Whole-genome screening in ankylosing spondylitis: Evidence of non-MHC genetic-susceptibility loci

Ankylosing spondylitis (AS) is a common inflammatory arthritis predominantly affecting the axial skeleton. Susceptibility to the disease is thought to be oligogenic. To identify the genes involved, we have performed a genomewide scan in 185 families containing 255 affected sibling pairs. Two-point and multipoint nonparametric linkage analysis was performed. Regions were identified showing "suggestive" or stronger linkage with the disease on chromosomes 1p, 2q, 6p, 9q, 10q, 16q, and 19q. The MHC locus was identified as encoding the greatest component of susceptibility, with an overall LOD score of 15.6. The strongest non-MHC linkage lies on chromosome 16q (overall LOD score 4.7). These results strongly support the presence of non-MHC genetic-susceptibility factors in AS and point to their likely locations.

铜-铝扩散焊及拉伸的分子动力学模拟

采用分子动力学方法模拟了铜-铝扩散焊过程,分析了理想平面铜-铝试件(001)晶面间扩散焊的过渡层厚度,并利用径向分布、键对分析方法分析了在不同的降温速率下过渡层的结构变化.降温速率大时,过渡层保持原有无序结构,降温速率小时,过渡层从无序结构向面心立方结构转变.还对扩散焊后的铜-铝试件进行了拉伸模拟,并与尺寸大小相近的单晶铜和单晶铝的拉伸模拟结果进行比较.结果发现焊接后的强度比单晶铝和单晶铜的强度都要小,最大应变值也小.

Estimates of genetic parameters for growth traits of the sea urchin, Strongylocentrotus intermedius

Heritabilities and genetic and phenotypic correlations were estimated for body weight, test diameter, and test height of the sea urchin from measurements on progeny resulting from 11 sires and 33 dams by artificial fertilization of 3 females by single males, and measurements at 8, 10, and 12 months after metamorphism. Point estimate for heritabilities based on the sire components of variance were moderate to high for body weight (0.21-0.49), test diameter (0.21-0.47), and test height (0.22-0.37). Genetic correlations were significant for body weight with test diameter (0.30similar to0.65) and test height (0.30similar to0.54) and test diameter with test height (0.31similar to0.65). Genetic correlation estimates, derived the nested design and half-sib correlation analysis used in this study, appear to provide reliable estimates. Significant phenotypic correlations were found for body weight with test diameter (0.82similar to0.86) and test height (0.49similar to0.83), and test diameter with test height (0.47similar to0.84). The phenotypic correlations for test height with body weight (0.491) and test diameter (0.467) at 12 months' of age were smaller than those earlier sampling periods.(C) 2004 Published by Elsevier B.V.

Genetic parameter estimates for growth traits at early stage of Pacific abalone, Haliotis discus hannai Ino

Heritability and genetic and phenotypic correlations were estimated for juvenile growth traits of Pacific abalone Haliotis discus hannai Ino. The estimates were calculated from shell length and shell width measurements on progeny resulting from 12 half-sib families and 36 full-sib families obtained using artificial fertilization of mating three females to each male. The measurements were taken at 10, 20 and 30 d after fertilization. It was found that heritability estimates based on sire component ranged from 0.23 to 0.36 for shell length and 0.21 to 0.32 for shell width. Heritability estimates from dam component were larger than those from sire component at three ages, indicating presence of maternal effects, non-additive genetic effects and common environmental effects. Phenotypic correlations were significant at three ages (P < 0.05), with values of 0.92, 0.93 and 0.92, respectively. Genetic correlations from the paternal half-sib correlation analysis were highly positive at three ages, with values of 0.50, 0.78 and 0.81, respectively. The results suggest that selective breeding is an effective approach to improving growth traits of Pacific abalone stocks.

Treatment Effects Produced by Fränkel Appliance in Patients with Class II, Division 1 Malocclusion

The purpose of this investigation was to evaluate the dentoalveolar and skeletal cephalometric changes produced by the Fränkel appliance in individuals with a Class II, division 1 malocclusion. Lateral cephalograms of 44 patients of both sexes were divided in two groups of 22 each. The control group was comprised of untreated Class II children with an initial mean age of eight years and seven months who were followed without treatment for a period of 13 months. The Fränkel group had an initial mean age of nine years and was treated for a mean period of 17 months. Lateral cephalometric headfilms of each patient were obtained at the beginning and end of treatment. The Fränkel appliance produced no significant changes in maxillary growth during the evaluation period, while a statistically significant increase in mandibular length was observed. The maxillomandibular relationship improved mostly because of an increase in mandibular length. In addition, there were no statistically significant differences in the craniofacial growth direction between the Fränkel and the control group, both showing a slight downward rotation of the palatal plane. The Fränkel appliance produced a labial tipping of the lower incisors and a lingual inclination of the upper incisors as well as a significant increase in mandibular posterior dentoalveolar height. It was concluded that the main effects of the Fränkel appliance during this time period were mostly dentoalveolar with a smaller but significant skeletal mandibular effect.

