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Sample records for epigallocatechin-3-gallate inhibits advanced

  1. Green tea polyphenol epigallocatechin-3-gallate inhibits advanced glycation end product-induced expression of tumor necrosis factor-alpha and matrix metalloproteinase-13 in human chondrocytes.

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    Rasheed, Zafar; Anbazhagan, Arivarasu N; Akhtar, Nahid; Ramamurthy, Sangeetha; Voss, Frank R; Haqqi, Tariq M

    2009-01-01

    The major risk factor for osteoarthritis (OA) is aging, but the mechanisms underlying this risk are only partly understood. Age-related accumulation of advanced glycation end products (AGEs) can activate chondrocytes and induce the production of proinflammatory cytokines and matrix metalloproteinases (MMPs). In the present study, we examined the effect of epigallocatechin-3-gallate (EGCG) on AGE-modified-BSA (AGE-BSA)-induced activation and production of TNFalpha and MMP-13 in human OA chondrocytes. Human chondrocytes were derived from OA cartilage by enzymatic digestion and stimulated with in vitro-generated AGE-BSA. Gene expression of TNFalpha and MMP-13 was measured by quantitative RT-PCR. TNFalpha protein in culture medium was determined using cytokine-specific ELISA. Western immunoblotting was used to analyze the MMP-13 production in the culture medium, phosphorylation of mitogen-activated protein kinases (MAPKs), and the activation of NF-kappaB. DNA binding activity of NF-kappaB p65 was determined using a highly sensitive and specific ELISA. IkappaB kinase (IKK) activity was determined using an in vitro kinase activity assay. MMP-13 activity in the culture medium was assayed by gelatin zymography. EGCG significantly decreased AGE-stimulated gene expression and production of TNFalpha and MMP-13 in human chondrocytes. The inhibitory effect of EGCG on the AGE-BSA-induced expression of TNFalpha and MMP-13 was mediated at least in part via suppression of p38-MAPK and JNK activation. In addition, EGCG inhibited the phosphorylating activity of IKKbeta kinase in an in vitro activity assay and EGCG inhibited the AGE-mediated activation and DNA binding activity of NF-kappaB by suppressing the degradation of its inhibitory protein IkappaBalpha in the cytoplasm. These novel pharmacological actions of EGCG on AGE-BSA-stimulated human OA chondrocytes provide new suggestions that EGCG or EGCG-derived compounds may inhibit cartilage degradation by suppressing AGE

  2. Green Tea Polyphenol Epigallocatechin-3-Gallate Enhance Glycogen Synthesis and Inhibit Lipogenesis in Hepatocytes

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    Jane J. Y. Kim

    2013-01-01

    Full Text Available The beneficial effects of green tea polyphenols (GTP against metabolic syndrome and type 2 diabetes by suppressing appetite and nutrient absorption have been well reported. However the direct effects and mechanisms of GTP on glucose and lipid metabolism remain to be elucidated. Since the liver is an important organ involved in glucose and lipid metabolism, we examined the effects and mechanisms of GTP on glycogen synthesis and lipogenesis in HepG2 cells. Concentrations of GTP containing 68% naturally occurring (−-epigallocatechin-3-gallate (EGCG were incubated in HepG2 cells with high glucose (30 mM under 100 nM of insulin stimulation for 24 h. GTP enhanced glycogen synthesis in a dose-dependent manner. 10 μM of EGCG significantly increased glycogen synthesis by 2fold (P<0.05 compared with insulin alone. Western blotting revealed that phosphorylation of Ser9 glycogen synthase kinase 3β and Ser641 glycogen synthase was significantly increased in GTP-treated HepG2 cells compared with nontreated cells. 10 μM of EGCG also significantly inhibited lipogenesis (P<0.01. We further demonstrated that this mechanism involves enhanced expression of phosphorylated AMP-activated protein kinase α and acetyl-CoA carboxylase in HepG2 cells. Our results showed that GTP is capable of enhancing insulin-mediated glucose and lipid metabolism by regulating enzymes involved in glycogen synthesis and lipogenesis.

  3. Epigallocatechin-3-gallate inhibits stem-like inflammatory breast cancer cells.

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    Nora D Mineva

    Full Text Available Inflammatory Breast Cancer (IBC is a highly aggressive form of cancer characterized by high rates of proliferation, lymphangiogenesis and metastasis, and an overall poor survival. As regular green tea consumption has been associated with improved prognosis of breast cancer patients, including decreased risk of recurrence, here the effects of the green tea polyphenol epigallocatechin-3-gallate (EGCG were tested on two IBC lines: SUM-149 and SUM-190. EGCG decreased expression of genes that promote proliferation, migration, invasion, and survival. Consistently, growth, invasive properties, and survival of IBC cells were reduced by EGCG treatment. EGCG also reduced lymphangiogenesis-promoting genes, in particular VEGF-D. Conditioned media from EGCG-treated IBC cells displayed decreased VEGF-D secretion and reduced ability to promote lymphangiogenesis in vitro as measured by hTERT-HDLEC lymphatic endothelial cell migration and tube formation. Tumorsphere formation by SUM-149 cells was robustly inhibited by EGCG, suggesting effects on self-renewal ability. Stem-like SUM-149 cells with high aldehyde dehydrogenase (ALDH activity, previously implicated in poor patient prognosis, were isolated. EGCG treatment reduced growth and induced apoptosis of the stem-like SUM-149 cells in culture. In an orthotopic mouse model, EGCG decreased growth of pre-existing tumors derived from ALDH-positive stem-like SUM-149 cells and their expression of VEGF-D, which correlated with a significant decrease in peritumoral lymphatic vessel density. Thus, EGCG inhibits the overall aggressive IBC phenotype. Reduction of the stem-like cell compartment by EGCG may explain the decreased risk of breast cancer recurrence among green tea drinkers. Recent clinical trials demonstrate the efficacy of green tea polyphenol extracts in treatment of prostate cancer and lymphocytic leukemia with low toxicity. Given the poor prognosis of IBC patients, our findings suggest further exploration

  4. Data in support of the negative influence of divalent cations on (?)-epigallocatechin-3-gallate (EGCG)-mediated inhibition of matrix metalloproteinase-2 (MMP-2)

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    Deb, Gauri; Batra, Sahil; Limaye, Anil M.

    2015-01-01

    In this data article we have provided evidence for the negative influence of divalent cations on (−)‐epigallocatechin-3-gallate (EGCG)-mediated inhibition of matrix metalloproteinase-2 (MMP-2) activity in cell-free experiments. Chelating agents, such as EDTA and sodium citrate alone, did not affect MMP-2 activity. While EDTA enhanced, excess of divalent cations interfered with EGCG-mediated inhibition of MMP-2.

  5. (−-Epigallocatechin 3-Gallate Synthetic Analogues Inhibit Fatty Acid Synthase and Show Anticancer Activity in Triple Negative Breast Cancer

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    Joan Crous-Masó

    2018-05-01

    Full Text Available (−-Epigallocatechin 3-gallate (EGCG is a natural polyphenol from green tea with reported anticancer activity and capacity to inhibit the lipogenic enzyme fatty acid synthase (FASN, which is overexpressed in several human carcinomas. To improve the pharmacological profile of EGCG, we previously developed a family of EGCG derivatives and the lead compounds G28, G37 and G56 were characterized in HER2-positive breast cancer cells overexpressing FASN. Here, diesters G28, G37 and G56 and two G28 derivatives, monoesters M1 and M2, were synthesized and assessed in vitro for their cytotoxic, FASN inhibition and apoptotic activities in MDA-MB-231 triple-negative breast cancer (TNBC cells. All compounds displayed moderate to high cytotoxicity and significantly blocked FASN activity, monoesters M1 and M2 being more potent inhibitors than diesters. Interestingly, G28, M1, and M2 also diminished FASN protein expression levels, but only monoesters M1 and M2 induced apoptosis. Our results indicate that FASN inhibition by such polyphenolic compounds could be a new strategy in TNBC treatment, and highlight the potential anticancer activities of monoesters. Thus, G28, G37, G56, and most importantly M1 and M2, are anticancer candidates (alone or in combination to be further characterized in vitro and in vivo.

  6. Epigallocatechin-3-gallate ameliorates intrahepatic cholestasis of pregnancy by inhibiting matrix metalloproteinase-2 and matrix metalloproteinase-9.

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    Zhang, Mei; Xu, Meimei

    2017-10-01

    Matrix metalloproteinase (MMP)-2 and matrix metalloproteinase-9 are involved in many illnesses affecting pregnant women, including intrahepatic cholestasis of pregnancy (ICP), a serious liver abnormality during pregnancy. Epigallocatechin-3-gallate (EGCG) has been widely reported to inhibit activities of MMP-2 and MMP-9. We aimed to investigate the role of EGCG in ameliorating ICP symptoms in a rat model. Using 17α-ethinylestradiol to induce ICP in pregnant rats, we investigated the efficacy of EGCG administration on ICP symptoms, including bile flow rate, total bile acids (TBA) and MMP-2 and MMP-9 activities. Correlation study was conducted among levels of the two MMPs with other ICP symptoms. In ICP rats, activities of both MMP-2 and MMP-9 were significantly elevated. EGCG administration could inhibit the upregulation of MMP-2 and MMP-9 post-transcriptionally. Furthermore, EGCG ameliorated ICP symptoms, as evidenced by restored bile flow rate and TBA, showing efficient treatment outcomes. At last, levels of TBA and the two MMPs were found to be strongly correlated. Our study demonstrates that, for the first time, the efficacy of EGCG in ameliorating ICP symptoms by inhibiting both MMP-2 and MMP-9, which supports its potential as a novel drug in ameliorating ICP. © 2017 Société Française de Pharmacologie et de Thérapeutique.

  7. (-)-Epigallocatechin 3-Gallate Synthetic Analogues Inhibit Fatty Acid Synthase and Show Anticancer Activity in Triple Negative Breast Cancer.

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    Crous-Masó, Joan; Palomeras, Sònia; Relat, Joana; Camó, Cristina; Martínez-Garza, Úrsula; Planas, Marta; Feliu, Lidia; Puig, Teresa

    2018-05-11

    (-)-Epigallocatechin 3-gallate (EGCG) is a natural polyphenol from green tea with reported anticancer activity and capacity to inhibit the lipogenic enzyme fatty acid synthase (FASN), which is overexpressed in several human carcinomas. To improve the pharmacological profile of EGCG, we previously developed a family of EGCG derivatives and the lead compounds G28, G37 and G56 were characterized in HER2-positive breast cancer cells overexpressing FASN. Here, diesters G28, G37 and G56 and two G28 derivatives, monoesters M1 and M2, were synthesized and assessed in vitro for their cytotoxic, FASN inhibition and apoptotic activities in MDA-MB-231 triple-negative breast cancer (TNBC) cells. All compounds displayed moderate to high cytotoxicity and significantly blocked FASN activity, monoesters M1 and M2 being more potent inhibitors than diesters. Interestingly, G28, M1, and M2 also diminished FASN protein expression levels, but only monoesters M1 and M2 induced apoptosis. Our results indicate that FASN inhibition by such polyphenolic compounds could be a new strategy in TNBC treatment, and highlight the potential anticancer activities of monoesters. Thus, G28, G37, G56, and most importantly M1 and M2, are anticancer candidates (alone or in combination) to be further characterized in vitro and in vivo.

  8. Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma growth by inhibiting inflammasome and IL-1β secretion

    International Nuclear Information System (INIS)

    Ellis, Lixia Z.; Liu, Weimin; Luo, Yuchun; Okamoto, Miyako; Qu, Dovina; Dunn, Jeffrey H.; Fujita, Mayumi

    2011-01-01

    Highlights: ► EGCG inhibits melanoma cell growth at physiological doses (0.1–1 μM). ► EGCG inhibits melanoma cell growth via inflammasomes and IL-1β suppression. ► Inflammasomes and IL-1β could be potential targets for future melanoma therapeutics. -- Abstract: Epigallocatechin-3-gallate (EGCG), the major polyphenolic component of green tea, has been demonstrated to possess anti-inflammatory, antioxidant, anti-mutagenic and anti-carcinogenic properties. The anti-melanoma effect of EGCG has been previously suggested, but no clear mechanism of action has been established. In this study, we demonstrated that EGCG inhibits melanoma cell growth at physiological doses (0.1–1 μM). In the search for mechanisms of EGCG-mediated melanoma cell suppression, we found that NF-κB was inhibited, and that reduced NF-κB activity was associated with decreased IL-1β secretion from melanoma cells. Since inflammasomes are involved in IL-1β secretion, we investigated whether IL-1β suppression was mediated by inflammasomes, and found that EGCG treatment led to downregulation of the inflammasome component, NLRP1, and reduced caspase-1 activation. Furthermore, silencing the expression of NLRP1 abolished EGCG-induced inhibition of tumor cell proliferation both in vitro and in vivo, suggesting a key role of inflammasomes in EGCG efficacy. This paper provides a novel mechanism for EGCG-induced melanoma inhibition: inflammasome downregulation → decreased IL-1β secretion → decreased NF-κB activities → decreased cell growth. In addition, it suggests inflammasomes and IL-1β could be potential targets for future melanoma therapeutics.

  9. Epigallocatechin-3-gallate attenuates apoptosis and autophagy in concanavalin A-induced hepatitis by inhibiting BNIP3

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    Li S

    2016-02-01

    Full Text Available Sainan Li, Yujing Xia, Kan Chen, Jingjing Li, Tong Liu, Fan Wang, Jie Lu, Yingqun Zhou, Chuanyong Guo Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China Background: Epigallocatechin-3-gallate (EGCG is the most effective compound in green tea, and possesses a wide range of beneficial effects, including anti-inflammatory, antioxidant, antiobesity, and anticancer effects. In this study, we investigated the protective effects of EGCG in concanavalin A (ConA-induced hepatitis in mice and explored the possible mechanisms involved in these effects.Methods: Balb/C mice were injected with ConA (25 mg/kg to induce acute autoimmune hepatitis, and EGCG (10 or 30 mg/kg was administered orally twice daily for 10 days before ConA injection. Serum liver enzymes, proinflammatory cytokines, and other marker proteins were determined 2, 8, and 24 hours after the ConA administration.Results: BNIP3 mediated cell apoptosis and autophagy in ConA-induced hepatitis. EGCG decreased the immunoreaction and pathological damage by reducing inflammatory factors, such as TNF-α, IL-6, IFN-γ, and IL-1β. EGCG also exhibited an antiapoptotic and antiautophagic effect by inhibiting BNIP3 via the IL-6/JAKs/STAT3 pathway.Conclusion: EGCG attenuated liver injury in ConA-induced hepatitis by downregulating IL-6/JAKs/STAT3/BNIP3-mediated apoptosis and autophagy. Keywords: concanavalin A, hepatitis, EGCG, autophagy, apoptosis, BNIP3, STAT3, JAKs, IL-6

  10. (--Epigallocatechin-3-Gallate Inhibits Arsenic-Induced Inflammation and Apoptosis through Suppression of Oxidative Stress in Mice

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    Nan-Hui Yu

    2017-04-01

    Full Text Available Background/Aims: Exposure to arsenic in individuals has been found to be associated with various health-related problems including skin lesions, cancer, and cardiovascular and immunological disorders. (--Epigallocatechin-3-gallate (EGCG, the main and active polyphenolic catechin present in green tea, has shown potent antioxidant, anti-apoptotic and anti-inflammatory activity in vivo and in vitro. Thus, the present study was conducted to investigate the protective effects of EGCG against arsenic-induced inflammation and immunotoxicity in mice. Methods: Serum IL-1β, IL-6 and TNF-α were determined by ELISA, tissue catalase (CAT, malonyldialdehyde (MDA, superoxide dismutase (SOD, glutathione (GSH, nitric oxide and caspase 3 by commercial kits, mitochondrial membrane potential with Rh 123, mitochondrial ROS with 2’,7’-dichlorofluorescin diacetate (DCFH-DA, apoptotic and necrotic cells and T-cell phenotyping with Flow cytometry analysis. Results: The results showed that arsenic treatment significantly increased oxidative stress levels (as indicated by catalase, malonyldialdehyde, superoxide dismutase, glutathione and reactive oxygen species, increased levels of inflammatory cytokines and promoted apoptosis. Arsenic exposure increased the relative frequency of the CD8+(Tc cell subpopulation (from 2.8 to 18.9% and decreased the frequency of CD4+(Th cells (from 5.2 to 2.7%. Arsenic exposure also significantly decreased the frequency of T(CD3 (from 32.5% to 19.2% and B(CD19 cells (from 55.1 to 32.5%. All of these effects induced by NaAsO2 were attenuated by EGCG. Conclusions: The present in vitro findings indicate that EGCG attenuates not only NaAsO2-induced immunosuppression but also inflammation and apoptosis.

