Rare semileptonic meson decays in R-parity violating MSSM

We discuss rare meson decays $K^ + \to \pi ^ - \ell ^ + \ell '^ +$ and $D^ + \to K^ - \ell ^ + \ell '^ +$ ($\ell, \ell'=e, \mu$) in a supersymmetric extension of the Standard Model with R-parity violation. Estimates of the branching ratios for these decays are presented.Comment: 5 pages, 1 figure; title modified to better reflect the contents, a normalization error corrected for D-meson decays, modifying parts of Table 1; a reference and DESY Report number added; to appear in the Proceedings of the 12th. Lomonosov Conference on Elementary Particle Physics, Moscow State University, Moscow, Russia, 25-31 August 200

Bilinear R-parity Violation in Rare Meson Decays

We discuss rare meson decays $K^ + \to \pi ^ - \ell ^ + \ell '^ +$ and $D^ + \to K^ - \ell ^ + \ell '^ +$ ($\ell ,\ell ' = e,\mu$) in a supersymmetric extension of the standard model with explicit breaking of R-parity by bilinear Yukawa couplings in the superpotential. Estimates of the branching ratios for these decays are given. We also compare our numerical results with analogous ones previously obtained for two other mechanisms of lepton number violation: exchange by massive Majorana neutrinos and trilinear R-parity violation.Comment: 5 pages, 1 figure; To appear in the Proceedings of the 13th Lomonosov Conference on Elementary Particle Physics, 23 -- 29 August, 2007, Moscow, Russi

Optimizing the management of financial flows based on assessment of regional multiplier effects

This article examines the issues of improving the effectiveness in the management of regional financial flows. As their main hypothesis, the authors provide a rationale for the argument that the management of regional financial flows must be optimized on the basis of multiplier economic effects that allow to better assess the performance of regional socio-economic policy. The article presents a multifactor model for managing the financial flows at the regional level, or the matrix of financial flows based on the principles of general economic equilibrium theory, Input—Output balancing method and methodology of national accounts system. The consolidated budgetary balance sheet of the region is presented as an important structural element of the model. A methodology has been developed for integrating the consolidated budgetary balance sheet of the region in the matrix of financial flows. By using the example of individual subjects of the Russian Federation, the authors calculated the matrix multipliers of consolidated budgetary balance sheet that allow to simulate the multiplier economic effects resulting from the impact of different types of exogenous economic factors on the development of regions, and to forecast the impact of changes in the fiscal reallocation on GRP and household income, assess the impact of external investment on the economic growth of the regions and study the effectiveness of federal tax policy at the regional level. The article demonstrates that the value of multiplier effect depends on several factors, including the external trade relations of the region, its dependence on imports, the share of value added in gross output, as well as the propensity of households to savings. The approach proposed by the authors can be used by the government authorities at different levels in the development of their strategies of socio-economic development, assessment of the extent and areas of impact made by various exogenous factors on the economy of the region, as well as in the analysis of the investment initiatives of the private sector seeking the financial support for its projects from the state. The authors propose the areas for improving the management of financial flows based on maximizing the multiplier economic effects in the short and medium term for the regions with a different level of fiscal capacity.The article has been prepared with the support of the Grant of the Russian Foundation for Humanities (project №15–02–00587)

Detecting oxidative stress biomarkers in neurodegenerative disease models and patients

Oxidative stress is prominent in many neurodegenerative diseases. Along with mitochondrial dysfunction and pathological protein aggregation, increased levels of reactive oxygen and nitrogen species, together with impaired antioxidant defense mechanisms, are frequently observed in Alzheimer’s, Parkinson’s, Huntington’s disease and amyotrophic lateral sclerosis. The presence of oxidative stress markers in patients’ plasma and cerebrospinal fluid may aid early disease diagnoses, as well as provide clues regarding the efficacy of experimental disease-modifying therapies in clinical trials. In preclinical animal models, the detection and localization of oxidatively damaged lipids, proteins and nucleic acids helps to identify most vulnerable neuronal populations and brain areas, and elucidate the molecular pathways and the timeline of pathology progression. Here, we describe the protocol for the detection of oxidative stress markers using immunohistochemistry on formaldehyde-fixed, paraffin-embedded tissue sections, applicable to the analysis of postmortem samples and tissues from animal models. In addition, we provide a simple method for the detection of malondialdehyde in tissue lysates and body fluids, which is useful for screening and the identification of tissues and structures in the nervous system which are most affected by oxidative stress. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.Peer reviewe

Can Growth Factors Cure Parkinson's Disease?

