Genetic variability of hepatitis C virus before and after combined therapy of interferon plus ribavirin

We present an analysis of the selective forces acting on two hepatitis C virus genome regions previously postulated to be involved in the viral response to combined antiviral therapy. One includes the three hypervariable regions in the envelope E2 glycoprotein, and the other encompasses the PKR binding domain and the V3 domain in the NS5A region. We used a cohort of 22 non-responder patients to combined therapy (interferon alpha-2a plus ribavirin) for which samples were obtained before initiation of therapy and after 6 or/and 12 months of treatment. A range of 25-100 clones per patient, genome region and time sample were sequenced. These were used to detect general patterns of adaptation, to identify particular adaptation mechanisms and to analyze the patterns of evolutionary change in both genome regions. These analyses failed to detect a common adaptive mechanism for the lack of response to antiviral treatment in these patients. On the contrary, a wide range of situations were observed, from patients showing no positively selected sites to others with many, and with completely different topologies in the reconstructed phylogenetic trees. Altogether, these results suggest that viral strategies to evade selection pressure from the immune system and antiviral therapies do not result from a single mechanism and they are likely based on a range of different alternatives, in which several different changes, or their combination, along the HCV genome confer viruses the ability to overcome strong selective [email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected]

Eigenvalue Problem in Two Dimension for An Irregular Boundary

An analytical perturbative method is suggested for solving the Helmholtz equation (\bigtriangledown^{2} + k^{2}){\psi} = 0 in two dimensions where {\psi} vanishes on an irregular closed curve. We can thus find the energy levels of a quantum mechanical particle confined in an infinitely deep potential well in two dimensions having an irregular boundary or the vibration frequencies of a membrane whose edge is an irregular closed curve. The method is tested by calculating the energy levels for an elliptical and a supercircular boundary and comparing with the results obtained numerically. Further, the phenomenon of level crossing due to shape variation is also discussed.Comment: 16 pages, 4 figures, v2 matches the journal versio

A Meta-Analysis of the Existing Knowledge of Immunoreactivity against Hepatitis C Virus (HCV)

Approximately 3% of the world population is infected by HCV, which represents a major global health challenge. Almost 400 different scientific reports present immunological data related to T cell and antibody epitopes derived from HCV literature. Analysis of all HCV-related epitope hosted in the Immune Epitope Database (IEDB), a repository of freely accessible immune epitope data, revealed more than 1500 and 1900 distinct T cell and antibody epitopes, respectively. The inventory of all data revealed specific trends in terms of the host and the HCV genotypes from which sequences were derived. Upon further analysis we found that this large number of epitopes reflects overlapping structures, and homologous sequences derived from different HCV isolates. To access and visualize this information we developed a novel strategy that assembles large sets of epitope data, maps them onto reference genomes and displays the frequency of positive responses. Compilation of the HCV immune reactivity from hundreds of different studies, revealed a complex and thorough picture of HCV immune epitope data to date. The results pinpoint areas of more intense reactivity or research activities at the level of antibody, CD4 and CD8 responses for each of the individual HCV proteins. In general, the areas targeted by the different effector immune functions were distinct and antibody reactivity was positively correlated with hydrophilicity, while T cell reactivity correlated with hydrophobicity. At the sequence level, epitopes frequently recognized by both T cell and B cell correlated with low variability, and our analysis thus highlighted areas of potential interest for practical applications. The human reactivity was further analyzed to pinpoint differential patterns of reactivity associated with acute versus chronic infection, to reveal the apparent impact of glycosylation on T cell, but not antibody responses, and to highlight a paucity of studies involved antibody epitopes associated with virus neutralization

Effect of Supplementation with Zinc and Other Micronutrients on Malaria in Tanzanian Children: A Randomised Trial

Hans Verhoef and colleagues report findings from a randomized trial conducted among Tanzanian children at high risk for malaria. Children in the trial received either daily oral supplementation with either zinc alone, multi-nutrients without zinc, multi-nutrients with zinc, or placebo. The investigators did not find evidence from this study that zinc or multi-nutrients protected against malaria episodes