  11. Inhibition of interaction between epigallocatechin-3-gallate and myofibrillar protein by cyclodextrin derivatives improves gel quality under oxidative stress.

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    Zhang, Yumeng; Chen, Lin; Lv, Yuanqi; Wang, Shuangxi; Suo, Zhiyao; Cheng, Xingguang; Xu, Xinglian; Zhou, Guanghong; Li, Zhixi; Feng, Xianchao

    2018-06-01

    High levels of polyphenols can interact with myofibrillar proteins (MPs), causing damage to a MP emulsion gel. In this study, β-cyclodextrins were used to reduce covalent and non-covalent interaction between epigallocatechin-3-gallate (EGCG) and MPs under oxidative stress. The loss of both thiol and free amine groups and the unfolding of MPs caused by EGCG (80 μM/g protein) were significantly prevented by β-cyclodextrins, and the structural stability and solubility were improved. MP emulsion gel treated with EGCG (80 μM/g protein) had the highest cooking loss (68.64%) and gel strength (0.51 N). Addition of β-cyclodextrins significantly reduced cooking loss (26.24-58.20%) and improved gel strength (0.31-0.41 N) of MP emulsion gel jeopardized by EGCG under oxidative stress. Damage to the emulsifying properties of MPs caused by EGCG was significantly prevented by addition of β-cyclodextrins. β-cyclodextrins reduced interaction between EGCG and MPs in the order Methyl-β-cyclodextrin > (2-Hydroxypropyl)-β-cyclodextrin > β-cyclodextrin. In absence of EGCG, addition of β-cyclodextrins partly protected MPs from oxidative attack and improved its solubility. It is concluded that β-cyclodextrins does not markedly reduce the antioxidant ability of EGCG according to carbonyl analysis, and can effectively increase EGCG loading to potentially provide more durable antioxidant effect for meat products during processing, transportation and storage. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Epigallocatechin-3-gallate Ameliorates Seawater Aspiration-Induced Acute Lung Injury via Regulating Inflammatory Cytokines and Inhibiting JAK/STAT1 Pathway in Rats

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    Liu, Wei; Dong, Mingqing; Bo, Liyan; Li, Congcong; Liu, Qingqing; Li, Yanyan; Ma, Lijie; Xie, Yonghong; Fu, Enqing; Mu, Deguang; Pan, Lei; Jin, Faguang; Li, Zhichao

    2014-01-01

    Signal transducers and activators of transcriptions 1 (STAT1) play an important role in the inflammation process of acute lung injury (ALI). Epigallocatechin-3-gallate (EGCG) exhibits a specific and strong anti-STAT1 activity. Therefore, our study is to explore whether EGCG pretreatment can ameliorate seawater aspiration-induced ALI and its possible mechanisms. We detected the arterial partial pressure of oxygen, lung wet/dry weight ratios, protein content in bronchoalveolar lavage fluid, and the histopathologic and ultrastructure staining of the lung. The levels of IL-1, TNF-α, and IL-10 and the total and the phosphorylated protein level of STAT1, JAK1, and JAK2 were assessed in vitro and in vivo. The results showed that EGCG pretreatment significantly improved hypoxemia and histopathologic changes, alleviated pulmonary edema and lung vascular leak, reduced the production of TNF-α and IL-1, and increased the production of IL-10 in seawater aspiration-induced ALI rats. EGCG also prevented the seawater aspiration-induced increase of TNF-α and IL-1 and decrease of IL-10 in NR8383 cell line. Moreover, EGCG pretreatment reduced the total and the phosphorylated protein level of STAT1 in vivo and in vitro and reduced the phosphorylated protein level of JAK1 and JAK2. The present study demonstrates that EGCG ameliorates seawater aspiration-induced ALI via regulating inflammatory cytokines and inhibiting JAK/STAT1 pathway in rats. PMID:24692852

  13. Green tea polyphenol epigallocatechin-3-gallate inhibits TLR4 signaling through the 67-kDa laminin receptor on lipopolysaccharide-stimulated dendritic cells

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    Byun, Eui-Baek; Choi, Han-Gyu; Sung, Nak-Yun; Byun, Eui-Hong

    2012-01-01

    Highlights: ► Expressions of CD80, CD86, and MHC class I/II were inhibited by EGCG via 67LR. ► EGCG-treated DCs inhibited LPS-induced pro-inflammatory cytokines via 67LR. ► EGCG-treated DCs inhibited MAPKs activation and NF-κB p65 translocation via 67LR. ► EGCG elevated the expression of the Tollip protein through 67LR in DCs. -- Abstract: Epigallocatechin-3-gallate (EGCG), a major active polyphenol of green tea, has been shown to down-regulate inflammatory responses in dendritic cells (DCs); however, the underlying mechanism has not been understood. Recently, we identified the 67-kDa laminin receptor (67LR) as a cell-surface EGCG receptor. In this study, we showed the molecular basis for the down-regulation of toll-like receptor 4 (TLR4) signal transduction by EGCG in DCs. The expressions of CD80, CD86, and MHC class I and II, which are molecules essential for antigen presentation by DCs, were inhibited by EGCG via 67LR. In addition, EGCG-treated DCs inhibited lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, and IL-6) and activation of mitogen-activated protein kinases (MAPKs), e.g., extracellular signal-regulated kinase 1/2 (ERK1/2), p38, c-Jun N-terminal kinase (JNK), and nuclear factor κB (NF-κB) p65 translocation through 67LR. Interestingly, we also found that EGCG markedly elevated the expression of the Tollip protein, a negative regulator of TLR signaling, through 67LR. These novel findings provide new insight into the understanding of negative regulatory mechanisms of the TLR4 signaling pathway and consequent inflammatory responses that are implicated in the development and progression of many chronic diseases.

  14. Green tea polyphenol epigallocatechin-3-gallate inhibits TLR4 signaling through the 67-kDa laminin receptor on lipopolysaccharide-stimulated dendritic cells

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    Byun, Eui-Baek [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Choi, Han-Gyu [Department of Microbiology and Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Sung, Nak-Yun [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Byun, Eui-Hong, E-mail: ehbyun80@gmail.com [Department of Microbiology and Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of)

    2012-10-05

    Highlights: Black-Right-Pointing-Pointer Expressions of CD80, CD86, and MHC class I/II were inhibited by EGCG via 67LR. Black-Right-Pointing-Pointer EGCG-treated DCs inhibited LPS-induced pro-inflammatory cytokines via 67LR. Black-Right-Pointing-Pointer EGCG-treated DCs inhibited MAPKs activation and NF-{kappa}B p65 translocation via 67LR. Black-Right-Pointing-Pointer EGCG elevated the expression of the Tollip protein through 67LR in DCs. -- Abstract: Epigallocatechin-3-gallate (EGCG), a major active polyphenol of green tea, has been shown to down-regulate inflammatory responses in dendritic cells (DCs); however, the underlying mechanism has not been understood. Recently, we identified the 67-kDa laminin receptor (67LR) as a cell-surface EGCG receptor. In this study, we showed the molecular basis for the down-regulation of toll-like receptor 4 (TLR4) signal transduction by EGCG in DCs. The expressions of CD80, CD86, and MHC class I and II, which are molecules essential for antigen presentation by DCs, were inhibited by EGCG via 67LR. In addition, EGCG-treated DCs inhibited lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokines (tumor necrosis factor [TNF]-{alpha}, interleukin [IL]-1{beta}, and IL-6) and activation of mitogen-activated protein kinases (MAPKs), e.g., extracellular signal-regulated kinase 1/2 (ERK1/2), p38, c-Jun N-terminal kinase (JNK), and nuclear factor {kappa}B (NF-{kappa}B) p65 translocation through 67LR. Interestingly, we also found that EGCG markedly elevated the expression of the Tollip protein, a negative regulator of TLR signaling, through 67LR. These novel findings provide new insight into the understanding of negative regulatory mechanisms of the TLR4 signaling pathway and consequent inflammatory responses that are implicated in the development and progression of many chronic diseases.

  15. Estrogen receptor-α36 is involved in epigallocatechin-3-gallate induced growth inhibition of ER-negative breast cancer stem/progenitor cells

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    Xiaohua Pan

    2016-02-01

    Full Text Available Epigallocatechin-3-gallate (EGCG is a type of catechin extracted from green tea, which is reported to have anticancer effects. EGCG is also reported to inhibit the cancer stem/progenitor cells in several estrogen receptor (ER-negative breast cancer cell lines, such as SUM-149, SUM-190 and MDA-MB-231. And all these cancer cells are highly expressed a new variant of ER-α, ER-α36. The aim of our present study is to determine the role of ER-α36 in the growth inhibitory activity of EGCG towards ER-negative breast cancer MDA-MB-231 and MDA-MB-436 cells. We found that EGCG potently inhibited the growth of cancer stem/progenitor cells in MDA-MB-231 and MDA-MB-436 cells, and also reduced the expression of ER-α36 in these cells. However, in ER-α36 knocked-down MDA-MB-231 and MDA-MB-436 cells, no significant inhibitory effects of EGCG on cancer stem/progenitor cells were observed. We also found that down-regulation of ER-α36 expression was in accordance with down-regulation of EGFR, which further verified a loop between ER-α36 and EGFR. Thus, our study indicated ER-α36 is involved in EGCG's inhibitory effects on ER-negative breast cancer stem/progenitor cells, which supports future preclinical and clinical evaluation of EGCG as a therapeutic option for ER-α36 positive breast cancer.

  16. Inhibition of EMMPRIN and MMP-9 Expression by Epigallocatechin-3-Gallate through 67-kDa Laminin Receptor in PMA-Induced Macrophages.

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    Wang, Qi-Ming; Wang, Hao; Li, Ya-Fei; Xie, Zhi-Yong; Ma, Yao; Yan, Jian-Jun; Gao, Yi Fan Wei; Wang, Ze-Mu; Wang, Lian-Sheng

    2016-01-01

    It is well documented that overexpression of EMMPRIN (extracellular matrix metalloproteinase inducer) and MMPs (matrix metalloproteinases) by monocytes/macrophages plays an important role in atherosclerotic plaque rupture. Green tea polyphenol epigallocatechin-3-gallate (EGCG) has a variety of pharmacological properties and exerts cardiovascular protective effects. Recently, the 67-kD laminin receptor (67LR) has been identified as a cell surface receptor of EGCG. The aim of the present study was to evaluate the effects of EGCG on the expression of EMMPRIN and MMP-9 in PMA-induced macrophages, and the potential mechanisms underlying its effects. Human monocytic THP-1 cells were induced to differentiate into macrophages with phorbol 12-myristate 13-acetate (PMA). Protein expression and MMP-9 activity were assayed by Western blot and Gelatin zymography, respectively. Real-time PCR was used to examine EMMPRIN and MMP-9 mRNA expression. We showed that EGCG (10-50µmol/L) significantly inhibited the expression of EMMPRIN and MMP-9 and activation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 and c-Jun N-terminal kinase (JNK) in PMA-induced macrophages. Downregulation of EMMPRIN by gene silencing hindered PMA-induced MMP-9 secretion and expression, indicating an important role of EMMPRIN in the inhibition of MMP-9 by EGCG. Moreover, 67LR was involved in EGCG-mediated suppression of EMMPRIN and MMP-9 expression. Anti-67LR antibody treatment led to abrogation of the inhibitory action of EGCG on the expression of EMMPRIN and MMP-9 and activation of ERK1/2, p38, and JNK. Our results indicate that EGCG restrains EMMPRIN and MMP-9 expression via 67LR in PMA-induced macrophages, which also suggests that EGCG may be a possible therapeutic agent for stabilizing atherosclerotic plaque. © 2016 The Author(s) Published by S. Karger AG, Basel.

  17. Inhibition of EMMPRIN and MMP-9 Expression by Epigallocatechin-3-Gallate through 67-kDa Laminin Receptor in PMA-Induced Macrophages

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    Qi-Ming Wang

    2016-11-01

    Full Text Available Background/Aims: It is well documented that overexpression of EMMPRIN (extracellular matrix metalloproteinase inducer and MMPs (matrix metalloproteinases by monocytes/macrophages plays an important role in atherosclerotic plaque rupture. Green tea polyphenol epigallocatechin-3-gallate (EGCG has a variety of pharmacological properties and exerts cardiovascular protective effects. Recently, the 67-kD laminin receptor (67LR has been identified as a cell surface receptor of EGCG. The aim of the present study was to evaluate the effects of EGCG on the expression of EMMPRIN and MMP-9 in PMA-induced macrophages, and the potential mechanisms underlying its effects. Methods: Human monocytic THP-1 cells were induced to differentiate into macrophages with phorbol 12-myristate 13-acetate (PMA. Protein expression and MMP-9 activity were assayed by Western blot and Gelatin zymography, respectively. Real-time PCR was used to examine EMMPRIN and MMP-9 mRNA expression. Results: We showed that EGCG (10-50µmol/L significantly inhibited the expression of EMMPRIN and MMP-9 and activation of extracellular signal-regulated kinase 1/2 (ERK1/2, p38 and c-Jun N-terminal kinase (JNK in PMA-induced macrophages. Downregulation of EMMPRIN by gene silencing hindered PMA-induced MMP-9 secretion and expression, indicating an important role of EMMPRIN in the inhibition of MMP-9 by EGCG. Moreover, 67LR was involved in EGCG-mediated suppression of EMMPRIN and MMP-9 expression. Anti-67LR antibody treatment led to abrogation of the inhibitory action of EGCG on the expression of EMMPRIN and MMP-9 and activation of ERK1/2, p38, and JNK. Conclusion: Our results indicate that EGCG restrains EMMPRIN and MMP-9 expression via 67LR in PMA-induced macrophages, which also suggests that EGCG may be a possible therapeutic agent for stabilizing atherosclerotic plaque.

  18. Epigallocatechin-3-gallate Promotes Osteoblastic Activity in Human ...

    African Journals Online (AJOL)

    Keywords: Epigallocatechin-3-gallate, Osteoporosis, Osteoclast, Proliferation, Estrogen receptor. Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (SciSearch), Scopus,. International Pharmaceutical Abstract, Chemical Abstracts, Embase, Index Copernicus, EBSCO, African. Index Medicus ...

  19. Potential benefit of (--epigallocatechin-3-gallate for macrovascular complications in diabetes

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    L. Tang

    2017-08-01

    Full Text Available Vascular problems are the most common complications in diabetes. Substantial evidence from epidemiological and pathophysiological studies show that hyperglycemia is a major risk factor for macrovascular complications in patients with diabetes. (--Epigallocatechin-3-gallate (EGCG, the major catechin derived from green tea, is known to exert a variety of cardiovascular beneficial effects. The protective effects of EGCG in diabetes are also evident. However, whether EGCG is beneficial against macrovascular complications that occur in diabetes remains unknown. Our previous studies demonstrated that treatment of EGCG inhibits high glucose-induced vascular smooth muscle cell proliferation and suppresses high glucose-mediated vascular inflammation in human umbilical vein endothelial cells. Therefore, we hypothesize that EGCG might be an effective potential candidate to reduce the macrovascular complications in diabetes.

