The NIKA2 instrument, a dual-band kilopixel KID array for millimetric astronomy

NIKA2 (New IRAM KID Array 2) is a camera dedicated to millimeter wave astronomy based upon kilopixel arrays of Kinetic Inductance Detectors (KID). The pathfinder instrument, NIKA, has already shown state-of-the-art detector performance. NIKA2 builds upon this experience but goes one step further, increasing the total pixel count by a factor $\sim$10 while maintaining the same per pixel performance. For the next decade, this camera will be the resident photometric instrument of the Institut de Radio Astronomie Millimetrique (IRAM) 30m telescope in Sierra Nevada (Spain). In this paper we give an overview of the main components of NIKA2, and describe the achieved detector performance. The camera has been permanently installed at the IRAM 30m telescope in October 2015. It will be made accessible to the scientific community at the end of 2016, after a one-year commissioning period. When this happens, NIKA2 will become a fundamental tool for astronomers worldwide.Comment: Proceedings of the 16th Low Temperature Detectors workshop. To be published in the Journal of Low Temperature Physics. 8 pages, 4 figures, 1 tabl

Muon-induced background in the EDELWEISS dark matter search

A dedicated analysis of the muon-induced background in the EDELWEISS dark matter search has been performed on a data set acquired in 2009 and 2010. The total muon flux underground in the Laboratoire Souterrain de Modane (LSM) was measured to be $\Phi_{\mu}=(5.4\pm 0.2 ^{+0.5}_{-0.9})$\,muons/m$^2$/d. The modular design of the muon-veto system allows the reconstruction of the muon trajectory and hence the determination of the angular dependent muon flux in LSM. The results are in good agreement with both MC simulations and earlier measurements. Synchronization of the muon-veto system with the phonon and ionization signals of the Ge detector array allowed identification of muon-induced events. Rates for all muon-induced events $\Gamma^{\mu}=(0.172 \pm 0.012)\, \rm{evts}/(\rm{kg \cdot d})$ and of WIMP-like events $\Gamma^{\mu-n} = 0.008^{+0.005}_{-0.004}\, \rm{evts}/(\rm{kg \cdot d})$ were extracted. After vetoing, the remaining rate of accepted muon-induced neutrons in the EDELWEISS-II dark matter search was determined to be $\Gamma^{\mu-n}_{\rm irred} < 6\cdot 10^{-4} \, \rm{evts}/(\rm{kg \cdot d})$ at 90%\,C.L. Based on these results, the muon-induced background expectation for an anticipated exposure of 3000\,\kgd\ for EDELWEISS-3 is $N^{\mu-n}_{3000 kg\cdot d} < 0.6$ events.Comment: 21 pages, 16 figures, Accepted for publication in Astropart. Phy

A wide field-of-view low-resolution spectrometer at APEX: Instrument design and scientific forecast

Context. Characterising the large-scale structure in the Universe from present times to the high redshift epoch of reionisation is essential to constraining the cosmology, the history of star formation, and reionisation, to measuring the gas content of the Universe, and to obtaining a better understanding of the physical processes that drive galaxy formation and evolution. Using the integrated emission from unresolved galaxies or gas clouds, line intensity mapping (LIM) provides a new observational window to measure the larger properties of structures. This very promising technique motivates the community to plan for LIM experiments. Aims. We describe the development of a large field-of-view instrument, named CONCERTO (for CarbON CII line in post-rEionisation and ReionisaTiOn epoch), operating in the range 130-310 GHz from the APEX 12-m telescope (5100 m above sea level). CONCERTO is a low-resolution spectrometer based on the lumped element kinetic inductance detectors (LEKID) technology. Spectra are obtained using a fast Fourier transform spectrometer (FTS), coupled to a dilution cryostat with a base temperature of 0.1 K. Two two kilo-pixel arrays of LEKID are mounted inside the cryostat that also contains the cold optics and the front-end electronics. Methods. We present, in detail, the technological choices leading to the instrumental concept, together with the design and fabrication of the instrument and preliminary laboratory tests on the detectors. We also give our best estimates for CONCERTO sensitivity and give predictions for two of the main scientific goals of CONCERTO, that is, a [CII]-intensity mapping survey and observations of galaxy clusters. Results. We provide a detailed description of the instrument design. Based on realistic comparisons with existing instruments developed by our group (NIKA, NIKA2, and KISS), and on the laboratory characterisation of our detectors, we provide an estimate for CONCERTO sensitivity on the sky. Finally, we describe, in detail, two of the main scientific goals offered by CONCERTO at APEX

Activation of HIV Transcription by the Viral Tat Protein Requires a Demethylation Step Mediated by Lysine-specific Demethylase 1 (LSD1/KDM1)

The essential transactivator function of the HIV Tat protein is regulated by multiple posttranslational modifications. Although individual modifications are well characterized, their crosstalk and dynamics of occurrence during the HIV transcription cycle remain unclear

