81 research outputs found
Π€ΠΈΠ½Π°Π½ΡΠΎΠ²Π°Ρ ΠΏΠΎΠ»ΠΈΡΠΈΠΊΠ° Π³ΠΎΡΡΠ΄Π°ΡΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΠΏΠΎΠ΄Π΄Π΅ΡΠΆΠΊΠΈ ΠΎΡΡΠ°ΡΠ»ΠΈ ΠΌΠΈΠΊΡΠΎΡΠ»Π΅ΠΊΡΡΠΎΠ½ΠΈΠΊΠΈ Π² Π ΠΎΡΡΠΈΠΈ Π² ΡΡΠ»ΠΎΠ²ΠΈΡΡ ΡΠ°Π½ΠΊΡΠΈΠΉ
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 worldβs 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 stateβs initiatives to promote the radio-electronics industry might provide Russia a chance to catch up to the worldβs leading countries in this industry.ΠΠΊΡΡΠ°Π»ΡΠ½ΠΎΡΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ΅ΡΡΡ Π½Π΅ΠΎΠ±Ρ
ΠΎΠ΄ΠΈΠΌΠΎΡΡΡΡ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΠΎΡΠ΅ΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΠΎΡΡΠ°ΡΠ»ΠΈ ΠΌΠΈΠΊΡΠΎΡΠ»Π΅ΠΊΡΡΠΎΠ½ΠΈΠΊΠΈ Π² Π ΠΎΡΡΠΈΠΈ Ρ ΡΡΠ΅ΡΠΎΠΌ ΡΠ»ΠΎΠΆΠΈΠ²ΡΠΈΡ
ΡΡ Π½Π΅Π³Π°ΡΠΈΠ²Π½ΡΡ
ΠΊΠ°ΠΊ Π²Π½ΡΡΡΠ΅Π½Π½ΠΈΡ
, ΡΠ°ΠΊ ΠΈ Π²Π½Π΅ΡΠ½ΠΈΡ
ΡΡΡΠ΅ΠΊΡΠΎΠ².Π¦Π΅Π»ΡΡ ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΏΡΠΎΠ²Π΅ΡΠΊΠ° Π³ΠΈΠΏΠΎΡΠ΅Π·Ρ ΠΎ ΠΏΠΎΠ»ΠΎΠΆΠΈΡΠ΅Π»ΡΠ½ΠΎΠΌ Π²Π»ΠΈΡΠ½ΠΈΠΈ ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΠ΅ΠΌΡΡ
Π³ΠΎΡΡΠ΄Π°ΡΡΡΠ²ΠΎΠΌ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² ΡΠΈΠ½Π°Π½ΡΠΎΠ²ΠΎΠΉ ΠΏΠΎΠ΄Π΄Π΅ΡΠΆΠΊΠΈ ΠΎΡΠ΅ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
ΠΊΠΎΠΌΠΏΠ°Π½ΠΈΠΉ Π΄Π»Ρ ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ ΠΏΡΠΎΡΡΠ²Π½ΡΡ
ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΠΉ Π² ΠΊΠΎΠ½ΠΊΡΠ΅ΡΠ½ΠΎΠΉ ΠΎΠ±Π»Π°ΡΡΠΈ Π² ΡΡΠ»ΠΎΠ²ΠΈΡΡ
Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΊΠ° ΡΠΈΠ½Π°Π½ΡΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈ ΡΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ ΠΎΡΡΡΠ°Π²Π°Π½ΠΈΡ Π½Π°ΡΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎΠΉ ΠΎΡΡΠ°ΡΠ»ΠΈ ΠΌΠΈΠΊΡΠΎΡΠ»Π΅ΠΊΡΡΠΎΠ½ΠΈΠΊΠΈ ΠΎΡ Π²Π΅Π΄ΡΡΠΈΡ