  20. Effects of Epigallocatechin-3-Gallate on Autophagic Lipolysis in Adipocytes

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    Sang-Nam Kim

    2017-06-01

    Full Text Available Previous studies demonstrated effects of green tea on weight loss; however, green tea-induced modulation of adipocyte function is not fully understood. Here, we investigated effects of the major green tea phytochemical, epigallocatechin-3-gallate (EGCG on triglyceride contents, lipolysis, mitochondrial function, and autophagy, in adipocytes differentiated from C3H10T1/2 cells and immortalized pre-adipocytes in vitro. EGCG reduced the triglycerol content significantly in adipocytes by 25%, comparable to the nutrient starvation state. EGCG did not affect protein kinase A signaling or brown adipocyte marker expression in adipocytes; however, EGCG increased autophagy, as measured by autophagy flux analysis and immunoblot analysis of LC3B, ATG7, and Beclin1. EGCG treatment reduced mitochondrial membrane potential by 56.8% and intracellular ATP levels by 49.1% compared to controls. Although mammalian target of rapamycin signaling was not upregulated by EGCG treatment, EGCG treatment induced AMP-activated protein kinase phosphorylation, indicating an energy-depleted state. In addition, EGCG increased the association between RAB7 and lipid droplets, suggesting that lipophagy was activated. Finally, knockdown of Rab7 attenuated the EGCG-dependent reduction in lipid contents. Collectively, these results indicated that EGCG upregulated autophagic lipolysis in adipocytes, supporting the therapeutic potential of EGCG as a caloric restriction mimetic to prevent obesity and obesity-related metabolic diseases.

  1. Selective Inhibitory Effect of Epigallocatechin-3-gallate on Migration of Vascular Smooth Muscle Cells

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    Jong-Chul Park

    2010-11-01

    Full Text Available In order to prevent restenosis after angioplasty or stenting, one of the most popular targets is suppression of the abnormal growth and excess migration of vascular smooth muscle cells (VSMCs with drugs. However, the drugs also adversely affect vascular endothelial cells (VECs, leading to the induction of late thrombosis. We have investigated the effect of epigallocatechin-3-gallate (EGCG on the proliferation and migration of VECs and VSMCs. Both cells showed dose-dependent decrease of viability in response to EGCG while they have different IC50 values of EGCG (VECs, 150 mM and VSMCs, 1050 mM. Incubating both cells with EGCG resulted in significant reduction in cell proliferation irrespective of cell type. The proliferation of VECs were greater affected than that of VSMCs at the same concentrations of EGCG. EGCG exerted differential migration-inhibitory activity in VECs vs. VSMCs. The migration of VECs was not attenuated by 200 mM EGCG, but that of VSMCs was significantly inhibited at the same concentration of EGCG. It is suggested that that EGCG can be effectively used as an efficient drug for vascular diseases or stents due to its selective activity, completely suppressing the proliferation and migration of VSMCs, but not adversely affecting VECs migration in blood vessels.

  2. Green tea polyphenol epigallocatechin-3-gallate differentially modulates oxidative stress in PC12 cell compartments

    International Nuclear Information System (INIS)

    Raza, Haider; John, Annie

    2005-01-01

    Tea polyphenols have been reported to be potent antioxidants and beneficial in oxidative stress related diseases. Prooxidant effects of tea polyphenols have also been reported in cell culture systems. In the present study, we have studied oxidative stress in the subcellular compartments of PC12 cells after treatment with different concentrations of the green tea polyphenol, epigallocatechin-3-gallate (EGCG). We have demonstrated that EGCG has differentially affected the production of reactive oxygen species (ROS), glutathione (GSH) metabolism and cytochrome P450 2E1 activity in the different subcellular compartments in PC12 cells. Our results have shown that although the cell survival was not inhibited by EGCG, there was, however, an increased DNA breakdown and activation of apoptotic markers, caspase 3 and poly- (ADP-ribose) polymerase (PARP) at higher concentrations of EGCG treatment. Our results suggest that the differential effects of EGCG might be related to the alterations in oxidative stress, GSH pools and CYP2E1 activity in different cellular compartments. These results may have implications in determining the chemopreventive therapeutic use of tea polyphenols in vivo

  3. Lysosomal trafficking of β-catenin induced by the tea polyphenol epigallocatechin-3-gallate

    International Nuclear Information System (INIS)

    Dashwood, Wan-Mohaiza; Carter, Orianna; Al-Fageeh, Mohamed; Li, Qingjie; Dashwood, Roderick H.

    2005-01-01

    β-Catenin is a cadherin-binding protein involved in cell-cell adhesion, which also functions as a transcriptional activator when complexed in the nucleus with members of the T-cell factor (TCF)/lymphoid enhancer factor (LEF) family of proteins. There is considerable interest in mechanisms that down-regulate β-catenin, since this provides an avenue for the prevention of colorectal and other cancers in which β-catenin is frequently over-expressed. We show here that physiologically relevant concentrations of the tea polyphenol epigallocatechin-3-gallate (EGCG) inhibited β-catenin/TCF-dependent reporter activity in human embryonic kidney 293 cells transfected with wild type or mutant β-catenins, and there was a corresponding decrease in β-catenin protein levels in the nuclear, cytosolic and membrane-associated fractions. However, β-catenin accumulated as punctate aggregates in response to EGCG treatment, including in human colon cancer cells over-expressing β-catenin endogenously. Confocal microscopy studies revealed that the aggregated β-catenin in HEK293 cells was extra-nuclear and co-localized with lysosomes, suggesting that EGCG activated a pathway involving lysosomal trafficking of β-catenin. Lysosomal inhibitors leupeptin and transepoxysuccinyl-L-leucylamido(4-guanido)butane produced an increase in β-catenin protein in total cell lysates, without a concomitant increase in β-catenin transcriptional activity. These data provide the first evidence that EGCG facilitates the trafficking of β-catenin into lysosomes, presumably as a mechanism for sequestering β-catenin and circumventing further nuclear transport and activation of β-catenin/TCF/LEF signaling

  4. Lysosomal trafficking of {beta}-catenin induced by the tea polyphenol epigallocatechin-3-gallate

    Energy Technology Data Exchange (ETDEWEB)

    Dashwood, Wan-Mohaiza [Linus Pauling Institute, 571 Weniger Hall, Oregon State University, Corvallis, OR 97331-6512 (United States); Carter, Orianna [Linus Pauling Institute, 571 Weniger Hall, Oregon State University, Corvallis, OR 97331-6512 (United States); Al-Fageeh, Mohamed [Linus Pauling Institute, 571 Weniger Hall, Oregon State University, Corvallis, OR 97331-6512 (United States); Li, Qingjie [Linus Pauling Institute, 571 Weniger Hall, Oregon State University, Corvallis, OR 97331-6512 (United States); Dashwood, Roderick H. [Linus Pauling Institute, 571 Weniger Hall, Oregon State University, Corvallis, OR 97331-6512 (United States)]. E-mail: Rod.Dashwood@oregonstate.edu

    2005-12-11

    {beta}-Catenin is a cadherin-binding protein involved in cell-cell adhesion, which also functions as a transcriptional activator when complexed in the nucleus with members of the T-cell factor (TCF)/lymphoid enhancer factor (LEF) family of proteins. There is considerable interest in mechanisms that down-regulate {beta}-catenin, since this provides an avenue for the prevention of colorectal and other cancers in which {beta}-catenin is frequently over-expressed. We show here that physiologically relevant concentrations of the tea polyphenol epigallocatechin-3-gallate (EGCG) inhibited {beta}-catenin/TCF-dependent reporter activity in human embryonic kidney 293 cells transfected with wild type or mutant {beta}-catenins, and there was a corresponding decrease in {beta}-catenin protein levels in the nuclear, cytosolic and membrane-associated fractions. However, {beta}-catenin accumulated as punctate aggregates in response to EGCG treatment, including in human colon cancer cells over-expressing {beta}-catenin endogenously. Confocal microscopy studies revealed that the aggregated {beta}-catenin in HEK293 cells was extra-nuclear and co-localized with lysosomes, suggesting that EGCG activated a pathway involving lysosomal trafficking of {beta}-catenin. Lysosomal inhibitors leupeptin and transepoxysuccinyl-L-leucylamido(4-guanido)butane produced an increase in {beta}-catenin protein in total cell lysates, without a concomitant increase in {beta}-catenin transcriptional activity. These data provide the first evidence that EGCG facilitates the trafficking of {beta}-catenin into lysosomes, presumably as a mechanism for sequestering {beta}-catenin and circumventing further nuclear transport and activation of {beta}-catenin/TCF/LEF signaling.

  5. Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Fen; Sun, Hong; Kluz, Thomas; Clancy, Hailey A.; Kiok, Kathrin; Costa, Max, E-mail: Max.Costa@nyumc.org

    2012-01-15

    Hexavalent chromium [Cr(VI)] is a human carcinogen that results in the generation of reactive oxygen species (ROS) and a variety of DNA lesions leading to cell death. Epigallocatechin-3-gallate (EGCG), the major polyphenol present in green tea, possesses potent antioxidative activity capable of protecting normal cells from various stimuli-induced oxidative stress and cell death. Here we demonstrated that co-treatment with EGCG protected human normal bronchial epithelial BEAS-2B cells from Cr(VI)-induced cell death in a dose-dependent manner. Cr(VI) induces apoptosis as the primary mode of cell death. Co-treatment of BEAS-2B cells with EGCG dose-dependently suppressed Cr(VI)-induced apoptosis. Fluorescence microscopic analyses and quantitative measurement revealed that EGCG significantly decreased intracellular levels of ROS induced by Cr(VI) exposure. Using a well-established K{sup +}/SDS precipitation assay, we further showed that EGCG was able to dose-dependently reduce DNA–protein cross-links (DPC), lesions that could be partially attributed to Cr(VI)-induced oxidative stress. Finally, analyses of Affymetrix microarray containing 28,869 well-annotated genes revealed that, among the 3412 genes changed more than 1.5-fold by Cr(VI) treatment, changes of 2404 genes (70%) were inhibited by pretreatment of EGCG. Real-time PCR confirmed the induction of 3 genes involved in cell death and apoptosis by Cr(VI), which was eliminated by EGCG. In contrast, Cr(VI) reduced the expression of 3 genes related to cellular defense, and this reduction was inhibited by EGCG. Our results indicate that EGCG protects BEAS-2B cells from Cr(VI)-induced cytotoxicity presumably by scavenging ROS and modulating a subset of genes. EGCG, therefore, might serve as a potential chemopreventive agent against Cr(VI) carcinogenesis. -- Highlights: ► EGCG protected human normal bronchial epithelial BEAS-2B cells from Cr(VI)-induced cell death and apoptosis. ► EGCG significantly decreased

  6. Synergistic Anticancer Effects of Vorinostat and Epigallocatechin-3-Gallate against HuCC-T1 Human Cholangiocarcinoma Cells

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    Tae Won Kwak

    2013-01-01

    Full Text Available The aim of this study was to investigate the effect of the combination of vorinostat and epigallocatechin-3-gallate against HuCC-T1 human cholangiocarcinoma cells. A novel chemotherapy strategy is required as cholangiocarcinomas rarely respond to conventional chemotherapeutic agents. Both vorinostat and EGCG induce apoptosis and suppress invasion, migration, and angiogenesis of tumor cells. The combination of vorinostat and EGCG showed synergistic growth inhibitory effects and induced apoptosis in tumor cells. The Bax/Bcl-2 expression ratio and caspase-3 and -7 activity increased, but poly (ADP-ribose polymerase expression decreased when compared to treatment with each agent alone. Furthermore, invasion, matrix metalloproteinase (MMP expression, and migration of tumor cells decreased following treatment with the vorinostat and EGCG combination compared to those of vorinostat or EGCG alone. Tube length and junction number of human umbilical vein endothelial cells (HUVECs decreased as well as vascular endothelial growth factor expression following vorinostat and EGCG combined treatment. These results indicate that the combination of vorinostat and EGCG had a synergistic effect on inhibiting tumor cell angiogenesis potential. We suggest that the combination of vorinostat and EGCG is a novel option for cholangiocarcinoma chemotherapy.

  7. Green tea epigallocatechin-3-gallate modulates differentiation of naive CD4+ T cells into specific lineage effector cells

    Science.gov (United States)

    CD4+ T helper (Th) subsets Th1, Th9, and Th17 cells are implicated in inducing autoimmunity whereas regulatory T cells (Treg) have a protective effect. We previously showed that epigallocatechin-3-gallate (EGCG) attenuated experimental autoimmune encephalomyelitis (EAE) and altered CD4+ T cell subpo...

  8. Induction of apoptosis by epigallocatechin-3-gallate in human lymphoblastoid B cells

    International Nuclear Information System (INIS)

    Noda, Chiseko; He, Jinsong; Takano, Tomoko; Tanaka, Chisato; Kondo, Toshinori; Tohyama, Kaoru; Yamamura, Hirohei; Tohyama, Yumi

    2007-01-01

    (-)-Epigallocatechin-3-gallate (EGCG), a major constituent of green tea polyphenols, has been shown to suppress cancer cell proliferation and induce apoptosis. In this study we investigated its efficacy and the mechanism underlying its effect using human B lymphoblastoid cell line Ramos, and effect of co-treatment with EGCG and a chemotherapeutic agent on apoptotic cell death. EGCG induced dose- and time-dependent apoptotic cell death accompanied by loss of mitochondrial transmembrane potential, release of cytochrome c into the cytosol, and cleavage of pro-caspase-9 to its active form. EGCG also enhanced production of intracellular reactive oxygen species (ROS). Pretreatment with diphenylene iodonium chloride, an inhibitor of NAD(P)H oxidase and an antioxidant, partially suppressed both EGCG-induced apoptosis and production of ROS, implying that oxidative stress is involved in the apoptotic response. Furthermore, we showed that combined-treatment with EGCG and a chemotherapeutic agent, etoposide, synergistically induced apoptosis in Ramos cells

  9. Combined Treatment With Environmental Enrichment and (-)-Epigallocatechin-3-Gallate Ameliorates Learning Deficits and Hippocampal Alterations in a Mouse Model of Down Syndrome.

    Science.gov (United States)

    Catuara-Solarz, Silvina; Espinosa-Carrasco, Jose; Erb, Ionas; Langohr, Klaus; Gonzalez, Juan Ramon; Notredame, Cedric; Dierssen, Mara

    2016-01-01

    Intellectual disability in Down syndrome (DS) is accompanied by altered neuro-architecture, deficient synaptic plasticity, and excitation-inhibition imbalance in critical brain regions for learning and memory. Recently, we have demonstrated beneficial effects of a combined treatment with green tea extract containing (-)-epigallocatechin-3-gallate (EGCG) and cognitive stimulation in young adult DS individuals. Although we could reproduce the cognitive-enhancing effects in mouse models, the underlying mechanisms of these beneficial effects are unknown. Here, we explored the effects of a combined therapy with environmental enrichment (EE) and EGCG in the Ts65Dn mouse model of DS at young age. Our results show that combined EE-EGCG treatment improved corticohippocampal-dependent learning and memory. Cognitive improvements were accompanied by a rescue of cornu ammonis 1 (CA1) dendritic spine density and a normalization of the proportion of excitatory and inhibitory synaptic markers in CA1 and dentate gyrus.

  10. Quantitation of chemopreventive synergism between (-)-epigallocatechin-3-gallate and curcumin in normal, premalignant and malignant human oral epithelial cells.

