Signatures of Dark Matter Scattering Inelastically Off Nuclei

Direct dark matter detection focuses on elastic scattering of dark matter particles off nuclei. In this study, we explore inelastic scattering where the nucleus is excited to a low-lying state of 10-100 keV, with subsequent prompt de-excitation. We calculate the inelastic structure factors for the odd-mass xenon isotopes based on state-of-the-art large-scale shell-model calculations with chiral effective field theory WIMP-nucleon currents. For these cases, we find that the inelastic channel is comparable to or can dominate the elastic channel for momentum transfers around 150 MeV. We calculate the inelastic recoil spectra in the standard halo model, compare these to the elastic case, and discuss the expected signatures in a xenon detector, along with implications for existing and future experiments. The combined information from elastic and inelastic scattering will allow to determine the dominant interaction channel within one experiment. In addition, the two channels probe different regions of the dark matter velocity distribution and can provide insight into the dark halo structure. The allowed recoil energy domain and the recoil energy at which the integrated inelastic rates start to dominate the elastic channel depend on the mass of the dark matter particle, thus providing a potential handle to constrain its mass.Comment: 9 pages, 7 figures. Matches resubmitted version to Phys. Rev. D. One figure added; supplemental material (fits to the structure functions) added as an Appendi

Continuum and Emission-Line Properties of Broad Absorption Line Quasars

We investigate the continuum and emission-line properties of 224 broad absorption line quasars (BALQSOs) with 0.9<z<4.4 drawn from the Sloan Digital Sky Survey (SDSS) Early Data Release (EDR), which contains 3814 bona fide quasars. We find that low-ionization BALQSOs (LoBALs) are significantly reddened as compared to normal quasars, in agreement with previous work. High-ionization BALQSOs (HiBALs) are also more reddened than the average nonBALQSO. Assuming SMC-like dust reddening at the quasar redshift, the amount of reddening needed to explain HiBALs is E(B-V)~0.023 and LoBALs is E(B-V)~0.077 (compared to the ensemble average of the entire quasar sample). We find that there are differences in the emission-line properties between the average HiBAL, LoBAL, and nonBAL quasar. These differences, along with differences in the absorption line troughs, may be related to intrinsic quasar properties such as the slope of the intrinsic (unreddened) continuum; more extreme absorption properties are correlated with bluer intrinsic continua. Despite the differences among BALQSO sub-types and nonBALQSOs, BALQSOs appear to be drawn from the same parent population as nonBALQSOs when both are selected by their UV/optical properties. We find that the overall fraction of traditionally defined BALQSOs, after correcting for color-dependent selection effects due to different SEDs of BALQSO and nonBALQSOs, is 13.4+/-1.2% and shows no significant redshift dependence for 1.7<z<3.45. After a rough completeness correction for the effects of dust extinction, we find that approximately one in every six quasars is a BALQSO.Comment: 35 pages, 11 figures (1 color), 1 table; accepted by A

Honokiol Blocks Store Operated Calcium Entry in CHO Cells Expressing the M3 Muscarinic Receptor: Honokiol and Muscarinic Signaling

Background: Honokiol, a cell-permeable phenolic compound derived from the bark of magnolia trees and present in Asian herbal teas, has a unique array of pharmacological actions, including the inhibition of multiple autonomic responses. We determined the effects of honokiol on calcium signaling underlying transmission mediated by human M3 muscarinic receptors expressed in Chinese hamster ovary (CHO) cells. Receptor binding was determined in radiolabelled ligand binding assays; changes in intracellular calcium concentrations were determined using a fura-2 ratiometric imaging protocol; cytotoxicity was determined using a dye reduction assay. Results: Honokiol had a potent (EC50 ≈ 5 μmol/l) inhibitory effect on store operated calcium entry (SOCE) that was induced by activation of the M3 receptors. This effect was specific, rapid and partially reversible, and was seen at concentrations not associated with cytotoxicity, inhibition of IP3 receptor-mediated calcium release, depletion of ER calcium stores, or disruption of M3 receptor binding. Conclusions: It is likely that an inhibition of SOCE contributes to honokiol disruption of parasympathetic motor functions, as well as many of its beneficial pharmacological properties

