Tension Development Research Articles

The influence of dapagliflozin on cardiac remodeling, myocardial function and metabolomics in type 1 diabetes mellitus rats

BackgroundSodium-glucose cotransporter (SGLT)2 inhibitors have displayed beneficial effects on the cardiovascular system in diabetes mellitus (DM) patients. As most clinical trials were performed in Type 2 DM, their effects in Type 1 DM have not been established.ObjectiveTo evaluate the influence of long-term treatment with SGLT2 inhibitor dapagliflozin on cardiac remodeling, myocardial function, energy metabolism, and metabolomics in rats with Type 1 DM.MethodsMale Wistar rats were divided into groups: Control (C, n = 15); DM (n = 15); and DM treated with dapagliflozin (DM + DAPA, n = 15) for 30 weeks. DM was induced by streptozotocin. Dapagliflozin 5 mg/kg/day was added to chow. Statistical analysis: ANOVA and Tukey or Kruskal-Wallis and Dunn.ResultsDM + DAPA presented lower glycemia and higher body weight than DM. Echocardiogram showed DM with left atrium dilation and left ventricular (LV) hypertrophy, dilation, and systolic and diastolic dysfunction. In LV isolated papillary muscles, DM had reduced developed tension, +dT/dt and -dT/dt in basal condition and after inotropic stimulation. All functional changes were attenuated by dapagliflozin. Hexokinase (HK), phosphofructokinase (PFK) and pyruvate kinase (PK) activity was lower in DM than C, and PFK and PK activity higher in DM + DAPA than DM. Metabolomics revealed 21 and 5 metabolites positively regulated in DM vs. C and DM + DAPA vs. DM, respectively; 6 and 3 metabolites were negatively regulated in DM vs. C and DM + DAPA vs. DM, respectively. Five metabolites that participate in cell membrane ultrastructure were higher in DM than C. Metabolites levels of N-oleoyl glutamic acid, chlorocresol and N-oleoyl-L-serine were lower and phosphatidylethanolamine and ceramide higher in DM + DAPA than DM.ConclusionLong-term treatment with dapagliflozin attenuates cardiac remodeling, myocardial dysfunction, and contractile reserve impairment in Type 1 diabetic rats. The functional improvement is combined with restored pyruvate kinase and phosphofructokinase activity and attenuated metabolomics changes.

Differences in Mechanical, Electrical and Calcium Transient Performance of the Isolated Right Atrial and Ventricular Myocardium of Guinea Pigs at Different Preloads (Lengths)

There are only a few studies devoted to the comparative and simultaneous study of the mechanisms of the length-dependent regulation of atrial and ventricular contractility. Therefore, an isometric force-length protocol was applied to isolated guinea pig right atrial (RA) strips and ventricular (RV) trabeculae, with a simultaneous measurement of force (Frank–Starling mechanism) and Ca2+ transients (CaT) or transmembrane action potentials (AP). Over the entire length-range studied, the duration of isometric contraction, CaT and AP, were shorter in the RA myocardium than in the RV myocardium. The RA myocardium was stiffer than the RV myocardium. With the increasing length of the RA and RV myocardium, the amplitude and duration of isometric contraction and CaT increased, as well as the amplitude and area of the “CaT difference curves” (shown for the first time). However, the rates of the tension development and relaxation decreased. No contribution of AP duration to the heterometric regulation of isometric tension was found in either the RA or RV myocardium of the guinea pig. Changes in the degree of overlap of the contractile proteins of the guinea pig RA and RV myocardium mainly affect CaT kinetics but not AP duration.

