The analysis of Raman optical activity spectra of proteins

Measurement of the Raman optical activity (ROA) spectra of biomolecules has become an experimental possibility due to significant advances in the available technology, and its successful implementation into the ROA instruments at the University of Glasgow. The ease with which the ROA spectra of biological molecules can be successfully measured lends itself perfectly to the ever-growing demand for biomolecular structural information, especially in the context of proteomics and the Human Genome Project. ROA spectroscopy is able to probe the chiral peptide backbone of proteins, and as such the ROA spectrum of a protein contains a wealth of structural information from within the whole molecule, across the whole vibrational spectrum. As well as containing detailed information from specific structural elements such as sections of secondary structure and motifs, the ability of ROA to see the molecule as a whole also enables the global fold of the protein to be deduced from the ROA spectrum. The development of the analysis of ROA spectra has largely been based upon the correlation of ROA spectra of proteins of known structure with structural information from alternative sources, chiefly X-ray crystallography and multidimensional nuclear magnetic resonance (NMR). As the database of ROA spectra of polypeptides and proteins has grown, it has been possible to tighten up the assignment of ROA spectral bands and band patterns to aspects of known structural content. With a basis for the correlation between the ROA spectrum and the known crystal structure (or NMR structure) being well established, it is possible to interpret the ROA spectra of proteins that do not have (for whatever reason) well defined structures. This means that ROA spectroscopy can provide invaluable structural information for proteins that are precluded from analysis by other techniques, and also cast new light on the structures of proteins that have not been well defined. In order to fully interpret an ROA spectrum of a protein, it is necessary to be familiar with protein structure and the ROA experiment as a whole. Analysing an ROA spectrum is a detailed and highly subjective process. Depending on the experience of the analyst, the information contained within the spectra can be extracted readily or not so readily. For this reason, it would be desirable to develop a technique that is capable of interpreting not only individual spectra, but also whole data sets in a manner that is independent of the analyst, and therefore independent of any preconceptions (or inexperience) the analyst may have. This project presents an up-to-date collection of newly obtained ROA spectra of a large number of proteins across a range of structural class types. In addition, the statistical technique of principal component analysis (PflA) has been used as a tool for the analysis of this new data. It is hoped that the result of this work will provide a basis for the future analysis of protein ROA spectra that is both mathematically rigorous and convenient

Frustration of crystallisation by a liquid–crystal phase

Frustration of crystallisation by locally favoured structures is critically important in linking the phenomena of supercooling, glass formation, and liquid-liquid transitions. Here we show that the putative liquid-liquid transition in n-butanol is in fact caused by geometric frustration associated with an isotropic to rippled lamellar liquid-crystal transition. Liquid-crystal phases are generally regarded as being “in between” the liquid and the crystalline state. In contrast, the liquid-crystal phase in supercooled n-butanol is found to inhibit transformation to the crystal. The observed frustrated phase is a template for similar ordering in other liquids and likely to play an important role in supercooling and liquid-liquid transitions in many other molecular liquids

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9(HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P = 1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Incarceration humane and inhumane Human values and health care in British prisons

Proceedings of a conference held by the Human Values in Health Care Forum, London (GB), Dec 1997SIGLEAvailable from British Library Document Supply Centre-DSC:6184.4135(11) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Surface-enhanced coherent anti-Stokes Raman imaging of lipids

This work describes in detail a wide-field surface-enhanced coherent anti-Stokes Raman scattering (CARS) microscope, which enables enhanced detection of sample structures in close proximity (∼100  nm) of the substrate interface. Unlike conventional CARS microscopy, where the sample is illuminated with freely propagating light, the current implementation uses evanescent fields to drive Raman coherences across the entire object plane. By coupling the pump and Stokes excitation beams to the surface plasmon-polariton mode at the interface of a 30 nm thick gold film, we obtained strong CARS signals from cholesteryl oleate droplets adhered to the surface. The surface-enhanced CARS imaging system visualizes lipid structures with vibrational selectivity using illumination doses per unit area that are more than four orders of magnitude lower than in point-scanning CARS microscopy

Order Parameter of the Liquid–Liquid Transition in a Molecular Liquid

Liquid–liquid transitions (LLTs) between amorphous phases of a single (chemically unchanged) liquid were predicted to occur in most molecular liquids but have only been observed in triphenyl phosphite (TPP) and <i>n</i>-butanol, and even these examples have been dismissed as “aborted crystallization”. One of the foremost reasons that LLTs remain so controversial is the lack of an obvious order parameter, that is, a physical parameter characterizing the phase transition. Here, using the technique of fluorescence lifetime imaging, we show for the first time that the LLT in TPP is characterized by a change in polarity linked to changes in molecular ordering associated with crystal polymorphs. We conclude that the LLT in TPP is a phase transition associated with frustrated molecular clusters, explaining the paucity of examples of LLTs seen in nature

Moving reflections Gender, faith and aesthetics in the work of Angela Figuera Aymerich

SIGLEAvailable from British Library Document Supply Centre-DSC:D063484 / BLDSC - British Library Document Supply CentreGBUnited Kingdo