data, and technical and material support. MvS handled the acquisition of the data, analysis and interpretation of the data, and technical and material support. SCNH handled the acquisition of the data and technical and material support. SL handled the acquisition of the data, analysis and interpretation of the data, critical revision of the manuscript for important intellectual content, and technical and material support. WCWC handled the Acquisition of the data, analysis and interpretation of the data, critical revision of the manuscript for important intellectual content, and supervision. JCY handled the acquisition of the data, analysis and interpretation of the data, and critical revision of the manuscript for important intellectual content and supervision. RMC handled the conception and design, analysis and interpretation of the data, critical revision of the manuscript for important intellectual content, obtaining funding, and supervision. All authors read and approved the final manuscript. Competing interests {#FPar4} =================== The authors declare that they have no competing interests. Consent for publication {#FPar5} ======================= All authors have given permission for publication. Consent for publication of the subject not applicable. Ethics approval and consent to participate {#FPar6} ========================================== The Medical Ethics Review Committee confirmed that the Medical Involving Human Subjects Act (WMO) does not apply to the abovementioned study and that therefore an official approval of this study by MERC UMC Utrecht is not required under the WMO.

Nutritional and physiological responses of broiler chickens to dietary supplementation with de-oiled soyabean lecithin at different metabolisable energy levels and various fat sources. A 42-d study was conducted to investigate the effects of an emulsifier supplementation (de-oiled soyabean lecithin (DSL)) of diets with different levels of metabolisable energy (ME) and various sources of fat on growth performance, nutrient digestibility, blood profile and jejunal morphology of broiler chickens. Diets were arranged factorially (2 × 2 × 2) and consisted of two concentrations of ME (normal and low), two fat sources (soyabean oil (SO) and poultry fat (PF)) and two levels of DSL supplementation (0 and 1 g/kg). A total of 800 1-d-old male broiler chickens were assigned to eight treatments with five replicates/treatment. The results showed the supplemental DSL caused improvements in the overall feed conversion ratio, fat digestibility and jejunal villus height:crypt depth ratio, but the magnitude of the responses was greater in the PF-containing diets, resulting in significant fat × DSL interactions (P<0·05). Abdominal fat percentage was also reduced by the PF-containing diet, but the response was greater in the normal ME diet, resulting in a significant ME × fat interaction (P = 0·048). Dietary DSL supplementation also increased nitrogen-corrected apparent ME values but decreased blood TAG (P = 0·041) and LDL (P = 0·049) concentrations, regardless of the source of fat used or the ME values in the diet. In conclusion, the present study suggests that the improvements in growth performance, fat digestibility and intestinal morphology that can be achieved with DSL supplementation are highly dependent on the degree of saturation of lipid incorporated into broiler chicken diets.

Archive for the ‘Museum Vitrines’ Category As a museum curator or designer trying to source a glass display case builder is not always that easy. There are many companies to choose from and many options to consider. When looking for a custom display cabinet with the latest finishes to achieve a specific look, you should always try to source out a manufacture in […]

Wound healing involves a series of complex biological processes whereby injured tissue is repaired, specialized tissue is regenerated, and new tissue is reorganized. The healing of wounds is generally divided into three phases: the inflammatory phase, the proliferative phase, and maturation and remodeling phase. In the inflammatory phase, the clotting cascade is initiated in order to stop blood loss. In addition, various factors, such as chemokines, cytokines, and growth factors, are released to attract and activate cells that phagocytize debris, bacteria, and damaged tissue. The proliferative phase is characterized by angiogenesis and rebuilding of the extracellular matrix architecture which includes collagen deposition, granulation tissue formation, and epithelialization. The formation of new blood vessels, such as capillaries, and the formation of extracellular matrix enable activated satellite cell to proliferate, differentiate, and fuse into new muscle fibers. Typically, the maturation and remodeling phase of wound healing is said to begin when the levels of collagen production and degradation equalize. During maturation, type III collagen, which is prevalent during proliferation, is gradually degraded and the stronger type I collagen is laid down in its place. The originally disorganized collagen fibers are rearranged, cross-linked, and aligned. In addition, the newly regenerated muscle matures and contracts with the reorganization of the scar tissue. An impairment in any of these complex phases leads to complications in wound healing. Therefore, it would be beneficial to provide methods for promoting wound healing and/or muscle regeneration.

Image caption Thorium could prove to be safer in reactors than uranium Nuclear scientists are being urged by the former UN weapons inspector Hans Blix to develop thorium as a new fuel. Mr Blix says that the radioactive element may prove much safer in reactors than uranium. It is also more difficult to use thorium for the production of nuclear weapons. His comments will add to growing levels of interest in thorium, but critics warn that developing new reactors could waste public funds. Mr Blix, the former Swedish foreign minister, told BBC News: "I’m a lawyer not a scientist but in my opinion we should be trying our best to develop the use of thorium. I realise there are many obstacles to be overcome but the benefits would be great. "I am told that thorium will be safer in reactors - and it is almost impossible to make a bomb out of thorium. These are very major factors as the world looks for future energy supplies." Image caption Hans Blix says the world should try its best to develop thorium His enthusiasm is shared by some in the British nuclear establishment. Scientists at the UK’s National Nuclear Laboratory (NNL) have been encouraged by the government to help research on an Indian thorium-based reactor, and on a test programme in Norway. The Norway tests at the OECD’s nuclear trials facility in Halden are conducted in a Bond-style underground bunker. A couple of charming Nordic homes perch on top of a hill at the edge of the town. Below them a garage door in a cliff face leads into a tunnel deep into the hill where the reactor hall lies. In theory, at least, the mountain protects the town from an accident. The thorium tests are being carried out by a private firm, Thor Energy (the element itself was discovered in Norway in 1828 and named after the Norse god of thunder). The company hopes to get thorium licensed alongside uranium in current water-cooled reactor plants. The British government says it would be useful to increase the fuel options for nuclear operators, as thorium is believed to be three times more plentiful than uranium. It is also currently being produced as a by-product from mining rare earths. Staff from NNL have been advising Thor on the use of mixed oxide fuels (MOX). NNL has also been helping the Indian authorities develop a thorium reactor, as India sits on top of the world’s biggest thorium reserves. Media playback is unsupported on your device Media caption Inside Norway's experimental nuclear power plant The Thor project represents an evolutionary approach, using thorium in existing reactors together with uranium or plutonium. Oystein Asphjell, chief executive of Thor Energy told BBC News: "There is lots of thorium in the world, very well distributed all over the globe. In operations, in a reactor, it has some chemical and physical properties that make it really superior to uranium as well. On the waste side, we don’t generate long lived waste." China is going for a revolutionary approach, devising a next-generation reactor which its supporters say will enable thorium to be used much more safely than uranium. Media playback is unsupported on your device Media caption Inside a mine rich in thorium When a uranium reactor overheats and the fuel rods can’t contain the chain reaction, as happened at Fukushima, the crisis continues. If something happened to a thorium reactor, technicians could simply switch off the stimulus which comes from uranium or plutonium in a small feeder plant and the thorium reaction would halt itself. Prof Carlo Rubbia from Cern previously told BBC News: "Thorium will be able to shut itself off without any human intervention... You just switch off the beam.” "There are also no long-lived waste products... We estimate that after something like 400-500 years all the radioactivity will be dissipated away." These advantages, if they were realised, would be huge. But thorium still has many technical problems to overcome. What is more, countless billions have been ploughed into uranium-based research and development, and in the words of Mr Blix, uranium has a very deep furrow, backed by vested interests. Canada, China, Germany, India, the Netherlands, the UK and the US have experimented with thorium as a substitute fuel in the past. Image caption The nuclear trials at Halden are conducted underground Questions are being raised, though, about the advisability of pinning the world’s energy ambitions on another nuclear dream. Environmentalists often allege that if renewable power had commanded a fraction as much research funding as nuclear it would already be much cheaper and more common. Dr Nils Bohmer, a nuclear physicist working for a Norwegian environmental NGO, Bellona, said developing thorium was a costly distraction from the need to cut emissions immediately to stave off the prospect of dangerous climate change. "The advantages of thorium are purely theoretical," he told BBC News. "The technology development is decades in the future. Instead I think we should focus on developing renewable technology - for example offshore wind technology - which I think has a huge potential to develop.” If thorium ever makes it as a commercial nuclear fuel, uranium may be seen as a massive and costly diversion. Some supporters of thorium believe that it was bypassed in the past because governments wanted the plutonium from certain conventional reactors to make atomic bombs. They believe thorium was rejected because it was simply too safe. Follow Roger on Twitter

import React from 'react'; import { withStyles, Card, CardContent, CardHeader, CardActions, Typography, } from 'material-ui'; import PropTypes from 'prop-types'; import chartCardStyle from 'variables/styles/chartCardStyle'; /* eslint-disable no-nested-ternary */ function ChartCard({ ...props }) { const { classes, chartColor, statIconColor, chart, title, text, statLink, statText, } = props; return ( <Card className={classes.card}> <CardHeader className={`${classes.cardHeader} ${ classes[`${chartColor}CardHeader`] }`} subheader={chart} /> <CardContent className={classes.cardContent}> <Typography variant="title" component="h4" className={classes.cardTitle} > {title} </Typography> <Typography component="p" className={classes.cardCategory}> {text} </Typography> </CardContent> <CardActions className={classes.cardActions}> <div className={classes.cardStats}> <props.statIcon className={`${classes.cardStatsIcon} ${ classes[`${statIconColor}CardStatsIcon`] }`} />{' '} {statLink !== undefined ? ( <a href={statLink.href} className={classes.cardStatsLink}> {statLink.text} </a> ) : statText !== undefined ? ( statText ) : null} </div> </CardActions> </Card> ); } ChartCard.defaultProps = { statIconColor: 'gray', chartColor: 'purple', }; ChartCard.propTypes = { classes: PropTypes.object.isRequired, chart: PropTypes.object.isRequired, title: PropTypes.node, text: PropTypes.node, statIcon: PropTypes.func.isRequired, statIconColor: PropTypes.oneOf([ 'warning', 'primary', 'danger', 'success', 'info', 'rose', 'gray', ]), chartColor: PropTypes.oneOf(['orange', 'green', 'red', 'blue', 'purple']), statLink: PropTypes.object, statText: PropTypes.node, }; export default withStyles(chartCardStyle)(ChartCard);

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In general, a vehicle generates power by mixing fuel and air and combusting the mixture of fuel and air. That is, fuel stored in a fuel tank of a vehicle passes through various types of fuel supply devices, is mixed with air introduced from the outside, and then is injected into a cylinder of an engine, and at the same time, the engine is operated by repeating intake, compression, combustion, and exhaust strokes, and thereby, the vehicle obtains power. As described above, a predetermined amount of air is needed to drive the engine, and air is supplied from the outside of the vehicle. That is, air flows into an air cleaner housing from the outside of the vehicle, flows toward an intake manifold through an air intake hose that is connected to the air cleaner housing, and then is supplied into the engine. That is, the intake manifold is formed so that air sucked from the outside passes through a filter and then flows toward the opposite side via the air cleaner, and purified air is supplied into the engine after filtering dust and impurities included in the air using the filter, thereby supplying air required for combustion. FIG. 1 is a view schematically illustrating an air cleaner 1 in the related art. Referring to FIG. 1, the air cleaner 1 in the related art includes a body portion 10 which has an air inlet 12 formed at one side of the body portion 10, a cover portion 20 which is coupled to an upper portion of the body portion 10 and has an outlet 22 formed at one side of the cover portion 20, an element 30 which is interposed between the body portion 10 and the cover portion 20. In the air cleaner 1 having the aforementioned configuration, air flows into the air cleaner 1 through the air inlet 12 formed in the body portion 10, the air flowing into the air cleaner 1 passes through the element 30 so as to filter impurities, and thereafter, the air is supplied into the engine through the outlet 22 formed in the cover portion 20. There is a problem in that when the air cleaner 1 is used for a long period of time, a large amount of impurities is attached to the element 30, and thereby, the air cleaner 1 does not properly perform a filtering function. Therefore, in order to filter air, the element 30, which is installed in the body portion 10 and the cover portion 20, needs to be replaced by a new element after a predetermined time has passed. However, because the body portion 10 and the cover portion 20 of the air cleaner 1 in the related art are coupled to each other by bolts, the bolts, which fix four corners of the body portion 10 and the cover portion 20, needs to be removed to replace the element 30, and therefore, there are problems in that it is inconvenient to replace the element 30, and it takes a long time to replace the element 30. In addition, because in the air cleaner 1 in the related art, the element 30 is positioned such that the element 30 merely lies on an upper side of the body portion 10, there are problems in that when air flows in from a lower portion of the element 30, that is, through the air inlet 12 of the body portion 10, the element 30 is shaken by flow pressure of the air, and the body portion 10 and the cover portion 20 collide with each other, which causes vibrating noise. Accordingly, in order to resolve the aforementioned problem in the related art, the present applicant filed Korean Patent Laid-Open Application No. 10-2013-0061599, entitled “Air Cleaner for Vehicle”. However, the aforementioned technology has a merit in that the air cleaner 1 is mounted in an air cleaner housing so as to be detachable like a drawer structure such that the air cleaner 1 may be easily and conveniently replaced, but has a problem in that because an element is not securely fixed when flow pressure occurs in the housing, which causes vibrating noise. Therefore, the present applicant has studied an air cleaner for a vehicle, which may resolve the aforementioned problems in the related art.

Get Connected to the Environment Do you ever stare at our phone aimlessly, even when there’s nothing to look at? Recent U communication graduate Keilian Meyer has created an app to help. It eliminates wasted time — and wasted resources. Social Organic Innovative Learning (SOIL) will connect users to environmental events and information for their local community. “That’s the most efficient form of sustainability — building a community so you’re less reliant on non-renewable resources and more dependent on each other,” Meyer said. SOIL is in development with plans to launch in early 2016. Find this article and a lot more in the 2016 “Student Innovation @ the U” report. The publication is presented by the Lassonde Entrepreneur Institute to celebrate student innovators, change-makers and entrepreneurs.

<?php return [ [ 'key' => 'account', 'name' => 'shop::app.layouts.my-account', 'route' =>'customer.profile.index', 'sort' => 1, ], [ 'key' => 'account.profile', 'name' => 'shop::app.layouts.profile', 'route' =>'customer.profile.index', 'sort' => 1, ], [ 'key' => 'account.address', 'name' => 'shop::app.layouts.address', 'route' =>'customer.address.index', 'sort' => 2, ], [ 'key' => 'account.reviews', 'name' => 'shop::app.layouts.reviews', 'route' =>'customer.reviews.index', 'sort' => 3, ], [ 'key' => 'account.wishlist', 'name' => 'shop::app.layouts.wishlist', 'route' =>'customer.wishlist.index', 'sort' => 4, ], [ 'key' => 'account.compare', 'name' => 'shop::app.customer.compare.text', 'route' =>'velocity.customer.product.compare', 'sort' => 5, ], [ 'key' => 'account.orders', 'name' => 'shop::app.layouts.orders', 'route' =>'customer.orders.index', 'sort' => 6, ], [ 'key' => 'account.downloadables', 'name' => 'shop::app.layouts.downloadable-products', 'route' =>'customer.downloadable_products.index', 'sort' => 7, ] ]; ?>

Stem cells: A path towards improved epilepsy therapies. Despite the immense growth of new anti-seizure drugs (ASDs), approximately one-third of epilepsy patients remain resistant to current treatment options. Advancements in whole genome sequencing technology continues to identify an increasing number of epilepsy-associated genes at a rate that is outpacing the development of in vivo animal models. Patient-derived induced pluripotent stem cells (iPSCs) show promise in providing a platform for modeling genetic epilepsies, high throughput drug screening, and personalized medicine. This is largely due to the ease of collecting donor cells for iPSC reprogramming, and their ability to be maintained in vitro, while preserving the patient's genetic background. In this review, we summarize the current state of iPSC research in epilepsy and closely related syndromes, discuss the growing need for high-throughput drug screening (HTS), and review the use of stem cell technology for the purpose of autologous transplantation for epilepsy stem cell therapy. Although the use of iPSC technology, as it applies to ASD discovery, is in its infancy, we highlight the significant progress that has been made in phenotype and assay development to facilitate systematic HTS for personalized medicine.

Neurochemical and genetic bases of psychopathology: current status. A review, which does not attempt to be exhaustive, is presented. Evidence for the operation of genetic factors in the etiology of mental disorders, including studies of natural families, twins, and adoptees and their biological and adoptive relatives, is briefly summarized and discussed. Environmental influences are also clearly involved, and observations bearing on their nature are described. Certain neurochemical correlates of psychopathology, particularly those related to chemical neurotransmitters, are discussed. Since schizophrenia and the affective disorders are phenomenological syndromes, it is likely that they represent heterogeneous collections of more specific disorders with common symptomatic features. Attempts to delineate more homogeneous subgroups in these disorders on the basis of morphological or biochemical features have achieved some success, and an example of each approach is described.

203 Cal.App.2d 772 (1962) 21 Cal. Rptr. 871 THE PEOPLE, Plaintiff and Respondent, v. DAVID G. LUGO, Defendant and Appellant. Docket No. 7866. Court of Appeals of California, Second District, Division One. May 21, 1962. *773 Ruffo Espinosa for Defendant and Appellant. Stanley Mosk, Attorney General, William E. James, Assistant Attorney General, and Peter H. Graber, Deputy Attorney General, for Plaintiff and Respondent. FOURT, J. This is an appeal from a judgment of conviction of selling heroin and an order denying a motion for a new trial. In an indictment filed in Los Angeles County on February 17, 1961, the appellant was charged with a violation of section 11501, Health & Safety Code, in that on December 15, 1960, appellant sold heroin. Appellant was also charged with a prior felony conviction. He pleaded not guilty and denied *774 the prior conviction. A jury trial was properly waived and appellant was found guilty as charged and the prior conviction was found to be true. A résumé of some of the facts is as follows: On or about the afternoon of December 15, 1960, Officer Martin, an undercover narcotics officer, was riding as a passenger in his automobile as it was being driven north on Broadway between Seventh and Sixth Streets in Los Angeles. Martin was seated to the right of the driver, Robert Mansfield. Two women, one known as Pat Haynes and the other as Ramona, were seated in the back seat of the automobile. Martin, who had been on the narcotics division assignment for six or eight weeks, saw appellant, who was walking on Broadway, at about 4:45 p.m., December 15, 1960. Pat Haynes called to appellant and invited him to enter the car, which he did, taking a seat to the right of Martin in the front seat. It was daylight and Martin observed appellant and his wearing apparel, and also noticed that appellant's teeth protruded somewhat. Appellant was introduced to Martin as "Louis." Upon entering the automobile appellant asked, "How much are you looking to score?" which meant in effect, "How much narcotics did you want to buy?" Pat Haynes answered, "We want to get two grams. We'll give you thirty five dollars" and appellant said, "I don't know how much I have at my stash, but I think I only have a gram and a half. Go down to Sixth and Main Streets." Mansfield, the driver, inquired of the appellant whether he had narcotics with him and appellant stated that he had a half gram of heroin. Martin offered appellant $9.50 for the half gram and appellant accepted the offer. Martin paid appellant the money and appellant thereupon took from his mouth a small balloon which was tied at one end and handed it and the contents thereof to the officer. During the conversation and the exchange the car was being driven from Broadway and Sixth Streets to Main and Sixth Streets. Martin observed the appellant quite closely. At Sixth and Main Streets Pat Haynes and appellant got out of the automobile. Martin went to the police administration building, where he opened the balloon which had been given to him by the appellant. It contained five capsules holding a white powdery substance. The capsules and the balloon were marked with the officer's initials and the date and thereupon placed in a small manila envelope. That envelope was then placed in a larger envelope which was sealed with sealing wax. *775 A police forensic chemist received the sealed manila envelope from the central property division of the police department on December 16, 1960, and selected at random one of the capsules for examination. The tests disclosed that the capsule examined contained heroin. The chemist returned the items to the envelope, which was then sealed and returned to the property division of the police department. The material remained within the sealed envelope in the property division of the police department until it was presented to the grand jury. The envelope and contents were introduced into evidence as Exhibit 1 at the trial. About two weeks after the sale of the heroin occurred Martin was shown by an informant a picture of a person known as "Apache" and Martin recognized the picture as being of one of the men who had made the sale of heroin to him. On February 18, 1961, Martin identified appellant at the police building and there talked to him. In appellant's presentation of his defense he admitted to having been convicted of the possession of narcotics on a previous occasion and that he was using narcotics in December of 1960. However he stated that he was not in the vicinity of where the sale in question occurred, although he did not know where he was on the date of the sale. Appellant now asserts that the chain of possession of the narcotics was inadequate, that the identification of appellant was inadequate, and that there is not competent evidence to sustain the judgment. [1a] Appellant claims that there is a gap in the chain of possession from the time the officer sealed the contents of the balloon into the envelope to the time the chemist obtained the sealed envelope from the property division of the police department. There was no showing of any tampering with the envelope otherwise, and no questions were put to the officer by appellant's counsel on the now asserted gap. It is proper to presume that an official duty has been regularly performed unless there is some evidence to the contrary. (Code Civ. Proc. § 1963, subd. 15. See People v. Pendarvis, 178 Cal. App.2d 239, 241 [2 Cal. Rptr. 824]; People v. Heath, 131 Cal. App.2d 172, 174 [280 P.2d 70]; People v. Coleman, 100 Cal. App.2d 797, 801-802 [224 P.2d 837]; People v. Brown, 92 Cal. App.2d 360, 365 [206 P.2d 1095]; People v. Reyes, 133 Cal. App. 574 [24 P.2d 531].) Appellant relies in great part upon some language contained in People v. Riser 47 Cal.2d 566, 580 [305 P.2d 1], to support *776 his contention. The facts of that case and the facts of the case before this court are in no sense comparable. In the Riser case there was evidence that the items in question were put in an open bookcase in an office which was shared by others, that the office was unlocked and flanked on one side by a hallway and on the other by an office shared by two or three persons. In Riser the defendant contended "... that in view of these facts the prosecution failed to establish continuous possession, which is a necessary foundation for the admission of demonstrative evidence; that since someone could have altered the prints or imposed wholly new ones during the four hours the glass and bottle were left unguarded in the book case, the prosecution has not sufficiently identified the prints as those that existed when the articles were removed from the bar. Defendant would require the prosecution to negative all possibility of tampering." [2] The court further said: "Undoubtedly the party relying on an expert analysis of demonstrative evidence must show that it is in fact the evidence found at the scene of the crime, and that between receipt and analysis there has been no substitution or tampering (see People v. Coleman, 100 Cal. App.2d 797, 801 [224 P.2d 837]; 21 A.L.R.2d 1216, 1219, 1236-1237), but it has never been suggested by the cases, what the practicalities of proof could not tolerate, that this burden is an absolute one requiring the party to negative all possibility of tampering. (See, e.g., People v. Brown, 92 Cal. App.2d 360, 365 [206 P.2d 1095]; Commonwealth v. Mazarella, 279 Pa. 465, 472 [124 A. 163].) [3] "The burden on the party offering the evidence is to show to the satisfaction of the trial court that, taking all the circumstances into account including the ease or difficulty with which the particular evidence could have been altered, it is reasonably certain that there was no alteration. "The requirement of reasonable certainty is not met when some vital link in the chain of possession is not accounted for, because then it is as likely as not that the evidence analyzed was not the evidence originally received. Left to such speculation the court must exclude the evidence. (See Dobson v. Industrial Acc. Com., 114 Cal. App.2d 782, 785 [251 P.2d 349]; McGowan v. Los Angeles, 100 Cal. App.2d 386, 389-392 [223 P.2d 862, 21 A.L.R.2d 1206]; People v. Smith, 55 Cal. App. 324, 327-329 [203 P. 816]; Novak v. District of Columbia, 160 F.2d 588 [82 App. D.C. 95].) [4] Conversely, when it is the barest speculation that there was tampering, it is *777 proper to admit the evidence and let what doubt remains go to its weight. (See People v. Tomasovich, 56 Cal. App. 520, 529 [206 P. 119]; State v. Smith (Mo.), 222 S.W. 455, 458-459.) In the present case defendant did not point to any indication of actual tampering, did not show how fingerprints could have been forged, and did not establish that anyone who might have been interested in tampering with the prints knew that the bottles and glasses were in Deputy Sheriff Lochry's book case. There was no error in the court's ruling." [1b] Had the appellant any thought of raising the question of a gap in the chain of possession his opportunity was made available when the stipulation was being entered into concerning the testimony of the police chemist and the route followed or taken by the evidence from the time Martin secured it from appellant to the time of the testing or analysis by the chemist. There was no objection to the procedure which was followed, nor was there even an expressed thought that the powder analyzed by the chemist was not the same powder as purchased by Martin from the appellant. It is now too late to make any such objection. [5] It is not the duty of the prosecution in the ordinary situation where there is no objection to the receipt of the evidence to negative all possibility of tampering. There is clear evidence in this case that the evidence in question is the heroin which was purchased from the appellant. The burden is to satisfy the trier of fact that under all of the circumstances of the case and taking into account every factor it is reasonably certain that there was no alteration or tampering with the evidence. There is no showing of the slightest likelihood that the evidence in this case which was analyzed by the chemist is not the heroin which was purchased from the appellant. [6] Appellant also contends that he was not adequately identified; that the prosecution should have called Pat Haynes or one of the other persons in the automobile to testify with reference to what occurred. Martin was a percipient witness to the transaction. He had every opportunity to see and observe the appellant. The inference is clear that Martin readily recognized appellant at the time of his arrest as the person who had made the sale of heroin to him on December 15, 1960. [7] The sale of narcotics requires only one witness. (People v. Casado, 181 Cal. App.2d 4, 8 [4 Cal. Rptr. 851]; People v. Smith, 174 Cal. App.2d 129, 134 [344 P.2d *778 435]; People v. Rodriguez, 169 Cal. App.2d 771, 778 [338 P.2d 41]; People v. Sterling, 162 Cal. App.2d 738, 739 [328 P.2d 462]; People v. McCrasky, 149 Cal. App.2d 630, 635 [309 P.2d 115].) Pat Haynes could have testified but her testimony would have been of no higher nature than that of the officer. The presumption of Code of Civil Procedure section 1963, subdivision 6, does not apply to the facts of this case. (People v. McShann, 177 Cal. App.2d 195, 198 [2 Cal. Rptr. 71]; People v. Williams, 174 Cal. App.2d 175 [344 P.2d 45]; People v. Alexander, 168 Cal. App.2d 753, 755 [336 P.2d 565]; People v. Taylor, 159 Cal. App.2d 752, 756-757 [324 P.2d 715].) [8] There is no evidence in this case so far as the record discloses to show suppression of any evidence. Appellant relies heavily upon People v. Kiihoa, 53 Cal.2d 748, 754 [3 Cal. Rptr. 1, 349 P.2d 673], however the facts of that case are in nowise similar to the facts in the instant case. Here the appellant was arrested approximately two months after the offense was committed. The police might very well have wanted to delay the arrest of appellant until the date it was made for fear of alerting other violators of police activity. Indeed the clerk's transcript shows that appellant's first appearance in court was with the defendants named in 31 secret indictments and 13 others, one of whom included Pat Haynes. There is no showing that any delay was engineered to the end that Pat Haynes or any other witness was to leave the state. There was no showing that the persons who were with Martin at the time of the purchase of the heroin were not available to testify had the appellant been of the mind to call any of them as his witness. (See People v. Castedy, 194 Cal. App.2d 763 [15 Cal. Rptr. 413].) There was no statement made by the appellant at the time of trial to the effect that it would be more desirable to call a witness other than Martin as to what occurred. With reference to the appellant's claim that the evidence is insufficient to support the conviction, a reading of the record, as heretofore indicated, belies any such claim. The trial judge accepted the prosecution's identification evidence. It was for the trial judge to determine the credibility of the witnesses. (People v. Williams, 174 Cal. App.2d 175, 183 [344 P.2d 45]; People v. Muniz, 172 Cal. App.2d 688, 691 [342 P.2d 53]; People v. Carr, 170 Cal. App.2d 181, 183, 186 [338 P.2d 479]; People v. Diaz, 160 Cal. App.2d 123, 133 [324 P.2d 887].) *779 The evidence of appellant's guilt in this case is crystal clear. He was fairly tried. The order denying a motion for a new trial and the judgment are and each is affirmed. Wood, P.J., and Lillie, J., concurred.

Ultrasound contrast agents (USCA) are used for improving diagnostic accuracy on ultrasound imaging. USCA have also been used as cavitation nuclei for therapeutic procedures such as sonothrombolysis useful for treating stroke and heart attack. At the current time, however, the main use of USCA is for diagnosis. A prior art ultrasound contrast agent is sold in commerce under the trademark DEFINITY. DEFINITY is a phospholipid-based ultrasound contrast agent comprising dipalmitoylphosphatidylcholine (“DPPC”), dipalmitoylphosphatidylethanolamine-PEG(5,000) (“DPPE-PEG5,000”), and dipalmitoylphosphatidic acid (“DPPA”). DEFINITY has a shelf-life of two-years at 4-8° C. Hydrolysis of the lipids is primarily responsible for degradation of the product. Clinical use of DEFINITY is known to cause back pain as a side-effect. The prescribing information for DEFINITY expressly discloses that back pain occurs in about 1.2% of patients. When such back pain does occur, that side effect can be very unpleasant for the patient and last up to 30 minutes or one hour.

Q: Making custom non-trivial loss function in pytorch I'm just started with pytorch and trying to understand how to deal with custom loss functions, especially with some non trivial ones. Problem 1. I'd like to stimulate my nn to maximize true positive rate and at the same time minimize false discovery rate. For example increase total score on +2 for true positive, and decrease on -5 for false positive. def tp_fp_loss(yhat, y): total_score = 0 for i in range(y.size()): if is_tp(yhat[i],y[i]): total_score += 2 if is_fp(yhat[i],y[i]): total_score -= 5 return -total_score Problem 2. In case when y is a list of positive and negative rewards (y = [10,-5, -40, 23, 11, -7]), stimulate nn to maximize sum of rewards. def max_reward_loss(yhat,y): r = torch.autograd.Variable(torch.Tensor(y[yhat >= .5]), requires_grad=True).sum() return -r Maybe I'm not completely understand some autograd mechanics, functions which I implemented correctly calculate loss but learning with them doesnt work :( What I'm doing wrong? Can anybody help me with some working solution of any of that problems? A: Your loss function is not differentiable - you cannot compute its gradient (go ahead and try). You should look as something like infogain loss A: @Shai already summed it up: Your loss function is not differentiable. One way to think about it is that your loss function should be plottable, and the "downhill" slope should "roll" toward the desired model output. In order to plot your loss function, fix y_true=1 then plot [loss(y_pred) for y_pred in np.linspace(0, 1, 101)] where loss is your loss function, and make sure your plotted loss function has the slope as desired. In your case, it sounds like you want to weight the the loss more strongly when it is on the wrong side of the threshold. As long as you can plot it, and the slope is always downhill toward your target value (no flat spots or uphill slopes on the way from a valid prediction to the target value), your model should learn from it. Also note that if you're just trying to take into account some business objective which prioritizes precision over recall, you could accomplish this by training to convergence with cross entropy or some well-known loss function, and then by tuning your model threshold based on your use case. A higher threshold would normally prioritize precision, and a lower threshold would normally prioritize recall. After you've trained, you can then evaluate your model at a variety of thresholds and choose the most appropriate.

