Characterizing the epoch of reionization with the small-scale CMB: Constraints on the optical depth and duration

Patchy reionization leaves a number of imprints on the small-scale cosmic microwave background (CMB) temperature fluctuations, the largest of which is the kinematic Sunyaev-Zel'dovich (kSZ), the Doppler shift of CMB photons scattering off moving electrons in ionized bubbles. It has long been known that in the CMB power spectrum, this imprint of reionization is largely degenerate with the kSZ signal produced by late-time galaxies and clusters, thus limiting our ability to constrain reionization. Following Smith & Ferraro (2017), it is possible to isolate the reionization contribution in a model independent way, by looking at the large scale modulation of the small scale CMB power spectrum. In this paper we extend the formalism to use the full shape information of the small scale power spectrum (rather than just its broadband average), and argue that this is necessary to break the degeneracy between the optical depth τ and parameters setting the duration of reionization. In particular, we show that the next generation of CMB experiments could achieve up to a factor of 3 improvement on the optical depth τ and at the same time, constrain the duration of reionization to ∼25%. This can help tighten the constrains on neutrino masses, which will be limited by our knowledge of τ, and shed light on the physical processes responsible for reionization

Patients' practices and experiences of using nebuliser therapy in the management of COPD at home.

How patients use their nebulisers at home is vital to ensure effective treatment and optimal health outcomes for patients with chronic obstructive pulmonary disease (COPD). The aim of the study was to identify the practicalities and problems associated with nebuliser use by patients with COPD at home, which may impact on the safety and effectiveness of therapy

The influence of submesoscales and vertical mixing on the export of sinking tracers in large-eddy simulations

AbstractWe use idealized large-eddy simulations (LES) and a simple analytical theory to study the influence of submesoscales on the concentration and export of sinking particles from the mixed layer. We find that restratification of the mixed layer following the development of submesoscales reduces the rate of vertical mixing which, in turn, enhances the export rate associated with gravitational settling. For a neutral tracer initially confined to the mixed layer, subinertial (submesoscale) motions enhance the downward tracer flux, consistent with previous studies. However, the sign of the advective flux associated with the concentration of sinking particles reverses, indicating reentrainment into the mixed layer. A new theory is developed to model the gravitational settling flux when the particle concentration is nonuniform. The theory broadly agrees with the LES results and allows us to extend the analysis to a wider range of parameters.</jats:p

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Gene therapy restores vision in rd1 mice after removal of a confounding mutation in Gpr179

The rd1 mouse with a mutation in the Pde6b gene was the first strain of mice identified with a retinal degeneration. However, AAV-mediated gene supplementation of rd1 mice only results in structural preservation of photoreceptors, and restoration of the photoreceptor-mediated a-wave, but not in restoration of the bipolar cell-mediated b-wave. Here we show that a mutation in Gpr179 prevents the full restoration of vision in rd1 mice. Backcrossing rd1 with C57BL6 mice reveals the complete lack of b-wave in a subset of mice, consistent with an autosomal recessive Mendelian inheritance pattern. We identify a mutation in the Gpr179 gene, which encodes for a G-protein coupled receptor localized to the dendrites of ON-bipolar cells. Gene replacement in rd1 mice that are devoid of the mutation in Gpr179 successfully restores the function of both photoreceptors and bipolar cells, which is maintained for up to 13 months. Our discovery may explain the failure of previous gene therapy attempts in rd1 mice, and we propose that Grp179 mutation status should be taken into account in future studies involving rd1 mice

Complete analysis of the B-cell response to a protein antigen, from in vivo germinal centre formation to 3-D modelling of affinity maturation

