Month: April 2007

Vioxx Follow-up Arcoxia Nixed

VioxxThe discovery of the life-threatening effects of Vioxx led to its rapid withdrawal by manufacturer Merck under pressure from drug agencies. Now, the successor to the notorious osteoarthritis drug, Arcoxia, is to be banned by the Food and Drug Administration.

Vioxx, a potent, yet purportedly selective, inhibitor of the inflammatory enzyme cyclooxygenase-2 (Cox-2) caused serious cardiovascular complications (heart attack, to put it bluntly) in too many patients once it was released to the wider prescribing world. Pharmaceutical giant Merck hoped that its Arcoxia follow-up in 2004 would fill the niche without being nixed. However doubts about the safety and potential side effects of all Cox-2 inhibitors in the eyes of the FDA has thrown the whole market into disarray.

The FDA’s report on the new drug suggested that its widespread use in treating arthritis could lead to 30,000 heart attacks each year. Merck’s counterargument suggested that the drug has a similar benefit-risk analysis profile as other drugs, such as diclofenac. FDA’s David Graham warned that Arcoxia could be “a potential public-health disaster” because of the increased risk of heart attack and stroke posed by long-term use of the drug. He suggested Arcoxia should be compared with its risk profile with naproxen, against which Vioxx had been compared originally and found wanting.

InChI=1/C17H14O4S/c1-22(19,20)14-9-7-12(8-10-14)15-11-21-17(18)16(15)13-5-3-2-4-6-13/h2-10H,11H2,1H3

Organic Kiwi Fruit

Organic kiwi fruitCould the claims of the “organic” farming movement be true after all? According to an international team who have analysed the antioxidant, mineral, and nitrate composition of kiwifruit, yes. Their findings published in the Journal of the Science of Food and Agriculture would suggest that growing the fuzzy green fruit using so-called organic principles leads to a higher content of health-promoting factors than those grown using conventional methods.

I asked team leader Adel Kader of the University of California, Davis, about his reasoning. “Most differences in composition between conventionally grown and organically grown fruits depend on differences in inputs,” he told us. These inputs include differences in fertilizers added and so results vary considerably from one study to the next, “In our kiwifruit study, the grower added more fertilizers to the organic kiwifruit plants than to the conventional ones and that is the reason for the higher mineral contents of the organic fruits,” he adds, “The one exception is phenolic [antioxidant] content, which has been shown in our study and in several other studies on a range of crops to be higher in organic than in conventional fruits.”

Kader believes that the difference is most likely due to the fruit having to survive against pests in the absence of synthetic pesticides. “Conventional agriculture practices utilize levels of pesticides that can result in a disruption of phenolic metabolites in the plant,” he says, “which have a protective role in plant defense mechanisms.” His hunch is further corroborated by the organic kiwifruit having thicker skins as well as the higher antioxidant activity which is thought to be a natural by-product of stress. He has a simple piece of advice for those dithering over whether to tuck into the fuzzy fruit: “My advice is that people eat more fruits regardless of whether they are conventionally or organically produced,” he told Sciencebase. More on this story in SpectroscopyNOW this week.

Large Hadron Collider at CERN

CERN magnetUPDATE: OCT 15, 2008 – Investigations at CERN* following a large helium leak into sector 3-4 of the Large Hadron Collider (LHC) tunnel have confirmed that cause of the incident was a faulty electrical connection between two of the accelerator’s magnets. This resulted in mechanical damage and release of helium from the magnet cold mass into the tunnel.

Proper safety procedures were in force, the safety systems performed as expected, and no one was put at risk. Sufficient spare components are in hand to ensure that the LHC is able to restart in 2009, and measures to prevent a similar incident in the future are being put in place.

‘This incident was unforeseen,’ said CERN Director General Robert Aymar, ‘but I am now confident that we can make the necessary repairs, ensure that a similar incident can not happen in the future and move forward to achieving our research objectives.’

