81 research outputs found

    Ѐинансовая ΠΏΠΎΠ»ΠΈΡ‚ΠΈΠΊΠ° государствСнной ΠΏΠΎΠ΄Π΄Π΅Ρ€ΠΆΠΊΠΈ отрасли микроэлСктроники Π² России Π² условиях санкций

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    The relevance of this study is determined by the need to develop the domestic semiconductors industry in Russia, taking into account the negative effects both internal and external.The purpose of this paper is to test the hypothesis of the positive impact of the methods used by the state of financial support of domestic companies to acquire advanced technologies in a specific area in the context of a lack of funding and the significant lag of the national semiconductor industry in the world’s leading countries.The target of this study is the analysis of possible tools of state support, including subsidies and grants, and methods of their application for the creation of competitive industry of domestic semiconductor production.The key methods used in this study include the collection and processing of statistical data, their comparative analysis, as well as the elaboration of the regulatory framework on tax regulation in this sector of the economy.The main methods applied in this study are data collection and processing, comparative analysis, and the development of a regulatory framework for tax regulation in this sector of the economy. The authors analyzed the semiconductors industry in the world, including the production of microprocessors and other semiconductor components. The situation in countries such as China, USA, Japan, Europe, Taiwan, India and Russia is discussed in more detail. The main problems with semiconductor industry development in Russia have been revealed. Additionally, researchers have evaluated and outlined fields of federal budget spendings in the industry in the period of years 2022 and 2025.The scientific novelty of this paper is to identify the relationship between the measures of state tax incentives provided to the radio-electronic industry and macroeconomic indicators. Based on that authors have developed evaluation criteria of the relevance and efficiency of fiscal preferences for the analyzed industry which is considered as the result of research.It concluded that the state’s initiatives to promote the radio-electronics industry might provide Russia a chance to catch up to the world’s leading countries in this industry.ΠΠΊΡ‚ΡƒΠ°Π»ΡŒΠ½ΠΎΡΡ‚ΡŒ исслСдования опрСдСляСтся Π½Π΅ΠΎΠ±Ρ…ΠΎΠ΄ΠΈΠΌΠΎΡΡ‚ΡŒΡŽ развития отСчСствСнной отрасли микроэлСктроники Π² России с ΡƒΡ‡Π΅Ρ‚ΠΎΠΌ ΡΠ»ΠΎΠΆΠΈΠ²ΡˆΠΈΡ…ΡΡ Π½Π΅Π³Π°Ρ‚ΠΈΠ²Π½Ρ‹Ρ… ΠΊΠ°ΠΊ Π²Π½ΡƒΡ‚Ρ€Π΅Π½Π½ΠΈΡ…, Ρ‚Π°ΠΊ ΠΈ Π²Π½Π΅ΡˆΠ½ΠΈΡ… эффСктов.