Development of a SiPM Camera for a Schwarzschild-Couder Cherenkov Telescope for the Cherenkov Telescope Array

We present the development of a novel 11328 pixel silicon photomultiplier (SiPM) camera for use with a ground-based Cherenkov telescope with Schwarzschild-Couder optics as a possible medium-sized telescope for the Cherenkov Telescope Array (CTA). The finely pixelated camera samples air-shower images with more than twice the optical resolution of cameras that are used in current Cherenkov telescopes. Advantages of the higher resolution will be a better event reconstruction yielding improved background suppression and angular resolution of the reconstructed gamma-ray events, which is crucial in morphology studies of, for example, Galactic particle accelerators and the search for gamma-ray halos around extragalactic sources. Packing such a large number of pixels into an area of only half a square meter and having a fast readout directly attached to the back of the sensors is a challenging task. For the prototype camera development, SiPMs from Hamamatsu with through silicon via (TSV) technology are used. We give a status report of the camera design and highlight a number of technological advancements that made this development possible.Comment: 8 pages, 5 figures, In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

Optimizing end-labeled free-solution electrophoresis by increasing the hydrodynamic friction of the drag-tag

We study the electrophoretic separation of polyelectrolytes of varying lengths by means of end-labeled free-solution electrophoresis (ELFSE). A coarse-grained molecular dynamics simulation model, using full electrostatic interactions and a mesoscopic Lattice Boltzmann fluid to account for hydrodynamic interactions, is used to characterize the drag coefficients of different label types: linear and branched polymeric labels, as well as transiently bound micelles. It is specifically shown that the label's drag coefficient is determined by its hydrodynamic size, and that the drag per label monomer is largest for linear labels. However, the addition of side chains to a linear label offers the possibility to increase the hydrodynamic size, and therefore the label efficiency, without having to increase the linear length of the label, thereby simplifying synthesis. The third class of labels investigated, transiently bound micelles, seems very promising for the usage in ELFSE, as they provide a significant higher hydrodynamic drag than the other label types. The results are compared to theoretical predictions, and we investigate how the efficiency of the ELFSE method can be improved by using smartly designed drag-tags.Comment: 32 pages, 11 figures, submitted to Macromolecule

Route of administration affects corticosteroid sensitivity of a combined ovalbumin and lipopolysaccharide model of asthma exacerbation in guinea-pigs

Lipopolysaccharide (LPS) contributes to asthma exacerbations and development of inhaled corticosteroid insensitivity. Complete resistance to systemic corticosteroids is rare and most patients lie on a continuum of steroid responsiveness. The objective of this study was to examine the sensitivity of combined ovalbumin- (Ova) and LPS-induced functional and inflammatory responses to inhaled and systemic corticosteroid in conscious guinea-pigs, to test the hypothesis that the route of administration affects its sensitivity. Guinea-pigs were sensitised to Ova and challenged with inhaled Ova alone or combined with LPS. Airways function was determined by measuring specific airways conductance via whole-body plethysmography. Airways hyperresponsiveness to histamine was determined pre- and 24h post-Ova challenge. Airways inflammation and underlying mechanisms were determined from bronchoalveolar lavage cell counts and lung tissue cytokines. Vehicle or dexamethasone was administered by once-daily intraperitoneal injection (5, 10 or 20 mg/kg) or twice-daily inhalation (4 or 20 mg/ml) for 6 days before Ova challenge or Ova with LPS. LPS exacerbated Ova-induced responses, elongating early asthmatic responses (EAR), prolonging bronchoconstriction by histamine and further elevating airways inflammation. Intraperitoneal dexamethasone (20 mg/kg) significantly reduced the elongated EAR and airways inflammation but not the increased bronchoconstriction to histamine. In contrast, inhaled dexamethasone (20 mg/ml), which inhibited responses to Ova alone, did not significantly reduce functional and inflammatory responses to combined Ova and LPS. Combined Ova and LPS-induced functional and inflammatory responses are insensitive to inhaled but only partially sensitive to systemic dexamethasone. These results suggest that the route of corticosteroid administration may be important in determining the sensitivity of asthmatic responses to these agents

Humoral Immune Response against Nontargeted Tumor Antigens after Treatment with Sipuleucel-T and Its Association with Improved Clinical Outcome

PURPOSE: Antitumor activity of cancer immunotherapies may elicit immune responses to nontargeted (secondary) tumor antigens, or antigen spread. We evaluated humoral antigen spread after treatment with sipuleucel-T, an immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC), designed to target prostatic acid phosphatase (PAP; primary antigen). EXPERIMENTAL DESIGN: Serum samples from patients with mCRPC enrolled in the placebo-controlled phase III IMPACT study (evaluable n = 142) were used to assess humoral antigen spread after treatment with sipuleucel-T. Immunoglobulin G (IgG) responses to self-antigens (including tumor antigens) were surveyed using protein microarrays and confirmed using Luminex xMAP. IgG responses were subsequently validated in ProACT (n = 33), an independent phase II study of sipuleucel-T. Association of IgG responses with overall survival (OS) was assessed using multivariate Cox models adjusted for baseline prostate-specific antigen (PSA) and lactate dehydrogenase levels. RESULTS: In patients from IMPACT and ProACT, levels of IgG against multiple secondary antigens, including PSA, KLK2/hK2, K-Ras, E-Ras, LGALS8/PCTA-1/galectin-8, and LGALS3/galectin-3, were elevated after treatment with sipuleucel-T (P \u3c 0.01), but not control. IgG responses (\u3e/= 2-fold elevation posttreatment) occurred in \u3e/= 25% of patients, appeared by 2 weeks after sipuleucel-T treatment, and persisted for up to 6 months. IgG responses to PSA and LGALS3 were associated with improved OS in sipuleucel-T-treated patients from IMPACT (

Gut microbiomes from Gambian infants reveal the development of a non-industrialized Prevotella-based trophic network.