ΡΡΡΠ°Π½ ΠΌΠΈΡΠ°.ΠΠ°Π΄Π°ΡΠ΅ΠΉ Π΄Π°Π½Π½ΠΎΠ³ΠΎ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΡΠ²Π»ΡΠ΅ΡΡΡ Π°Π½Π°Π»ΠΈΠ· Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΡΡ
ΠΈΠ½ΡΡΡΡΠΌΠ΅Π½ΡΠΎΠ² Π³ΠΎΡΡΠ΄Π°ΡΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΠΏΠΎΠ΄Π΄Π΅ΡΠΆΠΊΠΈ, Π²ΠΊΠ»ΡΡΠ°Ρ ΡΡΠ±ΡΠΈΠ΄ΠΈΠΈ ΠΈ Π³ΡΠ°Π½ΡΡ, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² ΠΈΡ
ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ Ρ ΡΠ΅Π»ΡΡ ΡΠΎΠ·Π΄Π°Π½ΠΈΡ ΠΊΠΎΠ½ΠΊΡΡΠ΅Π½ΡΠ½ΠΎΠΉ ΠΎΡΡΠ°ΡΠ»ΠΈ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄ΡΡΠ²Π° ΠΎΡΠ΅ΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΠΌΠΈΠΊΡΠΎΡΠ»Π΅ΠΊΡΡΠΎΠ½ΠΈΠΊΠΈ.ΠΡΠ½ΠΎΠ²Π½ΡΠ΅ ΠΌΠ΅ΡΠΎΠ΄Ρ, ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΠ΅ΠΌΡΠ΅ Π² Π΄Π°Π½Π½ΠΎΠΌ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΈ, Π²ΠΊΠ»ΡΡΠ°ΡΡ Π² ΡΠ΅Π±Ρ ΡΠ±ΠΎΡ ΠΈ ΠΎΠ±ΡΠ°Π±ΠΎΡΠΊΡ ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π΄Π°Π½Π½ΡΡ
, ΠΈΡ
ΡΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ·, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΏΡΠΎΡΠ°Π±ΠΎΡΠΊΡ Π½ΠΎΡΠΌΠ°ΡΠΈΠ²Π½ΠΎΠΉ Π±Π°Π·Ρ ΠΏΠΎ Π½Π°Π»ΠΎΠ³ΠΎΠ²ΠΎΠΌΡ ΡΠ΅Π³ΡΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π² Π΄Π°Π½Π½ΠΎΠΌ ΡΠ΅ΠΊΡΠΎΡΠ΅ ΡΠΊΠΎΠ½ΠΎΠΌΠΈΠΊΠΈ. ΠΠ²ΡΠΎΡΡ ΠΏΡΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡΠΎΠ²Π°Π»ΠΈ ΡΠΎΡΡΠΎΡΠ½ΠΈΠ΅ ΠΎΡΡΠ°ΡΠ»ΠΈ ΠΌΠΈΠΊΡΠΎΡΠ»Π΅ΠΊΡΡΠΎΠ½ΠΈΠΊΠΈ Π² ΠΌΠΈΡΠ΅, Π²ΠΊΠ»ΡΡΠ°Ρ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄ΡΡΠ²ΠΎ ΠΌΠΈΠΊΡΠΎΠΏΡΠΎΡΠ΅ΡΡΠΎΡΠΎΠ² ΠΈ Π΄ΡΡΠ³ΠΈΡ
ΠΏΠΎΠ»ΡΠΏΡΠΎΠ²ΠΎΠ΄Π½ΠΈΠΊΠΎΠ²ΡΡ
ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠΎΠ². ΠΠΎΠ»Π΅Π΅ Π΄Π΅ΡΠ°Π»ΡΠ½ΠΎ ΡΠ°ΡΡΠΌΠΎΡΡΠ΅Π½Π° ΡΠΈΡΡΠ°ΡΠΈΡ Π² ΡΠ°ΠΊΠΈΡ
ΡΡΡΠ°Π½Π°Ρ
