Intergenerational Associations of Chronic Disease and Polycystic Ovary Syndrome

Extent: 4p.Background: Polycystic ovary syndrome (PCOS) is a common female endocrine disorder of heterogeneous clinical presentation, high disease burden, and unknown aetiology. The disease and associated conditions cluster in families, suggesting that PCOS may be the reproductive consequence of underlying chronic disease susceptibility. Objective: To determine whether parents of young women with PCOS were more likely to have a history of diabetes or cardiovascular disease in later adult life. Design, Setting and Participants: Structured interviews with 715 members of a cohort constructed by tracing female infants born at a single general hospital in Adelaide between 1973 and 1975. Participants were asked whether they had a pre-existing medical diagnosis of PCOS, and whether each parent had ever had high blood pressure, high cholesterol, diabetes, stroke, or heart disease. Maternal high blood pressure during pregnancy was taken from the medical record of the pregnancy with the study participant. Results and Conclusions: Mothers of women with PCOS were more likely than mothers of other women to have any cardiovascular disease (RR 1.78, 95% CI 1.29, 2.47), and nearly twice as likely to have high blood pressure (RR 1.95, 95% CI 1.38, 2.76). Fathers of women with PCOS were more than twice as likely to have heart disease (RR 2.36, 95% CI 1.44, 3.88) and over four times as likely to have had a stroke (RR 4.37, 95% CI 1.97, 9.70). Occurrence of cardiovascular disease in both mother and father are associated with the risk of PCOS in daughters. Further detailed study is required to elucidate the precise pathways that may be causally related to the observations.Michael J. Davies, Jennifer L. Marino, Kristyn J. Willson, Wendy A. March and Vivienne M. Moor

Effects of Space Charge, Dopants, and Strain Fields on Surfaces and Grain Boundaries in YBCO Compounds

Statistical thermodynamical and kinetically-limited models are applied to study the origin and evolution of space charges and band-bending effects at low angle [001] tilt grain boundaries in YBa$_2$Cu$_3$O$_7$ and the effects of Ca doping upon them. Atomistic simulations, using shell models of interatomic forces, are used to calculate the energetics of various relevant point defects. The intrinsic space charge profiles at ideal surfaces are calculated for two limits of oxygen contents, i.e. YBa$_2$Cu$_3$O$_6$ and YBa$_2$Cu$_3$O$_7$. At one limit, O$_6$, the system is an insulator, while at O$_7$, a metal. This is analogous to the intrinsic and doping cases of semiconductors. The site selections for doping calcium and creating holes are also investigated by calculating the heat of solution. In a continuum treatment, the volume of formation of doping calcium at Y-sites is computed. It is then applied to study the segregation of calcium ions to grain boundaries in the Y-123 compound. The influences of the segregation of calcium ions on space charge profiles are finally studied to provide one guide for understanding the improvement of transport properties by doping calcium at grain boundaries in Y-123 compound.Comment: 13 pages, 5 figure

K∗(892)K^{*}(892) Production in Au+Au and pp Collisions at sNN\sqrt{s_{NN}} = 200GeV at STAR

Mid-rapidity $K^{*0}(892)\to K\pi$ and $K^{*\pm}(892)\to K_S^0\pi^{\pm}$ are measured in Au+Au and pp collisions at $\sqrt{s_{NN}}$=200GeV using the STAR detector at RHIC. The $K^{*0}(892)$ mass is systematically shifted at small transverse momentum for both Au+Au and pp collisions. The $K^{*0}(892)$ transverse mass spectra are measured in Au+Au collisions at different centralities and in pp collisions. The $K^{*0}(892)$ mean transverse momentum as a function of the collision centrality is compared to those of identified $\pi^{-}$, $K^{-}$ and $\bar{p}$. The $K^{*}/K$ and $\phi/K^{*}$ ratios are compared to measurements in A+A, $pp$, $\bar{p}p$, $e^{+}e^{-}$ collisions at various colliding energies. The physics implications of these measurements are also discussed.Comment: 6 pages, 4 figures, proceedings of Strange Quarks in Matter (SQM2003), Atlantic Beach, USA, to be published in J. Phys.

