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There is, in fact, some evidence of viral resistance to Tamiflu. In Vietnam, eight of 10 people recently infected by H5N1 died despite being treated with Tamiflu.
There are other problems with Tamiflu and neuraminidase inhibitors. To be effective, current versions must be taken within two days of infection. Treatment requires twice-daily doses for up to eight days. And there isn't enough of the drug around. Bush's flu epidemic plan calls for stockpiling 22 million treatment courses. Existing stockpiles can treat just 2.3 million people. Some infectious disease experts advise stockpiling enough Tamiflu to treat up to half the population in the event of a pandemic, more than 130 million courses.
Still, neuraminidase inhibitors continue to be a major avenue of flu research. BioCryst Pharmaceuticals in Birmingham, Ala., is developing a new NI called peramivir that would require just a single injection. Hemispherx Biopharma of Philadelphia is exploring whether combining its antiviral drug, Ampligen, with Tamiflu or other NIs will increase their overall effectiveness.
"Basically, we're looking for a kind of synergy," said Doug Hulse, president of Hemispherx. "From tests, it looks like adding a very small amount of Ampligen reduces the amount of Tamiflu needed by a factor of 10 or 20. That means you could dramatically boost the number of available doses."
The company has applied to the FDA for approval to begin treating avian flu next year.
Successfully fighting the flu, though, will require ideas beyond vaccines or neuraminidase inhibitors. One such approach, cited by Scientific American magazine as one of the top 50 scientific innovations of 2005, is NexBio's drug, Fludase.
Fludase acts against influenza and other viruses before the infection process begins. Inhaled, the drug coats respiratory lining cells, zeroing in on the same receptors that are exploited by viral hemagglutinin.
"Fludase acts as an enzyme, chopping off the flu viral receptors, disabling them," said Mang Yu, who conceived the idea and founded NexBio. "The virus can't get into the cells. It just sits there until the immune system removes it."
All flu viruses enter cells the same way, said Yu, a molecular biologist, which means that, in theory at least, Fludase should effectively prevent infection by any existing or future stain of flu.
"There is no reason to believe a virus would be able to evolve a different mode of entry," he said. "If you disable the gateway into the host cell, you take care of all viruses."
All that is needed now, of course, is conclusive, FDA-acceptable proof. Yu and Fang say first phase safety trials are slated for midyear, involving about three dozen healthy volunteers and lasting three months. They hope to mimic Tamiflu's rapid approval process and have a drug ready for market within three years. If a pandemic strikes sooner, Yu said the company will seek authorization from the FDA for emergency use.
From basic scientists to biotech entrepreneurs, everybody is looking for new weapons to fend off a flu pandemic.
Some efforts are relatively straightforward. A Pennsylvania firm hopes to market face masks treated with compounds it says kill or prevent the passage of most viruses. University of Chicago researchers are investigating drugs not previously used against the flu, in particular compounds that reduce inflammation - an immune response that can cause more bodily damage than the disease itself.
Other anti-flu efforts are more experimental. An Oregon pharmaceutical company is testing a drug that targets the genetic code in viruses responsible for replication, slowing it enough to allow the body's immune response to kick into gear. At the Massachusetts Institute of Technology, researchers are investigating whether a kind of RNA called "short interfering RNA" can effectively disrupt virus reproduction in host cells.
"RNA interference is cool stuff," said Shane Crotty, a vaccine researcher at the La Jolla Institute for Allergy and Immunology, "but it's way off in the distance. A lot of very basic science still needs to be done, including how you would deliver the RNA into the cell."
Whether RNA interference or other, more immediate efforts will actually pay off is hard to say. They offer hope, but the harsh reality is that the enemy they must defeat - or at least render less deadly - has long defied subjugation, let alone eradication.
The virus H5N1 causes the greatest current concern because, as an avian flu bug, there is no existing human immunity to it. Some researchers say the transition of H5N1 from bird flu to human flu will be difficult, requiring one of two things to happen.
In one scenario, the virus would acquire the ability to easily infect humans through random mutation. There's no way to determine how, when - or if - that will happen.
In the second scenario, a person would be infected simultaneously by both H5N1 and an existing human virus. The viruses would exchange genetic material - reassort - and produce an easily transmitted hybrid.
The odds of contracting both H5N1 and a human flu at the same time are generally remote, say health officials, except perhaps among Asian farmers and others who spend much of their time in close proximity to potentially infected animals.