Silicon hydride Silicon hydride may refer to either of the following: Silanes, SinH2n+2 Disilane, Si2H6 Silane, SiH4 Trisilane, Si3H8 Tetrasilane, Si4H10 Silenes, SinH2n Disilene, Si2H4 Silynes, SinH2n-2 Disilyne, Si2H2 Hexasilabenzene, Si6H6 Hexasilaprismane, Si6H6 Polysilicon hydride Category:Silicon hydrides

package com.hubspot.singularity.data.history; import com.hubspot.singularity.ExtendedTaskState; import com.hubspot.singularity.SingularityDeployHistory; import com.hubspot.singularity.SingularityRequest; import com.hubspot.singularity.SingularityTaskHistory; import com.hubspot.singularity.data.history.SingularityMappers.SingularityRequestIdCount; import java.util.Date; import java.util.List; import java.util.Optional; import org.jdbi.v3.json.Json; import org.jdbi.v3.sqlobject.SingleValue; import org.jdbi.v3.sqlobject.customizer.Bind; import org.jdbi.v3.sqlobject.statement.SqlQuery; import org.jdbi.v3.sqlobject.statement.SqlUpdate; public interface PostgresHistoryJDBI extends AbstractHistoryJDBI { @SqlUpdate( "INSERT INTO requestHistory (requestId, json, createdAt, requestState, f_user, message) VALUES (:requestId, :json, :createdAt, :requestState, :user, :message)" ) void insertRequestHistory( @Bind("requestId") String requestId, @Bind("json") @Json SingularityRequest request, @Bind("createdAt") Date createdAt, @Bind("requestState") String requestState, @Bind("user") String user, @Bind("message") String message ); @SqlUpdate( "INSERT INTO deployHistory (requestId, deployId, createdAt, f_user, message, deployStateAt, deployState, json) VALUES (:requestId, :deployId, :createdAt, :user, :message, :deployStateAt, :deployState, :json)" ) void insertDeployHistory( @Bind("requestId") String requestId, @Bind("deployId") String deployId, @Bind("createdAt") Date createdAt, @Bind("user") String user, @Bind("message") String message, @Bind("deployStateAt") Date deployStateAt, @Bind("deployState") String deployState, @Bind("json") @Json SingularityDeployHistory deployHistory ); @SqlUpdate( "INSERT INTO taskHistory (requestId, taskId, json, updatedAt, lastTaskStatus, runId, deployId, host, startedAt, purged) VALUES (:requestId, :taskId, :json, :updatedAt, :lastTaskStatus, :runId, :deployId, :host, :startedAt, false)" ) void insertTaskHistory( @Bind("requestId") String requestId, @Bind("taskId") String taskId, @Bind("json") @Json SingularityTaskHistory taskHistory, @Bind("updatedAt") Date updatedAt, @Bind("lastTaskStatus") String lastTaskStatus, @Bind("runId") String runId, @Bind("deployId") String deployId, @Bind("host") String host, @Bind("startedAt") Date startedAt ); @SingleValue @SqlQuery("SELECT json FROM taskHistory WHERE taskId = :taskId") @Json SingularityTaskHistory getTaskHistoryForTask(@Bind("taskId") String taskId); @SingleValue @SqlQuery( "SELECT json FROM taskHistory WHERE requestId = :requestId AND runId = :runId" ) @Json SingularityTaskHistory getTaskHistoryForTaskByRunId( @Bind("requestId") String requestId, @Bind("runId") String runId ); @SingleValue @SqlQuery( "SELECT json FROM deployHistory WHERE requestId = :requestId AND deployId = :deployId" ) @Json SingularityDeployHistory getDeployHistoryForDeploy( @Bind("requestId") String requestId, @Bind("deployId") String deployId ); @SqlQuery( "SELECT requestId, deployId, createdAt, f_user, message, deployStateAt, deployState FROM deployHistory WHERE requestId = :requestId ORDER BY createdAt DESC OFFSET :limitStart LIMIT :limitCount" ) List<SingularityDeployHistory> getDeployHistoryForRequest( @Bind("requestId") String requestId, @Bind("limitStart") Integer limitStart, @Bind("limitCount") Integer limitCount ); @SqlQuery("SELECT COUNT(*) FROM deployHistory WHERE requestId = :requestId") int getDeployHistoryForRequestCount(@Bind("requestId") String requestId); @SqlQuery("SELECT COUNT(*) FROM requestHistory WHERE requestId = :requestId") int getRequestHistoryCount(@Bind("requestId") String requestId); @SqlQuery( "SELECT DISTINCT requestId as id FROM requestHistory WHERE requestId LIKE CONCAT(:requestIdLike, '%') OFFSET :limitStart LIMIT :limitCount" ) List<String> getRequestHistoryLike( @Bind("requestIdLike") String requestIdLike, @Bind("limitStart") Integer limitStart, @Bind("limitCount") Integer limitCount ); @SqlQuery( "SELECT requestId, COUNT(*) as count FROM taskHistory WHERE updatedAt \\< :updatedAt GROUP BY requestId" ) List<SingularityRequestIdCount> getRequestIdCounts(@Bind("updatedAt") Date updatedAt); @SqlQuery( "SELECT MIN(updatedAt) from (SELECT updatedAt FROM taskHistory WHERE requestId = :requestId ORDER BY updatedAt DESC LIMIT :limit) as alias" ) Date getMinUpdatedAtWithLimitForRequest( @Bind("requestId") String requestId, @Bind("limit") Integer limit ); @SqlUpdate( "UPDATE taskHistory SET json = NULL, purged = true WHERE requestId = :requestId AND purged = false AND updatedAt \\< :updatedAtBefore LIMIT :purgeLimitPerQuery" ) void updateTaskHistoryNullBytesForRequestBefore( @Bind("requestId") String requestId, @Bind("updatedAtBefore") Date updatedAtBefore, @Bind("purgeLimitPerQuery") Integer purgeLimitPerQuery ); @SqlUpdate( "DELETE FROM taskHistory WHERE requestId = :requestId AND updatedAt \\< :updatedAtBefore LIMIT :purgeLimitPerQuery" ) void deleteTaskHistoryForRequestBefore( @Bind("requestId") String requestId, @Bind("updatedAtBefore") Date updatedAtBefore, @Bind("purgeLimitPerQuery") Integer purgeLimitPerQuery ); @SqlQuery("SELECT DISTINCT requestId as id FROM taskHistory") List<String> getRequestIdsInTaskHistory(); @SqlQuery( "SELECT COUNT(*) FROM taskHistory WHERE requestId = :requestId AND purged = false AND updatedAt \\< :updatedAtBefore" ) int getUnpurgedTaskHistoryCountByRequestBefore( @Bind("requestId") String requestId, @Bind("updatedAtBefore") Date updatedAtBefore ); @SqlQuery("SELECT DISTINCT requestId AS id FROM requestHistory") List<String> getRequestIdsWithHistory(); @SqlUpdate( "DELETE FROM requestHistory WHERE requestId = :requestId AND createdAt \\< :threshold LIMIT :batchSize" ) int purgeRequestHistory( @Bind("requestId") String requestId, @Bind("threshold") Date threshold, @Bind("batchSize") int batchSize ); @SqlQuery("SELECT DISTINCT requestId AS id FROM deployHistory") List<String> getRequestIdsWithDeploys(); @SqlUpdate( "DELETE FROM deployHistory WHERE requestId = :requestId AND createdAt \\< :threshold LIMIT :batchSize" ) int purgeDeployHistory( @Bind("requestId") String requestId, @Bind("threshold") Date threshold, @Bind("batchSize") int batchSize ); // Deprecated queries for before json backfill is finished @Deprecated @SingleValue @SqlQuery("SELECT bytes FROM taskHistory WHERE taskId = :taskId") byte[] getTaskHistoryBytesForTask(@Bind("taskId") String taskId); @Deprecated @SingleValue @SqlQuery( "SELECT bytes FROM taskHistory WHERE requestId = :requestId AND runId = :runId" ) byte[] getTaskHistoryBytesForTaskByRunId( @Bind("requestId") String requestId, @Bind("runId") String runId ); @Deprecated @SingleValue @SqlQuery( "SELECT bytes FROM deployHistory WHERE requestId = :requestId AND deployId = :deployId" ) byte[] getDeployHistoryBytesForDeploy( @Bind("requestId") String requestId, @Bind("deployId") String deployId ); // Queries for history migration @SqlQuery( "SELECT bytes FROM taskHistory WHERE requestId = :requestId AND purged = false AND bytes != '' AND bytes IS NOT NULL LIMIT :limit" ) List<byte[]> getTasksWithBytes( @Bind("requestId") String requestId, @Bind("limit") int limit ); @SqlUpdate("UPDATE taskHistory SET json = :json, bytes = '' WHERE taskId = :taskId") void setTaskJson( @Bind("taskId") String taskId, @Bind("json") @Json SingularityTaskHistory taskHistory ); @SqlQuery( "SELECT request, createdAt FROM requestHistory WHERE request != '' AND request IS NOT NULL LIMIT :limit" ) List<SingularityRequestAndTime> getRequestsWithBytes(@Bind("limit") int limit); @SqlUpdate( "UPDATE requestHistory SET json = :json, request = '' WHERE requestId = :requestId AND createdAt = :createdAt" ) void setRequestJson( @Bind("requestId") String requestId, @Bind("createdAt") Date createdAt, @Bind("json") @Json SingularityRequest request ); @SqlQuery( "SELECT bytes FROM deployHistory WHERE requestId = :requestId AND bytes != '' AND bytes IS NOT NULL LIMIT :limit" ) List<byte[]> getDeploysWithBytes( @Bind("requestId") String requestId, @Bind("limit") int limit ); @SqlUpdate( "UPDATE deployHistory SET json = :json, bytes = '' WHERE requestId = :requestId AND deployId = :deployId" ) void setDeployJson( @Bind("requestId") String requestId, @Bind("deployId") String deployId, @Bind("json") @Json SingularityDeployHistory deployHistory ); //Postgres doesn't support index hinting @Override default boolean shouldAddForceIndexClause( Optional<String> requestId, Optional<String> deployId, Optional<String> runId, Optional<String> host, Optional<ExtendedTaskState> lastTaskStatus, Optional<Long> updatedBefore, Optional<Long> updatedAfter ) { return false; } @Override default String getRequestHistoryBaseQuery() { return "SELECT json, request, createdAt, requestState, f_user, message FROM requestHistory"; } default void close() {} }

Main menu Tag Archives: Vegas Post navigation As some of you might already know, I recently celebrated the last birthday of my 20s. If anyone asks, I recently turned 25. That’s my story, and I’m sticking with it. A while back, I wrote about turning 27— how 27 was my “scary” age, and how I was closer to being “almost 30.” Well…as people like to remind me, the big 3-0 is now looming, and while I feel somewhat my age, I recall yelling at my friends over the music in the club: “This is not where I imagined myself at 29!!” In actuality, it was even better than what I had imagined. I had the best time. I danced until the sun came up, had countless drinks, enjoyed the warm weather poolside, stayed in a beautiful hotel, and even won $2.19! It’s a strange phenomenon, Las Vegas. Each time I go, I can’t imagine how I could have a better time than before. Each time, I’m surprised. The people were personable and fun; everyone did the mandatory “surprised face” when I told them how old I was turning. One bouncer even exclaimed “Aw, you’re 20, aren’t you? This isn’t a real ID. We’re letting you in? You’re not even legal!” Well played, sir. Although I can’t imagine staying much longer than three days at a time, coming home from Las Vegas is the hardest part. It’s truly the adult equivalent of Disneyland. There are few cities that have the energy of Vegas—it’s a “choose your own adventure” kind of place. There’s a seedy grittiness to it, as well as ridiculous excess and glamour. At one point, I watched cocktail waitresses spray over a dozen bottles of champagne into a pool full of people. You can’t make this stuff up. I won’t deny that I perhaps imagined that my life would turn out a bit differently when I was younger (homeowner, ex-pat, novelist?), but I must say that I’m very happy it’s turned out the way it has.

The present invention is generally directed to ink jet printing devices. More particularly, the invention is directed to determining optimum characteristics of energy pulses provided to resistive heating elements in an ink jet print head, and to determining optimum characteristics of the resistive heating elements. A thermal ink jet printer forms an image on a print medium by ejecting small droplets of ink from an array of nozzles in an ink jet print head as the print head traverses the print medium. The ink droplets are formed when ink in contact with a resistive heating element is nucleated due to heat produced when a pulse of electrical current flows through the heating element. Typically, there is one resistive heating element corresponding to each nozzle of the array. The activation of any particular resistive heating element is usually controlled by a microprocessor controller in the printer. Once a bubble of ink begins to form due to heat energy transferred from the heating element into the ink, the ink is thermally isolated from the surface of the heating element. Thus, after the bubble forms, any additional energy provided to the heating element does not transfer into the ink, but is dissipated in the print head heater chip. This results in undesirable overheating of the chip. One solution to this problem is to provide to the heating element only the minimum amount of energy necessary to nucleate the ink. This requires that the printer controller precisely control characteristics of the energy pulses provided to the heating element. Since the amount of heat energy transferred from the heating element into the ink depends upon characteristics of the ink and characteristics of the heating element, the characteristics of the minimum energy pulse should be determined taking into account the ink and heating element characteristics. Therefore, a need exists for an ink jet printer that determines characteristics of a minimum energy pulse to be provided to a resistive heating element based on characteristics of the ink and the heating element. The foregoing and other needs are met by a system for providing an optimum energy pulse to a resistive heating element in an ink jet print head. The optimum energy pulse generated by the invention provides an optimal energy density at a surface of the resistive heating element to cause optimal nucleation of ink near the surface of the resistive heating element. The system includes (a) storing in memory at least one heating element dimensional value that describes at least one physical dimension of the resistive heating element, (b) storing in memory at least one heating element electrical value that describes at least one electrical characteristic of the resistive heating element, and (c) storing in memory an expression that provides a mathematical relationship between the heating element dimensional value, the heating element electrical value, and a current value representing an optimum value of electrical current flowing through the heating element to generate the optimum energy pulse. The system also includes (d) retrieving from memory the heating element in dimensional value, the heating element electrical value, and the expression, (e) determining, based on the expression, the current value representing the optimum value of electrical current flowing through the heating element to generate the optimum energy pulse, (f) generating the optimum energy pulse corresponding to the value determined in step (e), and (g) providing the optimum energy pulse to the heating element. In another aspect, the invention provides a system for providing an optimum energy pulse to a resistive heating element covered by a protective overcoat layer in an ink jet print head. The optimum energy pulse generated by the invention provides an optimal energy density at a surface of the resistive heating element to cause optimal nucleation of ink that is adjacent the surface of the protective overcoat layer. The system includes (a) storing in memory at least one protective overcoat dimensional value that describes at least one physical dimension of the protective overcoat, (b) storing in memory at least one heating element electrical value that describes at least one electrical characteristic of the resistive heating element, (c) storing in memory at least one ink-related coefficient that relates to at least one characteristic of the ink, and (d) storing in memory an expression that provides a mathematical relationship between the protective overcoat dimensional value, the heating element electrical value, the ink-related coefficient, and an optimum time duration of the optimum energy pulse. The system also includes (e) retrieving from memory the protective overcoat dimensional value, the heating element electrical value, the ink-related coefficient, and the expression, (f) determining, based on the expression, the optimum time duration of the optimum energy pulse, (g) generating the optimum energy pulse corresponding to the optimum time duration determined in step (f), and (h) providing the optimum energy pulse to the heating element. Thus, by proper adjustment of the amplitude and duration of the energy pulse provided to the resistive heating elements in the print head, the present invention provides an optimum energy density at the surface of the heating elements. This optimum energy density is just large enough to cause the ink near the heating elements to form a bubble and a droplet. Little or no energy is wasted in excess energy that cannot be transferred into the ink after the bubble is formed. To adjust the amplitude and duration of the energy pulse in providing the optimum energy density, the invention takes into account several factors related to characteristics of the print head, characteristics of the resistive heating elements and the protective overcoat layer, and characteristics of the ink. By storing these factors in memory on the print head and on ink cartridges, and by expressing in mathematical form the relationship between these factors and the optimum pulse energy density, the invention can determine and provide the optimum pulse energy density for practically any combination of ink type and print head design. In another aspect, the invention provides a system for determining a maximum optimal thickness of a protective overcoat layer covering a print head resistive heating element so that energy is optimally transferred into the adjacent ink. The system is implemented by a computer that includes a processor and a memory. The system includes (a) inputting one or more heating element dimensional values that describe one or more physical dimensions of the resistive heating element, (b) inputting one or more heating element electrical values that describe one or more electrical characteristics of the resistive heating element, (c) inputting one or more ink-related coefficients that relate to one or more characteristics of the ink, (d) inputting one or more print head thermal values relate to a thermal characteristic of the print head. The system also includes (e) retrieving from the memory an expression that provides a mathematical relationship between the one or more heating element dimensional values, the one or more heating element electrical values, the one or more ink-related coefficients, the one or more thermal values, and the maximum optimal thickness of the protective overcoat. The system further includes (f) determining, based on the expression, a thickness value representing the maximum optimal thickness of the protective overcoat.

Q: Connotation of "appease" Is "Bob did what he could in his capability to appease them" a positive or negative comment about Bob? A: The term appease itself is fairly neutral: appease - verb pacify or placate (someone) by acceding to their demands. assuage or satisfy (a demand or a feeling). It's not defined as being disparaging, and you can use it fairly neutrally. I appeased my growling stomach by eating a sandwich. We appeased the opposing parties, by throwing some concessions in. However, it does have some negative connotations, going back to pre-World War II, where Britain's policy toward Hitler under Neville Chamberlain was one of appeasement. This has been heavily criticised as allowing Hitler to gain momentum and power, and World War II happening. See the Wikipedia article on Appeasement for more details. See also this question: What is the polite word describing a person who unreasonably says and does things to make a person happy? A: Appeasement as a national policy got negative connotation during WWII: "The term is most often applied to the foreign policy of the British Prime Minister Neville Chamberlain towards Nazi Germany between 1937 and 1939. His policies of avoiding war with Germany have been the subject of intense debate for seventy years among academics, politicians and diplomats. The historians' assessments have ranged from condemnation for allowing Adolf Hitler's Germany to grow too strong, to the judgment that he had no alternative and acted in Britain's best interests. At the time, these concessions were widely seen as positive, and the Munich Pact concluded on 30 September 1938 among Germany, Britain, France, and Italy prompted Chamberlain to announce that he had secured "peace for our time." (http://en.wikipedia.org/wiki/Appeasement) Regarding actions of a single human, I'd say the connotations are fairly neutral. A: Bob did what he could to appease them. I would consider them to be the insulted party here. Appease is being used in the sense of soothing or pacifying. Adults don't need to be soothed or pacified.

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A Field Test for the Estimation of Heart Rate at Lactate Threshold : The 30-minute Cycling Time Trial PublicDeposited Descriptions The purpose of this study was to examine the validity and reliability of the 30-minute cycling time trial to estimate the heart rate at lactate threshold. Recreationally trained cyclists and triathletes (n = 47) performed 3 tests in random order: 1) One graded exercise test to directly determine lactate threshold (Dmax and 1.5mmol increase methods) 2) Two 30-minute stationary cycling time trials on a bicycle ergometer. The average heart rate and power over the last 20 minutes of the time trial was used to estimate lactate threshold. A subset of participants had respiratory gases measured during the graded test to determine ventilatory threshold and VO₂max (n=31). The heart rate and power during the two time trials were not different. The 30-minute cycling time trial over estimated the heart rate at lactate threshold (1.5mmol mean difference = 6.8 bpm, p < 0.0001; Dmax mean difference = 6.0 bpm, p < 0.001). Power during the last 20 minutes of the time trial did not differ from lactate threshold. In the subset of participants, ventilatory threshold heart rate and power were not significantly different than lactate threshold heart rate or power. These findings suggest the 30-minute stationary cycling time trial is reliable but should not be used for estimating the heart rate at lactate threshold.

1. Field of the Invention The present invention pertains to containers used for packaging, shipping, and displaying goods. More particularly, the invention relates to containers having a bottom container section for holding goods therein, and an upper cover section for covering the goods held within the bottom section. 2. Description of the Related Art Display ready containers have become very popular, particularly in retail stores where goods for sale are displayed in the container in which they were shipped. A typical display ready container has separate top and bottom sections formed from separate blanks. The bottom section has side walls and flaps for forming the container bottom. The upper section has side walls and flaps for forming the container top. The upper section typically fits over the side walls of the bottom section to enclose the interior of the container and protect the goods inside, although other configurations are possible. The upper and bottom sections can then be secured together for shipping. Once the container is at the retailer, the upper section can be removed to display the goods within the bottom section. Display ready containers are particularly useful as shipping-display containers. Used to package and ship goods for retail, the outside face of the bottom section can be printed and/or designed with promotional information suitable for display on the retail floor. The retailer, after removing the upper section of the container, places the bottom container section containing the goods on the retail floor. A previous disadvantage of such two piece containers was the number of steps necessary to assemble the container. This disadvantage was overcome with the development of display ready containers that allow for the automation of the set up, packaging and sealing of such containers. One such display ready container is disclosed in U.S. Pat. No. 5,505,368 which is hereby incorporated herein by reference. This patent provides a container assembly having an unopened outer sleeve (that forms the outer cover section when erected), and an unopened inner sleeve (that forms the inner container section when erected) positioned inside the outer sleeve. The inner and outer sleeves, in a flat unopened form also known as a knockdown, are adhered together relative to one another in the positional relationship of the final erected container assembly which allows the top forming flaps of the container assembly to be closed. This allows the container to be assembled and filled with goods with the outer cover section (upper section) already secured to the bottom container section. Once the container is filled with the goods, the top forming flaps attached to the outer cover section are folded over and sealed shut to enclose the container for shipment, thereby eliminating the step of placing the outer cover section over the bottom section, and thereby improving the automation of the packaging process. The retailer then separates the two container sections by breaking the adhesive joints between the two container sections, discarding the upper cover section, and using the bottom container section to hold and display goods on the retail floor. A major advantage of display ready containers of the type described in U.S. Pat. No. 5,505,368 is the ability to automate much of the manufacture, assembly, and filling of the container with goods, thereby minimizing costs. In particular, automation of the manufacturing process has allowed major improvements in minimizing costs and manufacturing time. Previously, older machinery required the lower/inner section of a knockdown to be formed separately, folded from a blank and glued. This lower/inner section was then combined with the blank of the upper/outer section which was glued to and folded around the lower section. Moreover, older machines require greater tolerances between the component sections of the container during manufacture. If the sections are slightly misaligned, the greater tolerances allow for completion of the container, but this also produces a higher percentage of containers that functioned improperly. This is particularly problematic with auto bottom containers where a slight misalignment of the two sections relative to one another may prevent the container from opening properly. Modern machinery, on the other hand, can combine, glue and fold the upper and lower container sections from flat blanks in a single pass through the machinery to make a completed knockdown ready for use, thereby reducing the number of steps needed to make the completed knockdown form of the container. Modern machines can also assemble the various components more precisely, allowing the construction of containers with smaller tolerances, thereby minimizing the percentage of containers that will fail, e.g., not open properly. As modern machines run faster and faster using less steps and with smaller tolerances, however, there is less room for misalignments of the two sections relative to one another when the two sections are combined. It has been found that existing containers are not capable of obtaining the full benefits of the new machinery as the higher production speeds may cause problems, and the tighter tolerances are difficult to obtain with current container configurations. Accordingly, one object of the present invention is to provide an improved display ready container that can be manufactured using high speed automated equipment. Another object is to provide an improved container made with smaller tolerances to minimize the percentage of non-functioning containers. Other advantages will be obvious or may be learned by practice of the invention.

/* * Copyright 2010-2018 JetBrains s.r.o. Use of this source code is governed by the Apache 2.0 license * that can be found in the LICENSE file. */ package codegen.boxing.boxing2 import kotlin.test.* fun printInt(x: Int) = println(x) fun printBoolean(x: Boolean) = println(x) fun foo(arg: Any) { if (arg is Int) printInt(arg) else if (arg is Boolean) printBoolean(arg) else println("other") } @Test fun runTest() { foo(1) foo(true) foo("Hello") }

Pelini resigned from FAU after the 2013 season. He spent the last three seasons as defensive coordinator at Youngstown State of the FCS for his brother, coach Bo Pelini. Carl Pelini spent four seasons as defensive coordinator at Nebraska under his brother. The Youngstown native also spent three seasons working in the Mid-American Conference at Ohio. Carl Pelini returns to the MAC to work for coach Mike Jinks, who is 6-18 in two seasons with the Falcons.

Classic Setup Creating the game deck All cards are used in the deck for the Base game. The Expansion games have station cards which are duplicates of the Base game but with additional lines added. When an Expansion deck is used in combination with a Base deck, any duplicate Base station cards should be removed. These are easily identified as duplicate cards in the Base deck have a black dot in the bottom left and top right corners. In the example below, the top red-backed Euston card is from the London Base deck and has the Northern and Victoria lines only and two black dots in the corners. The bottom blue-backed Euston card is from the London Expansion deck and also has the Overground line, and no black dots. The top card is the one that is removed from the combined game deck. Card deal and setup Shuffle the game pack and deal 7 cards face down to each player, and place the remaining undealt cards face down to form a stock. Turn the top 4 cards of the stock face up to form a set of selection cards. The example below shows the initial game setup for 3 players.

Q: Let $(G,\cdot)$ be a set with an associative operation. Show that the following two Axioms are equivalent Let $(G,\cdot)$ be a set with an associative operation. Show that the following two Axioms are equivalent: (a) : there exists a left-hand neutral element $e'$, so that $\forall a \in G: e'a=a$ (b): There exists a neutral element $e$, so that $\forall a\in G:ea=ae=a$ My attempt: $(a)\Longrightarrow (b) :$ Let $e'$ be the left-hand inverse on $(G,\cdot)$. Now let's take $a,b \in G$: $$ab=a(e'b)=(ae')b=ab.$$ So in order for the associativity on $(G,\cdot)$ to hold, $e'$ has to be right-hand neutral as well. $(b) \Longrightarrow (a):$ Is obvious ? Is this correct? I mean, its quit obvious, thats why I suspect myself jumping to conclusions.. A: The two statements are not equivalent. Although (b) implies (a), it is not the case that (a) implies (b). To verify this, let $G=\{e,a\}$, and define the operation as follows: $ea=a$, $aa=a$, $ae=e$, $ee=e$. That is, the result of multiplying $x$ by $y$ is always $y$. This is easily seen to be associative, since $x(yz) = yz = z$ and $(xy)z=z$. It is also clear that both $e$ and $a$ are left inverses, since $ee=e$, $ea=a$ (and also $ae=e$ and $aa=a$). However, neither $e$ nor $a$ are two-sided inverses. The flaw in your attempt, as has been pointed out, is that associativity does not imply cancellativity. You cannot go from $xy=xz$ to $y=z$, or from $xy=zy$ to $x=z$, from just knowing the operation is associative. But that is what you are attempting to do when claiming that $(ae’)b = ab$ requires $ae’=a$.

Lifeline (2015 video game) Lifeline is a text-based adventure mobile game developed by Three Minute Games for iOS and Android. The player guides the main character, Taylor, through a texting conversation, to survive an unknown moon after their spaceship crashed. Lifeline was written by Dave Justus and published in 2015. Gameplay In the game, players interact by choosing from two different responses to help the main character progress in the story. Taylor responds in real time, taking a regular amount of time to respond after telling the player they are going to sleep, for example. Taylor takes time to complete tasks, and the player has to wait for their response, only seeing the text: [Taylor is busy]. Some decisions require looking up additional information, and if the player makes a wrong decision, it can cause Taylor to die. In the event that Taylor dies, the player can rewind to a past decision and try again. Once the game is completed to any ending, Fast Mode is unlocked, which removes wait times between messages. Plot The plot follows Taylor as they try to find a way back home after crashing on a foreign planet that turns out to be inhabited by hostile, hive-minded parasitic lifeforms known as the Greens. Taylor must overcome natural and unnatural elements in order to manipulate the structures of the planet and call a spaceship to come rescue them. The game is played in real time as Taylor explores, sleeps, and interacts on the planet, so sometimes the player is left waiting for hours before they will hear from the main character again. Characters Taylor is the main character of Lifeline. Taylor is a sassy science student from Earth, acting as a Cadet of the recently crashed Starship Varia. Taylor is resourceful with the material around them, and when in a stressful situation, resorts to quips and humour. As a part of the game, Taylor's gender is left ambiguous, leaving the player to decide. The Lifeline is the character the player plays. The Lifeline is in constant communication with Taylor throughout the game. The player must decide whether to let them die or attempt to save them, using valuable resources. The Lifeline is connected to Taylor through a signal from their EVA suit. Captain Aya is the former captain of the Starship Varia. Taylor finds her in critical condition after the crash. Sequels Lifeline 2: Bloodline (2015) Lifeline 2: Bloodline follows a teenage witch, Arika Lanphear, who is trying to rescue her younger brother. Through the plot, Arika finds many magical objects to assist her in her mission. The Lifeline is connected to Lanphear by blood magic. Lifeline 2: Bloodline was also written by Dave Justus. This game introduces the feature of being able to give the player a name. Arika will respond in certain ways if a specific name is entered. Another difference from the first game is that when a player selects an option in the game, the actual message sent to Arika is different, sounding more natural and allowing the fictional conversation to flow smoothly. Lifeline: Silent Night (2015) Lifeline: Silent Night takes place shortly after Lifeline, following Taylor in another adventure fighting against the Greens. This game was released around Christmas time, and has a very slight Christmas theme. Lifeline: Silent Night was also written by Dave Justus. Lifeline: Whiteout (2016) Lifeline: Whiteout follows another character, V. Adams, who awakes in the middle of a frozen wasteland, with the Lifeline as his only form of communication. This is one of the two games as of current to not involve the Greens. Lifeline: Whiteout was created in collaboration with Eipix Entertainment. Lifeline: Crisis Line (2016) Lifeline: Crisis Line takes place in Austin, Texas, following Austin Police Department Detective Alex Esposito. Esposito is investigating the murder of Jason Leder, which leads him into a load of trouble. The Lifeline is connected to Esposito through a mobile app called HelpText. Lifeline: Crisis Line was written by Lilah Sturges. This game requires more external efforts than prior games, which would only require one or two internet searches for information. Alex requires the player to visit an external site and a fake Twitter page to find information for him. Lifeline: Flatline (2016) Lifeline: Flatline follows a medical patient, Wynn, as she tries to escape from the hospital that she's trapped in. Unlike the other games, this story plays out more like a horror story. The Lifeline is connected to Wynn telepathically. Lifeline: Flatline was written by Daryl Gregory. Lifeline: Halfway To Infinity (2016) Lifeline: Halfway To Infinity is the third installment in the Taylor series, taking place shortly after the last two games. This time, Taylor is stranded in space, taking on a strangely familiar foe. Lifeline: Halfway to Infinity was also written by Dave Justus, and was the last story in Taylor's chronology to be written by him. Lifeline: Whiteout 2 (2017, partial release) Lifeline: Whiteout 2 is the mostly unreleased sequel to Lifeline: Whiteout, following V. Adams in another adventure, shortly after his last. The Lifeline Library app allows for a part of the game to be played. Lifeline: Whiteout 2 was created in collaboration with Eipix Entertainment. Other Media Lifeline Jump Lifeline Jump is an online platformer loosely based on the events of Lifeline. The game is hosted on the Big Fish Games website. Lifeline Library Lifeline Library is a mobile app designed to give users "exclusive first access to news, updates, and new stories." Users have access to artwork relating to the game, and access to Lifeline: Silent Night, Lifeline: Whiteout, and the first chapter of Lifeline: Whiteout 2. Lifeline Official Twitter The Official Twitter account promotes the upcoming and existing games and stories. On certain occasions in the past, Twitter users could converse with one of the Lifeline characters via the Twitter account. A special Twitter-only interactive event took place called Lifeline Float. Rather than an individual player making decisions in the app, many Twitter followers would interact with the character, Arthur, through Tweets and replies made on the twitter page. After a change of management on the Lifeline Twitter account, most of these events and occasions ceased, including their previous retweeting of fan art. For awhile they were strictly promoting Lifeline Universe, but as if June 2018 that too has ceased. Lifeline Universe After the release of Lifeline: Whiteout 2, Three Minute Games introduced a new app, Lifeline Universe in 2017. This app hosts all previous Lifeline stories, and all new ones, as released. The new installments are written by established authors and contributors from the "Author Program", who have applied and partnered with the company. These new stories vary from being continuations of past series, to original stories. Stories are hidden behind micro transactions. So far, the app has only been released on the Google Play Store, and has a rating of 3.6. Interest has declined in the series after the release of Lifeline Universe, with users accusing the company of selling out, and claiming the stories and app have worsened in quality. Replies to the Lifeline Twitter account are often negative, wishing for the series to return to the old characters and the old style, or asking for a release for the App Store. The Lifeline Universe Twitter and Instagram have been silent since June 29, 2018. On August 15, 2018, Big Fish Games has noted in a Zendesk that they are still working on new content for players. However, they soon followed up with another notice, announcing that the Lifeline Universe service would come to a close early November of the same year. Reception Lifeline received 3 and a half stars on TouchArcade, which said the game, "Manages to create an emotional connection to Taylor is a fantastic writing achievement". The game received 8/10 on Pocket Gamer, praising it by saying, "For a few brief hours I cared - really cared - about the fate of a completely fictional character. I don't think any other game I've played has made me feel that way before." Metacritic gave the game a score of 77/100. References Category:2010s interactive fiction Category:2015 video games Category:Android (operating system) games Category:IOS games Category:Mobile games Category:Video games developed in the United States Category:Adventure games Category:Single-player video games

Index: gcc-4.9.2/gcc/cp/Make-lang.in =================================================================== --- gcc-4.9.2/gcc/cp/Make-lang.in (revision 233574) +++ gcc-4.9.2/gcc/cp/Make-lang.in (working copy) @@ -111,7 +111,7 @@ else # deleting the $(srcdir)/cp/cfns.h file. $(srcdir)/cp/cfns.h: endif - gperf -o -C -E -k '1-6,$$' -j1 -D -N 'libc_name_p' -L ANSI-C \ + gperf -o -C -E -k '1-6,$$' -j1 -D -N 'libc_name_p' -L C++ \ $(srcdir)/cp/cfns.gperf --output-file $(srcdir)/cp/cfns.h # Index: gcc-4.9.2/gcc/cp/cfns.gperf =================================================================== --- gcc-4.9.2/gcc/cp/cfns.gperf (revision 233574) +++ gcc-4.9.2/gcc/cp/cfns.gperf (working copy) @@ -1,3 +1,5 @@ +%language=C++ +%define class-name libc_name %{ /* Copyright (C) 2000-2015 Free Software Foundation, Inc. @@ -16,14 +18,6 @@ for more details. You should have received a copy of the GNU General Public License along with GCC; see the file COPYING3. If not see <http://www.gnu.org/licenses/>. */ -#ifdef __GNUC__ -__inline -#endif -static unsigned int hash (const char *, unsigned int); -#ifdef __GNUC__ -__inline -#endif -const char * libc_name_p (const char *, unsigned int); %} %% # The standard C library functions, for feeding to gperf; the result is used Index: gcc-4.9.2/gcc/cp/cfns.h =================================================================== --- gcc-4.9.2/gcc/cp/cfns.h (revision 233574) +++ gcc-4.9.2/gcc/cp/cfns.h (working copy) @@ -1,5 +1,5 @@ -/* ANSI-C code produced by gperf version 3.0.3 */ -/* Command-line: gperf -o -C -E -k '1-6,$' -j1 -D -N libc_name_p -L ANSI-C cfns.gperf */ +/* C++ code produced by gperf version 3.0.4 */ +/* Command-line: gperf -o -C -E -k '1-6,$' -j1 -D -N libc_name_p -L C++ --output-file cfns.h cfns.gperf */ #if !((' ' == 32) && ('!' == 33) && ('"' == 34) && ('#' == 35) \ && ('%' == 37) && ('&' == 38) && ('\'' == 39) && ('(' == 40) \ @@ -28,7 +28,7 @@ #error "gperf generated tables don't work with this execution character set. Please report a bug to <bug-gnu-gperf@gnu.org>." #endif -#line 1 "cfns.gperf" +#line 3 "cfns.gperf" /* Copyright (C) 2000-2015 Free Software Foundation, Inc. @@ -47,26 +47,19 @@ for more details. You should have received a copy of the GNU General Public License along with GCC; see the file COPYING3. If not see <http://www.gnu.org/licenses/>. */ -#ifdef __GNUC__ -__inline -#endif -static unsigned int hash (const char *, unsigned int); -#ifdef __GNUC__ -__inline -#endif -const char * libc_name_p (const char *, unsigned int); /* maximum key range = 391, duplicates = 0 */ -#ifdef __GNUC__ -__inline -#else -#ifdef __cplusplus -inline -#endif -#endif -static unsigned int -hash (register const char *str, register unsigned int len) +class libc_name { +private: + static inline unsigned int hash (const char *str, unsigned int len); +public: + static const char *libc_name_p (const char *str, unsigned int len); +}; + +inline unsigned int +libc_name::hash (register const char *str, register unsigned int len) +{ static const unsigned short asso_values[] = { 400, 400, 400, 400, 400, 400, 400, 400, 400, 400, @@ -122,14 +115,8 @@ along with GCC; see the file COPYING3. If not see return hval + asso_values[(unsigned char)str[len - 1]]; } -#ifdef __GNUC__ -__inline -#ifdef __GNUC_STDC_INLINE__ -__attribute__ ((__gnu_inline__)) -#endif -#endif const char * -libc_name_p (register const char *str, register unsigned int len) +libc_name::libc_name_p (register const char *str, register unsigned int len) { enum { Index: gcc-4.9.2/gcc/cp/except.c =================================================================== --- gcc-4.9.2/gcc/cp/except.c (revision 233574) +++ gcc-4.9.2/gcc/cp/except.c (working copy) @@ -1030,7 +1030,8 @@ nothrow_libfn_p (const_tree fn) unless the system headers are playing rename tricks, and if they are, we don't want to be confused by them. */ id = DECL_NAME (fn); - return !!libc_name_p (IDENTIFIER_POINTER (id), IDENTIFIER_LENGTH (id)); + return !!libc_name::libc_name_p (IDENTIFIER_POINTER (id), + IDENTIFIER_LENGTH (id)); } /* Returns nonzero if an exception of type FROM will be caught by a

Lymphocyte replicating ability in individuals exposed to arsenic via drinking water. A human monitoring study was carried out to explore the effect on lymphocyte proliferation of chronic exposure to arsenic (As) via drinking water. Blood and urine samples were taken from volunteers from a town where levels of As in the drinking water averaged 412 micrograms/l, and from a matched group of individuals, with similar socioeconomic status, that drank water with As average levels of 37.2 micrograms/l. Exposure was assessed by questionnaires and by determining the levels of As in urine and water samples. The evaluation of the peripheral blood lymphocyte proliferation was done at different culture times using labelling (LI), mitotic (MI) and replication indexes (RI) as endpoints. No significant differences were seen for either LI or MI, except for MI in 72 h cultures and in LI in males and females with skin lesions vs. those without lesions. Significant differences in RI were seen for exposed females but not for males. Correlations between LI and MI showed that progression from the initial S-to M-phase is altered in exposed individuals. Arsenic exposure as well as lead and mercury affect cellular immune response, making the endpoints of cell proliferation variables of interest in population monitoring study design, since they might provide information in health impairment due to exposure, which is important in risk assessment.

