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Modest Number (modest + number)
Selected AbstractsLIKELIHOOD-BASED INFERENCE IN ISOLATION-BY-DISTANCE MODELS USING THE SPATIAL DISTRIBUTION OF LOW-FREQUENCY ALLELESEVOLUTION, Issue 11 2009John Novembre Estimating dispersal distances from population genetic data provides an important alternative to logistically taxing methods for directly observing dispersal. Although methods for estimating dispersal rates between a modest number of discrete demes are well developed, methods of inference applicable to "isolation-by-distance" models are much less established. Here, we present a method for estimating ,,2, the product of population density (,) and the variance of the dispersal displacement distribution (,2). The method is based on the assumption that low-frequency alleles are identical by descent. Hence, the extent of geographic clustering of such alleles, relative to their frequency in the population, provides information about ,,2. We show that a novel likelihood-based method can infer this composite parameter with a modest bias in a lattice model of isolation-by-distance. For calculating the likelihood, we use an importance sampling approach to average over the unobserved intraallelic genealogies, where the intraallelic genealogies are modeled as a pure birth process. The approach also leads to a likelihood-ratio test of isotropy of dispersal, that is, whether dispersal distances on two axes are different. We test the performance of our methods using simulations of new mutations in a lattice model and illustrate its use with a dataset from Arabidopsis thaliana. [source] From grid cells to place cells: A mathematical modelHIPPOCAMPUS, Issue 12 2006Trygve Solstad Abstract Anatomical connectivity and recent neurophysiological results imply that grid cells in the medial entorhinal cortex are the principal cortical inputs to place cells in the hippocampus. The authors propose a model in which place fields of hippocampal pyramidal cells are formed by linear summation of appropriately weighted inputs from entorhinal grid cells. Single confined place fields could be formed by summing input from a modest number (10,50) of grid cells with relatively similar grid phases, diverse grid orientations, and a biologically plausible range of grid spacings. When the spatial phase variation in the grid-cell input was higher, multiple, and irregularly spaced firing fields were formed. These observations point to a number of possible constraints in the organization of functional connections between grid cells and place cells. © 2006 Wiley-Liss, Inc. [source] Phenotology of disease-linked proteins,HUMAN MUTATION, Issue 1 2005Jeffrey K. Myers Abstract Are there analogous sequence positions in families of related proteins where disease-linked mutations occur with unusually high frequency? We attempt to answer this question by examining sequence alignments for G-protein coupled receptors (GPCRs) and voltage-gated potassium channels that have a significant number of missense mutations linked to some form of human disease. When the disease-linked mutations are mapped onto the sequences for each family, there are a large number of aligned sites at which disease-linked mutations occur in more than one protein. The statistical significance of the aligned sites is judged by analysis of artificially-generated random datasets. There are a modest number of aligned sites that are statistically significant,we refer to these as "phenotologous" sequence positions. Phenotologous sites represent aligned positions at which mutations linked to disease phenotypes occur with high frequency within a family of proteins. The most interesting of these sites are those which are not conserved,such sites are apparently critical in defining structural or functional differences between related proteins. Phenotology may be used to make experimentally testable predictions regarding medical genetics, the molecular basis of disease, and protein structure,function relationships. Hum Mutat 25:90,97, 2005. © 2004 Wiley-Liss, Inc. [source] High resolution analysis of mating systems: inbreeding in natural populations of Pinus radiataJOURNAL OF EVOLUTIONARY BIOLOGY, Issue 3 2002C. Vogl Pinus radiata has a history of population bottlenecks and is currently restricted to five relatively small populations, three in mainland California, and two on islands off the coast of Baja California. Using highly polymorphic microsatellite markers and a newly developed statistical approach, we were able to estimate individual inbreeding coefficients and can thus analyse the mating system with high resolution. We find a bimodal distribution of inbreeding coefficients: most individuals result from selfing whereas few (in the mainland populations) to a modest number (in the island populations) are likely selfed. In most other pine species and presumably in the ancestral P. radiata population, occurrence of mature selfed individuals would be impossible because of the high genetic load. We therefore conclude that inbreeding depression has been purged in P. radiata and that the mating system has changed as a consequence. [source] Cardiovascular pharmacogenetics in the SNP eraJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2003V. Mooser Summary., In the past pharmacological agents have contributed to a significant reduction in age-adjusted incidence of cardiovascular events. However, not all patients treated with these agents respond favorably, and some individuals may develop side-effects. With aging of the population and the growing prevalence of cardiovascular risk factors worldwide, it is expected that the demand for cardiovascular drugs will increase in the future. Accordingly, there is a growing need to identify the ,good' responders as well as the persons at risk for developing adverse events. Evidence is accumulating to indicate that responses to drugs are at least partly under genetic control. As such, pharmacogenetics , the study of variability in drug responses attributed to hereditary factors in different populations , may significantly assist in providing answers toward meeting this challenge. Pharmacogenetics mostly relies on associations between a specific genetic marker like single nucleotide polymorphisms (SNPs), either alone or arranged in a specific linear order on a certain chromosomal region (haplotypes), and a particular response to drugs. Numerous associations have been reported between selected genotypes and specific responses to cardiovascular drugs. Recently, for instance, associations have been reported between specific alleles of the apoE gene and the lipid-lowering response to statins, or the lipid-elevating effect of isotretinoin. Thus far, these types of studies have been mostly limited to a priori selected candidate genes due to restricted genotyping and analytical capacities. Thanks to the large number of SNPs now available in