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Cellular metabolism is regulated over space and time to ensure that energy production is efficiently matched with consumption. Fluorescent biosensors are useful tools for studying metabolism as they enable real-time detection of metabolite abundance with single-cell resolution. For monitoring glycolysis, the intermediate fructose 1,6-bisphosphate (FBP) is a particularly informative signal as its concentration is strongly correlated with flux through the whole pathway. Using GFP insertion into the ligand-binding domain of theBacillus subtilistranscriptional regulator CggR, we developed a fluorescent biosensor for FBP termed HYlight. We demonstrate that HYlight can reliably report the real-time dynamics of glycolysis in living cells and tissues, driven by various metabolic or pharmacological perturbations, alone or in combination with other physiologically relevant signals. Using this sensor, we uncovered previously unknown aspects of β-cell glycolytic heterogeneity and dynamics.

The article considers the possibility of using quarry technology in the construction of a roadbed. Stable roadbed is the basis of a railway track, for its construction rocky, clay soils or sedimentary massifs are usually used. During the construction of the roadbed, heavy vehicles and special equipment (ice rinks, excavators, bulldozers, etc.) are used. Mining and road construction works, despite their diversity, consist of repeated identical operations: digging of the earth (mountain) mass, its loading and transportation, unloading into the dump or laying. For the production of these works, the same type of equipment is used: excavators, bulldozers, scrapers, graders and dump trucks. Most of the newly discovered explored deposits are located in the northern territories of Russia, so there is a high probability of launching intensive construction of railways and roads. The construction of transport high-ways is the most material-intensive area for the use of non-metallic materials and is associated with the movement of significant volumes of earth mass. In addition, the cost of performing earthworks is quite significant, so the correct choice of the method and means of mechanization of these works is a necessary condition for their successful implementation. For the construction of transport corridors under conditions of low-load soils and off-road conditions of the Arctic and northern territories of Russia, it is proposed to develop new types of vehicles based on BelAZ heavy duty quarry vehicles, which allow building embankments for roads and railways up to 10 m high (and in exceptional cases even more). When building transport highways and, if possible, preserving the environment, it is of great importance to reduce the cost of transporting earthen mass by reducing the consumption of fuel and lubricants, which account for 15-25 % of the total cost of operating powerful off-road vehicles.

Exocytosis of peptides and steroids stored in a dense core vesicular (DCV) form is the final step of every secretory pathway, indispensable for the function of nervous, endocrine and immune systems. The lack of live imaging techniques capable of direct, label-free visualisation of DCV release makes many aspects of the exocytotic process inaccessible to investigation. We describe the application of correlative scanning ion conductance and fluorescence confocal microscopy (SICM-FCM) to study the exocytosis of individual granules of insulin from the top, nonadherent, surface of pancreatic β-cells. Using SICM-FCM, we were first to directly follow the topographical changes associated with physiologically induced release of insulin DCVs. This allowed us to report the kinetics of the full fusion of the insulin vesicle as well as the subsequent solubilisation of the released insulin crystal.

The southernmost Russian Far East represents a soil biodiversity hotspot in which settlements of ancient to modern ages form a mosaic within seminatural vegetation. We explored whether these settle...

Aim. To study the influence of social determinants on the frequency of glomerular filtration rate (GFR) categories of various levels, as well as associations with a number of cardiovascular diseases (CVD) and cardiovascular risk factors among the population of four Russian regions included in the ESSE-RF-2.Material and methods. The study was performed as part of a multicenter epidemiological study “Epidemiology of cardiovascular diseases in the regions of the Russian Federation. The second study (ESSE-RF-2)”. In total, 6681 people 25-64 years old from 4 regions of Russian Federation were included in the analysis. The CKD-EPI formula was used to calculate GFR by blood creatinine level. Groups with normal GFR (≥90 ml/min/1.73 m²), with an initial decrease in GFR (Results. The average GFR level in the total sample was 97.8±16.6 ml/min/1.73 m2 ; 29.0% of individuals had an initial decrease in GFR, 1.6% had a reduced GFR. Age was significantly associated with GFR. A statistically significant association with an initial decrease in GFR was found for: hypercholesterolemia (odds ratio [OR] 1.22; 95% clearance interval [95%CI] 1.14-1.30), hypertriglyceridemia (OR 1.09; 95%CI 1.02-1.17), hyperuricemia (OR 1.51; 95%CI 1.39-1.63), no smoking (OR 0.79; 95%CI 0.73-0.85), history of kidney disease (OR 1.13; 95%CI 1.04-1.22). A more pronounced decrease in GFR was associated with the following factors and diseases: arterial hypertension (OR 1.48; 95%CI 1.07-2.05), low level of high-density lipoproteins (OR 1.36; 95%CI 1.04-1.79), hypertriglyceridemia (OR 1.37; 95%CI 1.08-1.76), hyperuricemia (OR 2.49; 95%CI 1.97-3.16), hyperglycemia (OR 1.35; 95%CI 1.01-1.80), a history of myocardial infarction (OR 1.63; 95%CI 1.13-2.36) and kidney disease (OR 1.50; 95%CI 1.16-1.93).Conclusion. The results of the study indicate a greater number of factors and diseases associated with low GFR compared with the initial decrease, which emphasizes the need for early detection of signs of chronic kidney disease, especially in the elderly, in people with metabolic syndrome, hypertension or diabetes mellitus, as well as a history of kidney disease.

