Paleostress field reconstruction and revised tectonic history of the Donbas fold and thrust belt (Ukraine and Russia).

In the WNW-ESE Donbas fold belt (DF), inversion of 3500 microtectonic data collected at 135 sites, in Proterozoic, Devonian, Carboniferous, and Cretaceous competent rocks allowed reconstruction of 123 local stress states. Accordingly, four successive paleostress fields reveal the tectonic evolution of the DF. At the numerous sites that have been affected by polyphase tectonics, the chronology between local paleostress states (also paleostress fields) was established using classical criteria (crosscutting striae, pre- or post-folding stress states, stratigraphic control). The oldest event is an extensional stress field with NNE-SSW σ<inf>3</inf>. It corresponds to the rifting phases that generated the basin in Devonian times and its early Visean reactivation. Later, the DF was affected by a transtension, with NW-SE σ<inf>3</inf> characterizing Early Permian tectonism, including the development of the "Main Anticline" of the DF and the pronounced uplift of its southern margin and Ukrainian Shield. Two paleostress fields characterize the Cretaceous/Paleocene inversion of the DF, which was accompanied by folding and thrusting. Both are compressional in type but differ by the trend of σ<inf>1</inf>, which was first NW-SE and subsequently N-S. The discrete paleostress history of the DF allows a revised interpretation of its tectonic evolution with significant implications for understanding the geodynamic evolution of the southern margin of the East European Craton. Copyright 2003 by the American Geophysical Union

Diagnostics of Human Middle-East Respiratory Syndrome

Middle-East respiratory syndrome is a human disease caused by a new coronavirus. In December, 2012 WHO published draft regulatory document on diagnostics of the virus. It was recommended to use two methods of disease diagnostics - two-phase reverse-transcription real-time PCR and enzyme immunoassay. The first phase of the PCR-diagnostics should include reverse-transcription real-time PCR targeted on the genome fragment upwards of upE. The second (control) PCR-test may be alternatively targeted within the bonds of the genome, its target being non-crisscross with upE gene. It should include sequencing of, at least, a segment of one of the viral genomes and comparative analysis of the obtained sequence along with the like ones deposited in the GenBank. Enzyme immunoassay is retrospectively used for virus-specific antibody detection in convalescents’ blood sera. Examined are the key specifications of the methods for the detection of ethiological agent or specific antibodies to it, and WHO methodological recommendations in case of Middle-East respiratory syndrome diagnostics

Emerging Coronavirus Which Gives Rise to the Disease in Humans

Coronaviruses are enveloped viruses with a single-strand “+” RNA, its genome size varying from 25 to 32 thousands of nucleotides. They cause respiratory and intestinal diseases in animals and humans. The review contains the data on human infection cases induced by a new coronavirus (NCoV), as well as the information about probable natural agent reservoirs, mechanisms of transmission, some characteristic features of the etiological agent, methods of diagnostics and identification, complete genome sequence, and NCoV relation to the established coronaviruses

Safety and immunogenicity of IMVAMUNE®, a third-generation vaccine based on the modified vaccinia Ankara (MVA) strain

In 1980, the World Health Assembly officially declared smallpox eradicated in the world, which allowed developed countries to stop preventive vaccination against this disease. However, circulating and emerging orthopoxviruses along with the lack of herd immunity prompt the need for emergency smallpox vaccines meeting the current requirements for biologicals.The aim of the study was to analyse the safety and efficacy of third-generation smallpox vaccines based on the MVA strain of vaccinia virus compliant with the current (stricter) immunogenicity and safety requirements in healthy subjects and especially in patients with underlying health conditions, considering the lack of herd immunity to orthopoxviruses.The authors analysed the existing experience with smallpox vaccines. The vaccines based on the modified vaccinia Ankara (MVA) strain hold a special place amongst other third-generation vaccines, as this strain is safe and can be used for creating vector vaccines. Bavarian Nordic produces the MVA-based vaccine under three brand names (Imvanex in the EU, Jynneos™ in the USA, and IMVAMUNE® in Canada). According to the results of MVA-based vaccine clinical trials in healthy volunteers and patients with various underlying conditions, the main mild adverse drug reactions (erythema, pain, pruritus, and swelling) were mostly registered at the injection site. The systemic adverse drug reactions included fatigue, headache, myalgia, and chills; several subjects developed upper respiratory tract infections, nausea, and gastroenteritis, which resolved spontaneously within a day. MVA-based vaccines did not cause any cardiac abnormalities, including myo- or pericarditis. Thus, the vaccines may be used in patients with eczema, atopic dermatitis, inflammatory skin conditions, HIV, tuberculosis, cardiac abnormalities, as well as in children, adolescents, and pregnant women. The optimal intradermal immunisation dose was 1×108 TCID50. Two injections at this dose induced a pronounced humoral and cell-mediated immune response comparable to that induced by one administration of a first-generation smallpox vaccine. At this dose, the study vaccine also boosted pre-existing immunity conferred by a first-generation vaccine. The US Centers for Disease Control and Prevention recommend Jynneos™ for preventing monkeypox in adults (18 years of age and older)