B-308 Focal Adhesion Kinase Activation is Involved in Tension Development During Contractile Stimulation of Mouse Detrusor Smooth Muscle to Modulate Bladder Dysfunction-Related Lower Urinary Tract Symptoms

Abstract Background The function of the bladder is to store and expel urine. Bladder dysfunction-related lower urinary tract symptoms (LUTS) is a common urological problem and negatively affects health-related quality of life. Investigation of detrusor muscle contraction mechanisms is necessary to understand its underlying pathophysiology. Voiding occurs through bladder muscle contraction, which is mediated primarily by the increased intracellular Ca2+ concentration-induced myosin regulatory light chain (MLC) phosphorylation. Recent studies showed that focal adhesion kinase (FAK)-regulated focal adhesion assembly and actin polymerization are involved in vascular and airway smooth muscle contraction. However, the role of FAK activation in visceral smooth muscle contraction is not well documented. This study aims to determine if FAK activation is involved in mouse detrusor smooth muscle contraction. Methods Normal adult male and female mouse bladders were harvested. The trigone and dome areas were cut, and the bladder body was used. The mucosa was carefully removed. Detrusor muscle strips (1.5–2 × 8–10 mm) were prepared and then suspended in a 20 mL tissue bath filled with physiological Krebs solution and bubbled with 95% O2 and 5% CO2 to obtain a pH of 7.4 at 37 °C. The isometric contraction was recorded. After establishing a stable baseline, the strips were stimulated with 120 mM potassium chloride (KCl), which was used to normalize the contractility induced by subsequent stimuli. One of the following specific inhibitors or the same volume of vehicle (DMSO) was applied and incubated for 30 min: PF-573228 (2 µM, a FAK inhibitor) or latrunculin B (1 µM, an inhibitor of actin polymerization). Then, the contractile responses to KCl (90 mM), electrical field stimulation (EFS, 2–32 Hz), or carbachol (CCh, 10−7.5–10−4.5 M ) were measured. In a separate experiment, the detrusor strips were stimulated with CCh (10 µM) after incubation with PF-573228 (2 µM) or vehicle (DMSO) for 30 min. Once the peak contraction was reached, the strips were snap-frozen for immunoblotting analysis of the phosphorylated FAK (p-FAK) and MLC (p-MLC). Statistical analysis was performed (GraphPad Prism 6). The contractile responses to KCl and EFS between vehicle and inhibitor groups were compared using a paired t-test. Nonlinear regression was used to compare CCh-induced dose-response curves. For the expression of phosphorylated proteins, one-way ANOVA, followed by Tukey’s posthoc test, was used for analysis. Results KCl-induced contractile responses decreased significantly after incubation with PF-573228 or latrunculin B compared to the corresponding vehicle group (P < 0.0001). The contractile responses induced by EFS were significantly inhibited by preincubation with PF-573228 at 8, 16, and 32 Hz (P < 0.05) or latrunculin B at 16 and 32 Hz (P < 0.01). Following the application of PF-573228 or latrunculin B, CCh-induced dose-response contractions were significantly lower than those in the corresponding vehicle-treated strips (P = 0.0021 and 0.0003, respectively). Immunoblotting analysis demonstrated that CCh stimulation caused increased expression of p-FAK and p-MLC, whereas preincubation with PF-573228 led to decreased expression of p-FAK but not p-MLC Conclusion FAK activation is involved in tension development induced by contractile stimulation in mouse detrusor muscle, probably through enhancing actin polymerization, but not MLC phosphorylation.

Methamphetamine increases force of contraction in isolated human atrial preparations through the release of noradrenaline