Research aim is to analyze the prospects for increasing the efficiency of heavy-duty mining dump trucks operation through the use of natural gas as the main energy carrier. Research methodology included bench tests of a gas piston engine (GPE) KAMAZ mod. 820.60-260 with a capacity of 191 kW and the construction of forecast values of GPE parameters for the BELAZ-75319 mining dump truck with a load capacity of 240 tons. Results. A mathematical model and technique have been developed that allows predicting the main parameters of a gas piston engine and optimizing its economic and environmental characteristics. The use of natural gas as a motor fuel, with an unchanged engine design, leads to a decrease in its power. Currently, gas modifications are being created on the basis of existing diesel engines, and it is not always possible to implement any design measures at this stage. To realize all the capabilities of a gas engine, it should initially be designed for gas motor fuel. This technique is based on the experimental data of low-power gas piston engines and can be used for high-power gas engines studies intended for installation on mining dump trucks. Conclusions. Increasing the efficiency of mining dump trucks in the near future is possible through the use of natural gas as the main energy carrier. The use of natural gas as a motor fuel allows to increase the life of the engine, reduce the noise level and toxicity of exhaust gases, and reduce fuel costs.

Electromagnetic fluctuation spectra in the peripheral area of the Uragan-3M trap and plasma density fluctuation spectra in the plasma confinement zone have been compared with the modulation spectra of escaping electron flux. The dependence of the form of fluctuation spectra on the escaping electron flux intensity has been studied. Plasma confinement and heating conditions in the Uragan-3M torsatron have been discussed.

Aims. The goal of the present case-control study was to assess associations of a panel of routine and experimental biomarkers with the risk for cardiovascular death and acute myocardial infarction (AMI) in a cohort recruited from the multicenter study “Cardiovascular Epidemiology in Russian Federation” (ESSE-RF).Methods and Results. A total of 222 subjects included cardiovascular death (N=48) and AMI cases (N=63) detected during 6.5-year follow up with corresponding numbers of matched healthy controls. The levels of 15 routine and experimental biochemical markers were assayed to analyze associations with the outcomes using logistic and Cox proportional hazard regressions validated by comparison between various groups to assess the estimated hazard ratio (eHR). Elevated levels of cardiac troponin I (cTnI), C-reactive protein (CRP), and metabolites of nitric oxide (NOx) were independently associated (P

Poorly controlled diabetes is characterised by a partial or complete loss of pancreatic islet β-cells, which deprives the remaining islet cells of important β-cell-derived soluble signals, such as insulin or GABA. We aimed to dissect the role of the two signals in the development of islet α-cells, focusing specifically on α-/β-cell transdifferentiation and using the stem cell differentiation factor nicotinamide as a comparator.Streptozotocin (STZ)-treated diabetic mice expressing a fluorescent reporter in pancreatic islet α-cells were injected with GABA (10 mg/kg once daily), nicotinamide (150 mg/kg once daily) or insulin (1U/kg three times daily) for 10 days. The impact of the treatment on metabolic status of the animals as well as the morphology, proliferative potential and transdifferentiation of pancreatic islet cells was assessed using biochemical methods and immunofluorescence.Metabolic status of STZ-diabetic mice was not dramatically altered by the treatment interventions, although GABA therapy did reduce circulating glucagon and augment pancreatic insulin stores. The effects of the exogenous agents on islet β-cells ranged from the attenuation of apoptosis (insulin, nicotinamide) to enhancement of proliferation (GABA). Furthermore, insulin and GABA but not nicotinamide enhanced the differentiation of α-cells into β-cells and increased relative number of 'bihormonal' cells, expressing both insulin and glucagon.Our data suggest a role for endogenous insulin and GABA signalling in α-cell plasticity, which is likely to bypass the common nicotinamide-sensitive stem cell differentiation pathway.

