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!
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
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 GarcÃÂa MartÃÂnez 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.
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 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.
TL:DR – Cocoa beans, and so chocolate, can contain a small amount of caffeine despite claims to the contrary.
A front page item on a social bookmarking site claimed that chocolate does not contain caffeine. The link was tied to an introductory paragraph that said: “There is a persistent urban legend that chocolate contains caffeine. It would seem that this rumor is based primarily on a confusion between two similar alkaloids: caffeine and theobromine. Theobromine is the active ingredient in chocolate and it occurs only in [the plant Theobroma cacao. The two stimulants are related and have similar structures.”
Yes, they most certainly do, theobromine (not in any way related to the element bromine by the way) and caffeine are almost the same chemical structure but in the caffeine molecule the hydrogen atom on a nitrogen atom in theobromine has been swapped for a methyl (CH3) group. Why is this important? Well, the difference in chemical and biological activity of two molecules that can differ by a couple of hydrogens and a carbon is astounding. More on that later. What about the site’s claims that chocolate does not contain caffeine?
A quick search on PubMed plucked out several papers all of which have carried out analyses of chocolate to demonstrate that it does indeed contain caffeine. As just one example, in 2006, German researchers Stark, Bareuther, and Hofmann of the German Research Institute for Food Chemistry, in Garching, provided a molecular definition of the taste of roasted cocoa nibs (Theobroma cacao) by means of quantitative studies and sensory experiments. In their paper they state: “theobromine and caffeine…were among the key compounds contributing to the bitter taste of roasted cocoa.” Their tests were carried out using solvent extraction, gel permeation chromatography, and reversed-phase high-performance liquid chromatography (RP-HPLC) and corroborated earlier findings. The actual quantity of caffeine in chocolate is very small, especially compared with the amount of theobromine.
To quote the UK’s Institute of Food Research on the subject of caffeine in chocolate:
“Chocolate contains bio-active compounds, e.g. caffeine and theobromine. Caffeine is only present in small amounts in chocolate – in fact, one would have to eat about eight 100-gram bars of milk chocolate to consume the amount of caffeine present in a cup of coffee. Theobromine is related to caffeine, and is present in chocolate in much higher amounts, although it has relatively weak stimulant effects. It is possible that in combination, these and other potentially bio-active constituents do influence our liking for chocolate. At present, however, there is no direct evidence to support this.”
Caffeine is a bitter-tasting alkaloid, a natural product, a xanthine, found in several plant species, coffee, tea, and cacao. It is a stimulant, like its close chemical cousin, theobromine. There have been dozens of media articles, purportedly based on solid research, that send out mixed messages regarding the health effects of caffeine on people and whether or not we should expose our bodies to this stimulant.
A quick search of the web for cacao theobromine and caffeine reveals several sites warning of the toxicity of stimulants in chocolate, coffee and other products. But, an NIH page also appears that says something along the line of caffeine content need only be reported if levels are above a certain threshold.
Most of us don’t really want to spend 24/7/365 online, occasionally there are times when we need to go, ahem, offline and find a peaceful place to read. Until they come up with a truly portable device that’s as easy to read as a print magazine, print magazines will under certain, ahem, circumstances be what we need.
That said, the chosen reading material can be about online matters, so we don’t need to abandon the online simply because we have to go offline. So, now you can choose from a virtual shelf of free computing magazines to read offline through Sciencebase. I have to admit some of the selection are a bit too esoteric even for an ubergeek like myself. CE Pro (Custom Electronics Professionals) is aimed at helping dealers and installers stay current with products, understand technology and run profitable businesses, not something I really need to read at this time. But, one magazine that should be on everyone’s easy-to-reach magazine rack is PC Magazine.
PC Magazine bills itself as America’s #1 technology magazine, I cannot vouch for that but it does deliver authoritative, lab-based comparative reviews of countless technology products and services. You can get it for free if you’re in the US by filling in the free PC Magazine form here. This is a time-limited offer so you get your free issues and pay a special discounted rate for the additional ones. Check the offer page for more details and the obligatory T&Cs.
