Reactions of the hydroperoxide anion with dimethyl methylphosphonate in an ion trap mass spectrometer : evidence for a gas phase alpha-effect

The gas phase degradation reactions of the chemical warfare agent (CWA) simulant, dimethyl methylphosphonate (DMMP), with the hydroperoxide anion (HOO(-)) were investigated using a modified quadrupole ion trap mass spectrometer. The HOO(-) anion reacts readily with neutral DMMP forming two significant product ions at m/z 109 and m/z 123. The major reaction pathways correspond to (i) the nucleophilic substitution at carbon to form \[CH(3)P(O)(OCH(3))O](-) (m/z 109) in a highly exothermic process and (ii) exothermic proton transfer. The branching ratios of the two reaction pathways, 89% and 11% respectively, indicate that the former reaction is significantly faster than the latter. This is in contrast to the trend for the methoxide anion with DMMP, where proton transfer dominates. The difference in the observed reactivities of the HOO(-) and CH(3)O(-) anions can be considered as evidence for an a-effect in the gas phase and is supported by electronic structure calculations at the B3LYP/aug-cc-pVTZ//B3LYP/6-31+G(d) level of theory that indicate the S(N)2(carbon) process has an activation energy 7.8 kJ mol(-1) lower for HOO(-) as compared to CH(3)O(-). A similar alpha-effect was calculated for nucleophilic addition-elimination at phosphorus, but this process an important step in the perhydrolysis degradation of CWAs in solution - was not observed to occur with DMMP in the gas phase. A theoretical investigation revealed that all processes are energetically accessible with negative activation energies. However, comparison of the relative Arrhenius pre-exponential factors indicate that substitution at phosphorus is not kinetically competitive with respect to the S(N)2(carbon) and deprotonation processes.

Formation of neutral molecules of potential stellar interest by neutralisation of negative ions in a mass spectrometer - The application of experiment and molecular modelling in concert

This paper is a modified version of a lecture which describes the synthesis, structure and reactivity of some neutral molecules of stellar significance. The neutrals are formed in the collision cell of a mass spectrometer following vertical Franck-Condon one electron oxidation of anions of known bond connectivity. Neutrals are characterised by conversion to positive ions and by extensive theoretical studies at the CCSD(T)/aug-cc-pVDZ//B3LYP/6-31G(d) level of theory. Four systems are considered in detail, viz (i) the formation of linear C-4 and its conversion to the rhombus C-4, (ii) linear C-5 and the atom scrambling of this system when energised, (iii) the stable cumulene oxide CCCCCO, and (iv) the elusive species O2C-CO. This paper is not intended to be a review of interstellar chemistry: examples are selected from our own work in this area. (C) 2002 Elsevier Science Inc. All rights reserved.

Type I collagen abrogates the clathrin-mediated internalization of membrane type 1 matrix metalloproteinase (MT1-MMP) via the MT1-MMP hemopexin domain

Type I collagen (Col I)-stimulated matrix metalloproteinase-2 (MMP-2) activation via membrane type 1 MMP (MT1-MMP) involves both a transcriptional increase in MT1-MMP expression and a nontranscriptional response mediated by preexisting MT1-MMP. In order to identify which MT1-MMP domains were required for the nontranscriptional response, MCF-7 cells that lack endogenous MT1-MMP were transfected with either wild type or domain mutant MT1-MMP constructs. We observed that mutant constructs lacking the MT1-MMP cytoplasmic tail were able to activate MMP-2 in response to Col I but not a construct lacking the MT1-MMP hemopexin domain. Col I did not alter total MT1-MMP protein levels; nor did it appear to directly induce MT1-MMP oligomerization. Col I did, however, redistribute preexisting MT1-MMP to the cell periphery compared with unstimulated cells that displayed amore diffuse staining pattern. In addition, Col I blocked the internalization of MT1-MMP in a dynamin-dependent manner via clathrin-coated pit-mediated endocytosis. This mechanism of impaired internalization is different from that reported for concanavalin A, since it is not mediated by the cytoplasmic tail of MT1-MMP but rather by the hemopexin domain. In summary, upon Col I binding to its cell surface receptor, MT1-MMP internalization via clathrin-coated pit-mediated endocytosis is impaired through interactions with the hemopexin domain, thereby regulating its function and ability to activate MMP-2.

Pulsed i-PVD of dielectric nanodot arrays using a nanoporous template

The results of multi-scale numerical simulations of pulsed i-PVD template-assisted nanofabrication of ZnO nanodot arrays on a silicon substrate are presented. The ratios and spatial distributions of the ion fluxes deposited on the lateral and bottom surfaces of the nanopores are computed as a function of the external bias and plasma parameters. The results show that the pulsed bias plays a significant role in the ion current distribution inside the nanopores. The results of numerical experiments of this work suggest that by finely adjusting the pulse voltage, the pulse duration and the duty cycle of the external pulsed bias, the nanopore clogging can be successfully avoided during the deposition and the shapes of the deposited ZnO nanodots can be effectively controlled. A figure is presented.

