Reliable sample delivery and efficient use of limited beam time have remained bottlenecks for serial crystallography (SX). Using a high-intensity polychromatic X-ray beam in combination with a newly developed charge-integrating JUNGFRAU detector, we have applied the method of fixed-target SX to collect data at a rate of 1 kHz at a synchrotron-radiation facility. According to our data analysis for the given experimental conditions, only about 3 000 diffraction patterns are required for a high-quality diffraction dataset. With indexing rates of up to 25%, recording of such a dataset takes less than 30 s.

For serial femtosecond crystallography at X-ray free-electron lasers, which entails collection of single-pulse diffraction patterns from a constantly refreshed supply of microcrystalline sample, delivery of the sample into the X-ray beam path while maintaining low background remains a technical challenge for some experiments, especially where this methodology is applied to relatively low-ordered samples or those difficult to purify and crystallize in large quantities. This work demonstrates a scheme to encapsulate biological samples using polymer thin films and graphene to maintain sample hydration in vacuum conditions. The encapsulated sample is delivered into the X-ray beam on fixed targets for rapid scanning using the Roadrunner fixed-target system towards a long-term goal of low-background measurements on weakly diffracting samples. As a proof of principle, we used microcrystals of the 24 kDa rapid encystment protein (REP24) to provide a benchmark for polymer/graphene sandwich performance. The REP24 microcrystal unit cell obtained from our sandwiched in-vacuum sample was consistent with previously established unit-cell parameters and with those measured by us without encapsulation in humidified helium, indicating that the platform is robust against evaporative losses. While significant scattering from water was observed because of the sample-deposition method, the polymer/graphene sandwich itself was shown to contribute minimally to background scattering.

Apoptosis is a crucial process by which multicellular organisms control tissue growth, removal and inflammation. Disruption of the normal apoptotic function is often observed in cancer, where cell death is avoided by the overexpression of anti-apoptotic proteins of the Bcl-2 (B-cell lymphoma 2) family, including Mcl-1 (myeloid cell leukaemia 1). This makes Mcl-1 a potential target for drug therapy, through which normal apoptosis may be restored by inhibiting the protective function of Mcl-1. Here, the discovery and biophysical properties of an anti-Mcl-1 antibody fragment are described and the utility of both the scFv and Fab are demonstrated in generating an Mcl-1 crystal system amenable to iterative structure-guided drug design.

The design and assembly of two 3D-printed holders for high-throughput in meso in situ fixed-target crystallographic data collection are described.

A putative open reading frame encoding GTP cyclohydrolase I from Listeria monocytogenes was expressed in a recombinant Escherichia coli strain. The recombinant protein was purified and was confirmed to convert GTP to dihydroneopterin triphosphate (Km = 53 µM; vmax = 180 nmol mg−1 min−1). The protein was crystallized from 1.3 M sodium citrate pH 7.3 and the crystal structure was solved at a resolution of 2.4 Å (Rfree = 0.226) by molecular replacement using human GTP cyclohydrolase I as a template. The protein is a D5-symmetric decamer with ten topologically equivalent active sites. Screening a small library of about 9000 compounds afforded several inhibitors with IC50 values in the low-micromolar range. Several inhibitors had significant selectivity with regard to human GTP cyclohydrolase I. Hence, GTP cyclohydrolase I may be a potential target for novel drugs directed at microbial infections, including listeriosis, a rare disease with high mortality.

Kelly L. Dunlevy, Valentina Medvedeva, Jade E. Wilson, Mohammed Hoque, Trinity Pellegrin, Adam Maynard, Madison M. Kremp, Jason S. Wasserman, Andrey Poleshko, and Richard A. Katz