Participants of the study ESSE-RF-2 and co-authors: Moscow: Konstantinov V. V., Pokrovskaya M.S., Efimova I.A., Sivakova O.V.; Krasnodar: Alekseenko S.N., Gubarev S.V.; Оmsk: Livzan M.A., Grishechkina I.A., Rozhkova M.Yu.; Republic of Karelia: Vezikova N.N., Skopec I. S.; Ryazan: Filippov E.V., Dobrynina N.V., Nikulina N.N., Pereverzeva K.G., Moseychuk K.A.Aim. Evaluate the prevalence, awareness, treatment, and control of hypertension among people aged 25-64 examined in 4 regions of the Russian Federation. Material and methods. Study materials were the representative selections of non-organized male (n=3000) and female (n=3714) inhabitants of aged 25-64 from 4 regions of the Russian Federation (Krasnodar region, Omsk region, Ryazan region, the Republic of Karelia), response rate>80%. Systematic stratified multilevel random election was formed with locality criteria (Kisch method). All the participants were interviewed using the standard questionnaire. The universal epidemiological methods and evaluation criteria were used. The study was approved by the local ethics Committee of National research center for preventive medicine. Participants signed informed consent. Hypertension was defined as an average systolic blood pressure (SBP)≥140 mmHg and/or average diastolic blood pressure (DBP)≥90 mmHg and/or antihypertensive therapy (AHT). The efficacy of treatment was the achievement of the target BP. Control group – patients with BP Results. Mean SBP and DBP were 128.7±0,3 mmHg and 82.8±0.1 mmHg, respectively, higher BP was detected among male (pAngiotensin-converting enzyme inhibitors were received by 49.9% of patients, angiotensin II receptor antagonists by 30.9%, beta blockers – 29.5%, diuretics – 22.7%, calcium antagonists – 15.7%, centrally acting drugs – 3.3%, others – 0.2%. The lack of AHT intake was negatively associated with age, ischemic heart disease, urban life and hypo-HDL especially among males. Heart rate >80 per min in females increased by 1.7 times the probability of absence of AHT. The prevalence of effectively treated was 49.7% of the participants with hypertension. The associations between ineffective treatment and abdominal obesity, ischemic heart disease (males), age, rural type of settlement, obesity (females) were found. Only 24.9% of patients had control of the hypertension.Conclusion. The prevalence of hypertension in Russian Federation remains high. An important task of the medical community is to identify the disease at an earlier stage of its development, before the appearance of complications. This approach can reduce the period from the onset of high blood pressure to a visit to the doctor.

The main trends in modifying the structure of bilayer metal-ceramic membranes developed in Russia to fabricate next-generation multilayer metal–ceramic membranes (MMCM) with a wide range of pore sizes from 0.4 to 100 nm and a narrow pore size distribution have been considered. The examples of MMCM structures of various morphologies, the possibilities of further approach to their modification, and possible applications have been shown. Schematic diagrams of existing and prospective membrane units based on metal–ceramic membranes have been demonstrated. The advantages and promising areas of application of such units are discussed.

The BONUS model of the formation, radioactive interactions, and transport of fission products in nuclear fuel is modified to describe the behavior of hydrogen and helium in irradiated nuclear fuel as well as to accumulate an expanded list of transuranium actinides. The program module developed on the basis of the model is included in the MFPR/R fuel code and the SFPR and the BERKUT-U fuel rod codes. The test calculations for mixed uranium-plutonium oxide fuel and mixed uranium-plutonium nitride fuel irradiated in fast reactors are in good agreement with high-precision neutronics calculations.

The MFPR/R code designed for mechanistic modelling of irradiated UO2 fuel, was further developed for characterization of the rim zone and high burnup structure (HBS) evolution in UO2 fuel pellets. The application of the MFPR/R semi-empirical criterion for fuel restructuring, related to the dislocation density threshold, allows calculating the penetration depth of HBS as a function of burnup, in a reasonable agreement with observations. For modelling of the porosity evolution in HBS at the UO2 fuel pellet periphery, the MFPR/R model for coalescence of randomly distributed immobile pores owing to their growth and impingement was further developed and validated. The advanced model considering multiple collisions provides a reasonable consent with experimental data, thus demonstrating the validity of the proposed pore coarsening mechanism in HBS.

