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191.
Zhongcai Ma Kenny Y.C. Kwong David Paek 《Biochemical and biophysical research communications》2010,400(4):569-574
Plaminogen activator inhibitor-1 (PAI-1), the key physiological inhibitor of the plasmin fibrinolytic system, plays important roles in the pathogenesis of asthma. Mast cells (MCs) are crucial effector cells and a major source of PAI-1 for asthma. Cyclic adenosine monophosphate (cAMP) is the important regulator of MCs; however, its effects on PAI-1 expression in MCs remain unknown. We reported cAMP/protein kinase A pathway positively regulates PAI-1 expression through cAMP-response element binding protein binding to hypoxia response element-1 at −158 to −153 bp of human PAI-1 promoter in human MCs. Moreover, cAMP synergistically augments PAI-1 expression with ionomycin- or IgE receptor cross-linking-mediated stimulation. 相似文献
192.
Quantum-chemical study of structures, energies, and effective partial charge distribution for several models of the Rieske protein redox center is performed in terms of the B3LYP density functional method in combination with the broken symmetry approach using three different atomic basis sets. The structure of the redox complex optimized in vacuum differs markedly from that inside the protein. This means that the protein matrix imposes some stress on the active site resulting in distortion of its structure. The redox potentials calculated for the real active site structure are in a substantially better agreement with the experiment than those calculated for the idealized structure. This shows an important role of the active site distortion in tuning its redox potential. The reference absolute electrode potential of the standard hydrogen electrode is used that accounts for the correction caused by the water surface potential. Electrostatic calculations are performed in the framework of the polarizable solute model. Two dielectric permittivities of the protein are employed: the optical permittivity for calculation of the intraprotein electric field, and the static permittivity for calculation of the dielectric response energy. Only this approach results in a reasonable agreement of the calculated and experimental redox potentials. 相似文献
193.
Summary A class of nonignorable models is presented for handling nonmonotone missingness in categorical longitudinal responses. This class of models includes the traditional selection models and shared parameter models. This allows us to perform a broader than usual sensitivity analysis. In particular, instead of considering variations to a chosen nonignorable model, we study sensitivity between different missing data frameworks. An appealing feature of the developed class is that parameters with a marginal interpretation are obtained, while algebraically simple models are considered. Specifically, marginalized mixed‐effects models ( Heagerty, 1999 , Biometrics 55, 688–698) are used for the longitudinal process that model separately the marginal mean and the correlation structure. For the correlation structure, random effects are introduced and their distribution is modeled either parametrically or non‐parametrically to avoid potential misspecifications. 相似文献
194.
Summary We propose a Bayesian chi‐squared model diagnostic for analysis of data subject to censoring. The test statistic has the form of Pearson's chi‐squared test statistic and is easy to calculate from standard output of Markov chain Monte Carlo algorithms. The key innovation of this diagnostic is that it is based only on observed failure times. Because it does not rely on the imputation of failure times for observations that have been censored, we show that under heavy censoring it can have higher power for detecting model departures than a comparable test based on the complete data. In a simulation study, we show that tests based on this diagnostic exhibit comparable power and better nominal Type I error rates than a commonly used alternative test proposed by Akritas (1988, Journal of the American Statistical Association 83, 222–230). An important advantage of the proposed diagnostic is that it can be applied to a broad class of censored data models, including generalized linear models and other models with nonidentically distributed and nonadditive error structures. We illustrate the proposed model diagnostic for testing the adequacy of two parametric survival models for Space Shuttle main engine failures. 相似文献
195.
We show that the number of segregating sites is a sufficient statistic for the scaled mutation parameter (θ) in the limit as the number of sites tends to infinity and there is free recombination between sites. We assume that the mutation parameter at each site tends to zero such than the total mutation parameter (θ) is constant in the limit. Our results show that Watterson’s estimator is the maximum likelihood estimator in this case, but that it estimates a composite parameter which is different for different mutation models. Some of our results hold when recombination is limited, because Watterson’s estimator is an unbiased, method-of-moments estimator regardless of the recombination rate. The quantity it estimates depends on the details of how mutations occur at each site. 相似文献
196.
