A novel DRD2 single-nucleotide polymorphism associated with schizophrenia predicts age of onset : HapMap tag-single-nucleotide polymorphism analysis

Background: Dopamine D2 receptor (DRD2) is thought to be critical in regulating the dopaminergic pathway in the brain which is known to be important in the aetiology of schizophrenia. It is therefore not surprising that most antipsychotic medication acts on the Dopamine D2 receptor. DRD2 is widely expressed in brain, levels are reduced in brains of schizophrenia patients and DRD2 polymorphisms have been associated with reduced brain expression. We have previously identified a genetic variant in DRD2, rs6277 to be strongly implicated in schizophrenia susceptibility. Methods: To identity new associations in the DRD2 gene with disease status and clinical severity, we genotyped seven single nucleotide polymorphisms (SNPs) in DRD2 using a multiplex mass spectrometry method. SNPs were chosen using a haplotype block-based gene-tagging approach so the entire DRD2 gene was represented. Results: One polymorphism rs2734839 was found to be significantly associated with schizophrenia as well as late onset age. Individuals carrying the genetic variation were more than twice as likely to have schizophrenia compared to controls. Conclusions: Our results suggest that DRD2 genetic variation is a good indicator for schizophrenia risk and may also be used as a predictor age of onset.

Contribution to single-point closure Reynolds-stress modelling of inhomogeneous flow

This paper is concerned with recent advances in the development of near wall-normal-free Reynolds-stress models, whose single point closure formulation, based on the inhomogeneity direction concept, is completely independent of the distance from the wall, and of the normal to the wall direction. In the present approach the direction of the inhomogeneity unit vector is decoupled from the coefficient functions of the inhomogeneous terms. A study of the relative influence of the particular closures used for the rapid redistribution terms and for the turbulent diffusion is undertaken, through comparison with measurements, and with a baseline Reynolds-stress model (RSM) using geometric wall normals. It is shown that wall-normal-free rsms can be reformulated as a projection on a tensorial basis that includes the inhomogeneity direction unit vector, suggesting that the theory of the redistribution tensor closure should be revised by taking into account inhomogeneity effects in the tensorial integrity basis used for its representation.

Welfare-to-work and the experience of single mothers in Australia : where are the benefits?

In July 2006 ‘welfare-to-work’ policies were introduced for single parents in Australia. These policies require most single parents with school aged children to be employed or seeking employment of 15-25 hours per week in return for their income support payment. The changes represented a sharp increase in the obligations applying to single parents on income support. This paper is concerned with how the well-being of single mothers who are combining income support and paid employment is being influenced by these stepped up activity requirements. The paper draws on data from semi-structured interviews with 21 Brisbane single mothers. The analysis explores participants’ experiences in the new policy environment utilizing the theoretical framework of ‘relational autonomy’. Relational approaches to autonomy emphasize the importance of relations of dependency and interdependency to the development of autonomy and well-being. The findings indicate that in their dealings with the welfare bureaucracy participants experienced a lack of recognition of their identities as mothers, paid workers and competent decision makers. These experiences have negative consequences for self worth, relational autonomy and ultimately the well-being of single parent families.

Melt textured Y123 bulk and thick film

YBa2Cu3O7-δ - 25mol%Y2BaCuO5 bars and thick films have been melt textured using a stationary furnace with a temperature gradient of 3 or 6°C/cm. Samples are heated above the peritectic reaction temperature and quenched to just above the solidification temperature and then slowly cooled below the solidification temperature. All bar shaped samples consist of 2-5 mm grains though the grain orientations strongly depend on the heat treatment conditions. The bar shows the maximum Jc of above 3,000 A/cm2, whereas the maximum Jc of 200 A/cm2 and Tczero of 88K are obtained for the thick film on (100) LaAlO3 single crystal.