Gut incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), enhance secretion of insulin in a glucose-dependent manner, predominantly by elevating cytosolic levels of cAMP in pancreatic β-cells. Successful targeting of the incretin pathway by several drugs, however, suggests the antidiabetic mechanism is likely to span beyond the acute effect on hormone secretion and include, for instance, stimulation of β-cell growth and/or proliferation. Likewise, the antidiabetic action of kidney sodium-glucose linked transporter-2 (SGLT-2) inhibitors exceeds simple increase glucose excretion. Potential reasons for these ‘added benefits’ may lie in the long-term effects of these signals on developmental aspects of pancreatic islet cells. In this work, we explored if the incretin mimetics or SGLT-2 inhibitors can affect the size of the islet α- or β-cell compartments, under the condition of β-cell stress.To that end, we utilised mice expressing YFP specifically in pancreatic α-cells, in which we modelled type 1 diabetes by injecting streptozotocin, followed by a 10-day administration of liraglutide, sitagliptin or dapagliflozin.We observed an onset of diabetic phenotype, which was partially reversed by the administration of the antidiabetic drugs. The mechanism for the reversal included induction of β-cell proliferation, due to a decrease in β-cell apoptosis and, for the incretin mimetics, transdifferentiation of α-cells into β-cells.Our data therefore emphasize the role of chronic incretin signalling in induction of α-/β-cell transdifferentiation. We conclude that incretin peptides may act directly on islet cells, making use of the endogenous local sites of ‘ectopic’ expression, whereas SGLT-2 inhibitors work via protecting β-cells from chronic hyperglycaemia.Graphical abstract

Рассматриваются свойства программируемых логических интегральных схем (ПЛИС) и возможности их применения в информационных системах управления производственным оборудованием. Предлагается архитектура системы, в которой ПЛИС выступают как элемент, осуществляющий сбор данных и их предварительную обработку, а также локальное управление исполнительными устройствами, реализуя таким образом подход туманных вычислений.

The dual role of the pancreas as both an endocrine and exocrine gland is vital for food digestion and control of nutrient metabolism. The exocrine pancreas secretes enzymes into the small intestine aiding digestion of sugars and fats, whereas the endocrine pancreas secretes a cocktail of hormones into the blood, which is responsible for blood glucose control and regulation of carbohydrate, protein and fat metabolism. Classical islet hormones, insulin, glucagon, pancreatic polypeptide and somatostatin, interact in an autocrine and paracrine manner, to fine-tube the islet function and insulin secretion to the needs of the body. Recently pancreatic islets have been reported to express a number of non-classical peptide hormones involved in metabolic signalling, whose major production site was believed to reside outside pancreas, e.g. in the small intestine. We highlight the key non-classical islet peptides, and consider their involvement, together with established islet hormones, in regulation of stimulus-secretion coupling as well as proliferation, survival and transdifferentiation of β-cells. We furthermore focus on the paracrine interaction between classical and non-classical islet hormones in the maintenance of β-cell function. Understanding the functional relationships between these islet peptides might help to develop novel, more efficient treatments for diabetes and related metabolic disorders.

Dynamic analysis of the molecules with large-amplitude motions (LAM) based on the pseudo-conformer approach has been successfully applied to various molecules. Floppy linear molecules present a special class of molecular structures that possess a pair of conjugate LAM coordinates but allow one-dimensional treatment. In this paper, previously developed treatment for the semirigid molecules is applied to the carbon suboxide molecule. This molecule characterized by the extremely large CCC bending has been thoroughly investigated by spectroscopic and ab initio methods. However, the earlier electron diffraction investigations were performed within a static approach, obtaining thermally averaged parameters. In this paper we apply a procedure aimed at obtaining the short list of self-consistent reference geometry parameters of a molecule, while all thermally averaged parameters are calculated based on reference geometry, relaxation dependencies and quadratic and cubic force constants. We show that such a model satisfactorily describes available electron diffraction evidence with various QC bending potential energy functions when r.m.s. CCC angle is in the interval 151 ± 2°. This leads to a self-consistent molecular model satisfying spectroscopic and GED data. The parameters for linear reference geometry have been defined as re(CO) = 1.161(2) A and re(CC) = 1.273(2) A.

