Spectropolarimetry of the Type Ib/c SN 2005bf

We present spectropolarimetric observations of the peculiar Type Ib/c SN 2005bf, in MCG+00-27-005, from 3600-8550\AA. The SN was observed on 2005 April 30.9, 18 days after the first B-band light-curve maximum and 6 days before the second B-band light-curve maximum. The degree of the Interstellar Polarization, determined from depolarized emission lines in the spectrum, is found to be large with $p_{max}(ISP)=1.6$ and $\theta(ISP)=149$\fdg$7\pm4.0$, but this may be an upper limit on the real value of the ISP. After ISP subtraction, significant polarization is observed over large wavelength regions, indicating a significant degree of global asymmetry, $\gtrsim 10$. Polarizations of 3.5% and 4% are observed for absorption components of Ca II H&K and IR triplet, and 1.3% for He I 5876\AA and Fe II. On the $Q-U$ plane clear velocity-dependent loop structure is observed for the He I 5876\AA line, suggestive of departures from an axial symmetry and possible clumping of the SN ejecta. Weak High Velocity components of $\mathrm{H\alpha}$, $\mathrm{H\beta}$ and $\mathrm{H\gamma}$ are observed, with velocities of -15 000\kms. The low degree of polarization observed at H$\beta$ suggests that the polarization observed for the other Balmer lines ($\sim 0.4$ above the background polarization) may rather be due to blending of $\mathrm{H\alpha}$ and $\mathrm{H\gamma}$ with polarized Si II and Fe II lines, respectively. We suggest a model in which a jet of material, that is rich in $\mathrm{^{56}Ni}$, has penetrated the C-O core, but not the He mantle. The jet axis is tilted with respect to the axis of the photosphere. This accounts for the lack of significant polarization of O I 7774\AA, the delayed excitation and, hence, observability of He I and, potentially, the varied geometries of He and Ca.Comment: 12 pages, 7 figures (3 colour), MNRAS accepte

Alternative Mechanisms for Tn5 Transposition

Bacterial transposons are known to move to new genomic sites using either a replicative or a conservative mechanism. The behavior of transposon Tn5 is anomalous. In vitro studies indicate that it uses a conservative mechanism while in vivo results point to a replicative mechanism. To explain this anomaly, a model is presented in which the two mechanisms are not independent—as widely believed—but could represent alternate outcomes of a common transpositional pathway

Impaired Mitochondrial Microbicidal Responses in Chronic Obstructive Pulmonary Disease Macrophages

RATIONALE: Chronic obstructive pulmonary disease (COPD) is characterized by impaired clearance of pulmonary bacteria. OBJECTIVES: The effect of COPD on alveolar macrophage (AM) microbicidal responses was investigated. METHODS: Alveolar macrophages (AMs) were obtained from bronchoalveolar lavage from healthy donors or COPD patients and challenged with opsonized serotype 14 Streptococcus pneumoniae. Cells were assessed for apoptosis, bactericidal activity and mitochondrial reactive oxygen species (mROS) production. A transgenic mouse line, in which the CD68 promoter ensures macrophage specific expression of human Mcl-1 (CD68.hMcl-1), was used to model the molecular aspects of COPD. MEASUREMENTS AND MAIN RESULTS: COPD AM had elevated levels of Mcl-1, an anti-apoptotic Bcl-2 family member, with selective reduction of delayed intracellular bacterial killing. CD68.hMcl-1 AM phenocopied the microbicidal defect since transgenic mice demonstrated impaired clearance of pulmonary bacteria and increased neutrophilic inflammation. Murine bone marrow-derived macrophages (BMDM) and human monocyte-derived macrophages (MDM) generated mitochondrial reactive oxygen species (mROS) in response to pneumococci, which co-localized with bacteria and phagolysosomes to enhance bacterial killing. The Mcl-1 transgene increased oxygen consumption rates and mROS expression in mock-infected BMDM but reduced caspase-dependent mROS production after pneumococcal challenge. COPD AM also increased basal mROS expression, but failed to increase production after pneumococcal challenge, in keeping with reduced intracellular bacterial killing. The defect in COPD AM intracellular killing was associated with a reduced ratio of mROS /superoxide dismutase 2. CONCLUSIONS: Upregulation of Mcl-1 and chronic adaption to oxidative stress alters mitochondrial metabolism and microbicidal function, reducing the delayed phase of intracellular bacterial clearance in COPD

