Calibration of the Gamma-RAy Polarimeter Experiment (GRAPE) at a Polarized Hard X-Ray Beam

The Gamma-RAy Polarimeter Experiment (GRAPE) is a concept for an astronomical hard X-ray Compton polarimeter operating in the 50 - 500 keV energy band. The instrument has been optimized for wide-field polarization measurements of transient outbursts from energetic astrophysical objects such as gamma-ray bursts and solar flares. The GRAPE instrument is composed of identical modules, each of which consists of an array of scintillator elements read out by a multi-anode photomultiplier tube (MAPMT). Incident photons Compton scatter in plastic scintillator elements and are subsequently absorbed in inorganic scintillator elements; a net polarization signal is revealed by a characteristic asymmetry in the azimuthal scattering angles. We have constructed a prototype GRAPE module containing a single CsI(Na) calorimeter element, at the center of the MAPMT, surrounded by 60 plastic elements. The prototype has been combined with custom readout electronics and software to create a complete "engineering model" of the GRAPE instrument. This engineering model has been calibrated using a nearly 100% polarized hard X-ray beam at the Advanced Photon Source at Argonne National Laboratory. We find modulation factors of 0.46 +/- 0.06 and 0.48 +/- 0.03 at 69.5 keV and 129.5 keV, respectively, in good agreement with Monte Carlo simulations. In this paper we present details of the beam test, data analysis, and simulations, and discuss the implications of our results for the further development of the GRAPE concept.Comment: 35 pages, 14 figures, accepted for publication in NIM-

Using behavior-analytic implicit tests to assess sexual interests among normal and sex-offender populations

The development of implicit tests for measuring biases and behavioral predispositions is a recent development within psychology. While such tests are usually researched within a social-cognitive paradigm, behavioral researchers have also begun to view these tests as potential tests of conditioning histories, including in the sexual domain. The objective of this paper is to illustrate the utility of a behavioral approach to implicit testing and means by which implicit tests can be built to the standards of behavioral psychologists. Research findings illustrating the short history of implicit testing within the experimental analysis of behavior are reviewed. Relevant parallel and overlapping research findings from the field of social cognition and on the Implicit Association Test are also outlined. New preliminary data obtained with both normal and sex offender populations are described in order to illustrate how behavior-analytically conceived implicit tests may have potential as investigative tools for assessing histories of sexual arousal conditioning and derived stimulus associations. It is concluded that popular implicit tests are likely sensitive to conditioned and derived stimulus associations in the history of the test-taker rather than 'unconscious cognitions', per se

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

A local human Vδ1 T cell population is associated with survival in nonsmall-cell lung cancer

Murine tissues harbor signature γδ T cell compartments with profound yet differential impacts on carcinogenesis. Conversely, human tissue-resident γδ cells are less well defined. In the present study, we show that human lung tissues harbor a resident Vδ1 γδ T cell population. Moreover, we demonstrate that Vδ1 T cells with resident memory and effector memory phenotypes were enriched in lung tumors compared with nontumor lung tissues. Intratumoral Vδ1 T cells possessed stem-like features and were skewed toward cytolysis and helper T cell type 1 function, akin to intratumoral natural killer and CD8+ T cells considered beneficial to the patient. Indeed, ongoing remission post-surgery was significantly associated with the numbers of CD45RA−CD27− effector memory Vδ1 T cells in tumors and, most strikingly, with the numbers of CD103+ tissue-resident Vδ1 T cells in nonmalignant lung tissues. Our findings offer basic insights into human body surface immunology that collectively support integrating Vδ1 T cell biology into immunotherapeutic strategies for nonsmall cell lung cancer

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Testing and simulation of silicon photomultiplier readouts for scintillators in high-energy astronomy and solar physics

Space-based gamma-ray detectors for high-energy astronomy and solar physics face severe constraints on mass, volume, and power, and must endure harsh launch conditions and operating environments. Historically, such instruments have usually been based on scintillator materials due to their relatively low cost, inherent ruggedness, high stopping power, and radiation hardness. New scintillator materials, such as LaBr3:Ce, feature improved energy and timing performance, making them attractive for future astronomy and solar physics space missions in an era of tightly constrained budgets. Despite this promise, the use of scintillators in space remains constrained by the volume, mass, power, and fragility of the associated light readout device, typically a vacuum photomultiplier tube (PMT). In recent years, silicon photomultipliers (SiPMs) have emerged as promising alternative light readout devices that offer gains and quantum efficiencies similar to those of PMTs, but with greatly reduced mass and volume, high ruggedness, low voltage requirements, and no sensitivity to magnetic fields. In order for SiPMs to replace PMTs in space-based instruments, however, it must be shown that they can provide comparable performance, and that their inherent temperature sensitivity can be corrected for. To this end, we have performed extensive testing and modeling of a small gamma-ray spectrometer composed of a 6 mm×6 mm SiPM coupled to a 6 mm×6 mm ×10 mm LaBr3:Ce crystal. A custom readout board monitors the temperature and adjusts the bias voltage to compensate for gain variations. We record an energy resolution of 5.7% (FWHM) at 662 keV at room temperature. We have also performed simulations of the scintillation process and optical light collection using Geant4, and of the SiPM response using the GosSiP package. The simulated energy resolution is in good agreement with the data from 22 keV to 662 keV. Above ~1 MeV, however, the measured energy resolution is systematically worse than the simulations. This discrepancy is likely due to the high input impedance of the readout board front-end electronics, which introduces a non-linear saturation effect in the SiPM for large light pulses. Analysis of the simulations indicates several additional steps that must be taken to optimize the energy resolution of SiPM-based scintillator detectors