Quantum-chemical, NMR and X-ray diffraction studies on (+/-)-1-[3,4-(methylenedioxy)phenyl]-2-methylaminopropane

Time-averaged conformations of (+/-)-1-[3,4-(methylenedioxy)phenyl]-2-methylaminopropane hydrochloride (MDMA, ""ecstasy"") in D(2)O, and of its free base and trifluoroacetate in CDCl(3), were deduced from their (1)H NMR spectra and used to calculate their conformer distribution. Their rotational potential energy surface (PES) was calculated at the RHF/6-31G(d,p), 133LYP/6-31G(d,p), B3LYP/cc-pVDZ and AM1 levels. Solvent effects were evaluated using the polarizable continuum model. The NMR and theoretical studies showed that, in the free base, the N-methyl group and the ring are preferentially trans. This preference is stronger in the salts and corresponds to the X-ray structure of the hydrochloride. However, the energy barriers separating these forms are very low. The X-ray diffraction crystal structures of the anhydrous salt and its monohydrate differed mainly in the trans or cis relationship of the N-methyl group to the a-methyl, although these two forms interconvert freely in solution. (C) 2007 Elsevier Inc. All rights reserved.

The Equilibrium Flux Method for the calculation of flows with non-equilbrium chemical reactions

The Equilibrium Flux Method [1] is a kinetic theory based finite volume method for calculating the flow of a compressible ideal gas. It is shown here that, in effect, the method solves the Euler equations with added pseudo-dissipative terms and that it is a natural upwinding scheme. The method can be easily modified so that the flow of a chemically reacting gas mixture can be calculated. Results from the method for a one-dimensional non-equilibrium reacting flow are shown to agree well with a conventional continuum solution. Results are also presented for the calculation of a plane two-dimensional flow, at hypersonic speed, of a dissociating gas around a blunt-nosed body.

Triple objective team mentoring: achieving learning objectives with chemical engineering students

A sophisticated style of mentoring has been found to be essential to support engineering student teams undertaking technically demanding, real-world problems as part of a Project-Centred Curriculum (PCC) at The University of Queensland. The term ‘triple-objective’ mentoring was coined to define mentoring that addresses not only the student’s technical goal achievement but also their time and team management. This is achieved through a number of formal mentor meetings that are informed by a confidential instrument which requires students to individually reflect on team processes prior to the meeting, and a checklist of technical requirements against which the interim student team progress and achievements are assessed. Triple-objective mentoring requires significant time input and coordination by the academic but has been shown to ensure effective student team work and learning undiminished by team dysfunction. Student feedback shows they value the process and agree that the tools developed to support the process are effective in developing and assessing team work and skills with average scores mostly above 3 on a four point scale.

Knowing your allies: Medical education and interprofessional exposure

Collaborative, team-based, interprofessional approaches to patient management are becoming increasingly recognized as beneficial to health outcomes. This project aimed to develop interprofessional skills among 134 third year medical students that were of clinical educational value to the students, and through activities that directly benefited the rural health professionals in their daily work. Placements were undertaken during a six week rural clinical attachment, mainly throughout South-West Queensland. Pre- and post-placement self-report questionnaires completed by both students and health professionals were used to evaluate the project. Results showed that over 80% of the health professional group reported the medical student placements were useful. Similarly, almost 80% of medical students reported positive changes in their attitude to other health professionals from the placement, and 91% indicated they had derived clinical educational benefit from their interprofessional activity. Despite difficulties due to poor communication between the various parties involved, the project proved successful in improving medical students' skills, knowledge and perceptions concerning interprofessional practice, through a placement and educational project which delivered practical benefits to rural health professionals and rural communities.

Chemical treatment of Escherichia coli. II. Direct extraction of recombinant protein from cytoplasmic inclusion bodies in intact cells

A method is presented for the direct extraction of the recombinant protein Long-R-3-IGF-I from inclusion bodies located in the cytoplasm of intact Escherichia coli cells. Chemical treatment with 6M urea, 3 mM EDTA, and 20 mM dithiothreitol (DTT) at pH 9.0 proved an effective combination for extracting recombinant protein from intact cells. Comparable levels of Long-R-3-IGF-I were recovered by direct extraction as achieved by in vitro dissolution following mechanical disruption. However, the purity of directly extracted recombinant protein was lower due to contamination by bacterial cell components. The kinetics of direct extraction are described using a first-order equation with the time constant of 3 min. Urea appears important for permeabilization of the cell and dissolution of the inclusion body. Conversely, EDTA is involved in permeabilization of the cell wall and DTT enhances protein release. pH proved to be important with lower levels of protein release achieved at low pH values (

