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Obtaining the best results: aspects of data collection, model finalization and interpretation of results in small-molecule crystal-structure determination

In small-molecule single-crystal structure determination, we now have at our disposal an inspiring range of fantastic diffractometers with better, brighter sources, and faster, more sensitive detectors. Faster and more powerful computers provide integrated tools and software with impressive graphical user interfaces. Yet these tools can lead to the temptation not to check the work thoroughly and one can too easily overlook tell-tale signs that something might be amiss in a structure determination; validation with checkCIF is not always revealing. This article aims to encourage practitioners, young and seasoned, by enhancing their structure-determination toolboxes with a selection tips and tricks on recognizing and handling aspects that one should constantly be aware of. Topics include a pitfall when setting up data collections, the usefulness of reciprocal lattice layer images, processing twinned data, tips for disorder modelling and the use of restraints, ensuring hydrogen atoms are added to a model correctly, validation beyond checkCIF, and the derivation and interpretation of the final results.




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Synthesis, decom­position studies and crystal structure of a three-dimensional CuCN network structure with protonated N-methyl­ethano­lamine as the guest cation

The com­pound poly[2-hy­droxy-N-methyl­ethan-1-aminium [μ3-cyanido-κ3C:C:N-di-μ-cyanido-κ4C:N-dicuprate(I)]], {(C3H10NO)[Cu2(CN)3]}n or [meoenH]Cu2(CN)3, crystallizes in the tetra­gonal space group P43. The structure consists of a three-dimensional (3D) anionic CuICN network with noncoordinated protonated N-methyl­ethano­lamine cations providing charge neutrality. Pairs of cuprophilic Cu atoms are bridged by the C atoms of μ3-cyanide ligands, which link these units into a 43 spiral along the c axis. The spirals are linked together into a 3D anionic network by the two other cyanide groups. The cationic moieties are linked into their own 43 spiral via N—H⋯O and O—H⋯O hydrogen bonds, and the cations inter­act with the 3D network via an unusual pair of N—H⋯N hydrogen bonds to one of the μ2-cyanide groups. Thermogravimetric analysis indicates an initial loss of the base cation and one cyanide as HCN at temperatures in the range 130–250 °C to form CuCN. We show how loss of a specific cyanide group from the 3D CuCN structure could form the linear CuCN structure. Further heating leaves a residue of elemental copper, isolated as the oxide.




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Wrestlemania 31 weekend: Jim Ross continues an epic career of storytelling

Jerry "The King" Lawler with Jim Ross.; Credit: WWE

Mike Roe

Jim Ross is the most famous pro wrestling play-by play commentator of all time. He's a native Californian, but grew up in Oklahoma and took his trademark drawl into doing commentary. He's worked in wrestling for more than 40 years, calling matches on shows seen by millions of people around the world.

This weekend, he's in the Bay Area for Wrestlemania weekend (the first Wrestlemania in Northern California, and the first in California in 10 years). Ross no longer commentates for WWE, but he's still a storyteller, online and in person. He hosts regular live storytelling shows with stories from his decades-long career and a bit of comedy, along with a live guest, and he also has a huge online presence including a podcast that went to number one in sports its first week out.

Ross has been watching wrestling since he was a kid.

"My dad wasn't a big fan of it. He missed the point. The point is not whether it's real or if it's staged. The point is, are you entertained by it, or not? And I was," Ross said.

He's been at ringside for numerous historic matches, helping the wrestlers to tell their stories ever since he got his first job in wrestling out of college at 22.

"The greater the star, the easier it is to tell their story," Ross said. "Those participants make music. They make different kinds of music, and the announcers, the broadcasters, have to be able to provide the adequate lyric to the competitors' music."

Ross's voice is so powerful that it's become a meme online to pair his voice with another dramatic footage, from sports and beyond — you can even find it paired with dramatic moments from shows like "Breaking Bad" and "Game of Thrones." Ross says that the first time he saw someone do that was with a hit by Michigan running back Jadaveon Clowney, a video which went viral and sparked others to do likewise.

