Design and Application of Membrane Nanodiscs for Biophysical Studies of Influenza A Proteins

Membrane proteins play a range of important roles in biological systems, yet they are underrepresented in the data base of high-resolution structures of all proteins. There is intense interest in developing new methodologies for studying membrane proteins. An essential step to membrane protein method development is devising reliable membrane mimics in which to embed membrane proteins. The goal of this thesis was to develop and apply nanodisc membrane mimics to the study of an influenza A membrane protein called M2. Nanodiscs provide a lipid bilayer environment with access to both sides of the bilayer and are smaller than commonly used liposome model membranes whose size provides challenges for some biophysical methods. This thesis shows how the sample composition of M2 containing nanodiscs was optimized. Dynamic light scattering and size exclusion chromatography was used to characterize M2-nanodiscs. Electrophysiological and budding assays showed that M2 in liposomes were in a functionally relevant conformation. Extensive previous work has been done on studying M2 protein in spherical liposome using site-directed spin label electron paramagnetic resonance (SDSL-EPR). We carried out SDSL-EPR studies of M2-nanodiscs and compared them to published work on M2 in liposomes. Our EPR data is consistent with M2 protein in nanodiscs having a similar conformation, mobility and membrane topology as that seen in previously published M2-liposome work. Furthermore, we probed the ability of nanodiscs to allow for conformational exchange by comparing the impact of drug binding on M2-nanodiscs with M2-liposomes

Gender and Rural Poverty in Myanmar: A Micro Level Study in the Dry Zone

The study investigates the poverty incidence, access to resources, and the factors influencing income of both male and female-headed households in the dry zone of Myanmar. A household survey was conducted in six villages with a sample of 220 households in 2003. The Cost of Basic Needs (CBN) method was applied in constructing the absolute poverty line. By applying the absolute poverty line of 252 Kyats per person per day, the female-headed households are more likely to be poor than the male-headed households with or without household size adjustment. Results of the regression analysis revealed that average per capita income of rural households is significantly influenced by 8 independent variables. They are: gender of household head, household size, land holding size, degraded land size, cattle heads, labour force, sources of income, and irrigation water. Moreover, the separate regression analyses were run for male and female-headed households. In addition to the some common significant variables (land, labour, cattle, degraded land, and household size), female-headed households’ income is significantly influenced by training attendance and schooling years of household head. In male-headed households, age of household head, number of income sources and irrigation water are highly linked with the average per capita income. The gender focus rural development strategies should be adopted for promoting the welfare status of both male and femaleheaded households in the dry zone

Efficacy of antiplatelet therapy in secondary prevention following lacunar stroke:Pooled analysis of randomized trials

Background and Purpose: Lacunar stroke accounts for ≈25% of ischemic stroke, but optimal antiplatelet regimen to prevent stroke recurrence remains unclear. We aimed to evaluate the efficacy of antiplatelet agents in secondary stroke prevention after a lacunar stroke. Methods: We searched MEDLINE, Embase, and the Cochrane library for randomized controlled trials that reported risk of recurrent stroke or death with antiplatelet therapy in patients with lacunar stroke. We used random effects meta-analysis and evaluated heterogeneity with I2. Results: We included 17 trials with 42 234 participants (mean age 64.4 years, 65% male) and follow up ranging from 4 weeks to 3.5 years. Compared with placebo, any single antiplatelet agent was associated with a significant reduction in recurrence of any stroke (risk ratio [RR] 0.77, 0.62–0.97, 2 studies) and ischemic stroke (RR 0.48, 0.30–0.78, 2 studies), but not for the composite outcome of any stroke, myocardial infarction, or death (RR 0.89, 0.75–1.05, 2 studies). When other antiplatelet agents (ticlodipine, cilostazol, and dipyridamole) were compared with aspirin, there was no consistent reduction in stroke recurrence (RR 0.91, 0.75–1.10, 3 studies). Dual antiplatelet therapy did not confer clear benefit over monotherapy (any stroke RR 0.83, 0.68–1.00, 3 studies; ischemic stroke RR 0.80, 0.62–1.02, 3 studies; composite outcome RR 0.90, 0.80–1.02, 3 studies). Conclusions: Our results suggest that any of the single antiplatelet agents compared with placebo in the included trials is adequate for secondary stroke prevention after lacunar stroke. Dual antiplatelet therapy should not be used for long-term stroke prevention in this stroke subtype

