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71.
72.
T Kam-Thong CA Azencott L Cayton B Pütz A Altmann N Karbalai PG Sämann B Schölkopf B Müller-Myhsok KM Borgwardt 《Human heredity》2012,73(4):220-236
Due to recent advances in genotyping technologies, mapping phenotypes to single loci in the genome has become a standard technique in statistical genetics. However, one-locus mapping fails to explain much of the phenotypic variance in complex traits. Here, we present GLIDE, which maps phenotypes to pairs of genetic loci and systematically searches for the epistatic interactions expected to reveal part of this missing heritability. GLIDE makes use of the computational power of consumer-grade graphics cards to detect such interactions via linear regression. This enabled us to conduct a systematic two-locus mapping study on seven disease data sets from the Wellcome Trust Case Control Consortium and on in-house hippocampal volume data in 6 h per data set, while current single CPU-based approaches require more than a year's time to complete the same task. 相似文献
73.
Javier Godar Emilio Jorge Tizado Benno Pokorny James Johnson 《Human ecology: an interdisciplinary journal》2012,40(2):251-267
This study develops criteria for classifying the actor groups shaping frontier development along the Transamazon Highway colonization
project in the Brazilian Amazon, as a basis to improve understanding of their specific contributions to environmental degradation
and socio-economic development. Based on an analysis of responses to questionnaires by 93 colonists representing different
migration trajectories, production systems, socio-economic strategies and deforestation patterns, actor groups could be statistically
classified according to their type of production and level of capitalization. A property size threshold discriminating small
and largeholders in the study area is presented and compared with previous attempts to establish such a threshold. Largeholders
practicing large-scale cattle ranching and smallholders practicing diversified family agriculture were found to be the two
predominant colonist types. Smallholder farming practices were found to be more appropriate to the local environmental conditions
than those implemented by cattle ranchers. 相似文献
74.
Kovacevic I Hu J Siehoff-Icking A Opitz N Griffin A Perkins AC Munn AL Müller-Esterl W Popp R Fleming I Jungblut B Hoffmeister M Oess S 《The EMBO journal》2012,31(15):3309-3322
F-BAR proteins are multivalent adaptors that link plasma membrane and cytoskeleton and coordinate cellular processes such as membrane protrusion and migration. Yet, little is known about the function of F-BAR proteins in vivo. Here we report, that the F-BAR protein NOSTRIN is necessary for proper vascular development in zebrafish and postnatal retinal angiogenesis in mice. The loss of NOSTRIN impacts on the migration of endothelial tip cells and leads to a reduction of tip cell filopodia number and length. NOSTRIN forms a complex with the GTPase Rac1 and its exchange factor Sos1 and overexpression of NOSTRIN in cells induces Rac1 activation. Furthermore, NOSTRIN is required for fibroblast growth factor 2 dependent activation of Rac1 in primary endothelial cells and the angiogenic response to fibroblast growth factor 2 in the in vivo matrigel plug assay. We propose a novel regulatory circuit, in which NOSTRIN assembles a signalling complex containing FGFR1, Rac1 and Sos1 thereby facilitating the activation of Rac1 in endothelial cells during developmental angiogenesis. 相似文献
75.
Ivano Bertini Frank Engelke Leonardo Gonnelli Benno Knott Claudio Luchinat David Osen Enrico Ravera 《Journal of biomolecular NMR》2012,54(2):123-127
We have recently proposed sedimented solute NMR (SedNMR) as a solid-state method to access biomolecules without the need of crystallization or other sample manipulation. The drawback of SedNMR is that samples are intrinsically diluted and this is detrimental for the signal intensity. Ultracentrifugal devices can be used to increase the amount of sample inside the rotor, overcoming the intrinsic sensitivity limitation of the method. We designed two different devices and we here report the directions for using such devices and the relevant equations for determining the parameters for sedimentation. 相似文献
76.
The Median M-N rule is a feature detection algorithm to detect peptide signals in Liquid Chromatography/Mass Spectrometry (LC/MS) images. As the procedure does not adequately control the statistical errors, we investigate an extension of the Median M-N rule to compute a statistical bound on the false-positive rate. We then study the false-negative rate and provide insights on the types of signal that can be detected by the M-N rule and the limit of detection. The resulting feature detection algorithm, which we term Quantile M-N rule, can be used in most feature detection algorithms to provide statistical control of the false-positive and false-negative rate. 相似文献
77.
Arjun Chatterjee Manan Shah Anna O D'Souza Benno Bechtel Glenn Crater Anand A Dalal 《Respiratory research》2012,13(1):15
Background
This retrospective cohort study compared the risks of exacerbations and COPD-related healthcare costs between patients with chronic obstructive pulmonary disease (COPD) initiating tiotropium (TIO) alone and patients initiating triple therapy with fluticasone-salmeterol combination (FSC) added to TIO.Methods
Managed-care enrollees who had an index event of ≥ 1 pharmacy claim for TIO during the study period (January 1, 2003-April 30, 2008) and met other eligibility criteria were categorized into one of two cohorts depending on their medication use. Patients in the TIO+FSC cohort had combination therapy with TIO and FSC, defined as having an FSC claim on the same date as the TIO claim. Patients in the TIO cohort had no such FSC use. The risks of COPD exacerbations and healthcare costs were compared between cohorts during 1 year of follow-up.Results
The sample comprised 3333 patients (n = 852 TIO+FSC cohort, n = 2481 TIO cohort). Triple therapy with FSC added to TIO compared with TIO monotherapy was associated with significant reductions in the adjusted risks of moderate exacerbation (hazard ratio 0.772; 95% confidence interval [CI] 0.641, 0.930) and any exacerbation (hazard ratio 0.763; 95% CI 0.646, 0.949) and a nonsignificant reduction in COPD-related adjusted monthly medical costs.Conclusions
Triple therapy with FSC added to TIO compared with TIO monotherapy was associated with significant reductions in the adjusted risks of moderate exacerbation and any exacerbation over a follow-up period of up to 1 year. These improvements were gained with triple therapy at roughly equal cost of that of TIO alone. 相似文献78.
79.
80.
Anett Reichert Jana Felbel Mark Kielpinski Matthias Urban Benno Steinbrecht Thomas Henkel 《仿生工程学报(英文版)》2008,5(4):291-298
Chip-based flow-through PCR implements the PCR as a continuous process for nucleic acid analytics. The sample is transported in a winding channel through temperature zones required for denaturation, annealing and extension. Main fields of application are the monitoring of continuous processes for rapid identification of contaminants and quality control as well as high throughput screening of cells or microorganisms. A modular arrangement with five heating zones for flow-through PCR is discussed and evaluated. The special heater arrangement allows the implementation of up to 40 cycles on the footprint of a microscope slide, which is placed on top ofa 5 zones heating plate. Liquid/liquid two phase flow of PCR reaction mixture and mineral oil have been applied to create a segmented flow process scheme. In that way, the developed system may provide flow-through PCR as a unit operation for the droplet based microfluidics platform. The single use of disposable devices is commonly preferred due to the sensitivity of the PCR process to contaminations. All-glass microfluidic chips and disposable chip devices, made from polycarbonate as a replication with identically geometry, have been fabricated and tested. For the first time, microchannel geometries with nearly circular profile developed by all-glass technology have been transferred to mass fabrication by injection compression molding. Both devices have been successfully applied for the detection of the tumor suppressor gene p53. Although product yield and selectivity of the amplification process do not depend on the chip material, a well defined, reliable segmented flow regime could only be realized in the all-glass chip. 相似文献