ЦСлью являСтся ΠΏΡ€ΠΎΠ²Π΅Ρ€ΠΊΠ° Π³ΠΈΠΏΠΎΡ‚Π΅Π·Ρ‹ ΠΎ ΠΏΠΎΠ»ΠΎΠΆΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎΠΌ влиянии ΠΈΡΠΏΠΎΠ»ΡŒΠ·ΡƒΠ΅ΠΌΡ‹Ρ… государством ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΎΠ² финансовой ΠΏΠΎΠ΄Π΄Π΅Ρ€ΠΆΠΊΠΈ отСчСствСнных ΠΊΠΎΠΌΠΏΠ°Π½ΠΈΠΉ для получСния ΠΏΡ€ΠΎΡ€Ρ‹Π²Π½Ρ‹Ρ… Ρ‚Π΅Ρ…Π½ΠΎΠ»ΠΎΠ³ΠΈΠΉ Π² ΠΊΠΎΠ½ΠΊΡ€Π΅Ρ‚Π½ΠΎΠΉ области Π² условиях нСдостатка финансирования ΠΈ сущСствСнного отставания Π½Π°Ρ†ΠΈΠΎΠ½Π°Π»ΡŒΠ½ΠΎΠΉ отрасли микроэлСктроники ΠΎΡ‚ Π²Π΅Π΄ΡƒΡ‰ΠΈΡ… стран ΠΌΠΈΡ€Π°.Π—Π°Π΄Π°Ρ‡Π΅ΠΉ Π΄Π°Π½Π½ΠΎΠ³ΠΎ исслСдования являСтся Π°Π½Π°Π»ΠΈΠ· Π²ΠΎΠ·ΠΌΠΎΠΆΠ½Ρ‹Ρ… инструмСнтов государствСнной ΠΏΠΎΠ΄Π΄Π΅Ρ€ΠΆΠΊΠΈ, Π²ΠΊΠ»ΡŽΡ‡Π°Ρ субсидии ΠΈ Π³Ρ€Π°Π½Ρ‚Ρ‹, Π° Ρ‚Π°ΠΊΠΆΠ΅ ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΎΠ² ΠΈΡ… примСнСния с Ρ†Π΅Π»ΡŒΡŽ создания ΠΊΠΎΠ½ΠΊΡƒΡ€Π΅Π½Ρ‚Π½ΠΎΠΉ отрасли производства отСчСствСнной микроэлСктроники.ΠžΡΠ½ΠΎΠ²Π½Ρ‹Π΅ ΠΌΠ΅Ρ‚ΠΎΠ΄Ρ‹, ΠΈΡΠΏΠΎΠ»ΡŒΠ·ΡƒΠ΅ΠΌΡ‹Π΅ Π² Π΄Π°Π½Π½ΠΎΠΌ исслСдовании, Π²ΠΊΠ»ΡŽΡ‡Π°ΡŽΡ‚ Π² сСбя сбор ΠΈ ΠΎΠ±Ρ€Π°Π±ΠΎΡ‚ΠΊΡƒ статистичСских Π΄Π°Π½Π½Ρ‹Ρ…, ΠΈΡ… ΡΡ€Π°Π²Π½ΠΈΡ‚Π΅Π»ΡŒΠ½Ρ‹ΠΉ Π°Π½Π°Π»ΠΈΠ·, Π° Ρ‚Π°ΠΊΠΆΠ΅ ΠΏΡ€ΠΎΡ€Π°Π±ΠΎΡ‚ΠΊΡƒ Π½ΠΎΡ€ΠΌΠ°Ρ‚ΠΈΠ²Π½ΠΎΠΉ Π±Π°Π·Ρ‹ ΠΏΠΎ Π½Π°Π»ΠΎΠ³ΠΎΠ²ΠΎΠΌΡƒ Ρ€Π΅Π³ΡƒΠ»ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΡŽ Π² Π΄Π°Π½Π½ΠΎΠΌ сСкторС экономики. Авторы ΠΏΡ€ΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡ€ΠΎΠ²Π°Π»ΠΈ состояниС отрасли микроэлСктроники Π² ΠΌΠΈΡ€Π΅, Π²ΠΊΠ»ΡŽΡ‡Π°Ρ производство микропроцСссоров ΠΈ Π΄Ρ€ΡƒΠ³ΠΈΡ… ΠΏΠΎΠ»ΡƒΠΏΡ€ΠΎΠ²ΠΎΠ΄Π½ΠΈΠΊΠΎΠ²Ρ‹Ρ… ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½Ρ‚ΠΎΠ². Π‘ΠΎΠ»Π΅Π΅ Π΄Π΅Ρ‚Π°Π»ΡŒΠ½ΠΎ рассмотрСна ситуация Π² Ρ‚Π°ΠΊΠΈΡ… странах, ΠΊΠ°ΠΊ ΠšΠΈΡ‚Π°ΠΉ, БША, Япония, Π•Π²Ρ€ΠΎΠΏΠ°, Вайвань, Индия ΠΈ Россия. На основС ΠΏΡ€ΠΎΠ²Π΅Π΄Π΅Π½Π½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π° выявлСны основныС ΠΏΡ€ΠΎΠ±Π»Π΅ΠΌΡ‹ развития отрасли микроэлСктроники Π² России. Π”Π°Π½Π° ΠΎΡ†Π΅Π½ΠΊΠ° ΠΌΠ°ΡΡˆΡ‚Π°Π±ΠΎΠ² ΠΈ выявлСны направлСния расходования срСдств Ρ„Π΅Π΄Π΅Ρ€Π°Π»ΡŒΠ½ΠΎΠ³ΠΎ Π±ΡŽΠ΄ΠΆΠ΅Ρ‚Π° Π½Π° Ρ€Π°Π·Π²ΠΈΡ‚ΠΈΠ΅ радиоэлСктронной ΠΏΡ€ΠΎΠΌΡ‹ΡˆΠ»Π΅Π½Π½ΠΎΡΡ‚ΠΈ Π² ΠΏΠ΅Ρ€ΠΈΠΎΠ΄ 2022–2025 Π³Π³.Научная Π½ΠΎΠ²ΠΈΠ·Π½Π° ΠΏΡ€ΠΎΠ²Π΅Π΄Π΅Π½Π½ΠΎΠ³ΠΎ исслСдования Π·Π°ΠΊΠ»ΡŽΡ‡Π°Π΅Ρ‚ΡΡ Π² выявлСнии взаимосвязи ΠΌΠ΅ΠΆΠ΄Ρƒ прСдоставляСмыми ΠΌΠ΅Ρ€Π°ΠΌΠΈ государствСнного Π½Π°Π»ΠΎΠ³ΠΎΠ²ΠΎΠ³ΠΎ стимулирования радиоэлСктронной ΠΏΡ€ΠΎΠΌΡ‹ΡˆΠ»Π΅Π½Π½ΠΎΡΡ‚ΠΈ ΠΈ макроэкономичСскими показатСлями.Π Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Ρ‹ ΠΏΠΎΠ·Π²ΠΎΠ»ΠΈΠ»ΠΈ Π°Π²Ρ‚ΠΎΡ€Π°ΠΌ Π²Ρ‹Ρ€Π°Π±ΠΎΡ‚Π°Ρ‚ΡŒ ΠΊΡ€ΠΈΡ‚Π΅Ρ€ΠΈΠΈ ΠΎΡ†Π΅Π½ΠΊΠΈ вострСбованности ΠΈ эффСктивности Ρ„ΠΈΡΠΊΠ°Π»ΡŒΠ½Ρ‹Ρ… ΠΏΡ€Π΅Ρ„Π΅Ρ€Π΅Π½Ρ†ΠΈΠΉ для исслСдуСмого Π²ΠΈΠ΄Π° Π΄Π΅ΡΡ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΠΈ.Π‘Π΄Π΅Π»Π°Π½ Π²Ρ‹Π²ΠΎΠ΄, Ρ‡Ρ‚ΠΎ ΠΈΡΠΏΠΎΠ»ΡŒΠ·ΡƒΠ΅ΠΌΡ‹Π΅ государством ΠΌΠ΅Ρ€Ρ‹ ΠΏΠΎΠ΄Π΄Π΅Ρ€ΠΆΠΊΠΈ радиоэлСктронной ΠΏΡ€ΠΎΠΌΡ‹ΡˆΠ»Π΅Π½Π½ΠΎΡΡ‚ΠΈ ΠΌΠΎΠ³ΡƒΡ‚ Π΄Π°Ρ‚ΡŒ России шанс ΠΏΡ€Π΅ΠΎΠ΄ΠΎΠ»Π΅Ρ‚ΡŒ Π·Π½Π°Ρ‡ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎΠ΅ отставаниС Π² этой отрасли ΠΎΡ‚ Π²Π΅Π΄ΡƒΡ‰ΠΈΡ… стран ΠΌΠΈΡ€Π°

