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Archive → August, 2011

Banking On A Bunker To Save Britain’s Film

Cellulose nitrate degradation that the BFI aims to avoid with their new archive. Credit: BFI

If I had to marry an inanimate object, I would not choose the Berlin Wall as Eija-Riitta has, but I might be tempted by a bunker, possibly the Boros bunker, whose dark history has been reclaimed by great art.

So you can imagine that I was super interested in a recent Guardian

article about a new archive for the British Film Institute, which will be located on top of the site of an old nuclear bunker.

The BFI is facing what’s already a become a major problem for many who possess collections of early cinema: How do you keep 450,000 cans of film from breaking down, particularly when the film is made of cellulose nitrate, a plastic not known for its longevity?

When cellulose nitrate breaks down, it causes the release of nitric acid, which can accelerate degradation in nearby film. Eventually all the degradation results in a gooey or powdery mess where there was once a fantastic film.

The BFI’s spokesperson Brian Robinson told me that in the new archive, fragile film will be kept at -5 C, which is “down a notch” from the previous temperature (3-4 C) that the film was stored at. According to studies done at the BFI, Robinson says that the cellulose nitrate degradation will “be arrested.”

I can’t imagine that it’s ever possible to completely

arrest degradation, but I’m guessing the drop in temperature seriously decreases the rate of chemical breakdown.

Finally, Robinson says the new £12 million facility will be well-ventilated, which I presume will suck away any amount of nitric acid that has managed to percolate off the valuable film.

Epic Fail: Solyndra files for bankruptcy

While you were at lunch, the nascent cleantech manufacturing industry in the U.S. collapsed.

Actually, that’s not quite true, but it is true that Solyndra will file for bankruptcy. This is a big deal – Google News lists 85 news outlets covering the story. Solyndra is famous for its stylish, glass tubular, CIGS-powered, solar rooftop modules. And for raising vast amounts of venture capital. And for getting a $535 million Department of Energy loan guarantee. And for filing for, and later cancelling, a planned IPO in late 2009.

Solyndra’s success in raising money was an early indicator that venture capitalists had turned to so-called cleantech industries, taking some of the shine off of internet and technology-based start-ups. It was the first company to benefit from the DOE’s loan program, part of the 2005 Energy Act.

But cleantech — particularly solar — has been looking a bit less shiny lately. Earlier this month, Evergreen Solar filed for bankruptcy protection, and its filing shows that the firm does not plan to emerge in anything like its current form. Evergreen also received government largess, getting more than $50 million in support from the state of Massachusetts.

Both Solyndra and Evergreen had proven technologies and they had the financial resources to scale up their manufacturing. Compared to many segments of cleantech, this sounded like a pretty good risk for investors. However, both technologies were based, at least in part, on solar module designs that minimized the use of polysilicon. That was smart at the time, because polysilicon supplies were very tight, and shortages threatened to choke the life out of (traditional) solar manufacturing. That was back in 2007-8. But by the end of 2008, chemical makers made plans to ramp up their manufacturing of polysilicon. The stuff was fetching record prices, after all, and it’s made from sand.

Beginning in 2009, polysilicon manufacturers like Hemlock Semiconductor (owned in part by Dow Corning) and Wacker Chemie began doubling, tripling, quadrupling etc their polysilicon capacity. Billion dollar plus-sized polysilicon plants in the US also won government support. By late 2009 there was an overabundance of polysilicon and an oversupplyof modules in inventory, crushing prices.

Firms like Solyndra and Evergreen had raised money and started scaling up manufacturing right as solar modules became a commodity. Chinese manufacturers at that point had their eye on making solar modules for close to $2 per watt. It was not a good time to have a technologically distinct – and more expensive – solar product.

In 2010-2011, European countries – especially Spain – cut back on solar subsidies. Germany has trimmed them as well. All solar makers were busy cutting costs amid strong competition, especially from China, and selling into a market with constrained demand.

Looking at the subject from a distance, it seems that polysilicon makers and their ambitious and steep increases in capacity are what doomed the non-polysilicon players. Materials suppliers, not just of polysilicon, but of also of polymer backing sheets, UV protecting films, and metal pastes, are doing very well selling into the photovoltaic market.

But government bets on cell manufacturing technology have not paid off. It is not clear yet how much of the loan gurantee Solyndra leveraged into actual financing. Still, Congress will likely have a great deal to say about lessons learned from Solyndra.

Difficult C. difficile Infections – New Drug, New Targets

Trust your gut . . . scientifically speaking.  From belly-button bacteria to classification of signature microflora (all the various microbes that populate the intestinal tract), it feels like recent popular “culture” grows best in a petri dish. Many scientists now classify humans as superorganisms, meaning our survival depends on a host of “good” internal bacteria that digest fiber, make vitamins, and help the immune system. But what happens when these good bacteria suddenly get wiped out by a non-selective antibiotic? This sets the stage for a Clostridium difficile intestinal conquest.

