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851.
P.A. Bretscher N. Ismail J.N. Menon C.A. Power J. Uzonna G. Wei 《Cellular and molecular life sciences : CMLS》2001,58(12-13):1879-1896
The occurrence of infectious disease represents a failure of the immune system, a failure that must be prevented by effective vaccination or remedied by treatment. Vaccination against acute diseases such as smallpox and polio are very effective, due to the rapid and increased immune response of vaccinated individuals upon natural infection. In contrast, effective vaccination against intracellular pathogens that cause chronic diseases, such as the leishmaniases, tuberculosis and AIDS, has not been achieved. Clinical observations suggest cell-mediated, Th1 responses, exclusive of antibody production and the generation of Th2 cells, are optimally protective against these intracellular pathogens. Effective vaccination must ensure the generation of such a protective response. We explore here whether understanding very broad features of the regulation of the immune response can accommodate modern findings on the immunological features of these diseases, and provide a perspective within which strategies for effective vaccination and treatment can be developed. 相似文献
852.
853.
We analyze the developments in mathematical rigor from the viewpoint of a Burgessian critique of nominalistic reconstructions.
We apply such a critique to the reconstruction of infinitesimal analysis accomplished through the efforts of Cantor, Dedekind,
and Weierstrass; to the reconstruction of Cauchy’s foundational work associated with the work of Boyer and Grabiner; and to
Bishop’s constructivist reconstruction of classical analysis. We examine the effects of a nominalist disposition on historiography,
teaching, and research. 相似文献
854.
There is substantial evidence that the martian volatile inventory and climate have changed markedly throughout the planet's history. Clues come from areas as disparate as the history and properties of the deep interior, the composition of the crust and regolith, the morphology of the surface, composition of the present-day atmosphere, and the nature of the interactions between the upper atmosphere and the solar wind. We piece together the relevant observations into a coherent view of the evolution of the martian climate, focusing in particular on the observations that provide the strongest constraints. 相似文献
855.
The stable propagation of genetic information requires that the entire genome of an organism be faithfully replicated once and only once each cell cycle. In eukaryotes, this replication is initiated at hundreds to thousands of replication origins distributed over the genome, each of which must be prohibited from re-initiating DNA replication within every cell cycle. How cells prevent re-initiation has been a long-standing question in cell biology. In several eukaryotes, cyclin-dependent kinases (CDKs) have been implicated in promoting the block to re-initiation, but exactly how they perform this function is unclear. Here we show that B-type CDKs in Saccharomyces cerevisiae prevent re-initiation through multiple overlapping mechanisms, including phosphorylation of the origin recognition complex (ORC), downregulation of Cdc6 activity, and nuclear exclusion of the Mcm2-7 complex. Only when all three inhibitory pathways are disrupted do origins re-initiate DNA replication in G2/M cells. These studies show that each of these three independent mechanisms of regulation is functionally important. 相似文献
856.
857.
本文报导用活性炭盒吸附方法对香港室内氡浓度的测量结果及其浓度分布规律。对室内氡浓度与建筑物表面氡析出率的关系进行了分析研究。证实室内空气中的氡主要来源于建材中的镭,而氡浓度水平只决定于室内建筑物表面氡的析出率及通风状况。 相似文献
858.
Membrane depolarization causes many kinds of ion channels to open, a process termed activation. For both Na+ channels and Ca2+ channels, kinetic analysis of current has suggested that during activation the channel undergoes several conformational changes before reaching the open state. Structurally, these channels share a common motif: the central element is a large polypeptide with four repeating units of homology (repeats I-IV), each containing a voltage-sensing region, the S4 segment. This suggests that the distinct conformational transitions inferred from kinetic analysis may be equated with conformational changes of the individual structural repeats. To investigate the molecular basis of channel activation, we constructed complementary DNAs encoding chimaeric Ca2+ channels in which one or more of the four repeats of the skeletal muscle dihydropyridine receptor are replaced by the corresponding repeats derived from the cardiac dihydropyridine receptor. We report here that repeat I determines whether the chimaeric Ca2+ channel shows slow (skeletal muscle-like) or rapid (cardiac-like) activation. 相似文献
859.
R E Hill J Favor B L Hogan C C Ton G F Saunders I M Hanson J Prosser T Jordan N D Hastie V van Heyningen 《Nature》1991,354(6354):522-525
860.
The L-type voltage-dependent calcium channel is an important link in excitation-contraction coupling of muscle cells (reviewed in refs 2 and 3). The channel has two functional characteristics: calcium permeation and receptor sites for calcium antagonists. In skeletal muscle the channel is a complex of five subunits, alpha 1, alpha 2, beta, gamma and delta. Complementary DNAs to these subunits have been cloned and their amino-acid sequences deduced. The skeletal muscle alpha 1 subunit cDNA expressed in L cells manifests as specific calcium-ion permeation, as well as sensitivity to the three classes of organic calcium-channel blockers. We report here that coexpression of the alpha 1 subunit with other subunits results in significant changes in dihydropyridine binding and gating properties. The available number of drug receptor sites increases 10-fold with an alpha 1 beta combination, whereas the affinity of the dihydropyridine binding site remains unchanged. Also, the presence of the beta subunit accelerates activation and inactivation kinetics of the calcium-channel current. 相似文献