, ΠΊΠ°ΠΊ ΠΠΈΡΠ°ΠΉ, Π‘Π¨Π, Π―ΠΏΠΎΠ½ΠΈΡ, ΠΠ²ΡΠΎΠΏΠ°, Π’Π°ΠΉΠ²Π°Π½Ρ, ΠΠ½Π΄ΠΈΡ ΠΈ Π ΠΎΡΡΠΈΡ. ΠΠ° ΠΎΡΠ½ΠΎΠ²Π΅ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π° Π²ΡΡΠ²Π»Π΅Π½Ρ ΠΎΡΠ½ΠΎΠ²Π½ΡΠ΅ ΠΏΡΠΎΠ±Π»Π΅ΠΌΡ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΠΎΡΡΠ°ΡΠ»ΠΈ ΠΌΠΈΠΊΡΠΎΡΠ»Π΅ΠΊΡΡΠΎΠ½ΠΈΠΊΠΈ Π² Π ΠΎΡΡΠΈΠΈ. ΠΠ°Π½Π° ΠΎΡΠ΅Π½ΠΊΠ° ΠΌΠ°ΡΡΡΠ°Π±ΠΎΠ² ΠΈ Π²ΡΡΠ²Π»Π΅Π½Ρ Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½ΠΈΡ ΡΠ°ΡΡ
ΠΎΠ΄ΠΎΠ²Π°Π½ΠΈΡ ΡΡΠ΅Π΄ΡΡΠ² ΡΠ΅Π΄Π΅ΡΠ°Π»ΡΠ½ΠΎΠ³ΠΎ Π±ΡΠ΄ΠΆΠ΅ΡΠ° Π½Π° ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ ΡΠ°Π΄ΠΈΠΎΡΠ»Π΅ΠΊΡΡΠΎΠ½Π½ΠΎΠΉ ΠΏΡΠΎΠΌΡΡΠ»Π΅Π½Π½ΠΎΡΡΠΈ Π² ΠΏΠ΅ΡΠΈΠΎΠ΄ 2022β2025 Π³Π³.ΠΠ°ΡΡΠ½Π°Ρ Π½ΠΎΠ²ΠΈΠ·Π½Π° ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π½ΠΎΠ³ΠΎ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Π·Π°ΠΊΠ»ΡΡΠ°Π΅ΡΡΡ Π² Π²ΡΡΠ²Π»Π΅Π½ΠΈΠΈ Π²Π·Π°ΠΈΠΌΠΎΡΠ²ΡΠ·ΠΈ ΠΌΠ΅ΠΆΠ΄Ρ ΠΏΡΠ΅Π΄ΠΎΡΡΠ°Π²Π»ΡΠ΅ΠΌΡΠΌΠΈ ΠΌΠ΅ΡΠ°ΠΌΠΈ Π³ΠΎΡΡΠ΄Π°ΡΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ Π½Π°Π»ΠΎΠ³ΠΎΠ²ΠΎΠ³ΠΎ ΡΡΠΈΠΌΡΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΠ°Π΄ΠΈΠΎΡΠ»Π΅ΠΊΡΡΠΎΠ½Π½ΠΎΠΉ ΠΏΡΠΎΠΌΡΡΠ»Π΅Π½Π½ΠΎΡΡΠΈ ΠΈ ΠΌΠ°ΠΊΡΠΎΡΠΊΠΎΠ½ΠΎΠΌΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»ΡΠΌΠΈ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΏΠΎΠ·Π²ΠΎΠ»ΠΈΠ»ΠΈ Π°Π²ΡΠΎΡΠ°ΠΌ Π²ΡΡΠ°Π±ΠΎΡΠ°ΡΡ ΠΊΡΠΈΡΠ΅ΡΠΈΠΈ ΠΎΡΠ΅Π½ΠΊΠΈ Π²ΠΎΡΡΡΠ΅Π±ΠΎΠ²Π°Π½Π½ΠΎΡΡΠΈ ΠΈ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΡΠΈΡΠΊΠ°Π»ΡΠ½ΡΡ
ΠΏΡΠ΅ΡΠ΅ΡΠ΅Π½ΡΠΈΠΉ Π΄Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΡΠ΅ΠΌΠΎΠ³ΠΎ Π²ΠΈΠ΄Π° Π΄Π΅ΡΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ.Π‘Π΄Π΅Π»Π°Π½ Π²ΡΠ²ΠΎΠ΄, ΡΡΠΎ ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΠ΅ΠΌΡΠ΅ Π³ΠΎΡΡΠ΄Π°ΡΡΡΠ²ΠΎΠΌ ΠΌΠ΅ΡΡ ΠΏΠΎΠ΄Π΄Π΅ΡΠΆΠΊΠΈ ΡΠ°Π΄ΠΈΠΎΡΠ»Π΅ΠΊΡΡΠΎΠ½Π½ΠΎΠΉ ΠΏΡΠΎΠΌΡΡΠ»Π΅Π½Π½ΠΎΡΡΠΈ ΠΌΠΎΠ³ΡΡ Π΄Π°ΡΡ Π ΠΎΡΡΠΈΠΈ ΡΠ°Π½Ρ ΠΏΡΠ΅ΠΎΠ΄ΠΎΠ»Π΅ΡΡ Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎΠ΅ ΠΎΡΡΡΠ°Π²Π°Π½ΠΈΠ΅ Π² ΡΡΠΎΠΉ ΠΎΡΡΠ°ΡΠ»ΠΈ ΠΎΡ Π²Π΅Π΄ΡΡΠΈΡ
ΡΡΡΠ°Π½ ΠΌΠΈΡΠ°
High-frequency homogenization for periodic media