INTER-ACT: prevention of pregnancy complications through an e-health driven interpregnancy lifestyle intervention – study protocol of a multicentre randomised controlled trial

Abstract Background Excessive maternal pre-pregnancy and gestational weight gain are related to pregnancy- and birth outcomes. The interpregnancy time window offers a unique opportunity to intervene in order to acquire a healthy lifestyle before the start of a new pregnancy. Methods INTER-ACT is an e-health driven multicentre randomised controlled intervention trial targeting women at high risk of pregnancy- and birth related complications. Eligible women are recruited for the study at day 2 or 3 postpartum. At week 6 postpartum, participants are randomised into the intervention or control arm of the study. The intervention focuses on weight, diet, physical activity and mental well-being, and comprises face-to-face coaching, in which behavioural change techniques are central, and use of a mobile application, which is Bluetooth-connected to a weighing scale and activity tracker. The intervention is rolled out postpartum (4 coaching sessions between week 6 and month 6) and in a new pregnancy (3 coaching sessions, one in each trimester of pregnancy); the mobile app is used throughout the two intervention phases. Data collection includes data from the medical record of the participants (pregnancy outcomes and medical history), anthropometric data (height, weight, waist- and hip circumferences, skinfold thickness and body composition by bio-electrical impedance analysis), data from the mobile app (physical activity and weight; intervention group only) and questionnaires (socio-demographics, breastfeeding, food intake, physical activity, lifestyle, psychosocial factors and process evaluation). Medical record data are collected at inclusion and at delivery of the subsequent pregnancy. All other data are collected at week 6 and month 6 postpartum and every subsequent 6 months until a new pregnancy, and in every trimester in the new pregnancy. Primary outcome is the composite endpoint score of pregnancy-induced hypertension, gestational diabetes mellitus, caesarean section, and large-for-gestational-age infant in the subsequent pregnancy. Discussion INTER-ACT is a unique randomised controlled lifestyle intervention trial in its implementation between pregnancies and during the subsequent pregnancy, with an e-health driven approach. Trial registration ClinicalTrials.gov Identifier: NCT02989142 . Registered August 2016

The longitudinal static stability of an aerodynamically alleviated marine vehicle, a mathematical model

An assessment of the relative speeds and payload capacities of airborne and waterborne vehicles highlights a gap that can be usefully filled by a new vehicle concept, utilizing both hydrodynamic and aerodynamic forces. A high- speed marine vehicle equipped with aerodynamic surfaces is one such concept. In 1904, Bryan & Williams (Bryan & Williams 1904 Proc. R. Soc. Lond. 73, 100-116 (doi: 10.1098/rspl.1904.0017)) published an article on the longitudinal dynamics of aerial gliders, and this approach remains the foundation of all the mathematical models studying the dynamics of airborne vehicles. In 1932, Perring & Glauert (Perring & Glauert 1932 Reports and Memoranda no. 1493) presented a mathematical approach to study the dynamics of seaplanes experiencing the planing effect. From this work, planing theory has developed. The authors propose a unified mathematical model to study the longitudinal stability of a high-speed planing marine vehicle with aerodynamic surfaces. A kinematics framework is developed. Then, taking into account the aerodynamic, hydrostatic and hydrodynamic forces, the full equations of motion, using a small perturbation assumption, are derived and solved specifically for this concept. This technique reveals a new static stability criterion that can be used to characterize the longitudinal stability of high-speed planing vehicles with aerodynamic surfaces

Eigenfrequencies of an elliptic membrane

The first few eigenfrequencies of a homogeneous elliptic membrane, which is fixed along its boundary, are given in a graph. It is explained in detail, how more accurate results can readily be obtained for special purposes. The known expansion of the eigenfrequencies for small and large eccentricities are summarized. As an application some nodal patterns for a membrane with a double eigenvalue are presented.</p