First test of a high voltage feedthrough for liquid Argon TPCs connected to a 300 kV power supply

Voltages above a hundred kilo-volt will be required to generate the drift field of future very large liquid Argon Time Projection Chambers. The most delicate component is the feedthrough whose role is to safely deliver the very high voltage to the cathode through the thick insulating walls of the cryostat without compromising the purity of the argon inside. This requires a feedthrough that is typically meters long and carefully designed to be vacuum tight and have small heat input. Furthermore, all materials should be carefully chosen to allow operation in cryogenic conditions. In addition, electric fields in liquid argon should be kept below a threshold to reduce risks of discharges. The combination of all above requirements represents significant challenges from the design and manufacturing perspective. In this paper, we report on the successful operation of a feedthrough satisfying all the above requirements. The details of the feedthrough design and its manufacturing steps are provided. Very high voltages up to unprecedented voltages of -300 kV could be applied during long periods repeatedly. A source of instability was observed, which was specific to the setup configuration which was used for the test and not due to the feedthrough itself.Comment: 13 pages, 9 figure

A 60 pc counter-rotating core in NGC 4621

We present adaptive optics assisted OASIS integral field spectrography of the S0 galaxy NGC 4621. Two-dimensional stellar kinematical maps (mean velocity and dispersion) reveal the presence of a 60 pc diameter counter-rotating core (CRC), the smallest observed to date. The OASIS data also suggests that the kinematic center of the CRC is slightly offset from the center of the outer isophotes. This seems to be confirmed by archival HST/STIS data. We also present the HST/WFPC2 V-I colour map, which exhibits a central elongated red structure, also slightly off-centered in the same direction as the kinematic centre. We then construct an axisymmetric model of NGC 4621: the two-integral distribution function is derived using the Multi-Gaussian Expansion and the Hunter & Qian (1993) formalisms. Although the stellar velocities are reasonably fitted, including the region of the counter-rotating core, significant discrepancies between the model and the observations demonstrate the need for a more general model (e.g. a three-integral model).Comment: 9 pages, 8 figure

New algorithms for adaptive optics point-spread function reconstruction

Context. The knowledge of the point-spread function compensated by adaptive optics is of prime importance in several image restoration techniques such as deconvolution and astrometric/photometric algorithms. Wavefront-related data from the adaptive optics real-time computer can be used to accurately estimate the point-spread function in adaptive optics observations. The only point-spread function reconstruction algorithm implemented on astronomical adaptive optics system makes use of particular functions, named $U\_{ij}$. These $U\_{ij}$ functions are derived from the mirror modes, and their number is proportional to the square number of these mirror modes. Aims. We present here two new algorithms for point-spread function reconstruction that aim at suppressing the use of these $U\_{ij}$ functions to avoid the storage of a large amount of data and to shorten the computation time of this PSF reconstruction. Methods. Both algorithms take advantage of the eigen decomposition of the residual parallel phase covariance matrix. In the first algorithm, the use of a basis in which the latter matrix is diagonal reduces the number of $U\_{ij}$ functions to the number of mirror modes. In the second algorithm, this eigen decomposition is used to compute phase screens that follow the same statistics as the residual parallel phase covariance matrix, and thus suppress the need for these $U\_{ij}$ functions. Results. Our algorithms dramatically reduce the number of $U\_{ij}$ functions to be computed for the point-spread function reconstruction. Adaptive optics simulations show the good accuracy of both algorithms to reconstruct the point-spread function.Comment: Accepte

The M 31 double nucleus probed with OASIS and HST. A natural m=1 mode?

We present observations with the adaptive optics assisted integral field spectrograph OASIS of the M 31 double nucleus at a spatial resolution better than 0.5 arcsec FWHM. These data are used to derive the two-dimensional stellar kinematics within the central 2 arcsec. Archival WFPC2/HST images are revisited to perform a photometric decomposition of the nuclear region. We also present STIS/HST kinematics obtained from the archive. The luminosity distribution of the central region is well separated into the respective contributions of the bulge, the nucleus including P1 and P2, and the so-called UV peak. We then show that the axis joining P1 and P2, the two local surface brightness maxima, does not coincide with the kinematic major-axis, which is also the major-axis of the nuclear isophotes (excluding P1). We also confirm that the velocity dispersion peak is offset by ~ 0.2 arcsec from the UV peak, assumed to mark the location of the supermassive black hole. The newly reduced STIS/HST velocity and dispersion profiles are then compared to OASIS and other published kinematics. We find significant offsets with previously published data. Simple parametric models are then built to successfully reconcile all the available kinematics. We finally interpret the observations using new N-body simulations. The nearly keplerian nuclear disk of M31 is subject to a natural m=1 mode, with a very slow pattern speed (3 km/s/pc for M_BH = 7 10^7~\Msun), that can be maintained during more than a thousand dynamical times. The resulting morphology and kinematics of the mode can reproduce the M~31 nuclear-disk photometry and mean stellar velocity, including the observed asymmetries. It requires a central mass concentration and a cold disk system representing between 20 and 40% of its mass. Abridged..Comment: 21 pages. accepted for publication in A&