This article is available open access through the publisherβs 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 βhigh-frequency homogenizationβ 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 βcell resonancesβ. 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
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
ΠΡΠΎΠ³Π½ΠΎΠ·ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΎΡΠΈΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΡΠ΅Π³ΠΈΠΎΠ½ΠΎΠ² Π ΠΎΡΡΠΈΠΈ
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 βPatternβ method. This method allows the objective assessment of the interregional βgapsβ 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 βgapβ 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.Π¦Π΅Π»Ρ ΡΡΠ°ΡΡΠΈ βΒ ΠΏΡΠ΅Π΄Π»ΠΎΠΆΠΈΡΡ Π°Π²ΡΠΎΡΡΠΊΡΡ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΡ ΠΎΡΠ΅Π½ΠΊΠΈ ΠΈ ΠΏΡΠΎΠ³Π½ΠΎΠ·ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΠΎΡΠΈΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΡΠ΅Π³ΠΈΠΎΠ½ΠΎΠ² Π ΠΎΡΡΠΈΠΈ. ΠΠ΅ΡΠΎΠ΄ΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΎΡΠ½ΠΎΠ²ΠΎΠΉ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΡΠ²Π»ΡΡΡΡΡ Π½Π΅ΠΉΡΠΎΡΠ΅ΡΠ΅Π²ΡΠ΅ ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΠΈ (ΡΠΎΡΠΌΠΈΡΡΠ΅ΡΡΡ Π±Π°ΠΉΠ΅ΡΠΎΠ²ΡΠΊΠΈΠΉ Π°Π½ΡΠ°ΠΌΠ±Π»Ρ Π΄ΠΈΠ½Π°ΠΌΠΈΡΠ΅ΡΠΊΠΈΡ
Π½Π΅ΠΉΡΠΎΡΠ΅ΡΠ΅ΠΉ ΡΠ°Π·Π»ΠΈΡΠ½ΠΎΠΉ ΠΊΠΎΠ½ΡΠΈΠ³ΡΡΠ°ΡΠΈΠΈ), ΠΎΠ±Π΅ΡΠΏΠ΅ΡΠΈΠ²Π°ΡΡΠΈΠ΅ Π²ΡΡΠΎΠΊΡΡ ΡΠΎΡΠ½ΠΎΡΡΡ ΠΏΡΠΎΠ³Π½ΠΎΠ·Π°. ΠΠ²ΡΠΎΡΠ°ΠΌΠΈ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½Π° ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠ° ΠΎΡΠ΅Π½ΠΊΠΈ ΡΠΎΡΠΈΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»Π° ΡΠ΅Π³ΠΈΠΎΠ½ΠΎΠ² Π ΠΎΡΡΠΈΠΈ. Π‘ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½Π° ΡΠΈΡΡΠ΅ΠΌΠ° ΡΠ°ΡΡΠ½ΡΡ
ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Π΅ΠΉ, Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΡΡΡΠΈΡ
ΡΡΠΎΠ²Π΅Π½Ρ ΡΠΎΡΠΈΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΡΠ΅Π³ΠΈΠΎΠ½ΠΎΠ² ΡΡΡΠ°Π½Ρ. ΠΠ½ΠΈ ΠΎΠ±ΡΠ΅Π΄ΠΈΠ½Π΅Π½Ρ Π² ΠΏΡΡΡ Π³ΡΡΠΏΠΏ: 1) Π½Π°ΡΠ΅Π»Π΅Π½ΠΈΠ΅ (ΠΎΠΆΠΈΠ΄Π°Π΅ΠΌΠ°Ρ ΠΏΡΠΎΠ΄ΠΎΠ»ΠΆΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΡ ΠΆΠΈΠ·Π½ΠΈ); 2) ΡΡΠΎΠ²Π΅Π½Ρ ΠΆΠΈΠ·Π½ΠΈ Π½Π°ΡΠ΅Π»Π΅Π½ΠΈΡ; 3) ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΠ΅; 4) Π·Π΄ΡΠ°Π²ΠΎΠΎΡ
ΡΠ°Π½Π΅Π½ΠΈΠ΅ (Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π΅ΠΌΠΎΡΡΡ); 5) Π½Π°ΡΡΠ½ΡΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΈ ΠΈΠ½Π½ΠΎΠ²Π°ΡΠΈΠΈ. Π‘ ΠΏΠΎΠΌΠΎΡΡΡ ΠΌΠ΅ΡΠΎΠ΄Π° Β«ΠΠ°ΡΡΠ΅ΡΠ½Β» ΡΠ°ΡΡΠ½ΡΠ΅ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»ΠΈ ΠΏΡΠΈΠ²Π΅Π΄Π΅Π½Ρ Π² ΡΠΎΠΏΠΎΡΡΠ°Π²ΠΈΠΌΡΠΉ Π²ΠΈΠ΄ ΠΏΡΡΠ΅ΠΌ Π½ΠΎΡΠΌΠ°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΠΈΡ
Π·Π½Π°ΡΠ΅Π½ΠΈΠΉ. ΠΠ°Π½Π½ΡΠΉ ΠΌΠ΅ΡΠΎΠ΄ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ ΠΎΠ±ΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎ ΠΎΡΠ΅Π½ΠΈΠ²Π°ΡΡ Β«Π³Π»ΡΠ±ΠΈΠ½ΡΒ» ΠΌΠ΅ΠΆΡΠ΅Π³ΠΈΠΎΠ½Π°Π»ΡΠ½ΡΡ
Β«ΡΠ°Π·ΡΡΠ²ΠΎΠ²Β» Π² ΡΡΡΠ°Π½Π΅ ΠΏΠΎ Π²ΡΠ΅ΠΉ ΡΠΈΡΡΠ΅ΠΌΠ΅ ΡΠΎΡΠΈΠ°Π»ΡΠ½ΡΡ
ΠΈΠ½Π΄ΠΈΠΊΠ°ΡΠΎΡΠΎΠ². ΠΡΠΎΠ²Π΅Π΄Π΅Π½ ΡΠ°ΡΡΠ΅Ρ ΠΈΠ½Π΄Π΅ΠΊΡΠ° ΡΠΎΡΠΈΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΡΡΠ±ΡΠ΅ΠΊΡΠΎΠ² Π Π€. ΠΠ° ΠΎΡΠ½ΠΎΠ²Π΅ Π½Π΅ΠΉΡΠΎΡΠ΅ΡΠ΅Π²ΡΡ
ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΠΉ (ΡΠ°ΠΌΠΎΠΎΡΠ³Π°Π½ΠΈΠ·ΡΡΡΠΈΡ
ΡΡ ΠΊΠ°ΡΡ ΠΠΎΡ
ΠΎΠ½Π΅Π½Π°) ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π° ΠΊΠ»Π°ΡΡΠ΅ΡΠΈΠ·Π°ΡΠΈΡ ΡΠ΅Π³ΠΈΠΎΠ½ΠΎΠ² Π ΠΎΡΡΠΈΠΈ ΠΏΠΎ ΡΡΠΎΠ²Π½Ρ ΡΠΎΡΠΈΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΡ. ΠΡΡΡΠ΅ΡΡΠ²Π»Π΅Π½ΠΎ ΠΏΡΠΎΠ³Π½ΠΎΠ·ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΎΡΠΈΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΡΠΎΡΡΠΈΠΉΡΠΊΠΈΡ