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/* Copyright The Kubernetes Authors. Licensed under the Apache License, Version 2.0 (the "License"); you may not use this file except in compliance with the License. You may obtain a copy of the License at http://www.apache.org/licenses/LICENSE-2.0 Unless required by applicable law or agreed to in writing, software distributed under the License is distributed on an "AS IS" BASIS, WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. See the License for the specific language governing permissions and limitations under the License. */ // Code generated by informer-gen. DO NOT EDIT. package v1 import ( "context" time "time" networkingv1 "k8s.io/api/networking/v1" metav1 "k8s.io/apimachinery/pkg/apis/meta/v1" runtime "k8s.io/apimachinery/pkg/runtime" watch "k8s.io/apimachinery/pkg/watch" internalinterfaces "k8s.io/client-go/informers/internalinterfaces" kubernetes "k8s.io/client-go/kubernetes" v1 "k8s.io/client-go/listers/networking/v1" cache "k8s.io/client-go/tools/cache" ) // IngressInformer provides access to a shared informer and lister for // Ingresses. type IngressInformer interface { Informer() cache.SharedIndexInformer Lister() v1.IngressLister } type ingressInformer struct { factory internalinterfaces.SharedInformerFactory tweakListOptions internalinterfaces.TweakListOptionsFunc namespace string } // NewIngressInformer constructs a new informer for Ingress type. // Always prefer using an informer factory to get a shared informer instead of getting an independent // one. This reduces memory footprint and number of connections to the server. func NewIngressInformer(client kubernetes.Interface, namespace string, resyncPeriod time.Duration, indexers cache.Indexers) cache.SharedIndexInformer { return NewFilteredIngressInformer(client, namespace, resyncPeriod, indexers, nil) } // NewFilteredIngressInformer constructs a new informer for Ingress type. // Always prefer using an informer factory to get a shared informer instead of getting an independent // one. This reduces memory footprint and number of connections to the server. func NewFilteredIngressInformer(client kubernetes.Interface, namespace string, resyncPeriod time.Duration, indexers cache.Indexers, tweakListOptions internalinterfaces.TweakListOptionsFunc) cache.SharedIndexInformer { return cache.NewSharedIndexInformer( &cache.ListWatch{ ListFunc: func(options metav1.ListOptions) (runtime.Object, error) { if tweakListOptions != nil { tweakListOptions(&options) } return client.NetworkingV1().Ingresses(namespace).List(context.TODO(), options) }, WatchFunc: func(options metav1.ListOptions) (watch.Interface, error) { if tweakListOptions != nil { tweakListOptions(&options) } return client.NetworkingV1().Ingresses(namespace).Watch(context.TODO(), options) }, }, &networkingv1.Ingress{}, resyncPeriod, indexers, ) } func (f *ingressInformer) defaultInformer(client kubernetes.Interface, resyncPeriod time.Duration) cache.SharedIndexInformer { return NewFilteredIngressInformer(client, f.namespace, resyncPeriod, cache.Indexers{cache.NamespaceIndex: cache.MetaNamespaceIndexFunc}, f.tweakListOptions) } func (f *ingressInformer) Informer() cache.SharedIndexInformer { return f.factory.InformerFor(&networkingv1.Ingress{}, f.defaultInformer) } func (f *ingressInformer) Lister() v1.IngressLister { return v1.NewIngressLister(f.Informer().GetIndexer()) }

#!/bin/sh basedir=$(dirname "$(echo "$0" | sed -e 's,\\,/,g')") case `uname` in *CYGWIN*) basedir=`cygpath -w "$basedir"`;; esac if [ -x "$basedir/node" ]; then "$basedir/node" "$basedir/../insert-module-globals/bin/cmd.js" "$@" ret=$? else node "$basedir/../insert-module-globals/bin/cmd.js" "$@" ret=$? fi exit $ret

OwnersDirect.co.uk is part of the HomeAway family, the world leader in holiday home rentals with over 1 million listings. We offer the largest selection of properties for any travel occasion and every budget. We're committed to helping families and friends find a perfect holiday home rental to create unforgettable travel experiences together. Alison Wilkie Overview Property Updated: 06-Dec-2016 2 bedrooms, 2 bathrooms, with stunning sea and mountain views Achbeag is a traditional croft house that has been converted into a very comfortable holiday cottage. It retains many of its original features, with exposed stonework in the sitting room and a multi-fuel stove. It has one en-suite double bedroom and one twin bedroom. The small, remote village of Fearnmore is approximately 25 minutes' drive from Applecross village and 25 minutes' drive from Shielding. Achbeag has stunning views across Loch Torridon towards the Torridonian mountains and the Western Isles, with beautiful beaches nearby. The surrounding landscapes are breathtaking. Achbeag is a perfect base for exploring the Applecross peninsula, which offers a beautiful coastline, mountaineering, sea kayaking, fishing, ancient woodlands with rare species of mosses and lichens, wildlife, and excellent local food. A lovely property in a beautiful setting, ideal for a'get away from it all break' Our intention was to spend a week in Scotland away from work, emails etc and do lots of walking And see lots of wildlife.... and that is exactly what we got. Otters, pine martins, sea eagles and lots of other stuff. After a busy day out walking, it was lovely coming back to such a warm and cosy cottage. Perfect! Review Submitted: 16-Nov-2016 Date of Stay: Oct 2016 Source: Owners Direct, from HomeAway Owner's Response: Thank you-I'm glad you had a lovely time and got a week-earned rest. About the Owner I live in East Lothian, Scotland, with my husband and 2 young boys. As a family, we love the outdoors and we bought Achbeag so that we could all enjoy spending time in one of our favourite parts of Scotland. The children love to go down to the little natural harbour at Fearnmore to potter around in the bay and on the rocks. Speaks English Calendar last updated: 6 December, 2016 Peace of mind when you complete your reservation online and finalise payment on HomeAway We'll back you with our Book with Confidence Guarantee You'll get comprehensive payment protection when you book and finalise payment on our website 4 Reviews 4.5 based on 4 holidaymaker reviews A lovely property in a beautiful setting, ideal for a'get away from it all break' Our intention was to spend a week in Scotland away from work, emails etc and do lots of walking And see lots of wildlife.... and that is exactly what we got. Otters, pine martins, sea eagles and lots of other stuff. After a busy day out walking, it was lovely coming back to such a warm and cosy cottage. Perfect! Review Submitted: Nov 16, 2016 Date of Stay: Oct 2016 Source: Owners Direct, from HomeAway Owner's Response: Thank you-I'm glad you had a lovely time and got a week-earned rest. Location From the Owner “We love Achbeag because it is hidden away and nestled in a sheltered part of Fearnmore, and it has wonderful sea views from every room. It is very cosy with its multi-fuel stove in the sitting room. It is the perfect size for a small family and it is warm and comfortable all year round. At Achbeag, we can be thoroughly disconnected from the rest of the world, and have a truly restful time.” Achbeag is a very remote cottage. There is a beautiful coastline and exceptional, natural wilderness. The nearest towns are Applecross and Shielding (each approximately 13 miles away). The Applecross Inn is famous for its fresh, local seafood, and it is open all year round. There are several other wonderful eateries in both Applecross and Shiledaig, although they may be closed in winter. There is an ancient hazel wood in Applecross, with many species of lichens and mosses, which has a lovely, short walk (0.5 km) through. There is a bird hide at Milton Loch, just outside of Applecross, with many species of birds, insects and an unusual orchid. There are many wonderful walks, including those from the visitor centre at Beinn Eighe. When would you like to stay? Your dates are Available! Have a question for the owner? Adults Children By clicking 'Send Email' you are agreeing to our Terms and Conditions and Privacy Policy. We will contact you with OwnersDirect news, special offers and other information. You can opt out at any time. Find out more here.

<Project Sdk="Microsoft.NET.Sdk" ToolsVersion="15.0" xmlns="http://schemas.microsoft.com/developer/msbuild/2003"> <PropertyGroup> <TargetFrameworks>netstandard2.0;net472</TargetFrameworks> <DefineConstants>$(DefineConstants);NO_DOTNETCORE_BOOTSTRAP</DefineConstants> <AssemblyName>Fake.Core.Xml</AssemblyName> <OutputType>Library</OutputType> </PropertyGroup> <PropertyGroup> <DefineConstants>$(DefineConstants);NETSTANDARD;USE_HTTPCLIENT</DefineConstants> </PropertyGroup> <PropertyGroup Condition=" '$(Configuration)' == 'Release' "> <DefineConstants>$(DefineConstants);RELEASE</DefineConstants> </PropertyGroup> <ItemGroup> <Compile Include="AssemblyInfo.fs" /> <Compile Include="Xml.fs" /> </ItemGroup> <ItemGroup> <ProjectReference Include="..\Fake.Core.String\Fake.Core.String.fsproj" /> </ItemGroup> <Import Project="..\..\..\.paket\Paket.Restore.targets" /> </Project>

The impact of uncertainties in the CT conversion algorithm when predicting proton beam ranges in patients from dose and PET-activity distributions. The advantages of a finite range of proton beams can only be partly exploited in radiation therapy unless the range can be predicted in patient anatomy with <2 mm accuracy (for non-moving targets). Monte Carlo dose calculation aims at 1-2 mm accuracy in dose prediction, and proton-induced PET imaging aims at ∼2 mm accuracy in range verification. The latter is done using Monte Carlo predicted PET images. Monte Carlo methods are based on CT images to describe patient anatomy. The dose calculation algorithm and the CT resolution/artifacts might affect dose calculation accuracy. Additionally, when using Monte Carlo for PET range verification, the biological decay model and the cross sections for positron emitter production affect predicted PET images. The goal of this work is to study the effect of uncertainties in the CT conversion on the proton beam range predicted by Monte Carlo dose calculations and proton-induced PET signals. Conversion schemes to assign density and elemental composition based on a CT image of the patient define a unique Hounsfield unit (HU) to tissue parameters relationship. Uncertainties are introduced because there is no unique relationship between HU and tissue parameters. In this work, different conversion schemes based on a stoichiometric calibration method as well as different numbers of tissue bins were considered in three head and neck patients. For Monte Carlo dose calculation, the results show close to zero (<0.5 mm) differences in range using different conversion schemes. Further, a reduction of the number of bins used to define individual tissues down to 13 did not affect the accuracy. In the case of simulated PET images we found a more pronounced sensitivity on the CT conversion scheme with a mean fall-off position variation of about 1 mm. We conclude that proton dose distributions based on Monte Carlo calculation are only slightly affected by the uncertainty on density and elemental composition introduced by unique assignment to each HU if a stoichiometric calibration is used. Calculated PET images used for range verification are more sensitive to conversion uncertainties causing an intrinsic limitation due to CT conversion alone of at least 1 mm.

Q: Isometry on a round n-Sphere preserves geodesic Q) If $(M,g)$ is a Riemannian manifold, $p \in M$ and $f \, : \, M \, \rightarrow \, M$ an isometry such that $\mathrm{D}_{p}f \cdot v = v$ for some $v \in T_{p}M$ then, for the geodesic $\gamma \, : \, [a,b] \, \rightarrow \, M$ with $\gamma(0) =p$ and $\gamma'(0)=v$, then prove that we have $f \circ \gamma = \gamma$ My work so far: Once I have proven that $f \circ \gamma$ is a geodesic, then by uniqueness of geodesic it automatically proves that its equal to $\gamma$. I have shown that $f \circ \gamma$ is locally length minimizing because $\gamma$ is a geodesic and they have the same integrated length due to isometry (chosen over any small interval). So the I have proven the last part of the question, but need to see that $f \circ \gamma$ would indeed be a geodesic initialized at $p$ My question is this: how do I show that $f \circ \gamma$ has constant speed and initialzed at the same $p$ that $\gamma$ is? A: First note that $D_pf$ is a linear mapping from $T_pM$ to $T_{f(p)}M$. Since $v\in T_pM$ and $D_pf$ maps $v$ to $v$, $(D_pf)v=v\in T_pM\cap T_{f(p)}M$, which implies $f(p)=p$. This proves $f\circ\gamma(0)=f(\gamma(0))=f(p)=p$. Second, the initial velocity of $f\circ\gamma$ is $(f\circ\gamma)'(0)=(D_{\gamma(0)}f)\gamma'(0)=(D_pf)v=v$.

basic: organization: 腾讯 cellPhone: - 0755-83765566 - 0755-86013388 - 010-62671188 - 021-54569595 - 028-85225111 - 020-81167888 url: https://www.tencent.com/

Want To Optimize Your Website For Search Engine Crawlers? Start With These Tips Menu Want To Optimize Your Website For Search Engine Crawlers? Start With These Tips Do you own a website or blog and want to get the most out of it by increasing your traffic without spending a dime? Then you should look into the world of search engine optimization! Search engine optimization gets more people to your site for free. Read on to learn how you, too, can do this! You should make sure that the search engine optimization you choose, uses a quality and proven technique. Stuffing keywords haphazardly throughout your site won't do anything but lower your audience's confidence in your legitimacy. Consider custom-made content that is specific to your business. you could check here will draw in the audience and encourage them to explore the rest of your website. When looking to ramp up your online profile, don't forget that image names count in search results - quite heavily, in fact. Be sure to give your images names that searchers will easily find. If you're writing about a particular product, be sure to include keywords for that product in the image name itself, so that the image will pop up in a Google image search result. Leave comments on other people's blogs to help the rankings for your website and increase your traffic. This is one way to get backlinks back to your site, but what's more is that you are interacting with your peers and possible customers by giving your relevant opinion. This makes people interested in you and what else you have to say. Just don't forget to link back to your own blog or website! Tag optimization is really the key to search engine optimization, because your tags are one of the most important aspects of your website. In days gone by tags were just a way to get across basic info, now tags are used in order to locate your site and to rank it accordingly! Before you do any extensive optimization on your web site, make sure that it shows up in a basic web search. Type the URL of your site into a search engine and check to see if it shows up in the results. It's also a good idea to search for your top products and services to see if they appear. New Business Development Program Debuts at the 2018 National Stationery Show - Gifts & Dec Using strong keywords can be beneficial when it comes to search engine optimization. Using keywords most relevant to your business or product will drive it to the top of different search engines, and help drive people to your site. Using agence de referencement web quebec may flag you as a spammer so keep it to a few strong relevant keywords. https://smallbiztrends.com/2018/01/mobile-seo-facts.html are another HTML formatting scheme that wise webmasters should try to avoid when optimizing a website for the search engines. Sometimes tables are indispensable; such as when you need to present complex data. However, table formatting that is used stylistically, or for convenience, should be avoided. Tables are indexed more slowly by search engines, and content in tables is more likely to be overlooked. When building your web presence, don't forget to add your website to the niche link directories. Whatever product you sell, from knitwear to financial services, there's bound to be a specialized website that caters to people interested in that type of business, so look for those sites and get your links listed. That will, of course, help boost your search engine rankings and bring in more traffic. Be descriptive with all your links, be they video, banner, text, or graphics. No one will be interested in clicking a link that simply says "Click me." They want to know what they are getting themselves into! Using your keywords in the description can also bump you up on the search engine lists, so it is a win-win! When you build your web site make sure that you do not use Flash for that. This is because many search engine crawlers do not understand Flash. Using HTML is the most popular option and it is the easiest to keep up with. Also remember to keep all of the flashy graphics to a minimum. Securing a steady volume of backlinks is critical to all internet marketers, but it is important to know that all backlinks to your site are not equal. Google assigns page ranks to all websites as part of its ranking process. Your goal should be to attract backlinks from websites that have a page rank that is at least equal to your own, but preferably higher. Higher page rank, signifies higher status in the eyes of the search engine and the fact they are linking back to you, can raise your own status in search rankings. Check your site often for broken links. You don't want to have links that you think are working, and your customers are not able to use. You can use Xenu, which is a tool that will tell you if links are broken. Test every single link you have often. There is no one single method of search engine optimization, but using meta tags is a good start. When choosing your tag be sure that the keyword actually matches your website. Use a search phrase that you think your target market would use to find your product or service. Figure out what .gov, .edu, and .us websites are linking to and provide it! Link juice from these websites will raise your page ranking substantially. So you have to think of content that they would want their readers visiting. When you are looking for an SEO services company, it's very hard to choose because they all claim to be the best in the business! http://all4webs.com/crationdesitewebquebec/ that may not occur to you is that you would be better off with an SEO service company that is located near you. Even though, it is possible to do business entirely online these days, it's not always desirable. Working closely with an SEO services company is something you should probably do in person. Add your keywords into headlines and subtitles. Sometimes, it's hard to write meaningful text with well-placed keywords, or maybe some people are just tired of it. Either way, an easy tip to work those keywords in is to use them in your page headline, and as section headers. This works especially well when you want to work in several long-tail keyword phrases. This also helps structure your content and make sure it really answers the promise of the page's title. When linking to content on your own website, use absolute links. These are links that never change, and typically have keywords in the file name. Also avoid using HTTPS unless you absolutely need to, like on an ordering page. If you avoid both of these pitfalls you'll get more link juice out of incoming links. Your goal should always be to achieve very high placement on the search engines, but you cannot fly blindly and hope that your site is somehow plucked from obscurity. You need to follow great advice like this, in order to formulate a proper plan of attack so that your site earns great placement.

The news that the Metropolitan Police is to reopen the investigation into the murder of PC Keith Blakelock comes as no surprise to me. The truth is that every time the black community of Tottenham feels that the scales of justice are finally turning in our direction, the Met does its best to remind us where power really lies. My name is Stafford Scott; I worked as the senior youth and community worker on Broadwater Farm Estate, Tottenham, in the immediate aftermath of 6 October 1985, a date now synonymous with the 'Tottenham riots' and the murder of PC Blakelock. I was arrested three times during the Farm investigations, twice on the grounds that I was involved in the Blakelock murder; I was never charged and successfully sued the police for their impertinence. My younger brother was charged with riot and affray; he was also found not guilty. My elder brother was charged with offences resulting from the raid on our family home to arrest me; he, too, was found not guilty of any offence and successfully sued the Met. Although I became a major target in the police investigation, I have also gained the somewhat 'privileged' position of being one of the few black men who can say publicly: 'I was there, I saw it from the start.' Because of what I saw that night - racist policing designed to suppress the community's right to protest at the death of a black mother - I was to become one of the 'leaders' of the Broadwater Farm Defence Campaign and, as such, have followed the police investigation and resulting court cases avidly. The prelude to this latest investigation, a case review, began almost to the day Winston Silcott was awarded damages of £50,000 in an out-of-court settlement from the Met. We were told at that time that it would take a year to complete, but it has taken more than three years, and news that there is now to be a new full-blown police inquiry comes just a few weeks after Winston's release from prison. This has nothing to do with justice, this is about revenge. A bobby was killed in horrific circumstances and no one has paid for it. It was OK as long as Winston was locked up, even though he was acquitted of this crime almost a decade ago. Isn't it strange that for 18 years the Met and the majority of the media have gone to great lengths to convince us that all the evidence led to Winston, yet now that he is free they have miraculously identified six new suspects? They claim to have gleaned new information by going over all the 6,000 statements that they took in the original investigation. However, that investigation has been discredited in the Court of Appeal; the forensic ESDA test revelations proved conclusively that Winston had been framed. So damning was the evidence against the police who led the original inquiry that the prosecutor, Roy Amlot QC, uttered the following words in response to a question from defence counsel: 'The answer is, unequivo cally, we would not have gone against Braithwaite, against Raghip, or against any other defendants having learned of the apparent dishonesty of the officer in charge of the case.' In essence, the Crown was accepting what the Broadwater Farm Defence Campaign had been saying all along - that this was a corrupt investigation Revenge, however, is not justice. The statements that the Met refer to now are, in many cases, complete fantasy and were dismissed as such by Mr Justice Hodgson, the judge in the original trial. This time around, I do not believe the judiciary is going to be as compliant and gullible as it was in 1987. Another thing that will not be the same is the community. We can never be made to be as frightened now as we were then. Like an army of occupation, hundreds of the Met's finest 'took back' the estate and stayed for almost 18 months. At the same time, armed police squads were dragging us to police stations all over London, denying us access to solicitors, and fitting up the most vulnerable among us. Some things have changed, though, now that the world knows about the 'institutional racism' within the Met. It would be nice to think that, as a result, white Britain will not turn its back on us as it did then. The initial investigation into the disturbances on Broadwater Farm was said to be the most expensive and intensive in the history of British policing. Since then, we have had at least two more equally intensive investigations. We will probably never be told the full costs. I do know one thing, though. If the Met employed just 1 per cent of the resources used in these investigations on stopping the guns and drugs from pervading our cities, my community would be in a healthier state. If the Met spent 1 per cent of the time and expense on investigating crimes committed against black people, especially crimes committed against us by the police, then there would be no need for riots. The Met had its chance of honouring its dead officer by getting it right the first time. It failed miserably, and it's time it accepted that because of its thirst for vengeance the real murderers of Keith Blakelock may never be found.

True MRI assessment of stem cell chondrogenesis in a tissue engineered matrix. Developing a non-invasive method to monitor the growth of tissue-engineered cartilage is of utmost importance for tracking the progress and predicting the success or failure of tissue-engineering approaches. Magnetic Resonance Imaging (MRI) is a leading non-invasive technique suitable for follow-through in preclinical and clinical stages. As complex tissue-engineering approaches are being developed for cartilage tissue engineering, it is important to develop strategies for true non-invasive MRI monitoring that can take into account contributions of the scaffold, cells and extracellular matrix (ECM) using MR parameters. In the current study, we present the preliminary MRI assessment of chondrogenic differentiation of human bone marrow derived stem cells seeded onto a specially designed osteochondral matrix system. We performed water relaxation times (T1 and T2) MRI measurements at 7, 14 and 28 days after cell seeding. The MRI experiments were performed for the tissue-engineered cartilage as well as for acellular scaffolds. We identified that the contribution of the scaffold is the dominant contribution in MR parameters of engineered cartilage and that it hinders observation of the tissue growth. An attempt is made to filter out this contribution, for the first time, in order to make a true observation of tissue growth using MRI.

Docker is in trouble - artsyca https://www.zdnet.com/article/docker-is-in-deep-trouble/ ====== mikece So who is the most likely buyer: Google, Amazon, Microsoft, or IBM? Or Oracle?? ~~~ mister_hn I think RedHat will do, probably ~~~ CrankyBear Red Hat's already replaced Docker's functionality with podman and buildah in RHEL 8. Technically, there's no reason for them to buy Docker. ------ artsyca I'm utterly tired of the way tech executives are dressing nowadays; this audience clearly doesn't believe it matters in the slightest, but I'm challenging anyone to come up with some inkling of why it actually might -- ~~~ artsyca Let me give you an argument from a functionalist perspective, as a designer -- If you're never going to wear a necktie, why bother ever wearing a collared shirt? The collar is in place to hold the tie, you don't need a tie, you don't need a collar, so don't wear one ~~~ flukus Pragmatic answer: because it crosses some threshold where it's deemed I'm dressed appropriately at work and a normal shirt wouldn't. > The collar is in place to hold the tie, you don't need a tie, you don't need > a collar, so don't wear one A collar can also be popped to provide extra shade to the neck, it has it's own functionality independent of the tie. I'm not sure if these execs are getting enough sun that it matters, but I certainly do.

Establishing differential gene expression in sporulating Bacillus subtilis: phosphorylation of SpoIIAA (anti-anti-sigmaF) alters its conformation and prevents formation of a SpoIIAA/SpoIIAB/ADP complex. Sigma-factor F (sigmaF) is a key transcription factor that initiates prespore development in Bacillus subtilis. Its activity is controlled by an anti-sigma factor, SpoIIAB, which is also a protein kinase that phosphorylates the anti-anti-sigma factor SpoIIAA. We have examined our earlier prediction that SpoIIAA must undergo a major change in its properties when phosphorylated. Upon gel filtration in the presence of ADP, SpoIIAA-P was eluted from a Superdex column much later than SpoIIAB, whereas SpoIIAA was coeluted with SpoIIAB, indicating the formation of a protein/protein complex. The complex contained ADP, and had two monomers of SpoIIAA to each SpoIIAB dimer. Its dissociation constant was 13 mu M. Gel permeation on high-performance liquid chromatography (HPLC) suggested an apparent molecular mass for SpoIIAA-P which was much higher (23.5 kDa) than that of SpoIIAA (15.8 kDa), but Ferguson plots showed that SpoIIAA-P was not a phosphorylated dimer of SpoIIAA. Our tentative conclusion, that SpoIIAA and SpoIIAA-P differ markedly in conformation, was confirmed by the results of partial digestion with chymotrypsin.

Q: Why do I get different results with same random seed, same computer, same program I am running a simulation with a lot of modules. I use random a number of times. I read input files. I use rounding. Of course, I am setting a random.seed(1) in the very first line of my program, immediately after importing random. Even though, shouldn't I get exactly the same result running the same program same parameters in the same computer with the same input files? A: Inject the source for random numbers as a service into the modules using it. You can then easily replace it with a deterministic version that gives a predefined sequence of numbers. This is for example a prerequisite for proper unit testing and it also applies to things like the time, too. Concerning your case, you could e.g. inject an instance of random.Random instead of using a global (the one provided by the random module). This generator could then be seeded appropriately (constructor argument) to provide reproducible sequences. Bad code: def simulation(): sum = 0 for i in range(10): sum += random.random() return sum / 10 # Think about how to test that code without # monkey-patching random.random. Good code: def simulation(rn_provider): sum = 0 for i in range(10): sum += rn_provider() return sum / 10 rng1 = random.Random(0) sum1 = simulation(rng1.random) rng2 = random.Random(0) sum2 = simulation(rng2.random) print(sum1 == sum2) The code here uses a simple function parameter. For classes, you could also use "dependency injection". BTW: Remember hearing that globals are bad? Here's your example why. ;)

Josephine Witt Josephine Witt (born June 22, 1993) is a German activist and former member of the FEMEN group. Witt, whose birth name is Josephine Marckmann, was born in Hamburg in 1993. Her mother is a physiotherapist, and her father owns a solar panel business. After high school, she worked for eight months for a charity in Bolivia. She studied philosophy and dentistry at the University of Hamburg. In April 2013, she was involved in a FEMEN topless protest against Russian president Vladimir Putin during his visit to the Hannover Messe with German chancellor Angela Merkel. The following month, Witt and two other FEMEN activists were arrested in Tunis, where they were protesting the detention of Amina Tyler, another activist. Witt and her two fellow activists were convicted of lewd conduct in June and sentenced to four months and one day in prison; after a month, the remainder of the sentence was suspended and they were released. In an interview with a student magazine, Witt described the purpose of the Tunisia protest: "In FEMEN, we are concerned with the question of who owns women's bodies, when we go naked into the street, we do so with confidence and determination. We emphasize control over our own bodies." Returning to her native Germany, Witt drew attention with another topless protest in December 2013, as she and another activist interrupted a television talk show to decry inhumane working conditions in Qatar, where the 2022 FIFA World Cup is to be held. In the middle of the show, the women bared their breasts, which had been painted to resemble soccer balls, and chanted "boycott FIFA mafia" and "don't play around with human rights." Later that month, she stormed the altar of the Catholic cathedral in Cologne during a Christmas mass to protest exclusion in the church. Again, she was topless, this time with the words "I am God" written on her breasts. Witt was later fined €1200 for disturbance of religious practice; a man who struck her in the face during the protest was also fined €500 and required to write a letter of apology. On April 15, 2015, Witt disturbed a press conference of the European Central Bank, jumping onto the table in front of ECB president Mario Draghi yelling "end the ECB dick-tatorship" [sic] and tossing confetti over Draghi. After being dragged out and briefly detained, Witt wrote on Twitter that the protest was not associated with FEMEN, and that she was a "freelance activist." Her protest was in opposition to the bank's policies, which she describes as "European neo-liberalism" and economic inequality. Speaking after her release, Witt said "The gap between the rich and the poor is bigger here than it's ever been before." In 2018, Witt directed a play, "Ein Bisschen Julia und Romeo" ("A Bit of Julia and Romeo"), which played for two nights at the Berlin Workers Theater in Berlin. References Sources Category:1993 births Category:German activists Category:German women activists Category:Living people Category:German feminists Category:People from Hamburg

900 F.2d 257Unpublished Disposition NOTICE: Fourth Circuit I.O.P. 36.6 states that citation of unpublished dispositions is disfavored except for establishing res judicata, estoppel, or the law of the case and requires service of copies of cited unpublished dispositions of the Fourth Circuit.UNITED STATES of America, Plaintiff-Appellee,v.Richard Earl Scott SELLARS, Defendant-Appellant. No. 89-5175. United States Court of Appeals, Fourth Circuit. Submitted: March 5, 1990.Decided: March 23, 1990. Appeal from the United States District Court for the District of South Carolina, at Spartanburg. G. Ross Anderson, Jr., District Judge. (CR No. 88-422) Charles Benjamin Patterson, Greenville, S.C., for appellant. Robert Claude Jendron, Jr., Assistant United States Attorney, Columbia, S.C., for appellee. D.S.C. AFFIRMED. Before ERVIN, Chief Judge, and PHILLIPS and WILKINSON, Circuit Judges. PER CURIAM: 1 Richard Earl Scott Sellars appeals his conviction of conspiracy to possess with intent to distribute cocaine (21 U.S.C. Secs. 841(a)(1), 841(b)(1)(B), and 846). Sellars's counsel filed a brief pursuant to Anders v. California, 386 U.S. 738 (1967), indicating that there are no meritorious issues for appeal. Sellars did not file a supplemental pro se appeal brief. In accordance with Anders, supra, we examined the entire record in this case and found no meritorious issues for appeal. We briefly address the issue raised by counsel. 2 Sellars contends that his sentence under the guidelines should be computed based on his personal responsibility for two ounces of cocaine, not the entire nineteen ounces of cocaine that was in the conspiracy. Upon review of the record, we find that Sellars pled guilty to conspiring to distribute more than 500 grams but less than five kilograms, and was sentenced for an amount within that range--nineteen ounces converts to 538 grams. 3 Where a defendant is convicted of conspiracy, yet only participated in transactions involving small quantities of drugs, if reasonably foreseeable, the entire amount of drugs distributed by co-conspirators is taken into account in sentencing under the guidelines. United States v. Vinson, 886 F.2d 740 (4th Cir.1989). The district court found that although Sellars only admitted personal involvement of two ounces of cocaine, it was reasonably foreseeable that the conspiracy included nineteen ounces of cocaine. These findings are supported by the record; they are not clearly erroneous. 4 Finding no merit in Sellars's contentions, and finding no error upon review of the entire record, we affirm the judgment of conviction. Pursuant to the plan adopted by the Fourth Circuit Judicial Council implementing the Criminal Justice Act of 1964, 18 U.S.C. Sec. 3006A, court appointed counsel has the obligation to advise Sellars of his right to petition the Supreme Court for a writ of certiorari and, if Sellars desires him to do so, prepare the necessary papers. We dispense with oral argument because the facts and legal contentions are adequately developed in the materials before the Court and argument would not aid the decisional process. AFFIRMED

Q: On Lao triphthongs / tones / orthography Information on the Lao language is a bit patchy, especially when you start getting a little deeper and find gaps, inconsistencies, and contradictions in and between sources on the Internet. Lao vowel sounds are spelled using one or more vowel characters and a couple of characters which are also used for consonants or semivowels. There is a distinction between long vowels and short vowels which plays an important part in determining the tone of a syllable. Various articles give lists of vowels and diphthongs and tables relating them to their spellings, their length, and their tone. But some words cannot be analysed using just the information in these sources: ເຂົ້າໜຽວ "sticky rice" /khao niao/ The second syllable appears to contain a triphthong, "ຽວ". Each of the letters "ຽ" and "ວ" can be used either alone or in combination with other letters, but none of the sources I can find mention them in combination with each other. As vowels "ຽ" usually represents /iːə/ and "ວ" usually represents /uːə/. As a consonant or semivowel "ວ" usually represents [ʋ] or [w] (depending on dialect). So what is this "iao" sound in the "niao" of the second syllable? Or should I regard it as two syllables? How can I reconcile this with Wikipedia's assertion that "Diphthongs are all centering diphthongs with falling sonority"? Where does the "ao" come from in this combination, is it the same sound that is usually spelled "ເ-ົາ" as seen in the first syllable of the word? A: "ໜຽວ" is 1 syllable, "ຽ" /iːə/ is a typical Lao diphthong with falling sonority, and "ວ" is a consonant /w/, so this is a CVC-type syllable, /n/-/iːə/-/w/, /niːəw/. Note, that /w/ is allowed as the coda in Lao syllables (See A Grammar of Lao, p. 35, section "3.3 Final consonants." Lower on that page there is a list of Lao vowel phonemes and there are no triphthongs there). Also, /iːə/ is written as "ຽ" only before final consonants, in open syllables /iːə/ is written as ເ◌ຍ, that is another proof that ວ" is onsonant /w/ here. (See this paper, pp. 10-11) In the first word, the "ເ-ົາ" stands for a combination of a vowel + consonant, /aw/, so the two words have just one thing in common, they both end in /w/. However this /w/ is realised phonetically and acoustically in the coda, it is still the same phoneme as /w/ as the initial consonant. Transliterating this /aw/ as "ao" is just a convention.

