619 research outputs found

    Structural morphology of Al-Mg-Si alloy friction stir welds through tool eccentricity

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    In this work, the microstructure development in the stir zone of Al-Mg-Si alloy is evaluated while employing tool eccentricity during friction stir welding. Low dislocation density with dispersoids were observed in the inner band region of the stir zone produced with aligned tooling. On the other hand, a high dislocation density with Mg2Si precipitates can be observed in the same region of the stir zone when a tool eccentricity of 0.2 mm was utilized. The discrepancy is attributed to the enhanced shearing activity imposed on the material during the welding process

    Crystalline phases involved in the hydration of calcium silicate-based cements: Semi-quantitative Rietveld X-ray diffraction analysis

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    Chemical comparisons of powder and hydrated forms of calcium silicate cements (CSCs) and calculation of alterations in tricalcium silicate (Ca3SiO5) calcium hydroxide (Ca(OH)2) are essential for understanding their hydration processes. This study aimed to evaluate and compare these changes in ProRoot MTA, Biodentine and CEM cement. Powder and hydrated forms of tooth coloured ProRoot MTA, Biodentine and CEM cement were subjected to X-ray diffraction (XRD) analysis with Rietveld refinement to semi-quantitatively identify and quantify the main phases involved in their hydration process. Data were reported descriptively. Reduction in Ca3SiO5 and formation of Ca(OH)2 were seen after the hydration of ProRoot MTA and Biodentine; however, in the case of CEM cement, no reduction of Ca3SiO5 and no formation of Ca(OH)2 were detected. The highest percentages of amorphous phases were seen in Biodentine samples. Ettringite was detected in the hydrated forms of ProRoot MTA and CEM cement but not in Biodentine

    River water quality assessment using environmentric techniques : case study of Jakara River Basin.

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    akara River Basin has been extensively studied to assess the overall water quality and to identify the major variables responsible for water quality variations in the basin. A total of 27 sampling points were selected in the riverine network of the Upper Jakara River Basin. Water samples were collected in triplicate and analyzed for physicochemical variables. Pearson product-moment correlation analysis was conducted to evaluate the relationship of water quality parameters and revealed a significant relationship between salinity, conductivity with dissolved solids (DS) and 5-day biochemical oxygen demand (BOD5), chemical oxygen demand (COD), and nitrogen in form of ammonia (NH4). Partial correlation analysis (r p) results showed that there is a strong relationship between salinity and turbidity (r p = 0.930, p = 0.001) and BOD5 and COD (r p = 0.839, p = 0.001) controlling for the linear effects of conductivity and NH4, respectively. Principal component analysis and or factor analysis was used to investigate the origin of each water quality parameter in the Jakara Basin and identified three major factors explaining 68.11 % of the total variance in water quality. The major variations are related to anthropogenic activities (irrigation agricultural, construction activities, clearing of land, and domestic waste disposal) and natural processes (erosion of river bank and runoff). Discriminant analysis (DA) was applied on the dataset to maximize the similarities between group relative to within-group variance of the parameters. DA provided better results with great discriminatory ability using eight variables (DO, BOD5, COD, SS, NH4, conductivity, salinity, and DS) as the most statistically significantly responsible for surface water quality variation in the area. The present study, however, makes several noteworthy contributions to the existing knowledge on the spatial variations of surface water quality and is believed to serve as a baseline data for further studies. Future research should therefore concentrate on the investigation of temporal variations of water quality in the basin

    Choline kinase alpha as an androgen receptor chaperone and prostate cancer therapeutic target