Mika Aaltonen of the BIT Research Centre at the Helsinki University of Technology in Finland argues that at the very fundamental level, human beings are storytelling animals, this premise may seem obvious but arises not because we like fairytales and fables but because of the way we perceive cause and effect. By learning from this revelation it might be possible to understand life stories, consciousness, biological systems, climate economic and business models, and countless physical processes that do not follow the simplistic beginning-middle-end narrative model of cause and effect.
Writing today in the International Journal of Management Concepts and Philosophy (2007, 2, 183-193), Aaltonen explains that our current view of causality is seriously limited because of our intrinsic need to frame a sequence of events as a kind of narrative even when such a storytelling approach does not fit with observations. The concept of time is usually used to connect information explain feedback loops and to provide a logical chronology for causes and their effects. However, things are not so simple in the real world.
Firstly, the way we perceive time is different from culture to culture and across human history and comes with its own baggage. For instance, some cultures have no concept of time at all, others see time as a river along which we flow looking to the future while others imagine our walking backwards away from past events. Modern physics too has destroyed any simplistic interpretation of time in relativity, gravitational theory, and quantum mechanics, in which time becomes not a steady stream from alpha to omega but a framework in which are embedded probability waves, matter, and energy.
Secondly, stretching back as far as Aristotle, and perhaps beyond, there were notions of cause not simply being a one thing must follow another scenario. This is not to suggest that there is anything mystical going on, but just that when we lay down strategies and plans these are often engineered again and again from a top-down position, like the re-working of a fairytale or fable. New characters and happenings may be incorporated but the gist of the process is simply to begin with a “Once upon a time…” and to end with an “…and they all lived happily ever after.” This is not the way things really are.
Aaltonen suggests that the discovery of complexity theory in science and the concept of chaotic and nonlinear behaviour show that cause and effect are much more complicated. However, if we can re-engineer the old philosophical tools we might better understand modern problems and find solutions to them. He suggests that there are three drivers, or forces, of causality – final cause, sensitivity to initial conditions, and circular cause.
“More than imagining and presenting the future as an extrapolation of the present, we should be looking for approaches that allow us to see and influence the future by responding to and influencing what is emerging,” Aaltonen told Sciencebase. This is the first force of causality, the sensitivity to initial conditions. The challenge and the inspiration for sense-making and strategic decision-making, he adds, lie in identifying and influencing the initial conditions of a system as they are emerging. We must prepare ourselves for coming change by identifying the initial conditions so we can shape the future to our advantage. We need foresight in other words!
In addition, circular causality can be used to model causal patterns. Activities on the very small scale do give rise to behaviour we can observe on the large scale. “The general term used for this phenomenon is ’emergence’,” explains Aaltonen, “Consciousness is an emergent property of the brain (and the rest of the body), inflation is an emergent property of an economic system, and meaning is an emergent property of language. Emergent properties are not, however, merely effects, there is multi-way communication.” He points out that phenomena on the large scale (macro level) can affect activity on the small scale (micro-level). “Causality,” he adds, “does not simply work from micro-causes to macro-effects. There is also a top-down process at work which means that causality in complex systems is circular.”
He suggests that if something outside an organism is seen as a final cause, a goal or objective, then voluntary behaviour embeds the organism in the environment. “People’s goal-seeking activities become sensitive to final conditions,” he explains. Small variations in the way a larger environment responds can and should dramatically influence how we ourselves respond to those changes. “This way, final cause becomes a target formed from continuous reflection,” he adds.
Understanding the interplay between these three causal forces is key to planning. It is ironic, he says, that we seem to place a natural emphasis on stories as efficient tools for understanding the world, given that strong stories of the past and the future themselves focus our attention and goals and so are reductive in nature, essentially bringing nothing new to the table.
“There is a need to integrate multiple views into strong and dominant stories and into sensemaking in order to add sensitivity to our understanding of the changes occurring in our world,” he argues. Moreover, strong stories actually drive us towards unobtainable goals in almost every walk of life whereas the essential properties of final cause, sensitivity to initial conditions and circular cause and their interplay demonstrate that causal relationships are shifting shapes in a nonlinear world. “If we are to understand the environments we live in, we require approaches that are reflexive, self-critical and nonlinear,” Aaltonen adds. That sentiment applies equally to stifling poverty and responding to climate change, managing a business or carrying out a scientific experiment.
As regular Sciencebase readers will know, I write a regular chemistry news round-up for ChemWeb under the plome-de-nume of The Alchemist. This is the latest incarnation of a column I first wrote for the original ChemWeb.com almost a decade ago. ChemWeb is now owned by chemical industry search engine chemindustry.com, which is fast developing the site into an indispensable resource for anyone working in the chemical sciences.
Anyway, here is a summary of the latest Alchemist chemistry news headlines.
This week, iron and chemical education skills are rewarded, while analytical and synthetic efforts finally pay off after almost four decades or work on a natural insecticide with the first total synthesis of the neem tree extract azadirachtin. The Alchemist also discovers that diamonds really are almost forever and nanoscopic polymer capsules can facilitate one-pot cascading biotransformations. Finally, a new range of fluorinated contrast agents for medical imaging could make cancer diagnostics stick and computational developments on actinide compounds could revolutionize our understanding of the chemistry of radioactive materials. That synthetic odyssey undertaken by Steve Ley and colleagues at Cambridge University to synthesise azadirachtin will feature in more detail here in a forthcoming post.
Sciencebase Exclusive – Careful experimentation and theoretical analysis of a double-slit experiment have finally quashed a controversy in fundamental physics — the complementarity-uncertainty debate.
Ever since the catflap to the quantum world was opened up to us and Schrödinger’s feline friend was idiomatically let out of the bag, to mix a metaphor or two, there have been more questions and controversies raised than conundrums solved in the world of the very, very small. How can something be both particle and wave, for instance? What allows particles of matter to tunnel through solid objects? And, how is the interference pattern destroyed in a double-slit experiment when measurements are performed on the path traversed by a particle?
What is a double slit experiment, you ask? Well, traditionally, Young’s double-slit experiment consists of shining a light through two narrow, closely spaced slits and observing the results on a screen placed beyond the slits.
Intuitively, you might think that the result would simply be two bright lines, aligned with the slits, representing where the light passes through the slits and hits the card. However, this is not seen in practice, instead, the light is diffracted by the slits and produces fringes corresponding to wave-like interference pattern. The fringes of light and dark regions correspond to where either the light waves constructively (add) and destructively (subtract) from each other. Two peaks in the light wave meet to make a brighter fringe whereas a dark fringe is formed when a peak and a trough coincide. This result seemingly settles a three-century conundrum about whether light is particle or wave, showing apparently that it is a wave.
However, a similar experiment carried out with beams of electrons or atoms fired through the slits produces a very similar interference pattern. How could that be? Particles are solid objects, surely? Well, the double-slit experiment shows that they are not. They produce an interference pattern, which suggests that the particles behave as waves.
The double-slit experiments work perfectly well and reveals interference patterns with light, electrons, and beams of other particles, but only if the experimenter does not try to find out through which slit a particular wave-particle passed before hitting the screen. Try to fire particles through the slits one at a time and as illustratd in the 5-minute video below, you will still see an interference pattern. It is as if each particle passes through both slits simultaneously, each slit individually and together and neither slit all at the same time; behaving some as waves…
As if this were not complicated enough, physicists reasoned that if they could discover which slit the individual particle really goes through each time in this experiment, they could solve the problem. So, they put a measuring device next to one slot and observed what happens as particles are fired through the slits one at a time. Astoundingly, the interference pattern disappears, simply having a measuring device present to observe the route taken by the particles somehow disturbs their wave-like nature and they revert to being tiny, solid objects and produce just two bands on the screen as if they were tiny marbles rather than wave. How could the particles know they were being watched.
