Abundance ratios of OH/CO and HCO+/CO as probes of the cosmic ray ionization rate in diffuse clouds

The cosmic-ray ionization rate (CRIR, $\zeta_2$) is one of the key parameters controlling the formation and destruction of various molecules in molecular clouds. However, the current most commonly used CRIR tracers, such as H$_3^+$, OH$^+$, and H$_2$O$^+$, are hard to detect and require the presence of background massive stars for absorption measurements. In this work, we propose an alternative method to infer the CRIR in diffuse clouds using the abundance ratios of OH/CO and HCO$^+$/CO. We have analyzed the response of chemical abundances of CO, OH, and HCO$^+$ on various environmental parameters of the interstellar medium in diffuse clouds and found that their abundances are proportional to $\zeta_2$. Our analytic expressions give an excellent calculation of the abundance of OH for $\zeta_2$ $\leq$10$^{-15}$ s$^{-1}$, which are potentially useful for modelling chemistry in hydrodynamical simulations. The abundances of OH and HCO$^+$ were found to monotonically decrease with increasing density, while the CO abundance shows the opposite trend. With high-sensitivity absorption transitions of both CO (1--0) and (2--1) lines from ALMA, we have derived the H$_2$ number densities ($n_{\rm H_2}$) toward 4 line-of-sights (LOSs); assuming a kinetic temperature of $T_{\rm k}=50\,{\rm K}$, we find a range of (0.14$\pm$0.03--1.2$\pm$0.1)$\times$10$^2$ cm$^{-3}$}. By comparing the observed and modelled HCO$^+$/CO ratios, we find that $\zeta_2$ in our diffuse gas sample is in the { range of $1.0_{-1.0}^{+14.8}$ $\times$10$^{-16}- 2.5_{-2.4}^{+1.4}$ $\times$10$^{-15}$ s$^{-1}$. This is $\sim$2 times higher than the average value measured at higher extinction, supporting an attenuation of CRs as suggested by theoretical models.Comment: 22 pages, 9 figures, accepted by Ap

Increased p38-MAPK is responsible for chemotherapy resistance in human gastric cancer cells

<p>Abstract</p> <p>Background</p> <p>Chemoresistance is one of the main obstacles to successful cancer therapy and is frequently associated with Multidrug resistance (MDR). Many different mechanisms have been suggested to explain the development of an MDR phenotype in cancer cells. One of the most studied mechanisms is the overexpression of P-glycoprotein (P-gp), which is a product of the <it>MDR1 </it>gene. Tumor cells often acquire the drug-resistance phenotype due to upregulation of the <it>MDR1 </it>gene. Overexpression of <it>MDR1 </it>gene has often been reported in primary gastric adenocarcinoma.</p> <p>Methods</p> <p>This study investigated the role of p38-MAPK signal pathway in vincristine-resistant SGC7901/VCR cells. P-gp and MDR1 RNA were detected by Western blot analysis and RT-PCR amplification. Mitgen-activated protein kinases and function of P-gp were demonstrated by Western blot and FACS Aria cytometer analysis. Ap-1 activity and cell apoptosis were detected by Dual-Luciferase Reporter Assay and annexin V-PI dual staining.</p> <p>Results</p> <p>The vincristine-resistant SGC7901/VCR cells with increased expression of the multidrug-resistance 1 (<it>MDR1</it>) gene were resistant to P-gp-related drug and P-gp-unrelated drugs. Constitutive increases of phosphorylated p38-MAPK and AP-1 activities were also found in the drug-resistant cells. Inhibition of p38-MAPK by SB202190 reduced activator protein-1 (AP-1) activity and <it>MDR1 </it>expression levels and increased the sensitivity of SGC7901/VCR cells to chemotherapy.</p> <p>Conclusion</p> <p>Activation of the p38-MAPK pathway might be responsible for the modulation of P-glycoprotein-mediated and P-glycoprotein-unmediated multidrug resistance in the SGC7901/VCR cell line.</p

Dependence of Chemical Abundance on the Cosmic Ray Ionization Rate in IC 348

Ions (e.g., H$_3^+$, H$_2$O$^+$) have been used extensively to quantify the cosmic-ray ionization rate (CRIR) in diffuse sightlines. However, measurements of CRIR in low-to-intermediate density gas environments are rare, especially when background stars are absent. In this work, we combine molecular line observations of CO, OH, CH, and HCO$^+$ in the star-forming cloud IC~348, and chemical models to constrain the value of CRIR and study the response of the chemical abundances distribution. The cloud boundary is found to have an $A_{\rm V}$ of approximately 4 mag. From the interior to the exterior of the cloud, the observed $^{13}$CO line intensities drop by an order of magnitude. The calculated average abundance of $^{12}$CO (assuming $^{12}$C/$^{13}$C = 65) is (1.2$\pm$0.9) $\times$10$^{-4}$, which increases by a factor of 6 from the interior to the outside regions. The average abundance of CH (3.3$\pm$0.7 $\times$ 10$^{-8}$) is in good agreement with previous findings in diffuse and translucent clouds ($A_{\rm V}$ $<$ 5 mag). However, we did not find a decline in CH abundance in regions of high extinction ($A_{\rm V}\simeq$8 mag) as previously reported in Taurus. By comparing the observed molecular abundances and chemical models, we find a decreasing trend of CRIR as $A_{\rm V}$ increases. The inferred CRIR of $\zeta_{cr}$ = (4.7$\pm$1.5) $\times$ 10$^{-16}$ s$^{-1}$ at low $A_{\rm V}$ is consistent with H$^+_3$ measurements toward two nearby massive stars.Comment: 21 pages, 11 figures. Submitted to Ap