Implementation of Web-Based Respondent-Driven Sampling among Men who Have Sex with Men in Vietnam

Objective: Lack of representative data about hidden groups, like men who have sex with men (MSM), hinders an evidence-based response to the HIV epidemics. Respondent-driven sampling (RDS) was developed to overcome sampling challenges in studies of populations like MSM for which sampling frames are absent. Internet-based RDS (webRDS) can potentially circumvent limitations of the original RDS method. We aimed to implement and evaluate webRDS among a hidden population. Methods and Design: This cross-sectional study took place 18 February to 12 April, 2011 among MSM in Vietnam. Inclusion criteria were men, aged 18 and above, who had ever had sex with another man and were living in Vietnam. Participants were invited by an MSM friend, logged in, and answered a survey. Participants could recruit up to four MSM friends. We evaluated the system by its success in generating sustained recruitment and the degree to which the sample compositions stabilized with increasing sample size. Results: Twenty starting participants generated 676 participants over 24 recruitment waves. Analyses did not show evidence of bias due to ineligible participation. Estimated mean age was 22 year and 82% came from the two large metropolitan areas. 32 out of 63 provinces were represented. The median number of sexual partners during the last six months was two. The sample composition stabilized well for 16 out of 17 variables. Conclusion: Results indicate that webRDS could be implemented at a low cost among Internet-using MSM in Vietnam. WebRDS may be a promising method for sampling of Internet-using MSM and other hidden groups. Key words: Respondent-driven sampling, Online sampling, Men who have sex with men, Vietnam, Sexual risk behavio

Caspase-2 is upregulated after sciatic nerve transection and its inhibition protects dorsal root ganglion neurons from Apoptosis after serum withdrawal

Sciatic nerve (SN) transection-induced apoptosis of dorsal root ganglion neurons (DRGN) is one factor determining the efficacy of peripheral axonal regeneration and the return of sensation. Here, we tested the hypothesis that caspase-2(CASP2) orchestrates apoptosis of axotomised DRGN both in vivo and in vitro by disrupting the local neurotrophic supply to DRGN. We observed significantly elevated levels of cleaved CASP2 (C-CASP2), compared to cleaved caspase-3 (C-CASP3), within TUNEL+DRGN and DRG glia (satellite and Schwann cells) after SN transection. A serum withdrawal cell culture model, which induced 40% apoptotic death in DRGN and 60% in glia, was used to model DRGN loss after neurotrophic factor withdrawal. Elevated C-CASP2 and TUNEL were observed in both DRGN and DRG glia, with C-CASP2 localisation shifting from the cytosol to the nucleus, a required step for induction of direct CASP2-mediated apoptosis. Furthermore, siRNAmediated downregulation of CASP2 protected 50% of DRGN from apoptosis after serum withdrawal, while downregulation of CASP3 had no effect on DRGN or DRG glia survival. We conclude that CASP2 orchestrates the death of SN-axotomised DRGN directly and also indirectly through loss of DRG glia and their local neurotrophic factor support. Accordingly, inhibiting CASP2 expression is a potential therapy for improving both the SN regeneration response and peripheral sensory recovery

Evaluation of machine-learning methods for ligand-based virtual screening

Machine-learning methods can be used for virtual screening by analysing the structural characteristics of molecules of known (in)activity, and we here discuss the use of kernel discrimination and naive Bayesian classifier (NBC) methods for this purpose. We report a kernel method that allows the processing of molecules represented by binary, integer and real-valued descriptors, and show that it is little different in screening performance from a previously described kernel that had been developed specifically for the analysis of binary fingerprint representations of molecular structure. We then evaluate the performance of an NBC when the training-set contains only a very few active molecules. In such cases, a simpler approach based on group fusion would appear to provide superior screening performance, especially when structurally heterogeneous datasets are to be processed

Imbibition in Disordered Media

The physics of liquids in porous media gives rise to many interesting phenomena, including imbibition where a viscous fluid displaces a less viscous one. Here we discuss the theoretical and experimental progress made in recent years in this field. The emphasis is on an interfacial description, akin to the focus of a statistical physics approach. Coarse-grained equations of motion have been recently presented in the literature. These contain terms that take into account the pertinent features of imbibition: non-locality and the quenched noise that arises from the random environment, fluctuations of the fluid flow and capillary forces. The theoretical progress has highlighted the presence of intrinsic length-scales that invalidate scale invariance often assumed to be present in kinetic roughening processes such as that of a two-phase boundary in liquid penetration. Another important fact is that the macroscopic fluid flow, the kinetic roughening properties, and the effective noise in the problem are all coupled. Many possible deviations from simple scaling behaviour exist, and we outline the experimental evidence. Finally, prospects for further work, both theoretical and experimental, are discussed.Comment: Review article, to appear in Advances in Physics, 53 pages LaTe