UPDATE: SEPT 10, 2008 – The first particle beam has been sent around the 27km long tunnel at the LHC. This is the equivalent of a computer POST (power on, self test), they are yet to collide any hadrons at near light speed (that will be the BOOT proper). Sciencebase has now published its Large Hadron Collider LHC-FAQ and will keep you up to date with the latest from the LHC via the site’s RSS newsfeed; subscribe for free now to stay informed, alternatively, you can get updates by email. For concerns about black holes and revelations at the Large Hadron Collider, you may wish to read an extended guest post on the subject.

Physics followers among our readers will have no doubt seen the ubiquitous LHC “typo” a million times, so we’ve been very careful to avoid it in this item (email me if you cannot work out what it is). But, one thing that is not unavoidable, is the huge number of news reports that claim there was some kind of mathematical error that led to the recent little big bang at the CERN site.

Jonathan Leake at The Times, for instance, in an article headlined: “Big Bang at the atomic lab after scientists get their maths wrong” says, “A £2 billion project to answer some of the biggest mysteries of the universe has been delayed by months after scientists building it made basic errors in their mathematical calculations.”

Tests were started on the enormous magnets that will pull particles around the accelerator to great speeds in a giant experiment to mimic conditions at the beginning of time. But, I just heard from Fermilab visiting scientist Peter Limon, who is helping to commission the LHC, and he tells an entirely different story. What exactly was the cause of the accident deep underground at the CERN particle accelerator complex near Geneva in Switzerland?

“The problem with the inner triplet magnets in the LHC is as follows,” Limon told me, “The superconducting magnets themselves are in a pressure vessel (called the cold mass) that will eventually be cooled to 1.9 K for operation. These cold masses are suspended inside a cryostat (a vacuum vessel) so that they can be isolated from the heat that would otherwise make it impossible to cool the magnet. The suspension is made of a composite glass/epoxy material to minimize the heat flow from the outside of the vessel into the magnet.”

Some reports have claimed that the magnet was lifted out of its mountings. “The magnets did not lift itself off its mountings,” Limon said emphatically, “The break was in suspension pieces inside the cryostat. There was no motion of the magnet on its mountings, as far as we can tell.”

Limon then explained that, “Because of the geometry and the connections between magnets in the inner triplet, there is an unbalanced longitudinal force on the cold mass when the cold mass is pressurized.” This force, he adds, is transmitted from the cold mass to the the cryostat through the composite suspensions. “The design of the suspensions is inadequate to withstand those forces, but at 20 atmospheres, they broke,” he says, “The pressure test would have been successful if the pressure had gotten to 25 atm.”

Engineering calculations completed independently by Fermilab and CERN on March 28, the day after the accident, showed that the G-11 support structure in the magnets was inadequate to withstand the associated longitudinal forces. The word “inadequate” is rather euphemistic in this context, in reality the equipment simply was not up to the job in hand and it broke under the strain.

“In short,” Limon told me, “this was not a mathematical error, but an engineering omission. The full extent of the unbalanced longitudinal force (as much as 15 tons!) was not taken into account when the suspension was designed.”

I don’t believe design sabotage has been ruled out, but it is rather unlikely. Although the cynical among us will note that Fermilab who designed the magnet is also a scientific rival of CERN itself. Fermilab operates a particle accelerator, Tevatron, that is less powerful than the LHC but which Fermilab scientists are continually pushing to its limits. Moreover, they hope to beat CERN in the race to find the key particle that could unlock the secrets of the universe – the Higgs boson – before the LHC is even fired up.

The repair work by Fermilab and CERN staff, is according to the CERN website “being closely coordinated”. Fermilab personnel are on site at CERN, no doubt working under a cloud. That phrase “closely coordinated” would suggest some serious monitoring of activities. Too right.

