Влияние облучения протонами на структуру наноразмерного металлического многослойного покрытия Zr/Nb

Образцы наноразмерного многослойного Zr/Nb покрытия, полученные путем магнетронного распыления, были подвергнуты облучению пучком протонов с током 2 и 4 мкА на линейном ускорителе ЭСГ-2,5. Анализ распределения протонов и дефектов по глубине был проведен в программном пакете SRIM. Методом рентгеноструктурного анализа определены размер кристаллитов и микронапряжения после облучения. Присутствие дефектной структуры в покрытии было определено по результатам измерения электросопротивления. Была установлена корреляционная зависимость данных электросопротивления и рентгеноструктурного анализа свидетельствующая о формировании дефектной структуры в покрытиях после облучения. Механические характеристики, такие как твердость и модуль Юнга были рассчитаны из данных по наноиндентированию.Nanoscale multilayer Zr/Nb coatings, received by magnetron sputtering, were been irradiated by proton beam with electrostatic Van De Graaff ion accelerator, ion current was 2 and 4 ?A. The penetration depth and distribution of defects was determined with SRIM simulation code. X–ray analyses before and after irradiation were performed to observe changes in crystalline sizes and microstrain values. Presence of defect structure in the coating was determined by electrical resistance measurements . There was observed correlation dependence between changes in electrical resistance and results of X-ray diffraction analyses. Mechanical properties, like hardness and Young’s modulus, were determined from nanoindentation tests

Effects of abciximab on key pattern of human coronary restenosis in vitro: impact of the SI/MPL-ratio

BACKGROUND: The significant reduction of angiographic restenosis rates in the ISAR-SWEET study (intracoronary stenting and antithrombotic regimen: is abciximab a superior way to eliminate elevated thrombotic risk in diabetes) raises the question of whether abciximab acts on clopidogrel-independent mechanisms in suppressing neointimal hyperplasia. The current study investigates the direct effect of abciximab on ICAM-1 expression, migration and proliferation. METHODS: ICAM-1: Part I of the study investigates in cytoflow studies the effect of abciximab (0.0002, 0.002, 0.02, 0.2, 2.0, and 20.0 μg/ml) on TNF-α induced expression of intercellular adhesion molecule 1 (ICAM-1). Migration: Part II of the study explored the effect of abciximab (0.0002, 0.002, 0.02, 0.2, 2.0, and 20.0 μg/ml) on migration of HCMSMC over a period of 24 h. Proliferation: Part III of the study investigated the effect of abciximab (0.0002, 0.002, 0.02, 0.2, 2.0, and 20.0 μg/ml) on proliferation of HUVEC, HCAEC, and HCMSMC after an incubation period of 5 days. RESULTS: ICAM-1: In human venous endothelial cells (HUVEC), human coronary endothelial cells (HCAEC) and human coronary medial smooth muscle cells (HCMSMC) no inhibitory or stimulatory effect on expression of ICAM-1 was detected. Migration: After incubation of HCMSMC with abciximab in concentrations of 0.0002 – 2 μg/ml a stimulatory effect on cell migration was detected, statistical significance was achieved after incubation with 0.002 μg/ml (p < 0.05), 0.002 μg/ml (p < 0.001), and 0.2 μg/ml (p < 0.05). Proliferation: Small but statistically significant antiproliferative effects of abciximab were detected after incubation of HUVEC (0.02 and 2.0 μg/ml; p = 0.01 and p < 0.01), HCAEC (2.0 and 20.0 μg/ml; p < 0.05 and p < 0,01), and HCMSMC (2.0 and 20.0 μg/ml; p < 0.05 and p < 0.05). The significant inhibition (SI) of cell proliferation found in HCAEC and HCMSMC was achieved with drug concentrations more than 10 times beyond the maximal plasma level (MPL), resulting in a SI/MPL-ratio > 1. CONCLUSION: Thus, the anti-restenotic effects of systemically administered abciximab reported in the ISAR-SWEET-study were not caused by a direct inhibitory effect on ICAM-1 expression, migration or proliferation