    High-frequency homogenization for periodic media

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    This article is available open access through the publisher’s website at the link below. Copyright @ 2010 The Royal Society.An asymptotic procedure based upon a two-scale approach is developed for wave propagation in a doubly periodic inhomogeneous medium with a characteristic length scale of microstructure far less than that of the macrostructure. In periodic media, there are frequencies for which standing waves, periodic with the period or double period of the cell, on the microscale emerge. These frequencies do not belong to the low-frequency range of validity covered by the classical homogenization theory, which motivates our use of the term β€˜high-frequency homogenization’ when perturbing about these standing waves. The resulting long-wave equations are deduced only explicitly dependent upon the macroscale, with the microscale represented by integral quantities. These equations accurately reproduce the behaviour of the Bloch mode spectrum near the edges of the Brillouin zone, hence yielding an explicit way for homogenizing periodic media in the vicinity of β€˜cell resonances’. The similarity of such model equations to high-frequency long wavelength asymptotics, for homogeneous acoustic and elastic waveguides, valid in the vicinities of thickness resonances is emphasized. Several illustrative examples are considered and show the efficacy of the developed techniques.NSERC (Canada) and the EPSRC

    New concept of pathogenesis of impaired circulation in traumatic cervical spinal cord injury and its impact on disease severity: case series of four patients

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    Purpose: The purpose of this study is to justify a new concept of the pathogenesis of secondary changes in the cervical spinal cord, and its correlation with the depth of development of neurological disorders in spinal injury. Methods: Standard magnetic resonance imaging examination and angiography of the cervical and vertebral arteries of four patients were performed to diagnose the prevalence rate of ischemia and edema, and examine the spinal cord vasculature. Correlation of the data obtained with the neurological status was performed. Results: Collateral circulation is most apparent in the upper-cervical region, above the C4 vertebra. Following occlusion of the vertebral artery, the circulation above the C4 vertebra is performed by collaterals of the ascending cervical artery. With extensive damage to the spinal cord, the intensity of edema and ischemia can be regarded as the effect of damage to radicular medullary arteries, which are injured in the intervertebral foramen. Secondary changes of the spinal cord are most apparent by impaired circulation in the artery of cervical enlargement. Conclusions: Collateral circulation is a significant factor that limits the damage to the cervical spinal cord. Impaired circulation in the artery of cervical enlargement is significant in extension of perifocal ischemia. The appearance of early arteriovenous shunting in the region of a primary spinal cord injury (contusion focus) by angiography is pathognomonic. The data obtained open a perspective for the endovascular treatment of spinal cord injury