Deep ALTAIR + NIRI Imaging of the Disk and Bulge of M31

Deep J, H, and K' images, recorded with the ALTAIR adaptive optics system and NIRI imager on Gemini North, are used to probe the stellar content of the disk and bulge of the Local Group galaxy M31. With FWHM near 0.08 arcsec in K, these are the highest angular resolution near-infrared images yet obtained of this galaxy. Four fields that sample M31 at galactocentric radii of 62, 9, 4, and 2 arcmin were observed. The RGB-tip occurs between K = 17.0 and 17.2, and the color of the RGB in the field closest to the center of M31 is consistent with that of NGC 6528. After accounting for random photometric errors, the upper RGB in each field has a width on the (K, J-K) CMD that is consistent with a +/- 0.5 dex dispersion in [Fe/H], in rough agreement with what is seen in other disk and spheroid fields in M31. A population of very bright red stars, which we identify as C stars, are seen in the three fields that are closest to the center of M31. The spatial distribution of these objects suggests that they are well mixed throughout this part of M31, and so likely did not form in a compact region near the galactic nucleus, but more probably formed in the inner disk. We speculate that these C stars may be the most luminous members of the intermediate age population that has been detected previously in studies of the integrated spectrum of the central regions of M31.Comment: 36 pages of text + 16 eps figures; Astronomical Journal in pres

Genome-Wide Studies of Histone Demethylation Catalysed by the Fission Yeast Homologues of Mammalian LSD1

In order to gain a more global view of the activity of histone demethylases, we report here genome-wide studies of the fission yeast SWIRM and polyamine oxidase (PAO) domain homologues of mammalian LSD1. Consistent with previous work we find that the two S. pombe proteins, which we name Swm1 and Swm2 (after SWIRM1 and SWIRM2), associate together in a complex. However, we find that this complex specifically demethylates lysine 9 in histone H3 (H3K9) and both up- and down-regulates expression of different groups of genes. Using chromatin-immunoprecipitation, to isolate fragments of chromatin containing either H3K4me2 or H3K9me2, and DNA microarray analysis (ChIP-chip), we have studied genome-wide changes in patterns of histone methylation, and their correlation with gene expression, upon deletion of the swm1+ gene. Using hyper-geometric probability comparisons we uncover genetic links between lysine-specific demethylases, the histone deacetylase Clr6, and the chromatin remodeller Hrp1. The data presented here demonstrate that in fission yeast the SWIRM/PAO domain proteins Swm1 and Swm2 are associated in complexes that can remove methyl groups from lysine 9 methylated histone H3. In vitro, we show that bacterially expressed Swm1 also possesses lysine 9 demethylase activity. In vivo, loss of Swm1 increases the global levels of both H3K9me2 and H3K4me2. A significant accumulation of H3K4me2 is observed at genes that are up-regulated in a swm1 deletion strain. In addition, H3K9me2 accumulates at some genes known to be direct Swm1/2 targets that are down-regulated in the swm1¿ strain. The in vivo data indicate that Swm1 acts in concert with the HDAC Clr6 and the chromatin remodeller Hrp1 to repress gene expression. In addition, our in vitro analyses suggest that the H3K9 demethylase activity requires an unidentified post-translational modification to allow it to act. Thus, our results highlight complex interactions between histone demethylase, deacetylase and chromatin remodelling activities in the regulation of gene expression

MCL-CAw: A refinement of MCL for detecting yeast complexes from weighted PPI networks by incorporating core-attachment structure

