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61.
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A combined oral contraceptive affects mucosal SHIV susceptibility factors in a pigtail macaque (Macaca nemestrina) model 下载免费PDF全文
64.
Seasonal resource availability may act as a constraint on plant phenology and thereby influence the range of growth responses
observed among populations of annual species, especially those occupying a wide range of environments. We compared a mesic
and a xeric population of the non-native, annual grass, Bromus tectorum, to examine phenology in response to interspecific competition and water availability. Using a target-neighborhood approach,
we assessed how phenological patterns of the two populations affected morphological and growth responses to enhanced resource
availability represented by late-season soil moisture. The xeric population exhibited a highly constrained phenology and was
unable to extend the growing season despite available soil resources. Because of the low phenotypic variation, allocation
to reproduction was similar across resource conditions. In contrast, the mesic population flowered later and showed a more
opportunistic phenology in response to late-season water availability. The mesic population was not able to maintain consistent
reproductive allocation at low resource levels. The responses of the two populations to late-season water availability were
not affected by the density of neighboring plants. We suggest that post-introduction selection pressure on B. tectorum in the xeric habitat has resulted in a more fixed phenology which limits opportunistic response to unpredictable, particularly
late-season resource availability. Opportunistic and fixed responses represent contrasting strategies for optimizing fitness
in temporally varying environments and, while both play important roles for ensuring reproductive success, these results suggest
that local adaptation to temporal resource variation may reflect a balance between flexible and inflexible phenology. 相似文献
65.
Brunilda Balliu Jeanine J. Houwing‐Duistermaat Stefan Bhringer 《Biometrical journal. Biometrische Zeitschrift》2019,61(3):747-768
Marginal tests based on individual SNPs are routinely used in genetic association studies. Studies have shown that haplotype‐based methods may provide more power in disease mapping than methods based on single markers when, for example, multiple disease‐susceptibility variants occur within the same gene. A limitation of haplotype‐based methods is that the number of parameters increases exponentially with the number of SNPs, inducing a commensurate increase in the degrees of freedom and weakening the power to detect associations. To address this limitation, we introduce a hierarchical linkage disequilibrium model for disease mapping, based on a reparametrization of the multinomial haplotype distribution, where every parameter corresponds to the cumulant of each possible subset of a set of loci. This hierarchy present in the parameters enables us to employ flexible testing strategies over a range of parameter sets: from standard single SNP analyses through the full haplotype distribution tests, reducing degrees of freedom and increasing the power to detect associations. We show via extensive simulations that our approach maintains the type I error at nominal level and has increased power under many realistic scenarios, as compared to single SNP and standard haplotype‐based studies. To evaluate the performance of our proposed methodology in real data, we analyze genome‐wide data from the Wellcome Trust Case‐Control Consortium. 相似文献
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Amaia Artal-Martinez de Narvajas Timothy S. Gomez Jin-San Zhang Alexander O. Mann Yoshiyuki Taoda Jacquelyn A. Gorman Marta Herreros-Villanueva Thomas M. Gress Volker Ellenrieder Luis Bujanda Do-Hyung Kim Alan P. Kozikowski Alexander Koenig Daniel D. Billadeau 《Molecular and cellular biology》2013,33(20):3983-3993
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Koenig SC Woolard C Drew G Unger L Gillars K Ewert D Gray L Pantalos G 《Biomedical instrumentation & technology / Association for the Advancement of Medical Instrumentation》2004,38(3):229-240
In seeking approval from the US Food and Drug Administration (FDA) for clinical trial evaluation of an experimental medical device, a sponsor is required to submit experimental findings and support documentation to demonstrate device safety and efficacy that are in compliance with Good Laboratory Practices (GLP). The objective of this project was to develop an integrated data acquisition (DAQ) system and documentation strategy for monitoring and recording physiological data when testing medical devices in accordance with GLP guidelines mandated by the FDA. Data aquisition systems were developed as stand-alone instrumentation racks containing transducer amplifiers and signal processors, analog-to-digital converters for data storage, visual display and graphical user-interfaces, power conditioners, and test measurement devices. Engineering standard operating procedures (SOP) were developed to provide a written step-by-step process for calibrating, validating, and certifying each individual instrumentation unit and the integrated DAQ system. Engineering staff received GLP and SOP training and then completed the calibration, validation, and certification process for the individual instrumentation components and integrated DAQ system. Eight integrated DAQ systems have been successfully developed that were inspected by regulatory affairs consultants and determined to meet GLP guidelines. Two of these DAQ systems were used to support 40 of the pre-clinical animal studies evaluating the AbiCor artificial heart (ABIOMED, Danvers, MA). Based in part on these pre-clinical animal data, the AbioCor clinical trials began in July 2001. The process of developing integrated DAQ systems, SOP, and the validation and certification methods used to ensure GLP compliance are presented in this article. 相似文献
70.
Rinder MR Spina RJ Peterson LR Koenig CJ Florence CR Ehsani AA 《American journal of physiology. Regulatory, integrative and comparative physiology》2004,287(2):R360-R368
To compare the effects of exercise training and hydrochlorothiazide on left ventricular (LV) geometry and mass, blood pressure (BP), and hyperinsulinemia in older hypertensive adults, we studied 28 patients randomized either to a group (age 66.4 +/- 1.3 yr; n = 16) that exercised or to a group (age 65.3 +/- 1.2 yr; n = 12) that received hydrochlorothiazide for 6 mo. Endurance exercise training induced a 15% increase in peak aerobic power. The reduction in systolic BP was twofold greater with thiazide than with exercise (26.6 +/- 12.2 vs. 11.5 +/- 10.9 mmHg). Exercise and thiazide reduced LV wall thickness, LV mass index (14% in each group), and the LV wall thickness-to-radius ratio (h/r) similarly (exercise: before 0.48 +/- 0.2, after 0.42 +/- 0.01; thiazide: before 0.47 +/- 0.04, after 0.40 +/- 0.04; P = 0.017). The reductions in systolic BP and h/r were correlated in the exercise group (r = 0.70, P = 0.005) but not in the thiazide group. Exercise training reduced glucose-stimulated hyperinsulinemia (before: 13.65 +/- 2.6 vs. 9.84 +/- 1.5 mU.ml(-1).min; P = 0.04) and insulin resistance. Thiazide did not affect plasma insulin levels. The results suggest that although exercise is less effective in reducing systolic BP than thiazide, it can induce regression of LV hypertrophy similar in magnitude to thiazide. Unlike hydrochlorothiazide, exercise training can improve insulin resistance and aerobic capacity in older hypertensive people. 相似文献