    ΠŸΡ€ΠΎΠ³Π½ΠΎΠ·ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΎΡ†ΠΈΠ°Π»ΡŒΠ½ΠΎΠ³ΠΎ развития Ρ€Π΅Π³ΠΈΠΎΠ½ΠΎΠ² России

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    The objective of the article is to offer a proprietary technology for assessment and forecasting of social development of Russian regions. The methodological basis of the study is neural network technology (a Bayesian ensemble of dynamic neural networks of different configurations is formed) that ensure high accuracy of the forecast. The authors developed a methodology for assessing the social potential of the Russian regions. They have also designed a system of private indicators characterising the level of social development of Russian regions. The indicators have been divided into five groups: 1) population (life expectancy); 2) standard of living of the population; 3) education; 4) health care (morbidity); 5) research and innovation. The private indicators have been made comparable by normalizing their values by means of β€œPattern” method. This method allows the objective assessment of the interregional β€œgaps” in the country across the entire system of social indicators. The social development index of the subjects of the Russian Federation has been calculated. Based on neural network technologies (Kohonen self-organizing maps) clustering of regions of Russia regarding social development has been conducted. The forecast of the social development of the Russian regions has been made. Due to the forecast, it has been established that in the leading region of the Russian Federation (Moscow) in 2017-2019 the decrease is expected in the index of social development in comparison with 2014-2016. In another leading region of the Russian Federation (St. Petersburg) the decline in comparison with 2016 is expected in the medium term. At the same time, for the Republic of Bashkortostan in 2017-2019, just a slight decrease in the level of social development is forecasted. However, it is expected that the Republic will still lag significantly behind the leading regions of Russia by social development. The example of the Republic of Bashkortostan helped to discover that the lag in