Abstract Background The reconstruction of protein complexes from the physical interactome of organisms serves as a building block towards understanding the higher level organization of the cell. Over the past few years, several independent high-throughput experiments have helped to catalogue enormous amount of physical protein interaction data from organisms such as yeast. However, these individual datasets show lack of correlation with each other and also contain substantial number of false positives (noise). Over these years, several affinity scoring schemes have also been devised to improve the qualities of these datasets. Therefore, the challenge now is to detect meaningful as well as novel complexes from protein interaction (PPI) networks derived by combining datasets from multiple sources and by making use of these affinity scoring schemes. In the attempt towards tackling this challenge, the Markov Clustering algorithm (MCL) has proved to be a popular and reasonably successful method, mainly due to its scalability, robustness, and ability to work on scored (weighted) networks. However, MCL produces many noisy clusters, which either do not match known complexes or have additional proteins that reduce the accuracies of correctly predicted complexes. Results Inspired by recent experimental observations by Gavin and colleagues on the modularity structure in yeast complexes and the distinctive properties of "core" and "attachment" proteins, we develop a core-attachment based refinement method coupled to MCL for reconstruction of yeast complexes from scored (weighted) PPI networks. We combine physical interactions from two recent "pull-down" experiments to generate an unscored PPI network. We then score this network using available affinity scoring schemes to generate multiple scored PPI networks. The evaluation of our method (called MCL-CAw) on these networks shows that: (i) MCL-CAw derives larger number of yeast complexes and with better accuracies than MCL, particularly in the presence of natural noise; (ii) Affinity scoring can effectively reduce the impact of noise on MCL-CAw and thereby improve the quality (precision and recall) of its predicted complexes; (iii) MCL-CAw responds well to most available scoring schemes. We discuss several instances where MCL-CAw was successful in deriving meaningful complexes, and where it missed a few proteins or whole complexes due to affinity scoring of the networks. We compare MCL-CAw with several recent complex detection algorithms on unscored and scored networks, and assess the relative performance of the algorithms on these networks. Further, we study the impact of augmenting physical datasets with computationally inferred interactions for complex detection. Finally, we analyse the essentiality of proteins within predicted complexes to understand a possible correlation between protein essentiality and their ability to form complexes. Conclusions We demonstrate that core-attachment based refinement in MCL-CAw improves the predictions of MCL on yeast PPI networks. We show that affinity scoring improves the performance of MCL-CAw.http://deepblue.lib.umich.edu/bitstream/2027.42/78256/1/1471-2105-11-504.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78256/2/1471-2105-11-504-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78256/3/1471-2105-11-504-S2.ZIPhttp://deepblue.lib.umich.edu/bitstream/2027.42/78256/4/1471-2105-11-504.pdfPeer Reviewe

Measuring Dissociation Rate Constants of Protein Complexes through Subunit Exchange: Experimental Design and Theoretical Modeling

Protein complexes are dynamic macromolecules that constantly dissociate into, and simultaneously are assembled from, free subunits. Dissociation rate constants, koff, provide structural and functional information on protein complexes. However, because all existing methods for measuring koff require high-quality purification and specific modifications of protein complexes, dissociation kinetics has only been studied for a small set of model complexes. Here, we propose a new method, called Metabolically-labeled Affinity-tagged Subunit Exchange (MASE), to measure koff using metabolic stable isotope labeling, affinity purification and mass spectrometry. MASE is based on a subunit exchange process between an unlabeled affinity-tagged variant and a metabolically-labeled untagged variant of a complex. The subunit exchange process was modeled theoretically for a heterodimeric complex. The results showed that koff determines, and hence can be estimated from, the observed rate of subunit exchange. This study provided the theoretical foundation for future experiments that can validate and apply the MASE method

Axion searches with the EDELWEISS-II experiment

We present new constraints on the couplings of axions and more generic axion-like particles using data from the EDELWEISS-II experiment. The EDELWEISS experiment, located at the Underground Laboratory of Modane, primarily aims at the direct detection of WIMPs using germanium bolometers. It is also sensitive to the low-energy electron recoils that would be induced by solar or dark matter axions. Using a total exposure of up to 448 kg.d, we searched for axion-induced electron recoils down to 2.5 keV within four scenarios involving different hypotheses on the origin and couplings of axions. We set a 95% CL limit on the coupling to photons $g_{A\gamma}<2.13\times 10^{-9}$ GeV$^{-1}$ in a mass range not fully covered by axion helioscopes. We also constrain the coupling to electrons, $g_{Ae} < 2.56\times 10^{-11}$, similar to the more indirect solar neutrino bound. Finally we place a limit on $g_{Ae}\times g_{AN}^{\rm eff}<4.70 \times 10^{-17}$, where $g_{AN}^{\rm eff}$ is the effective axion-nucleon coupling for $^{57}$Fe. Combining these results we fully exclude the mass range $0.91\,{\rm eV}<m_A<80$ keV for DFSZ axions and $5.73\,{\rm eV}<m_A<40$ keV for KSVZ axions

In Vivo Analysis of the Notch Receptor S1 Cleavage

A ligand-independent cleavage (S1) in the extracellular domain of the mammalian Notch receptor results in what is considered to be the canonical heterodimeric form of Notch on the cell surface. The in vivo consequences and significance of this cleavage on Drosophila Notch signaling remain unclear and contradictory. We determined the cleavage site in Drosophila and examined its in vivo function by a transgenic analysis of receptors that cannot be cleaved. Our results demonstrate a correlation between loss of cleavage and loss of in vivo function of the Notch receptor, supporting the notion that S1 cleavage is an in vivo mechanism of Notch signal control