Exploratory Study of the X-Ray Properties of Quasars With Intrinsic Narrow Absorption Lines

We have used archival Chandra and XMM-Newton observations of quasars hosting intrinsic narrow UV absorption lines (intrinsic NALs) to carry out an exploratory survey of their X-ray properties. Our sample consists of three intrinsic-NAL quasars and one "mini-BAL" quasar, plus four quasars without intrinsic absorption lines for comparison. These were drawn in a systematic manner from an optical/UV-selected sample. The X-ray properties of intrinsic-NAL quasars are indistinguishable from those of "normal" quasars. We do not find any excess absorption in quasars with intrinsic NALs, with upper limits of a few times 10^22 cm^-2. We compare the X-ray and UV properties of our sample quasars by plotting the equivalent width and blueshift velocity of the intrinsic NALs and the X-ray spectral index against the "optical-to-X-ray" slope, alpha-ox. When BAL quasars and other AGNs with intrinsic NALs are included, the plots suggest that intrinsic-NAL quasars form an extension of the BAL sequences and tend to bridge the gap between BAL and "normal" quasars. Observations of larger samples of intrinsic-NAL quasars are needed to verify these conclusions. We also test two competing scenarios for the location of the NAL gas in an accretion-disk wind. Our results strongly support a location of the NAL gas at high latitudes above the disk, closer to the disk axis than the dense BAL wind. We detect excess X-ray absorption only in Q0014+8118, which does not host intrinsic NALs. The absorbing medium very likely corresponds to an intervening system at z=1.1, which also produces strong absorption lines in the rest-frame UV spectrum of this quasar. In the appendix we discuss the connection between UV and X-ray attenuation and its effect on alpha-ox.Comment: Accepted by the Astrophysical Journa

The pharmacological rationale for combining muscarinic receptor antagonists and beta-adrenoceptor agonists in the treatment of airway and bladder disease

Muscarinic receptor antagonists and beta-adrenoceptor agonists are used in the treatment of obstructive airway disease and overactive bladder syndrome. Here we review the pharmacological rationale for their combination. Muscarinic receptors and beta-adrenoceptors are physiological antagonists for smooth muscle tone in airways and bladder. Muscarinic agonism may attenuate beta-adrenoceptor-mediated relaxation more than other contractile stimuli. Chronic treatment with one drug class may regulate expression of the target receptor but also that of the opposing receptor. Prejunctional beta(2)-adrenoceptors can enhance neuronal acetylcholine release. Moreover, at least in the airways, muscarinic receptors and beta-adrenoceptors are expressed in different locations, indicating that only a combined modulation of both systems may cause dilatation along the entire bronchial tree. While all of these factors contribute to a rationale for a combination of muscarinic receptor antagonists and beta-adrenoceptor agonists, the full value of such combination as compared to monotherapy can only be determined in clinical studies

Palmitoleate attenuates palmitate-induced Bim and PUMA up-regulation and hepatocyte lipoapoptosis.

BACKGROUND & AIMS: Saturated free fatty acids induce hepatocyte lipoapoptosis. This lipotoxicity involves an endoplasmic reticulum stress response, activation of JNK, and altered expression and function of Bcl-2 proteins. The mono-unsaturated free fatty acid palmitoleate is an adipose-derived lipokine which suppresses free fatty acid-mediated lipotoxicity by unclear mechanisms. Herein we examined the mechanisms responsible for cytoprotection. METHODS: We employed isolated human and mouse primary hepatocytes, and the Huh-7 and Hep 3B cell lines for these studies. Cells were incubated in presence and absence of palmitate (16:0), stearate (18:0), and or palmitoleate (16:1, n-7). RESULTS: Palmitoleate significantly reduced lipoapoptosis by palmitate or stearate in both primary cells and cell lines. Palmitoleate accentuated palmitate-induced steatosis in Huh-7 cells excluding inhibition of steatosis as a mechanism for reduced apoptosis. Palmitoleate inhibited palmitate induction of the endoplasmic reticulum stress response as demonstrated by reductions in CHOP expression, eIF2-alpha phosphorylation, XBP-1 splicing, and JNK activation. Palmitate increased expression of the BH3-only proteins PUMA and Bim, which was attenuated by palmitoleate. Consistent with its inhibition of PUMA and Bim induction, palmitoleate prevented activation of the downstream death mediator Bax. CONCLUSIONS: These data suggest palmitoleate inhibits lipoapoptosis by blocking endoplasmic reticulum stress-associated increases of the BH3-only proteins Bim and PUMA

A role for miR-296 in the regulation of lipoapoptosis by targeting PUMA.