Simple contact transmits this bacterium between patients in hospitals, causing antibiotic-assisted diarrhea, bloating, and potential colitis. When a patient is treated with a broad-spectrum antibiotic, C. difficile survive by forming spores with tough outer coats, only to thrive again when there are few other bugs in the gut with which to compete.

Two new players have recently entered the fight against the difficult C. difficile: first, Optimer Pharmaceuticals’ new narrow-spectrum antibiotic for C. diff. treatment, Dificid (fidaxomicin), approved in May 2011. This antibiotic macrolide belongs to the tiacumicin class of natural products, members of which have been known since Abbott first isolated compounds from fermentation broths in 1987. Dificid specifically inhibits Clostridium RNA polymerase enzymes; without these enzymes, gene transcription halts, and the cells die.

Clearing the infection is great, but wouldn’t it be nice to ease the intestinal pain while the drug takes hold?

Researchers at UTMB-Galveston might have found a good target for drugs that could do just that. In the August advanced online publications at Nature Medicine, Tor C. Savidge at UTMB-Galveston reports on human metabolites that can inhibit C. difficile toxins TcdA and TcdB, the major agents behind painful antibiotic-assisted diarrhea.  S-nitroso-glutathione, a nitroso (NO)-conjugated version of glutathione found in stool samples of infected patients, can “pass off” its NO group to the sulfur of a specific cystine amino acid residue in the toxins, shutting down their activity. The authors point out that instead of active site binding, the normal mode of action for most enzyme inhibitors, this NO seems to inhibit the toxins via an allosteric site, meaning they bind somewhere else on the toxin but still impair its function. Potency for in vitro inhibition is still in the high micromolar range (43-57 µm), but the study may point the way to the development of more selective NO-transfer drugs.

Talking about safety culture at #ACSDenver

While we certainly missed our friends who were unable to make it to Denver because of the hurricane on the East Coast, I’d still say it has been an excellent meeting for both the Committee on Chemical Safety (CCS) and the Division of Chemical Health & Safety (CHAS).

Safety culture in academic laboratories has become a popular topic. Efforts by CCS to raise the issue’s profile within ACS will result in today’s Council discussion on the discussion. Both CHAS & CCS meetings included presentations from the Chemical Safety & Hazard Investigation Board on their investigation of academic safety incidents and causes. I also saw several National Academies senior staff members in Denver; they continue to work on raising the necessary money to follow through on their initial meeting on the topic.  It looks like this will continue to move forward on multiple levels. Hopefully there will be a consolidated effort to advance this important cause.

On another subject, several former ACS Presidents have approached me about CHAS developing an online laboratory safety certificate program for graduate students. The objective is to give graduate students a “leg up” on preparing for life after academia. As many of you know, a major complaint by industry is that students don’t have the safety experience they need to succeed when they’re hired. By developing a comprehensive course with testing and a certificate, these graduates could add something helpful to their resumes. I’ll throw a disclaimer right here that hands-on experience in using safety equipment and PPE is also necessary, but a well-designed program could be a strong basis. I’ll be talking soon with both ACS staff and outside providers to determine the best approach. Feel free to chime in if you have ideas!

Last but not least, thanks to the C&EN staff, particularly Jyllian and Amanda Yarnell, for including me in their get-together this weekend. I had a great time and would say they are not only professional and hard-working in their efforts to keep C&EN’s high profile, they’re also fun people!

Climate Change Schizophrenia

That the discussion of global climate change, even among professional scientists, has become utterly schizophrenic was dramatically demonstrated by a symposium—or was it symposia?—at the Denver meeting sponsored by the Division of Small Chemical Business.

The Sunday morning session, entitled “Global Climate Change: What Citizens of the World Need to Know,” featured five prominent climate scientists talking about measurements of how the Earth’s climate is changing and how emissions of greenhouse gases is forcing that change. The afternoon session, entitled “A Critical Look at Global Warming Data: An Examination of Driving Factors in the Wickedly Complex System Called Climate,” featured six speakers whose focus is undermining the data and analyses of scientists like the ones who spoke during the morning session. There was almost no overlap in the audiences.

Because of a prior commitment, I was able to attend only the first four of the morning session talks. That was unfortunate because I am very interested in ocean acidification resulting from increased atmospheric CO2, the topic of the fifth talk. Nevertheless, the first four talks built solidly on each other to make the case that humans are dramatically disrupting Earth’s climate.

Stanley Manahan, an emeritus chemistry professor at the University of Missouri, published the first edition of the textbook “Environmental Chemistry” in 1972; the ninth edition is now out and Manahan is working on the 10th edition. In his talk, Manahan compared the current debate over climate change to the debate over chlorofluorocarbons and Earth’s stratospheric ozone layer 30 years ago. “Rowland and Molina’s findings on CFCs were ridiculed by some,” Manahan said, but the discovery of the ozone hole over Antarctica in the early 1980s vindicated their ideas and resulted in regulations that eventually banned CFC production and use.

