Bending oscillations of a cylinder, surrounded by an elastic medium and containing a viscous liquid and an oscillator

The article considers dynamic processes mathematical modeling in a mechanical system, consisting of an elastic hollow cylinder, surrounded by an elastic medium and containing viscous liquid and vibrating coaxial rigid cylinder. The amplitude frequency characteristic for investigating bending cylinder oscillations as one-mass system is defined. It is shown, that the constructed amplitude characteristic makes it possible to define the considered system resonance frequencies oscillations. The calculations demonstrated the significance of taking into account viscous liquid inertia and the surrounding elastic medium

Hydroelasticity of three elastic coaxial shells interacting with viscous incompressible fluids between them under vibration

Elastic cylindrical shells interacting with a viscous incompressible fluid are widely used in various branches of science and technology, such as engineering and aviation engineering. They provide the possibility for solving a lot of problems, such as: reducing constructing weight and dimensions, equalizing dynamic influences and vibration level, as well as reducing friction and wearing, cooling. Mathematical model of the system, representing three coaxial cylindrical shells, freely supported at the ends, and interacting with viscous incompressible fluid between them under mechanical system harmonic vibration is constructed. This mathematical model represents a coupled system consisting of the Navier-Stokes, continuity for each fluid and equations and the ones of elastic coaxial cylindrical shells dynamics which are based on the Kirchhoff-Love hypotheses and the corresponding boundary conditions, namely: for the fluid non-flow and for free attaching for the shells. The constructed mathematical model allows to investigate the oscillations of a mechanical system consisting of coaxial elastic cylindrical shells interacting with viscous incompressible liquids in order to identify dangerous operating modes

Circadian Clock Controls Rhythms in Ketogenesis by Interfering with PPAR alpha Transcriptional Network

Ketone bodies are energy-rich metabolites and signaling molecules whose production is mainly regulated by diet. Caloric restriction (CR) is a dietary intervention that improves metabolism and extends longevity across the taxa. We found that CR induced high -amplitude daily rhythms in blood ketone bodies (beta-hydroxybutyrate [beta OHB]) that correlated with liver beta OHB level. Time-restricted feeding, another periodic fasting-based diet, also led to rhythmic beta OHB but with reduced amplitude. CR induced strong circadian rhythms in the expression of fatty acid oxidation and ketogenesis genes in the liver. The transcriptional factor peroxisome-proliferator-activated-receptor alpha (PPAR alpha) and its transcriptional target hepatokine fibroblast growth factor 21 (FGF21) are pri-mary regulators of ketogenesis. Fgf21 expression and the PPAR alpha transcriptional network became highly rhythmic in the CR liver, which implicated the involvement of the circa-dian clock. Mechanistically, the circadian clock proteins CLOCK, BMAL1, and crypto-chromes (CRYs) interfered with PPAR alpha transcriptional activity. Daily rhythms in the blood beta OHB level and in the expression of PPAR alpha target genes were significantly impaired in circadian clock-deficient Cry1,22(-/-) mice. These data suggest that blood beta OHB level is tightly controlled and that the circadian clock is a regulator of diet -induced ketogenesis

Mathematical model of elastic ribbed shell dynamics interaction with viscous liquid under vibration

The mechanical model of the system, formed by two surfaces of the coaxial cylindrical shells interacting with viscous incompressible liquid between them under vibration, is considered. The outer shell is geometrically irregular, and inner one is an absolutely rigid cylinder. The mathematical model of this system, consisting of differential equations in partial derivatives for describing dynamics of viscous incompressible liquid and an elastic ribbed shell together with boundary conditions is constructed. The expressions for amplitude frequency characteristics of outer geometrically irregular shell are discovered

