Prototype ATLAS IBL Modules using the FE-I4A Front-End Readout Chip

The ATLAS Collaboration will upgrade its semiconductor pixel tracking detector with a new Insertable B-layer (IBL) between the existing pixel detector and the vacuum pipe of the Large Hadron Collider. The extreme operating conditions at this location have necessitated the development of new radiation hard pixel sensor technologies and a new front-end readout chip, called the FE-I4. Planar pixel sensors and 3D pixel sensors have been investigated to equip this new pixel layer, and prototype modules using the FE-I4A have been fabricated and characterized using 120 GeV pions at the CERN SPS and 4 GeV positrons at DESY, before and after module irradiation. Beam test results are presented, including charge collection efficiency, tracking efficiency and charge sharing.Comment: 45 pages, 30 figures, submitted to JINS

Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition

Hedgehog signaling drives oncogenesis in several cancers and strategies targeting this pathway have been developed, most notably through inhibition of Smoothened. However, resistance to Smoothened inhibitors occurs via genetic changes of Smoothened or other downstream Hedgehog components. Here, we overcome these resistance mechanisms by modulating GLI transcription via inhibition of BET bromodomain proteins. We show the BET bromodomain protein, BRD4, regulates GLI transcription downstream of SMO and SUFU and chromatin immunoprecipitation studies reveal BRD4 directly occupies GLI1 and GLI2 promoters, with a substantial decrease in engagement of these sites upon treatment with JQ1, a small molecule inhibitor targeting BRD4. Globally, genes associated with medulloblastoma-specific GLI1 binding sites are downregulated in response to JQ1 treatment, supporting direct regulation of GLI activity by BRD4. Notably, patient- and GEMM-derived Hedgehog-driven tumors (basal cell carcinoma, medulloblastoma and atypical teratoid/rhabdoid tumor) respond to JQ1 even when harboring genetic lesions rendering them resistant to Smoothened antagonists

Identification of Small Molecule Lead Compounds for Visceral Leishmaniasis Using a Novel Ex Vivo Splenic Explant Model System

Visceral leishmaniasis is a life threatening parasitic disease present in several countries of the world. New drugs are needed to treat this disease because treatments are becoming increasingly ineffective. We established a novel system to screen for new anti-leishmanial compounds that utilizes spleen cells from hamsters infected with the parasite Leishmania donovani. The parasite strain we used was genetically engineered to emit light by the incorporation of the firefly luciferase gen. This laboratory test system has the advantage of reproducing the cellular environment where the drug has to combat the infection. The efficacy of the compounds is easily determined by measuring the light emitted by the surviving parasites in a luminometer after exposing the infected cells to the test compounds. The screening of more than 4,000 molecules showed that 84 (2.1%) of them showed anti-leishmanial activity and had an acceptable toxicity evaluation. Eighty two percent of these molecules, which had varied chemical structures, were previously unknown to have anti-leishmanial activity. Further studies in animals of these new chemical entities may identify drug candidates for the treatment of visceral leishmaniasis

Demonstration of surface electron rejection with interleaved germanium detectors for dark matter searches

The following article appeared in Applied Physics Letters 103.16 (2013): 164105 and may be found at http://scitation.aip.org/content/aip/journal/apl/100/26/10.1063/1.4729825The SuperCDMS experiment in the Soudan Underground Laboratory searches for dark matter with a 9-kg array of cryogenic germanium detectors. Symmetric sensors on opposite sides measure both charge and phonons from each particle interaction, providing excellent discrimination between electron and nuclear recoils, and between surface and interior events. Surface event rejection capabilities were tested with two 210 Pb sources producing ∼130 beta decays/hr. In ∼800 live hours, no events leaked into the 8–115 keV signal region, giving upper limit leakage fraction 1.7 × 10−5 at 90% C.L., corresponding to < 0.6 surface event background in the future 200-kg SuperCDMS SNOLAB experiment.This work is supported in part by the National Science Foundation (Grant Nos. AST-9978911, NSF-0847342, PHY-1102795,NSF-1151869, PHY-0542066, PHY-0503729, PHY-0503629, PHY-0503641, PHY-0504224, PHY-0705052,PHY-0801708, PHY-0801712, PHY-0802575, PHY-0847342, PHY-0855299, PHY-0855525, and PHY-1205898), by the Department of Energy (Contract Nos. DE-AC03-76SF00098, DE-FG02-92ER40701, DE-FG02-94ER40823,DE-FG03-90ER40569, DE-FG03-91ER40618, and DESC0004022),by NSERC Canada (Grant Nos. SAPIN 341314 and SAPPJ 386399), and by MULTIDARK CSD2009-00064 and FPA2012-34694. Fermilab is operated by Fermi Research Alliance, LLC under Contract No. De-AC02-07CH11359, while SLAC is operated under Contract No. DE-AC02-76SF00515 with the United States Department of Energy

Perspectives on Humanizing and Liberatory Qualitative Research with Racially/Ethnically Minoritized Youth

The visible impacts of COVID-19 and racial injustice have resulted in renewed funding commitments and research within minoritized communities. However, this work is too often anchored in deficit and damage-centered research approaches and practices. In this brief, we call on the qualitative research community to reframe their perspectives and terminate harmful, pain-driven research. We underscore the importance of humanizing and liberatory approaches to research with youth who are racially/ethnically minoritized. Specifically, we contend that the emotional health and overall well-being of youth are impacted by the approaches employed by researchers and the experiences racially/ethnically minoritized youth have with research. Thus, we offer specific anti-oppressive strategies and recommendations for qualitative researchers to consider in their work with racial/ethnically minoritized youth and communities