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

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

A model for community representation and participation in HIV prevention trials among women who engage in transactional sex in Africa.

Actively engaging communities in effective partnerships for the design and implementation of HIV prevention research is vital to the successful conduct of ethically robust, locally-appropriate clinical trials in developing countries. This is especially true in vulnerable at-risk sub-populations, where definitions of "community", "participation" and "representation" can be difficult to apply. This study was conducted to investigate the feasibility of a participatory model of community liaison among an occupational cohort of women at high-risk of HIV and sexually-transmitted infections in Mwanza City, northwest Tanzania in preparation for a Phase III vaginal microbicide trial. This approach was rooted in participatory action-orientated research and used tools adapted from participatory learning and action techniques. During the feasibility study, a mobile community-based sexual and reproductive health service for women working as informal food vendors or in traditional and modern bars, restaurants, hotels and guesthouses was established in 10 city wards. Participatory mapping was carried out by project fieldworkers and wards divided into 78 geographical clusters of facilities in consultation with community members and study participants. Representatives at cluster and ward level were elected in a process facilitated by the site Community Liaison Officer and a site-level Community Advisory Committee established. A logical framework was used to guide the implementation, monitoring and evaluation of the community liaison system (CLS) within the broader feasibility study. The CLS was essential to the successful conduct of the feasibility study and has now been consolidated and expanded as part of the on-going MDP301 Phase III microbicide trial in Mwanza. The participatory model presented in this paper is likely to be generalisable to other vulnerable, stigmatised, at-risk study populations in resource-limited settings

In vivo imaging of matrix metalloproteinase 12 and matrix metalloproteinase 13 activities in the mouse model of collagen-induced arthritis.

OBJECTIVE: To develop enzyme-activatable Förster resonance energy transfer (FRET) substrate probes to detect matrix metalloproteinase 12 (MMP-12) and MMP-13 activities in vivo in mouse models of inflammatory arthritis. METHODS: Peptidic FRET probes activated by MMP-12 and MMP-13 were reverse designed from inhibitors selected from a phosphinic peptide inhibitor library. Selectivity of the probes was demonstrated in vitro using MMP-1, MMP-2, MMP-3, MMP-12, and MMP-13. In vivo activation of the probes was tested in the zymosan-induced mouse model of inflammation, and probe specificity was evaluated by the MMP inhibitor GM6001 and specific synthetic inhibitors of MMP-12 and MMP-13. The probes were used to monitor these enzyme activities in the collagen-induced arthritis (CIA) model in vivo. RESULTS: The MMP-12 and MMP-13 activity probes (MMP12ap and MMP13ap, respectively) discriminated between the activities of the 2 enzymes. The in vivo activation of these probes was inhibited by GM6001 and by their respective specific inhibitors. In the CIA model, MMP12ap activation peaked 5 days after disease onset and showed strong correlation with disease severity during this time (r = 0.85, P &lt; 0.0001). MMP13ap activation increased gradually after disease onset and correlated with disease severity over a longer period of 15 days (r = 0.58, P &lt; 0.0001). CONCLUSION: We generated two selective FRET probes that can be used to monitor MMP-12 and MMP-13 activities in live animals. MMP12ap follows the initial stage of inflammation in CIA, while MMP13ap follows the progression of the disease. The specificity of these probes is useful in monitoring the efficacy of MMP inhibitors.</p

Rechteklärung: Riesiger Aufwand der British Library für 1 feministisches Magazin

http://britishlibrary.typepad.co.uk/living-knowledge/2015/05/digitising-spare-rib-magazine-the-inside-story.htm

Optical imaging of MMP-12 active form in inflammation and aneurysm

Matrix metalloproteinase (MMP)-12 plays a key role in the development of aneurysm. Like other members of MMP family, MMP-12 is produced as a proenzyme, mainly by macrophages, and undergoes proteolytic activation to generate an active form. Accordingly, molecular imaging of the MMP-12 active form can inform of the pathogenic process in aneurysm. Here, we developed a novel family of fluorescent probes based on a selective MMP-12 inhibitor, RXP470.1 to target the active form of MMP-12. These probes were stable in complex media and retained the high affinity and selectivity of RXP470.1 for MMP-12. Amongst these, probe 3 containing a zwitterionic fluorophore, ZW800-1, combined a favorable affinity profile toward MMP-12 and faster blood clearance. In vivo binding of probe 3 was observed in murine models of sterile inflammation and carotid aneurysm. Binding specificity was demonstrated using a non-binding homolog. Co-immunostaining localized MMP-12 probe binding to MMP-12 positive areas and F4/80 positive macrophages in aneurysm. In conclusion, the active form of MMP-12 can be detected by optical imaging using RXP470.1-based probes. This is a valuable adjunct for pathophysiology research, drug development, and potentially clinical applications

Novel Matrix Metalloproteinase 12 Selective Radiotracers for Vascular Molecular Imaging

Matrix metalloproteinase-12 (MMP-12) is highly upregulated in several inflammatory diseases, including abdominal aortic aneurysm (AAA). Here we report four novel 99mTc-labeled radiotracers derived from a highly selective competitive MMP-12 inhibitor. These tracers in their 99gTc version were assessed in vitro on a set of human metalloproteases and displayed high affinity and selectivity toward MMP-12. Their radiolabeling with 99mTc was shown to be efficient and stable in both buffer and mouse blood. The tracers showed major differences in their biodistribution and blood clearance. On the basis of its in vivo performance, [99mTc]-1 was selected for evaluation in murine AAA, where MMP-12 gene expression is upregulated. Autoradiography of aortae at 2 h postinjection revealed high uptake of [99mTc]-1 in AAA relative to adjacent aorta. Tracer uptake specificity was demonstrated through in vivo competition. This study paves the way for further evaluation of [99mTc]-1 for imaging AAA and other MMP-12-associated diseases. Copyright © 2019 American Chemical Society

Synthesis and in Vitro and in Vivo Evaluation of MMP-12 Selective Optical Probes

In designing new tracers consisting of a small peptide conjugated to a reporter of comparable size, particular attention needs to be paid to the selection of the reporter group, which can dictate both the in vitro and the in vivo performances of the whole conjugate. In the case of fluorescent tracers, this is particularly true given the large numbers of available dye moieties differing in their structures and properties. Here, we have investigated the in vitro and in vivo properties of a novel series of MMP-12 selective probes composed of cyanine dyes varying in their structure, net charge, and hydrophilic character, tethered through a linker to a potent and specific MMP-12 phosphinic pseudopeptide inhibitor. The impact of linker length has been also explored. The crystallographic structure of one tracer in complex with MMP-12 has been obtained, providing the first crystal structure of a Cy5.5-derived probe and confirming that the binding of the targeting moiety is unaffected. MMP-12 remains the tracers&apos; privileged target, as attested by their affinity selectivity profile evaluated in solution toward a panel of 12 metalloproteases. In vivo assessment of four selected probes has highlighted not only the impact of the dye structure but also that of the linker length on the probes&apos; blood clearance rates and their biodistributions. These experiments have also provided valuable data on the stability of the dye moieties in vivo. This has permitted the identification of one probe, which combines favorable binding to MMP-12 in solution and on cells with optimized in vivo performance including blood clearance rate suitable for short-time imaging. Through this series of tracers, we have identified various critical factors modulating the tracers&apos; in vivo behavior, which is both useful for the development and optimization of MMP-12 selective radiolabeled tracers and informative for the design of fluorescent probes in general. © 2016 American Chemical Society