Somatic hypermutation of immunoglobulin variable region genes occurs within germinal centres (GCs) and is the process responsible for affinity maturation of antibodies during an immune response. Previous studies have focused almost exclusively on the immune response to haptens, which may be unrepresentative of epitopes on protein antigens. In this study, we have exploited a model system that uses transgenic B and CD4&lt;sup&gt;+&lt;/sup&gt; T cells specific for hen egg lysozyme (HEL) and a chicken ovalbumin peptide, respectively, to investigate a tightly synchronized immune response to protein antigens of widely differing affinities, thus allowing us to track many facets of the development of an antibody response at the antigen-specific B cell level in an integrated system &lt;i&gt;in&lt;/i&gt; &lt;i&gt;vivo&lt;/i&gt;. Somatic hypermutation of immunoglobulin variable genes was analysed in clones of transgenic B cells proliferating in individual GCs in response to HEL or the cross-reactive low-affinity antigen, duck egg lysozyme (DEL). Molecular modelling of the antibody–antigen interface demonstrates that recurring mutations in the antigen-binding site, selected in GCs, enhance interactions of the antibody with DEL. The effects of these mutations on affinity maturation are demonstrated by a shift of transgenic serum antibodies towards higher affinity for DEL in DEL-cOVA immunized mice. The results show that B cells with high affinity antigen receptors can revise their specificity by somatic hypermutation and antigen selection in response to a low-affinity, cross-reactive antigen. These observations shed further light on the nature of the immune response to pathogens and autoimmunity and demonstrate the utility of this novel model for studies of the mechanisms of somatic hypermutation

Intensities and self-broadening coefficients of the strongest water vapour lines in the 2.7 and 6.25 mu m absorption bands

Intensities and self-broadening coefficients are presented for about 460 of the strongest water vapour lines in the spectral regions 1400–1840 cm−1 and 3440–3970 cm^{-1} at room temperature, obtained from rather unique measurements using a 5-mm-path-length cell. The retrieved spectral line parameters are compared with those in the HITRAN database ver. 2008 and 2012 and with recent ab-initio calculations. Both the retrieved intensities and half-widths are on average in reasonable agreement with those in HITRAN-2012. Maximum systematic differences do not exceed 4% for intensities (1600 cm^{-1} band) and 7% for self-broadening coefficients (3600 cm^{-1} band). For many lines however significant disagreements were detected with the HITRAN-2012 data, exceeding the average uncertainty of the retrieval. In addition, water vapour line parameters for 5300 cm^{-1} (1.9 μm) band reported by us in 2005 were also compared with HITRAN-2012, and show average differences of 4–5% for both intensities and half-widths

Bullous pemphigoid and pemphigus vulgaris--incidence and mortality in the UK: population based cohort study.

OBJECTIVE: To determine the incidence of and mortality from bullous pemphigoid and pemphigus vulgaris in the United Kingdom. DESIGN: Retrospective historical cohort study. SETTING: Computerised medical records from the health improvement network, a large population based UK general practice database. PARTICIPANTS: Patients with pemphigus vulgaris and bullous pemphigoid diagnostic codes and age, sex, and practice matched controls. MAIN OUTCOME MEASURES: Incidence and mortality compared with the control population by calendar period, age group, sex, geographical region, and degree of social deprivation. RESULTS: 869 people with bullous pemphigoid and 138 people with pemphigus vulgaris were identified. The median age at presentation for bullous pemphigoid was 80 (range 23-102) years, and 534 (61%) patients were female. The median age at presentation for pemphigus vulgaris was 71 (21-102) years, and 91 (66%) patients were female. Incidences of bullous pemphigoid and pemphigus vulgaris were 4.3 (95% confidence interval 4.0 to 4.6) and 0.7 (0.6 to 0.8) per 100 000 person years. The incidence of bullous pemphigoid increased over time; the average yearly increase was 17% (incidence rate ratio=1.2, 95% confidence interval 1.1 to 1.2). An average yearly increase in incidence of pemphigus vulgaris of 11% (incidence rate ratio=1.1, 1.0 to 1.2) occurred. The risk of death for patients with bullous pemphigoid was twice as great as for controls (adjusted hazard ratio=2.3, 95% confidence interval 2.0 to 2.7). For pemphigus vulgaris, the risk of death was three times greater than for controls (adjusted hazard ratio=3.3, 2.2 to 5.2). CONCLUSIONS: Incidences of bullous pemphigoid and pemphigus vulgaris are increasing. The reasons for the changes in incidence are not clearly understood but have implications for identifying causative factors. Both disorders are associated with a high risk of death. Previous estimates may have underestimated the risk of death associated with these diseases