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    Background: The androgen receptor (AR) is a major drug target in prostate cancer (PCa). We profiled the AR-regulated kinome to identify clinically relevant and druggable effectors of AR signaling. Methods: Using genome-wide approaches, we interrogated all AR regulated kinases. Among these, choline kinase alpha (CHKA) expression was evaluated in benign (n = 195), prostatic intraepithelial neoplasia (PIN) (n = 153) and prostate cancer (PCa) lesions (n = 359). We interrogated how CHKA regulates AR signaling using biochemical assays and investigated androgen regulation of CHKA expression in men with PCa, both untreated (n = 20) and treated with an androgen biosynthesis inhibitor degarelix (n = 27). We studied the effect of CHKA inhibition on the PCa transcriptome using RNA sequencing and tested the effect of CHKA inhibition on cell growth, clonogenic survival and invasion. Tumor xenografts (n = 6 per group) were generated in mice using genetically engineered prostate cancer cells with inducible CHKA knockdown. Data were analyzed with χ 2 tests, Cox regression analysis, and Kaplan-Meier methods. All statistical tests were two-sided. Results: CHKA expression was shown to be androgen regulated in cell lines, xenografts, and human tissue (log fold change from 6.75 to 6.59, P = .002) and was positively associated with tumor stage. CHKA binds directly to the ligand-binding domain (LBD) of AR, enhancing its stability. As such, CHKA is the first kinase identified as an AR chaperone. Inhibition of CHKA repressed the AR transcriptional program including pathways enriched for regulation of protein folding, decreased AR protein levels, and inhibited the growth of PCa cell lines, human PCa explants, and tumor xenografts. Conclusions: CHKA can act as an AR chaperone, providing, to our knowledge, the first evidence for kinases as molecular chaperones, making CHKA both a marker of tumor progression and a potential therapeutic target for PCa.Mohammad Asim ... Luke A. Selth ... Wayne D. Tilley et al

    Lipid Alterations in Experimental Murine Colitis: Role of Ceramide and Imipramine for Matrix Metalloproteinase-1 Expression

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    BACKGROUND:Dietary lipids or pharmacologic modulation of lipid metabolism are potential therapeutic strategies in inflammatory bowel disease (IBD). Therefore, we analysed alterations of bioactive lipids in experimental models of colitis and examined the functional consequence of the second messenger ceramide in inflammatory pathways leading to tissue destruction. METHODOLOGY/PRINCIPAL FINDINGS:Chronic colitis was induced by dextran-sulphate-sodium (DSS) or transfer of CD4(+)CD62L(+) cells into RAG1(-/-)-mice. Lipid content of isolated murine intestinal epithelial cells (IEC) was analysed by tandem mass spectrometry. Concentrations of MMP-1 in supernatants of Caco-2-IEC and human intestinal fibroblasts from patients with ulcerative colitis were determined by ELISA. Imipramine was used for pharmacologic inhibition of acid sphingomyelinase (ASM). Ceramide increased by 71% in chronic DSS-induced colitis and by 159% in the transfer model of colitis. Lysophosphatidylcholine (LPC) decreased by 22% in both models. No changes were detected for phosphatidylcholine. Generation of ceramide by exogenous SMase increased MMP-1-protein production of Caco-2-IEC up to 7-fold. Inhibition of ASM completely abolished the induction of MMP-1 by TNF or IL-1beta in Caco-2-IEC and human intestinal fibroblasts. CONCLUSIONS/SIGNIFICANCE:Mucosal inflammation leads to accumulation of ceramide and decrease of LPC in the intestinal epithelium. One aspect of ceramide generation is an increase of MMP-1. Induction of MMP-1 by TNF or IL-1beta is completely blocked by inhibition of ASM with imipramine. Therefore, inhibition of ASM may offer a treatment strategy to reduce MMP-1 expression and tissue destruction in inflammatory conditions

    International comparisons of behavioral and emotional problems in preschool children: parents’ reports from 24 societies