Current State of the Development of Therapies for Emergency Prophylaxis and Treatment of Ebola Virus Disease

Nowadays vaccination of the population living in the endemic regions and widespread implementation of the potent therapies for the emergency prophylaxis and treatment into the clinical practice are regarded as the basic efficient and cost-effective measures for Ebola epidemic spread control. Objective of the review is to analyze current state of the development of aids for the immediate prophylaxis and treatment of Ebola fever. Focus area of the activities is the construction of drugs on the basis of virus-specific anti-bodies (including monoclonal), small interfering RNA, and anti-sense phosphordiamidate morpholine oligomers and interferons. The paper discusses the most significant achievements in this sphere

The Molecular Genetic Peculiarities of Genomic Structure of Members of the <i>Ebolavirus</i> Genus

The molecular genetic peculiarities of genomic structure of the Ebolavirus genus members are viewed in the review. The Ebola virus disease outbreaks in West African countries constitute a threat not only for Africa, but for the whole world in view of possible introduction of the agent in non-endemic regions. The members of the Ebolavirus genus have different pathogenicity for humans, thus differ severity and mortality of the disease they cause. There is a significant genetic divergence among members of the Ebolavirus genus. The differences of pathogenic potential of members of the Ebolavirus genus may be explained as the result of mutations in the genes of virus structural proteins. It is possible, that some of these mutations may affect virulence of strains within one virus species. So far as most effective modern medicines for specific prophylaxis and treatment of Ebola fever are target-oriented, genotyping of the agent will promote elaboration of strategy of such preparations development

Безопасность и иммуногенность вакцины третьего поколения IMVAMUNE® на основе вируса вакцины, штамм MVA

In 1980, the World Health Assembly officially declared smallpox eradicated in the world, which allowed developed countries to stop preventive vaccination against this disease. However, circulating and emerging orthopoxviruses along with the lack of herd immunity prompt the need for emergency smallpox vaccines meeting the current requirements for biologicals.The aim of the study was to analyse the safety and efficacy of third-generation smallpox vaccines based on the MVA strain of vaccinia virus compliant with the current (stricter) immunogenicity and safety requirements in healthy subjects and especially in patients with underlying health conditions, considering the lack of herd immunity to orthopoxviruses.The authors analysed the existing experience with smallpox vaccines. The vaccines based on the modified vaccinia Ankara (MVA) strain hold a special place amongst other third-generation vaccines, as this strain is safe and can be used for creating vector vaccines. Bavarian Nordic produces the MVA-based vaccine under three brand names (Imvanex in the EU, Jynneos™ in the USA, and IMVAMUNE® in Canada). According to the results of MVA-based vaccine clinical trials in healthy volunteers and patients with various underlying conditions, the main mild adverse drug reactions (erythema, pain, pruritus, and swelling) were mostly registered at the injection site. The systemic adverse drug reactions included fatigue, headache, myalgia, and chills; several subjects developed upper respiratory tract infections, nausea, and gastroenteritis, which resolved spontaneously within a day. MVA-based vaccines did not cause any cardiac abnormalities, including myo- or pericarditis. Thus, the vaccines may be used in patients with eczema, atopic dermatitis, inflammatory skin conditions, HIV, tuberculosis, cardiac abnormalities, as well as in children, adolescents, and pregnant women. The optimal intradermal immunisation dose was 1×108 TCID50. Two injections at this dose induced a pronounced humoral and cell-mediated immune response comparable to that induced by one administration of a first-generation smallpox vaccine. At this dose, the study vaccine also boosted pre-existing immunity conferred by a first-generation vaccine. The US Centers for Disease Control and Prevention recommend Jynneos™ for preventing monkeypox in adults (18 years of age and older).В 1980 г. Всемирная ассамблея здравоохранения официально провозгласила искоренение натуральной оспы в мире, что позволило в развитых странах отменить профилактическую вакцинацию против этого заболевания. Однако из-за постоянно циркулирующих и вновь возникающих ортопоксвирусов, а также отсутствия популяционного иммунитета необходимо наличие в чрезвычайных ситуациях противооспенных вакцин, отвечающих современным требованиям к иммунобиологическим препаратам.Цель работы — анализ безопасности и эффективности в условиях отсутствия популяционного иммунитета к ортопоксвирусам оспенной вакцины третьего поколения на основе штамма MVA вируса вакцины, отвечающей повышенным требованиям иммуногенности и безопасности, особенно с учетом применения ее для лиц с отклонениями в состоянии здоровья. Проанализирован опыт применения противооспенных вакцин. Среди противооспенных вакцин третьего поколения особое место занимает вакцина на основе вируса вакцины, штамм MVA (modified vaccinia virus Ankara), выпускаемая компанией Bavarian Nordic под тремя названиями (в Европе — Imvanex, в США — Jynneos™, в Канаде — IMVAMUNE®), поскольку он безопасен и может использоваться для конструирования векторных вакцин. Результаты клинических исследований вакцины на основе штамма MVA на здоровых добровольцах и лицах с различными отклонениями в здоровье показали, что основные побочные реакции легкой степени тяжести (эритема, болезненность, зуд, припухлость) в основном регистрировали в месте введения вакцины. Из системных побочных реакций отмечены утомление, головная боль, миалгия, озноб; у незначительной части — инфекция верхних дыхательных путей, тошнота, гастроэнтерит, которые самопроизвольно проходили в течение первых суток. Вакцина не вызывает нарушений сердечной деятельности, включая миоперикардит, может быть применена для лиц с экземой, атопическим дерматитом и воспалительными кожными заболеваниями, ею можно вакцинировать ВИЧ-инфицированных, больных туберкулезом, лиц с нарушениями сердечной деятельности, а также детей младшего возраста, подростков и беременных женщин. Определена оптимальная иммунизирующая доза вакцины при внутрикожном введении, равная 1×108 ЦПД50. Выявлено, что при двукратном введении в данной дозе вакцина индуцирует выраженный гуморальный и клеточный иммунный ответ, сопоставимый по уровню с иммунитетом после однократного введения вакцины первого поколения, а также бустирует иммунитет, ранее сформировавшийся при иммунизации противооспенной вакциной первого поколения. Вакцина Jynneos™ в настоящее время одобрена CDC (США) для профилактики оспы обезьян у взрослых в возрасте 18 лет и старше