A large fraction of epigenetically silent heterochromatin is anchored to the nuclear periphery via "tethering proteins" that function to bridge heterochromatin and the nuclear membrane or nuclear lamina. We identified previously a human tethering protein, PRR14, that binds heterochromatin through an N-terminal domain, but the mechanism and regulation of nuclear lamina association remained to be investigated. Here we identify an evolutionarily conserved PRR14 nuclear lamina binding domain (LBD) that is both necessary and sufficient for positioning of PRR14 at the nuclear lamina. We also show that PRR14 associates dynamically with the nuclear lamina, and provide evidence that such dynamics are regulated through phosphorylation-dephosphorylation of the LBD. Furthermore, we identified a PP2A phosphatase recognition motif within the evolutionarily conserved PRR14 C-terminal Tantalus domain. Disruption of this motif affected PRR14 localization to the nuclear lamina. The overall findings demonstrate a heterochromatin anchoring mechanism whereby the PRR14 tether simultaneously binds heterochromatin and the nuclear lamina through two separable, modular domains. The findings also describe an optimal PRR14 LBD fragment that could be used for efficient targeting of fusion proteins to the nuclear lamina.

Source: Knox Henderson for Streetwise Reports   05/05/2020

News Update: A quick update since FansUnite Entertainment Inc. went live on Tuesday, May 5, because big things are happening in the industry, thus showing there is an enormous appetite for this kind of technology especially now, as we (very slowly) emerge out of this COVID pandemic. . .FansUnite is at a small-cap entry point with tremendous upside. After a financing at $0.35, the now-trading company rests slightly above that as a relatively new and unknown entity—so far—which is why now is great opportunity participate in a smaller scale, yet leveraged, consolidation play. "We have a great opportunity to use our stock as currency, and then grow and scale companies through our team and resources," says CEO Darius Eghdami. Read the entire update here.

Lets face it: gamers love games. While currently there's a dearth of real sports activity, that doesn't mean people aren't starving something to speculate on. No sports? No problem. Consider that there is $50 billion dollars placed online every year, according to ESPN. That's a lot of hungry money looking for a place to play.

So, despite the absence of the NFL, NHL, NBA and MLB, new online platforms are offering fun times for taking your chances on everything from reality TV shows, award shows, online gaming and virtual sports along with real in-the-flesh nail-biters like horse racing, table tennis and snooker. Who cares? It's all about the thrill of playing and winning. According to The The Guardian, just last week, "as coronavirus and the subsequent shelter-in-place orders have shut businesses around the globe and forced people to stay inside, some jobs have proven more stable than others," it said referring to online players. "The four U.S. states with legal sites—New Jersey, Nevada, Delaware, and Pennsylvania—reported record revenues in March." Meanwhile despite our current "modified behaviors" and "slowing of the economy," investors are also very keen on speculation in the gaming industry itself.

"FansUnite is at a small-cap entry point with tremendous upside."

Take, for example, DraftKings (NASDAQ:DKNG), which launched as recently as April 23, in the thick of this stay-at-home pandemic. After completing a merger with Diamond Eagle, a special purpose acquisition company, and back-end technology provider SBTech, its stock soared. Not only did DraftKings' stock jump 14% in its first day of trading before closing up 10.38% at $19.35, but the company was also able to add another half a billion dollars on the balance sheet at a time when it's not easy to raise money. The company is currently nearing a $1 billion market capitalization.

In this game, consolidation is key. Another highly successful big gaming conglomerate over-the-pond is UK-based GVC Gaming Group, which has been consolidating gaming assets over the last 15 years and is now worth $7.5 billion.

This week on the Canadian Securities Exchange (CSE) an emerging player is launching its platform onto the public market. FansUnite Entertainment Inc. (FANS:CSE), a company active in the gaming industry since 2014, is led by industry veterans who are looking to unleash their own high-growth consolidation strategy. The company is focusing on technology related to regulated and lawful internet activity and other related products.

Its business is to consolidate business-to-business (B2B) partnerships worldwide, operate its FansUnite business-to-consumer (B2C) coined Sportsbook launching later this year, and operate its recently acquired (March 26) Scottish subsidiary, McBookie, an online white-label sportsbook licensed and regulated by the U.K. Commission. Even considering the "COVID" delays in traditional sports, the company expects to generate at least $1 million in 2020. Considering FansUnite's experience in the space and its established technologies in an industry that is truly trending, FansUnite has a long runway from its current $25 million market cap to the billions-dollar peers it's chasing, and that is why this looks be a great stock to hold right out of the gate.

