Удосконалення моделей управління проектами створення систем управління інформаційною безпекою

Рудник, О. В. Удосконалення моделей управління проектами створення систем управління інформаційною безпекою = Improving project management models for creating information project management systems : магістерська робота ; спец. 122 “Комп’ютерні науки“ / О. В. Рудник ; наук. кер. В. Д. Гогунський. – Миколаїв : НУК, 2020. – 94 с.Рудник О. В. Удосконалення моделей управління проектами створення систем управління інформаційною безпекою. – На правах рукопису. Магістерська робота за спеціальністю 122 – Комп’ютерні науки, освітня програма – Управління проектами. Національний університет кораблебудування ім. адм. Макарова. Миколаїв, 2020. В данній магістерській роботі було проведено удосконалення моделей управління проектами створення систем управління інформаційною безпекою. В процесі виконання роботи був проведенний аналіз основних методів та функцій управління данним проектом, їх вплив та значення як для кожного окремого етапу проекту (ключового та другорядного), так і для всього проекту в цілому. В процесі аналізу на окремих єтапах виконання роботи були використані наступні методи та підходи: • Графоаналітичний метод дослідження потоків інформації. • Метод схем інформаційних зв’язків. • Метод аналізу ієрархій. • Метод аналізу дерева відмов. • Мотивація персоналу Данні підходи дозволили не лише виявити потенційні проблеми в управлінні проектом створення СУІБ, але й можливі шляхи та підходи стосовно їх усунення. Все це дозволило як підвищити єфективність управління процесів проекту, так і сприяло виявленню можливих шляхів зменшення витрат по проекту.Rudnik O. V. Improving project management models for creating information project management systems. – On the rights of the manuscript. Master's thesis in 122-Computer Science, educational program - Project Management. National University of Shipbuilding. adm. Makarova. Nikolaev, 2020. In this master's work was carried out improvements to create models of project management systems, information security management. In carrying out the work was carried out by analysis of the basic techniques and management functions in this project, their impact and value for each phase of the project (and a minor key), and for the whole project. During the analysis phase of individual performance were used the following methods and approaches: • Graphic-analytical method for studying the flow of information. • A description of the flow of information in the form of a graph. • The method of information communications circuits. • The method of analysis of hierarchies. • The method of fault tree analysis. • Motivation of staff These approaches have allowed not only to identify potential problems in project management to create an ISMS and possible ways and approaches to address them. All this is possible how to improve management processes efektivnist project and spiyalo identify possible ways to reduce project costs

Оценка подлинности и стабильности производственных и контрольных штаммов - возбудителей актуальных инфекций бактериальной этиологии

The paper presents the results of identification of a spectrum of biochemical activity and certification of 140 bacterial strains of I-II risk level deposited in the State collection of pathogenic microorganisms of Scientific centre for expert evaluation of medicinal products of the Ministry of health of the Russian Federation. Causative agents of meningitis, dysentery, salmonellosis and other acute gastrointestinal, pyoinflammatory infections, including nosocomial, and other epidemiologically significant infections which can be applied for manufacturing and an quality assessment medicinal and diagnostic preparations, including vaccines, toxoids, therapeutic and prophylactic bacteriophages, antimicrobic drugs, diagnostic serum, test system, nutrient media were evaluated. Correction of a taxonomic nomenclature of collection strains according to requirements of Bergey’s manual of systematic bacteriology (2nd ed) was provided. A possibility of selection of the analogs of cultures of the microorganisms deposited in national collections of other countries and applied by production and quality control of immunobiological medicines and also for quality assessment of laboratory researches is proved. Stability of pivotal phenotypic properties and lack of dissociation master-seed and test strains is confirmed at freeze-drying for over 40 years.Проведено определение спектра биохимической активности и паспортизация 140 коллекционных штаммов бактерий III-IV групп патогенности, депонированных в Государственной коллекции патогенных микроорганизмов ФГБУ «НЦЭСМП» Минздрава России, возбудителей менингита, дизентерии, сальмонеллеза и других острых кишечных инфекций, гнойно-воспалительных, в том числе нозокомиальных, и других эпидемиологически значимых инфекций, которые могут применяться для производства и оценки качества лекарственных и диагностических препаратов, в том числе вакцин, анатоксинов, лечебно-профилактических бактериофагов, антимикробных препаратов, сывороток диагностических, диагностикумов эритроцитарных, тест-систем, наборов реагентов для биохимической идентификации патогенных микроорганизмов, дифференциально-дагностических и селективных питательных сред. Выполнена коррекция таксономической номенлатуры коллекционных штаммов в соответствии со Вторым изданием систематики бактерий Берджи (Bergey’s manual of systematic bacteriology. 2nd ed). Получена возможность подбора аналогов культур микроорганизмов, депонированных в национальных коллекциях других стран и применяемых при производстве и контроле качества иммунобиологических лекарственных препаратов, а также для оценки качества лабораторных исследований. Подтверждена стабильность ключевых фенотипических свойств и отсутствие диссоциации производственных и тест-штаммов при хранении в лиофилизированном состоянии на протяжении свыше 40 лет

