Atomic data for S II - Toward Better Diagnostics of Chemical Evolution in High-redshift Galaxies

Absorption-line spectroscopy is a powerful tool used to estimate element abundances in the nearby as well as distant universe. The accuracy of the abundances thus derived is, naturally, limited by the accuracy of the atomic data assumed for the spectral lines. We have recently started a project to perform the new extensive atomic data calculations used for optical/UV spectral lines in the plasma modeling code Cloudy using state-of-the-art quantal calculations. Here we demonstrate our approach by focussing on S II, an ion used to estimate metallicities for Milky Way interstellar clouds as well as distant damped Lyman-alpha (DLA) and sub-DLA absorber galaxies detected in the spectra of quasars and gamma-ray bursts (GRBs). We report new extensive calculations of a large number of energy levels of S II, and the line strengths of the resulting radiative transitions. Our calculations are based on the configuration interaction approach within a numerical Hartree-Fock framework, and utilize both non-ralativistic and quasirelativistic one-electron radial orbitals. The results of these new atomic calculations are then incorporated into Cloudy and applied to a lab plasma, and a typical DLA, for illustrative purposes. The new results imply relatively modest changes (~0.04 dex) to the metallicities estimated from S II in past studies. These results will be readily applicable to other studies of S II in the Milky Way and other galaxies.Comment: Accepted for publication in The Astrophysical Journal; 34 pages, 10 figure

Atomic data for Zn II - Improving Spectral Diagnostics of Chemical Evolution in High-redshift Galaxies

Damped Lyman-alpha (DLA) and sub-DLA absorbers in quasar spectra provide the most sensitive tools for measuring element abundances of distant galaxies. Estimation of abundances from absorption lines depends sensitively on the accuracy of the atomic data used. We have started a project to produce new atomic spectroscopic parameters for optical/UV spectral lines using state-of-the-art computer codes employing very broad configuration interaction basis. Here we report our results for Zn II, an ion used widely in studies of the interstellar medium (ISM) as well as DLA/sub-DLAs. We report new calculations of many energy levels of Zn II, and the line strengths of the resulting radiative transitions. Our calculations use the configuration interaction approach within a numerical Hartree-Fock framework. We use both non-relativistic and quasi-relativistic one-electron radial orbitals. We have incorporated the results of these atomic calculations into the plasma simulation code Cloudy, and applied them to a lab plasma and examples of a DLA and a sub-DLA. Our values of the Zn II {\lambda}{\lambda} 2026, 2062 oscillator strengths are higher than previous values by 0.10 dex. Cloudy calculations for representative absorbers with the revised Zn atomic data imply ionization corrections lower than calculated before by 0.05 dex. The new results imply Zn metallicities should be lower by 0.1 dex for DLAs and by 0.13-0.15 dex for sub-DLAs than in past studies. Our results can be applied to other studies of Zn II in the Galactic and extragalactic ISM.Comment: accepted The Astrophysical Journa

Pre-clinical evaluation of antiproteases as potential candidates for HIV-1 pre-exposure prophylaxis

Previous studies on highly HIV-1-exposed, yet persistently seronegative women from the Punwami Sex Worker cohort in Kenya, have shed light on putative protective mechanisms, suggesting that mucosal immunological factors, such as antiproteases, could be mediating resistance to HIV-1 transmission in the female reproductive tract. Nine protease inhibitors were selected for this study: serpin B4, serpin A1, serpin A3, serpin C1, cystatin A, cystatin B, serpin B13, serpin B1 and α-2-macroglobulin-like-protein 1. We assessed in a pilot study, the activity of these antiproteases with cellular assays and an ex vivo HIV-1 challenge model of human ecto-cervical tissue explants. Preliminary findings with both models, cellular and tissue explants, established an order of inhibitory potency for the mucosal proteins as candidates for pre-exposure prophylaxis when mimicking pre-coital use. Combination of all antiproteases considered in this study was more active than any of the individual mucosal proteins. Furthermore, the migration of cells out of ecto-cervical explants was blocked indicating potential prevention of viral dissemination following amplification of the founder population. These findings constitute the base for further development of these mucosal protease inhibitors for prevention strategies

