Nod1 signaling overcomes resistance of S. pneumoniae to opsonophagocytic killing

Airway infection by the Gram-positive pathogen Streptococcus pneumoniae (Sp) leads to recruitment of neutrophils but limited bacterial killing by these cells. Co-colonization by Sp and a Gram-negative species, Haemophilus influenzae (Hi), provides sufficient stimulus to induce neutrophil and complement-mediated clearance of Sp from the mucosal surface in a murine model. Products from Hi, but not Sp, also promote killing of Sp by ex vivo neutrophil-enriched peritoneal exudate cells. Here we identify the stimulus from Hi as its peptidoglycan. Enhancement of opsonophagocytic killing was facilitated by signaling through nucleotide-binding oligomerization domain-1 (Nod1), which is involved in recognition of γ-D-glutamyl-meso-diaminopimelic acid (meso-DAP) contained in cell walls of Hi but not Sp. Neutrophils from mice treated with Hi or compounds containing meso-DAP, including synthetic peptidoglycan fragments, showed increased Sp killing in a Nod1-dependent manner. Moreover, Nod1-/- mice showed reduced Hi-induced clearance of Sp during co-colonization. These observations offer insight into mechanisms of microbial competition and demonstrate the importance of Nod1 in neutrophil-mediated clearance of bacteria in vivo

Новые ядерные технологии: проблемы и перспективы международно-правового регулирования

The article is devoted to practical and legal aspects of small modular reactors (SMRs). Their technology combines safety and a variety of flexibilities, such as reasonable costs, longer terms of operation without refueling and mobility. SMRs can be used locally in remote areas with severe climatic conditions, such as Arctic region. SMRs have great export potential. The question arises how SMRs fit into rules of International Law? The research was based on the legal analysis on SMRs’ application in the system of national and international legal regulations – nuclear, maritime, environmental and tort law. The analysis showed that there are several gaps and grey areas in SMRs’ export scenarios implementation, which are described belowСтатья посвящена практическим и правовым аспектам использования малых модульных АЭС. Технология малых модульных атомных реакторов (ММР) совмещает в себе необходимый уровень безопасности и ряд преимуществ, таких как доступная стоимость, длительный срок эксплуатации без перезагрузки ядерного топлива, мобильность и доступность к отдаленным территориям. Малые АЭС могут использоваться в труднодоступных районах с суровыми климатическими условиями, например в Арктике. ММР обладают серьезным экспортным потенциалом. Основным вопросом остается – насколько действующие международно-правовые нормы применимы к регулированию трансграничной эксплуатации малых модульных атомных электростанций. Исследование основано на правовом анализе национальных и международных правовых документов в областях ядерного, морского, природоохранного и деликтного права на предмет их применимости к регулированию процесса эксплуатации малых модульных АЭС. Результаты проведенного правового анализа продемонстрировали, что существуют определенные пробелы и серые зоны в сферах эксплуатации ММР, описанные ниж

Analysis of the process of internal audit in Ministry of defense of Ukraine

The article is of interest to specialists of internal audit, internal and financial control, and heads (commanders) of structural subdivisions of the Ministry of Defense of Ukraine and the Armed Forces of Ukraine, military units, institutions and organizations in the systems, which directly organize internal control. The article substantiates the lack of preliminary coverage in the scientific works of the retrospective development of the system of internal audit and financial control. The scientific task of structuring existing information with the use of guidance documents and practical experience for the hierarchical construction of the transformation of approaches and views on the activities of structural units that monitored the effective management of state property and resources in the system of the Ministry of Defense and the Armed Forces of Ukraine was formulated. The article focuses on the delineation of internal control and internal audit. The necessity of implementation of internal control and its effectiveness is substantiated. The study analyzed the guidance documents that regulated the activities and the establishment of internal audit and internal control at the stages of its formation. The meeting covered the issues of transformation of financial control bodies in the Ministry of Defense of Ukraine and the Armed Forces of Ukraine, their main directions of activity and tasks were determined. Three stages of reforming financial and control bodies in the Ministry of Defense of Ukraine were identified, in which there were changes in approaches to the construction of the internal control and internal audit system. The article presents a retrospective analysis of the evolution of views on the purpose and objectives stated in the relevant provisions of the financial control bodies of the Ministry of Defense of Ukraine during the period of Ukraine's independence from the standpoint of implementing the declared goals of Ukraine's integration into the international professional community. The introduction of internal audit as an independent activity is aimed at improvement of the control system, prevention of the facts of illegal, inefficient and inefficient use of budget funds, errors occurrence or other deficiencies in military units and budget institutions, improvement of internal control, and the adoption of sound management decisions in modern conditions

Methodical recommendations for conducting an audit of the financial institution of the manager of the lower level

The methodological recommendations highlighted in the article will be useful for auditors who carry out audits of financial and economic activity in the system of the Ministry of Defense of Ukraine and other components of the security and defense sector. It is determined that the subject matter of the article is not sufficiently investigated, both from a practical and a theoretical point of view. The article presents a retrospective analysis of the activities of the second-level funds managers in the overall construction of funds managers in the system of the Ministry of Defense of Ukraine and the Armed Forces of Ukraine. The main directions of activity of second level managers are determined. The article analyzes the legislative and regulatory acts regulating the second level manager at both the state and departmental levels. The analysis carried out in the article made it possible to highlight a number of key functions of the financial authority of the second-level funds manager. The article outlines nine areas for conducting an audit, the need for a second-tier administrator in a financial institution and identifies specific areas of verification. Also, the article deals with issues that are to be investigated when assessing the activity of a financial institution of the manager of lower-level funds, which, in its functions, is the organ of provision for subordinate military units, institutions (hereinafter - the manager of lower-level funds), depending on its functions and tasks they are executed. Taking into account the practical experience, the methodical recommendations for conducting a check on the activity of the financial institution of the manager of the lower level funds are presented, and the questions, which according to the authors, are subject to compulsory study, are presented. The substantiated conclusions concerning the necessity of determining a number of other (additional) areas of verification are formulated depending on the peculiarities of functioning of the other financial institution of the second level administrator and the mandatory inclusion in the audits of the overall indicator of the state of financial and economic activity of military units, institutions and organizations, which are in financial security

