Structural optimization and biological evaluation of 2-substituted 5-hydroxyindole-3-carboxylates as potent inhibitors of human 5-lipoxygenase.

Pharmacological suppression of leukotriene biosynthesis by inhibitors of 5-lipoxygenase (5-LO) is a strategy to intervene with inflammatory and allergic disorders. We recently presented 2-amino-5-hydroxy-1H-indoles as efficient 5-LO inhibitors in cell-based and cell-free assays. Structural optimization led to novel benzo[g]indole-3-carboxylates exemplified by ethyl 2-(3-chlorobenzyl)-5- hydroxy-1H-benzo[g]indole-3-carboxylate (compound 11a), which inhibits 5-LO activity in human neutrophils and recombinant human 5-LO with IC50 values of 0.23 and 0.086 μM, respectively. Notably, 11a efficiently blocks 5-LO product formation in human whole blood assays (IC50 = 0.83-1.6 μM) and significantly prevented leukotriene B4 production in pleural exudates of carrageenan-treated rats, associated with reduced severity of pleurisy. Together, on the basis of their high potency against 5-LO and the marked efficacy in biological systems, these novel and straightforward benzo[g]indole-3-carboxylates may have potential as anti-inflammatory therapeutics

Effect of climate change on sporulation of the teleomorphs of Leptosphaeria species causing stem canker of brassicas

Leptosphaeria maculans and L. biglobosa are closely related sibling fungal pathogens that cause phoma leaf spotting, stem canker (blackleg) and stem necrosis of oilseed rape (Brassica napus). The disease is distributed worldwide, and it is one of the main causes of considerable decrease in seed yield and quality. Information about the time of ascospore release at a particular location provides important data for decision making in plant protection, thereby enabling fungicides to be used only when necessary and at optimal times and doses. Although the pathogens have been studied very extensively, the effect of climate change on the frequencies and distributions of their aerially dispersed primary inoculum has not been reported to date. We have collected a large dataset of spore counts from Poznan, located in central-west part of Poland, and studied the relationships between climate and the daily concentrations of airborne propagules over a period of 17 years (1998–2014). The average air temperature and precipitation for the time of development of pseudothecia and ascospore release (July–November), increased during the years under study at the rates of 0.1 °C and 6.3 mm per year. The day of the year (DOY) for the first detection of spores, as well as the date with maximum of spores, shifted from 270 to 248 DOY, and from 315 to 265 DOY, respectively. The acceleration of the former parameter by 22 days and the latter by 50 days has great influence on the severity of stem canker of oilseed rape

Two-phonon 1- state in 112Sn observed in resonant photon scattering

Results of a photon scattering experiment on 112Sn using bremsstrahlung with an endpoint energy of E_0 = 3.8 MeV are reported. A J = 1 state at E_x = 3434(1) keV has been excited. Its decay width into the ground state amounts to Gamma_0 = 151(17) meV, making it a candidate for a [2+ x 3-]1- two-phonon state. The results for 112Sn are compared with quasiparticle-phonon model calculations as well as the systematics of the lowest-lying 1- states established in other even-mass tin isotopes. Contrary to findings in the heavier stable even-mass Sn isotopes, no 2+ states between 2 and 3.5 MeV excitation energy have been detected in the present experiment.Comment: 10 pages, including 2 figures, Phys. Rev. C, in pres

Current practice of blood pressure measurement in Germany: a nationwide questionnaire-based survey in medical practices

PURPOSE: Discrepancies exist between guideline recommendations and real-world practice of blood pressure (BP) measurements. The aim of this study was to assess, with a nationwide, questionnaire-based survey, the current practice of BP measurement and associated BP values in German medical practices. MATERIAL AND METHODS: A nationwide survey in German medical practices was performed in the period from 10 May 2021 to 15 August 2021. The questionnaire was divided into five sections. The current office BP (OBP) values as well as the current drug therapy were recorded. In addition, the implementation of office BP (OBP) and home BP monitoring (HBPM) was queried. For analysis, questionnaires were scanned and automatically digitised. RESULTS: A total of 7049 questionnaires were analysed, the majority of which came from general practitioners (66%) and internal medicine practices (34%). The average OBP (SD) was 140.0 (18)/82.7 (11) mmHg. 40.8% of treated patients had OBP in the controlled range, with monotherapy (34.7%) or dual combination therapy (38.2%) prescribed in most cases. OBP was taken from a single measurement in 66.3% of cases, and in 21.8% from 23 measurements. OBP was mostly measured after a rest period (87.1%) and in a separate room (80.4%). HBPM was performed in 62.3% of patients; however, in 24.9% of the participants HBP measurements were recorded once a week or less. CONCLUSION: In this nationwide survey in German medical practices, BP control remains at below 50%, while monotherapy is prescribed in around one third of patients. Moreover, office measurements and HBPM are often not performed according to current guideline recommendations

