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This paper presents the calibration of the most commonly used Volume Delay Functions (VDF): BPR, Conical, Akcelik and Modified Davidson, for an urban area populated by over 1 million inhabitants, the city of Thessaloniki in Greece. The estimation of the unknown coefficients was carried out for a typical freeway, the ring road of the city, and selected arterial and collected roads of the city center, through recent data of hourly observed vehicle speeds and volumes obtained from video recordings and loop detectors. The BPR function yielded the highest accuracy across all the examined road sections and was characterized as the most suitable to simulate and interpret the existing traffic conditions. The estimated coefficients differed significantly from the values proposed in the pertinent literature, which highlights the importance of using locally derived data for the calibration of the VDFs.

Object The relevance of the article is that the breast cancer is a leading oncological disease in women in developed countries and has the highest mortality caused by malignant neoplasms in women. The purpose of the study is to evaluate vaginal microbiota in women with various breast cancer subtypes and compared groups. Methods The study involved 278 women with breast cancer, of whom 174 were patients receiving combination therapy; the control group consisted of 104 patients who had had breast cancer 2-4 years ago. Results It was found that despite a significant decrease in the total number of Lactobacillus spp., there were no statistically significant changes in the numbers of microorganisms in patients with different subtypes of breast cancer. According to the results of the comparative analysis, the representatives of obligate anaerobic flora Peptostreptococcus spp. prevailed in vaginal microbiota in luminal A and luminal B subtypes, and the representative of the facultative anaerobic organisms Staphylococcus spp. - in unfavourable outcomes in Her2/Neu+ and triple-negative subtypes. Conclusion The observed features of the vaginal microbiota in women with different subtypes of breast cancer require further studies for preventive purposes. .

This article presents a computational method for solving a problem with parameter for a system of Fredholm integro-differential equations. Some additional parameters are introduced and the problem under consideration is reduced to solving a system of linear algebraic equations. The coefficients and right-hand side of the system are calculated by solving the Cauchy problems for ordinary differential equations. We establish a criterion for the unique solvability of the problem under consideration. A numerical algorithm is offered for solving the problem with parameter. The results are illustrated by numerical examples.

В статье излагается содержание программы историко-краеведческого кружка, разработанного автором. Подчеркивается, что изучение истории родного края способствует развитию творческих способностей учащихся, повышению эффективности исторического образования и позволяет создать условия для реализации самообразования, потребности к самообразованию.

Made available in DSpace on 2021-06-25T10:16:38Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-11-01 Water flow is a typical hydrodynamic variable of natural occurrence in fish's lifetime and understanding its impact on biological processes (e.g. stress) can contribute to improve welfare in captive/farmed fish. For that, we tested whether water flow is a stressor by itself in a non-rheophilic (i.e. theoretically sensitive to water flow) fish species: Nile tilapia (Oreochromis niloticus). Additionally, this species was chosen due to its importance for world aquaculture and because is cultivated in a number of systems which the water flow could potentially be a stressor such as indoor tanks, recirculating aquaculture systems, biofloc system and cages. Here, we exposed fish to a novel environment with (520 L h−1) or without a deliberated water flow, and we measured plasma cortisol and ventilation rate (VR) as indicators of stress. In a first experiment, the VR was reduced by flow immediately after tilapia transference to a novel environment (16 min of evaluation), but cortisol was not affected. The plasma cortisol levels were also measured in a second experiment, 30 min, 1, 2 and 4 h after transference to a novel environment, but was also not affected by the presence of flow. In a theoretical perspective, flow is not a stressor by itself in a non-rheophilic species. It acted as a hydrodynamic factor that decrease the magnitude of ventilation response in a fish introduced into a novel environment, without effects on plasma cortisol levels. Therefore, the water flow eventually can be used to assist fish oxygenation after a disturbance event, such as introduction into a novel environment. Department of Structural and Functional Biology Institute of Biosciences of Botucatu UNESP CAUNESP Department of Ocean Sciences Memorial University of Newfoundland Department of Structural and Functional Biology Institute of Biosciences of Botucatu UNESP CAUNESP

3-Hydroxypyridine undergoes a smooth reaction with dialkyl acetylenedicarboxylates in the presence of triphenylphosphine to produce alkyl 2-oxo-2H-pyrano[3,2-b]pyridine-4-carboxylate and dialkyl -2-[4-(alkoxycarbonyl)-2-oxo-2-H-pyrano[3,2-b]pyridin-6-yl]-2-butenedioate in high yields. (doi: 10.5562/cca1725)

The purpose of this article is aimed at improving the professional activity of teachers of higher education. The relevance of the topic is determined by the need of society in highly qualified university teachers with a high level of readiness for the implementation of scientific-methodical activities, systematic professional development. The methodological basis of the presented work is the idea of project-goal approach, which enables to justify the essential characteristics, the structure and content of the scientific-methodical activity of teachers in modern conditions. The authors presented the diagnostic system of management of university teachers’ scientific-methodical work and the further training program, providing the increase of social and professional competency level. This article is intended for teachers, researchers, heads of educational institutions involved in the design, management, scientific-methodical service in higher education.

