A Multi-Code Analysis Toolkit for Astrophysical Simulation Data

The analysis of complex multiphysics astrophysical simulations presents a unique and rapidly growing set of challenges: reproducibility, parallelization, and vast increases in data size and complexity chief among them. In order to meet these challenges, and in order to open up new avenues for collaboration between users of multiple simulation platforms, we present yt (available at http://yt.enzotools.org/), an open source, community-developed astrophysical analysis and visualization toolkit. Analysis and visualization with yt are oriented around physically relevant quantities rather than quantities native to astrophysical simulation codes. While originally designed for handling Enzo's structure adaptive mesh refinement (AMR) data, yt has been extended to work with several different simulation methods and simulation codes including Orion, RAMSES, and FLASH. We report on its methods for reading, handling, and visualizing data, including projections, multivariate volume rendering, multi-dimensional histograms, halo finding, light cone generation and topologically-connected isocontour identification. Furthermore, we discuss the underlying algorithms yt uses for processing and visualizing data, and its mechanisms for parallelization of analysis tasks.Comment: 18 pages, 6 figures, emulateapj format. Resubmitted to Astrophysical Journal Supplement Series with revisions from referee. yt can be found at http://yt.enzotools.org

Disturbances in Response Inhibition and Emotional Processing as Potential Pathways to Violence in Schizophrenia: A High-Density Event-Related Potential Study

OBJECTIVE: Increased susceptibility to emotional triggers and poor response inhibition are important in the etiology of violence in schizophrenia. Our goal was to evaluate abnormalities in neurophysiological mechanisms underlying response inhibition and emotional processing in violent patients with schizophrenia (VS) and 3 different comparison groups: nonviolent patients (NV), healthy controls (HC) and nonpsychotic violent subjects (NPV). METHODS: We recorded high-density Event-Related Potentials (ERPs) and behavioral responses during an Emotional Go/NoGo Task in 35 VS, 24 NV, 28 HC and 31 NPV subjects. We also evaluated psychiatric symptoms and impulsivity. RESULTS: The neural and behavioral deficits in violent patients were most pronounced when they were presented with negative emotional stimuli: They responded more quickly than NV when they made commission errors (ie, failure of inhibition), and evidenced N2 increases and P3 decreases. In contrast, NVs showed little change in reaction time or ERP amplitude with emotional stimuli. These N2 and P3 amplitude changes in VSs showed a strong association with greater impulsivity. Besides these group specific changes, VSs shared deficits with NV, mostly N2 reduction, and with violent nonpsychotic subjects, particularly P3 reduction. CONCLUSION: Negative affective triggers have a strong impact on violent patients with schizophrenia which may have both behavioral and neural manifestations. The resulting activation could interfere with response inhibition. The affective disruption of response inhibition, identified in this study, may index an important pathway to violence in schizophrenia and suggest new modes of treatment

Diabetes reversal by inhibition of the low-molecular-weight tyrosine phosphatase.

Obesity-associated insulin resistance plays a central role in type 2 diabetes. As such, tyrosine phosphatases that dephosphorylate the insulin receptor (IR) are potential therapeutic targets. The low-molecular-weight protein tyrosine phosphatase (LMPTP) is a proposed IR phosphatase, yet its role in insulin signaling in vivo has not been defined. Here we show that global and liver-specific LMPTP deletion protects mice from high-fat diet-induced diabetes without affecting body weight. To examine the role of the catalytic activity of LMPTP, we developed a small-molecule inhibitor with a novel uncompetitive mechanism, a unique binding site at the opening of the catalytic pocket, and an exquisite selectivity over other phosphatases. This inhibitor is orally bioavailable, and it increases liver IR phosphorylation in vivo and reverses high-fat diet-induced diabetes. Our findings suggest that LMPTP is a key promoter of insulin resistance and that LMPTP inhibitors would be beneficial for treating type 2 diabetes

The Unusual Infrared Object HDF-N J123656.3+621322

We describe an object in the Hubble Deep Field North with very unusual near-infrared properties. It is readily visible in Hubble Space Telescope NICMOS images at 1.6um and from the ground at 2.2um, but is undetected (with signal-to-noise <~ 2) in very deep WFPC2 and NICMOS data from 0.3 to 1.1um. The f_nu flux density drops by a factor >~ 8.3 (97.7% confidence) from 1.6 to 1.1um. The object is compact but may be slightly resolved in the NICMOS 1.6um image. In a low-resolution, near-infrared spectrogram, we find a possible emission line at 1.643um, but a reobservation at higher spectral resolution failed to confirm the line, leaving its reality in doubt. We consider various hypotheses for the nature of this object. Its colors are unlike those of known galactic stars, except perhaps the most extreme carbon stars or Mira variables with thick circumstellar dust shells. It does not appear to be possible to explain its spectral energy distribution as that of a normal galaxy at any redshift without additional opacity from either dust or intergalactic neutral hydrogen. The colors can be matched by those of a dusty galaxy at z >~ 2, by a maximally old elliptical galaxy at z >~ 3 (perhaps with some additional reddening), or by an object at z >~ 10 whose optical and 1.1um light have been suppressed by the intergalactic medium. Under the latter hypothesis, if the luminosity results from stars and not an AGN, the object would resemble a classical, unobscured protogalaxy, with a star formation rate >~ 100 M_sun/yr. Such UV-bright objects are evidently rare at 2 < z < 12.5, however, with a space density several hundred times lower than that of present-day L* galaxies.Comment: Accepted for publication in the Astrophysical Journal. 27 pages, LaTeX, with 7 figures (8 files); citations & references updated + minor format change