Additionally, Fermilab is currently examining all aspects of the US-supplied components for the LHC just in case there are any other “potential vulnerabilities.” Whether CERN’s problems were mathematical or engineering in origin, CERN’s plans have been seriously delayed, which could give the Tevatron, with its dearth of “potential vulnerabilities” a particular advantage in the quest for the secrets of the universe.

NEWS FLASH

On Thursday 26 April, the last superconducting magnet of the Large Hadron Collider (LHC), a 15 metre long dipole weighing 34 tonnes, will be lowered in to the 27 km tunnel of the accelerator. With this magnet, the world’s largest superconducting installation receives its final component. The LHC is made up of some 1700 superconducting magnet assemblies, which will guide and focus the LHC’s particle beams. Teams are at work in the tunnel to conclude the complex task of magnet interconnection, and the sequence of procedures necessary before the machine’s scheduled start-up at the end of the year.

Coming soon: The Large Hadron Collider FAQ (the LHCFAQ) from Sciencebase.

Save a balloon with water

Balloon in a candle flameWhat connects cooling computer chips, melting car engines, and a balloon that will not pop? This week’s science video sees Robert Krampf explaining the principles behind heat sinks, car radiators, water cooling, and how to hold a balloon above a burning candle without it ever popping.

Krampf points out that, “Because we’re using fire, always be sure you keep safety in mind, and be sure you’ve got an adult around, so that you’ll have somebody to blame if something goes wrong!”

So, what is it about water that makes it absorb the heat from the candle flame so fast and so protect the rubber of the balloon from melting or burning? Water has the second highest specific heat capacity of any known chemical compound, after ammonia. This is due to the extensive but transient network of temporary hydrogen bonds that form between the oxygen atom at the centre of each water molecule and a hydrogen atom from a neighbouring water molecule. This fluxional network of loose bonds allows liquid water to rapidly absorb heat and also allows the heat to quickly be dispersed through the bulk liquid.

WARNING: Please don’t attempt this experiment with anything but water in the balloon. Water is about the only fluid that is safe to use but more to the point, it won’t work properly with any other fluid.

Stay Calm, Beat Cancer

EpinephrineA constant flux of the stress hormone, released by the adrenal glands, could underpin certain forms of prostate and breast cancer. According the George Kulik and his colleages at Wake Forest University in North Carolina, epinephrine can change these cells make them resistant to programmed cell death (apoptosis) and so susceptible to the runaway cell division characteristic of cancer. Moreover, triggering cell death is the basis of cancer therapy.

Levels of epinephrine are chronically raised in the stressed and depressed, so Kulik’s research would suggest that overcoming these two problems might lead to a reduced risk of cancer. Writing in JBC, Kulik says that “Stress may both contribute to the development of cancer and may also reduce the effectiveness of cancer treatments.”

InChI=1/C9H13NO3/c1-10-5-9(13)6-2-3-7(11)8(12)4-6/h2-4,9-13H,5H2,1H3

Obesity Gene

Obesity overweightToday’s claims in the media about the recently discovered obesity gene are at best overwrought and at worst downright dangerous. A vast study involving more than twenty research centres across the UK has allegedly demonstrated that almost one fifth of us carry a variant of the gene known as FTO that predisposes us to obesity or overweight.

According to the researchers, “Obesity is a serious international health problem that increases the risk of several common diseases.” Fair comment. They add that, “The genetic factors predisposing to obesity are poorly understood.” Another fair comment.

They then report that while carrying out a genome-wide search for type 2 diabetes susceptibility genes among 13 groups of almost 40000 participants they have identified a common variant in the FTO gene that predisposes to diabetes through an effect on body mass index (BMI).

Additionally, the team reports that there is a cumulative, or additive, association of the variant with BMI. They found that 16% of the adults with the risky genetics weighed about 3 kilograms more than the others and were almost twice as likely to be obese, when compared to people without the risk allele. Moreover, the team says that they observe this genetic risk factor in individuals age 7 years and older and say that it reflects a specific increase in fat mass.