    Science.gov (United States)

    Khafif, A; Schantz, S P; Chou, T C; Edelstein, D; Sacks, P G

    1998-03-01

    An in vitro model for oral cancer was used to examine the growth inhibitory effects of chemopreventive agents when used singly and in combination. The model consists of primary cultures of normal oral epithelial cells, newly established cell lines derived from dysplastic leukoplakia and squamous cell carcinoma. Two naturally occurring substances, (-)-epigallocatechin-3-gallate (EGCG) from green tea and curcumin from the spice turmeric were tested. Cells were treated singly and in combination and effects on growth determined in 5-day growth assays and by cell cycle analysis. Effective dose 50s and the combination index were calculated with the computerized Chou-Talalay method which is based on the median-effect principle. Agents were shown to differ in their inhibitory potency. EGCG was less effective with cell progression; the cancer cells were more resistant than normal or dysplastic cells. In contrast, curcumin was equally effective regardless of the cell type tested. Cell cycle analysis indicated that EGCG blocked cells in G1, whereas curcumin blocked cells in S/G2M. The combination of both agents showed synergistic interactions in growth inhibition and increased sigmoidicity (steepness) of the dose-effect curves, a response that was dose and cell type dependent. Combinations allowed for a dose reduction of 4.4-8.5-fold for EGCG and 2.2-2.8-fold for curcumin at ED50s as indicated by the dose reduction index (DRI). Even greater DRI values were observed above ED50 levels. Our results demonstrate that this model which includes normal, premalignant and malignant oral cells can be used to analyse the relative potential of various chemopreventive agents. Two such naturally-occurring agents, EGCG and curcumin, were noted to inhibit growth by different mechanisms, a factor which may account for their demonstrable interactive synergistic effect.

  11. Different fatty acid metabolism effects of (−-Epigallocatechin-3-Gallate and C75 in Adenocarcinoma lung cancer

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    Relat Joana

    2012-07-01

    Full Text Available Abstract Background Fatty acid synthase (FASN is overexpressed and hyperactivated in several human carcinomas, including lung cancer. We characterize and compare the anti-cancer effects of the FASN inhibitors C75 and (−-epigallocatechin-3-gallate (EGCG in a lung cancer model. Methods We evaluated in vitro the effects of C75 and EGCG on fatty acid metabolism (FASN and CPT enzymes, cellular proliferation, apoptosis and cell signaling (EGFR, ERK1/2, AKT and mTOR in human A549 lung carcinoma cells. In vivo, we evaluated their anti-tumour activity and their effect on body weight in a mice model of human adenocarcinoma xenograft. Results C75 and EGCG had comparable effects in blocking FASN activity (96,9% and 89,3% of inhibition, respectively. In contrast, EGCG had either no significant effect in CPT activity, the rate-limiting enzyme of fatty acid β-oxidation, while C75 stimulated CPT up to 130%. Treating lung cancer cells with EGCG or C75 induced apoptosis and affected EGFR-signaling. While EGCG abolished p-EGFR, p-AKT, p-ERK1/2 and p-mTOR, C75 was less active in decreasing the levels of EGFR and p-AKT. In vivo, EGCG and C75 blocked the growth of lung cancer xenografts but C75 treatment, not EGCG, caused a marked animal weight loss. Conclusions In lung cancer, inhibition of FASN using EGCG can be achieved without parallel stimulation of fatty acid oxidation and this effect is related mainly to EGFR signaling pathway. EGCG reduce the growth of adenocarcinoma human lung cancer xenografts without inducing body weight loss. Taken together, EGCG may be a candidate for future pre-clinical development.

  12. Evaluation of nanohydroxyapaptite (nano-HA) coated epigallocatechin-3-gallate (EGCG) cross-linked collagen membranes.

    Science.gov (United States)

    Chu, Chenyu; Deng, Jia; Man, Yi; Qu, Yili

    2017-09-01

    Collagen is the main component of extracellular matrix (ECM) with desirable biological activities and low antigenicity. Collagen materials have been widely utilized in guided bone regeneration (GBR) surgery due to its abilities to maintain space for hard tissue growth. However, pure collagen lacks optimal mechanical properties. In our previous study, epigallocatechin-3-gallate (EGCG) cross-linked collagen membranes, with better biological activities and enhanced mechanical properties, may promote osteoblast proliferation, but their effect on osteoblast differentiation is not very significant. Nanohydroxyapatite (nano-HA) is the main component of mineral bone, which possesses exceptional bioactivity properties including good biocompatibility, high osteoconductivity and osteoinductivity, non-immunogenicity and non-inflammatory behavior. Herein, by analyzing the physical and chemical properties as well as the effects on promoting bone regeneration, we have attempted to present a novel EGCG-modified collagen membrane with nano-HA coating, and have found evidence that the novel collagen membrane may promote bone regeneration with a better surface morphology, without destroying collagen backbone. To evaluate the surface morphologies, chemical and mechanical properties of pure collagen membranes, epigallocatechin-3-gallate (EGCG) cross-linked collagen membranes, nano-HA coated collagen membranes, nano-HA coated EGCG-collagen membranes, (ii) to evaluate the bone regeneration promoted by theses membranes. In the present study, collagen membranes were divided into 4 groups: (1) untreated collagen membranes (2) EGCG cross-linked collagen membranes (3) nano-HA modified collagen membranes (4) nano-HA modified EGCG-collagen membranes. Scanning electron microscope (SEM) and Fourier transform infrared spectroscopy (FTIR) were used to evaluate surface morphologies and chemical properties, respectively. Mechanical properties were determined by differential scanning calorimeter (DSC

  13. Transdermal solid delivery of epigallocatechin-3-gallate using self-double-emulsifying drug delivery system as vehicle: Formulation, evaluation and vesicle-skin interaction.

    Science.gov (United States)

    Hu, Caibiao; Gu, Chengyu; Fang, Qiao; Wang, Qiang; Xia, Qiang

    2016-02-01

    The present study investigated a self-double-emulsifying drug delivery system loaded with epigallocatechin-3-gallate to improve epigallocatechin-3-gallate skin retention. The long chain solid lipids (cetostearyl alcohol) and macadamia oil were utilized as a carrier to deliver the bioactive ingredient. Response surface methodology was used to optimize the formulation, and the solid lipid to total lipid weight ratio, concentration of epigallocatechin-3-gallate and hydrophilic surfactant on skin retention were found to be the principal factors. The optimum formulation with high encapsulation efficiency (95.75%), self-double-emulsification performance (99.58%) and skin retention (87.24%) were derived from the fitted models and experimentally examined, demonstrating a reasonable agreement between experimental and predicted values. Epigallocatechin-3-gallate-self-double-emulsifying drug delivery system was found to be stable for 3 months. Transdermal studies could explain a higher skin diffusion of epigallocatechin-3-gallate from the self-double-emulsifying drug delivery system compared with EGCG aqueous solution. In vitro cytotoxicity showed that epigallocatechin-3-gallate-self-double-emulsifying drug delivery system did not exert hazardous effect on L929 cells up to 1:10. © The Author(s) 2015.

  14. Epigallocatechin-3-Gallate Protects Erythrocyte Ca2+-ATPase and Na+/K+-ATPase Against Oxidative Induced Damage During Aging in Humans

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    Prabhanshu Kumar

    2014-10-01

    Full Text Available Purpose: The main purpose of this study was to investigate the protective role of epigallocatechin-3-gallate on tertiary butyl hydroperoxide induced oxidative damage in erythrocyte during aging in humans. Methods: Human erythrocyte membrane bound Ca2+-ATPase and Na+/K+-ATPase activities were determined as a function of human age. Protective role of epigallocatechin-3-gallate was evaluated by in vitro experiments by adding epigallocatechin-3-gallate in concentration dependent manner (final concentration range 10-7M to 10-4M to the enzyme assay medium. Oxidative stress was induced in vitro by incubating washed erythrocyte ghosts with tertiary butyl hydroperoxide (10-5 M final concentration. Results: We have reported concentration dependent effect of epigallocatechin-3-gallate on tertiary butyl hydroperoxide induced damage on activities of Ca2+-ATPase and Na+/K+-ATPase during aging in humans. We have detected a significant (p < 0.001 decreased activity of Ca2+-ATPase and Na+/K+ -ATPase as a function of human age. Epigallocatechin-3-gallate protected ATPases against tertiary butyl hydroperoxide induced damage in concentration dependent manner during aging in humans. Conclusion: Epigallocatechin-3-gallate is a powerful antioxidant that is capable of protecting erythrocyte Ca2+-ATPase and Na+/K+ -ATPase against oxidative stress during aging in humans. We may propose hypothesis that a high intake of catechin rich diet may provide some protection against development of aging and age related diseases.

  15. Green tea (-)-epigallocatechin-3-gallate counteracts daytime overeating induced by high-fat diet in mice.

    Science.gov (United States)

    Li, Hongyu; Kek, Huiling Calvina; Lim, Joy; Gelling, Richard Wayne; Han, Weiping

    2016-12-01

    High-fat diet (HFD) induces overeating and obesity. Green tea (-)-epigallocatechin-3-gallate (EGCG) reduces HFD-induced body weight and body fat gain mainly through increased lipid metabolism and fat oxidation. However, little is known about its effect on HFD-induced alterations in feeding behavior. Three diet groups of wildtype C57B/6j male mice at 5 months old were fed on normal chow diet, 1 week of HFD (60% of energy) and 3 months of HFD (diet-induced obesity (DIO)) prior to EGCG supplement in respective diet. EGCG had no effect on feeding behavior in normal chow diet group. Increased daytime feeding induced by HFD was selectively corrected by EGCG treatment in HFD groups, including reversed food intake, feeding frequency and meal size in HFD + EGCG group, and reduced food intake and feeding frequency in DIO + EGCG group. Moreover, EGCG treatment altered diurnally oscillating expression pattern of key appetite-regulating genes, including AGRP, POMC, and CART, and key circadian genes Clock and Bmal1 in hypothalamus of DIO mice, indicating its central effect on feeding regulation. Our study demonstrates that EGCG supplement specifically counteracts daytime overeating induced by HFD in mice, suggesting its central role in regulating feeding behavior and energy homeostasis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Effect of processing on physicochemical characteristics and bioefficacy of β-lactoglobulin-epigallocatechin-3-gallate complexes.

    Science.gov (United States)

    Lestringant, Pauline; Guri, Anilda; Gülseren, Ibrahim; Relkin, Perla; Corredig, Milena

    2014-08-20

    Varying amounts of epigallocatechin-3-gallate (EGCG) were encapsulated in β-lactoglobulin (β-Lg) nanoparticles, either native or processed, denoted as heated or desolvated protein. The stability, physical properties, and bioactivity of the β-Lg-EGCG complexes were tested. Native β-Lg-EGCG complexes showed comparable stability and binding efficacy (EGCG/β-Lg molar ratio of 1:1) to heated β-Lg nanoparticles (1% and 5% protein w/w). The sizes of heated and desolvated β-Lg nanoparticles were comparable, but the latter showed the highest binding affinity for EGCG. The presence of EGCG complexed with β-Lg did not affect the interfacial tension of the protein when tested at the soy oil-water interface but caused a decrease in dilational elasticity. All β-Lg complexes (native, heated, or desolvated) showed a decrease in cellular proliferation similar to that of free ECGC. In summary, protein-EGCG complexes did not alter the bioefficacy of EGCG and contributed to increased stability with storage, demonstrating the potential benefits of nanoencapsulation.

  17. Mechanisms of saccharide protection against epigallocatechin-3-gallate deterioration in aqueous solutions.

    Science.gov (United States)

    Shpigelman, Avi; Zisapel, Adi; Cohen, Yifat; Livney, Yoav D

    2013-08-15

    We investigated the mechanisms of the protection conferred by sugars to epigallocatechin-3-gallate (EGCG) against deterioration. Additionally, we present a rapid method for evaluating the deterioration rate of EGCG using absorbance spectroscopy. We found that various sugars provided different levels of protection at identical weight percentage, and the combination of sugars and β-lactoglobulin nanocomplexes provided greater protection for EGCG than each protective component alone. We suggest that the concentration-dependent protection by sugars resulted from a combination of mechanisms, including: (1) reduced aqueous O2 solubility, (2) scavenging of reactive oxygen species, and (3) chelation of traces of transition metal ions, which is suggested to be the main reason for the differences among the sugars. The observed protective effect of sugars can be easily applied by the industry in proper selection of sugars for enrichment of syrups or concentrates with EGCG and for the preparation of enriched beverages and foods for health promotion. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Hippocampal Neuroprotection by Minocycline and Epigallo-Catechin-3-Gallate Against Cardiopulmonary Bypass-Associated Injury.

    Science.gov (United States)

    Salameh, Aida; Einenkel, Anne; Kühne, Lydia; Grassl, Maria; von Salisch, Sandy; Kiefer, Phillip; Vollroth, Marcel; Dähnert, Ingo; Dhein, Stefan

    2015-11-01

    Surgical correction of congenital cardiac malformations mostly implies the use of cardiopulmonary bypass (CPB). However, a possible negative impact of CPB on cerebral structures like the hippocampus cannot be neglected. Therefore, we investigated the effect of CPB on hippocampus CA1 and CA3 regions without or with the addition of epigallocatechin-3-gallate (EGCG) or minocycline. We studied 42 piglets and divided them into six experimental groups: control without or with EGCG or minocycline, CPB without or with EGCG or minocycline. The piglets underwent 90 minutes CPB and subsequently, a 120-minute recovery and reperfusion phase. Thereafter, histology of the hippocampus was performed and the adenosine triphosphate (ATP) content was measured. Histologic evaluation revealed that CPB produced a significant peri-cellular edema in both CA regions. Moreover, we found an increased number of cells stained with markers for hypoxia, apoptosis and nitrosative stress. Most of these alterations were significantly reduced to or near to control levels by application of EGCG or minocycline. ATP content was significantly reduced within the hippocampus after CPB. This reduction could not be antagonized by EGCG or minocycline. In conclusion, CPB had a significant negative impact on the integrity of hippocampal neural cells. This cellular damage could be significantly attenuated by addition of EGCG or minocycline. © 2015 International Society of Neuropathology.

  19. Epigallocatechin-3-gallate protects Kuruma shrimp Marsupeneaus japonicus from white spot syndrome virus and Vibrio alginolyticus.

    Science.gov (United States)

    Wang, Zhi; Sun, Baozhen; Zhu, Fei

    2018-07-01

    Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea and exhibits potential antibacterial and anticancer activities. In this study, EGCG was used in pathogen-challenge experiments in shrimp to discover its effect on the innate immune system of an invertebrate. Kuruma shrimp Marsupeneaus japonicus was used as an experimental model and challenged with white spot syndrome virus (WSSV) and the Gram-negative bacterium Vibrio alginolyticus. Pathogen-challenge experiments showed that EGCG pretreatment significantly delayed and reduced mortality upon WSSV and V. alginolyticus infection, with VP-28 copies of WSSV also reduced. Quantitative reverse transcription polymerase chain reaction revealed the positive influence of EGCG on several innate immune-related genes, including IMD, proPO, QM, myosin, Rho, Rab7, p53, TNF-alpha, MAPK, and NOS, and we observed positive influences on three immune parameters, including total hemocyte count and phenoloxidase and superoxide dismutase activities, by EGCG treatment. Additionally, results showed that EGCG treatment significantly reduced apoptosis upon V. alginolyticus challenge. These results indicated the positive role of EGCG in the shrimp innate immune system as an enhancer of immune parameters and an inhibitor of apoptosis, thereby delaying and reducing mortality upon pathogen challenge. Our findings provide insight into potential therapeutic or preventive functions associated with EGCG to enhance shrimp immunity and protect shrimp from pathogen infection. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. The effects of (-)-epigallocatechin-3-gallate on the proliferation and differentiation of human megakaryocytic progenitor cells

    International Nuclear Information System (INIS)

    Monzen, Satoru; Takahashi, Kenji; Abe, Yoshinao; Kashiwakura, Ikuo; Mori, Takao; Inanami, Osamu; Kuwabara, Mikinori

    2006-01-01

    Epigallocatechin-3-gallate (EGCg) has been widely recognized as a powerful antioxidant and free radical scavenger. The effects of EGCg on the proliferation and differentiation of X-irradiated megakaryocytic progenitor cells (colony-forming unit-megakaryocyte, CFU-Meg) using CD34 + cells prepared from human placental and umbilical cord blood have been shown. In the absence of exogenous thrombopoietin (TPO), no colonies are observed in cultures containing or lacking EGCg (1 nM-100 μM). In the presence of TPO, in contrast, EGCg significantly promotes CFU-Meg-derived colony formations within the 10-100 nM range. A 1.5-fold increase in the total number of CFU-Meg has been counted compared with the control. These favorable effects of EGCg are also observed in the culture of CD34 + cells before and after X irradiation with 2 Gy. Moreover, in order to investigate the function of EGCg promoting megakaryocyto-poiesis and thrombopoiesis in ex vivo cultures, both non-irradiated and X-irradiated CD34 + cells are grown in liquid cultures supplemented with TPO. In both cultures, EGCg increases the total number of cells and megakaryocytes. It has been suggested that the favorable effects of EGCg reduce the risk factor from radiation damage in megakaryocytopoiesis. (author)

  1. Photodegradation of (-)-epigallocatechin-3-gallate in topical cream formulations and its photostabilization.

    Science.gov (United States)

    Bianchi, Anna; Marchetti, Nicola; Scalia, Santo

    2011-12-05

    The aim of the study was to examine the photostability of the major catechin of green tea, (-)-epigallocatechin-3-gallate (EGCG), which possesses important antioxidant and skin photoprotective properties. In order to simulate realistic conditions of use of topical preparations, the photolysis studies were performed in model creams (oil-in-water emulsions) containing 1% (w/w) EGCG and exposed to a solar simulator at an irradiance corresponding to natural sunlight. The extent of photodegradation was measured by HPLC-UV and HPLC-ESI-MS. EGCG was found to decompose by 68.9±2.3%, after 1h irradiation. Addition of the coantioxidants, vitamin E or butylated hydroxytoluene to the emulsion formulation, significantly enhanced the photolability of the catechin, the EGCG loss reached 85.7±1.3% and 80.5±1.4%, respectively. On the other hand, inclusion of the UVB (290-320nm) filter, ethylhexyl methoxycinnamate in the cream produced a small but significant reduction of EGCG photodegradation to 61.0±2.9%, while the UVA (320-400nm) filter, butyl methoxydibenzoylmethane was ineffective (EGCG degradation, 67.8±1.5%). A more marked decrease in the light-induced decomposition of EGCG to 51.6±2.7% was achieved, under the same conditions, using the water-soluble UVB filter, benzophenone-4 (BP-4). This effect was concentration dependent, maximal EGCG photostabilization (catechin loss, 29.4±2.2%) was attained in the presence of 2.1% (w/w) BP-4. Therefore, BP-4 represents a useful additive to improve the light stability of EGCG in topical formulations for skin photoprotection. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Inhibitory effects of epigallocatechin-3-gallate on cell proliferation and the expression of HIF-1α and P-gp in the human pancreatic carcinoma cell line PANC-1.