We measured the cardiac contractile effects of the sympathomimetic amphetamine-like drug methamphetamine alone and in the presence of cocaine or propranolol in human atrial preparations. For a more comprehensive analysis, we also examined the effects of methamphetamine in preparations from the left and right atria of mice and, for comparison, analyzed the cardiac effects of amphetamine itself. In human atrial preparations, methamphetamine and amphetamine increased the contractile force, the relaxation rate, and the rate of tension development, and shortened the time to maximum tension and the time to relaxation. Likewise, in mice preparations, methamphetamine and amphetamine increased the contractile force in the left atrium and increased the beating rate in the right atrium. The effect in human atrial preparations started at 1 µM, therefore methamphetamine was less effective and potent than isoproterenol in increasing contractile force. These positive inotropic effects of methamphetamine were greatly attenuated by 10 µM cocaine and abolished by 10 µM propranolol. The inotropic effects of methamphetamine in human atrial preparations were associated with, and are believed to be mediated at least in part by, an increase in the phosphorylation state of the inhibitory subunit of troponin. In conclusion, the sympathomimetic central stimulant drug methamphetamine (as well as amphetamine) increased contractile force and protein phosphorylation, presumably through a release of noradrenaline in isolated human atrial preparations. Thus, methamphetamine acts as an indirect sympathomimetic in the human atrium.

Methods for Assessing the Psychological Tension of Social Network Users during the Coronavirus Pandemic and Its Uses for Predictive Analysis

This article address approaches to the development of methods for assessing the psychological state of social network members during the coronavirus pandemic through sentiment analysis of messages. The purpose of the work is to determine the psychological tension index by using a previously developed thematically ranked dictionary. Researchers have investigated methods to evaluate psychological tension among social network users and to forecast the psychological distress. The approach is novel in the sense that it ranks emojis by mood, considering both the emotional tone of tweets and the emoji’s dictionary meanings. A novel method is proposed to assess the dynamics of the psychological state of social network users as an indicator of their subjective well-being, and develop targeted interventions for help. Based on the ranking of the Emotional Vocabulary Index (EVI) and Subjective Well-being Index (SWI), a scheme is developed to predict the development of psychological tension. The significance lies in the efficient assessment of the fluctuations in the mental wellness of network users as an indication of their emotions and a prerequisite for further predictive analysis. The findings gave a computed value of EVI of 306.15 for April 2022. The prediction accuracy of 88.75% was achieved.

An Essential Tension in Sustainable Development: Narrative Identity in Adult Learning

Sustainable development can be thought of as changes required by a nation, a community and beyond that can foster a context for individuals to imagine and recreate parts of their tradition to live a different and better life. Intrusions, external or internal, whether in the form of technology, economic, environmental, educational or health can bring dramatic disruptions to those whose lives are based in deep-seated traditions. Adults who learn to fuse old ways of understandings with new can embrace the tension between the two and can emplot a narrative that makes sense to them. Moreover, this narrative holds one’s identity intact, which is particularly important for the adult undergoing major changes in life. Narrative identity is one of the mainstays of sustainable development because the identity of the adult living through development is not designated simply by one’s place or language, but by a story that becomes part of one’s past as well as future. Herein is a discussion of the place narrative identity, as a research directive, can have in sustainable development with practical application exemplified in a malaria reduction project.

Focal adhesion kinase activation is involved in contractile stimulation-induced detrusor muscle contraction in mice

Recent studies suggested smooth muscle contraction may involve mechanisms besides the myosin regulatory light chain (MLC) phosphorylation-induced actomyosin crossbridge cycling. This study aims to determine if focal adhesion kinase (FAK) activation is involved in mouse detrusor muscle contraction. The mouse detrusor muscle strips were preincubated with PF-573228 (2 μM), latrunculin B (1 μM), or the same volume of vehicle (DMSO) for 30 min. The contractile responses to KCl (90 mM), electrical field stimulation (EFS, 2–32 Hz), or carbachol (CCh, 10−7.5-10−4.5 M) were measured. In a separate experiment, the phosphorylated FAK (p-FAK) and MLC (p-MLC) levels were measured in the detrusor strips stimulated with CCh (10 μM) after incubation with PF-573228 or vehicle (DMSO) compared to those with vehicle incubation but without CCh stimulation. KCl-induced contractile responses decreased significantly after incubation with PF-573228 or latrunculin B compared to the corresponding vehicle-treated strips (p < 0.0001). The contractile responses induced by EFS were markedly inhibited by preincubation with PF-573228 at 8, 16, and 32 Hz (p < 0.05) or latrunculin B at 16 and 32 Hz (p < 0.01). Following the application of PF-573228 or Latrunculin B, CCh-induced dose-response contractions were lower than the corresponding vehicle group (p = 0.0021 and 0.0003, respectively). Western blot examination showed that CCh stimulation enhanced the expression of p-FAK and p-MLC, while preincubation with PF-573228 prevented the increase of p-FAK but not p-MLC. In conclusion, FAK activation involves tension development induced by contractile stimulation in the mouse detrusor muscle. This effect is likely caused by promoting actin polymerization rather than elevating MLC phosphorylation.