Mechanisms of autoimmune pathology in post-COVID syndrome

One of the delayed consequences of SARS-CoV-2 infection is post-acute COVID-19 – polymorphic disorders of various organ systems that affect COVID-19 convalescents and persist for more than four weeks after an acute infection. Due to the infectious nature of the COVID-19, we would like to pay special attention to complications from the immune system, especially concomitant and new-onset autoimmune pathology. This review analyzes the current state of the issue of post-acute COVID-19 complications, discusses the molecular features of the SARS-CoV-2 virus and the mechanisms underlying the impaired immune response during acute COVID-19 infection and the occurrence of autoimmune and autoinflammatory conditions during convalescence. Particular attention is paid to the molecular mimicry of antigenic determinants of the SARS-CoV-2 virus, which are structurally similar to the epitopes of human autoantigens. The current data on post-acute COVID-19 autoimmune complications from humoral immunity and the endocrine system, as well as reproductive disorders faced by male patients are presented. For the first time, we hypothesize a role of the structural homology of the human SOX13 autoantigen (HMG box factor SOX13) associated with diabetes mellitus and SARS-CoV-2 envelope (E) protein in the development of the post-acute COVID-19 autoimmune pathologies. Due to the structural similarity of the two proteins and the overlap of their immunogenic regions, we suggest that the increased risk of developing diabetes mellitus and reproductive disorders in men after suffering from COVID-19 may be associated with immunological cross-reactivity

How accurately can we predict the melting points of drug-like compounds?

© 2014 American Chemical Society. This article contributes a highly accurate model for predicting the melting points (MPs) of medicinal chemistry compounds. The model was developed using the largest published data set, comprising more than 47k compounds. The distributions of MPs in drug-like and drug lead sets showed that >90% of molecules melt within [50,250]°C. The final model calculated an RMSE of less than 33 °C for molecules from this temperature interval, which is the most important for medicinal chemistry users. This performance was achieved using a consensus model that performed calculations to a significantly higher accuracy than the individual models. We found that compounds with reactive and unstable groups were overrepresented among outlying compounds. These compounds could decompose during storage or measurement, thus introducing experimental errors. While filtering the data by removing outliers generally increased the accuracy of individual models, it did not significantly affect the results of the consensus models. Three analyzed distance to models did not allow us to flag molecules, which had MP values fell outside the applicability domain of the model. We believe that this negative result and the public availability of data from this article will encourage future studies to develop better approaches to define the applicability domain of models. The final model, MP data, and identified reactive groups are available online at http://ochem.eu/article/55638

Development of DNA aptamer selection approach based on membrane ultrafiltration of aptamer/target complex

Background. Aptamers are small single-stranded DNA or RNA molecules that have an affinity for a specific target molecule. The main method of aptamers construction is the technology of systematic evolution of ligands with exponential enrichment (SELEX). However, the exact approach depends on the nature of target molecules, and is selected and optimized by each researcher independently. The article describes the technique of production of aptamers to the tick-borne encephalitis virus (TBEV) using membrane ultrafiltration with a molecular weight cut-off of 100 kDa. As a result, the pool of aptamers with observable affinity for TBEV is successfully selected and enriched.The aim. To develop the technique suitable for selection of specific DNA aptamers to a live, crude TBEV suspension directly in cell culture supernatant.Materials and methods. The selection of aptamers was carried out using a modified SELEX DNA aptamer technology in combination with semipermeable membrane ultrafiltration using Vivaspin 6 (Sartorius, Germany) concentrators of molecular weight cut-off of 100 kDa. Enrichment of a specific pool of aptamers was performed using real time polymerase chain reaction. Aptamers were sequenced with automated Sanger sequencing method. The direct virucidal effect of the aptamers was determined by the decrease in the titer of the infectious virus after incubation with the aptamer.Results. The pool of aptamers to TBEV was selected and enriched. This aptamer pool expressed affinity both to the infectious TBEV and to the TBEV antigen. Sixteen aptamers were sequenced from this pool and four of them were synthesized and tested for antiviral activity against TBEV. No antiviral activity was observed.Conclusions. The technique developed that can be successfully used to select aptamers to a live virus culture for the viruses comparable in size to TBEV or larger

6-gene promoter methylation assay is potentially applicable for prostate cancer clinical staging based on urine collection following prostatic massage

The detection of prostate cancer (PCa) biomarkers in bodily fluids, a process known as liquid biopsy, is a promising approach and particularly beneficial when performed in urine samples due to their maximal non‑invasiveness requirement of collection. A number of gene panels proposed for this purpose have allowed discrimination between disease‑free prostate and PCa; however, they bear no significant prognostic value. With the purpose to develop a gene panel for PCa diagnosis and prognosis, the methylation status of 17 cancer-associated genes were analyzed in urine cell‑free DNA obtained from 31 patients with PCa and 33 control individuals using methylation‑specific polymerase chain reaction (MSP). Among these, 13 genes indicated the increase in methylation frequency in patients with PCa compared with controls. No prior association has been reported between adenomatosis polyposis coli 2 (APC2), homeobox A9, Wnt family member 7A (WNT7A) and N‑Myc downstream‑regulated gene 4 protein genes with PCa. The 6‑gene panel consisting of APC2, cadherin 1, forkhead box P1, leucine rich repeat containing 3B, WNT7A and zinc family protein of the cerebellum 4 was subsequently developed providing PCa detection with 78% sensitivity and 100% specificity. The number of genes methylated (NGM) value introduced for this panel was indicated to rise monotonically from 0.27 in control individuals to 4.6 and 4.25 in patients with highly developed and metastatic T2/T3 stage cancer, respectively. Therefore, the approach of defining the NGM value may not only allow for the detection of PCa, but also provide a rough evaluation of tumor malignancy and metastatic potential by non‑invasive MSP analysis of urine samples

