Protein-tyrosine Phosphatase (PTP) Wedge Domain Peptides: A NOVEL APPROACH FOR INHIBITION OF PTP FUNCTION AND AUGMENTATION OF PROTEIN-TYROSINE KINASE FUNCTION

Inhibition of protein-tyrosine phosphatases (PTPs) counterbalancing protein-tyrosine kinases (PTKs) offers a strategy for augmenting PTK actions. Conservation of PTP catalytic sites limits development of specific PTP inhibitors. A number of receptor PTPs, including the leukocyte common antigen-related (LAR) receptor and PTPmu, contain a wedge-shaped helix-loop-helix located near the first catalytic domain. Helix-loop-helix domains in other proteins demonstrate homophilic binding and inhibit function; therefore, we tested the hypothesis that LAR wedge domain peptides would exhibit homophilic binding, bind to LAR, and inhibit LAR function. Fluorescent beads coated with LAR or PTPmu wedge peptides demonstrated PTP-specific homophilic binding, and LAR wedge peptide-coated beads precipitated LAR protein. Administration of LAR wedge Tat peptide to PC12 cells resulted in increased proliferation, decreased cell death, increased neurite outgrowth, and augmented Trk PTK-mediated responses to nerve growth factor (NGF), a phenotype matching that found in PC12 cells with reduced LAR levels. PTPmu wedge Tat peptide had no effect on PC12 cells but blocked the PTPmu-dependent phenotype of neurite outgrowth of retinal ganglion neurons on a PTPmu substrate, whereas LAR wedge peptide had no effect. The survival- and neurite-promoting effect of the LAR wedge peptide was blocked by the Trk inhibitor K252a, and reciprocal co-immunoprecipitation demonstrated LAR/TrkA association. The addition of LAR wedge peptide inhibited LAR co-immunoprecipitation with TrkA, augmented NGF-induced activation of TrkA, ERK, and AKT, and in the absence of exogenous NGF, induced activation of TrkA, ERK, and AKT. PTP wedge domain peptides provide a unique PTP inhibition strategy and offer a novel approach for augmenting PTK function

Colour reconnection in e+e- -> W+W- at sqrt(s) = 189 - 209 GeV

The effects of the final state interaction phenomenon known as colour reconnection are investigated at centre-of-mass energies in the range sqrt(s) ~ 189-209 GeV using the OPAL detector at LEP. Colour reconnection is expected to affect observables based on charged particles in hadronic decays of W+W-. Measurements of inclusive charged particle multiplicities, and of their angular distribution with respect to the four jet axes of the events, are used to test models of colour reconnection. The data are found to exclude extreme scenarios of the Sjostrand-Khoze Type I (SK-I) model and are compatible with other models, both with and without colour reconnection effects. In the context of the SK-I model, the best agreement with data is obtained for a reconnection probability of 37%. Assuming no colour reconnection, the charged particle multiplicity in hadronically decaying W bosons is measured to be (nqqch) = 19.38+-0.05(stat.)+-0.08 (syst.).Comment: 30 pages, 9 figures, Submitted to Euro. Phys. J.

Search for the Standard Model Higgs Boson with the OPAL Detector at LEP

This paper summarises the search for the Standard Model Higgs boson in e+e- collisions at centre-of-mass energies up to 209 GeV performed by the OPAL Collaboration at LEP. The consistency of the data with the background hypothesis and various Higgs boson mass hypotheses is examined. No indication of a signal is found in the data and a lower bound of 112.7GeV/C^2 is obtained on the mass of the Standard Model Higgs boson at the 95% CL.Comment: 51 pages, 21 figure

Measurement of the Hadronic Photon Structure Function F_2^gamma at LEP2

The hadronic structure function of the photon F_2^gamma is measured as a function of Bjorken x and of the factorisation scale Q^2 using data taken by the OPAL detector at LEP. Previous OPAL measurements of the x dependence of F_2^gamma are extended to an average Q^2 of 767 GeV^2. The Q^2 evolution of F_2^gamma is studied for average Q^2 between 11.9 and 1051 GeV^2. As predicted by QCD, the data show positive scaling violations in F_2^gamma. Several parameterisations of F_2^gamma are in agreement with the measurements whereas the quark-parton model prediction fails to describe the data.Comment: 4 pages, 2 figures, to appear in the proceedings of Photon 2001, Ascona, Switzerlan