The JR Treatment

"I get sent these memes all the time. 'Hey JR, check this one out.' Or people will say, somebody will make a great dunk at an NBA game, and somebody will say 'I can't wait to see this get the JR treatment.' And now there are major sports websites that will send out a tweet, 'Here's a great play from Sunday's 49er-Charger game that's got the JR treatment.' So now it's got a name. 'The JR Treatment.'"

Those viral videos have even helped him land new commentating roles since leaving WWE. He did a call of a fight between NASCAR drivers for the Daytona 500 for a special pre-show video, and it's led to him having opportunities in traditional sports.

"It's been done in boxing, and MMA. Believe it or not, I've gotten feelers that we're entertaining now from a variety of combat sports entities that actually heard what my call would sound like doing their product," Ross said. "It had my tone, had my inflection, had my level of enthusiasm."

Ross also played a huge role behind the scenes, working as WWE's executive vice president of talent and signing future stars like the Rock, Mick Foley and more. He says that Mick Foley's match against the Undertaker in 1998's Hell in a Cell match was his most memorable to call.

"I have people walk up to me and start quoting my commentary when Undertaker threw Foley off the Hell in a Cell, this massive cage with a roof on it, that was about 17 feet high from the roof to the floor," Ross said. "It looked like no human being, quite honestly, could survive that fall. You don't practice falls like that in wrestling school."

Ross has managed to stay relevant with the help of a popular podcast and 1.3 million followers on Twitter, where he regularly dispenses his thoughts on wrestling and beyond. He started doing that podcast after being lobbied to do it by "Stone Cold" Steve Austin, and continues to try new things.

"I was very reluctant to engage in social media, and primarily because we sometimes get set in our ways, especially the older we get," Ross said. "But change, for any of us, in any walk of life, whether it's your diet, it's your relationships, the way you approach your job, or any changes that you need to affect, whether it's on doctor's orders, your significant other's suggestions — change is not always a negative thing. So I got on Twitter, and then Twitter connected me to so many people."

While some may feel that pro wrestling, given its predetermined results, doesn't need real athletes, Ross disagrees and says there are plenty of reasons to want real athletes.

"They're competitive. They don't want to be on the second team. They want to be in the game. And they've been in that mindset since some of them were in little league, or Pop Warner football, or elementary school wrestling, or whatever it may be."

He says they also understand how to be coached and how to play well with others, as well as handling the bumps and bruises that come with the territory and the difficult travel schedule.

"I don't know that anybody in any entity, unless you're the most well-traveled comedian or entertainer, has that. Because the thing about pro wrestling is it doesn't have an off-season, so you don't get a chance to really go recharge your batteries. You've got to maintain that competitive edge to survive."

Ross says there's one match he wishes he had another shot at calling: Ric Flair's retirement match against Shawn Michaels at Wrestlemania 24 in Orlando at the Citrus Bowl. While Ross has traditionally been a play-by-play commentator, that night he was assigned to be a color commentator, which gave him some different challenges.

"I thought I had great stories to tell because of my relationship with Ric — I've known him for 25 years — and I didn't think that I contributed as much to that match from an emotional standpoint as I could. I was obligated to get in soundbites and get in, get out," Ross said. "That's the biggest match at the biggest stage, and I love both those guys, and I really wanted to be extra special that night, and I just don't know in my heart that we got there."

He says California has its own wrestling legacy to be proud of. The California Wrestlemania match that Ross says he'll always remember: Bret Hart versus Shawn Michaels at Wrestlemania 12 in Anaheim, where two now wrestling legends wrestled for more than an hour.

He also thinks the economics of Wrestlemania make a lot of sense for whichever city hosts it, thanks to the travelers it draws in from around the world. Cities now bid to try to bring in Wrestlemania, Ross says. With Los Angeles gearing up to build a new stadium, Ross has a Wrestlemania prediction for that stadium.

