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Eleven mumps vaccine strains, all containing live attenuated virus, have been used throughout the world. Although L-Zagreb mumps vaccine has been licensed since 1972, only its partial nucleotide sequence was previously determined (accession numbers , and ). Therefore, we sequenced the entire genome of L-Zagreb vaccine strain (Institute of Immunology Inc., Zagreb, Croatia). In order to investigate the genetic stability of the vaccine, sequences of both L-Zagreb master seed and currently produced vaccine batch were determined and no difference between them was observed. A phylogenetic analysis based on SH gene sequence has shown that L-Zagreb strain does not belong to any of established mumps genotypes and that it is most similar to old, laboratory preserved European strains (1950s-1970s). L-Zagreb nucleotide and deduced protein sequences were compared with other mumps virus sequences obtained from the GenBank. Emphasis was put on functionally important protein regions and known antigenic epitopes. The extensive comparisons of nucleotide and deduced protein sequences between L-Zagreb vaccine strain and other previously determined mumps virus sequences have shown that while the functional regions of HN, V, and L proteins are well conserved among various mumps strains, there can be a substantial amino acid difference in antigenic epitopes of all proteins and in functional regions of F protein. No molecular pattern was identified that can be used as a distinction marker between virulent and attenuated strains.  相似文献   
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We measured brain activity using magnetoencephalography in five participants during ongoing tasks that included prospective memory, retrospective memory, and oddball trials. Sources were identified in the hippocampal formation and posterior parietal and frontal lobes. Posterior parietal cortex activation had an earlier onset in the prospective memory condition than retrospective memory or oddball conditions, a higher level of theta activity in the retrospective condition, and higher levels of upper alpha in the prospective and oddball conditions. Activation of the hippocampal formation had a longer duration in the retrospective memory and prospective memory conditions than the oddball condition, but prominent alpha and theta band activity was present in all three conditions. We interpret the early (87 ms) onset of activity in parietal cortex as evidence for an initial noticing of appropriate conditions for a PM response. Hippocampal activity may reflect a subsequent memory search for the intended action.  相似文献   
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Inhibitor design by wrapping packing defects in HIV-1 proteins   总被引:1,自引:0,他引:1  
Two viral proteins, HIV-1 protease and HIV-1 integrase, have been targeted for inhibitor design to prevent assembly and maturation of HIV-1 virions. The enzymatic mechanism of these proteins involves side-chain groups that serve as general acids or bases. Furthermore, catalytic activity requires that water be removed from the microenvironment surrounding the chemical reaction site or be constrained to serve as an activated nucleophile. Here, we identify previously unrecognized structural features that promote water removal from polar catalytic regions. Packing defects in the form of hydrogen bonds that are insufficiently dehydrated intramolecularly, named "dehydrons," are strategically placed in the structure to induce an anhydrous enzymatic pathway. Dehydrons become electrostatically enhanced and stabilized upon further desolvation. Thus, packing defects act synergistically with the polar active groups to enhance the enzymatic electrostatics. However, because dehydrons are sticky, they constitute targets for inhibitor design. We noticed that inhibitors attach to polar surfaces by further desolvating dehydrons, thus blocking the active sites or the sites involved in harnessing the substrate. The dehydrons are thus required for functional reasons, making them suitable targets. The differences in success when targeting HIV-1 protease, feline immunodeficiency virus protease, and HIV-1 integrase are rationalized in terms of the dehydron distribution, revealing possible improvements in the targeting strategy. Principles of design optimization are proposed to create an inhibitor that can be neutralized only at the expense of the loss of catalytic function. The possibility of using drugs that wrap dehydrons to block protein-protein associations is also discussed.  相似文献   
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This paper presents a conjugate gradient‐based algorithm for feedback min–max optimal control of nonlinear systems. The algorithm has a backward‐in‐time recurrent structure similar to the back propagation through time (BPTT) algorithm. The control law is given as the output of the one‐layer NN. Main contribution of the paper includes the integration of BPTT techniques, conjugate gradient methods, Adams method for solving ODEs and automatic differentiation, to provide an effective, numerically robust algorithm for solving optimal min–max control problems. The proposed algorithm is evaluated on a robotic system with two DOFs. Copyright © 2012 John Wiley & Sons, Ltd.  相似文献   
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Cytoprotector amifostine (AMI) was given in a dose of 50, 100 or 150?mg/kg ip in rats treated with several highly toxic doses of T-2 toxin. The best survival rate (24?h and 7?days after treatment) was obtained with AMI50 (50?mg/kg ip). After T-2 intoxication, a peak in the mean number of gastric lesions (petechiae and ulcerations) was reached on the third day (26.40?±?6.24). Administration of AMI50 reduced, almost completely, the total number of gastric lesions in rats acutely poisoned by 0.5 LD50 T-2 (1.5?mg/kg sc), starting with day 1 after intoxication (5.60?±?3.42).  相似文献   
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Electrically conductive yarns (ECYs) are gaining increasing applications in woven textile materials, especially in woven sensors suitable for incorporation into clothing. In this paper, the effect of the yarn count of ECYs woven into fabric on values of electrical resistance is analyzed. We also observe how the direction of action of elongation force, considering the position of the woven ECY, effects the change in the electrical resistance of the electrically conductive fabric. The measurements were performed on nine different samples of fabric in a plain weave, into which were woven ECYs with three different yarn counts and three different directions. Relationship curves between values of elongation forces and elongation to break, as well as relationship curves between values of electrical resistance of fabrics with ECYs and elongation, were experimentally obtained. An analytical mathematical model was also established, and analysis was conducted, which determined the models of function of connection between force and elongation, and between electrical resistance and elongation. The connection between the measurement results and the mathematical model was confirmed. The connection between the mathematical model and the experimental results enables the design of ECY properties in woven materials, especially textile force and elongation sensors.  相似文献   
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