Mian Deh, Chalus Mian Deh (, also Romanized as Mīān Deh) is a village in Kelarestaq-e Gharbi Rural District, in the Central District of Chalus County, Mazandaran Province, Iran. At the 2006 census, its population was 303, in 83 families. References Category:Populated places in Chalus County

Introduction ============ Corneal diseases represent the second leading cause of blindness, affecting 4.9 million people worldwide; these individuals could potentially have their sight restored through corneal transplantation \[[@r1],[@r2]\]. Penetrating keratoplasty is the standard procedure used for the treatment of corneal blindness. However, this procedure faces two primary problems: a shortage of graft donors and a decrease in endothelial cell density within 5 years of transplantation \[[@r3]\]. The corneal endothelium (CE) is responsible for maintaining corneal hydration through a pump--leak mechanism \[[@r4]\]. Although CE cells (CECs) are normally arrested in the early G1 phase of the cell cycle, they retain their proliferative capacity \[[@r5]\]. Tissue engineering can take advantage of this capacity to address the lack of available donor tissue. To accomplish this aim, a robust system for the isolation and propagation of CECs is needed. Several studies exploring complex culture media have reported the increased proliferative capacity of CECs \[[@r6]-[@r10]\]. The addition of growth factors to culture media enhances CEC proliferation; however, this effect is associated with changes in cell morphology (from hexagonal to fibroblastic) and alterations in the expression of characteristic molecular markers, which raises questions concerning the CECs' identity \[[@r6],[@r8],[@r11]-[@r13]\]. The use of culture media without growth factors is able to maintain the hexagonal morphology of the CECs; however, it yields low proliferation rates that cannot be propagated beyond the first passage \[[@r10],[@r14]\]. In this study, with the aim of improving the identity of CECs after proliferation, we first used a widely used supplemented culture medium to proliferate CECs \[[@r9]\], which was then followed by a resting step that incorporated basal medium to provide evidence of the development of a convenient CEC expansion strategy. We compared the morphology and transcriptome of CECs in two conditions and validated CEC markers using immunohistochemistry and quantitative PCR. The results suggest that the resting step helps maintain the identity of cultured CECs. Methods ======= This study was approved by the institutional local ethics committee (School of Medicine of Tecnologico de Monterrey), number 2013-Re-002. All animals were treated according to the Guide for the Care and Use of Laboratory Animals adhering to the guidelines for the human treatment and ethical use of animals for vision research stated by the Association for Research in Vision and Ophthalmology. Corneal endothelial tissue isolation ------------------------------------ Eight corneas were obtained from four 3-month-old New Zealand rabbits weighing about 3 kg. The rabbits were euthanized under general anesthesia with 30 mg/kg of ketamine (Pisa Farmaceutica, Guadalajara, México), followed by a lethal intracardiac injection of sodic pentobarbital (Pets Pharma, Estado de Mexico, Mexico). The corneas were excised, rinsed with OptiMEM-I (Gibco®; Thermo Fisher Scientific, Waltham, MA) supplemented with 8% fetal bovine serum (FBS; Cellgro, Manassas, VA) and 1% streptomycin/penicillin antibiotics (Thermo Fisher Scientific), and placed in a sterile tissue culture dish. Two sets of rabbits were used at different times. The first set of two rabbits was used for culture followed by transcriptome analyses while the second was used for culture followed by validation (immunocytochemistry and quantitative PCR \[qPCR\]). Isolation of CECs ----------------- CECs were isolated using the "peel-and-digest" approach. Briefly, using sterile surgical forceps, Descemet's membrane (DM) with the intact endothelium (DM/CE) was carefully dissected from the corneal stroma, and then was washed several times with Dulbecco\'s Modified Eagle Medium: Nutrient Mixture F-12 (DMEM-F12, Gibco®; Thermo Fisher Scientific, Grand Island, NY) supplemented with 10% FBS and 1% antibiotic combination. DM/CE complexes were incubated in OptiMEM-I 8% FBS and the 1% antibiotic combination overnight to stabilize the cells before culture. They were then incubated with 2 mg/ml of collagenase type I (Sigma-Aldrich Co., St. Louis, MO) at 37 °C for 1 h to release the CECs from DM. CEC clusters were treated with trypsin/EDTA (0.25% trypsin/0.53 mM EDTA; Sigma-Aldrich Co.) for 10 min to dissociate aggregates into smaller cell clumps. They were collected following centrifugation at 375 ×g for 10 min. CEC culture ----------- CECs were first cultured in a previously reported medium (MitoM) \[[@r9]\] containing OptiMEM-I supplemented with 8% FBS, 20 ng/ml of nerve growth factor (NGF; Sigma-Aldrich Co.), 5 ng/ml of epidermal growth factor (EGF; Sigma-Aldrich Co.), 100 µg/ml of pituitary extract (Sigma-Aldrich Co.), 200 µg/l of calcium chloride (Sigma-Aldrich Co.), 20 µg/ml of ascorbic acid (Sigma-Aldrich Co.), 0.08% chondroitin sulfate (Sigma-Aldrich Co.), and antibiotics. Isolated cells were incubated at 37 °C in a 5% CO~2~ humidified atmosphere. The medium was changed every third day until 80% confluence. At passage 1, the CECs were subcultured at a 1:2 split ratio. Population 1 continued to be cultured in MitoM, while population 2 was cultured in OptiMEM-I supplemented with only 8% FBS and 1% antibiotics (RestM) up to 80% confluence for an additional passage. We refer to the RestM procedure as "resting" because it lacks growth factors to decrease proliferation rates. An Axiovert 40 CFL contrast microscope (CFL; Carl Zeiss AG, Oberkochen, Germany) featuring a PowerShot A640 digital camera (Canon Inc., Tokyo, Japan) was used to register cell morphology. Morphology analysis ------------------- NIH [Image J](https://imagej.net/) software \[[@r15]\] was used to analyze the morphology of human CECs from three healthy biomicroscopies from a public database \[[@r16]\], basal rabbit CECs (before culture), in MitoM and RestM. A similar scale was set on each photograph. Then about 40 CECs were delimited and analyzed for human MitoM and RestM, whereas about 20 cells were analyzed for basal rabbit CECs with free shape region of interest. Area and perimeter were obtained using Image J (Analysis menu, Measure tool). Circularity was calculated as 4π (area/perimeter\^2), and values near from 1 were taken as high circularity indices, thus near hexagonality \[[@r17]\]. Cellular yield analysis ----------------------- Cellular yield was calculated for CECs cultured in MitoM and RestM. For this analysis, the quotient of cellular concentration (cells/ml) at the end of passage 2 divided by the cellular concentration at the end of passage 1 was calculated for each culture condition (MitoM and RestM). The average and the standard error were calculated. A *t* test was used to analyze statistically significant differences between the calculated yields. RNA isolation ------------- Total RNA was extracted with the RNeasy mini Kit (Qiagen, Hilden, Germany) from CECs before culture, and then after culture in MitoM and RestM. Cells were harvested at 80--90% confluence around day 9 of culture. RNA concentration and purity were determined by spectrophotometry using a NanoDrop ND-1000 UV-VIS spectrophotometer (Waltham, MA); only RNA samples with an A260/A280 ratio ≥1.8 were used for further experiments. The Experion RNA HighSense (Hercules, CA) was used to determine the concentration and integrity of mRNA. Yields were 62--182 ng/µl per confluent dish, and a total of 3 µg/µl was used for sample preparation. Microarray hybridization ------------------------ RNA preparation, labeling, and hybridization were performed according to the manufacturer's recommendations (Agilent Technologies, Santa Clara, CA) using the customized rabbit microarray (G2519F) containing around 44,000 probes. Briefly, cyanine-3- (Cy3-) and cyanine-5 (Cy5)-labeled cRNA were prepared from the total RNA using a labeling kit (Quick Amp; Agilent Technologies). This was followed by column purification (RNeasy Mini Kit; Qiagen). Cy3 was used for the CECs in MitoM, and Cy5 was used for the CECs in RestM. Dye incorporation and cRNA yield were assessed with spectrophotometry (ND-1000; Thermo Fisher Scientific). Equal amounts of the Cy3- or Cy5-labeled cRNA mixture were hybridized to the microarrays (Rabbit Gene Expression Microarrays; Agilent) for 17 h at 65 °C in a rotating hybridization oven (Agilent), followed by washing and scanning. Data were obtained immediately after washing on a microarray scanner (GenePix 4000B; Molecular Devices LLC, Sunnyvale, CA). Microarray data analysis ------------------------ The R statistical environment was used to process and analyze the data (<https://cran.r-project.org/>). Raw data were transformed using log~2~ and subsequently, were quantile-normalized before statistical analysis. The differentially expressed genes were obtained with a paired *t* test that was conducted between the four replicates of MitoM and RestM. A functional analysis of the differentially expressed genes was performed using the Database for Annotation, Visualization, and Integrated Discovery ([DAVID](https://david.ncifcrf.gov)) \[[@r18]\]. Only those probes with human annotations were used for this process. Each microarray probe was aligned to the human transcriptome annotations (hg19) using BLAST (included in Appendix 1). Only those DAVID terms where the p value was less than 0.01, the adjusted false discovery rate p value was less than 0.25, and the gene count was greater than three were examined. Quantitative PCR ---------------- Validation of expression levels for different corneal endothelial markers was performed by quantitative PCR (qPCR) using (m)RNA from CECs before culture, after cultured in MitoM, and RestM. Primers design was conducted in Blast Primer platform (NCBI) and synthetized by T4 oligo company (Guanajuato, Mexico). GAPDH F: CGA GCT GAA CGG GAA ACT CA, R: CCC AGC ATC GAA GGT AGA GG; ATP1A1 F:GAT CCA CGA AGC TGA CAC GA, R: CTG TTA CAG AGG CCT GCG AT; GPC4 F: CGC CAA ATC ATG GCT CTT CG, R: GGC ACT GCT GGT ACT CAC AT; BTG2 F: GGC TTA AGG TTT TCA GCG GG, R: CTT GTG GTT GAT GCG GAT GC; TJP1 F: CTC AAG TTC CTG AAG CCC GT, R: TAG GAT CAC CCG ACG AGG AG. Amplification was performed with the PowerUp SYBR Green Master Mix kit in a Step One 48-well thermocycler (Applied Biosystems, Foster City, CA), under these conditions: initial denaturing at 95 ºC 1 min, 40 cycles: 95 ºC/30 s, 61 ºC/30 s, 72 ºC/30 s; final extension 72 ºC/5 min. Finally, ΔCt method was used to analyze expression levels. Immunocytochemistry ------------------- Immunocytochemistry was performed in CECs before culture, after culture in MitoM, and in RestM to analyze the presence of GPC4 (Abcam, ab150517, Cambridge, UK), CD166 (Abcam, ab78649), ZO-1/TJP1 (ThermoFisher, 61--7300, Waltham, MA), and Na/K-ATPase (Abcam, ab176163, Cambridge, UK). Immunocytochemistry consisted of overnight cell stabilization over coverslips with poly-D lysine (Sigma-Aldrich, P7280), fixation with 4% paraformaldehyde, nonspecific bonding blockage with 5% bovine serum albumin (BSA; Sigma-Aldrich, A-7030), overnight 4 °C incubation with primary antibodies (GPC4 5 µg/ml, CD166 1 µg/ml, ZO-1 5 µg/ml, and Na/K-ATPase 1:100), and incubation with Alexa Fluor 488 secondary antibody (Abcam, ab150077) for 1 h at room temperature. Fluoroshield Mounting Medium with 4′,6-Diamidine-2′-phenylindole dihydrochloride (DAPI; Abcam, ab104139) counterstain was used. For the complete corneas, we followed a previously described protocol for immunostaining on a flat-mounted whole intact cornea \[[@r19]\]. Briefly, corneas were rinsed in Phosphate-Buffered Saline (PBS 1X; 140 mM NaCl, 3 mM KCl, 10 mM NaPO~4~, pH 7.4 at 25 °C), cut into four pie-shaped wedges and immediately fixed. Fixation occurred for 30 min in 0.5% paraformaldehyde (Sigma-Aldrich Co.) in PBS pH 7.45 at 4 °C. Then, cell membranes were permeabilized with 1% Triton X-100 (Sigma-Aldrich Co.) in PBS for 5 min at room temperature. Blockage of non-specific binding sites was performed by incubation for 30 min at 37 °C with 5% BSA (Sigma-Aldrich Co). Primary and secondary antibodies, as well as counterstaining, were used in the same fashion as for CECs immunocytochemistry but, corneal pieces were fully immersed in the corresponding solutions. Epifluorescence was registered with a widefield fluorescence microscope (Zeiss Imager Z1) with an AxioCam HRm (Zeiss) camera (Göttingen, Germany). Results ======= Isolation of corneal endothelial tissue --------------------------------------- The peel-and-digest approach for the isolation of CECs yielded small groups of cells that showed a polygonal morphology, and they were cultured in MitoM (Appendix 1). This evidence also support that the protocol was successfully implemented, and that CECs can be used for further experiments. Effects of culture conditions on the morphology of CECs ------------------------------------------------------- The cultured CECs showed variations in morphology throughout the 5 days in MitoM at P0 ([Figure 1A--E](#f1){ref-type="fig"}). The morphological changes in the CECs in MitoM and RestM culture medium started at around day 2 and became more evident after 5 days of incubation ([Figure1B,C](#f1){ref-type="fig"}). The passaged cells cultured in MitoM acquired a fibroblastic morphology, whereas those in RestM were far less elongated and had formed a monolayer. At day 9, the effect of the MitoM became more evident, particularly when the CECs were compared to those at P0 ([Figure 1D](#f1){ref-type="fig"}). Conversely, the RestM CECs became polygonal ([Figure 1C,E](#f1){ref-type="fig"}). The average of the circularity index of the specular microscopy of the human CECs was 0.79±0.072, of the rabbit CECs before culture was 0.77±0.063, after culture in MitoM was 0.41±0.19, in RestM passage 1 was 0.73±0.09, and in RestM passage 2 was 0.6±0.18 ([Figure 1G](#f1){ref-type="fig"}). There was no statistically significant difference between the circularity of human and basal rabbit CECs or between CECs in RestM P1 and human CECs. The difference in the circularity of human versus MitoM, human versus RestM P2, and basal versus RestM P2 CECs was statistically significant (p\<0.05). These results showed that the resting phase of this culture system enhances the morphology of the CECs, as they take on a corneal--endothelial-like shape. Nevertheless, these results also warn that prolonged passages may also be detrimental. {#f1} Cellular yield analysis ----------------------- CECs in MitoM showed a fold-change increase in the cellular yield of 1.52 from passage 1 to passage 2, whereas CECs in RestM showed an increase of 1.27 ([Figure 2H](#f2){ref-type="fig"}). Although the difference between the yields obtained in the two culture conditions was not statistically significant (p=0.2583), lower proliferation was apparent in RestM. {#f2} Gene expression and functional analysis --------------------------------------- We first tested whether the cell identities were lost during culture by comparing the overall similarity of normalized gene expressions. Hierarchical clustering showed that those cells in the culture were more similar to those of the subject from which the cells were obtained than to the cells in the culture conditions ([Figure 2](#f2){ref-type="fig"}). Nevertheless, a principal component analysis (PCA) revealed that the major source of variation was the culture condition ([Figure 2B](#f2){ref-type="fig"}), which was confirmed with hierarchical clustering, estimated from 5% of the gene expression profiles that had a higher coefficient of variation ([Figure 2C](#f2){ref-type="fig"}). These results support the validity of the assays, treatments, and collected data. We then compared the expression of specific CEC markers between the RestM and MitoM conditions. We assessed 26 selected genes (in gene: probeID from Appendix 1 these are *AQP1*: A_04_P030932, *COL8A1*: A_04_P001586, *ATP1A1*: A_04_P004696, *ATP1B1:* A_04_P002527,*TJP1*: A_04_P086632, *TJP2*: A_04_P067042, *CDH2*: A_04_P031967, *SLC4A11*: A_04_P094717, *GPC4*: A_04_P095302, *CD200*: A_04_P095118, *CLRN1*: A_04_P082648, *GLP1R*: A_04_P079252, *CNTN3*: A_04_P098144, *PCDHB7*, *HTRD1*: A_04_P004265, *GRIP1*: A_04_P098464, *PKD1*: A_04_P012501, *ZP4*: A_04_P003166, *CNTN6*: CNTN6, *SLC3A2*: A_04_P003146, *ALCAM/CD166*: A_04_P020128, ERBB2/CD340: A_04_P049357, *CD9*: A_04_P018111, *CD44*: A_04_P101042, *ITGA5/CD49e*: A_04_P088227, and *NT5E/CD73*: A_04_P084588).which serve as markers for adult CECs, fetal CECs, non-fibroblast CEC phenotypes, and fibroblast CEC phenotypes \[[@r20],[@r21]\]. Of these genes, nine demonstrated expression changes (p\<0.05; [Figure 3A](#f3){ref-type="fig"}). {#f3} The results suggested that adult CECs markers (*ATP1A1, ATP1B1, COL8A2, GPC4, CDH2*, and*TJP1*) were more expressed in the RestM condition, while three non-adult CEC markers (*CD44, CNTN3,*and *CD166*) were more expressed in the MitoM condition. These results showed that markers of specific corneal functions had begun to diverge between the two conditions. Nevertheless, the number of altered genes observed from these CEC markers was too low to compare the overall changes in the biological function. Therefore, to expand the functional analysis, we used the detected differential gene expression profiles to characterize the functional differences in the CECs between the MitoM and RestM conditions. We identified 781 differentially expressed probe genes, as obtained with paired *t* tests between the four replicates of MitoM and RestM at a statistical significance level of p\<0.01, whose fold change was greater than 1, and had an associated known human gene (Appendix 1). A DAVID analysis was performed using the 308 unique genes represented in the 781 differential probes. To summarize these results, we performed hierarchical clustering that resulted from the estimated fold change, and which included the intersection of functional terms and genes. From the results shown in [Figure 3B](#f3){ref-type="fig"}, we identified around 13 functional clusters related to extracellular matrix, collagen type 4, protein modifications, response to a stimulus, apoptosis and antiapoptosis, nuclear lumen, ribosome biogenesis, signal transduction, immune responses, cell proliferation, and wound healing, among others. The details of the biological terms are shown in Appendix 2. From the functional analysis, we chose some functional terms related to relevant biological functions and compared the gene expression levels of the significant genes as the levels related to those functions ([Figure 3C](#f3){ref-type="fig"}). The analysis revealed that CECs in RestM clearly showed a greater expression of genes related to collagen type IV and the extracellular matrix, suggesting remodeling processes. For example, four types of collagen type IV were overexpressed in RestM together with *TIMP3* to inhibit collagenases. Moreover, they were also overexpressed with *LUM*, which binds collagen fibrils; *SMOC2*, which promotes matrix assembly; and *CRTAP*, which is involved in the hydroxylation of fibrillar collagen. Conversely, in MitoM, *MMP1*was more greatly expressed and it is involved in the cleavage of various types of collagen. The function and expression of these genes suggest that they are associated with the different shapes observed under the microscope. Although the term cell proliferation showed that similar numbers of genes were more greatly expressed in MitoM and RestM, some of the terms were clearly related to proliferation states, such as nuclear lumen and ribosome biogenesis, which demonstrated higher expression levels in those genes in the MitoM condition. These results suggested that cells in the MitoM condition are more likely to be related to proliferative processes. In terms of wound healing, CECs in the MitoM condition overexpressed *IL-6*, *F3*, and *ITGB3*, which are related to inflammation, complement cascade, and cell adhesion, respectively. Conversely, CECs in the RestM condition showed higher expression levels of *FBLN5*, which is known to promote endothelial cell adhesion; *insulin-like growth factor (IGF)-1*, which promotes cell growth and development; and *TIMP3*, an inhibitor of matrix metalloproteinases (MMPs). These results suggested that CECs are involved in the remodeling in MitoM, while they are involved during assembly states in RestM. Other functional terms showed a similar number of genes that were more greatly expressed in either condition, such as those related to apoptosis, acetylation/phosphorylation, and response to stimulus. These terms require further analysis. Validation of gene expression ----------------------------- To compare the results with native expression of transcripts and proteins from adult rabbits and to validate the microarray results, we performed qPCR and immunocytochemistry analyses of four genes. *ATP1A1*, *TJP1*,*GPC4*, and *BTG2* were selected for this purpose because they are good markers of CEC functions. We first tested the protein expression of TJP1 (ZO-1), an adult marker of CECs \[[@r20],[@r21]\], which was also overexpressed in RestM, comparing the immunostaining in basal conditions from complete corneas with the growth in both conditions. The fluorescence images shown in [Figure 4A](#f4){ref-type="fig"} support the previous results where the protein expression of ZO-1 was localized more clearly in membranes in cornea and RestM, whereas in MitoM the expression localization was diffuse. For ATP1A1, TJP1, and GPC4, the overall protein expression at P2 seems higher in RestM than in MitoM ([Figure 4B](#f4){ref-type="fig"}), which is consistent with transcriptional measurements where three out of the four genes show a statistically significant increase in expression between RestM and MitoM ([Figure 4C](#f4){ref-type="fig"}). {#f4} Discussion ========== Culture methods for rabbit and human CEC culture have been previously reported. The culture of rabbit CECs using a supplemented medium demonstrated proliferation for up to 67 passages \[[@r22]\]. However, the CECs in the cited study exhibited chromosomal aneuploidy, and they presented a fibroblastic shape \[[@r22]\]. The changes made to a non-supplemented medium for 1 week (MEM 5% BCF) facilitated the recovery of the cells' polygonal shape. In human CECs, it was demonstrated that the combination of vascular endothelial growth factor (VEGF), EGF, fibroblast growth factor (FGF), and IGF yields better cell attachment and cuboidal morphology up to the first passage (approximately 10 days) when compared to the CECs in the basal media \[[@r8]\]. A different study reported that the use of a supplemented culture media, using the same composition of MitoM used in this study, resulted in polygonal CEC proliferation up until the fifth passage, but the expression of specific molecular markers was evident up until the second passage \[[@r6]\]. In a study in which four different media were used, the best outcomes in terms of proliferation, morphology, and molecular marker expression were obtained with the MitoM medium used here, as well as with another medium containing ascorbic acid, insulin--transferrin--sodium selenite (ITS), and bFGF. These two media allowed the CECs to retain their polygonal morphology, and they further expressed ZO-1 and Na/K-ATPase up until the third passage \[[@r10]\]. ZO-1 and Na/K-ATPase are markers of cell identity and the lack of epithelial to mesenchymal transition \[[@r23]\]. The same research group recently reported the use of a supplemented culture medium featuring ascorbic acid, ITS, and bFGF to proliferate CECs. This approach was coupled with a second step in which a maintenance medium (endothelial SFM 5% FBS) was used. In their method, human CECs were cultured for three passages, each consisting of 14 days in the supplemented medium and 7 days in the maintenance medium. This is different from our method, which involved culturing the cells for 5 days in MitoM until confluence, followed by two additional passages in RestM medium (where the composition was the same as in MitoM, but without growth factors). The authors of the previous work reported that the CECs demonstrated a spindle morphology when they were cultured in supplemented medium alone, and they exhibited an enhancement of cell circularity when the non-supplemented medium was added, which persisted throughout the three passages. In the present experiment, the CECs showed a spindle morphology when cultured in MitoM, and they recovered their polygonal morphology after 48 h in RestM, which persisted during the following passage in the same medium. The results of these studies were in accordance with ours with respect to the recovery of the cells' polygonal morphology after the supplemented medium was changed to a basal medium. Further experiments will determine if multiple cycles of proliferation and recuperation retain the characteristics of CECs without demonstrating senescence. Meanwhile, we observed that shape was maintained around the fourth passage. The role of cell senescence and culture media supplementation has been demonstrated in studies using human CECs. The protein tyrosine phosphate *PTP1B*, known to negatively regulate EGF-induced signaling by dephosphorylating the *EGF receptor* (*EGFR*), is more greatly expressed in CECs obtained from younger donors \[[@r14]\]. In this context, the proliferation response to an EGF stimulus in cultured CECs is dependent on the synergy between *PTP1B* and *EGFR*, and it is lower in older donor and senescent cells. This explains why the EGF stimuli response decreased in senescent cells even when the level of EGFR remained relatively constant. Our culture system prevented the CECs from entering into a senescent state by adding a stabilization step. The *PTP1B* gene was not among the differentially expressed genes observed for the CECs in MitoM and RestM, which could be an indicator of the potential of this system for corneal engineering. To better understand the molecular mechanisms underlying the morphological changes recorded throughout the two-culture media, a microarray analysis was performed. The identification of the Gene Ontology (GO) term related to wound healing suggested that CECs in MitoM can act to signal tissue damage, and they further activate a series of events with the objective of restoring cell integrity following an injury. The movement of cells from the G1 to S phase implicates the inhibition of cell--cell contact \[[@r24]\]. Kimura demonstrated that in the presence of harmful stimuli, it is possible to redistribute tight junctions without affecting adherent junctions \[[@r25]\]. This result correlates with the present results, in which the biological process GO term cell adhesion molecule binding, the CC-GO adherens junction, and the pathway for the adherent junction were established, while no changes were observed for tight junctions. GO terms related to the actin cytoskeleton and the regulation of cell projection assembly suggest dynamic actin cytoskeletal organization. Actin cytoskeletal reorganization can be related to the protrusive forces involved in cell migration \[[@r26]\]. The identification of the MF-GO terms related to metalloendopeptidase activity, collagen metabolic processes, and collagen degradation, along with the GO-BP-positive regulation of catalytic activity, suggest that a catalytic process is involved in extracellular collagen composition, which is controlled by MMPs. MMPs are important in the process of connective tissue remodeling \[[@r27]\], and they may be involved in the reorganization of the TJ protein seen in CECs in MitoM. CECs in MitoM did not express MMP inhibitors; thus, the changes in cell morphology could be related to dynamic actin cytoskeletal reorganization, changes in the extracellular matrix composition, and reorganization of the cell junctions. CECs in RestM showed GO terms related to wound healing as well, such as focal adhesion, remodeling in the extracellular matrix, and extracellular matrix receptor interaction, which suggests that RestM also acts as a signal to indicate damage, ultimately activating a series of events related to restoring the monolayer's integrity. The polygonal morphology seen in CECs in RestM is a good index of the progress of endothelial restoration \[[@r28]\], and together with the rearrangement of the cytoskeleton, it recalls the tissue remodeling state. The expression of collagen IV suggests that RestM can promote the reestablishment of the structure and composition of the extracellular matrix, which is essential for the attachment of CECs to DM. qPCR validated the difference in the expression of the *ATP1A1, TJP1,*and*GPC4* genes among the CECs before culture, in MitoM, and in RestM. The CECs in RestM showed higher expression level of these markers. However, the expression levels were higher than those observed in basal CECs. We hypothesize that activation of the proliferative state during MitoM before the RestM condition could lead to these results. Because we analyzed the expression level at 80% cell confluence, expression levels during an increased rate of transcription were obtained, in contrast to basal expression, in which corneal endothelium is in an expression steady-state. Further experiments with a different rate of confluence would confirm these insights. Immunocytochemistry analysis demonstrated similar locations and expression levels of TJP1/ZO-1 in flat CE and in CECs in RestM. In addition, CECs in RestM showed higher expression of adult CE markers GPC4 and Na/K-ATPase compared to CECs in MitoM. The differentially expressed genes obtained in this system are similar to those reported by Peh et al. following the use of a different proliferative medium coupled with a maintenance medium \[[@r29]\]. Cell proliferation and wound healing were among the top pathways evident in both approaches. Although there are methodological differences between their study and the present study, the results demonstrated the effectiveness of a coupled system in the proliferation of CECs, as well as in the maintenance of their morphological and molecular characteristics. Further in vivo analyses will determine the efficacy of CECs cultured with these systems in restoring corneal function. It has been shown that the proliferative capacity of CECs is age-dependent in humans and rabbits \[[@r30],[@r31]\]. In the present experiments, we used 3-month-old rabbits which show high mitotic activity. It would be interesting to compare the behavior of the present culture system at different ages. CONCLUSIONS ----------- We showed a two-phase system with novel medium and transcriptome data, analysis, and validation. Other research groups used a different medium \[[@r29]\] or did not analyze the transcriptome \[[@r32]\]. The differences in the morphology, pathways, and gene expression observed between CECs in RestM and MitoM suggest that although MitoM enhances CEC proliferation, it could result in cell differentiation and drive the culture to exhibit a wound-like state. The resting step facilitated the recovery of the cells' hexagonal shape; it further benefitted the maintenance of pump function, cell-cycle arrest, the cells' barrier function (via junction reorganization), the reconstruction of the extracellular matrix's structural constituent, and the production of collagen IV (a component of DM), all of which are related to the final events involved in remodeling during the wound-healing process. Future experiments focused on analyzing the number of cycles in which the CECs cultured in this system are able to proliferate and recover specific markers will provide additional evidence for this system's potential in regenerative medicine. Cells cultured in this system may ultimately address the shortage of tissue donors available for corneal grafts. English-language editing of this manuscript was provided by Journal Prep. This work was funded by Consejo Nacional de Ciencia y Tecnología (CONACyT) grant PN6558 and Tecnologico de Monterrey. To access the data, click or select the words "[Appendix 1](http://www.molvis.org/molvis/v25/appendices/mv-v25-745-app-1.tif)." A) Tissue conglomerates obtained after collagenase I treatment. B) Cell clusters obtained after trypsin/EDTA treatment. C) Adherent cells after enzymatic digestion. To access the data, click or select the words "[Appendix 2](http://www.molvis.org/molvis/v25/appendices/mv-v25-745-app-2.tif)." The heat map shows the genes (horizontal axis) contained within functional biologic terms (vertical axis). The color represents the fold change in gene expression (cyan is used to represent those genes that were more greatly expressed in MitoM, while purple represents those genes more greatly expressed in RestM). Genes whose *t* test p values were \<0.01, and which demonstrated a fold change \>1, were used. Only over-represented biologic terms with a p value \<0.01, a false discovery rate \<0.25, and those that contained \>3 genes were used in this analysis.

p21 gene polymorphisms in systemic lupus erythematosus. Cyclin-dependent kinase inhibitor 1A (p21) is a negative regulator in the cell cycle. Development of sex-linked lupus-like syndrome in p21-/- mice and reduced p21 gene expression in patients with systemic lupus erythematosus (SLE) compared with those in healthy controls suggested that p21 is a susceptibility gene of SLE. We investigated the same by a case-control association study. Six single nucleotide polymorphisms, p21US G/A, p21DS C/A, p21-1022 G/A, p21C31 C/A, p21In2 G/C and p21UTR T/C, were genotyped in 516 SLE patients and 693 healthy controls. Association of genotypes and alleles with disease, disease phenotypes, haplotypes construction, linkage disequilibrium analysis and p21 mRNA expression were performed. We found a significant association of p21US A allele (OR = 0.23, 95% CI: 0.14-0.38, P < 0.001) and p21-1022 A allele (OR = 1.95, 95% CI: 1.37-2.78, P < 0.001) with SLE. We identified significant differences in the frequencies of haplotypes ht1-ACACCC, which contains p21US A allele, and ht2-GCACCC, which contains p21-1022 A allele, between SLE patients and controls (P < 0.0001). Besides, the p21US GA was associated with SLE patients suffering from arthritis (P = 0.003). We also observed differential p21 mRNA expressions among different genotypes of p21US and p21-1022 which were statistically significant. Our results suggested that the p21US A allele and p21-1022 A allele were both associated with the development of SLE, and the p21US A allele was associated with arthritis in SLE patients.