B(d) --> phi K(S) CP asymmetries as an important probe of supersymmetry

The decay $B_d \to \phi K_S$ is a special probe of physics beyond the Standard Model (SM), since it has no SM tree level contribution. Motivated by recent data suggesting a deviation from the SM for its time-dependent CP asymmetry, we examine supersymmetric explanations. Chirality preserving contributions are generically small, unless gluino is relatively light. Higgs contributions are also too small to explain a large asymmetry. Chirality flipping $LR$ and $RL$ gluino contributions actually can provide sizable effects without conflict with all related results. We discuss how various insertions can be distinguished, and argue the needed sizes of mass insertions are reasonable.Comment: 5 pages, 4 figures. A few typos in the abstract are corrected. This is a shortened version of hep-ph/021209

Hydrogen vs batteries : comparative safety assessments for a high-speed passenger ferry

Batteries and hydrogen constitute two of the most promising solutions for decarbonising international shipping. This paper presents the comparison between a battery and a proton-exchange membrane hydrogen fuel cell version of a high-speed catamaran ferry with a main focus on safety. The systems required for each version are properly sized and fitted according to the applicable rules, and their impact on the overall design is discussed. Hazards for both designs were identified; frequency and consequence indexes for them were input qualitatively, following Novel Technology Qualification and SOLAS Alternative Designs and Arrangements, while certain risk control options were proposed in order to reduce the risks of the most concerned accidental events. The highest ranked risks were analysed by quantitative risk assessments in PyroSim software. The gas dispersion analysis performed for the hydrogen version indicated that it is crucial for the leakage in the fuel cell room to be stopped within 1 s after being detected to prevent the formation of explosive masses under full pipe rupture of 33 mm diameter, even with 120 air changes per hour. For the battery version, the smoke/fire simulation in the battery room indicated that the firefighting system could achieve a 30% reduction in fire duration, with firedoors closed and ventilation shut, compared to the scenario without a firefighting system

B --> Phi K_S and Supersymmetry

The rare decay B --> Phi K_S is a well-known probe of physics beyond the Standard Model because it arises only through loop effects yet has the same time-dependent CP asymmetry as B --> Psi K_S. Motivated by recent data suggesting new physics in B --> Phi K_S, we look to supersymmetry for possible explanations, including contributions mediated by gluino loops and by Higgs bosons. Chirality-preserving LL and RR gluino contributions are generically small, unless gluinos and squarks masses are close to the current lower bounds. Higgs contributions are also too small to explain a large asymmetry if we impose the current upper limit on B(B_s --> mu mu). On the other hand, chirality-flipping LR and RL gluino contributions can provide sizable effects and while remaining consistent with related results in B --> Psi K_S, Delta M_s, B --> X_s gamma and other processes. We discuss how the LR and RL insertions can be distinguished using other observables, and we provide a string-based model and other estimates to show that the needed sizes of mass insertions are reasonable.Comment: 33 pages, 32 figures, Updated version for PRD. Includes discussions of other recent works on this topic. Added discussions & plots for gluino mass dependence and effects of theoretical uncertaintie

Learning pair-wise gene functional similarity by multiplex gene expression maps

Abstract Background The relationships between the gene functional similarity and gene expression profile, and between gene function annotation and gene sequence have been studied extensively. However, not much work has considered the connection between gene functions and location of a gene's expression in the mammalian tissues. On the other hand, although unsupervised learning methods have been commonly used in functional genomics, supervised learning cannot be directly applied to a set of normal genes without having a target (class) attribute. Results Here, we propose a supervised learning methodology to predict pair-wise gene functional similarity from multiplex gene expression maps that provide information about the location of gene expression. The features are extracted from expression maps and the labels denote the functional similarities of pairs of genes. We make use of wavelet features, original expression values, difference and average values of neighboring voxels and other features to perform boosting analysis. The experimental results show that with increasing similarities of gene expression maps, the functional similarities are increased too. The model predicts the functional similarities between genes to a certain degree. The weights of the features in the model indicate the features that are more significant for this prediction. Conclusions By considering pairs of genes, we propose a supervised learning methodology to predict pair-wise gene functional similarity from multiplex gene expression maps. We also explore the relationship between similarities of gene maps and gene functions. By using AdaBoost coupled with our proposed weak classifier we analyze a large-scale gene expression dataset and predict gene functional similarities. We also detect the most significant single voxels and pairs of neighboring voxels and visualize them in the expression map image of a mouse brain. This work is very important for predicting functions of unknown genes. It also has broader applicability since the methodology can be applied to analyze any large-scale dataset without a target attribute and is not restricted to gene expressions

Type-1 Cannabinoid Receptors Reduce Membrane Fluidity of Capacitated Boar Sperm by Impairing Their Activation by Bicarbonate