Other scientists, however, see no great hurdles to H5N1 evolving into a pandemic threat. They note that it would take changes in just a few amino acids to convert the bug from bird virus to human virus.
Henry Niman, a veteran flu researcher who once worked at Scripps Research Institute and founded a biotech company that became Ligand Pharmaceuticals in San Diego, believes conversion is inevitable, that H5N1 will become an established human flu virus within the next year or two.
"What that will mean in terms of a pandemic depends on exactly what version of the virus gains human status," he said. "Some versions of H5N1 are milder than others. If one of them prevails, any resulting pandemic might be more like 1957 or 1968. If a more deadly version prevails, it might be 1918 all over."
Flu scientists, public health officials - even Niman himself - hope he is wrong, that H5N1 will not blossom into a global killer. In the meantime, they watch, work and wait: hoping for the best, preparing for the worst.
Can Spain Redeem Themselves After The Netherlands Thrashing?
The Dutch are coming off the back of their greatest-ever group stage victory. Against Spain, the Netherlands exorcised the demons of their World Cup final loss with the force and brutality of a Nigel de Jong karate kick.
The long balls which led to such joy can now be eschewed in favor of a more typically Dutch style, though. They can reasonably expect a deep-lying Australian team to shell and counter, a tactical approach they are more than familiar with from lesser opponents. If the Dutch qualification record is any hint, they should be able to find a way through.
Like a band of teenagers in a slasher film, Australia hung in there admirably against Chile after conceding two early goals. Had a refereeing decision or two gone their way, they might have even escaped with a point. Unfortunately for the Australians, Chile was probably the game they'd circled on their schedule to get something from. Now the task ahead is obvious—stay alive by any means necessary and make sure that fixture three has relevance. Set pieces will be massive for the Socceroos. They play the Netherlands today at noon.
Wesley Sneijder, Robin van Persie, and Arjen Robben give the Dutch arguably the most dynamic a set of free kick takers in the competition. Stupid fouls near the Australian box should prove more costly this time. On the other end of the field, you have to like Tim Cahill's chance against the soft underbelly of the Dutch side. Without an established international center back to speak of, the Dutch look ripe for the taking in dead ball situations. Ron Vlaar, no stranger to an own goal, seems like the ideal candidate to target. For the Socceroos, this Dutch team is probably a better match up than Chile—no need to wake in fright.
If Chile were a pragmatic side they'd look at today's 3 p.m. fixture with Spain and play for the draw. The goal difference between Chile and Spain is significant enough that a draw should pretty well cover them, regardless of what happens in fixture three against Netherlands. Chile are not a pragmatic side, as we all now know, and, like the sharks they are, will smell the blood in the water. The potential absence of Arturo Vidal could be massive but considering that Chile's version of protecting a one-goal lead was to leave two munchkins in defense and hunt a third goal, I think it's fair to say that this shouldn't change their approach much.
For Spain, Chile at the Maracanã is their most important fixture in years. The collective dream of becoming the most dominant champion in the history of the sport could die with a game to spare in the group stage. If the Dutch beat Australia—as every major betting house in the world suggests—Spain are out with a loss. Win, and Spain can feel confident of advancing with only a match against Australia remaining. Vicente del Bosque has never lost consecutive games during his tenure as manager; now would not be a good time to start. Spain and Chile faced each other in a 2013 friendly in Geneva. That night, Spain needed a late Jesús Navas goal to salvage a draw. A draw won't be enough this time. Del Bosque's great advantage is knowing exactly what Chile will do. Chile aren't going to change. Will he? The tiki-taka grave dancers have never been more excited.
Screamer is Deadspin's soccer site. We're @ScreamerDS on Twitter. We'll be partnering with our friends at Howler Magazinethroughout the World Cup. Follow them on Twitter, @whatahowler.
It’s every venture capitalist’s dream to see their early startup bets grow into unicorns (companies valued at more than $1 billion) and find an exit, AKA an acquisition by a large company or an initial public offering. On Friday, when ride-hailing unicorn Lyft makes its hotly anticipated debut on the Nasdaq, over 100 investors will see their dreams come true.
Lyft plans to sell about 30 million Class A shares at a price range between $62 and $72 apiece, which will put the company’s total valuation north of $20 billion, a huge premium over its most recent private market valuation of $15 billion.
