Combinations of isoform-targeted histone deacetylase inhibitors and bryostatin analogues display remarkable potency to activate latent HIV without global T-cell activation

AbstractCurrent antiretroviral therapy (ART) for HIV/AIDS slows disease progression by reducing viral loads and increasing CD4 counts. Yet ART is not curative due to the persistence of CD4+ T-cell proviral reservoirs that chronically resupply active virus. Elimination of these reservoirs through the administration of synergistic combinations of latency reversing agents (LRAs), such as histone deacetylase (HDAC) inhibitors and protein kinase C (PKC) modulators, provides a promising strategy to reduce if not eradicate the viral reservoir. Here, we demonstrate that largazole and its analogues are isoform-targeted histone deacetylase inhibitors and potent LRAs. Significantly, these isoform-targeted HDAC inhibitors synergize with PKC modulators, namely bryostatin-1 analogues (bryologs). Implementation of this unprecedented LRA combination induces HIV-1 reactivation to unparalleled levels and avoids global T-cell activation within resting CD4+ T-cells.</jats:p

No Evidence of HIV and SIV Sequences in Two Separate Lots of Polio Vaccines Used in the First U.S. Polio Vaccine Campaign

AbstractWe obtained sealed vials of two different polio vaccine lots, expiration date 1955, which were used in the first U.S. polio vaccine campaign. These early lots were pulled from the market because they contained live infectious poliovirus which caused polio in some of the vaccines. Theoretically, these vaccines could have contained other infectious retroviruses, including HIV. No viral sequences were detected using RT-PCR analyses with primers capable of amplifying chimpanzee SIV and HIV-1-related viruses nor with primers for macaque SIV, sooty mangabey SIV, and HIV-2-related viruses. Poliovirus sequences were readily amplified by RT-PCR, suggesting that the technique used would have detected SIV or HIV sequences, if present

Europe's Energy Security: Options and Challenges to Natural Gas Supply Diversification

This report focuses on potential approaches that Europe might employ to diversify its sources of natural gas supply, and Russia's role, as well as identifying some of the issues hindering efforts to develop alternative suppliers of natural gas. The report assesses the potential suppliers of natural gas to Europe and the short- to medium-term hurdles needed to be overcome for those suppliers to be credible, long-term providers of natural gas to Europe. The report looks at North Africa and Central Asia as possible sources of future energy supply

Development and characterization of a stable adhesive bond between a poly(dimethylsiloxane) catheter material and a bacterial biofilm resistant acrylate polymer coating

Catheter associated urinary tract infections (CA-UTIs) are the most common health related infections world wide, contributing significantly to patient morbidity and mortality and increased health care costs. To reduce the incidence of these infections, new materials that resist bacterial biofilm formation are needed. A composite catheter material, consisting of bulk PDMS coated with a novel bacterial biofilm resistant polyacrylate (EGDPEA–co-DEGMA) has been proposed. The coated material shows excellent bacterial resistance when compared to commercial catheter materials but delamination of the coatings under mechanical stress presents a challenge. In this work, the use of oxygen plasma treatment to improve the wettability and reactivity of the PDMS catheter material and improve adhesion with the EGDPEA–co-DEGMA coating has been investigated. Argon Cluster 3D-imaging Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) has been used to probe the buried adhesive interface between the EGDPEA–co-DEGMA coating and the treated PDMS. ToF-SIMS analysis was performed in both dry and frozen-hydrated states and results were compared to mechanical tests. From the ToF-SIMS data we have been able to observe the presence of PDMS, silicates, salt particles, cracks and water at the adhesive interface. In the dry catheters, low molecular weight PDMS oligomers at the interface were associated with poor adhesion. When hydrated, the hydrophilic silicates attracted water to the interface and led to easy delamination of the coating. The best adhesion results, under hydrated conditions, were obtained using a combination of 5 min O2 plasma treatment and silane primers. Cryo-ToF-SIMS analysis of the hydrated catheter material showed that the bond between the primed PDMS catheter and the EGDPEA–co-DEGMA coating was stable in the presence of water. The resulting catheter material was resisted Escherichia coli and Proteus mirabilis biofilm colonization by up to 95 % compared with uncoated PDMS after 10 days of continuous bacterial exposure and had the mechanical properties necessary for use as a urinary catheter

"A place where I can be me": a role for social and leisure provision to support young people with language impairment