Commentary {#Sec1} ========== "*Complexity is the enemy of transparency*" \[[@CR1]\]. Today, *BMC Medicine* publishes another paper on journalology (publication science) \[[@CR2]\]. Attributing authorship, and authorship order, is complex and often a 'black box' for prospective authors. Professor Marušić and colleagues have tried to peel back the black box concerning the assigning of authorship for industry-sponsored clinical trials. Their methods are good and reported in sufficient detail to allow interested readers to replicate them \[[@CR3]\]. The research team have used an integrated knowledge translation approach to developing their proposed five-steps for transparently disclosing authorship. Participants from pharmaceutical companies that conduct clinical trials, academics, editors, and the Medical Publishing Insights and Practices initiative were involved in the entire process; this facilitates buy-in and support for the process and outcome. These same people are likely to become front-line ambassadors and early adopters for disseminating and implementing the five-step framework within their own working environments, and hopefully, more broadly. What is positive about this research is that the proposed attribution process for authorship is brief, and not complex; it's only five-steps. It is meant to augment the guidance provided by the International Committee of Medical Journal Editors \[[@CR4]\]. To enhance uptake of the framework it will be important for the team, or others, to develop a bank of worked examples for each step in the five-step process. Using worked examples from specific trials will likely facilitate implementation. The authors have started the process with seven case examples included in their publication. A dedicated website for the framework whereby authorship examples can be submitted by pharmaceutical companies and others, vetted and added to a bank of examples, freely accessible to anybody, is worth considering. This will help prospective clinical trialists ensure a transparent process in deciding on authorship. If this authorship initiative is to be successful it requires endorsement and, more importantly, implementation. As Marušić and colleagues note \[[@CR2]\], previous efforts, such as contributorship, have not been broadly implemented. What is less clear is how the proposed framework is going to be endorsed and implemented. Important initial steps should include strong and consistent language of endorsement across all of the pharmaceutical companies involved in the development of the five-step process. Support and endorsement from umbrella groups, such as the Pharmaceutical Research and Manufacturers of America \[[@CR5]\], and others such as CONSORT \[[@CR6]\], is also worth considering. While endorsement is a useful step, it is difficult to measure and likely not the most relevant outcome. More important will be to develop plans based on appropriately developed approaches \[[@CR7],[@CR8]\] to implement the framework. This is likely to be most effective when pharmaceutical companies modify their authorship practices and polices when conducting any clinical trial. An effective policy would require all clinical trials to implement the five-step framework at their inception. Without strong implementation the framework is less likely to affect positive change. This has been observed when trying to implement reporting guidelines in biomedical journals \[[@CR9],[@CR10]\]. Part of any implementation plan also needs to include an evaluation of the framework. It is important to collect data that will inform its usefulness. There is little merit in maintaining policies that are not supported by evidence. Marušić et al. are silent on whether their framework can be used when developing authorship for submitting clinical trial protocols for publication consideration \[[@CR2]\]. Making clinical trial protocols accessible is important and at least one Biomed Central journal -- *Trials* -- regularly publishes them. Additionally, with the requirement of trial registration, this framework could also be used when completing the investigator information part of the registration. Most of us are not born authors. It is an acquired skill that often starts during graduate school. This is where all journalology issues, including those pertaining to authorship issues (e.g., attributing authorship, authorship order, and ghost and guest authorship, author responsibilities) should be formally taught and discussed. Developing such skills early can translate into something useful throughout a researcher's (author's) career. It is unfortunate that almost all universities, and other centres of higher learning, appear to have abdicated their responsibilities regarding formally teaching journalology; the irony is not lost on me. These institutions are the very same places developing the next generation of biomedical researchers. Universities need to set aside appropriate resources to enable and promote such courses, and others, related to journalology \[[@CR11]\]. While authors have rights and privileges, they also have important responsibilities that require much greater attention. Given the opportunity of authorship, it is equally important to assert this responsibility. Authors must ensure that papers baring their name are "fit for purpose" \[[@CR12]\]. Here, authors need to ensure that every report baring their name is a completely reported and transparent account of what was done (methods) and found (results) to enable interested readers to replicate the methods and use the results. Collectively, authors have not performed appropriately with regards to reporting their clinical trials. This avoidable waste is troublesome for shareholders of publicly traded pharmaceutical companies and tax payers of publicly-funded clinical trials. It is not a good return of a fiscal investment when reports of trials are so inadequate that their results cannot be used. For example, Duff et al. \[[@CR13]\] examined 262 reports of trials from the most prominent oncology journals assessing them for 10 essential elements regarding the description of their interventions, such as the drug's name and route of administration. The authors reported that only 11% of the articles reported all 10 characteristics. Although we have seen improvements over time in reporting the unique characteristics of randomized trials -- sequence generation, allocation concealment, and implementation -- these items are adequately reported in less than half of the trial reports \[[@CR14]\]. In some clinical specialties, the situation is much worse \[[@CR15]\]. Disclosing authorship transparently is important for any manuscript being submitted to a biomedical journal for publication consideration. The responsibilities associated with authorship must be taken seriously. This might help increase value and reduce avoidable waste of biomedical research. **Competing interests** The author declares that he has no competing interests.

// Copyright Aleksey Gurtovoy 2000-2004 // // Distributed under the Boost Software License, Version 1.0. // (See accompanying file LICENSE_1_0.txt or copy at // http://www.boost.org/LICENSE_1_0.txt) // // Preprocessed version of "boost/mpl/aux_/lambda_no_ctps.hpp" header // -- DO NOT modify by hand! namespace boost { namespace mpl { namespace aux { template< bool C1 = false, bool C2 = false, bool C3 = false, bool C4 = false , bool C5 = false > struct lambda_or : true_ { }; template<> struct lambda_or< false,false,false,false,false > : false_ { }; template< typename Arity > struct lambda_impl { template< typename T, typename Tag, typename Protect > struct result_ { typedef T type; typedef is_placeholder<T> is_le; }; }; template<> struct lambda_impl< int_<1> > { template< typename F, typename Tag, typename Protect > struct result_ { typedef lambda< typename F::arg1, Tag, false_ > l1; typedef typename l1::is_le is_le1; typedef aux::lambda_or< BOOST_MPL_AUX_MSVC_VALUE_WKND(is_le1)::value > is_le; typedef bind1< typename F::rebind , typename l1::type > bind_; typedef typename if_< is_le , if_< Protect, mpl::protect<bind_>, bind_ > , identity<F> >::type type_; typedef typename type_::type type; }; }; template<> struct lambda_impl< int_<2> > { template< typename F, typename Tag, typename Protect > struct result_ { typedef lambda< typename F::arg1, Tag, false_ > l1; typedef lambda< typename F::arg2, Tag, false_ > l2; typedef typename l1::is_le is_le1; typedef typename l2::is_le is_le2; typedef aux::lambda_or< BOOST_MPL_AUX_MSVC_VALUE_WKND(is_le1)::value, BOOST_MPL_AUX_MSVC_VALUE_WKND(is_le2)::value > is_le; typedef bind2< typename F::rebind , typename l1::type, typename l2::type > bind_; typedef typename if_< is_le , if_< Protect, mpl::protect<bind_>, bind_ > , identity<F> >::type type_; typedef typename type_::type type; }; }; template<> struct lambda_impl< int_<3> > { template< typename F, typename Tag, typename Protect > struct result_ { typedef lambda< typename F::arg1, Tag, false_ > l1; typedef lambda< typename F::arg2, Tag, false_ > l2; typedef lambda< typename F::arg3, Tag, false_ > l3; typedef typename l1::is_le is_le1; typedef typename l2::is_le is_le2; typedef typename l3::is_le is_le3; typedef aux::lambda_or< BOOST_MPL_AUX_MSVC_VALUE_WKND(is_le1)::value, BOOST_MPL_AUX_MSVC_VALUE_WKND(is_le2)::value, BOOST_MPL_AUX_MSVC_VALUE_WKND(is_le3)::value > is_le; typedef bind3< typename F::rebind , typename l1::type, typename l2::type, typename l3::type > bind_; typedef typename if_< is_le , if_< Protect, mpl::protect<bind_>, bind_ > , identity<F> >::type type_; typedef typename type_::type type; }; }; template<> struct lambda_impl< int_<4> > { template< typename F, typename Tag, typename Protect > struct result_ { typedef lambda< typename F::arg1, Tag, false_ > l1; typedef lambda< typename F::arg2, Tag, false_ > l2; typedef lambda< typename F::arg3, Tag, false_ > l3; typedef lambda< typename F::arg4, Tag, false_ > l4; typedef typename l1::is_le is_le1; typedef typename l2::is_le is_le2; typedef typename l3::is_le is_le3; typedef typename l4::is_le is_le4; typedef aux::lambda_or< BOOST_MPL_AUX_MSVC_VALUE_WKND(is_le1)::value, BOOST_MPL_AUX_MSVC_VALUE_WKND(is_le2)::value, BOOST_MPL_AUX_MSVC_VALUE_WKND(is_le3)::value, BOOST_MPL_AUX_MSVC_VALUE_WKND(is_le4)::value > is_le; typedef bind4< typename F::rebind , typename l1::type, typename l2::type, typename l3::type , typename l4::type > bind_; typedef typename if_< is_le , if_< Protect, mpl::protect<bind_>, bind_ > , identity<F> >::type type_; typedef typename type_::type type; }; }; template<> struct lambda_impl< int_<5> > { template< typename F, typename Tag, typename Protect > struct result_ { typedef lambda< typename F::arg1, Tag, false_ > l1; typedef lambda< typename F::arg2, Tag, false_ > l2; typedef lambda< typename F::arg3, Tag, false_ > l3; typedef lambda< typename F::arg4, Tag, false_ > l4; typedef lambda< typename F::arg5, Tag, false_ > l5; typedef typename l1::is_le is_le1; typedef typename l2::is_le is_le2; typedef typename l3::is_le is_le3; typedef typename l4::is_le is_le4; typedef typename l5::is_le is_le5; typedef aux::lambda_or< BOOST_MPL_AUX_MSVC_VALUE_WKND(is_le1)::value, BOOST_MPL_AUX_MSVC_VALUE_WKND(is_le2)::value, BOOST_MPL_AUX_MSVC_VALUE_WKND(is_le3)::value, BOOST_MPL_AUX_MSVC_VALUE_WKND(is_le4)::value, BOOST_MPL_AUX_MSVC_VALUE_WKND(is_le5)::value > is_le; typedef bind5< typename F::rebind , typename l1::type, typename l2::type, typename l3::type , typename l4::type, typename l5::type > bind_; typedef typename if_< is_le , if_< Protect, mpl::protect<bind_>, bind_ > , identity<F> >::type type_; typedef typename type_::type type; }; }; } // namespace aux template< typename T , typename Tag , typename Protect > struct lambda { /// Metafunction forwarding confuses MSVC 6.x typedef typename aux::template_arity<T>::type arity_; typedef typename aux::lambda_impl<arity_> ::template result_< T,Tag,Protect > l_; typedef typename l_::type type; typedef typename l_::is_le is_le; BOOST_MPL_AUX_LAMBDA_SUPPORT(3, lambda, (T, Tag, Protect)) }; BOOST_MPL_AUX_NA_SPEC2(1, 3, lambda) template< typename T > struct is_lambda_expression : lambda<T>::is_le { }; }}

One of the NFL's most classic-looking teams -- or its most boring-looking team, depending on your point of view -- is headed for a face-lift. That's the word out of Cleveland, where Browns owner Jimmy Haslam has announced that the team will be getting new uniforms for 2014. Haslam says the team's helmets won't be changed, but everything else is presumably fair game. Naturally, we can't trust the Browns, the NFL or Nike to do this job correctly, so the task falls to you: Fire up your digital design software -- or break out your pack of magic markers, as the case might be -- and come up with a new uniform set for the Browns. The rules are simple: • Your entry must include a primary logo, a dark-jersey uniform and a white-jersey uniform. (If you like, you can also include secondary logos and one alternate uniform, but those aren't required.) • Your uniform designs must include the team's current helmet, since that won't be changing. Sorry. • Your designs can be created in any digital or analog medium (Illustrator, Photoshop, crayon, whatever) and can be submitted in any standard digital format (JPG, PDF, tiff, etc.). • Please include your name and email address somewhere on the image file, like this. Also, your file names should include your last name (examples: Lukas.jpg, Lukas-home.pdf, etc.). • Email your entry here. If you have more than one concept, feel free to enter as many times as you like. • Deadline: Thursday, Jan. 31, noon ET. The winning entries will be showcased in a future Uni Watch column. OK? OK! Now get crackin'.

Proliferation of NG2 cells in the epileptic hippocampus. NG2 cells are oligodendrocyte progenitor cells, and have been shown to receive synaptic input from pyramidal neurons to generate action potentials. Whether any change of these cells occurs after status epilepticus (SE) and subsequent temporal lobe epilepsy remains unknown. In the present study, the expression of NG2 was investigated in the mouse hippocampus after pilocarpine-induced status epilepticus (PISE). We showed that reactive NG2 cells were significantly increased from 1 day to 2 months after PISE. Double immunofluorescence indicated that few NG2 cells differentiated into neurons and astrocytes after PISE, whereas the number of NG2 cells was increased significantly in the stratum lucidum of CA3 area from 1 day onwards after PISE. Our results suggest that the significantly increased reactive NG2 cells from acute to chronic stage after PISE may be involved in epileptogenesis.

Queenstown Day Trips by Car: Arrowtown and Lake Wakatipu This post on Queenstown day trips by car shows you two short self-drive trips from Queenstown: one takes you to Arrowtown and the other follows Lake Wakatipu shores. Arrowtown is a postcard-pretty mining settlement full of historical buildings and just 20 km north of Queenstown. It’s a must-see destination if you are visiting Queenstown. Lake Wakatipu again is on the other side of Queenstown and you can follow the lake shore either south or north. We went south to Kingston and the scenery was majestic! A tree-lined street in Arrowtown with gold-mining cottages. My Queenstown day trips by car are short trips that need half a day or a whole day depending on your travel schedule. This post is one (number 5) of my posts on our South Island road trip. We made a South Island self-drive tour in 11 days and you can find the whole itinerary and the all other posts here: New Zealand South Island Road Trip in 11 Days Queenstown and its Surroundings So Queenstown is located in the middle of the South Island of New Zealand and has an amazing setting. It’s certainly one of the most scenic locations any city in the in the world has. It’s on the north shore of Lake Wakatipu backed and protected by high mountains in the north. And what’s best, the whole area around Queenstown is just as beautiful as the city itself, wherever you go. So Queenstown is an ideal travel destination for nature lovers but of course for sport lovers and adventure seekers as well. Queenstown Day Trips by Car: Itinerary This Google map shows you Queenstown and the two day trip itineraries. You can zoom in the map to see the details or zoom out if needed. The Arrowtown day trip makes a loop north from Queenstown and the Lake Wakatipu drive follows the lakeshore down to the small community of Kingston and returns the same way. 1. Day Trip to Arrowtown So we went to Arrowtown, and to see more on the road we took the Malaghans Road up to Arrowtown, that’s the route in the west, and the eastern Lake Hayes road back to Queenstown. Malaghans Road to Arrowtown Right outside the city center there is the Skyline Gondola that brings you up a mountain called Bob’s Peak. It’s worth taking that, from the top you’ll have a fantastic panorama of Lake Wakatipu, Queenstown and the whole region. Bob’s Peak has a restaurant and nice walking tracks. More about the Skyline Gondola And another roadside attraction is the Kiwi and Birdlife Park. Then you drive uphill along the steep gorge road and there is a scenic spot, Arthurs Point. Arthurs Point has a high bridge above a winding river deep down in the gorge. An incredible view! In this place you can take a jetboat ride in the gorge. If you are interested, read here about the Shotover Jet. Driving on you will reach the plain of Speargrass Flat with that has high mountain chains on both sides, snow-capped in the autumn. Pretty, pretty! And your destination Arrowtown is close, at the other end of this plateau. Arrowtown I really like this Arrowtown scenery. The location between the mountains is fantastic and it is the best-preserved old gold-mining town in the region. In 1862 they found gold in Fox river that flows through the community and people flocked to the area to search for gold. Today there’s no gold left and no miners at work and Arrowtown is just a small town. But now too people flock here – for the beauty of the place and the old gold town atmosphere. We in fact decided to stay longer than a day in the pretty Arrowtown. We took a campervan site at Arrowtown Camping that is located just a short stroll from the main street. And we had an ideal autumn weather for sightseeing in Arrowtown. There was frost every morning but the days were sunny and pretty warm. This is the tree-lined Centennial Avenue, one of the most atmospheric spots in Arrowtown. A whole row of tiny cottages that have remained from the gold-mining era. Bedford Street This is Bedford Street, the main street where most shops and restaurants are. And there are many old colonial shops that sell local products and handicraft. A bit touristic but the buildings really have style. Arrowtown Riverbank Beyond Bedford Street there is a wooded park and the riverbank, that is Arrowtown Recreational Reserve. This is where it’s easiest to park your car in Arrowtown. The river looks great with yellow leaves in the trees and and you can walk long ways along the riverbank. There is also a former Chinese Mining Settlement where you can learn about the history of Arrowtown. Chinese miners lived in these small huts in the 19th century after European miners had left. At that time the Europeans left Arrowtown to find gold elsewhere. Some of the huts of the Chinese still remain, and in addition there is a small shop and an old outhouse. Arrowtowners still today remember their roots and they want Arrowtown to be a miners’ town. They also have an active miners band that plays on village occasions. If you don’t want to make a self-drive trip to Arrowtown you can alternatively take a tourist bus from Queenstown, there are many tour providers. But we had to leave by them time the tourists came. We took the Lake Hayes road back to Queenstown. Lake Hayes Road to Queenstown And the Lake Hayes Road turned out to be still more beautiful than the road we had taken to Arrowtown. Rolling hills, snow-capped mountains and bright autumn colours. Lake Hayes is like a postcard. This is one of the most photographed lakes in New Zealand that often appears travel promotion materials. And they say Lake Hayes is at its prettiest in clear autumn weather. I haven’t seen it in any other season but I can tell that Lake Hayes and autumn together make a striking combination! If you have energy you can walk around Lake Hayes, they have built a circuit walking track along the lake shore. The track also takes to a coffee cottage, a winery and a lunch bistro in pretty lakeside locations. On the Queenstown Trail website you’ll find the instructions. So this was the Arrowtown day trip and our second of my Queenstown day trips by car shows you Lake Wakatipu shores: 2. Lake Wakatipu Day Trip So we set off from Queenstown and took the Southern Scenic Route towards the Fiorland National Park. This is what it looked like after the first bends and turns. And we followed Lake Wakatipu down to the small community of Kingston that is located at the southernmost end of the lake. The photo above shows the Kawarau Falls just a few kilometres south of Queenstown Airport. That’s a beautiful place and needs a stop. You can see Kawarau river on the photo. We continued south and had a mountain ridge on the left hand side and Lake Wakatipu on the other side, all the way down to Kingston. These mountains are really high and there’s a skiing area in the winter, the Double Cone skiing centre. And on the right hand side there is the hilly Kelvin Heights peninsula. Kelvin Heights is a residential area and imagine the views they fave from their living room windows. Stunning views to the deep-blue Lake Wakatipu and the slopes of Queenstown. Lake Wakatipu The road to Fiordland National Park follows Lake Wakatipu for 47 km. The views are amazing all the way and we just had to stop all the time. For short walks or just for sitting in silence for a while and looking at the view. Lake Wakatipu has an exceptionally strong blue color. That’s because it is a glacial lake and the water comes from melting snow. Lake Wakatipu is the second largest glacial lake in the south, only Te Anau is bigger. There are many world-famous areas you might want to visit in New Zealand: along this road there are the Fiordland National Park, Milford Sound, Lake Manapouri and Te Anau. But since driving on New Zealand roads takes so much time we couldn’t to go that far south nor try to get all the way around Lake Wakatipu. But to get a feeling of the fiords we decided at least to drive down to where the lake ends. Kingston Kingston is a small settlement and quite isolated from everything. But in earlier days Kingston was an important port from where all travelers from the south took a steamship to get north along the lake. There still remains a museum railroad that reminds us of those days when horses, railroad and steamships were the only way of transportation. But we had another way of transportation and prepared a picnic in our rental campervan band then turned back north. And if you like walking, don’t miss this: a short drive from Kingston there is a walking track called the Devils Staircase. It is a one and half hour track in the lush native forest. Driving back to Queenstown we knew the lake already and there was more time to look at the mountain side of the road: was deep forests, high mountains and lots of farming area. And this flock of deer in afternoon sun, what a roadside view!

Socks the Cat Rocks the Hill Socks the Cat Rocks the Hill is one of the most sought after and intriguing unreleased SNES games now that Star Fox 2 has been released. The game was one of many licensed platformers set to be released for the SNES, but its concept has captured the imagination of SNES fans everywhere. What is the story of this lost game? Read on. Thanks to Ellen Fuog for a bunch of the information here, as well as many great scans! Also thanks to billscat-socks, Jonny and Nathan Eveland for information used in this article. By: Evan G Last updated: April 1, 2012 First off, I'd like to thank Nathan Eveland who produced an earlier article that appeared on this site for many years. It was of high quality, though as I have dug into this game during the past month, it became apparent there were several factual errors, and I felt it was time to update it. Socks the Cat Rocks the Hill was one of two games planned by Kaneko USA featuring the Socks the Cat license. A Genesis game, Socks Rocks the Hill, was going to be a completely different game, not a port, and is also unreleased. The Socks the Cat license actually was not owned by the Clinton administration - rather a not-for-profit fan club based in Arlington, Virginia, known as Presidential Socks Partnership, Inc., controlled this license. The fan club was run by Robert Platt and Jay Wind, and their website on Geocities still exists in archives. In exchange for use of the license, Kaneko donated money to charity. The June 20, 1993 issue of the Chicago Tribune gave the details of this agreement: Then there is Socks, barely out of his first 100 days as First Cat and already starring in two video games-one from Sega and another from Nintendo - as well as appearing as a plush toy and a logo for coffee mugs and key chains. How does anybody go about securing licensing rights to Chelsea Clinton's personal cat? The answer is, by law, Socks is nobody's personal cat. His image belongs to the person who copyrights it first, and Bob Pratt, of Presidential Socks Partnership, won the race, along with the right to license his image. Though he didn't have to do it, Pratt has promised a share of his profits to the Humane Society and the Children's Defense Fund, which happens to be one of Hillary Rodham Clinton's favorite charities. Socks himself didn't even get a bag of catnip out of the deal. Kaneko was featured in Playthings Magazine (scan courtesy of Ellen Fuog) Even back when it was announced, this game was a curiosity, if not scoffed at for its unusual concept. Though at the time of its announcement, Socks was a big deal, and even when I was a kid, I remember the celebrity position that Socks had. The game was developed by Realtime Associates, who developed a number of games during the 16-bit era, such as Aaaaah! Real Monsters and Beavis & Butt-head: The Game. Apparently the game was complete. Kaneko gets the Socks The Cat license Being an upstart video game company, Kaneko quickly latched onto big name licenses to survive in the crowded 16-bit platforming market. The only two games that came out using this strategy carried the Chester Cheetah license, though they had plans to release games based on Fido Dido (the mascot for 7-Up) and Socks the Cat. In the June 1993 issue of Playthings magazine, there is a feature piece on Kaneko's products, and they clearly thought they had a winner in these licenses. Socks mania was in full force, and there was a big demand for anything Socks related. Given the popularity of the 16-bit systems was ramping up by the middle of 1993, it was a logical choice to create a video game. Without raising a whisker, "Socks the Cat" has settled into his new White House home and created "Socksmania" across the country. In less than four months of the new administration, the White House cat has gained national attention by appearing on numerous episodes of "Entertainment Tonight" and in newspaper and magazine articles including Time Magazine and The Wall Street Journal. Socks the Cat was the hit of the recent International Toy Fair in New York City and now graces everything from his own plush doll likeness to T-Shirts, bumper stickers, and of course, socks. In his video game debut, entitled "Socks Rocks the House", he will venture from the basement of the White House to the Oval Office to create havoc with the President's allergies. Along the way, while the cat's at play, Socks must push Millie the dog out the front door as well as avoid Arab terrorist felines. Early box art for Socks the Cat "Rocks the House", from Playthings Magazine (courtesy of Ellen Fuog). The Playthings article gives an early working title of the game (Socks the Cat Rocks the House), as well as an initial release date of fourth quarter 1993. A later blurb from the June 15 1993 issue of US Today narrowed the release to January 1994 (and the Genesis game to November 1994). CRUSADER CAT: At least one member of the Clinton clan is as popular today as he was upon entering the White House. Socks has shown up on T-shirts, mugs, stationery. Next up? Socks Rocks the House, a video game from Surge Entertainment in which the four-footed furball searches for an ex-KGB agent intent on detonating the Rush Lim-Bomb and destroying Washington, D.C. The $49.95, 16-bit video game from licensee Kaneko USA, Ltd., will be out in November for use on the Sega Genesis Entertainment System; Socks Rocks the Hill, the Super Nintendo Entertainment System 16-bit format, is due in January. I tried to find information on Surge Entertainment, but I came up empty. I think it must have been an error. Socks shown at Summer CES Back before E3 became the dominant trade show for video games, CES was the primary place for developers to show off new games. At the Summer CES held on June 1993 in Chicago, Kaneko showed off their games based on Chester Cheetah, Fido Dido and Socks the Cat. They held a cocktail party event to unveil the games on June 2nd. Needless to say, Socks the Cat stood out among all of the games shown at the CES. From the June 18, 1993 issue of the Chicago Tribune's overview of the games shown at the CES: Most Politically Correct Software: Socks the Cat Rocks the House (Kaneko) puts you in the role of the First Cat, escaping "from the basement to the Oval Office to create havoc with the president's allergies." I am not making this up. The August 1993 Nintendo power also mentioned the game along with the other Kaneko games in their CES overview. It was clear that Socks the Cat was attracting attention. This is a flyer which likely was given out at CES, with a real picture of Bill Clinton playing the saxophone. Early advertisement presumably for CES (courtesy of Ellen Fuog) Late '93 release? Clearly, Kaneko did intend to push for the release to be in the fourth quarter. It is mentioned in the September 1993 issue of Gamepro that it would be released in January 1994 (probably reiterating what was said at CES). There is a small preview in the November 1993 issue of EGM. A full page advertisement of the game appeared in the November and January 1993 issues of Gamepro. The ad says the game should have been available in Fall 1993. Call it 'capital punishment,' but Socks the Cat, the nation's first feline, is at play on Capital Hill. Suddenly, 'political party' takes on a new meaning in these two new humorous games for Genesis and SNES. 'Socks Rocks the Hill', is a madcap adventure to save the world from nuclear annihilation. Socks, the White House cat, discovers the missing portable nuclear launch unit in his favorite napping spot, the basement of a foreign embassy. To avoid mass destruction, he must return to the White House and alert the first family. But, a foreign spy ring has their own political agenda. They want to see Socks run, and not for political office! The chase begins. Socks must overcome the likes of foreign spies, Enemy Animal Agents, politicians, secret service agents and the ever-present media corp. To keep the party alive, Socks pounces, tumbles, and negotiates his way out of the intricate secret passages and puzzles of Washington. This cat is in a ring of trouble, but not over the hill yet! 'Socks Rocks the Hill' is a one or two player 8 MEG game for Genesis and SNES. Comedic action, scrolling graphics and playful movement make this game a platform to run on, and on and on. Rock on with Kaneko USA's 'Socks Rocks the Hill.' Available nationwide this fall! Advertisement for Socks the Cat, from the November 1993 issue of Gamepro (scan courtesy of Retromags). Screenshot from the advertisement Courtesy of Retromags Kaneko shuts down Clearly, the game did not meet its original deadline. Nintendo Power had a short preview in the May 1994 issue. In it, they state that the content might be considered a bit controversial, but that enemies were quite comical. Preview from Nintendo Power Reviews for Socks the Cat started to appear in magazines between June and July 1994, indicating the game was reaching completion. From the June 1994 issue of Nintendo Power: Review in Nintendo Power (scan courtesy of Retromags). From the July 1994 issue of Gamepro: Review in Gamepro (scan courtesy of Retromags). From the June 1994 issue of EGM: Review in Gamepro (scan courtesy of Retromags). Clearly, Socks the Cat was considered an above average platformer with some imaginative enemies based on political figures. As a bit of a political junkie, I probably would have enjoyed this cute game. The Ross Perot boss seems to have really impressed the reviewers. The Nintendo Power review mentions that the game can be challenging due to poor control, though confusingly the Gamepro review gives it a "beginner" challenge rating. Gamepro review screenshots. Nintendo Power review screenshots Alas, the game was not to be. Kaneko closed its doors shortly before the release of the game. Though the game was reviewed, the former Kaneko employees I contacted say it was not complete. There has been speculation on the Internet that this game met its end because of Nintendo's censorship policies, but this was not the case. I asked Ellen Fuog, former VP of marketing for Kaneko USA about this: Socks absolutely did not fall victim to any Nintendo censorship policies. Quite the contrary, they liked the idea; they liked the game. Everyone did. Most unfortunately, Kaneko did, indeed, shut down its US office around that time (summer 1994). Jeff Hill, the former director of product development at Kaneko, says the game was nowhere near completion: Socks the Cat pretty much headed straight for the litterbox. The game barely got off the drawing board and never got close to being a finished product. All we had at the time development was canceled was part of its first level. Discontinuation of its development had nothing to do with censorship. The game had a long, long way to go and Kaneko closed its US office in July of ’94. The game was never submitted for approval either to NOA or Sega – and certainly never manufactured. I was the guy who would have submitted it! Honestly, the game was nowhere near complete – and development was stopped at least six months before Kaneko closed the US office. I was there to the bitter end – and about five months beyond (retained as a subcontractor to close up shop). Someone says they have a copy and like the game! Someone else has a screenshot of the title screen. Amazing – because there was no game other than some early-development eproms (there were screenshots, though!). I also asked Ellen about the status of the game when Kaneko shut down, and she thought it wasn't close to completion. However, Anne McDonald, who worked on the game at Realtime Associates, says the game was complete: The game was never released. Kaneko Japan chose not to produce it when Kaneko U.S. was closed. The game did clear Nintendo and was complete. No know copies exist. I also asked David Warhol, the owner of Realtime Associates: Yes, we developed and completed Socks Rocks the Hill for SNES. The Genesis version was done by another studio and was called "Socks Rocks the House". I'll tell you this - it was VERY irreverent. The level bosses were main political figures of the time in situations that parodied their political lives. All I remember is that we had Nixon calling in bomb raids and we had Ted Kennedy driving a car around on a bridge. Maybe it's better it didn't come out after all! So, the developer of Socks the Cat says the game was complete and ready for release. The fact that box art was ready for this game also suggests it was close to production. Socks the Cat box - front Socks the Cat box - back Prototype DreamTR owns a prototype of Socks the Cat Rocks the Hill. There is a short film of one of the levels: The video supports the assertion by Realtime Associates that the game was near or at completion. The graphics in the level are the same two of the screenshots available from the reviews of the game. In all likelihood, we'll never see any gameplay beyond this shaky video. Summary Socks the Cat Rocks the Hill probably would have been lost in the sea of 16-Bit platforming games had it been released in 1994. However, its unique political concept has given it an air of legendary mystique amongst us SNES fans. I for one would have loved to see the Rush Lim-Bomb move. Scans Socks The Cat ad (large) Preview in the November 1993 issue of EGM review of the game in Gamepro (large) review of the game in Nintendo Power (large) Cover of the article in Playthings Magazine Playthings Magazine article CES pamphlet (large) Article in Forbes (includes artwork for the Genesis version of the game) Article in the CES Trade News Daily from June 2nd, 1993 Invitation to the Kaneko cocktail event, where they unveiled Socks the Cat Bibliography Gamepro , Review (score: 3.5/5) , Publication date: July 1994, Volume: 60 , Pages: 100 , , Publication date: July 1994, Volume: , Pages: 100 Electronic Gaming Monthly , Preview , Publication date: November 1993, Volume: 52 , Pages: 131 , , Publication date: November 1993, Volume: , Pages: 131 Electronic Gaming Monthly , Review (scores: 6, 5, 5, 7, 6) , Publication date: June 1994, Volume: 59 , Pages: 33 , , Publication date: June 1994, Volume: , Pages: 33 Nintendo Power , Pak Watch - Summer CES , Publication date: August 1993, Volume: 51 , Pages: 113 , , Publication date: August 1993, Volume: , Pages: 113 Nintendo Power , Pak Watch - preview , Publication date: May 1994, Volume: 60 , Pages: 113 , , Publication date: May 1994, Volume: , Pages: 113 Nintendo Power , Review (score: 3.1/5) , Publication date: June 1994, Volume: 61 , Pages: 102-107 , , Publication date: June 1994, Volume: , Pages: 102-107 Playthings Magazine , featured article on licensing in video games , Publication date: June 1993, Volume: , Pages: 50 , , Publication date: June 1993, Volume: , Pages: 50 Socks the Cat on Unseen64 (link) Discussion of Socks the Cat on the Lost Levels forum (link) Discussion of Socks the Cat on Digital Press (link) Discussion of the prototype on Nintendo Age (link)