James D. Stamey Dean M. Young Tom L. Bratcher 《Biometrical journal. Biometrische Zeitschrift》2004,46(5):572-578
We develop three Bayesian predictive probability functions based on data in the form of a double sample. One Bayesian predictive probability function is for predicting the true unobservable count of interest in a future sample for a Poisson model with data subject to misclassification and two Bayesian predictive probability functions for predicting the number of misclassified counts in a current observable fallible count for an event of interest. We formulate a Gibbs sampler to calculate prediction intervals for these three unobservable random variables and apply our new predictive models to calculate prediction intervals for a real‐data example. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) 相似文献
197.
Chromium(III) is often claimed to have a positive effect on body composition, while the responses in researches with supplementation
of different chemical form of chromium are various and inconsistent. We have studied the effects of 6 weeks of treatment with
three different forms of chromium (300 μg/kg) as chromium chloride, chromium tripicolinate, and chromium nanocomposite (CrNano)
on growth, body composition, serum parameters, and tissue chromium in rats. The supplementataion of CrNano significantly increased
average daily gain, food efficiency, and lean body mass and decreased fat mass and body fat proportion and serum levels of
glucose, urea nitrogen, triglyceride, and insulin. Chromium contents in liver, kidney, and hind leg muscle were increased
significantly with the addition of CrNano in diet. The results indicate that chromium nanocomposite has higher efficacy on
growth and body composition compared to the traditional chromium agents. 相似文献
198.
This paper considers a model developed to study the cardiovascular control system response to orthostatic stress as induced by two variations of lower body negative pressure (LBNP) experiments. This modeling approach has been previously applied to study control responses to transition from rest to aerobic exercise, to transition to non-REM sleep and to orthostatic stress as produced by the head up tilt (HUT) experiment. LBNP induces a blood volume shift because negative pressure changes the volume loading characteristics of the compartment which is subject to the negative pressure. This volume shift induces a fall in blood pressure which must be counteracted by a complicated control response involving a variety of mechanisms of the cardiovascular control system. There are a number of medical issues connected to these questions such as orthostatic intolerance in the elderly resulting in dizziness or fainting during the transition from sitting to standing. The model presented here is used to study the interaction of changes in systemic resistance, unstressed venous volume, venous compliance, heart rate, and contractility in the control of orthostatic stress. The overall short term response depends on a combination of these physiological reactions which may vary from individual to individual. There remain open questions about which factors have greater importance. The model simulations are compared to experimental data collected for LBNP exerted from the hips to feet and from ribs to feet. 相似文献
199.
200.
A detailed analysis of the 13C relaxation of 13C-labelled spermine bound to duplex and quadruplex DNA is presented. T1, T2 and heteronuclear NOE data were collected at four 13C frequencies (75.4, 125.7, 150.9 and 201.2 MHz). The data were analyzed in terms of a frequency-dependent order parameter,
S
2(ω), to estimate the generalized order parameter and the contributions to the relaxation from different motional frequencies
in the picosecond–nanosecond timescale and from any exchange processes that may be occurring on the microsecond–millisecond
timescale. The relaxation data was surprisingly similar for spermine bound to two different duplexes and a linear parallel
quadruplex. Analysis of the relaxation data from these complexes confirmed the conclusions of previous studies that the dominant
motion of spermine is independent of the macroscopic tumbling of the DNA and has an effective correlation time of ∼50 ps.
In contrast, spermine bound to a folded antiparallel quadruplex had faster relaxation rates, especially R
2. As with the other complexes, a fast internal motion of the order of 50 ps makes a substantial contribution to the relaxation.
The generalized order parameter for spermine bound to duplex DNA and the linear quadruplex is small but is larger for spermine
bound to the folded quadruplex. In the latter case, there is evidence for exchange between at least two populations of spermine
occurring on the microsecond–millisecond timescale.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献