APOBEC mutagenesis in drug resistance and immune escape in HIV and cancer evolution

The APOBEC mutational signature has only recently been detected in a multitude of cancers through next-generation sequencing. In contrast, APOBEC has been a focus of virology research for over a decade. Many lessons learnt regarding APOBEC within virology are likely to be applicable to cancer. In this review, we explore the parallels between the role of APOBEC enzymes in HIV and cancer evolution. We discuss data supporting the role of APOBEC mutagenesis in creating HIV genome heterogeneity, drug resistance, and immune escape variants. We hypothesize similar functions of APOBEC will also hold true in cancer

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Use of Balloon-Tipped Catheters in the Critically Ill Child

A retrospective study of our experience in the placement of 19 consecutive balloon-tipped catheters in the pulmonary artery of 18 children disclosed that the procedure can be performed with relative ease in the intensive care unit without the aid of fluoroscopy. Insertion of the catheters was not associated with any serious complications. Catheter malfunction, however, occurred in 9 of 18 patients: balloon rupture in 6 and clot formation in 3. Comparison of pulmonary capillary pressure through a balloon-tipped catheter and venous pressure through a central venous line indicates that, in the absence of significant pulmonary disease requiring high positive end expiratory pressure, or significant left heart dysfunction, a central venous pressure line is frequently adequate for monitoring right heart pressures and as a guidance to fluid therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67256/2/10.1177_000992288202100302.pd

Affective evolutionary music composition with MetaCompose

This paper describes the MetaCompose music generator, a compositional, extensible framework for affective music composition. In this context ‘affective’ refers to the music generator’s ability to express emotional information. The main purpose of MetaCompose is to create music in real-time that can express different mood-states, which we achieve through a unique combination of a graph traversal-based chord sequence generator, a search-based melody generator, a pattern-based accompaniment generator, and a theory for mood expression. Melody generation uses a novel evolutionary technique combining FI-2POP with multi-objective optimization. This allows us to explore a Pareto front of diverse solutions that are creatively equivalent under the terms of a multi-criteria objective function. Two quantitative user studies were performed to evaluate the system: one focusing on the music generation technique, and the other that explores valence expression, via the introduction of dissonances. The results of these studies demonstrate (i) that each part of the generation system improves the perceived quality of the music produced, and (ii) how valence expression via dissonance produces the perceived affective state. This system, which can reliably generate affect-expressive music, can subsequently be integrated in any kind of interactive application (e.g., games) to create an adaptive and dynamic soundtrack

Predictors of nurses’ and midwives’ intentions to provide maternal and child healthcare services to adolescents in South Africa

BACKGROUND: Adolescent mothers are at a much higher risk for maternal mortality compared to mothers aged 20 years and above. Newborns born to adolescent mothers are also more likely to have low birth weight, with the risk of long-term effects such as early onset of adult diabetes than newborns of older mothers. Few studies have investigated the determinants of adequate quality maternal and child healthcare services to pregnant adolescents. This study was conducted to gain an understanding of nurses’ and midwives’ intentions to provide maternal and child healthcare and family planning services to adolescents in South Africa. METHODS: A total of 190 nurses and midwives completed a cross-sectional survey. The survey included components on demographics, knowledge of maternal and child healthcare (MCH) and family planning (FP) services, attitude towards family planning services, subjective norms regarding maternal and child healthcare and family planning services, self-efficacy with maternal and child healthcare and family planning services, and intentions to provide maternal and child healthcare and family planning services to adolescents. Pearson’s correlation analysis was conducted to determine the association between knowledge, attitude, subjective norms, self-efficacy, and intention variables for FP and MCH services. A 2-step linear regression analysis was then conducted for both FP and MCH services to predict the intentions to provide FP and MCH services to adolescents. RESULTS: Self-efficacy to conduct MCH services (β = 0.55, p < 0.01) and years of experience as a nurse- midwife (β = 0.14, p < 0.05) were associated with stronger intentions to provide the services. Self-efficacy to provide FP services (β = 0.30, p < 0.01) was associated with stronger intentions to provide FP services. CONCLUSIONS: Self-efficacy has a strong and positive association with the intentions to provide both MCH and FP services, while there is a moderate association with attitude and norms. There is a need to improve and strengthen nurses’ and midwives’ self-efficacy in conducting both MCH and FP services in order to improve the quality and utilization of the services by adolescents in South Africa.IS

Search for R-parity-violating supersymmetry in events with four or more leptons in sqrt(s) =7 TeV pp collisions with the ATLAS detector

A search for new phenomena in final states with four or more leptons (electrons or muons) is presented. The analysis is based on 4.7 fb−1 of $\sqrt{s}=7\;\mathrm{TeV}$ proton-proton collisions delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in two signal regions: one that requires moderate values of missing transverse momentum and another that requires large effective mass. The results are interpreted in a simplified model of R-parity-violating supersymmetry in which a 95% CL exclusion region is set for charged wino masses up to 540 GeV. In an R-parity-violating MSUGRA/CMSSM model, values of m 1/2 up to 820 GeV are excluded for 10 < tan β < 40

Identification and Structural Characterization of a New Three-Finger Toxin Hemachatoxin from Hemachatus haemachatus Venom

10.1371/journal.pone.0048112PLoS ONE710

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

Revision Rotator Cuff Repair With Versus Without an Arthroscopically Inserted Onlay Bioinductive Implant in Workers’ Compensation Patients

Background: The addition of onlay biological grafts to augment difficult rotator cuff repairs has shown encouraging results in a case series. Purpose/Hypothesis: The purpose of this study was to determine whether the addition of an onlay bioinductive implant would improve repair integrity, shear wave elastographic appearance of the repaired tendon and patch, and patient-rated and/or surgeon-measured shoulder function when used in workers' compensation patients undergoing revision arthroscopic rotator cuff repair. We hypothesized that the addition of the bioinductive implant would enhance repair integrity and clinical outcomes compared with standard repair. Study Design: Cohort study; Level of evidence, 3. Methods: A post hoc matched-cohort study was conducted on prospectively recruited workers’ compensation patients who received a bioinductive implant for revision rotator cuff repair (n = 19). The control group was selected from consecutive workers’ compensation revision rotator cuff repair patients before the introduction of bioinductive implants. Then, they were matched for age and tear size (n = 32). Kaplan-Meier curves were generated to compare the primary outcome of repair integrity between groups. The secondary outcomes were to evaluate the elastographic appearance of the tendon and patch in the bioinductive implant group and to compare patient-rated and surgeon-measured shoulder function between groups preoperatively and at 1 week, 6 weeks, 3 months, and 6 months postoperatively. Results: No major complications associated with the bioinductive implants were identified. Six months after the revision rotator cuff repair, the retear rate in the bioinductive implant group was 16% (3/19), compared with 19% (6/32) in the age- and tear size-matched control group (P =.458). At the final follow-up, the retear rate in the bioinductive implant group was 47% (9/19) at a mean of 14 months compared with 38% (12/32) at a mean of 29 months in the control group (P =.489). The shear wave elastographic stiffness of repaired tendons augmented with the bioinductive implant remained unchanged at 6 m/s from 1 week to 6 months postoperatively, which is lower than the stiffness of 10 m/s in healthy tendons. There were no significant differences in patient-rated or surgeon-measured outcomes between groups 6 months postoperatively. Conclusion: There were no differences in repair integrity or clinical outcomes between workers’ compensation patients who underwent revision arthroscopic rotator cuff repair with an onlay bioinductive implant compared to those who underwent standard revision rotator cuff repair