Integrated TEM, XRD and electron-microprobe investigation of mixed-layer chlorite smectite from the Point-Sal ophiolite, California

Five basalt samples from the Point Sal ophiolite, California, were examined using HRTEM and AEM in order to compare observations with interpretations of XRD patterns and microprobe analyses. XRD data from ethylene-glycol-saturated samples indicate the following percentages of chlorite in mixed-layer chlorite-smectite identified for each specimen: (i) L2036 almost-equal-to 50%, (ii) L2035 almost-equal-to 70 and 20%, (iii) 1A-13 almost-equal-to 70%, (iv) 1B-42 almost-equal-to 70%, and (v) 1B-55 = 100%. Detailed electron microprobe analyses show that 'chlorite' analyses with high Si, K, Na and Ca contents are the result of interlayering with smectite-like layers. The Fe/(Fe + Mg) ratios of mixed-layer phyllosilicates from Point Sal samples are influenced by the bulk rock composition, not by the percentage of chlorite nor the structure of the phyllosilicate. Measurements of lattice-fringe images indicate that both smectite and chlorite layers are present in the Point Sal samples in abundances similar to those predicted with XRD techniques and that regular alternation of chlorite and smectite occurs at the unit-cell scale. Both 10- and 14-angstrom layers were recorded with HRTEM and interpreted to be smectite and chlorite, respectively. Regular alternation of chlorite and smectite (24-angstrom periodicity) occurs in upper lava samples L2036 and 1A-13, and lower lava sample 1B-42 for as many as seven alternations per crystallite with local layer mistakes. Sample L2035 shows disordered alternation of chlorite and smectite, with juxtaposition of smectite-like layers, suggesting that randomly interlayered chlorite (< 0.5)-smectite exists. Images of lower lava sample 1B-55 show predominantly 14-angstrom layers. Units of 24 angstrom tend to cluster in what may otherwise appear to be disordered mixtures, suggesting the existence of a corrensite end-member having thermodynamic significance.

Oxide reduction in NiO-containing solid solution systems during transmission electron microscopy

The effects of electron irradiation on NiO-containing solid solution systems are described. Partially hydrated NiO solid solutions, e. g. , NiO-MgO, undergo surface reduction to Ni metal after examination by TEM. This surface layer results in the formation of Moire interference patterns.

Layer silicates in a chondritic porous interplanetary dust particle

Analytical electron microscopy on individual grains from a portion of a chondritic porous interplanetary dust particle (aggregate W7029C1 from the NASA Johnson Space Center Cosmic Dust Collection) shows that layer silicates compose 50 percent of the silicate fraction examined. These layer silicates can be classified into two distinct crystallochemical groups: (1) fine-grained, polycrystalline smectite minerals; and (2) well-ordered, single crystals of kaolinite and Mg-poor talc. The layer silicates in this portion of sample W7029(asterisk)A are dissimilar to those described in other chondritic porous aggregates. The predominant layer silicate assemblage in W7029(asterisk)A indicates that heating of the aggregate during atmospheric entry was brief and probably to a temperature less than 300C. Comparison with terrestrial phyllosilicate occurrences suggests that some layer silicates in aggregate W7029(asterisk)A may have been formed by alteratiton from preexisting silicate minerals at low temperatures (less than 25C) after aggregate formation.

Structure of the immature retroviral capsid at 8 Å resolution by cryo-electron microscopy

The assembly of retroviruses such as HIV-1 is driven by oligomerization of their major structural protein, Gag. Gag is a multidomain polyprotein including three conserved folded domains: MA (matrix), CA (capsid) and NC (nucleocapsid)(1). Assembly of an infectious virion proceeds in two stages(2). In the first stage, Gag oligomerization into a hexameric protein lattice leads to the formation of an incomplete, roughly spherical protein shell that buds through the plasma membrane of the infected cell to release an enveloped immature virus particle. In the second stage, cleavage of Gag by the viral protease leads to rearrangement of the particle interior, converting the non-infectious immature virus particle into a mature infectious virion. The immature Gag shell acts as the pivotal intermediate in assembly and is a potential target for anti-retroviral drugs both in inhibiting virus assembly and in disrupting virus maturation(3). However, detailed structural information on the immature Gag shell has not previously been available. For this reason it is unclear what protein conformations and interfaces mediate the interactions between domains and therefore the assembly of retrovirus particles, and what structural transitions are associated with retrovirus maturation. Here we solve the structure of the immature retroviral Gag shell from Mason-Pfizer monkey virus by combining cryo-electron microscopy and tomography. The 8-angstrom resolution structure permits the derivation of a pseudo-atomic model of CA in the immature retrovirus, which defines the protein interfaces mediating retrovirus assembly. We show that transition of an immature retrovirus into its mature infectious form involves marked rotations and translations of CA domains, that the roles of the amino-terminal and carboxy-terminal domains of CA in assembling the immature and mature hexameric lattices are exchanged, and that the CA interactions that stabilize the immature and mature viruses are almost completely distinct.

