Matrix geometries and Matrix Models

We study a two parameter single trace 3-matrix model with SO(3) global symmetry. The model has two phases, a fuzzy sphere phase and a matrix phase. Configurations in the matrix phase are consistent with fluctuations around a background of commuting matrices whose eigenvalues are confined to the interior of a ball of radius R=2.0. We study the co-existence curve of the model and find evidence that it has two distinct portions one with a discontinuous internal energy yet critical fluctuations of the specific heat but only on the low temperature side of the transition and the other portion has a continuous internal energy with a discontinuous specific heat of finite jump. We study in detail the eigenvalue distributions of different observables.Comment: 20 page

Phase 1b study of pegylated arginine deiminase (ADI-PEG 20) plus Pembrolizumab in advanced solid cancers

[[abstract]]Background Pegylated arginine deiminase (ADI-PEG 20) is a metabolism-based strategy that depletes arginine, resulting in tumoral stress and cytotoxicity. Preclinically, ADI-PEG 20 modulates T-cell activity and enhances the therapeutic efficacy of programmed death-1 (PD-1) inhibition. Methods A phase 1b study, including a dose-escalation cohort and an expansion cohort, was undertaken to explore the effects of ADI-PEG 20 in combination with pembrolizumab, an anti-PD-1 antibody, for safety, pharmacodynamics, and response. CD3 levels and programmed death-ligand 1 (PD-L1) expression were assessed in paired biopsies collected prior to and after ADI-PEG 20 treatment but before pembrolizumab. Results Twenty-five patients, nine in the dose-escalation cohort and sixteen in the expansion cohort, were recruited. Treatment was feasible with adverse events consistent with those known for each agent, except for Grade 3/4 neutropenia which was higher than expected, occurring in 10/25 (40%) patients. Mean arginine levels were suppressed for 1-3 weeks, but increased gradually. CD3(+) T cells increased in 10/12 (83.3%) subjects following ADI-PEG 20 treatment, including in three partial responders (p = .02). PD-L1 expression was low and increased in 3/10 (30%) of subjects. Partial responses occurred in 6/25 (24%) heavily pretreated patients, in both argininosuccinate synthetase 1 proficient and deficient subjects. Conclusions The immunometabolic combination was safe with the caveat that the incidence of neutropenia might be increased compared with either agent alone. ADI-PEG 20 treatment increased T cell infiltration in the low PD-L1 tumor microenvironment. The recommended phase 2 doses are 36 mg/m(2) weekly for ADI-PEG 20 and 200 mg every 3 weeks for pembrolizumab

The Effects of Aging on the Molecular and Cellular Composition of the Prostate Microenvironment

Advancing age is associated with substantial increases in the incidence rates of common diseases affecting the prostate gland including benign prostatic hyperplasia (BPH) and prostate carcinoma. The prostate is comprised of a functional secretory epithelium, a basal epithelium, and a supporting stroma comprised of structural elements, and a spectrum of cell types that includes smooth muscle cells, fibroblasts, and inflammatory cells. As reciprocal interactions between epithelium and stromal constituents are essential for normal organogenesis and serve to maintain normal functions, discordance within the stroma could permit or promote disease processes. In this study we sought to identify aging-associated alterations in the mouse prostate microenvironment that could influence pathology.We quantitated transcript levels in microdissected glandular-adjacent stroma from young (age 4 months) and old (age 20-24 months) C57BL/6 mice, and identified a significant change in the expression of 1259 genes (p<0.05). These included increases in transcripts encoding proteins associated with inflammation (e.g., Ccl8, Ccl12), genotoxic/oxidative stress (e.g., Apod, Serpinb5) and other paracrine-acting effects (e.g., Cyr61). The expression of several collagen genes (e.g., Col1a1 and Col3a1) exhibited age-associated declines. By histology, immunofluorescence, and electron microscopy we determined that the collagen matrix is abundant and disorganized, smooth muscle cell orientation is disordered, and inflammatory infiltrates are significantly increased, and are comprised of macrophages, T cells and, to a lesser extent, B cells.These findings demonstrate that during normal aging the prostate stroma exhibits phenotypic and molecular characteristics plausibly contributing to the striking age associated pathologies affecting the prostate

Understanding atmospheric organic aerosols via factor analysis of aerosol mass spectrometry: a review