"I will bet you money — I will bet you some of my barbecue sauce — if L.A. builds a stadium, that Wrestlemania will be one of the first non-football events in that stadium. And they will sell it out. They'll fill every seat. And it'll be great for the city, and the businesses of Los Angeles.

Ross says that what made him a great broadcaster is the same thing that can make someone a success in wrestling or anywhere else — most importantly, don't talk down to your audience.

"You have to be a fan of the genre, or a fan of the game, and you have to be willing to prepare and be ready for your broadcast," Ross said. "You have to be willing to tell the story that the average fan — not the hardcore fan, but the average, casual fan can understand and relate to. ... You know, we're storytellers, and some people are just natural-born storytellers."

Ross plans to continue telling stories for the foreseeable future, on stage, online, calling matches in the legit sports world and wherever else his life takes him. He's even gotten into acting — you can see him in the new film "What Now."

"I think retirement is overblown. How many days can you go fishing? How many rounds of golf can you play?" Ross said. "I had the idea when I left WWE after 21 years, I'm going to reinvent myself. I'm not going to become a trivia answer. ... I don't think you're going to read anywhere, anytime soon, that Jim Ross has finally retired — until you read my eulogy."

Listen to the audio for the full hour-long interview with Jim Ross, talking his career past, present and future — along with the origins of his signature barbecue sauce.

This content is from Southern California Public Radio. View the original story at SCPR.org.




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WWE looks to springboard from Wrestlemania 31 into new audiences

Brock Lesnar after losing his championship in the main event of Wrestlemania 31.; Credit: WWE

Mike Roe

World Wrestling Entertainment held their annual Wrestlemania show last weekend in Northern California, the culmination of another year's worth of spectacle. According to the company, it was their highest grossing event of all-time, drawing $12.6 million, with an official attendance placing it fifth on their list of all-time crowds for the event. The show was headlined by former UFC Heavyweight Champion Brock Lesnar going up against up-and-coming star (and a relative of Dwayne "The Rock" Johnson) Roman Reigns.

WWE Network

It comes at a time when the company has embarked on a new way of making money: their over-the-top online programming provider, the WWE Network, where fans can pay $9.99 a month to see programming including what formerly used to cost $45 for most shows and $60 for Wrestlemania. They're one year in now on gambling that enough fans will want the Network that it will ultimately make them more money in the long-term, despite losing that pay-per-view revenue. Wall Street doesn't appear to be buying it — after announcing the day after Wrestlemania that they'd hit 1.3 million subscribers, WWE's stock took a significant loss.

"The point is not whether it's real or if it's staged. The point is, are you entertained by it, or not?" former WWE announcer Jim Ross told KPCC in an interview. WWE is looking for more fans to be entertained enough to plunk down $9.99 for all the pro wrestling content they want.

NXT

They're also in a transitional period with their audiences. They've launched a new show that's only on the Network called "NXT," turning their minor league into a program targeting hardcore pro wrestling fans with a different style of show than the more family-targeted "Raw" and "Smackdown." It's also where they groom potential future stars, many of whom seem to break the mold of some of the traditional stars on WWE's main roster.

They're signing up talent that's been getting buzz on the independent circuits, trying to create their own underground movement that hopefully spells money, and taking the NXT brand on tour for the first time. On the Raw after Wrestlemania, several NXT stars made their debut on the main roster. That follows a sell-out crowd (albeit at a smaller 5,000 seat venue) on the Friday night before Wrestlemania for a non-televised NXT show.

Give Divas a chance

WWE also faces cultural forces pushing them in new directions, including a difference in how society deals with gender. When WWE executive Stephanie McMahon, daughter of the famed Vince McMahon, tweeted in support of Patricia Arquette's speech calling for greater equality for women at the Academy Awards, one of their own wrestlers, AJ Lee, responded by publicly calling Stephanie McMahon out on Twitter for not promoting the women in her own company equally and paying them less than the male stars.