social development can be explained by the β€œgap” in research and innovations. The authors have concluded that it is necessary to improve the effectiveness of social policy at the regional level. Thus, it is necessary not only to increase financing of the social sphere of the subjects of the Russian Federation, but also to ensure proper control of budget spending. The developed methodology can be an effective tool for forecasting and managing social development of the Russian regions by the relevant ministries and departments.ЦСль ΡΡ‚Π°Ρ‚ΡŒΠΈ β€”Β  ΠΏΡ€Π΅Π΄Π»ΠΎΠΆΠΈΡ‚ΡŒ Π°Π²Ρ‚ΠΎΡ€ΡΠΊΡƒΡŽ ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΈΠΊΡƒ ΠΎΡ†Π΅Π½ΠΊΠΈ ΠΈ прогнозирования ΡΠΎΡ†ΠΈΠ°Π»ΡŒΠ½ΠΎΠ³ΠΎ развития Ρ€Π΅Π³ΠΈΠΎΠ½ΠΎΠ² России. ΠœΠ΅Ρ‚ΠΎΠ΄ΠΎΠ»ΠΎΠ³ΠΈΡ‡Π΅ΡΠΊΠΎΠΉ основой исслСдования ΡΠ²Π»ΡΡŽΡ‚ΡΡ нСйросСтСвыС Ρ‚Π΅Ρ…Π½ΠΎΠ»ΠΎΠ³ΠΈΠΈ (формируСтся байСсовский ансамбль динамичСских нСйросСтСй Ρ€Π°Π·Π»ΠΈΡ‡Π½ΠΎΠΉ ΠΊΠΎΠ½Ρ„ΠΈΠ³ΡƒΡ€Π°Ρ†ΠΈΠΈ), ΠΎΠ±Π΅ΡΠΏΠ΅Ρ‡ΠΈΠ²Π°ΡŽΡ‰ΠΈΠ΅ Π²Ρ‹ΡΠΎΠΊΡƒΡŽ Ρ‚ΠΎΡ‡Π½ΠΎΡΡ‚ΡŒ ΠΏΡ€ΠΎΠ³Π½ΠΎΠ·Π°. Авторами Ρ€Π°Π·Ρ€Π°Π±ΠΎΡ‚Π°Π½Π° ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΈΠΊΠ° ΠΎΡ†Π΅Π½ΠΊΠΈ ΡΠΎΡ†ΠΈΠ°Π»ΡŒΠ½ΠΎΠ³ΠΎ ΠΏΠΎΡ‚Π΅Π½Ρ†ΠΈΠ°Π»Π° Ρ€Π΅Π³ΠΈΠΎΠ½ΠΎΠ² России. Π‘Ρ„ΠΎΡ€ΠΌΠΈΡ€ΠΎΠ²Π°Π½Π° систСма частных ΠΏΠΎΠΊΠ°Π·Π°Ρ‚Π΅Π»Π΅ΠΉ, Ρ…Π°Ρ€Π°ΠΊΡ‚Π΅Ρ€ΠΈΠ·ΡƒΡŽΡ‰ΠΈΡ… ΡƒΡ€ΠΎΠ²Π΅Π½ΡŒ ΡΠΎΡ†ΠΈΠ°Π»ΡŒΠ½ΠΎΠ³ΠΎ развития Ρ€Π΅Π³ΠΈΠΎΠ½ΠΎΠ² страны. Они ΠΎΠ±ΡŠΠ΅Π΄ΠΈΠ½Π΅Π½Ρ‹ Π² ΠΏΡΡ‚ΡŒ Π³Ρ€ΡƒΠΏΠΏ: 1) насСлСниС (оТидаСмая ΠΏΡ€ΠΎΠ΄ΠΎΠ»ΠΆΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΡŒ ΠΆΠΈΠ·Π½ΠΈ); 2) ΡƒΡ€ΠΎΠ²Π΅Π½ΡŒ ΠΆΠΈΠ·Π½ΠΈ насСлСния; 3) ΠΎΠ±Ρ€Π°Π·ΠΎΠ²Π°Π½ΠΈΠ΅; 4) Π·Π΄Ρ€Π°Π²ΠΎΠΎΡ…Ρ€Π°Π½Π΅Π½ΠΈΠ΅ (Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π΅ΠΌΠΎΡΡ‚ΡŒ); 5) Π½Π°ΡƒΡ‡Π½Ρ‹Π΅ исслСдования ΠΈ ΠΈΠ½Π½ΠΎΠ²Π°Ρ†ΠΈΠΈ. Π‘ ΠΏΠΎΠΌΠΎΡ‰ΡŒΡŽ ΠΌΠ΅Ρ‚ΠΎΠ΄Π° Β«ΠŸΠ°Ρ‚Ρ‚Π΅Ρ€Π½Β» частныС ΠΏΠΎΠΊΠ°Π·Π°Ρ‚Π΅Π»ΠΈ ΠΏΡ€ΠΈΠ²Π΅Π΄Π΅Π½Ρ‹ Π² сопоставимый Π²ΠΈΠ΄ ΠΏΡƒΡ‚Π΅ΠΌ Π½ΠΎΡ€ΠΌΠ°Π»ΠΈΠ·Π°Ρ†ΠΈΠΈ ΠΈΡ… Π·Π½Π°Ρ‡Π΅Π½ΠΈΠΉ. Π”Π°Π½Π½Ρ‹ΠΉ ΠΌΠ΅Ρ‚ΠΎΠ΄ позволяСт ΠΎΠ±ΡŠΠ΅ΠΊΡ‚ΠΈΠ²Π½ΠΎ ΠΎΡ†Π΅Π½ΠΈΠ²Π°Ρ‚ΡŒ Β«Π³Π»ΡƒΠ±ΠΈΠ½ΡƒΒ» ΠΌΠ΅ΠΆΡ€Π΅Π³ΠΈΠΎΠ½Π°Π»ΡŒΠ½Ρ‹Ρ… Β«Ρ€Π°Π·Ρ€Ρ‹Π²ΠΎΠ²Β» Π² странС ΠΏΠΎ всСй систСмС ΡΠΎΡ†ΠΈΠ°Π»ΡŒΠ½Ρ‹Ρ… ΠΈΠ½Π΄ΠΈΠΊΠ°Ρ‚ΠΎΡ€ΠΎΠ². ΠŸΡ€ΠΎΠ²Π΅Π΄Π΅Π½ расчСт индСкса ΡΠΎΡ†ΠΈΠ°Π»ΡŒΠ½ΠΎΠ³ΠΎ развития ΡΡƒΠ±ΡŠΠ΅ΠΊΡ‚ΠΎΠ² Π Π€. На основС нСйросСтСвых Ρ‚Π΅Ρ…Π½ΠΎΠ»ΠΎΠ³ΠΈΠΉ (ΡΠ°ΠΌΠΎΠΎΡ€Π³Π°Π½ΠΈΠ·ΡƒΡŽΡ‰ΠΈΡ…ΡΡ ΠΊΠ°Ρ€Ρ‚ ΠšΠΎΡ…ΠΎΠ½Π΅Π½Π°) ΠΏΡ€ΠΎΠ²Π΅Π΄Π΅Π½Π° кластСризация Ρ€Π΅Π³ΠΈΠΎΠ½ΠΎΠ² России ΠΏΠΎ ΡƒΡ€ΠΎΠ²Π½ΡŽ ΡΠΎΡ†ΠΈΠ°Π»ΡŒΠ½ΠΎΠ³ΠΎ развития. ΠžΡΡƒΡ‰Π΅ΡΡ‚Π²Π»Π΅Π½ΠΎ ΠΏΡ€ΠΎΠ³Π½ΠΎΠ·ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΎΡ†ΠΈΠ°Π»ΡŒΠ½ΠΎΠ³ΠΎ развития российских Ρ€Π΅Π³ΠΈΠΎΠ½ΠΎΠ². Π’ Ρ€Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Π΅ прогнозирования установлСно, Ρ‡Ρ‚ΠΎ Ρƒ Ρ€Π΅Π³ΠΈΠΎΠ½Π° β€”Β  Π»ΠΈΠ΄Π΅Ρ€Π° Π Π€ (Π³. Москва) Π² 2017–2019 Π³Π³. оТидаСтся сниТСниС индСкса ΡΠΎΡ†ΠΈΠ°Π»ΡŒΠ½ΠΎΠ³ΠΎ развития ΠΏΠΎ ΡΡ€Π°Π²Π½Π΅Π½ΠΈΡŽ с 2014–2016 Π³Π³. Π£ Π΄Ρ€ΡƒΠ³ΠΎΠ³ΠΎ Ρ€Π΅Π³ΠΈΠΎΠ½Π° β€”Β  Π»ΠΈΠ΄Π΅Ρ€Π° Π Π€ (Π³. Π‘Π°Π½ΠΊΡ‚-ΠŸΠ΅Ρ‚Π΅Ρ€Π±ΡƒΡ€Π³) Π² срСднСсрочной пСрспСктивС Ρ‚Π°ΠΊΠΆΠ΅ оТидаСтся сниТСниС показатСля, Π½ΠΎ Ρ‚ΠΎΠ»ΡŒΠΊΠΎ ΠΏΠΎ ΡΡ€Π°Π²Π½Π΅Π½ΠΈΡŽ с 2016 Π³. ΠŸΡ€ΠΈ этом ΠΏΠΎ РСспубликС Π‘Π°ΡˆΠΊΠΎΡ€Ρ‚ΠΎΡΡ‚Π°Π½ Π² 2017–2019 Π³Π³. прогнозируСтся лишь Π½Π΅Π·Π½Π°Ρ‡ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎΠ΅ сниТСниС уровня ΡΠΎΡ†ΠΈΠ°Π»ΡŒΠ½ΠΎΠ³ΠΎ развития. Однако оТидаСтся, Ρ‡Ρ‚ΠΎ рСспублика ΠΏΠΎ-ΠΏΡ€Π΅ΠΆΠ½Π΅ΠΌΡƒ Π±ΡƒΠ΄Π΅Ρ‚ сущСствСнно ΠΎΡ‚ΡΡ‚Π°Π²Π°Ρ‚ΡŒ ΠΎΡ‚ Ρ€Π΅Π³ΠΈΠΎΠ½ΠΎΠ² β€”Β  Π»ΠΈΠ΄Π΅Ρ€ΠΎΠ² России ΠΏΠΎ ΡƒΡ€ΠΎΠ²Π½ΡŽ ΡΠΎΡ†ΠΈΠ°Π»ΡŒΠ½ΠΎΠ³ΠΎ развития. На ΠΏΡ€ΠΈΠΌΠ΅Ρ€Π΅ РСспублики Π‘Π°ΡˆΠΊΠΎΡ€Ρ‚ΠΎΡΡ‚Π°Π½ выявлСно, Ρ‡Ρ‚ΠΎ отставаниС Π² сфСрС ΡΠΎΡ†ΠΈΠ°Π»ΡŒΠ½ΠΎΠ³ΠΎ развития ΠΎΠ±ΡŠΡΡΠ½ΡΠ΅Ρ‚ΡΡ Β«Ρ€Π°Π·Ρ€Ρ‹Π²ΠΎΠΌΒ» Π² области Π½Π°ΡƒΡ‡Π½Ρ‹Ρ… исслСдований ΠΈ ΠΈΠ½Π½ΠΎΠ²Π°Ρ†ΠΈΠΉ. Авторы Π΄Π΅Π»Π°ΡŽΡ‚ Π²Ρ‹Π²ΠΎΠ΄ ΠΎ нСобходимости ΠΏΠΎΠ²Ρ‹ΡˆΠ΅Π½ΠΈΡ эффСктивности ΡΠΎΡ†ΠΈΠ°Π»ΡŒΠ½ΠΎΠΉ ΠΏΠΎΠ»ΠΈΡ‚ΠΈΠΊΠΈ Π½Π° Ρ€Π΅Π³ΠΈΠΎΠ½Π°Π»ΡŒΠ½ΠΎΠΌ ΡƒΡ€ΠΎΠ²Π½Π΅. Для этого Π½Π΅ΠΎΠ±Ρ…ΠΎΠ΄ΠΈΠΌΠΎ Π½Π΅ Ρ‚ΠΎΠ»ΡŒΠΊΠΎ ΡƒΠ²Π΅Π»ΠΈΡ‡ΠΈΡ‚ΡŒ финансированиС ΡΠΎΡ†ΠΈΠ°Π»ΡŒΠ½ΠΎΠΉ сфСры ΡΡƒΠ±ΡŠΠ΅ΠΊΡ‚ΠΎΠ² Π Π€, Π½ΠΎ ΠΈ ΠΎΠ±Π΅ΡΠΏΠ΅Ρ‡ΠΈΡ‚ΡŒ Π½Π°Π΄Π»Π΅ΠΆΠ°Ρ‰ΠΈΠΉ ΠΊΠΎΠ½Ρ‚Ρ€ΠΎΠ»ΡŒ расходования Π±ΡŽΠ΄ΠΆΠ΅Ρ‚Π½Ρ‹Ρ… срСдств. Разработанная ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΈΠΊΠ° ΠΌΠΎΠΆΠ΅Ρ‚ ΡΠ²Π»ΡΡ‚ΡŒΡΡ эффСктивным инструмСнтом прогнозирования ΠΈ управлСния ΡΠΎΡ†ΠΈΠ°Π»ΡŒΠ½Ρ‹ΠΌ Ρ€Π°Π·Π²ΠΈΡ‚ΠΈΠ΅ΠΌ Ρ€Π΅Π³ΠΈΠΎΠ½ΠΎΠ² Π Π€ ΡΠΎΠΎΡ‚Π²Π΅Ρ‚ΡΡ‚Π²ΡƒΡŽΡ‰ΠΈΠΌΠΈ министСрствами ΠΈ вСдомствами