Analytical electron microscope investigation of boron carbide microstructures at elevated temperatures

The microstructures of hot-pressed B4C were monitored during in situ heating experiments from room temperature to 1000C by analytical electron microscopy (AEM). Variations in the microstructure of B4C were not observed. However, during heating, secondary phases formed in voids and on the surfaces of the specimen.

Thin-film analyses of silicate standards at 200 kv : the effect of temperature on element loss

Preliminary data is presented on a detailed statistical analysis of k-factor determination for a single class of minerals (amphiboles) which contain a wide range of element concentrations. These amphiboles are homogeneous, contain few (if any) subsolidus microstructures and can be readily prepared for thin film analysis. In previous studies, element loss during the period of irradiation has been assumed negligible for the determination of k-factors. Since this phenomena may be significant for certain mineral systems, we also report on the effect of temperature on k-factor determination for various elements using small probe sizes (approx.20 nm).

Harmonic elimination technique for a single-phase multilevel converter with unequal DC link voltage levels

Multilevel converters, because of the benefits they attract in generating high quality output voltage, are used in several applications. Various modulation and control techniques are introduced by several researchers to control the output voltage of the multilevel converters like space vector modulation and harmonic elimination (HE) methods. Multilevel converters may have a DC link with equal or unequal DC voltages. In this study a new HE technique based on the HE method is proposed for multilevel converters with unequal DC link voltage. The DC link voltage levels are considered as additional variables for the HE method and the voltage levels are defined based on the HE results. Increasing the number of voltage levels can reduce lower order harmonic content because of the fact that more variables are created. In comparison to previous methods, this new technique has a positive effect on the output voltage quality by reducing its total harmonic distortion, which must take into consideration for some applications such as uninterruptable power supply, motor drive systems and piezoelectric transducer excitation. In order to verify the proposed modulation technique, MATLAB simulations and experimental tests are carried out for a single-phase four-level diode-clamped converter.

Community interventions for physical activity : the role of a new Cochrane systematic review

Introduction: Systematic reviews are essential in summarising the results of a range of research studies on a specific topic into a single report. They serve as a key source of evidence-based information to support and develop policy and practice for healthy communities. This presentation will examine a new review of community-wide strategies to increase population levels of physical activity and compare it to an earlier Community Guide Review (CGR) of Community-wide campaigns to increase physical activity which recommended community wide interventions. Methods: We registered a Cochrane Systematic Review (CSR) title, published a protocol and recently completed the review of Community-wide interventions to increase physical activity. We compared the definitions, design and findings of the CSR to the CGR. Results: The two reviews differed remarkably in their conclusions with the CGR recommending “strong evidence exists that community-wide campaigns are effective in increasing levels of physical activity”, and the new CSR stating “The body of evidence in this review does not support the hypothesis that multi-component community wide interventions effectively increase population levels of physical activity”. We observed that both reviews examined multi-component interventions as a “combined package”. Possible explanations for the different conclusions may be due to the definition of community (CSR defined community as “comprising those persons residing in a geographically defined community, such as a village, town, or city”, excluding interventions which were whole of state or country, and CGR as “a group of individuals who share one or more characteristics. The CSR utilised a logic model at various stages of the review process and explicitly defined a combination of strategies encompassed within the intervention. The CSR included 25 and CGR 10 studies, respectively. Six of the 10 studies that were included in CGR were excluded from the CSR due to issues relating to study design, intervention definition or duration. The two reviews also differ in function as the CSR seeks to summarise global evidence and included 7 studies in low-income countries, where as the CGR contained only studies deemed relevant to the USA context. Discussion: Differences in the findings between older and newer reviews can be due to a variety of factors. For example, in updating a review the definition of an intervention can be changed. Further, differences may also be due to improvements in the standards and methodologies for systematic reviews as well as the inclusion of newer studies. These factors need to be understood whenever differences between newer and older reviews are considered.