Dependence of cardiomyocyte force, velocity, and power generation on ATP concentration

Theoretical analysis and computer modeling of myocardial energy metabolism under physiological and heart failure conditions predicts that cytoplasmic ATP and ADP levels both fall roughly in proportion to reductions in total adenine nucleotide pool observed in heart failure. Assessing sub-maximal force and velocity in loaded myocardial muscle at MgATP levels in the range of 2 to 8 mM, Beard et al. ( Biophys. J. 2022. 121: 3213–3223) observed effects of MgATP on myocardial power generation that suggest that although maximal force and velocity are not substantially sensitive to differences in [MgATP] that occur in the normal versus failing myocardium, maximal power generation, which occurs at submaximal force and velocity, is sensitive to [MgATP]. Previously developed computational models are not able to reproduce the observed dependence on MgATP. The goals of the present study are to construct and analyze a computational model of muscle dynamics to analyze data on the dependence of maximal force, velocity, and power generation on [MgATP] in order to determine a potential mechanism to explain the MgATP-dependent phenomena. Model development and identification was guided by dynamic measurements on permeabilized mouse trabecular fibers. The data include force-velocity relation and time constant of tension development. The mathematical model used to simulate cardiomyocyte crossbridge mechanics was based on the previous crossbridge and calcium models from Tewari et al. (J Mol Cell Cardiol, 2016. 96: 11-25) and Campbell et al. (Biophys J, 2018. 115: 543-553). The developed model includes strain- and metabolite-dependent transition between attachment states, and ATP-dependent destabilization of the super-relaxed (SRX) myosin state. Model-based analysis of force and velocity dyanmics is consistent with the hypothesis that ATP assocition with the myosin protein influence the kinetics and thermodynamics of transitions between the SRX and disorded (DRX) states. Funding: Department of Veterans Affairs Merit Review Award I01BX000740 (A.J.B.) and National Heart, Lung, and Blood Institute grant R01 HL154624 (A.J.B., D.A.B.) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of the thromboxane receptor antagonist S18886 in the porcine coronary circulation

Thromboxane A2 (TxA 2 ) is a potent coronary vasoconstrictor that has been implicated in promoting decreases in myocardial perfusion in a variety of (patho)-physiologic conditions. S18886 is a promising orally-active TxA 2 receptor antagonist currently approved for investigational clinical use. However, the coronary vascular effects of S18886 are unknown and its specificity and affinity for the thromboxane receptor in the coronary circulation remain unclear. We tested the hypothesis that administration of S18886 dose-dependently attenuates coronary vasoconstriction to the TxA 2 mimetic U46619 without influencing coronary responses to prostaglandin F 2α , acetylcholine, or smooth muscle depolarization (K + ). Experiments to test this hypothesis were performed in male (n = 5) and female (n = 6) domestic swine. Hearts were excised and the left circumflex coronary artery isolated, cleaned of periadventitial fat, and cut into 3 mm rings. Isometric tension of coronary artery rings was measured in response to log order increments of U46619 (1 nM to 1 μM) with and without S18886 (0.1-100 nM). Similar isometric studies were conducted with prostaglandin F 2α (10 nM-10 μM), acetylcholine (0.1-10 μM), and KCl (5-90 mM). U46619 induced concentration dependent increases in tension development of isolated coronary artery rings (average EC50 of 42 ± 19 nM). Incubation of coronary arteries with S18886 (1 nM) significantly attenuated coronary vasoconstriction to U46619 resulting in a rightward shift of the EC50 to 187 ± 38 nM (P &lt; 0.02). Vehicle had no effect on U46619-induced contractions. Higher concentrations of S18886 (10nM and 100nM) dose-dependently reduced U46619-induced contractions by 77% ± 3 and 93% ± 6 respectively. S18886 (1 nM) antagonized coronary vasoconstriction of prostaglandin F2α (10 μM) by 68% ± 5 (P &lt; 0.0001) but had no effect on either acetylcholine or KCl-induced contraction. Data from this investigation indicate that S18886 is an effective antagonist of U46619-induced vasoconstriction in the porcine coronary circulation. While S18886 does not influence coronary smooth muscle response to either acetylcholine or activation of L-type Ca 2+ channels, attenuation of prostaglandin F 2α suggests the antagonists specificity may extend beyond TxA 2 receptor signaling. NIH R01HL158723 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