    Calcium Homeostasis in Myogenic Differentiation Factor 1 (MyoD)-Transformed, Virally-Transduced, Skin-Derived Equine Myotubes

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    Dysfunctional skeletal muscle calcium homeostasis plays a central role in the pathophysiology of several human and animal skeletal muscle disorders, in particular, genetic disorders associated with ryanodine receptor 1 (RYR1) mutations, such as malignant hyperthermia, central core disease, multiminicore disease and certain centronuclear myopathies. In addition, aberrant skeletal muscle calcium handling is believed to play a pivotal role in the highly prevalent disorder of Thoroughbred racehorses, known as Recurrent Exertional Rhabdomyolysis. Traditionally, such defects were studied in human and equine subjects by examining the contractile responses of biopsied muscle strips exposed to caffeine, a potent RYR1 agonist. However, this test is not widely available and, due to its invasive nature, is potentially less suitable for valuable animals in training or in the human paediatric setting. Furthermore, increasingly, RYR1 gene polymorphisms (of unknown pathogenicity and significance) are being identified through next generation sequencing projects. Consequently, we have investigated a less invasive test that can be used to study calcium homeostasis in cultured, skin-derived fibroblasts that are converted to the muscle lineage by viral transduction with a MyoD (myogenic differentiation 1) transgene. Similar models have been utilised to examine calcium homeostasis in human patient cells, however, to date, there has been no detailed assessment of the cells’ calcium homeostasis, and in particular, the responses to agonists and antagonists of RYR1. Here we describe experiments conducted to assess calcium handling of the cells and examine responses to treatment with dantrolene, a drug commonly used for prophylaxis of recurrent exertional rhabdomyolysis in horses and malignant hyperthermia in humans

    Main outcomes of the Phebus FPT1 uncertainty and sensitivity analysis in the EU-MUSA project

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    The Management and Uncertainties of Severe Accidents (MUSA) project was funded in HORIZON 2020 and is coordinated by CIEMAT (Spain). The project aims at consolidating a harmonized approach for the analysis of uncertainties and sensitivities associated with Severe Accidents (SAs) analysis, focusing on source term figures of merit. The Application of Uncertainty Quantification (UQ) Methods against Integral Experiments (AUQMIE – Work Package 4 (WP4)), led by ENEA (Italy), was devoted to apply and test UQ methodologies adopting the internationally recognized PHEBUS FPT1 test. FPT1 was chosen to test UQ methodologies because, even though it is a simplified SA scenario, it was representative of the in-vessel phase of a severe accident initiated by a break in the cold leg of a PWR primary circuit. WP4 served as a platform to identify and discuss the issues encountered in the application of UQ methodol ogies to SA analyses (e.g. discuss the UQ methodology, perform the coupling between the SA codes and the UQ tools, define the results post-processing methods, etc.). The purpose of this paper is to describe the MUSA PHEBUS FPT1 uncertainty application exercise with the related specifications and the methodologies used by the partners to perform the UQ exercise. The main outcomes and lessons learned of the analysis are: scripting was in general needed for the SA code and uncertainty tool coupling and to have more flexibility; particular attention should be devoted to the proper choice of the input uncertain parameters; outlier values of figures of merit should be carefully analyzed; the computational time is a key element to perform UQ in SA; the large number of uncertain input parameters may complicate the interpretation of correlation or sensitivity analysis; there is the need for a statistically solid handling of failed calculations

    First outcomes from the PHEBUS FPT1 uncertainty application done in the EU MUSA project

