Role of the HSP70 Co-Chaperone SIL1 in Health and Disease

Cell surface and secreted proteins provide essential functions for multicellular life. They enter the endoplasmic reticulum (ER) lumen co-translationally, where they mature and fold into their complex three-dimensional structures. The ER is populated with a host of molecular chaperones, associated co-factors, and enzymes that assist and stabilize folded states. Together, they ensure that nascent proteins mature properly or, if this process fails, target them for degradation. BiP, the ER HSP70 chaperone, interacts with unfolded client proteins in a nucleotide-dependent manner, which is tightly regulated by eight DnaJ-type proteins and two nucleotide exchange factors (NEFs), SIL1 and GRP170. Loss of SIL1′s function is the leading cause of Marinesco-Sjögren syndrome (MSS), an autosomal recessive, multisystem disorder. The development of animal models has provided insights into SIL1′s functions and MSS-associated pathologies. This review provides an in-depth update on the current understanding of the molecular mechanisms underlying SIL1′s NEF activity and its role in maintaining ER homeostasis and normal physiology. A precise understanding of the underlying molecular mechanisms associated with the loss of SIL1 may allow for the development of new pharmacological approaches to treat MSS.     

An experiential account of phantom vibration syndrome

A small handful of recent studies have addressed a phenomenon known as “phantom vibration syndrome”. This refers to when phone users perceive their device to vibrate, indicating that a call or text is incoming, when in fact the phone did not vibrate at all. Though these studies show that most users do not find phantom vibration hallucinations to be very bothersome, they also find that a large majority of users experience this phenomenon. This paper explores what the striking prevalence of phantom vibration syndrome means for our contemporary relationships with technology. I begin with a review of the theories purporting to explain these data, which largely rely on particular understandings of the brain. Next I develop an alternative theory of phantom vibration syndrome based on insights from the philosophical tradition of phenomenology. This account considers the ways users develop bodily and perceptual habits regarding how the phone is understood and used. By critically contrasting these different theories, we can refine our questions about what the high prevalence of phantom vibration syndrome implies about our contemporary technological situation.     

A unified critical state model for geomaterials with an application to tunnelling

This paper is prepared in honour of Professor E.T. Brown for his outstanding contributions to rock mechanics and geotechnical engineering and also for his personal influence on the first author's research career in geomechanics and geotechnical engineering. As a result, we have picked a topic that reflects two key research areas in which Professor E.T. Brown has made seminal contributions over a long and distinguished career. These two areas are concerned with the application of the critical state concept to modelling geomaterials and the analysis of underground excavation or tunnelling in geomaterials.Partially due to Professor Brown's influence, the first author has also been conducting research in these two areas over many years. In particular, this paper aims to describe briefly the development of a unified critical state model for geomaterials together with an application to cavity contraction problems and tunnelling in soils.     

Sleep Disorders Reduce Health-Related Quality of Life in Multiple Sclerosis (Nottingham Health Profile Data in Patients with Multiple Sclerosis)

Quality of Life (QoL) is decreased in multiple sclerosis (MS), but studies about the impact of sleep disorders (SD) on health-related quality of Life (HRQoL) are lacking. From our original cohort, a cross-sectional polysomnographic (PSG) study in consecutive MS patients, we retrospectively analysed the previously unpublished data of the Nottingham Health Profile (NHP). Those MS patients suffering from sleep disorders (n = 49) showed significantly lower HRQoL compared to MS patients without sleep disorders (n = 17). Subsequently, we classified the patients into four subgroups: insomnia (n = 17), restless-legs syndrome, periodic limb movement disorder and SD due to leg pain (n = 24), obstructive sleep apnea (n = 8) and patients without sleep disorder (n = 17). OSA and insomnia patients showed significantly higher NHP values and decreased HRQoL not only for the sleep subscale but also for the “energy” and “emotional” area of the NHP. In addition, OSA patients also showed increased NHP values in the “physical abilities” area. Interestingly, we did not find a correlation between the objective PSG parameters and the subjective sleep items of the NHP. However, this study demonstrates that sleep disorders can reduce HRQoL in MS patients and should be considered as an important confounder in all studies investigating HRQoL in MS.     

聚合物熔体的非等温平板收缩流动的数值模拟

用有限元法模拟了Carreau流体在4：1平板收缩口模中的非等温挤出流动，采用3节点的三角形单元对速度、压力和温度进行等阶插值，运用特殊的罚函数处理流体的不可压缩条件，解决了压力场的数值振荡问题，并用改进的Newton迭代法对非线性方程进行求解，成功地计算了Carreau流体在平板收缩流动中的速度、压力、粘度以及应力的分布，同时得到温度场的分布，计算的应力分布与实验的结果及Renardy的分析结构相符。     

Topology optimization of trusses using genetic algorithm,force method and graph theory

In this article size/topology optimization of trusses is performed using a genetic algorithm (GA), the force method and some concepts of graph theory. One of the main difficulties with optimization with a GA is that the parameters involved are not completely known and the number of operations needed is often quite high. Application of some concepts of the force method, together with theory of graphs, make the generation of a suitable initial population well‐matched with critical paths for the transformation of internal forces feasible. In the process of optimization generated topologically unstable trusses are identified without any matrix manipulation and highly penalized. Identifying a suitable range for the cross‐section of each member for the ground structure in the list of profiles, the length of the substrings representing the cross‐sectional design variables are reduced. Using a contraction algorithm, the length of the strings is further reduced and a GA is performed in a smaller domain of design space. The above process is accompanied by efficient methods for selection, and by using a suitable penalty function in order to reduce the number of numerical operations and to increase the speed of the optimization toward a global optimum. The efficiency of the present method is illustrated using some examples, and compared to those of previous studies. Copyright © 2003 John Wiley & Sons, Ltd.     

永升城基础大体积混凝土施工的裂缝预控

基础大体积混凝土施工的裂缝控制 ,从分析产生裂缝的原因来阐述 ,将冷缝作为结构性裂缝来预控     

延迟破胶及强制裂缝闭合技术的研究及应用

采用延迟破胶技术,在压裂施工过程中加入不同浓度的胶囊破胶剂,利用它的延缓释放特性,使植物胶压裂液耐温、耐剪切稳定性增强,并且可以在不造成压裂液的流变性、滤失性和携砂性等过早丧失的前提下高浓度使用胶囊破胶剂。该技术与常规破胶技术相比,延缓释放率达50%,能更有效地清除液体残渣,减少压裂液对储层的伤害。同时由于有延缓破胶的特性,放喷采用相应的措施,可以降低支撑剂沉降速度,形成较好的沉砂剖面,提供高的裂缝导流能力,并且可以降低滤饼和压裂液残渣的伤害。