The structure and internal rotation of the bromonitromethane molecule are studied using electron diffraction analysis and quantum chemical calculations. The electron diffraction data are analyzed within the models of a general intramolecular anharmonic force field and quantum chemical pseudoconformers to account for the adiabatic separation of a large amplitude motion associated with the internal rotation of the NO2 group. The following experimental bond lengths and valence angles are obtained for the equilibrium orthogonal configuration of the molecule with Cs symmetry: re(N=O) = 1.217(5) A, re(C–N) = 1.48(2) A, re(C–Br) = 1.919(5) A, ∠еBr–C–N = 109.6(9)°, ∠еO=N=O = 125.9(9)°. The equilibrium geometry parameters are in good agreement with CCSD(T)/cc-pVTZ calculations. Thermally averaged parameters are calculated using the equilibrium geometry and quadratic and cubic quantum chemical force constants. The barrier to internal rotation cannot be determined reliably based on the electron diffraction data used in this work. There is a 82% probability that the equilibrium configuration with orthogonal C–Br and N=O bonds is most preferable, and internal rotation barrier does not exceed 280 cm-1, which agrees with CCSD(T)/cc-pVTZ calculations.

The theory of bipolar charging of aerosol particles is developed for large particles (≥10 µm), taking into consideration the Coulomb field screening effect, which becomes relatively strong under co...

A new interpretation of the breakaway swelling observed in high-density dispersion fuels (U6Fe, U3Si, etc.) under irradiation in research reactors is proposed on the base of Mansur's pore coalescence mechanism for randomly distributed immobile pores owing to their growth and pair impingement. This mechanism was further developed in the previous papers of the authors by considering triple and multiple collisions and was modified in the current paper in application to equilibrium gas-filled pores (bubbles). New analytical solutions in the mean-field approximation for the case of pair and triple collisions of equilibrium pores at the early stage of irradiation (with the swelling less than 50–60%) are presented. For higher swellings it is necessary to use a more accurate statistical approach, based on kinetic Monte Carlo calculations and considering multiple collisions of growing pores. It is shown that at high burnups, a sharp increase in the growth rate of the fuel swelling begins at a relatively high value of the fuel swelling (about 60%), in a qualitative agreement with observations for various intermetallic compounds.

The Republic of Sakha (Yakutia) is one of the richest regions of Russia. However, the hardness of the climate in this region amends its full development. The Republic of Sakha (Yakutia) has a poorly developed network of highways and railroads. The active development of the fields of the region has been in progress since the middle of last century. However, more than 16 thousand potential deposits remain understudied. Thus, it is necessary to build highways with due regard for modern techniques and technologies of construction for the development of industry as well as socio-economic spheres in this region. This article deals with the issues of potential use of tailings of the diamond mining industry for the construction of highways. Moreover, the amounts of dumps available would be enough to construct more than 20 thousand km of double-track highways, for the industrial and civil purposes. The advantage of the use of the refuse heaps is their proximity to the potential route. First of all, it is necessary to build a transport road, which would connect the Trans-Siberian railway with the Northern sea route. Construction technology should be adapted to the climatic characteristics of the region, therefore providing a uniform resource usage all year round. For the accelerated construction of subgrade, the two lines of railway should be placed on the same roadbed. After the construction of the subgrade of the entire section one of the ways could be dismantled and the movement of vehicles could be organized in its stead, after the preparation of the pavement. This will result in the construction of the roads with combined traffic for road transport as well as railroad transport. The construction of highways in this region must be associated with the transport strategy of Russia until 2030 and 2050.

Basic knowledge of mankind so far relates to the description of electrons and atoms in the material in a state of equilibrium, where the behavior changes slowly over time. The electron diffraction with a high temporal and space resolution has opened the possibility of direct observation of the processes occurring in the transient state of the substance (molecular movie). Here it is necessary to provide a temporary resolution of the order of 100 fs, which corresponds to the transition of the system through the energy barrier of the potential surface, which describes the chemical reaction - the process of the breaking and the formation of new bonds between the interacting agents. Thus, the possibility of the investigation of the coherent nuclear dynamics of molecular systems and the condensed matter can be opened. In the past two decades, it has been possible to observe the nuclear motion in the temporal interval corresponding to the period of the nuclear oscillation. The observed coherent changes in the nuclear system at such temporal intervals determine the fundamental shift from the standard kinetics of chemical reactions to the dynamics of the phase trajectory of a single molecule, the molecular quantum state tomography.