Electron energy distribution function in low-pressure complex plasmas

The effect of density and size of dust grains on the electron energy distribution function (EEDF) in low-temperature complex plasmas is studied. It is found that the EEDF depends strongly on the dust density and size. The behavior of the electron temperature can differ significantly from that of a pristine plasma. For low-pressure argon glow discharge, the Druyvesteyn-like EEDF often found in pristine plasmas can become nearly Maxwellian if the dust density and/or sizes are large. One can thus control the plasma parameters by the dust grains.

New Dawn (Parts I & II)

New Dawn is a cross-media visual art project that comprises a multi–channel video work (Boxcopy ARI, Brisbane) and a series of sculptural works (MetroArts, Brisbane) both of which conflate the online spectacle of real events with virtual gaming. The purpose of this project is to question this new phenomenon and what are the political, social and economic repercussions for these new technological developments on our bodies and subjectivities. By doing this my work asks us to reflect on how we function as a society in response to these new spaces of interaction, how we might respond to the political dimensions of these expanded sites of inhabitation, and how they might also represent a more troubling scenario for the possibility of dissent or opposition in our media saturated culture. The work was shown at multiple venues simultaneously. One of the components of the work won the 2013 Sunshine Coast Art Prize for sculpture.

Characterization of acyl chain position in unsaturated phosphatidylcholines using differential mobility-mass spectrometry

Glycerophospholipids (GPs) that differ in the relative position of the two fatty acyl chains on the glycerol backbone (i.e., sn-positional isomers) can have distinct physicochemical properties. The unambiguous assignment of acyl chain position to an individual GP represents a significant analytical challenge. Here we describe a workflow where phosphatidylcholines (PCs) are subjected to ESI for characterization by a combination of differential mobility spectrometry and MS (DMS-MS). When infused as a mixture, ions formed from silver adduction of each phospholipid isomer {e.g., [PC (16:0/18:1) + Ag]+ and [PC (18:1/16:0) + Ag]+} are transmitted through the DMS device at discrete compensation voltages. Varying their relative amounts allows facile and unambiguous assignment of the sn-positions of the fatty acyl chains for each isomer. Integration of the well-resolved ion populations provides a rapid method (< 3 min) for relative quantification of these lipid isomers. The DMS-MS results show excellent agreement with established, but time-consuming, enzymatic approaches and also provide superior accuracy to methods that rely on MS alone. The advantages of this DMS-MS method in identification and quantification of GP isomer populations is demonstrated by direct analysis of complex biological extracts without any prior fractionation.

Telomere length in circulating leukocytes is associated with lung function and disease

Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (β= −0.0452, p=0.024) as well as COPD (β= −0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07×10−7), FVC (p=2.07×10−5), and FEV1/FVC (p=5.27×10−3). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.

Cross-cultural adaptation and validation of the Foot Function Index to Spanish

Background The purpose of this study was to adapt and validate the Foot Function Index to the Spanish (FFI-Sp) following the guidelines of the American Academy of Orthopaedic Surgeons. Methods A cross-sectional study 80 participants with some foot pathology. A statistical analysis was made, including a correlation study with other questionnaires (the Foot Health Status Questionnaire, EuroQol 5-D, Visual Analogue Pain Scale, and the Short Form SF-12 Health Survey). Data analysis included reliability, construct and criterion-related validity and factor analyses. Results The principal components analysis with varimax rotation produced 3 principal factors that explained 80% of the variance. The confirmatory factor analysis showed an acceptable fit with a comparative fit index of 0.78. The FFI-Sp demonstrated excellent internal consistency on the three subscales: pain 0.95; disability 0.96; and activity limitation 0.69, the subscale that scored lowest. The correlation between the FFI-Sp and the other questionnaires was high to moderate. Conclusions The Spanish version of the Foot Function Index (FFI-Sp) is a tool that is a valid and reliable tool with a very good internal consistency for use in the assessment of pain, disability and limitation of the function of the foot, for use both in clinic and research.

A kinematic analysis of the hand function

Background The evaluation of the hand function is an essential element within the clinical practice. The usual assessments are focus on the ability to perform activities of daily life. The inclusion of instruments to measure kinematic variables provides a new approach to the assessment. Inertial sensors adapted to the hand could be used as a complementary instrument to the traditional assessment. Material: clinimetric assessment (Upper Limb Functional Index, Quick Dash), antrophometric variables (eight and weight), dynamometry (palm preasure) was taken. Functional analysis was made with Acceleglove system for the right hand and computer system. The glove has six acceleration sensor, one on each finger and another one on the reverse palm. Method Analytic, transversal approach. Ten healthy subject made six task on evaluation table (tripod pinch, lateral pinch and tip pinch, extension grip, spherical grip and power grip). Each task was made and measure three times, the second one was analyze for the results section. A Matlab script was created for the analysis of each movement and detection phase based on module vector. Results The module acceleration vector offers useful information of the hand function. The data analysis obtained during the performance of functional gestures allows to identify five different phases within the movement, three static phase and tow dynamic, each module vector was allied to one task. Conclusion Module vector variables could be used for the analysis of the different task made by the hand. Inertial sensor could be use as a complement for the traditional assessment system.