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Special Delivery For A Synthesis Victory #ACSDenver

Courtesy of John Wood

When John Wood read about the first total synthesis of N-methylwelwitindolinone C isothiocyanate, he was impressed. After all, the densely functionalized welwitindolinone family of alkaloids has been in synthetic chemists’ crosshairs for the better part of two decades. Fifteen different labs, including Wood’s own at Colorado State, have published over 20 “progress toward” papers on one subset of welwitindolinones alone. And this particular natural product, with intriguing bioactivity on drug-resistant tumor cells, has proven to be among the most desirable targets.
Once he really studied the synthesis (J. Am. Chem. Soc., DOI: 10.1021/ja206538k), presented today at ACS Denver by UCLA’s Neil Garg and his grad students Alex Huters, Kyle Quasdorf, and Evan Styduhar, he decided the work merited more than just the customary “Nice job” email that floats between professors as a means of congratulation. Fortunately, he knew just what would fit the bill.
“A few years ago as part of a woodworking project I was doing I learned how to sandblast images onto glass,” Wood says. “I was so taken with Garg’s synthesis that after I read it I went home and sandblasted the image of his retrosynthetic scheme onto four beer glasses,” one for each team member. He then shipped the package to California, where an unsuspecting Garg received it in his office.
“I called the students in before I opened the box,” Garg says. When he pulled the package open, it contained the four glasses, carefully decorated with the team’s names and their chemistry. But the box held something more. “There was a nice card and a $20 bill in there,” he recounts. In the card, Wood advised Garg to use the $20 to take his students out for a beer as they deserved it on account of their fine work.
“This is a really competitive field, so it’s been great to have support” from the community, Garg says. He notes that his own Ph.D. adviser, Caltech’s Brian Stoltz, worked on this same natural product family as a graduate student with Wood.
The $20 was spent as instructed, Garg reports. “But nobody wants to use the glasses because they’re really cool.”

A Visit To The Opificio, Italy’s Primary Restoration Lab

An Opificio restorer working on a Vasari panel painting. © Sarah Everts.

Italy has no shortage of art, and when that art needs a face-lift, it takes a trip to the Opificio delle Pietre Dure e Laboratori di Restauro, the country’s national restoration laboratory.

Located in an elegant old stable in Florence, the Opificio is like a spa for cultural heritage artifacts, where paintings, frescoes and sculptures go for age-extending treatments.

When I visited, Cecilia Frosinini, an art historian and the Opificio’s director of mural paintings, was kind enough to give me a tour.

As we wandered through the extensive labs, dozens of restorers were working on a wide variety of pieces including Renaissance paintings sent from Budapest for anti-aging therapy, ceramic sculptures, water-damaged frescoes and a wooden statue of Christ that had been painted to look like bronze during an era when bronze was popular but too expensive for some budgets.

Looks like bronze but it's actually wood. © Sarah Everts

The Opificio has also been recently involved in everything from using ultraviolet light to bring out cool, hidden details in Giotto paintings to the restoration of Santa Croce Basilica’s famous frescoes.

Like many great things in Florence, the Opificio has its root with the city’s famous Medici family. The first half the Opificio’s Italian name translates to “workshop of semi precious stones.” And as the name suggests, the Medicis founded the Opificio in 1580s to produce furniture decorated with semi precious stones, Frosinini told me.

Time passed and the workshop began restoring their own pieces. By the 19th century, art made from other materials such ceramic, marble and jewelry, was also being restored, she added.
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Bristol-Myers, Pfizer’s Apixaban Tops Warfarin In Anticoagulant Face-Off

Over the weekend Bristol-Myers Squibb and Pfizer announced that their blood-clot-preventing drug candidate, Eliquis (apixaban), bested the workhorse anticoagulant Coumadin (warfarin) in a large clinical trial. The results were announced at the European Society of Cardiology congress and simultaneously published in the New England Journal of Medicine. This is the first time that one of the cadre of anticoagulants seeking to replace warfarin has been shown to be superior to warfarin at preventing dangerous blood clots that can lead to strokes while also having a lower rate of bleeding compared to warfarin.

In the 18,201 patient Phase III clinical trial, called ARISTOTLE, apixaban reduced the risk of stroke in patients with an abnormal heart rhythm called atrial fibrillation by 21 percent, major bleeding by 31 percent, and mortality by 11 percent.

More statistics are available in the announcement, the journal article, and in this Forbes report, which plucks out these illustrative numbers:

The investigators calculated that for every 1000 patients treated with apixaban instead of warfarin for 1.8 years

•stroke would be avoided in 6 patients,
•major bleeding would be avoided in 15 patients, and
•death would be avoided in 8 patients.

Analysts reacted positively to the data, with Leerink Swann analyst Seamus Fernandez raising his 2017 sales estimate for apixaban by $1.1 billion to $4.1 billion in a note to investors.

We’ve previously explained how apixaban works– briefly, it blocks Factor Xa, a protease enzyme near the end of the complex biochemical pathway that regulates blood clotting. Another Factor Xa inhibitor, rivaroxaban, has been approved in Europe but awaits FDA approval. Pradaxa (dabigatran), which blocks the enzyme thrombin, has been approved by FDA for reducing the risk of stroke associated with atrial fibrillation.

So what’s the secret of apixaban’s success? Continue reading →