COMPREHENSIVE ASSESSMENT OF PSYCHOPHYSIOLOGICAL FACTORS IN THE PROFESSIONAL ADAPTATION OF CADET-GRADUATES TO MILITARY SERVICE

The article provides a comprehensive assessment of the psychophysiological factors affecting the professional adaptation of cadets. It emphasizes that professional development entails the formation of professional orientation, competence, socially significant and professionally important qualities, their integration, readiness for continuous professional growth, and the search for optimal methods to perform activities of high quality and creativity in accordance with individual psychological characteristics. Various approaches to specialist development have been examined by researchers and practitioners, including professional self-determination, stages of specialization, development of professionally important qualities, motivation in work activities, and the fundamentals of labor activity. The main theories that unify these approaches are the theory of types of professional life (structural concepts), motivational theories, and theories of individuality. The study highlights that the adaptation process is influenced by personal factors such as stress resistance, personality type, and emotional perception. The research utilized data obtained through a rhythmograph system, which monitors ECG signals and heart rate variability in the first standard lead, allowing for statistical time and spectral analysis of heart rate. In the initial stage, the assessment of nonverbal and general intelligence development levels was analyzed using the "Color Progressive Matrices" test by J. C. Raven. In the subsequent stage, the correlation between intelligence level and LF norm, HF norm, and LnLF/HF under load was determined. Finally, the adaptability level of the respondents to modern functioning conditions was assessed using the multi-level personality questionnaire "Adaptability" by A. Maklakov and S. Chermianin. The obtained data indicate an inverse proportional relationship between these indicators: "high stress - low adaptability" and vice versa. The article also highlights the significance of nervous-psychic tension, in addition to stress, as an unfavorable factor affecting performance. It lists the main causes contributing to the development of nervous-psychic tension. Furthermore, the works of M. Agadzhanyan, V. Kaznacheev, and S. Kaznacheev identify three qualitatively different types of adaptive human response: "sprinter," "stayer," and "intermediate" types (based on the criterion of time to perform submaximal work). To enhance adaptive abilities, the article proposes the utilization of the bioactivation optimization technique, which effectively enhances a person's psychophysiological functions and meets the requirements for psychophysiological support in military professional activities.

