Role of ERAB/L-3-hydroxyacyl-coenzyme A dehydrogenase type II activity in Abeta-induced cytotoxicity

Endoplasmic reticulum-associated amyloid beta-peptide (Abeta)-binding protein (ERAB)/L-3-hydroxyacyl-CoA dehydrogenase type II (HADH II) is expressed at high levels in Alzheimer's disease (AD)-affected brain, binds Abeta, and contributes to Abeta-induced cytotoxicity. Purified recombinant ERAB/HADH II catalyzed the NADH-dependent reduction of S-acetoacetyl-CoA with a Km of approximately 68 microM and a Vmax of approximately 430 micromol/min/mg. The contribution of ERAB/HADH II enzymatic activity to Abeta-mediated cellular dysfunction was studied by site-directed mutagenesis in the catalytic domain (Y168G/K172G). Although COS cells cotransfected to overexpress wild-type ERAB/HADH II and variant beta-amyloid precursor protein (betaAPP(V717G)) showed DNA fragmentation, cotransfection with Y168G/K172G-altered ERAB and betaAPP(V717G) was without effect. We thus asked whether the enzyme might recognize alcohol substrates of which the aldehyde products could be cytotoxic; ERAB/HADH II catalyzed oxidation of a variety of simple alcohols (C2-C10) to their respective aldehydes in the presence of NAD+ and NAD-dependent oxidation of 17beta-estradiol. Addition of micromolar levels of synthetic Abeta(1-40) to purified ERAB/HADH II inhibited, in parallel, reduction of S-acetoacetyl-CoA (Ki approximately 1.6 microM), as well as oxidation of 17beta-estradiol (Ki approximately 3.2 microM) and (-)-2-octanol (Ki approximately 2.6 microM). Because micromolar levels of Abeta were required to inhibit ERAB/HADH II activity, whereas Abeta binding to ERAB/HADH II occurred at much lower concentrations (Km approximately 40-70 nM), the latter more closely simulating Abeta levels within cells, Abeta perturbation of ERAB/HADH II was likely to result from mechanisms other than the direct modulation of enzymatic activity. Cells cotransfected to overexpress ERAB/HADH II and betaAPP(V717G) generated malondialdehyde-protein and 4-hydroxynonenal-protein epitopes, which were detectable only at the lowest levels in cells overexpressing either ERAB/HADH II or betaAPP(V717G) alone. Generation of such toxic aldehydes was not observed in cells contransfected to overexpress Y168G/K172G-altered ERAB and betaAPP(V717G). We conclude that the generalized alcohol dehydrogenase activity of ERAB/HADH II is central to the cytotoxicity observed in an Abeta-rich environment.     

Superior–Subordinate Relationships in Korean Civil Engineering Companies

The Leader–Member Exchange (LMX) relationship quality between superiors and subordinates in Korean civil engineering companies were empirically examined for superiors’ feedback-seeking behaviors. The results showed that for superiors, affect, loyalty, and contribution toward subordinates were positively related to seeking negative as well as positive feedback from subordinates. From subordinates’ point of view, affect, contribution, and professional respect toward their superiors were positively related to superiors’ negative feedback seeking, but affect was negatively related to superiors’ positive feedback seeking. It was also found that superiors and subordinates were not consensual in LMX and superiors’ feedback-seeking behaviors. For example, for superiors, all of the four LMX dimensions were positively related to superiors’ asking subordinates directly for feedback, whereas for subordinates, none of the LMX dimensions were significantly related to superiors’ asking subordinates directly for feedback. These and other findings are discussed in detail, and implications for the findings are provided.     

Investigation of wall mass transfer characteristics downstream of an orifice

Numerical simulations were performed to determine the effect of Reynolds number and orifice to pipe diameter ratio (d_o/d) on the wall mass transfer rate downstream of an orifice. The simulations were performed for d_o/d of 0.475 for Reynolds number up to 70,000. The effect of d_o/d was determined by performing simulations at a Reynolds number of 70,000 for d_o/d of 0.375, 0.475 and 0.575. The momentum and mass transport equations were solved using the Low Reynolds Number (LRN) K-? turbulence model. The Sherwood number (Sh) profile downstream of the orifice was in relatively good agreement with existing experimental results. The Sh increases sharply downstream of the orifice, reaching a maximum within 1–2 diameters downstream of the orifice, before relaxing back to the fully developed pipe flow value. The Sh number well downstream of the orifice was in good agreement with results for fully developed pipe flow estimated from the correlation of Berger and Hau (1977). The peak Sh numbers from the simulations were higher than that predicted from Tagg et al. (1979) and Coney (1980).     

