Automated generation of heuristics for biological sequence comparison

BACKGROUND: Exhaustive methods of sequence alignment are accurate but slow, whereas heuristic approaches run quickly, but their complexity makes them more difficult to implement. We introduce bounded sparse dynamic programming (BSDP) to allow rapid approximation to exhaustive alignment. This is used within a framework whereby the alignment algorithms are described in terms of their underlying model, to allow automated development of efficient heuristic implementations which may be applied to a general set of sequence comparison problems. RESULTS: The speed and accuracy of this approach compares favourably with existing methods. Examples of its use in the context of genome annotation are given. CONCLUSIONS: This system allows rapid implementation of heuristics approximating to many complex alignment models, and has been incorporated into the freely available sequence alignment program, exonerate

Hall Normalization Constants for the Bures Volumes of the n-State Quantum Systems

We report the results of certain integrations of quantum-theoretic interest, relying, in this regard, upon recently developed parameterizations of Boya et al of the n x n density matrices, in terms of squared components of the unit (n-1)-sphere and the n x n unitary matrices. Firstly, we express the normalized volume elements of the Bures (minimal monotone) metric for n = 2 and 3, obtaining thereby "Bures prior probability distributions" over the two- and three-state systems. Then, as an essential first step in extending these results to n > 3, we determine that the "Hall normalization constant" (C_{n}) for the marginal Bures prior probability distribution over the (n-1)-dimensional simplex of the n eigenvalues of the n x n density matrices is, for n = 4, equal to 71680/pi^2. Since we also find that C_{3} = 35/pi, it follows that C_{4} is simply equal to 2^{11} C_{3}/pi. (C_{2} itself is known to equal 2/pi.) The constant C_{5} is also found. It too is associated with a remarkably simple decompositon, involving the product of the eight consecutive prime numbers from 2 to 23. We also preliminarily investigate several cases, n > 5, with the use of quasi-Monte Carlo integration. We hope that the various analyses reported will prove useful in deriving a general formula (which evidence suggests will involve the Bernoulli numbers) for the Hall normalization constant for arbitrary n. This would have diverse applications, including quantum inference and universal quantum coding.Comment: 14 pages, LaTeX, 6 postscript figures. Revised version to appear in J. Phys. A. We make a few slight changes from the previous version, but also add a subsection (III G) in which several variations of the basic problem are newly studied. Rather strong evidence is adduced that the Hall constants are related to partial sums of denominators of the even-indexed Bernoulli numbers, although a general formula is still lackin

A formal asymmetric synthesis of both enantiomers of the Erythrina Alkaloid 3-Demethoxyerythratidinone

A formal asymmetric synthesis of both enantiomers of the Erythrina alkaloid 3- demethoxyerythratidinone is reported through the application of a highly functionalised lactam template as an N-acyliminium precursor

Effect of Training Phase on Physical and Physiological Parameters of Male Powerlifters

Longitudinal research on training and dietary practices of natural powerlifters is limited. This study investigated the effect of phases of training on physical and physiological parameters in male natural powerlifters. Nine participants completed testing at two time points: (i) preparatory phase (~3 months prior to a major competition) and (ii) competition phase (1–2 weeks from a major competition). No significant changes between training phases were found for muscle strength and power. A trend for significance was found for decreased muscle endurance of the lower body (−24.4%, p = 0.08). A significant increase in leg lean mass was found at the competition phase (2.3%, p = 0.04), although no changes for other body composition measures were observed. No change was observed for any health marker except a trend for increased urinary creatinine clearance at the competition phase (12.5%, p = 0.08). A significant reduction in training volume for the lower body (−75.0%, p = 0.04) and a trend for a decrease in total energy intake (−17.0%, p = 0.06) was observed during the competition phase. Despite modifications in training and dietary practices, it appears that muscle performance, body composition, and health status remain relatively stable between training phases in male natural powerlifters

