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91.
While loss-of-function mutations in Gsalpha are invariably associated with the short stature and brachydactyly of Albright hereditary osteodystrophy (AHO), the association with hormone resistance (to parathyroid hormone and thyrotropin) typical of pseudohypoparathyroidism type Ia (PHP-Ia) is much more variable. Observational studies and DNA polymorphism analysis suggest that maternal transmission of the Gsalpha mutation may be required for full expression of clinical hormone resistance. To test this hypothesis, we studied transmission of a frameshift mutation in Gsalpha through three generations of a pedigree affected by AHO and PHP-Ia. While all family members carrying this loss-of-function mutation in one Gsalpha allele had AHO, neither the presence of the mutation nor the degree of reduction of erythrocyte Gsalpha bioactivity allowed prediction of phenotype (AHO alone versus AHO and PHP-Ia). Paternal transmission of the mutation (from the patriarch of the first generation to three members of the second generation) was not associated with concurrent PHP-Ia, but maternal transmission (from two women in the second generation to four children in the third generation) was invariably associated with PHP-Ia. No expansion of an upstream short CCG nucleotide repeat region was detected, nor was there evidence of uniparental disomy by polymorphism analysis. This report, the first to document the effects across three generations of both paternal and maternal transmission of a specific Gsalpha mutation, strongly supports the hypothesis that a maternal factor determines full expression of Gsalpha dysfunction as PHP-Ia.  相似文献   
92.
Melanomas develop with high frequency in transgenic mice in which oncogenic sequences of the SV40 DNA tumor virus have been specifically targeted to melanocytes. To investigate the role of SV40 in melanomagenesis, cultured human melanocytes were transformed with a retroviral shuttle vector encoding the SV40 large T antigen and examined for changes in cell-cycle kinetics and growth-factor dependence. Colonies expressing the viral oncogene were morphologically indistinguishable from their non-T-antigen-transformed counterparts. Also like normal melanocytes, the infected cells remained anchorage dependent and non-tumorigenic in nude mice. However, T-antigen-positive cultures exhibited significantly accelerated population doubling times, increased saturation densities with highly confluent monolayers and a three- to fourfold extended life span. Most interestingly, cell-cycle analysis revealed a measurable shift from quiescent to cycling cells in T-antigen-expressing cultures and an acquired ability to progress more rapidly through G1. Moreover, T-antigen-positive melanocytes proliferated in the absence of PMA and required markedly reduced levels of exogenous bFGF. These studies indicate that the viral oncogen of simian virus 40 provides melanocytes with distinct growth advantages that may render these cells unusually susceptible to additional environmental challenges necessary for full expression of the malignant phenotype.  相似文献   
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The effects of regional and global ischemia on cellular electrical activity and on arrhythmias induced by reperfusion were studied at different Mg2+ concentrations (Mg2+o, 0, 1.2, and 4.8 mM) in perfused rat hearts. Surface electrograms and transmembrane potentials were recorded during control, 10 min of ischemia (perfusion arrest or coronary ligation), and reperfusion. Increasing Mg2+o from 0-4.8 mM decreased heart rate, did not alter action potential morphology, and had a strong antiarrhythmic action on reperfusion following coronary ligation. At low and normal Mg2+o, the incidence of tachyarrhythmias was between 70 and 80%. Global ischemia led to progressive atrioventricular block and the final ventricular beating rate was similar at all Mg2+o despite unequal initial values. The severity of arrhythmias was similar to that found after regional ischemia in Mg2+o = 0, but much lower at normal and high Mg2+o. The resting depolarization induced by coronary ligation decreased as Mg2+o was raised, but such a relation was not seen during global ischemia where the depolarization was less marked. The action potential duration did not vary with the ventricular rate between 160 and 380 beats per min but increased considerably when sinus rate was markedly slowed (40 to 80 bpm) by raising Mg2+o to 9.6 mM. Our data show that a high Mg2+o exerts a strong protection against reperfusion arrhythmias regardless of the type of ischemia. Modulation of the sinus rhythm by Mg2+ may contribute to its protective effect by decreasing K+o accumulation and Na+i loading during ischemia.  相似文献   
95.