Hubble Space Telescope Imaging of the CFRS and LDSS Redshift Surveys---III. Field elliptical galaxies at 0.2 < z < 1.0

Surface photometry has been performed on a sample of 46 field elliptical galaxies. These galaxies are described well by a deVaucouleurs R^{1/4} profile. The sample was selected from the combined Canada-France and LDSS redshift surveys and spans the range 0.20 < z < 1.00. The relationship between galaxy half-light radius and luminosity evolves such that a galaxy of a given size is more luminous by Delta M_B=-0.97 \pm 0.14 mag at z=0.92 and the mean rest-frame color shifts blueward by Delta (U-V) =-0.68 \pm 0.11 at z=0.92 relative to the local cluster relations. Approximately 1/3 of these elliptical galaxies exhibit [OII] 3727 emission lines with equivalent widths > 15 angstroms indicating ongoing star formation. Estimated star-formation rates imply that \le 5% of the stellar mass in the elliptical galaxy population has been formed since z=1. We see no evidence for a decline in the space density of early-type galaxies with look-back time. The statistics and a comparison with local luminosity functions are both consistent with the view that the population of massive early-type galaxies was largely in place by z~1. This implies that merging is not required since that time to produce the present-day space density of elliptical galaxies.Comment: 21 pages plus 8 figures plus 5 tables. Accepted by Astrophysical Journa

High-throughput screen using a single-cell tyrosine phosphatase assay reveals biologically active inhibitors of tyrosine phosphatase CD45

Many cellular signaling events are regulated by tyrosine phosphorylation and mediated by the opposing actions of protein tyrosine kinases and phosphatases. Protein tyrosine phosphatases are emerging as drug targets, but poor cell permeability of inhibitors has limited the development of drugs targeting these enzymes [Tautz L, et al. (2006) Expert Opin Ther Targets 10:157–177]. Here we developed a method to monitor tyrosine phosphatase activity at the single-cell level and applied it to the identification of cell-permeable inhibitors. The method takes advantage of the fluorogenic properties of phosphorylated coumaryl amino propionic acid (pCAP), an analog of phosphotyrosine, which can be incorporated into peptides. Once delivered into cells, pCAP peptides were dephosphorylated by protein tyrosine phosphatases, and the resulting cell fluorescence could be monitored by flow cytometry and high-content imaging. The robustness and sensitivity of the assay was validated using peptides preferentially dephosphorylated by CD45 and T-cell tyrosine phosphatase and available inhibitors of these two enzymes. The assay was applied to high-throughput screening for inhibitors of CD45, an important target for autoimmunity and infectious diseases [Hermiston ML, et al. (2003) Annu Rev Immunol 21:107–137]. We identified four CD45 inhibitors that showed activity in T cells and macrophages. These results indicate that our assay can be applied to primary screening for inhibitors of CD45 and of other protein tyrosine phosphatases to increase the yield of biologically active inhibitors

Synthesis and characterisation of stereoregular cyclic poly(lactide)s

Poly(lactide)s is a biocompatible and biodegradable polymer available from renewable feed stocks and has therefore received a great deal of attention in recent years. Although significant research has been carried out examining its properties, architectural differences have received little attention. Notably, cyclic polymers are known to have strikingly different properties from their linear counterparts. This research will examine possible new routes for the synthesis of cyclic poly(lactide)s.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Assessment of platelet function in patients with stroke using multiple electrode platelet aggregometry: a prospective observational study

Background There is a link between high on-treatment platelet reactivity (HPR) and adverse vascular events in stroke. This study aimed to compare multiple electrode platelet aggregometry (MEA), in healthy subjects and ischaemic stroke patients, and between patients naive to antiplatelet drugs (AP) and those on regular low dose AP. We also aimed to determine prevalence of HPR at baseline and at 3–5 days after loading doses of aspirin. Methods Patients with first ever ischaemic stroke were age and sex-matched to a healthy control group. Three venous blood samples were collected: on admission before any treatment given (baseline); at 24 h and 3–5 days after standard treatment. MEA was determined using a Mutliplate® analyser and agonists tested were arachidonic acid (ASPI), adenosine diphosphate (ADP) and collagen (COL). Results Seventy patients (mean age 73 years [SD 13]; 42 men, 28 women) were age and sex-matched to 72 healthy subjects. Thirty-three patients were on antiplatelet drugs (AP) prior to stroke onset and 37 were AP-naive. MEA results for all agonists were significantly increased in AP-naive patients compared to healthy subjects: ADP 98 ± 31 vs 81 ± 24, p < 0.005; ASPI 117 ± 31 vs 98 ± 27, p < 0.005; COL 100 ± 25 vs 82 ± 20, p < 0.005. For patients on long term AP, 33% (10/30) of patients were considered aspirin-resistant. At 3–5 days following loading doses of aspirin, only 11.1% were aspirin resistant based on an ASPI cut-off value of 40 AU*min. Conclusions Many patients receiving low dose aspirin met the criteria of aspirin resistance but this was much lower at 3–5 days following loading doses of aspirin. Future studies are needed to establish the causes of HPR and potential benefits of individualizing AP treatment based on platelet function testing