ACBAR: The Arcminute Cosmology Bolometer Array Receiver

We describe the Arcminute Cosmology Bolometer Array Receiver (ACBAR); a multifrequency millimeter-wave receiver designed for observations of the Cosmic Microwave Background (CMB) and the Sunyaev-Zel'dovich effect in clusters of galaxies. The ACBAR focal plane consists of a 16-pixel, background-limited, 240 mK bolometer array that can be configured to observe simultaneously at 150, 220, 280, and 350 GHz. With 4-5' FWHM Gaussian beam sizes and a 3 degree azimuth chop, ACBAR is sensitive to a wide range of angular scales. ACBAR was installed on the 2 m Viper telescope at the South Pole in January 2001. We describe the design of the instrument and its performance during the 2001 and 2002 observing seasons.Comment: 59 pages, 16 figures -- updated to reflect version published in ApJ

High resolution CMB power spectrum from the complete ACBAR data set

In this paper, we present results from the complete set of cosmic microwave background (CMB) radiation temperature anisotropy observations made with the Arcminute Cosmology Bolometer Array Receiver (ACBAR) operating at 150 GHz. We include new data from the final 2005 observing season, expanding the number of detector-hours by 210% and the sky coverage by 490% over that used for the previous ACBAR release. As a result, the band-power uncertainties have been reduced by more than a factor of two on angular scales encompassing the third to fifth acoustic peaks as well as the damping tail of the CMB power spectrum. The calibration uncertainty has been reduced from 6% to 2.1% in temperature through a direct comparison of the CMB anisotropy measured by ACBAR with that of the dipole-calibrated WMAP5 experiment. The measured power spectrum is consistent with a spatially flat, LambdaCDM cosmological model. We include the effects of weak lensing in the power spectrum model computations and find that this significantly improves the fits of the models to the combined ACBAR+WMAP5 power spectrum. The preferred strength of the lensing is consistent with theoretical expectations. On fine angular scales, there is weak evidence (1.1 sigma) for excess power above the level expected from primary anisotropies. We expect any excess power to be dominated by the combination of emission from dusty protogalaxies and the Sunyaev-Zel'dovich effect (SZE). However, the excess observed by ACBAR is significantly smaller than the excess power at ell > 2000 reported by the CBI experiment operating at 30 GHz. Therefore, while it is unlikely that the CBI excess has a primordial origin; the combined ACBAR and CBI results are consistent with the source of the CBI excess being either the SZE or radio source contamination.Comment: Submitted to ApJ; Changed to apply a WMAP5-based calibration. The cosmological parameter estimation has been updated to include WMAP

MesonNet 2013 International Workshop. Mini-proceedings

The mini-proceedings of the MesonNet 2013 International Workshop held in Prague from June 17th to 19th, 2013, are presented. MesonNet is a research network within EU HadronPhysics3 project (1/2012 -- 12/2014). The web page of the conference, which contains all talks, can be found at http://ipnp.mff.cuni.cz/mesonnet13Comment: 106 pages, 53 contributions. Mini-proceedings of the MesonNet 2013 International Workshop. Editors: K. Kampf, A. Kupsc, and P. Masjua

Improved Measurements of the CMB Power Spectrum with ACBAR

We report improved measurements of temperature anisotropies in the cosmic microwave background (CMB) radiation made with the Arcminute Cosmology Bolometer Array Receiver (ACBAR). In this paper, we use a new analysis technique and include 30% more data from the 2001 and 2002 observing seasons than the first release to derive a new set of band-power measurements with significantly smaller uncertainties. The planet-based calibration used previously has been replaced by comparing the flux of RCW38 as measured by ACBAR and BOOMERANG to transfer the WMAP-based BOOMERANG calibration to ACBAR. The resulting power spectrum is consistent with the theoretical predictions for a spatially flat, dark energy dominated LCDM cosmology including the effects of gravitational lensing. Despite the exponential damping on small angular scales, the primary CMB fluctuations are detected with a signal-to-noise ratio of greater than 4 up to multipoles of l=2000. This increase in the precision of the fine-scale CMB power spectrum leads to only a modest decrease in the uncertainties on the parameters of the standard cosmological model. At high angular resolution, secondary anisotropies are predicted to be a significant contribution to the measured anisotropy. A joint analysis of the ACBAR results at 150 GHz and the CBI results at 30 GHz in the multipole range 2000 < l < 3000 shows that the power, reported by CBI in excess of the predicted primary anisotropy, has a frequency spectrum consistent with the thermal Sunyaev-Zel'dovich effect and inconsistent with primary CMB. The results reported here are derived from a subset of the total ACBAR data set; the final ACBAR power spectrum at 150 GHz will include 3.7 times more effective integration time and 6.5 times more sky coverage than is used here