Endothelial progenitor cells and integrins: adhesive needs

In the last decade there have been multiple studies concerning the contribution of endothelial progenitor cells (EPCs) to new vessel formation in different physiological and pathological settings. The process by which EPCs contribute to new vessel formation in adults is termed postnatal vasculogenesis and occurs via four inter-related steps. They must respond to chemoattractant signals and mobilize from the bone marrow to the peripheral blood; home in on sites of new vessel formation; invade and migrate at the same sites; and differentiate into mature endothelial cells (ECs) and/or regulate pre-existing ECs via paracrine or juxtacrine signals. During these four steps, EPCs interact with different physiological compartments, namely bone marrow, peripheral blood, blood vessels and homing tissues. The success of each step depends on the ability of EPCs to interact, adapt and respond to multiple molecular cues. The present review summarizes the interactions between integrins expressed by EPCs and their ligands: extracellular matrix components and cell surface proteins present at sites of postnatal vasculogenesis. The data summarized here indicate that integrins represent a major molecular determinant of EPC function, with different integrin subunits regulating different steps of EPC biology. Specifically, integrin α4β1 is a key regulator of EPC retention and/or mobilization from the bone marrow, while integrins α5β1, α6β1, αvβ3 and αvβ5 are major determinants of EPC homing, invasion, differentiation and paracrine factor production. β2 integrins are the major regulators of EPC transendothelial migration. The relevance of integrins in EPC biology is also demonstrated by many studies that use extracellular matrix-based scaffolds as a clinical tool to improve the vasculogenic functions of EPCs. We propose that targeted and tissue-specific manipulation of EPC integrin-mediated interactions may be crucial to further improve the usage of this cell population as a relevant clinical agent

Stable or improved neurological manifestations during miglustat therapy in patients from the international disease registry for Niemann-Pick disease type C: an observational cohort study

Background: Niemann-Pick disease type C (NP-C) is a rare neurovisceral disease characterised by progressive neurological degeneration, where the rate of neurological disease progression varies depending on age at neurological onset. We report longitudinal data on functional disease progression and safety observations in patients in the international NPC Registry who received continuous treatment with miglustat. Methods: The NPC Registry is a prospective observational cohort of NP-C patients. Enrolled patients who received ≥1 year of continuous miglustat therapy (for ≥90 % of the observation period, with no single treatment interruption >28 days) were included in this analysis. Disability was measured using a scale rating the four domains, ambulation, manipulation, language and swallowing from 0 (normal) to 1 (worst). Neurological disease progression was analysed in all patients based on: 1) annual progression rates between enrolment and last follow up, and; 2) categorical analysis with patients categorised as 'improved/stable' if ≥3/4 domain scores were lower/unchanged, and as 'progressed' if <3 scores were lower/unchanged between enrolment and last follow-up visit. Results: In total, 283 patients were enrolled from 28 centers in 13 European countries, Canada and Australia between September 2009 and October 2013; 92 patients received continuous miglustat therapy. The mean (SD) miglustat exposure during the observation period (enrolment to last follow-up) was 2.0 (0.7) years. Among 84 evaluable patients, 9 (11 %) had early-infantile (<2 years), 27 (32 %) had late-infantile (2 to <6 years), 30 (36 %) had juvenile (6 to <15 years) and 18 (21 %) had adolescent/adult (≥15 years) onset of neurological manifestations. The mean (95%CI) composite disability score among all patients was 0.37 (0.32,0.42) at enrolment and 0.44 (0.38,0.50) at last follow-up visit, and the mean annual progression rate was 0.038 (0.018,0.059). Progression of composite disability scores appeared highest among patients with neurological onset during infancy or childhood and lowest in those with adolescent/adult-onset. Overall, 59/86 evaluable patients (69 %) were categorized as improved/stable and the proportion of improved/stable patients increased with age at neurological onset. Safety findings were consistent with previous data. Conclusions: Disability status was improved/stable in the majority of patients who received continuous miglustat therapy for an average period of 2 years

A high power ultrasonic array based test cell

This paper describes the use of finite element (FE) analysis as a tool in the design process for laboratory based ultrasonic test cells. The system was designed to incorporate an array of ultrasonic transducers to provide a pressure focus in the centre of the cell and importantly, operate both above and below the cavitation threshold of the load medium. Furthermore, the cell incorporates a coolant jacket to accommodate temperature control of the load material associated with the process. A 2D FE model corresponding to a slice through the operational plane of the cell was developed and used to investigate the influence of cell wall material and thickness, transducer configuration, rotation of a metallic stirrer blade and heat transfer fluid on the cell acoustic response. Importantly, experimentally measured pressure field maps demonstrate good correlation with the FE predicted fields. A final manufactured test cell is shown to produce a highly focussed region of cavitation. Finally, the importance in accurately representing the acoustic properties of the constituent materials used in such FE models is demonstrated through an illustrated example