Atomistic simulations of radiation impact due to collision cascades in oxide and nitride nuclear fuels are performed in this work using combination of Monte Carlo and molecular dynamics techniques. The key parameters of MFPR code models for the athermal self-diffusivity and irradiation-assisted fission product release from fuel are evaluated. The general solution of Olander's integro-differential equation for the knockout mechanism is developed, which allowed extension of the earlier approaches for the long-lived and stable nuclides.

The structure and internal rotation of the 2-methyl-2-nitropropane molecule is studied by electron diffraction and quantum chemical calculations with the use of microwave and vibrational spectroscopy data. The electron diffraction data are analyzed within the general intramolecular anharmonic force field model and the quantum chemical pseudoconformer model, considering the adiabatic separation of the degree of freedom of large amplitude motion, i.e., the internal rotation of the NO2 group. The equilibrium eclipsed configuration of the C s symmetry molecule has the following experimental bond lengths and valence angles: r e(N=O) = 1.226//1.226(8) A, r e(C–N)//r e(C–C) = 1.520//1.515/1,521(4) A, ∠еC–C–N = = 109.1/106,1(8)°, ∠еO=N=O = 124.2(6)°, ∠eC–C–Havg = 110(3)°. The equilibrium geometry parameters are well consistent with MP2/cc-pVTZ quantum chemical calculations and microwave spectroscopy data. The thermally average parameters previously obtained within the small vibration model show a satisfactory agreement with the new results. The electron diffraction data used in this work do not allow a reliable determination of the barrier to internal rotation. However, at a barrier of 203(2) cal/mol, which is derived from the microwave study, it follows from the electron diffraction data that the equilibrium configuration must correspond to an eclipsed arrangement of C–C and N=O bonds, which is also consistent with the results of quantum chemical calculations of various levels.

To understand the dynamic features of molecular systems with a complex landscape of potential energy surfaces, it is necessary to study them in the associated 4D space-time continuum. The introduction of time in the diffraction methods and the development of coherent principles of the research process opened up new approaches for the study of the dynamics of wave packets, intermediates and transient states of the chemical reactions, short-lived compounds in the gaseous and condensed media. Time-resolved electron diffraction, the new method for the structural dynamic studies of free molecules, clusters and condensed matter, differs from the traditional method of electron diffraction both in the experimental part and in the theoretical approaches used in the interpretation of diffraction data. Here there is particularly pronounced the need of a corresponding theoretical basis for the processing of the electron diffraction data and the results of spectral investigations of the coherent dynamics in the field of intense ultrashort laser radiation. Such unified and integrated approach can be formulated using the adiabatic potential energy surfaces of the ground and excited states of the systems under study. The combination of state-of-the-art optical techniques and electron diffraction methods based on different physical phenomena, but complementing each other, opens up new possibilities of the structural studies at time sequences of ultrashort duration. It provides the required integration of the triad, "structure - dynamics - functions" in chemistry, biology and materials science.

There exists a noticeable disagreement in the difference of axial and equatorial bond lengths in D 3h symmetry arsenic and phosphorus pentafluorides between the GED data and high level quantum chemical results. In order to resolve this disagreement, a new structural analysis of the original experiment of (Clippard & Bartell, Inorg. Chem., 9 (1970) 805–811) was undertaken on the basis of modern approach incorporating spectroscopic evidence and quantum chemical information and allowing for intramolecular large-amplitude motion. The results of the analysis prove the internal insufficiency of the experimental material in the description of the accurate positions of the peaks on the radial distribution function. Additional experimental investigation of pentahalide molecules, especially at high temperatures, is of interest.

Pancreatic islets are complex micro-organs consisting of at least three different cell types: glucagon-secreting α-, insulin-producing β- and somatostatin-releasing δ-cells1. Somatostatin is a powerful paracrine inhibitor of insulin and glucagon secretion2. In diabetes, increased somatostatinergic signalling leads to defective counter-regulatory glucagon secretion3. This increases the risk of severe hypoglycaemia, a dangerous complication of insulin therapy4. The regulation of somatostatin secretion involves both intrinsic and paracrine mechanisms5 but their relative contributions and whether they interact remains unclear. Here we show that dapagliflozin-sensitive glucose- and insulin-dependent sodium uptake stimulates somatostatin secretion by elevating the cytoplasmic Na+ concentration ([Na+]i) and promoting intracellular Ca2+-induced Ca2+ release (CICR). This mechanism also becomes activated when [Na+]i is elevated following the inhibition of the plasmalemmal Na+-K+ pump by reductions of the extracellular K+ concentration emulating those produced by exogenous insulin in vivo6. Islets from some donors with type-2 diabetes hypersecrete somatostatin, leading to suppression of glucagon secretion that can be alleviated by a somatostatin receptor antagonist. Our data highlight the role of Na+ as an intracellular second messenger, illustrate the significance of the intraislet paracrine network and provide a mechanistic framework for pharmacological correction of the hormone secretion defects associated with diabetes that selectively target the δ-cells.

