Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes

Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases of ageing such as type 2 diabetes. SIRT1, an NAD+-dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produce beneficial effects on glucose homeostasis and insulin sensitivity. Resveratrol, a polyphenolic SIRT1 activator, mimics the anti-ageing effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance, increases mitochondrial content, and prolongs survival. Here we describe the identification and characterization of small molecule activators of SIRT1 that are structurally unrelated to, and 1,000-fold more potent than, resveratrol. These compounds bind to the SIRT1 enzyme-peptide substrate complex at an allosteric site amino-terminal to the catalytic domain and lower the Michaelis constant for acetylated substrates. In diet-induced obese and genetically obese mice, these compounds improve insulin sensitivity, lower plasma glucose, and increase mitochondrial capacity. In Zucker fa/fa rats, hyperinsulinaemic-euglycaemic clamp studies demonstrate that SIRT1 activators improve whole-body glucose homeostasis and insulin sensitivity in adipose tissue, skeletal muscle and liver. Thus, SIRT1 activation is a promising new therapeutic approach for treating diseases of ageing such as type 2 diabetes.     

英语专业精读教师话语分析

教师话语是大学英语课堂的重要交际媒介,它既是目的语的来源,也是管理课堂的手段。教师话语成功运用与否,直接关系到教学效果的好坏。本文通过对精读英语教师话语类型、特征和功能的描写,对英语精读教师话语和课堂互动活动进行分析和评价的基础上,得出结论:教师应转变传统角色,应更关注教师话语的质量而不是数量,课堂上应以提高学习者的语言水平和培养学习者意义协商的能力为主,以便学习者从外部环境获取更多的优化语言输入。     

Effect of minor Sc on the microstructure and mechanical properties of AZ91 Magnesium Alloy

The as-cast and heat-treated microstructures and mechanical properties of the AZ91 magnesium alloys with and without minor Sc addition were investigated and compared in this paper. The results indicated that adding0.15–0.45 wt% Sc to the as-cast AZ91 alloy not only could modify and refine the Mg_(17)Al_(12) phase but also suppress the formation of the Mg_(17)Al_(12) phase. At the same time, the grains of the Sc-containing as-cast AZ91 alloys were also effectively refined. As a result, the mechanical properties at room temperature(RT) for the Sccontaining as-cast AZ91 alloys were effectively improved. In addition, adding 0.15–0.45 wt%Sc to the AZ91 alloy promoted the formation of the continuous precipitates(CP) during the aging treatment in spite of that the formation of the discontinuous precipitates(DP) was simultaneously suppressed. Accordingly, the Sc-containing as-aged AZ91 alloys obtained the relatively higher mechanical properties at RT than the as-aged AZ91 alloy.     

Dynamic characteristics of the planetary gear train excited by time-varying meshing stiffness in the wind turbine

Wind power has attracted increasing attention as a renewable and clean energy. Gear fault frequently occurs under extreme environment and complex loads. The time-varying meshing stiffness is one of the main excitations. This study proposes a 5 degree-of-freedom torsional vibration model for the planetary gear system. The influence of some parameters (e.g., contact ratio and phase difference) is discussed under different conditions of a single teeth pair and double pairs of teeth. The impact load caused by the teeth face fault, ramped load induced by the complex wind conditions, and the harmonic excitation are investigated. The analysis of the time-varying meshing stiffness and the dynamic meshing force shows that the dynamic design under different loads can be made to avoid resonance, can provide the basis for the gear fault location of a wind turbine, and distinguish the fault characteristics from the vibration signals.     

Morphology,size and distribution of MnS inclusions in non-quenched and tempered steel during heat treatment

This article reports the morphology, size, and distribution evolution of MnS inclusions in non-quenched and tempered steel during heat treatment. The variation of single large-sized MnS inclusions at high temperature was observed in situ using a confocal scanning laser microscope (CSLM). The slender MnS inclusions first changed to pearl-like strings. These small-sized pearls subsequently coalesced and became closer together as the temperature increased. Large-sized MnS inclusions in non-quenched and tempered steel samples with different thermal histories were investigated with respect to the evolution of their morphology, size, and distribution. After 30 min of ovulation at 1573 K, the percentage of MnS inclusions larger than 3 μm decreased from 50.5% to 3.0%. After a 3 h soaking period, Ostwald ripening occurred. Most MnS inclusions moved from the grain boundaries to the interior. The present study demonstrates that heat treatment is an effective method of changing the morphology, size, and distribution of MnS inclusions, especially large-sized ones.     

A Novel Immune System Model and Its Application to Network Intrusion Detection

Based on analyzing the techniques and architecture of existing network Intrusion Detection System (IDS), and probing into the fundament of Immune System (IS), a novel immune model is presented and applied to network IDS, which is helpful to design an effective IDS. Besides, this paper suggests a scheme to represent the self profile of network. And an automated self profile extraction algorithm is provided to extract self profile from packets. The experimental results prove validity of the scheme and algorithm, which is the foundation of the immune model.     

岩质边坡稳定性分析理论探讨

近些年来,岩质边坡的变形失稳问题一直备受岩土工作者的关注。通过对岩质边坡在一定地质环境条件下的本构问题研究,利用变形的有限性分析判断边坡是否稳定。结合多目标权重分析模型综合分析边坡失稳的影响因素,通过正交实验推断出各影响因素对边坡变形速率的作用程度,进而对不同边坡进行稳定性评价。通过定性分析与定量分析的结合,并用岩石破坏准则加以判断,对滑坡的区域危险性进行预测,从而得出岩质边坡失稳的危险等级。     

Hydrogen-induced cracking behaviors of Incoloy alloy 825

The effect of hydrogen on the fracture behaviors of Incoloy alloy 825 was investigated by means of slow strain rate testing (SSRT). Hydrogen was introduced into the sample by electrochemical charging. The results show that surface microcracks form gradually during aging at room temperature when desorption of hydrogen takes place after hydrogen charging at a current density of 5 mA/cm2 for 24 h. SSRT shows that the increase of ductility loss is significantly obvious as the hydrogen charging current density increases. Scanning electron microscopy (SEM) images reveal ductile fracture in the pre-charged sample with low current densities, while the fracture includes small quasi-cleavage regions and tends to be brittle fracture as the hydrogen charging current density increases to 5 mA/cm2.     

An abundance of X-linked genes expressed in spermatogonia

Spermatogonia are the self-renewing, mitotic germ cells of the testis from which sperm arise by means of the differentiation pathway known as spermatogenesis. By contrast with hematopoietic and other mammalian stem-cell populations, which have been subjects of intense molecular genetic investigation, spermatogonia have remained largely unexplored at the molecular level. Here we describe a systematic search for genes expressed in mouse spermatogonia, but not in somatic tissues. We identified 25 genes (19 of which are novel) that are expressed in only male germ cells. Of the 25 genes, 3 are Y-linked and 10 are X-linked. If these genes had been distributed randomly in the genome, one would have expected zero to two of the genes to be X-linked. Our findings indicate that the X chromosome has a predominant role in pre-meiotic stages of mammalian spermatogenesis. We hypothesize that the X chromosome acquired this prominent role in male germ-cell development as it evolved from an ordinary, unspecialized autosome.