Genetic and expression studies of SMN2 gene in Russian patients with spinal muscular atrophy type II and III

<p>Abstract</p> <p>Background</p> <p>Spinal muscular atrophy (SMA type I, II and III) is an autosomal recessive neuromuscular disorder caused by mutations in the survival motor neuron gene (<it>SMN1</it>). <it>SMN2 </it>is a centromeric copy gene that has been characterized as a major modifier of SMA severity. SMA type I patients have one or two <it>SMN2 </it>copies while most SMA type II patients carry three <it>SMN2 </it>copies and SMA III patients have three or four <it>SMN2 </it>copies. The <it>SMN1 </it>gene produces a full-length transcript (FL-SMN) while <it>SMN2 </it>is only able to produce a small portion of the FL-SMN because of a splice mutation which results in the production of abnormal SMNΔ7 mRNA.</p> <p>Methods</p> <p>In this study we performed quantification of the <it>SMN2 </it>gene copy number in Russian patients affected by SMA type II and III (42 and 19 patients, respectively) by means of real-time PCR. Moreover, we present two families consisting of asymptomatic carriers of a homozygous absence of the <it>SMN1 </it>gene. We also developed a novel RT-qPCR-based assay to determine the FL-SMN/SMNΔ7 mRNA ratio as SMA biomarker.</p> <p>Results</p> <p>Comparison of the <it>SMN2 </it>copy number and clinical features revealed a significant correlation between mild clinical phenotype (SMA type III) and presence of four copies of the <it>SMN2 </it>gene. In both asymptomatic cases we found an increased number of <it>SMN2 </it>copies in the healthy carriers and a biallelic <it>SMN1 </it>absence. Furthermore, the novel assay revealed a difference between SMA patients and healthy controls.</p> <p>Conclusions</p> <p>We suggest that the <it>SMN2 </it>gene copy quantification in SMA patients could be used as a prognostic tool for discrimination between the SMA type II and SMA type III diagnoses, whereas the FL-SMN/SMNΔ7 mRNA ratio could be a useful biomarker for detecting changes during SMA pharmacotherapy.</p

Measures for verification of contractors by means of information and analytical systems based on existing methods

The article presents the main measures to determine the reliability of contractors based on existing methods of the Federal tax service and the use of information and analytical systems