Optimal Design, Development and Experimental Analysis of a Tension–Torsion Hopkinson Bar for the Understanding of Complex Impact Loading Scenarios

BackgroundAdvanced testing methodologies and measurement techniques to identify complex deformation and failure at high strain rates have drawn increasing attention in recent years.ObjectiveThe objective of the current study is the development of a novel combined tension–torsion split Hopkinson bar (TTHB) conceived to generate a combination of tensile and torsional stress waves in a single loading case, and to measure material data representative of real case impact scenarios.MethodsAn energy store and release mechanism was employed to generate both the longitudinal and shear waves via the rapid release of a bespoke clamp assembly. A parametric study of the material and geometry of the clamp was implemented via numerical simulations to optimise critical aspects of the wave generation. Thin-walled tube specimens made of two metallic materials were utilised to examine the capability of the developed TTHB system by comparing the experimental measurements with those obtained from conventional split Hopkinson tension and torsion bars.ResultsThe experimental results demonstrate that the synchronisation of the longitudinal and torsional waves was achieved within 15 microseconds. Different wave rise time were obtained via the controlled release of the clamp using fracture pins of various materials. The analysis indicates that the developed TTHB is capable of characterising the dynamic behaviour of materials under tension, torsion, as well as under a wide range of complex stress states.ConclusionsThe presented apparatus, testing and analysis methods allow for the direct population of the dynamic failure stress envelopes of engineering materials and for the accurate evaluation of existing and novel constitutive models.

Structure and regulation of the myotonic dystrophy kinase-related Cdc42-binding kinase

Protein kinases of the dystonia myotonica protein kinase (DMPK) family are critical regulators of actomyosin contractility in cells. The DMPK kinase MRCK1 is required for the activation of myosin, leading to the development of cortical tension, apical constriction, and early gastrulation. Here, we present the structure, conformation, and membrane-binding properties of Caenorhabditis elegans MRCK1. MRCK1 forms a homodimer with N-terminal kinase domains, a parallel coiled coil of 55nm, and a C-terminal tripartite module of C1, pleckstrin homology (PH), and citron homology (CNH) domains. We report the high-resolution structure of the membrane-binding C1-PH-CNH module of MRCK1 and, using high-throughput and conventional liposome-binding assays, determine its binding to specific phospholipids. We further characterize the interaction of the C-terminal CRIB motif with Cdc42. The length of the coiled-coil domain of DMPK kinases is remarkably conserved over millions of years of evolution, suggesting that they may function as molecular rulers to position kinase activity at a fixed distance from the membrane.

Framing the change and changing frames: Tensions in participative strategy development

AbstractParticipative strategy development serves to integrate the interests and perspectives of multiple stakeholders involved in today's complex environmental challenges, aiming at a better‐informed strategy for tackling these challenges, increased stakeholder ownership, and more democratic decision making. Prior research has observed inherent tensions between the need for participative strategy to be open to stakeholders' input and the need for closure and guidance. We extend this reasoning using a framing perspective. Our evidence from the development of the England Peat Action Plan suggests that tensions can emerge between the necessary ambiguous initial framing of intended change and the persistence of stakeholders' different framings of this change as well as perceptions of lacking knowledge, guidance, and control. We argue that strategy openness can thereby impede stakeholders' willingness and ability to change and counteract the strategy's aim for major transformation. Interactive spaces help mitigate the tensions and facilitate stakeholders' willingness and ability for change.Related ArticlesBrant, Hanna K., Nathan Myers, and Katherine L. Runge. 2017. “Promotion, Protection, and Entrepreneurship: Stakeholder Participation and Policy Change in the 21st Century Cures Initiative.” Politics &amp; Policy 45(3): 372–404. https://doi.org/10.1111/polp.12201.Bryson, John R., Michael Taylor, and Peter W. Daniels. 2008. “Commercializing ‘Creative’ Expertise: Business and Professional Services and Regional Economic Development in the West Midlands, United Kingdom.” Politics &amp; Policy 36(2): 306–28. https://doi.org/10.1111/j.1747‐1346.2008.00107.x.Falkenström, Erica, and Stefan Svallfors. 2022. “The Knowledge–Management Complex: From Quality Registries to National Knowledge‐Driven Management in Swedish Health Care Governance.” Politics &amp; Policy 50(5): 1053–66. https://doi.org/10.1111/polp.12497.