Search for R-Parity Violating Decays of Scalar Fermions at LEP

A search for pair-produced scalar fermions under the assumption that R-parity is not conserved has been performed using data collected with the OPAL detector at LEP. The data samples analysed correspond to an integrated luminosity of about 610 pb-1 collected at centre-of-mass energies of sqrt(s) 189-209 GeV. An important consequence of R-parity violation is that the lightest supersymmetric particle is expected to be unstable. Searches of R-parity violating decays of charged sleptons, sneutrinos and squarks have been performed under the assumptions that the lightest supersymmetric particle decays promptly and that only one of the R-parity violating couplings is dominant for each of the decay modes considered. Such processes would yield final states consisting of leptons, jets, or both with or without missing energy. No significant single-like excess of events has been observed with respect to the Standard Model expectations. Limits on the production cross- section of scalar fermions in R-parity violating scenarios are obtained. Constraints on the supersymmetric particle masses are also presented in an R-parity violating framework analogous to the Constrained Minimal Supersymmetric Standard Model.Comment: 51 pages, 24 figures, Submitted to Eur. Phys. J.

Стартап выведения на внутриигровой рынок IT-продукта на базе платформы Steam

Анализ способов ведения коммерческой деятельности в рамках платформы Steam и игры Counter-Strike: Global Offensive. Разработка it-продукта для повышения эффективности работы на платформе Steam. Оформление разработки в качестве стартапа.Analysis of ways of doing business within the Steam platform and the game Counter-Strike: Global Offensive. Development of an it-product to improve the efficiency of work on the Steam platform. Registration of development as a startup

Оценка воздействия социальных медиа на политические и социокультурные взгляды молодежи в условиях глобальной трансформации общества (на примере видеоблогинга)

Исследование социальных медиа - одна из самых динамично развивающихся областей современной социологии. Актуальность исследования обусловлена трансформацией общественных ценностей, формированием глобальной политической и культурной среды и значительным влиянием современных информационных технологий на всю социокультурную систему. Целью исследования является оценка воздействия социальных медиа на социокультурную трансформацию общества и анализ влияния видеоблогинга как формы социальных медиа на молодых людей в возрасте от 17 до 30 лет. Методы. В процессе исследования был использован абстрактно-логический подход на основе системного анализа существующих эмпирических данных и онлайн-опроса, проведенного в социальной сети «ВКонтакте» среди студентов МГУ им. М.В. Ломоносова и студентов Национального исследовательского университета «Высшая школа экономики». Опрос содержал большое количество вариантов ответов (перечисление имен известных блогеров) и возможность добавления респондентом собственных вариантов ответов и комментариев. Результаты. Выяснилось, что воздействие блогеров на мировоззрение зрителей молодого поколения значительно. Половина опрошенных респондентов в возрасте от 17 до 30 лет интересуются политическими блогами, что говорит о возрастающей роли видеоблогинга среди молодежи в сети Интернет. Этот вид социальных медиа становится ареной политической борьбы за влияние на мировоззрение молодежи. Большинство участников опроса уделяют внимание политизированным блогерам, в частности Алексею Навальному. Значительная часть респондентов также следит за научно-популярными блогами, что может говорить о желании получать новые знания в сжатом и упрощенном виде.The study of social media is one of the most dynamically developing areas of modern sociology. The relevance of the study is caused by transformation of social values, emergence of global political and cultural environment, and significant impact of modern information technologies on the entire socio-cultural system. The aim of the study is to assess the impact of social media on the socio-cultural transformation of society and to analyze the impact of video blogging as a form of social media on young people aged 17 to 30 years. The method. The abstract-logical approach based on the system analysis of existing empirical data and an online-survey was used. The survey was conducted in the social network Vkontakte among students of the Lomonosov Moscow State University and National Research University «Higher School of Economics». The survey had a large number of answers and the possibility for respondents to add their own answers and comments. Results. It was found that the impact of bloggers on the worldview of the younger generation is significant. Half of the respondents aged 17 to 30 are interested in political blogs, which indicates the increasing role of video blogging among young people on the internet. This type of social media becomes battleground for political struggle for influence on the worldview of young people. The majority of respondents pay attention to politicized bloggers, in particular Alexei Navalny. A significant part of respondents also follows popular science blogs, which may indicate a desire to gain new knowledge in a concise and simplified form

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570