869 research outputs found

    Evolutionary Biology and Drug Development

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    Evolutionary rates at codon sites may be used to align sequences and infer protein domain function

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    <p>Abstract</p> <p>Background</p> <p>Sequence alignments form part of many investigations in molecular biology, including the determination of phylogenetic relationships, the prediction of protein structure and function, and the measurement of evolutionary rates. However, to obtain meaningful results, a significant degree of sequence similarity is required to ensure that the alignments are accurate and the inferences correct. Limitations arise when sequence similarity is low, which is particularly problematic when working with fast-evolving genes, evolutionary distant taxa, genomes with nucleotide biases, and cases of convergent evolution.</p> <p>Results</p> <p>A novel approach was conceptualized to address the "low sequence similarity" alignment problem. We developed an alignment algorithm termed FIRE (<b><it>F</it></b>unctional <b><it>I</it></b>nference using the <b><it>R</it></b>ates of <b><it>E</it></b>volution), which aligns sequences using the evolutionary rate at codon sites, as measured by the <it>dN</it>/<it>dS </it>ratio, rather than nucleotide or amino acid residues. FIRE was used to test the hypotheses that evolutionary rates can be used to align sequences and that the alignments may be used to infer protein domain function. Using a range of test data, we found that aligning domains based on evolutionary rates was possible even when sequence similarity was very low (for example, antibody variable regions). Furthermore, the alignment has the potential to infer protein domain function, indicating that domains with similar functions are subject to similar evolutionary constraints. These data suggest that an evolutionary rate-based approach to sequence analysis (particularly when combined with structural data) may be used to study cases of convergent evolution or when sequences have very low similarity. However, when aligning homologous gene sets with sequence similarity, FIRE did not perform as well as the best traditional alignment algorithms indicating that the conventional approach of aligning residues as opposed to evolutionary rates remains the method of choice in these cases.</p> <p>Conclusions</p> <p>FIRE provides proof of concept that it is possible to align sequences and infer domain function by using evolutionary rates rather than residue similarity. This represents a new approach to sequence analysis with a wide range of potential applications in molecular biology.</p

    The concepts and origins of cell mortality

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    Organismal death is foundational to the evolution of life, and many biological concepts such as natural selection and life history strategy are so fashioned only because individuals are mortal. Organisms, irrespective of their organization, are composed of basic functional units—cells—and it is our understanding of cell death that lies at the heart of most general explanatory frameworks for organismal mortality. Cell death can be exogenous, arising from transmissible diseases, predation, or other misfortunes, but there are also endogenous forms of death that are sometimes the result of adaptive evolution. These endogenous forms of death—often labeled programmed cell death, PCD—originated in the earliest cells and are maintained across the tree of life. Here, we consider two problematic issues related to PCD (and cell mortality generally). First, we trace the original discoveries of cell death from the nineteenth century and place current conceptions of PCD in their historical context. Revisions of our understanding of PCD demand a reassessment of its origin. Our second aim is thus to structure the proposed origin explanations of PCD into coherent arguments. In our analysis we argue for the evolutionary concept of PCD and the viral defense-immunity hypothesis for the origin of PCD. We suggest that this framework offers a plausible account of PCD early in the history of life, and also provides an epistemic basis for the future development of a general evolutionary account of mortality

    Niobium sputter-coated copper resonators

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    Niobium sputter-coated copper resonators are successfully employed in operating particle accelerators, the most outstanding example being LEP2 at CERN. In this review we present recent progress in the understanding of the basic principles governing their behaviour, based on an extensive R&D programme carried out at CERN on 1.5 GHz resonators operated in the TM010 mode. At the present stage of the s tudy, no fundamental limitation has been found which would prevent the use of this technology for future high-field, high-Q accelerating cavities

    Magnetic flux trapping in superconducting niobium

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    In a systematic study of the RF response of superconducting niobium cavities operated in their fundamental TM010 mode at 1.5 GHz, magnetic flux trapping has been used as a tool to diagnose the presenc e of pinning centres. In addition to bulk niobium cavities the study covers copper cavities, the inner walls of which are coated with 1.5 ”m thick niobium films grown by magnetron sputtering in a nobl e gas atmosphere. The use of different gases (Xe, Kr, Ar and Ne) or gas mixtures has made it possible to vary the concentration of noble gas atoms in the films. Film contamination is characterised by an electron mean free path l calculated from the results of systematic measurements of the penetration depth at T = 0 K, l0, and from RRR measurements made on samples prepared under similar conditions as the cavity films

    Tracking River Flows from Space

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    Satellite observations, combined with algorithms borrowed from river engineering, could fill large gaps in our knowledge of global river flows where field data are lacking

    Structural and RF properties of niobium films deposited onto annealed niobium resonators

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    Studies have been performed on the properties of niobium thin films sputtered onto solid niobium TM010 resonators at 1.5 GHz. The purpose of the work is to study the behaviour of the film's RF and str uctural properties as a function of heat treatment temperature in order to determine if and at what treatment temperature the properties of the films merge with those of the bulk. Niobium resonators h ave been heat treated at temperatures up to 1100°C in a vacuum furnace inside a niobium box surrounded by a titanium gettering protection. Subsequently, they have been sputter coated with a niobium fi lm. Following RF measurements of the coated resonators, the cavities have undergone heat treatments as described above at 800°C, 900°C, 1000°C and 1100°C, each time followed by RF measurements. Before heat treatment, the RF response of the film was similar to that of a film coated on a copper substrate. A marked transition towards bulk-like RF behaviour was observed after the 900°C treatment. The c hanges include a sharp variation of the BCS resistance and of the sensitivity to externally applied magnetic field, quantities believed to be closely linked to the amount and nature of defects in the coating

    Amplitude equations for systems with long-range interactions

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    We derive amplitude equations for interface dynamics in pattern forming systems with long-range interactions. The basic condition for the applicability of the method developed here is that the bulk equations are linear and solvable by integral transforms. We arrive at the interface equation via long-wave asymptotics. As an example, we treat the Grinfeld instability, and we also give a result for the Saffman-Taylor instability. It turns out that the long-range interaction survives the long-wave limit and shows up in the final equation as a nonlocal and nonlinear term, a feature that to our knowledge is not shared by any other known long-wave equation. The form of this particular equation will then allow us to draw conclusions regarding the universal dynamics of systems in which nonlocal effects persist at the level of the amplitude description.Comment: LaTeX source, 12 pages, 4 figures, accepted for Physical Review

    An 11th century a.d. burnt granary at La Gravette, south-western France : preliminary archaeobotanical results

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    International audienceA thick layer of carbonised seeds was encountered in an 11th century a.d. room situated in the seigneurial part of the village of La Gravette. This paper presents the first results of charcoal and seed analyses which give information on the food products stored in the granary and on their arrangement there. Triticum aestivum/durum/turgidum was by far the most important stored crop, while Avena sp., then Hordeum vulgare, Secale cereale, Triticum monococcum and Vitis vinifera were secondary. Weeds were poorly represented. Charcoals were dominated by deciduous Quercus sp., and 11 additional wood taxa were recorded, including especially Fagus sylvatica, Fraxinus sp., Rosaceae, Corylus avellana, Acer campestre and Ulmus sp. According to the charcoal distribution, Quercus and Fagus were probably building materials while most of other taxa would have been used for basketry, wattling or joinery work. In the western part of the granary, naked wheat was stored in bulk. In the eastern part, various crops (at least naked wheat, barley, rye, oat and grape) were stored in small amounts, most of which were probably separated by light wooden structures. The cereal crops had largely been processed and cleaned. The stored products probably represent taxes paid to the lord who owned the granary
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