Serotonin tranporter methylation and response to cognitive behaviour therapy in children with anxiety disorders

Anxiety disorders that are the most commonly occurring psychiatric disorders in childhood, are associated with a range of social and educational impairments and often continue into adulthood. Cognitive behaviour therapy (CBT) is an effective treatment option for the majority of cases, although up to 35-45% of children do not achieve remission. Recent research suggests that some genetic variants may be associated with a more beneficial response to psychological therapy. Epigenetic mechanisms such as DNA methylation work at the interface between genetic and environmental influences. Furthermore, epigenetic alterations at the serotonin transporter (SERT) promoter region have been associated with environmental influences such as stressful life experiences. In this study, we measured DNA methylation upstream of SERT in 116 children with an anxiety disorder, before and after receiving CBT. Change during treatment in percentage DNA methylation was significantly different in treatment responders vs nonresponders. This effect was driven by one CpG site in particular, at which responders increased in methylation, whereas nonresponders showed a decrease in DNA methylation. This is the first study to demonstrate differences in SERT methylation change in association with response to a purely psychological therapy. These findings confirm that biological changes occur alongside changes in symptomatology following a psychological therapy such as CBT

Spectroscopic investigation of the deeply buried Cu In,Ga S,Se 2 Mo interface in thin film solar cells

The Cu In,Ga S,Se 2 Mo interface in thin film solar cells has been investigated by surface sensitive photoelectron spectroscopy, bulk sensitive X ray emission spectroscopy, and atomic force microscopy. It is possible to access this deeply buried interface by using a suitable lift off technique, which allows to investigate the back side of the absorber layer as well as the front side of the Mo back contact. We find a layer of Mo S,Se 2 on the surface of the Mo back contact and a copper poor stoichiometry at the back side of the Cu In,Ga S,Se 2 absorber. Furthermore, we observe that the Na content at the Cu In,Ga S,Se 2 Mo interface as well as at the inner grain boundaries in the back contact region is significantly lower than at the absorber front surfac

Разработка технологии сборки-сварки системы отопления административно-бытового корпуса

Актуальность работы: в данной выпускной квалификационной работе производится разработка и сравнение технологий: сварка стальных труб, сварка полипропиленовых труб и пайка медных труб при монтаже системы отопления административно-бытового корпуса. Объектом исследования является процесс изготовления системы отопления административно-бытового корпуса. Цели и задачи исследования: в результате данной работы следует выбрать технологию монтажа с наибольшей степенью надежности получаемого изделия и оптимальной себестоимостью производства.The relevance of the work: in this prom qualification development work and comparison technology: steel pipe welding, welding of polypropylene pipes and solder copper pipe when installing the heating system of the administrative Corps. The object of research is the process of manufacturing heating systems the administrative Corps. The goals and objectives of the study: As a result of this work, you must select the mounting technology with the highest degree of reliability of the resulting products and optimal cost price of production

Calibration and Characterization of the IceCube Photomultiplier Tube

Over 5,000 PMTs are being deployed at the South Pole to compose the IceCube neutrino observatory. Many are placed deep in the ice to detect Cherenkov light emitted by the products of high-energy neutrino interactions, and others are frozen into tanks on the surface to detect particles from atmospheric cosmic ray showers. IceCube is using the 10-inch diameter R7081-02 made by Hamamatsu Photonics. This paper describes the laboratory characterization and calibration of these PMTs before deployment. PMTs were illuminated with pulses ranging from single photons to saturation level. Parameterizations are given for the single photoelectron charge spectrum and the saturation behavior. Time resolution, late pulses and afterpulses are characterized. Because the PMTs are relatively large, the cathode sensitivity uniformity was measured. The absolute photon detection efficiency was calibrated using Rayleigh-scattered photons from a nitrogen laser. Measured characteristics are discussed in the context of their relevance to IceCube event reconstruction and simulation efforts.Comment: 40 pages, 12 figure