Study of Neutron-Induced Ionization in Helium and Argon Chamber Gases

Ion chambers used to monitor the secondary hadron and tertiary muon beam in the NuMI neutrino beamline will be exposed to background particles, including low energy neutrons produced in the beam dump. To understand these backgrounds, we have studied Helium- and Argon-filled ionization chambers exposed to intense neutron fluxes from PuBe neutron sources ($E_n=1-10$ MeV). The sources emit about 10$^8$ neutrons per second. The number of ion pairs in the chamber gas volume per incident neutron is derived. While limited in precision because of a large gamma ray background from the PuBe sources, our results are consistent with the expectation that the neutrons interact purely elastically in the chamber gas.Comment: accepted for publication in NIM

The HERMES Back Drift Chambers

The tracking system of the HERMES spectrometer behind the bending magnet consists of two pairs of large planar 6-plane drift chambers. The design and performance of these chambers is described. This description comprises details on the mechanical and electronical design, information about the gas mixture used and its properties, results on alignment, calibration, resolution, and efficiencies, and a discussion of the experience gained through the first three years of operation.Comment: 21 pages, LaTex, 16 figures include

Background Rejection in the DMTPC Dark Matter Search Using Charge Signals

The Dark Matter Time Projection Chamber (DMTPC) collaboration is developing low-pressure gas TPC detectors for measuring WIMP-nucleon interactions. Optical readout with CCD cameras allows for the detection for the daily modulation in the direction of the dark matter wind, while several charge readout channels allow for the measurement of additional recoil properties. In this article, we show that the addition of the charge readout analysis to the CCD allows us too obtain a statistics-limited 90% C.L. upper limit on the $e^-$ rejection factor of $5.6\times10^{-6}$ for recoils with energies between 40 and 200 keV$_{\mathrm{ee}}$. In addition, requiring coincidence between charge signals and light in the CCD reduces CCD-specific backgrounds by more than two orders of magnitude.Comment: 8 pages, 6 figures. For proceedings of DPF 2011 conferenc

Gaseous Dark Matter Detectors

Dark Matter detectors with directional sensitivity have the potential of yielding an unambiguous positive observation of WIMPs as well as discriminating between galactic Dark Matter halo models. In this article, we introduce the motivation for directional detectors, discuss the experimental techniques that make directional detection possible, and review the status of the experimental effort in this field.Comment: 19 pages, review on gaseous directional dark matter detectors submitted to New Journal of Physic

Positron-molecule interactions: resonant attachment, annihilation, and bound states

This article presents an overview of current understanding of the interaction of low-energy positrons with molecules with emphasis on resonances, positron attachment and annihilation. Annihilation rates measured as a function of positron energy reveal the presence of vibrational Feshbach resonances (VFR) for many polyatomic molecules. These resonances lead to strong enhancement of the annihilation rates. They also provide evidence that positrons bind to many molecular species. A quantitative theory of VFR-mediated attachment to small molecules is presented. It is tested successfully for selected molecules (e.g., methyl halides and methanol) where all modes couple to the positron continuum. Combination and overtone resonances are observed and their role is elucidated. In larger molecules, annihilation rates from VFR far exceed those explicable on the basis of single-mode resonances. These enhancements increase rapidly with the number of vibrational degrees of freedom. While the details are as yet unclear, intramolecular vibrational energy redistribution to states that do not couple directly to the positron continuum appears to be responsible for these enhanced annihilation rates. Downshifts of the VFR from the vibrational mode energies have provided binding energies for thirty species. Their dependence upon molecular parameters and their relationship to positron-atom and positron-molecule binding energy calculations are discussed. Feshbach resonances and positron binding to molecules are compared with the analogous electron-molecule (negative ion) cases. The relationship of VFR-mediated annihilation to other phenomena such as Doppler-broadening of the gamma-ray annihilation spectra, annihilation of thermalized positrons in gases, and annihilation-induced fragmentation of molecules is discussed.Comment: 50 pages, 40 figure

Photoelectric Emission from Interstellar Dust: Grain Charging and Gas Heating

We model the photoelectric emission from and charging of interstellar dust and obtain photoelectric gas heating efficiencies as a function of grain size and the relevant ambient conditions. Using realistic grain size distributions, we evaluate the net gas heating rate for various interstellar environments, and find less heating for dense regions characterized by R_V=5.5 than for diffuse regions with R_V=3.1. We provide fitting functions which reproduce our numerical results for photoelectric heating and recombination cooling for a wide range of interstellar conditions. In a separate paper we will examine the implications of these results for the thermal structure of the interstellar medium. Finally, we investigate the potential importance of photoelectric heating in H II regions, including the warm ionized medium. We find that photoelectric heating could be comparable to or exceed heating due to photoionization of H for high ratios of the radiation intensity to the gas density. We also find that photoelectric heating by dust can account for the observed variation of temperature with distance from the galactic midplane in the warm ionized medium.Comment: 50 pages, including 18 figures; corrected title and abstract field

Specific and effective gene knock-down in early chick embryos using morpholinos but not pRFPRNAi vectors

In the chick embryo, two methods are now used for studying the developmental role of genes by loss-of-function approaches: vector-based shRNA and morpholino oligonucleotides. Both have the advantage that loss-of-function can be conducted in a spatially and temporally controlled way by focal electroporation. Here, we compare these two methods. We find that the shRNA expressing vectors pRFPRNAi, even when targeting a non-expressed protein like GFP, cause morphological phenotypes, mis-regulation of non-targeted genes and activation of the p53 pathway. These effects are highly reproducible, appear to be independent of the targeting sequence and are particularly severe at primitive streak and early somite stages. By contrast, morpholinos do not cause these effects. We propose that pRFPRNAi should only be used with considerable caution and that morpholinos are a preferable approach for gene knock-down during early chick development

Mutant Kras copy number defines metabolic reprogramming and therapeutic susceptibilities.

