СЛУЧАЙНЫЕ ПРОЦЕССЫ ВОЗМУЩЕНИЯ В ДИНАМИКЕ РЕЛЬСОВЫХ ЭКИПАЖЕЙ

Previous works contained correlation and spectral  analysis of the four-dimensional  disturbance  process in the form of vertical and horizontal irregularities of left and right rails, causing oscillations in rail vehicles. But when speed increases, the disturbance frequency range shifts to high frequencies and can go beyond natural frequencies of the system. Then disturbance almost ceases to excite a part of vibration frequencies and obtained results will be incorrect.The article considers requirements to the procedure of computer generating a multidimensional stationary random disturbance process, causing vibrations of rail vehicles.  Using  modeling,  computer  simulation,  and mathematical analysis it is shown that when the speed alters it is necessary to change terms of the composition of the random process of geometrical irregularities of the  track.  The  requirements  for  parameters  of  the probabilistic analysis are determined, examples of generating and the results of spectral analysis of irregularities generated for different speeds are shown.В статье рассмотрены требования к процедуре генерации на ЭВМ многомерного стационарного случайного процесса возмущения, вызывающего колебания рельсовых экипажей. Показано, что при изменении скорости движения необходимо менять состав слагаемых случайного процесса геометрических неровностей рельсового пути. Определены требования к параметрам вероятностного анализа, приведены примеры генерации и результаты спектрального анализа случайных неровностей для различных скоростей движения

Synthesis of Structurally Related Coumarin Derivatives as Antiproliferative Agents

A library of structurally related coumarins was generated through synthesis reactions and chemical modification reactions to obtain derivatives with antiproliferative activity both in vivo and in vitro. Out of a total of 35 structurally related coumarin derivatives, seven of them showed inhibitory activity in in vitro tests against Taq DNA polymerase with IC50 values lower than 250 μM. The derivatives 4-(chloromethyl)-5,7-dihydroxy-2H-chromen-2-one (2d) and 4-((acetylthio)methyl)-2-oxo-2H-chromen-7-yl acetate (3c) showed the most promising anti-polymerase activity with IC50 values of 20.7 ± 2.10 and 48.25 ± 1.20 μM, respectively. Assays with tumor cell lines (HEK 293 and HCT-116) were carried out, and the derivative 4-(chloromethyl)-7,8-dihydroxy-2H-chromen-2-one (2c) was the most promising, with an IC50 value of 8.47 μM and a selectivity index of 1.87. In addition, the derivatives were evaluated against Saccharomyces cerevisiae strains that report about common modes of actions, including DNA damage, that are expected for agents that cause replicative stress. The coumarin derivatives 7-(2-(oxiran-2-yl)ethoxy)-2H-chromen-2-one (5b) and 7-(3-(oxiran-2-yl)propoxy)-2H-chromen-2-one (5c) caused DNA damage in S. cerevisiae. The O-alkenylepoxy group stands out as that with the most important functionality within this family of 35 derivatives, presenting a very good profile as an antiproliferative scaffold. Finally, the in vitro antiretroviral capacity was tested through RT-PCR assays. Derivative 5c showed inhibitory activity below 150 μM with an IC50 value of 134.22 ± 2.37 μM, highlighting the O-butylepoxy group as the functionalization responsible for the activity.This research was supported by CONICET (PIP 11220200101091CO 2021-2023), PICT 2017-0785 Type D of the National Agency for Scientific and Technological Promotion, UNSL (PROICO 02-2620), and RGLP from AvH Foundation. E.F.B.-H. thanks CONICET for doctoral fellowship and specially to Graphic Designer Bruna-Haupt L. for his help. H.A.G. thanks CONICET for belonging to the CIC. We wish thank to Dr. Di Marco N. I. for the genetic material gently provided. C.R.P. thanks CONICET for belonging to the CIC and Alexander von Humboldt Foundation for the different subsidies. We appreciate language revision by staff from the Instituto de Lenguas, UNSL, and specially Mg. Rezzano S.F.M. thanks to the Spanish Ministry of Science (research grant BFU2017-83954-R), ACIISI (research grant ProID2017010167), and FIISC (research grant PIFIIS19/04). C.G. thanks Ministerio de Ciencia, Innovación y Universidades (MCIU) of Spain-European Regional Development Fund (ERDF) (PGC2018-094503-B-C22). This work is a part of the cotutelled (UNSL-ULL) Ph.D. of E.F.B.-H.Peer reviewe

