Determining Tangential Peculiar Velocities of Clusters of Galaxies using Gravitational Lensing

We propose two new methods for measuring tangential peculiar velocities of rich clusters of galaxies. Our first method is based on weak gravitational lensing and takes advantage of the differing images of background galaxies caused by moving and stationary gravitational potentials. Our second method is based on measuring relative frequency shifts between multiple images of a single strongly lensed background galaxy. We illustrate this method using the example of galaxy cluster CL 0024+1654.Comment: LateX, 4 pages, 2 figures, accepted for publication in Part 1 of The Astrophysical Journa

MicroRNA regulation of type 2 innate lymphoid cell homeostasis and function in allergic inflammation.

MicroRNAs (miRNAs) exert powerful effects on immunity through coordinate regulation of multiple target genes in a wide variety of cells. Type 2 innate lymphoid cells (ILC2s) are tissue sentinel mediators of allergic inflammation. We established the physiological requirements for miRNAs in ILC2 homeostasis and immune function and compared the global miRNA repertoire of resting and activated ILC2s and T helper type 2 (TH2) cells. After exposure to the natural allergen papain, mice selectively lacking the miR-17∼92 cluster in ILC2s displayed reduced lung inflammation. Moreover, miR-17∼92-deficient ILC2s exhibited defective growth and cytokine expression in response to IL-33 and thymic stromal lymphopoietin in vitro. The miR-17∼92 cluster member miR-19a promoted IL-13 and IL-5 production and inhibited expression of several targets, including SOCS1 and A20, signaling inhibitors that limit IL-13 and IL-5 production. These findings establish miRNAs as important regulators of ILC2 biology, reveal overlapping but nonidentical miRNA-regulated gene expression networks in ILC2s and TH2 cells, and reinforce the therapeutic potential of targeting miR-19 to alleviate pathogenic allergic responses

IgA as a potential candidate for enteric monoclonal antibody therapeutics with improved gastrointestinal stability

Mucosal surfaces of the gastrointestinal tract play an important role in immune homeostasis and defense and may be compromised by enteric disorders or infection. Therapeutic intervention using monoclonal antibody (mAb) offers the potential for treatment with minimal off-target effects as well as the possibility of limited systemic exposure when administered orally. Critically, to achieve efficacy at luminal surfaces, mAb must remain stable and functionally active in the gastrointestinal environment. To better understand the impact of isotype, class, and molecular structure on the intestinal stability of recombinant antibodies, we used an in vitro simulated intestinal fluid (SIF) assay to evaluate a panel of antibody candidates for enteric mAb-based therapeutics. Recombinant IgG1 was the least stable following SIF incubation, while the stability of IgA generally increased upon polymerization, with subtle differences between subclasses. Notably, patterns of variability within and between mAbs suggest that variable regions contribute to mAb stability and potentially mediate mAb susceptibility to proteases. Despite relatively rapid degradation in SIF, mAbs targeting Enterotoxigenic Escherichia coli (ETEC) displayed functional activity following SIF treatment, with SIgA1 showing improved function compared to SIgA2. The results of this study have implications for the design of enteric therapeutics and subsequent selection of lead candidates based upon in vitro intestinal stability assessments

Performance comparison of small-pixel CdZnTe radiation detectors with gold contacts formed by sputter and electroless deposition

Recent improvements in the growth of wide-bandgap semiconductors, such as cadmium zinc telluride (CdZnTe or CZT), has enabled spectroscopic X/γ-ray imaging detectors to be developed. These detectors have applications covering homeland security, industrial analysis, space science and medical imaging. At the Rutherford Appleton Laboratory (RAL) a promising range of spectroscopic, position sensitive, small-pixel Cd(Zn)Te detectors have been developed. The challenge now is to improve the quality of metal contacts on CdZnTe in order to meet the demanding energy and spatial resolution requirements of these applications. The choice of metal deposition method and fabrication process are of fundamental importance. Presented is a comparison of two CdZnTe detectors with contacts formed by sputter and electroless deposition. The detectors were fabricated with a 74 × 74 array of 200 μm pixels on a 250 μm pitch and bump-bonded to the HEXITEC ASIC. The X/γ-ray emissions from an 241Am source were measured to form energy spectra for comparison. It was found that the detector with contacts formed by electroless deposition produced the best uniformity and energy resolution; the best pixel produced a FWHM of 560 eV at 59.54 keV and 50% of pixels produced a FWHM better than 1.7 keV . This compared with a FWHM of 1.5 keV for the best pixel and 50% of pixels better than 4.4 keV for the detector with sputtered contacts

Association between Participation in a Multiplayer Medical Home Intervention and Changes in Quality, Utilization, and Costs of Care