The RAS/MAPK (mitogen-activated protein kinase) signalling pathway is frequently deregulated in non-small-cell lung cancer, often through KRAS activating mutations. A single endogenous mutant Kras allele is sufficient to promote lung tumour formation in mice but malignant progression requires additional genetic alterations. We recently showed that advanced lung tumours from Kras(G12D/+);p53-null mice frequently exhibit Kras(G12D) allelic enrichment (Kras(G12D)/Kras(wild-type) > 1) (ref. 7), implying that mutant Kras copy gains are positively selected during progression. Here we show, through a comprehensive analysis of mutant Kras homozygous and heterozygous mouse embryonic fibroblasts and lung cancer cells, that these genotypes are phenotypically distinct. In particular, Kras(G12D/G12D) cells exhibit a glycolytic switch coupled to increased channelling of glucose-derived metabolites into the tricarboxylic acid cycle and glutathione biosynthesis, resulting in enhanced glutathione-mediated detoxification. This metabolic rewiring is recapitulated in mutant KRAS homozygous non-small-cell lung cancer cells and in vivo, in spontaneous advanced murine lung tumours (which display a high frequency of Kras(G12D) copy gain), but not in the corresponding early tumours (Kras(G12D) heterozygous). Finally, we demonstrate that mutant Kras copy gain creates unique metabolic dependences that can be exploited to selectively target these aggressive mutant Kras tumours. Our data demonstrate that mutant Kras lung tumours are not a single disease but rather a heterogeneous group comprising two classes of tumours with distinct metabolic profiles, prognosis and therapeutic susceptibility, which can be discriminated on the basis of their relative mutant allelic content. We also provide the first, to our knowledge, in vivo evidence of metabolic rewiring during lung cancer malignant progression.We thank T. Jacks (Kras^LSL-G12D), A. Berns (p53^Fx) and the NIH Mouse repository for mice. We also thank Sam Kleeman and Patricia Ogger for assistance with redox cell profiling and cell viability assays, respectively. We are very thankful to CRUK CI BRU staff for support with in vivo work and all the members of the Martins lab for critical comments and advice. This work was supported by the Medical Research Council.This is the author accepted manuscript. The final version is available at http://www.nature.com/nature/journal/v531/n7592/full/nature16967.html

Multidimentional proteomics for cell biology

The proteome is a dynamic system in which each protein has interconnected properties — dimensions — that together contribute to the phenotype of a cell. Measuring these properties has proved challenging owing to their diversity and dynamic nature. Advances in mass spectrometry-based proteomics now enable the measurement of multiple properties for thousands of proteins, including their abundance, isoform expression, turnover rate, subcellular localization, post-translational modifications and interactions. Complementing these experimental developments are new data analysis, integration and visualization tools as well as data-sharing resources. Together, these advances in the multidimensional analysis of the proteome are transforming our understanding of various cellular and physiological processes

Characterization of a medium size Xe/TMA TPC instrumented with microbulk Micromegas, using low-energy gamma-rays

NEXT-MM is a general-purpose high pressure (10 bar, ~ 25 l active volume) Xenon-based TPC, read out in charge mode with an 0.8 cm × 0.8 cm-segmented 700 cm2 plane (1152 ch) of the latest microbulk-Micromegas technology. It has been recently commissioned at University of Zaragoza as part of the R&D of the NEXT 0νββ experiment, although the experiment's first stage is currently being built based on a SiPM/PMT-readout concept relying on electroluminescence. Around 2 million events were collected during the last months, stemming from the low energy γ-rays emitted by a 241Am source when interacting with the Xenon gas (Eγ = 26, 30, 59.5 keV). The localized nature of such events around atmospheric pressure, the long drift times, as well as the possibility to determine their production time from the associated α particle in coincidence, allow the extraction of primordial properties of the TPC filling gas, namely the drift velocity, diffusion and attachment coefficients. In this work we focus on the little explored combination of Xe and trimethylamine (TMA) for which, in particular, such properties are largely unknown. This gas mixture offers potential advantages over pure Xenon when aimed at Rare Event Searches, mainly due to its Penning characteristics, wave-length shifting properties and reduced diffusion, and it is being actively investigated by our collaboration. The chamber is currently operated at 2.7 bar, as an intermediate step towards the envisaged 10 bar. We report here its performance as well as a first implementation of the calibration procedures that have allowed the extension of the previously reported energy resolution to the whole readout plane (10.6% FWHM@30 keV)