Over its 12-year lifespan, Lyft has raised nearly $5 billion as a startup from about 115 individuals and companies, according to data compiled by Pitchbook. Some investors will reap bigger winnings than others from Friday’s IPO because of either their early involvement or large check sizes.
Ownership in private companies is often secretive information. But in Lyft’s IPO filing with the SEC earlier this month, we were able to get peek at the company’s top shareholders, with corporate giants like General Motors and Japanese e-commerce platform Rakuten at the top of the list, followed by key individuals such as the company’s co-founders Logan Green and John Zimmer.
Green and Zimmer are Lyft’s largest shareholders of Class B stock, which comes with voting power. Class B won’t be publicly traded, but Green’s and Zimmer’s stakes will be worth about $523 million and $346 million, respectively, after the IPO.
Aggarwal, a former executive at eBay and Paypal, invested $30,000 in Lyft in 2007. He is the company’s largest individual stakeholder of Class A shares (1.41 million shares), which will be worth over $120 million after the IPO.
Interestingly, Aggarwal wasn’t fully convinced of the ride-sharing concept until 2011, but chose to stay committed due to his confidence in Green and Zimmer. “You guys are a great team. I’m just not sure about this carpool thing,” he reportedly told them.
Another early investor, Andreessen Horowitz pulled the trigger on Lyft during its series C fundraising in 2013 with a $60 million check. The prestigious venture capital firm also participated in several subsequent rounds, amassing a total of 15 million shares, or 6.25 percent of the company.
The whole stake will be worth just over $1 billion after Friday’s IPO.
Rakuten became Lyft’s largest shareholder through several rounds of investments since 2015. It owns 31.4 million shares, or 13 percent of the company. This stake will be worth $2.26 billion if Lyft goes public at $72 per share.
Rakuten is also a major investor in Uber and several smaller ride-hailing companies.
Second to Rakuten, GM and mutual fund giant Fidelity are both Lyft’s second largest shareholder, each owning an eight percent stake in the company, which will be worth $1.4 billion after the IPO.
Percentage-wise, their net earnings from the IPO won’t be as big as those early backers, because GM didn’t invest until series F (in December 2015) and Fidelity wrote its largest check only nine months ago.
CapitalG is an investment arm of Google parent company Alphabet specializing in growth-stage startups.
The firm led a $1 billion round for Lyft in 2017 in exchange for just over five percent of the company, or 12.6 million shares. The stake will be worth up to $900 million.
An unbelievable story from the world of crime: William M. Jenkins was shot through the stomach and back on Oct 21, 1960 during a gang scuffle in Spanish Harlem, and the 49-year-old incident is now blamed for his recent death. Wheelchair Willie, as he became known, died two weeks ago from complications caused by the gunshot wounds, which arose when a member of a rival gang insulted another's mother. Despite occurring over four dozen years ago, Jenkins' death was ruled a homicide and is part of New York's 2009 statistics for murders, writes The Times. George Lemus, one of the brothers imprisoned for the crime, will not face new charges. The injury didn't stop Willie's wayward behavior: the ne'er do well was arrested four times between 1971 and 1991 for attempted murder and robbery from his wheelchair.
Get ready for an epic party, New Orleans-style.
The Lehigh Valley Food & Wine Festival will take on the feeling of Mardi Gras when it returns for its 10th year, May 31- June 2 at the Sands Bethlehem Event Center.
Every year the festival showcases cuisine from the region's top restaurants, offerings from vineyards and distilleries from around the world and cooking demonstrations and workshops. The event is hosted by the Sands Bethlehem Event Center and Northampton Community College in partnership with Southern Glazer's Wine & Spirits.
Festival organizers unveiled this year’s plans with an elaborate news conference Tuesday — complete with New Orleans-style brass band, a traditional second line parade and king cake — in the new Zime Cafe inside NCC’s Fowler Family Southside Center in South Bethlehem.
* New Orleans flair: Festival-goers will enjoy New Orleans inspired dishes, second line parades, a themed selfie station, festive beads and even a signature Food & Wine event cocktail.
* Celebrity chef Emeril Lagasse will return, but his popular cooking demo moves from Friday afternoon to Saturday morning. The timing allows festival-goers to arrive in the morning for the demo, then enjoy the Grand Tasting in the afternoon.