Свойства гетерологичного иммуноглобулина против лихорадки Эбола после длительного хранения

Ebola outbreak in eastern parts of the Democratic Republic of the Congo in 2018–2020 proved that the virus remains highly hazardous for humans, and the outbreak in West Africa in 2014–2016, which was the largest Ebola outbreak in history, showed that it could be imported to other continents, including Russia. In 1993 the Federal State Budgetary Institution “48th Central Scientific Research Institute” of the Russian Ministry of Defence developed a specific equine immunoglobulin for emergency prophylaxis of Ebola in risk groups. The evaluation and improvement of the product’s properties is an important area in the development of biological defence technologies.The aim of the study was to examine the properties of the equine anti-Ebola immunoglobulin which had been stored for a long time at 2–8 °C.Materials and methods: the authors studied batches of heterologous anti-Ebola immunoglobulin that had been stored for 17–22 years. The properties of the product were evaluated according to the requirements of the State Pharmacopoeia of the Russian Federation, 14th ed. (Ph. Rus. 14 ed.). The specific activity of the product was determined in a plaque reduction neutralisation test using Ebola virus and African green monkey kidney cells (GMK-AH-1(D)). Immunoglobulin molecular parameters were determined by size-exclusion high-performance liquid chromatography using the test methods described in the European Pharmacopoeia 9.6 and Ph. Rus. 14 ed.Results: the storage of anti-Ebola immunoglobulin for 17–22 years at 2–8 °C resulted in a four-fold reduction of the level of virus-neutralising antibodies against Ebola, decrease in the proportion of monomers from 98 to 74–90%, increase in the proportion of dimers and polymers, and formation of immunoglobulin molecules’ fragments. Signs of toxicity for mice were observed in one of the three product batches. Conclusions: the obtained results suggest the need to perform more studies to test the quality of antiEbola immunoglobulin batches that were stored for shorter periods of time in order to assess the stability of their initial characteristics.Вспышка геморрагической лихорадки Эбола в восточных районах Демократической Республики Конго в 2018–2020 гг. показала сохраняющуюся высокую опасность вируса для человечества, а вспышка в Западной Африке в 2014–2016 гг., самая крупная с момента обнаружения вируса – возможность его ввоза в другие страны, в том числе в Россию. В ФГБУ «48 ЦНИИ» Минобороны России в 1993 г. разработан специфический лошадиный иммуноглобулин для экстренной профилактики лихорадки Эбола в группах риска. Изучение и совершенствование его защитных свойств является актуальным направлением разработки средств биологической защиты. Цель работы: оценить свойства иммуноглобулина против лихорадки Эбола из сыворотки крови лошадей после длительного хранения при температуре от 2 до 8 °С. Материалы и методы: серии гетерологичного иммуноглобулина против лихорадки Эбола, хранившиеся от 17 до 22 лет. Свойства иммуноглобулина оценивали согласно требованиям Государственной фармакопеи Российской Федерации XIV издания (ГФ РФ XIV изд.). Специфическую активность препарата определяли в реакции нейтрализации с вирусом Эбола в культуре клеток почки африканской зеленой мартышки (GМК-АН-1(Д)) методом подавления образования негативных колоний (бляшкообразования). Определение молекулярных параметров иммуноглобулина проводили методом эксклюзионной высокоэффективной жидкостной хроматографии согласно методикам, представленным в Европейской фармакопее 9.6 и ГФ РФ XIV изд. Результаты: хранение препарата иммуноглобулина против лихорадки Эбола в течение 17–22 лет при температуре от 2 до 8 °С привело к снижению уровня вируснейтрализующих антител к вирусу Эбола в 4 раза, уменьшению доли мономеров c 98 до 74–90%, увеличению доли димеров и полимеров, а также появлению фрагментов молекул иммуноглобулина. В одной из трех серий препарата была выявлена токсичность для белых нелинейных мышей. Выводы: полученные результаты свидетельствуют о целесообразности проведения дальнейших исследований по определению показателей качества серий иммуноглобулина против лихорадки Эбола, хранившихся менее продолжительные сроки, с целью оценки стабильности их исходных характеристик