Effect of donor-specific transfusions on the outcome of renal allografts in the cyclosporine era

Despite the introduction of new immunosuppressive agents, a steady decline of functioning renal allografts after living donation is observed. Thus nonpharmacological strategies to prevent graft loss have to be reconsidered, including donor-specific transfusions (DST). We introduced a cyclosporine-based DST protocol for renal allograft recipients from living-related/unrelated donation. From 1993 to 2003, 200 ml of whole blood, or the respective mononuclear cells from the potential living donor were administered twice to all of our 61 recipient candidates. The transplanted subjects were compared with three groups of patients without DST from the Collaborative Transplant Study (Heidelberg, Germany) during a 6-year period. Six patients were sensitized without delay for a subsequent cadaveric kidney. DST patients had less often treatment for rejection and graft survival was superior compared with subjects from the other Swiss transplant centers (n = 513) or from Western Europe (n = 7024). To diminish the probability that superior results reflect patient selection rather than effects of DST, a 'matched-pair' analysis controlling for relevant factors of transplant outcome was performed. Again, this analysis indicated that recipients with DST had better outcome. Thus, our observation suggests that DST improve the outcome of living kidney transplants even when modern immunosuppressive drugs are prescribed.

Elderly age is not a negative predictive factor for virological response to therapy with pegylated interferon-α and ribavirin in chronic hepatitis C virus patients

BACKGROUND & AIMS: Age is frequently discussed as negative host factor to achieve a sustained virological response (SVR) to antiviral therapy of chronic hepatitis C. However, elderly patients often show advanced fibrosis/cirrhosis as known negative predictive factor. The aim of this study was to assess age as an independent predictive factor during antiviral therapy. METHODS: Overall, 516 hepatitis C patients were treated with pegylated interferon-α and ribavirin, thereof 66 patients ≥60 years. We analysed the impact of host factors (age, gender, fibrosis, haemoglobin, previous hepatitis C treatment) and viral factors (genotype, viral load) on SVR per therapy course by performing a generalized estimating equations (GEE) regression modelling, a matched pair analysis and a classification tree analysis. RESULTS: Overall, SVR per therapy course was 42.9 and 26.1%, respectively, in young and elderly patients with hepatitis C virus (HCV) genotypes 1/4/6. The corresponding figures for HCV genotypes 2/3 were 74.4 and 84%. In the GEE model, age had no significant influence on achieving SVR. In matched pair analysis, SVR was not different in young and elderly patients (54.2 and 55.9% respectively; P = 0.795 in binominal test). In classification tree analysis, age was not a relevant splitting variable. CONCLUSIONS: Age is not a significant predictive factor for achieving SVR, when relevant confounders are taken into account. As life expectancy in Western Europe at age 60 is more than 20 years, it is reasonable to treat chronic hepatitis C in selected elderly patients with relevant fibrosis or cirrhosis but without major concomitant diseases, as SVR improves survival and reduces carcinogenesis.

Psychiatric genetics in Australia

Australian research in psychiatric genetics covers molecular genetic studies of depression, anxiety, alcohol dependence, Alzheimer's disease, bipolar disorder, schizophrenia, autism, and attention deficit hyperactivity disorder. For each disorder, a variety of clinical cohorts have been recruited including affected sib pair families, trios, case/controls, and twins from a large population-based twin registry. These studies are taking place both independently and in collaboration with international groups. Microarray studies now complement DNA investigations, while animal models are in development An Australian government genome facility provides a high throughput genotyping and mutation detection service to the Australian scientific community, enhancing the contribution of Australian psychiatric genetics groups to gene discovery. (C) 2003 Lippincott Williams Wilkins.

The impact of information technology on organizations: A study of enterprise resource planning system influences on job design and organizational culture

The primary purpose of this research is to study the linkage between perceived job design characteristics and information system environment characteristics before and after the replacement of a legacy information system with a new type of information system (referred to as an Enterprise Resource Planning or ERP system). A public state University implementing an academic version of an ERP system was selected for the study. Three survey instruments were used to examine the perception of the information system, the job characteristics, and the organizational culture before and after the system implementation. The research participants included two large departments resulting in a sample of 130 workers. Research questions were analyzed using multivariate procedures including factor analysis, path analysis, step-wise regression, and matched pair analysis. ^ Results indicated that the ERP system has introduced new elements into the working environment that has changed the perception of how the job design characteristics and organization culture dimensions are viewed by the workers. The understanding of how the perceived system characteristics align with an individual's perceived job design characteristics is supported by each of the system characteristics significantly correlated in the proposed direction. The stronger support of this relationship becomes visible in the causal flow of the effects seen in the path diagram and in the step-wise regression. The perceived job design characteristics aligning with dimensions of organizational culture are not as strong as the literature suggests. Although there are significant correlations between the job and culture variables, only one relationship can be seen in the causal flow. ^ This research has demonstrated that system characteristics of ERP do contribute to the perception of change in an organization and do support organizational culture behaviors and job characteristics. ^