Objective— Focal adhesions (FAs) link the cytoskeleton to the extracellular matrix and as such play important roles in growth, migration, and contractile properties of vascular smooth muscle cells. Recently, it has been shown that downregulation of Nox4, a transforming growth factor (TGF) β-inducible, hydrogen peroxide (H 2 O 2 )–producing enzyme, affects the number of FAs. However, the effectors downstream of Nox4 that mediate FA regulation are unknown. The FA resident protein H 2 O 2 -inducible clone (Hic)-5 is H 2 O 2 and TGFβ inducible, and a binding partner of the heat shock protein (Hsp) 27. The objective of this study was to elucidate the mechanism, by which Hic-5 and Hsp27 participate in TGFβ-induced, Nox4-mediated vascular smooth muscle cell adhesion and migration. Approach and Results— Through a combination of molecular biology and biochemistry techniques, we found that TGFβ, by a Nox4-dependent mechanism, induces the expression and interaction of Hic-5 and Hsp27, which is essential for Hic-5 localization to FAs. Importantly, we found that Hic-5 expression is required for the TGFβ-mediated increase in FA number, adhesive forces and migration. Mechanistically, Nox4 downregulation impedes Smad (small body size and mothers against decapentaplegic) signaling by TGFβ, and Hsp27 and Hic-5 upregulation by TGFβ is blocked in small body size and mothers against decapentaplegic 4–deficient cells. Conclusions— Hic-5 and Hsp27 are effectors of Nox4 required for TGFβ-stimulated FA formation, adhesion strength and migration in vascular smooth muscle cell.

Reactive oxygen species (ROS) have been shown to function as important signaling molecules in the cardiovascular system. Vascular smooth muscle cells (VSMCs) contain several sources of ROS, among which the NADPH oxidases are predominant. In VSMCs, ROS mediate many pathophysiological processes, such as growth, migration, apoptosis and secretion of inflammatory cytokines, as well as physiological processes, such as differentiation, by direct and indirect effects at multiple signaling levels. Therefore, it becomes critical to understand the different roles ROS play in the physiology and pathophysiology of VSMCs.

Modified low-density lipoprotein (LDL) induces reactive oxygen species (ROS) production by vascular cells. It is unknown if specific oxidized components in these LDL particles such as oxidized-1-palmitoyl-2-arachidonoyl- sn -glycero-3-phosphorylcholine (ox-PAPC) can stimulate ROS production. Bovine aortic endothelial cells (BAEC) were incubated with ox-PAPC (50 μg/ml). At 4 h, ox-PAPC significantly enhanced the rate of O 2 − production. Pretreatment of BAEC in glucose-free Dulbecco’s modified Eagle’s medium plus 10 mM 2-deoxyglucose (2-DOG), the latter being an antimetabolite that blocks NADPH production by the pentose shunt, significantly reduced the rate of O 2 − production. The intensity of NAD(P)H autofluorescence decreased by 28 ± 12% in BAEC incubated with ox-PAPC compared to untreated cells, with a further decrease in the presence of 2-DOG. Ox-PAPC also increased Nox4 mRNA expression by 2.4-fold ± 0.1 while pretreatment of BAEC with the small interfering RNA (siNox4) attenuated Nox4 RNA expression. Ox-PAPC further reduced the level of glutathione while pretreatment with apocynin (100 μM) restored the GSH level (control = 22.54 ± 0.23, GSH = 18.06 ± 0.98, apocynin = 22.55 ± 0.60, ox-PAPC + apocynin = 21.17 ± 0.36 nmol/10 6 cells). Treatment with ox-PAPC also increased MMP-2 mRNA expression accompanied by a 1.5-fold increase in MMP-2 activity. Ox-PAPC induced vascular endothelial O 2 - production that appears to be mediated largely by NADPH oxidase activity.