Organic species are an important but poorly characterized constituent of airborne particulate matter. A quantitative understanding of the organic fraction of particles (organic aerosol, OA) is necessary to reduce some of the largest uncertainties that confound the assessment of the radiative forcing of climate and air quality management policies. In recent years, aerosol mass spectrometry has been increasingly relied upon for highly time-resolved characterization of OA chemistry and for elucidation of aerosol sources and lifecycle processes. Aerodyne aerosol mass spectrometers (AMS) are particularly widely used, because of their ability to quantitatively characterize the size-resolved composition of submicron particles (PM1). AMS report the bulk composition and temporal variations of OA in the form of ensemble mass spectra (MS) acquired over short time intervals. Because each MS represents the linear superposition of the spectra of individual components weighed by their concentrations, multivariate factor analysis of the MS matrix has proved effective at retrieving OA factors that offer a quantitative and simplified description of the thousands of individual organic species. The sum of the factors accounts for nearly 100% of the OA mass and each individual factor typically corresponds to a large group of OA constituents with similar chemical composition and temporal behavior that are characteristic of different sources and/or atmospheric processes. The application of this technique in aerosol mass spectrometry has grown rapidly in the last six years. Here we review multivariate factor analysis techniques applied to AMS and other aerosol mass spectrometers, and summarize key findings from field observations. Results that provide valuable information about aerosol sources and, in particular, secondary OA evolution on regional and global scales are highlighted. Advanced methods, for example a-priori constraints on factor mass spectra and the application of factor analysis to combined aerosol and gas phase data are discussed. Integrated analysis of worldwide OA factors is used to present a holistic regional and global description of OA. Finally, different ways in which OA factors can constrain global and regional models are discussed

Short-Lived Trace Gases in the Surface Ocean and the Atmosphere

The two-way exchange of trace gases between the ocean and the atmosphere is important for both the chemistry and physics of the atmosphere and the biogeochemistry of the oceans, including the global cycling of elements. Here we review these exchanges and their importance for a range of gases whose lifetimes are generally short compared to the main greenhouse gases and which are, in most cases, more reactive than them. Gases considered include sulphur and related compounds, organohalogens, non-methane hydrocarbons, ozone, ammonia and related compounds, hydrogen and carbon monoxide. Finally, we stress the interactivity of the system, the importance of process understanding for modeling, the need for more extensive field measurements and their better seasonal coverage, the importance of inter-calibration exercises and finally the need to show the importance of air-sea exchanges for global cycling and how the field fits into the broader context of Earth System Science

Effects of aging and dietary supplementation with polyphenols from Pinus taeda hydrolysed lignin on quality parameters, fatty acid profile and oxidative stability of beef

Context: The inclusion of Pinus taeda hydrolysed lignin (PTHL) in beef diets could improve quality and stability of meat, but effects could vary through the aging period (AP). Aim: The aim was to evaluate the effects of the PTHL inclusion in the diet of finishing beef cattle on meat quality, fatty acid composition and oxidative stability at Days 1, 8, 11 and 15 of aging. Methods: Forty Limousin bulls (340 ± 42 kg) were fed ad libitum on a total mixed ration (TMR). The control group received exclusively TMR for 120 days, while the experimental group received the same TMR as the control group but supplemented with PTHL (Oxifenol, I-Green, Padua, Italy; 35 g/day per head at 1–90 days and 70 g/day per head at 91–120 days). Key results: Diet did not influence the chemical composition, pH, cooking loss, Warner–Bratzler shear force and hydroperoxide content. The Warner–Bratzler shear force (P &lt; 0.001) decreased, while lightness (P &lt; 0.01) and hydroperoxides (P &lt; 0.001) increased through the aging period. Thiobarbituric acid reactive substances were similar for both diets at 1 and 15 days. However, thiobarbituric acid reactive substances at 8 and 11 days were higher for control than for the PTHL diet (P = 0.023 for interaction). Protein carbonyls were higher for control than for the PTHL diet at 8 days (P = 0.003 for interaction), but similar for both diets for the other dates. Saturated, monounsaturated and polyunsaturated fatty acids varied through the AP with PTHL diet, while no changes were observed with control diet (P &lt; 0.01 for interactions). At 11 days, the n-6 : n-3 ratio passed from being the minimum value with the PTHL diet to be the maximum with control diet (P &lt; 0.01 for interaction). Conclusions: The effects of PTHL inclusion in bull finishing diets depends on the AP but, generally, may result in beef with meat with beneficial effects on human health. Implications: Including PTHL in the diet of finishing bulls can be useful to improve meat quality, favouring the use of natural waste substances deriving from vegetal production