The Grand Tasting, which will run 1 to 4 p.m. June 1 and 2, is the festival’s signature event. A ticket option will allow guests to buy early access VIP tickets and gain entrance to the festival at noon. Guests will enjoy plates from Emeril’s most popular eateries as well as the region’s most prestigious restaurants along with an impressive array of wines from around the world.
It’s fitting that the theme of this year’s festival is Mardi Gras as Lagasse is known for his New Orleans-focused cuisine. Lagasse is a pioneer in the world of celebrity chefs and arguably one of the most recognizable names in food.
A James Beard Award winner, Lagasse is the author of 19 cookbooks, star of several TV shows including Amazon Prime’s “Eat the World with Emeril,” Food Network's long-running “Essence of Emeril” and “Emeril Live” as well as Bravo’s “Top Chef.” Chances are you’ve heard someone use his catchphrases “Bam!” and “Kick it up a notch.” He is owner of a dozen restaurants across the country, including three in the Sands Casino Resort Bethlehem, his only East Coast sites.
At the demo, Lagasse will also announce which NCC students won highly competitive externships to work in his New Orleans restaurants. Each year, a group of students from NCC’s culinary and hospitality management program receive all-expenses-paid externships to gain experience honing their skills in the acclaimed chef’s kitchens.
* A new celebrity: Bethlehem’s Daniel Roebuck will be the master of ceremonies for the May 31 opening night premiere party, which will feature an extravagant four-course dinner prepared by Lagasse. The night will also include a live auction to raise money for NCC student scholarships.
From horror films with Rob Zombie to character actor roles on TV shows such as “Lost” to a Geico commercial, the Bethlehem native has a successful 30-year career in entertainment. He also has a deep appreciation for his Lehigh Valley roots, having shot his first film as a director, “Getting Grace,” here and making plans to shoot two more in the Lehigh Valley.
* Designated driver ticket: A new ticket option, festival-goers can simply enjoy all the foods without the alcohol.
How much: In advance, tickets for each day of the Grand Tasting are $85 for general admission, $100 for VIP, which includes access at noon and access to the champagne and spirits room; and $50 for a designated driver ticket (food only). Each attendee will receive a souvenir wine glass. Advance purchase is recommended at lehighvalleyfoodandwine.com or at the Sands Event Center box office.
Shaheen Sadeghi, president and founder of LAB Holding in Costa Mesa, stands inside the Anaheim Packing House. The collection of 20-plus local eateries and artisans is ever changing since opening in 2014. The latest: two original shops have closed, but three new tenants are open, or coming.
Buy n' Bulk, a center aisle tenant near The Kroft, closed recently. A craft soda shop is moving into the space.
A husband and wife team of chocolatiers ran Dark 180. The shop sold decadent chocolate drinks and truffles. It recently closed.
The owners of the The Chippy at the Anaheim Packing House have opened a second food concept in the dining hall: Mix it Up.
Two years after its grand opening, the Anaheim Packing House is undergoing more change. Two restaurants have closed, but three others have either opened or plan to open.
The Anaheim Packing House dining hall has turned into a popular destination for foodies in Orange County and beyond.
The Anaheim Packing District is an open, airy culinary marketplace with soaring ceilings and suspended air plants. The renovated produce plant opened in 2014. Two original tenants recently closed.
Shaheen Sadeghi has plans to expand his empire in Anaheim. He recently acquired several downtown properties. He is planning to open a winery, craft brewery and whiskey distillery later this year.
Two food stands have closed and two others have opened at the Anaheim Packing House, the popular downtown food hall that has triggered a few copycats across the county.
Buy ’n Bulk and Dark180 Chocolate, both original tenants when the food hall opened two years ago, have closed.
At Dark180, Bay Area transplant Kevin Nosworthy tempted foodies with a line of chocolate drinks and truffles. It’s unclear why it closed.
MINI Monster has replaced the chocolate shop, said Grace Chung, a representative for developer LAB Holding of Costa Mesa. MINI Monster is a limited menu version of Snow Monster, a shaved snow and dessert shop with several locations in Orange County.
MINI only sells boba milk tea drinks and cotton candy, not shaved snow. Chung said the menu on some days will include macaron ice cream sandwiches. Snow Monster has other locations in Irvine, Westminster, Long Beach and Huntington Beach.
The Doggone Good Soda Company is replacing Buy ’n Bulk, which sold scoop-your-own snacks, spices, grains and dried fruits.
