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51.
The expansion of trinucleotide repeat sequences has now been shown to be the underlying cause of at least ten human disorders. Unifying features among these diseases include the unstable behavior of the triplet repeat during germline transmission when the length of the repeat exceeds a critical value. However, the trinucleotide repeat disorders can be divided into two distinct groups. Type I disorders involve the expansion of CAG repeats, which encode an expanded polyglutamine, inserted into the open-reading frame of a gene that is usually quite broadly expressed. Recently, mouse models for type I disorders have been developed and the basis of pathology is under study, both in these models and through biochemical and cell biological approaches. The type II disorders involve repeat expansions in noncoding regions of genes. The mechanisms by which these repeat expansions lead to pathology may be quite diverse. 相似文献
52.
The effect of external calcium concentration ([Ca2+]o) on membrane potential-dependent calcium signals in isolated tiger salamander rod and cone photoreceptor inner segments was investigated with patch-clamp and calcium imaging techniques. Mild depolarizations led to increases in intracellular Ca2+ levels ([Ca2+]i) that were smaller when [Ca2+]o was elevated to 10 mM than when it was 3 mM, even though maximum Ca2+ conductance increased 30% with the increase in [Ca2+]o. When external calcium was lowered to 1 mM [Ca2+]o, maximum Ca2+ conductance was reduced, as expected, but the mild depolarization-induced increase in [Ca2+]i was larger than in 3 mM [Ca2+]o. In contrast, when photoreceptors were strongly depolarized, the increase in [Ca2+]i was less when [Ca2+]o was reduced. An explanation for these observations comes from an assessment of Ca2+ channel gating in voltage-clamped photoreceptors under changing conditions of [Ca2+]o. Although Ca2+ conductance increased with increasing [Ca2+]o, surface charge effects dictated large shifts in the voltage dependence of Ca2+ channel gating. Relative to the control condition (3 mM [Ca2+]o), 10 mM [Ca2+]o shifted Ca2+ channel activation 8 mV positive, reducing channel open probability over a broad range of potentials. Reducing [Ca2+]o to 1 mM reduced Ca2+ conductance but shifted Ca2+ channel activation negative by 6 mV. Thus the intracellular calcium signals reflect a balance between competing changes in gating and permeation of Ca2+ channels mediated by [Ca2+]o. In mildly depolarized cells, the [Ca2+]o-induced changes in Ca2+ channel activation proved stronger than the [Ca2+]o-induced changes in conductance. In response to the larger depolarizations caused by 80 mM [K+]o, the opposite is true, with conductance changes dominating the effects on channel activation. 相似文献
53.
PA Wallace DE Minnikin K McCrudden A Pizzarello 《Canadian Metallurgical Quarterly》1994,71(2):145-162
Tuberculostearic acid, (R)-10-methyloctadecanoic acid, is a characteristic component of pathogenic mycobacteria and related organisms. Sensitive detection of this acid in infected material allows rapid detection of mycobacterial disease. A novel, convergent synthesis of tuberculostearic acid and key chiral intermediates is described in this communication, to provide a reference compound. Racemic and (R)- and (S)-1-iodo-2-methyldecanes were synthesised from 1-octanal and 1-carboethoxyethylidenetriphenylphosphorane as initial starting materials. 1-Hydroxyoct-7-yne was made from 1,6-hexanediol by two alternative methods and coupled with the above racemic iodide. Hydrogenation and oxidation of the resulting (R,S)-10-methyloctadec-7-yn-1-ol gave racemic tuberculostearic acid. 相似文献
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All boiling water reactor (BWR) degraded core experiments performed prior to CORA-33 were conducted under ‘wet’ core degradation conditions, in which water remains within the core and continuous steaming feeds metal-steam oxidation reactions on the in-core metallic surfaces. However, one dominant set of accident scenarios would occur with reduced metal oxidation under ‘dry’ core degradation conditions and, prior to CORA-33, this set had been neglected experimentally. The CORA-33 experiment was designed specifically to address this dominant set of BWR ‘dry’ core severe accident scenarios and to resolve partially phenomenological uncertainties concerning the behavior of relocating metallic melts that drain into the lower regions of a ‘dry’ BWR core (the ex-reactor experiments at Sandia National Laboratories will further address these uncertainties). CORA-33 was conducted on 1 October 1992, in the CORA test facility at Karlsruhe. A review of the CORA-33 data indicates that the objectives were achieved; i.e. core degradation occurred at a core heat-up rate (characterized by the absence of any temperature escalation caused by oxidation) and a test section axial temperature profile (at incipient structural melting) that are prototypic of full-core nuclear power plant simulations under ‘dry’ core conditions. Simulations of the CORA-33 test at Oak Ridge National Laboratory (ORNL) have required the modification of existing control blade-canister materials interaction models to include the eutectic melting of the stainless steel-zircaloy interaction products and the heat of mixing of stainless steel and zircaloy. The timing and location of canister failure and melt intrusion into the fuel assembly appear to be adequately simulated by the ORNL models. This paper will present the results of the post-test analyses carried out at ORNL based on the experimental data and the post-test examination of the test bundle at Karlsruhe. The implications of these results with respect to degraded core modelling and the associated safety issues are also discussed. 相似文献
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57.
M Agelli P Dello Sbarba ED Halay RA Faris DE Hixson LM Reid 《Canadian Metallurgical Quarterly》1997,29(3):205-217
BACKGROUND AND OBJECTIVES: We operated on three patients with leiomyosarcoma of the inferior vena cava. METHODS: Complete excision was possible in all three patients. RESULTS: One patient developed widespread metastasis at 23 months, one patient is alive with no evidence of disease at 70 months, and one patient is alive at 15 months. The third patient had subcutaneous and pulmonary metastases at the time of presentation, which are radiologically nondetectable at present following postoperative chemotherapy. CONCLUSIONS: The clinicopathologic features, prognostic factors, and treatment of 130 cases found in a comprehensive literature search and our three cases are reported. 相似文献
58.
The common way to construct Voronoi tessellations is to compare the distances between given reference points using a given
distance function. To generalize this distance-function concept we expand an existing approach which defines distance functions
by their ``unit circles'. Our new approach allows modeling the ``unit circles' by a closed Spline curve. Changing the control
polygon directly affects the tessellation's appearance. Typically generalized Voronoi diagrams are represented by Voronoi
vertices and curves separating the individual tiles. To obtain interactive modeling we extended an existing hardware accelerated
rendering approach computing a bitmap-representation using different colors for individual tiles. With our extension, we are
able to use our Spline distance representations as input for a growing process. This growing process easily takes into account
weighting approaches like multiplicative, additive, and even free functional weighting. 相似文献
59.
60.