Interactions, star formation and AGN activity

It has long been known that galaxy interactions are associated with enhanced star formation. In a companion paper, we explored this connection by applying a variety of statistics to SDSS data. In particular, we showed that specific star formation rates of galaxies are higher if they have close neighbours. Here we apply exactly the same techniques to AGN in the survey, showing that close neighbours are not associated with any similar enhancement of nuclear activity. Star formation is enhanced in AGN with close neighbours in exactly the same way as in inactive galaxies, but the accretion rate onto the black hole, as estimated from the extinction-corrected [O III] luminosity, is not influenced by the presence or absence of companions. Previous work has shown that galaxies with more strongly accreting black holes contain more young stars in their inner regions. This leads us to conclude that star formation induced by a close companion and star formation associated with black hole accretion are distinct events. These events may be part of the same physical process, for example a merger, provided they are separated in time. In this case, accretion onto the black hole and its associated star formation would occur only after the two interacting galaxies have merged. The major caveat in this work is our assumption that the extinction-corrected [O III] luminosity is a robust indicator of the bolometric luminosity of the central black hole. It is thus important to check our results using indicators of AGN activity at other wavelengths.Comment: v1: 10 pages, 9 figures, submitted for publication in Monthly Notices; v2: accepted, minor changes in summary and reference list update

Differential kinetic profiles and metabolism of primaquine enantiomers by human hepatocytes

BACKGROUND: The clinical utility of primaquine (PQ), used as a racemic mixture of two enantiomers, is limited due to metabolism-linked hemolytic toxicity in individuals with genetic deficiency in glucose-6-phosphate dehydrogenase. The current study investigated differential metabolism of PQ enantiomers in light of the suggestions that toxicity and efficacy might be largely enantioselective. METHODS: Stable isotope (13)C-labelled primaquine and its two enantiomers (+)-PQ, (−)-PQ were separately incubated with cryopreserved human hepatocytes. Time-tracked substrate depletion and metabolite production were monitored via UHPLC–MS/MS. RESULTS: The initial half-life of 217 and 65 min; elimination rate constants (λ) of 0.19 and 0.64 h(−1); intrinsic clearance (Cl(int)) of 2.55 and 8.49 (µL/min)/million cells, which when up-scaled yielded Cl(int) of 6.49 and 21.6 (mL/min)/kg body mass was obtained respectively for (+)- and (−)-PQ. The extrapolation of in vitro intrinsic clearance to in vivo human hepatic blood clearance, performed using the well-stirred liver model, showed that the rate of hepatic clearance of (+)-PQ was only 45 % that of (−)-PQ. Two major primary routes of metabolism were observed—oxidative deamination of the terminal amine and hydroxylations on the quinoline moiety of PQ. The major deaminated metabolite, carboxyprimaquine (CPQ) was preferentially generated from the (−)-PQ. Other deaminated metabolites including PQ terminal alcohol (m/z 261), a cyclized side chain derivative from the aldehyde (m/z 241), cyclized carboxylic acid derivative (m/z 257), a quinone-imine product of hydroxylated CPQ (m/z 289), CPQ glucuronide (m/z 451) and the glucuronide of PQ alcohol (m/z 437) were all preferentially generated from the (−)-PQ. The major quinoline oxidation product (m/z 274) was preferentially generated from (+)-PQ. In addition to the products of the two metabolic pathways, two other major metabolites were observed: a prominent glycosylated conjugate of PQ on the terminal amine (m/z 422), peaking by 30 min and preferentially generated by (+)-PQ; and the carbamoyl glucuronide of PQ (m/z 480) exclusively generated from (+)-PQ. CONCLUSION: Metabolism of PQ showed enantioselectivity. These findings may provide important information in establishing clinical differences in PQ enantiomers

