Influenced of Fe buffer thickness on the crystalline quality and the transport properties of Fe/Ba(Fe1-xCox)2As2 bilayers

The implementation of an Fe buffer layer is a promising way to obtain epitaxial growth of Co-doped BaFe2As2 (Ba-122). However, the crystalline quality and the superconducting properties of Co-doped Ba-122 are influenced by the Fe buffer layer thickness, dFe. The well-textured growth of the Fe/Ba-122 bilayer with dFe = 15 nm results in a high Jc of 0.45 MAcm$^{-2}$ at 12 K in self-field, whereas a low Jc value of 61000 Acm$^{-2}$ is recorded for the bilayer with dFe = 4 nm at the corresponding reduced temperature due to the presence of grain boundaries

Low pH immobilizes and kills human leukocytes and prevents transmission of cell-associated HIV in a mouse model

BACKGROUND: Both cell-associated and cell-free HIV virions are present in semen and cervical secretions of HIV-infected individuals. Thus, topical microbicides may need to inactivate both cell-associated and cell-free HIV to prevent sexual transmission of HIV/AIDS. To determine if the mild acidity of the healthy vagina and acid buffering microbicides would prevent transmission by HIV-infected leukocytes, we measured the effect of pH on leukocyte motility, viability and intracellular pH and tested the ability of an acidic buffering microbicide (BufferGel(®)) to prevent the transmission of cell-associated HIV in a HuPBL-SCID mouse model. METHODS: Human lymphocyte, monocyte, and macrophage motilities were measured as a function of time and pH using various acidifying agents. Lymphocyte and macrophage motilities were measured using video microscopy. Monocyte motility was measured using video microscopy and chemotactic chambers. Peripheral blood mononuclear cell (PBMC) viability and intracellular pH were determined as a function of time and pH using fluorescent dyes. HuPBL-SCID mice were pretreated with BufferGel, saline, or a control gel and challenged with HIV-1-infected human PBMCs. RESULTS: Progressive motility was completely abolished in all cell types between pH 5.5 and 6.0. Concomitantly, at and below pH 5.5, the intracellular pH of PBMCs dropped precipitously to match the extracellular medium and did not recover. After acidification with hydrochloric acid to pH 4.5 for 60 min, although completely immotile, 58% of PBMCs excluded ethidium homodimer-1 (dead-cell dye). In contrast, when acidified to this pH with BufferGel, a microbicide designed to maintain vaginal acidity in the presence of semen, only 4% excluded dye at 10 min and none excluded dye after 30 min. BufferGel significantly reduced transmission of HIV-1 in HuPBL-SCID mice (1 of 12 infected) compared to saline (12 of 12 infected) and a control gel (5 of 7 infected). CONCLUSION: These results suggest that physiologic or microbicide-induced acid immobilization and killing of infected white blood cells may be effective in preventing sexual transmission of cell-associated HIV

Groundwater resources in the Indo-Gangetic Basin : resilience to climate change and abstraction

Groundwater within the Indo‐Gangetic Basin (IGB) alluvial aquifer system forms one of the world’s most important and heavily exploited reservoirs of freshwater. In this study we have examined the groundwater system through the lens of its resilience to change – both from the impact of climate change and increases in abstraction. This has led to the development of a series of new maps for the IGB aquifer, building on existing datasets held in Pakistan, India, Nepal and Bangladesh, a review of approximately 500 reports and papers, and three targeted field studies on under‐researched topics within the region. The major findings of the study are described below. The IGB groundwater system 1. The IGB alluvial aquifer system comprises a large volume of heterogeneous unconsolidated sediment in a complex environmental setting. Annual rainfall varies from 2000mm in the Bengal basin, and the system is dissected by the major river systems of the Indus, Ganges and Brahmaputra. The groundwater system has been modified by the introduction of large scale canal irrigation schemes using water from the Indus and Ganges since the 19th and early 20th centuries. 2. High yielding tubewells can be sustained in most parts of the alluvial aquifer system; permeability is often in the range of 10 – 60 m/d and specific yield (the drainable porosity) varies from 5 – 20%, making it highly productive. 3. High salinity and elevated arsenic concentrations exist in parts of the basin limiting the usefulness of the groundwater resource. Saline water predominates in the Lower Indus, and near to the coast in the Bengal Delta, and is also a major concern in the Middle Ganges and Upper Ganges (covering much of the Punjab Region in Pakistan, southern Punjab, Haryana and parts of Uttar Pradesh in India). Arsenic severely impacts the development of shallow groundwater in the fluvial influenced deltaic area of the Bengal Basin. 4. Recharge to the IGB aquifer system is substantial and dynamic, controlled by monsoonal rainfall, leakage from canals, river infiltration and irrigation returns. Recharge from rainfall can occur even with low annual rainfall (350 mm) and appears to dominate where rainfall is higher (> 750 mm). Canal leakage is also highly significant and constitutes the largest proportion of groundwater recharge in the drier parts of the aquifer, partially mitigating the effects of abstraction on groundwater storage. 5. Deep groundwater (>150 m) in the Bengal basin has strategic value for water supply, health and economic development. Excessive abstraction poses a greater threat to the quality of this deep groundwater than climate change. Heavy pumping may induce the downward migration of arsenic in parts of Bangladesh, and of saline water in coastal regions, but field evidence and modelling both suggest that deep groundwater abstraction for public water supply in southern Bangladesh is in general secure against widespread ingress of arsenic and saline water for at least 100 years