Importance Interventions to transform primary care practices into medical homes are increasingly common, but their effectiveness in improving quality and containing costs is unclear. Objective To measure associations between participation in the Southeastern Pennsylvania Chronic Care Initiative, one of the earliest and largest multipayer medical home pilots conducted in the United States, and changes in the quality, utilization, and costs of care. Design, Setting, and Participants Thirty-two volunteering primary care practices participated in the pilot (conducted from June 1, 2008, to May 31, 2011). We surveyed pilot practices to compare their structural capabilities at the pilot’s beginning and end. Using claims data from 4 participating health plans, we compared changes (in each year, relative to before the intervention) in the quality, utilization, and costs of care delivered to 64 243 patients who were attributed to pilot practices and 55 959 patients attributed to 29 comparison practices (selected for size, specialty, and location similar to pilot practices) using a difference-in-differences design. Exposures Pilot practices received disease registries and technical assistance and could earn bonus payments for achieving patient-centered medical home recognition by the National Committee for Quality Assurance (NCQA). Main Outcomes and Measures Practice structural capabilities; performance on 11 quality measures for diabetes, asthma, and preventive care; utilization of hospital, emergency department, and ambulatory care; standardized costs of care. Results Pilot practices successfully achieved NCQA recognition and adopted new structural capabilities such as registries to identify patients overdue for chronic disease services. Pilot participation was associated with statistically significantly greater performance improvement, relative to comparison practices, on 1 of 11 investigated quality measures: nephropathy screening in diabetes (adjusted performance of 82.7% vs 71.7% by year 3, P \u3c .001). Pilot participation was not associated with statistically significant changes in utilization or costs of care. Pilot practices accumulated average bonuses of $92 000 per primary care physician during the 3-year intervention. Conclusions and Relevance A multipayer medical home pilot, in which participating practices adopted new structural capabilities and received NCQA certification, was associated with limited improvements in quality and was not associated with reductions in utilization of hospital, emergency department, or ambulatory care services or total costs over 3 years. These findings suggest that medical home interventions may need further refinement

Distinction of representations via Bruhat-Tits buildings of p-adic groups

Introductory and pedagogical treatmeant of the article : P. Broussous "Distinction of the Steinberg representation", with an appendix by Fran\c{c}ois Court\`es, IMRN 2014, no 11, 3140-3157. To appear in Proceedings of Chaire Jean Morlet, Dipendra Prasad, Volker Heiermann Ed. 2017. Contains modified and simplified proofs of loc. cit. This article is written in memory of Fran\c{c}ois Court\`es who passed away in september 2016.Comment: 33 pages, 4 figure

Discovery of an 86 AU Radius Debris Ring Around HD 181327

HST/NICMOS PSF-subtracted coronagraphic observations of HD 181327 have revealed the presence of a ring-like disk of circumstellar debris seen in 1.1 micron light scattered by the disk grains, surrounded by a di use outer region of lower surface brightness. The annular disk appears to be inclined by 31.7 +/- 1.6 deg from face on with the disk major axis PA at 107 +/-2 deg . The total 1.1 micron flux density of the light scattered by the disk (at 1.2" < r < 5.0") of 9.6 mJy +/- 0.8 mJy is 0.17% +/- 0.015% of the starlight. Seventy percent of the light from the scattering grains appears to be confined in a 36 AU wide annulus centered on the peak of the radial surface brightness (SB) profile 86.3 +/- 3.9 AU from the star, well beyond the characteristic radius of thermal emission estimated from IRAS and Spitzer flux densities assuming blackbody grains (~ 22 AU). The light scattered by the ring appears bilaterally symmetric, exhibits directionally preferential scattering well represented by a Henyey-Greenstein scattering phase function with g = 0.30 +/- 0.03, and has an azimuthally medianed SB at the 86.3 AU radius of peak SB of 1.00 +/- 0.07 mJy arcsec^-2. No photocentric offset is seen in the ring relative to the position of the central star. A low surface brightness diffuse halo is seen in the NICMOS image to a distance of ~ 4" Deeper 0.6 micron HST/ACS PSF-subtracted coronagraphic observations reveal a faint outer nebulosity, asymmetrically brighter to the North of the star. We discuss models of the disk and properties of its grains, from which we infer a maximum vertical scale height of 4 - 8 AU at the 87.6 AU radius of maximum surface density, and a total maximum dust mass of collisionally replenished grains with minimum grain sizes of ~ 1 micron of ~ 4 M(moon).Comment: 45 pages, 15 figures, accepted for publication in Ap

Does the Debris Disk around HD 32297 Contain Cometary Grains?

We present an adaptive optics imaging detection of the HD 32297 debris disk at L' (3.8 \microns) obtained with the LBTI/LMIRcam infrared instrument at the LBT. The disk is detected at signal-to-noise per resolution element ~ 3-7.5 from ~ 0.3-1.1" (30-120 AU). The disk at L' is bowed, as was seen at shorter wavelengths. This likely indicates the disk is not perfectly edge-on and contains highly forward scattering grains. Interior to ~ 50 AU, the surface brightness at L' rises sharply on both sides of the disk, which was also previously seen at Ks band. This evidence together points to the disk containing a second inner component located at $\lesssim$ 50 AU. Comparing the color of the outer (50 $< r$/AU $< 120$) portion of the disk at L' with archival HST/NICMOS images of the disk at 1-2 \microns allows us to test the recently proposed cometary grains model of Donaldson et al. 2013. We find that the model fails to match the disk's surface brightness and spectrum simultaneously (reduced chi-square = 17.9). When we modify the density distribution of the model disk, we obtain a better overall fit (reduced chi-square = 2.9). The best fit to all of the data is a pure water ice model (reduced chi-square = 1.06), but additional resolved imaging at 3.1 \microns is necessary to constrain how much (if any) water ice exists in the disk, which can then help refine the originally proposed cometary grains model.Comment: Accepted to ApJ January 13, 2014. 12 pages (emulateapj style), 9 figures, 1 tabl