Saturated free fatty acids (FFA) induce hepatocyte lipoapoptosis, a key mediator of liver injury in nonalcoholic fatty liver disease (NAFLD). Lipoapoptosis involves the upregulation of the BH3-only protein PUMA, a potent pro-apoptotic protein. Given that dysregulation of hepatic microRNA expression has been observed in NAFLD, we examined the role of miRNA in regulating PUMA expression during lipotoxicity. By in silico analysis, we identified two putative binding sites for miR-296-5p within the 3\u27 untranslated region (UTR) of PUMA mRNA. Enforced miR-296-5p levels efficiently reduced PUMA protein expression in Huh-7 cells, while antagonism of miR-296-5p function increased PUMA cellular levels. Reporter gene assays identified PUMA 3\u27UTR as a direct target of miR-296-5p. The saturated FFA, palmitate, repressed miR-296-5p expression; and Huh-7 cells were sensitized to palmitate-induced lipotoxicity by antagonism of miR-296-5p function using a targeted locked nucleic acid (LNA). Finally, miR-296-5p was reduced in liver samples from nonalcoholic steatohepatitis (NASH) patients compared with patients with simple steatosis (SS) or controls. Also miR-296-5p levels inversely varied with PUMA mRNA levels in human liver specimens. Our results implicate miR-296-5p in the regulation of PUMA expression during hepatic lipoapoptosis. We speculate that enhancement of miR-296-5p expression may represent a novel approach to minimize apoptotic damage in human fatty liver diseases

Constraints on proximity-induced ferromagnetism in a Dirac semimetal (Cd3_3As2_2)/ferromagnetic semiconductor (Ga1−x_{1-x}Mnx_xSb) heterostructure

Breaking time-reversal symmetry in a Dirac semimetal Cd$_3$As$_2$ through doping with magnetic ions or by the magnetic proximity effect is expected to cause a transition to other topological phases (such as a Weyl semimetal). To this end, we investigate the possibility of proximity-induced ferromagnetic ordering in epitaxial Dirac semimetal (Cd$_3$As$_2$)/ferromagnetic semiconductor (Ga$_{1-x}$Mn$_x$Sb) heterostructures grown by molecular beam epitaxy. We report the comprehensive characterization of these heterostructures using structural probes (atomic force microscopy, x-ray diffraction, scanning transmission electron microscopy), angle-resolved photoemission spectroscopy, electrical magneto-transport, magnetometry, and polarized neutron reflectometry. Measurements of the magnetoresistance and Hall effect in the temperature range 2 K - 20 K show signatures that could be consistent with either a proximity effect or spin-dependent scattering of charge carriers in the Cd$_3$As$_2$ channel. Polarized neutron reflectometry sets constraints on the interpretation of the magnetotransport studies by showing that (at least for temperatures above 6 K) any induced magnetization in the Cd$_3$As$_2$ itself must be relatively small ($<$ 14 emu/cm$^3$)

Co2MnSi:Pt multilayers for giant spin Seebeck devices

The spin Seebeck effect (SSE) has been widely studied as a potential mechanism for energy harvesting. However, the efficiency of such devices, utilizing the spin thermoelectric effect in thin film form, has not yet reached a sufficient value to make them economically viable. It is therefore imperative that advances are made to investigate means by which the thermoelectric signal can be enhanced. Multilayers of Co2MnSi and Pt are fabricated and characterized in an attempt to observe enhanced voltages. We report that bilayers of ferromagnetic conductor/normal metal (FM/NM) exhibit a Longitudinal SSE response and that repetitive stacking of such bilayers results in an increased thermoelectric voltage that is highly dependent upon the quality of CMS/Pt and Pt/CMS interfaces

