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81.
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
82.
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83.
84.
Caitlin M. Cossaboom Laura Córdoba Dianjun Cao Yan-Yan Ni Xiang-Jin Meng 《Journal of virology》2012,86(23):13124-13125
Hepatitis E virus (HEV) is a single-strand positive-sense RNA virus in the family Hepeviridae. The disease caused by HEV, hepatitis E, is an important public health problem in developing countries of Asia and Africa and is also endemic in many industrialized countries, including the United States. HEV has been identified from several other animal species in addition to humans, including the pig, chicken, mongoose, deer, rabbit, ferret, bat, and fish. Here we report the complete genome sequence of the first strain of HEV from rabbits in the United States. Sequence and phylogenetic analyses revealed that the U.S. rabbit HEV is a distant member of the zoonotic genotype 3 HEV, thus raising a concern for potential zoonotic human infection. A unique 90-nucleotide insertion within the X domain of the ORF1 was identified in the rabbit HEV, and this insertion may play a role in the species tropism of HEV. 相似文献
85.
C L Rümke 《Blood cells》1985,11(1):137-140
Ratios of two percentages observed in differential counts of leukocytes or lymphocytes are very imprecise if they are based on relatively small numbers of cells. This is shown by the length of the 95% confidence intervals for such ratios. A formula is given for computing the limits of such intervals. They should accompany each observed value for a ratio. 相似文献
86.
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
87.
Molecular dynamics (MD) simulations of phosphatidylinositol (4,5)-bisphosphate (PIP2) and phosphatidylinositol (3,4,5)-trisphosphate (PIP3) in 1-palmitoyl 2-oleoyl phosphatidylcholine (POPC) bilayers indicate that the inositol rings are tilted ∼40° with respect to the bilayer surface, as compared with 17° for the P-N vector of POPC. Multiple minima were obtained for the ring twist (analogous to roll for an airplane). The phosphates at position 1 of PIP2 and PIP3 are within an Ångström of the plane formed by the phosphates of POPC; lipids in the surrounding shell are depressed by 0.5-0.8 Å, but otherwise the phosphoinositides do not substantially perturb the bilayer. Finite size artifacts for ion distributions are apparent for systems of ∼26 waters/lipid, but, based on simulations with a fourfold increase of the aqueous phase, the phosphoinositide positions and orientations do not show significant size effects. Electrostatic potentials evaluated from Poisson-Boltzmann (PB) calculations show a strong dependence of potential height and ring orientation, with the maxima on the −25 mV surfaces (17.1 ± 0.1 Å for PIP2 and 19.4 ± 0.3 Å for PIP3) occurring near the most populated orientations from MD. These surfaces are well above the background height of 10 Å estimated for negatively charged cell membranes, as would be expected for lipids involved in cellular signaling. PB calculations on microscopically flat bilayers yield similar maxima as the MD-based (microscopically rough) systems, but show less fine structure and do not clearly indicate the most probable regions. Electrostatic free energies of interaction with pentalysine are also similar for the rough and flat systems. These results support the utility of a rigid/flat bilayer model for PB-based studies of PIP2 and PIP3 as long as the orientations are judiciously chosen. 相似文献
88.
Jürgen Sühnel 《Bulletin of mathematical biology》1998,60(2):197-213
A possible experimental design for combination experiments is to compare the doseresponse curve of a single agent with the
corresponding curve of the same agent using either a fixed amount of a second one or a fixed dose ratio. No interaction is
then often defined by a parallel shift of these curves. We have performed a systematic study for various types of doseresponse
relations both for the dose-additivity (Loewe additivity) and for the independence (Bliss independence) criteria for defining
zero interaction. Parallelism between doseresponse curves of a single agent and those of the same agent in the presence of
a fixed amount of another one is found for the Loewe-additivity criterion for linear doseresponse relations. For nonlinear
relations, one has to differentiate between effect parallelism (parallel shift on the effect scale) and dose parallelism (parallel
shift on the dose scale). In the case of Loewe additivity, zero-interaction dose parallelism is found for power, Weibull,
median-effect and logistic doseresponse relations, given that special parameter relationships are fulfilled. The mechanistic
model of competitive interaction exhibits dose parallelism but not effect parallelism for Loewe additivity. Bliss independence
and Loewe additivity lead to identical results for exponential doseresponse curves. This is the only case for which dose parallelism
was found for Bliss independence. Parallelism between single-agent doseresponse relations and Loewe additivity mixture relations
is found for examples with a fixed doseratio design. However, this is again not a general property of the design adopted but
holds only if special conditions are fulfilled. The comparison of combination doseresponse curves with single-agent relations
has to be performed taking into account both potency and shape parameters. The results of this analysis lead to the conclusion
that parallelism between zero interaction combination and single-agent doseresponse relations is found only for special cases
and cannot be used as a general criterion for defining zero-interaction in combined-action assessment even if the correct
potency shift is taken into account. 相似文献
89.
The results of recent randomized trials to test the influence of antioxidants on coronary-event rates and prognosis in patients
with coronary-artery disease were disappointing. In none of these studies did the use of vitamin E improve prognosis. In contrast,
treatment of coronary-artery disease with angiotensin-converting-enzyme (ACE) inhibitors reduced coronary-event rates and
improved prognosis. ACE inhibition prevents the formation of angiotensin II, which has been shown to be a potent stimulus
of superoxide-producing enzymes in atherosclerosis. The findings suggest that inhibition of superoxide production at enzymatic
levels, rather than symptomatic superoxide scavenging, may be the better choice of treatment. 相似文献
90.
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