Q: Why didn't battleship Bismarck have more support? The primary objective of battleship Bismarck was to sink transporters coming from the U.S. and sailing to Europe transporting goods (oil, food). It encountered HMS Hood and sank it. German cruiser Prinz Eugen was sailing along with the Bismarck all the time apart from the time the Royal Navy engaged heavy forces to sink it. Why didn't the Bismarck have decent battleships, carriers and other fleet types sailing with it all the time? It was certain to German admirals that after the sinking of HMS Hood the Brits would employ forces in order to destroy the Bismarck. Why didn't Otto Ernst Lindemann (naval captain, only commander of the Bismarck) ask for reinforcements after the HMS Hood event? A: The Germans wanted to send more, but there were none available. Most were unsuitable to escort Bismarck. Those which were suitable were damaged. A good warship for commerce raiding is fast, both to catch enemy ships and run from warships, fuel efficient to keep at sea for as long as possible, and carries heavy armament to rapidly sink enemy ships from long range. Bismarck could make 30 knots and cruise for 10,000 miles, there were few heavy ships in the Germany Navy which could keep up. Her sister, Tirpitz, was still working up. The battleships Scharnhorst and Gneisenau were both under repair in Brest on the wrong side of the North Sea. The old pre-Dreadnaught Deutschland battleships were far too slow. Germany had build a small fleet of brand new Admiral Hipper heavy cruisers. Blücher had been sunk, Admiral Hipper was being overhauled in Kiel, Seydlitz was never completed, and Lützow had been sold to the Soviets. Prinz Eugen which was damaged but hastily repaired and ready. This left the older and slightly slower Deutschland class "pocket battleships" designed as commerce raiders. Of the pocket battleships, Admiral Graf Spee had been famously scuttled in her own commerce raid. Lützow nee Deutschland had recently finished repairs from a British torpedo attack and was waiting to go on its own raid with Admiral Sheer. Admiral Scheer had just returned from a five month long shipping raid in the Atlantic and was undergoing repairs in Kiel. The rest of the Germany Navy was light cruisers, destroyers and smaller ships. While they had the speed, they did not have the endurance. They also didn't have the firepower. The heavy 203mm and 380mm guns of the Prinz Eugen and Bismarck will be in range long before the 150mm guns of a German light cruiser. Since you're not planning on fighting a fleet of warships there's no need for a screen of light ships. They're just a liability. As for carriers, Germany never had one. Bismarck was used as a commerce raider because she could destroy most British ships before they could even get in range and run from the rest. Prinz Eugen was the only available consort. But they were caught by equally fast and powerful units of the British Navy sent to find them, the Hood and the Prince of Wales, and forced to fight. Sending more warships risks the commander thinking they should be fighting enemy warships. This was not their mission, though the German commanders often did not agree. The diminutive German Navy had no hope of defeating the Royal Navy in a fair fight on the high seas, but it didn't stop officers from thinking they could, especially with a ship as new and powerful as the Bismarck. Captain Lindeman, commanding Bismarck, was eager for a fight to use his powerful new ship. But Admiral Lütjens strictly held them to their mission. Then there is the problem of supply, in particular food and fuel. A successful commerce raider will be out as sea for as long as possible. Even if they fail to sink a single ship, their existence can tie up enemy naval assets hugely out of proportion. A commerce raider can resupply from friendly overseas ports, and from friendly supply units, but mainly from scavenging from the commerce they raid. The more fuel hungry warships you have in your fleet, and their very large and hungry crews to feed, the more thinly you need to spread your supplies. The Bismarck's mission was to raid commerce, not engage enemy warships. A good commerce raider will hide or run, only as a last resort should it fight. Why? It jeopardizes its mission of raiding commerce. Fighting a warship risks damage, damage that could force it to return to port early (thus aborting its primary mission), or make it vulnerable. The Bismarck's victory against the Hood caused both these consequences. The Admiral Graf Spee had a similar fate after its victory in the Battle of the River Plate. Even with no damage, engaging a warship means firing a lot of precious main battery armament. Fuel can be taken from enemy ships, but ammunition cannot be replaced without returning to port or a risky at-sea resupply mission. Resupply at sea leaves you stopped and vulnerable with more ships for the enemy to track. Returning to port both cuts short its primary mission, and it leaves it open to bombing and blockade by the much more powerful British Navy, as happened to its sister Tirpitz. If you sink a Royal Navy warship you risk the wrath of the Royal Navy, far more powerful and numerous than the German Navy. It makes it difficult to raid commerce when you're dodging an ocean full of British warships. It happened in WWI after a German victory by von Spee's powerful commerce raiding squadron at the Battle of Coronel, they were destroyed a month later by an even more powerful British task force sent to hunt them down at the Battle of the Falkland Islands. Sinking the Hood, pride of the Royal Navy, and in such a spectacular fashion, signaled the death of the Bismarck, failure of her mission, and the loss of an irreplaceable German battleship. See Also Operation Rheinübung - First and Last Voyage of the Bismarck by Drachinifel A: As identified in the first paragraph of the question, the purpose of Operation Rheinübung was a continuation of the commerce raids on allied shipping in the Atlantic. The Scharnhorst and Gneisenau had previously performed a similar exercise with great success. Commerce raiding was a common tactic used against a superior (or simply numerically larger) naval force. It allowed the smaller force to do disproportionate damage against the enemy shipping while avoiding the risk of putting all of their warships at risk at once. By keeping their own ships dispersed, the Germans would force the British to spread their own forces to find and attack them. In that situation, there was the possibility that the German battleship would be able to out-fight the force it encountered (or simply out-run, as was the case when the Scharnhorst and Gneisenau encountered a couple of British battleships). Had the Germans committed a larger flotilla (or even fleet) to the operation, it would have allowed the British to concentrate their forces too. In a fleet action the Germans would have, almost certainly, been outnumbered and outgunned. In which, case they would have been at risk of losing a considerable part of their surface fleet in a single action. A: As far as "battleships" go, the Germans only had the Bismarck. The Tirpitz had just completed construction and wasn't quite "ready" for major duty, and the battle-cruisers Scharnhorst and Gneisenau were undergoing repairs. A more interesting question is why didn't Germany send out cruisers and destroyers with the Bismarck to protect it from "cheap shots." Apparently, no one felt that they were needed. The Bismarck originally had a cruiser escort, the Prinz Eugen, that did a great job of shielding the Bismarck against the opening fire of the Hood. But Bismarck's Admiral Luetgens apparently didn't feel the need for such an escort, and detached the Prinz Eugen for "independent" duty. The idea was that the Prinz Eugen could do more damage by itself than by accompanying a Bismarck that was damaged, and needed to head to port for repairs. With benefit of hindsight, the Prinz Eugen's anti-aircraft fire might have helped save the Bismarck from air attack by the bombers of Britain's Ark Royal. But that's with hindsight, because no one thought in those terms at the time.

Combined lesions of cholinergic and serotonergic neurons in the rat brain using 192 IgG-saporin and 5,7-dihydroxytryptamine: neurochemical and behavioural characterization. This study assessed behavioural and neurochemical effects of i.c.v. injections of both the cholinergic toxin 192 IgG-saporin (2 microgram) and the serotonergic toxin 5,7-dihydroxytryptamine (5,7-DHT; 150 microgram) in Long-Evans female rats. Dependent behavioural variables were locomotor activity, forced T-maze alternation, beam walking, Morris water-maze (working and reference memory) and radial-maze performances. After killing by microwave irradiation, the concentrations of acetylcholine, monoamines and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the hippocampus, frontoparietal cortex and striatum. 192 IgG-saporin reduced the concentration of acetylcholine by approximately 40% in the frontoparietal cortex and hippocampus, but had no effect in the striatum. 5,7-DHT lesions reduced the concentration of serotonin by 60% in the frontoparietal cortex and 80% in the hippocampus and striatum. Noradrenaline was unchanged in all structures except the ventral hippocampus where it was slightly increased in rats given 192 IgG-saporin. Cholinergic lesions induced severe motor deficits but had no other effect. Serotonergic lesions produced diurnal and nocturnal hyperactivity but had no other effect. Rats with combined lesions were more active than those with only serotonergic lesions, showed motor dysfunctions similar to those found in rats with cholinergic lesions alone, and exhibited impaired performances in the T-maze alternation test, the water-maze working memory test and the radial-maze. Taken together and although cholinergic lesions were not maximal, these data show that 192 IgG-saporin and 5,7-DHT lesions can be combined to selectively damage cholinergic and serotonergic neurons, and confirm that cholinergic-serotonergic interactions play an important role in some aspects of memory, particularly in spatial working memory.

Activation of specific glutamate receptor subtypes increases C-fos proto-oncogene expression in primary cultures of neonatal rat cerebellar granule cells. In primary cultures of rat cerebellar granule cells the activation of excitatory amino acid receptors by 1-glutamate enhances the steady state level of c-fos proto-oncogene messenger RNA. This effect is blocked by magnesium (1mM) as well as by the glutamate receptor antagonist 2-amino-5-phosphono-valerate (APV). Among the other excitatory amino acid agonists N-methyl-D-Aspartate (NMDA) and quisqualate also increased c-fos mRNA content, the latter however to a significantly lesser extent, while kainate failed to modify the basal level of c-fos expression. The addition of the muscarinic agonist carbachol or of the inhibitory neurotransmitter GABA did not affect the basal level of c-fos mRNA. This data demonstrate for the first time that activation of signal transduction at a specific excitatory amino acid receptor subtype can increase the steady state level of c-fos proto-oncogene mRNA in primary culture of cerebellar neurons.

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Q: A webapp that uses Spring AMQP is that consired to be 1 client? Hi there i am wondering if i create a webapp that uses Spring AMQP. Is that single webapp 1 AMQP client? Or is every request made by a user that results into an AMQP call a client, so potentially x numbers of clients? A: I don't know AMQP much, but I suspect it has the same terminology as jms. In that sense your application is probably pooling connections to AMQP broker for better performance. Each connection in a pool is treated as a separate client (competing consumer). Thus each request is not really creating a new connection (client), but your application isn't a single client as well. In fact, when your application tries to access AMQP broker, it picks any connection from the pool and puts it back once it's done. Another request can reuse the same connection (client) or use a different, idle one.