IgG in cervicovaginal mucus traps HSV and prevents vaginal Herpes infections

IgG is the predominant immunoglobulin in cervicovaginal mucus (CVM), yet how IgG in mucus can protect against infections is not fully understood. IgG diffuses rapidly through cervical mucus, slowed only slightly by transient adhesive interactions with mucins. We hypothesize this almost unhindered diffusion allows IgG to accumulate rapidly on pathogen surfaces, and the resulting IgG array forms multiple weak adhesive crosslinks to mucus gel that effectively trap (immobilize) pathogens, preventing them from initiating infections. Here, we report herpes simplex virus serotype 1 (HSV-1) readily penetrated fresh, pH-neutralized ex vivo samples of CVM with low or no detectable levels of anti-HSV-1 IgG, but was trapped in samples with even modest levels of anti-HSV-1 IgG. In samples with little or no endogenous anti-HSV-1 IgG, addition of exogenous anti-HSV-1 IgG, affinity purified from intravenous immunoglobulin, trapped virions at concentrations below those needed for neutralization and with similar potency as endogenous IgG. Deglycosylating purified anti-HSV-1 IgG, or removing its Fc component, markedly reduced trapping potency. Finally, a non-neutralizing IgG against HSV-gG significantly protected mice against vaginal infection, and removing vaginal mucus by gentle lavage abolished protection. These observations suggest IgG-Fc has a glycan dependent “muco-trapping” effector function that may provide exceptionally potent protection at mucosal surfaces

The Diaphragm and Lubricant Gel for Prevention of Cervical Sexually Transmitted Infections: Results of a Randomized Controlled Trial

BACKGROUND: We evaluated the effectiveness of the Ortho All-Flex Diaphragm, lubricant gel (Replens) and condoms compared to condoms alone on the incidence of chlamydial and gonococcal infections in an open-label randomized controlled trial among women at risk of HIV/STI infections. METHODS: We randomized 5045 sexually-active women at three sites in Southern Africa. Participants who tested positive for curable STIs were treated prior to enrollment as per local guidelines. Women were followed quarterly and tested for Chlamydia trachomatis (CT) or Neisseria gonorrhoeae (GC) infection by nucleic-acid amplification testing (Roche Amplicor) using first-catch urine specimens. STIs detected at follow-up visits were treated. We compared the incidence of first infection after randomization between study arms in both intent-to-treat (ITT) and per-protocol populations. FINDINGS: Baseline demographic, behavioral and clinical characteristics were balanced across study arms. Nearly 80% of participants were under 35 years of age. Median follow-up time was 21 months and the retention rate was over 93%. There were 471 first chlamydia infections, 247 in the intervention arm and 224 in the control arm with an overall incidence of 6.2/100 woman-years (wy) (relative hazard (RH) 1.11, 95% Confidence Interval (CI): 0.93-1.33; p = 0.25) and 192 first gonococcal infections, 95 in the intervention arm and 97 in the control arm with an overall incidence of 2.4/100wy (RH 0.98, 95%CI: 0.74-1.30; p = 0.90). Per protocol results indicated that when diaphragm adherence was defined as "always use" since the last visit, there was a significant reduction in the incidence of GC infection among women randomized to the intervention arm (RH 0.61, 95%CI: 0.41-0.91, P = 0.02). INTERPRETATION: There was no difference by study arm in the rate of acquisition of CT or GC. However, our per-protocol results suggest that consistent use of the diaphragm may reduce acquisition of GC. TRIAL REGISTRATION: ClinicalTrials.gov NCT00121459