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    International comparisons were conducted of preschool children’s behavioral and emotional problems as reported on the Child Behavior Checklist for Ages 1½–5 by parents in 24 societies (N¼19,850). Item ratings were aggregated into scores on syndromes; Diagnostic and Statistical Manual of Mental Disorders–oriented scales; a Stress Problems scale; and Internalizing, Externalizing, and Total Problems scales. Effect sizes for scale score differences among the 24 societies ranged from small to medium (3–12%). Although societies differed greatly in language, culture, and other characteristics, Total Problems scores for 18 of the 24 societies were within 7.1 points of the omnicultural mean of 33.3 (on a scale of 0–198). Gender and age differences, as well as gender and age interactions with society, were all very small (effect sizes<1%). Across all pairs of societies, correlations between mean item ratings averaged .78, and correlations between internal consistency alphas for the scales averaged .92, indicating that the rank orders of mean item ratings and internal consistencies of scales were very similar across diverse societies

    Surface stiffening and enhanced photoluminescence of ion implanted cellulose - polyvinyl alcohol - silica composite

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    Novel Cellulose (Cel) reinforced polyvinyl alcohol (PVA)-Silica (Si) composite which has good stability and in vitro degradation was prepared by lyophilization technique and implanted using N3+ ions of energy 24 keV in the fluences of 1 x 10(15), 5 x 10(15) and 1 x 10(16) ions/cm(2). SEM analysis revealed the formation of microstructures, and improved the surface roughness on ion implantation. In addition to these structural changes, the implantation significantly modified the luminescent, thermal and mechanical properties of the samples. The elastic modulus of the implanted samples has increased by about 50 times compared to the pristine which confirms that the stiffness of the sample surface has increased remarkably on ion implantation. The photoluminescence of the native cellulose has improved greatly due to defect site, dangling bonds and hydrogen passivation. Electric conductivity of the ion implanted samples was improved by about 25%. Hence, low energy ion implantation tunes the mechanical property, surface roughness and further induces the formation of nano structures. MG63 cells seeded onto the scaffolds reveals that with the increase in implantation fluence, the cell attachment, viability and proliferation have improved greatly compared to pristine. The enhancement of cell growth of about 59% was observed in the implanted samples compared to pristine. These properties will enable the scaffolds to be ideal for bone tissue engineering and imaging applications.G.M.S. acknowledges CSIR, India (Grant no: 09/468 (0474)/2013-EMR-I) and S.N.K. thanks the award of Erasmus-Mundus Svaagata for providing financial support to carry out this research. G.M.S., N.S. and S.N.K. acknowledge the support of UGC National facility for characterization facility. J.A.G.T. acknowledges the support of the Spanish Ministry of Economy and Competitiveness (MINECO) through the project DPI2015-65401-C3-2-R (including the FEDER financial support). CIBER-BBN, Spain is an initiative funded by the VI National R&D Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program. CIBER actions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. AFM was conducted by the microscopy service of the UPV, whose advice was greatly appreciated.Shanthini, GM.; Sakthivel, N.; Menon, R.; Nabhiraj, PY.; Gómez-Tejedor, JA.; Meseguer Dueñas, JM.; Gómez Ribelles, JL.... (2016). Surface stiffening and enhanced photoluminescence of ion implanted cellulose - polyvinyl alcohol - silica composite. Carbohydrate Polymers. 153:619-630. https://doi.org/10.1016/j.carbpol.2016.08.016S61963015

    Past, present, and future of global health financing: a review of development assistance, government, out-of-pocket, and other private spending on health for 195 countries, 1995–2050

