Waiting for a call

first_imgThe Serbian tactician, the brains behind the Tornadoes’ epic sweep of Petron in the best-of-three title series on Saturday, was quick to shrug off credit for Foton’s second title.Instead, Branislav will be sitting back for some much-needed rest while awaiting a call to return calling the shots for the league’s newest toast.FEATURED STORIESSPORTSFreddie Roach: Manny Pacquiao is my Muhammad AliSPORTS‘It’s his turn’: Kiefer Ravena named Gilas captainSPORTSWe are young“I like every time that I win a championship,” Branislav said after the celebration on the court died down following a 25-20, 25-20, 22-25, 25-17 decision of the gritty Tri-Activ Spikers at Philsports Arena.“This is my life. I’m just a coach, this is a normal job for me and I always like to [finish] first.” MOST READ Branislav though, bared something that is out of the usual.“But tomorrow, I will just drink coffee and wait for a proposal [to return] to work,” he said after winning his 21st championship coaching in 12 different countries.Branislav admitted to not yet hearing from Foton executives about a contract renewal, though team owner Rommel Sytin said that “most likely, [Branislav] will be back next year.”The fiery coach, after all, wants to stick it out with the team to help make it better.“In my opinion, give this Foton team maybe five more months and it will be better for the next PSL conference,” Branislav said.ADVERTISEMENT Where did they go? Millions left Wuhan before quarantine So breaches Elo 2800, climbs to world No. 4 We are young EDITORS’ PICK Magical could be the only way to describe how Foton played in the finals of the Philippine Superliga Grand Prix.Coach Moro Branislav, though, sees it as just another day in the office.ADVERTISEMENT Where did they go? Millions left Wuhan before quarantine Don’t miss out on the latest news and information. China’s virus death toll surpasses SARS but new cases fallcenter_img Smart’s Siklab Saya: A multi-city approach to esports Coronavirus case in HK building becomes game changer for Filipinos working there Behind the exploits of the courageous and prolific Lindsay Stalzer, the Tornadoes fought back from two sets down and 3-8 behind in the fifth set of Game 1 to gather all the momentum they needed for the dominating second game performance.Branislav deserves credit as much as Stalzer and the other players do.But in the meantime, while he awaits what his part in the future of Foton in particular and Philippine volleyball in general would be, getting a tan doesn’t sound to be a bad idea.“I don’t know what will be next for me [because] I have not yet received any information [if I will still coach the team],” he said. “Maybe I will go to Boracay for three days, I don’t know.”Sports Related Videospowered by AdSparcRead Next Robredo: What’s the truth about VFA termination? Taiwan minister boards cruise ship turned away by Japan PLAY LIST 01:31Taiwan minister boards cruise ship turned away by Japan01:33WHO: ‘Global stocks of masks and respirators are now insufficient’01:01WHO: now 31,211 virus cases in China 102:02Vitamin C prevents but doesn’t cure diseases like coronavirus—medic03:07’HINDI PANG-SPORTS LANG!’03:03SILIP SA INTEL FUND China’s virus death toll surpasses SARS but new cases fall Shanghai officials reveal novel coronavirus transmission modes Smart hosts first 5G-powered esports exhibition match in PH View commentslast_img read more

United partners with app to battle jetlag

first_imgPhoto: United. United Airlines has joined other ultra-long-haul operators in the battle against jetlag by partnering with an app designed by top sleep scientists.The US airline has teamed up with an app called Timeshifter that tells users the best time to see and avoid light, sleep and enjoy caffeine to adjust quickly to a new time zone.The app is targeted at passengers flying across three or more time zones and was developed, United says, by top researchers in sleep and circadian neuroscience.These include Dr. Steven Lockley, an associate professor of medicine at Harvard Medical School’s division of sleep medicine.READ: Wine for breakfast on second Qantas Sunrise trialThe airline is making a jetlag plan available to all MileagePlus members and giving its top tier Premier 1K members a complimentary annual subscription with unlimited plans.The plan available to MileagePlus members is in addition to a complimentary trial plan from the company, giving the airline’s frequent flyers a total of two free flight plans.Users enter their travel schedule information, their normal sleep pattern and individual preferences into the app.It gives them a personalized jet lag alleviation plan that includes when they should prioritize exposure to bright light and when to avoid it as well as a personal sleep and napping schedule.There is also a plan to optimize caffeine intake for alertness and sleep as well as a schedule for taking melatonin where travelers choose to do so.“We want to do everything we can to help improve the experience of traveling across time zones, whether it’s a business trip to Tel Aviv or a vacation to Tahiti, our customers should arrive feeling fresh and ready to hit the ground running,” said MileagePlus president Luc Bondar.“Timeshifter takes all the guesswork out of avoiding jet lag and instead uses science and algorithms to design a customized, step-by-step trip across time zones.“I was a believer the first time I used the app and I think our customers will love it too.”United flies some of the longest routes in the world, including the two longest flights operated by a U.S. carrier with non-stop service between Houston and Sydney and between San Francisco and Singapore.last_img read more

Data Storage: Bit Rot Threatens to Leave Behind a Digital Dark Age

first_imgVint Cerf, a “father of the Internet” and now Google Vice President, is warning that we’re at risk of losing massive amounts data to future generations.  Our current culture might well become a “digital dark age” mystery to historians.Cerf said that “when you think about the quantity of documentation from our daily lives that is captured in digital form, like our interactions by email, people’s tweets, and all of the World Wide Web, it’s clear that we stand to lose an awful lot of our history.  We are nonchalantly throwing all of our data into what could become an information black hole without realizing it. We digitize things because we think we will preserve them, but what we don’t understand is that unless we take other steps, those digital versions may not be any better, and may even be worse, than the artifacts that we digitized. If there are photos you really care about, print them out.”‘Bit Rot’ may be part of the problem.  As hardware and software continues to evolve at a breakneck speed obsoleting older less-efficient technologies, data not migrated forward to be stored with newer technologies are at risk of being irrecoverably lost.  Storage media and today’s proprietary file formats may not be accessible in the future.In 2007, the Storage Networking Industry Association offered a plan to build a “100 year archive”, but it was never implemented.  The problem is that right now the problem doesn’t seem urgent and no company, group or agency that sees any incentive for funding such a project.Cerf said that “we don’t want our digital lives to fade away. If we want to preserve them, we need to make sure that the digital objects we create today can still be rendered far into the future.”last_img read more

