Этимологический анализ специальных единиц лексико-семантического поля "интеллектуальные энергетические системы" в системе современного английского языка

В данной статье описываются результаты этимологического анализа лексико-семантического поля "Интеллектуальные энергетические системы" современного английского языка. Этимологический анализ проводится в аспекте "семантической эволюции слова", а также принадлежности слова к собственному или заимствованному языковому материалу

Исследование точности отверстий и их усадки в обрабатываемых дорнованием втулках

В работе рассмотрены область применения ,виды дорнов, схема процесса дорнования отверстия, схема параметры дорнования отверстия, плюсы и минусы дорнования, и оборудование для дорнования. Потом использование конечно-элементного программного обеспечения ANSYS для моделирования процесса обработки. Затем проведено исследование зависимости усадки отверстия от натяга, степени толстостенности, механических свойств материала, а также исследована кривизна обработанных отверстий. В заключении изложены выводы о проделанной работе и представлено уравнение описывающее исследованные зависимости.In the work, the scope of application, types of mandrels, a diagram of the mandrel process of a hole, a diagram of the parameters of a mandrel of a hole, the pros and cons of mandrel, and equipment for mandrel are considered. Then the use of ANSYS finite element software to simulate the processing process. Then the study of the dependence of the hole shrinkage on the tightness, the degree of thickness, the mechanical properties of the material was carried out, and the curvature of the machined holes was also investigated. In the conclusion, the conclusions about the work done are presented and the equation describing the investigated dependences is presented

Early XXI century English-Russian bilingual learner's lexicographyreview

The state and trends of the modern English-Russian learner's lexicography are described in the original review considering such dictionaries as one of the principal instruments for decoding the RFL and EFL learner's environment

Late-Stage Diversification of Phosphinic Dehydroalanine Pseudopeptides Based on a Giese-Type Radical C-Alkylation Strategy

A straightforward, late-stage diversification strategy for the installation of side chains on readily accessible unsaturated phosphinopeptidic scaffolds based on a Giese-type addition of alkyl radicals has been investigated. Among different alternatives, the preferred methodology is operationally simple as it can be carried out in an open flask with no need for protection of acidic moieties. Direct application to the synthesis of SPPS-compatible building blocks or to longer peptides is also reported. © 2019 American Chemical Society

Discovery of a New Class of Potent MMP Inhibitors by Structure-Based Optimization of the Arylsulfonamide Scaffold

[Image: see text] A new class of potent matrix metalloproteinase (MMP) inhibitors designed by structure-based optimization of the well-known arylsulfonamide scaffold is presented. Molecules show an ethylene linker connecting the sulfonamide group with the P1′ aromatic portion and a d-proline residue bearing the zinc-binding group. The affinity improvement provided by these modifications led us to discover a nanomolar MMP inhibitor bearing a carboxylate moiety as zinc-binding group, which might be a promising lead molecule. Notably, a significant selectivity for MMP-8, MMP-12, and MMP-13 was observed with respect to MMP-1 and MMP-7

Third generation of matrix metalloprotease inhibitors: Gain in selectivity by targeting the depth of the S1' cavity

Following the disappointment of clinical trials with early broad-spectrum synthetic inhibitors of matrix metalloproteases (MMPs), the field is now resurging with a new focus on the development of more selective inhibitors. Compounds able to fully discriminate between different members of the MMP family are sorely needed for therapeutic applications. Chemical efforts over the past years have led to very few selective inhibitors of MMPs. The over-exploitation of the hydroxamate function, or other strong zinc-binding groups, might be responsible for this failure. By resorting to weaker zinc-chelating groups, like phosphoryl or carboxylic groups, inhibitors with improved selectivity profiles have been developed. However, the most encouraging results have been obtained with compounds that avoid targeting the zinc but gain their affinity from plunging deeper into the MMP S1' cavity. Analyses of the crystal structures of MMP-13 and MMP-8 complexes with such compounds provide novel insights for the design of more selective inhibitors for other members of the MMP family. © 2010 Elsevier Masson SAS

