Hubble Beater, Bottom Up and Explosives

Nebula Lucky

The latest edition of Intute Spotlight is now online. In it I discuss a 300 year old chemical conundrum completed, a ground-based Hubble beater, and IBM’s plans to move from the micro world to the nano, although it won’t mean smaller premises.

Explosive Crystal [Sep 2007 – chemistry,materials]

Three centuries after its discovery by alchemists, the crystal structure of mercury fulminate – an explosive detonation …

Hubble Beater [Sep 2007 – astronomy]

Cambridge and Caltech astronomers have devised a new digital sensor for their telescopes that effectively cancels out the “twinkling” caused by the Earth’s atmosphere and allows them …

Bottom up to nanotech [Sep 2007 – materials,physics]

Two back-to-back papers published by IBM scientists could herald the long-awaited advent of molecular or nanotech computing devices. …

ChemModLab Enters ChemSpider Web

A new project that combines work from two distinct cheminformatics groups will form a new system for the delivery of modeling and identification of commercially available compounds for biological testing.

The North Carolina State University Exploratory Center for Cheminformatics Research group, developed ChemModLab to compute quantitative structure-activity relationship (QSAR) models and this will be pulled together with the almost 18million structures currently in the ChemSpider database. These structures are sourced from the scientific literature, chemistry database providers and commercial chemical vendors and screening library providers.

“This data collection provides an ideal basis for combing the QSAR capabilities of ChemModLab with the compound collection and indexing of ChemSpider to allow identification of virtual hit compounds via in silico screening, says ChemSpider boss Antony Williams.

Office depot

Some of us are old enough to recall a time when forward-thinking TV shows like the BBC’s classic Tomorrow’s World promised us the “paperless” office. This was during a period of massive technological development when mainframe computers were coming to the fore and the very first personal computer was being hinted at. It seems that the paperless office never happened. By the time I’d left University and started work in a publishers there was more paper than ever, almost every document was either faxed, duplicated or printed out using the new-fangled laserjet printers that nudged out the dot-matrix machines just as I arrived…

Even today, with everyone existing in a virtual second world and doing far more online than ever before offices are still piled high with email printouts and memos, and downloaded computer software manuals that simply must be printed for easy reading by the less technophilic members of staff. Maybe there will come a time when we have a chip embedded in a temple at birth and it links us up directly with all those invaluable Web 4.0 services we’ll be using by then…but you can bet your life there will still be someone demanding a printout. I hate to think where they’ll stick the ink cartridges.

Droning On About Bee Chemistry

 9-oxo-2-decenoic acid structure

Not spiders, but bees. Researchers at the University of Illinois Urbana-Champaign have identified an odorant receptor that allows male bee drones to find a queen in flight. The receptor is present on the male antennae and can detect an available queen up to 60 metres away, which is quite a feat in chemical detection. This is the first time an odorant receptor has been linked to a specific pheromone in honey bees.

The “queen substance”, a pheromone, was first identified decades ago, but scientists have only recently begun to understand its structure and its role in hive life. The pheromone is a primary source of the queen’s authority. It is made up of eight components, one of which, 9-oxo-2-decenoic acid (9-ODA), attracts the drones during mating flights. It also draws workers to the queen and retards their reproductive growth.

More on this direct from Illinois

MMR and Statistical Manipulation

Measles virus

When I was still at high school, way back in the late 1970s, there was a health scare that got a lot of media attention. Apparently, there was a perceived risk that the whooping cough vaccine could cause brain damage. The fall off in vaccination for this disease is claimed to have led to the widespread outbreaks of whooping cough in 1979 and 1982, there having previously been almost zero annual cases. At the peak there were some 60,000 cases.

Fast forward to the near present and you will recall similar scare stories about the combined measles-mumps-rubella vaccine, the MMR, and claims by researcher Andrew Wakefield (Lancet, 1998) that MMR could cause autism in some children. It’s a topic guest blogger Michael Marshall covered on Sciencebase in November 2004. It seemed that, at the time, the debate was pretty much over. However, despite repeated demonstrations of the apparent inadequacies of the original research into a link between MMR and autism, the issue is resurrected on a regular basis. Most recently in a cover story in The Observer, which drew much flack, but also left the chattering classes once more in a flap.

Right now, I’m looking at an article from the print edition of The Times offering an answer to the Question of the Week – “Measles or vaccine?” – the article talks of how measles has reappeared and it is apparently all down to many parents’ reluctance to have their children vaccinated with the MMR jab. The article talks of “herd immunity” and how enough children have had a double dose of MMR which should stave off an epidemic. The emergence of herd immunity, of course, will be little comfort for a parent whose child experience any of the potentially severe side-effects of vaccination.

In the article, pictured alongside a blow-up of the measles virus and an image of a nasty-looking hypodermic needle, are two charts, one showing the number of cases of measles in the UK from 1940 to the present day and the other showing the number of deaths over the same period. Incidence of the disease ebbed and flowed during the period up to the early 1970s whereupon cases began to fall rapidly from a peak of 800,000 a year in the early 1960s to just one or two hundred a year by the mid-1970s.