AJ tweet 1

AJ tweet 2

Of course, the women in the company aren't given the same prominence as the men in part because it's felt that they won't make the company as much money. Still, it forced WWE's hand and Stephanie McMahon and the company as a whole publicly embraced the idea of giving the women (who WWE brands as "divas") a chance with the Give Divas A Chance movement (and accompanying trending hashtag).

What's next

The women have been promoted nearly equal to the men in that underground NXT league, but only time will tell if it continues to trickle upward. Wrestlemania didn't seem to show huge promise of that happening, with the one women's match of the show only getting a few minutes in the ring. However, the show also included a high-profile storyline with UFC female fighter and champion Ronda Rousey alongside the Rock, going up against Stephanie McMahon and Triple H, so there appears to be the room for women in prominent positions when they have the right storyline.

Whether WWE is able to wade through these forces of change to make more money — and perhaps regain some of the cultural currency that they've lost since becoming a monopoly and purchasing their top competition in 2001 — remains to be seen. They've stayed relatively steady despite a challenge from UFC, which many see as being what pro wrestling would be like if WWE didn't present fictional  They'll have to hope that giving new stars, including "divas," a chance will take them to another level.

This content is from Southern California Public Radio. View the original story at SCPR.org.




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Testing of a `hard' X-ray interferometer for experimental investigations

A new type of X-ray LLL interferometer, a `hard' interferometer, which has both a base and a `ceiling', is tested for experimental investigations. The tested interferometer has no preliminary uncontrollable moiré and can be used for object and deformation investigations.




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DC think tank: California online schools group should be investigated

A Washington, D.C., think tank issued a report that says California Virtual Acadmies, a major online school network, has had more dropouts than graduates in most years.; Credit: Jeff J Mitchell/Getty Images

Adolfo Guzman-Lopez

A report released Thursday by a labor group-affiliated Washington think tank is questioning the education provided by an online public school program that says it is in a union fight.

The report by In the Public Interest, a group funded by unions, says the thousands of students enrolled in the California Virtual Academies online public school known as CAVA are receiving a  substandard education by most measures.

"So in every year since CAVA began graduating students, with the exception of 2013, it has produced more dropouts than graduates,” said Shahrzad Habibi, who authored the report.

She said state test score data show that 71 percent of California public schools performed better than the virtual academies.

The report calls on California officials to investigate the online schools’ administration and finances.

California Virtual Academies enrolls about 14,000 kindergarten to 12th grade students through 11 sites, including those in Los Angeles, San Diego, and Fresno. It is run by a national for-profit company called K12 Inc.

In a written statement, California Virtual Academies did not dispute the reported low student performance numbers, but denied other allegations in the study, which it called “inaccurate and deeply flawed.”

“The report relies primarily on misinformation from the California Teachers Association — the union currently engaged in a coordinated and well-funded distortion campaign to unionize the eleven independent California Virtual Academies charter schools.”

In the Public Interest, which supports the work of labor unions, partnered with the American Federation of Teachers last year on a website to track for-profit charter school companies.

This content is from Southern California Public Radio. View the original story at SCPR.org.




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Effects of congestion charging increase

Congestion charging in Stockholm has become more successful over time, according to a study by Swedish researchers. Although the total cost of a journey that enters the congestion charge zone has fallen in real terms since the charges were first introduced in 2006, there has consistently been around 29% less traffic within the zone, compared with levels in 2005.