the public domain through the SNP Consortium and the newly developed technologies (high throughput genotyping, bioinformatics software), it is now possible to interrogate more than 200 000 SNPs distributed over the entire human genome. One pharmacogenetic study using this approach has been launched by GlaxoSmithKline to identify the approximately 4% of patients who are predisposed to developing a hypersensitivity reaction to abacavir, an anti-HIV agent. Data collected thus far on the HLA locus on chromosome 6 indicate that this approach is feasible. Extended linkage disequilibrium can be detected readily, even across several haplotype blocks, thus potentially reducing the number of SNPs for future whole-genome scans. Finally, a modest number of cases and controls appears to be sufficient to detect genetic associations. There is little doubt that this type of approach will have an impact on the way cardiovascular drugs will be developed and prescribed in the future. [source] Association analysis of fibre traits in Gossypium arboreum accessionsPLANT BREEDING, Issue 2 2008S. K. Kantartzi Abstract Advances in the use of diploid Asiatic species in cotton breeding require an understanding of the relatedness and ancestry of diploid cotton accessions, and identification of simple sequence repeat (SSR) markers associated with agronomically important phenotypic traits, for example, fibre quality. Fifty-six Gossypium arboreum germplasm accessions introduced from nine regions of Africa, Asia and Europe were evaluated for eight fibre characters (lint percentage, lint colour, elongation, micronaire, strength, 50% span length, 2.5% span length and maturity%) and genotyped with 98 SSR markers. When viewed across all accessions most of the SSR markers were polymorphic. Population structure analysis identified six main clusters for the accessions which corresponded to different geographic regions, indicating agreement between genetic and predefined populations. The general linear model method was used to disclose marker,trait associations. Marker,trait associations were investigated by fitting single marker regression models for phenotypic traits on marker band intensities with correction for population structure. This paper illustrates the potential of association mapping in diploid cotton, because existing phenotypic data, a modest number of SSR markers, and a pioneering statistical analysis, identified interesting associations. [source] Spatulated end-to-end bile duct reconstruction in orthotopic liver transplantationCLINICAL TRANSPLANTATION, Issue 1 2007Andrzej K Buczkowski Abstract:, Biliary complications continue to be a major source of morbidity following orthotopic liver transplantation. The aim of this study was to analyze the incidence and management of biliary complications related to the technique of bile duct reconstruction. The patients were stratified into two groups: group I (n = 39) had bile duct reconstruction performed by an end-to-end single interrupted suture choledochocholedochostomy (EE-CDCD) and group II (n = 38) had a spatulated end-to-end CDCD (spEE-CDCD) reconstruction; both groups had an intraductal stent. The groups were similar in age, gender, liver transplant indications and Pugh score. Ten biliary complications (26%), including five bile leaks (13%) and five biliary strictures (13%), were observed in the EE-CDCD group, while one biliary stricture (2.6%) occurred in the spEE-CDCD group (p < 0.05). Subsequent imaging studies and endoscopic retrograde cholangiopancreatography were performed less often in patients undergoing spEE-CDCD reconstruction (p < 0.05). The technique of a spatulated end-to-end bile duct reconstruction provides a significant improvement in lowering biliary complication rates in liver transplant patients. Despite the modest number of cases in this study this technique shows promise and has become the technique of choice in our institution. [source] Multistep correlations via covariance processing of COSY/GCOSY spectra: opportunities and artifactsMAGNETIC RESONANCE IN CHEMISTRY, Issue 11 2008Gary E. Martin Abstract Long-range homonuclear coupling pathways can be observed in COSY or GCOSY spectra by the acquisition of spectra with larger numbers of increments of the evolution period, t1, than would normally be used. Alternatively, covariance processing of COSY-type spectra acquired with modest numbers of t1 increments, allows the observation of multistage correlations. In this work results obtained from covariance-processed GCOSY spectra are fully analyzed and compared to normally processed COSY and 80 ms TOCSY spectra. Multistage or ,RCOSY-type' correlations are observed when remote protons both exhibit correlations to the same coupling partner e.g. A , B and B , C gives rise to an A , C correlation. In the strict sense, RCOSY-type responses are artifacts albeit providing useful information. Nonbeneficial artifact correlations are observed when protons couple to other protons that overlap or partially overlap. The origin of artifact responses is also analyzed. Copyright © 2008 John Wiley & Sons, Ltd. [source] The psychosocial impact of parental cancer on children and adolescents: a systematic reviewPSYCHO-ONCOLOGY, Issue 2 2007Tessa Osborn Abstract This review aimed to identify (i) whether early stage parental cancer is associated with an increased risk of psychosocial difficulties amongst children and adolescents; (ii) which factors are associated with variations in psychosocial functioning amongst these children and adolescents. Searches of four electronic databases and the reference lists of relevant articles revealed 10 studies which satisfied the inclusion criteria for the first review question and thirteen studies for the second. Limitations in methodological quality and modest numbers of studies examining the same variables, restricted the conclusions which could be drawn. Overall, the evidence suggests that children and adolescents do not generally experience elevated levels of serious psychosocial difficulties compared to reference groups, but they are at a slightly increased risk for internalising type problems. Adolescent daughters appear to be the most negatively affected group. The prevalent use of measures of child psychopathology may be masking more context-specific problems and lower levels of distress. Family variables, especially family communication/expressiveness, are consistently associated with child/adolescent psychosocial functioning and there is suggestive evidence for the role of maternal depression/adjustment and parenting variables. There is little evidence that medical/treatment variables are important predictors of child outcomes. These findings have implications for identifying families with children most in need of support and indicating variables to target in interventions. Copyright © 2007 John Wiley & Sons, Ltd. 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