MILCH SHAKE: An efficient method for constraint dynamics applied to alkanes

We describe a method to impose constraints in a molecular dynamics simulation. A technique developed to solve the special case of a linear topology (MILC SHAKE) is hybridized with the SHAKE algorithm. The methodology, which we term MILC‐hybridized SHAKE (or MILCH SHAKE), applies to more complex topologies. Here we consider the important case of all atom models of alkanes. Exploiting the mass difference between carbon and hydrogen we show that for higher alkanes MILCH SHAKE can be an order of magnitude faster than SHAKE. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009     

A validated positive chemical ionization GC/MS method for the identification and quantification of amphetamine, opiates, cocaine, and metabolites in human postmortem brain

A sensitive and specific method for the simultaneous detection and quantification of amphetamine, opiates, and cocaine and metabolites in human postmortem brain was developed and validated. Analytes of interest included amphetamine, morphine, codeine, 6-acetylmorphine, cocaine, benzoylecgonine, ecgonine methyl ester, ecgonine ethyl ester, cocaethylene, and anhydroecgonine methyl ester. The method employed ultrasonic homogenization of brain tissue in pH 4.0 sodium acetate buffer and solid phase extraction. Extracts were derivatized with N-methyl-N-(tert-butyldimethylsilyl) trifluoroacetamide and N,O-bis(trimethylsilyl) trifluoroacetamide. Separation and quantification were accomplished on a bench-top positive chemical ionization capillary gas chromatograph/mass spectrometer with selected ion monitoring. Eight deuterated analogs were used as internal standards. Limits of quantification were 50 ng/g of brain. Calibration curves were linear to 1000 ng/g for anhydroecgonine methyl ester and 6-acetylmorphine, and to 2000 ng/g for all other analytes. Accuracy across the linear range of the assay ranged from 90.2 to 112.2%, and precision, as percent relative standard deviation, was less than 16.6%. Quantification of drug concentrations in brain is a useful research tool in neurobiology and in forensic and postmortem toxicology, identifying the type, relative magnitude, and recency of abused drug exposure. This method will be employed to quantify drug concentrations in human postmortem brain in support of basic and clinical research on the physiologic, biochemical, and behavioral effects of drugs in humans.     

Evidence for substrate preorganization in the peptidylglycine α-amidating monooxygenase reaction describing the contribution of ground state structure to hydrogen tunneling

Peptidylglycine α-amidating monooxygenase (PAM) is a bifunctional enzyme which catalyzes the post-translational modification of inactive C-terminal glycine-extended peptide precursors to the corresponding bioactive α-amidated peptide hormone. This conversion involves two sequential reactions both of which are catalyzed by the separate catalytic domains of PAM. The first step, the copper-, ascorbate-, and O(2)-dependent stereospecific hydroxylation at the α-carbon of the C-terminal glycine, is catalyzed by peptidylglycine α-hydroxylating monooxygenase (PHM). The second step, the zinc-dependent dealkylation of the carbinolamide intermediate, is catalyzed by peptidylglycine amidoglycolate lyase. Quantum mechanical tunneling dominates PHM-dependent C(α)-H bond activation. This study probes the substrate structure dependence of this chemistry using a set of N-acylglycine substrates of varying hydrophobicity. Primary deuterium kinetic isotope effects (KIEs), molecular mechanical docking, alchemical free energy perturbation, and equilibrium molecular dynamics were used to study the role played by ground-state substrate structure on PHM catalysis. Our data show that all Ν-acylglycines bind sequentially to PHM in an equilibrium-ordered fashion. The primary deuterium KIE displays a linear decrease with respect to acyl chain length for straight-chain N-acylglycine substrates. Docking orientation of these substrates displayed increased dissociation energy proportional to hydrophobic pocket interaction. The decrease in KIE with hydrophobicity was attributed to a preorganization event which decreased reorganization energy by decreasing the conformational sampling associated with ground state substrate binding. This is the first example of preorganization in the family of noncoupled copper monooxygenases.     