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Study finds big increase in ocean carbon dioxide absorption along West Antarctic Peninsula

Full Text:

A new study shows that the West Antarctic Peninsula is experiencing some of the most rapid climate change on Earth, featuring dramatic increases in temperatures, retreats in glaciers and declines in sea ice. The Southern Ocean absorbs nearly half of the carbon dioxide -- the key greenhouse gas linked to climate change -- that is absorbed by all the world's oceans. The study tapped an unprecedented 25 years of oceanographic measurements in the Southern Ocean and highlights the need for more monitoring in the region. The research revealed that carbon dioxide absorption by surface waters off the West Antarctic Peninsula is linked to the stability of the upper ocean, along with the amount and type of algae present. A stable upper ocean provides algae with ideal growing conditions. During photosynthesis, algae remove carbon dioxide from the surface ocean, which in turn draws carbon dioxide out of the atmosphere. From 1993 to 2017, changes in sea ice dynamics off the West Antarctic Peninsula stabilized the upper ocean, resulting in greater algal concentrations and a shift in the mix of algal species. That's led to a nearly five-fold increase in carbon dioxide absorption during the summertime. The research also found a strong north-south difference in the trend of carbon dioxide absorption. The southern portion of the peninsula, which to date has been less impacted by climate change, experienced the most dramatic increase in carbon dioxide absorption, demonstrating the poleward progression of climate change in the region.

Image credit: Drew Spacht/The Ohio State University




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Alexion's Buyout of Portola Pharmaceuticals Gets Investors' Blood Flowing

Source: Streetwise Reports   05/05/2020

Shares of Portola Pharmaceuticals traded 130% higher after the company reported that it has received an $18 per share buyout offer from Alexion Pharmaceuticals.

Commercial-stage biotechnology company Portola Pharmaceuticals Inc. (PTLA:NASDAQ), which focuses on blood-related disorders, and global biopharmaceuticals firm Alexion Pharmaceuticals Inc. (ALXN:NASDAQ) announced that they have entered into a definitive merger agreement for Portola to be acquired by Alexion.

The acquisition is said to provide a key addition to Alexion's diversified commercial portfolio. The report indicated that the merger agreement has already been unanimously approved each of the company's boards of directors.

The report explained that "Portola's commercialized medicine, Andexxa® [coagulation factor Xa (recombinant), inactivated-zhzo], marketed as Ondexxya® in Europe, is the first and only approved Factor Xa inhibitor reversal agent, and has demonstrated transformative clinical value by rapidly reversing the anticoagulant effects of Factor Xa inhibitors rivaroxaban and apixaban in severe and uncontrolled bleeding."

Portola's President and CEO Scott Garland commented, "In developing and launching Andexxa, Portola has established a strong foundation for changing the standard of care for patients receiving Factor Xa inhibitors that experience a major, life-threatening bleed. Andexxa rapidly reverses the pharmacologic effect of rivaroxaban and apixaban within two minutes, reducing anti-Factor Xa activity by 92 percent...Given their enhanced resources, global footprint and proven commercial expertise, we look forward to working with Alexion to maximize the value of Andexxa. With their commitment to commercial excellence, together, we will be able to drive stronger utilization of Andexxa, increase penetration and accelerate adoption in the critical care setting."

Ludwig Hantson, Ph.D., CEO of Alexion, remarked, "The acquisition of Portola represents an important next step in our strategy to diversify beyond C5. Andexxa is a strategic fit with our existing portfolio of transformative medicines and is well-aligned with our demonstrated expertise in hematology, neurology and critical care...We believe Andexxa has the potential to become the global standard of care for patients who experience life-threatening bleeds while taking Factor Xa inhibitors apixaban and rivaroxaban. By leveraging Alexion's strong operational and sales infrastructure and deep relationships in hospital channels, we are well positioned to expand the number of patients helped by Andexxa, while also driving value for shareholders."

The firms advised that "under the terms of the merger agreement, a subsidiary of Alexion will commence a tender offer to acquire all of the outstanding shares of Portola's common stock at a price of $18 per share in cash." Alexion plans to fund the purchase with existing cash on hand and the transaction is expected to close in Q3/20. The purchase is subject to approval by a majority interest of Portola's common stockholders tendering their shares along with ordinary closing conditions and regulatory approvals. The company noted that "following successful completion of the tender offer, Alexion will acquire all remaining shares not tendered in the offer at the same price of $18 per share through a merger."