The evolutionary development of the leading world states leads to the post-industrial, and subsequently the newest economy creation, which is the knowledge, innovation, intellectual, scientific, and digital economy. The paper covers the functioning and improvement of the Russian national economy’s high-tech sectors based on their clustering, taking into account the digital development aspect declared and implemented by the government. The authors identified the following problem points: (1) the research insufficiency in the scientific analysis of cluster policy features in the economy’s high-tech sectors; (2) the need to study foreign experience in conducting similar studies, evaluating innovative processes and potentials of high-tech industries, and introducing digital technologies. The scientific novelty of this study is represented by two key provisions. First, the author proposes a typology of key factors for improving the activities of the high-tech sector of the national economy (military-industrial complex). The typology is based on the industry clustering approach, in accordance with the strategic planning documents adopted in Russia in 2017 with the purpose of advancing the introduction of digital technologies. Second, we provide recommendations for improving the functioning of the national defense industry, using its competitive advantages, such as the main directions of developing and implementing the cluster strategy to improve the functioning of this state system-forming industry. The main takeaway is that the effective implementation of the cluster strategy in the defense production field will provide an opportunity to form and develop competitive high-tech clusters with a strong market position, digital technological superiority in the defense industry, and the ability to innovate.

Pancreatic islet hormones regulate blood glucose homeostasis. Changes in blood glucose induce oscillations of cytosolic calcium in pancreatic islet cells that trigger secretion of three main hormones: insulin (from β-cells), glucagon (α-cells) and somatostatin (δ-cells). β-Cells, which make up the majority of islet cells and are electrically coupled to each other, respond to the glucose stimulus as one single entity. The excitability of the minor subpopulations, α-cells and δ-cells (making up around 20% (30%) and 4% (10%) of the total rodent1 (human2) islet cell numbers, respectively) is less predictable and is therefore of special interest. Calcium sensors are delivered into the peripheral layer of cells within the isolated islet. The islet or a group of islets is then immobilized and imaged using a fluorescence microscope. The choice of the imaging mode is between higher throughput (wide-field) and better spatial resolution (confocal). Conventionally, laser scanning confocal microscopy is used for imaging tissue, as it provides the best separation of the signal between the neighboring cells. A wide-field system can be utilized too, if the contaminating signal from the dominating population of β-cells is minimized. Once calcium dynamics in response to specific stimuli have been recorded, data are expressed in numerical form as fluorescence intensity vs. time, normalized to the initial fluorescence and baseline-corrected, to remove the effects linked to bleaching of the fluorophore. Changes in the spike frequency or partial area under the curve (pAUC) are computed vs. time, to quantify the observed effects. pAUC is more sensitive and quite robust whereas spiking frequency provides more information on the mechanism of calcium increase. Minor cell subpopulations can be identified using functional responses to marker compounds, such as adrenaline and ghrelin, that induce changes in cytosolic calcium in a specific populations of islet cells.

Glucagon, the body's main hyperglycemic hormone, is produced by α-cells of the islets of Langerhans. A fall in plasma glucose stimulates glucagon release and it acts by increasing hepatic glucose production. How glucose regulates glucagon secretion remains debated and both intrinsic and paracrine mechanisms have been proposed. The fact that glucagon secretion becomes dysregulated in diabetes warrants detailed studies of the cell physiology of its release. We generated mice that express the light-sensitive cation channel Channelrhodopsin-2 (ChR2) under the control of the proglucagon promoter in the α-cells. This allowed us to selectively depolarize the plasma membrane of α-cells within intact isolated islets (using 488 nm laser) and record membrane potential, cytoplasmic Ca2+ ([Ca2+]i) glucagon release in response to the optical activation. At low (1mM) glucose, optoactivation depolarized the α-cells, induced a transient increase in [Ca2+]i, decreased peak voltage of the action potentials (from -2±1mV to -11±1mV, n=5, p Disclosure C.A. Miranda: None. H. Dou: None. J. Tolö: None. A.I. Tarasov: Employee; Spouse/Partner; Vaccitech Ltd, Oxford, UK. P. Rorsman: None. Funding Swedish Research Council

The elastoplastic strain processes in the protective casings of the fittings used to position coolant temperature sensors are analyzed. The expected cyclic elastoplastic strain due to scheduled and forced shutdown of equipment in power-generating units is evaluated.