Resolution of hyposmotic stress in isolated mouse ventricular myocytes causes sealing of t‐tubules

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98789/1/expphysiol.2013.072470.pd

Evaluation of Analytical Methods to Study Aquifer Properties with Pumping Tests in Coastal Aquifers with Numerical Modelling (Motril-Salobreña Aquifer)

Two pumping tests were performed in the unconfined Motril-Salobreña detrital aquifer in a 250 m-deep well 300 m from the coastline containing both freshwater and saltwater. It is an artesian well as it is in the discharge zone of this coastal aquifer. The two observation wells where the drawdowns are measured record the influence of tidal fluctuations, and the well lithological columns reveal high vertical heterogeneity in the aquifer. The Theis and Cooper-Jacob approaches give average transmissivity (T) and storage coefficient (S) values of 1460 m2 /d and 0.027, respectively. Other analytical solutions, modified to be more accurate in the boundary conditions found in coastal aquifers, provide similar T values to those found with the Theis and Cooper-Jacob methods, but give very different S values or could not estimate them. Numerical modelling in a synthetic model was applied to analyse the sensitivity of the Theis and Cooper-Jacob approaches to the usual boundary conditions in coastal aquifers. The T and S values calculated from the numerical modelling drawdowns indicate that the regional flow, variable pumping flows, and tidal effect produce an error of under 10 % compared to results obtained with classic methods. Fluids of different density (freshwater and saltwater) cause an error of 20 % in estimating T and of over 100 % in calculating S. The factor most affecting T and S results in the pumping test interpretation is vertical heterogeneity in sediments, which can produce errors of over 100 % in both parameters.This research has been financed by Project CGL2012-32892 (Ministerio de Economía y Competitividad of Spain) and by the Research Group Sedimentary Geology and Groundwater (RNM-369) of the Junta de Andalucía

Microbicide excipients can greatly increase susceptibility to genital herpes transmission in the mouse

<p>Abstract</p> <p>Background</p> <p>Several active ingredients proposed as vaginal microbicides have been shown paradoxically to <it>increase </it>susceptibility to infection in mouse genital herpes (HSV-2) vaginal susceptibility models and in clinical trials. In addition, "inactive ingredients" (or excipients) used in topical products to formulate and deliver the active ingredient might also cause epithelial toxicities that increase viral susceptibility. However, excipients have not previously been tested in susceptibility models.</p> <p>Methods</p> <p>Excipients commonly used in topical products were formulated in a non-toxic vehicle (the "HEC universal placebo"), or other formulations as specified. Twelve hours after exposure to the excipient or a control treatment, mice were challenged with a vaginal dose of HSV-2, and three days later were assessed for infection by vaginal lavage culture to assess susceptibility.</p> <p>Results</p> <p>The following excipients markedly increased susceptibility to HSV-2 after a single exposure: 5% glycerol monolaurate (GML) formulated in K-Y^®Warming Jelly, 5% GML as a colloidal suspension in phosphate buffered saline, K-Y Warming Jelly alone, and both of its humectant/solvent ingredients (neat propylene glycol and neat PEG-8). For excipients formulated in the HEC vehicle, 30% glycerin significantly increased susceptibility, and a trend toward increased HSV-2 susceptibility was observed after 10% glycerin, and 0.1% disodium EDTA, but not after 0.0186% disodium EDTA. The following excipients did not increase susceptibility: 10% propylene glycol, 0.18%, methylparaben plus 0.02% propylparaben, and 1% benzyl alcohol.</p> <p>Conclusions</p> <p>As reported with other surfactants, the surfactant/emulsifier GML markedly increased susceptibility to HSV-2. Glycerin at 30% significantly increased susceptibility, and, undiluted propylene glycol and PEG-8 greatly increased susceptibility.</p