Enhancing tool life of hot isostatically pressed silicon nitride inserts in machining inconel 718 with different susceptors through hybrid microwave post sintering

Hybrid Microwave sintering has become a growing interest for heating and synthesizing ceramic materials due to its capabilities in successfully enhancing densification and improving mechanical and structural properties. Silicon Nitride (Si3N4) based cutting inserts have outstanding properties for machining hard materials such as cast iron, hard steel and nickel based super alloys. This research aims to analyze the effect of different susceptors on the tool life of various Si3N4 inserts (90Si3N4 4Y2O3 2.5MgO 2Al2O3 1.5SiO) that have been synthesized in machining Inconel 718. The Si3N4 inserts have been synthesized by means of Hot Isostatic Pressing (HIP) at 1800°C and followed by Hybrid Microwave (HMW) post-sintering at 200°C for 10 minutes with the aid of three different susceptors; Silicon Carbide (SiC), Graphite (G) and mixture of (SiC + G) powders. Density, hardness, micro structural properties and tool wear were analyzed. HMW post sintering for only 10 minutes using SiC, G and SiC+G susceptors enhanced the density (97-98%TD) and hardness (27-58%) significantly. Finer uniform grains and less porosities were produced particularly for Si3N4 inserts produced by HMW (SiC+G) when compared with HMW (SiC) and HMW (G). Tool life for the Si3N4 inserts were improved by 10-17% HMW(SiC), 20-53 % HMW(G) and 32-88% HMW(SiC+G) for the cutting speeds of 100, 125 and 160 m/min. Hence, the mixture of SiC +G powders as susceptors produced the best outcome for Si3N4 inserts with enhanced densification, hardness, wear resistance, and longer tool life (88% increment at 100 m/min) when compared with the commercial tool (RNGN 6060) in machining Inconel 718

Adipose-Derived Stem Cells Stimulate Regeneration of Peripheral Nerves: BDNF Secreted by These Cells Promotes Nerve Healing and Axon Growth De Novo

Transplantation of adipose-derived mesenchymal stem cells (ASCs) induces tissue regeneration by accelerating the growth of blood vessels and nerve. However, mechanisms by which they accelerate the growth of nerve fibers are only partially understood. We used transplantation of ASCs with subcutaneous matrigel implants (well-known in vivo model of angiogenesis) and model of mice limb reinnervation to check the influence of ASC on nerve growth. Here we show that ASCs stimulate the regeneration of nerves in innervated mice's limbs and induce axon growth in subcutaneous matrigel implants. To investigate the mechanism of this action we analyzed different properties of these cells and showed that they express numerous genes of neurotrophins and extracellular matrix proteins required for the nerve growth and myelination. Induction of neural differentiation of ASCs enhances production of brain-derived neurotrophic factor (BDNF) as well as ability of these cells to induce nerve fiber growth. BDNF neutralizing antibodies abrogated the stimulatory effects of ASCs on the growth of nerve sprouts. These data suggest that ASCs induce nerve repair and growth via BDNF production. This stimulatory effect can be further enhanced by culturing the cells in neural differentiation medium prior to transplantation

Copper-catalyzed diastereo- and enantioselective desymmetrization of cyclopropenes: Synthesis of cyclopropylboronates

This document is the accepted manuscript version of a Published Work that appeared in final form in Journal of American Chemical Society 136.45, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see DOI: 10.1021/ja510419zA novel Cu-catalyzed diastereo- and enantioselective desymmetrization of cyclopropenes to afford nonracemic cyclopropylboronates is described. Trapping the cyclopropylcopper intermediate with electrophilic amines allows for the synthesis of cyclopropylaminoboronic esters and demonstrates the potential of the approach for the synthesis of functionalized cyclopropanesWe thank the European Research Council (ERC-337776) and MINECO (CTQ2012-35957) for financial support. M. T. and A. P. thank MICINN for RyC and JdC contract

CD8 coreceptor-mediated focusing can reorder the agonist hierarchy of peptide ligands recognized via the T cell receptor