SummaryMetabolic dysregulation in multiple tissues alters glucose homeostasis and influences risk for type 2 diabetes (T2D). To identify pathways and tissues influencing T2D-relevant glycemic traits (fasting glucose [FG], fasting insulin [FI], two-hour glucose [2hGlu] and glycated hemoglobin [HbA1c]), we investigated associations of exome-array variants in up to 144,060 individuals without diabetes of multiple ancestries. Single-variant analyses identified novel associations at 21 coding variants in 18 novel loci, whilst gene-based tests revealed signals at two genes, TF (HbA1c) and G6PC (FG, FI). Pathway and tissue enrichment analyses of trait-associated transcripts confirmed the importance of liver and kidney for FI and pancreatic islets for FG regulation, implicated adipose tissue in FI and the gut in 2hGlu, and suggested a role for the non-endocrine pancreas in glucose homeostasis. Functional studies demonstrated that a novel FG/FI association at the liver-enriched G6PC transcript was driven by multiple rare loss-of-function variants. The FG/HbA1c-associated, islet-specific G6PC2 transcript also contained multiple rare functional variants, including two alleles within the same codon with divergent effects on glucose levels. Our findings highlight the value of integrating genomic and functional data to maximize biological inference.Highlights23 novel coding variant associations (single-point and gene-based) for glycemic traits51 effector transcripts highlighted different pathway/tissue signatures for each traitThe exocrine pancreas and gut influence fasting and 2h glucose, respectivelyMultiple variants in liver-enriched G6PC and islet-specific G6PC2 influence glycemia

The High Luminosity phase of the Large Hadron Collider will deliver 10 times more integrated luminosity than the existing collider, posing significant challenges for radiation tolerance and event pileup on detectors, especially for forward calorimetry. As part of its upgrade program, the Compact Muon Solenoid collaboration is designing a high-granularity calorimeter (HGCAL) to replace the existing endcap calorimeters. It will feature unprecedented transverse and longitudinal readout and triggering segmentation for both electromagnetic and hadronic sections. The electromagnetic section and a large fraction of the hadronic section will be based on hexagonal silicon sensors of 0.5-1 cm2 cell size, with the remainder of the hadronic section being based on highly-segmented scintillators with silicon photomultiplier readout. The intrinsic high-precision timing capabilities of the silicon sensors will add an extra dimension to event reconstruction, especially in terms of pileup rejection. First hexagonal silicon modules, using the existing Skiroc2 front-end ASIC developed for CALICE, have been tested in beams at Fermilab and CERN in 2016. We present results from these tests, in terms of system stability, calibration with minimum-ionizing particles and resolution (energy, position and timing) for electrons, and the comparisons of these quantities with GEANT4-based simulation. © 2018 CERN for the benefit of the CMS collaboration.. Nuclear Physics Collegio Ghislieri di Pavia China Medical University, Taiwan Institute for Research in Fundamental Sciences aInsitute for High Energy Physics, Beijing, China bLaboratoire Leprince-Ringuet, Palaiseau, France cOrganization for Microelectronics design and Applications (OMEGA), Palaiseau, France dSaha Institute of Nuclear Physics, Kolkata, India eTata Institute for Fundamental Research, Bombay, India fUniversity of Pavia, Pavia, Italy gCERN, Geneva, Switzerland hNational Central University, Chung-Li, Taiwan iNational Taiwan University, Taipei, Taiwan jCukurova University, Adana, Turkey kImperial College of Science, Technology and Medicine, London, U.K. lBoston University, Boston, U.S.A. mCalifornia Insitute of Technology, Pasadena, U.S.A. nCarnegie Mellon University, Pittsburg, U.S.A. oFermi National Accelerator Laboratory, Batavia, U.S.A. pFlorida State University, Tallahassee, U.S.A. qNorthwestern University, Evanston, U.S.A.