When you consider "B2B" in this scenario, consider an entity that wants to create a sportsbook, to become "the house," if you will. That company would turn to FansUnite to set up a turnkey "white-label" (as in use FansUnite technology but with its own brand) online platform, complete with user onboarding, fan integration and access to fulfillment in fiat currency (hard dollars) or cryptocurrency. For this service FansUnite takes a percentage of the "house earnings" and also charges for its Software as a Service (SaaS) platform. In the B2C scenario, FansUnite itself is the "house," using its own sportsbook and technology platform, and executes the marketing efforts to on-board new users.

McBookie, the company's first acquisition, is a white-label sportsbook in the UK, focusing on the Scottish market. It offers 200,000 members active in sports, and virtual games and boasts over $100 million turnover cumulatively the last three years. "It's a great brand with an experienced team operating for over a decade," says FansUnite CEO Darius Eghdami. "We completed this acquisition late March, and our focus currently is going to continue building our presence in the Scottish market."

Moving forward, Eghdami says the team will be putting an emphasis on M&A activity. "We'll continue to look for strong assets with either great technology or a strong database of users where we can come in with our team and resources and really grow and scale the business," he says.

With strong financial backing, Eghdami is also looking at potential opportunities in the colossal U.S. market. "The big heavyweights are coming into the U.S.. We don't intend to be an operator in the U.S., so we're looking at other ways to get in the market and that includes social peer activity, fan engagement, as well as licensed affiliate opportunities."

Eghdami points to another big success story in Canada, Amaya (TSE:TSGI), which is now The Stars Group and has a market capitalization of $11.5 billion. "It's a tremendous story of how they built the company and started to acquire assets. It's a model that we would love to follow."

After a crushing dip into the pandemic, TSGI.T is big-board player that has catapulted to new highs once the reality set in that social isolation might not necessarily be a bad thing for online gaming providers. According to Bloomberg, "The Stars Group Inc. says it saw record revenue in its first quarter as COVID-19 led to an increase in online activity starting in March. And, it says, it has continued to see increased activity in its online playing into the second quarter. In an update to its expectations for the three-month period ended March 31, the company says it expects revenue of approximately US$735 million, up from US$580 million in the first quarter of 2019."

"The stay-at-home lifestyle we now face in 2020 could result in a massive shift in the habits of players," says Eghdami. "Players that are used to going to the physical house, or the horse track, may now shift their habits to online. The older generation now may be signing up on online platforms and realize they can do this a lot easier. We're getting new users on the platform every day, and players starting to turn to virtual sports as well."

FansUnite is the brainchild of three entrepreneurs who have each already carved out more than a decade of in-the-trenches experience in the industry. Two of them including founder Eghdami and his former associate at KMPG, Graeme Moore, are chartered accountants, while co-founder Duncan McIntyre is a practicing lawyer schooled in mergers, acquisitions and corporate development. The teams' first success was the development of the FansUnite B2C social platform, which they eventually sold to a public company in 2016. FansUnite Social uses a free virtual currency for members to simulate the real thing while following and learning from their online heroes. The endgame, of course, is toward transferring the activity to the real-dollar platforms.

FansUnite Technology—B2C Social Platform

After the sale of the social peer platform, Eghdami and company decided to maintain the "FansUnite" brand equity in their new venture, launched in 2017. "We had the idea of getting into real-money sports gaming, spun it out of the pubic company, raised money in 2018 and started down this path. For the last year and a half we've been building our own technology to launch our sportsbook from a B2C perspective as well as prepare it for a full turn-key B2B solution. An option on the B2B platform will be a "smart contract sports book" whereby the funds are held "in-trust" and not accessible to FansUnite or end users until the event is completed and funds are directly sent to the winning party. The FansUnite platform is expected to accept cryptocurrency and regular fiat currency on its sportsbooks.

As part of FansUnite's roll-up strategy of entering into other world markets, acquiring yet maintaining well-established brands is the key to building its global B2B customers and B2C end users. The company is well funded with access to capital. Much of its support comes from industry leaders on the board like Shafin Diamond, CEO of Victory Square since 2015, a venture builder that builds start-ups in web, mobile, gaming, AI and AR/VR. Diamond has launched 40 start-ups in 24 countries, employed more than 350 people, and has generated over $100 million in annual revenues. He has received numerous awards, including the BC Tech Person of the Year Award, BC Angel Investor of the Year in 2014, and Business in Vancouver's Top 40 under 40.