用~(14)N(d,α_1)~(12)C核反应研究注入氮在纯铁和GCr15钢中的深度分布

本文描述了利用~(14)N(d,a_1)~(12)C核反应测量固体样品表面层内氮原子含量及深度分布的方法。在Si_3N_4标准样品中,所得到的表面处的深度分辨为48nm。利用该分析手段,研究了在不同注入温度条件下,氮离子注入纯铁和GCr15钢的保留量及深度分布的变化情况。     

水产品加工废水深度处理的试验

进行了用"生物接触氧化-微滤膜"组合工艺对水产品加工废水深度处理的试验研究.试验结果表明:在进水COD约900~1 200 ms/L,水力停留时间>16 h的情况下,平均出水COD<50 ms/t,达到再生水杂用水质标准.同时,研究探讨了处理过程中膜组件的污染及清洗问题,为实际工程中膜的运行提供了必要的参考.     

基于物联网技术的交通信息采集和服务

通过分析我国智能交通系统建设现状和存在问题,结合目前道路交通管理信息采集与服务需求,设计了基于物联网技术的道路交通信息采集与服务框架,以公安交通指挥平台为核心,集成各类交通信息采集与服务系统,实现交通路况信息全天候采集和智能分析、交通信息服务和出行诱导,以及区域交通流协调组织等功能。基于该框架体系,分别从交通流信息采集、交通信息发布与诱导服务、交通信号协调控制、公交优先等方面,对比分析了基于ITS技术的传统应用与基于物联网技术的新型应用的优缺点。结论:物联网技术应用将有利于突破现有ITS应用模式的弊端,提高交通信息采集精度,提升公众出行服务水平。     

热轧钢管加速冷却自动检测及控制系统的研究

介绍了在热轧钢管加速冷却的工艺过程中如何建立自动调节系统，以及用来实现自动检测和控制所需要的软、硬件的设计思想和设计方法，对研究和试验过程中新的加速冷却工艺所取得的实际效果进行了全面分析。     

辊底式加热炉下降烟道耐火材料改造实践

通化钢铁股份有限公司的连铸连轧生产线采用了先进的辊底式加热炉技术,其烟道工作衬设计采用1260℃绝热涂抹浇注料,耐火材料在使用六七个月后出现较严重的剥落现象。经过试验和生产使用证明,把浇注料改造成纤维模块应用于烟道工作层,在满足了生产工艺要求的前提下,使用寿命可达到18个月以上。     

The influence of temperature, pressure, salinity and capillary force on the formation of methane hydrate

We present here a thermodynamic model for predicting multi-phase equilibrium of methane hydrate liquid and vapor phases under conditions of different temperature, pressure, salinity and pore sizes. The model is based on the 1959 van der Waals-Platteeuw model, angle-dependent ab initio inter- molecular potentials, the DMW-92 equation of state and Pitzer theory. Comparison with all available experimental data shows that this model can accurately predict the effects of temperature, pressure, salinity and capillary radius on the formation and dissociation of methane hydrate. Online calculations of the p-T conditions for the formation of methane hydrate at given salinities and pore sizes of sediments are available on: www.geochem-model.org/models.htm.     

Transfection of glutathione S-transferase (GST)-pi antisense complementary DNA increases the sensitivity of a colon cancer cell line to adriamycin, cisplatin, melphalan, and etoposide

The goal of this study was to demonstrate that glutathione S-transferase (GST)-pi is directly involved in the intrinsic and acquired resistance of cancer cells to anticancer drugs. To this end, GST-pi antisense cDNA was transfected into the cultured human colon cancer cell line M7609, which expresses an innately high level of GST-pi and shows intrinsic drug resistance, and into an M7609 strain with acquired resistance to Adriamycin (ADR;i.e., M7609/ADR cells). The changes in the sensitivity of these transfectants to various anticancer drugs were investigated. The intracellular concentrations of GST-pi in M7609/anti-1 cells and M7609/anti-2 cells, two clones that were established by transfection of GST-pi antisense cDNA into M7609 cells, were decreased to approximately half of those detected in the parent cells (M7609) and in the control cells transfected with vector alone (M7609/pLJ). The sensitivities of the antisense transfectants in relation to ADR, cisplatin, melphalan, and etoposide were increased -3.3-fold, 2.3-fold, 2.2-fold, and 2.1-fold, respectively, compared with those of M7609 and M7609/pLJ. On the other hand, the sensitivities of the antisense transfectants to Taxol, vincristine, 5-fluorouracil, and mitomycin C were not significantly changed. Similarly, the transfection of antisense cDNA into M7609/ADR cells resulted in the reduction of intracellular GST-pi concentration (by about half) and an increased sensitivity to ADR (4.4-fold), but no increase in 5-fluorouracil sensitivity. Thus, GST-pi is considered to be a multidrug resistance factor that is responsible for both the intrinsic and acquired resistance of cancer cells to anticancer drugs such as ADR, cisplatin, melphalan, and etoposide.