ΡΠ΅Π³ΠΈΠΎΠ½ΠΎΠ². Π ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΠΏΡΠΎΠ³Π½ΠΎΠ·ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ Ρ ΡΠ΅Π³ΠΈΠΎΠ½Π° βΒ Π»ΠΈΠ΄Π΅ΡΠ° Π Π€ (Π³. ΠΠΎΡΠΊΠ²Π°) Π² 2017β2019 Π³Π³. ΠΎΠΆΠΈΠ΄Π°Π΅ΡΡΡ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅ ΠΈΠ½Π΄Π΅ΠΊΡΠ° ΡΠΎΡΠΈΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ 2014β2016 Π³Π³. Π£ Π΄ΡΡΠ³ΠΎΠ³ΠΎ ΡΠ΅Π³ΠΈΠΎΠ½Π° βΒ Π»ΠΈΠ΄Π΅ΡΠ° Π Π€ (Π³. Π‘Π°Π½ΠΊΡ-ΠΠ΅ΡΠ΅ΡΠ±ΡΡΠ³) Π² ΡΡΠ΅Π΄Π½Π΅ΡΡΠΎΡΠ½ΠΎΠΉ ΠΏΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Π΅ ΡΠ°ΠΊΠΆΠ΅ ΠΎΠΆΠΈΠ΄Π°Π΅ΡΡΡ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Ρ, Π½ΠΎ ΡΠΎΠ»ΡΠΊΠΎ ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ 2016 Π³. ΠΡΠΈ ΡΡΠΎΠΌ ΠΏΠΎ Π Π΅ΡΠΏΡΠ±Π»ΠΈΠΊΠ΅ ΠΠ°ΡΠΊΠΎΡΡΠΎΡΡΠ°Π½ Π² 2017β2019 Π³Π³. ΠΏΡΠΎΠ³Π½ΠΎΠ·ΠΈΡΡΠ΅ΡΡΡ Π»ΠΈΡΡ Π½Π΅Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎΠ΅ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅ ΡΡΠΎΠ²Π½Ρ ΡΠΎΡΠΈΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΡ. ΠΠ΄Π½Π°ΠΊΠΎ ΠΎΠΆΠΈΠ΄Π°Π΅ΡΡΡ, ΡΡΠΎ ΡΠ΅ΡΠΏΡΠ±Π»ΠΈΠΊΠ° ΠΏΠΎ-ΠΏΡΠ΅ΠΆΠ½Π΅ΠΌΡ Π±ΡΠ΄Π΅Ρ ΡΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎ ΠΎΡΡΡΠ°Π²Π°ΡΡ ΠΎΡ ΡΠ΅Π³ΠΈΠΎΠ½ΠΎΠ² βΒ Π»ΠΈΠ΄Π΅ΡΠΎΠ² Π ΠΎΡΡΠΈΠΈ ΠΏΠΎ ΡΡΠΎΠ²Π½Ρ ΡΠΎΡΠΈΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΡ. ΠΠ° ΠΏΡΠΈΠΌΠ΅ΡΠ΅ Π Π΅ΡΠΏΡΠ±Π»ΠΈΠΊΠΈ ΠΠ°ΡΠΊΠΎΡΡΠΎΡΡΠ°Π½ Π²ΡΡΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ ΠΎΡΡΡΠ°Π²Π°Π½ΠΈΠ΅ Π² ΡΡΠ΅ΡΠ΅ ΡΠΎΡΠΈΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΠΎΠ±ΡΡΡΠ½ΡΠ΅ΡΡΡ Β«ΡΠ°Π·ΡΡΠ²ΠΎΠΌΒ» Π² ΠΎΠ±Π»Π°ΡΡΠΈ Π½Π°ΡΡΠ½ΡΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΈ ΠΈΠ½Π½ΠΎΠ²Π°ΡΠΈΠΉ. ΠΠ²ΡΠΎΡΡ Π΄Π΅Π»Π°ΡΡ Π²ΡΠ²ΠΎΠ΄ ΠΎ Π½Π΅ΠΎΠ±Ρ
ΠΎΠ΄ΠΈΠΌΠΎΡΡΠΈ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΡΠΎΡΠΈΠ°Π»ΡΠ½ΠΎΠΉ ΠΏΠΎΠ»ΠΈΡΠΈΠΊΠΈ Π½Π° ΡΠ΅Π³ΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎΠΌ ΡΡΠΎΠ²Π½Π΅. ΠΠ»Ρ ΡΡΠΎΠ³ΠΎ Π½Π΅ΠΎΠ±Ρ