Probability of sepsis after infection consultations in primary care in the United Kingdom in 2002-17:population-based cohort study and decision analytic model

BackgroundEfforts to reduce unnecessary antibiotic prescribing have coincided with increasing awareness of sepsis. We aimed to estimate the probability of sepsis following infection consultations in primary care when antibiotics were or were not prescribed.Methods and findingsWe conducted a cohort study including all registered patients at 706 general practices in the United Kingdom Clinical Practice Research Datalink, with 66.2 million person-years of follow-up from 2002 to 2017. There were 35,244 first episodes of sepsis (17,886, 51%, female; median age 71 years, interquartile range 57-82 years). Consultations for respiratory tract infection (RTI), skin or urinary tract infection (UTI), and antibiotic prescriptions were exposures. A Bayesian decision tree was used to estimate the probability (95% uncertainty intervals [UIs]) of sepsis following an infection consultation. Age, gender, and frailty were evaluated as association modifiers. The probability of sepsis was lower if an antibiotic was prescribed, but the number of antibiotic prescriptions required to prevent one episode of sepsis (number needed to treat [NNT]) decreased with age. At 0-4 years old, the NNT was 29,773 (95% UI 18,458-71,091) in boys and 27,014 (16,739-65,709) in girls; over 85 years old, NNT was 262 (236-293) in men and 385 (352-421) in women. Frailty was associated with greater risk of sepsis and lower NNT. For severely frail patients aged 55-64 years, the NNT was 247 (156-459) in men and 343 (234-556) in women. At all ages, the probability of sepsis was greatest for UTI, followed by skin infection, followed by RTI. At 65-74 years, the NNT following RTI was 1,257 (1,112-1,434) in men and 2,278 (1,966-2,686) in women; the NNT following skin infection was 503 (398-646) in men and 784 (602-1,051) in women; following UTI, the NNT was 121 (102-145) in men and 284 (241-342) in women. NNT values were generally smaller for the period from 2014 to 2017, when sepsis was diagnosed more frequently. Lack of random allocation to antibiotic therapy might have biased estimates; patients may sometimes experience sepsis or receive antibiotic prescriptions without these being recorded in primary care; recording of sepsis has increased over the study period.ConclusionsThese stratified estimates of risk help to identify groups in which antibiotic prescribing may be more safely reduced. Risks of sepsis and benefits of antibiotics are more substantial among older adults, persons with more advanced frailty, or following UTIs

Prevalence and clinical consequences of Hepatitis E in patients who underwent liver transplantation for chronic Hepatitis C in the United States

Background: Infection with hepatitis E virus (HEV) in immunocompromised patients can lead to severe liver disease. Treatment options for HEV include peginterferon or ribavirin, routinely also used for the treatment of hepatitis C virus (HCV) infection. We determined the prevalence and clinical consequences of HEV in United States (US) based patients who underwent liver transplantation (LT) for chronic HCV. Methods: Seroprevalence of HEV in 145 US LT recipients with a history of chronic HCV was determined pre-LT, 1, 3 and 5 years post-LT. All last available samples and all samples in IgM positive patients and post-LT IgG seroconverters were tested for HEV RNA. Results: Overall anti-HEV seroprevalence was 42 %. Five patients were HEV IgM positive pre-LT, one patient had IgM seroconversion post-LT and eight patients had IgG seroconversion post-LT. None of the tested samples were positive for HEV RNA. Eight out of nine of the post-LT seroconverters had been treated for HCV recurrence before or at the moment of seroconversion. Conclusions: LT recipients in the US are at risk of acquiring HEV. Post-LT HCV treatment with interferons and/or ribavirin may have protected patients against chronic HEV. With the arrival of new direct antiviral agents for the treatment of HCV and the elimination of peginterferon and ribavirin from HCV treatment regimens, the prevalence of chronic HEV in this population may rise again