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    The Management and Uncertainties of Severe Accidents (MUSA) project, founded in HORIZON 2020 and coordinated by CIEMAT (Spain), aims to consolidate a harmonized approach for the analysis of uncertainties and sensitivities associated with Severe Accidents (SAs) by focusing on Source Term (ST) Figure of Merits (FOM). In this framework, among the 7 MUSA WPs the Application of Uncertainty Quantification (UQ) Methods against Integral Experiments (AUQMIE – Work Package 4 (WP4)), led by ENEA (Italy), looked at applying and testing UQ methodologies, against the internationally recognized PHEBUS FPT1 test. Considering that FPT1 is a simplified but representative SA scenario, the main target of the WP4 is to train project partners to perform UQ for SA analyses. WP4 is also a collaborative platform for highlighting and discussing results and issues arising from the application of UQ methodologies, already used for design basis accidents, and in MUSA for SA analyses. As a consequence, WP4 application creates the technical background useful for the full plant and spent fuel pool applications planned along the MUSA project, and it also gives a first contribution for MUSA best practices and lessons learned. 16 partners from different world regions are involved in the WP4 activities. The purpose of this paper is to describe the MUSA PHEBUS FPT1 uncertainty application exercise, the methodologies used by the partners to perform the UQ exercise, and the first insights coming out from the calculation phase

    Triadin/Junctin Double Null Mouse Reveals a Differential Role for Triadin and Junctin in Anchoring CASQ to the jSR and Regulating Ca2+ Homeostasis

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    Triadin (Tdn) and Junctin (Jct) are structurally related transmembrane proteins thought to be key mediators of structural and functional interactions between calsequestrin (CASQ) and ryanodine receptor (RyRs) at the junctional sarcoplasmic reticulum (jSR). However, the specific contribution of each protein to the jSR architecture and to excitation-contraction (e-c) coupling has not been fully established. Here, using mouse models lacking either Tdn (Tdn-null), Jct (Jct-null) or both (Tdn/Jct-null), we identify Tdn as the main component of periodically located anchors connecting CASQ to the RyR-bearing jSR membrane. Both proteins proved to be important for the structural organization of jSR cisternae and retention of CASQ within them, but with different degrees of impact. Our results also suggest that the presence of CASQ is responsible for the wide lumen of the jSR cisternae. Using Ca2+ imaging and Ca2+ selective microelectrodes we found that changes in e-c coupling, SR Ca2+content and resting [Ca2+] in Jct, Tdn and Tdn/Jct-null muscles are directly correlated to the effect of each deletion on CASQ content and its organization within the jSR. These data suggest that in skeletal muscle the disruption of Tdn/CASQ link has a more profound effect on jSR architecture and myoplasmic Ca2+ regulation than Jct/CASQ association

    Contribution of NADPH Oxidase to Membrane CD38 Internalization and Activation in Coronary Arterial Myocytes

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    The CD38-ADP-ribosylcyclase-mediated Ca2+ signaling pathway importantly contributes to the vasomotor response in different arteries. Although there is evidence indicating that the activation of CD38-ADP-ribosylcyclase is associated with CD38 internalization, the molecular mechanism mediating CD38 internalization and consequent activation in response to a variety of physiological and pathological stimuli remains poorly understood. Recent studies have shown that CD38 may sense redox signals and is thereby activated to produce cellular response and that the NADPH oxidase isoform, NOX1, is a major resource to produce superoxide (O2Β·βˆ’) in coronary arterial myocytes (CAMs) in response to muscarinic receptor agonist, which uses CD38-ADP-ribosylcyclase signaling pathway to exert its action in these CAMs. These findings led us hypothesize that NOX1-derived O2Β·βˆ’ serves in an autocrine fashion to enhance CD38 internalization, leading to redox activation of CD38-ADP-ribosylcyclase activity in mouse CAMs. To test this hypothesis, confocal microscopy, flow cytometry and a membrane protein biotinylation assay were used in the present study. We first demonstrated that CD38 internalization induced by endothelin-1 (ET-1) was inhibited by silencing of NOX1 gene, but not NOX4 gene. Correspondingly, NOX1 gene silencing abolished ET-1-induced O2Β·βˆ’ production and increased CD38-ADP-ribosylcyclase activity in CAMs, while activation of NOX1 by overexpression of Rac1 or Vav2 or administration of exogenous O2Β·βˆ’significantly increased CD38 internalization in CAMs. Lastly, ET-1 was found to markedly increase membrane raft clustering as shown by increased colocalization of cholera toxin-B with CD38 and NOX1. Taken together, these results provide direct evidence that Rac1-NOX1-dependent O2Β·βˆ’ production mediates CD38 internalization in CAMs, which may represent an important mechanism linking receptor activation with CD38 activity in these cells
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