But, all this talk of obesity being down to genes will provide many individuals with an excuse along the lines of “it’s my glands”, which has become something of a serious cliche for some people who simply refuse to reduce the calorie intake and to add serious amounts of exercise to their daily routine.

The politics of obesity aside, I contacted metabolic expert Jeremy Nicholson of Imperial College London who recently discovered that calorie restriction in dogs extends life, reduces the risk of diabetes and metabolic disorders, and could be due to a change in the behaviour of microbes in the gut. He is less than impressed with the response of the media to the Science paper on FTO. “Basically, no amount of genetics can explain how humans have got fat so fast,” he told me. I would have to agree, genetics has long-term effects one usually does not see major changes in body function and form happening across a single generation.

So, might there be an alternative explanation for the apparent obesity epidemic in the developed world? Nicholson thinks so. “Changes in the gut microbes and caloric bioavailability probably could be the explanation,” he says. If we are suffering severe disturbances in the profile of gut bacteria – either they have changed behaviour or the species have changed – then those heading for overweight or who are already obese could be absorbing far more calories even from the same amount of food because of it.

Liposuction, like Vaser, Smartlipo and laser liposuction is one option, but could a dose of live yogurt or an antibiotic regimen be the solution to obesity? We are only just starting the hors d’heuvre when it comes to understanding the interplay between our bodies and microbes. Much more work into metabolism and the role of the guy microflora needs to be done before we can cast aside obesity as yet another genetic construct and so abandon sufferers to the realm of the untreatable.

Nicholson explains that the microflora in our gut are laid down in infancy and there is not a lot we can do about that. However, he says, “The real secret is eating a lot of beans and pulses (lentils etc) – lots of them every day, they keep the lower gut microbes very happy and the products of their
breakdown (catabolism) do not cause diabetes.” Nicholson laments that the windy side-effects of such a diet are far less malign than the problems associated with a diet deficient in beans and pulses.

Genetics, microbes, and beans aside, Nicholson has what I think has to be the final word on the debate: “Even genes and bugs added together still fade into insignificance if you sit on your butt all day eating pork rinds – you will get fat but its not genetic!”

Fault finding and interplanetary rubble

Fault findingThe latest issue of Intute Spotlight from David Bradley and the physical sciences portal is now online:

Fault finding [earth]

Almost half a million US dollars, about £250k, was earmarked by the National Science Foundation (NSF) for a project to map California’s San Andreas Fault, …

Science comes in from the cold [physics]

Research into the phenomenon formerly known as cold fusion is heating up again. Despite an initial chilly reception to anything related to this once-maverick science, it seems that studies of what are now called …

Interplanetary rubble [astronomy]

It’s not the most romantic image of heavenly bodies, but the latest observations of a pair of asteroids suggest that the pair is essentially two piles of rubble dancing an eternal pas de deux. The description emerges from a collation of observations from the world’s largest telescopes as well as the small instrument of a backyard amateur …

Spinneret Secret Unraveled

Spider silk is “pound for pound” stronger than steel and has a greater elasticity than rubber. Such properties would make it a rather useful material for a large variety of medical and engineering applications if only it could be made in large enough quantities and with a useful thickness and consistency.

Thomas Scheibel at the Technical University of Munich has now taken a step towards understanding the spider’s secret with a view to creating an artificial spinneret for producing unlimited quantities of spider silk. Writing in in Angewandte, the team explain how they have discovered that the interaction between the hydrophilic and lipophilic properties of the silk proteins plays an important role in the spinning process.

Fundamentally, the spinning of spider silk represents a phase change from a solution into a solid thread. The silk used by orb weaver spiders to spin the edges and spokes of their webs and to make a quick escape when attacked is composed of two different proteins. The Munich team has now successfully used genetic engineering to produce one of the spider silk proteins of the European garden spider (Araneus daidematus).

