Point Mutations of Nicotinic Receptor α1 Subunit Reveal New Molecular Features of G153S Slow-Channel Myasthenia

Slow-channel congenital myasthenic syndromes (SCCMSs) are rare genetic diseases caused by mutations in muscle nicotinic acetylcholine receptor (nAChR) subunits. Most of the known SCCMS-associated mutations localize at the transmembrane region near the ion pore. Only two SCCMS point mutations are at the extracellular domains near the acetylcholine binding site, α1(G153S) being one of them. In this work, a combination of molecular dynamics, targeted mutagenesis, fluorescent Ca²⁺ imaging and patch-clamp electrophysiology has been applied to G153S mutant muscle nAChR to investigate the role of hydrogen bonds formed by Ser 153 with C-loop residues near the acetylcholine-binding site. Introduction of L199T mutation to the C-loop in the vicinity of Ser 153 changed hydrogen bonds distribution, decreased acetylcholine potency (EC₅₀ 2607 vs. 146 nM) of the double mutant and decay kinetics of acetylcholine-evoked cytoplasmic Ca²⁺ rise (τ 14.2 ± 0.3 vs. 34.0 ± 0.4 s). These results shed light on molecular mechanisms of nAChR activation-desensitization and on the involvement of such mechanisms in channelopathy genesis.     

Physical aging in amorphous poly(ethylene furanoate): Enthalpic recovery,density, and oxygen transport considerations

The current work utilizes three separate techniques to study the physical aging process in amorphous poly(ethylene furanoate) (PEF), which is a recently introduced engineering thermoplastic with enhanced properties compared to petroleum‐sourced poly(ethylene terephthalate). Differential scanning calorimetry aging experiments were conducted at multiple aging temperatures and times, and the resultant enthalpic recovery values compared to the theoretical maximum enthalpy loss evaluated from calculations involving extrapolation of the equilibrium liquid line. Density measurements reveal densification of the matrix for the aged versus unaged samples, and provide an estimate for the reduction in free volume for the aged samples. Complementary oxygen permeation and pressure‐decay sorption experiments provide independent verification of the free volume reduction mechanism for physical aging in glassy polymers. The current work provides the first detailed aging study for PEF. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 389–399     

Molecular dynamics and information on possible sites of interaction of intramyocellular metabolites in vivo from resolved dipolar couplings in localized H NMR spectra

Proton NMR resonances of the endogenous metabolites creatine and phosphocreatine ((P)Cr), taurine (Tau), and carnosine (Cs, β-alanyl-l-histidine) were studied with regard to residual dipolar couplings and molecular mobility. We present an analysis of the direct ¹H–¹H interaction that provides information on motional reorientation of subgroups in these molecules in vivo. For this purpose, localized ¹H NMR experiments were performed on m. gastrocnemius of healthy volunteers using a 1.5-T clinical whole-body MR scanner. We evaluated the observable dipolar coupling strength SD₀ (S = order parameter) of the (P)Cr-methyl triplet and the Tau-methylene doublet by means of the apparent line splitting. These were compared to the dipolar coupling strength of the (P)Cr-methylene doublet. In contrast to the aliphatic protons of (P)Cr and Tau, the aromatic H2 (δ = 8 ppm) and H4 (δ = 7 ppm) protons of the imidazole ring of Cs exhibit second-order spectra at 1.5 T. This effect is the consequence of incomplete transition from Zeeman to Paschen-Back regime and allows a determination of SD₀ from H2 and H4 of Cs as an alternative to evaluating the multiplet splitting which can be measured directly in high-resolution ¹H NMR spectra. Experimental data showed striking differences in the mobility of the metabolites when the dipolar coupling constant D₀ (calculated with the internuclear distance known from molecular geometry in the case of complete absence of molecular dynamics and motion) is used for comparison. The aliphatic signals involve very small order parameters S ≈ (1.4 − 3) × 10⁻⁴ indicating rapid reorientation of the corresponding subgroups in these metabolites. In contrast, analysis of the Cs resonances yielded S ≈ (113 − 137) × 10⁻⁴. Thus, the immobilization of the Cs imidazole ring owing to an anisotropic cellular substructure in human m. gastrocnemius is much more effective than for (P)Cr and Tau subgroups. Furthermore, ¹H NMR experiments on aqueous model solutions of histidine and N-acetyl-l-aspartate (NAA) enabled the assignment of an additional signal component at δ = 8 ppm of Cs in vivo to the amide group at the peptide bond. The visibility of this proton could result from hydrogen bonding which would agree with the anticipated stronger motional restriction of Cs. Referring to the observation that all dipolar-coupled multiplets resolved in localized in vivo ¹H NMR spectra of human m. gastrocnemius collapse simultaneously when the fibre structure is tilted towards the magic angle (θ ≈ 55°), a common model for molecular confinement in muscle tissue is proposed on the basis of an interaction of the studied metabolites with myocellular membrane phospholipids.     

一种漂移室定位子性能反常现象的研究

研究了一种漂移室定位子性能的反常现象,它关系到定位子的使用寿命．着重测量了暗电流和随机噪声与时间、高压及温度的关系.     

高压电场作用下乙醇-水溶液体系变化红外光谱分析

本文报道了用红外光谱分析电磁场作用下乙醇 水溶液体系变化情况。分析结果表明 :当乙醇溶液受到 2 0kV·cm- 1 的交变电磁场处理 (5 0Hz)时 ,分子之间的氢键缔合先增大后减少 ;高乙醇含量溶液受到同样强度电场较长时间处理时 ,有乙醇发生氧化反应 ,从红外谱中可看到νCO 峰及ν(OH) (H2 O) 峰的出现 ;经处理后的溶液自然放置 7天再测定 ,其红外谱图基本保持不变。文中对各出现变化的峰进行了分析 ,并对其机理进行了推导     

Change point estimation in non-monotonic aging models

The problem of estimating change points in various non-monotonic aging models is considered. A general methodology for consistent estimation of the change point is developed and applied to non-monotonic aging models based on the hazard rate function as well as on the mean residual life function.     

多气隙电阻板室抗辐照性能研究

给出了为RHIC-STAR飞行时间探测器设计的多气隙电阻板室(MRPC)的辐照实验结果. 实验采用100mCi⁶⁰Co γ源, 采用不同的剂量率对MRPC进行辐照. 一个室在大剂量率2.87×10^－2Gy/h下辐照了24h后, 其性能如噪声计数率, 暗电流等均大大退化. 另一个室在相对低剂量率5.31×10^－4Gy/h下辐照了530h, 其性能没有见到任何变坏. 实验的目的是为了了解这种探测器在几年的运行中经过大剂量的辐照后的性能变化情况.     

3004铝合金“反常”锯齿屈服现象的研究

在应变速率为5.56×10^-5s^-1—5.56×10^-3s^-1的范围内，在不同温度下(从223K至773K)，对3004铝合金进行系列拉伸试验，探索其锯齿屈服规律；通过激活能的计算、内耗研究、微观组织观察和能谱分析，探讨锯齿屈服的机理与物理本质.结果表明，3004铝合金在形变过程中会出现动态应变时效现象；发现了一种“反常”的锯齿屈服现象：在出现锯齿屈服的温区内，存在锯齿屈服临界应变量转变温度T_t， 关键词： 动态应变时效 锯齿屈服 铝合金 内耗     

Physical aging of a polyetherimide: Creep and DSC measurements

Creep and differential scanning calorimetry (DSC) measurements have been used to study the physical aging behavior of a polyetherimide. Isothermal aging temperatures ranged from 160°C to T_g with aging times ranging from 10 min to 8 days. The only measurable effect of physical aging on the short-time creep curves is a shift of the creep compliance to longer times. Andrade plots of the compliance versus the cube root of time are linear at short times with the slope β decreasing with increasing aging time to a constant value once equilibrium is reached. Log β³ is related directly to the degree to which the creep curves shift to longer times with physical aging, and is used in this work as a measure of physical aging. A reduced curve of log β³ versus log aging time is obtained for the aging temperatures investigated by appropriate vertical and horizontal shifts. The enthalpy change during aging increases linearly with the logarithm of the aging time, t_a, leveling off at equilibrium at values which increase with decreasing aging temperature. Hence, both nonequilibrium and equilibrium temperature shift factors can be calculated from the DSC data. Good agreement is observed between the equilibrium temperature shift factors obtained from the creep and DSC data. The temperature dependence of the nonequilibrium temperature shift factors is found to be an order of magnitude smaller than that of the equilibrium shift factors. The time scales to reach equilibrium for enthalpy and for mechanical measurements are found to be the same within experimental error. © 1995 John Wiley & Sons, Inc.     

基于cDNA宏阵列的系统聚类分析猪发育阶段的基因表达谱

取杜洛克猪胚胎第33,45,55，65．75天的背最长肌样本．用cDNA Macroarray分析方法和聚类分析技术分析了327个EST在骨骼肌内不同发育阶段的基因表达谱．结果表明有98条EST在不同发育时期显著差异表达．第33天和第45天两阶段基因表达状态相似．第55天和第65天基因表达状态相似．而第75天的基因表达与第55天和第65天两个阶段的基因表达具有相近的聚类关系．表达状态相近，基因功能相似的基因大都被聚类在一起．