The MMR vaccine was introduced in the US in 1971 and later in the UK, thereafter incidence of measles has pretty much fallen to levels close to zero. It seems that the pre-vaccine drop had another cause, presumably reduced overcrowding, improved nutrition, better hygiene and healthcare. No one knows at what point this fall would have reached a plateau.

In contrast, the second chart of death rates shows an exponential decline in measles deaths since the 1940s, by about 1970 measles deaths were also close to zero. The risk of getting measles is about one in three, assuming no vaccination coverage at all. The risk of serious consequences to this disease, which personally I had in 1972 or thereabouts, is somewhere between 1 in 5000 and 1 in 15,000. Compare that to the risk of death in a road accident. According to Transport2000 , the UK’s national environmental transport body, each of us has a 1 in 17 chance of being killed or seriously injured in a road crash during our lives. Such figures damn the disease statistics somewhat. Of course, vaccination does come with some risks, but adverse reactions, such as seizures with an associated risk of brain damage, exist at the 1 in 10,000 level.

There has been one UK death from measles since 1992 (as opposed to the several hundred each year during the 1940s). The unfortunate victim was apparently suffering an underlying lung disease for which he required long-term immunosuppressant drugs. He was very unfortunate to be exposed to the measles virus, and when he contracted the disease he was very unlikely to have recovered. This is one fatal case. Even with near 100% vaccination, there would still be a finite risk of any random member of the population contracting the disease. Unfortunate, but true. The statistics would not lie surely?

Googling InchiKeys

What it is to be an InChI – at once unique and representative of so much and yet meandering and potentially far too long. Now, IUPAC has launched a new version – InChIKey – a condensed version of the InChI chemical identifier that will be a fixed 25-characters long.

This new format will make searching for molecules on the web much simpler by preventing unpredictable breaks that happen with the conventional seemingly endless InChI strings for some of the more complex compounds. It will thus facilitate a web-based InChI lookup service and allow InChI to be stored in fixed length database fields and so make chemical structure database indexing far easier. One of the most important aspects of this new approach to the InChI is that it will allow verification of InChI strings across networks. Imagine the woe, for instance, if the tail of your Viagra InChI were cropped short in transmission…

IUPAC admits that there is a finite, but very small probability of finding two structures with the same InChIKey. The odds are of the order of billions to one against, but chemists are making more and more new substances as we speak so you never know when there might be a data collision. It is very, very unlikely, however.

The new release can be downloaded from the IUPAC web site (www.iupac.org/inchi). What effect this will have on my passwords for chemists idea, I simply don’t know!

My Grid Luxuries and Ontologies

myGrid SCUFL

Grid computing, in which clusters of computers or vast distributed networks, often connected through links far faster than conventional internet pipes are now allowing scientists, engineers, clinicians, designers, and others to access distributed databases, powerful computing resources and instrumentation and so creating opportunities for faster, better or different approaches to research.

Grid computing allows scientists to collaborate more effectively than ever before, sharing, data and knowledge. Until recently, however, much of the developments had focused on storage, computation, and resource management. The myGrid project concentrates on the higher-level components and services that will support the scientific research process itself as well as enabling core scientific collaboration. It will allow dynamic groupings to tackle research problems and provide a workbench for the e-scientist that will underpin the scientific process for many researchers.

Writing today in the International Journal of Bioinformatics Research and Applications (2007, 3, 303-325), Katy Wolstencroft, Pinar Alper, Duncan Hull, Robert Stevens, and Carole Goble of The School of Computer Science, at the University of Manchester, Christopher Wroe of BT Global Services, London (previously at Manchester), and Philip Lord of The School of Computing Science, at the University of Newcastle upon Tyne explain how myGrid supports in silicolife sciences research, computational experiments, in other words. The project essentially focuses on bioinformatics, which uses the rich data of genomes and gene function, to help scientists understand life.

Bioinformaticians chain database searches and analytical tools using often complex scripts or workflows to extract knowledge and information. These “in silico” experiments use different interfaces and data formats but myGrid is using a special workflow language (SCUFL) to capture data and bring disparate resources together. It does this by presenting them directly as Web Services or as components within a single framework. Workflows can then be shared, reused and adapted by collaborating users. A single query will meet a user’s needs once all the relevant resources are Grid-enabled.

In addition, the myGrid Information Repository (mIR) is a central component that allows a team to preserve, organize and share their data and metadata – data about data. Principal among the data are the laboratory results that will comprise the input to workflows, the workflows themselves and their outputs. Provenance information – the “who, how, what, where, and when” information – is just as important as workflows and their results. Such information is routinely collected in bench experiments but now myGrid allows users to capture provenance information as metadata stored in the mIR for their in silico experiments. The workflow enactor builds a provenance record identifying precise service details, date and time of execution and intermediate results.