Orexinergic Input to Dopaminergic Neurons of the Human Ventral Tegmental Area

The mesolimbic reward pathway arising from dopaminergic (DA) neurons of the ventral tegmental area (VTA) has been strongly implicated in reward processing and drug abuse. In rodents, behaviors associated with this projection are profoundly influenced by an orexinergic input from the lateral hypothalamus to the VTA. Because the existence and significance of an analogous orexigenic regulatory mechanism acting in the human VTA have been elusive, here we addressed the possibility that orexinergic neurons provide direct input to DA neurons of the human VTA. Dual-label immunohistochemistry was used and orexinergic projections to the VTA and to DA neurons of the neighboring substantia nigra (SN) were analyzed comparatively in adult male humans and rats. Orexin B-immunoreactive (IR) axons apposed to tyrosine hydroxylase (TH)-IR DA and to non-DA neurons were scarce in the VTA and SN of both species. In the VTA, 15.062.8% of TH-IR perikarya in humans and 3.260.3% in rats received orexin B-IR afferent contacts. On average, 0.2460.05 and 0.0560.005 orexinergic appositions per TH-IR perikaryon were detected in humans and rats, respectively. The majority(86–88%) of randomly encountered orexinergic contacts targeted the dendritic compartment of DA neurons. Finally, DA neurons of the SN also received orexinergic innervation in both species. Based on the observation of five times heavierorexinergic input to TH-IR neurons of the human, compared with the rat, VTA, we propose that orexinergic mechanism acting in the VTA may play just as important roles in reward processing and drug abuse in humans, as already established well in rodents

High energy emission from microquasars

The microquasar phenomenon is associated with the production of jets by X-ray binaries and, as such, may be associated with the majority of such systems. In this chapter we briefly outline the associations, definite, probable, possible, and speculative, between such jets and X-ray, gamma-ray and particle emission.Comment: Contributing chapter to the book Cosmic Gamma-Ray Sources, K.S. Cheng and G.E. Romero (eds.), to be published by Kluwer Academic Publishers, Dordrecht, 2004. (19 pages

Fission Yeast Sec3 and Exo70 Are Transported on Actin Cables and Localize the Exocyst Complex to Cell Poles

The exocyst complex is essential for many exocytic events, by tethering vesicles at the plasma membrane for fusion. In fission yeast, polarized exocytosis for growth relies on the combined action of the exocyst at cell poles and myosin-driven transport along actin cables. We report here the identification of fission yeast Schizosaccharomyces pombe Sec3 protein, which we identified through sequence homology of its PH-like domain. Like other exocyst subunits, sec3 is required for secretion and cell division. Cells deleted for sec3 are only conditionally lethal and can proliferate when osmotically stabilized. Sec3 is redundant with Exo70 for viability and for the localization of other exocyst subunits, suggesting these components act as exocyst tethers at the plasma membrane. Consistently, Sec3 localizes to zones of growth independently of other exocyst subunits but depends on PIP2 and functional Cdc42. FRAP analysis shows that Sec3, like all other exocyst subunits, localizes to cell poles largely independently of the actin cytoskeleton. However, we show that Sec3, Exo70 and Sec5 are transported by the myosin V Myo52 along actin cables. These data suggest that the exocyst holocomplex, including Sec3 and Exo70, is present on exocytic vesicles, which can reach cell poles by either myosin-driven transport or random walk

The Endogenous Th17 Response in NO<inf>2</inf>-Promoted Allergic Airway Disease Is Dispensable for Airway Hyperresponsiveness and Distinct from Th17 Adoptive Transfer