Probabilistic multi-tensor estimation using the tensor distribution function

Diffusion weighted magnetic resonance (MR) imaging is a powerful tool that can be employed to study white matter microstructure by examining the 3D displacement profile of water molecules in brain tissue. By applying diffusion-sensitized gradients along a minimum of 6 directions, second-order tensors can be computed to model dominant diffusion processes. However, conventional DTI is not sufficient to resolve crossing fiber tracts. Recently, a number of high-angular resolution schemes with greater than 6 gradient directions have been employed to address this issue. In this paper, we introduce the Tensor Distribution Function (TDF), a probability function defined on the space of symmetric positive definite matrices. Here, fiber crossing is modeled as an ensemble of Gaussian diffusion processes with weights specified by the TDF. Once this optimal TDF is determined, the diffusion orientation distribution function (ODF) can easily be computed by analytic integration of the resulting displacement probability function.

A novel measure of fractional anisotropy based on the tensor distribution function

Fractional anisotropy (FA), a very widely used measure of fiber integrity based on diffusion tensor imaging (DTI), is a problematic concept as it is influenced by several quantities including the number of dominant fiber directions within each voxel, each fiber's anisotropy, and partial volume effects from neighboring gray matter. With High-angular resolution diffusion imaging (HARDI) and the tensor distribution function (TDF), one can reconstruct multiple underlying fibers per voxel and their individual anisotropy measures by representing the diffusion profile as a probabilistic mixture of tensors. We found that FA, when compared with TDF-derived anisotropy measures, correlates poorly with individual fiber anisotropy, and may sub-optimally detect disease processes that affect myelination. By contrast, mean diffusivity (MD) as defined in standard DTI appears to be more accurate. Overall, we argue that novel measures derived from the TDF approach may yield more sensitive and accurate information than DTI-derived measures.

The tensor distribution function

Diffusion weighted magnetic resonance imaging is a powerful tool that can be employed to study white matter microstructure by examining the 3D displacement profile of water molecules in brain tissue. By applying diffusion-sensitized gradients along a minimum of six directions, second-order tensors (represented by three-by-three positive definite matrices) can be computed to model dominant diffusion processes. However, conventional DTI is not sufficient to resolve more complicated white matter configurations, e.g., crossing fiber tracts. Recently, a number of high-angular resolution schemes with more than six gradient directions have been employed to address this issue. In this article, we introduce the tensor distribution function (TDF), a probability function defined on the space of symmetric positive definite matrices. Using the calculus of variations, we solve the TDF that optimally describes the observed data. Here, fiber crossing is modeled as an ensemble of Gaussian diffusion processes with weights specified by the TDF. Once this optimal TDF is determined, the orientation distribution function (ODF) can easily be computed by analytic integration of the resulting displacement probability function. Moreover, a tensor orientation distribution function (TOD) may also be derived from the TDF, allowing for the estimation of principal fiber directions and their corresponding eigenvalues.

Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk

Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55-85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or -4.0 to -1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD-associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies. © 2011 Duncan et al.

The MS risk allele of CD40 is associated with reduced cell-membrane bound expression in antigen presenting cells: Implications for gene function

Human genetic and animal studies have implicated the costimulatory molecule CD40 in the development of multiple sclerosis (MS). We investigated the cell specific gene and protein expression variation controlled by the CD40 genetic variant(s) associated with MS, i.e. the T-allele at rs1883832. Previously we had shown that the risk allele is expressed at a lower level in whole blood, especially in people with MS. Here, we have defined the immune cell subsets responsible for genotype and disease effects on CD40 expression at the mRNA and protein level. In cell subsets in which CD40 is most highly expressed, B lymphocytes and dendritic cells, the MS-associated risk variant is associated with reduced CD40 cell-surface protein expression. In monocytes and dendritic cells, the risk allele additionally reduces the ratio of expression of full-length versus truncated CD40 mRNA, the latter encoding secreted CD40. We additionally show that MS patients, regardless of genotype, express significantly lower levels of CD40 cell-surface protein compared to unaffected controls in B lymphocytes. Thus, both genotype-dependent and independent down-regulation of cell-surface CD40 is a feature of MS. Lower expression of a co-stimulator of T cell activation, CD40, is therefore associated with increased MS risk despite the same CD40 variant being associated with reduced risk of other inflammatory autoimmune diseases. Our results highlight the complexity and likely individuality of autoimmune pathogenesis, and could be consistent with antiviral and/or immunoregulatory functions of CD40 playing an important role in protection from MS. © 2015 Field et al.