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

Matrixyl Patch vs Matrixyl Cream: A Comparative In Vivo Investigation of Matrixyl (MTI) Effect on Wound Healing

[Image: see text] Wound healing is one of the most complex biological processes. Studies show that Matrixyl (MTI), known as a cosmetic peptide, can lead to a faster healing process. The contribution of MTI to collagen formation during wound healing also depends on its mode of delivery and its release over time. Here, we investigate two modes of MTI-delivery system, the influence of MTI patch for wound healing application in comparison with MTI cream. In this study, animals were randomly divided into seven groups and studied for 21 days: patches containing two different concentrations of MTI (P-MTI-0.1 mg and P-MTI-1 mg), a cream containing MTI (C-MTI-1 mg), a patch (P-MTI-0), a cream with no MTI (C-MTI-0), a positive control (Comfeel), and a negative control (sham) group. To study the wound healing process, the change in collagen density, angiogenesis, epitheliogenesis, histopathology, immunohistochemical analysis, and wound area through imaging was monitored and measured. The macroscopic results showed that wound healing was improved from 63.5 up to 81.81% in treatment groups compared to that in the negative control group (P < 0.05 and P < 0.001). In addition, C-MTI-1 and P-MTI-1 had a larger impact on wound healing compared to that in the positive control group (Comfeel, P < 0.05). In hematoxylin and eosin (H&E) staining analysis, the rejuvenation of skin appendage was visible in both groups of cream and patches with MTI. According to the obtained results, the re-epithelialization had a higher range for the patch with MTI in comparison with cream containing MTI and positive control

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

Inhibition of Octreotide Acylation Inside PLGA Microspheres by Derivatization of the Amines of the Peptide with a Self-Immolative Protecting Group

Acylation of biopharmaceuticals such as peptides has been identified as a major obstacle for the successful development of PLGA controlled release formulations. The purpose of this study was to develop a method to inhibit peptide acylation in poly(d,l-lactide-co-glycolide) (PLGA) formulations by reversibly and temporarily blocking the amine groups of a model peptide (octreotide) with a self-immolative protecting group (SIP), O-4-nitrophenyl-O'-4-acetoxybenzyl carbonate. The octreotide with two self-immolative protecting groups (OctdiSIP) on the N-terminus and lysine side chain was synthesized by reaction of the peptide with O-4-nitrophenyl-O'-4-acetoxybenzyl carbonate, purified by preparative RP-HPLC and characterized by mass spectrometry. Degradation studies of OctdiSIP in aqueous solutions of different pH values showed that protected octreotide was stable at low pH (pH 5) whereas the protecting group was eliminated at physiological pH, especially in the presence of an esterase, to generate native octreotide. OctdiSIP encapsulated in PLGA microspheres, prepared using a double emulsion solvent evaporation method, showed substantial inhibition of acylation as compared to the unprotected octreotide: 52.5% of unprotected octreotide was acylated after 50 days incubation of microspheres in PBS pH 7.4 at 37 °C, whereas OctdiSIP showed only 5.0% acylation in the same time frame. In conclusion, the incorporation of self-immolative protection groups provides a viable approach for inhibition of acylation of peptides in PLGA delivery systems

Methyleneation of peptides by N, N, N, N -tetramethylethylenediamine (TEMED) under conditions used for free radical polymerization : A mechanistic study

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

Inhibition of Octreotide Acylation Inside PLGA Microspheres by Derivatization of the Amines of the Peptide with a Self-Immolative Protecting Group

Acylation of biopharmaceuticals such as peptides has been identified as a major obstacle for the successful development of PLGA controlled release formulations. The purpose of this study was to develop a method to inhibit peptide acylation in poly(d,l-lactide-co-glycolide) (PLGA) formulations by reversibly and temporarily blocking the amine groups of a model peptide (octreotide) with a self-immolative protecting group (SIP), O-4-nitrophenyl-O'-4-acetoxybenzyl carbonate. The octreotide with two self-immolative protecting groups (OctdiSIP) on the N-terminus and lysine side chain was synthesized by reaction of the peptide with O-4-nitrophenyl-O'-4-acetoxybenzyl carbonate, purified by preparative RP-HPLC and characterized by mass spectrometry. Degradation studies of OctdiSIP in aqueous solutions of different pH values showed that protected octreotide was stable at low pH (pH 5) whereas the protecting group was eliminated at physiological pH, especially in the presence of an esterase, to generate native octreotide. OctdiSIP encapsulated in PLGA microspheres, prepared using a double emulsion solvent evaporation method, showed substantial inhibition of acylation as compared to the unprotected octreotide: 52.5% of unprotected octreotide was acylated after 50 days incubation of microspheres in PBS pH 7.4 at 37 °C, whereas OctdiSIP showed only 5.0% acylation in the same time frame. In conclusion, the incorporation of self-immolative protection groups provides a viable approach for inhibition of acylation of peptides in PLGA delivery systems

Methyleneation of Peptides by <i>N</i>,<i>N</i>,<i>N</i>,<i>N</i>‑Tetramethylethylenediamine (TEMED) under Conditions Used for Free Radical Polymerization: A Mechanistic Study

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 <i>N</i>,<i>N</i>,<i>N</i>,<i>N</i>-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 <i>in situ</i> polymerization systems. The use of an alternative catalyst such as sodium bisulfite may preserve the chemical integrity of peptides during in situ polymerization