Severe, glucocorticoid-resistant asthma comprises 5-7% of patients with asthma. IL-17 is a biomarker of severe asthma, and the adoptive transfer of Th17 cells in mice is sufficient to induce glucocorticoid-resistant allergic airway disease. Nitrogen dioxide (NO2) is an environmental toxin that correlates with asthma severity, exacerbation, and risk of adverse outcomes. Mice that are allergically sensitized to the antigen ovalbumin by exposure to NO2 exhibit a mixed Th2/Th17 adaptive immune response and eosinophil and neutrophil recruitment to the airway following antigen challenge, a phenotype reminiscent of severe clinical asthma. Because IL-1 receptor (IL-1R) signaling is critical in the generation of the Th17 response in vivo, we hypothesized that the IL-1R/Th17 axis contributes to pulmonary inflammation and airway hyperresponsiveness (AHR) in NO2-promoted allergic airway disease and manifests in glucocorticoid-resistant cytokine production. IL-17A neutralization at the time of antigen challenge or genetic deficiency in IL-1R resulted in decreased neutrophil recruitment to the airway following antigen challenge but did not protect against the development of AHR. Instead, IL-1R-/- mice developed exacerbated AHR compared to WT mice. Lung cells from NO2-allergically inflamed mice that were treated in vitro with dexamethasone (Dex) during antigen restimulation exhibited reduced Th17 cytokine production, whereas Th17 cytokine production by lung cells from recipient mice of in vitro Th17-polarized OTII T-cells was resistant to Dex. These results demonstrate that the IL-1R/Th17 axis does not contribute to AHR development in NO2-promoted allergic airway disease, that Th17 adoptive transfer does not necessarily reflect an endogenously-generated Th17 response, and that functions of Th17 responses are contingent on the experimental conditions in which they are generated. © 2013 Martin et al

Practical and Theoretical Considerations in Study Design for Detecting Gene-Gene Interactions Using MDR and GMDR Approaches

Detection of interacting risk factors for complex traits is challenging. The choice of an appropriate method, sample size, and allocation of cases and controls are serious concerns. To provide empirical guidelines for planning such studies and data analyses, we investigated the performance of the multifactor dimensionality reduction (MDR) and generalized MDR (GMDR) methods under various experimental scenarios. We developed the mathematical expectation of accuracy and used it as an indicator parameter to perform a gene-gene interaction study. We then examined the statistical power of GMDR and MDR within the plausible range of accuracy (0.50∼0.65) reported in the literature. The GMDR with covariate adjustment had a power of>80% in a case-control design with a sample size of≥2000, with theoretical accuracy ranging from 0.56 to 0.62. However, when the accuracy was<0.56, a sample size of≥4000 was required to have sufficient power. In our simulations, the GMDR outperformed the MDR under all models with accuracy ranging from 0.56∼0.62 for a sample size of 1000–2000. However, the two methods performed similarly when the accuracy was outside this range or the sample was significantly larger. We conclude that with adjustment of a covariate, GMDR performs better than MDR and a sample size of 1000∼2000 is reasonably large for detecting gene-gene interactions in the range of effect size reported by the current literature; whereas larger sample size is required for more subtle interactions with accuracy<0.56

Identification of N-acyl-l-homoserine lactones produced by non-pigmented Chromobacterium aquaticum CC-SEYA-1T and pigmented Chromobacterium subtsugae PRAA4-1T

Many members of the genus Chromobacterium produce violacein, a characteristic purple pigment which is induced by small diffusible N-acyl homoserine lactones (AHL) quorum-sensing molecules. In this study, the production of AHL of the non-pigmented C. aquaticum CC-SEYA-1T and the pigmented C. subtsugae PRAA4-1T were determined by using a CV026 biosensor assay. The profile of AHL was identified from the extracts of stationary phase cultures using gas chromatography–mass spectroscopy (GC–MS) and thin layer chromatography (TLC). CV026 biosensor assay revealed that both the non-pigmented C. aquaticum CC-SEYA-1T and the pigmented C. subtsugae PRAA4-1T produced AHL molecules, which were identified, respectively, as N-octanoyl homoserine lactone (OHL) [also known as C-8 homoserine lactone (C8-HSL)] and N-hexanoyl homoserine lactone (HHL) [also known as C-6 homoserine lactone (C6-HSL)]. The pigment produced by C. subtsugae PRAA4-1T was similar to that of Chromobacterium violaceum ATCC12472T but no characteristic visible spectral peaks of the pigment were observed in the extracts of C. aquaticum CC-SEYA-1T. In addition, C. aquaticum CC-SEYA-1T and C. subtsugae PRAA4-1T showed hemolytic activities