Spectral analysis of pair-correlation bandwidth: Application to cell biology images

Images from cell biology experiments often indicate the presence of cell clustering, which can provide insight into the mechanisms driving the collective cell behaviour. Pair-correlation functions provide quantitative information about the presence, or absence, of clustering in a spatial distribution of cells. This is because the pair-correlation function describes the ratio of the abundance of pairs of cells, separated by a particular distance, relative to a randomly distributed reference population. Pair-correlation functions are often presented as a kernel density estimate where the frequency of pairs of objects are grouped using a particular bandwidth (or bin width), Δ>0. The choice of bandwidth has a dramatic impact: choosing Δ too large produces a pair-correlation function that contains insufficient information, whereas choosing Δ too small produces a pair-correlation signal dominated by fluctuations. Presently, there is little guidance available regarding how to make an objective choice of Δ. We present a new technique to choose Δ by analysing the power spectrum of the discrete Fourier transform of the pair-correlation function. Using synthetic simulation data, we confirm that our approach allows us to objectively choose Δ such that the appropriately binned pair-correlation function captures known features in uniform and clustered synthetic images. We also apply our technique to images from two different cell biology assays. The first assay corresponds to an approximately uniform distribution of cells, while the second assay involves a time series of images of a cell population which forms aggregates over time. The appropriately binned pair-correlation function allows us to make quantitative inferences about the average aggregate size, as well as quantifying how the average aggregate size changes with time.

Network signatures based on gene pair expression ratios improve classification and the analysis of muscle-invasive urothelial cancer

Urothelial cancer (UC) is highly recurrent and can progress from non-invasive (NMIUC) to a more aggressive muscle-invasive (MIUC) subtype that invades the muscle tissue layer of the bladder. We present a proof of principle study that network-based features of gene pairs can be used to improve classifier performance and the functional analysis of urothelial cancer gene expression data. In the first step of our procedure each individual sample of a UC gene expression dataset is inflated by gene pair expression ratios that are defined based on a given network structure. In the second step an elastic net feature selection procedure for network-based signatures is applied to discriminate between NMIUC and MIUC samples. We performed a repeated random subsampling cross validation in three independent datasets. The network signatures were characterized by a functional enrichment analysis and studied for the enrichment of known cancer genes. We observed that the network-based gene signatures from meta collections of proteinprotein interaction (PPI) databases such as CPDB and the PPI databases HPRD and BioGrid improved the classification performance compared to single gene based signatures. The network based signatures that were derived from PPI databases showed a prominent enrichment of cancer genes (e.g., TP53, TRIM27 and HNRNPA2Bl). We provide a novel integrative approach for large-scale gene expression analysis for the identification and development of novel diagnostical targets in bladder cancer. Further, our method allowed to link cancer gene associations to network-based expression signatures that are not observed in gene-based expression signatures.

Pair trading: Clustering based on principal component analysis

This study focuses on the implementation of several pair trading strategies across three emerging markets, with the objective of comparing the results obtained from the different strategies and assessing if pair trading benefits from a more volatile environment. The results show that, indeed, there are higher potential profits arising from emerging markets. However, the higher excess return will be partially offset by higher transaction costs, which will be a determinant factor to the profitability of pair trading strategies. Also, a new clustering approach based on the Principal Component Analysis was tested as an alternative to the more standard clustering by Industry Groups. The new clustering approach delivers promising results, consistently reducing volatility to a greater extent than the Industry Group approach, with no significant harm to the excess returns.

Analysis of genetic parentage in the tawny owl (Strix aluco) reveals extra-pair paternity is low

We have investigated genetic parentage in a Swiss population of tawny owls (Strix aluco). To this end, we performed genetic analysis for six polymorphic loci of 49 avian microsatellite loci tested for cross-species amplification. We found one extra-pair young out of 137 (0.7%) nestlings in 37 families (2.7%). There was no intra-specific brood parasitism. Our results are in accordance with previous findings for other raptors and owls that genetic monogamy is the rule. Female tawny owls cannot raise offspring without a substantial contribution by their mates. Hence one favoured hypothesis is that high paternal investment in reproduction selects for behaviour that prevents cuckoldry.