Вплив екологічного стану Донецького регіону на його демографічний розвиток

В статті розглянуто важливу проблему впливу забрудненості навколишнього природного середовища на захворюваність та смертність в регіоні. Визначено кореляційну залежність між обсягом викидів забруднюючих речовин та окремими видами захворюваності, а також ступінь їх впливу, побудовано функції, що описують їх.В статье рассмотрена важная проблема влияния загрязненности окружающей естественной среды на заболеваемость и смертность в регионе. Определена корреляционная зависимость между объемом выбросов загрязняющих веществ и отдельными видами заболеваемости, а также степень их влияния, построены функции, которые описывают их.In the article the important problem of influence of muddiness of natural environment is considered on morbidity and death rate in a region. Certainly cross-correlation dependence between the volume of extrass of contaminents and separate types of morbidity, and also degree of their influence, functions which describe them are built. Keywords: environment

Oxidative Stress Disruption of Receptor-Mediated Calcium Signaling Mechanisms

Background: Oxidative stress increases the cytosolic content of calcium in the cytoplasm through a combination of effects on calcium pumps, exchangers, channels and binding proteins. In this study, oxidative stress was produced by exposure to tert-butyl hydroperoxide (tBHP); cell viability was assessed using a dye reduction assay; receptor binding was characterized using [3H]N-methylscopolamine ([3H]MS); and cytosolic and luminal endoplasmic reticulum (ER) calcium concentrations ([Ca2+]i and [Ca2+]L, respectively) were measured by fluorescent imaging. Results: Activation of M3 muscarinic receptors induced a biphasic increase in [Ca2+]i: an initial, inositol trisphosphate (IP3)-mediated release of Ca2+ from endoplasmic reticulum (ER) stores followed by a sustained phase of Ca2+ entry (i.e., store-operated calcium entry; SOCE). Under non-cytotoxic conditions, tBHP increased resting [Ca2+]i; a 90 minute exposure to tBHP (0.5-10 mM) increased [Ca2+]i from 26 to up to 127 nM and decreased [Ca2+]L by 55%. The initial response to 10 μM carbamylcholine was depressed by tBHP in the absence, but not the presence, of extracellular calcium. SOCE, however, was depressed in both the presence and absence of extracellular calcium. Acute exposure to tBHP did not block calcium influx through open SOCE channels. Activation of SOCE following thapsigargin-induced depletion of ER calcium was depressed by tBHP exposure. In calcium-free media, tBHP depressed both SOCE and the extent of thapsigargin-induced release of Ca2+ from the ER. M3 receptor binding parameters (ligand affinity, guanine nucleotide sensitivity, allosteric modulation) were not affected by exposure to tBHP. Conclusions: Oxidative stress induced by tBHP affected several aspects of M3 receptor signaling pathway in CHO cells, including resting [Ca2+]i, [Ca2+]L, IP3 receptor mediated release of calcium from the ER, and calcium entry through the SOCE. tBHP had little effect on M3 receptor binding or G protein coupling. Thus, oxidative stress affects multiple aspects of calcium homeostasis and calcium dependent signaling

Herschel-ATLAS: the far-infrared properties and star-formation rates of broad absorption line quasi-stellar objects

We have used data from the Herschel-ATLAS at 250, 350 and 500 \mu m to determine the far-infrared (FIR) properties of 50 Broad Absorption Line Quasars (BAL QSOs). Our sample contains 49 high-ionization BAL QSOs (HiBALs) and 1 low-ionization BAL QSO (LoBAL) which are compared against a sample of 329 non-BAL QSOs. These samples are matched over the redshift range 1.5 \leq z < 2.3 and in absolute i-band magnitude over the range -28 \leq M_{i} \leq -24. Of these, 3 BAL QSOs (HiBALs) and 27 non-BAL QSOs are detected at the > 5 sigma level. We calculate star-formation rates (SFR) for our individually detected HiBAL QSOs and the non-detected LoBAL QSO as well as average SFRs for the BAL and non-BAL QSO samples based on stacking the Herschel data. We find no difference between the HiBAL and non-BAL QSO samples in the FIR, even when separated based on differing BAL QSO classifications. Using Mrk 231 as a template, the weighted mean SFR is estimated to be \approx240\pm21 M_{\odot} yr^{-1} for the full sample, although this figure should be treated as an upper limit if AGN-heated dust makes a contribution to the FIR emission. Despite tentative claims in the literature, we do not find a dependence of {\sc C\,iv} equivalent width on FIR emission, suggesting that the strength of any outflow in these objects is not linked to their FIR output. These results strongly suggest that BAL QSOs (more specifically HiBALs) can be accommodated within a simple AGN unified scheme in which our line-of-sight to the nucleus intersects outflowing material. Models in which HiBALs are caught towards the end of a period of enhanced spheroid and black-hole growth, during which a wind terminates the star-formation activity, are not supported by the observed FIR properties.Comment: 11 pages, 4 figures, 4 tables. Accepted for publication in MNRA

