457 research outputs found
Improving the scalability of parallel N-body applications with an event driven constraint based execution model
The scalability and efficiency of graph applications are significantly
constrained by conventional systems and their supporting programming models.
Technology trends like multicore, manycore, and heterogeneous system
architectures are introducing further challenges and possibilities for emerging
application domains such as graph applications. This paper explores the space
of effective parallel execution of ephemeral graphs that are dynamically
generated using the Barnes-Hut algorithm to exemplify dynamic workloads. The
workloads are expressed using the semantics of an Exascale computing execution
model called ParalleX. For comparison, results using conventional execution
model semantics are also presented. We find improved load balancing during
runtime and automatic parallelism discovery improving efficiency using the
advanced semantics for Exascale computing.Comment: 11 figure
Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1
Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases
The Underestimation Of Egocentric Distance: Evidence From Frontal Matching Tasks
There is controversy over the existence, nature, and cause of error in egocentric distance judgments. One proposal is that the systematic biases often found in explicit judgments of egocentric distance along the ground may be related to recently observed biases in the perceived declination of gaze (Durgin & Li, Attention, Perception, & Psychophysics, in press), To measure perceived egocentric distance nonverbally, observers in a field were asked to position themselves so that their distance from one of two experimenters was equal to the frontal distance between the experimenters. Observers placed themselves too far away, consistent with egocentric distance underestimation. A similar experiment was conducted with vertical frontal extents. Both experiments were replicated in panoramic virtual reality. Perceived egocentric distance was quantitatively consistent with angular bias in perceived gaze declination (1.5 gain). Finally, an exocentric distance-matching task was contrasted with a variant of the egocentric matching task. The egocentric matching data approximate a constant compression of perceived egocentric distance with a power function exponent of nearly 1; exocentric matches had an exponent of about 0.67. The divergent pattern between egocentric and exocentric matches suggests that they depend on different visual cues
Epigenetic mechanisms in virus-induced tumorigenesis
About 15–20% of human cancers worldwide have viral etiology. Emerging data clearly indicate that several human DNA and RNA viruses, such as human papillomavirus, Epstein–Barr virus, Kaposi’s sarcoma-associated herpesvirus, hepatitis B virus, hepatitis C virus, and human T-cell lymphotropic virus, contribute to cancer development. Human tumor-associated viruses have evolved multiple molecular mechanisms to disrupt specific cellular pathways to facilitate aberrant replication. Although oncogenic viruses belong to different families, their strategies in human cancer development show many similarities and involve viral-encoded oncoproteins targeting the key cellular proteins that regulate cell growth. Recent studies show that virus and host interactions also occur at the epigenetic level. In this review, we summarize the published information related to the interactions between viral proteins and epigenetic machinery which lead to alterations in the epigenetic landscape of the cell contributing to carcinogenesis
The effector T cell response to influenza infection
Influenza virus infection induces a potent initial innate immune response, which serves to limit the extent of viral replication and virus spread. However, efficient (and eventual) viral clearance within the respiratory tract requires the subsequent activation, rapid proliferation, recruitment, and expression of effector activities by the adaptive immune system, consisting of antibody producing B cells and influenza-specific T lymphocytes with diverse functions. The ensuing effector activities of these T lymphocytes ultimately determine (along with antibodies) the capacity of the host to eliminate the viruses and the extent of tissue damage. In this review, we describe this effector T cell response to influenza virus infection. Based on information largely obtained in experimental settings (i.e., murine models), we will illustrate the factors regulating the induction of adaptive immune T cell responses to influenza, the effector activities displayed by these activated T cells, the mechanisms underlying the expression of these effector mechanisms, and the control of the activation/differentiation of these T cells, in situ, in the infected lungs
