Reactive astrocytes potentiate tumor aggressiveness in a murine glioma resection and recurrence model

Surgical resection is a universal component of glioma therapy. Little is known about the postoperative microenvironment due to limited preclinical models. Thus, we sought to develop a glioma resection and recurrence model in syngeneic immune-competent mice to understand how surgical resection influences tumor biology and the local microenvironment

Statistical-mechanical lattice models for protein-DNA binding in chromatin

Statistical-mechanical lattice models for protein-DNA binding are well established as a method to describe complex ligand binding equilibriums measured in vitro with purified DNA and protein components. Recently, a new field of applications has opened up for this approach since it has become possible to experimentally quantify genome-wide protein occupancies in relation to the DNA sequence. In particular, the organization of the eukaryotic genome by histone proteins into a nucleoprotein complex termed chromatin has been recognized as a key parameter that controls the access of transcription factors to the DNA sequence. New approaches have to be developed to derive statistical mechanical lattice descriptions of chromatin-associated protein-DNA interactions. Here, we present the theoretical framework for lattice models of histone-DNA interactions in chromatin and investigate the (competitive) DNA binding of other chromosomal proteins and transcription factors. The results have a number of applications for quantitative models for the regulation of gene expression.Comment: 19 pages, 7 figures, accepted author manuscript, to appear in J. Phys.: Cond. Mat

Incremental testing of the Community Multiscale Air Quality (CMAQ) modeling system version 4.7

This paper describes the scientific and structural updates to the latest release of the Community Multiscale Air Quality (CMAQ) modeling system version 4.7 (v4.7) and points the reader to additional resources for further details. The model updates were evaluated relative to observations and results from previous model versions in a series of simulations conducted to incrementally assess the effect of each change. The focus of this paper is on five major scientific upgrades: (a) updates to the heterogeneous N<sub>2</sub>O<sub>5</sub> parameterization, (b) improvement in the treatment of secondary organic aerosol (SOA), (c) inclusion of dynamic mass transfer for coarse-mode aerosol, (d) revisions to the cloud model, and (e) new options for the calculation of photolysis rates. Incremental test simulations over the eastern United States during January and August 2006 are evaluated to assess the model response to each scientific improvement, providing explanations of differences in results between v4.7 and previously released CMAQ model versions. Particulate sulfate predictions are improved across all monitoring networks during both seasons due to cloud module updates. Numerous updates to the SOA module improve the simulation of seasonal variability and decrease the bias in organic carbon predictions at urban sites in the winter. Bias in the total mass of fine particulate matter (PM<sub>2.5</sub>) is dominated by overpredictions of unspeciated PM<sub>2.5</sub> (PM<sub>other</sub>) in the winter and by underpredictions of carbon in the summer. The CMAQv4.7 model results show slightly worse performance for ozone predictions. However, changes to the meteorological inputs are found to have a much greater impact on ozone predictions compared to changes to the CMAQ modules described here. Model updates had little effect on existing biases in wet deposition predictions

Research Progress Reports: Fruit and Vegetable Processing and Technology Division, Department of Horticulture [1967]

Evaluation of snap bean varieties for processing / Wilbur A. Gould and William Hildebolt -- Evaluation of various grape cultivars for processing. I. Table wines ; Recommended fruit varieties for canning and freezing / J. F. Gallander -- Evaluation of tomato varieties for processing / W. A. Gould, J. R. Geisman, C. S. Parrott, J. H. McClelland and W. N. Brown -- The effect of different levels of sugar and acid on the quality of apple fruit juice blends / James Gallander and Harold Stammer -- Epidermal sloughing of snap beans as influenced by processing variables / William Hildebolt and W. A. Gould -- Effect of stannous chloride on the color of glass packed kraut / J. R. Geisman -- Proteins and enzymes in the apple fruit in relation to variety and maturation ; Proteins and enzymes in tomato fruits / Robert L. Clements -- Effect of food additives on quality of canned tomatoes / Wilbur A. Gould -- Effects of selective herbicides on the composition and quality of tomatoes / W. A. Gould, J. R. Geisman, E. K. Alban and John Deppen -- Trace levels of pesticide residues in agricultural commodities in marketing channels / W. A. Gould, J. R. Geisman, E. K. Alban, John Deppen, and P. van Pottlesberghe -- Removal of DDT residues by unit operations in preparing and processing spinach / J. R. Geisman, John Deppen and Benita Yao -- The use of chlorine dioxide in handling and holding mechanically harvested tomatoes / J. R. Geisman, Winston D. Bash, Edwin Schmidt, Jr., Linda Hamrick and W. A. Gould -- Effect of mechanical harvesting and handling of tomatoes on quality of canned tomatoes / Wilbur A. Gould, J. R. Geisman, Edwin Schmidt, Jr., John McClelland and W. N. Brow

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Extrapolating SMBH correlations down the mass scale: the case for IMBHs in globular clusters

Empirical evidence for both stellar mass black holes M_bh<10^2 M_sun) and supermassive black holes (SMBHs, M_bh>10^5 M_sun) is well established. Moreover, every galaxy with a bulge appears to host a SMBH, whose mass is correlated with the bulge mass, and even more strongly with the central stellar velocity dispersion sigma_c, the `M-sigma' relation. On the other hand, evidence for "intermediate-mass" black holes (IMBHs, with masses in the range 1^2 - 10^5 M_sun) is relatively sparse, with only a few mass measurements reported in globular clusters (GCs), dwarf galaxies and low-mass AGNs. We explore the question of whether globular clusters extend the M-sigma relationship for galaxies to lower black hole masses and find that available data for globular clusters are consistent with the extrapolation of this relationship. We use this extrapolated M-sigma relationship to predict the putative black hole masses of those globular clusters where existence of central IMBH was proposed. We discuss how globular clusters can be used as a constraint on theories making specific predictions for the low-mass end of the M-sigma relation.Comment: 14 pages, 3 figures, accepted for publication in Astrophysics and Space Science; fixed typos and a quote in Sec.