Defect formation on surfaces bombarded by energetic multiply charged proteins: Implications for the conformation of gas-phase electrosprayed ions

Indirect information on the conformation of highly charged molecular ions may be obtained by monitoring their collisional cross sections and the course of simple gas-phase reactions such as hydrogen-deuterium exchange. In this work, another indirect but more visually oriented approach is explored: electrosprayed protein ions are accelerated toward a highly oriented pyrolytic graphite surface and the resulting single-ion defects are imaged by scanning force and tunneling microscopy. All protein impacts generated shallow hillocks: the shapes depended on the identity and charge state of the incident protein. Lysozyme and myoglobin, both compact, globular proteins in the native state, produced compact, almost circular hillocks. However, hillocks generated by myoglobin that had been denatured in the solution phase were elongated, and the elongation was positively correlated with the charge state of the ion. It appears that structural information about gas-phase multiply charged proteins can be derived from imprints generated by energetic protein impacts on surfaces

Automorphism groups of polycyclic-by-finite groups and arithmetic groups

We show that the outer automorphism group of a polycyclic-by-finite group is an arithmetic group. This result follows from a detailed structural analysis of the automorphism groups of such groups. We use an extended version of the theory of the algebraic hull functor initiated by Mostow. We thus make applicable refined methods from the theory of algebraic and arithmetic groups. We also construct examples of polycyclic-by-finite groups which have an automorphism group which does not contain an arithmetic group of finite index. Finally we discuss applications of our results to the groups of homotopy self-equivalences of K(\Gamma, 1)-spaces and obtain an extension of arithmeticity results of Sullivan in rational homotopy theory

Nebular spectra and abundance tomography of the Type Ia supernova SN 2011fe: a normal SN Ia with a stable Fe core

A series of optical and one near-infrared nebular spectra covering the first year of the Type Ia supernova SN 2011fe are presented and modelled. The density profile that proved best for the early optical/ultraviolet spectra, ‘?-11fe’, was extended to lower velocities to include the regions that emit at nebular epochs. Model ?-11fe is intermediate between the fast deflagration model W7 and a low-energy delayed-detonation. Good fits to the nebular spectra are obtained if the innermost ejecta are dominated by neutron-rich, stable Fe-group species, which contribute to cooling but not to heating. The correct thermal balance can thus be reached for the strongest [Fe ii] and [Fe iii] lines to be reproduced with the observed ratio. The 56Ni mass thus obtained is ?0.47 ± 0.05?M?. The bulk of 56Ni has an outermost velocity of ?8500 km s?1. The mass of stable iron is ?0.23 ± 0.03?M?. Stable Ni has low abundance, ?10?2?M?. This is sufficient to reproduce an observed emission line near 7400 Å. A sub-Chandrasekhar explosion model with mass 1.02?M? and no central stable Fe does not reproduce the observed line ratios. A mock model where neutron-rich Fe-group species are located above 56Ni following recent suggestions is also shown to yield spectra that are less compatible with the observations. The densities and abundances in the inner layers obtained from the nebular analysis, combined with those of the outer layers previously obtained, are used to compute a synthetic bolometric light curve, which compares favourably with the light curve of SN 2011fe

Parenthood and pregnancy in Australians receiving treatment for end-stage kidney disease: protocol of a national study of perinatal and parental outcomes through population record linkage.

Introduction Achieving parenthood is challenging in individuals receiving renal replacement therapy (RRT; dialysis or kidney transplantation) for end-stage kidney disease. Decision-making regarding parenthood in RRT recipients should be underpinned by robust data, yet there is limited data on parental factors that drive adverse health outcomes. Therefore, we aim to investigate the perinatal risks and outcomes in parents receiving RRT. Methods and analysis This is a multijurisdictional probabilistic data linkage study of perinatal, hospital, birth, death and renal registers from 1991 to 2013 from New South Wales, Western Australia, South Australia and the Australian Capital Territory. This study includes all babies born ≥20 weeks’ gestation or 400 g birth weight captured through mandated data collection in the perinatal data sets. Through linkage with the Australian and New Zealand Dialysis and Transplant (ANZDATA) registry, babies exposed to RRT (and their parents) will be compared with babies who have not been exposed to RRT (and their parents) to determine obstetric and fetal outcomes, birth rates and fertility rates. One of the novel aspects of this study is the method that will be used to link fathers receiving RRT to the mothers and their babies within the perinatal data sets, using the birth register, enabling the identification of family units. The linked data set will be used to validate the parenthood events directly reported to ANZDATA. Ethics and dissemination Ethics approval was obtained from Human Research Ethics Committees (HREC) and Aboriginal HREC in each jurisdiction. Findings of this study will be disseminated at scientific conferences and in peer-reviewed journals in tabular and aggregated forms. De-identified data will be presented and individual patients will not be identified. We will aim to present findings to relevant stakeholders (eg, patients, clinicians and policymakers) to maximise translational impact of research findings.Erandi Hewawasam, Aarti Gulyani, Christopher E Davies, Elizabeth Sullivan, Sally Wark, Philip A Clayton, Stephen P McDonald, Shilpanjali Jesudaso

The PKC, HOG and Ca2+ signalling pathways co-ordinately regulate chitin synthesis in Candida albicans

Open Access via PMC2649417Peer reviewedPublisher PD

Clinical activity of ipilimumab for metastatic uveal melanoma: a retrospective review of the Dana-Farber Cancer Institute, Massachusetts General Hospital, Memorial Sloan-Kettering Cancer Center, and University Hospital of Lausanne experience.

