Инструментарий минимизации риска защищенности в распределенных системах (РКС)

Разработана структура средств минимизации риска защищенности распределенных компьютерных систем, выполнена формализация функционирования основных блоков предложенной структуры. Предложена оценка уровня угроз безопасности, интегральная оценка ущерба вследствие атак на уязвимости, а также оценка степени риска реализации угроз безопасности в компьютерных системах. Также предложен подход к анализу риска на основе оценок степени опасности факторов угроз безопасности и вероятности реализации угроз безопасности с разделением их на соответствующие группы, а также на основе построения специальной матрицы рисков защищенности для минимизации риска защищенности.Розроблено структуру засобів мінімізації ризику захищеності розподілених комп’ютерних систем, виконано формалізацію функціонування основних блоків запропонованої структури. Запропоновано оцінку рівня загроз безпеки, інтегральну оцінку збитку внаслідок атак на вразливості, а також оцінку ступеня ризику реалізації загроз безпеки в комп’ютерних системах. Також запропоновано підхід до аналізу ризику на основі оцінок ступеня небезпеки факторів загроз безпеки та ймовірності реалізації загроз безпеки з розділенням їх на відповідні групи, а також на основі побудови спеціальної матриці ризиків захищеності для мінімізації ризику захищеності.The structure of means for security risk minimization in distributed computer systems is developed, and the functioning of the basic blocks of the suggested structure is formalized. Also, estimation of the security threat level, the integrated assessment of the damage due to attacks on to the vulnerabilities, and the risk assessment for the security threat realization are proposed. An approach to the risk analysis on the basis of estimation of the danger level of safety threat factors and the probability of safety threat realization with division of the factors into related groups is suggested, which is also based on the constructed special security risk matrix for security risk minimization

Этноконфликт как причина агрессии: проблема национальной безопасности Украины

Межэтнические и межнациональные противоречия являются сегодня одной из наиболее актуальных проблем многих стран мира, в том числе и Украины. Она относится к числу полиэтнических государств, где неизбежны межэтнические и межнациональные противоречия и конфликты. Анализу последних, их причин и возможных следствий и посвящена данная статья.Міжетнічні та міжнаціональні протиріччя сьогодні є однією з найбільш актуальних проблем багатьох країн світу, у тому числі і України. Вона належить до числа поліетнічних держав, де неминучі міжетнічні та міжнаціональні протиріччя та конфлікти, аналізу яких, їх причин і можливих наслідків присвячена дана стаття.Today interethnic and international contradictions are the most topical problems of many countries of the world including Ukraine. It belongs to those polyethnic states where interethnic and international contradictions and conflicts are unavoided. This article is devoted to analysis, causes and possible consequences of the last ones

A single-step preparation of carbohydrate functionalized monoliths for separation and trapping of polar compounds

A single-step copolymerization strategy was developed for the preparation of carbohydrate (glucose and maltose) functionalized monoliths using click reaction. Firstly, novel carbohydrate-functionalized methacrylate monomers were synthesized through Cu(I)-catalyzed 1,3-dipolar cycloaddition (alkyne-azide reaction) of terminal alkyne with azide of carbohydrate derivatives. The corresponding carbohydrate functionalized monolithic columns were then prepared through a single-step in-situ copolymerization. The physicochemical properties and performance of the fabricated monolithic columns were evaluated using scanning electron microscopy, Fourier-transform infrared spectroscopy, and nano-liquid chromatography. For the optimized monolithic column, satisfactory column permeability and good separation performance were demonstrated for polar compounds including nucleoside, phenolic compounds and benzoic acid derivatives. The monolithic column is also highly useful for selective and efficient enrichment of glycopeptides from human IgG tryptic digests. This study not only provided a novel hydrophilic column for separation and selective trapping of polar compounds, but also proposed a facile and efficient approach for preparing carbohydrate functionalized monoliths

Подарунок Сталіна радянському електорату. (До 70-річчя «великого терору»)

The article is dedicated to mass terror of Soviet period as the tool of state policy

Развитие инвестиционного кредитования в Украине

Free radical polymerization is often used to prepare protein and peptide-loaded hydrogels for the design of controlled release systems and molecular imprinting materials. Peroxodisulfates (ammonium peroxodisulfates (APS) or potassium peroxodisulfates (KPS)) with N,N,N,N-tetramethylethylenediamine (TEMED) are frequently used as initiator and catalyst. However, exposure to these free radical polymerization reagents may lead to modification of the protein and peptide. In this work, we show the modification of lysine residues by ammonium peroxodisulfate (APS)/TEMED of the immunostimulant thymopentin (TP5). Parallel studies on a decapeptide and a library of 15 dipeptides were performed to reveal the mechanism of modification. LC-MS of APS/TEMED-exposed TP5 revealed a major reaction product with an increased mass (+12 Da) with respect to TP5. LC-MS2 and LC-MS3 were performed to obtain structural information on the modified peptide and localize the actual modification site. Interpretation of the obtained data demonstrates the formation of a methylene bridge between the lysine and arginine residue in the presence of TEMED, while replacing TEMED with a sodium bisulfite catalyst did not show this modification. Studies with the other peptides showed that the TEMED radical can induce methyleneation on peptides when lysine is next to arginine, proline, cysteine, aspargine, glutamine, histidine, tyrosine, tryptophan, and aspartic acid residues. Stability of peptides and protein needs to be considered when using APS/TEMED in in situ polymerization systems. The use of an alternative catalyst such as sodium bisulfite may preserve the chemical integrity of peptides during in situ polymerization