An ESR and NMR study of the gamma radiolysis of a bisphenol-A based polycarbonate and a phthalic acid ester

A study of the gamma-radiolysis of the commercial polymers U-polymer, UP (Unitake) and polycarbonate, PC, (Aldrich) has been undertaken using ESR spectroscopy. The G-value of radical formation at 77 K has been found to be 0.31 +/- 0.01 for UP and 0.5 +/- 0.02 for PC. By using thermal annealing and spectral subtraction, the paramagnetic species formed on irradiation has been assigned. The effect of radiation on the chemical structure of UP and PC has been investigated at ambient temperature and at 423 K. The NMR results show that a new phenol type chain end is formed in the polymers on exposure to gamma-radiation. The G-value of formation of the new phenol ends was estimated to be 0.7 for PC (423 K) and 0.4 for UP (300 K). (C) 1998 John Wiley & Sons, Ltd.

Prediction of the chemical composition of lamb carcasses from multi-frequency impedance data

Multi-frequency bioimpedance analysis (MFBIA) was used to determine the impedance, reactance and resistance of 103 lamb carcasses (17.1-34.2 kg) immediately after slaughter and evisceration. Carcasses were halved, frozen and one half subsequently homogenized and analysed for water, crude protein and fat content. Three measures of carcass length were obtained. Diagonal length between the electrodes (right side biceps femoris to left side of neck) explained a greater proportion of the variance in water mass than did estimates of spinal length and was selected for use in the index L-2/Z to predict the mass of chemical components in the carcass. Use of impedance (Z) measured at the characteristic frequency (Z(c)) instead of 50 kHz (Z(50)) did not improve the power of the model to predict the mass of water, protein or fat in the carcass. While L-2/Z(50) explained a significant proportion of variation in the masses of body water (r(2) 0.64), protein (r(2) 0.34) and fat (r(2) 0.35), its inclusion in multi-variate indices offered small or no increases in predictive capacity when hot carcass weight (HCW) and a measure of rib fat-depth (GR) were present in the model. Optimized equations were able to account for 65-90 % of the variance observed in the weight of chemical components in the carcass. It is concluded that single frequency impedance data do not provide better prediction of carcass composition than can be obtained from measures of HCW and GR. Indices of intracellular water mass derived from impedance at zero frequency and the characteristic frequency explained a similar proportion of the variance in carcass protein mass as did the index L-2/Z(50).

Modeling ex vivo hematopoiesis using chemical engineering metaphors

Ex vivo hematopoiesis is increasingly used for clinical applications. Models of ex vivo hematopoiesis are required to better understand the complex dynamics and to optimize hematopoietic culture processes. A general mathematical modeling framework is developed which uses traditional chemical engineering metaphors to describe the complex hematopoietic dynamics. Tanks and tubular reactors are used to describe the (pseudo-) stochastic and deterministic elements of hematopoiesis, respectively. Cells at any point in the differentiation process can belong to either an immobilized, inert phase (quiescent cells) or a mobile, active phase (cycling cells). The model describes five processes: (1) flow (differentiation), (2) autocatalytic formation (growth),(3) degradation (death), (4) phase transition from immobilized to mobile phase (quiescent to cycling transition), and (5) phase transition from mobile to immobilized phase (cycling to quiescent transition). The modeling framework is illustrated with an example concerning the effect of TGF-beta 1 on erythropoiesis. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.

Chemical treatment of Escherichia coli: 3. Selective extraction of a recombinant protein from cytoplasmic inclusion bodies in intact cells

In previous parts of this study we developed procedures for the high-efficiency chemical extraction of soluble and insoluble protein from intact Escherichia coli cells. Although high yields were obtained, extraction of recombinant protein directly from cytoplasmic inclusion bodies led to low product purity due to coextraction of soluble contaminants. In this work, a two-stage procedure for the selective extraction of recombinant protein at high efficiency and high purity is reported. In the first stage, inclusion-body stability is promoted by the addition of 15 mM 2-hydroxyethyldisulfide (2-HEDS), also known as oxidized P-mercaptoethanol, to the permeabil ization buffer (6 M urea + 3 mM ethylenediaminetetra-acetate [EDTA]). 2-HEDS is an oxidizing agent believed to promote disulfide bond formation, rendering the inclusion body resistant to solubilization in 6 M urea. Contaminating proteins are separated from the inclusion-body fraction by centrifugation. in the second stage, disulfide bonds are readily eliminated by including reducing agent (20 mM dithiothreitol [DTT]) into the permeabilization buffer. Extraction using this selective two-stage process yielded an 81% (w/w) recovery of the recombinant protein Long-R-3-IGF-I from inclusion bodies located in the cytoplasm of intact E. coli, at a purity of 46% (w/w). This was comparable to that achieved by conventional extraction (mechanical disruption followed by centrifugation and solubilization). A pilot-scale procedure was also demonstrated using a stirred reactor and diafiltration. This is the first reported study that achieves both high extraction efficiency and selectivity by the chemical treatment of cytoplasmic inclusion bodies in intact bacterial cells. (C) 1999 John Wiley & Sons, Inc.