96.
PURPOSE: To examine how common patient factors affect screening mammographic sensitivity and cancer stage at diagnosis. MATERIALS AND METHODS: The authors used a population-based database of 183,134 screening mammograms and a statewide tumor registry to identify 807 breast cancers detected at screening mammography. RESULTS: Sensitivity varied significantly with ethnicity, use of estrogen replacement therapy, mammographic breast density, and age. Sensitivity was 54% (13 of 24) in women younger than 40 years, 77% (121 of 157) in women aged 40-49 years, 78% (224 of 286) in women aged 50-64 years, and 81% (277 of 340) in women older than 64 years. Sensitivity was 68% (162 of 237) for dense breasts and 85% (302 of 356) for nondense breasts and 74% (180 of 244) in estrogen replacement therapy users and 81% (417 of 513) in nonusers. Sensitivity was most markedly reduced with the combination of dense breasts and estrogen replacement therapy use; there was little difference when only one factor was present. Median cancer size and the percentage of early cancers showed little change with any factors. CONCLUSION: Age is a minor determinant of mammographic sensitivity in women aged 40 years or older. Sensitivity is substantially decreased with the combination of higher breast density and estrogen replacement therapy use. There was not a notable shift in cancer outcomes in the groups with lower mammographic sensitivity. These data do not support different screening recommendations in women aged 40-49 years or in estrogen replacement therapy users.  相似文献   
97.
通过对高校网络教学现状的调查与分析,提出了总体的设计目标以及设计方案,包括系统运行环境以及系统展现内容.系统采用C/S模式,通过主机与客户机发送数据包,利用网络包截获的相应技术以及包过滤等策略,对特定的数据包进行分析,将各类协议首部用的二进制代码展现,可更直观的看到网络传输的具体方式,同时可将二进制代码转换为十进制,使系统具有更强的可视性.  相似文献   
98.
全面地阐述了邓小平关于发展科学技术的思想.从发展科学技术的重要性与发展科学技术的方法、目标、前提、核心等方面,将邓小平关于我国发展科学技术的论述,概括为科的论述,概括为科技关键论、引进吸收创新论、科技前沿论、教育基础论和人才为本论.  相似文献   
99.
Direct numerical simulations (DNS) of hypersonic flow about a swept parabolic body have been performed to study the global stability of flow in the leading-edge region of a swept blunt body. Previous stability investigations have been based on local models but have not fully succeeded in reproducing the established experimental findings. The current flow configuration represents a more realistic model and is thus expected to resolve some of the remaining questions. However, novel approaches like DNS-based global stability theory are necessary for such flow models and are employed in this study. As a result, boundary-layer modes have been identified by different but complementary techniques as the dominant instability mechanism. The DNS starting with small-amplitude white noise provide further evidence for the presence of non-modal effects which may be important in the subcritical regime. From a methodological point of view, the potential for quantitative flow analysis by combining numerical simulations with advanced iterative techniques represents a promising direction for investigating the governing physical processes of complex flows.  相似文献   
100.
针对锁集合算法误报率高的缺点,采用增强型数据竞争检测方法对锁集合算法及算法实现两方面进行改进.增强型锁集合算法提出了更强必要条件的检测算法.该算法通过分析线程结束情况和理解变量的线程信息,精化数据竞争检测条件.算法实现采用系统体系结构扩展的方法,通过扩展锁表部件,将集合操作精确映射到位图操作,进一步提高检测精度和减少误报.实现了无干扰免插桩检测技术,避免了二进制代码插桩带来的干扰性和不确定性问题.与同类系统的对比实验结果表明,该方法能够有效地将误报率减小到0.67,并且具有很高的检测效率.  相似文献   
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