Non-Equilibrium Chemistry and Destruction of CO by X-ray Flares

Sources of X-rays such as active galactic nuclei and X-ray binaries are often variable by orders of magnitude in luminosity over timescales of years. During and after these flares the surrounding gas is out of chemical and thermal equilibrium. We introduce a new implementation of X-ray radiative transfer coupled to a time-dependent chemical network for use in 3D magnetohydrodynamical simulations. A static fractal molecular cloud is irradiated with X-rays of different intensity, and the chemical and thermal evolution of the cloud are studied. For a simulated $10^5$ M$_\odot$ fractal cloud an X-ray flux $<0.01$ erg cm$^{-2}$ s$^{-1}$ allows the cloud to remain molecular, whereas most of the CO and H$_2$ are destroyed for a flux of $>1$ erg cm$^{-2}$ s$^{-1}$. The effects of an X-ray flare, which suddenly increases the X-ray flux by $10^5 \times$ are then studied. A cloud exposed to a bright flare has 99% of its CO destroyed in 10-20 years, whereas it takes $>10^3$ years for 99% of the H$_2$ to be destroyed. CO is primarily destroyed by locally generated far-UV emission from collisions between non-thermal electrons and H$_2$; He$^+$ only becomes an important destruction agent when the CO abundance is already very small. After the flare is over, CO re-forms and approaches its equilibrium abundance after $10^3-10^5$ years. This implies that molecular clouds close to Sgr A$^*$ in the Galactic Centre may still be out of chemical equilibrium, and we predict the existence of clouds near flaring X-ray sources in which CO has been mostly destroyed but H is fully molecular.Comment: Accepted for publication in MNRAS; this version has some additions following the refereeing proces

On the resolution requirements for modelling molecular gas formation in solar neighbourhood conditions

The formation of molecular hydrogen (H$_2$) and carbon monoxide (CO) is sensitive to the volume and column density distribution of the turbulent interstellar medium. In this paper, we study H$_2$ and CO formation in a large set of hydrodynamical simulations of periodic boxes with driven supersonic turbulence, as well as in colliding flows with the \textsc{Flash} code. The simulations include a non-equilibrium chemistry network, gas self-gravity, and diffuse radiative transfer. We investigate the spatial resolution required to obtain a converged H$_2$ and CO mass fraction and formation history. From the numerical tests we find that H$_2$ converges at a spatial resolution of $\lesssim0.2$~pc, while the required resolution for CO convergence is $\lesssim 0.04$~pc in gas with solar metallicity which is subject to a solar neighbourhood interstellar radiation field. We derive two critical conditions from our numerical results: the simulation has to at least resolve the densities at which (1) the molecule formation time in each cell in the computational domain is equal to the dissociation time, and (2) the formation time is equal to the the typical cell crossing time. For both H$_2$ and CO, the second criterion is more restrictive. The formulae we derive can be used to check whether molecule formation is converged in any given simulation.Comment: 22 pages, 21 figures, submitte

A Novel Liquid Multi-Phytonutrient Supplement Demonstrates DNA-Protective Effects

This study explored the DNA protective (anti-mutagenic) effects of an oral, liquid, multi-phytonutrient dietary supplement containing a proprietary blend of fruits, vegetables and aloe vera concentrated components in addition to a proprietary catechin complex from green tea (VIBE Cardiac & Life, Eniva Nutraceuticals, Anoka, MN; herein described as “VIBE”). This study tested the hypothesis that VIBE would reduce DNA damage in skin cells exposed to UVR. Human epidermal cells, from the cell line A431NS, were treated with 0% (control), 0.125%, 0.5%, 1% and 2% VIBE, and then exposed to 240 J/m2 UVR. The amount of DNA damage was assessed using the COMET assay. At each concentration tested, a significantly smaller amount of DNA damage was measured by the COMET assay for the VIBE treated cells compared to the control cells exposed to UVR without VIBE. The dose response curves showed a maximal response at 0.5% VIBE with a threefold reduction in COMET tail density compared to the control samples without VIBE (p < 0.001). Additional research is warranted in human clinical trials to further explore the results of this study which demonstrated the DNA protective and anti-mutagenic effects of VIBE for human skin cells exposed to UVR-induced DNA damage

Associations of plasma fibrinogen assays, C-reactive protein and interleukin-6 with previous myocardial infarction

