Соціальна культура громадян - найкращий антикризовий засіб

An anthracene-functionalized thermosensitive block copolymer was synthesized, which formed micelles by heating its aqueous solution above the lower critical solution temperature (LCST). The micelles were subsequently crosslinked by UV illumination at 365 nm with a normal handheld UV lamp. The micelles showed a small size (30 nm) and high loading capacity (16.0 ± 0.1%) for paclitaxel and released paclitaxel for more than ten days

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

Photopolymerized thermosensitive poly(HPMAlactate)-PEG-based hydrogels : effect of network design on mechanical properties, degradation, and release behavior

Photopolymerized thermosensitive A-B-A triblock copolymer hydrogels composed of poly(N-(2-hydroxypropyl)-methacrylamide lactate) A-blocks, partly derivatizal with methacrylate groups to different extents (10, 20, and 30%) and hydrophilic poly(ethylene glycol) B-blocks of different molecular weights (4, 10, and 20 kDa) were synthesized. The aim of the present study was to correlate the polymer architecture with the hydrogel properties, particularly rheological, swelling, degradation properties and release behavior. It was found that an increasing methacrylation extent and a decreasing PEG molecular weight resulted in increasing gel strength and cross-link density, which tailored the degradation profiles from 25 to more than 300 days. Polymers having small PEG blocks showed a remarkable phase separation into polymer- and water-rich domains, as demonstrated by confocal microscopy. Depending on the hydrophobic domain density, the loaded protein resides in the hydrophilic pores or is partitioned into hydrophilic and hydrophobic domains, and its release from these compartments is tailored by the extent of methacrylation and by PEG length, respectively. As the mechanical properties, degradation, and release profiles can be fully controlled by polymer design and concentration, these hydrogels are suitable for controlled protein release

Preparation of acid-responsive antibubbles from CaCO3-based Pickering emulsions.

HYPOTHESIS: Hydrophobized fumed silica particles were previously reported for producing antibubbles that are quite stable in neutral as well as in acidic media. To produce acid-responsive antibubbles (e.g., for gastric drug delivery), the silica nanoparticles must be replaced by suitable particles, e.g., calcium carbonate (CaCO 3), which can degrade at low pH to release the encapsulated drug. EXPERIMENTS: Two variants of CaCO 3-stabilized antibubbles were prepared (by using CaCO 3 particles pre-coated with stearic acid, or by using native CaCO 3 particles in combination with sodium stearoyl lactylate) and drug release was compared with classic antibubbles produced with hydrophobized fumed silica particles. FINDINGS: CaCO 3 particles (pre-coated with stearic acid) can be used to produce stable antibubbles, which provided an entrapment efficiency of a model drug (methylene blue, MB) of around 85%. A burst release of MB (∼60%) from the antibubbles was observed at pH 2 (i.e., the pH of the stomach), which was further increased to 80% during the next 30 min. On the contrary, at neutral pH, about 70% of the drug remained encapsulated for at least 2 h. We further demonstrated that the acidic conditions led to the desorption of CaCO 3 particles from the air-liquid interface resulting in the destabilization of the antibubbles and the release of drug-containing cores

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

Utility of Intravenous Curcumin Nanodelivery Systems for Improving In Vivo Pharmacokinetics and Anticancer Pharmacodynamics

Curcumin nanoformulations for intravenous injection have been developed to offset poor absorption, biotransformation, degradation, and excessive clearance associated with parenteral delivery. This review investigates (1) whether intravenous nanoformulations improve curcumin pharmacokinetics (PK) and (2) whether improved PK yields greater therapeutic efficacy. Standard PK parameters (measured maximum concentration [ C max], area under the curve [AUC], distribution volume [ V d], and clearance [CL]) of intravenously administered free curcumin in mice and rats were sourced from literature and compared to curcumin formulated in nanoparticles, micelles, and liposomes. The studies that also featured analysis of pharmacodynamics (PD) in murine cancer models were used to determine whether improved PK of nanoencapsulated curcumin resulted in improved PD. The distribution and clearance of free and nanoformulated curcumin were very fast, typically accounting for >80% curcumin elimination from plasma within 60 min. Case-matched analysis demonstrated that curcumin nanoencapsulation generally improved curcumin PK in terms of measured C max ( n = 27) and AUC ( n = 33), and to a lesser extent V d and CL. However, when the data were unpaired and clustered for comparative analysis, only 5 out of the 12 analyzed nanoformulations maintained a higher relative curcumin concentration in plasma over time compared to free curcumin. Quantitative analysis of the mean plasma concentration of free curcumin versus nanoformulated curcumin did not reveal an overall marked improvement in curcumin PK. No correlation was found between PK and PD, suggesting that augmentation of the systemic presence of curcumin does not necessarily lead to greater therapeutic efficacy