Quantum phases in artificial molecules

The many-body state of carriers confined in a quantum dot is controlled by the balance between their kinetic energy and their Coulomb correlation. In coupled quantum dots, both can be tuned by varying the inter-dot tunneling and interactions. Using a theoretical approach based on the diagonalization of the exact Hamiltonian, we show that transitions between different quantum phases can be induced through inter-dot coupling both for a system of few electrons (or holes) and for aggregates of electrons and holes. We discuss their manifestations in addition energy spectra (accessible through capacitance or transport experiments) and optical spectra.Comment: 29 pages, 8 figures (ps and eps), LaTeX 2e, ELSART package. To appear in Solid State Communications - Special Issue on Spin Effects in Mesoscopic System

Neuron type-specific increase in lamin B1 contributes to nuclear dysfunction in Huntington's disease

Lamins are crucial proteins for nuclear functionality. Here, we provide new evidence showing that increased lamin B1 levels contribute to the pathophysiology of Huntington's disease (HD), a CAG repeat-associated neurodegenerative disorder. Through fluorescence-activated nuclear suspension imaging, we show that nucleus from striatal medium-sized spiny and CA1 hippocampal neurons display increased lamin B1 levels, in correlation with altered nuclear morphology and nucleocytoplasmic transport disruption. Moreover, ChIP-sequencing analysis shows an alteration of lamin-associated chromatin domains in hippocampal nuclei, accompanied by changes in chromatin accessibility and transcriptional dysregulation. Supporting lamin B1 alterations as a causal role in mutant huntingtin-mediated neurodegeneration, pharmacological normalization of lamin B1 levels in the hippocampus of the R6/1 mouse model of HD by betulinic acid administration restored nuclear homeostasis and prevented motor and cognitive dysfunction. Collectively, our work points increased lamin B1 levels as a new pathogenic mechanism in HD and provides a novel target for its intervention

Improvements to services at the European Nucleotide Archive

The European Nucleotide Archive (ENA; http://www.ebi.ac.uk/ena) is Europe’s primary nucleotide sequence archival resource, safeguarding open nucleotide data access, engaging in worldwide collaborative data exchange and integrating with the scientific publication process. ENA has made significant contributions to the collaborative nucleotide archival arena as an active proponent of extending the traditional collaboration to cover capillary and next-generation sequencing information. We have continued to co-develop data and metadata representation formats with our collaborators for both data exchange and public data dissemination. In addition to the DDBJ/EMBL/GenBank feature table format, we share metadata formats for capillary and next-generation sequencing traces and are using and contributing to the NCBI SRA Toolkit for the long-term storage of the next-generation sequence traces. During the course of 2009, ENA has significantly improved sequence submission, search and access functionalities provided at EMBL–EBI. In this article, we briefly describe the content and scope of our archive and introduce major improvements to our services

Assessing the Quality of Care for Pneumonia in Integrated Community Case Management: A Cross-Sectional Mixed Methods Study

Background Pneumonia is the leading infectious cause of mortality in children under five worldwide. Community-level interventions, such as integrated community case management, have great potential to reduce the burden of pneumonia, as well as other diseases, especially in remote populations. However, there are still questions as to whether community health workers (CHW) are able to accurately assess symptoms of pneumonia and prescribe appropriate treatment. This research addresses limitations of previous studies using innovative methodology to assess the accuracy of respiratory rate measurement by CHWs and provides new evidence on the quality of care given for children with symptoms of pneumonia. It is one of few that assesses CHW performance in their usual setting, with independent re-examination by experts, following a considerable period of time post-training of CHWs. Methods In this cross-sectional mixed methods study, 1,497 CHW consultations, conducted by 90 CHWs in two districts of Luapula province, Zambia, were directly observed, with measurement of respiratory rate for children with suspected pneumonia recorded by video. Using the video footage, a retrospective reference standard assessment of respiratory rate was conducted by experts. Counts taken by CHWs were compared against the reference standard and appropriateness of the treatment prescribed by CHWs was assessed. To supplement observational findings, three focus group discussions and nine in depth interviews with CHWs were conducted. Results and Conclusion The findings support existing literature that CHWs are capable of measuring respiratory rates and providing appropriate treatment, with 81% and 78% agreement, respectively, between CHWs and experts. Accuracy in diagnosis could be strengthened through further training and the development of improved diagnostic tools appropriate for resource-poor settings