Вивчення фенольного складу лікувально-профілактичного засобу у формі капсул андрогенної дії

Topicality. Taking into account sexual pathologies prevalence and the male fertility reduction , as well as the limited availability of medicines for the prevention and treatment of these disorders in the pharmaceutical market of Ukraine, it is important to expand their nomenclature by creating new extemporal medicines based on natural raw materials and amino acids.Aim. To identify the phenolic compounds of developed extemporal medicine in the form of androgenic action capsules.Materials and methods. The study of phenolic composition of the developed medicine under the conditional name “Apinin” has been carried out using the methods specified in the State Pharmacopoeia of Ukraine, results of which allowed to evaluate objectively the developed capsules quality.Results and discussion. During the conducted studies of the phenolic compounds identification, it was found the appearence of identical spots on chromatograms of tested alcoholic solution of “Apinin” capsules and FGPP alcoholic solution. Correspondence to compounds of phenolic nature: phenolecarboxylic acids, oxycoumarins, and flavones, as well as flavonols, are revealed. It was established that excipients introduced into the formulation do not interfere with the release of phenolic compounds from the formulation. The quantitative determination of phenolic compounds in the medicine performed by absorption spectrophotometry in the UV-region using a SF-46 device, followed by computerized processing of results of the study using the Spectrum software for Windows. The quantitative content of the amount of phenolic compounds in the medicine “Apinin” was determined, which amounts to 0.028 ± 0.001 g per capsule.Conclusions. Methods for determining the qualitative composition of phenolic compounds of FGPP and their quantitative content in androgenic action capsules of extemporal production have been developed. One-way ascending chromatography on paper used to identify active pharmaceutical ingredients, and a spectrophotometric method used to study the quantitative content of phenolic compounds in medicine. Tests have been performed according to methods of the State Pharmacopoeia of Ukraine.Актуальность. Учитывая распространенность патологий половой сферы и снижение фертильности мужчин, а также ограниченность лекарственных средств для профилактики и лечения указанных расстройств, на фармацевтическом рынке Украины актуальным является расширение их номенклатуры за счет создания новых экстемпоральных средств на основе природного сырья и аминокислот.Цель исследования. Идентификация фенольных соединений разработанного экстемпорального лечебно-профилактического средства в форме капсул андрогенного действия.Материалы и методы. Изучение фенольного состава разработанного лечебно-профилактического средства под условным названием «Апинин» проводили с использованием приведенных в ГФУ методов физико-химических исследований, результаты которых позволяют объективно оценивать качество разработанных капсул.Результаты и их обсуждение. В ходе проведенных исследований идентификации фенольных соединений установлено, что на хроматограммах исследованного спиртового раствора капсул «Апинин» и спиртового раствора ФГПП проявляются идентичные пятна, соответствующие соединениям фенольной природы: фенолкарбоновым кислотам, оксикумаринам, а также флавонам и флавонолам. Установлено, что введенные в состав препарата вспомогательные вещества не мешают высвобождению соединений фенольной природы из состава препарата. Количественное определение фенольных соединений в препарате проводили методом абсорбционной спектрофотометрии в УФ-области с использованием прибора СФ-46 с последующей компьютерной обработкой результатов исследования с помощью программного обеспечения «Спектр» для «Windows». Установлено количественное содержание суммы фенольных соединений в препарате «Апинин», которое составляет в пересчете на одну капсулу 0,028 ± 0,001 г.Выводы. Разработаны методики определения качественного состава фенольных соединений ФГПП и их количественного содержания в капсулах андрогенного действия экстемпорального производства. Для проведения идентификации АФИ использовали одномерную восходящую хроматографию на бумаге, для исследования количественного содержания фенольных соединений в препарате был применен спектрофотометрический метод. Испытания были проведены по методикам ГФУ.Актуальність. Враховуючи розповсюдженість патологій статевої сфери та зниження фертильності чоловіків, а також обмеженість лікарських засобів для профілактики та лікування вказаних розладів на фармацевтичному ринку України, актуальним є розширення їх номенклатури за рахунок створення нових екстемпоральних засобів на основі природної сировини та амінокислот.Мета дослідження. Ідентифікація фенольних сполук розробленого екстемпорального лікувально-профілактичного засобу у формі капсул андрогенної дії.Матеріали та методи. Вивчення фенольного складу розробленого лікувально-профілактичного засобу під умовною назвою «Апінін» проводили з використанням наведених у ДФУ методів фізико-хімічних досліджень, результати яких дозволяють об’єктивно оцінювати якість розроблених капсул.Результати та їх обговорення. У ході проведених досліджень ідентифікації фенольних сполук встановлено, що на хроматограмах дослідженого спиртового розчину капсул «Апінін» та спиртового розчину ФГПП проявляються ідентичні плями, що відповідають сполукам фенольної природи: фенолкарбоновим кислотам, оксикумаринам, а також є сліди флавонів та флавонолів. Встановлено, що введені до складу препарату допоміжні речовини не заважають вивільненню сполук фенольної природи зі складу препарату. Кількісне визначення фенольних сполук у препараті проводили методом абсорбційної спектрофотометрії в УФ-області з використанням приладу СФ-46 з подальшою комп’ютерною обробкою результатів дослідження за допомогою програмного забезпечення «Спектр» для «Windows». Встановлено кількісний вміст суми фенольних сполук у препараті «Апінін», який складає в перерахунку на одну капсулу 0,028 ± 0,001 г.Висновок. Розроблені методики визначення якісного складу фенольних сполук ФГПП та їх кількісного вмісту у капсулах андрогенної дії екстемпорального виробництва. Для проведення ідентифікації АФІ використовували одномірну висхідну хроматографію на папері, для дослідження кількісного вмісту фенольних сполук у препараті було застосовано спектрофотометричний метод. Випробування були проведені за методиками ДФУ

