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91.
Chromosomal effects of adeno-associated virus vector integration.   总被引:17,自引:0,他引:17  
Adeno-associated virus (AAV) vectors are currently being used in several clinical gene-therapy trials (see the NIH OBA Human Gene Transfer Clinical Trials Database); however, little is known about the chromosomal effects of vector integration. Here we report that integrated vector proviruses are associated with chromosomal deletions and other rearrangements and are frequently located on chromosome 19 (although not at the wildtype AAV integration site).  相似文献   
92.
During the evolution of proteins the pressure to optimize biological activity is moderated by a need for efficient folding. For most proteins, this is accomplished through spontaneous folding to a thermodynamically stable and active native state. However, in the extracellular bacterial alpha-lytic protease (alphaLP) these two processes have become decoupled. The native state of alphaLP is thermodynamically unstable, and when denatured, requires millennia (t1/2 approximately 1,800 years) to refold. Folding is made possible by an attached folding catalyst, the pro-region, which is degraded on completion of folding, leaving alphaLP trapped in its native state by a large kinetic unfolding barrier (t1/2 approximately 1.2 years). alphaLP faces two very different folding landscapes: one in the presence of the pro-region controlling folding, and one in its absence restricting unfolding. Here we demonstrate that this separation of folding and unfolding pathways has removed constraints placed on the folding of thermodynamically stable proteins, and allowed the evolution of a native state having markedly reduced dynamic fluctuations. This, in turn, has led to a significant extension of the functional lifetime of alphaLP by the optimal suppression of proteolytic sensitivity.  相似文献   
93.
We discuss a generalization of the standard notion of probability space and show that the emerging framework, to be called operational probability theory, can be considered as underlying quantal theories. The proposed framework makes special reference to the convex structure of states and to a family of observables which is wider than the familiar set of random variables: it appears as an alternative to the known algebraic approach to quantum probability.  相似文献   
94.
A detailed karyotypic analysis of two Egyptian species of bats,Taphozous perforatus andTaphozous nudiventris, was made on the basis of conventional data and G-band patterns. No detectable karyotypic difference was found between the two species (2n=42, F.N. 64). By comparison of G-band patterns, some differences between the two species were seen in the corresponding autosomal pairs. These results are reported for the first time in Egypt.  相似文献   
95.
本文研究了地下矿井内,电波沿巷道内线缆传播的可行性及单线波模的传播与衰减规律,研究巷道内电小天线与线缆之间的耦合情况,从而为实际工作提供理论依据。  相似文献   
96.
A topoisomerase II inhibitor, novobiocin, and a deacetylase inhibitor, butyrate, synergistically transformed human liver cells into fibroblast-like cells. This morphological change was associated with an increased production of procollagen type III peptide and a simultaneous assembly of actin, tubulin, vimentin and cytokeratin. Novobiocin and butyrate had no marked effect on the phosphorylation state of cytokeratin proteins, but synergistically enhanced [3H]acetate uptake. From these results, it can be speculated that protein acetylation plays an important role in inducing the assembly of cytoskeletal proteins and the morphological transformation of human liver cells.  相似文献   
97.
A diffusion chamber technique based on time-lag analysis for the estimation of effective diffusion coefficients of radiolabelled macromolecules of varying molecular weights through native mucus gel is reported. For all solutes studied, a reduction in effective diffusion coefficients was observed with a retardation of solute flux in both aqueous and mucus layers. Over the molecular weight range of solutes investigated (126-186,000 Daltons), a consistent effect of molecular weight was evident with regard to the retarding effect of mucus. No apparent or absolute molecular weight cut-off for macromolecular transfer was exhibited. However, at high molecular weights (greater than 30,000 Daltons) the retardation was greatly enhanced. The results confirm that mucus can be regarded as a gel with finite pores, but that it does not constitute an absolute barrier to even high molecular weight solutes.  相似文献   
98.
99.
从高校非中文专业学生知识结构的现状出发,阐述加强人文素质教育的重要性;“中国古典文学鉴赏”课的课程特点及其在人文素质教育中所起的作用决定了在高校非中文专业学生中开设这门课程的必要性和可行性。  相似文献   
100.
就近几年图书馆界关于新世纪馆员意识转换及社会角色转换等方面的研究进行了综述,指出新时期的馆员要实现自我社会角色的转换,首先是要明确转换的必要性,然后采取有效的策略逐步地、系统地推进转换,才能取得较好的效果。  相似文献   
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