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    © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Comprehensive and comparable estimates of health spending in each country are a key input for health policy and planning, and are necessary to support the achievement of national and international health goals. Previous studies have tracked past and projected future health spending until 2040 and shown that, with economic development, countries tend to spend more on health per capita, with a decreasing share of spending from development assistance and out-of-pocket sources. We aimed to characterise the past, present, and predicted future of global health spending, with an emphasis on equity in spending across countries. Methods: We estimated domestic health spending for 195 countries and territories from 1995 to 2016, split into three categories—government, out-of-pocket, and prepaid private health spending—and estimated development assistance for health (DAH) from 1990 to 2018. We estimated future scenarios of health spending using an ensemble of linear mixed-effects models with time series specifications to project domestic health spending from 2017 through 2050 and DAH from 2019 through 2050. Data were extracted from a broad set of sources tracking health spending and revenue, and were standardised and converted to inflation-adjusted 2018 US dollars. Incomplete or low-quality data were modelled and uncertainty was estimated, leading to a complete data series of total, government, prepaid private, and out-of-pocket health spending, and DAH. Estimates are reported in 2018 US dollars, 2018 purchasing-power parity-adjusted dollars, and as a percentage of gross domestic product. We used demographic decomposition methods to assess a set of factors associated with changes in government health spending between 1995 and 2016 and to examine evidence to support the theory of the health financing transition. We projected two alternative future scenarios based on higher government health spending to assess the potential ability of governments to generate more resources for health. Findings: Between 1995 and 2016, health spending grew at a rate of 4·00% (95% uncertainty interval 3·89–4·12) annually, although it grew slower in per capita terms (2·72% [2·61–2·84]) and increased by less than 1percapitaoverthisperiodin22of195countries.Thehighestannualgrowthratesinpercapitahealthspendingwereobservedinuppermiddleincomecountries(5551 per capita over this period in 22 of 195 countries. The highest annual growth rates in per capita health spending were observed in upper-middle-income countries (5·55% [5·18–5·95]), mainly due to growth in government health spending, and in lower-middle-income countries (3·71% [3·10–4·34]), mainly from DAH. Health spending globally reached 8·0 trillion (7·8–8·1) in 2016 (comprising 8·6% [8·4–8·7] of the global economy and 103trillion[101106]inpurchasingpowerparityadjusteddollars),withapercapitaspendingofUS10·3 trillion [10·1–10·6] in purchasing-power parity-adjusted dollars), with a per capita spending of US5252 (5184–5319) in high-income countries, 491(461524)inuppermiddleincomecountries,491 (461–524) in upper-middle-income countries, 81 (74–89) in lower-middle-income countries, and 40(3843)inlowincomecountries.In2016,0440 (38–43) in low-income countries. In 2016, 0·4% (0·3–0·4) of health spending globally was in low-income countries, despite these countries comprising 10·0% of the global population. In 2018, the largest proportion of DAH targeted HIV/AIDS (9·5 billion, 24·3% of total DAH), although spending on other infectious diseases (excluding tuberculosis and malaria) grew fastest from 2010 to 2018 (6·27% per year). The leading sources of DAH were the USA and private philanthropy (excluding corporate donations and the Bill & Melinda Gates Foundation). For the first time, we included estimates of China's contribution to DAH (6447millionin2018).Globally,healthspendingisprojectedtoincreaseto644·7 million in 2018). Globally, health spending is projected to increase to 15·0 trillion (14·0–16·0) by 2050 (reaching 9·4% [7·6–11·3] of the global economy and $21·3 trillion [19·8–23·1] in purchasing-power parity-adjusted dollars), but at a lower growth rate of 1·84% (1·68–2·02) annually, and with continuing disparities in spending between countries. In 2050, we estimate that 0·6% (0·6–0·7) of health spending will occur in currently low-income countries, despite these countries comprising an estimated 15·7% of the global population by 2050. The ratio between per capita health spending in high-income and low-income countries was 130·2 (122·9–136·9) in 2016 and is projected to remain at similar levels in 2050 (125·9 [113·7–138·1]). The decomposition analysis identified governments’ increased prioritisation of the health sector and economic development as the strongest factors associated with increases in government health spending globally. Future government health spending scenarios suggest that, with greater prioritisation of the health sector and increased government spending, health spending per capita could more than double, with greater impacts in countries that currently have the lowest levels of government health spending. Interpretation: Financing for global health has increased steadily over the past two decades and is projected to continue increasing in the future, although at a slower pace of growth and with persistent disparities in per-capita health spending between countries. Out-of-pocket spending is projected to remain substantial outside of high-income countries. Many low-income countries are expected to remain dependent on development assistance, although with greater government spending, larger investments in health are feasible. In the absence of sustained new investments in health, increasing efficiency in health spending is essential to meet global health targets. Funding: Bill & Melinda Gates Foundation
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