The long-term well-being of children with language impairment is an area of increasing interest to families, educators and employers as language impairment is often life-long. Furthermore, language impairment and psychiatric difficulty are known to overlap in both populations originally diagnosed as having language impairment and those receiving mental health services. However, there are currently little data available about the wider quality of life for people with language impairment, especially from the perspective of the young people themselves. There is a dearth of information about community-based activities provided for the support and leisure of this population. The Afasic Youth Project meets once a week and is one of only a handful of such groups across the United Kingdom

U.S. Natural Gas Exports: New Opportunities, Uncertain Outcomes

This report examines what has changed in the U.S. natural gas market and the prospects and implications of the United States becoming a larger net exporter of natural gas. Bills to expedite and expand liquefied natural gas (LNG) exports have been introduced in the 114th Congress, including the LNG Permitting Certainty and Transparency Act (H.R. 351 and S. 33), the American Job Creation and Strategic Alliances LNG Act (H.R. 287), the Crude Oil Export Act (H.R. 156), the Domestic Prosperity and Global Freedom Act (H.R. 89), and the Export American Natural Gas Act of 2015 (H.R. 428)

U.S. Natural Gas Exports: New Opportunities, Uncertain Outcomes

This report examines what has changed in the U.S. natural gas market and the prospects and implications of the United States becoming a significant net natural gas exporter

Effects of microwave sintering in aging resistance of zirconia-based ceramics

[EN] Innovative techniques for materials processing that result in shorter times and lower energy consumption than conventional methods, such as microwave sintering, are currently under investigation in order to obtain fully-consolidated ceramic materials. Microwave sintering has important effects on the resulting properties of zirconia-based ceramics, which, in turn, affectits performance and durability, as in the case of their susceptibility to low temperature hydrothermal degradation (LTD), an ageing phenomenon that deteriorates their mechanical performance. The purpose of this work consists on assessing the effects of microwave sintering on the microstructure and mechanical performance of zirconia composites by comparing itto conventional sintering. Resistance to LTD of 3Y-TZP-only materials has also been evaluated. The results obtained in this work suggest that microwave sintering can reduce processing times and sintering temperatures when compared to conventional sintering while still obtaining dense zirconia-based ceramics and complying with the expected mechanical properties. At the same time, an increase in the resistance to LTD is also observed.This work has been supported by the Spanish Ministry of Economy and Competitiveness MINECO (project MAT2015-67586-C3-R). The authors acknowledge to CAPES Programa Ciencias sem Fronteiras (Brazil) for the concession of a PVE project No. A086/2013. A. Presenda acknowledges the Generalitat Valenciana for his Santiago Grisolia scholarship (GRISOLIA/2013/035). A. Borrell acknowledges the MINECO for her Juan de la Cierva-Incorporacion contract (IJCI-2014-19839).Presenda-Barrera, A.; Salvador Moya, MD.; Penaranda-Foix, FL.; Catalá Civera, JM.; Pallone, E.; Ferreira, J.; Borrell Tomás, MA. (2017). Effects of microwave sintering in aging resistance of zirconia-based ceramics. Chemical Engineering and Processing Process Intensification. 112:404-412. https://doi.org/10.1016/j.cep.2017.03.002S40441211

Central obesity as a precursor to the metabolic syndrome in the AusDiab study and Mauritius

Evidence from epidemiologic studies that central obesity precedes future metabolic change and does not occur concurrently with the appearance of the blood pressure, glucose, and lipid abnormalities that characterize the metabolic syndrome (MetS) has been lacking. Longitudinal surveys were conducted in Mauritius in 1987, 1992, and 1998, and in Australia in 2000 and 2005 (AusDiab). This analysis included men and women (aged 25 years) in three cohorts: AusDiab 2000&ndash;2005 (n = 5,039), Mauritius 1987&ndash;1992 (n = 2,849), and Mauritius 1987&ndash;1998 (n = 1,999). MetS components included waist circumference, systolic blood pressure, fasting and 2-h postload plasma glucose, high-density lipoprotein (HDL) cholesterol, triglycerides, and homeostasis model assessment of insulin sensitivity (HOMA-S) (representing insulin sensitivity). Linear regression was used to determine which baseline components predicted deterioration in other MetS components over 5 years in AusDiab and 5 and 11 years in Mauritius, adjusted for age, sex, and ethnic group. Baseline waist circumference predicted deterioration (P &lt; 0.01) in four of the other six MetS variables tested in AusDiab, five of six in Mauritius 1987&ndash;1992, and four of six in Mauritius 1987&ndash;1998. In contrast, an increase in waist circumference between baseline and follow-up was only predicted by insulin sensitivity (HOMA-S) at baseline, and only in one of the three cohorts. These results suggest that central obesity plays a central role in the development of the MetS and appears to precede the appearance of the other MetS components.<br /