Классификация моделей комплексной оценки финансового состояния предприятия

There is an urgent need to develop reliable strategies for the rapid assembly of complex oligosaccharides. This paper presents a set of strategically selected orthogonal protecting groups, glycosyl donors modified by a (S)-phenylthiomethylbenzyl ether at C-2, and a glycosyl acceptor containing a fluorous tag, which makes it possible to rapidly prepare complex branched oligosaccharides of biological importance. The C-2 auxiliary controlled the 1,2-cis anomeric selectivity of the various galactosylations. The orthogonal protecting groups, 2-naphthylmethyl ether (Nap) and levulinic ester (Lev), made it possible to generate glycosyl acceptors and allowed the installation of a crowded branching point. After the glycosylations, the chiral auxiliary could be removed using acidic conditions, which was compatible with the presence of the orthogonal protecting groups Lev and Nap, thereby allowing the efficient installation of 1,2-linked glycosides. The light fluorous tag made it possible to purify the compounds by a simple filtration method using silica gel modified by fluorocarbons. The set of building blocks was successfully employed for the preparation of the carbohydrate moiety of the GPI anchor of Trypanosoma brucei, which is a parasite that causes sleeping sickness in humans and similar diseases in domestic animals

Chemoenzymatic Synthesis of Heparan Sulfate Oligosaccharides having a Domain Structure

Heparan sulfate (HS) has a domain structure in which regions that are modified by epimerization and sulfonation (NS domains) are interspersed by unmodified fragments (NA domains). There is data to support that domain organization of HS can regulate binding of proteins, however, such model has been difficult to probe. Here, we report a chemoenzymatic methodology that can provide HS oligosaccharides composed of two or more NS domains separated by NA domains of different length. It is based on the chemical synthesis of a HS oligosaccharide that enzymatically was extended by various GlcA-GlcNAc units and terminated in GlcNAc having an azido moiety at C-6 position. HS oligosaccharides having an azide and alkyne moiety could be assembled by copper catalyzed alkyne-azide cycloaddition to give compounds having various NS domains separated by unsulfonated regions. Competition binding studies showed that the length of an NA domain modulates the binding of the chemokines CCL5 and CXCL8

Guillain-Barre syndrome:expanding the concept of molecular mimicry

Guillain-Barre syndrome (GBS) is a rapidly progressive, monophasic, and potentially devastating immune-mediated neuropathy in humans. Preceding infections trigger the production of cross-reactive antibodies against gangliosides concentrated in human peripheral nerves. GBS is elicited by at least five distinct common bacterial and viral pathogens, speaking to the notion of polymicrobial disease causation. This opinion emphasizes that GBS is the best-supported example of true molecular mimicry at the B cell level. Moreover, we argue that mechanistically, single and multiplexed microbial carbohydrate epitopes induce IgM, IgA, and IgG subclasses in ways that challenge the classic concept of GBS. Finally, we discuss how GBS can be exemplary for driving innovation in diagnostics and immunotherapy for other antibody-driven neurological diseases

Метод измерения ударной вязкости как критерий оценки качества углеграфитовых материалов