Hsp90 orchestrates transcriptional regulation by Hsf1 and cell wall remodelling by MAPK signalling during thermal adaptation in a pathogenic yeast

Acknowledgments We thank Rebecca Shapiro for creating CaLC1819, CaLC1855 and CaLC1875, Gillian Milne for help with EM, Aaron Mitchell for generously providing the transposon insertion mutant library, Jesus Pla for generously providing the hog1 hst7 mutant, and Cathy Collins for technical assistance.Peer reviewedPublisher PD

Gravitational Waves From Known Pulsars: Results From The Initial Detector Era

We present the results of searches for gravitational waves from a large selection of pulsars using data from the most recent science runs (S6, VSR2 and VSR4) of the initial generation of interferometric gravitational wave detectors LIGO (Laser Interferometric Gravitational-wave Observatory) and Virgo. We do not see evidence for gravitational wave emission from any of the targeted sources but produce upper limits on the emission amplitude. We highlight the results from seven young pulsars with large spin-down luminosities. We reach within a factor of five of the canonical spin-down limit for all seven of these, whilst for the Crab and Vela pulsars we further surpass their spin-down limits. We present new or updated limits for 172 other pulsars (including both young and millisecond pulsars). Now that the detectors are undergoing major upgrades, and, for completeness, we bring together all of the most up-to-date results from all pulsars searched for during the operations of the first-generation LIGO, Virgo and GEO600 detectors. This gives a total of 195 pulsars including the most recent results described in this paper.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyAustralian Research CouncilInternational Science Linkages program of the Commonwealth of AustraliaCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Economia y CompetitividadConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsNetherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFOCUS Programme of Foundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space AdministrationOTKA of HungaryLyon Institute of Origins (LIO)National Research Foundation of KoreaIndustry CanadaProvince of Ontario through the Ministry of Economic Development and InnovationNational Science and Engineering Research Council CanadaCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationAstronom

Testing gravitational-wave searches with numerical relativity waveforms: Results from the first Numerical INJection Analysis (NINJA) project

The Numerical INJection Analysis (NINJA) project is a collaborative effort between members of the numerical relativity and gravitational-wave data analysis communities. The purpose of NINJA is to study the sensitivity of existing gravitational-wave search algorithms using numerically generated waveforms and to foster closer collaboration between the numerical relativity and data analysis communities. We describe the results of the first NINJA analysis which focused on gravitational waveforms from binary black hole coalescence. Ten numerical relativity groups contributed numerical data which were used to generate a set of gravitational-wave signals. These signals were injected into a simulated data set, designed to mimic the response of the Initial LIGO and Virgo gravitational-wave detectors. Nine groups analysed this data using search and parameter-estimation pipelines. Matched filter algorithms, un-modelled-burst searches and Bayesian parameter-estimation and model-selection algorithms were applied to the data. We report the efficiency of these search methods in detecting the numerical waveforms and measuring their parameters. We describe preliminary comparisons between the different search methods and suggest improvements for future NINJA analyses.Comment: 56 pages, 25 figures; various clarifications; accepted to CQ

Multidecadal variations in the early Holocene outflow of Red Sea Water into the Arabian Sea

We present Holocene stable oxygen isotope data from the deep Arabian Sea off Somalia at a decadal time resolution as a proxy for the history of intermediate/upper deep water. These data show an overall δ18O reduction by 0.5‰ between 10 and ~6.5 kyr B.P. superimposed upon short-term δ18O variations at a decadal-centennial timescale. The amplitude of the decadal variations is 0.3‰ prior, and up to 0.6‰ subsequent, to ~8.1 kyr B.P. We conclude from modeling experiments that the short-term δ18O variations between 10 and ~6.5 kyr B.P. most likely document changes in the evaporation-precipitation balance in the central Red Sea. Changes in water temperature and salinity cause the outflowing Red Sea Water to settle roughly 800 m deeper than today

Effect of Lanadelumab Compared with Placebo on Prevention of Hereditary Angioedema Attacks : a Randomized Clinical Trial