This mysterious $2 billion biotech is revealing the secrets behind its new drugs and vaccines

first_img By Kelly ServickFeb. 1, 2017 , 2:30 PM Mind-blowing dataModerna now has more money to throw at those molecules than most biotechs can dream of, though it’s far from the only group chasing mRNA drugs. The German biotech CureVac, for example, has brought mRNA-based vaccines for rabies and cancer to clinical trials, and Karikó now heads a research team at BioNTech in Mainz, Germany, that focuses on mRNA-based drugs.But few companies have delved into nucleoside engineering the way Moderna has, or pursued such a broad range of diseases from the start. Beyond its $100-millionper-year platform research, Moderna runs four wholly owned ventures focused on drugs for infectious diseases, rare diseases, immuno-oncology, and personalized cancer vaccines. It has about 430 full-time employees, spilling across three buildings around biotech-dense Kendall Square. Higher-ups are identified by black-and-white headshots hanging at their office doors.Lavish funding has allowed Moderna to set up production facilities that can manufacture more than 1000 new, made-to-order mRNA a month. (“Moderna has probably made more RNA by in vitro transcription than all of humankind ever,” quips Edward Miracco, a senior scientist on its process innovation team.) And it has allowed for many parallel animal experiments to characterize different mRNA and select the most promising. “If you need to run a 25-arm experiment, just do it,” Bancel recalls telling his team. “We have the money, we have the infrastructure. Just do the right science.” V. Altounian/Science Hacking the kingdom of lifeThe vision of an mRNA drug has beguiled scientists for decades. “It’s a huge idea,” says Michael Heartlein, who heads mRNA research at a competing biotech called RaNA Therapeutics just a few blocks away. “Any protein target [where] you can think of a potential therapeutic, you can approach that with mRNA.” The single-stranded molecule sets up a temporary protein factory outside a cell’s nucleus and attaches to ribosomes. This cellular machinery translates its sequence of four kinds of nucleosides—adenosine, cytidine, uridine, and guanosine—into a protein. Then it degrades within a day.Assembling these chemical instructions could be a faster and more adaptable way to make drugs than manufacturing the individual proteins themselves in large bioreactors. And it would allow scientists to deliver proteins that act inside cells or span their membranes, which are a challenge to introduce from the outside. An mRNA drug would also be easier to control than traditional gene therapy. Like mRNA, gene therapy can induce cells to make therapeutic proteins, but it typically introduces DNA that can integrate unpredictably into the genome.If you can hack the rules of mRNA, “essentially the entire kingdom of life is available for you to play with,” says Hoge, a physician by training who left a position as a health care analyst to become Moderna’s president in 2012. Adjusting mRNA translation to fight disease “isn’t actually super high-risk biology,” he adds. “It’s what your genes would do if they were rational actors.”One key problem, however, is that our bodies would normally destroy incoming mRNA before it could get cranking. It’s a relatively large molecule that is prone to degradation, and as far as our cells are concerned, it’s supposed to come from the nucleus, where it’s transcribed from DNA. RNA invading from outside the cell is the hallmark of a virus, and our immune system has evolved ways to recognize and destroy it. CAMBRIDGE, MASSACHUSETTS—In a recent morning meeting of scientific leaders at Moderna Therapeutics, conversation swerved toward the philosophical. Biochemist Melissa Moore, recently hired to head RNA research at the Boston-area biotech, had something on her mind: hype.Specifically, she was thinking about Gartner’s hype cycle, a glib model cooked up by an IT research firm, in which every new technology ascends a “peak of inflated expectations,” sinks into a “trough of disillusionment,” then climbs the “slope of enlightenment” to reach a “plateau of productivity.” Where on this curve, she wondered to Moderna’s president, Stephen Hoge, was their technology?The question is apt. Moderna was founded on the idea that messenger RNA (mRNA), the molecule that relays genetic instructions from DNA to the cell’s proteinmaking machinery, could be re-engineered into a versatile set of drugs and vaccines. These strands of instructions could teach our cells to make whatever was needed to treat or prevent disease—virus-slaying antibodies, wastegobbling enzymes, heart-mending growth factors. The willingness of pharmaceutical giants and investors to bet on that premise to the tune of nearly $2 billion has unleashed waves of both hype and skepticism.Sign up for our daily newsletterGet more great content like this delivered right to you!Country *AfghanistanAland IslandsAlbaniaAlgeriaAndorraAngolaAnguillaAntarcticaAntigua and BarbudaArgentinaArmeniaArubaAustraliaAustriaAzerbaijanBahamasBahrainBangladeshBarbadosBelarusBelgiumBelizeBeninBermudaBhutanBolivia, Plurinational State ofBonaire, Sint Eustatius and SabaBosnia and HerzegovinaBotswanaBouvet IslandBrazilBritish Indian Ocean TerritoryBrunei DarussalamBulgariaBurkina FasoBurundiCambodiaCameroonCanadaCape VerdeCayman IslandsCentral African RepublicChadChileChinaChristmas IslandCocos (Keeling) IslandsColombiaComorosCongoCongo, The Democratic Republic of theCook IslandsCosta RicaCote D’IvoireCroatiaCubaCuraçaoCyprusCzech RepublicDenmarkDjiboutiDominicaDominican RepublicEcuadorEgyptEl SalvadorEquatorial GuineaEritreaEstoniaEthiopiaFalkland Islands (Malvinas)Faroe IslandsFijiFinlandFranceFrench GuianaFrench PolynesiaFrench Southern TerritoriesGabonGambiaGeorgiaGermanyGhanaGibraltarGreeceGreenlandGrenadaGuadeloupeGuatemalaGuernseyGuineaGuinea-BissauGuyanaHaitiHeard Island and Mcdonald IslandsHoly See (Vatican City State)HondurasHong KongHungaryIcelandIndiaIndonesiaIran, Islamic Republic ofIraqIrelandIsle of ManIsraelItalyJamaicaJapanJerseyJordanKazakhstanKenyaKiribatiKorea, Democratic People’s Republic ofKorea, Republic ofKuwaitKyrgyzstanLao People’s Democratic RepublicLatviaLebanonLesothoLiberiaLibyan Arab JamahiriyaLiechtensteinLithuaniaLuxembourgMacaoMacedonia, The Former Yugoslav Republic ofMadagascarMalawiMalaysiaMaldivesMaliMaltaMartiniqueMauritaniaMauritiusMayotteMexicoMoldova, Republic ofMonacoMongoliaMontenegroMontserratMoroccoMozambiqueMyanmarNamibiaNauruNepalNetherlandsNew CaledoniaNew ZealandNicaraguaNigerNigeriaNiueNorfolk IslandNorwayOmanPakistanPalestinianPanamaPapua New GuineaParaguayPeruPhilippinesPitcairnPolandPortugalQatarReunionRomaniaRussian FederationRWANDASaint Barthélemy Saint Helena, Ascension