Validation of the Applied Biosystems Prism 377 automated sequencer for the forensic short tandem repeat analysis

The Applied Biosystems (ABI) Prism 377 DNA sequencer has been evaluated in an attempt to increase the throughput of samples for short tandem repeat (STR) analysis, in both forensic casework and the UK National Criminal Intelligence DNA Database. The gel system assessed consisted of 0.2 mm, 4% acrylamide 6 M urea gels, with a well-to-read distance of 36 cm. Gels were run at a constant voltage of 3 kV and constant temperature of 51 degrees C. The run time of our second generation multiplex (SGM) STR system was achieved in less than 2 h. Rigorous validation has been performed on the instrument hardware and software. Complete resolution of 1 base differences was obtained, up to and beyond 350 bases; sizing precision across gels was more than 2-fold higher than the 373A and the sensitivity was increased by one third.     

On the transport of a suspended particle in flow through the entrance region of a tube

The motion of a single, spherical particle, released at different radial positions at the inlet of the entrance region of a straight circular laminar flow tube (Re = 260), was studied theoretically. Radial migration of the particle, either toward the tube center or toward the tube wall, was predicted. Based on the hypothesis that the particle experienced a lift force which was produced by the vorticity in the boundary layer and a velocity difference between the center of the suspended particle and the fluid medium, an inertia-vorticity fluid dynamic model was formulated to analyze the particle radial motions. Computational flow dynamics (CFD) solutions obtained from a 9.8 mm diameter tube model included the resulting particle loci for three particle radii (a = 0.1 cm, 0.085 cm, 0.050 cm), with the particle entry at various radial positions. The computation also covered a range of different particle entry speeds. The results showed that the particle migrates toward the tube center if it lags behind the medium in the core region; otherwise, it migrates toward the tube wall. Additional flow experiments were conducted in a circular (2R = 10.2 mm), 300 mm long straight tube. A small polystyrene sphere (2a = 1.72 mm, density rho p = 1.014 g.cm-3) was released at the inlet (X = 0, eta/R = 0.48) with two dimesionless release velocities (omega p = 0, and omega p > 1.0). The recorded particle traces agree well with the computational model.     

Proadrenomedullin N-terminal 20 peptide: minimal active region to regulate nicotinic receptors

Proadrenomedullin N-terminal 20 peptide (PAMP-[1-20]; ARLDVASEFRKKWNKWALSR-amide) is a potent hypotensive and catecholamine release-inhibitory peptide released from chromaffin cells. We studied the mechanism of PAMP action and how its function is linked to structure. We tested human PAMP-[1-20] on catecholamine secretion in PC12 pheochromocytoma cells and found it to be a potent, dose-dependent (IC50 approximately 350 nmol/L) secretory inhibitor. Inhibition was specific for nicotinic cholinergic stimulation since PAMP-[1-20] failed to inhibit release by agents that bypass the nicotinic receptor. Nicotinic cationic (22Na+,45Ca2+) signal transduction was disrupted by this peptide, and potencies for inhibition of 22Na+ uptake and catecholamine secretion were comparable. Even high-dose nicotine failed to overcome the inhibition, suggesting noncompetitive nicotinic antagonism. N- and C-terminal PAMP truncation peptides indicated a role for the C-terminal amide and refined the minimal active region to the C-terminal 8 amino acids (WNKWALSR-amide), a region likely to be alpha-helical. PAMP also blocked (EC50 approximately 270 nmol/L) nicotinic cholinergic agonist desensitization of catecholamine release, as well as desensitization of nicotinic signal transduction (22Na+ uptake). Thus, PAMP may exert both inhibitory and facilitatory effects on nicotinic signaling, depending on the prior state of nicotinic stimulation. PAMP may therefore contribute to a novel, autocrine, homeostatic (negative-feedback) mechanism controlling catecholamine release.     

Do birthplans empower women? A study of their views

The birthplans has become a common practice in many maternity units to improve continuity of care and enable women to gain control over the experience of childbirth. In this study, semi-structured interviews were employed to explore the perception of empowerment from the women's point of view. Next week, the author highlights the midwives' experience of using birthplans.     

复合顶板软弱岩层外错式相邻区段巷道联合支护技术研究

为解决传统巷道布置条件下复合顶板软弱岩层沿空巷道存在顶板易变形、易失稳、易冒落，无法长久维持巷道围岩稳定性等一系列难题，本文基于错层位外错式巷道布置方式，利用相邻区段间巷道空间化结构关系，提出综放复合顶板错层位外错式相邻区段巷道联合支护技术，理论分析该支护技术的围岩控制作用机理，采用FLAC3D数值模拟软件对错层位外错式巷道布置条件下相邻区段巷道联合支护方案进行研究并与传统巷道布置下常规支护方案进行对比。模拟结果表明：采用“错层位外错式巷道布置+相邻区段间巷道联合支护技术”为核心的综合围岩控制措施，可加强易离层垮落顶板的支护强度，使围岩应力在联合支护的作用下趋于均衡，从而最大限度地发挥支护体系的支撑作用，达到巷道稳定的目的。     

Synthesis of 6-aziridinylbenzimidazole derivatives and their in vitro antitumor activities

In search for new antitumor agents, twelve 6-aziridinylbenzimidazole derivatives were synthesized and their cytotoxicities were tested against three cancer cell lines (mouse lymphocytic leukemia P388 and B16, and human gastric carcinoma SNU-16). From 4-amino-3-nitrotoluene as the starting material, 2-(acetoxymethyl)benzimidazoles (5a-d) were obtained by Phillips reaction. These benzimidazoles were then reacted with Fremy's salt to give a mixture of three 2-(acetoxymethyl) (8a-c) and four 2-(hydroxymethyl)benzimidazole-4,7-diones (9a-d). Addition of these quinones with aziridine afforded 6-aziridinyl-2-(acetoxymethyl) (10a-c) and 6-aziridinyl-2-(hydroxymethyl)benzimidazole-4,7-diones (11a-d). Utilizing 2-(hydroxymethyl)benzimidazole-4,7-diones (9b,d), esters 10d and 13e-h were prepared by the sequential reactions of esterification and addition. The synthesized compounds show potent cytotoxicity against all of three cell lines tested. The cytotoxicities of 10a-d or 11a-d against SNU-16 were superior to those of 13e-h, and were equal to or slightly higher than that of mitomycin C. Compounds 11a-d were slightly more cytotoxic than 10a-d in all cell lines tested.