CD8+ T cells are inherently cross-reactive and recognize numerous peptide antigens in the context of a given major histocompatibility complex class I (MHCI) molecule via the clonotypically expressed T cell receptor (TCR). The lineally expressed coreceptor CD8 interacts coordinately with MHCI at a distinct and largely invariant site to slow the TCR/peptide-MHCI (pMHCI) dissociation rate and enhance antigen sensitivity. However, this biological effect is not necessarily uniform, and theoretical models suggest that antigen sensitivity can be modulated in a differential manner by CD8. We used two intrinsically controlled systems to determine how the relationship between the TCR/pMHCI interaction and the pMHCI/CD8 interaction affects the functional sensitivity of antigen recognition. Our data show that modulation of the pMHCI/CD8 interaction can reorder the agonist hierarchy of peptide ligands across a spectrum of affinities for the TCR

ВЛИЯНИЕ ОЖИРЕНИЯ НА РАЗВИТИЕ И ПРОГРЕССИЮ ЗЛОКАЧЕСТВЕННЫХ НОВООБРАЗОВАНИЙ: ОБЗОР СОВРЕМЕННЫХ ДАННЫХ И НОВЫХ ТЕРАПЕВТИЧЕСКИХ МИШЕНЕЙ

Background. Type 2 diabetes mellitus, obstructive sleep apnea, osteoarthritis and certain types of cancer are known to correlate with obesity. The mechanisms underlying the link between metabolic disorders and cancer remain obscure, yet assuming a potentially important role of reduced insulin sensitivity, altered glucose metabolism in tumor cells (the so-called Warburg effect), changes in the spectrum of secreted adipokines or interaction with their cognitive receptors as well as changes in steroid sex hormone production.Material and methods. A search for articles published in peer-reviewed journals indexed in pubmed, Wos, scopus and Rsci was carried out. More than 150 articles devoted to the study of the relationship between metabolic disorders and tumor progression were analyzed, of which 69 were included in this review.Results. The main strategy of anticancer therapy is to suppress the proliferation of tumor cells and metastasis. However, one should take into consideration a significant role of additional factors that can enhance side effects of anticancer therapy, ensure the resistance of tumor cells to chemotherapy or change cancer cell metabolic profile. New data recently emerging in the literature indicate an important function of proteins such as t-cadherin and urokinase receptor (upar) and their possible involvement in the regulation of tumor cell metabolism, in particular, sensitivity to insulin and adipose tissue hormones. The review encompasses recent data on the involvement of t-cadherin and upar in the regulation of metabolism and proposes a model explaining the relationship between these proteins and metabolic disorders associated with the processes of carcinogenesis and chemoresistance of cancer cells.Conclusion. Understanding of the factors and mechanisms that support obesity and metabolic disorders is relevant both for the development of cancer preventive measures and optimization of therapeutic strategies for combating cancer.Актуальность. Известно, что диабет 2-го типа, синдром обструктивного апноэ сна, остеоартроз и ряд злокачественных новообразований коррелируют с ожирением. Механизмы, обусловливающие взаимосвязь метаболических нарушений с возникновением злокачественных опухолей, пока неизвестны; значительную роль может играть изменение чувствительности к инсулину и факторам роста, изменение спектра секретируемых адипокинов или особенности их взаимодействия с рецепторами, изменение содержания стероидных половых гормонов в организме, а также особенности метаболизма глюкозы в опухолевых клетках (так называемый эффект Варбурга).Материал и методы. Проведен поиск источников, включая научные, клинические и обзорные статьи, опубликованные в рецензируемых журналах, индексируемых в pubmed, Wos, scopus и РИНЦ. Проанализировано более 150 статей, посвященных изучению взаимосвязи метаболических нарушений с опухолевой прогрессией, из которых 69 включены в данный обзор.Результаты. Основная стратегия лечения опухолевых заболеваний заключается в подавлении пролиферации опухолевых клеток и процессов метастазирования. Возможно, что значительную роль в этих процессах играет ряд факторов, способных усиливать побочные эффекты противоопухолевой терапии, поддерживать резистентность опухолевых клеток или изменять их метаболический профиль. Имеются новые данные о функции таких белков, как Т-кадгерин и рецептор урокиназы (upaR), и их возможном участии в регуляции метаболизма опухолевых клеток, в частности чувствительности к инсулину и гормонам жировой ткани. Помимо адипокинов как уже известных посредников, участвующих в канцерогенезе, в обзоре описаны новые данные о роли Т-кадгерина и урокиназного рецептора upaR в регуляции обменных процессов. Предложена модель, объясняющая взаимосвязь этих белков и метаболических нарушений, ассоциированных с процессами канцерогенеза и химиорезистентности опухолевых клеток.Заключение. Понимание факторов и механизмов, поддерживающих ожирение и нарушения метаболизма, с точки зрения их роли в канцерогенезе актуально как для разработки профилактических мер, так и для оптимизации терапевтических стратегий борьбы с опухолевыми заболеваниями