and Tristan da CunhaSaint Kitts and NevisSaint LuciaSaint Martin (French part)Saint Pierre and MiquelonSaint Vincent and the GrenadinesSamoaSan MarinoSao Tome and PrincipeSaudi ArabiaSenegalSerbiaSeychellesSierra LeoneSingaporeSint Maarten (Dutch part)SlovakiaSloveniaSolomon IslandsSomaliaSouth AfricaSouth Georgia and the South Sandwich IslandsSouth SudanSpainSri LankaSudanSurinameSvalbard and Jan MayenSwazilandSwedenSwitzerlandSyrian Arab RepublicTaiwanTajikistanTanzania, United Republic ofThailandTimor-LesteTogoTokelauTongaTrinidad and TobagoTunisiaTurkeyTurkmenistanTurks and Caicos IslandsTuvaluUgandaUkraineUnited Arab EmiratesUnited KingdomUnited StatesUruguayUzbekistanVanuatuVenezuela, Bolivarian Republic ofVietnamVirgin Islands, BritishWallis and FutunaWestern SaharaYemenZambiaZimbabweI also wish to receive emails from AAAS/Science and Science advertisers, including information on products, services and special offers which may include but are not limited to news, careers information & upcoming events.Required fields are included by an asterisk(*)Moderna has shared little detail in published papers about the technology it’s developing, though there are clues in its abundant patent filings. Until recently, even the targets of drugs already in clinical trials weren’t publicized. We’ve had failures. We’ve gone down blind alleys. But because we’ve been quiet about it, nobody’s seen that. Moderna’s President Stephen Hoge (left), RNA research director Melissa Moore, and CEO Stéphane Bancel aim to transform messenger RNA into drugs and vaccines. Melissa Moore, Moderna Therapeutics But as more trials get underway, Moderna is gingerly opening up. The company agreed to Science’s request for access to some of its researchers and labs over the past few months. And last month, at the annual J.P. Morgan Healthcare Conference in San Francisco, California, CEO Stéphane Bancel unveiled Moderna’s first round of drug candidates, which include vaccines for Zika and flu, and a therapy for heart failure.Expectations are high. Being a startup valued at more than a billion dollars—an anomaly that venture capitalists dub a unicorn—comes with scrutiny, and many wonder whether Moderna’s pipeline, consisting mostly of vaccines for now, will expand to match the company’s original vision of mRNA as a broad treatment platform. “There were a lot of really big promises made,” says Jason Schrum, a biotechnology consultant in San Francisco and a former Moderna employee. “That’s what people latched onto; they want the promises to be true, and they want to see the investment really turn it into something meaningful.”In other words, the trough of disillusionment, if it’s still ahead, threatens to be deep. Biochemist Katalin Karikó heard this argument over and over as she tinkered with mRNA in her University of Pennsylvania (UPenn) biochemistry lab in the early 2000s. But she and her UPenn colleague Drew Weissman found a way to tame cells’ typical inflammatory response by modifying one of mRNA’s four building blocks, uridine. Assembling mRNA using pseudouridine, a nucleoside variant that occurs naturally in the body, greatly reduced the tendency of immune sentinels called dendritic cells to shoot out inflammatory molecules in response, they reported in 2005.In mouse studies, this mRNA proved stable enough to stick around in the body and make proteins. Karikó and Weissman founded a company hoping to develop drugs from the discovery, and won nearly a million dollars in small business grants from the U.S. government for animal studies. But shortly after the money came through, Karikó says, the university sold the intellectual property license, and the effort never reached clinical trials. “I could not find any ear,” she recalls, “someone that would say, ‘Oh, let’s try it.’”But when stem cell biologist Derrick Rossi’s team at Boston Children’s Hospital used pseudouridine-containing mRNA to encode proteins that transformed mature cells into stem cells, he found quite a few ears. Serial entrepreneur Robert Langer of the Massachusetts Institute of Technology (MIT) and Noubar Afeyan, CEO of the venture capital firm Flagship Pioneering, both in Cambridge, saw the makings of a whole new class of drugs—and the idea of Moderna was born.The company, which launched operations in 2011 with Flagship funding, quickly set its sights on new (and patentable) nucleoside modifications that would provoke an even smaller immune response than pseudouridine. “This stuff was working a little bit,” says Hoge, “so why not make it work a lot?”Initially operating in “stealth mode”—without announcement of its existence—Moderna’s team screened mRNA assembled from various modified nucleosides and hit on one called 1-methylpseudouridine. It bore a chemical “bump” that the team suspected kept it from locking into key receptors on the surface of immune cells.As the data flowed in during 2011 and 2012, Bancel, who had come to Moderna from the French diagnostics company bioMérieux, began to work up a pitch. He was catching potential investors at an inauspicious time: Many were smarting from disappointing trials of RNA interference therapies, which use short, double-stranded RNA to disrupt the production of disease-causing proteins. “No one had cracked how to make RNA stable enough to be a therapeutic,” says Mene Pangalos, who heads the Innovative Medicines and Early Development Biotech Unit at AstraZeneca in Cambridge, U.K.Bancel showed Pangalos and his team two studies in which an injection of modified mRNA containing pseudouridine prompted nonhuman primates to express two human proteins. Among dozens of mouse studies, he presented work led by Moderna Co-Founder Kenneth Chien, then at Harvard Medical School in Boston, showing that mice recovering from induced heart attacks survived longer and had stronger hearts when injected with mRNA encoding a protein that drives blood vessel formation—vascular endothelial growth factor (VEGF).”That got us excited,” says Pangalos, who was eager to build up AstraZeneca’s pipeline of cardiovascular drugs. “It was incredibly high risk. It was untried and untested.” But if it could work for one disease, it would likely work for many. Changing the disease target didn’t require developing or identifying a whole new drug, just altering the mRNA sequence. And although many of the initial animal studies used mRNAs with pseudouridine, Moderna’s new chemistry was already starting to outperform that first generation in rodent studies. “I don’t think it was such a stretch to imagine the technology would continue to improve, given what they were doing,” Pangalos says. In March 2013, a few months after Moderna announced itself to the world, AstraZeneca put an up-front $240 million into a partnership to pursue up to 40 drug candidates using Moderna’s technology.Schrum, who led early chemistry research at Moderna and made some of the discoveries behind its initial patents, had left the company by the time the AstraZeneca deal was sealed. To him, the sum was astonishing, given the preliminary findings he had seen. “There was a lot of excitement that this [technology] can be applied to anything, and that this is a panacea,” he says. Before meetings with potential investors and partners, he remembers the Moderna team being “frantic to get some sort of data, just general data, without a whole lot of specifics attached.” Winning those early investments, by his estimate, “comes down to salesmanship.”Moderna’s bold premise inspired headlines comparing it to a young Genentech, the most famously successful of all biotechs. Bancel, meanwhile, insists that he never hyped the company. “We never said, ‘Oh look at mRNA; we’re going to cure 2 million diseases.’ No, we said, ‘What if? What if this could work?’” But as more cash poured in—$100 million from Alexion Pharmaceuticals to pursue rare diseases, $100 million from Merck for a set of antiviral drugs—the image of Bancel as a brash newcomer with a crisp suit and an audacious pitch became part of the company’s mystique.Afeyan at Flagship, who recruited Bancel, calls such a portrayal irrelevant “social science” that gives Moderna’s technology short shrift. “There is real science here,” he says. “There’s real data, there’s real molecules.” Engineering the messenger Moderna aims to design messenger RNA (mRNA) that directs cells to make a protein that works as a drug or vaccine. To succeed, the mRNA has to enter the cell, avoid degradation, and be translated efficiently.center_img This mysterious $2 billion biotech is revealing the secrets behind its new drugs and vaccines The biotech Moderna delivers messenger RNA (blue) into cells to be translated into proteins by ribosomes. © Ken Richardson J. You/ Science It has taken a lot of science to make mRNA act like a drug. Some of Moderna’s most promising early candidates, although they could tiptoe past the immune system, produced underwhelming amounts of protein in animal studies. The same nucleoside modifications that made mRNA more stealthy also made it less recognizable to the ribosome. “If you’re trying to sneak in there and make a thing, you have to look pretty darn natural,” Hoge says. Moderna needed to figure out what features of naturally occurring mRNA were most important for translation, and how to restore them.By the summer of 2013, word of the company’s ambitions was wafting through academic labs, including Melissa Moore’s at the University of Massachusetts Medical School in Worcester. Moore had spent her career studying the intricacies of how nascent mRNA gets spliced in the nucleus and loaded with proteins to become a complex known as a messenger ribonucleoprotein (mRNP). Over those years, she had also grown frustrated by how many more male than female scientists held consulting roles at biotech companies. When a colleague told her about Moderna, she decided to go out on a limb.”Although we have many common connections, I don’t believe you and I have ever met,” she wrote in an email to Tony de Fougerolles, who was then Moderna’s chief scientific officer. “I am arguably the world’s expert on how the synthetic history and protein complements of mRNPs contribute to gene expression.” Maybe, Moore suggested, her knowledge could improve Moderna’s product. “I remember going home and being emotionally depleted, because I had completely just put myself out there,” she says. “I had never done anything like that before, but I knew I had to do it.”De Fougerolles invited Moore to give a seminar, which led to a sponsored research agreement, and, eventually, a position on the scientific advisory board. Last year, Moore left her tenured position to become chief scientific officer of Moderna’s research platform. “I could have spent the next 15 years turning the crank, putting out more papers, training more students,” she says, “but when I’m 80 or 90 and I look back at my life, I would regret that decision.”Moore’s academic work has advanced a counterintuitive theory about mRNA. It might seem that secondary structure—the folds and loops caused by bonding between nucleosides in the strand—should hinder protein production. Too much structure could force the ribosome to do extra work untangling the strand or even stall translation altogether. But findings in Moore’s lab supported the view that mRNA strands with more of the nucleosides that tend to form tight bonds are, in fact, easier for ribosomes to translate.The bioinformatics team at Moderna was making parallel discoveries. Even between mRNAs with the same sequence, they were finding that different modified nucleosides produced different amounts of protein. And nucleosides with a tendency to form tighter structures were more productive. The team knew that the frequency and placement of the modified nucleosides in the strand changed how it folded, and hence how it interacted with the ribosome. And because trillions upon trillions of different nucleoside sequences can code for the same protein, there were plenty of ways to engineer more efficient ones—providing they could be predicted.Doing so took the Moderna team deep into the structure of mRNA. To model how single-atom changes affected bonding between nucleosides, they enlisted a quantum chemistry expert, Michelle Hall. “When I started looking for industry jobs, people were like, ‘Oh that’s adorable. Nobody does that in industry,’” Hall remembers. “Turns out, not true.”Her calculations informed an algorithm that predicts, for a given protein, what mRNA sequence would produce the structure most appealing to a ribosome. Across many drug candidates, the team saw a several-fold increase in protein production using the new designs. Bancel recalls the meeting when they described this breakthrough: “They blew my brain on the walls.” Avoiding the hype curveOutside researchers can’t yet weigh in on how mind-blowing Moderna’s fundamental research might be. “It would be stupendous to see the data out of Moderna,” says Paul Agris, an analytical biochemist at the State University of New York in Albany’s RNA Institute who has spent decades studying the consequences of modifying RNA nucleosides.But for now, the company’s only published paper is the one from Chien’s group on producing VEGF in mice. It hasn’t revealed which modified nucleoside is in its newest generation of drug candidates. And it launched its first two phase I trials without announcing what diseases they targeted—a decision Bancel attributes to fears that financial markets would prematurely pigeonhole the company into a particular field. (Investigators are not required to register