Coronary events and exposure to environmental tobacco smoke: a case-control study from Australia and New Zealand

Objectives-To estimate the relative risk of coronary heart disease (CHD) associated with exposure to environmental tobacco smoke (ETS). Design-Population-based case-control study. Subjects-Cases were 953 people identified in a population register of coronary events, and controls were 3189 participants in independent community-based risk factor prevalence surveys from the same study populations. Setting-Newcastle, Australia and Auckland, New Zealand. Main outcome measures-Acute myocardial infarction or coronary death. Results-After adjusting for the effects of age, education, history of heart disease, and body mass index, women had a statistically significant increased risk of a coronary event associated with exposure to ETS (relative risk (RR) = 1.99; 95% confidence interval (CI)= 1.40-2.81). There was little statistical evidence of increased risk found in men (RR = 1.02, 95% CI = 0.81-1.28). Conclusion-Our study found evidence for the adverse effects of exposure to ETS on risk of coronary heart disease among women, especially at home. For men the issue is unclear according to the data from our study. Additional studies with detailed information on possible confounders and adequate statistical power are needed. Most importantly, they should use methods for measuring exposure to ETS that are sufficiently accurate to permit the investigation of dose-response relationships.

Chronic ethanol exposure and withdrawal influence NMDA receptor subunit and splice variant mRNA expression in the rat cerebral cortex

Chronic ethanol exposure and subsequent withdrawal are known to change NMDA receptor activity. This study examined the effects of chronic ethanol administration and withdrawal on the expression of several NMDA receptor subunit and splice variant mRNAs in the rat cerebral cortex. Ethanol dependence was induced by ethanol vapour exposure. To delineate between seizure-induced changes in expression during withdrawal and those due to withdrawal per se, another group of naive rats was treated with pentylenetetrazol (PTZ) injection (30 mg/kg, i.p.). RNA samples from the cortices of chronically treated and withdrawing animals were compared to those from pairfed controls. Changes in NMDA receptor mRNA expression were determined using ribonuclease protection assays targetting the NR2A, -2B, -2C and NR1-pan subunits as well as the three alternatively spliced NR1 inserts (NR1-pan describes all the known NR1 splice variants generated from the 5' insert and the two 3' inserts). The ratio of NR1 mRNA incorporating the 5' insert vs, that lacking it was decreased during ethanol exposure and up to 48 h after withdrawal. NR2B mRNA expression was elevated during exposure, but returned to control levels 18 h after withdrawal. Levels of NR2A, NR2C, NR1-pan and both 3' NR1 insert mRNAs from the ethanol-treated groups did not alter compared with the pair-fed control group. No changes in the level of any NMDA receptor subunit mRNA was detected in the PTZ-treated animals. These data support the hypothesis that changes in NMDA receptor subunit composition may underlie a neuronal adaptation to the chronic ethanol-inhibition and may therefore be important in the precipitation of withdrawal hyperactivity. (C) 1999 Elsevier Science B.V. All rights reserved.

Determination of chemical shielding tensor of an indole carbon and application of tryptophan orientation of a membrane peptide

Using tryptophan C-13-enriched at the C-4 (C epsilon(3)) of the indole, the orientation of the C epsilon(3) chemical shift tensor relative to the C epsilon(3)-H dipolar axis was determined from the C-13 chemical shift/C-13-H-1 dipolar 2D NMR powder pattern. The principal values obtained were 208, 137 and 15 ppm with sigma(33) perpendicular to the indole plane, and sigma(11) (least shielded direction) 5 degrees off the C epsilon(3)-H bond toward C xi(3). The side off the C epsilon(3)-H bond was determined by comparing the reduced chemical shift anisotropies obtained by solid-state NMR and from molecular dynamics calculations of [4-C-13] tryptophans in gramicidin A aligned in phospholipid membranes. (C) 1999 Elsevier Science B.V. All rights reserved.