ΠΎΠ΄ΠΈΠΌΠΎ Π½Π΅ ΡΠΎΠ»ΡΠΊΠΎ ΡΠ²Π΅Π»ΠΈΡΠΈΡΡ ΡΠΈΠ½Π°Π½ΡΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΎΡΠΈΠ°Π»ΡΠ½ΠΎΠΉ ΡΡΠ΅ΡΡ ΡΡΠ±ΡΠ΅ΠΊΡΠΎΠ² Π Π€, Π½ΠΎ ΠΈ ΠΎΠ±Π΅ΡΠΏΠ΅ΡΠΈΡΡ Π½Π°Π΄Π»Π΅ΠΆΠ°ΡΠΈΠΉ ΠΊΠΎΠ½ΡΡΠΎΠ»Ρ ΡΠ°ΡΡ
ΠΎΠ΄ΠΎΠ²Π°Π½ΠΈΡ Π±ΡΠ΄ΠΆΠ΅ΡΠ½ΡΡ
ΡΡΠ΅Π΄ΡΡΠ². Π Π°Π·ΡΠ°Π±ΠΎΡΠ°Π½Π½Π°Ρ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠ° ΠΌΠΎΠΆΠ΅Ρ ΡΠ²Π»ΡΡΡΡΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΠΌ ΠΈΠ½ΡΡΡΡΠΌΠ΅Π½ΡΠΎΠΌ ΠΏΡΠΎΠ³Π½ΠΎΠ·ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈ ΡΠΏΡΠ°Π²Π»Π΅Π½ΠΈΡ ΡΠΎΡΠΈΠ°Π»ΡΠ½ΡΠΌ ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ΠΌ ΡΠ΅Π³ΠΈΠΎΠ½ΠΎΠ² Π Π€ ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΡΡΡΠΈΠΌΠΈ ΠΌΠΈΠ½ΠΈΡΡΠ΅ΡΡΡΠ²Π°ΠΌΠΈ ΠΈ Π²Π΅Π΄ΠΎΠΌΡΡΠ²Π°ΠΌΠΈ
Calcium Homeostasis in Myogenic Differentiation Factor 1 (MyoD)-Transformed, Virally-Transduced, Skin-Derived Equine Myotubes
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 cellsβ 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
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 β
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
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 β 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
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
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·β) 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·β 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·β production and increased CD38-ADP-ribosylcyclase activity in CAMs, while activation of NOX1 by overexpression of Rac1 or Vav2 or administration of exogenous O2Β·βsignificantly 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·β 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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