Atomic Data for Zn ɪɪ: Improving Spectral Diagnostics of Chemical Evolution in High-Redshift Galaxies

Damped Lyα (DLA) and sub-DLA absorbers in quasar spectra provide the most sensitive tools for measuring the element abundances of distant galaxies. The estimation of abundances from absorption lines depends sensitively on the accuracy of the atomic data used. We have started a project to produce new atomic spectroscopic parameters for optical and UV spectral lines using state-of-the-art computer codes employing a very broad configuration interaction (CI) basis. Here we report our results for Zn ii, an ion used widely in studies of the interstellar medium (ISM) as well as DLAs and sub-DLAs. We report new calculations of many energy levels of Zn ii and the line strengths of the resulting radiative transitions. Our calculations use the CI approach within a numerical Hartree–Fock framework. We use both nonrelativistic and quasi-relativistic one-electron radial orbitals. We have incorporated the results of these atomic calculations into the plasma simulation code Cloudy and applied them to a lab plasma and examples of a DLA and a sub-DLA. Our values of the Zn ii 2026, 2062 oscillator strengths are higher than previous values by 0.10 dex. The Cloudy calculations for representative absorbers with the revised Zn atomic data imply ionization corrections lower than calculated earlier by 0.05 dex. The new results imply that Zn metallicities should be lower by 0.1 dex for DLAs and by 0.13–0.15 dex for sub-DLAs than in past studies. Our results can be applied to other studies of Zn ii in the Galactic and extragalactic ISM

Neutrino Oscillations in Supersymmetry without Lepton number conservation and R-parity