Production of dust by massive stars at high redshift
The large amounts of dust detected in sub-millimeter galaxies and quasars at
high redshift pose a challenge to galaxy formation models and theories of
cosmic dust formation. At z > 6 only stars of relatively high mass (> 3 Msun)
are sufficiently short-lived to be potential stellar sources of dust. This
review is devoted to identifying and quantifying the most important stellar
channels of rapid dust formation. We ascertain the dust production efficiency
of stars in the mass range 3-40 Msun using both observed and theoretical dust
yields of evolved massive stars and supernovae (SNe) and provide analytical
expressions for the dust production efficiencies in various scenarios. We also
address the strong sensitivity of the total dust productivity to the initial
mass function. From simple considerations, we find that, in the early Universe,
high-mass (> 3 Msun) asymptotic giant branch stars can only be dominant dust
producers if SNe generate <~ 3 x 10^-3 Msun of dust whereas SNe prevail if they
are more efficient. We address the challenges in inferring dust masses and
star-formation rates from observations of high-redshift galaxies. We conclude
that significant SN dust production at high redshift is likely required to
reproduce current dust mass estimates, possibly coupled with rapid dust grain
growth in the interstellar medium.Comment: 72 pages, 9 figures, 5 tables; to be published in The Astronomy and
Astrophysics Revie
Operation and performance of the ATLAS Tile Calorimeter in Run 1
The Tile Calorimeter is the hadron calorimeter covering the central region of the ATLAS experiment at the Large Hadron Collider. Approximately 10,000 photomultipliers collect light from scintillating tiles acting as the active material sandwiched between slabs of steel absorber. This paper gives an overview of the calorimeter’s performance during the years 2008–2012 using cosmic-ray muon events and proton–proton collision data at centre-of-mass energies of 7 and 8TeV with a total integrated luminosity of nearly 30 fb−1. The signal reconstruction methods, calibration systems as well as the detector operation status are presented. The energy and time calibration methods performed excellently, resulting in good stability of the calorimeter response under varying conditions during the LHC Run 1. Finally, the Tile Calorimeter response to isolated muons and hadrons as well as to jets from proton–proton collisions is presented. The results demonstrate excellent performance in accord with specifications mentioned in the Technical Design Report
Search for supersymmetry in events with four or more leptons in √s =13 TeV pp collisions with ATLAS
Results from a search for supersymmetry in events with four or more charged leptons (electrons, muons and taus) are presented. The analysis uses a data sample corresponding to 36.1 fb −1 of proton-proton collisions delivered by the Large Hadron Collider at s √ =13 TeV and recorded by the ATLAS detector. Four-lepton signal regions with up to two hadronically decaying taus are designed to target a range of supersymmetric scenarios that can be either enriched in or depleted of events involving the production and decay of a Z boson. Data yields are consistent with Standard Model expectations and results are used to set upper limits on the event yields from processes beyond the Standard Model. Exclusion limits are set at the 95% confidence level in simplified models of General Gauge Mediated supersymmetry, where higgsino masses are excluded up to 295 GeV. In R -parity-violating simplified models with decays of the lightest supersymmetric particle to charged leptons, lower limits of 1.46 TeV, 1.06 TeV, and 2.25 TeV are placed on wino, slepton and gluino masses, respectively
Measurement of the t¯tZ and t¯tW cross sections in proton-proton collisions at √s=13 TeV with the ATLAS detector
A measurement of the associated production of a top-quark pair (t¯t) with a vector boson (W, Z) in proton-proton collisions at a center-of-mass energy of 13 TeV is presented, using 36.1 fb−1 of integrated luminosity collected by the ATLAS detector at the Large Hadron Collider. Events are selected in channels with two same- or opposite-sign leptons (electrons or muons), three leptons or four leptons, and each channel is further divided into multiple regions to maximize the sensitivity of the measurement. The t¯tZ and t¯tW production cross sections are simultaneously measured using a combined fit to all regions. The best-fit values of the production cross sections are σt¯tZ=0.95±0.08stat±0.10syst pb and σt¯tW=0.87±0.13stat±0.14syst pb in agreement with the Standard Model predictions. The measurement of the t¯tZ cross section is used to set constraints on effective field theory operators which modify the t¯tZ vertex
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