Online screening of acetylcholinesterase inhibitors in natural products using monolith-based immobilized capillary enzyme reactors combined with liquid chromatography-mass spectrometry

In order to develop a direct and reliable method for discovering lead compounds from traditional Chinese medicines (TCMs), a comparative online ligand fishing platform was developed using immobilized capillary enzyme reactors (ICERs) in combination with liquid chromatography-mass spectrometry (LC–MS). Methacrylate-based monolithic capillaries (400 μm I.D. × 10 cm) containing epoxy reactive groups were used as support to immobilize the target enzyme acetylcholinesterase (AChE). The activity and kinetic parameters of the AChE-ICER were investigated using micro-LC-UV. Subsequently, ligand fishing and identification from mixtures was carried out using the complete AChE-ICER-LC–MS platform. For efficient distinction of true actives from false positives, highly automated comparative analyses were run alternatingly using AChE-ICERs and negative control-ICERs, both online installed in the system. After washing unbound compounds to the waste, bound ligands were eluted from the AChE-ICER to a trapping loop using a denaturing solution. The trapped ligands were further separated and identified using LC–MS. Non-specific binding to the monolith support or non-functional sites of the immobilized enzyme was investigated by exposing analytes to the negative control-ICER. The specificity of the proposed approach was verified by analyzing a known AChE inhibitor in the presence of an inactive compound. The platform was applied to screen for AChE inhibitors in extracts of Corydalis yanhusuo. Eight compounds (columbamine, jatrorrhizine, coptisine, palmatine, berberine, dehydrocorydaline, tetrahydropalmatine and corydaline) with AChE binding affinity were detected and identified, and their AChE inhibitory activities were further verified by an in vitro enzymatic inhibition assay. Experimental results show that the proposed comparative online ligand fishing platform is suitable for rapid screening and mass-selective detection of AChE inhibitors in complex mixtures

Linking the concentrations of itraconazole and 2-hydroxypropyl-β-cyclodextrin in human intestinal fluids after oral intake of Sporanox^®

In a previously performed small-scale clinical study, healthy volunteers were asked to ingest an oral solution of itraconazole (Sporanox®) containing 40% 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) (i) with or (ii) without a standardized volume of water (240 mL) after which gastrointestinal and blood samples were collected. Although omitting water during the administration of Sporanox® resulted in noticeably higher duodenal concentrations of itraconazole, systemic exposure was almost unaffected. It is assumed that this discrepancy can be explained by differences in the extent of entrapment of itraconazole in the duodenum caused by differential complexation depending on the concentration of cyclodextrins. To further substantiate this hypothesis, the quantification of HP-β-CD concentrations in the aspirated intestinal fluids was performed by LC-MS/MS. When comparing the intestinal concentrations of itraconazole and HP-β-CD for one single healthy volunteer (HV02) in both test conditions, an excellent correlation was observed (Spearman's rank coefficient of 0.96). Moreover, the data suggest that, similar to aqueous buffer media, also in human intestinal fluids a non-linear relationship exists between itraconazole solubility and HP-β-CD concentration (Ap-type profile; Spearman's rank coefficient of 0.78), indicating that higher order complexes are formed at higher concentrations of HP-β-CD. This difference in extent of entrapment in the inclusion complexes helps to understand the observed impact of water intake on precipitation and permeation behavior of itraconazole in man. Without water intake, higher HP-β-CD concentrations resulted in less precipitation and increased duodenal concentrations of itraconazole. On the other hand, the stronger interaction at higher HP-β-CD concentrations reduced the free fraction of the drug explaining that increased intraluminal concentrations of itraconazole were not translated into an enhanced uptake. In conclusion, quantifying the concentrations of the solubilizing agent HP-β-CD in human intestinal fluids appeared to be of crucial importance to interpret the intraluminal behavior of an orally administered cyclodextrin-based solution

Development of a surface plasmon resonance sensor for coupling to capillary electrophoresis allowing affinity assessment of protein mixture components

Surface plasmon resonance (SPR) currently is the major platform to study protein–protein interactions, but it lacks the selectivity to distinguish between binding components within one sample. Capillary electrophoresis (CE) can provide efficient separation of intact proteins under near-physiological conditions. We have hyphenated CE with SPR to achieve affinity assessment of mixture components. A microfluidic flow cell allowing straightforward coupling of CE and SPR was developed. Initial testing with non-interacting dyes showed good performance using a flow-cell channel volume of 100 nL until the detection point. Appropriate closing of the CE electric circuit was achieved using the SPR gold-sensor as grounding electrode. Division of the (bio)sensor into an electrode part (providing grounding) and a detection part (bearing the affinity surface) was crucial to avoid disturbance of the SPR signal by the CE voltage. This approach permitted CE separation and binding assessment for separation voltages up to 30 kV. Human serum albumin (HSA) or aprotinin were immobilized on carboxymethyldextran hydrogel-coated gold sensors and target proteins (anti-HSA, and trypsin and α-chymotrypsin, respectively) were analyzed. Efficient CE separation of the intact protein analytes was accomplished under native conditions by employing neutral and positively-charged capillary coatings. Selective binding of separated proteins to the target surface could be monitored by SPR down to 2 ng of injected protein. Regeneration of the biosensor surface was achieved by an on-line rising, allowing repeatable CE-SPR analyses of proteins with RSDs below 1% and 5% for migration time and signal intensity, respectively