993 resultados para specific genotype


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An application specific programmable processor (ASIP) suitable for the real-time implementation of matrix computations such as Singular Value and QR Decomposition is presented. The processor incorporates facilities for the issue of parallel instructions and a dual-bus architecture that are designed to achieve high performance. Internally, it uses a CORDIC module to perform arithmetic operations, with pipelining of the internal recursive loop exploited to multiplex the two independent micro-rotations onto a single piece of hardware. The net result is a flexible processing element whose functionality can be changed under program control, which combines high performance with efficient silicon implementation. This is illustrated through the results of a detailed silicon design study and the applications of the techniques to a combined SVD/QRD system.

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A simple molecular analytical theory of dielectric relaxation in strongly polar fluids is considered in terms of a semi- phenomenological approach. Theoretical spectra epsilon(v), a(v) of complex permittivity and absorption coefficient are fully determined by a form of intermolecular potential well, in which a dipole reorients. In a recent publication by VI. Gaiduk, O.F. Nielsen, and T.S. Perova [J. Molliq 95 (1002) 1-25] the wideband spectra of liquid H2O and D2O were described in terms of a composite model comprising the rectangular and the cosine squared potential wells. Much better results are achieved in this work, where the rectangular well is replaced by a well with a rounded bottom termed the hat-curved well. The spectrum of the auto-correlation function (ACF) is calculated for such a potential. The proposed theory of a composite model, comprising hat-curved and parabolic wells, is applied for liquid water. This model is capable for describing the Debye relaxation region, the second relaxation region in the submillimeter wavelength range, and the far infra-red (FIR) e(v), a(v) spectra, where an intense librational band and an additional weak band are placed, respectively, near 700 cm(-1) and 200 cm(-1). The latter band reflects the features of so-called specific (viz. directly related to H-bonds) interactions and the former band reflects the features of unspecific interactions. The physical mechanisms connected with these types of interactions are discussed in terms of two relevant types of water structure (types of molecular rotation). The proposed theory is also applied to a non-associated liquid in terms of one hat-curved potential well. (C) 2004 Elsevier B.V. All rights reserved.

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This article reports the findings of a mixed-method evaluation of a pilot educational programme undertaken with 6-7 year olds in a sample of primary schools in England with the aim of increasing their awareness of and respect for diversity through theatre, workshops and related teacher-led classroom activities. The qualitative feedback from the teachers involved was extremely positive and encouraging and an analysis of the actual impact of the pilot programme on the children’s attitudes and awareness, using an experimental design, demonstrated some positive effects. In particular, the programme was found to increase the children’s general awareness of diversity and their ability to recognise instances of exclusion. While not a planned objective of the pilot programme, the evaluation also examined whether it had any effects on the children’s attitudes to specific differences, in this particular case racial differences. Interestingly, however, no evidence was found of any change in the children’s racial attitudes. With this in mind the article suggests that there is a need to distinguish between the general and specific effects of such educational programmes. The article considers the implications of this for future work in the area and also stresses the need to undertake more thorough and rigorous evaluations of such initiatives.

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Background: TORCH (Towards a Revolution in COPD Health) is an international multicentre, randomised, placebo-controlled clinical trial of inhaled fluticasone propionate/salmeterol combination treatment and its monotherapy components for maintenance treatment of moderately to severely impaired patients with chronic obstructive pulmonary disease (COPD). The primary outcome is all-cause mortality. Cause-specific mortality and deaths related to COPD are additional outcome measures, but systematic methods for ascertainment of these outcomes have not previously been described. Methods: A Clinical Endpoint Committee (CEC) was tasked with categorising the cause of death and the relationship of deaths to COPD in a systematic, unbiased and independent manner. The key elements of the operation of the committee were the use of predefined principles of operation and definitions of cause of death and COPD-relatedness; the independent review of cases by all members with development of a consensus opinion; and a substantial infrastructure to collect medical information. Results: 911 deaths were reviewed and consensus was reached in all. Cause-specific mortality was: cardiovascular 27%, respiratory 35%, cancer 21%, other 10% and unknown 8%. 40% of deaths were definitely or probably related to COPD. Adjudications were identical in 83% of blindly re-adjudicated cases ( = 0.80). COPD-relatedness was reproduced 84% of the time ( = 0.73). The CEC adjudication was equivalent to the primary cause of death recorded by the site investigator in 52% of cases. Conclusion: A CEC can provide standardised, reliable and informative adjudication of COPD mortality that provides information which frequently differs from data collected from assessment by site investigators.

