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Arterial wall remodeling underlies increased pulmonary vascular resistance and right heart failure in pulmonary arterial hypertension (PAH). None of the established vasodilator drug therapies for PAH prevents or reverse established arterial wall thickening, stiffening, and hypercontractility. Therefore, new approaches are needed to achieve long-acting prevention and reversal of occlusive pulmonary vascular remodeling. Several promising new drug classes are emerging from a better understanding of pulmonary vascular gene expression programs. In this review, potential epigenetic targets for small molecules and oligonucleotides will be described. Most are in preclinical studies aimed at modifying the growth of vascular wall cells in vitro or normalizing vascular remodeling in PAH animal models. Initial success with lung-directed delivery of oligonucleotides targeting microRNAs suggests other epigenetic mechanisms might also be suitable drug targets. Those targets include DNA methylation, proteins of the chromatin remodeling machinery, and long noncoding RNAs, all of which act as epigenetic regulators of vascular wall structure and function. The progress in testing small molecules and oligonucleotide-based drugs in PAH models is summarized. 相似文献
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《Food Control》2015
The Technical Regulation of Good Practices for Brazilian Food Services (Regulamento Técnico de Boas Práticas para Serviços de Alimentação do Brasil) can be complemented by sanitary surveillance agencies at the state, district and municipal levels by tailoring it to location-specific requirements. The purpose of the present study was to survey sanitary legislation governing Brazilian Food Services. During the period from November 2011 to November 2012, a survey was conducted with the sanitary surveillance agencies from the various states, capitals and the Federal District. A previously prepared and tested tool was used for data collection, comprising 10 questions. Only 10 (19.2%) of the sanitary codes had been established prior to RDC Resolution n° 216/2004 and were not complementary. Of the legislation cited as complementary, only the states of Santa Catarina, Rio Grande do Sul and São Paulo and the capital of the state of São Paulo truly presented additional and location-specific aspects. No legislation that was specific to hospital kitchens was found. The majority of participating coordination, including the Evaluation List for Good Practices in Food Services, was also verified; however, it had not been published. In conclusion, a gap in sanitary surveillance services exists, which was caused by the lack of location-specific food service regulations. 相似文献
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介绍一种基于快速平台测井要求的多通道核能谱测井仪设计方案。复杂可编程逻辑器件的应用使仪器功能增强,规模减小。该系统可对岩性密度长短源距脉冲信号、自然γ能谱脉冲信号进行多道脉冲幅度分析,并对补偿中子测井信号及井下多路常规模拟信号、脉冲信号进行数字化采集。数据传输采用曼彻斯特编码,传输方式可选择20kB/s半双工(兼容Atlas 3508)或下行20kB/s、上行41.66或93.75kB/s全双工方式(兼容Atlas WTS),适应挂接到不同测井系统的需要。 相似文献
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通过工程实例及理论分析 ,对横向风振“锁住区”问题进行了探讨 ,对《建筑结构荷载规范》(GB5 0 0 0 9— 2 0 0 1 )中有关这一方面内容存在的一些问题进行了分析 ,希望对工程设计人员能有所帮助 相似文献
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Gennaro Costagliola Vincenzo Deufemia Filomena Ferrucci Carmine Gravino 《Information and Computation》2003,187(2):209-245
Drawn symbolic pictures are an extension of drawn pictures obtained by associating a symbol from an alphabet to each point of the picture. In the paper we will address some new interesting issues derived from the introduction of the symbols and we will identify the conditions, which ensure the preservation of properties holding for drawn pictures in the setting of the proposed extension. 相似文献
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