ТЕОРЕТИЧЕСКИЕ АСПЕКТЫ РАЗРАБОТКИ СТРАТЕГИИ УСТОЙЧИВОГО РАЗВИТИЯ СЕЛЬСКИХ ТЕРРИТОРИЙ НА РЕГИОНАЛЬНОМ УРОВНЕ

In the article the necessity of elaboration of the sustainable development strategy of rural territories at the regional level is grounding. The long-terms trends of Russian conception of the sustainable development of rural territories are summarizing. The algorithm of elaboration of the sustainable development strategy of rural territories of a region is presented.В статье обосновывается необходимость разработки стратегии устойчивого развития сельских территорий на региональном уровне. Обобщены перспективные направления формирования российской концепции устойчивого развития сельской местности. Представлен алгоритм разработки стратегии устойчивого развития сельских территорий региона

Se me perdieron las llaves, or Back to the Phenomenon of Guilt in Philosophy of Law Again

The article is dedicated to the consideration of the phenomenon of guilt in the sphere of legal philosophy. The reasoning of the similar issue is fulfilled both synchronically and diachronically. In the synchronic field of research authors consider the specificity of guilt in the sphere of private law (civil law, commercial law) as such as in the region of public law (criminal law, administrative law). In the context of the diachronic research of the phenomenon of guilt authors turn themselves to the origin of the legal thought — legislation and legal philosophy of Ancient Greece (first of all, pre-Socratic philosophy of law — Parmenides, Heraclitus etc.) and Ancient Rome. The result of the diachronic analyses is the following conclusion. The guilt in its legal-philosophical aspect presents itself originally as the transformed category of the causality. During the contemporary development of the legal thought the latter is substituted by the interpretation of the guilt as the psychological relation of the person, who has committed the legal deed towards its socially dangerous consequences. The similar conclusion is grounded partly on the comparative examination of the obligations, which derivate from contract and from the infliction of the harm (contractual obligation and delict obligation). In the similar case the guilt as the causal relation is existed between the deliberate or negligent action from oneside and the harm, which is derivated from the similar action — from the other. In this situation the category of delict (the break of the norms and rules) is interpreted as the secondary in historical relation and taking place later than phenomenon of causing the harm. In its turn, the synchronic analyze of the phenomenon of guilt leads authors to the hypotheses, that the form of guilt (criminal intent or criminal negligence) is a criterion, which gives us possibility to distinguish the fields of private law and public law. It`s worth to underline that sphere of gross negligence is the border line (so-called mixed zone) between the public and the private law. As the special case authors underline such institute of the civil law as the responsibility without guilt, when the fact of the committing deed (or even the possession of the certain estate) as such creates the ground of the legal responsibility of the person. Finally authors come to conclusion that the real foundation of the legal responsibility is guilt as the fact of involving in the occurrence, i. e. that concrete situation, “case” which is an ontological ground to turn to the law