Ras proteins,which are important for cellular signaling and cancer development,are activated by guanine nucleotide exchange factors,among which son-of-sevenless(Sos)plays a pivotal role.The catalytic activity of Sos i...Ras proteins,which are important for cellular signaling and cancer development,are activated by guanine nucleotide exchange factors,among which son-of-sevenless(Sos)plays a pivotal role.The catalytic activity of Sos is regulated by its interaction with Ras·GTP at the allosteric site of Sos.Although much research has been conducted,the structural details of the dynamic interactions between Ras·GTP and Sos at the allosteric site in solution are not completely understood.In this study,paramagnetic relaxation enhancement(PRE)was used to examine the binding of HRas·GTP to the allosteric site of Soscat.A site-specific paramagnetic probe was attached to Soscat,revealing crucial interface information,which was then used to build structural models of the HRas-Soscat complex via HADDOCK.Our results indicate that the dominant conformation of HRas·GTP bound to Soscat at the allosteric site is highly consistent with the established crystal structure while also identifying a transient conformation with a novel interface between HRas and Sos unseen in previous crystal structures.展开更多
This review describes the conceptual and clinical relations between irritable bowel syndrome (IBS), other functional, somatoform, and mental disorders, and points to appropriate future conceptualizations. IBS is consi...This review describes the conceptual and clinical relations between irritable bowel syndrome (IBS), other functional, somatoform, and mental disorders, and points to appropriate future conceptualizations. IBS is considered to be a functional somatic syndrome (FSS) with a considerable symptom overlap with other FSSs like chronic fatigue syndrome or fibromyalgia syndrome. IBS patients show an increased prevalence of psychiatric symptoms and disorders, especially depression and anxiety. IBS is largely congruent with the concepts of somatoform and somatic symptom disorders. Roughly 50% of IBS patients complain of gastrointestinal symptoms only and have no psychiatric comorbidity. IBS concepts, treatment approaches, as well as health care structures should acknowledge its variability and multidimensionality by: (1) awareness of additional extraintestinal and psychobehavioral symptoms in patients with IBS; (2) general and collaborative care rather than specialist and separated care; and (3) implementation of “interface disorders” to abandon the dualistic classification of purely organic or purely mental disorders.展开更多
目前,直流微电网在全球范围内快速发展,开展充分的稳定性分析工作是其稳定运行的前提。伴随着大量电力电子装置的接入,相较于传统电网,直流微电网系统等效惯性不足,在经历电网故障、电压暂降或恒功率负载接入接出等大扰动场景后,其状态...目前,直流微电网在全球范围内快速发展,开展充分的稳定性分析工作是其稳定运行的前提。伴随着大量电力电子装置的接入,相较于传统电网,直流微电网系统等效惯性不足,在经历电网故障、电压暂降或恒功率负载接入接出等大扰动场景后,其状态变量易发生大范围变化,暂态稳定性问题突出。Lyapunov方法是分析暂态稳定性问题的常用方法,但在直流微电网领域中缺少指导构建Lyapunov函数的通用策略,很难直接进行应用。此外,为了提高稳定性,亟待开展以提升暂态稳定性为导向的控制参数优化设计研究。针对以上问题,针对直流微电网系统,考虑DC-DC变换器控制环路,基于平方和(sum of squares,SOS)规划方法开展暂态稳定域估计与参数优化研究,首先,通过设计SOS优化问题,改进传统拓展内部算法求解并获得最大化Lyapunov函数水平集实现对系统稳定域的估计,通过与系统实际稳定域进行对比,验证了所提方法的准确性,与其他现有方法估计的稳定域相比,所提方法保守性大幅降低。随后,基于SOS规划,以拓展稳定域为目标,对电压控制环路参数进行优化。最后,硬件在环仿真实验结果表明,采用优化控制参数后,直流微电网系统稳定域得到扩展,抗扰动能力有效提升,暂态稳定性进一步增强。展开更多
基金supported by the Fundamental Research Funds for the Central Universities(WK9100000046).
文摘Ras proteins,which are important for cellular signaling and cancer development,are activated by guanine nucleotide exchange factors,among which son-of-sevenless(Sos)plays a pivotal role.The catalytic activity of Sos is regulated by its interaction with Ras·GTP at the allosteric site of Sos.Although much research has been conducted,the structural details of the dynamic interactions between Ras·GTP and Sos at the allosteric site in solution are not completely understood.In this study,paramagnetic relaxation enhancement(PRE)was used to examine the binding of HRas·GTP to the allosteric site of Soscat.A site-specific paramagnetic probe was attached to Soscat,revealing crucial interface information,which was then used to build structural models of the HRas-Soscat complex via HADDOCK.Our results indicate that the dominant conformation of HRas·GTP bound to Soscat at the allosteric site is highly consistent with the established crystal structure while also identifying a transient conformation with a novel interface between HRas and Sos unseen in previous crystal structures.
文摘This review describes the conceptual and clinical relations between irritable bowel syndrome (IBS), other functional, somatoform, and mental disorders, and points to appropriate future conceptualizations. IBS is considered to be a functional somatic syndrome (FSS) with a considerable symptom overlap with other FSSs like chronic fatigue syndrome or fibromyalgia syndrome. IBS patients show an increased prevalence of psychiatric symptoms and disorders, especially depression and anxiety. IBS is largely congruent with the concepts of somatoform and somatic symptom disorders. Roughly 50% of IBS patients complain of gastrointestinal symptoms only and have no psychiatric comorbidity. IBS concepts, treatment approaches, as well as health care structures should acknowledge its variability and multidimensionality by: (1) awareness of additional extraintestinal and psychobehavioral symptoms in patients with IBS; (2) general and collaborative care rather than specialist and separated care; and (3) implementation of “interface disorders” to abandon the dualistic classification of purely organic or purely mental disorders.
文摘目前,直流微电网在全球范围内快速发展,开展充分的稳定性分析工作是其稳定运行的前提。伴随着大量电力电子装置的接入,相较于传统电网,直流微电网系统等效惯性不足,在经历电网故障、电压暂降或恒功率负载接入接出等大扰动场景后,其状态变量易发生大范围变化,暂态稳定性问题突出。Lyapunov方法是分析暂态稳定性问题的常用方法,但在直流微电网领域中缺少指导构建Lyapunov函数的通用策略,很难直接进行应用。此外,为了提高稳定性,亟待开展以提升暂态稳定性为导向的控制参数优化设计研究。针对以上问题,针对直流微电网系统,考虑DC-DC变换器控制环路,基于平方和(sum of squares,SOS)规划方法开展暂态稳定域估计与参数优化研究,首先,通过设计SOS优化问题,改进传统拓展内部算法求解并获得最大化Lyapunov函数水平集实现对系统稳定域的估计,通过与系统实际稳定域进行对比,验证了所提方法的准确性,与其他现有方法估计的稳定域相比,所提方法保守性大幅降低。随后,基于SOS规划,以拓展稳定域为目标,对电压控制环路参数进行优化。最后,硬件在环仿真实验结果表明,采用优化控制参数后,直流微电网系统稳定域得到扩展,抗扰动能力有效提升,暂态稳定性进一步增强。
