In situ polymerisation of isoeugenol as a green consolidation method for waterlogged archaeological wood

Waterlogged archaeological wood is often in need of consolidation prior to drying to prevent shrinkage and cracking of the object. There is a need for new greener materials (than for example polyethylene glycol) and methods for consolidation to be developed. The use of wood-based components could provide good interaction between the consolidant and the remaining wood structure and would also support a shift away from fossil fuel-based materials to those with more sustainable sources. Based on this, lignin-like structures have been investigated for their ability to consolidate waterlogged archaeological wood. The in situ formation of a lignin-like material has been carried out using isoeugenol polymerised by horse radish peroxidase in aqueous solution. The formation of the oligomeric/polymeric materials within the wood following this reaction has been determined by Attenuated Total Reflectance Fourier Transform Infra Red (ATR-FTIR) spectroscopy. The oligomers remaining in solution have been characterised by ATR-FTIR and nuclear magnetic resonance (NMR) spectroscopy as well as analytical ultracentrifugation, showing that they have a weight average Mw of 0.4–0.9 kDa and a lignin-like structure rich in the β-5′ moiety. Therefore, this approach is proposed as a basis to further develop a green consolidation method for waterlogged archaeological wood

Thermodynamic analysis of humidification dehumidification desalination cycles

Humidification–dehumidification desalination (HDH) is a promising technology for small-scale water production applications. There are several embodiments of this technology which have been investigated by researchers around the world. However, from a previous literature [1], we have found that no study carried out a detailed thermodynamic analysis in order to improve and/ or optimize the system performance. In this paper, we analyze the thermodynamic performance of various HDH cycles by way of a theoretical cycle analysis. In addition, we propose novel high performance variations on those cycles. These high-performance cycles include multi-extraction, multi-pressure and thermal vapor compression cycles. It is predicted that the systems based on these novel cycles will have gained output ratio in excess of 5 and will outperform existing HDH systems.King Fahd University of Petroleum and MineralsCenter for Clean Water and Clean Energy at MIT and KFUP

An Observational Cohort Comparison of Facilitators of Retention in Care and Adherence to Anti-Eetroviral Therapy at an HIV Treatment Center in Kenya

BACKGROUND: Most HIV treatment programs in resource-limited settings utilize multiple facilitators of adherence and retention in care but there is little data on the efficacy of these methods. We performed an observational cohort analysis of a treatment program in Kenya to assess which program components promote adherence and retention in HIV care in East Africa. METHODS: Patients initiating ART at A.I.C. Kijabe Hospital were prospectively enrolled in an observational study. Kijabe has an intensive program to promote adherence and retention in care during the first 6 months of ART that incorporates the following facilitators: home visits by community health workers, community based support groups, pharmacy counseling, and unannounced pill counts by clinicians. The primary endpoint was time to treatment failure, defined as a detectable HIV-1 viral load; discontinuation of ART; death; or loss to follow-up. Time to treatment failure for each facilitator was calculated using Kaplan-Meier analysis. The relative effects of the facilitators were determined by the Cox Proportional Hazards Model. RESULTS: 301 patients were enrolled. Time to treatment failure was longer in patients participating in support groups (448 days vs. 337 days, P<0.001), pharmacy counseling (480 days vs. 386 days, P = 0.002), pill counts (482 days vs. 189 days, P<0.001) and home visits (485 days vs. 426 days, P = 0.024). Better adherence was seen with support groups (89% vs. 82%, P = 0.05) and pill counts (89% vs. 75%, P = 0.02). Multivariate analysis using the Cox Model found significant reductions in risk of treatment failure associated with pill counts (HR = 0.19, P<0.001) and support groups (HR = 0.43, P = 0.003). CONCLUSION: Unannounced pill counts by the clinician and community based support groups were associated with better long term treatment success and with better adherence

Ubiquitylation in ERAD: Reversing to Go Forward?

Proteins are co-translationally inserted into the endoplasmic reticulum (ER) where they undergo maturation. Homeostasis in the ER requires a highly sensitive and selective means of quality control. This occurs through ER-associated degradation (ERAD).This complex ubiquitin-proteasome–mediated process involves ubiquitin conjugating enzymes (E2) and ubiquitin ligases (E3),lumenal and cytosolic chaperones, and other proteins, including the AAA ATPase p97 (VCP; Cdc48 in yeast). Probing of processes involving proteasomal degradation has generally depended on proteasome inhibitors or knockdown of specific E2s or E3s. In this issue of PLoS Biology, Ernst et al. demonstrate the utility of expressing the catalytic domain of a viral deubiquitylating enzyme to probe the ubiquitin system. Convincing evidence is provided that deubiquitylation is integral to dislocation of ERAD substrates from the ER membrane. The implications of this work for understanding ERAD and the potential of expressing deubiquitylating enzyme domains for studying ubiquitin-mediated processes are discussed