FansUnite recently completed a financing of $3.1 million at $0.35 (free trading upon listing) and used $500,000 cash for the McBookie transaction before launching its IPO on the CSE. Total consideration for the McBookie deal was for approximately CAD$2.2 million, composed of the $500,000 cash up front, and $500,000 cash to be paid within 12 months, the rest in stock, at $0.35 a share, vesting and unrestricting over a course of 36 months.

Currently, management and insiders hold about 20% of the 70 million shares outstanding, and there are 3.5 million options and 1.4 million warrants with a weighted average price of $0.48 and $0.17 respectively, so no scary skeletons in the closet. Eghdami says the company is now sitting on about a $2 million war chest and burning about $175,000 per month. Should investor speculation lift its share price (as predicted here), it should be able to execute is M&A activity with a much stronger currency.

With $1 trillion waged annually, according to UK-based Football Report, the global market for this kind of technology is insane. Apparently, due to "COVID self-containment," it's "trending" even more as digital consumers are quarantined in their homes with nothing better to do but play on their computers.

As we hopefully ease out of this economic situation, FansUnite will have to execute fast and furiously. Now launching on the CSE at C$0.35 with a current market capitalization of $25 million, it has a long way to go, and much to prove, toward reaching the billion-dollar heights of its gaming peers, but the pie is big and the appetite is certainly there.

This is one race worth watching.

Knox Henderson is a journalist and capital markets communications consultant. He has advised for a broad range of small cap companies in the resource, life sciences and technology sectors for more than 25 years.

Disclosure:
1) 1) Knox Henderson: I, or members of my immediate household or family, own shares of the following companies mentioned in this article: None. I personally am, or members of my immediate household or family are, paid by the following companies mentioned in this article: FansUnite Entertainment Inc. My company has a financial relationship with the following companies mentioned in this article: None. I determined which companies would be included in this article based on my research and understanding of the sector.
2) The following companies mentioned in this article are billboard sponsors of Streetwise Reports: None. Click here for important disclosures about sponsor fees. As of the date of this article, an affiliate of Streetwise Reports has a consulting relationship with FansUnite. Please click here for more information. An affiliate of Streetwise Reports is conducting a digital media marketing campaign for this article on behalf of FansUnite. Please click here for more information. The information provided above is for informational purposes only and is not a recommendation to buy or sell any security.
3) Statements and opinions expressed are the opinions of the author and not of Streetwise Reports or its officers. The author is wholly responsible for the validity of the statements. The author was not paid by Streetwise Reports for this article. Streetwise Reports was not paid by the author to publish or syndicate this article. Streetwise Reports requires contributing authors to disclose any shareholdings in, or economic relationships with, companies that they write about. Streetwise Reports relies upon the authors to accurately provide this information and Streetwise Reports has no means of verifying its accuracy.
4) This 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 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 FansUnite, a company mentioned in this article.

( Companies Mentioned: FANS:CSE, )

By expending too many resources to inspect cleaner low-emitting vehicles, coupled with a lack of effective ways to deal with the dirtiest ones, states are missing opportunities to reduce air pollution.

To meet the bodys daily energy and nutritional needs while minimizing risk for chronic disease, adults should get 45 percent to 65 percent of their calories from carbohydrates, 20 percent to 35 percent from fat, and 10 percent to 35 percent from protein.

Potentially useful biomarker tests for molecularly targeted therapies are not being adopted appropriately into clinical practice because of a lack of common evidentiary standards necessary for regulatory, reimbursement, and treatment decisions, says a new report by the National Academies of Sciences, Engineering, and Medicine.

Data from studies monitoring the amount of plastic eaten by seabirds suggest that levels in the North Sea are well above targets established for the North East Atlantic Ocean by OSPAR (the Oslo and Paris Convention). For the most recent monitoring period, the target amount was exceeded in well over half the birds studied.