As a practical application of myGrid, the team worked with researchers at Newcastle University’s Centre for Life to investigate the genetic background to Graves’ disease, the leading cause of hyperthyroidism. This study of Graves’ disease involves a combination of experiments at the laboratory and bioinformatics experiments, in the form of workflows performed in silico. The myGrid team has developed a set of workflows that take the results of bench experiments and help the researchers choose follow-up experiments.

In the current research paper, the team points out that there are about 3000 services (including web services) offering programmatic access to bioinformatics resources. “The distribution and frequent lack of documentation, however, creates the requirement for easy service discovery,” they explain. In other words there are thousands of services available for solving problems in the life sciences but most of the scientists who might make use of them in their research do not even know that many of them even exist. “If services are available but unknown to the user, the advantages gained from using web service technology could be lost,” Wolstencroft and colleagues explain, “This drives the need for the myGrid ontology of services. In computing, an ontology is basically an annotated list of everything and how each item is related to the others.

The team has designed the myGrid ontology to help life scientists find all these various web services in the area of bioinformatics. The ontology has evolved since inception and new ways to exploit and adapt it have been discovered along the way. The main conclusion, the researchers draw from their efforts is that ontologies are an essential component for service discovery and interpretation. Without ontologies, many of the resources and services out there will remain hidden and essentially unused by the life sciences community.

In practice, the automated discovery of services usually requires a fine-grained description, ontology reasoning, and ranking of discovered matches. In contrast, a scientist doing the search requires course-grained matches and a short list of services that they can then investigate further until they find the best hit for their research project. Underpinning the success is expert curation of the services and key to the success of that is the development of a way to standardise the annotations associated with each entry in the ontologies, or at the very least the development of a standardised way of interpreting those annotations. “Our experiences have shown that using an ontology for service discovery is not a luxury, but a requirement,” the researchers conclude.

Further Reading: Workflows for E-science: Scientific Workflows for Grids

Painkiller Slows Bone Growth

Paracetamol structure, Tylenol

A press release just in announced that “Paracetamol, one of most used analgesics, could slow down bone growth”. In vitro tests apparently demonstrated that the compound slows bone regeneration in the proverbial test-tube.

The press release writer missed a serious trick in using the word paracetamol throughout and not mentioning some of the proprietary formulations of the analgesic, which include the far more familiar names Tylenol, Acetaminofen, Acetaminophen, and Amadil, it may be picked up by the US media with that name, but I suspect a headline mentioning Tylenol would be a far stronger grab.

Olga García Martínez of the Departamento de Enfermeria at the University of Granada and colleagues based their analysis on several clinical processes in which accelerating bone growth is required. “Certain anti-inflammatories such as paracetamol should be cautiously taken, especially in situations in which require a rapid bone tissue regeneration, such as after placement of a prosthesis or dental implant is needed,” she says. Other anti-inflammatories that have no such effect on bone growth should be used instead.

The research has not been confirmed in people yet, but somehow the tests on isolated osteoblasts are taken as definitive evidence that the drug will slow bone regeneration in vivo.

Post-Labor Day SpectroscopyNOW

Earth's core

My latest science news round-up for SpectroscopyNOW.com is now live:

The problem of the core – Understanding how the bulk iron at the earth’s core is packed together and with what other lighter elements is critical to revealing the origins and evolution of the earth and precisely how it generates its magnetic field.

Fluorinated agents at the ready Intrusive biopsies for people with cancer could be sidestepped thanks to the development of fluorine-containing contrast agents by David Parker and colleagues at Durham University.

Baby light – Near-infrared light could allow researchers to see activity within the infant brain even while the tot wriggles and giggles.

High-field NMR morphs caffeine structure – High-field NMR has overcome the problem of spectral ambiguity in nitrogen-rich compounds, thanks to efforts by Canadian scientists. The team has studied two anhydrous polymorphs of the stimulant, caffeine, and has found that, despite extensive disorder, both caffeine polymorphs reveal the characteristic structural signatures of crystalline compounds.

Diamonds out of Hades – Raman spectroscopy could turn the history of the early Earth upside down and hint that conditions were suitable for life as little as 250 million years after its formation, pushing back the so-called Hadean era several hundred million years.

Sweet nanoreactor – A one-pot chemical reaction system based on nanoscopic capsules embedded in a polymer membrane has been devised by researchers in The Netherlands. The nanoreactor system allows cascade reactions to be carried out that would otherwise require multiple distinct reaction steps with time-consuming and wasteful separation and purification stages.

ChemAxon Hits a Nerve

ChemAxon recently announced version 2 of its Instant JChem, a desktop application for working with chemical and
other data on local and remote databases. Version 2 adds forms and form building, relational data support, advanced query
building and multiuser access.

Instant JChem is a software application for all major operating systems which bundles ChemAxon’s Marvin and JChem enterprise cheminformatics toolkits with a local database engine to give an ‘out of the box’ solution for research informatics. Personal use is free, although if you want to go “enterprise” you will have to check out their price list.