This loss of interference has been explained by several of the biggest names in twentieth century physics, among them Niels Bohr and Richard Feynman. They suggested that whenever the path is measured within the double-slit, the momentum of the wave-particle is uncontrollably and irreversibly disturbed. Think about it, it has to be affected by the observer somehow because the very act of observing involves some kind of sharing of information either via photons, charge, energy or matter. This process “washes out” the interference fringes.
Most physicists simply accept this as being precisely what happens. It is a little vague and some might say “handwaving” because it does not pin down the nature of this washing out nor say anything about how the momentum is disturbed by the transaction between observer and observed. More precisely, it is simply what happens because of the back-reaction resulting from the Heisenberg uncertainty relation that says we cannot know simultaneously both the energy and position of any quantum wave or particle with absolute precision. While that kind of folds the argument into a loop, Feynman famously pointed out that, ‘No one has ever thought of a way around the uncertainty principle.’
But, not everyone was happy with this. In 1991, Marlan Scully, Berthold-Georg Englert, and Herbert Walther (Nature 1991, 351, 111) suggested that a microscopic pointer could be used to carry out the observation in such a way that the very act of observation would not disturb the momentum of the particle and so bypass the uncontrollable and irreversible effects suggested by Bohr that leads to interference breakdown. However, Pippa Storey, Sze Tan, Matthew Collett, and Daniel Walls (Nature, 1994, 367, 626), countered this argument, demonstrating that no matter how small the observer nor how the measurements are made, momentum is affected and the interference pattern would disappear. A long and controversial debate has raged between the two scientific factions that back either the Scully or Walls teams.
A theoretical solution was posited by Howard Wiseman and colleagues in 2003 (Phys Rev A, 2003, 311, 285) and refined in 2004 (J. Opt. B: Quant. Semiclass. Opt. 2004, 6, S506-S517). Now, in a seminal paper published today in the New Journal of Physics, Aephraim Steinberg together with Wiseman and colleagues Mir, Lundeen, Mitchell, and Garretson have applied the theory in a novel double-slit setup. Their experimental results suggest that, as is the way with all things quantum, both camps are equally correct and equally wrong. Somehow, you can have your quantum cake and eat it.
They found that by using only weak measurements, they can directly observe the momentum transfer that causes interference breakdown but equally do so without disturbing the two-slit superposition. They effectively verify both the Scully and Walls views. In terms of the Scully position, the team shows that there is no change in the mean momentum, or the mean energy, whereas with respect to the Walls work, they show that the momentum is spread, as one would expect given the uncertainty inherent in the quantum world, according to Heisenberg’s principle.
Feynman always held that the double-slit setup was central to quantum theory, but would never be fully understood. This work by Wiseman and colleagues shows that the humble double-slit experiment can still throw up new quantum mysteries to baffle us.
Marlan Scully, Berthold-Georg Englert, and Herbert Walther (Nature 1991, 351, 111) suggested that a microscopic pointer could be used to carry out the observation in such a way that the very act of observation would not disturb the momentum of the particle and so bypass the uncontrollable and irreversible effects suggested by Bohr that leads to interference breakdown. However, Pippa Storey, Sze Tan, Matthew Collett, and Daniel Walls (Nature, 1994, 367, 626), countered this argument, demonstrating that no matter how small the observer nor how the measurements are made, momentum is affected and the interference pattern would disappear. A long and controversial debate has raged between the two scientific factions that back either the Scully or Walls teams.
Howard Wiseman and colleagues in 2003 (Phys Rev A, 2003, 311, 285) and refined in 2004 (J. Opt. B: Quant. Semiclass. Opt. 2004, 6, S506-S517). Now, in a seminal paper published today in the New Journal of Physics, Aephraim Steinberg together with Wiseman and colleagues Mir, Lundeen, Mitchell, and Garretson have applied the theory in a novel double-slit setup. Their experimental results suggest that, as is the way with all things quantum, both camps are equally correct and equally wrong. Somehow, you can have your quantum cake and eat it.