Alexion is a global biopharmaceutical company based in Boston, Mass., with offices in 50 countries worldwide. The company states that it has been "the global leader in complement biology and inhibition for more than 20 years and that it has developed and commercializes two approved complement inhibitors to treat patients with paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome, as well as the first and only approved complement inhibitor to treat anti-acetylcholine receptor antibody-positive generalized myasthenia gravis and neuromyelitis optica spectrum disorder."

Portola is headquartered in South San Francisco, Calif., and is a commercial-stage biopharmaceutical company focused on treating patients with serious blood-related disorders. Specifically, the company is engaged in developing and commercializing novel therapeutics in order to advance the fields of thrombosis and other hematologic conditions. The firm listed that its first two commercialized products are Andexxa® and Bevyxxa® (betrixaban), and that it is also advancing and developing cerdulatinib, a SYK/JAK inhibitor for use in treatment of hematologic cancers.

Portola Pharmaceuticals started off the day with a market capitalization of around $609.0 million with approximately 78.5 million shares outstanding and a short interest of about 23.0%. PTLA shares opened 130% higher today at $17.85 (+$10.09, +130.03%) over yesterday's $7.85 closing price. The stock has traded today between $17.71 and $17.91 per share and is currently trading at $17.83 (+$10.07, +129.77%).

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Disclosure:
1) Stephen Hytha compiled this article for Streetwise Reports LLC and provides services to Streetwise Reports as an independent contractor. He or members of his household own securities of the following companies mentioned in the article: None. He or members of his household are paid by the following companies mentioned in this article: None.
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5) From time to time, Streetwise Reports LLC and its directors, officers, employees or members of their families, as well as persons interviewed for articles and interviews on the site, may have a long or short position in securities mentioned. Directors, officers, employees or members of their immediate families are prohibited from making purchases and/or sales of those securities in the open market or otherwise from the time of the interview or the decision to write an article until three business days after the publication of the interview or article. The foregoing prohibition does not apply to articles that in substance only restate previously published company releases.
6) This article does not constitute medical advice. Officers, employees and contributors to Streetwise Reports are not licensed medical professionals. Readers should always contact their healthcare professionals for medical advice.




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Building a Better Covid-19 Antibody Test

Source: Streetwise Reports   05/06/2020

ProMIS is harnessing its unique technology platform to develop a more error-free antibody test.

Testing has been an Achilles heel of the coronavirus pandemic, but ProMIS Neurosciences Inc. (PMN:TSX; ARFXF:OTCQB) has partnered with Dr. Hans Frykman and the BC Neuroimmunology Lab to use its unique technology to create a more accurate antibody test for SARS-CoV-2, the virus that causes Covid-19.

Two main types of tests exist for Covid-19: one that detects the presence of the virus that causes Covid-19, which indicates a person has an active infection, and another that detects antibodies, showing that a person has been exposed to the virus.

The first test that was developed, a test for the presence of the virus, is used mainly to confirm diagnosis of Covid-19 in people who are showing symptoms such as a fever, a dry, persistent cough, difficulty breathing, a sense of restriction in the chest. "They are typical signs of Covid-19, but we would want to know if these are signs of the common flu or a bad cold or Covid-19. We know that Covid can progress really significantly very quickly, especially in individuals with underlying conditions," ProMIS CEO Dr. Elliot Goldstein told Streetwise Reports. "The number of tests is limited, but it's not actually the tests themselves but the reagents and systems you need to run the test that are in short supply."

"Anytime you conduct a test for the virus and get a negative response, the test indicates only that on that day at that time, the person does not have the virus. The person could have had Covid and recovered, or might have had an asymptomatic or very mild case. Or that person could get the virus tomorrow or in three days," Dr. Goldstein explained. "At any point in time the virus test helps indicate the prevalence of the virus—how many people are actually infected—if you test broadly, and at the time you do it, you can determine whether an individual is currently infected or not."