Consumer Adoption of Self-Service Technologies in the Context of the Jordanian Banking Industry: Examining the Moderating Role of Channel Types

YesThis study aimed to examine the key factors predicting Jordanian consumers’ intentions and usage of three types of self-service banking technologies. This study also sought to test if the impacts of these main predictors could be moderated by channel type. This study proposed a conceptual model by integrating factors from the unified theory of acceptance and use of technology (UTAUT), along with perceived risk. The required data were collected from a convenience sample of Jordanian banking customers using a survey questionnaire. The statistical results strongly support the significant influence of performance expectancy, social influence, and perceived risk on customer intentions for the three types of SSTs examined. The results of the X2 differences test also indicate that there are significant differences in the influence of the main predictors due to the moderating effect of channel type. One of the key contributions of this study is that three types of SSTs were tested in a single study, which had not been done before, leading to the identification of the factors common to all three types, as well as the salient factors unique to each type

Peculiarities of heart rate variability in patients with obstructive sleep apnea and comorbid pathology in neurological practice

The aim of the study was to reveal HRV peculiarities in patients with AOS and comorbid pathology.Цель исследования – выявить особенности ВСР у пациентов с ОАС и коморбидной патологией

Blocking Tumor-Educated MSC Paracrine Activity Halts Osteosarcoma Progression

Purpose: Human osteosarcoma is a genetically heterogeneous bone malignancy with poor prognosis despite the employment of aggressive chemotherapy regimens. Because druggable driver mutations have not been established, dissecting the interactions between osteosarcoma cells and supporting stroma may provide insights into novel therapeutic targets.Experimental Design: By using a bioluminescent orthotopic xenograft mouse model of osteosarcoma, we evaluated the effect of tumor extracellular vesicle (EV)-educated mesenchymal stem cells (TEMSC) on osteosarcoma progression. Characterization and functional studies were designed to assess the mechanisms underlying MSC education. Independent series of tissue specimens were analyzed to corroborate the preclinical findings, and the composition of patient serum EVs was analyzed after isolation with size-exclusion chromatography.Results: We show that EVs secreted by highly malignant osteosarcoma cells selectively incorporate a membrane-associated form of TGF\u3b2, which induces proinflammatory IL6 production by MSCs. TEMSCs promote tumor growth, accompanied with intratumor STAT3 activation and lung metastasis formation, which was not observed with control MSCs. Importantly, intravenous administration of the anti-IL6 receptor antibody tocilizumab abrogated the tumor-promoting effects of TEMSCs. RNA-seq analysis of human osteosarcoma tissues revealed a distinct TGF\u3b2-induced prometastatic gene signature. Tissue microarray immunostaining indicated active STAT3 signaling in human osteosarcoma, consistent with the observations in TEMSC-treated mice. Finally, we isolated pure populations of EVs from serum and demonstrated that circulating levels of EV-associated TGF\u3b2 are increased in osteosarcoma patients.Conclusions: Collectively, our findings suggest that TEMSCs promote osteosarcoma progression and provide the basis for testing IL6- and TGF\u3b2-blocking agents as new therapeutic options for osteosarcoma patients. Clin Cancer Res; 23(14); 3721-33. \ua92017 AACR