Рассмотрены результаты внедрения метода измерения ударной вязкости в условиях ОАО «Укрграфит». НТУУ «КПИ» и ОАО «Укрграфит» cовместно выполнили работу по адаптации стандартного метода измерения ударной вязкости к испытанию графитированных материалов. Подобран размер образца, выполнен проект и изготовлен маятник для копра МК-5. Проведено измерение ударной вязкости материалов графитированных электродов различных марок. Установлена зависимость ударной вязкости от критерия термостойкости материала ЭГСП. Выявлена прямая пропорциональность между этими параметрами. В результате ряда технологических приемов удалось добиться повышения ударной вязкости материалов (%): ЭГСП – на 7; ниппеля – 20.Розглянуто результати впровадження методу вимірювання ударної в’язкості в умовах ВАТ «Укрграфіт». НТУУ «КПІ» і ВАТ «Укрграфіт» спільно виконали роботу з адаптації стандартного методу виміру ударної в’язкості до випробування графітованих матеріалів. Підібрано розмір зразка, виконано проект і виготовлено маятник для копра МК-5. Проведено вимірювання ударної в’язкості матеріалів графітованих електродів різних марок. Встановлено залежність ударної в’язкості від критерію термостійкості матеріалу ЕГСП. Виявлено пряму пропорційність між цими параметрами. В результаті ряду технологічних прийомів вдалося досягти підвищення ударної в’язкості матеріалів (%): ЕГСП – на 7; ніпеля – 20.The results of introduction of impact strength measurement method at JSC «Ukrgrafit» are described. Ukrainian UST «KPI» and JSC «Ukrgrafit» in common performed work on adaptation of standard impact strength measurement method to graphite material tests. The size of a sample was selected, the design was performed and a pendulum for impact testing machine MK-5 was manufactured. Impact strength measurement for various grade graphite electrode materials was performed. Impact strength depends on the conditions of manufacturing and raw material used. Dependence of impact strength on the heat resistance criterion of EGSP material was established. Direct proportionality between those parameters was revealed. As a result of a number of techniques better impact strength was achieved (%): for EGSP material – by 7; for nipple material – 20

Ценовая стратегия устойчивого развития предприятий зернопродуктового подкомплекса

Цель. Обосновать ценовую стратегию овладения устойчивым положением предприятий зернопродуктовогоподкомплекса на рынке зерна, муки, круп и хлебобулочных изделий

Salt-free fractionation of complex isomeric mixtures of glycosaminoglycan oligosaccharides compatible with ESI-MS and microarray analysis

© 2018 Sociedade Brasileira de Farmacognosia The present work investigates the leaf and stem anatomy, chemical composition and insecticidal activities (against Cimex lectularius Linnaeus, 1758) of the volatile oils of Schinus molle L., Anacardiaceae, a Brazilian native traditional medicinal plant. Noteworthy micro-morphological features that can help in the identification and quality control of the species include the presence of isobilateral and amphistomatic leaves, anomocytic and cyclocytic stomata, capitate glandular and conical non-glandular trichomes, large secretory ducts in the midrib, presence of druses and prismatic crystals, and the petiole vascular system comprising of five vascular bundles arranged in U-shape and an additional dorsal bundle. The major components of the volatile oil include β-pinene (14.7%), α-pinene (14.1%), limonene (9.4%) and muurolol (11.8%). Insecticidal activities of the volatile oil against bed bugs were investigated for the first time; strong toxicity by fumigation with the volatile oil of S. molle was observed and reported herein

Selective C-13-Labels on Repeating Glycan Oligomers to Reveal Protein Binding Epitopes through NMR: Polylactosamine Binding to Galectins

A combined chemo-enzymatic synthesis/NMR-based methodology is presented to identify, in unambiguous manner, the distinctive binding epitope within repeating sugar oligomers when binding to protein receptors. The concept is based on the incorporation of C-13-labels at specific monosaccharide units, selected within a repeating glycan oligomeric structure. No new chemical tags are added, and thus the chemical entity remains the same, while the presence of the C-13-labeled monosaccharide breaks the NMR chemical shift degeneracy that occurs in the non-labeled compound and allows the unique identification of the different components of the oligomer. The approach is demonstrated by a proof-of-concept study dealing with the interaction of a polylactosamine hexasaccharide with five different galectins that display distinct preferences for these entities.This research was funded by European Research Council for financial support (ERC-2017-AdG, project number 788143-RECGLYCANMR). We also thank Agencia Estatal de Investigacion (Spain) for project RTI2018-094751-B-C21 and the Severo Ochoa Excellence Accreditation (SEV-2016-0644

Selective C-13-Labels on Repeating Glycan Oligomers to Reveal Protein Binding Epitopes through NMR: Polylactosamine Binding to Galectins