phase I trials with ClinicalTrials.gov.)Moderna’s leaders argue that they’ve disclosed research the way most private companies do—by detailing it in patent filings. “It wasn’t a deliberate effort to be secretive,” Hoge says. “The act of publication was not, in and of itself, a focus for us. In fact, it wasn’t even clear that it was anywhere on our priority list.”For many researchers who have worked with companies, that isn’t surprising. “It’s a highly competitive field, and they’ve made the decision that they don’t want to publish a bunch of papers. That makes sense,” says Daniel Anderson, a molecular geneticist who develops drug delivery systems at MIT. “Publishing papers can generate excitement. … But if you have a whole lot of people and a whole lot of money, it may be smart just to stay quiet and develop your technology and patent the heck out of it.” Votes of confidence Venture capitalists, pharmaceutical companies, and others have invested heavily in Moderna’s vision of mRNA-based drugs. V. Altounian/Science Holding its data close doesn’t seem to have hurt Moderna’s ability to raise money and advance its drugs. But now that treatments are being injected into people, “there’s a certain obligation to patients to start to tell that story,” Hoge says. The company has submitted several manuscripts to journals, and last month described the collection of drugs in its pipeline.Human safety trials have already begun for vaccines against two flu strains and the Zika virus, and for a fourth undisclosed viral vaccine developed in collaboration with Merck. In each case, the mRNA encodes viral proteins that infected cells would normally present to activate the immune system and beat back an infection. Last month, Moderna also began trials of its VEGF drug, developed with AstraZeneca. Intended to treat cardiovascular diseases as well as slow wound healing in diabetes, the growth factor-encoding mRNA is first being injected under the skin of trial participants to evaluate safety.Moderna is also doing animal safety tests of a personalized cancer vaccine that would code for immune-activating proteins unique to a person’s cancer cells, based on genetic sequencing of their tumor. Another possible cancer drug, awaiting regulatory approval for a clinical trial, consists of mRNA for a surface protein called OX40L that would, when injected into a tumor, prompt T cells to proliferate and attack.Last month’s presentation also got attention for what it didn’t describe—trials of drugs that replace missing or deficient proteins to treat chronic diseases. Most of Moderna’s advanced candidates are vaccines, which require just a low dose of mRNA that makes enough protein to kick the immune system into gear. And all of them are administered locally, under the skin or into a muscle or tumor. To tackle lifelong diseases where patients are missing a key protein, such as an enzyme that removes toxic compounds from the body, mRNA drugs will likely have to be delivered intravenously for decades. That makes even mild toxicity or subtle immune reactions a potential deal-breaker.Much of the risk comes down to formulation—the molecular packaging that ferries mRNA into cells and protects it from being hacked apart by enzymes along the way. “That’s where the breakthroughs are really needed,” says RaNA’s Heartlein. Many RNA drugs to date have encapsulated the nucleic acid in nanoparticles made of lipids. But because mRNA is so large—roughly 100 times the length of the RNA used for interference therapies—it’s harder to stabilize and to encapsulate. And many lipid nanoparticles are not easily degraded in the body, so they can cause toxic buildup in the liver. “We’re going to find applications [for mRNA drugs],” Heartlein says, but “it may not be as broadly applicable at the end of the day as people are thinking.”Hoge acknowledges that some conditions may be off limits to mRNA drugs simply because they require higher levels of protein than the mRNA can make at a safe dose. Muscular dystrophies or skin disorders where patients lack a key structural protein, for example, are a long shot. “A lot of people think that gene therapy might be the only solution for some of these diseases. And certainly for some of them, it might be,” he says.Moderna is developing delivery systems that may limit toxicity. Among its proprietary nanoparticles is a family of engineered lipids that its scientists have found to be more biodegradable—and thus more tolerable at higher doses—than existing formulations. A separate “delivery innovation” team is developing nonlipid formulations, such as polymers that form solid, porous structures interspersed with mRNA.AstraZeneca’s Pangalos says his group has its sights set firmly on mRNA drugs for chronic use, and expects a drug intended for repeated dosing to enter trials in the next 18 months. But Moderna has had to retreat from optimistic predictions about a partnership with Alexion to treat a rare disease called Crigler-Najjar syndrome. The mRNA treatment would code for an enzyme that breaks down bilirubin, a toxic substance that builds up in patients’ blood. Before it can enter human testing, the companies must be sure the dose needed to impact the disease is many-fold lower than the dose that causes toxicity.In 2015, Moderna and Alexion predicted that the drug would advance to clinical trials in 2016, but late last year they informed investors that the trials would be delayed, so that the formulation could be optimized. “Lavishly funded Moderna hits safety problems,” announced an article published by STAT after Bancel left the drug out of last month’s presentation.A missed milestone, particularly in preclinical studies, hardly signals a catastrophe, says Eric Schmidt, a biotech analyst at Cowen Group in New York City. “I’m just surprised at the drama around the situation,” he says. “Why, just because this company has been successful at raising money, is it being treated differently in the popular press?” That may be the price of Moderna’s unicorn status: The higher the hopes are for a new treatment approach, the more consequential its warts and blunders become.But wealth and secrecy may also be protective. Maybe, as Moore and Hoge concluded from their morning meeting, you don’t have to ride up and down Gartner’s hype curve if you can work through the biggest setbacks before the public ever sees them.Most small biotechs have to publicize every step of their early research in a scramble to raise money, Moore notes. “Then people get to see all the failures. We’ve had failures. We’ve gone down blind alleys. But because we’ve been quiet about it, nobody’s seen that,” she says. “That’s why I think we’re going to end up on the slope of enlightenment without passing the trough of disillusionment.”last_img read more