Importance: Current treatments for long-term prophylaxis in hereditary angioedema have limitations. Objective: To assess the efficacy of lanadelumab, a fully human monoclonal antibody that selectively inhibits active plasma kallikrein, in preventing hereditary angioedema attacks. Design, Setting, and Participants: Phase 3, randomized, double-blind, parallel-group, placebo-controlled trial conducted at 41 sites in Canada, Europe, Jordan, and the United States. Patients were randomized between March 3, 2016, and September 9, 2016; last day of follow-up was April 13, 2017. Randomization was 2:1 lanadelumab to placebo; patients assigned to lanadelumab were further randomized 1:1:1 to 1 of the 3 dose regimens. Patients 12 years or older with hereditary angioedema type I or II underwent a 4-week run-in period and those with 1 or more hereditary angioedema attacks during run-in were randomized. Interventions: Twenty-six-week treatment with subcutaneous lanadelumab 150 mg every 4 weeks (n = 28), 300 mg every 4 weeks (n = 29), 300 mg every 2 weeks (n = 27), or placebo (n = 41). All patients received injections every 2 weeks, with those in the every-4-week group receiving placebo in between active treatments. Main Outcome and Measures: Primary efficacy end point was the number of investigator-confirmed attacks of hereditary angioedema over the treatment period. Results: Among 125 patients randomized (mean age, 40.7 years [SD, 14.7 years]; 88 females [70.4%]; 113 white [90.4%]), 113 (90.4%) completed the study. During the run-in period, the mean number of hereditary angioedema attacks per month in the placebo group was 4.0; for the lanadelumab groups, 3.2 for the every-4-week 150-mg group; 3.7 for the every-4-week 300-mg group; and 3.5 for the every-2-week 300-mg group. During the treatment period, the mean number of attacks per month for the placebo group was 1.97; for the lanadelumab groups, 0.48 for the every-4-week 150-mg group; 0.53 for the every-4-week 300-mg group; and 0.26 for the every-2-week 300-mg group. Compared with placebo, the mean differences in the attack rate per month were -1.49 (95% CI, -1.90 to -1.08; P <.001); -1.44 (95% CI, -1.84 to -1.04; P <.001); and -1.71 (95% CI, -2.09 to -1.33; P <.001). The most commonly occurring adverse events with greater frequency in the lanadelumab treatment groups were injection site reactions (34.1% placebo, 52.4% lanadelumab) and dizziness (0% placebo, 6.0% lanadelumab). Conclusions and Relevance: Among patients with hereditary angioedema type I or II, treatment with subcutaneous lanadelumab for 26 weeks significantly reduced the attack rate compared with placebo. These findings support the use of lanadelumab as a prophylactic therapy for hereditary angioedema. Further research is needed to determine long-term safety and efficacy. Trial Registration: EudraCT Identifier: 2015-003943-20; ClinicalTrials.gov Identifier: NCT02586805

Comparative study of imaging at 3.0 T versus 1.5 T of the knee

The objectives of the study were to compare MR imaging at 1.5 and 3.0 T in the same patients concerning image quality and visualization of cartilage pathology and to assess diagnostic performance using arthroscopy as a standard of reference. Twenty-six patients were identified retrospectively as having comparative 1.5 and 3.0 T MR studies of the knee within an average of 102 days. Standard protocols included T1-weighted and fat-saturated intermediate-weighted fast spin-echo sequences in three planes; sequence parameters had been adjusted to account for differences in relaxation at 3.0 T. Arthroscopy was performed in 19 patients. Four radiologists reviewed each study independently, scored image quality, and analyzed pathological findings. Sensitivities, specificities, and accuracies in diagnosing cartilage lesions were calculated in the 19 patients with arthroscopy, and differences between 1.5 and 3.0 T exams were compared using paired Student’s t tests with a significance threshold of p < 0.05. Each radiologist scored the 3.0 T studies higher than those obtained at 1.5 T in visualizing anatomical structures and abnormalities (p < 0.05). Using arthroscopy as a standard of reference, diagnosis of cartilage abnormalities was improved at 3.0 T with higher sensitivity (75.7% versus 70.6%), accuracy (88.2% versus 86.4%), and correct grading of cartilage lesions (51.3% versus 42.9%). Diagnostic confidence scores were higher at 3.0 than 1.5 T (p < 0.05) and signal-to-noise ratio at 3.0 T was approximately twofold higher than at 1.5 T. MRI at 3.0 T improved visualization of anatomical structures and improved diagnostic confidence compared to 1.5 T. This resulted in significantly better sensitivity and grading of cartilage lesions at the knee

One-year outcomes of the ARTISAN-SNM study with the Axonics System for the treatment of urinary urgency incontinence

Aims: Sacral neuromodulation (SNM) is a guideline-recommended treatment for voiding dysfunction including urgency, urge incontinence, and nonobstructive retention as well