New insights into determining the “time zero” of autogenous shrinkage in low water/binder cement-based composites (LW/B-CC) system based on relaxation theory

This study proposes a novel insight to accurately determine the time zero of autogenous shrinkage in low water/binder cement-based composites (LW/B-CC) based on relaxation theory. Firstly, low-field nuclear magnetic resonance (NMR) technology is used to study the process of water consumption inside the LW/B-CC and clarify the evolution of capillary tension to determine the time zero of autogenous shrinkage. Then, the Laplace equation is used to establish the relationship between water consumption, capillary tension, and autogenous shrinkage in LW/B-CC. The results show that the time corresponding to the development of capillary tension and water consumption in pores is considered as “time zero” of autogenous shrinkage. Furthermore, the capillary tension generated by internal water consumption, about 100 KPa ∼200 KPa, can cause enormous autogenous shrinkage, which easily leads to cracking. In addition, expansion products produced by calcium sulfoaluminate cement (CSA) hydration facilitate the formation of the matrix skeleton and reduce autogenous shrinkage in LW/B-CC. In general, low-field NMR technology is an effective tool to determine the time zero of autogenous shrinkage.

Etničko nasilje i terorizam kao unutrašnji izazovi nacionalnoj bezbednosti Kine - studija slučaja Sinđanga

The national security of the People's Republic of China is susceptible to an array of intricate internal challenges, risks and threats. This includes challenges that may be of a political nature, risks caused by economic and social differences, threats caused by tensions in ethnic relations, as well as many others. This paper seeks to concentrate on ethnic tensions, namely ethnic violence and terrorism, as the most substantial factors that pose a significant threat to the country's stability and security. The paper delves into the development of ethnic tensions and conflicts resulting from the interaction between Chinese authorities and factions within the Uyghur movement for national self-determination. It emphasizes the extremist current within the broader Uyghur ethnonational movement that utilizes violence and acts of terrorism in political activism. This paper aims to follow the evolution and changes of strategies and tactics employed by Uyghur nationalists in Xinjiang over time and present the most characteristic violent and terrorist incidents that occurred in Xinjiang to exemplify these alterations. These changes are reflected in increased violence, a shift in targets from primarily security forces to civilians, including violent clashes between Uyghur and Han citizens and an expansion in the geographic reach of attacks.

Уровень благосостояния населения в регионах Российской Федерации: институциональное и инфраструктурное обеспечение

The article examines the level of population well-being in the regions of the Russian Federation from the standpoint of their institutional and infrastructural support. It is a high-quality institutional environment and developed infrastructure that are the most important conditions for ensuring the population well-being in Russian regions. The authors note a significant differentiation in income levels and their polarization (by fund ratio, decile ratio), which is reflected in the poverty level of the population of the regions. The article presents the results of a study on two regions of the Russian Federation: one leading region and one outsider region, identified by the results of an earlier study conducted by the authors. Yamalo-Nenets Autonomous District is represented as the leader in terms of well-being, while the Republic of Ingushetia is an outsider. The authors proved that the Yamalo-Nenets Autonomous District, being in an unfavorable climatic zone, forms institutional and infrastructural conditions conducive to systematic work on social development and support of the population. At the same time, there is an increase in indicators of social inequality in the region, which may contribute to the development of social tension. Regarding the outsider, the Republic of Ingushetia, it was shown that, having conditions favorable for life and work, and forming an adequate institutional environment and social infrastructure, the region is characterized by an unfavorable social situation: low incomes of the population, high unemployment. The authors believe that it is possible to solve problems in the social sphere with the effective realization of the potential of the region and significant support from the federal center.