Sealant inspired by slug slime could plug holes in the heart

first_imgSealant inspired by slug slime could plug holes in the heart By Giorgia GuglielmiJul. 27, 2017 , 2:00 PM The whitish, slimy trail that slugs leave behind has inspired a novel type of glue—one that’s extremely flexible and compatible with body fluids. Unlike other types of surgical glues, the new class of sealants, dubbed tough adhesives, is nontoxic and sticks to wet tissues such as heart (pictured) and liver, even when their surfaces are covered with blood. This is because the sealant contains positively charged molecules that form stable bonds with biological tissues, researchers report today in Science. To prove how tough the slime-inspired glue is, the scientists used it to seal a large hole in an explanted pig heart. As the heart was filled up with liquid, the adhesive patch expanded with it and did not leak under up to a 100% strain and tens of thousands of cycles of pumping. When the researchers simulated an emergency surgery and sudden blood loss, the glue effectively stemmed bleeding from a rat liver. Tough adhesives could also be injected to fix cartilage discs, the cushions between vertebrae, or used as band-aids to close wounds on pig skin, the scientists say. Sign up for our daily newsletterGet more great content like this delivered right to you!Country *AfghanistanAland IslandsAlbaniaAlgeriaAndorraAngolaAnguillaAntarcticaAntigua and BarbudaArgentinaArmeniaArubaAustraliaAustriaAzerbaijanBahamasBahrainBangladeshBarbadosBelarusBelgiumBelizeBeninBermudaBhutanBolivia, Plurinational State ofBonaire, Sint Eustatius and SabaBosnia and HerzegovinaBotswanaBouvet IslandBrazilBritish Indian Ocean TerritoryBrunei DarussalamBulgariaBurkina FasoBurundiCambodiaCameroonCanadaCape VerdeCayman IslandsCentral African RepublicChadChileChinaChristmas IslandCocos (Keeling) IslandsColombiaComorosCongoCongo, The Democratic Republic of theCook IslandsCosta RicaCote D’IvoireCroatiaCubaCuraçaoCyprusCzech RepublicDenmarkDjiboutiDominicaDominican RepublicEcuadorEgyptEl SalvadorEquatorial GuineaEritreaEstoniaEthiopiaFalkland Islands (Malvinas)Faroe IslandsFijiFinlandFranceFrench GuianaFrench PolynesiaFrench Southern TerritoriesGabonGambiaGeorgiaGermanyGhanaGibraltarGreeceGreenlandGrenadaGuadeloupeGuatemalaGuernseyGuineaGuinea-BissauGuyanaHaitiHeard Island and Mcdonald IslandsHoly See (Vatican City State)HondurasHong KongHungaryIcelandIndiaIndonesiaIran, Islamic Republic ofIraqIrelandIsle of ManIsraelItalyJamaicaJapanJerseyJordanKazakhstanKenyaKiribatiKorea, Democratic People’s Republic ofKorea, Republic ofKuwaitKyrgyzstanLao People’s Democratic RepublicLatviaLebanonLesothoLiberiaLibyan Arab JamahiriyaLiechtensteinLithuaniaLuxembourgMacaoMacedonia, The Former Yugoslav Republic ofMadagascarMalawiMalaysiaMaldivesMaliMaltaMartiniqueMauritaniaMauritiusMayotteMexicoMoldova, Republic ofMonacoMongoliaMontenegroMontserratMoroccoMozambiqueMyanmarNamibiaNauruNepalNetherlandsNew CaledoniaNew ZealandNicaraguaNigerNigeriaNiueNorfolk IslandNorwayOmanPakistanPalestinianPanamaPapua New GuineaParaguayPeruPhilippinesPitcairnPolandPortugalQatarReunionRomaniaRussian FederationRWANDASaint Barthélemy Saint Helena, Ascension and Tristan da CunhaSaint Kitts and NevisSaint LuciaSaint Martin (French part)Saint Pierre and MiquelonSaint Vincent and the GrenadinesSamoaSan MarinoSao Tome and PrincipeSaudi ArabiaSenegalSerbiaSeychellesSierra LeoneSingaporeSint Maarten (Dutch part)SlovakiaSloveniaSolomon IslandsSomaliaSouth AfricaSouth Georgia and the South Sandwich IslandsSouth SudanSpainSri LankaSudanSurinameSvalbard and Jan MayenSwazilandSwedenSwitzerlandSyrian Arab RepublicTaiwanTajikistanTanzania, United Republic ofThailandTimor-LesteTogoTokelauTongaTrinidad and TobagoTunisiaTurkeyTurkmenistanTurks and Caicos IslandsTuvaluUgandaUkraineUnited Arab EmiratesUnited KingdomUnited StatesUruguayUzbekistanVanuatuVenezuela, Bolivarian Republic ofVietnamVirgin Islands, BritishWallis and FutunaWestern SaharaYemenZambiaZimbabweI also wish to receive emails from AAAS/Science and Science advertisers, including information on products, services and special offers which may include but are not limited to news, careers information & upcoming events.Required fields are included by an asterisk(*)last_img read more