Carboxylate-directed highly stereoselective homogeneous hydrogenation of cyclic olefins with Wilkinson's catalyst

A highly efficient diastereoselective, carboxylate-directed homogeneous hydrogenation of cyclic olefins with use of Wilkinson's catalyst is described. Under the optimized reaction conditions, better than 99% de was achieved. The experimental protocol is very simple and readily amenable to scale-up. [reaction: see text]     

CORRELATION OF UVC AND UVB CYTOTOXICITY WITH THE INDUCTION OF SPECIFIC PHOTOPRODUCTS IN T-LYMPHOCYTES AND FIBROBLASTS FROM NORMAL HUMAN DONORS

Abstract— By using specific monoclonal antibodies in situ and a computer-assisted image analysis system we have determined the relative induction of cyclobutane dimers, (6–4) photoproducts and Dewar isomers in human mononuclear cells and fibroblasts following irradiation with UVC, broad-spectrum UVB and narrow-spectrum UVB. The lamps produced these lesions in different proportions, with broad-spectrum UVB inducing a greater combined yield of (6–4) photoproducts and Dewar isomers per cyclobutane dimer than UVC or narrow-spectrum UVB. The relative induction ratios of (6–4) photoproducts compared to cyclobutane dimers were 0.15, 0.21 and 0.10 following irradiation with UVC, broad- or narrow-spectrum UVB, respectively. Although Dewar isomers were induced by UVC, their relative rate of formation compared to cyclobutane dimers was significantly greater after irradiation with either broad-spectrum or narrow-spectrum UVB. These values were 0.001, 0.07 and 0.07, respectively. With each lamp source, we have determined the survival of normal human T-lymphocytes and fibroblasts at fiuences, which induce equivalent yields of cyclobutane dimers, (6–4) photoproducts or (6–4) photoproducts plus Dewar isomers. Killing of fibroblasts appears to be associated with (6–4) photoproduct formation, whereas killing of T-lymphocytes seems to be mediated by combined (6–4) plus Dewar yields. These results emphasize the need to study the biological effects of UVB because cellular responses may be different from those following UVC irradiation.     

Guiding interventions in a multi-organisational context: combining the Viable System Model and Hierarchical Process Modelling for use as a Problem Structuring Method

This paper describes the development and application of an innovative Problem Structuring Method to guide interventions in the way in which the UK Ministry of Defence delivers infrastructure projects and services. This method uses an adaptation of the Viable System Model to structure a set of stakeholder assessments that leads to the building of a Hierarchical Process Model. The resultant model, which appears readily transferrable to other multi-organisational contexts, represents the functions required for a specified system to be effective in its environment and affords insight into the processes and capabilities that require intervention—either to increase performance (addressing weaknesses) or to increase understanding (addressing uncertainty). The paper also describes a number of methodological learning points identified through the use of a structured approach to evaluation, which again appear to be readily transferrable to other multi-organisational contexts.     

Differential perturbed angular correlation measurements of the electric quadrupole interaction of 181Ta IN K3 HfF7

The differential perturbed angular correlation of the ¹⁸¹Ta 133–482 γ-γ cascade was studied in K₃HfF₇. The results indicate a change from a two site model for the ¹⁸¹Ta nuclei at ?196°C to a one site model at 21°C.     

An analysis of PTFE surfaces modified by exposure to glow discharges

A detailed analysis is reported of the chemical and physical modifications which occur to PTFE surfaces exposed to glow discharges in ammonia gas and in air. The analytical methods used were infra-red attenuated total reflectance and differential attenuated total reflectance spectroscopy, X-ray photoelectron spectroscopy, contact angle measurements and scanning electron microscopy. The suitability for bonding with adhesives and the stability of the modified surfaces to attack by oxidizing acids are also reported.     

等离子体原子荧光光谱仪激发光源空心阴极灯脉冲发生和信号处理控制系统的研制和评估

本文用带３８６处理器的微型计算机,通过自行研制的接口,在ＢａｉｒｄＰｌａｓｍａＡＦＳ－２０００原子荧光光谱仪上实现了荧光激发光源空心阴极灯供电脉冲发生和信号处理的控制。典型元素的检测限、相对标准偏差和线性相关系数表明,系统性能良好。新系统增强了仪器的功能。