Integrative gene-metabolite network with implemented causality deciphers informational fluxes of sulphur stress response

The systematic accumulation of gene expression data, although revolutionary, is insufficient in itself for an understanding of system-level physiology. In the post-genomic era, the next cognitive step is linking genes to biological processes and assembling a mosaic of data into global models of biosystem function. A dynamic network of informational flows in Arabidopsis plants perturbed by sulphur depletion is presented here. With the use of an original protocol, the first blosystem response network was reconstructed from a time series of transcript and metabolite profiles, which, on the one hand, integrates complex metabolic and transcript data and, on the other hand, possesses a causal relationship. Using the informational fluxes within this reconstruction, it was possible to link system perturbation to response endpoints. Robustness and stress tolerance, as consequences of scale-free network topology, and hubs, as potential controllers of homeostasis maintenance, were revealed. Communication paths of propagating system excitement directed to physiological endpoints, such as anthocyanin accumulation and enforced root formation were dissected from the network. An auxin regulatory circuit involved in the control of a hypo-sulphur stress response was uncovered

Functional Diversity and Structural Disorder in the Human Ubiquitination Pathway

The ubiquitin-proteasome system plays a central role in cellular regulation and protein quality control (PQC). The system is built as a pyramid of increasing complexity, with two E1 (ubiquitin activating), few dozen E2 (ubiquitin conjugating) and several hundred E3 (ubiquitin ligase) enzymes. By collecting and analyzing E3 sequences from the KEGG BRITE database and literature, we assembled a coherent dataset of 563 human E3s and analyzed their various physical features. We found an increase in structural disorder of the system with multiple disorder predictors (IUPred - E1: 5.97%, E2: 17.74%, E3: 20.03%). E3s that can bind E2 and substrate simultaneously (single subunit E3, ssE3) have significantly higher disorder (22.98%) than E3s in which E2 binding (multi RING-finger, mRF, 0.62%), scaffolding (6.01%) and substrate binding (adaptor/substrate recognition subunits, 17.33%) functions are separated. In ssE3s, the disorder was localized in the substrate/adaptor binding domains, whereas the E2-binding RING/HECT-domains were structured. To demonstrate the involvement of disorder in E3 function, we applied normal modes and molecular dynamics analyses to show how a disordered and highly flexible linker in human CBL (an E3 that acts as a regulator of several tyrosine kinase-mediated signalling pathways) facilitates long-range conformational changes bringing substrate and E2-binding domains towards each other and thus assisting in ubiquitin transfer. E3s with multiple interaction partners (as evidenced by data in STRING) also possess elevated levels of disorder (hubs, 22.90% vs. non-hubs, 18.36%). Furthermore, a search in PDB uncovered 21 distinct human E3 interactions, in 7 of which the disordered region of E3s undergoes induced folding (or mutual induced folding) in the presence of the partner. In conclusion, our data highlights the primary role of structural disorder in the functions of E3 ligases that manifests itself in the substrate/adaptor binding functions as well as the mechanism of ubiquitin transfer by long-range conformational transitions. © 2013 Bhowmick et al

Kinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast cancer.