Roundup Lawsuit Studies have linked Roundup to non-Hodgkin’s lymphoma, a deadly form of cancer. In March 2015, the World Health Organization published a report stating that Roundup is “probably carcinogenic to humans.” Since that time our firm has filed thousands of lawsuits against Roundup’s manufacturer. With Billions of dollars in settlement money currently being negotiated; you should contact our law firm immediately if you or a loved one has been harmed by this dangerous product. Recent studies have linked Monsanto Roundup weed killer to non-Hodgkin lymphoma, a deadly type of cancer that attacks the lymphatic system, and many other life-threatening side effects. In March 2015, the World Health Organization (WHO) published a report stating that Roundup is “probably carcinogenic to humans.” Free Roundup Lawsuit Review If you or a loved one was diagnosed with any form of non-Hodgkin lymphoma after using or being exposed to Roundup herbicide, you should contact our law firm immediately. You may be entitled to compensation by filing a Roundup lawsuit and we can help. Please click the button below for a Free Confidential Case Evaluation or call us toll-free 24 hrs/day by dialing (866) 588-0600. Update: New Mexico City Bans Glyphosate August 22, 2019 – Las Cruces, New Mexico, voted on Monday to remove all glyphosate herbicides from use on city property once remaining stocks are depleted, according to Las Cruces Sun News. Parks and recreation director Sonia Delgado said the city’s supplies of the weed killer have mostly been used. Monday’s resolution bars future use of any herbicides containing glyphosate. What is Roundup? Roundup is a herbicide used to control many varieties of invasive exotic plants. Glyphosate, the primary ingredient in Roundup, inhibits a specific enzyme called EPSP synthase, which plants need to grow1. Without EPSP synthase, plants are unable to produce other proteins essential to growth, so they wither and die over a period of days or weeks. Since most plants require EPSP synthase, almost all forms of vegetation succumb to Roundup. Use of glyphosate has soared in recent years due to Monsanto’s Roundup Ready crops, which account for most corn and soybeans now grown in the U.S. These crops are genetically modified (GMO) to be resistant to glyphosate, allowing farmers to spray their fields without damaging the crops. Monsanto’s History of Deception From 1996 to 2011, the use of Roundup Ready GMO crops increased herbicide use in the U.S. by 527 million pounds — even though Monsanto claimed its GMO products would reduce pesticide and herbicide use.2 Monsanto has continually falsified data on Roundup’s safety, and marketed the herbicide as “environmentally friendly” and “biodegradable,” to promote sales, according to EcoWatch. In January 2007, a French court ruled that these claims amounted to false advertising.3 Roundup ‘Probably’ Causes Cancer: Report In 1985, an EPA committee found that Roundup may cause cancer, according to the New York Times. Six years later, the agency reversed itself after re-evaluating the study it had based its original conclusion on. Now the issue is back again. In March 2015, the International Agency for Research on Cancer (IARC), which is the cancer research arm of the World Health Organization (WHO), published a report in The Lancet Oncology which found that the glyphosate contained in Roundup “probably” causes cancer in humans.5 “All three lines of evidence sort of said the same thing, which is we ought to be concerned about this,” said Aaron Blair, a retired epidemiologist from the National Cancer Institute (NCI) and chairman of the group of 17 reviewers who unanimously agreed with the classification. Monsanto Still Trying to Cover Up Deadly Risks of Roundup: Ring of Fire Video Types of Cancer Linked to Roundup Our lawyers are accepting potential lawsuits for people who developed the following forms of cancer after using or being exposed to Roundup weed killer: How Toxic is Roundup? Glyphosate has long been considered by many to be completely safe because it works by inhibiting an enzyme pathway that only exists in green plants, and not in humans or other animals. Since the introduction of Roundup-Ready crops — which Monsanto engineered to be resistant to glyphosate — in the mid 1990s, American farmers have been able to use large quantities of the herbicide to kill weeds selectively. However, over the past 20 years, numerous studies have also suggested that glyphosate may not be as safe as originally believed. A recent collaborative study published in Mutation Research reported that individuals with particularly high exposures to glyphosate (i.e. those who spray it) could have a 41% increased relative risk of developing non-Hodgkin lymphoma. There has been much speculation concerning what exactly causes the increased risk for lymphoma, including the notion that glyphosate may mimic the behavior of certain hormones in humans. One study, conducted by researchers in Thailand, found that by taking on the traits of these hormones, even minuscule amounts of glyphosate could increase the rate of breast cancer cell growth in petri dishes. Numerous research papers have been published stating that glyphosate is harmless, and just as many have entered the literature contending the opposite. Still other studies have failed to reach any definitive conclusion. A recent 20-year analysis of data on nearly 45,000 farmworkers who applied glyphosate herbicides to their crops found no association with lymphoma and overall cancer risk. St. Louis Judge Denies Monsanto Bid to Postpone Roundup Cancer Trial August 14, 2019 – Monsanto’s attempt to postpone the next St. Louis trial it faces involving Roundup cancer allegations has been snubbed by Circuit Court Judge Michael Mullen, who said the case shall proceed as scheduled in October, according to the American Council on Science and Health (USRTK). The trial, Walter Winston v. Monsanto, would mark the 4th time Monsanto has had to defend lymphoma claims over Roundup, but just the first time in its hometown of St. Louis, Missouri. Another trial that had been set to begin in St. Louis on Aug. 19 was delayed by court order last week, and a trial that was slated for September has also been continued. Judge Mullen refused to do the same with the Winston case, saying depositions and discovery should continue until Sept. 16, with the jury selection to begin on Oct. 10. Bayer Proposes $8 Billion Settlement for Roundup Cancer Suits August 9, 2019 – Bayer AG is proposing to settle the Roundup litigation — nearly 18,000 products liability lawsuits alleging glyphosate caused cancer — for about $8 billion and change, according to Bloomberg. The agreement, which would take months to work out even if all parties agreed to the terms, would do wonders to reduce the stress on Bayer, which purchased Monsanto last year for around $66 billion. The ensuing litigation has decreased Bayer’s market value by $30 billion, prompted an unprecedented shareholder vote of no confidence, and even sparked rumors of a company breakup. Plaintiffs’ lawyers have stated they want more than $10 billion to resolve the claims, and there’s no sure way to deal with future plaintiffs who have yet to be diagnosed, which means there’s a high likelihood the lawsuits will stay put for the time being. Santa Barbara to Eliminate Roundup Use in City Parks July 31, 2019 – As part of its updated integrated pest management Program, the city of Santa Barbara, California, has announced plans to eliminate the use of glyphosate herbicides in parks, according to NOOZHAWK. The city already avoids the chemical in most parks, but will add Cabrillo Ball Field, Dwight Murphy Park, Franceschi Park, MacKenzie Park, Orpet Park, Pershing Park, San Roque Park, Sylvan Park and Hidden Valley Park. Santa Barbara uses neem oil, a natural product, instead of glyphosate to combat insects and fungus. May 6, 2019 – Watsonville banned glyphosate from use on city-owned land in a unanimous City Council vote on April 23, according to the Santa Cruz Sentinel. The ban is to take effect on July 1. Concerns that glyphosate may have the potential to cause non-Hodgkin lymphoma and other types of cancer have been mounting for years, with allegations coming to a head in the form of more than 10,000 lawsuits filed against Bayer AG, which purchased the Monsanto Company last August for about $63 billion. A peer-reviewed study published in October by the Environmental Working Group (EWG) found trace amounts of glyphosate in at least 28 cereals and other foods marketed toward younger consumers. All but 2 of the 28 samples had levels of glyphosate above EWG’s own benchmark of 160 parts per billion (ppb). Foods tested included 10 samples of General Mills’ Cheerios and 18 samples of Quaker brand products, including instant oatmeal, breakfast cereal and snack bars. In addition to the new moratorium in Watsonville, the use of Roundup and other glyphosate weed killers has already been banned or heavily restricted in more than 25 California cities, counties and school districts, including: Arcata Belvedere Benicia Berkeley Burbank Carlsbad Corte Madera Davis Encinitas Fairfax Fresno Irvine Lodi Long Beach Los Angeles County Mill Valley Novato Oakland Palo Alto Petaluma Richmond San Anselmo San Francisco San Lorenzo Valley Santa Rosa Sonoma Thousand Oaks Woodland Los Angeles County became the largest California government to ban glyphosate in March, issuing a moratorium on the herbicide and citing the need for additional studies into the potential health risks posed by the chemical. Watsonville Mayor Francisco Estrada acknowledged the decision to ban glyphosate outright could complicate maintenance, but said it was a necessary step to put public health concerns first. “I think that this was something that was within our reach and something I could participate in to make a positive change,” Estrada said. “Will there be a cost, yes, will there be consequences, yes. I’m ready for the consequences.” General Mills Sued Over Glyphosate in Nature Valley Granola Bars Three nonprofit organizations have filed a lawsuit against General Mills for allegedly misleading the public by labeling Nature Valley granola bars as “100% natural” when they actually contain glyphosate. The lawsuit was filed under the District of Columbia’s Consumer Protection Procedures Act, according to Bloomberg. Plaintiffs include Moms Across America, Beyond Pesticides, and the Organic Consumers Association. “As a mother, when I read ‘100% Natural,’ I would expect that to mean no synthetic or toxic chemicals at all,” said Zen Honeycutt, founder and executive director of Moms Across America. “Glyphosate is a toxic chemical that the EPA recognizes as a ‘reproductive effector’ which ‘can cause liver and kidney damage’ and ‘digestive effects.’ It is unacceptable that Nature Valley granola bars contain any amount of this chemical.” A 2015 Consumer Reports survey found that 66% of consumers look for foods with the word “natural” on the labeling under the assumption they are produced without pesticides, genetically modified organisms (GMOs), hormones, or artificial ingredients. Glyphosate is used in production of oats, the major ingredient in Nature Valley granola bars, which are marketed as “natural” and labeled “Made with 100% Natural Whole Grain Oats.” Monsanto says the residue levels found in many foods and beverages in the U.S. are below allowable levels established by the Environmental Protection Agency (EPA) in 2014, and therefore consumers have no reason to be concerned. However, a 2015 study published in the journal Environmental Health found that chronic, low-dose exposure to glyphosate — as low as 0.1 parts per billion — can cause adverse effects on the liver and kidneys. Another study published earlier this year determined that glyphosate exposure can cause changes to DNA function resulting in the onset of chronic diseases including type 2 diabetes, obesity and Alzheimer’s disease. The complaint alleges that General Mills misled consumers by failing to disclose the presence of glyphosate in its Natural Valley products and warn of its harmful effects. Plaintiffs claim that General Mills’ “natural” labeling is deceptive, misleading and unlawful, and require its removal from the market. Caltech Bans Use of Glyphosate at Student Housing July 24, 2019 – The discovery that a landscaper applied the glyphosate-containing weed killer Ranger Pro at a Caltech housing facility has sparked some controversy among staff and the student body, but in a Monday announcement the university defended the herbicide and the landscape vendor’s manner of applying it, according to Pasadena Now. Caltech Director of Housing Maria A. Katsas claimed the Institute will stop using “pesticides” in the near future, and is committed to any needed clean-up efforts. “We are … consulting with a toxicologist to determine what clean-up measures would be needed and most effective,” Katsas said. “We regret that you were not notified in advance of the use of RangerPro at the Villa student housing complex in the past.” May 14, 2019 – A jury in San Francisco, California, on Monday awarded more than $2 billion to a couple who claimed Roundup herbicide caused their cancer. The recent verdict spells bad news for Bayer, which still faces more than 13,000 similar lawsuits alleging Roundup and other glyphosate-based herbicides cause cancer. Bayer shares fell 2% on the news, and have plummeted more than 45% this year, according to CNN Business. As in its previous defeats, Bayer vows to fight the verdict, and maintains that Roundup is completely safe, and one of the most thoroughly tested chemicals in existence. Although Bayer did see a bit of good news last month when the U.S. Environmental Protection Agency (EPA) declared that glyphosate is not carcinogenic, its best bet may be to settle the remainder of the litigation, else the company may never hear the end of claims over Roundup. EPA Says Roundup Chemical Not Linked to Cancer May 3, 2019 – EPA’s declaration opposes a growing body of research which suggests that glyphosate increases the risk for lymphoma and other deadly forms of cancer. “Today’s decision by Administrator Wheeler, like virtually every one he and the Trump administration make, completely ignores science in favor of polluters like Bayer,” said Ken Cook, President of the Environmental Working Group (EWG). “This move by EPA should not come as a surprise. Under the control of Trump and Wheeler, the agency is virtually incapable of taking steps to protect people from dangerous chemicals like glyphosate.” EPA’s ruling marks a welcome — albeit temporary — sigh of relief for Bayer, which purchased Monsanto last August for $63 billion, and has recently lost 2 straight Roundup cancer trials in the Northern District of California, where MDL 2741 is being overseen by Judge Vince Chhabria. In March 2017, Judge Chhabria released records exposing how a corrupt former EPA official bragged to Monsanto that he deserved a medal if he could kill an investigation into the cancer risk with glyphosate. Monsanto was seeking the help of Jess Rowland, former manager of EPA’s pesticide division, to help stop an investigation into the glyphosate cancer risk by the Agency for Toxic Substances and Disease Registry (ATSDR). “If I can kill this I should get a medal,” Rowland told a Monsanto regulatory affairs manager, who recounted the conversation in an email to his colleagues. Rowland’s statements illustrate how the EPA, which was supposed to be policing Monsanto’s activities, was actually colluding with the agrochemical giant to downplay the Roundup cancer link. He apparently succeeded, as ATSDR never published a toxicological profile of glyphosate. April 9, 2019 – A pathologist from the City of Hope National Medical Center in Duarte, California, who claims to have poured over more than 2,000 pages of medical records for plaintiffs in the next Roundup cancer trial concluded that exposure to glyphosate was the “most significant contributing factor” in causing their development of non-Hodgkin lymphoma. Dr. Dennis Weisenburger, a pathologist hired by the plaintiffs who has studied the significant increase in lymphoma cases since glyphosate has been on the market and authored nearly 400 peer-reviewed articles, seemed confident in his assertion that Roundup was the likely causative agent in both plaintiffs’ development of the disease. “It’s not a hard call,” Weisenburger said. Weisenburger is the most recent witness to testify in a jury trial alleging that the plaintiffs’ regular exposure to thousands of gallons of Roundup on their 4 properties for more than 3 decades caused them to develop non-Hodgkin lymphoma. The trial is expected to conclude sometime next month. During his testimony on Tuesday, Weisenburger spent a good portion of his time on the stand explaining epidemiological studies on glyphosate to the jury. He mentioned one study in particular which found that the Roundup mixture was 200 times more genotoxic, or DNA damaging, than glyphosate alone. Weisenburger estimated that Mr. Alva had sprayed Roundup a total of at least 729 times, and Alberta sprayed it approximately 270 times, on their 4 properties over the previous 35 years. Both used the herbicide without taking extra safety protections and in casual clothing, he said. The couple were diagnosed with lymphoma within years of each other, Weisenburger said, and that Alva continued to spray Roundup even after he was diagnosed with cancer in 2011. The lawsuit is: Pilliod v. Monsanto Co., case number RG17862702, in the Superior Court of the State of California, County of Alameda. Monsanto has been ordered to pay an $80 million settlement to a San Francisco man who claims that his development of non-Hodgkin lymphoma was the result of his use of Roundup weed killer, in a rare split-trial which could influence the outcome of thousands more cases. Monsanto’s request to bifurcate the first federal trial involving allegations that Roundup caused cancer seems to have backfired, as the jury on Friday reached verdicts against the Bayer AG unit, awarding the Plaintiff over $80 million in damages. The trial got underway in federal court in San Francisco on Feb. 25, overseen by the honorable U.S. District Judge Vince Chhabria. Ed Hardeman, the 70-year-old Santa Rosa man who filed the claim, alleged that his use of Roundup for decades on and around his property significantly contributed to his development of lymphoma. The jury deliberated for about a week over the first portion of the trial, and just 1 day for the second, unanimously ruling in favor of Hardeman in both instances. Monsanto was found guilty on a failure to warn claim, a design defect claim, and a negligence claim. The jury awarded Plaintiff over $80 million in damages, including $75 million in punitive damages. Bayer’s Shares Plummet Following Consecutive Roundup Trial Losses March 22, 2019 – Shares of Bayer AG dropped over 12% on Wednesday after a jury in federal court in San Francisco ruled for the second time that its Monsanto Roundup weed killer caused cancer. It was the pharmaceutical giant’s biggest 1-day loss in 16 years, according to Reuters. The lawsuit was filed on behalf of Edwin Hardeman, who claimed that decades of using Monsanto Roundup on his 56-acre property in Santa Rosa, California, caused his non-Hodgkin lymphoma. After deliberating for a week, the San Francisco jury unanimously agreed, finding that Roundup was likely a “substantial factor” in causing Hardeman’s cancer. The decision dealt Bayer a hefty second blow in the Roundup litigation, having been defeated last August in a similar lawsuit filed by Dwayne Johnson, who now has terminal stage 4 cancer and was not even expected to survive the end of his trial. “This looks like 2-0 plaintiffs, and clearly not helpful for the overall payout calculus and resolution of the litigation,” said Bernstein analyst Gunther Zechmann. The Hardeman case marked the first federal bellwether trial in MDL 2741. The lawsuit is unique in that the trial consists of 2 phases: the first to cover scientific disputes, and the second to address allegations of wrongdoing by Monsanto. Bayer still faces thousands of additional lawsuits alleging Roundup herbicide caused cancer. San Francisco Jury Rules Plaintiff’s Cancer Caused by Roundup March 19, 2019 – The jury of 5 women and 1 man reached a unanimous decision in favor of plaintiff Ed Hardeman after deliberating for a week, according to Law360. The verdict marks another costly setback for Bayer AG, which purchased Monsanto last August for about $63 billion, but which had to have seen at least a portion of these woes coming, as the litigation was already in full swing at the time. During the trial, Hardeman testified that he used Roundup for more than a quarter century (1986-2012) on his 56-acre property in Santa Rosa, CA, to kill weeds and poison oak. During this process, Hardeman said mist from the herbicide fell onto his skin and face. He was diagnosed with stage 3 non-Hodgkin lymphoma in 2015 at age 66, and has since been forced to undergo cancer treatment. A series of medical professionals testified for both sides during the trial, presenting the jury with vastly different opinions regarding the link between Roundup and cancer. During closing statements, Hardeman’s legal team argued that his exposure to Roundup had been extreme and that their side had shown “overwhelming evidence” from animal studies, mechanistic data and epidemiological data confirming the link between Roundup and cancer. Monsanto contended on rebuttal that Harderman’s cancer studies were inadequate and unreliable, and that he has the most common form of non-Hodgkin lymphoma which makes it impossible to rule out chronic hepatitis C and hepatitis B as a contributing factor to his disease. The jury ultimately sided with the prosecution, determining that it was more than 50% likely that Roundup “significantly contributed” to his cancer. Monsanto Cancer Report Deemed Admissible in Roundup Lawsuit March 7, 2019 – U.S. District Judge Vince Chhabria said Monsanto’s attorneys “opened the door” to allowing the report by arguing that glyphosate is not genotoxic — meaning that it can’t cause genetic damage to human cells. The judge said Monsanto’s position is contradicted by its own internal report, which was produced by Dr. James M. Parry. The issue came up during a hearing for the bellwether trial, which began last week only to be paused momentarily for a sick juror, according to Law360. Last August, a California jury found Monsanto liable in a similar lawsuit filed by a man alleging that Roundup caused his cancer and ordered the company to pay $289 million in damages, which was later slashed to $78 million. In the Hardeman case, pathologist Dr. Dennis Weisenburger testified on Wednesday that he believed Roundup caused the plaintiff’s lymphoma, refuting an argument by Monsanto that the disease was a result of the man’s hepatitis C and age-related factors. “If he was going to get lymphoma, he would have gotten it when he had the infection, not nine years after he was cured,” Weisenburger said. The pathologist also said when Hardeman was cured of hepatitis in 2006, any cells damaged by the virus would have died off, rejecting Monsanto’s claims that his 2015 diagnosis of non-Hodgkin lymphoma was caused by the hepatitis. New Study Finds Glyphosate in Dozens More Cereals, Children’s Foods October 25, 2018 – A new study conducted by the Environmental Working Group (EWG) found the controversial herbicide glyphosate in at least 28 cereals and other children’s foods, less than 3 months after another study found “a hefty dose” of the weed killer in dozens of similar products. EWG’s peer-reviewed study focused on oat-based cereals and other foods marketed at children, and arrived at conclusions which “fly in the face of claims by two companies, Quaker and General Mills, which have said there is no reason for concern,” the watchdog group claims. EWG tested 28 products—all of which were made from “conventionally grown” (i.e. non-organic) oats—and found only 2 had glyphosate levels below its benchmark of 160 parts per billion (ppb). “Almost all of the samples tested by EWG had residues of glyphosate at levels higher than what EWG scientists consider protective of children’s health with an adequate margin of safety,” the group said. “If those companies would just switch to oats that aren’t sprayed with glyphosate, parents wouldn’t have to wonder if their kids’ breakfasts contained a chemical linked to cancer.” Manufacturers say their products are safe, but the new study argues that most of the foods tested have glyphosate in amounts that could pose a cancer risk with long-term exposure. None of the foods violated EPA limits on the herbicide; however, EWG uses a far more conservative health benchmark. California’s proposed glyphosate limit, which would be the most restrictive in the U.S., still allows for glyphosate levels that are over a hundred times higher than EWG’s allowance. Landmark Roundup Trial Ends in $289 Million Award to Plaintiff August 13, 2018 – The jury ruled that Roundup herbicide and Ranger Pro products presented a “substantial danger” to the now 46-year-old Dewayne “Lee” Johnson, who developed non-Hodgkin lymphoma after using the spray for more than 2 years as a groundskeeper in San Francisco. Jurors concluded that Monsanto knew or should have known of the potential health risks associated with the chemicals. The jury awarded Johnson $289 million — mostly in the form of punitive damages intended to dissuade Monsanto from allowing the same fate to befall others that Johnson was forced to endure. The now 46-year-old used Roundup weedkiller 20 to 30 times per year while working as a groundskeeper for a San Francisco area school district, according to the lawsuit. He claims that during this time, he had 2 accidents in which he was soaked with the herbicide. Johnson’s case was the first to go to trial because doctors said he didn’t have long to live, and in California, dying plaintiffs can be granted expedited trials. Next up to trial is 48-year-old Aaron Johnson, a former macadamia nut field manager who was diagnosed with lymphoma in 2014, after using Roundup for 12 years. Roundup Cancer Trial Moves Forward July 12, 2018 – Hundreds of lawsuits alleging Roundup caused cancer advanced a crucial step forward on Thursday when a judge in San Francisco Superior Court ruled that a cancer victim could present expert testimony linking the herbicide to non-Hodgkin lymphoma. Judge Chhabria said evidence linking glyphosate was “rather weak”; however, he also affirmed that the opinions of 3 experts linking the weed killer to cancer were relevant, and not tantamount to “junk science.” The suits allege that Monsanto has known for decades about the cancer risk with Roundup, yet failed to adequately warn the public, medical, and scientific communities. Chhabria’s ruling allows the complaints to advance a crucial step forward, though Chhabria warned it could be a “daunting challenge” to convince him that glyphosate causes non-Hodgkin lymphoma. Many U.S. government agencies have rejected the link between cancer and glyphosate. Monsanto has, of course, forcefully denied the connection, claiming that the chemical is among the most tested of all-time, and that hundreds of studies have established that the chemical is safe. Human Glyphosate Levels Increased 500% Since 1993, Study Finds October 31, 2017 – A new study has found that humans levels of glyphosate have more than doubled since 1993. The study, which analyzed glyphosate levels in the urine of 100 people in California, was conducted by the San Diego School of Medicine and published in the Journal of the American Medical Association (JAMA). “The data compares excretion levels of glyphosate and its metabolite aminomethylphosphonic acid in the human body over a 23-year time span, starting in 1993, just before the introduction of genetically modified crops into the United States,” said Dr. Paul J. Mills, who led the study. The researchers found that detectable amounts of glyphosate increased from about 0.2 micrograms per liter to .44 micrograms per liter between 2014 and 2016. The daily limit set by the U.S. Environmental Protection Agency (EPA) is 1.75 milligrams (MGs) per kilogram. Mills said the next step for the study’s authors is to investigate the overall health of participants who had increased levels of glyphosate in their urine. “I am concerned,” Mills said. “This is one of the reasons I put together this study, because there wasn’t such information in the biomedical literature, and I thought we needed it, and we needed to start having some good data to have a conversation around these questions.” Use of glyphosate has increased about 500% since the early ’90s, the researchers found. Regulators to Consider Tighter Restrictions on Glyphosate Use Whether or not the IARC report affects sales of Roundup depends on if regulators decide to impose tighter restrictions on glyphosate use. A spokesman for the California Office of Environmental Health Hazard Assessment (OEHHA) said it was evaluating whether glyphosate-containing products may have to be re-labeled as posing a cancer hazard under Proposition 65, according to the Times. EPA to Re-evaluate Herbicide Toxicity Some consumer and environmental groups have called on the EPA to strengthen the labeling of genetically modified foods, and to re-evaluate the safety of glyphosate and a newer weed killer made by Dow Chemical that combines glyphosate and another herbicide, 2,4-D. EPA said it would consider the findings of the new report in its own review of glyphosate; however, the agency continues to maintain its classification for the chemical as having “evidence of non-carcinogenicity for humans” since 1991, according to the Times. Working to Limit Roundup Use Over Health Concerns In April 2013, a study published in the journal Entropy6 looked at glyphosate’s ability to interfere with normal bodily functions. The authors state “[Glyphosate’s] negative impact on the body is insidious and manifests slowly over time as inflammation damages cellular systems throughout the body.” Stephanie Seneff, a research scientist at the Massachusetts Institute of Technology (MIT) and co-author of the study, highlighted the need for additional research into the potential health effects of Roundup, stating that the team’s research has “hit upon something very important that needs to be taken seriously and further investigated.” Danish Authority Reclassifies Roundup as Cancer-Causing Substance June 8, 2015 – Roundup weed killer is now listed as a carcinogen, or cancer-causing substance, by Denmark’s Working Environment Authority (WEA). Lymphoma diagnoses have been increasing in Denmark for unknown reasons in recent years; the disease now affects over 1,000 Danes annually. These findings raised concerns from Philippe Grandjean, a professor of environmental medicine at the University of Southern Denmark. “We know that glyphosate causes cancer in other mammals, but it has not been demonstrated in humans. That is because the effects are not investigated thoroughly enough in people yet. But when we see that other mammals get cancer from glyphosate, we must assume that people who are exposed to the substance can also develop cancer,” Grandjean said. Roundup is the most popular pesticide and weed killer in Denmark, and Grandjean encourages people to stop using it. “Gardeners should remove Roundup as hazardous waste,” Grandjean said. “Pesticides have often proved more dangerous than we thought, and I do not think they belong in our homes.” Despite its widespread use in home gardens, the vast majority of Roundup in Denmark is used in agricultural applications. In 2013, nearly 1,400 tons of glyphosate was sprayed on Danish soil. “It is so common a substance, and our use of it is so extensive that this WHO report must be taken seriously,” Grandjean said. “Philippe Grandjean is one of the world’s leading professors on toxicity especially on brain damage due to chemicals,” said Ib Borup Pederson, a Danish pig farmer who documented the significant change in the health and productivity of his livestock, as well as the profitability of his farm when he stopped using feed contaminated by glyphosate 4 years ago. “His appearance is of great importance; nobody in Denmark from the industry has clout enough to go against him, as he is both professor in Denmark and USA (at Harvard School of Public Health), and is widely recognized for his work.” Monsanto Lobbyists Banned from EU Parliament October 10, 2017 – Lobbyists working for the Monsanto Company have been barred from entering the European parliament after the company refused to attend a hearing regarding allegations of regulatory interference into Roundup safety studies. Members of European parliament (MEPs) took the unprecedented step after Monsanto skipped a hearing called to discuss allegations that it tampered with studies investigating the safety of glyphosate. This is the first time MEPs have implemented new rules granting it the power to block access to companies that ignore a summons to attend parliamentary inquiries or hearings, according to The Guardian. Leaders of all parliamentary blocks voted to back the ban on Thursday. Monsanto officials will now be unable to meet MEPs, attend meetings, or use digital resources on parliament grounds at Brussels or Strasbourg. A public hearing has been scheduled for Wednesday to discuss allegations that Monsanto unlawfully influenced studies into the safety of glyphosate. “Those who ignore the rules of democracy also lose their rights as a lobbyist in the European Parliament,” said Philippe Lamberts, President of the Group of the Greens/European Free Alliance. “There remain many uncertainties in the assessment of the pesticide glyphosate. Monsanto has to face the questions of parliamentarians and should not hinder the clarification process.” France to Phase Out Glyphosate Over 5 Years October 6, 2017 – French Prime Minister Edouard Philippe has announced that France will phase out glyphosate over the next 5 years until the herbicide is banned outright in 2022. In response to worries from French farmers about an outright ban on glyphosate, Philippe proposed a gradual drawdown over the next 5 years, according to Organic Authority. The majority of French farmers have reacted in favor of the proposal, with Christiane Lambert, head of France’s largest farm union, FNSEA, saying it meant the government was “starting to understand that a full ban would be impossible to apply in France.” France’s Ministry of Environment announced in September that the county would be voting against renewal of the chemical’s license in the EU. Last week, about 300 French farmers took to the Champs-Elysées in protest of an outright ban on glyphosate. FNSEA argued that seeing as there is no current alternative to the herbicide, an across-the-board ban placed French farmers at a severe disadvantage in the EU and across the globe. The European Commission has proposed extending the licence for glyphosate for a decade, which France has said it will vote against and try to block. FNSEA is fighting the block, fearing that any type of ban would put farmers at a competitive disadvantage. Roundup Labels to Carry Cancer Warning in California June 27, 2017 – A California judge has ruled that state health officials can require Monsanto to include a cancer warning on the labeling of Roundup weed killer. If California carries out the proposal, it would be the first state in the U.S. to require such strict labeling for Monsanto Roundup, the most widely-used agricultural chemical on earth. Monsanto rejects any notion of health risk associated with Roundup, and sued California to block the proposed labeling, claiming that it unconstitutionally made its claims based on IARC’s claim that glyphosate is “probably carcinogenic.” Fresno County Superior Court Judge Kristi Kapetan still must issue a formal decision, which she said would come soon. California regulators are waiting for the formal ruling before moving forward with the warnings. Once a chemical is added to a list of probable carcinogens, the manufacturer has a year before it must attach the label. With so much suspicion surrounding Monsanto due to its dubious track record, and the numerous studies linking Roundup to cancer and many other serious health risks, the ruling is being applauded by many as a victory for the people against the widely-criticized agrochemical giant. Monsanto Sued for Mislabeling Roundup June 22, 2017 – A lawsuit has been filed against Monsanto in Wisconsin federal court by a group of plaintiffs who claim that Roundup herbicide is mislabeled with the statement that its active ingredient targets an enzyme not found in humans or pets. The complaint (PDF), filed Tuesday by 6 consumers from states across the U.S., focuses on the promotion, marketing and sale of Roundup, rather than physical injuries alleged from the weed killer. Scotts Miracle-Gro Co., which also markets Roundup products, is named as a co-defendant in the case. The lawsuit claims that Monsanto and Scotts label, market, and promote Roundup products with the “false statement that Roundup’s active ingredient, glyphosate, targets an enzyme that is not found ‘in people or pets.’” Plaintiffs contend this is a false and deceptive claim, as the enzyme has been identified in the gut bacteria of humans and pets, and glyphosate can adversely affect their immune system. Monsanto aggressively markets Roundup as safe for humans and animals, despite recent studies which have found that glyphosate may be carcinogenic (cancer-causing) and affect human and animal cardiovascular, endocrine, nervous, and reproductive systems. No reasonable consumer seeing these representations would expect that Roundup actually targets a bacterial enzyme that is found in humans and animals, and that affects their immune system health. Plaintiffs are seeking equitable relief on behalf of the general public, with all profits earned by Monsanto for sales of Roundup in D.C. to be deposited into a charitable fund for the raising of consumer awareness regarding the effects of glyphosate. Glyphosate vs. Dicamba Even more toxic than glyphosate is dicamba, a new herbicide designed for use on Monsanto’s next generation of biotech crops. According to the Pesticide Management Education Program (PMEP) at Cornell University, dicamba is toxic by ingestion, inhalation and dermal exposure. Signs and symptoms of dicamba toxicity include: Loss of appetite (anorexia) Vomiting Muscle weakness Slowed heart rate Shortness of breath Central nervous system effects (victim may become excited or depressed) Benzoic acid in the urine Incontinence Cyanosis (bluing of the skin and gums) Exhaustion following repeated muscle spasms EU Approves Roundup Ready Soybeans The European Union (EU) has approved the import and processing of Monsanto Roundup Ready 2 Xtend soybeans, after debates over the potential health risks of glyphosate delayed introduction of the genetically modified crops for months. The Roundup Ready 2 Xtend soybeans have gone through a rigorous authorization protocol, including a favorable scientific assessment by the European Food Safety Authority (EFSA). The GMO crops are now authorized to be used both in human and animal food, but not for planting in the EU. The authorization is valid for a decade; however, “any products produced from these GMOs will be subject to the EU’s strict labeling and traceability rules,” according to the European Commission. “Today the Commission authorized three GMOs for food/feed uses (soybean MON 87708 x MON 89788, soybean MON 87705 x MON 89788 and soybean FG72), all of which have gone through a comprehensive authorization procedure, including a favorable scientific assessment by EFSA,” the commission said on Friday. Although Roundup Ready soybeans are tolerant to both glyphosate and dicamba weed killers, use of dicamba on the crops has not yet been approved by the EPA. The soybeans were approved earlier this year by a major Chinese importer. Monsanto is now planning on supplying 15 million U.S. soy acres to meet export needs. The new crops make up what the company has called the ‘Roundup Ready Xtend crop system,’ designed to kill superweeds that have adapted to tolerate glyphosate herbicides. EPA approved Dicamba in 1967, and the chemical has since been linked to high rates of cancer and birth defects in the families of food growers. Consumer, health and environmental advocates have fiercely opposed Monsanto’s Roundup Ready Xtend crop system over health and environmental concerns. 40 Californians File Roundup Cancer Lawsuit April 5, 2017 – Forty California residents have filed a products liability lawsuit against Monsanto alleging that Roundup weedkiller caused them to develop “non-Hodgkin lymphoma and other cancers, other permanent defects and permanent bodily impairments.” The complaint, filed last month in Alameda Superior Court, alleges that Monsanto says Roundup is safe to use and poses no unreasonable health risk to humans or the environment. Study Links Glyphosate to Autism March 8, 2017 – A new study has been published linking glyphosate to an increased risk for autism. For the study (PDF), a research team led by William Shaw, Ph.D. of The Great Plains Laboratory, Inc. found extremely high levels of glyphosate in urine samples taken from a set of triplets. The amount of glyphosate dropped significantly after implementing a strict diet of organic foods, with improvements noted in the functioning of the children. The two boys from the triplet set have autism while the girl has significant medical problems but does not have autism. Shaw found the results significant because previous research has shown that the rate of autism in the U.S. is highly correlated with the increased use of glyphosate. The findings could also demonstrate a potential mechanism by which glyphosate could lead to brain damage. People are exposed to high amounts of glyphosate when they eat genetically modified foods that are engineered to survive glyphosate toxicity. Weeds that are not genetically modified die when exposed to the chemical. It was previously believed that humans and other animals lack the enzymes that weeds possess, so therefore would not be affected by glyphosate toxicity. However, recent studies have found that glyphosate also kills beneficial bacteria in the environment and in the intestinal tracts of farm animals and humans by the same mechanism which it kills weeds. Pathogenic bacteria such as Clostridia and Salmonella, on the other hand, lack the genes that kill beneficial bacteria. This factor was important since the two boys with autism had elevated markers which indicated Clostridia overgrowth. These markers may alter brain function by inhibition of the enzyme dopamine-beta-hydroxylase (DBH), which is responsible for the conversion of dopamine to a brain chemical called norepinephrine. Over time, this inhibition of DBH leads to the overproduction of dopamine, which may be toxic and cause brain damage at high concentrations. Some medications used to treat autism like Risperdal (generic: risperidone) block the effects of excessive dopamine. Roundup Linked to Liver Disease, Study Finds January 10, 2017 – A new study has found that glyphosate causes non-alcoholic fatty liver disease (NAFLD) in laboratory rats at very low doses. The study, published Monday in Scientific Reports, used cutting edge profiling methods to analyze the molecular composition of the livers of female rats that were given extremely low doses of Roundup herbicide (thousands of times lower than what is permitted by worldwide health regulators) over a 2-year period. The results indicated that these animals developed NAFLD. According to the researchers, this study is unique in that it is the first to show a causative link between exposure to Roundup and a serious disease. “The findings of our study are very worrying as they demonstrate for the first time a causative link between an environmentally relevant level of Roundup consumption over the long-term and a serious disease – namely non-alcoholic fatty liver disease,” said Dr Michael Antoniou of King’s College London, lead author of the study. “Our results also suggest that regulators should reconsider the safety evaluation of glyphosate-based herbicides.” The study indicates that long-term consumption of an ultra-low dose of Roundup at a glyphosate intake level of just 4 nanograms per kilogram of body weight per day — which is 437,500 times below the level permitted in the U.S. — results in NAFLD. Health regulators accept toxicity studies in rats as an indicator of potential human health risks. Therefore, the new findings may have serious consequences for human health, according to the researchers. NAFLD currently affects about 25% of the U.S. population. Risk factors include being overweight or obese, having diabetes, high cholesterol or high triglycerides in the blood. Rapid weight loss and poor eating habits also may lead to the disease. Symptoms of non-alcoholic fatty liver disease include: Fatigue Weakness Weight loss Loss of appetite Nausea Abdominal pain Spider-like blood vessels Yellowing of the skin and eyes (jaundice) Itching Fluid buildup and swelling of the legs (edema) and abdomen (ascites) Mental confusion If left untreated, non-alcoholic fatty liver disease can progress to the more serious condition non-alcoholic steatohepatitis (NASH). EPA Panel to Investigate Roundup Cancer Link December 13, 2016 – The EPA is holding a three-day series of meetings this week dedicated to examining evidence linking Monsanto Roundup to cancer, according to The Hill. The Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (FIFRA) will meet first on Tuesday to review a set of scientific issues regarding EPA’s evaluation of the carcinogenic potential of glyphosate. The goal of the meetings is to determine how the agency should interpret relevant data and how this information should translate into a “carcinogen risk” classification for glyphosate. Glyphosate Found in Oatmeal, Baby Food October 3, 2016 – The FDA has found residues of glyphosate in a variety of oat products including plain and flavored oat cereals for babies. Data (PDF) presented by FDA chemists at a meeting in Florida showed residues of glyphosate in the following products: “Cinnamon spice” instant oatmeal “Maple brown sugar” instant oatmeal “Peach and cream” instant oatmeal Banana strawberry and other banana-flavored varieties of infant oat cereal Other similar products Glyphosate levels ranged from none found in several different oat products to 1.67 parts per million (PPM), according to the FDA. The EPA maintains that glyphosate is “not likely” to cause cancer, and has established tolerance levels for the chemical in oats and other foods. The levels identified by FDA in the above products fall within EPA’s guidelines, which for oats is 30 ppm. The U.S. typically allows far more glyphosate residue in food than other countries. In the EU, for example, the tolerance for glyphosate in oats is 20 PPM. Monsanto, which generates nearly one-third of its $15 billion annual revenues from glyphosate products, helped the EPA in setting tolerance levels for glyphosate, and in 2013 asked for and received higher tolerances for the chemical in a large number of foods. The company has developed genetically engineered (GMO) crops including corn, soybeans, canola and sugar beets that are designed to tolerate direct spraying with glyphosate. In May, San Francisco resident Danielle Cooper filed a class action lawsuit (PDF) against Quaker Oats Co. after glyphosate was found in the company’s oat products, which are used by millions of consumers as cereal and for baking. Cooper said she expected the oats, which are labeled as “100% Natural,” to be free of pesticides and other harmful chemicals. “Glyphosate is a dangerous substance, the presence and dangers of which should be disclosed,” the class action states. Glyphosate Restrictions go into Effect in EU August 24, 2016 – New restrictions concerning the use of glyphosate came into effect across the European Union (EU) on Monday, according to AgriLand. Under the new regulations: There is a ban of a co-formulant called polyethoxylated tallow amine (POEA) from glyphosate-containing products; Greater scrutiny will be placed on the pre-harvest use of glyphosate, and Reduction of the chemical’s use in specific areas such as public parks, playgrounds and sports grounds. Glyphosate Linked to Alzheimer’s, Parkinson’s and ALS, Study Finds A new study has found that glyphosate alters DNA function, increasing the risk for a number of serious, potentially life-threatening diseases. According to the study, glyphosate substitution for glycine is associated with a number of serious diseases including (but not limited to): Type 2 diabetes Obesity Asthma Alzheimer’s disease Amyotrophic lateral sclerosis (ALS) Parkinson’s disease Glycine, the smallest of the 20 amino acids found in proteins, has unique properties that have the ability to anchor to the plasma membrane or cytoskeleton. The new study, taken in conjunction with correlating data, makes a compelling argument that glyphosate action as a glycine analogue accounts for a high percentage of glyphosate’s toxicity. Additionally, the researchers found that the herbicide may be incorporated into polypeptide chains during protein synthesis, which affects the structure and function of the proteins. Proteins fold up, and glycine is a tiny molecule that is often found in the folding spaces. Since glyphosate is much larger, it prevents the protein molecule from folding correctly, disrupting the function of proteins involved with metabolism and regulatory processes, according to the study. This mechanism affects humans and other organisms in a number of ways including: Impaired fatty acid release leading to obesity; Impaired insulin receptor response leading to type 2 diabetes; Impaired one-carbon metabolism leading to neural tube defects and autism; Monsanto touts glyphosate as a “low toxicity” herbicide and “safer” than other weedkillers. However, the chemical has also been shown to have negative effects on humans and the environment. Given its massive use on residential and agricultural sites, its toxicity is of growing concern. Glyphosate Approved in Europe Despite Cancer Fears June 30, 2016 – A European Commission has extended approval of the herbicide glyphosate through 2017 after EU member states failed to either approve or ban the chemical. The EU’s current approval of glyphosate was set to expire today, according to EcoWatch. Had that happened, manufacturers would have had to phase out products containing the ingredient within 6 months. Health Commissioner Vytenis Andriukaitis announced the last-minute extension on Tuesday, despite failing 3 consecutive times to secure a majority decision from the EU member states. Europe’s view on glyphosate has been divided since March 2015, when the World Health Organization published a report stating that the herbicide is “probably carcinogenic to humans.” To complicate matters, other regulatory agencies including the European Food Safety Authority (EFSA) have since declared glyphosate to be safe. The 18 month extension will allow the European Chemicals Agency (ECHA) to further investigate the chemical’s safety. However, because the commission initially proposed to extend glyphosate for another 15 years but has now reduced it to a temporary approval underscores the uncertain fate of glyphosate in Europe. “There are clear concerns about the health risks with glyphosate, both as regards it being a carcinogen and an endocrine disruptor,” said Green Party MEP Bart Staes. “Moreover, glyphosate’s devastating impact on biodiversity should have already led to its ban. The process of phasing-out glyphosate and other toxic herbicides and pesticides from agriculture must begin now, and this means reorienting the EU’s Common Agricultural Policy towards a more sustainable agricultural model and a Common Food Policy.” Staes further noted that under the current legislation, EU member states have the power to impose restrictions on glyphosate, with France and others already saying they will do so. Scientists Urge EPA to Ban Glyphosate June 17, 2016 – A delegation of independent scientists have urged the EPA to ban Monsanto’s flagship weed killer Roundup. Providing testimony that Roundup poses an unreasonable environmental and public health threat, scientists spoke with EPA officials in a closed meeting at the O’Neill House Office Building in Washington, D.C. The scientists laid out the physiological reasons why exposure to glyphosate can increase the risk of autism, Alzheimer’s, cancer, birth defects, obesity and other serious health problems. “When a cell is trying to form proteins, it may grab glyphosate instead of glycine to form a damaged, mis-folded protein,” said Dr. Stephen Frantz, a pathobiologist research scientist who led the team. “After that it’s medical chaos. Where glyphosate replaces glycine, the cell can no longer conduct business as usual causing unpredicted consequences with many diseases and disorders as a result.” Roundup also damages a crop’s ability to extract carbon from the air, a fundamental component of climate change. “Glyphosate negatively affects the soil microbiome,” Frantz said. “It is destroying the ability of soil to be a nutritive medium for producing crops…We call for a ban on glyphosate.” Frantz also said that Roundup is a patented antimicrobial. “By eating glyphosate-laden foods, we are exposed to a chronic, low dose antibiotic. This is likely causing antibiotic resistance and superbugs.” At least 300 million pounds of Roundup are sprayed on U.S. crops each year, and nearly half of Monsanto’s annual sales (about $5 billion) come from the weed killer, according to the Huffington Post. Moms Across America founder Zen Honeycutt was also at the meeting in Washington. Her son was diagnosed with autism, allegedly the result of his consumption of processed foods, until his mother switched to an all-organic diet. “Mothers and caretakers are seeing their loved ones get sick on GMOs and glyphosate/herbicide sprayed foods and get better when they avoid them,” Honeycutt said. “Because glyphosate is contaminating our urine, water, breast milk and nearly all our foods, we are systematically causing sickness throughout America. For the sake of our country, this must stop. We simply cannot afford glyphosate.” The Deputy Director of EPA’s Pesticide Programs said it could take until late next year before a decision is made on whether the agency will re-register glyphosate for continued use in the U.S. Frantz is demanding immediate action because he views use of the chemical as outright poisoning of our food sources and environment. “By the end of 2016, the EPA will have something done and then comment periods, and then there’s another step, and there’s more comment periods, and this is like business as usual,” Frantz said. “The evidence we presented about this chemical being a glycine analog, that really should excite people. And I didn’t see any excitement. It should upset people.” EU Rejects Extension on Glyphosate June 6, 2016 – European Union nations have refused to back a limited extension on glyphosate, threatening withdrawal of the weed killer if no decision is reached by the end of the month. EU representatives in Brussels today failed to pass a 1-2 year re-authorization of glyphosate to allow for completion of a safety assessment currently underway at the ECHA, according to Reuters. If the commission fails to reauthorize the chemical’s use by the end of the month, it will be illegal to use throughout the EU, and all products containing glyphosate would be removed from the European market within 6 months. A number of countries including the Netherlands and France have already moved to restrict public access to the herbicide over health and environmental concerns. Following today’s vote, the commission now has 2 options. The issue will either be referred to an appeal committee which would be scheduled June 20 to allow for a resolution by the end of the month, or the committee can do nothing and allow the June 30 deadline to pass, resulting in an across-the-board market pull of all glyphosate products. However, EU officials are acutely aware of the potential lawsuits that would likely be filed by Monsanto and other glyphosate producers if this were to happen. Lawsuit Alleges Roundup Caused Bone Cancer in Farm Worker A former California farm worker has filed a federal lawsuit against Monsanto alleging that the company’s Roundup weed killer caused her to develop bone cancer after years of exposure to the herbicide. According to the lawsuit, plaintiff Enrique Rubio sprayed Roundup on crops in California, Oregon and Texas from 1986 to 1995, and was subsequently diagnosed with bone cancer at 38-years-old. Rubio claims that during her years as a field worker, she drove a tractor and used a hand pump to spray vegetables with the weed killer with nothing more than a paper mask to protect her from the chemicals. The complaint alleges that Monsanto’s “prolonged campaign of misinformation” about the safety of Roundup amounted to willful negligence, and that there was no way Rubio could have known about the health risks of the herbicide. To support this claim, the lawsuit notes that the EPA found that 2 laboratories hired by Monsanto falsified test results; however, the company was allowed to sell the weedkiller in the U.S. and around the world. The lawsuit furthermore contends that in light of numerous recent peer-reviewed studies, Monsanto can no longer deny the herbicide’s health effects. As a result of the study’s findings, the California Environmental Protection Agency (Cal/EPA) earlier this month officially classified glyphosate as a known carcinogen under the Safe Drinking Water and Toxic Enforcement Act of 1986. Rubio’s lawsuit alleges that Monsanto has known for years about Roundup’s toxicity to humans and the environment, but continues to claim that the weed killer poses no unreasonable risk. The complaint accuses Monsanto of: Strict liability over a known design defect that could have been made less harmful; Failure to warn of the dangers of Roundup; Willful negligence, and Breach of implied warranty. As a result of these alleged misdeeds, Rubio “has suffered and continues to suffer grave injuries” including economic hardship and medical expenses that will continue indefinitely. Since being diagnosed with bone cancer in 1995, Rubio has become disabled and is no longer able to work, according to the lawsuit. She is seeking unspecified compensatory and punitive damages, as well as payment of legal expenses. Wrongful Death Lawsuit Filed Against Monsanto in California May 9, 2016 – The widow of a California farmer has filed a wrongful death lawsuit against Monsanto alleging that the company purposely downplayed the cancer risk associated with its Roundup weed killer. According to the lawsuit (PDF), Jack McCall developed terminal cancer after using Roundup herbicide for nearly 30 years. In September 2015, McCall was admitted to a hospital with swollen lymph nodes in his neck. His doctor informed him that the swelling was caused by anaplastic large cell lymphoma (ALCL), a rare and aggressive form of non-Hodgkin lymphoma. No one on his farm knew that Roundup could cause cancer since Monsanto maintained for decades that the weed killer was non-toxic to humans, according to the complaint. After being diagnosed with ALCL and learning of the link between Roundup and cancer, he stopped using the herbicide on his farm. Unfortunately, by then it was too late. Three months after his diagnosis, while undergoing treatment on Christmas Eve 2015, McCall had a massive stroke and died 2 days later. He was 69-years-old. According to allegations raised in the complaint, Monsanto has known for decades that glyphosate is carcinogenic, but failed to adequately warn consumers of its potential health risks. Instead, the company continued to market the herbicide as non-toxic, and hid the dangers as it generated billions in profits worldwide. To this day, Monsanto has failed to adequately and accurately warn of the true risks associated with Roundup and glyphosate, according to the lawsuit. The complaint was filed on May 4 in federal court in Los Angeles, California, on behalf of Jack McCall’s widow, Teri McCall, under case number 2:16-cv-01609. The lawsuit seeks wrongful death and punitive damages, alleging that Monsanto designed a dangerous and defective product, committed gross negligence, and defrauded millions of farmers about the safety of Roundup. Lawmakers Pressure EPA Over Glyphosate Safety Report May 13, 2016 – U.S. lawmakers have put pressure on the EPA to explain why it released and then quickly withdrew documents concerning its review of glyphosate. The documents, which included a report indicating that glyphosate is probably not carcinogenic to humans, were posted to the EPA’s website on April 29 and then taken down 4 days later. In response, the U.S. House Committee on Agriculture sent a letter to the EPA which said that it is looking into its review of glyphosate and atrazine, another widely-used chemical found in agricultural herbicides. The aim of the report, which started in 2009, is to examine the chemicals and their potential human health and environmental risks. “We are troubled that EPA mistakenly posted and later removed documents related to assessments of two different chemicals within one week,” the letter said. “These mistakes indicate systemic problems with EPA’s management of its chemical review and publication processes.” The committee asked EPA who is in charge of managing the risk assessment protocol for chemicals, and for a step-by-step description of its publication approval process. The letter also inquired about the steps needed to finalize the glyphosate report, which is expected in July. “We are concerned that EPA has continually delayed its review of glyphosate,” the letter said. The committee will consider what action to take after the EPA responds. The agency told Reuters it has received the letter “and will respond appropriately.” EPA Pulls Report Saying Glyphosate is Safe May 5, 2016 – The EPA says it accidentally released an 87-page report which concluded that glyphosate is “not likely” to cause cancer in humans. EPA said it doesn’t expect to finish its review of glyphosate until later this year. The agency periodically reviews chemicals to ensure they’re performing as designed and aren’t causing harm to people or the environment. “Documents on glyphosate that are still in development were taken down from the agency’s docket because our assessment is still ongoing and not final,” said EPA spokesman Nick Conger. Monsanto argued that the agency’s findings contradicted decades of studies which have found that glyphosate is safe. The company criticized the IARC for “cherry picking” data, and accused it of promoting “an agenda-driven bias.” Monsanto said the revoked EPA report was just the latest piece of data to concluding that glyphosate doesn’t cause cancer. Jennifer Sass, a senior scientist at the Natural Resources Defense Council (NRDC), said the EPA report should be the final assessment on the cancer risk associated with glyphosate. She said the agency still needs to release data on the chemical’s impact on the environment and wildlife. “Monsanto could have written (this report),” said Sass. “It’s really outrageous that (the EPA) came out so different than where the World Health Organization and other agencies are.” Class Action Lawsuit Filed Over Glyphosate in Quaker Oats May 2, 2016 – Quaker Oats is being sued for $5 million by a New York man who alleges the company uses glyphosate during production, according to the New York Post. The class action was filed by Lewis Daly, a Brooklyn resident who claims Quaker Oats’ advertising is “false, deceptive and misleading.” Daly says the carcinogenic substance glyphosate is used to grow the oats and sprayed on them during harvest, undermining the company’s claims that its products are “100 per cent Natural.” Glyphosate Found in Many Breakfast Foods, Study Finds April 20, 2016 – Glyphosate has found its way into many common breakfast foods including bagels, cereals and eggs, according to a new report. According to the report, which was issued by the Alliance for Natural Health USA (ANH-USA), testing procured from Microbe Inotech Laboratories in St. Louis found detectable levels of glyphosate in 10 out of 24 breakfast food items including oatmeal, bagels and coffee creamer. “Americans are consuming glyphosate in common foods on a daily basis,” ANH said. Notably, some of the highest levels of glyphosate were detected in organic foods such as eggs which are advertised as being “organic, cage-free, antibiotic-free;” and in organic bagels and bread. Indeed, the organic cage-free eggs contained more glyphosate than health authorities allow, ANH said. The agency also tested flour, corn flakes, instant oatmeal, yogurt and frozen hash browns. ANH said the test results indicate that glyphosate is entering the food supply in a number of ways, including being sprayed on crops like wheat to help speed the crop to harvest, and through genetically engineered livestock feed that builds up in poultry and other farm animals. The agency acknowledged that most samples which detected glyphosate residue were at levels under what American health officials classify as “allowable daily intake.” However, ANH also noted that what is considered safe in the U.S. is far higher than that allowed by the EU, and that some critics believe commercial formulations of glyphosate weed killers are more toxic than the chemical alone. “The fact that it is showing up in foods like eggs and coffee creamer, which don’t directly contact the herbicide, shows that it’s being passed on by animals who ingest it in their feed,” said Gretchen DuBeau, executive and legal director of ANH-USA. “This is contrary to everything that regulators and industry scientists have been telling the public.” Pollack, Andrew. “Weed Killer, Long Cleared, Is Doubted.” The New York Times. March 27, 2015; B1.<http://www.nytimes.com/2015/03/28/business/energy-environment/decades-after-monsantos-roundup-gets-an-all-clear-a-cancer-agency-raises-concerns.html?_r=0>. Do I Have a Roundup Lawsuit? The Product Liability Litigation Group at our law firm is an experienced team of trial lawyers that focus on the representation of plaintiffs in Roundup Lawsuits. We are handling individual litigation nationwide and currently investigating potential settlements in all 50 states. Free Confidential Case Evaluation: Again, if you developed lymphoma after using or being exposed to Roundup, you should contact our law firm immediately. You may be entitled to a settlement by filing a suit and we can help.