Phosphatase and tensin homologue: a therapeutic target for SMA

Spinal muscular atrophy (SMA) is one of the most common juvenile neurodegenerative diseases, which can be associated with child mortality. SMA is caused by a mutation of ubiquitously expressed gene, Survival Motor Neuron1 (SMN1), leading to reduced SMN protein and the motor neuron death. The disease is incurable and the only therapeutic strategy to follow is to improve the expression of SMN protein levels in motor neurons. Significant numbers of motor neurons in SMA mice and SMA cultures are caspase positive with condensed nuclei, suggesting that these cells are prone to a process of cell death called apoptosis. Searching for other potential molecules or signaling pathways that are neuroprotective for central nervous system (CNS) insults is essential for widening the scope of developmental medicine. PTEN, a Phosphatase and Tensin homologue, is a tumor suppressor, which is widely expressed in CNS. PTEN depletion activates anti-apoptotic factors and it is evident that the pathway plays an important protective role in many neurodegenerative disorders. It functions as a negative regulator of PIP3/AKT pathway and thereby modulates its downstream cellular functions through lipid phosphatase activity. Moreover, previous reports from our group demonstrated that, PTEN depletion using viral vector delivery system in SMN delta7 mice reduces disease pathology, with significant rescue on survival rate and the body weight of the SMA mice. Thus knockdown/depletion/mutation of PTEN and manipulation of PTEN medicated Akt/PKB signaling pathway may represent an important therapeutic strategy to promote motor neuron survival in SMA

Bi-allelic <em>ACBD6</em> variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology. Using exome sequencing and extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 and characterized the role of ACBD6 on protein N-myristoylation with myristic acid alkyne (YnMyr) chemical proteomics in the model organisms and human cells, with the latter also being subjected further to ACBD6 peroxisomal localization studies. The affected individuals (23 males and 22 females), aged 1-50 years, typically present with a complex and progressive disease involving moderate-to-severe global developmental delay/intellectual disability (100%) with significant expressive language impairment (98%), movement disorders (97%), facial dysmorphism (95%) and mild cerebellar ataxia (85%) associated with gait impairment (94%), limb spasticity/hypertonia (76%), oculomotor (71%) and behavioural abnormalities (65%), overweight (59%), microcephaly (39%) and epilepsy (33%). The most conspicuous and common movement disorder was dystonia (94%), frequently leading to early-onset progressive postural deformities (97%), limb dystonia (55%) and cervical dystonia (31%). A jerky tremor in the upper limbs (63%), a mild head tremor (59%), parkinsonism/hypokinesia developing with advancing age (32%) and simple motor and vocal tics were among other frequent movement disorders. Midline brain malformations including corpus callosum abnormalities (70%), hypoplasia/agenesis of the anterior commissure (66%), short midbrain and small inferior cerebellar vermis (38% each) as well as hypertrophy of the clava (24%) were common neuroimaging findings. Acbd6-deficient zebrafish and Xenopus models effectively recapitulated many clinical phenotypes reported in patients including movement disorders, progressive neuromotor impairment, seizures, microcephaly, craniofacial dysmorphism and midbrain defects accompanied by developmental delay with increased mortality over time. Unlike ACBD5, ACBD6 did not show a peroxisomal localization and ACBD6-deficiency was not associated with altered peroxisomal parameters in patient fibroblasts. Significant differences in YnMyr-labelling were observed for 68 co- and 18 post-translationally N-myristoylated proteins in patient-derived fibroblasts. N-myristoylation was similarly affected in acbd6-deficient zebrafish and X. tropicalis models, including Fus, Marcks and Chchd-related proteins implicated in neurological diseases. The present study provides evidence that bi-allelic pathogenic variants in ACBD6 lead to a distinct neurodevelopmental syndrome accompanied by complex and progressive cognitive and movement disorders

Synaptic Defects in the Spinal and Neuromuscular Circuitry in a Mouse Model of Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNΔ7). In the neuromuscular circuitry, we found that nearly all neuromuscular junctions (NMJs) in hindlimb muscles of SMNΔ7 mice remained fully innervated at the disease end stage and were capable of eliciting muscle contraction, despite a modest reduction in quantal content. In the spinal circuitry, we observed a ∼28% loss of synapses onto spinal motoneurons in the lateral column of lumbar segments 3–5, and a significant reduction in proprioceptive sensory neurons, which may contribute to the 50% reduction in vesicular glutamate transporter 1(VGLUT1)-positive synapses onto SMNΔ7 motoneurons. In addition, there was an increase in the association of activated microglia with SMNΔ7 motoneurons. Together, our results present a novel concept that synaptic defects occur at multiple levels of the spinal and neuromuscular circuitry in SMNΔ7 mice, and that proprioceptive spinal synapses could be a potential target for SMA therapy