Defects in Regulation of Local Immune Responses Resulting in Atherosclerosis

Atherosclerosis is nowadays generally accepted as an inflammatory disease but the mechanism of its origin and development have not yet been fully clarified. The present review focuses on the role of the local immune system as one of the key players in the pathogenesis of the complex process. Its part represented by vascular-associated lymphoid tissue (VALT) within the arterial wall participates directly in the vascular wall's homeostatis. Its inordinate activation during ontogenic development of an individual, this formerly defensive and physiologic mechanism transform into a pathological process resulting in an impairing inflammation. Hsp60, CRP and oxidized or otherwise modified LDL are serious candidates for triggering these pathological changes. The principal role is played by anti-Hsp60 antibodies and by shear stress originating on the surface of endothelium due to blood flow. The experimental and clinical data supporting this immunological hypothesis of atherosclerosis are discussed

Planck intermediate results V : Pressure profiles of galaxy clusters from the Sunyaev-Zeldovich effect

This article has an erratum: http://dx.doi.org/10.1051/0004-6361/201220040ePeer reviewe

Relationship between the Clinical Frailty Scale and short-term mortality in patients ≥ 80 years old acutely admitted to the ICU: a prospective cohort study.

BACKGROUND: The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context. METHODS: We analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient's age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score. RESULTS: The median age in the sample of 7487 consecutive patients was 84 years (IQR 81-87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p < 0.001). The relationship between the CFS score and mortality was nonlinear (p < 0.01). CONCLUSION: Knowledge about a patient's frailty status adds a substantial amount of new prognostic information at the moment of admission to the ICU. Arbitrary simplification of the CFS score into fewer groups than originally intended leads to a loss of information and should be avoided. Trial registration NCT03134807 (VIP1), NCT03370692 (VIP2)

A Fluorescent Cage for Supramolecular Sensing of 3-Nitrotyrosine in Human Blood Serum

3-Nitrotyrosine (NT) is generated by the action of peroxynitrite and other reactive nitrogen species (RNS), and as a consequence it is accumulated in inflammation-associated conditions. This is particularly relevant in kidney disease, where NT concentration in blood is considerably high. Therefore, NT is a crucial biomarker of renal damage, although it has been underestimated in clinical diagnosis due to the lack of an appropriate sensing method. Herein we report the first fluorescent supramolecular sensor for such a relevant compound: Fluorescence by rotational restriction of tetraphenylethenes (TPE) in a covalent cage is selectively quenched in human blood serum by 3-nitrotyrosine (NT) that binds to the cage with high affinity, allowing a limit of detection within the reported physiological concentrations of NT in chronic kidney disease.Ministerio de Ciencia e Innovación. Grant Numbers: PGC2018-094503-B-C21, PID2019-110430GB-C21, PID2019-107335RA-I00, PGC2018-096880-A-I0

ВИБІР МІСЦЬ УСТАНОВКИ ПРИСТРОЇВ ТА КІЛЬКІСТЬ ЗАЇЗДІВ ПРИ ПРОВЕДЕНІ ВИПРОБУВАНЬ ПО ВПЛИВОВІ НА ШЛЯХ

An analysis of existing approaches to defining the sites of installation of measuring devices and the number of runs for getting reliable information in rolling stock track impact tests has been performed. A method of correction of the number of runs and selection of the sites for installation of measuring devices on the tested track section has been offered.Проведен анализ существующих подходов определения мест установки приборов и количества заездов для получения достаточной информации во время проведения испытаний подвижного состава для определения сил и напряжения в элементах рельсовой колеи. Приведен метод корректировки числа заездов, выбора мест установки приборов на опытном участке.Проведено аналіз існуючих підходів визначення місць установлення приладів та кількості заїздів для отримання достатньої інформації під час проведення випробувань рухомого складу для визначення сил та напруги в елементах рейкової колії. Наведено метод коректування числа заїздів, вибору місць установлення приладів на дослідній ділянці