    Science.gov (United States)

    Zhu, Zhenni; Wang, Yu; Liu, Zhiqing; Wang, Fan; Zhao, Qiu

    2012-05-01

    The aim of this study was to verify the inhibitory effects of epigallocatechin-3-gallate (EGCG) on cell proliferation and the expression of hypoxia-inducible factor 1 (HIF-1α) and multidrug resistance protein 1 (MDR1/P-gp) in the human pancreatic carcinoma cell line PANC-1, thereby, reversing drug resistance of pancreatic carcinoma and improving its sensitivity to cancer chemotherapy. The human pancreatic carcinoma cell line PANC-1 was incubated under hypoxic conditions with different concentrations of epigallocatechin-3-gallate (EGCG) for indicated hours. The effects of EGCG on the mRNA or protein expression of HIF-1α and MDR1 were determined by RT-PCR or western blotting. Cellular proliferation and viability assays were measured using Cell Counting Kit-8. Western blotting revealed that EGCG inhibits the expression of the HIF-1α protein in a dose-dependent manner, while RT-PCR showed that it does not have any effects on HIF-1α mRNA. In addition, EGCG attenuated the mRNA and protein levels of P-gp in a dose-dependent manner, reaching a peak at the highest concentration. Furthermore, EGCG inhibited the proliferation of PANC-1 cells in a concentration- and time-dependent manner. The attenuation of HIF-1α and the consequently reduced P-gp could contribute to the inhibitory effects of EGCG on the proliferation of PANC-1 cells.

  3. Evaluation of epigallocatechin-3-gallate (EGCG) cross-linked collagen membranes and concerns on osteoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Chenyu; Deng, Jia [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 (China); Xiang, Lin; Wu, Yingying [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 (China); Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 (China); Wei, Xiawei [State Key Laboratory of Biotherapy and Laboratory for Aging Research, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041 (China); Qu, Yili [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 (China); Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 (China); Man, Yi, E-mail: manyi780203@126.com [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 (China); Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 (China)

    2016-10-01

    Collagen membranes have ideal biological and mechanical properties for supporting infiltration and proliferation of osteoblasts and play a vital role in guided bone regeneration (GBR). However, pure collagen can lead to inflammation, resulting in progressive bone resorption. Therefore, a method for regulating the level of inflammatory cytokines at surgical sites is paramount for the healing process. Epigallocatechin-3-gallate (EGCG) is a component extracted from green tea with numerous biological activities including an anti-inflammatory effect. Herein, we present a novel cross-linked collagen membrane containing different concentrations of EGCG (0.0064%, 0.064%, and 0.64%) to regulate the level of inflammatory factors secreted by pre-osteoblast cells; improve cell proliferation; and increase the tensile strength, wettability, and thermal stability of collagen membranes. Scanning electron microscope images show that the surfaces of collagen membranes became smoother and the collagen fiber diameters became larger with EGCG treatment. Measurement of the water contact angle demonstrated that introducing EGCG improved membrane wettability. Fourier transform infrared spectroscopy analyses indicated that the backbone of collagen was intact, and the thermal stability was significant improved in differential scanning calorimetry. The mechanical properties of 0.064% and 0.64% EGCG-treated collagen membranes were 1.5-fold greater than those of the control. The extent of cross-linking was significantly increased, as determined by a 2,4,6-trinitrobenzenesulfonic acid solution assay. The Cell Counting Kit-8 (CCK-8) and live/dead assays revealed that collagen membrane cross-linked by 0.0064% EGCG induced greater cell proliferation than pure collagen membranes. Additionally, real-time polymerase chain reaction and enzyme-linked immunosorbent assay results showed that EGCG significantly affected the production of inflammatory factors secreted by MC3T3-E1 cells. Taken together, our

  4. Epigallocatechin-3-gallate suppresses the expression of HSP70 and HSP90 and exhibits anti-tumor activity in vitro and in vivo

    International Nuclear Information System (INIS)

    Tran, Phan LCHB; Kim, Soo-A; Choi, Hong Seok; Yoon, Jung-Hoon; Ahn, Sang-Gun

    2010-01-01

    Epigallocatechin-3-gallate (EGCG), one of the major catechins in green tea, is a potential chemopreventive agent for various cancers. The aim of this study was to examine the effect of EGCG on the expression of heat shock proteins (HSPs) and tumor suppression. Cell colony formation was evaluated by a soft agar assay. Transcriptional activity of HSP70 and HSP90 was determined by luciferase reporter assay. An EGCG-HSPs complex was prepared using EGCG attached to the cyanogen bromide (CNBr)-activated Sepharose 4B. In vivo effect of EGCG on tumor growth was examined in a xenograft model. Treatment with EGCG decreased cell proliferation and colony formation of MCF-7 human breast cancer cells. EGCG specifically inhibited the expression of HSP70 and HSP90 by inhibiting the promoter activity of HSP70 and HSP90. Pretreatment with EGCG increased the stress sensitivity of MCF-7 cells upon heat shock (44°C for 1 h) or oxidative stress (H 2 O 2 , 500 μM for 24 h). Moreover, treatment with EGCG (10 mg/kg) in a xenograft model resulted in delayed tumor incidence and reduced tumor size, as well as the inhibition of HSP70 and HSP90 expression. Overall, these findings demonstrate that HSP70 and HSP90 are potent molecular targets of EGCG and suggest EGCG as a drug candidate for the treatment of human cancer

  5. Epigallocatechin-3-Gallate (EGCG Promotes Autophagy-Dependent Survival via Influencing the Balance of mTOR-AMPK Pathways upon Endoplasmic Reticulum Stress

    Directory of Open Access Journals (Sweden)

    Marianna Holczer

    2018-01-01

    Full Text Available The maintenance of cellular homeostasis is largely dependent on the ability of cells to give an adequate response to various internal and external stimuli. We have recently proposed that the life-and-death decision in endoplasmic reticulum (ER stress response is defined by a crosstalk between autophagy, apoptosis, and mTOR-AMPK pathways, where the transient switch from autophagy-dependent survival to apoptotic cell death is controlled by GADD34. The aim of the present study was to investigate the role of epigallocatechin-3-gallate (EGCG, the major polyphenol of green tea, in promoting autophagy-dependent survival and to verify the key role in connecting GADD34 with mTOR-AMPK pathways upon prolonged ER stress. Our findings, obtained by using HEK293T cells, revealed that EGCG treatment is able to extend cell viability by inducing autophagy. We confirmed that EGCG-induced autophagy is mTOR-dependent and PKA-independent; furthermore, it also required ULK1. We show that pretreatment of cells with EGCG diminishes the negative effect of GADD34 inhibition (by guanabenz or siGADD34 treatment on autophagy. EGCG was able to delay apoptotic cell death by upregulating autophagy-dependent survival even in the absence of GADD34. Our data suggest a novel role for EGCG in promoting cell survival via shifting the balance of mTOR-AMPK pathways in ER stress.

  6. Epigallocatechin-3-Gallate Suppresses Human Herpesvirus 8 Replication and Induces ROS Leading to Apoptosis and Autophagy in Primary Effusion Lymphoma Cells

    Directory of Open Access Journals (Sweden)

    Ching-Yi Tsai

    2017-12-01

    Full Text Available Epigallocatechin-3-gallate (EGCG, the major constituent of green tea, has been shown to induce cell death in cancer cells. Primary effusion lymphoma (PEL is an aggressive neoplasm caused by human herpesvirus 8 (HHV8. In this study, we examined the role of EGCG on PEL cells in cell death and HHV8 replication. We performed trypan blue exclusion assay to assess the cell viability of PEL cells, flow cytometry analysis to examine the cell cycle distribution and reactive oxygen species (ROS generation, caspase-3 activity to assay apoptosis, acridine orange staining to determine autophagy, and immunoblotting to detect the protein levels involved in apoptosis and autophagy as well as mitogen activated protein kinases (MAPKs activation upon EGCG treatment. The expression of the HHV8 lytic gene was determined by luciferase reporter assay and reverse transcription-PCR, and viral progeny production was determined by PCR. Results revealed that EGCG induced cell death and ROS generation in PEL cells in a dose-dependent manner. N-acetylcysteine (NAC inhibited the EGCG-induced ROS and rescued the cell from EGCG-induced cell death. Even though EGCG induced ROS generation in PEL cells, it reduced the production of progeny virus from PEL cells without causing HHV8 reactivation. These results suggest that EGCG may represent a novel strategy for the treatment of HHV8 infection and HHV8-associated lymphomas.

  7. Combined epigallocatechin-3-gallate and resveratrol supplementation for 12 wk increases mitochondrial capacity and fat oxidation, but not insulin sensitivity, in obese humans: a randomized controlled trial

    NARCIS (Netherlands)

    Most, Jasper; Timmers, S.; Warnke, I.; Jocken, J.J.W.; Boekschoten, M.V.; Groot, de Philip; Bendik, Igor; Schrauwen, Patrick; Goossens, Gijs H.; Blaak, Ellen E.

    2016-01-01

    Background: The obese insulin-resistant state is characterized by
    impairments in lipid metabolism.We previously showed that 3-d supplementation
    of combined epigallocatechin-3-gallate and resveratrol
    (EGCG+RES) increased energy expenditure and improved the
    capacity to switch from fat

  8. New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate

    Directory of Open Access Journals (Sweden)

    Hae-Suk Kim

    2014-01-01

    Full Text Available Green tea is rich in polyphenol flavonoids including catechins. Epigallocatechin 3-gallate (EGCG is the most abundant and potent green tea catechin. EGCG has been extensively studied for its beneficial health effects as a nutriceutical agent. Based upon its chemical structure, EGCG is often classified as an antioxidant. However, treatment of cells with EGCG results in production of hydrogen peroxide and hydroxyl radicals in the presence of Fe (III. Thus, EGCG functions as a pro-oxidant in some cellular contexts. Recent investigations have revealed many other direct actions of EGCG that are independent from anti-oxidative mechanisms. In this review, we discuss these novel molecular mechanisms of action for EGCG. In particular, EGCG directly interacts with proteins and phospholipids in the plasma membrane and regulates signal transduction pathways, transcription factors, DNA methylation, mitochondrial function, and autophagy to exert many of its beneficial biological actions.

  9. Impact of 5-aza-2'-deoxycytidine and epigallocatechin-3-gallate for induction of human regulatory T cells.

    Science.gov (United States)

    Kehrmann, Jan; Tatura, Roman; Zeschnigk, Michael; Probst-Kepper, Michael; Geffers, Robert; Steinmann, Joerg; Buer, Jan

    2014-07-01

    The epigenetic regulation of transcription factor genes is critical for T-cell lineage specification. A specific methylation pattern within a conserved region of the lineage specifying transcription factor gene FOXP3, the Treg-specific demethylated region (TSDR), is restricted to regulatory T (Treg) cells and is required for stable expression of FOXP3 and suppressive function. We analysed the impact of hypomethylating agents 5-aza-2'-deoxycytidine and epigallocatechin-3-gallate on human CD4(+)  CD25(-) T cells for generating demethylation within FOXP3-TSDR and inducing functional Treg cells. Gene expression, including lineage-specifying transcription factors of the major T-cell lineages and their leading cytokines, functional properties and global transcriptome changes were analysed. The FOXP3-TSDR methylation pattern was determined by using deep amplicon bisulphite sequencing. 5-aza-2'-deoxycytidine induced FOXP3-TSDR hypomethylation and expression of the Treg-cell-specific genes FOXP3 and LRRC32. Proliferation of 5-aza-2'-deoxycytidine-treated cells was reduced, but the cells did not show suppressive function. Hypomethylation was not restricted to FOXP3-TSDR and expression of master transcription factors and leading cytokines of T helper type 1 and type 17 cells were induced. Epigallocatechin-3-gallate induced global DNA hypomethylation to a lesser extent than 5-aza-2'-deoxycitidine, but no relevant hypomethylation within FOXP3-TSDR or expression of Treg-cell-specific genes. Neither of the DNA methyltransferase inhibitors induced fully functional human Treg cells. 5-aza-2'-deoxycitidine-treated cells resembled Treg cells, but they did not suppress proliferation of responder cells, which is an essential capability to be used for Treg cell transfer therapy. Using a recently developed targeted demethylation technology might be a more promising approach for the generation of functional Treg cells. © 2014 John Wiley & Sons Ltd.

  10. Epigallocatechin-3-gallate increases intracellular [Ca2+] in U87 cells mainly by influx of extracellular Ca2+ and partly by release of intracellular stores.

    Science.gov (United States)

    Kim, Hee Jung; Yum, Keun Sang; Sung, Jong-Ho; Rhie, Duck-Joo; Kim, Myung-Jun; Min, Do Sik; Hahn, Sang June; Kim, Myung-Suk; Jo, Yang-Hyeok; Yoon, Shin Hee

    2004-02-01

    Green tea has been receiving considerable attention as a possible preventive agent against cancer and cardiovascular disease. Epigallocatechin-3-gallate (EGCG) is a major polyphenol component of green tea. Using digital calcium imaging and an assay for [3H]-inositol phosphates, we determined whether EGCG increases intracellular [Ca2+] ([Ca2+]i) in non-excitable human astrocytoma U87 cells. EGCG induced concentration-dependent increases in [Ca2+]i. The EGCG-induced [Ca2+]i increases were reduced to 20.9% of control by removal of extracellular Ca2+. The increases were also inhibited markedly by treatment with the non-specific Ca2+ channel inhibitors cobalt (3 mM) for 3 min and lanthanum (1 mM) for 5 min. The increases were not significantly inhibited by treatment for 10 min with the L-type Ca2+ channel blocker nifedipine (100 nM). Treatment with the inhibitor of endoplasmic reticulum Ca2+-ATPase thapsigargin (1 micro M) also significantly inhibited the EGCG-induced [Ca2+]i increases. Treatment for 15 min with the phospholipase C (PLC) inhibitor neomycin (300 micro M) attenuated the increases significantly, while the tyrosine kinase inhibitor genistein (30 micro M) had no effect. EGCG increased [3H]-inositol phosphates formation via PLC activation. Treatment for 10 min with mefenamic acid (100 micro M) and flufenamic acid (100 micro M), derivatives of diphenylamine-2-carboxylate, blocked the EGCG-induced [Ca2+]i increase in non-treated and thapsigargin-treated cells but indomethacin (100 micro M) did not affect the increases. Collectively, these data suggest that EGCG increases [Ca2+]i in non-excitable U87 cells mainly by eliciting influx of extracellular Ca2+ and partly by mobilizing intracellular Ca2+ stores by PLC activation. The EGCG-induced [Ca2+]i influx is mediated mainly through channels sensitive to diphenylamine-2-carboxylate derivatives.