BACKGROUND: Uveal melanoma exhibits a high incidence of metastases; and, to date, there is no systemic therapy that clearly improves outcomes. The anticytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab is a standard of care for metastatic melanoma; however, the clinical activity of CTLA-4 inhibition in patients with metastatic uveal melanoma is poorly defined. METHODS: To assess ipilimumab in this setting, the authors performed a multicenter, retrospective analysis of 4 hospitals in the United States and Europe. Clinical characteristics, toxicities, and radiographic disease burden, as determined by central, blinded radiology review, were evaluated. RESULTS: Thirty-nine patients with uveal melanoma were identified, including 34 patients who received 3 mg/kg ipilimumab and 5 who received 10 mg/kg ipilimumab. Immune-related response criteria and modified World Health Organization criteria were used to assess the response rate (RR) and the combined response plus stable disease (SD) rate after 12 weeks, after 23 weeks, and overall (median follow-up, 50.4 weeks [12.6 months]). At week 12, the RR was 2.6%, and the response plus SD rate was 46.%; at week 23, the RR was 2.6%, and the response plus SD rate was 28.2%. There was 1 complete response and 1 late partial response (at 100 weeks after initial SD) for an immune-related RR of 5.1%. Immune-related adverse events were observed in 28 patients (71.8%) and included 7 (17.9%) grade 3 and 4 events. Immune-related adverse events were more frequent in patients who received 10 mg/kg ipilimumab than in those who received 3 mg/kg ipilimumab. The median overall survival from the first dose of ipilimumab was 9.6 months (95% confidence interval, 6.3-13.4 months; range, 1.6-41.6 months). Performance status, lactate dehydrogenase level, and an absolute lymphocyte count ≥ 1000 cells/μL at week 7 were associated significantly with survival. CONCLUSIONS: In this multicenter, retrospective analysis of 4 hospitals in the United States and Europe of patients with uveal melanoma, durable responses to ipilimumab and manageable toxicity were observed

Emoções, “stress”, ansiedade e “coping": estudo qualitativo com treinadores de nível internacional

A influência dos fatores e processos psicológicos no desempenho desportivo dos atletas está, de uma forma geral, amplamente demonstrada; todavia, poucas investigações procuraram estudar esta relação nos treinadores. Neste sentido, empregando uma entrevista semi-estruturada, a presente investigação procurou, junto de seis treinadores de elite com idades compreendidas entre os 55 e os 63 anos (M = 59 ± 3,03) de diversas modalidades, identificar as características/competências psicológicas mais importantes para o sucesso desportivo, as principais fontes de “stress” e ansiedade experienciadas e as estratégias de “coping” a que recorriam em situações estressantes e/ou problemáticas, adicionalmente, pretendeu explorar o papel de outras emoções no seu desempenho. Os resultados revelaram que: 1) a motivação era uma das competências/características psicológicas percepcionadas pelos treinadores como mais importantes para o sucesso; 2) as principais fontes de “stress” estavam relacionadas com preocupações com o desempenho dos atletas, sendo comuns a diferentes modalidades; 3) os treinadores recorriam a diversas estratégias de “coping” em simultâneo, geralmente adaptativas; e 4) para além da ansiedade, outras emoções, positivas e negativas, pareciam influenciar o desempenho dos treinadores.Fundação para a Ciência e Tecnologia (FCT

Field Measurements of Terrestrial and Martian Dust Devils

Surface-based measurements of terrestrial and martian dust devils/convective vortices provided from mobile and stationary platforms are discussed. Imaging of terrestrial dust devils has quantified their rotational and vertical wind speeds, translation speeds, dimensions, dust load, and frequency of occurrence. Imaging of martian dust devils has provided translation speeds and constraints on dimensions, but only limited constraints on vertical motion within a vortex. The longer mission durations on Mars afforded by long operating robotic landers and rovers have provided statistical quantification of vortex occurrence (time-of-sol, and recently seasonal) that has until recently not been a primary outcome of more temporally limited terrestrial dust devil measurement campaigns. Terrestrial measurement campaigns have included a more extensive range of measured vortex parameters (pressure, wind, morphology, etc.) than have martian opportunities, with electric field and direct measure of dust abundance not yet obtained on Mars. No martian robotic mission has yet provided contemporaneous high frequency wind and pressure measurements. Comparison of measured terrestrial and martian dust devil characteristics suggests that martian dust devils are larger and possess faster maximum rotational wind speeds, that the absolute magnitude of the pressure deficit within a terrestrial dust devil is an order of magnitude greater than a martian dust devil, and that the time-of-day variation in vortex frequency is similar. Recent terrestrial investigations have demonstrated the presence of diagnostic dust devil signals within seismic and infrasound measurements; an upcoming Mars robotic mission will obtain similar measurement types

IceCube - the next generation neutrino telescope at the South Pole

IceCube is a large neutrino telescope of the next generation to be constructed in the Antarctic Ice Sheet near the South Pole. We present the conceptual design and the sensitivity of the IceCube detector to predicted fluxes of neutrinos, both atmospheric and extra-terrestrial. A complete simulation of the detector design has been used to study the detector's capability to search for neutrinos from sources such as active galaxies, and gamma-ray bursts.Comment: 8 pages, to be published with the proceedings of the XXth International Conference on Neutrino Physics and Astrophysics, Munich 200