Insights from selective non-phosphinic inhibitors of MMP-12 tailored to fit with an S1′ loop canonical conformation

After the disappointment of clinical trials with early broad spectrum synthetic inhibitors of matrix metalloproteinases (MMPs), the field is now resurging with a new focus on the development of selective inhibitors that fully discriminate between different members of the MMP family with several therapeutic applications in perspective. Here, we report a novel class of highly selective MMP-12 inhibitors, without a phosphinic zinc-binding group, designed to plunge deeper into the S1′ cavity of the enzyme. The best inhibitor from this series, identified through a systematic chemical exploration, displays nanomolar potency toward MMP-12 and selectivity factors that range between 2 and 4 orders of magnitude toward a large set of MMPs. Comparison of the high resolution x-ray structures of MMP-12 in free state or bound to this new MMP-12 selective inhibitor reveals that this compound fits deeply within the S1′ specificity cavity, maximizing surface/volume ratios, without perturbing the S1′ loop conformation. This is in contrast with highly selective MMP-13 inhibitors that were shown to select a particular S1′ loop conformation. The search for such compounds that fit precisely to preponderant S 1′ loop conformation of a particular MMP may prove to be an alternative effective strategy for developing selective inhibitors of MMPs. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc

Development of selective inhibitors and substrate of matrix metalloproteinase-12

Four phosphinic peptide libraries with compounds having the general formula p-Br-Ph-(PO2-CH2)-Xaa′-Yaa′-Zaa′- NH2 have been prepared and screened against 10 matrix metalloproteinases (MMPs). We identified two phosphinic peptides with Ki values of 0.19 and 4.4 nM toward MMP-12 (macrophage elastase) that are more than 2-3 orders of magnitude less potent toward the other MMPs tested. These highly selective MMP-12 inhibitors contain a Glu-Glu motif in their Yaa′-Zaa′ positions. Incorporation of this Glu-Glu motif into the sequence of a nonspecific fluorogenic peptide cleaved by MMPs provides a highly selective substrate for MMP-12. A model of one of these inhibitors interacting with MMP-12 suggests that the selectivity observed might be due, in part, to the presence of two unique polar residues in MMP-12, Thr239 and Lys 177. These MMP-12-selective inhibitors may have important therapeutic applications to diseases in which MMP-12 has been suggested to play a key role, such as in emphysema, atherosclerosis, and aortic abdominal aneurysm. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc

Future challenges facing the development of specific active-site-directed synthetic inhibitors of MMPs

Despite a deep knowledge on the 3D-structure of several catalytic domains of MMPs, the development of highly specific synthetic active-site-directed inhibitors of MMPs, able to differentiate the different members of this protease family, remains a strong challenge. Due to the flexible nature of NIMP active-site, the development of specific NIMP inhibitors will need to combine sophisticated theoretical and experimental approaches to decipher in each MMP the specific structural and dynamic features that can be exploited to obtain the desired selectivity. (c) 2004 Elsevier SAS. All rights reserved

Probing the mechanism of allylic substitution of morita-baylis- Hillman acetates (MBHAS) by using the silyl phosphonite paradigm: Scope and applications of a versatile transformation

A P-C bond-forming reaction between silyl phosphonites and Morita-Baylis-Hillman acetates (MBHAs) is explored as a general alternative towards medicinally relevant β;-carboxyphosphinic structural motifs. Conversion rates of diversely substituted MBHAs to phosphinic acids 9 or 14that were recorded by using 31P NMR spectroscopy revealed unexpected reactivity differences between ester and nitrile derivatives. These kinetic profiles and DFT calculations support a mechanistic scenario in which observed differences can be explained from the "lateness" of transition states. In addition, we provide experimental evidence suggesting that enolates due to initial P-Michael addition are not formed. Based on the proposed mechanistic scenario in conjunction with DFT calculations, an interpretation of the E/Z stereoselectivity differences between ester and nitriles is proposed. Synthetic opportunities stemming from this transformation are presented, which deal with the preparation of several synthetically capricious phosphinic building blocks, whose access through the classical P-Michael synthetic route is not straightforward. © 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim