An extended HLA-DQ-DR haplotype rather than DRB1 alone contributes to RA predisposition

A family with 1 case of retinitis pigmentosa (III-1) and 2 cases of Oguchi's disease (III-2, 3) was examined in terms of electrophysiology as well as molecular biology. The proband (III-3), a 42-year-old female, and 2 older brothers (III-1, 2, aged 52 and 45 years) and 2 unaffected members in the same family participated in this study. Corrected visual acuities of the individuals with Oguchi's disease (III-2, 3) were 1.2. On funduscopy, blood vessels stood out in relief against a metallic-appearing background and a Mizuo-Nakamura phenomenon was evident. Full-field electroretinograms (ERGs) recorded from the proband were indicative of rod dystrophy, but results of other electrophysiological examinations (multifocal ERG, pattern ERG and visual-evoked cortical potential recordings) were within normal limits. Patient III-1 had corrected visual acuities of RE 20 cm/m.m. and LE 30 cm/n.d., severe chorioretinal atrophy in both fundi, and full-field ERG revealed rod-cone dystrophy. Mutation of the arrestin gene (1147de1A) was detected in all 3 patients. Visual function in each patient coincides with that of retinitis pigmentosa or Oguchi's disease, respectively.     

Reduced serotonergic immunoreactive fibers in the forebrain of alcohol-preferring rats

Our previous study indicated that 5-hydroxytryptamine (5-HT) immunoreactive fiber densities were decreased in specific areas of the brain in alcohol-preferring rats (P) when compared with alcohol-nonpreferring rats (NP). The results of our current study show that there are quantitative and qualitative differences in 5-HT innervation in other selected regions of the forebrains of P rats. The 5-HT fiber density in the brains of young adult P and NP rats was measured by immunocytochemistry and quantitative image analysis. A routine error of two-dimensional quantitation of nerve fiber was addressed and an adjustment was made. The amount of 5-HT fibers was significantly lower in CA4 and fasciola cinereum of the dorsal hippocampus, caudate-putamen, and hypothalamus of the P as compared with NP rats (unpaired Student's t tests). In examining the fiber types, we found that, in the frontal cortical and hippocampal regions, where normally fine 5-HT fibers with small varicosities and thick 5-HT fibers with large varicosities coexist, fewer fine 5-HT fibers were seen in P rats as compared with NP rats. The fine fibers are known to be vulnerable to abusive drugs. These observations indicate that (a) there are quantitative differences in 5-HT innervation or that the 5-HT in some 5-HT fibers is reduced to a level undetectable by immunocytochemistry, and (b) the fine 5-HT fibers are specifically reduced to a greater degree in the selected brain regions of P rats when compared with that of NP rats. The involvement of the 5-HT system in the alcohol abuse is discussed.     

Synthesis and antitumor evaluation of 2,5-disubstituted-indazolo[4, 3-gh]isoquinolin-6(2H)-ones (9-aza-anthrapyrazoles)

The synthesis and antitumor evaluation of 2, 5-disubstituted-indazolo[4,3-gh]isoquinolin-6(2H)-ones (9-aza-APs) are described. The key intermediates in the synthesis are benz[g]isoquinoline-5,10-diones which are substituted at positions 6 and 9 with groups of different nucleofugacity for SNAr displacements. The initial displacement of fluoride by a substituted hydrazine leads to the pyrazole analogues. Substitution of the remaining leaving group by an amine or BOC-protected amines leads to the 9-aza-APs 12. These analogues were converted into their maleate or hydrochloride salts 13. In two cases, namely, 13x and 13z, sidearm buildup was also employed in the synthetic pathway. In vitro evaluation of 9-aza-APs against the human colon tumor cell line LoVo uncovered for most of the compounds a cytotoxic potency lower than that of DuP-941 or mitoxantrone and comparable to that of doxorubicin. Only analogues 13c, 13n, and 13ff were as cytotoxic as DuP-941. Interestingly, while DuP-941 was highly cross-resistant in the LoVo cell line resistant to doxorubicin (LoVo/Dx), the 9-aza-APs carrying a distal lipophilic tertiary amine moiety in both chains were capable of overcoming the MDR resistance induced in this cell line. The 9-aza-APs show outstanding in vivo antitumor activity against both systemic P388 murine leukemia and MX-1 human mammary carcinoma transplanted in nude mice. At their optimal dosages, congeners 13a-c, 13f, 13n, 13q, 13x, and 13dd were highly effective against P388 leukemia with T/C% of 200-381, while the T/C% value of DuP-941 was 147. In the MX-1 tumor model, 24 compounds elicited percentages of tumor weight inhibitions (TWI) ranging from 50% to 99%. Congeners 13d, 13k, 13l, 13x, 13z, and 13ee emerged as the most effective ones, with TWI% 96, simliar to that of DuP-941 (TWI% = 95). On the basis of their efficacy profile in additional experimental tumors and lack of cardiotoxicity in preclinical models, two congeners have surfaced as potential clinical candidates.     

Pharmacokinetics of phenprobamate after oral administration to healthy subjects

Phenprobamate (CAS 673-31-4) is a centrally acting skeletal-muscle relaxant agent. There are only two studies in the literature about the pharmacokinetics of phenoprobamate in man. The inconsistency between the results of these studies can be attributed partly to the different analytical methodologies used. A sensitive, specific and reproducible HPLC-assay, which may increase the reliability of the pharmacokinetic studies of phenprobamate in plasma, has been developed recently. The objective of this investigation was to assess the single-dose kinetics of phenprobamate in human and to determine the pharmacokinetic parameters of clinical and regulatory concern. The plasma pharmacokinetics of phenprobamate have been investigated following single oral administration at a dose of 800 mg in eleven healthy volunteers.     

地方时与区时在电离层研究中的差异

本文指出混淆地时与区时两个时间概念在电离层研究中带来的差异的严重性，建议使用地方与区时这两个名词，而抛弃“本地时”和“当地时”等容易引起混淆的名词。     

台儿庄城区饮用水水源地水质放射性水平分析

为了解和掌握台儿庄城区饮用水水源地放射性水平和动态变化,本文以枣庄市生态环境局台儿庄分局提供的饮用水水源地水质放射性数据为基础,探讨了台儿庄城区饮用水水源地水质中α、β放射性质量浓度的动态变化。结果显示:水源地总α、β放射性质量浓度均低于标准限值,总α放射性质量浓度小于总β放射性质量浓度,总α、β放射性水平在水源地和季节变化中差异均不显著(P>0.05)。水源地水质总放射性水平符合我国规定的饮用水指导值。     

基于云自适应遗传算法的NoC路径分配研究

路径分配是NoC设计流程中的两个关键步骤之一;路径分配的结果对NoC系统的性能尤其是通讯延时有着很重要的影响;多约束条件下的NoC路径分配问题是NP完全问题,要求出其最优解比较困难,目前常用的方法是利用启发式算法求得其较优解;文中提出一种基于云自适应遗传算法的NoC路径分配解决方案,该算法利用云模型对传统遗传算法加以改进,采取新的方法自动调整遗传算法过程中的交叉概率pc和变异概率pm,将适应度与云模型的3个参数Ex、En、He相互结合,从而达到优化遗传算法的目的;将此算法应用于2D-Mesh拓扑结构的NoC中,以平衡链路负载和联合优化为实验目标,以优化静态通讯分配结果;实验证明,文章所采取的算法在平衡链路负载和联合优化方面均取得了良好的效果。     

A power-free deposited microbead plug-based microfluidic chip for whole-blood immunoassay

We present a deposited microbead plug (DMBP)-based microfluidic chip capable of performing plasma extraction and on-chip immunoassay. The DMBP used as a porous blood filter provides pure blood plasma without the contamination of blood cells or beads. Capillary-driven flow eliminates the requirement of external pumps. The human IgG and goat anti-human IgG sample-to-answer assay was performed in this chip within 600 s using only a 10 μl whole-blood sample. This easy-to-use, rapid, inexpensive, and disposable DMBP-based chip holds a great promise for point-of-care application.     

The α- to β-Si3N4 transformation in the presence of liquid silicon

The compacts consisted of , -Si₃N₄ and free silicon are heat treated in the range 1650° C to 1750° C in an argon atmosphere in order to observe the following behaviours; the to phase transformation and variations of the microstructure during heat treatment in silicon nitride. For the microstructural observation of the heat treated specimens, the same grains in the polished surface were investigated before and after eliminating the retained silicon by etching. The to phase transformation, in this case, occurs via silicon melts irrespective of added -Si₃N₄. Both and phases are soluted and precipitated into molten silicon and their morphology are changed from an equiaxed shape to prismatic one. Although elongated grains are precipitated at low temperature or in the early stage of heat treatment, fine precipitated grains are mainly observed with increasing heat treating temperature.     

SERT结晶器液位控制系统

介绍一种梅山冶金公司板坯连同上应用的新型的结晶器液位控制系统，它由浮式式液位检测装置，ＲＳＥ１０００控制器和电动塞棒执行机构所组成，由法国ＳＥＲＴ公司成套制造。