We reported last week that layoffs were coming soon to Warner Brothers, but how many positions will be cut is still unknown.  

A spokesman for Warner Brothers Entertainment, Paul McGuire, told KPCC there's no exact number yet. "There is no headcount reduction target, but there is a substantial financial target," Maguire said. 

“This is a budget issue, not a head count issue,” Dee Dee Myers, Warner Brothers Vice President of Corporation Communications told Variety.  The trade publication reports that Warner Brothers is expected to eliminate as many as 1,000 positions worldwide - or about 10 percent of its workforce:

Senior managers are currently assessing their businesses to come up with ways to trim overhead. Only at the end of that process will an exact reduction figure be known. It could be somewhat lower than the current numbers being speculated, but cuts are expected to be substantial.  

News of coming layoffs became public two weeks ago, when KPCC and other media outlets obtained an internal memo written by Warner Bros. Chairman and Chief Executive Officer Kevin Tsujihara.   

"It pains me to say this, positions will be eliminated—at every level—across the Studio," Tsujihara wrote in the memo. 

Morningstar Analyst Neil Macker told KPCC that management at Warner Brothers is trying to protect the company from another takeover play by Rupert Murdoch.  In July, Murdoch offered to buy parent company Time Warner for $80 billion. He withdrew the offer in August. 

An unknown threat actor is exploiting vulnerabilities in plugins for which patches have been available for months, or even years

The post Almost a million WordPress websites targeted in massive campaign appeared first on WeLiveSecurity

The world’s marine ecosystems are at risk of sudden and damaging changes. The authors of a recent study say that co-ordinated management of the many drivers of marine changes, such as overfishing and pollution, is needed across international, national and local scales to help avoid the ‘regime shifts’ that affect ecosystem services and human wellbeing.

Indonesia’s plans to double palm oil production by 2020 have obvious financial benefits, but implications for food, biodiversity and carbon stocks are not so clear. A new model predicts the impacts of five possible palm oil production strategies and indicates the best approach is to target degraded and agricultural land that is most productive for palm oil.

'Feed the crop not the soil' is the message of a new review into sustainable phosphorus use. Currently, phosphorus fertiliser is applied to the soil, and plants then take it up through the roots. However, more precise nutrient management is needed on farms, the researchers say, so that the phosphorus is targeted at the crop just as it needs it.

This Thematic Issue reports on research into policy targets for sustainability, and associated indicators, to tie in with the launch of the EU's 7th Environmental Action Programme.

The social, political, technological and geophysical factors that affect the control of climate change have been assessed in a recent study. The results suggest that political factors, in terms of delaying the implementation of mitigation strategies, have the biggest effect on limiting global warming to below 2C.

Greenhouse gas (GHG) emissions from municipal waste in Europe could be reduced by 62 million tonnes, or 1.23% of total emissions in 2008, by 2020 if the diversion targets of the EU Landfill Directive are fully met, according to a recent report. This could be largely achieved through reducing methane emissions from landfill and increased recycling levels.

European policies have eliminated the most visible and harmful effects of air pollution, but current rates of emissions still pose a threat to the environment and to human health. A new study has assessed the policy scope to make further environmental improvements by applying the GAINS (Greenhouse gas-Air pollution Interactions and Synergies) model.

While energy-efficiency gains are needed to lower Europe’s greenhouse gas emissions, low-carbon technologies are also crucial if we are to meet ambitious EU emissions targets in the long term, new comparative research concludes.

Agri-environmental measures (AEM) are designed to encourage farmers to protect and enhance the environment on their farmland by paying them for the provision of environmental services. This study suggests that AEM would be more effective if payments were targeted to areas under the greatest environmental pressures, such as intensive agricultural regions — to gain maximum environmental benefits.

Europe could struggle to meet the target set by the renewable energy sector of 25% of electricity produced by solar energy by 2040 because the supply of materials, including rare metals, needed to produce photovoltaics (PV) is unlikely to meet demand. Production rates need to be drastically improved, according to a new study.

