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61.
Growth-related expression of a double-stranded RNA-dependent protein kinase in 3T3 cells 总被引:14,自引:0,他引:14
Cultured mouse 3T3-F442A and 3T3-C2 fibroblasts exhibit a transient double-stranded RNA (dsRNA)-dependent phosphorylation of a 67,000-dalton protein (67K) without prior treatment with interferon (IFN). This phosphoprotein is similar but not identical to the dsRNA-dependent eukaryotic initiation factor-2 (eIF-2) alpha protein kinase (dsI), which regulates protein synthesis in rabbit reticulocytes. We have studied the relationship between cell growth and phosphorylation of the 67K protein (designated 3T3-dsRNA-dependent eIF-2 alpha kinase). A low level of dsRNA-dependent phosphorylation of 3T3-dsI was detectable in extracts prepared from cells not treated with IFN and grown at a low cell density. The phosphorylation of dsI and the phosphorylation of a 38K protein identified as the alpha-subunit (38K) of 3T3-eIF-2 (eIF-2 alpha) occurred concomitantly; the levels of these phosphorylations confluent and thereafter decreased markedly. Treatment of cells with IFN at all stages of growth resulted in an increase in phosphorylation of dsI. 3T3-F442A and 3T3-C2 fibroblasts were found to produce and secrete IFN at levels sufficient to induce an elevated dsI activity. 相似文献
62.
TNF inhibitors are currently considered both effective and cost-effective in patients with active rheumatoid arthritis (RA),
particularly in patients who have not responded fully to methotrexate. There is substantial doubt about the cost-effectiveness
of TNF inhibitors as initial treatment for active RA. New data from the National Data Bank for Rheumatic Diseases now question
the current consensus in methotrexate failures. The data suggest that in routine clinical practice TNF inhibitors provide
only modest incremental benefits over best conventional therapy. If confirmed, these observational studies suggest that the
economic argument underpinning the widespread use of TNF inhibitors in established RA is unsustainable. 相似文献
63.
Background
DNA Microarrays have become the standard method for large scale analyses of gene expression and epigenomics. The increasing complexity and inherent noisiness of the generated data makes visual data exploration ever more important. Fast deployment of new methods as well as a combination of predefined, easy to apply methods with programmer's access to the data are important requirements for any analysis framework. Mayday is an open source platform with emphasis on visual data exploration and analysis. Many built-in methods for clustering, machine learning and classification are provided for dissecting complex datasets. Plugins can easily be written to extend Mayday's functionality in a large number of ways. As Java program, Mayday is platform-independent and can be used as Java WebStart application without any installation. Mayday can import data from several file formats, database connectivity is included for efficient data organization. Numerous interactive visualization tools, including box plots, profile plots, principal component plots and a heatmap are available, can be enhanced with metadata and exported as publication quality vector files. 相似文献64.
65.
Emin Oguzhan Oguz Hayati Yuksel Yasar Enli A. Cevik Tufan Gunfer Turgut 《Biological trace element research》2010,133(3):335-341
Copper is an essential trace element that is extremely toxic to organisms and organs at high doses. We have investigated the
histological and biochemical effects of a toxic dose of copper sulfate on the liver of term Ross broiler chicks. Fertilized
eggs were divided into three groups: experimental, injected with 50 mcg/0.1 ml copper sulfate in the air chambers on day 1;
sham, injected with 0.1 ml saline; and control, no injection. Term chicks were killed and their livers investigated histologically,
with hematoxylin–eosin-stained sections examined under light microscopy, and biochemically, for malondialdehyde and glutathione
levels. Histological examinations showed copper-treated samples with granular degeneration and necrosis of hepatocytes and
impairment to the cell lining of the remark cords. The samples had a congestive appearance, with blood in the vena centralis
and sinusoids, slight connective tissue increase, and lymphocyte infiltration. Control and sham group sections had normal
appearances. As oxidative damage parameters, in the copper-treated group, malondialdehyde levels were increased and glutathione
levels decreased. In the sham and control groups, there were no significant differences. At this toxic dose, copper sulfate
shows oxidative damage according to the histology of term chick liver that are confirmed biochemically by the changes in malondialdehyde
and glutathione levels. 相似文献
66.
Vinyl chloride (VC) is used as an example to demonstrate how biological information can be incorporated into quantitative risk assessment. The information included is the pharmacokinetics of VC in animals and humans and the data-generated hypothesis that VC primarily affects the initiation stage of the multistage carcinogenesis. The emphasis in this paper is on the improvement of risk assessment methodology rather than the risk assessment of VC per se.Sufficient data are available to construct physiologically-based pharmacokinetic models for both animals and humans. These models are used to calculate the metabolized dose corresponding to exposure scenarios in animals and in humans.On the basis of the data on liver angiosarcomas and carcinomas in rats, the cancer risk per unit of metabolized dose is comparable, irrespective of routes (oral or inhalation) of exposure. The tumor response from an intermittent/partial lifetime exposure is shown to be consistent with that from a lifetime exposure when VC is assumed to affect the first (initiation) stage of the multistage carcinogenic process. Furthermore, the risk estimates calculated on the basis of animal data are shown to be consistent with the human experience. 相似文献
67.
68.
The purpose of this review is to provide a global perspective on Oncorhynchus salmonine introductions and put-and-take fisheries based on modern stocking programs, with special emphasis on freshwater
ecosystems. We survey the global introductions of nine selected salmonines of the genus Oncorhynchus: golden trout, cutthroat trout, pink salmon, chum salmon, coho salmon, masu/cherry salmon, rainbow trout/steelhead, sockeye
salmon/kokanee, and chinook salmon. The information is organized on a geographical basis by continent, and then by species
and chronology. Two different objectives and associated definitions of ‘success’ for introductions are distinguished: (a)
seed introduction: release of individuals with the purpose of creating a wild-reproducing, self-sustaining population; and
(b) put-and-take introduction: release of individuals with the purpose of maintaining some level of wild population abundance,
regardless of wild reproduction. We identify four major phenomena regarding global salmonine introductions: (1) general inadequacy
of documentation regarding introductions; (2) a fundamental disconnect between management actions and ecological consequences
of introductions; (3) the importance of global climate change on success of previous and future introductions; and (4) the
significance of aquaculture as a key uncertainty in accidental introductions. We conclude this review with a recognition of
the need to terminate ongoing stocking programs for introduced salmonines worldwide. 相似文献
69.
70.
Semiparametric Regression in Size-Biased Sampling 总被引:1,自引:0,他引:1
Ying Qing Chen 《Biometrics》2010,66(1):149-158
Summary . Size-biased sampling arises when a positive-valued outcome variable is sampled with selection probability proportional to its size. In this article, we propose a semiparametric linear regression model to analyze size-biased outcomes. In our proposed model, the regression parameters of covariates are of major interest, while the distribution of random errors is unspecified. Under the proposed model, we discover that regression parameters are invariant regardless of size-biased sampling. Following this invariance property, we develop a simple estimation procedure for inferences. Our proposed methods are evaluated in simulation studies and applied to two real data analyses. 相似文献