Gain Stabilization of a Submillimeter SIS Heterodyne Receiver

We have designed a system to stabilize the gain of a submillimeter heterodyne receiver against thermal fluctuations of the mixing element. In the most sensitive heterodyne receivers, the mixer is usually cooled to 4 K using a closed-cycle cryocooler, which can introduce ~1% fluctuations in the physical temperature of the receiver components. We compensate for the resulting mixer conversion gain fluctuations by monitoring the physical temperature of the mixer and adjusting the gain of the intermediate frequency (IF) amplifier that immediately follows the mixer. This IF power stabilization scheme, developed for use at the Submillimeter Array (SMA), a submillimeter interferometer telescope on Mauna Kea in Hawaii, routinely achieves a receiver gain stability of 1 part in 6,000 (rms to mean). This is an order of magnitude improvement over the typical uncorrected stability of 1 part in a few hundred. Our gain stabilization scheme is a useful addition to SIS heterodyne receivers that are cooled using closed-cycle cryocoolers in which the 4 K temperature fluctuations tend to be the leading cause of IF power fluctuations.Comment: 7 pages, 6 figures accepted to IEEE Transactions on Microwave Theory and Technique

Transcriptional activation of the Lats1 tumor suppressor gene in tumors of CUX1 transgenic mice

<p>Abstract</p> <p>Background</p> <p><it>Lats1 </it>(large tumor suppressor 1) codes for a serine/threonine kinase that plays a role in the progression through mitosis. Genetic studies demonstrated that the loss of LATS1 in mouse, and of its ortholog <it>wts </it>(warts) in Drosophila, is associated with increased cancer incidence. There are conflicting reports, however, as to whether overexpression of <it>Lats1 </it>inhibits cell proliferation. CUX1 is a transcription factor that exists in different isoforms as a result of proteolytic processing or alternative transcription initiation. Expression of p110 and p75 CUX1 in transgenic mice increases the susceptibility to cancer in various organs and tissues. In tissue culture, p110 CUX1 was shown to accelerate entry into S phase and stimulate cell proliferation.</p> <p>Results</p> <p>Genome-wide location arrays in cell lines of various cell types revealed that <it>Lats1 </it>was a transcriptional target of CUX1. Scanning ChIP analysis confirmed that CUX1 binds to the immediate promoter of <it>Lats1</it>. Expression of <it>Lats1 </it>was reduced in cux1^-/-MEFs, whereas it was increased in cells stably or transiently expressing p110 or p75 CUX1. Reporter assays confirmed that the immediate promoter of <it>Lats1 </it>was sufficient to confer transcriptional activation by CUX1. <it>Lats1 </it>was found to be overexpressed in tumors from the mammary gland, uterus and spleen that arise in p110 or p75 CUX1 transgenic mice. In tissue culture, such elevated LATS1 expression did not hinder cell cycle progression in cells overexpressing p110 CUX1.</p> <p>Conclusion</p> <p>While inactivation of <it>Lats1</it>/<it>wts </it>in mouse and Drosophila can increase cancer incidence, results from the present study demonstrate that <it>Lats1 </it>is a transcriptional target of CUX1 that can be overexpressed in tumors of various tissue-types. Interestingly, two other studies documented the overexpression of <it>LATS1 </it>in human cervical cancers and basal-like breast cancers. We conclude that, similarly to other genes involved in mitotic checkpoint, cancer can be associated with either loss-of-function or overexpression of <it>Lats1</it>.</p

Global health competencies and approaches in medical education: a literature review

<p>Abstract</p> <p>Background</p> <p>Physicians today are increasingly faced with healthcare challenges that require an understanding of global health trends and practices, yet little is known about what constitutes appropriate global health training.</p> <p>Methods</p> <p>A literature review was undertaken to identify competencies and educational approaches for teaching global health in medical schools.</p> <p>Results</p> <p>Using a pre-defined search strategy, 32 articles were identified; 11 articles describing 15 global health competencies for undergraduate medical training were found. The most frequently mentioned competencies included an understanding of: the global burden of disease, travel medicine, healthcare disparities between countries, immigrant health, primary care within diverse cultural settings and skills to better interface with different populations, cultures and healthcare systems. However, no consensus on global health competencies for medical students was apparent. Didactics and experiential learning were the most common educational methods used, mentioned in 12 and 13 articles respectively. Of the 11 articles discussing competencies, 8 linked competencies directly to educational approaches.</p> <p>Conclusions</p> <p>This review highlights the imperative to document global health educational competencies and approaches used in medical schools and the need to facilitate greater consensus amongst medical educators on appropriate global health training for future physicians.</p

An International Consensus to Standardize Integration of Histopathology in Ulcerative Colitis Clinical Trials