Doggone beverage bar sells specialty craft sodas. Popular flavors include root beer, red currant, cola, sarsaparilla, orange crème, grape and strawberry. The store also plans to sell drinks by the bottle.
Doggone got its start at Old Towne Grinder & Ice Cream Parlour in Orange. Owner Bill King closed the shop last summer so he could focus on expanding the vintage craft soda company. He started it as a side business to the sandwich shop, but it became the “main reason why people came to the store,” he told the Register last year.
It’s unclear when Doggone will open.
Last weekend, Mix it Up also opened at the packing house.
Chung said the soup and salad eatery took over previously unoccupied space across from Georgia’s soul food restaurant. It is run by the same operators of The Chippy Fish & Grill, which has locations at the food hall and in Irvine.
Shaheen Sadeghi recently purchased the Packing House, along with several other properties, as part of his overall plan to revive downtown Anaheim.
With his new properties, he is planning a few other culinary and hospitality projects in the city.
The projects include a boutique hotel, farm-to-table restaurants and a brewery.
Unsung Brewing Company of Tustinis opening a nano brewery inside the 10,500-square-foot building that once was a marmalade factory in the 1900s. Dubbed the Make Building, it also will have a whiskey distillery and a winery with classes to teach amateurs how to create their own beer, whiskey and wine. Unsung, which does not have a tasting room in Tustin, will be producing small batch experimental brews, said founder and brewmasterMike Crea. Each facility will have tasting rooms. Make, across the street from the Packing House, is slated to be open later this year.
Contact the writer: nluna@ocregister.com and follow the Fast Food Maven on Twitter, Facebook and Instagram.
With a deadline for a decision less than a month away, representatives of New York City and a cable television operator have reached agreement on most points in the renewal of two cable television franchises in Manhattan.
But a few important issues - particularly the length of the new franchises - have still not been resolved in time for a meeting of the Board of Estimate scheduled for May 15.
Although there is always a possibility that the city might decide not to renew the franchises of Manhattan Cable and Paragon Manhattan, it is regarded as unlikely.
For one thing, it would embroil the Manhattan cable process in protracted controversy and undoubtedly confusion. For another, under the Federal Cable Act of 1984, grounds for denying renewals are very limited. Still, the threat of not renewing the franchises gives the city its principle leverage in pressing its position.
Even so, Mr. Hanks, who as director of the Bureau of Franchises has a leading role in the negotiations, made it clear that he had not decided whether to recommend approval or denial.
Richard Aurelio, the president of Time Warner's New York City Cable Group, which operates the two Manhattan cable systems and four systems in other boroughs, said he could not see how the city could justify denying the Manhattan renewals. $200 Million Renovation ''I think things are going quite well in terms of achieving an agreement,'' Mr. Aurelio said.
Mr. Aurelio noted that Time Warner agreed last year to a $200 million renovation of the Manhattan systems that is scheduled to be completed by the end of 1992 and to steps intended to meet customer complaints about poor service and treatment.
The renovation is to extend cable service to areas not wired for cable, including central and east Harlem and part of the Lower East Side. It will also expand the number of available channels to 70 from the current 31 for Paragon subscribers and to a maximum of 43 for Manhattan Cable customers.
Manhattan Cable, which is owned by Time Warner, covers the West Side south of 79th Street and the East Side south of 86th Street. Paragon Manhattan, which covers the rest of Manhattan, is a 50-50 partnership between Houston Industries and the American Television and Communications Corporation, a Time Warner subsidiary.
Both Manhattan franchises will expire this summer after 20 years. Until the franchises are renewed or new franchises are awarded to other companies, Manhattan Cable and Paragon will continue to provide service under the earlier arrangement. The two companies have about 380,000 subscribers, a figure that Mr. Hanks said represents more than half the households.
If the franchises should be awarded to other companies, the city would be obligated to give Manhattan Cable and Paragon Manhattan the ''fair market value'' for their assets, including underground cables, electronic equipment and transmission centers.
The Board of Estimate can vote at its hearing on May 15 to renew the franchises or to preliminarily deny the renewals.
Two board members, Mayor David N. Dinkins and City Council President Andrew J. Stein, have been barred by a city ethics panel from taking part in the decision because of relatives' stock holdings in companies that are affiliated with Time Warner.
Should the board vote for a preliminary denial, the city would be required under the 1984 Federal act to hold an administrative hearing to justify a formal denial and give the cable companies an opportunity to present their side.