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

A Phase 2b randomised, controlled, partially blinded trial of the HIV Nucleoside Reverse Transcriptase Inhibitor BMS-986001 (AI467003): Weeks 24 and 48 Efficacy, Safety, Bone and Metabolic Results

Background BMS-986001 is a thymidine analogue nucleoside reverse transcriptase inhibitor (NRTI) designed to maintain in-vitro antiviral activity while minimising off-target effects. We assessed the efficacy and safety of BMS-986001 versus tenofovir disoproxil fumarate in treatment-naive patients with HIV-1. Methods In this phase 2b, randomised, active-controlled trial (AI467003), we recruited treatment-naive (no current or previous exposure to an antiretroviral drug for >1 week) adults (aged at least 18 years) with HIV-1 from 47 sites across Asia, Australia, Europe, North America, South Africa, and South America. Patients with plasma HIV-1 RNA greater than 5000 copies per mL and CD4 counts greater than 200 cells per μL were randomly assigned (2:2:2:3) to receive BMS-986001 100 mg, 200 mg, or 400 mg once a day or to receive tenofovir disoproxil fumarate 300 mg once a day; each allocation was given with efavirenz 600 mg once a day and lamivudine 300 mg once a day. Both patients and investigators were masked to BMS-986001 dose (achieved with similar looking placebo tablets), but not allocation up to and including week 48. The primary endpoints were the proportion of patients with plasma HIV-1 RNA less than 50 copies per mL and safety events (serious adverse events and adverse events leading to discontinuation) through week 24; the main analysis was with a modified intention-to-treat population. Resistance analysis was a secondary endpoint, and additional safety parameters were exploratory endpoints. This trial is registered with ClinicalTrials.gov, number NCT01489046, and the European Clinical Trials Database, number EudraCT 2011-003329-89. Findings Patients were recruited between Jan 25, 2012, and Oct 3, 2012; 757 patients were assessed for eligibility and 301 were randomly assigned to receive either BMS-986001 once a day (67 patients to 100 mg, 67 to 200 mg, and 66 to 400 mg) or tenofovir disoproxil fumarate (n=101). 297 patients received at least one dose of study drug. At week 24, 57 (88%) of 65 patients for whom there were data in the 100 mg group, 54 (81%) of 67 in the 200 mg group, 62 (94%) of 66 in the 400 mg group achieved HIV-1 RNA less than 50 copies per mL, compared with 88 (89%) of 99 in the tenofovir disoproxil fumarate group (modified intention-to-treat population). BMS-986001 was generally well tolerated through week 48. Two patients had BMS-986001-related serious adverse events (atypical drug eruption and thrombocytopenia) and two in the tenofovir disoproxil fumarate group had study drug-related serious adverse events (potential drug-induced liver injury and depression or lipodystrophy) that led to discontinuation. NRTI resistance-associated mutations were reported in four (2%) of 198 patients, and non-NRTI mutations in 17 (9%) of 198 patients receiving BMS-986001 versus none of 99 and one (1%) of 99 patients receiving tenofovir disoproxil fumarate, respectively. Compared with tenofovir disoproxil fumarate, individuals in the BMS-986001 groups showed a smaller decrease in lumbar spine and hip bone mineral density but greater accumulation of limb and trunk fat, subcutaneous and visceral adipose tissue, and increased total cholesterol. Interpretation BMS-986001 had similar efficacy to that of tenofovir disoproxil fumarate and was associated with a smaller decrease in bone mineral density; however, greater resistance and gains in both peripheral and central fat accumulation were recorded for the investigational drug. Bristol-Myers Squibb has discontinued its involvement in the development of BMS-986001, and future decisions on development will be made by Oncolys BioPharma

PEER Testbed Study on a Laboratory Building: Exercising Seismic Performance Assessment

From 2002 to 2004 (years five and six of a ten-year funding cycle), the PEER Center organized the majority of its research around six testbeds. Two buildings and two bridges, a campus, and a transportation network were selected as case studies to “exercise” the PEER performance-based earthquake engineering methodology. All projects involved interdisciplinary teams of researchers, each producing data to be used by other colleagues in their research. The testbeds demonstrated that it is possible to create the data necessary to populate the PEER performancebased framing equation, linking the hazard analysis, the structural analysis, the development of damage measures, loss analysis, and decision variables. This report describes one of the building testbeds—the UC Science Building. The project was chosen to focus attention on the consequences of losses of laboratory contents, particularly downtime. The UC Science testbed evaluated the earthquake hazard and the structural performance of a well-designed recently built reinforced concrete laboratory building using the OpenSees platform. Researchers conducted shake table tests on samples of critical laboratory contents in order to develop fragility curves used to analyze the probability of losses based on equipment failure. The UC Science testbed undertook an extreme case in performance assessment—linking performance of contents to operational failure. The research shows the interdependence of building structure, systems, and contents in performance assessment, and highlights where further research is needed. The Executive Summary provides a short description of the overall testbed research program, while the main body of the report includes summary chapters from individual researchers. More extensive research reports are cited in the reference section of each chapter