The second type of test, called serological tests or assays, is also known as an antibody test. "When a person is recovering from a viral infection, the immune system makes antibodies—also called immunoglobulins—that are specific to the virus. They neutralize the virus and help clear it out; that's part of the mechanism of why you get better," Dr. Goldstein explained.

One way to see if a person has had Covid is to test for antibodies. "A positive test means you've been exposed to the virus because, in the absence of a vaccine, that's the only way you would have the antibodies. While it's not 100% certain that antibodies neutralize the virus, based on experience with other coronaviruses, it is likely," Dr. Goldstein said. Having the virus neutralized should offer at least some protection against future re-infections.

People who have had positive virus tests know that they have Covid or had Covid and recovered, but many people are asymptomatic or may have had what felt like a light cold, and they want to know if they are at risk, or if they have some protection against the disease. "This is really important for frontline healthcare workers, people working 8-10 hours a day in intensive care or the emergency room with patients known to be very sick with Covid-19; even with protective equipment, they have significant exposure to the virus," Dr. Goldstein explained. "If someone has been through the disease and has natural antibodies, they can't infect someone else. What you want to know on an individual level is am I safe from infection and am I safe for other people."

Generally, antibody testing is a fairly common procedure, Dr. Goldstein explained. When you spin blood in a centrifuge, it separates into three parts: red blood cells, plasma and serum. Serum is where you find antibodies. "ELISA (enzyme-linked immunosorbent assay) is a standard test that looks for antibodies, but it is not specific enough for the Covid-19 virus."

The challenge is there are multiple coronaviruses. "Four different coronaviruses are responsible for the common cold, and then there are others like SARS and MERS. They all have the same sort of halo or corona of protein around the outside of it," Dr. Goldstein said. "They look like the old naval mines used in war. The whole family of coronaviruses look like that. The amino acid sequences of different coronaviruses are not identical but very similar; they share a lot of common structures. There are only really small differences and you can't really pick them up using the usual physical methods."

Studies have shown that up to 90% of individuals in Western countries have been exposed to one or more of the common cold coronaviruses and have antibodies against them. "They look very similar to the coronavirus causing Covid-19. So in Covid-19 antibody tests, the most important thing is it has to be highly specific for the Covid-19 antibodies and doesn't test positive when it identifies a common cold antibody. That is a false positive," said Dr. Goldstein. "It's actually much safer not to have a test that has a lot of false positives because you could base a behavioral decision on faulty information."

Dr. Goldstein cited an example. "If you are testing 1,000 people and there is a 90% prevalence for the cold virus, that means around 900 people have antibodies to the common cold. If the prevalence of the Covid-19 virus is 2%, roughly 20 of the 1,000 would have antibodies to the Covid-19 virus. Let's say the serology test has 95% specificity. That means five times out of 100, it will give a false positive, indicating the presence of Covid-19 antibodies when it is really picking up antibodies against the cold virus. What this means is 5% of 900, or 45 people, will test positive for Covid when they have not had it, and are making decisions based on incorrect information. The consequences of being wrong are dramatic and highlight the need for a very good, high-quality serological test."

How does this relate to Alzheimer's and other neurological diseases that are ProMIS' core competency? "In Alzheimer's, ALS, frontotemporal dementia, Parkinson's disease and other neurological disease, we've been able to use our proprietary, unique technology to identify sites on misfolded proteins that are driving these diseases. Our core technology is the capability to understand what's special about the bad proteins that are causing these diseases and then we can make antibodies highly selective against them. Our technology allows us to identify a region, an epitopes target, which is a series of four to six amino acids where the protein has misfolded. Not only do we know where this target site is located, importantly we also determine the shape (conformation) of this site. Proteins like amyloid and alpha synuclein and TDP 43 misfold and when these proteins misfold they become toxic, they kill neurons, resulting in disease," Dr. Goldstein explained.