Managing tensions in resilience development: a paradox theory perspective on the role of digital transformation

PurposeThe study aims to identify the central paradoxical tensions existing in developing resilience in organisations. The main thrust of this study is to develop a thorough understanding of diverse conflicting tensions in building resilience and develop the possible strategies to surmount these tensions.Design/methodology/approachUsing the case study approach, the study applied theory-elaboration strategy as this study is based on well-established literature from both digitalisation and resilience. The study uses the paradox theory lens in a case study to reconcile both theories with contextual idiosyncrasies.FindingsThe paradox theory lens provides perspectives to understand tensions during resilience development and the role of digital transformation in this process. It assesses the potential solutions for surmounting tensions in resilient operations. The mapping of workable solutions with different paradoxes and propositions has been proposed for future empirical research.Research limitations/implicationsThe study suggests that practitioners should not consider resilience and sustainability as mutually exclusive; instead, managers must embrace ongoing tensions to bring solutions to address these two essential organisational priorities.Originality/valueTo the best of the authors' knowledge, this is the first empirical study that applies paradox theory to understand how an organisation can build resilience while confronting several paradoxes. The study findings support that resilience practices can move in tandem with environmental sustainability goals rather than being usually mutually exclusive.

Seeing Infrastructure, Interrogating Infrastructure: Making explicit the implicit of LIS education and learning environments

Seeing Infrastructure, Interrogating Infrastructure: Making explicit the implicit of LIS education and learning environments

ТӘШЕНЕВ ЖҰМАБЕК АХМЕТҰЛЫ –КЕҢЕСТІК ҚАЗАҚСТАННЫҢ ЖЕТЕКШІ САЯСИ ҚАЙРАТКЕРІ

The article is devoted to public, political personalityof the famous statesman and public figure Tashenev Zhumabek Akhmetovich. The situation of Kazakhstan in the Soviet period, the central government is characterized by the arbitrariness of Moscow. Through the essence ofpersonality, the stages of the development of social relations and social tension of that time are indicated. The fate of fifteen countries, which are legally considered Union republics, was decided only centrally. They lacked not only political will, butalso territorial integrity. The Center pursued its policy by changing the borders of the historical lands of these countries. The main node of this article is the personality of the head of Kazakhstani government Zhumabek Tashenev, who opposed such arbitrariness and preserved his Homeland.Zhumabek Tashenev is a man who has had a huge impact on the spiritual life of the republic. In the article, these points seem to be completely differentiated and systematized.His personality should become a vivid embodiment of the past for the history of the Fatherland, the basis of growth and spirit for the futureand national ideology.

New Thiazole Acetic Acid Derivatives: A Study to Screen Cardiovascular Activity Using Isolated Rat Hearts and Blood Vessels.

Cardiovascular diseases are one of the major causes of mortalities worldwide. In the present research, new synthetic derivatives of thiazole were studied using isolated hearts and blood vessels of rats. The heart and thoracic aorta were tested with six new synthesized thiazole acetic acid derivatives (SMVA-10, SMVA-35, SMVA-40, SMVA-41, SMVA-42 and SMVA-60), and the data obtained were statistically analyzed and compared. Isolated rat hearts were used to record the changes in developed tension and heart rate, while thoracic aortas were used to measure the contractile response, before and after treatments. Analysis of the results indicated a significant (p < 0.01) increase in developed tension with the addition of SMVA-35, SMVA-40, SMVA-41 and SMVA-42, which was augmented in the presence of adrenaline without affecting the heart rate. On the other hand, acetylcholine significantly decreased the developed tension, which was significantly reversed (p < 0.01) in the presence of compounds (SMVA-35 and SMVA-60). However, in the presence of SMVA-35 and SMVA-40, acetylcholine-induced bradycardia was significantly (p < 0.01) reduced. Furthermore, only SMVA-42 induced a dose-dependent contractile response in the isolated blood vessel, which was abolished in the presence of prazosin. Therefore, it can be concluded that some of the new synthesized thiazole derivatives exhibited promising results by raising the developed tension without changing the heart rate or blood vessel function, which could be helpful in failing heart conditions. However, more research is required to fully comprehend the function, mechanism and effectiveness of the compounds.