Dysregulation of the PI3K-AKT-mTOR signaling network is a prominent feature of breast cancers. However, clinical responses to drugs targeting this pathway have been modest, possibly because of dynamic changes in cellular signaling that drive resistance and limit drug efficacy. Using a quantitative chemoproteomics approach, we mapped kinome dynamics in response to inhibitors of this pathway and identified signaling changes that correlate with drug sensitivity. Maintenance of AURKA after drug treatment was associated with resistance in breast cancer models. Incomplete inhibition of AURKA was a common source of therapy failure, and combinations of PI3K, AKT or mTOR inhibitors with the AURKA inhibitor MLN8237 were highly synergistic and durably suppressed mTOR signaling, resulting in apoptosis and tumor regression in vivo. This signaling map identifies survival factors whose presence limits the efficacy of targeted therapies and reveals new drug combinations that may unlock the full potential of PI3K-AKT-mTOR pathway inhibitors in breast cancer

γ-ray decay from neutron-bound and unbound states in Mo 95 and a novel technique for spin determination

The emission of γ rays from neutron-bound and neutron-unbound states in Mo95, populated in the Mo94(d,p) reaction, has been investigated. Charged particles and γ radiation were detected with arrays of annular silicon and Clover-type high-purity Germanium detectors, respectively. Utilizing p-γ and p-γ-γ coincidences, the Mo95 level scheme was greatly enhanced with 102 new transitions and 43 new states. It agrees well with shell model calculations for excitation energies below ≈2 MeV. From p-γ coincidence data, a new method for the determination of spins of discrete levels is proposed. The method exploits the suppression of high-angular momentum neutron emission from levels with high spins populated in the (d,p) reaction above the neutron separation energy. Spins for almost all Mo95 levels below 2 MeV (and for a few levels above) have been determined with this method

MiR-107 and MiR-185 Can Induce Cell Cycle Arrest in Human Non Small Cell Lung Cancer Cell Lines

Background: MicroRNAs (miRNAs) are short single stranded noncoding RNAs that suppress gene expression through either translational repression or degradation of target mRNAs. The annealing between messenger RNAs and 5' seed region of miRNAs is believed to be essential for the specific suppression of target gene expression. One miRNA can have several hundred different targets in a cell. Rapidly accumulating evidence suggests that many miRNAs are involved in cell cycle regulation and consequentially play critical roles in carcinogenesis. Methodology/Principal Findings: Introduction of synthetic miR-107 or miR-185 suppressed growth of the human non-small cell lung cancer cell lines. Flow cytometry analysis revealed these miRNAs induce a G1 cell cycle arrest in H1299 cells and the suppression of cell cycle progression is stronger than that by Let-7 miRNA. By the gene expression analyses with oligonucleotide microarrays, we find hundreds of genes are affected by transfection of these miRNAs. Using miRNA-target prediction analyses and the array data, we listed up a set of likely targets of miR-107 and miR-185 for G1 cell cycle arrest and validate a subset of them using real-time RT-PCR and immunoblotting for CDK6. Conclusions/Significance: We identified new cell cycle regulating miRNAs, miR-107 and miR-185, localized in frequently altered chromosomal regions in human lung cancers. Especially for miR-107, a large number of down-regulated genes are annotated with the gene ontology term 'cell cycle'. Our results suggest that these miRNAs may contribute to regulate cell cycle in human malignant tumors.Full Tex

Detection of regulator genes and eQTLs in gene networks

Genetic differences between individuals associated to quantitative phenotypic traits, including disease states, are usually found in non-coding genomic regions. These genetic variants are often also associated to differences in expression levels of nearby genes (they are "expression quantitative trait loci" or eQTLs for short) and presumably play a gene regulatory role, affecting the status of molecular networks of interacting genes, proteins and metabolites. Computational systems biology approaches to reconstruct causal gene networks from large-scale omics data have therefore become essential to understand the structure of networks controlled by eQTLs together with other regulatory genes, and to generate detailed hypotheses about the molecular mechanisms that lead from genotype to phenotype. Here we review the main analytical methods and softwares to identify eQTLs and their associated genes, to reconstruct co-expression networks and modules, to reconstruct causal Bayesian gene and module networks, and to validate predicted networks in silico.Comment: minor revision with typos corrected; review article; 24 pages, 2 figure