Funder: Bill & Melinda Gates Foundation Grand Challenges New Interventions in Global Health awardFunder: MRC Unit The Gambia/MRC International Nutrition Group by the UK MRC and the UK Department for the International DevelopmentDistinct bacterial trophic networks exist in the gut microbiota of individuals in industrialized and non-industrialized countries. In particular, non-industrialized gut microbiomes tend to be enriched with Prevotella species. To study the development of these Prevotella-rich compositions, we investigated the gut microbiota of children aged between 7 and 37 months living in rural Gambia (616 children, 1,389 stool samples, stratified by 3-month age groups). These infants, who typically eat a high-fibre, low-protein diet, were part of a double-blind, randomized iron intervention trial (NCT02941081) and here we report the secondary outcome. We found that child age was the largest discriminating factor between samples and that anthropometric indices (collection time points, season, geographic collection site, and iron supplementation) did not significantly influence the gut microbiome. Prevotella copri, Faecalibacterium prausnitzii and Prevotella stercorea were, on average, the most abundant species in these 1,389 samples (35%, 11% and 7%, respectively). Distinct bacterial trophic network clusters were identified, centred around either P. stercorea or F. prausnitzii and were found to develop steadily with age, whereas P. copri, independently of other species, rapidly became dominant after weaning. This dataset, set within a critical gut microbial developmental time frame, provides insights into the development of Prevotella-rich gut microbiomes, which are typically understudied and are underrepresented in western populations

Gut microbiomes from Gambian infants reveal the development of a non-industrialized Prevotella-based trophic network.

Funder: Bill & Melinda Gates Foundation Grand Challenges New Interventions in Global Health awardFunder: MRC Unit The Gambia/MRC International Nutrition Group by the UK MRC and the UK Department for the International DevelopmentDistinct bacterial trophic networks exist in the gut microbiota of individuals in industrialized and non-industrialized countries. In particular, non-industrialized gut microbiomes tend to be enriched with Prevotella species. To study the development of these Prevotella-rich compositions, we investigated the gut microbiota of children aged between 7 and 37 months living in rural Gambia (616 children, 1,389 stool samples, stratified by 3-month age groups). These infants, who typically eat a high-fibre, low-protein diet, were part of a double-blind, randomized iron intervention trial (NCT02941081) and here we report the secondary outcome. We found that child age was the largest discriminating factor between samples and that anthropometric indices (collection time points, season, geographic collection site, and iron supplementation) did not significantly influence the gut microbiome. Prevotella copri, Faecalibacterium prausnitzii and Prevotella stercorea were, on average, the most abundant species in these 1,389 samples (35%, 11% and 7%, respectively). Distinct bacterial trophic network clusters were identified, centred around either P. stercorea or F. prausnitzii and were found to develop steadily with age, whereas P. copri, independently of other species, rapidly became dominant after weaning. This dataset, set within a critical gut microbial developmental time frame, provides insights into the development of Prevotella-rich gut microbiomes, which are typically understudied and are underrepresented in western populations

Investigating the TeV Morphology of MGRO J1908+06 with VERITAS

We report on deep observations of the extended TeV gamma-ray source MGRO J1908+06 made with the VERITAS very high energy (VHE) gamma-ray observatory. Previously, the TeV emission has been attributed to the pulsar wind nebula (PWN) of the Fermi-LAT pulsar PSR J1907+0602. We detect MGRO J1908+06 at a significance level of 14 standard deviations (14 sigma) and measure a photon index of 2.20 +/- 0.10_stat +/- 0.20_sys. The TeV emission is extended, covering the region near PSR J1907+0602 and also extending towards SNR G40.5--0.5. When fitted with a 2-dimensional Gaussian, the intrinsic extension has a standard deviation of sigma_src = 0.44 +/- 0.02 degrees. In contrast to other TeV PWNe of similar age in which the TeV spectrum softens with distance from the pulsar, the TeV spectrum measured near the pulsar location is consistent with that measured at a position near the rim of G40.5--0.5, 0.33 degrees away.Comment: To appear in ApJ, 8 page

Discovery of Very High Energy Gamma Rays from 1ES 1440+122

The BL Lacertae object 1ES 1440+122 was observed in the energy range from 85 GeV to 30 TeV by the VERITAS array of imaging atmospheric Cherenkov telescopes. The observations, taken between 2008 May and 2010 June and totalling 53 hours, resulted in the discovery of $\gamma$-ray emission from the blazar, which has a redshift $z$=0.163. 1ES 1440+122 is detected at a statistical significance of 5.5 standard deviations above the background with an integral flux of (2.8$\pm0.7_{\mathrm{stat}}\pm0.8_{\mathrm{sys}}$) $\times$ 10$^{-12}$ cm$^{-2}$ s$^{-1}$ (1.2\% of the Crab Nebula's flux) above 200 GeV. The measured spectrum is described well by a power law from 0.2 TeV to 1.3 TeV with a photon index of 3.1 $\pm$ 0.4$_{\mathrm{stat}}$ $\pm$ 0.2$_{\mathrm{sys}}$. Quasi-simultaneous multi-wavelength data from the Fermi Large Area Telescope (0.3--300 GeV) and the Swift X-ray Telescope (0.2--10 keV) are additionally used to model the properties of the emission region. A synchrotron self-Compton model produces a good representation of the multi-wavelength data. Adding an external-Compton or a hadronic component also adequately describes the data.Comment: 8 pages, 4 figures. Accepted for publication in MNRA