Efficacy and effectiveness of dihydroartemisinin-piperaquine versus artesunate-mefloquine in falciparum malaria: an open-label randomised comparison.

BACKGROUND: Artemisinin-based combinations are judged the best treatments for multidrug-resistant Plasmodium falciparum malaria. Artesunate-mefloquine is widely recommended in southeast Asia, but its high cost and tolerability profile remain obstacles to widespread deployment. To assess whether dihydroartemisinin-piperaquine is a suitable alternative to artesunate-mefloquine, we compared the safety, tolerability, efficacy, and effectiveness of the two regimens for the treatment of uncomplicated falciparum in western Myanmar (Burma). METHODS: We did an open randomised comparison of 3-day regimens of artesunate-mefloquine (12/25 mg/kg) versus dihydroartemisinin-piperaquine (6.3/50 mg/kg) for the treatment of children aged 1 year or older and in adults with uncomplicated falciparum malaria in Rakhine State, western Myanmar. Within each group, patients were randomly assigned supervised or non-supervised treatment. The primary endpoint was the PCR-confirmed parasitological failure rate by day 42. Failure rates at day 42 were estimated by Kaplan-Meier survival analysis. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN27914471. FINDINGS: Of 652 patients enrolled, 327 were assigned dihydroartemisinin-piperaquine (156 supervised and 171 not supervised), and 325 artesunate-mefloquine (162 and 163, respectively). 16 patients were lost to follow-up, and one patient died 22 days after receiving dihydroartemisinin-piperaquine. Recrudescent parasitaemias were confirmed in only two patients; the day 42 failure rate was 0.6% (95% CI 0.2-2.5) for dihydroartemisinin-piperaquine and 0 (0-1.2) for artesunate-mefloquine. Whole-blood piperaquine concentrations at day 7 were similar for patients with observed and non-observed dihydroartemisinin-piperaquine treatment. Gametocytaemia developed more frequently in patients who had received dihydroartemisinin-piperaquine than in those on artesunate-mefloquine: day 7, 18 (10%) of 188 versus five (2%) of 218; relative risk 4.2 (1.6-11.0) p=0.011. INTERPRETATION: Dihydroartemisinin-piperaquine is a highly efficacious and inexpensive treatment of multidrug-resistant falciparum malaria and is well tolerated by all age groups. The effectiveness of the unsupervised treatment, as in the usual context of use, equalled its supervised efficacy, indicating good adherence without supervision. Dihydroartemisinin-piperaquine is a good alternative to artesunate-mefloquine

Microstructured porous ZnO thin film for increased light scattering and improved efficiency in inverted organic photovoltaics

Cataloged from PDF version of article.Microstructured porous zinc oxide (ZnO) thin film was developed and demonstrated as an electron selective layer for enhancing light scattering and efficiency in inverted organic photovoltaics. High degree of porosity was induced and controlled in the ZnO layer by incorporation of polyethylene glycol (PEG) organic template. Scanning electron microscopy, contact angle and absorption measurements prove that the ZnO: PEG ratio of 4:1 is optimal for the best performance of porous ZnO. Ensuring sufficient pore-filling, the use of porous ZnO leads to a marked improvement in device performance compared to non-porous ZnO, with 35% increase in current density and 30% increase in efficiency. Haze factor studies indicate that the performance improvement can be primarily attributed to the improved light scattering enabled by such a highly porous structure. (C) 2014 Optical Society of Americ