When COVID-19 exacerbates inequities: The path forward for generating wellbeing

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Identification of new genes in human chromosome 3 contig 7 by graphical representation technique

The rapidly growing library of genomic length sequences and the working draft of the human genome sequence imply a concomitant need to determine new methods to analyse the sequences for rapid identification of new genes and their functions. We have developed a graphical technique for quick determination of probable coding regions in DNA sequences. In this article we apply this technique to the new sequence data from human chromosome 3 contig 7 to test the efficacy of the proposed system in a live case, and also compare with results from other genomic sequences. We report here a sampling of sequence segments that pass theoretical tests of likelihood of being genes and list several that have close homology with sequences from the expressed sequence tag (EST) databases. We also comment on the possible use of the graphical representation technique in the shotgun method of gene sequencing

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Essential role for ALCAM gene silencing in megakaryocytic differentiation of K562 cells

<p>Abstract</p> <p>Background</p> <p>Activated leukocyte cell adhesion molecule (ALCAM/CD166) is expressed by hematopoietic stem cells. However, its role in hematopoietic differentiation has not previously been defined.</p> <p>Results</p> <p>In this study, we show that ALCAM expression is silenced in erythromegakaryocytic progenitor cell lines. In agreement with this finding, the ALCAM promoter is occupied by GATA-1 <it>in vivo</it>, and a cognate motif at -850 inhibited promoter activity in K562 and MEG-01 cells. Gain-of-function studies showed that ALCAM clusters K562 cells in a process that requires PKC. Induction of megakaryocytic differentiation in K562 clones expressing ALCAM activated PKC-δ and triggered apoptosis.</p> <p>Conclusions</p> <p>There is a lineage-specific silencing of ALCAM in bi-potential erythromegakaryocytic progenitor cell lines. Marked apoptosis of ALCAM-expressing K562 clones treated with PMA suggests that aberrant ALCAM expression in erythromegakaryocytic progenitors may contribute to megakaryocytopenia.</p

A Study of Four Minimization Approaches for Iterative Reconstruction in X-Ray CT

This paper compares four different minimization approaches for iterative reconstruction in CT:(1) iterative coordinate descent approach (ICD), (2) conjugate gradient approach (CG), (3) separable parabolic surrogate approach with ordered subsets (OS), and (4) convergent ordered subsets approach (COS). In addition to showing that all approaches result in the same final image, the paper gives an indication of the number of iterations and time to convergence for the studied approaches.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85952/1/Fessler210.pd

Onchocerciasis-associated epilepsy in Maridi, South Sudan:Modelling and exploring the impact of control measures against river blindness

BackgroundOnchocerciasis, also known as "river blindness", is caused by the bite of infected female blackflies (genus Simuliidae) that transmit the parasite Onchocerca volvulus. A high onchocerciasis microfarial load increases the risk to develop epilepsy in children between the ages of 3 and 18 years. In resource-limited settings in Africa where onchocerciasis has been poorly controlled, high numbers of onchocerciasis-associated epilepsy (OAE) are reported. We use mathematical modeling to predict the impact of onchocerciasis control strategies on the incidence and prevalence of OAE.MethodologyWe developed an OAE model within the well-established mathematical modelling framework ONCHOSIM. Using Latin-Hypercube Sampling (LHS), and grid search technique, we quantified transmission and disease parameters using OAE data from Maridi County, an onchocerciasis endemic area, in southern Republic of South Sudan. Using ONCHOSIM, we predicted the impact of ivermectin mass drug administration (MDA) and vector control on the epidemiology of OAE in Maridi.Principal findingsThe model estimated an OAE prevalence of 4.1% in Maridi County, close to the 3.7% OAE prevalence reported in field studies. The OAE incidence is expected to rapidly decrease by >50% within the first five years of implementing annual MDA with good coverage (≥70%). With vector control at a high efficacy level (around 80% reduction of blackfly biting rates) as the sole strategy, the reduction is slower, requiring about 10 years to halve the OAE incidence. Increasing the efficacy levels of vector control, and implementing vector control simultaneously with MDA, yielded better results in preventing new cases of OAE.Conclusions/significancesOur modeling study demonstrates that intensifying onchocerciasis eradication efforts could substantially reduce OAE incidence and prevalence in endemic foci. Our model may be useful for optimizing OAE control strategies