ths? 2320 How many milligrams are there in 82.82843 kilograms? 82828430 What is fifty-nine quarters of a kilogram in grams? 14750 What is 77.57902 millilitres in litres? 0.07757902 What is fourty-five quarters of a millennium in decades? 1125 How many decades are there in 7/25 of a millennium? 28 How many millimeters are there in 45/2 of a centimeter? 225 What is 1/16 of a centimeter in micrometers? 625 Convert 458.7097nm to centimeters. 0.00004587097 How many years are there in 24.987 centuries? 2498.7 What is one quarter of a litre in millilitres? 250 What is three eighths of a millimeter in micrometers? 375 What is 43.0398 millennia in centuries? 430.398 How many litres are there in 235.0694ml? 0.2350694 How many nanometers are there in 1/4 of a micrometer? 250 How many millilitres are there in 0.6491159l? 649.1159 Convert 203.0697km to centimeters. 20306970 How many centimeters are there in fourty-five quarters of a meter? 1125 What is 1/10 of a millisecond in microseconds? 100 How many micrometers are there in three eighths of a centimeter? 3750 What is 835886.6nm in micrometers? 835.8866 What is 500.7439l in millilitres? 500743.9 How many months are there in 0.6781056 years? 8.1372672 What is 21/2 of a micrometer in nanometers? 10500 How many millilitres are there in eleven eighths of a litre? 1375 How many kilograms are there in twenty-one fifths of a tonne? 4200 What is 7918.478 centimeters in meters? 79.18478 How many millilitres are there in fifty-four fifths of a litre? 10800 How many micrometers are there in 6/25 of a millimeter? 240 What is 28.643625 milliseconds in days? 0.0000003315234375 How many months are there in twenty-seven fifths of a century? 6480 Convert 3173.302 millilitres to litres. 3.173302 How many nanometers are there in 62414.4 kilometers? 62414400000000000 How many micrometers are there in 262725.6 nanometers? 262.7256 How many millimeters are there in 74.49234 centimeters? 744.9234 How many months are there in 1/4 of a decade? 30 What is thirty-two fifths of a millennium in centuries? 64 What is 372.519 minutes in microseconds? 22351140000 How many millilitres are there in 43/4 of a litre? 10750 What is 398629.6 millimeters in meters? 398.6296 What is one quarter of a litre in millilitres? 250 How many years are there in 11/2 of a century? 550 What is thirteen quarters of a millimeter in micrometers? 3250 Convert 156065.4 nanograms to milligrams. 0.1560654 What is 34.8135um in millimeters? 0.0348135 What is 31066.68 decades in months? 3728001.6 What is 8.546297 nanograms in tonnes? 0.000000000000008546297 What is fifty-three quarters of a litre in millilitres? 13250 How many nanometers are there in one quarter of a micrometer? 250 How many minutes are there in 995.5833 days? 1433639.952 Convert 30124.5 micrometers to kilometers. 0.0000301245 How many centimeters are there in 9/25 of a meter? 36 How many grams are there in 1304.304 kilograms? 1304304 Convert 5.050947 millennia to centuries. 50.50947 How many kilometers are there in 319.6336nm? 0.0000000003196336 What is 448290.9 centuries in decades? 4482909 Convert 40257.4473 minutes to weeks. 3.993794375 How many months are there in 30.09985 decades? 3611.982 How many millimeters are there in eleven halves of a meter? 5500 How many millilitres are there in twenty-one eighths of a litre? 2625 What is 1077.347 grams in micrograms? 1077347000 How many months are there in seven quarters of a decade? 210 How many weeks are there in 10918819.8 minutes? 1083.21625 What is 12/25 of a gram in milligrams? 480 How many nanoseconds are there in 3/5 of a microsecond? 600 What is 2.576596 meters in nanometers? 2576596000 Convert 825709.2 centuries to decades. 8257092 Convert 79.89188mm to micrometers. 79891.88 What is one quarter of a litre in millilitres? 250 What is 299.20068 months in decades? 2.493339 What is 0.9567151m in nanometers? 956715100 How many grams are there in 55/2 of a kilogram? 27500 What is 6/25 of a tonne in kilograms? 240 How many milligrams are there in three eighths of a gram? 375 How many nanograms are there in 21/4 of a microgram? 5250 Convert 7.560324 milliseconds to days. 0.00000008750375 What is 42.68334 decades in millennia? 0.4268334 How many decades are there in 1744.52 millennia? 174452 What is fourty-two fifths of a kilometer in meters? 8400 Convert 0.6303679ms to microseconds. 630.3679 How many litres are there in 6.692678ml? 0.006692678 What is 1/4 of a kilometer in centimeters? 25000 Convert 0.1167218kg to tonnes. 0.0001167218 How many kilograms are there in seven eighths of a tonne? 875 How many millilitres are there in thirty-one fifths of a litre? 6200 How many nanograms are there in one tenth of a microgram? 100 How many nanometers are there in 2325.692mm? 2325692000 What is 454.5342 litres in millilitres? 454534.2 How many years are there in eighteen fifths of a decade? 36 Convert 16.18822 days to nanoseconds. 1398662208000000 How many months are there in 81/2 of a year? 486 How many grams are there in seventy-nine halves of a kilogram? 39500 How many kilograms are there in 1.738999t? 1738.999 How many centuries are there in 61/2 of a millennium? 305 How many nanometers are there in 2144.073mm? 2144073000 Convert 9.252632 years to millennia. 0.009252632 What is thirteen quarters of a decade in months? 390 What is 34/5 of a millennium in decades? 680 What is 9/10 of a microsecond in nanoseconds? 900 Convert 99964.04cm to kilometers. 0.9996404 What is 424794.9ml in litres? 424.7949 How many litres are there in 94724.84 millilitres? 94.72484 Convert 654.31818 microseconds to hours. 0.00000018175505 How many seconds are there in 1/36 of a day? 2400 How many decades are there in 4.276078 years? 0.4276078 How many nanometers are there in one tenth of a micrometer? 100 Convert 227769.084us to days. 0.00000263621625 How many nanometers are there in 0.4755198 millimeters? 475519.8 What is 48/5 of a tonne in kilograms? 9600 Convert 0.5227243 hours to microseconds. 1881807480 How many minutes are there in 406766.2 weeks? 4100203296 What is 29/5 of a centimeter in millimeters? 58 How many nanometers are there in twenty-seven fifths of a micrometer? 5400 Convert 7495.571 micrometers to meters. 0.007495571 What is 49.40286 minutes in hours? 0.823381 Convert 177823.6ml to litres. 177.8236 How many milligrams are there in 839.2507 kilograms? 839250700 How many days are there in 247.05567 seconds? 0.002859440625 How many microseconds are there in 602360.2 days? 52043921280000000 How many millennia are there in 25.87365 months? 0.0021561375 What is 1/4 of a week in hours? 42 What is 7/8 of a second in milliseconds? 875 How many centimeters are there in 6185.173um? 0.6185173 What is 1/20 of a kilogram in grams? 50 What is 3/5 of a century in years? 60 What is 51/8 of a centimeter in micrometers? 63750 How many months are there in 3/10 of a millennium? 3600 How many centuries are there in 3600.714 decades? 360.0714 How many months are there in eight thirds of a millennium? 32000 How many millilitres are there in 3/5 of a litre? 600 What is 4451.238cm in meters? 44.51238 Convert 647.2918mg to nanograms. 647291800 How many centimeters are there in 11/10 of a meter? 110 What is 0.7147458 millilitres in litres? 0.0007147458 How many months are there in 5/6 of a century? 1000 How many litres are there in 6337.908ml? 6.337908 What is 0.2998724 millilitres in litres? 0.0002998724 How many micrometers are there in 47708.89 nanometers? 47.70889 What is thirty-two fifths of a meter in millimeters? 6400 How many micrograms are there in 9624.892 tonnes? 9624892000000000 How many micrograms are there in 40773.09g? 40773090000 What is 0.6346648 centuries in years? 63.46648 Convert 1376.851 millennia to years. 1376851 What is one tenth of a week in seconds? 60480 What is 34/5 of a centimeter in millimeters? 68 What is fourty-three halves of a kilometer in meters? 21500 How many micrometers are there in 1/4 of a millimeter? 250 How many millilitres are there in 3/50 of a litre? 60 How many years are there in 3/50 of a century? 6 How many weeks are there in 119.7714735 nanoseconds? 0.00000000000019803484375 How many micrometers are there in thirteen fifths of a mil

The present invention relates to methods of increasing abiotic stress tolerance and/or biomass in plants and, more particularly, to plants expressing exogenous abiotic stress-tolerance genes. Abiotic stress (also referred to as “environmental stress”) conditions such as salinity, drought, flood, suboptimal temperature and toxic chemical pollution, cause substantial damage to agricultural plants. Most plants have evolved strategies to protect themselves against these conditions. However, if the severity and duration of the stress conditions are too great, the effects on plant development, growth and yield of most crop plants are profound. Furthermore, most of the crop plants are very susceptible to abiotic stress (ABS) and thus necessitate optimal growth conditions for commercial crop yields. Continuous exposure to stress causes major alterations in the plant metabolism which ultimately lead to cell death and consequently yield losses. Thus, despite extensive research and the use of sophisticated and intensive crop-protection measures, losses due to abiotic stress conditions remain in the billions of dollars annually (1,2). The following summarizes the implications of exemplary abiotic stress conditions. Problems associated with drought. A drought is a period of abnormally dry weather that persists long enough to produce a serious hydrologic imbalance (for example crop damage, water supply shortage, etc.). While much of the weather that we experience is brief and short-lived, drought is a more gradual phenomenon, slowly taking hold of an area and tightening its grip with time. In severe cases, drought can last for many years and can have devastating effects on agriculture and water supplies. With burgeoning population and chronic shortage of available fresh water, drought is not only the number one weather related problem in agriculture, it also ranks as one of the major natural disasters of all time, causing not only economic damage, but also loss of human lives. For example, losses from the US drought of 1988 exceeded $40 billion, exceeding the losses caused by Hurricane Andrew in 1992, the Mississippi River floods of 1993, and the San Francisco earthquake in 1989. In some areas of the world, the effects of drought can be far more severe. In the Horn of Africa the 1984-1985 drought led to a famine that killed 750,000 people. Problems for plants caused by low water availability include mechanical stresses caused by the withdrawal of cellular water. Drought also causes plants to become more susceptible to various diseases (Simpson (1981). “The Value of Physiological Knowledge of Water Stress in Plants”, In Water Stress on Plants, (Simpson, G. M., ed.), Praeger, N.Y., pp. 235-265). In addition to the many land regions of the world that are too arid for most if not all crop plants, overuse and over-utilization of available water is resulting in an increasing loss of agriculturally-usable land, a process which, in the extreme, results in desertification. The problem is further compounded by increasing salt accumulation in soils, as described above, which adds to the loss of available water in soils. Problems associated with high salt levels. One in five hectares of irrigated land is damaged by salt, an important historical factor in the decline of ancient agrarian societies. This condition is only expected to worsen, further reducing the availability of arable land and crop production, since none of the top five food crops—wheat, corn, rice, potatoes, and soybean—can tolerate excessive salt. Detrimental effects of salt on plants are a consequence of both water deficit resulting in osmotic stress (similar to drought stress) and the effects of excess sodium ions on critical biochemical processes. As with freezing and drought, high saline causes water deficit; the presence of high salt makes it difficult for plant roots to extract water from their environment (Buchanan et al. (2000) in Biochemistry and Molecular Biology of Plants, American Society of Plant Physiologists, Rockville, Md.). Soil salinity is thus one of the more important variables that determines where a plant may thrive. In many parts of the world, sizable land areas are uncultivable due to naturally high soil salinity. To compound the problem, salination of soils that are used for agricultural production is a significant and increasing problem in regions that rely heavily on agriculture. The latter is compounded by over-utilization, over-fertilization and water shortage, typically caused by climatic change and the demands of increasing population. Salt tolerance is of particular importance early in a plant's lifecycle, since evaporation from the soil surface causes upward water movement, and salt accumulates in the upper soil layer where the seeds are placed. Thus, germination normally takes place at a salt concentration much higher than the mean salt level in the whole soil profile. Problems associated with excessive heat. Germination of many crops is very sensitive to temperature. A gene that would enhance germination in hot conditions would be useful for crops that are planted late in the season or in hot climates. Seedlings and mature plants that are exposed to excess heat may experience heat shock, which may arise in various organs, including leaves and particularly fruit, when transpiration is insufficient to overcome heat stress. Heat also damages cellular structures, including organelles and cytoskeleton, and impairs membrane function [Buchanan et al. (2000) in Biochemistry and Molecular Biology of Plants, American Society of Plant Physiologists, Rockville, Md. Heat shock may produce a decrease in overall protein synthesis, accompanied by expression of heat shock proteins. Heat shock proteins function as chaperones and are involved in refolding proteins denatured by heat. Heat stress often accompanies conditions of low water availability. Heat itself is seen as an interacting stress and adds to the detrimental effects caused by water deficit conditions. Evaporative demand exhibits near exponential increases with increases in daytime temperatures and can result in high transpiration rates and low plant water potentials [Hall et al. (2000) Plant Physiol. 123: 1449-1458]. High-temperature damage to pollen almost always occurs in conjunction with drought stress, and rarely occurs under well-watered conditions. Thus, separating the effects of heat and drought stress on pollination is difficult. Combined stress can alter plant metabolism in novel ways; therefore understanding the interaction between different stresses may be important for the development of strategies to enhance stress tolerance by genetic manipulation. Problems associated with excessive chilling conditions. The term “chilling sensitivity” has been used to describe many types of physiological damage produced at low, but above freezing, temperatures. Most crops of tropical origins, such as soybean, rice, maize, and cotton are easily damaged by chilling. Typical chilling damage includes wilting, necrosis, chlorosis or leakage of ions from cell membranes. The underlying mechanisms of chilling sensitivity are not completely understood yet, but probably involve the level of membrane saturation and other physiological deficiencies. For example, photoinhibition of photosynthesis (disruption of photosynthesis due to high light intensities) often occurs under clear atmospheric conditions subsequent to cold late summer/autumn nights. For example, chilling may lead to yield losses and lower product quality through the delayed ripening of maize. Another consequence of poor growth is the rather poor ground cover of maize fields in spring, often resulting in soil erosion, increased occurrence of weeds, and reduced uptake of nutrients. A retarded uptake of mineral nitrogen could also lead to increased losses of nitrate into the ground water. By some estimates, chilling accounts for monetary losses in the United States (US) behind only to drought and flooding. Water deficit is a common component of many plant stresses. Water deficit occurs in plant cells when the whole plant transpiration rate exceeds the water uptake. In addition to drought, other stresses, such as salinity and low temperature, produce cellular dehydration (McCue and Hanson (1990) Trends Biotechnol. 8: 358-362). Salt and drought stress signal transduction consist of ionic and osmotic homeostasis signaling pathways. The ionic aspect of salt stress is signaled via the SOS pathway where a calcium-responsive SOS3-SOS2 protein kinase complex controls the expression and activity of ion transporters such as SOS1. The pathway regulating ion homeostasis in response to salt stress has been reviewed recently by Xiong and Zhu (2002) Plant Cell Environ. 25: 131-139. The osmotic component of salt stress involves complex plant reactions that overlap with drought and/or cold stress responses. Common aspects of drought, cold and salt stress response have been reviewed recently by Xiong and Zhu (2002) supra). Those include: (a) transient changes in the cytoplasmic calcium levels very early in the signaling event (Knight, (2000) Int. Rev. Cytol. 195: 269-324; Sanders et al. (1999) Plant Cell 11: 691-706); (b) signal transduction via mitogen-activated and/or calcium dependent protein kinases (CDPKs; see Xiong et al., 2002) and protein phosphatases (Merlot et al. (2001) Plant J. 25: 295-303; Tahtiharju and Palva (2001) Plant J. 26: 461-470); (c) increases in abscisic acid levels in response to stress triggering a subset of responses (Xiong et al. (2002) supra, and references therein); (d) inositol phosphates as signal molecules (at least for a subset of the stress responsive transcriptional changes (Xiong et al. (2001) Genes Dev. 15: 1971-1984); (e) activation of phospholipases which in turn generate a diverse array of second messenger molecules, some of which might regulate the activity of stress responsive kinases (phospholipase D functions in an ABA independent pathway, Frank et al. (2000) Plant Cell 12: 111-124); [0026] (f) induction of late embryogenesis abundant (LEA) type genes including the CRT/DRE responsive COR/RD genes (Xiong and Zhu (2002) supra); (g) increased levels of antioxidants and compatible osmolytes such as proline and soluble sugars (Hasegawa et al. (2000) Annu. Rev. Plant Mol. Plant Physiol. 51: 463-499); and [0028] (h) accumulation of reactive oxygen species such as superoxide, hydrogen peroxide, and hydroxyl radicals (Hasegawa et al. (2000) supra). Abscisic acid biosynthesis is regulated by osmotic stress at multiple steps. Both ABA-dependent and -independent osmotic stress signaling first modify constitutively expressed transcription factors, leading to the expression of early response transcriptional activators, which then activate downstream stress tolerance effector genes. Based on the commonality of many aspects of cold, drought and salt stress responses, it can be concluded that genes that increase tolerance to cold or salt stress can also improve drought stress protection. In fact this has already been demonstrated for transcription factors (in the case of AtCBF/DREB 1) and for other genes such as OsCDPK7 (Saijo et al. (2000) Plant J. 23: 319-327), or AVP1 (a vacuolar pyrophosphatase-proton-pump, Gaxiola et al. (2001) Proc. Natl. Acad. Sci. USA 98: 11444-11449). Developing stress-tolerant plants is a strategy that has the potential to solve or mediate at least some of these problems. However, traditional plant breeding strategies used to develop new lines of plants that exhibit tolerance to ABS are relatively inefficient since they are tedious, time consuming and of unpredictable outcome. Furthermore, limited germplasm resources for stress tolerance and incompatibility in crosses between distantly related plant species represent significant problems encountered in conventional breeding. Additionally, the cellular processes leading to ABS tolerance are complex in nature and involve multiple mechanisms of cellular adaptation and numerous metabolic pathways (4-7). Genetic engineering efforts, aimed at conferring abiotic stress tolerance to transgenic crops, have been described in the prior art. Studies by Apse and Blumwald (Curr Opin Biotechnol. 13:146-150, 2002), Quesada et al. (Plant Physiol. 130:951-963, 2002), Holmström et al. (Nature 379: 683-684, 1996), Xu et al. (Plant Physiol 110: 249-257, 1996), Pilon-Smits and Ebskamp (Plant Physiol 107: 125-130, 1995) and Tarczynski et al. (Science 259: 508-510, 1993) have all attempted at generating stress tolerant plants. In addition, several U.S. patents and patent applications also describe polynucleotides associated with stress tolerance and their use in generating stress tolerant plants. U.S. Pat. Nos. 5,296,462 and 5,356,816 describe transforming plants with polynucleotides encoding proteins involved in cold adaptation in Arabidopsis thaliana, to thereby promote cold tolerance in the transformed plants. U.S. Pat. No. 6,670,528 describes transforming plants with polynucleotides encoding polypeptides binding to stress responsive elements, to thereby promote tolerance of the transformed plants to abiotic stress. U.S. Pat. No. 6,720,477 describes transforming plants with a polynucleotide encoding a signal transduction stress-related protein, capable of increasing tolerance of the transformed plants to abiotic stress. U.S. application Ser. Nos. 09/938,842 and 10/342,224 describe abiotic stress-related genes and their use to confer upon plants tolerance to abiotic stress. U.S. application Ser. No. 10/231,035 describes overexpressing a molybdenum cofactor sulfurase in plants to thereby increase their tolerance to abiotic stress. Although the above described studies were at least partially successful in generating stress tolerant plants, there remains a need for stress tolerant genes which can be utilized to generate plants tolerant of a wide range of abiotic stress conditions. While reducing the present invention to practice, the present inventors have identified through bioinformatic and laboratory studies several novel abiotic stress-tolerance genes, which can be utilized to increase tolerance to abiotic stress and/or biomass, vigor and yield in plants.

Q: How create a JLabel when I pass with mouse on the button (JAVA) I would that when I move my mouse on a particular button I can read the function of this button like a Jlabel that it is created expressly for this event under the mouse position. I think at this approach: 1) capture mouseEvent and in particular MouseEntered 2) create a Jlabel and display it I want know if exists another approach to do this or only my method. Anyone can help me? A: The easiest way is to provide a ToolTip. The framework then takes care about the label and event handling. Note: setToolTipText is a method of JControl, so this work with other controls as well.

Menu Privacy Policy This privacy policy explains how Hollybush Gardens uses and protects any information that you give us when you: Use www.hollybushgardens.co.uk. Engage with Hollybush Gardens employees in person, by phone, by email or post. Consent to receive our email marketing newsletters and announcements. Consent to be emailed about artists of interest. Hollybush Gardens is committed to ensuring that your privacy is protected. Should we ask you to provide certain information by which you can be identified when using this website or communicating with gallery staff, then you can be assured that it will only be used in accordance with this privacy statement. Hollybush Gardens may change this policy from time to time by updating this page. You should check this page occasionally to ensure that you are happy with any changes. This policy is effective from 15 May 2018. 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All-wheel drive vehicles are known, and have the advantage that, under difficult operating conditions, such as snow, ice, sand or the like, the traction available for the vehicle is substantially improved. In order to avoid starting difficulties of the vehicle if the wheels slip or are difficult to turn, it has been customary to provide lock-up elements for one or all of the differentials; the rear wheels, particularly, were often supplied with locking-type differentials in which the respective wheels are securely connected together so that spin of one wheel with respect to another is eliminated. Non-slip or low-slip differentials or lock-up differentials may be used in the position of any of the differentials in the drive system. Lock-up differentials, or low-slip or non-slip differentials have a disadvantage; critical operating conditions may occur upon application of braking, so that the control of the vehicle can be impaired. This is particularly so if, in addition to the four-wheel drive and the no-slip or locking differentials, the vehicle has an automatic brake control system (ABS) in which the braking pressure, typically hydraulic pressure, applied to the respective wheels is controlled in accordance with slip of the wheels. Such ABSs are well known.

madals Profile Blog Joined June 2011 United Kingdom 623 Posts Last Edited: 2014-05-30 15:30:28 #1 Hi Everyone, I'm pleased to announce another show matches I am going to be putting on! The $200 prize pool has been kindly sponsored by xtornzvt - check him out on twitter. If you would like to contribute, look below for how you can help make more events like this possible! When? Tuesday, Jun 03 5:00pm GMT (GMT+00:00) Welmu (P) vs Sacsri (Z) Welmu is currently 25th on the WCS global standings for 2014 and is a very well established Protoss player. He has been a professional player since May 2010 - with $30,000 of prize money so far! Sacsri is newer to SC2 than Welmu, having had his first game in May 2012. This first map though was in Proleague season 2 vs sOs! Until recently he was on SKT1, having left at the start of May - now, he has recently joined mYi! What the stats say: + Show Spoiler + The main English stream will be Madals VODS: will be uploaded immediately after the showmatch to Youtube There is $200 on the line. Winner gets $150, loser $50. As I said earlier, the $200 prize pool has been kindly sponsored by xtornzvt - check him out on twitter. If you would like to help more events like this happen though, please consider if you could.... There are 3 ways you can contribute that will allow me to put on more events in the future. As this is a new venture, please be assured that 100% of revenue is currently going into the prize pool for more events. I am not "paying" myself with these events. So how can you help and contribute? Subscribe to my twitch channel. It is $5/month but means I have some consistent money to put on this sort of event / show match. More subs = more content. Consider donating! Not as fantastic as subs, as it isn't monthly and therefore I cannot plan around it but still is hugely helpful. You can donate any amount you want here: Click here to donate via Pay Pal Turn off Adblock when watching streams you enjoy. This one is simple, it is free and gives the broadcaster a SMALL amount of revenue per ad. Hi Everyone, I'm pleased to announce another show matches I am going to be putting on!The $200 prize pool has been kindly sponsored byIf you would like to contribute, look below for how you can help make more events like this possible!When?Welmu is currently 25th on the WCS global standings for 2014 and is a very well established Protoss player. He has been a professional player since May 2010 - with $30,000 of prize money so far!Sacsri is newer to SC2 than Welmu, having had his first game in May 2012. This first map though was in Proleague season 2 vs sOs! Until recently he was on SKT1, having left at the start of May - now, he has recently joined mYi!What the stats say:VODS:As I said earlier, the $200 prize pool has been kindly sponsored byIf you would like to help more events like this happen though, please consider if you could....There are 3 ways you can contribute that will allow me to put on more events in the future. As this is a new venture, please be assured thatof revenue is currently going into the prize pool for more events. I am not "paying" myself with these events. Caster: @Madals91 http://www.youtube.com/Madals91 <--

Ricky Wells Ricky Wells (born 27 July 1991 in Auckland, New Zealand), is an American international motorcycle speedway rider who rides for Poole in the SGB Premiership he doubles-up with Edinburgh who he also captains in the SGB Championship. He was the 2009 US National Champion. He is also a two time U.S. Under 21 National Champion. He has been an international rider for the USA in the old Speedway World Cup. US National Championship On 19 September 2009 Ricky won the US national Championship, winning all of his heat races and the main event. Doing so beat out Mike Bast's record of being the youngest rider to ever win that event. He was victorious over former US Champions like, Billy Janniro, Bobby Schwartz, Charlie Venegas, Chris Manchester, Mike Faria and Josh Larsen. World U21 Wells made his first appearance in the World Under 21 Championships in 2008 by winning the 2007 U.S. Under 21 National Championship. He scored 9 points in Qualifying Round 1 held in Norden, Germany which qualified him to move onto Semi-Final Round 1 held in Rye House. Only scoring 6 points which did not qualify him to move onto The Final Round. Wells came home and won the 2008 U.S. Under 21 National Championship also which placed him in the 2009 World Under 21 Championships. Scoring 9, and beating off Pawel Zmarzlik and Kozza Smith in a race-off, in Qualifying Round 3 held in Rye House moved him into Semi-Final 2 held in Kumla. In Kumla, Ricky scored 5 and again was in a race-off situation, in which he beat Justin Sedgman and Patrik Pawlaszczyk to securing a reserve spot in the Final held in Goričan. Through the injury off Przemyslaw Pawlicki, Wells was awarded a place in the main line-up of the Final, where he scored 2 points, finishing in 16th place, ahead of Ludvig Lindgren. British speedway Wells rode for Elite League Coventry Bees in 2009 and for the Stoke Potters in the Premier League in 2010 on loan from Coventry. In 2011 he rode for the Elite Shield-winning Wolverhampton Wolves team in the Elite League and Plymouth Devils in the Premier. He has remained with Wolves since, while riding for Sheffield Tigers in the Premier League since 2012. Honours World Championships Team World Championship (Speedway World Cup) 2009 - 4th place in the Qualifying Round 2 Individual Under-21 World Championship 2008 - 12th placed in the Semi-Final One 2009 - Goričan - 16th place (2 pts) References Category:1991 births Category:Living people Category:American speedway riders Category:New Zealand expatriates in the United States Category:Coventry Bees riders Category:Stoke Potters riders Category:Plymouth Devils riders Category:Sheffield Tigers riders Category:Wolverhampton Wolves riders

Identification of poorly differentiated synovial sarcoma: a comparison of clinicopathological and cytogenetic features with those of typical synovial sarcoma. Poorly differentiated areas in synovial sarcomas (SS) are known to be associated with a poorer prognosis. The aim of our study was to describe the morphological spectrum of poorly differentiated synovial sarcomas (PDSS) and refine the criteria for their recognition. The clinicopathological features of 28 PDSS were compared with those of 26 classic SS. Common cell types in PDSS included epithelioid, spindle and Ewing sarcoma-like small round cells. Unusual features included presence of desmoplastic small cell tumour-like areas and extraskeletal myxoid chondrosarcoma-like areas. The presence of necrosis (P = 0.002), a mitotic rate over 10/10 high-power fields (P < 0.001), a haemangiopericytomatous vascular pattern (P < 0.001) and vascular invasion (P = 0.003) were significantly associated with PDSS, while mast cells (P < 0.001), calcification (P < 0.001) and hyaline bands (P < 0.001) were significantly associated with classic SS. Poorly differentiated areas showed increased proliferative activity with Ki67. PDSS showed a tendency to be larger (P = 0.008) and to be located in proximal more than distal sites (P = 0.025). Three entirely poorly differentiated tumours were diagnosed by demonstration of the t(X;18)(p11;q11) translocation. PDSS showed additional cytogenetic abnormalities. Poorly differentiated synovial sarcomas show a spectrum of histological features, which may simulate other malignant neoplasms. The diagnosis of entirely poorly differentiated synovial sarcomas requires cytogenetic analysis.

The 74-year-old head coach of the University of San Diego football team begins a conversation on concussions in football with a pronouncement of perspective. “I played during the dark ages,” Dale Lindsey said. There were no facemasks when Lindsey first pulled on a hard leather helmet in middle school. He suffered, by his count, six concussions. And to be sure, spending any time at all with the man who played in the NFL from 1965 to ‘73 is cause to hope to be nearly as mentally and physically agile as he is in his eighth decade. Lindsey occasionally demonstrates a dismissive air about the relationship between football and long-term brain trauma. But he is no Neanderthal. He is knowledgeable about the science of concussions and said he won’t compromise his stance of not allowing one his players who has been “dinged in the head” to continue playing that day. “Nobody is going to be permanently damaged here for a football game,” he said. The scary fact, however, is no one can say that with any authority. And across the USD campus, there are those who wonder how long it can be pretended that anyone can. So it was that the Faculty Assembly of the College of Arts & Sciences at USD, whose monthly meetings often delve into the tedium of bureaucracy, was the occasion of a spirited 35-minute discussion on the prudence of an institution of higher education sanctioning an activity that may be dooming its participants to debilitation. At the behest of three faculty members, a non-binding resolution was proposed to ban USD’s highly successful football program. “As faculty members, one of our primary duties is to safeguard the well being of our students,” history professor Kenneth Serbin explained of the trio’s opposition to football on the basis of its purported links to long-term brain trauma. “… We believe playing tackle football, especially in (light of) the scientific evidence, is a danger to our students. The vote was not close — a 50-26 defeat with 30 abstentions. Even had the resolution passed, there would have been many more steps before it had any chance of leading to the abolishment of football on the campus. School President James Harris is on record saying he supports the football program and that the concussion issue is “complicated” but that he is open to further discussion pending new information. “I think we are at the end of the road,” associate professor of psychology Nadav Goldschmied said of the effort put forth by he, Serbin and physics professor Daniel Sheehan. Maybe. For now. But it is not impossible to believe that one day we would look back and tell about the time the psychology professor, the history professor and the physics professor walked into a meeting. And it wouldn’t be a joke. Is it so absurd to think that universities, where the chief aim is to improve minds, could someday not too far in the future decide they can’t be party to an endeavor that has the unfortunate side effect of harming minds? Remember, there was a time the world didn’t look twice at a pregnant woman sipping wine. Even more recently, inhaling smoke filled with toxins was not seen as all that ridiculous of a behavior. “We would hope this would spark other universities to follow in our footsteps,” said Serbin, who believes this was the first vote of its kind on any college campus. “We don’t see the vote as a total loss. We see the vote as a starting place.” For the record, these educators are sounding the alarm on a sport they respect for its abundance of redeeming qualities. Especially as it is played at USD, even the most strident believers that football is a danger to those who play it would acknowledge the game provides lessons in perseverance and teamwork that are difficult to replicate even in other sports. The Toreros, who don’t award football scholarships, graduate their players at a greater rate than the general student population. While they are highly competitive in the Football Championship Series level, having just won their fourth consecutive Pioneer Football League title and made their third FCS playoff appearance, it is a source of pride among coaches that players sometimes miss practice for required classwork. “We have a model intercollegiate football program,” Athletic Director Bill McGillis said. “… Performance is important while focusing on outstanding academic achievement.” The problem, as the professors see it, is this, in the words of Serbin: “If you don’t have a healthy brain you cannot enjoy those experiences.” For Sheehan, it got to be too much for too long. He would on occasion over the years see football players in his class with their heads down, unable to concentrate. As a physicist, he began looking into the effects of head collisions in football, conducting his own research and absorbing the growing number of studies that indicate head trauma inherent to football causes long-term damage. There is, famously now, the recent Boston University study of 111 brains of deceased NFL players in which the degenerative brain disease Chronic Traumatic Encephalopathy was found in 110. The same researcher found CTE in 48 out of 53 (91 percent) brains of football players who stopped playing after college, and almost half of those exhibited severe pathology. The NFL and others have dismissed this and other studies as subjective. And perhaps that will prove to be the case. But what if it’s half-right. What if 45 percent of college football players end up with CTE and 28 percent of those exhibit severe pathology? For the professors, this data, even if it needs more replicable study, cannot be ignored. To them, those sanctioning football might not have the inherent evilness of Big Tobacco, but the results of their complicity is just as devastating. “We are pretty dumb,” Goldschmied said. “If you see two people banging their heads repeatedly against each other, this is likely to bring about danger, sickness. It’s so obvious. Now we have scientific evidence, we have something to back it up. … This is not a healthy game. This is a dangerous game. It is clear. There is no gray area here.” Where McGillis, Lindsey and so many others almost unfailingly point out research that says football results in fewer concussions than girls’ soccer, basketball and volleyball, Sheehan counters that the rules of those sports can be sufficiently altered to greatly reduce head trauma. Football is a collision sport played by increasingly large men who are increasingly strong and are running increasingly fast into each other. “The laws of physics are stringent, and they make it very difficult for football to be safe without head impacts,” Sheehan said. “You either slow the game down or outlaw head impacts. … In 20 years, football as we know it will not exist, I don’t think. Too much is being known.” That is a thought taking hold in many corners, including within the NFL. The sport’s future most likely hinges on as-yet-unrealized advances in helmet safety. Perhaps technology progresses as rapidly in developing “safe” helmets and/or helmets that can measure the force of hits to the head as it does with mobile phones. An incredulous Lindsey said this: “We have sent men to the moon. You mean to tell me there isn’t some dude out there who can’t figure this out, that could make something would give us more protection?” Those of us who love and appreciate football can only hope. Otherwise, time is running out — if not for football itself, then for people who sanction the sport to continue to not address the very same questions posed by the psychology and physics and history professors. kevin.acee@sduniontribune.com

WFC Donchanka WFC Donchanka, also known as Donchanka TsPOR for sponsorship reasons, is a Ukrainian women's football club from Donetsk. Founded in 1992 as Tekstilshchik Donetsk, it was renamed as Donetsk-Ros in 1994 before taking its current name in 1997. Donchanka was the leading Ukrainian team for much of the 1990s, winning five championships and four national cups between 1994 and 1999. In 1999, the club lost its sponsors and leading players, and the shift was made to young talented players. It was third in the 2012 championship, its best result since 2003. Titles Ukrainian League Winners (5): 1994, 1995, 1996, 1998, 1999 Runners-up (2): 2000, 2001 Third place (5):, 1997, 2002, 2003, 2012, 2013 Ukrainian Cup (4) Winners (4): 1994, 1996, 1998, 1999 Runners-up (4): 1995, 1997, 1999, 2012 2012 squad As of 20 December 2012, according to the club's website References Category:Women's football clubs in Ukraine Category:Association football clubs established in 1992 Category:Football clubs in Donetsk Category:Ukrainian Women's League clubs Category:1992 establishments in Ukraine

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