Sergio Aguero collapses at halftime as Argentina lose to Nigeria in friendly

first_imgArgentina striker Sergio Aguero collapsed in the dressing room at halftime before they lost 4-2 to fellow World Cup qualifiers Nigeria after taking a two-goal lead in a friendly in Krasnodar, Russia on Tuesday.The Argentine Football Association (AFA) said in a statement that Aguero, who scored in the first half, was taken away for routine examinations but added: “The player is well”.His Premier League club Manchester City said the 29-year-old Aguero had been cleared by doctors to return to England as planned after he suffered what they called “a dizzy spell”.”Sergio never lost consciousness, and was taken to hospital for precautionary medical checks,” City said on their official website (www.mancity.com).Argentina coach Jorge Sampaoli rested Lionel Messi following the 1-0 win over next year’s World Cup hosts Russia on Saturday and it seemed that they could cope without him.Ever Banega curled in a free kick, awarded after Nigeria goalkeeper Daniel Akpeyi picked the ball up outside his area, in the 28th minute and Aguero finished off a sweeping counter-attack eight minutes later.But Kelechi Iheanacho inspired Nigeria’s fightback.First, he emulated Banega by scoring from a free kick on the stroke of halftime and then set up the equaliser by pulling the ball back for Alex Iwobi to net seven minutes after the re-start.The Super Eagles took the lead two minutes after that when Brian Idowu sidefooted home from the edge of the area to finish off a counter attack.A superb goal by Iwobi completed the comeback in the 73rd minute as he collected the ball, slipped it between Javier Mascherano’s legs and fired past Agustin Marchesin.advertisementArgentina staggered through their World Cup qualifying campaign, only clinching their place at the finals with a 3-1 win in Ecuador in their final match.”It’s a difficult game to explain,” said Sampaoli. “We could have been 3-0 or 4-0 ahead in the first half and we went in with a 2-1 lead.”My biggest worry was the way the team played when we were behind. I know we are capable and have the individual talent to be able to get out of these situations and I’m worried about what happened tonight.”We played an incredible first half but we lost our way in a match which could confuse a lot of people.”Aguero will be assessed by Manchester City’s medical team ahead of this weekend’s Premier League trip to Leicester City.last_img read more

Floridas Odds Are Dropping

Which NCAA team had the worst day on Thursday? The obvious answer might be Ohio State, Cincinnati or Oklahoma, all of which succumbed to lower-ranked teams in the basketball tournament’s round of 64. Or perhaps North Carolina State, which squandered a 16-point lead against Saint Louis and lost in overtime.But none of those teams had much chance of winning the championship. Meanwhile, Florida, a tournament favorite, ended Thursday in a worse position than it started, despite winning its opening game against Albany. (Of course, Ohio State would still probably trade places with the Gators.)In the latest FiveThirtyEight forecast, updated with game results and injury information as of early Friday morning, Florida’s probability of winning the tournament is 11 percent. Twenty-four hours ago, it was 14.5 percent.How did the Gators’ odds get worse? There are three contributing factors:A closer-than-expected game against Albany. Florida defeated No. 16 seed Albany by 12 points, a final score that conceals a game that was competitive until late in the second half. But the Gators were favored by 22 to 23 points according to Las Vegas sportsbooks and power ratings. Our research suggests that performance relative to power ratings and point spreads early in the tournament has a fair amount of say in predicting how a team fares later on. Florida’s performance was forgivable, and the team remains the favorite in the South region, but the Gators will need to be sharper as the competition improves. A tough third-round matchup. Pittsburgh, despite a No. 9 seed, was a reasonably clear favorite against No. 8-seeded Colorado on Thursday, according to our model. And the Panthers dominated the Buffaloes, pulling ahead 46-18 by halftime and eventually winning by 29 points. Computer systems like Ken Pomeroy’s regard Pittsburgh as having the strength of a typical No. 4 or No. 5 seed. This could be a challenging matchup for Florida. The Gators played a tough out-of-conference schedule, but they’ve faced just two ranked teams since Jan. 1 in a weak basketball year for the SEC. Threats in the regional finals. The South may not be as loaded as the East or the Midwest. But the No. 3-seeded team, Syracuse, turned in an excellent performance in its win against Western Michigan. The Gators will likely have to defeat either the Orange or No. 2-seeded Kansas to reach the Final Four. Meanwhile, Kansas coach Bill Self sounds increasingly confident that injured center Joel Embiid will be able to return at some point in the tournament, even as he confirmed that Embiid is likely out for the opening weekend. read more