  11. Short- and long-term effects of neonatal pharmacotherapy with epigallocatechin-3-gallate on hippocampal development in the Ts65Dn mouse model of Down syndrome.

    Science.gov (United States)

    Stagni, Fiorenza; Giacomini, Andrea; Emili, Marco; Trazzi, Stefania; Guidi, Sandra; Sassi, Martina; Ciani, Elisabetta; Rimondini, Roberto; Bartesaghi, Renata

    2016-10-01

    Cognitive disability is an unavoidable feature of Down syndrome (DS), a genetic disorder due to the triplication of human chromosome 21. DS is associated with alterations of neurogenesis, neuron maturation and connectivity that are already present at prenatal life stages. Recent evidence shows that pharmacotherapies can have a large impact on the trisomic brain provided that they are administered perinatally. Epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea, performs many actions in the brain, including inhibition of DYRK1A, a kinase that is over-expressed in the DS brain and contributes to the DS phenotype. Young adults with DS treated with EGCG exhibit some cognitive benefits, although these effects disappear with time. We deemed it extremely important, however, to establish whether treatment with EGCG at the initial stages of brain development leads to plastic changes that outlast treatment cessation. In the current study, we exploited the Ts65Dn mouse model of DS in order to establish whether pharmacotherapy with EGCG during peak of neurogenesis in the hippocampal dentate gyrus (DG) enduringly restores hippocampal development and memory performance. Euploid and Ts65Dn mice were treated with EGCG from postnatal day 3 (P3) to P15. The effects of treatment were examined at its cessation (at P15) or after one month (at P45). We found that at P15 treated trisomic pups exhibited restoration of neurogenesis, total hippocampal granule cell number and levels of pre- and postsynaptic proteins in the DG, hippocampus and neocortex. However, at P45 none of these effects were still present, nor did treated Ts65Dn mice exhibit any improvement in hippocampus-dependent tasks. These findings show that treatment with EGCG carried out in the neonatal period rescues numerous trisomy-linked brain alterations. However, even during this, the most critical time window for hippocampal development, EGCG does not elicit enduring effects on the hippocampal physiology

  12. The Bmi-1 helix–turn and ring finger domains are required for Bmi-1 antagonism of (–) epigallocatechin-3-gallate suppression of skin cancer cell survival

    Science.gov (United States)

    Balasubramanian, Sivaprakasam; Scharadin, Tiffany M.; Han, Bingshe; Xu, Wen; Eckert, Richard L.

    2016-01-01

    The Bmi-1 Polycomb group (PcG) protein is an important epigenetic regulator of chromatin status. Elevated Bmi-1 expression is observed in skin cancer and contributes to cancer cell survival. (–) Epigallocatechin-3-gallate (EGCG), an important green tea-derived cancer prevention agent, reduces Bmi-1 level resulting in reduced skin cancer cell survival. This is associated with increased p21Cip1 and p27Kip1 expression, reduced cyclin, and cyclin dependent kinase expression, and increased cleavage of apoptotic markers. These EGCG-dependent changes are attenuated by vector-mediated maintenance of Bmi-1 expression. In the present study, we identify Bmi-1 functional domains that are required for this response. Bmi-1 expression reverses the EGCG-dependent reduction in SCC-13 cell survival, but Bmi-1 mutants lacking the helix–turn–helix–turn–helix–turn (Bmi-1ΔHT) or ring finger (Bmi-1ΔRF) domains do not reverse the EGCG impact. The reduction in Ring1B ubiquitin ligase activity, observed in the presence of mutant Bmi-1, is associated with reduced ability of these mutants to interact with and activate Ring1B ubiquitin ligase, the major ligase responsible for the ubiquitination of histone H2A during chromatin condensation. This results in less chromatin condensation leading to increased tumor suppressor gene expression and reduced cell survival; thereby making the cells more susceptible to the anti-survival action of EGCG. We further show that these mutants act in a dominant-negative manner to inhibit the action of endogenous Bmi-1. Our results suggest that the HT and RF domains are required for Bmi-1 ability to maintain skin cancer cell survival in response to cancer preventive agents. PMID:25843776

  13. Antibacterial activity of epigallocatechin-3-gallate (EGCG) and its synergism with β-lactam antibiotics sensitizing carbapenem-associated multidrug resistant clinical isolates of Acinetobacter baumannii.

    Science.gov (United States)

    Lee, Spencer; Razqan, Ghaida Saleh Al; Kwon, Dong H

    2017-01-15

    Infections caused by Acinetobacter baumannii were responsive to conventional antibiotic therapy. However, recently, carbapenem-associated multidrug resistant isolates have been reported worldwide and present a major therapeutic challenge. Epigallocatechin-3-Gallate (EGCG) extracted from green tea exhibits antibacterial activity. We evaluated the antibacterial activity of EGCG and possible synergism with antibiotics in carbapenem-associated multidrug resistant A. baumannii. A potential mechanism for synergism was also explored. Seventy clinical isolates of A. baumannii collected from geographically different areas were analyzed by minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of EGCG. Checkerboard and time-killing assays were performed to exam the synergism between EGCG and antibiotics. The effects of EGCG on a multidrug efflux pump inhibitor (1-[1-naphthylmethyl] piperazine; NMP) and β-lactamase production were also examined in A. baumannii. Sixty-three of 70 clinical isolates of A. baumannii carried carbapenemase-encoding genes with carbapenem-associated multidrug resistance. Levels of MIC and MBC of EGCG ranged from 64 to 512µg/ml and from 128 to ≥1024µg/ml, respectively among the clinical isolates. MIC 90 and MBC 86 levels were 256µg/ml and 512µg/ml of EGCG, respectively. Subinhibitory concentration of EGCG in combination with all antibiotics tested, including carbapenem, sensitized (MICs fall≤1.0µg/ml) all carbapenem-associated multidrug resistant isolates. Checkerboard and time-killing assays showed synergism between EGCG and meropenem (or carbenicillin) counted as fractional inhibitory concentration of 2log10 within 12h, respectively. EGCG significantly increased the effect of NMP but was unrelated to β-lactamase production in A. baumannii, suggesting EGCG may be associated with inhibition of efflux pumps. Overall we suggest that EGCG-antibiotic combinations might provide an alternative approach to treat

  14. Repeated dose studies with pure Epigallocatechin-3-gallate demonstrated dose and route dependant hepatotoxicity with associated dyslipidemia.

    Science.gov (United States)

    Ramachandran, Balaji; Jayavelu, Subramani; Murhekar, Kanchan; Rajkumar, Thangarajan

    2016-01-01

    EGCG (Epigallocatechin-3-gallate) is the major active principle catechin found in green tea. Skepticism regarding the safety of consuming EGCG is gaining attention, despite the fact that it is widely being touted for its potential health benefits, including anti-cancer properties. The lack of scientific data on safe dose levels of pure EGCG is of concern, while EGCG has been commonly studied as a component of GTE (Green tea extract) and not as a single active constituent. This study has been carried out to estimate the maximum tolerated non-toxic dose of pure EGCG and to identify the treatment related risk factors. In a fourteen day consecutive treatment, two different administration modalities were compared, offering an improved [i.p (intraperitoneal)] and limited [p.o (oral)] bioavailability. A trend of dose and route dependant hepatotoxicity was observed particularly with i.p treatment and EGCG increased serum lipid profile in parallel to hepatotoxicity. Fourteen day tolerable dose of EGCG was established as 21.1 mg/kg for i.p and 67.8 mg/kg for p.o. We also observed that, EGCG induced effects by both treatment routes are reversible, subsequent to an observation period for further fourteen days after cessation of treatment. It was demonstrated that the severity of EGCG induced toxicity appears to be a function of dose, route of administration and period of treatment.

  15. Epigallocatechin-3-gallate (EGCG) protects skin cells from ionizing radiation via heme oxygenase-1 (HO-1) overexpression

    International Nuclear Information System (INIS)

    Zhu Wei; Xu Jing; Ge Yangyang

    2014-01-01

    Epigallocatechin-3-gallate (EGCG), the major polyphenolic constituent of green tea, is a potent antioxidant and free radical scavenger that may have therapeutic applications for the treatment of many disorders. Radiation therapy is widely used for the treatment of various types of cancers; however, radiation-induced skin injury remains a serious concern. EGCG has not yet been reported as protecting skin cells against ionizing radiation. In the present study, we investigated whether EGCG confers cytoprotection against ionizing radiation. We found that, compared with the control, pretreatment with EGCG significantly enhanced the viability of human skin cells that were irradiated with X-rays, and decreased apoptosis induced by X-ray irradiation. Mito-Tracker assay showed that EGCG suppressed the damage to mitochondria induced by ionizing radiation via upregulation of SOD2. Reactive oxygen species (ROS) in HaCaT cells were significantly reduced when pretreated with EGCG before irradiation. Radiation-induced γH2AX foci, which are representative of DNA double-strand breaks, were decreased by pretreatment with EGCG. Furthermore, EGCG induced the expression of the cytoprotective molecule heme oxygenase-1 (HO-1) in a dose-dependent manner via transcriptional activation. HO-1 knockdown or treatment with the HO-1 inhibitor tin protoporphyrin (SnPPIX) reversed the protective role of EGCG, indicating an important role for HO-1. These results suggest that EGCG offers a new strategy for protecting skin against ionizing radiation. (author)

  16. Combination of ascorbate/epigallocatechin-3-gallate/gemcitabine synergistically induces cell cycle deregulation and apoptosis in mesothelioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Martinotti, Simona [Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale “Amedeo Avogadro”, viale T. Michel 11, 15121 Alessandria (Italy); Ranzato, Elia, E-mail: ranzato@unipmn.it [Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale “Amedeo Avogadro”, viale T. Michel 11, 15121 Alessandria (Italy); Parodi, Monica [IRCCS A.O.U. S. Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, 16132 Genova (Italy); DI.ME.S., Università degli Studi di Genova, Via L. Alberti 2, 16132 Genova (Italy); Vitale, Massimo [IRCCS A.O.U. S. Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, 16132 Genova (Italy); Burlando, Bruno [Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale “Amedeo Avogadro”, viale T. Michel 11, 15121 Alessandria (Italy)

    2014-01-01

    Malignant mesothelioma (MMe) is a poor-prognosis tumor in need of innovative therapies. In a previous in vivo study, we showed synergistic anti-MMe properties of the ascorbate/epigallocatechin-3-gallate/gemcitabine combination. We have now focused on the mechanism of action, showing the induction of apoptosis and cell cycle arrest through measurements of caspase 3, intracellular Ca{sup 2+}, annexin V, and DNA content. StellArray™ PCR technology and Western immunoblotting revealed DAPK2-dependent apoptosis, upregulation of cell cycle promoters, downregulation of cell cycle checkpoints and repression of NFκB expression. The complex of data indicates that the mixture is synergistic in inducing cell cycle deregulation and non-inflammatory apoptosis, suggesting its possible use in MMe treatment. - Highlights: • Ascorbate/epigallocathechin-gallate/gemcitabine has been tested on mesothelioma cells • A synergistic mechanism has been shown for cell cycle arrest and apoptosis • PCR-array analysis has revealed the de-regulation of apoptosis and cell cycle genes • Maximum upregulation has been found for the Death-Associated Protein Kinase-2 gene • Data suggest that the mixture could be used as a clinical treatment.

  17. Survivin knockdown increased anti-cancer effects of (-)-epigallocatechin-3-gallate in human malignant neuroblastoma SK-N-BE2 and SH-SY5Y cells

    Energy Technology Data Exchange (ETDEWEB)

    Hossain, Md. Motarab [Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC (United States); Banik, Naren L. [Department of Neurosciences, Medical University of South Carolina, Charleston, SC (United States); Ray, Swapan K., E-mail: swapan.ray@uscmed.sc.edu [Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC (United States)

    2012-08-01

    Neuroblastoma is a solid tumor that mostly occurs in children. Malignant neuroblastomas have poor prognosis because conventional chemotherapeutic agents are hardly effective. Survivin, which is highly expressed in some malignant neuroblastomas, plays a significant role in inhibiting differentiation and apoptosis and promoting cell proliferation, invasion, and angiogenesis. We examined consequences of survivin knockdown by survivin short hairpin RNA (shRNA) plasmid and then treatment with (-)-epigallocatechin-3-gallate (EGCG), a green tea flavonoid, in malignant neuroblastoma cells. Our Western blotting and laser scanning confocal immunofluorescence microscopy showed that survivin was highly expressed in malignant neuroblastoma SK-N-BE2 and SH-SY5Y cell lines and slightly in SK-N-DZ cell line. Expression of survivin was very faint in malignant neuroblastoma IMR32 cell line. We transfected SK-N-BE2 and SH-SY-5Y cells with survivin shRNA, treated with EGCG, and confirmed knockdown of survivin at mRNA and protein levels. Survivin knockdown induced morphological features of neuronal differentiation, as we observed following in situ methylene blue staining. Combination of survivin shRNA and EGCG promoted neuronal differentiation biochemically by increases in the expression of NFP, NSE, and e-cadherin and also decreases in the expression of Notch-1, ID2, hTERT, and PCNA. Our in situ Wright staining and Annexin V-FITC/PI staining showed that combination therapy was highly effective in inducing, respectively, morphological and biochemical features of apoptosis. Apoptosis occurred with activation of caspase-8 and cleavage of Bid to tBid, increase in Bax:Bcl-2 ratio, mitochondrial release of cytochrome c, and increases in the expression and activity of calpain and caspase-3. Combination therapy decreased migration of cells through matrigel and inhibited proliferative (p-Akt and NF-{kappa}B), invasive (MMP-2 and MMP-9), and angiogenic (VEGF and b-FGF) factors. Also, in vitro

  18. Survivin knockdown increased anti-cancer effects of (-)-epigallocatechin-3-gallate in human malignant neuroblastoma SK-N-BE2 and SH-SY5Y cells.