Background & Aims: Histopathology is an emerging treatment target in ulcerative colitis (UC) clinical trials. Our aim was to provide guidance on standardizing biopsy collection protocols, identifying optimal evaluative indices, and defining thresholds for histologic response and remission after treatment. Methods: An international, interdisciplinary expert panel of 19 gastroenterologists and gastrointestinal pathologists was assembled. A modified RAND/University of California, Los Angeles appropriateness methodology was used to address relevant issues. A total of 138 statements were derived from a systematic review of the literature and expert opinion. Each statement was anonymously rated as appropriate, uncertain, or inappropriate using a 9-point scale. Survey results were reviewed and discussed before a second round of voting. Results: Histologic measurements collected using a uniform biopsy strategy are important for assessing disease activity and determining therapeutic efficacy in UC clinical trials. Multiple biopsy strategies were deemed acceptable, including segmental biopsies collected according to the endoscopic appearance. Biopsies should be scored for architectural change, lamina propria chronic inflammation, basal plasmacytosis, lamina propria and epithelial neutrophils, epithelial damage, and erosions/ulcerations. The Geboes score, Robarts Histopathology Index, and Nancy Index were considered appropriate for assessing histologic activity; use of the modified Riley score and Harpaz Index were uncertain. Histologic activity at baseline should be required for enrollment, recognizing this carries operational implications. Achievement of histologic improvement or remission was considered an appropriate and realistic therapeutic target. Current histologic indices require validation for pediatric populations. Conclusions: These recommendations provide a framework for standardized implementation of histopathology in UC trials. Additional work is required to address operational considerations and areas of uncertainty

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Low exposure long-baseline neutrino oscillation sensitivity of the DUNE experiment

The Deep Underground Neutrino Experiment (DUNE) will produce world-leading neutrino oscillation measurements over the lifetime of the experiment. In this work, we explore DUNE's sensitivity to observe charge-parity violation (CPV) in the neutrino sector, and to resolve the mass ordering, for exposures of up to 100 kiloton-megawatt-years (kt-MW-yr). The analysis includes detailed uncertainties on the flux prediction, the neutrino interaction model, and detector effects. We demonstrate that DUNE will be able to unambiguously resolve the neutrino mass ordering at a 3$\sigma$ (5$\sigma$) level, with a 66 (100) kt-MW-yr far detector exposure, and has the ability to make strong statements at significantly shorter exposures depending on the true value of other oscillation parameters. We also show that DUNE has the potential to make a robust measurement of CPV at a 3$\sigma$ level with a 100 kt-MW-yr exposure for the maximally CP-violating values \delta_{\rm CP}} = \pm\pi/2. Additionally, the dependence of DUNE's sensitivity on the exposure taken in neutrino-enhanced and antineutrino-enhanced running is discussed. An equal fraction of exposure taken in each beam mode is found to be close to optimal when considered over the entire space of interest

A Gaseous Argon-Based Near Detector to Enhance the Physics Capabilities of DUNE

This document presents the concept and physics case for a magnetized gaseous argon-based detector system (ND-GAr) for the Deep Underground Neutrino Experiment (DUNE) Near Detector. This detector system is required in order for DUNE to reach its full physics potential in the measurement of CP violation and in delivering precision measurements of oscillation parameters. In addition to its critical role in the long-baseline oscillation program, ND-GAr will extend the overall physics program of DUNE. The LBNF high-intensity proton beam will provide a large flux of neutrinos that is sampled by ND-GAr, enabling DUNE to discover new particles and search for new interactions and symmetries beyond those predicted in the Standard Model

Snowmass Neutrino Frontier: DUNE Physics Summary

The Deep Underground Neutrino Experiment (DUNE) is a next-generation long-baseline neutrino oscillation experiment with a primary physics goal of observing neutrino and antineutrino oscillation patterns to precisely measure the parameters governing long-baseline neutrino oscillation in a single experiment, and to test the three-flavor paradigm. DUNE's design has been developed by a large, international collaboration of scientists and engineers to have unique capability to measure neutrino oscillation as a function of energy in a broadband beam, to resolve degeneracy among oscillation parameters, and to control systematic uncertainty using the exquisite imaging capability of massive LArTPC far detector modules and an argon-based near detector. DUNE's neutrino oscillation measurements will unambiguously resolve the neutrino mass ordering and provide the sensitivity to discover CP violation in neutrinos for a wide range of possible values of δCP. DUNE is also uniquely sensitive to electron neutrinos from a galactic supernova burst, and to a broad range of physics beyond the Standard Model (BSM), including nucleon decays. DUNE is anticipated to begin collecting physics data with Phase I, an initial experiment configuration consisting of two far detector modules and a minimal suite of near detector components, with a 1.2 MW proton beam. To realize its extensive, world-leading physics potential requires the full scope of DUNE be completed in Phase II. The three Phase II upgrades are all necessary to achieve DUNE's physics goals: (1) addition of far detector modules three and four for a total FD fiducial mass of at least 40 kt, (2) upgrade of the proton beam power from 1.2 MW to 2.4 MW, and (3) replacement of the near detector's temporary muon spectrometer with a magnetized, high-pressure gaseous argon TPC and calorimeter