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The aim of the 5-year European Union (EU)-Integrated Project GEnetics of Healthy Aging (GEHA), constituted by 25 partners (24 from Europe plus the Beijing Genomics Institute from China), is to identify genes involved in healthy aging and longevity, which allow individuals to survive to advanced old age in good cognitive and physical function and in the absence of major age-related diseases. To achieve this aim a coherent, tightly integrated program of research that unites demographers, geriatricians, geneticists, genetic epidemiologists, molecular biologists, bioinfomaticians, and statisticians has been set up. The working plan is to: (a) collect DNA and information on the health status from an unprecedented number of long-lived 90+ sibpairs (n = 2650) and of younger ethnically matched controls (n = 2650) from 11 European countries; (b) perform a genome-wide linkage scannning in all the sibpairs (a total of 5300 individuals); this investigation will be followed by linkage disequilibrium mapping (LD mapping) of the candidate chromosomal regions; (c) study in cases (i.e., the 2650 probands of the sibpairs) and controls (2650 younger people), genomic regions (chromosome 4, D4S1564, chromosome 11, 11.p15.5) which were identified in previous studies as possible candidates to harbor longevity genes; (d) genotype all recruited subjects for apoE polymorphisms; and (e) genotype all recruited subjects for inherited as well as epigenetic variability of the mitochondrial DNA (mtDNA). The genetic analysis will be performed by 9 high-throughput platforms, within the framework of centralized databases for phenotypic, genetic, and mtDNA data. Additional advanced approaches (bioinformatics, advanced statistics, mathematical modeling, functional genomics and proteomics, molecular biology, molecular genetics) are envisaged to identify the gene variant(s) of interest. The experimental design will also allow (a) to identify gender-specific genes involved in healthy aging and longevity in women and men stratified for ethnic and geographic origin and apoE genotype; (b) to perform a longitudinal survival study to assess the impact of the identified genetic loci on 90+ people mortality; and (c) to develop mathematical and statistical models capable of combining genetic data with demographic characteristics, health status, socioeconomic factors, lifestyle habits.

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Freshwater populations of three-spined sticklebacks (Gasterosteus aculeatus) in northern Germany are found as distinct lake and river ecotypes. Adaptation to habitat-specific parasites might influence immune capabilities of stickleback ecotypes. Here, naive laboratory-bred sticklebacks from lake and river populations were exposed reciprocally to parasite environments in a lake and a river habitat. Sticklebacks exposed to lake conditions were infected with higher numbers of parasite species when compared with the river. River sticklebacks in the lake had higher parasite loads than lake sticklebacks in the same habitat. Respiratory burst, granulocyte counts and lymphocyte proliferation of head kidney leucocytes were increased in river sticklebacks exposed to lake when compared with river conditions. Although river sticklebacks exposed to lake conditions showed elevated activation of their immune system, parasites could not be diminished as effectively as by lake sticklebacks in their native habitat. River sticklebacks seem to have reduced their immune-competence potential due to lower parasite diversity in rivers

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The recently discovered aging-dependent large accumulation of point mutations in the human fibroblast mtDNA control region raised the question of their occurrence in postmitotic tissues. In the present work, analysis of biopsied or autopsied human skeletal muscle revealed the absence or only minimal presence of those mutations. By contrast, surprisingly, most of 26 individuals 53 to 92 years old, without a known history of neuromuscular disease, exhibited at mtDNA replication control sites in muscle an accumulation of two new point mutations, i.e., A189G and T408A, which were absent or marginally present in 19 individuals younger than 34 years. These two mutations were not found in fibroblasts from 22 subjects 64 to 101 years of age (T408A), or were present only in three subjects in very low amounts (A189G). Furthermore, in several older individuals exhibiting an accumulation in muscle of one or both of these mutations, they were nearly absent in other tissues, whereas the most frequent fibroblast-specific mutation (T414G) was present in skin, but not in muscle. Among eight additional individuals exhibiting partial denervation of their biopsied muscle, four subjects >80 years old had accumulated the two muscle-specific point mutations, which were, conversely, present at only very low levels in four subjects <or =40 years old. The striking tissue specificity of the muscle mtDNA mutations detected here and their mapping at critical sites for mtDNA replication strongly point to the involvement of a specific mutagenic machinery and to the functional relevance of these mutations.