A combined chemo-enzymatic synthesis/NMR-based methodology is presented to identify, in unambiguous manner, the distinctive binding epitope within repeating sugar oligomers when binding to protein receptors. The concept is based on the incorporation of C-13-labels at specific monosaccharide units, selected within a repeating glycan oligomeric structure. No new chemical tags are added, and thus the chemical entity remains the same, while the presence of the C-13-labeled monosaccharide breaks the NMR chemical shift degeneracy that occurs in the non-labeled compound and allows the unique identification of the different components of the oligomer. The approach is demonstrated by a proof-of-concept study dealing with the interaction of a polylactosamine hexasaccharide with five different galectins that display distinct preferences for these entities.This research was funded by European Research Council for financial support (ERC-2017-AdG, project number 788143-RECGLYCANMR). We also thank Agencia Estatal de Investigacion (Spain) for project RTI2018-094751-B-C21 and the Severo Ochoa Excellence Accreditation (SEV-2016-0644

Site-Specific Multi-Functionalization of the Carrier Protein CRM197 by Disulfide Rebridging for Conjugate Vaccine Development

Conjugation of an antigen to a carrier protein is widely used for vaccine development. To develop the next generation of conjugate vaccines, we describe here a method for the controlled multi-functionalization of the widely employed carrier protein CRM197 with a carbohydrate-based antigen and an immune potentiator. The approach is based on the selective reduction of one of the disulfides of CRM197 followed by disulfide rebridging employing an appropriately functionalized dibromopyridazinedione. Efficient protein modification required that the reduction and functionalization with a dibromopyridazinedione was performed as a one-step procedure with control over the reaction temperature. Furthermore, ligations were most successful when dibromopyridazinediones were employed having a functional entity such as a TLR7/8 agonist and a cyclooctyne for further modification. Site-specific conjugation avoids modification of T-epitopes of the carrier protein and covalent attachment of an immune potentiator will ensure that cytokines are produced where the vaccine interacts with relevant immune cells resulting in efficient immune potentiation

Mono and Di-Fucosylated Glycans of the Parasitic Worm S. Mansoniare Recognized Differently by the Innate Immune Receptor DC-SIGN

The parasitic worm,Schistosoma mansoni, expresses unusual fucosylated glycans in a stage-dependent manner that can be recognized by the human innate immune receptor DC-SIGN, thereby shaping host immune responses. We have developed a synthetic approach for mono- and bis-fucosylated LacdiNAc (LDN-F and LDN-DF, respectively), which are epitopes expressed on glycolipids and glycoproteins ofS. mansoni. It is based on the use of monosaccharide building blocks having carefully selected amino-protecting groups, facilitating high yielding and stereoselective glycosylations. The molecular interaction between the synthetic glycans and DC-SIGN was studied by NMR and molecular modeling, which demonstrated that the alpha 1,3-fucoside of LDN-F can coordinate with the Ca2+-ion of the canonical binding site of DC-SIGN allowing for additional interactions with the underlying LDN backbone. The 1,2-fucoside of LDN-DF can be complexed in a similar manner, however, in this binding mode GlcNAc and GalNAc of the LDN backbone are placed away from the protein surface resulting in a substantially lower binding affinity. Glycan microarray binding studies showed that the avidity and selectivity of binding is greatly enhanced when the glycans are presented multivalently, and in this format Le(x)and LDN-F gave strong responsiveness, whereas no binding was detected for LDN-DF. The data indicates thatS. mansonihas developed a strategy to avoid detection by DC-SIGN in a stage-dependent manner by the addition of a fucoside to a number of its ligands.This research was supported by the Netherlands Organization for Scientific Research (NWO; TOP-PUNT grant 718.015.003 to G.-J.B.), the Human Frontier Science Program Organization (HFSP; grant LT000747/2018-C to L.U.), the European Research Council (ERC-2017-AdG, project number 788143-RECGLYC-ANMR to J.J.-B.), the Agencia Estatal Investigacion of Spain (AEI; grant RTI2018-094751-B-C21 to J.J.-B.) and the Severo Ochoa Excellence Accreditation (SEV-2016-0644 to J.J.-B.)