Синтез цис- та транс-3-(4-гідроксифеніл)циклобутанкарбонових кислот та дослідження їх похідних як лігандів рецептора GPR-40

Aim. To synthesize cis- and trans-isomers of 3-(4-hydroxyphenyl)cyclobutanecarboxylic acid and evaluate the biological activity of their derivatives against GPR-40.Results and discussion. Cis- and trans-isomers of 3-(4-hydroxyphenyl)cyclobutanecarboxylic acid were synthesized. The derivatives of this compound were tested as GPR-40 agonists and exhibited the micromolar activity.Experimental part. The methyl ester of 3-(4-hydroxyphenyl)cyclobutanecarboxylic acid was obtained as a mixture of cis/trans-isomers in 3 steps starting from a commercially available 3-oxocyclobutanecarboxylic acid. Further transformation of this compound into isomerically pure 3-(4-hydroxyphenyl)cyclobutanecarboxylic acids was achieved in five steps based on the chromatographic separation of diastereomeric amide derivatives. New GPR-40 ligands were obtained by O-alkylation of a phenolic oxygen atom of the corresponding carboxylic acid methyl ester. The biological activity of the agonists synthesized was studied using a fluorometric bioassay and the engineered Chinese hamster ovary (CHO) stable cell line expressing the human GPR-40.Conclusions. An effective synthetic approach to 3-(4-hydroxyphenyl)cyclobutanecarboxylic acid allowing to isolate two single cis/trans-stereoisomers of this compound has been developed. In order to demonstrate the possibility for the bioisosteric replacement of the ethylene moiety in the structures of free fatty acid receptor (FFAR) agonists by the cyclobutane ring, four new GPR-40 ligands possessing the micromolar activity have been synthesized.Received: 22.08.2020 Revised: 11.10.2020 Accepted: 17.10.2020Мета. Синтезувати цис- та транс-ізомери 3-(4-гідроксифеніл)циклобутанкарбонової кислоти та виявити біологічну активність їх похідних щодо рецептора GPR-40.Результати та їх обговорення. Було синтезовано цис- та транс-ізомери 3-(4-гідроксифеніл)циклобутанкарбонової кислоти, а також їх похідні, що виявили мікромолярну активність як агоністи рецептора GPR-40.Експериментальна частина. Метиловий естер 3-(4-гідроксифеніл)циклобутанкарбонової кислоти було одержано у вигляді суміші цис- та транс-ізомерів у три стадії, виходячи з комерційно доступної 3-оксоциклобутанкарбонової кислоти. Подальше перетворення цієї речовини на ізомерно чисті 3-(4-гідроксифеніл)циклобутанкарбонові кислоти було досягнуто у п’ять стадій, що ґрунтувалося на хроматографічному розділенні діастереомерних амідних похідних. Нові ліганди рецептора GPR-40 одержано шляхом О-алкілування за фенольним атомом оксигену відповідного метилового естеру кислоти. Біологічну активність синтезованих агоністів досліджено на стабільній лінії клітин яєчників китайського хом’яка (CHO), яка експресує людський рецептор GPR-40, за допомогою флуориметричного біотесту.Висновки. Розроблено ефективний підхід до синтезу 3-(4-гідроксифеніл)циклобутанкарбонової кислоти, що дозволяє одержати її у вигляді двох індивідуальних цис/транс-стереоізомерів. Для демонстрації можливості біоізостерної заміни етиленової ланки в структурі агоністів рецепторів вільних жирних кислот (FFAR) на циклобутанове кільце було також синтезовано чотири нові ліганди GPR-40, що мали мікромолярну активність.Received: 22.08.2020 Revised: 11.10.2020 Accepted: 17.10.202