Background: The association of plasma fibrinogen with myocardial infarction (MI) may (like that of C-reactive protein, CRP) be a marker of subclinical inflammation, mediated by cytokines such as interleukin-6 (IL-6). There are well- recognized discrepancies between commonly performed fibrinogen assays. Increased ratio of clottable fibrinogen to intact fibrinogen (measured by a recently developed immunoassay) has been proposed as a measure of hyperfunctional fibrinogen, and is elevated in acute MI.&lt;br/&gt; Objective: To compare the associations of intact fibrinogen and four routine fibrinogen assays (two von Clauss assays; one prothrombin-time derived; and one immunonephelometric) in a case-control study of previous MI. Patients/methods: Cases (n = 399) were recruited 3-9 months after their event; 413 controls were age- and sex-matched from the case-control study local population. Intact fibrinogen was measured in 50% of subjects. Results: All routine fibrinogen assays showed high intercorrelations (r = 0.82-0.93) and significant (P lt 0.0001) increased mean levels in cases vs. controls. These four routine assays correlated only moderately with intact fibrinogen (r = 0.45-0.62), while intact fibrinogen showed only a small, nonsignificant increase in cases vs. controls. Consequently, the ratio of each of the four routine assays to the intact fibrinogen assay was significantly higher (P lt 0.0003) in cases vs. controls. Each fibrinogen assay correlated with plasma levels of CRP and IL-6 (which were also elevated in cases vs. controls). Each routine fibrinogen assay remained significantly elevated in cases vs. controls after further adjustment for C-reactive protein and interleukin-6. Conclusions: These data provide evidence for acquired, increased hyperfunctional plasma fibrinogen in MI survivors, which is not associated with markers of inflammatory reactions. The causes and significance of these results remain to be established in prospective studies

Reporters to mark and eliminate basal or luminal epithelial cells in culture and in vivo

The contribution of basal and luminal cells to cancer progression and metastasis is poorly understood. We report generation of reporter systems driven by either keratin-14 (K14) or keratin-8 (K8) promoter that not only express a fluorescent protein but also an inducible suicide gene. Transgenic mice express the reporter genes in the right cell compartments of mammary gland epithelia and respond to treatment with toxins. In addition, we engineered the reporters into 4T1 metastatic mouse tumor cell line and demonstrate that K14+ cells, but not K14- or K8+, are both highly invasive in three-dimensional (3D) culture and metastatic in vivo. Treatment of cells in culture, or tumors in mice, with reporter-targeting toxin inhibited both invasive behavior and metastasis in vivo. RNA sequencing (RNA-seq), secretome, and epigenome analysis of K14+ and K14- cells led to the identification of amphoterin-induced protein 2 (Amigo2) as a new cell invasion driver whose expression correlated with decreased relapse-free survival in patients with TP53 wild-type (WT) breast cancer

Study of the effect of contact force model on the dynamic response of mechanical systems with dry clearance joints : computational and experimental approaches

The main objective of this work is to present a computational and experimental study on the contact forces developed in revolute clearance joints. For this purpose, a well-known slider-crank mechanism with a revolute clearance joint between the connecting rod and slider is utilized. The intra-joint contact forces that generated at this clearance joints are computed by considered several different elastic and dissipative approaches, namely those based on the Hertz contact theory and the ESDU tribology-based for cylindrical contacts, along with a hysteresis-type dissipative damping. The normal contact force is augmented with the dry Coulomb’s friction force. In addition, an experimental apparatus is use to obtained some experimental data in order to verify and validate the computational models. From the outcomes reported in this paper, it is concluded that the selection of the appropriate contact force model with proper dissipative damping plays a significant role in the dynamic response of mechanical systems involving contact events at low or moderate impact velocities.Fundação para a Ciência e a Tecnologia (FCT

cis-Expression QTL Analysis of Established Colorectal Cancer Risk Variants in Colon Tumors and Adjacent Normal Tissue

Genome-wide association studies (GWAS) have identified 19 risk variants associated with colorectal cancer. As most of these risk variants reside outside the coding regions of genes, we conducted cis-expression quantitative trait loci (cis-eQTL) analyses to investigate possible regulatory functions on the expression of neighboring genes. Forty microsatellite stable and CpG island methylator phenotype-negative colorectal tumors and paired adjacent normal colon tissues were used for genome-wide SNP and gene expression profiling. We found that three risk variants (rs10795668, rs4444235 and rs9929218, using near perfect proxies rs706771, rs11623717 and rs2059252, respectively) were significantly associated (FDR q-value ≤0.05) with expression levels of nearby genes (<2 Mb up- or down-stream). We observed an association between the low colorectal cancer risk allele (A) for rs10795668 at 10p14 and increased expression of ATP5C1 (q = 0.024) and between the colorectal cancer high risk allele (C) for rs4444235 at 14q22.2 and increased expression of DLGAP5 (q = 0.041), both in tumor samples. The colorectal cancer low risk allele (A) for rs9929218 at 16q22.1 was associated with a significant decrease in expression of both NOL3 (q = 0.017) and DDX28 (q = 0.046) in the adjacent normal colon tissue samples. Of the four genes, DLGAP5 and NOL3 have been previously reported to play a role in colon carcinogenesis and ATP5C1 and DDX28 are mitochondrial proteins involved in cellular metabolism and division, respectively. The combination of GWAS findings, prior functional studies, and the cis-eQTL analyses described here suggest putative functional activities for three of the colorectal cancer GWAS identified risk loci as regulating the expression of neighboring genes