While purifying the protein by dialysis, the researchers observed the separation of two different fluid phases. Whereas one phase consisted of protein dimers, the second consisted of oligomers. After adding potassium phosphate, a natural initiator of silk aggregation, the liquid could be pulled into threads. “It is clearly not a structural change in the protein, but rather the degree of oligomerization that is crucial for thread formation,” concludes Scheibel.

Five times faster than BitTorrent

Similarity Enhanced TransferAnyone who has dared to download, a large file using the Bit Torrent system in which chunks of the file are pulled from other BT users in a form of distributed file sharing will know how slow (and sometimes how fast) the method can be. Although much of the BT system is exploited to share pirated movies and music it has a serious, legitimate side that also allows scientists, engineers and programmers to share the burden of huge database and ISO image downloads. Now, thousands of US tax dollars (in the form of an NSF CAREER grant) have been spent on improving on the Bit Torrent system.

David Andersen and colleagues at Carnegie Mellon University spotted the fatal flaw in torrents that often leads to the file sharing system grinding to a halt if the number of users with the complete or almost complete file are offline.

In conventional BT downloads, the files being shared must match exactly across the distributed sharing network or else they are ignored for download purposes. Anderson realized that identifying relevant chunks of files that may not be identical but are similar to a desired file could speed up Bit Torrent downloads. Anderson and his colleagues have designed Similarity-Enhanced Transfer (SET) to exploit this concept.

Anderson claims SET could make some transfers five times faster. “This is a technique that I would like people to steal,” Andersen said. Though he and his colleagues hope to implement SET in a service for sharing software or academic papers, they have no intention of applying it themselves to movie- or music-sharing services. “But it would make P2P transfers faster and more efficient,” he added, “and developers should just take the idea and use it in their own systems.”

SET works in a similar way to BitTorrent. Once a download is started, the source file is broken down into unique chunks. These chunks are downloaded simultaneously from accessible sources on the sharing network and then reassembled on the user’s computer. While this is underway, the SET program continues to search for similar files using a process called handprinting. In this method, sampling of non-identical files is used to find chunks that match the required chunks. Relevant chunks can then be downloaded from the similar files identified by this method, making the overall process much faster.

Although the researchers hope to use the SET approach for legitimate academic file sharing, they tested it on more common music and movie downloads. They saw a more than 70% improvement in downloading an mp3 file. A larger 55 Mb movie trailer was 30% faster when it could pull chunks from movie trailers that were 47 percent similar.

The researchers hope that such efficiency improvements will make SET part of the next generation of high-speed online multimedia delivery. “We believe that handprinting strikes an attractive balance for multi-source transfers. It efficiently locates the sources of exploitable similarity that have the most chunks to contribute to a receiver, and it does so using only a small, constant number of lookups. For these reasons, we believe that this technique is an attractive one to use in any multi-source file transfer system,” say the researchers.

R&R leads to molecular recovery

Mark Kuzyk is at it again. The physicist continues to explore a range of novel, light-sensitive compounds and has found one that degrades over time…but if kept in the dark for a short period of time, spontaneously heals itself. This amazing property could be exploited in industrial processes such as optical data storage and photolithography, which could use the recyclable material instead of having to replace the expensive stuff for every turn over.

Kuzyk and colleagues at Washington State University have found a molecule that loses its ability to fluoresce when bathed with laser light but regains this talent if it gets plenty of rest in the dark. Recovery starts during a half hour power nap and is complete after a good eight hours R&R, say the resarchers.

“It’s almost as if you have a piece of paper that’s yellowed over time, and you put it in a dark room for a day, and it comes back brand-new,” enthuses Kuzyk. Previously, I discussed Kuzyk’s work on Sciencebase and Intute Spotlight.

Kuzyk and students Ye Zhu and Juefei Zhou discovered the “self-healing” property of the dye AF455, which excels at two-photon absorption, an important property in optical data storage and in producing microelectronics for photolithography. The team will report details in the April 15 issue of the journal Optics Letters.

I received a follow-up email to this from Kuzyk: I’ve reproduced the Mark Kuzyk email here.