Sustainable development aims to improve quality of life without compromising the well-being of future generations. A new study highlights the challenges of setting environmental sustainability goals and cites the EU Climate and Energy policy package, with its ‘20-20-20’ targets, as a model example.

A number of EU policy targets and indicators exist to improve the efficiency of natural resource use. A new report produced for the European Commission concludes that although indicators of resource use need improvement, they are still a valuable policy tool to monitor progress towards sustainable material, energy, water and land use.

With ever-increasing global consumption, the impacts of resource depletion, land use change and pollution are being felt worldwide. A new study reveals how international trade is shifting the environmental burden from the consuming nation to other parts of the world, and calls for changes in the way national material use is accounted for.

Regional governments lack the support required to meet EU-wide targets for greenhouse gas (GHG) emission reductions in the building, transportation, agriculture and waste sectors, according to a new study. The researchers outline a five-step process to help regional governments develop indicators and policy measures to help ensure national targets are met.

Environmental targets for sustainable agriculture can usually be met in a variety of ways, but their exact impacts are rarely known. A new study has compared the social, economic and environmental impacts of different policy approaches to hitting conservation targets in Australia, to help regional governments understand the costs, benefits and trade-offs of different policy options.

Google blocked and removed 2.7 billion bad ads more than 5,000 bad ads per minute and suspended nearly 1 million advertiser accounts for policy violations, the company announced on Thursday.

Cybercriminals are unleashing a surprisingly high volume of new threats in this short period of time to take advantage of inadvertent security gaps as organizations are in a rush to ensure business continuity.

The group has been very active during the last five years, especially in 2019-20.

Facebook has revealed that it removed a network of 37 Facebook accounts, 32 Pages, 11 Groups and 42 Instagram accounts that originated in India and used fake accounts masquerading as media outlets to target the Gulf region, the US, the UK and Canada.

The group has been very active during the last five years, especially in 2019-20.

The Aichi biodiversity targets, set by the UN Convention on Biological Diversity, are unlikely to be achieved by 2020, a new study suggests — despite some progress towards halting the global loss of biodiversity. The authors of the study call for policy responses to be strengthened if the ongoing loss of nature is to be stopped.

A new long-term monitoring study is the first to demonstrate that climate changes are having divergent effects on populations of bird species across Europe and the United States. The study identifies broad-scale impacts on the abundance of common bird species over a 30-year period, to show that, overall, populations of bird species across both continents are being affected by changes in climate. The research adds to a growing body of evidence that climate change is affecting biodiversity either positively or adversely, depending on species’ climate preferences.

20 years of policies in Europe to reduce emissions that contribute to the formation of ozone have successfully reduced short-term peak ozone levels, according to a new study conducted in central England. However, tougher targets are needed to further reduce average annual levels.

Levels of particulate matter (PM) in the atmosphere are linked to ammonia emissions. However, reducing ammonia emissions only as far as targets set out by the Gothenburg Protocol will not necessarily ensure compliance with EU PM limits, according to a new study. Greater reductions in ammonia emissions would reduce the number of days when PM limit values are exceeded, the researchers found.

...

Total SA set out bolder commitments to eliminate most of its carbon emissions by 2050, while curbing spending on oil and gas projects due to the crude-price slump.

A new Sierra Club campaign urges environmentalists to fight oil sands to preserve winter sports.

NASA asked the internet for help in choosing a nickname for the Kuiper Belt object named '(486958) 2014 MU69.'

EPA head Lisa Jackson will decide if dust standards for U.S. farms and ranches should be left alone or tightened.

Massive twitter campaign invites @barackobama to visit Appalachia and see mountaintop removal first hand.

Fan MNN on Facebook and you'll be automatically entered to win an organic kit that will help you score green cred before you leave the house in the morning.

Soon, customers may be able to shop and sip at a Target store in Chicago.

The affordable organic cotton fashion line threw a star-studded private shopping party in Venice, Calif.

A bee memorial service is being held this Sunday to remember the 50,000 pollinators killed by pesticides at an Oregon Target store.

The store is offering a valuable way to get rid of your old — but fully functional and scratch-free, of course — iPad models in exchange for store credit.

The retailer will give vertical farming a go at several locations.