With the on-shell renormalization scheme, we discuss neutrino masses up to one-loop approximation in the Supersymmetry without lepton number conservation and R-parity. Ii is shown that in this model with experimentally allowed parameters, $\Delta m^2_{23}, \Delta m^2_{12}$ and the mixing angles $|\sin\theta{23}|,|\sin\theta_{12}|$ which are consistent with the present observation values can be produced. We find that small neutrino mass ($\leq$ 1 eV) sets a loose constraint on the R-parity violation parameters in the soft breaking terms.Comment: 22 pages, plus one ps figure, accepted for publication in PR

Rapid Seeding of the Viral Reservoir Prior to SIV Viremia in Rhesus Monkeys

The viral reservoir represents a critical challenge facing HIV-1 eradication strategies1–5. However, it remains unclear when and where the viral reservoir is seeded during acute infection and the extent to which it is susceptible to early antiretroviral therapy (ART). Here we show that the viral reservoir is seeded very early following mucosal SIV infection of rhesus monkeys and prior to systemic viremia. We initiated suppressive ART in groups of monkeys on days 3, 7, 10, and 14 following intrarectal SIVmac251 infection. Treatment on day 3 blocked the emergence of viral RNA and proviral DNA in peripheral blood and also substantially reduced levels of proviral DNA in lymph nodes and gastrointestinal mucosa as compared with treatment at later timepoints. In addition, treatment on day 3 abrogated the induction of SIV-specific humoral and cellular immune responses. Nevertheless, following discontinuation of ART after 24 weeks of fully suppressive therapy, virus rebounded in all animals, although animals treated on day 3 exhibited a delayed viral rebound as compared with animals treated on days 7, 10 and 14. The time to viral rebound correlated with total viremia during acute infection and with proviral DNA at the time of ART discontinuation. These data demonstrate that the viral reservoir is seeded very early following intrarectal SIV infection of rhesus monkeys, during the “eclipse” phase, and prior to viremia. This strikingly early seeding of the refractory viral reservoir raises important new challenges for HIV-1 eradication strategies

Histone Deacetylase Inhibitor Romidepsin Induces HIV Expression in CD4 T Cells from Patients on Suppressive Antiretroviral Therapy at Concentrations Achieved by Clinical Dosing

Persistent latent reservoir of replication-competent proviruses in memory CD4 T cells is a major obstacle to curing HIV infection. Pharmacological activation of HIV expression in latently infected cells is being explored as one of the strategies to deplete the latent HIV reservoir. In this study, we characterized the ability of romidepsin (RMD), a histone deacetylase inhibitor approved for the treatment of T-cell lymphomas, to activate the expression of latent HIV. In an in vitro T-cell model of HIV latency, RMD was the most potent inducer of HIV (EC50 = 4.5 nM) compared with vorinostat (VOR; EC50 = 3,950 nM) and other histone deacetylase (HDAC) inhibitors in clinical development including panobinostat (PNB; EC50 = 10 nM). The HIV induction potencies of RMD, VOR, and PNB paralleled their inhibitory activities against multiple human HDAC isoenzymes. In both resting and memory CD4 T cells isolated from HIV-infected patients on suppressive combination antiretroviral therapy (cART), a 4-hour exposure to 40 nM RMD induced a mean 6-fold increase in intracellular HIV RNA levels, whereas a 24-hour treatment with 1 μM VOR resulted in 2- to 3-fold increases. RMD-induced intracellular HIV RNA expression persisted for 48 hours and correlated with sustained inhibition of cell-associated HDAC activity. By comparison, the induction of HIV RNA by VOR and PNB was transient and diminished after 24 hours. RMD also increased levels of extracellular HIV RNA and virions from both memory and resting CD4 T-cell cultures. The activation of HIV expression was observed at RMD concentrations below the drug plasma levels achieved by doses used in patients treated for T-cell lymphomas. In conclusion, RMD induces HIV expression ex vivo at concentrations that can be achieved clinically, indicating that the drug may reactivate latent HIV in patients on suppressive cART