    Science.gov (United States)

    Hossain, Md Motarab; Banik, Naren L; Ray, Swapan K

    2012-08-01

    Neuroblastoma is a solid tumor that mostly occurs in children. Malignant neuroblastomas have poor prognosis because conventional chemotherapeutic agents are hardly effective. Survivin, which is highly expressed in some malignant neuroblastomas, plays a significant role in inhibiting differentiation and apoptosis and promoting cell proliferation, invasion, and angiogenesis. We examined consequences of survivin knockdown by survivin short hairpin RNA (shRNA) plasmid and then treatment with (-)-epigallocatechin-3-gallate (EGCG), a green tea flavonoid, in malignant neuroblastoma cells. Our Western blotting and laser scanning confocal immunofluorescence microscopy showed that survivin was highly expressed in malignant neuroblastoma SK-N-BE2 and SH-SY5Y cell lines and slightly in SK-N-DZ cell line. Expression of survivin was very faint in malignant neuroblastoma IMR32 cell line. We transfected SK-N-BE2 and SH-SY-5Y cells with survivin shRNA, treated with EGCG, and confirmed knockdown of survivin at mRNA and protein levels. Survivin knockdown induced morphological features of neuronal differentiation, as we observed following in situ methylene blue staining. Combination of survivin shRNA and EGCG promoted neuronal differentiation biochemically by increases in the expression of NFP, NSE, and e-cadherin and also decreases in the expression of Notch-1, ID2, hTERT, and PCNA. Our in situ Wright staining and Annexin V-FITC/PI staining showed that combination therapy was highly effective in inducing, respectively, morphological and biochemical features of apoptosis. Apoptosis occurred with activation of caspase-8 and cleavage of Bid to tBid, increase in Bax:Bcl-2 ratio, mitochondrial release of cytochrome c, and increases in the expression and activity of calpain and caspase-3. Combination therapy decreased migration of cells through matrigel and inhibited proliferative (p-Akt and NF-κB), invasive (MMP-2 and MMP-9), and angiogenic (VEGF and b-FGF) factors. Also, in vitro

  19. Green tea polyphenol, (−)-epigallocatechin-3-gallate, induces toxicity in human skin cancer cells by targeting β-catenin signaling

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    Singh, Tripti [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Katiyar, Santosh K., E-mail: skatiyar@uab.edu [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Birmingham Veterans Affairs Medical Center, Birmingham, AL 35233 (United States)

    2013-12-01

    The green tea polyphenol, (−)-epigallocatechin-3-gallate (EGCG), has been shown to have anti-carcinogenic effects in several skin tumor models, and efforts are continued to investigate the molecular targets responsible for its cytotoxic effects to cancer cells. Our recent observation that β-catenin is upregulated in skin tumors suggested the possibility that the anti-skin carcinogenic effects of EGCG are mediated, at least in part, through its effects on β-catenin signaling. We have found that treatment of the A431 and SCC13 human skin cancer cell lines with EGCG resulted in reduced cell viability and increased cell death and that these cytotoxic effects were associated with inactivation of β-catenin signaling. Evidence of EGCG-induced inactivation of β-catenin included: (i) reduced accumulation of nuclear β-catenin; (ii) enhanced levels of casein kinase1α, reduced phosphorylation of glycogen synthase kinase-3β, and increased phosphorylation of β-catenin on critical serine{sup 45,33/37} residues; and (iii) reduced levels of matrix metalloproteinase (MMP)-2 and MMP-9, which are down-stream targets of β-catenin. Treatment of cells with prostaglandin E2 (PGE{sub 2}) enhanced the accumulation of β-catenin and enhanced β-catenin signaling. Treatment with either EGCG or an EP2 antagonist (AH6809) reduced the PGE{sub 2}-enhanced levels of cAMP, an upstream regulator of β-catenin. Inactivation of β-catenin by EGCG resulted in suppression of cell survival signaling proteins. siRNA knockdown of β-catenin in A431 and SCC13 cells reduced cell viability. Collectively, these data suggest that induction of cytotoxicity in skin cancer cells by EGCG is mediated by targeting of β-catenin signaling and that the β-catenin signaling is upregulated by inflammatory mediators. - Highlights: • EGCG inhibits cancer cell viability through inactivation of β-catenin signaling. • Inactivation of β-catenin involves the downregulation of inflammatory mediators. • EGCG

  20. Repeated dose studies with pure Epigallocatechin-3-gallate demonstrated dose and route dependant hepatotoxicity with associated dyslipidemia

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    Balaji Ramachandran

    Full Text Available EGCG (Epigallocatechin-3-gallate is the major active principle catechin found in green tea. Skepticism regarding the safety of consuming EGCG is gaining attention, despite the fact that it is widely being touted for its potential health benefits, including anti-cancer properties. The lack of scientific data on safe dose levels of pure EGCG is of concern, while EGCG has been commonly studied as a component of GTE (Green tea extract and not as a single active constituent. This study has been carried out to estimate the maximum tolerated non-toxic dose of pure EGCG and to identify the treatment related risk factors. In a fourteen day consecutive treatment, two different administration modalities were compared, offering an improved [i.p (intraperitoneal] and limited [p.o (oral] bioavailability. A trend of dose and route dependant hepatotoxicity was observed particularly with i.p treatment and EGCG increased serum lipid profile in parallel to hepatotoxicity. Fourteen day tolerable dose of EGCG was established as 21.1 mg/kg for i.p and 67.8 mg/kg for p.o. We also observed that, EGCG induced effects by both treatment routes are reversible, subsequent to an observation period for further fourteen days after cessation of treatment. It was demonstrated that the severity of EGCG induced toxicity appears to be a function of dose, route of administration and period of treatment. Keywords: EGCG, Green tea, Serum lipids, Dose dependant toxicity, Route dependant toxicity, Liver toxicity, Dyslipidemia

  1. Epigallocatechin-3-gallate (EGCG) consumption in the Ts65Dn model of Down syndrome fails to improve behavioral deficits and is detrimental to skeletal phenotypes.

    Science.gov (United States)

    Stringer, Megan; Abeysekera, Irushi; Thomas, Jared; LaCombe, Jonathan; Stancombe, Kailey; Stewart, Robert J; Dria, Karl J; Wallace, Joseph M; Goodlett, Charles R; Roper, Randall J

    2017-08-01

    Down syndrome (DS) is caused by three copies of human chromosome 21 (Hsa21) and results in phenotypes including intellectual disability and skeletal deficits. Ts65Dn mice have three copies of ~50% of the genes homologous to Hsa21 and display phenotypes associated with DS, including cognitive deficits and skeletal abnormalities. DYRK1A is found in three copies in humans with Trisomy 21 and in Ts65Dn mice, and is involved in a number of critical pathways including neurological development and osteoclastogenesis. Epigallocatechin-3-gallate (EGCG), the main polyphenol in green tea, inhibits Dyrk1a activity. We have previously shown that EGCG treatment (~10mg/kg/day) improves skeletal abnormalities in Ts65Dn mice, yet the same dose, as well as ~20mg/kg/day did not rescue deficits in the Morris water maze spatial learning task (MWM), novel object recognition (NOR) or balance beam task (BB). In contrast, a recent study reported that an EGCG-containing supplement with a dose of 2-3mg per day (~40-60mg/kg/day) improved hippocampal-dependent task deficits in Ts65Dn mice. The current study investigated if an EGCG dosage similar to that study would yield similar improvements in either cognitive or skeletal deficits. Ts65Dn mice and euploid littermates were given EGCG [0.4mg/mL] or a water control, with treatments yielding average daily intakes of ~50mg/kg/day EGCG, and tested on the multivariate concentric square field (MCSF)-which assesses activity, exploratory behavior, risk assessment, risk taking, and shelter seeking-and NOR, BB, and MWM. EGCG treatment failed to improve cognitive deficits; EGCG also produced several detrimental effects on skeleton in both genotypes. In a refined HPLC-based assay, its first application in Ts65Dn mice, EGCG treatment significantly reduced kinase activity in femora but not in the cerebral cortex, cerebellum, or hippocampus. Counter to expectation, 9-week-old Ts65Dn mice exhibited a decrease in Dyrk1a protein levels in Western blot analysis

  2. Epigallocatechin-3-gallate rapidly remodels PAP85-120, SEM1(45-107, and SEM2(49-107 seminal amyloid fibrils

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    Laura M. Castellano

    2015-09-01

    Full Text Available Semen harbors amyloid fibrils formed by proteolytic fragments of prostatic acid phosphatase (PAP248-286 and PAP85-120 and semenogelins (SEM1 and SEM2 that potently enhance HIV infectivity. Amyloid but not soluble forms of these peptides enhance HIV infection. Thus, agents that remodel these amyloid fibrils could prevent HIV transmission. Here, we confirm that the green tea polyphenol, epigallocatechin-3-gallate (EGCG, slowly remodels fibrils formed by PAP248-286 termed SEVI (semen derived enhancer of viral infection and also exerts a direct anti-viral effect. We elucidate for the first time that EGCG remodels PAP85-120, SEM1(45-107, and SEM2(49-107 fibrils more rapidly than SEVI fibrils. We establish EGCG as the first small molecule that can remodel all four classes of seminal amyloid. The combined anti-amyloid and anti-viral properties of EGCG could have utility in preventing HIV transmission.

  3. Bioactivity-guided fractionation of an antidiarrheal Chinese herb Rhodiola kirilowii (Regel) Maxim reveals (-)-epicatechin-3-gallate and (-)-epigallocatechin-3-gallate as inhibitors of cystic fibrosis transmembrane conductance regulator.

    Science.gov (United States)

    Chen, Lei; Yu, Bo; Zhang, Yaofang; Gao, Xin; Zhu, Liang; Ma, Tonghui; Yang, Hong

    2015-01-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) is the principal apical route for transepithelial fluid transport induced by enterotoxin. Inhibition of CFTR has been confirmed as a pharmaceutical approach for the treatment of secretory diarrhea. Many traditional Chinese herbal medicines, like Rhodiola kirilowii (Regel) Maxim, have long been used for the treatment of secretory diarrhea. However, the active ingredients responsible for their therapeutic effectiveness remain unknown. The purpose of this study is to identify CFTR inhibitors from Rhodiola kirilowii (Regel) Maxim via bioactivity-directed isolation strategy. We first identified fractions of Rhodiola kirilowii (Regel) Maxim that inhibited CFTR Cl- channel activity. Further bioactivity-directed fractionation led to the identification of (-)-epigallocatechin-3-gallate (EGCG) as CFTR Cl- channel inhibitor. Analysis of 5 commercially available EGCG analogs including (+)-catechins (C), (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin-3-gallate (ECG) and EGCG revealed that ECG also had CFTR inhibitory activity. EGCG dose-dependently and reversibly inhibited CFTR Cl- channel activity in transfected FRT cells with an IC50 value around 100 μM. In ex vivo studies, EGCG and ECG inhibited CFTR-mediated short-circuit currents in isolated rat colonic mucosa in a dose-dependent manner. In an intestinal closed-loop model in mice, intraluminal application of EGCG (10 μg) and ECG (10 μg) significantly reduced cholera toxin-induced intestinal fluid secretion. CFTR Cl- channel is a molecular target of natural compounds EGCG and ECG. CFTR inhibition may account, at least in part, for the antidiarrheal activity of Rhodiola kirilowii (Regel) Maxim. EGCG and ECG could be new lead compounds for development of CFTR-related diseases such as secretory diarrhea.

  4. Role of Spm-Cer-S1P signalling pathway in MMP-2 mediated U46619-induced proliferation of pulmonary artery smooth muscle cells: protective role of epigallocatechin-3-gallate.

    Science.gov (United States)

    Chowdhury, Animesh; Sarkar, Jaganmay; Chakraborti, Tapati; Chakraborti, Sajal

    2015-10-01

    During remodelling of pulmonary artery, marked proliferation of pulmonary artery smooth muscle cells (PASMCs) occurs, which contributes to pulmonary hypertension. Thromboxane A2 (TxA2) has been shown to produce pulmonary hypertension. The present study investigates the inhibitory effect of epigallocatechin-3-gallate (EGCG) on the TxA2 mimetic, U46619-induced proliferation of PASMCs. U46619 at a concentration of 10 nM induces maximum proliferation of bovine PASMCs. Both pharmacological and genetic inhibitors of p(38)MAPK, NF-κB and MMP-2 significantly inhibit U46619-induced cell proliferation. EGCG markedly abrogate U46619-induced p(38)MAPK phosphorylation, NF-κB activation, proMMP-2 expression and activation, and also the cell proliferation. U46619 causes an increase in the activation of sphingomyelinase (SMase) and sphingosine kinase (SPHK) and also increase sphingosine 1 phosphate (S1P) level. U46619 also induces phosphorylation of ERK1/2, which phosphorylates SPHK leading to an increase in S1P level. Both pharmacological and genetic inhibitors of SMase and SPHK markedly inhibit U46619-induced cell proliferation. Additionally, pharmacological and genetic inhibitors of MMP-2 markedly abrogate U46619-induced SMase activity and S1P level. EGCG markedly inhibit U46619-induced SMase activity, ERK1/2 and SPHK phosphorylation and S1P level in the cells. Overall, Sphingomyeline-Ceramide-Sphingosine-1-phosphate (Spm-Cer-S1P) signalling axis plays an important role in MMP-2 mediated U46619-induced proliferation of PASMCs. Importantly, EGCG inhibits U46619 induced increase in MMP-2 activation by modulating p(38)MAPK-NFκB pathway and subsequently prevents the cell proliferation. Copyright © 2015 John Wiley & Sons, Ltd.

  5. Protective effects of a green tea polyphenol, epigallocatechin-3-gallate, against sevoflurane-induced neuronal apoptosis involve regulation of CREB/BDNF/TrkB and PI3K/Akt/mTOR signalling pathways in neonatal mice.

    Science.gov (United States)

    Ding, Mei-Li; Ma, Hui; Man, Yi-Gang; Lv, Hong-Yan

    2017-12-01

    Epigallocatechin-3-gallate (EGCG), a polyphenol in green tea, is an effective antioxidant and possesses neuroprotective effects. Brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB) are crucial for neurogenesis and synaptic plasticity. In this study, we aimed to assess the protective effects of EGCG against sevoflurane-induced neurotoxicity in neonatal mice. Distinct groups of C57BL/6 mice were given EGCG (25, 50, or 75 mg/kg body weight) from postnatal day 3 (P3) to P21 and were subjected to sevoflurane (3%; 6 h) exposure on P7. EGCG significantly inhibited sevoflurane-induced neuroapoptosis as determined by Fluoro-Jade B staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Increased levels of cleaved caspase-3, downregulated Bad and Bax, and significantly enhanced Bcl-2, Bcl-xL, xIAP, c-IAP-1, and survivin expression were observed. EGCG induced activation of the PI3K/Akt pathway as evidenced by increased Akt, phospho-Akt, GSK-3β, phospho-GSK-3β, and mTORc1 levels. Sevoflurane-mediated downregulation of cAMP/CREB and BDNF/TrkB signalling was inhibited by EGCG. Reverse transcription PCR analysis revealed enhanced BDNF and TrkB mRNA levels upon EGCG administration. Improved performance of mice in Morris water maze tests suggested enhanced learning and memory. The study indicates that EGCG was able to effectively inhibit sevoflurane-induced neurodegeneration and improve learning and memory retention of mice via activation of CREB/BDNF/TrkB-PI3K/Akt signalling.

  6. Prolonged Exposure of Cortical Neurons to Oligomeric Amyloid-β Impairs NMDA Receptor Function Via NADPH Oxidase-Mediated ROS Production: Protective Effect of Green Tea (--Epigallocatechin-3-Gallate

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    Yan He

    2011-01-01

    Full Text Available Excessive production of Aβ (amyloid β-peptide has been shown to play an important role in the pathogenesis of AD (Alzheimer's disease. Although not yet well understood, aggregation of Aβ is known to cause toxicity to neurons. Our recent study demonstrated the ability for oligomeric Aβ to stimulate the production of ROS (reactive oxygen species in neurons through an NMDA (N-methyl-D-aspartate-dependent pathway. However, whether prolonged exposure of neurons to aggregated Aβ is associated with impairment of NMDA receptor function has not been extensively investigated. In the present study, we show that prolonged exposure of primary cortical neurons to Aβ oligomers caused mitochondrial dysfunction, an attenuation of NMDA receptor-mediated Ca2+ influx and inhibition of NMDA-induced AA (arachidonic acid release. Mitochondrial dysfunction and the decrease in NMDA receptor activity due to oligomeric Aβ are associated with an increase in ROS production. Gp91ds-tat, a specific peptide inhibitor of NADPH oxidase, and Mn(III-tetrakis(4-benzoic acid-porphyrin chloride, an ROS scavenger, effectively abrogated Aβ-induced ROS production. Furthermore, Aβ-induced mitochondrial dysfunction, impairment of NMDA Ca2+ influx and ROS production were prevented by pretreatment of neurons with EGCG [(–-epigallocatechin-3-gallate], a major polyphenolic component of green tea. Taken together, these results support a role for NADPH oxidase-mediated ROS production in the cytotoxic effects of Aβ, and demonstrate the therapeutic potential of EGCG and other dietary polyphenols in delaying onset or retarding the progression of AD.