Enantioselective metabolism of primaquine by human CYP2D6

BACKGROUND: Primaquine, currently the only approved drug for the treatment and radical cure of Plasmodium vivax malaria, is still used as a racemic mixture. Clinical use of primaquine has been limited due to haemolytic toxicity in individuals with genetic deficiency in glucose-6-phosphate dehydrogenase. Earlier studies have linked its therapeutic effects to CYP2D6-generated metabolites. The aim of the current study was to investigate the differential generation of the CYP2D6 metabolites by racemic primaquine and its individual enantiomers. METHODS: Stable isotope (13)C-labelled primaquine and its two enantiomers were incubated with recombinant cytochrome-P450 supersomes containing CYP2D6 under optimized conditions. Metabolite identification and time-point quantitative analysis were performed using LC-MS/MS. UHPLC retention time, twin peaks with a mass difference of 6, MS-MS fragmentation pattern, and relative peak area with respect to parent compound were used for phenotyping and quantitative analysis of metabolites. RESULTS: The rate of metabolism of (+)-(S)-primaquine was significantly higher (50% depletion of 20 μM in 120 min) compared to (−)-(R)-primaquine (30% depletion) when incubated with CYP2D6. The estimated V(max) (μmol/min/mg) were 0.75, 0.98 and 0.42, with K(m) (μM) of 24.2, 33.1 and 21.6 for (±)-primaquine, (+)-primaquine and (−)-primaquine, respectively. Three stable mono-hydroxylated metabolites, namely, 2-, 3- and 4-hydroxyprimaquine (2-OH-PQ, 3-OH-PQ, and 4-OH-PQ), were identified and quantified. 2-OH-PQ was preferentially formed from (+)-primaquine in a ratio of 4:1 compared to (−)-primaquine. The racemic (±)-primaquine showed a pattern similar to the (−)-primaquine; 2-OH-PQ accounted for about 15–17% of total CYP2D6-mediated conversion of (+)-primaquine. In contrast, 4-OH-PQ was preferentially formed with (−)-primaquine (5:1), accounting for 22% of the total (−)-primaquine conversion. 3-OH-PQ was generated from both enantiomers and racemate. 5-hydroxyprimaquine was unstable. Its orthoquinone degradation product (twice as abundant in (+)-primaquine compared to (−)-primaquine) was identified and accounted for 18–20% of the CYP2D6-mediated conversion of (+)-primaquine. Other minor metabolites included dihydroxyprimaquine species, two quinone-imine products of dihydroxylated primaquine, and a primaquine terminal alcohol with variable generation from the individual enantiomers. CONCLUSION: The metabolism of primaquine by human CYP2D6 and the generation of its metabolites display enantio-selectivity regarding formation of hydroxylated product profiles. This may partly explain differential pharmacologic and toxicologic properties of primaquine enantiomers

Lowering the radioactivity of the photomultiplier tubes for the XENON1T dark matter experiment

The low-background, VUV-sensitive 3-inch diameter photomultiplier tube R11410 has been developed by Hamamatsu for dark matter direct detection experiments using liquid xenon as the target material. We present the results from the joint effort between the XENON collaboration and the Hamamatsu company to produce a highly radio-pure photosensor (version R11410-21) for the XENON1T dark matter experiment. After introducing the photosensor and its components, we show the methods and results of the radioactive contamination measurements of the individual materials employed in the photomultiplier production. We then discuss the adopted strategies to reduce the radioactivity of the various PMT versions. Finally, we detail the results from screening 216 tubes with ultra-low background germanium detectors, as well as their implications for the expected electronic and nuclear recoil background of the XENON1T experiment.Comment: 10 pages, 5 figure