Metabolic pathways variability and sequence/networks comparisons

BACKGROUND: In this work a simple method for the computation of relative similarities between homologous metabolic network modules is presented. The method is similar to classical sequence alignment and allows for the generation of phenotypic trees amenable to be compared with correspondent sequence based trees. The procedure can be applied to both single metabolic modules and whole metabolic network data without the need of any specific assumption. RESULTS: We demonstrate both the ability of the proposed method to build reliable biological classification of a set of microrganisms and the strong correlation between the metabolic network wiringand involved enzymes sequence space. CONCLUSION: The method represents a valuable tool for the investigation of genotype/phenotype correlationsallowing for a direct comparison of different species as for their metabolic machinery. In addition the detection of enzymes whose sequence space is maximally correlated with the metabolicnetwork space gives an indication of the most crucial (on an evolutionary viewpoint) steps of the metabolic process

Bariatric surgery and its impact on cardiovascular disease and mortality : A systematic review and meta-analysis

Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.Peer reviewedPostprin

Risk prediction models for mortality in community-acquired pneumonia : a systematic review

Peer reviewedPublisher PD

Can Board Gender Diversity Promote Corporate Social Performance?

Purpose: This paper examines if gender diversity on corporate boards promotes corporate social performance (CSP) across industries and across countries. Design/methodology/approach: Fixed-effect panel models are estimated using Europe-wide data from 2002 through 2013. Instrumental variable estimation and propensity score matching are also used to control for potential endogeneity. Findings: Board gender diversity (BGD) improves environmental and social performance and consequently the CSP. Although the positive effect of gender diversity is prevalent across industries, the effect is more pronounced for firms in emerging markets. Practical implications: The findings suggest that gender law that fosters gender diversity can promote CSP in firms, and the benefit can be enjoyed with just an introduction of one female director to the board. Promotion of gender diversity in Europe is most beneficial in emerging markets. Originality/value: The results provide new insights to the literature, as we find that a critical mass of female directors on boards is not required to promote CSP. The research also highlights that BGD enhances CSP irrespective of the industry, and the effect on CSP is more pronounced in emerging markets where regulations regarding CSR are not so clear-cut

Computational modeling of blast-induced traumatic brain injury

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 2010.Cataloged from PDF version of thesis.Includes bibliographical references (p. 105-113).Blast-induced TBI has gained prominence in recent years due to the conflicts in Iraq and Afghanistan, yet little is known about the mechanical effects of blasts on the human head; no injury thresholds have been established for blast effects on the head, and even direct transmission of the shock wave to the intracranial cavity is disputed. Still less is known about how personal protective equipment such as the Advanced Combat Helmet (ACH) affect the brain's response to blasts. The goal of this thesis is to investigate the mechanical response of the human brain to blasts and to study the effect of the ACH on the blast response of the head. To that end, a biofidelic computational model of the human head consisting of 11 distinct structures was developed from high-resolution medical imaging data. The model, known as the DVBIC/MIT Full Head Model (FHM), was subjected to blasts with incident overpressures of 6 atm and 30 atm and to a 5 m/s lateral impact. Results from the simulations demonstrate that blasts can penetrate the intracranial cavity and generate intracranial pressures that exceed the pressures produced during impact; the results suggest that blasts can plausibly directly cause traumatic brain injury. Subsequent investigation of the effect of the ACH on the blast response of the head found that the ACH provided minimal mitigation of blast effects. Results from the simulations conducted with the FHM extended to include the ACH suggest that the ACH can slightly reduce peak pressure magnitudes and delay peak pressure arrival times, but the benefits are minimal because the ACH does not protect the main pathways of load transmission from the blast to brain tissue. A more effective blast mitigation strategy might involve altering the helmet design to more completely surround the head in order to protect it from direct exposure to blast waves.by Michelle K. Nyein.S.M