Virat Kohli to drop Ambati Rayudu Date of World Cup squad announcement

first_imgIndia will announce its 15-member squad for the ICC World Cup 2019 on April 15, confirmed the Board of Control for Cricket in India on Monday, April 8. It has been learnt that skipper of the Indian cricket team Virat Kohli will meet with the senior selection committee to decide the squad which will travel to England in May. The meeting between Kohli and the selection committee led by MSK Prasad will take place at the BCCI headquarters in Mumbai next Monday. Prasad had earlier said that the squad will be announced on or before April 20. The deadline for announcing the squad is April 23 and till now only New Zealand has announced their World Cup squad.Prasad is confident that a very good Indian team will be travelling to England in order to reclaim the world title. “I am confident that we are going to announce a good team. We have worked on this for almost one and a half years. We have observed all the players, tested good combinations,” he had said last week. It must be noted that changes can be made to the final World Cup squad till seven days are left for the tournament to begin. Any changes made after that will have to be approved by the International Cricket Council’s Event Technical Committee.  Quinn Rooney/Getty Images Kohli had earlier said that performances in the IPL will have no bearing in the national team’s mindset but one has to factor in the constant failures of Ambati Rayudu going into the tournament. The right-hand batsman has not been among the runs since the series against the Windies at home last year with his only noteworthy contribution being the 90 runs he scored against New Zealand in the fifth ODI of India’s tour at the Westpac Stadium in Wellington. The other place that is still up for grabs is that of the second wicketkeeper with Dinesh Karthik and Rishabh Pant fighting for that slot. While Pant has failed to come good in his limited opportunities, the team management is extremely sold on his potential. He is a match-winner on his day but that potential has not translated into performances in the Indian blue. Dinesh Karthik, on the other hand, is a reliable finisher and is perhaps one of the best in the world at the moment. But Kedar Jadhav’s all-round ability makes him better suited for the number 6 slot. Here are the players who look certain to board the flight that will take the team to England. Virat Kohli (C), Rohit Sharma, Shikhar Dhawan, MS Dhoni (WK), Kedar Jadhav, Hardik Pandya, Jasprit Bumrah, Mohammed Shami, Bhuvneshwar Kumar, Kuldeep Yadav, Yuzvendra Chahal, Vijay Shankar and KL Rahul. India needs to constantly assess the fitness of the players who will be selected in the squad. The IPL can be a strenuous tournament with the schedule and the frequent travelling. The likes of Bumrah, Shami, Bhuvi and Pandya may need some rest given the workload and injury record. India will play its first match of the World Cup against South Africa at the Rose Bowl in Southampton on June 5.center_img The Indian contingent after winning the ODI series 4-1 against New Zealand.Hagen Hopkins/Getty Imageslast_img read more

Digital Security Act to criminilise legitimate media freedoms European diplomats

first_imgDigital security act.Prothom Alo IllustrationEuropean diplomats stationed in Dhaka on Thursday said the just-enacted Digital Security Act will “unduly restrict the freedom of expression and the freedom of the media”.This law, they added, will “undermine judicial procedural guarantees” as enshrined in the constitution of Bangladesh.The heads of mission of the European Union (EU) member states, the EU Delegation and the heads of mission of Norway and Switzerland iterated their concerns around several provisions of the law that were being widely opposed by the stakeholders.”In its current form the Act could be used to suppress and criminalise the legitimate exercise of these freedoms,” they observed in their joint statement, after parliament passed the law on 19 September.Different stakeholders including the Editors’ Council have already expressed apprehensions that this law might be used to limit the freedom of expressions and the media.The diplomats called upon the government of Bangladesh to continue consultations on this law and pursue the commitments taken during the Universal Periodic Review in last May.The government, including the law minister, had then assured stakeholders that consultations would be made on whether to retain a number of provisions in the law before its passage.Now the European diplomats asked the government to continue consultation to make the law compatible with the Universal Declaration of Human Rights, the International Covenant on Civil and Political Rights, as well as the constitution of Bangladesh.Those who issued the joint statement are Rensje Teerink, ambassador of EU Delegation, Mario Palma, ambassador of Italy, D Álvaro de Salas Giménez de Azcárate, ambassador of Spain, Charlotta Schlyter, ambassador of Sweden, Marie-Annick Bourdin, ambassador of France, Peter Fahrenholtz of German embassy, Harry Verweij, ambassador-designate at the Netherlands embassy, Winnie Estrup Petersen, ambassador-designate at Danish embassy, Kanbar Hossein-Bor, acting high commissioner of the British high commission, Sidsel Bleken, ambassador of Norway and René Holenstein, ambassador of Switzerland embassy.last_img read more

WB tops in curbing parenttochild HIV transmission Mamata

first_imgKolkata: West Bengal has been certified as the number one state in preventing parent-to-child transmission of HIV, Chief Minister Mamata Banerjee said today. “I am proud to say that the central government agency NACO has recently certified Bengal as Number 1 in preventing parent-to-child transmission of HIV,” Banerjee tweeted on the HIV Vaccine Awareness Day.The National AIDS Control Organisation (NACO), an agency under the Union Ministry of Health and Family Welfare, has played an important role in controlling the spread of HIV and the treatment of AIDS patients since early 1990s. Also Read – Heavy rain hits traffic, flightsBanerjee had earlier said that with the implementation of the ‘Prevention of Parent to Child Transmission’ programme, the state health department enabled 16.5 lakh pregnant women of Bengal in preventing the transmission of HIV to their children.The state health department has been providing free treatment to HIV positive people through Anti-Retroviral Therapy centres in sub-divisional, district and medical college hospitals, officials said.last_img read more