Transcriptional control by adenovirus E1A conserved region 3 via p300/CBP

The human adenovirus type 5 (HAdV-5) E1A 13S oncoprotein is a potent regulator of gene expression and is used extensively as a model for transcriptional activation. It possesses two independent transcriptional activation domains located in the N-terminus/conserved region (CR) 1 and CR3. The protein acetyltransferase p300 was previously identified by its association with the N-terminus/CR1 portion of E1A and this association is required for oncogenic transformation by E1A. We report here that transcriptional activation by 13S E1A is inhibited by co-expression of sub-stoichiometric amounts of the smaller 12S E1A isoform, which lacks CR3. Transcriptional inhibition by E1A 12S maps to the N-terminus and correlates with the ability to bind p300/CBP, suggesting that E1A 12S is sequestering this limiting factor from 13S E1A. This is supported by the observation that the repressive effect of E1A 12S is reversed by expression of exogenous p300 or CBP, but not by a CBP mutant lacking actyltransferase activity. Furthermore, we show that transcriptional activation by 13S E1A is greatly reduced by siRNA knockdown of p300 and that CR3 binds p300 independently of the well-characterized N-terminal/CR1-binding site. Importantly, CR3 is also required to recruit p300 to the adenovirus E4 promoter during infection. These results identify a new functionally significant interaction between E1A CR3 and the p300/CBP acetyltransferases, expanding our understanding of the mechanism by which this potent transcriptional activator functions

Protein Kinase A Regulates Molecular Chaperone Transcription and Protein Aggregation

Heat shock factor 1 (HSF1) regulates one of the major pathways of protein quality control and is essential for deterrence of protein-folding disorders, particularly in neuronal cells. However, HSF1 activity declines with age, a change that may open the door to progression of neurodegenerative disorders such as Huntington's disease. We have investigated mechanisms of HSF1 regulation that may become compromised with age. HSF1 binds stably to the catalytic domain of protein kinase A (PKAcα) and becomes phosphorylated on at least one regulatory serine residue (S320). We show here that PKA is essential for effective transcription of HSP genes by HSF1. PKA triggers a cascade involving HSF1 binding to the histone acetylase p300 and positive translation elongation factor 1 (p-TEFb) and phosphorylation of the c-terminal domain of RNA polymerase II, a key mechanism in the downstream steps of HSF1-mediated transcription. This cascade appears to play a key role in protein quality control in neuronal cells expressing aggregation-prone proteins with long poly-glutamine (poly-Q) tracts. Such proteins formed inclusion bodies that could be resolved by HSF1 activation during heat shock. Resolution of the inclusions was inhibited by knockdown of HSF1, PKAcα, or the pTEFb component CDK9, indicating a key role for the HSF1-PKA cascade in protein quality control

Saccharomyces boulardii Improves Intestinal Cell Restitution through Activation of the α2β1 Integrin Collagen Receptor

Intestinal epithelial cell damage is frequently seen in the mucosal lesions of inflammatory bowel diseases such as ulcerative colitis or Crohn's disease. Complete remission of these diseases requires both the cessation of inflammation and the migration of enterocytes to repair the damaged epithelium. Lyophilized Saccharomyces boulardii (Sb, Biocodex) is a nonpathogenic yeast widely used as a therapeutic agent for the treatment and prevention of diarrhea and other gastrointestinal disorders. In this study, we determined whether Sb could accelerate enterocyte migration. Cell migration was determined in Sb force-fed C57BL6J mice and in an in vitro wound model. The impact on α2β1 integrin activity was assessed using adhesion assays and the analysis of α2β1 mediated signaling pathways both in vitro and in vivo. We demonstrated that Sb secretes compounds that enhance the migration of enterocytes independently of cell proliferation. This enhanced migration was associated with the ability of Sb to favor cell-extracellular matrix interaction. Indeed, the yeast activates α2β1 integrin collagen receptors. This leads to an increase in tyrosine phosphorylation of cytoplasmic molecules, including focal adhesion kinase and paxillin, involved in the integrin signaling pathway. These changes are associated with the reorganization of focal adhesion structures. In conclusion Sb secretes motogenic factors that enhance cell restitution through the dynamic regulation of α2β1 integrin activity. This could be of major importance in the development of novel therapies targeting diseases characterized by severe mucosal injury, such as inflammatory and infectious bowel diseases

Caffeine Prevents Transcription Inhibition and P-TEFb/7SK Dissociation Following UV-Induced DNA Damage

Background: The mechanisms by which DNA damage triggers suppression of transcription of a large number of genes are poorly understood. DNA damage rapidly induces a release of the positive transcription elongation factor b (P-TEFb) from the large inactive multisubunit 7SK snRNP complex. P-TEFb is required for transcription of most class II genes through stimulation of RNA polymerase II elongation and cotranscriptional pre-mRNA processing. Methodology/Principal Findings: We show here that caffeine prevents UV-induced dissociation of P-TEFb as well as transcription inhibition. The caffeine-effect does not involve PI3-kinase-related protein kinases, because inhibition of phosphatidylinositol 3-kinase family members (ATM, ATR and DNA-PK) neither prevents P-TEFb dissociation nor transcription inhibition. Finally, caffeine prevention of transcription inhibition is independent from DNA damage. Conclusion/Significance: Pharmacological prevention of P-TEFb/7SK snRNP dissociation and transcription inhibitio