Human cardiac fibroblasts are the main source of cardiac fibrosis associated with cardiac hypertrophy and heart failure. Transforming growth factor-β1 (TGF-β1) irreversibly converts fibroblasts into pathological myofibroblasts, which express smooth muscle α-actin (SM α-actin) de novo and produce extracellular matrix. We hypothesized that TGF-β1–stimulated conversion of fibroblasts to myofibroblasts requires reactive oxygen species derived from NAD(P)H oxidases (Nox). We found that TGF-β1 potently upregulates the contractile marker SM α-actin mRNA (7.5±0.8-fold versus control). To determine whether Nox enzymes are involved, we first performed quantitative real time polymerase chain reaction and found that Nox5 and Nox4 are abundantly expressed in cardiac fibroblasts, whereas Nox1 and Nox2 are barely detectable. On stimulation with TGF-β1, Nox4 mRNA is dramatically upregulated by 16.2±0.8-fold (n=3, P P P

Background— Reactive oxygen species (ROS) have been implicated in the development of cardiovascular pathologies. NAD(P)H oxidases (Noxes) are major sources of reactive oxygen species in the vessel wall, but the importance of individual Nox homologues in specific layers of the vascular wall is unclear. Nox1 upregulation has been implicated in cardiovascular pathologies such as hypertension and restenosis. Methods and Results— To investigate the pathological role of Nox1 upregulation in vascular smooth muscle, transgenic mice overexpressing Nox1 in smooth muscle cells (Tg SMCnox1 ) were created, and the impact of Nox1 upregulation on the medial hypertrophic response during angiotensin II (Ang II)–induced hypertension was studied. These mice have increased expression of Nox1 protein in the vasculature, which is accompanied by increased superoxide production. Infusion of Ang II (0.7 mg/kg per day) into these mice for 2 weeks led to a potentiation of superoxide production compared with similarly treated negative littermate controls. Systolic blood pressure and aortic hypertrophy were also markedly greater in Tg SMCnox1 mice than in their littermate controls. To confirm that this potentiation of vascular hypertrophy and hypertension was due to increased ROS formation, additional groups of mice were coinfused with the antioxidant Tempol. Tempol decreased the level of Ang II-induced aortic superoxide production and partially reversed the hypertrophic and hypertensive responses in these animals. Conclusions— These data indicate that smooth muscle-specific Nox1 overexpression augments the oxidative, pressor, and hypertrophic responses to Ang II, supporting the concept that medial Nox1 participates in the development of cardiovascular pathologies.

Objective— Reactive oxygen species (ROS) that act as signaling molecules in vascular smooth muscle cells (VSMC) and contribute to growth, hypertrophy, and migration in atherogenesis are produced by multi-subunit NAD(P)H oxidases. Nox1 and Nox4, two homologues to the phagocytic NAD(P)H subunit gp91 phox , both generate ROS in VSMC but differ in their response to growth factors. We hypothesize that the opposing functions of Nox1 and Nox4 are reflected in their differential subcellular locations. Methods and Results— We used immunofluorescence to visualize the NAD(P)H subunits Nox1, Nox4, and p22 phox in cultured rat and human VSMC. Optical sectioning using confocal microscopy showed that Nox1 is co-localized with caveolin in punctate patches on the surface and along the cellular margins, whereas Nox4 is co-localized with vinculin in focal adhesions. These immunocytochemical distributions are supported by membrane fractionation experiments. Interestingly, p22 phox , a membrane subunit that interacts with the Nox proteins, is found in surface labeling and in focal adhesions in patterns similar to Nox1 and Nox4, respectively. Conclusions— The differential roles of Nox1 and Nox4 in VSMC may be correlated with their differential compartmentalization in specific signaling domains in the membrane and focal adhesions.

The importance of reactive oxygen species (ROS) in vascular physiology and pathology is becoming increasingly evident. All cell types in the vascular wall produce ROS derived from superoxide-generating protein complexes similar to the leukocyte NADPH oxidase. Specific features of the vascular enzymes include constitutive and inducible activities, substrate specificity, and intracellular superoxide production. Most phagocyte enzyme subunits are found in vascular cells, including the catalytic gp91phox (aka, nox2), which was the earliest member of the newly discovered nox family. However, smooth muscle frequently expresses nox1 rather than gp91phox, and nox4 is additionally present in all cell types. In cell culture, agonists increase ROS production by activating multiple signals, including protein kinase C and Rac, and by upregulating oxidase subunits. The oxidases are also upregulated in vascular disease and are involved in the development of atherosclerosis and a significant part of angiotensin II-induced hypertension, possibly via nox1 and nox4. Likewise, enhanced vascular oxidase activity is associated with diabetes. Therefore, members of this enzyme family appear to be important in vascular biology and disease and constitute promising targets for future therapeutic interventions.