Growth factors (GFs) hold considerable promise for disease modification in neurodegenerative disorders because they can protect and restore degenerating neurons and also enhance their functional activity. However, extensive efforts applied to utilize their therapeutic potential in humans have achieved limited success so far. Multiple clinical trials with GFs were performed in Parkinson's disease (PD) patients, in whom diagnostic symptoms of the disease are caused by advanced degeneration of nigrostriatal dopamine neurons (DNs), but the results of these trials are controversial. This review discusses recent developments in the field of therapeutic use of GFs, problems and obstacles related to this use, suggests the ways to overcome these issues, and alternative approaches that can be used to utilize the potential of GFs in PD management.Peer reviewe

Small Molecules and Peptides Targeting Glial Cell Line-Derived Neurotrophic Factor Receptors for the Treatment of Neurodegeneration

Glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) are able to promote the survival of multiple neuronal populations in the body and, therefore, hold considerable promise for disease-modifying treatments of diseases and conditions caused by neurodegeneration. Available data reveal the potential of GFLs for the therapy of Parkinson’s disease, neuropathic pain and diseases caused by retinal degeneration but, also, amyotrophic lateral sclerosis and, possibly, Alzheimer’s disease. Despite promising data collected in preclinical models, clinical translation of GFLs is yet to be conducted. The main reasons for the limited success of GFLs clinical development are the poor pharmacological characteristics of GFL proteins, such as the inability of GFLs to cross tissue barriers, poor diffusion in tissues, biphasic dose-response and activation of several receptors in the organism in different cell types, along with ethical limitations on patients’ selection in clinical trials. The development of small molecules selectively targeting particular GFL receptors with improved pharmacokinetic properties can overcome many of the difficulties and limitations associated with the clinical use of GFL proteins. The current review lists several strategies to target the GFL receptor complex with drug-like molecules, discusses their advantages, provides an overview of available chemical scaffolds and peptides able to activate GFL receptors and describes the effects of these molecules in cultured cells and animal models

Glial Cell Line-Derived Neurotrophic Factor Family Ligands, Players at the Interface of Neuroinflammation and Neuroprotection : Focus Onto the Glia

Well-known effects of neurotrophic factors are related to supporting the survival and functioning of various neuronal populations in the body. However, these proteins seem to also play less well-documented roles in glial cells, thus, influencing neuroinflammation. This article summarizes available data on the effects of glial cell line derived neurotrophic factor (GDNF) family ligands (GFLs), proteins providing trophic support to dopaminergic, sensory, motor and many other neuronal populations, in non-neuronal cells contributing to the development and maintenance of neuropathic pain. The paper also contains our own limited data describing the effects of small molecules targeting GFL receptors on the expression of the satellite glial marker IBA1 in dorsal root ganglia of rats with surgery- and diabetes-induced neuropathy. In our experiments activation of GFLs receptors with either GFLs or small molecule agonists downregulated the expression of IBA1 in this tissue of experimental animals. While it can be a secondary effect due to a supportive role of GFLs in neuronal cells, growing body of evidence indicates that GFL receptors are expressed in glial and peripheral immune system cells. Thus, targeting GFL receptors with either proteins or small molecules may directly suppress the activation of glial and immune system cells and, therefore, reduce neuroinflammation. As neuroinflammation is considered to be an important contributor to the process of neurodegeneration these data further support research efforts to modulate the activity of GFL receptors in order to develop disease-modifying treatments for neurodegenerative disorders and neuropathic pain that target both neuronal and glial cells.Peer reviewe

Development of the management system of a professional educational organization in the conditions of preparation of well-educated and flexible graduates

Changes in the socioeconomic and productive areas of our country, will inevitably lead to a natural change in the labour market. In this regard, there is a growing need for changes in the system of education in Russia, especially with regard to vocational education. The VET can distinguish five interrelated elements inside Wednesday: the objectives of the Organization, tasks, technology, management and human resourcesИзменения, происходящие в социально-экономической и производственной сферах нашей страны, неизбежно ведут к закономерным преобразованиям на рынке труда. В связи с этим возрастает потребность внесения изменений в систему образования России, особенно это касается профессионального образования. В ПОО можно выделить пять взаимосвязанных элементов внутренней среды: цели организации, задачи, технологии, структура управления и кадровые ресурс

Development of instruments to management adaptation of personnel of trade organization

В данной статье показано, что управление адаптацией персонала – одна из важных проблем кадровой работы на торговых предприятиях. Разработана классификация инструментов адаптации, даны рекомендации по успешной адаптации новых сотрудников.This article shows that the management of the adaptation of the personnel – one of the important problems of personnel working in trade enterprise. The developed classification of adaptation tools and recommendations for successful adaptation of new employees

Development of instruments to management adaptation of personnel of trade organization

В данной статье показано, что управление адаптацией персонала – одна из важных проблем кадровой работы на торговых предприятиях. Разработана классификация инструментов адаптации, даны рекомендации по успешной адаптации новых сотрудников.This article shows that the management of the adaptation of the personnel – one of the important problems of personnel working in trade enterprise. The developed classification of adaptation tools and recommendations for successful adaptation of new employees