Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression.

Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s) that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was associated with epigenetics silencing of the MIR34B/C locus and increased DNA copy number loss, selectively in androgen-dependent prostate cancer. In turn, loss of miR-34b resulted in downstream deregulation and overexpression of the stemness marker, Sox2. These findings identify loss of miR-34b as a robust biomarker for prostate cancer progression in androgen-sensitive tumors, and anticipate a potential role of progenitor/stem cell signaling in this stage of disease

Laboratory and modeling studies on the effects of water and soot emissions and ambient conditions on the properties of contrail ice particles in the jet regime

Contrails and contrail-induced cirrus clouds are identified as the most uncertain components in determining aviation impacts on global climate change. Parameters affecting contrail ice particle formation immediately after the engine exit plane (< 5 s in plume age) may be critical to ice particle properties used in large-scale models predicting contrail radiative forcing. Despite this, detailed understanding of these parametric effects is still limited. In this paper, we present results from recent laboratory and modeling studies conducted to investigate the effects of water and soot emissions and ambient conditions on near-field formation of contrail ice particles and ice particle properties. The Particle Aerosol Laboratory (PAL) at the NASA Glenn Research Center and the Aerodyne microphysical parcel model for contrail ice particle formation were employed. Our studies show that exhaust water concentration has a significant impact on contrail ice particle formation and properties. When soot particles were introduced, ice particle formation was observed only when exhaust water concentration was above a critical level. When no soot or sulfuric acid was introduced, no ice particle formation was observed, suggesting that ice particle formation from homogeneous nucleation followed by homogeneous freezing of liquid water was unfavorable. Soot particles were found to compete for water vapor condensation, and higher soot concentrations emitted into the chamber resulted in smaller ice particles being formed. Chamber conditions corresponding to higher cruising altitudes were found to favor ice particle formation. The microphysical model captures trends of particle extinction measurements well, but discrepancies between the model and the optical particle counter measurements exist as the model predicts narrower ice particle size distributions and ice particle sizes nearly a factor of two larger than measured. These discrepancies are likely due to particle loss and scatter during the experimental sampling process and the lack of treatment of turbulent mixing in the model. Our combined experimental and modeling work demonstrates that formation of contrail ice particles can be reproduced in the NASA PAL facility, and the parametric understanding of the ice particle properties from the model and experiments can potentially be used in large-scale models to provide better estimates of the impact of aviation contrails on climate change

Sensitivity of a tonne-scale NEXT detector for neutrinoless double beta decay searches

The Neutrino Experiment with a Xenon TPC (NEXT) searches for the neutrinoless double-beta decay of Xe-136 using high-pressure xenon gas TPCs with electroluminescent amplification. A scaled-up version of this technology with about 1 tonne of enriched xenon could reach in less than 5 years of operation a sensitivity to the half-life of neutrinoless double-beta decay decay better than 1E27 years, improving the current limits by at least one order of magnitude. This prediction is based on a well-understood background model dominated by radiogenic sources. The detector concept presented here represents a first step on a compelling path towards sensitivity to the parameter space defined by the inverted ordering of neutrino masses, and beyond.Comment: 22 pages, 11 figure

Loving to Straighten Out Development: Sexuality and ‘Ethnodevelopment’ in the World Bank’s Ecuadorian Lending

Gender staff in the World Bank -- the world's largest and most influential development institution -- have a policy problem. Having prioritised efforts to get women into paid employment as the "cure-all" for gender inequality they must deal with the work that women already do -- the unpaid labour of caring, socialisation, and human needs fulfilment. This article explores the most prominent policy solution enacted by the Bank to this tension between paid and unpaid work: the restructuring of normative heterosexuality to encourage a two-partner model of love and labour wherein women work more and men care better. Through a case study of Bank gender lending in Ecuador I argue that staff are trying to (re)forge normative arrangements of intimacy, a policy preference that remains invisible unless sexuality is taken seriously as a category of analysis in development studies. Specifically, I focus on four themes that emerge from the attempt to restructure heteronormativity in the loan: (1) the definition of good gender analysis as requiring complementary sharing and dichotomous sex; (2) the Bank's attempt to inculcate limited rationality in women such that they operate as better workers while retaining altruistic attachments to loved ones; (3) the Bank's attempt to inculcate better loving in men, such that they pick up the slack of caring labour when their (partially) rational wives move into productive work, and; (4) the invocation of a racialised hierarchy resting on the extent to which communities approximate ideals of sharing monogamous partnership. Aside from providing clear evidence that the world's largest development institution is involved in micro-processes of sexuality adjustment alongside macro-processes of economic restructuring, I also critique the Bank's sexualised policy interventions and suggest that they warrant contestation

Reconstruction and measurement of (100) MeV energy electromagnetic activity from π0 arrow γγ decays in the MicroBooNE LArTPC

We present results on the reconstruction of electromagnetic (EM) activity from photons produced in charged current νμ interactions with final state π0s. We employ a fully-automated reconstruction chain capable of identifying EM showers of (100) MeV energy, relying on a combination of traditional reconstruction techniques together with novel machine-learning approaches. These studies demonstrate good energy resolution, and good agreement between data and simulation, relying on the reconstructed invariant π0 mass and other photon distributions for validation. The reconstruction techniques developed are applied to a selection of νμ + Ar → μ + π0 + X candidate events to demonstrate the potential for calorimetric separation of photons from electrons and reconstruction of π0 kinematics

Measurement of the production of charged pions by protons on a tantalum target

A measurement of the double-differential cross-section for the production of charged pions in proton--tantalum collisions emitted at large angles from the incoming beam direction is presented. The data were taken in 2002 with the HARP detector in the T9 beam line of the CERN PS. The pions were produced by proton beams in a momentum range from 3 \GeVc to 12 \GeVc hitting a tantalum target with a thickness of 5% of a nuclear interaction length. The angular and momentum range covered by the experiment (100 \MeVc \le p < 800 \MeVc and 0.35 \rad \le \theta <2.15 \rad) is of particular importance for the design of a neutrino factory. The produced particles were detected using a small-radius cylindrical time projection chamber (TPC) placed in a solenoidal magnet. Track recognition, momentum determination and particle identification were all performed based on the measurements made with the TPC. An elaborate system of detectors in the beam line ensured the identification of the incident particles. Results are shown for the double-differential cross-sections ${{\mathrm{d}^2 \sigma}} / {{\mathrm{d}p\mathrm{d}\theta}}$ at four incident proton beam momenta (3 \GeVc, 5 \GeVc, 8 \GeVc and 12 \GeVc). In addition, the pion yields within the acceptance of typical neutrino factory designs are shown as a function of beam momentum. The measurement of these yields within a single experiment eliminates most systematic errors in the comparison between rates at different beam momenta and between positive and negative pion production.Comment: 49 pages, 31 figures. Version accepted for publication on Eur. Phys. J.