Differential Association between HERG and KCNE1 or KCNE2

The small proteins encoded by KCNE1 and KCNE2 have both been proposed as accessory subunits for the HERG channel. Here we report our investigation into the cell biology of the KCNE-HERG interaction. In a co-expression system, KCNE1 was more readily co-precipitated with co-expressed HERG than was KCNE2. When forward protein trafficking was prevented (either by Brefeldin A or engineering an ER-retention/retrieval signal onto KCNE cDNA) the intracellular abundance of KCNE2 and its association with HERG markedly increased relative to KCNE1. HERG co-localized more completely with KCNE1 than with KCNE2 in all the membrane-processing compartments of the cell (ER, Golgi and plasma membrane). By surface labeling and confocal immunofluorescence, KCNE2 appeared more abundant at the cell surface compared to KCNE1, which exhibited greater co-localization with the ER-marker calnexin. Examination of the extracellular culture media showed that a significant amount of KCNE2 was extracellular (both soluble and membrane-vesicle-associated). Taken together, these results suggest that during biogenesis of channels HERG is more likely to assemble with KCNE1 than KCNE2 due to distinctly different trafficking rates and retention in the cell rather than differences in relative affinity. The final channel subunit constitution, in vivo, is likely to be determined by a combination of relative cell-to-cell expression rates and differential protein processing and trafficking

Abortive Autophagy Induces Endoplasmic Reticulum Stress and Cell Death in Cancer Cells

Autophagic cell death or abortive autophagy has been proposed to eliminate damaged as well as cancer cells, but there remains a critical gap in our knowledge in how this process is regulated. The goal of this study was to identify modulators of the autophagic cell death pathway and elucidate their effects on cellular signaling and function. The result of our siRNA library screenings show that an intact coatomer complex I (COPI) is obligatory for productive autophagy. Depletion of COPI complex members decreased cell survival and impaired productive autophagy which preceded endoplasmic reticulum stress. Further, abortive autophagy provoked by COPI depletion significantly altered growth factor signaling in multiple cancer cell lines. Finally, we show that COPI complex members are overexpressed in an array of cancer cell lines and several types of cancer tissues as compared to normal cell lines or tissues. In cancer tissues, overexpression of COPI members is associated with poor prognosis. Our results demonstrate that the coatomer complex is essential for productive autophagy and cellular survival, and thus inhibition of COPI members may promote cell death of cancer cells when apoptosis is compromised

Windborne long-distance migration of malaria mosquitoes in the Sahel

Over the past two decades efforts to control malaria have halved the number of cases globally, yet burdens remain high in much of Africa and the elimination of malaria has not been achieved even in areas where extreme reductions have been sustained, such as South Africa1,2. Studies seeking to understand the paradoxical persistence of malaria in areas in which surface water is absent for 3–8 months of the year have suggested that some species of Anopheles mosquito use long-distance migration3. Here we confirm this hypothesis through aerial sampling of mosquitoes at 40–290 m above ground level and provide—to our knowledge—the first evidence of windborne migration of African malaria vectors, and consequently of the pathogens that they transmit. Ten species, including the primary malaria vector Anopheles coluzzii, were identified among 235 anopheline mosquitoes that were captured during 617 nocturnal aerial collections in the Sahel of Mali. Notably, females accounted for more than 80% of all of the mosquitoes that we collected. Of these, 90% had taken a blood meal before their migration, which implies that pathogens are probably transported over long distances by migrating females. The likelihood of capturing Anopheles species increased with altitude (the height of the sampling panel above ground level) and during the wet seasons, but variation between years and localities was minimal. Simulated trajectories of mosquito flights indicated that there would be mean nightly displacements of up to 300 km for 9-h flight durations. Annually, the estimated numbers of mosquitoes at altitude that cross a 100-km line perpendicular to the prevailing wind direction included 81,000 Anopheles gambiae sensu stricto, 6 million A. coluzzii and 44 million Anopheles squamosus. These results provide compelling evidence that millions of malaria vectors that have previously fed on blood frequently migrate over hundreds of kilometres, and thus almost certainly spread malaria over these distances. The successful elimination of malaria may therefore depend on whether the sources of migrant vectors can be identified and controlled

Protocol for north of England and Scotland study of tonsillectomy and adeno-tonsillectomy in children (NESSTAC). A pragmatic randomised controlled trial comparing surgical intervention with conventional medical treatment in children with recurrent sore throats

BACKGROUND: Uncertainties surrounding the effectiveness and cost-effectiveness of childhood tonsillectomy for recurrent sore throat led the NHS Health Technology Assessment Programme to commission this research to evaluate the effectiveness and cost-effectiveness of tonsillectomy and adeno-tonsillectomy in comparison with standard non-surgical management in children aged under 16 with recurrent throat infections. The aim is to evaluate if tonsillectomy and adeno-tonsillectomy reduces the number of episodes of sore throats among children to a clinically significant extent. METHODS/DESIGN: A simple prospective pragmatic randomised controlled trial with economic analysis and prospective cohort study of non-trial participants comparing surgical intervention with conventional medical treatment. The treatment arm will receive tonsillectomy and adeno-tonsillectomy while in the control arm non-surgical conventional medical treatment only will be used. The primary outcome measure will be reported number of episodes of sore throat over two years with secondary outcomes measures of reported number of episodes of sore throat, otitis media and upper respiratory tract infection which invoke a GP consultation; reported number of symptom-free days; reported severity of sore throats and surgical and anaesthetic morbidity. The study will take place in five hospitals in the UK. The trial population will be 406 children aged 4–15 on their last birthday with recurrent sore throat referred by primary care to the 5 otolaryngology departments. The duration of the study is seven years (July 2001- July 2008). DISCUSSION: As with all pragmatic randomised controlled trials it is impossible to control the external environment in which the research is taking place. Since this trial began a number of factors have arisen which could affect the outcome including; a reduction in the incidence of respiratory tract infections, marked socio-economic differences in consultation rates, the results from the National Prospective Tonsillectomy Audit and the Government's waiting list initiatives