ProMIS has transferred that thinking to the virus causing Covid-19. "The corona is composed of the spiky protein. Remember, we want to be able to distinguish between the coronavirus causing the common cold and the coronavirus causing Covid-19," Dr. Goldstein said. "If we can distinguish between the two, we can have an antibody test that's specific for Covid-19. We are looking at a region of the virus called the receptor binding domain, the RBD, that is part of the spike protein and how it attaches to cells. We have a core competency that allows us to identify sites, and not just the location of the sites, but the shape of the sites on complex protein molecules. That allows us then to use that knowledge to create either antibodies or to create serum tests, or even quite frankly, we can use those targets to create vaccines."

Using ProMIS' proprietary technology, the company has been able to "identify a site that we believe is only present on the Covid-19 virus and not on other coronaviruses. We are now initiating the synthesis of several different forms of that site; it's a small area," Dr. Goldstein stated. "That would then transfer to Dr. Hans Frykman's lab at University of British Columbia, a world-class serology lab. Then we will see if the targets we've identified are specific and selective antibodies against Covid-19."

When you test the serum of an individual, if they've been exposed to the virus and have the antibodies, "those antibodies should bind selectively and specifically to the target. So if the antibodies from the patient's serum are binding to the target site, we know it's a Covid-19 virus because that site is only visible in that shape on the Covid-19 virus and not the others. For the validation of our test, only in patients known to have had Covid-19 should we see binding of antibodies against Covid-19 to our target. The second validation is based on testing in serum from subjects known to have never been exposed to Covid-19 virus—such subjects have antibodies only from cold or other coronaviruses, and therefore the antibody test should be negative; there should be no binding. So we should only see binding in serum from a patient known to have recovered from COVID-19, and we should not see binding in serum from an individual known not to have been exposed to COVID-19," Dr. Goldstein explained.

"Our technology basically allows us to zero in with sniper-like precision on the structure of a protein and understand it, not only the structure overall but the shape of the regions on that protein and then that allows us to identify what is specific to that protein, in this case the spiky protein on the virus causing COVID-19," said Dr. Goldstein.

ProMIS expects to have initial results in June.

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Disclosure:
1) Patrice Fusillo compiled this article for Streetwise Reports LLC and provides services to Streetwise Reports as an employee. She or members of her household own securities of the following companies mentioned in the article: None. She or members of her household are paid by the following companies mentioned in this article: None.
2) The following companies mentioned in this article are billboard sponsors of Streetwise Reports: ProMIS Neurosciences. Click here for important disclosures about sponsor fees.
3) Comments and opinions expressed are those of the specific experts and not of Streetwise Reports or its officers. The information provided above is for informational purposes only and is not a recommendation to buy or sell any security.
4) The article does not constitute investment advice. Each reader is encouraged to consult with his or her individual financial professional and any action a reader takes as a result of information presented here is his or her own responsibility. By opening this page, each reader accepts and agrees to Streetwise Reports' terms of use and full legal disclaimer. This article is not a solicitation for investment. Streetwise Reports does not render general or specific investment advice and the information on Streetwise Reports should not be considered a recommendation to buy or sell any security. Streetwise Reports does not endorse or recommend the business, products, services or securities of any company mentioned on Streetwise Reports.
5) From time to time, Streetwise Reports LLC and its directors, officers, employees or members of their families, as well as persons interviewed for articles and interviews on the site, may have a long or short position in securities mentioned. Directors, officers, employees or members of their immediate families are prohibited from making purchases and/or sales of those securities in the open market or otherwise from the time of the interview or the decision to write an article until three business days after the publication of the interview or article. The foregoing prohibition does not apply to articles that in substance only restate previously published company releases. As of the date of this article, officers and/or employees of Streetwise Reports LLC (including members of their household) own securities of ProMIS, a company mentioned in this article.
6) This article does not constitute medical advice. Officers, employees and contributors to Streetwise Reports are not licensed medical professionals. Readers should always contact their healthcare professionals for medical advice.

( Companies Mentioned: PMN:TSX; ARFXF:OTCQB, )




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