GRB 221009A, The BOAT

GRB 221009A has been referred to as the Brightest Of All Time (the BOAT). We investigate the veracity of this statement by comparing it with a half century of prompt gamma-ray burst observations. This burst is the brightest ever detected by the measures of peak flux and fluence. Unexpectedly, GRB 221009A has the highest isotropic-equivalent total energy ever identified, while the peak luminosity is at the $\sim99$th percentile of the known distribution. We explore how such a burst can be powered and discuss potential implications for ultra-long and high-redshift gamma-ray bursts. By geometric extrapolation of the total fluence and peak flux distributions GRB 221009A appears to be a once in 10,000 year event. Thus, while it almost certainly not the BOAT over all of cosmic history, it may be the brightest gamma-ray burst since human civilization began.Comment: Resubmitted to ApJ

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

ON THE LEGITIMACY OF THE USE OF MILITARY FORCE BY FOREIGN STATES (THE SYRIAN CASE)

INTRODUCTION. Military interventions in Syria by the US and its allies confirm a tendency in the policy of Western countries to ignore international law and to act in accordance with the “rule of force”, without the sanction of the UN Security Council. Russia, as a state that respects its sovereignty and international law, does not accept this approach. Russia stands for diplomatic dialogue at all venues in order to stop destabilization in international relations, including the confrontation in Syria, and to find proper legal solutions. The article recommends specific options for such solutions.MATERIALS AND METHODS. The study relies on such legal sources as the UN Charter, generally recognized principles of international law, UN Security Council resolutions, the Joint Statement of the Presidents of Russia and the United States on Syria of November 11, 2017, the joint press conference of the Presidents of Russia and the United States in Helsinki on July 17, 2018 as well as scientific studies of Russian and foreign researches. The research involved general scientific and comparative legal and historical methods of study.RESEARCH RESULTS. The author concludes that the United States and its allies using military force in Syria act in violation of the UN Charter. Russia, on the contrary, uses its military contingent in Syria in full accordance with the provisions of the UN Charter on the collective self-defense, at the request of the legitimate government of Syria.DISCUSSION AND CONCLUSIONS. The author makes a concrete proposal for the search of a peaceful settlement in Syria on the basis of the Joint Statement, which was approved by the Presidents of Russia and the United States in November 11, 2017 following their meeting on the margins of the Asia-Pacific Economic Cooperation summit meeting in Danang, Vietnam. The author advocates that Russian and American experts jointly reconsider main elements of this document and provide an up-dated version with due account of new realities, and submit it to the UN Security Council for the adoption of a consensus resolution that would lay down the international legal framework for a peaceful settlement in Syria

Nuclear Safety and Security in the Arctic: Crafting an Effective Regional Governance System

The Arctic is saturated with nuclear facilities bringing both benefits for regional economic and social development and risks of nuclear and radiological accidents and concerns about radioactive wastes. There is every reason to expect the Arctic will remain a nuclearized region during the foreseeable future. This makes it important to direct attention to issues of nuclear safety and security in the region. We identify several clusters of these issues in the Arctic, including the challenges of potential nuclear accidents, the handling of spent nuclear fuel and radioactive waste, the cleanup of radiological contaminants, and concerns about nuclear security. An analysis of international conventions and voluntary codes of conduct shows that they are applicable to Arctic nuclear safety and security, but only in general terms. This suggests a need for an Arctic-specific agreement on nuclear and radiological safety, emergency preparedness and response, and cleanup of radiological contaminants. The outbreak of military hostilities in Ukraine in February 2022 has disrupted normal procedures for addressing issues of common concern in the Arctic. But the need for co-operation regarding matters like nuclear safety and security will not go away. Assuming it is possible to devise “necessary modalities” for restarting the work of the Arctic Council following the acute phase of the Ukraine crisis, an Arctic-specific agreement on nuclear safety and security could be developed under the auspices of the Arctic Council, which already has taken an interest in nuclear safety through the activities of its Working Group on Emergency Prevention, Preparedness and Response. Once such an agreement is in place, it will become important to consider the infrastructure needed to ensure that its provisions are implemented effectively

VOLUNTEERING IN THE CASE OF INCLUSIVE AND INFORMAL EDUCATION IN RUSSIA

Volunteering in the case of inclusive and informal education is widespread in Russia and is represented by numerous organizationsfoundations. The article presents the results of a study of some of these foundations. The article considers the peculiarity of the influence of such factors as gender and education of participants on their volunteer work

Path Planning in Threat Environment for UUV with Non-Uniform Radiation Pattern

The problem of optimal trajectory planning of the unmanned underwater vehicle (UUV) is considered and analytically solved. The task is to minimize the risk of detection of the moving object by a static sonar while moving between two given points on a plane. The detection is based on the primary acoustic field radiated by the object with a non-uniform radiation pattern. In the first part of the article, the probability of non-detection is derived. Further, it is used as an optimization criterion. The non-uniform radiation pattern of the object differentiates this work from previous research in the area. The optimal trajectory and velocity law of the moving object are found, as well as the criterion value on it