Background Mammalian spermatozoa acquire their full fertilizing ability (so called capacitation) within the female genital tract, where they are progressively exposed to inverse gradients of inhibiting and stimulating molecules. Methodology/Principal Findings In the present research, the effect on this process of anandamide, an endocannabinoid that can either activate or inhibit cannabinoid receptors depending on its concentration, and bicarbonate, an oviductal activatory molecule, was assessed, in order to study the role exerted by the type 1 cannabinoid receptor (CB1R) in the process of lipid membrane remodeling crucial to complete capacitation. To this aim, boar sperm were incubated in vitro under capacitating conditions (stimulated by bicarbonate) in the presence or in the absence of methanandamide (Met-AEA), a non-hydrolysable analogue of anandamide. The CB1R involvement was studied by using the specific inhibitor (SR141716) or mimicking its activation by adding a permeable cAMP analogue (8Br-cAMP). By an immunocytochemistry approach it was shown that the Met-AEA inhibits the bicarbonate-dependent translocation of CB1R from the post-equatorial to equatorial region of sperm head. In addition it was found that Met-AEA is able to prevent the bicarbonate-induced increase in membrane disorder and the cholesterol extraction, both preliminary to capacitation, acting through a CB1R-cAMP mediated pathway, as indicated by MC540 and filipin staining, EPR spectroscopy and biochemical analysis on whole membranes (CB1R activity) and on membrane enriched fraction (C/P content and anisotropy). Conclusions/Significance Altogether, these data demonstrate that the endocannabinoid system strongly inhibits the process of sperm capacitation, acting as membrane stabilizing agent, thus increasing the basic knowledge on capacitation-related signaling and potentially opening new perspectives in diagnostics and therapeutics of male infertility

Effect of Differential N-linked and O-linked Mannosylation on Recognition of Fungal Antigens by Dendritic Cells

BACKGROUND. An experimental approach for improving vaccine efficacy involves targeting antigens to mannose receptors (MRs) on dendritic cells (DCs) and other professional antigen presenting cells. Previously, we demonstrated that mannosylated Pichia pastoris-derived recombinant proteins exhibited increased immunogenicity compared to proteins lacking mannosylation. In order to gain insight into the mechanisms responsible for this observation, the present study examined the cellular uptake of the mannosylated and deglycosylated recombinant proteins. METHODOLOGY/PRINCIPAL FINDINGS. Utilizing transfected cell lines, roles for the macrophage mannose receptor (MMR, CD206) and DC-SIGN (CD209) in the recognition of the mannosylated, but not deglycosylated, antigens were demonstrated. The uptake of mannosylated antigens into murine bone marrow-derived DCs (BMDCs) was inhibited by yeast mannans (YMs), suggesting a mannose-specific C-type lectin receptor-dependent process, while the uptake of deglycosylated antigens remained unaffected. In particular, antigens with both N-linked and extensive O-linked mannosylation showed the highest binding and uptake by BMDCs. Finally, confocal microscopy studies revealed that both mannosylated and deglycosylated P. pastoris-derived recombinant proteins localized in MHC class II+ compartments within BMDCs. CONCLUSIONS/SIGNIFICANCE. Taken together with our previous results, these data suggest that increased uptake by mannose-specific C-type lectin receptors is the major mechanism responsible for the enhanced antigenicity seen with mannosylated proteins. These findings have important implications for vaccine design and contribute to our understanding of how glycosylation affects the immune response to eukaryotic pathogens.National Institutes of Health (RO1 AI25780, RO1 AI37532

The Role of Cilostazol, a Phosphodiesterase 3 Inhibitor, on Oocyte Maturation and Subsequent Pregnancy in Mice

It is important to identify effective contraceptive drugs that cause minimal disruption to physiological processes. Phosphodiesterase 3 (PDE3) inhibitors suppress meiosis in oocytes by decreasing the level of cAMP and blocking the extrusion of the first polar body. In this study, we tested the PDE3 inhibitor, cilostazol, as a potential contraceptive agent. The effects of cilostazol treatment in vitro and in vivo on the suppression of oocyte maturation in a mouse model were investigated. The results indicated that treatment with increasing concentrations of cilostazol led to a dose-dependent arrest in meiosis progression. The effective in vitro concentration was 1 µM and was 300 mg/kg in vivo. The effect of cilostazol was reversible. After removal of the drug, meiosis resumed and mouse oocytes matured in vitro, and showed normal chromosome alignment and spindle organization. After fertilization using an ICSI method, the oocytes showed normal morphology, fertilization rate, embryo cleavage, blastocyst formation, and number of viable pups when compared with controls. The offspring showed similar body weight and fertility. In vivo, the mice became infertile if the drug was injected sequentially, and became pregnant following discontinuation of cilostazol. More importantly, no side effects of cilostazol were observed in treated female mice as demonstrated by blood pressure and heart rate monitoring. It is concluded that cilostazol, a drug routinely used for intermittent claudication, can effectively inhibit oocyte maturation in vitro and in vivo, does not affect the developmental potential of oocytes following drug removal and has few side effects in female mice treated with this drug. These findings suggest that cilostazol may be a potential new contraceptive agent that may facilitate an efficacy and safety study of this drug