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.     

Apparent power-law distributions in animal movements can arise from intraspecific interactions

Lévy flights have gained prominence for analysis of animal movement. In a Lévy flight, step-lengths are drawn from a heavy-tailed distribution such as a power law (PL), and a large number of empirical demonstrations have been published. Others, however, have suggested that animal movement is ill fit by PL distributions or contend a state-switching process better explains apparent Lévy flight movement patterns. We used a mix of direct behavioural observations and GPS tracking to understand step-length patterns in females of two related butterflies. We initially found movement in one species (Euphydryas editha taylori) was best fit by a bounded PL, evidence of a Lévy flight, while the other (Euphydryas phaeton) was best fit by an exponential distribution. Subsequent analyses introduced additional candidate models and used behavioural observations to sort steps based on intraspecific interactions (interactions were rare in E. phaeton but common in E. e. taylori). These analyses showed a mixed-exponential is favoured over the bounded PL for E. e. taylori and that when step-lengths were sorted into states based on the influence of harassing conspecific males, both states were best fit by simple exponential distributions. The direct behavioural observations allowed us to infer the underlying behavioural mechanism is a state-switching process driven by intraspecific interactions rather than a Lévy flight.     

氮在钌单晶表面Ru(0001)上的吸附

钌系氨合成催化剂作为第二代氨合成催化剂,近年来日益受到重视。研究氮分子在钌表面上的离解吸附对提高钌催化剂的催化性能有着十分重要的意义。综述了氮分子在Ru(0001)单晶表面吸附的研究进展，并指出钌催化剂的发展方向。     

华润贵港5000t/d燃无烟煤生产线预分解系统的设计与工程应用

分解炉是烧成系统的关键设备，尤其是对于燃无烟煤的分解炉，既要保证无烟煤粉在炉内的充分燃烧．又要利于系统的操作控制。基于分解炉煤粉燃烧机理，并通过分析影响炉内煤粉燃烧的各种因素及依据所用无烟煤的热失重分析结果，中材国际南京水泥设计研究院开发设计出了用于华润贵港5000砌工程的喷旋管道式在线分解炉，并与高效、低阻、防堵的旋风预热系统组成了性能优异的预分解系统。从实际运行情况看，该预分解系统易于操作控制，且对物料适应性强、阻力损耗小。     

宽带直流放大器的增益控制设计与研究

首先进行了方案论证与比较,分析各种方案的优点缺点,最后选择亚德诺半导体公司生产的低噪声增益可控集成运算放大器AD603和电流反馈型宽带运算放大器AD811等器件设计宽带直流放大器。输入级采用两级AD603级联,输出级设计通频带0~10MHz的带宽,通过单片机可以对放大器增益进行控制。该放大器具有频带宽、功率高、增益可调、带宽可选择等特点。此外,对提高直流放大器的各种性能指标提出了多种具体措施,在要求较高的系统中具有较强的实用性。     

1000MW水轮发电机不对称运行时阻尼条涡流损耗计算分析

针对大型水轮发电机不对称运行时阻尼条易熔断的现象,在建立电机二维电磁场-电路-运动耦合时步有限元模型的基础上,对一台1000MW水轮发电机不对称运行时阻尼条涡流损耗进行深入研究.全面考虑了定子开槽、磁极转动以及定子电流等因素对阻尼条涡流损耗的影响,准确计算出不同运行工况下一个磁极内各根阻尼条涡流损耗,分析其变化规律,并在此基础上讨论了阻尼系统连接方式、阻尼条半径、阻尼条材料对阻尼条涡流损耗的影响.研究结果表明,不对称运行时,沿旋转方向最后一根阻尼条涡流损耗最大,阻尼系统结构参数对阻尼条中涡流损耗分布有较大影响.     

1000 MW机组高压厂用电电压等级优化

针对1 000 MW机组高压厂用电系统短路电流增大和大电动机启动困难等诸多问题,分析了选择高压厂用电电压须考虑的几个因素。经过对各方案选择、论述及比较,选择10 kV 1个电压等级方案。10 kV小容量电机与其他两个方案的电机相比除损耗及体积略大外,在总投资方面基本与选择第2个方案持平,此外,电厂的运行管理均优于其他两个方案,因此,推荐采用10 kV 1个电压等级。     

后热温度对1000MPa级高强钢焊缝组织与性能的影响

采用GHS90高强焊丝为填充材料对1 000 MPa级工程机械用高强钢进行熔化极活性气体保护(Metal active gas,MAG)焊,并对接头进行250℃、480℃、600℃保温2 h的焊后热处理。通过拉伸试验、显微硬度测试、光学显微镜(Optical microscope,OM)、扫面电镜(Scanning electron microscope,SEM)、透射电镜(Transmission electron microscopy,TEM)及电子背散射衍射(Electron back-scattered diffraction,EBSD)观察不同热处理温度后的焊缝微观组织及力学性能进行对比研究。结果表明,随后热温度从250℃升高到600℃,接头抗拉强度从1 014.5 MPa降低到934.5 MPa;焊缝平均冲击吸收能量从66 J降低到24 J;随后热温度升高,焊缝板条组织粗化,碳化物析出长大且连续分布是导致焊缝韧性降低的原因之一;同时焊缝有效晶粒尺寸变大和大角度晶界密度降低也是导致其韧性降低的原因。     

Collective foraging in heterogeneous landscapes

Animals foraging alone are hypothesized to optimize the encounter rates with resources through Lévy walks. However, the issue of how the interactions between multiple foragers influence their search efficiency is still not completely understood. To address this, we consider a model to study the optimal strategy for a group of foragers searching for targets distributed heterogeneously. In our model, foragers move on a square lattice containing immobile but regenerative targets. At any instant, a forager is able to detect only those targets that happen to be in the same site. However, we allow the foragers to have information about the state of other foragers. A forager who has not detected any target walks towards the nearest location, where another forager has detected a target, with a probability exp(−αd), where d is the distance between the foragers and α is a parameter characterizing the propensity of the foragers to aggregate. The model reveals that neither overcrowding (α → 0) nor independent searching (α → ∞) is beneficial for the foragers. For a patchy distribution of targets, the efficiency is maximum for intermediate values of α. In addition, in the limit α → 0, the length of the walks can become scale-free.     

Mouse Models of Sjögren’s Syndrome with Ocular Surface Disease

Sjögren’s syndrome (SS) is a systemic rheumatic disease that predominantly affects salivary and lacrimal glands resulting in oral and ocular dryness, respectively, referred to as sicca symptoms. The clinical presentation of ocular dryness includes keratoconjunctivitis sicca (KCS), resulting from the inflammatory damage to the ocular surface tissues of cornea and conjunctiva. The diagnostic evaluation of KCS is a critical component of the classification criteria used by clinicians worldwide to confirm SS diagnosis. Therapeutic management of SS requires both topical and systemic treatments. Several mouse models of SS have contributed to our current understanding of immunopathologic mechanisms underlying the disease. This information also helps develop novel therapeutic interventions. Although these models address glandular aspects of SS pathology, their impact on ocular surface tissues is addressed only in a few models such as thrombospondin (TSP)-1 deficient, C57BL/6.NOD.Aec1Aec2, NOD.H2^b, NOD.Aire KO, and IL-2Rα (CD25) KO mice. While corneal and/or conjunctival damage is reported in most of these models, the characteristic SS specific autoantibodies are only reported in the TSP-1 deficient mouse model, which is also validated as a preclinical model. This review summarizes valuable insights provided by investigations on the ocular spectrum of the SS pathology in these models.