Oral pretreatment with β-lactoglobulin derived peptide and CpG co-encapsulated in PLGA nanoparticles prior to sensitizations attenuates cow's milk allergy development in mice

Cow's milk allergy is a common food allergy among infants. Improved hygiene conditions and loss of microbial diversity are associated with increased risk of allergy development. The intestinal immune system is essential for oral tolerance induction. In this respect, bacterial CpG DNA is known to drive Th1 and regulatory T-cell (Treg) development via Toll-Like-Receptor 9 (TLR-9) signaling, skewing away from the allergic Th2 phenotype. We aimed to induce allergen specific tolerance via oral delivery of poly (lactic-co-glycolic acid) nanoparticles (NP) co-encapsulated with a selected β-lactoglobulin derived peptide (BLG-Pep) and TLR-9 ligand CpG oligodeoxynucleotide (CpG). In vivo, 3-4-week-old female C3H/HeOuJ mice housed in individually ventilated cages received 6-consecutive-daily gavages of either PBS, whey, BLG-Pep/NP, CpG/NP, a mixture of BLG-Pep/NP plus CpG/NP or co-encapsulated BLG-Pep+CpG/NP, before 5-weekly oral sensitizations with whey plus cholera toxin (CT) or only CT (sham) and were challenged with whey 5 days after the last sensitization. The co-encapsulated BLG-Pep+CpG/NP pretreatment, but not BLG-Pep/NP, CpG/NP or the mixture of BLG-Pep/NP plus CpG/NP, prevented the whey-induced allergic skin reactivity and prevented rise in serum BLG-specific IgE compared to whey-sensitized mice. Importantly, co-encapsulated BLG-Pep+CpG/NP pretreatment reduced dendritic cell (DC) activation and lowered the frequencies of PD-L1+ DC in the mesenteric lymph nodes compared to whey-sensitized mice. By contrast, co-encapsulated BLG-Pep+CpG/NP pretreatment increased the frequency of splenic PD-L1+ DC compared to the BLG-Pep/NP plus CpG/NP recipients, in association with lower Th2 development and increased Treg/Th2 and Th1/Th2 ratios in the spleen. Oral administration of PLGA NP co-encapsulated with BLG-Pep and CpG prevented rise in serum BLG-specific IgE and symptom development while lowering splenic Th2 cell frequency in these mice which were kept under strict hygienic conditions

Inhibition of cow’s milk allergy development in mice by oral delivery of β-lactoglobulin-derived peptides loaded PLGA nanoparticles is associated with systemic whey-specific immune silencing

Background: Two to four percentage of infants are affected by cow's milk allergy (CMA), which persists in 20% of cases. Intervention approaches using early oral exposure to cow's milk protein or hydrolysed cow's milk formula are being studied for CMA prevention. Yet, concerns regarding safety and/or efficacy remain to be tackled in particular for high-risk non-exclusively breastfed infants. Therefore, safe and effective strategies to improve early life oral tolerance induction may be considered. Objective: We aim to investigate the efficacy of CMA prevention using oral pre-exposure of two selected 18-AA β-lactoglobulin-derived peptides loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) in a whey-protein induced CMA murine model. Methods: The peptides were loaded in PLGA NPs via a double emulsion solvent evaporation technique. In vivo, 3-week-old female C3H/HeOuJ mice received 6 daily gavages with PBS, whey, Peptide-mix, a high- or low-dose Peptide-NPs or empty-NP plus Peptide-mix, prior to 5 weekly oral sensitizations with cholera toxin plus whey or PBS (sham). One week after the last sensitization, the challenge induced acute allergic skin response, anaphylactic shock score, allergen-specific serum immunoglobulins and ex vivo whey-stimulated cytokine release by splenocytes was measured. Results: Mice pre-treated with high-dose Peptide-NPs but not low-dose or empty-NP plus Peptide-mix, were protected from anaphylaxis and showed a significantly lower acute allergic skin response upon intradermal whey challenge compared to whey-sensitized mice. Compared with the Peptide-mix or empty-NP plus Peptide-mix pre-treatment, the high-dose Peptide-NPs-pre-treatment inhibited ex vivo whey-stimulated pro-inflammatory cytokine TNF-α release by splenocytes. Conclusion & Clinical relevance: Oral pre-exposure of mice to two β-lactoglobulin-derived peptides loaded PLGA NPs induced a dose-related partial prevention of CMA symptoms upon challenge to whole whey protein and silenced whey-specific systemic immune response. These findings encourage further development of the concept of peptide-loaded PLGA NPs for CMA prevention towards clinical application