  7. Effect of the consumption of β-lactoglobulin and epigallocatechin-3-gallate with or without calcium on glucose tolerance in C57BL/6 mice.

    Science.gov (United States)

    Carnovale, Valérie; Pilon, Geneviève; Britten, Michel; Bazinet, Laurent; Couillard, Charles

    2016-01-01

    Interactions between β-lactoglobulin (β-lg) and epigallocatechin-3-gallate (EGCG) may modulate their health benefits. The objective of this study was therefore to investigate the synergistic effect of consuming β-lg and EGCG complexes on glucose tolerance of C57BL/6 male mice given an oral glucose tolerance test (OGTT) and randomized to one of the following treatments administered prior to the OGTT: 1) simulated milk ultrafiltrate (SMUF(-)), 2) SMUF(-) + EGCG, 3) SMUF(-) + β-lg, 4) SMUF(-) + EGCG + β-lg, 5) SMUF + calcium (SMUF(+)) and 6) SMUF(+) + EGCG + β-lg. We found no significant between-group difference in postprandial glucose response. However, when mice were separated in those who received β-lg from those who did not, we found that the latter displayed significantly higher postprandial glucose concentrations. Our results support the beneficial impact of β-lg on glycemic control and suggest that concomitant EGCG or calcium consumption does not improve this effect.

  8. Cellular determinants involving mitochondrial dysfunction, oxidative stress and apoptosis correlate with the synergic cytotoxicity of epigallocatechin-3-gallate and menadione in human leukemia Jurkat T cells.

    Science.gov (United States)

    Tofolean, Ioana Teodora; Ganea, Constanta; Ionescu, Diana; Filippi, Alexandru; Garaiman, Alexandru; Goicea, Alexandru; Gaman, Mihnea-Alexandru; Dimancea, Alexandru; Baran, Irina

    2016-01-01

    We have investigated the growth-suppressive action of epigallocatechin-3-gallate (EGCG) on human leukemia Jurkat T cells. Results show a strong correlation between the dose-dependent reduction of clonogenic survival following acute EGCG treatments and the EGCG-induced decline of the mitochondrial level of Ca(2+). The cell killing ability of EGCG was synergistically enhanced by menadione. In addition, the cytotoxic effect of EGCG applied alone or in combination with menadione was accompanied by apoptosis induction. We also observed that in acute treatments EGCG displays strong antioxidant properties in the intracellular milieu, but concurrently triggers some oxidative stress generating mechanisms that can fully develop on a longer timescale. In parallel, EGCG dose-dependently induced mitochondrial depolarization during exposure, but this condition was subsequently reversed to a persistent hyperpolarized mitochondrial state that was dependent on the activity of respiratory Complex I. Fluorimetric measurements suggest that EGCG is a mitochondrial Complex III inhibitor and indicate that EGCG evokes a specific cellular fluorescence with emission at 400nm and two main excitation bands (at 330nm and 350nm) that may originate from a mitochondrial supercomplex containing dimeric Complex III and dimeric ATP-synthase, and therefore could provide a valuable means to characterize the functional properties of the respiratory chain. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Punicalagin and (-)-Epigallocatechin-3-Gallate Rescue Cell Viability and Attenuate Inflammatory Responses of Human Epidermal Keratinocytes Exposed to Airborne Particulate Matter PM10.

    Science.gov (United States)

    Seok, Jin Kyung; Lee, Jeong-Won; Kim, Young Mi; Boo, Yong Chool

    2018-01-01

    Airborne particulate matter with a diameter of < 10 µm (PM10) causes oxidative damage, inflammation, and premature skin aging. In this study, we evaluated whether polyphenolic antioxidants attenuate the inflammatory responses of PM10-exposed keratinocytes. Primary human epidermal keratinocytes were exposed in vitro to PM10 in the absence or presence of punicalagin and (-)-epigallocatechin-3-gallate (EGCG), which are the major polyphenolic antioxidants found in pomegranate and green tea, respectively. Assays were performed to determine cell viability, production of reactive oxygen species (ROS), and expression of NADPH oxidases (NOX), proinflammatory cytokines, and matrix metalloproteinase (MMP)-1. PM10 decreased cell viability and increased ROS production in a dose-dependent manner. It also increased the expression levels of NOX-1, NOX-2, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-8, and MMP-1. Punicalagin was not cytotoxic up to 300 μM, and (-)-EGCG was cytotoxic above 30 μM, respectively. Further, punicalagin (3-30 μM) and EGCG (3-10 μM) rescued the viability of PM10-exposed cells. They also attenuated ROS production and the expression of NOX-1, NOX-2, TNF-α, IL-1β, IL-6, IL-8, and MMP-1 stimulated by PM10. This study demonstrates that polyphenolic antioxidants, such as punicalagin and (-)-EGCG, rescue keratinocyte viability and attenuate the inflammatory responses of these cells due to airborne particles. © 2018 S. Karger AG, Basel.

  10. Anti-proliferative and differentiation-inducing activities of the green tea catechin epigallocatechin-3-gallate (EGCG) on the human eosinophilic leukemia EoL-1 cell line.

    Science.gov (United States)

    Lung, H L; Ip, W K; Wong, C K; Mak, N K; Chen, Z Y; Leung, K N

    2002-12-06

    A novel approach for the treatment of leukemia is the differentiation therapy in which immature leukemia cells are induced to attain a mature phenotype when exposed to differentiation inducers, either alone or in combinations with other chemotherapeutic or chemopreventive drugs. Over the past decade, numerous studies indicated that green tea catechins (GTC) could suppress the growth and induce apoptosis on a number of human cancer cell lines. However, the differentiation-inducing activity of GTC on human tumors remains poorly understood. In the present study, the effect of the major GTC epigallocatechin-3-gallate (EGCG) on the proliferation and differentiation of a human eosinophilc leukemic cell line, EoL-1, was examined. Our results showed that EGCG suppressed the proliferation of the EoL-1 cells in a dose-dependent manner, with an estimated IC(50) value of 31.5 microM. On the other hand, EGCG at a concentration of 40 microM could trigger the EoL-1 cells to undergo morphological differentiation into mature eosinophil-like cells. Using RT-PCR and flow cytometry, it was found that EGCG upregulated the gene and protein expression of two eosinophil-specific granule proteins, the major basic protein (MBP) and eosinophil peroxidase (EPO), in EoL-1 cells. Taken together, our findings suggest that EGCG can exhibit anti-leukemic activity on a human eosinophilic cell line EoL-1 by suppressing the proliferation and by inducing the differentiation of the leukemia cells.

  11. Survivin knockdown increased anti-cancer effects of (−)-epigallocatechin-3-gallate in human malignant neuroblastoma SK-N-BE2 and SH-SY5Y cells

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    Hossain, Md. Motarab; Banik, Naren L.; Ray, Swapan K.

    2012-01-01

    Neuroblastoma is a solid tumor that mostly occurs in children. Malignant neuroblastomas have poor prognosis because conventional chemotherapeutic agents are hardly effective. Survivin, which is highly expressed in some malignant neuroblastomas, plays a significant role in inhibiting differentiation and apoptosis and promoting cell proliferation, invasion, and angiogenesis. We examined consequences of survivin knockdown by survivin short hairpin RNA (shRNA) plasmid and then treatment with (−)-epigallocatechin-3-gallate (EGCG), a green tea flavonoid, in malignant neuroblastoma cells. Our Western blotting and laser scanning confocal immunofluorescence microscopy showed that survivin was highly expressed in malignant neuroblastoma SK-N-BE2 and SH-SY5Y cell lines and slightly in SK-N-DZ cell line. Expression of survivin was very faint in malignant neuroblastoma IMR32 cell line. We transfected SK-N-BE2 and SH-SY-5Y cells with survivin shRNA, treated with EGCG, and confirmed knockdown of survivin at mRNA and protein levels. Survivin knockdown induced morphological features of neuronal differentiation, as we observed following in situ methylene blue staining. Combination of survivin shRNA and EGCG promoted neuronal differentiation biochemically by increases in the expression of NFP, NSE, and e-cadherin and also decreases in the expression of Notch-1, ID2, hTERT, and PCNA. Our in situ Wright staining and Annexin V-FITC/PI staining showed that combination therapy was highly effective in inducing, respectively, morphological and biochemical features of apoptosis. Apoptosis occurred with activation of caspase-8 and cleavage of Bid to tBid, increase in Bax:Bcl-2 ratio, mitochondrial release of cytochrome c, and increases in the expression and activity of calpain and caspase-3. Combination therapy decreased migration of cells through matrigel and inhibited proliferative (p-Akt and NF-κB), invasive (MMP-2 and MMP-9), and angiogenic (VEGF and b-FGF) factors. Also, in vitro

  12. Survivin knockdown increased anti-cancer effects of (−)-epigallocatechin-3-gallate in human malignant neuroblastoma SK-N- BE2 and SH-SY5Y cells

    Science.gov (United States)

    Hossain, Md. Motarab; Banik, Naren L.; Ray, Swapan K.

    2012-01-01

    Neuroblastoma is a solid tumor that mostly occurs in children. Malignant neuroblastomas have poor prognosis because conventional chemotherapeutic agents are hardly effective. Survivin, which is highly expressed in some malignant neuroblastomas, plays a significant role in inhibiting differentiation and apoptosis and promoting cell proliferation, invasion, and angiogenesis. We examined consequences of survivin knockdown by survivin short hairpin RNA (shRNA) plasmid and then treatment with (−)-epigallocatechin-3-gallate (EGCG), a green tea flavonoid, in malignant neuroblastoma cells. Our Western blotting and laser scanning confocal immunofluorescence microscopy showed that survivin was highly expressed in malignant neuroblastoma SK-N-BE2 and SH-SY5Y cell lines and slightly in SK-N-DZ cell line. Expression of survivin was very faint in malignant neuroblastoma IMR32 cell line. We transfected SK-N-BE2 and SH-SY-5Y cells with survivin shRNA, treated with EGCG, and confirmed knockdown of survivin at mRNA and protein levels. Survivin knockdown induced morphological features of neuronal differentiation, as we observed following in situ methylene blue staining. Combination of survivin shRNA and EGCG promoted neuronal differentiation biochemically by increases in expression of NFP, NSE, and e-cadherin and also decreases in expression of Notch-1, ID2, hTERT, and PCNA. Our in situ Wright staining and Annexin V-FITC/PI staining showed that combination therapy was highly effective in inducing, respectively, morphological and biochemical features of apoptosis. Apoptosis occurred with activation of caspase-8 and cleavage of Bid to tBid, increase in Bax:Bcl-2 ratio, mitochondrial release of cytochrome c, and increases in expression and activity of calpain and caspase-3. Combination therapy decreased migration of cells through matrigel and inhibited proliferative (p-Akt and NF-κB), invasive (MMP-2 and MMP-9), and angiogenic (VEGF and b-FGF) factors. Also, in vitro network

  13. Effects of green tea epigallocatechin-3-gallate on the proteolipid protein and oligodendrocyte transcription factor 1 messenger RNA gene expression in a mouse model of multiple sclerosis

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    Mohammadreza Semnani

    2017-09-01

    Full Text Available The cuprizone multiple sclerosis (MS animal model is characteristic for toxic demyelination and represents a reversible demyelination and remyelination system. It has been shown that green tea epigallocatechin-3-gallate (EGCG might be effective in improving the symptoms and pathological conditions associated with autoimmune inflammatory diseases in several animal models. In this study the effects of EGCG on proteolipid protein (PLP and oligodendrocyte transcription factor 1 (Olig1 expression in the cerebral cortex of a murine model of cuprizone-induced demyelination was investigated. C57BL/6 mice were treated with cuprizone for six weeks in order to induce demyelination. Immediately after the cessation of cuprizone the animals were divided into 6 groups (n = 10 for each group. The first two groups were injected intraperitoneally (IP with EGCG in the amount of 50 mg/kg/daily body weight for 2 and 4 weeks. The second two groups (SHAM were injected IP with phosphate-buffered saline (PBS for 2 and 4 weeks, and the third two groups were left without injection as controls. After two and four weeks the mice were killed and the cerebral cortex was collected and the expression of Plp and Olig1 was studied by real-time PCR. The results showed significant increases in PLP and Olig1 expression in the EGCG-treated groups as compared to the SHAM and control groups (p < 0.0001. It is concluded that EGCG increases PLP and Olig1 expression in the cerebral cortex of a mouse model of MS induced by cuprizone.

  14. Epigallocatechin-3-gallate accelerates relaxation and Ca2+ transient decay and desensitizes myofilaments in healthy and Mybpc3-targeted knock-in cardiomyopathic mice

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    Felix W. Friedrich

    2016-12-01

    Full Text Available Background. Hypertrophic cardiomyopathy (HCM is the most common inherited cardiac muscle disease with left ventricular hypertrophy, interstitial fibrosis and diastolic dysfunction. Increased myofilament Ca2+ sensitivity could be the underlying cause of diastolic dysfunction. Epigallocatechin-3-gallate (EGCg, a catechin found in green tea has, been reported to decrease myofilament Ca2+ sensitivity in HCM models with troponin mutations. However, whether this is also the case for HCM-associated thick filament mutations is not known. Therefore, we evaluated whether EGCg affects the behavior of cardiomyocytes and myofilaments of a HCM mouse model carrying a gene mutation in cardiac myosin-binding protein C and exhibiting both increased myofilament Ca2+ sensitivity and diastolic dysfunction.Methods and Results. Acute effects of EGCg were tested on fractional sarcomere shortening and Ca2+ transients in intact ventricular myocytes and on force-Ca2+ relationship of skinned ventricular muscle strips isolated from Mybpc3-targeted knock-in (KI and wild-type (WT mice. Fractional sarcomere shortening and Ca2+ transients were analyzed at 37 °C under 1-Hz pacing in the absence or presence of EGCg (1.8 µM. At baseline and in the absence of Fura-2, KI cardiomyocytes displayed lower diastolic sarcomere length, higher fractional sarcomere shortening, longer time to peak shortening and time to 50% relengthening than WT cardiomyocytes. In WT and KI neither diastolic sarcomere length nor fractional sarcomere shortening were influenced by EGCg treatment, but relaxation time was reduced, to a greater extent in KI cells. EGCg shortened time to peak Ca2+ and Ca2+ transient decay in Fura-2-loaded WT and KI cardiomyocytes. EGCg did not influence phosphorylation of phospholamban. In skinned cardiac muscle strips, EGCg (30 µM decreased Ca2+ sensitivity in both groups. Conclusion. EGCg fastened relaxation and Ca2+ transient decay to a larger extent in KI than in WT

  15. Mitochondrial Modulation by Epigallocatechin 3-Gallate Ameliorates Cisplatin Induced Renal Injury through Decreasing Oxidative/Nitrative Stress, Inflammation and NF-kB in Mice

    Science.gov (United States)

    Wang, Xueping; Wang, Ping; Fu, Guanghou; Meng, Hongzhou; Wang, Yimin; Jin, Baiye

    2015-01-01

    Cancer chemotherapy drug cisplatin is known for its nephrotoxicity. The aim of this study is to investigate whether Epigallocatechin 3-Gallate (EGCG) can reduce cisplatin mediated side effect in kidney and to understand its mechanism of protection against tissue injury. We used a well-established 3-day cisplatin induced nephrotoxicity mice model where EGCG were administered. EGCG is a major active compound in Green Tea and have strong anti-oxidant and anti-inflammatory properties. EGCG protected against cisplatin induced renal dysfunction as measured by serum creatinine and blood urea nitrogen (BUN). EGCG improved cisplatin induced kidney structural damages such as tubular dilatation, cast formation, granulovaculoar degeneration and tubular cell necrosis as evident by PAS staining. Cisplatin induced kidney specific mitochondrial oxidative stress, impaired activities of mitochondrial electron transport chain enzyme complexes, impaired anti-oxidant defense enzyme activities such as glutathione peroxidase (GPX) and manganese superoxide dismutase (MnSOD) in mitochondria, inflammation (tumor necrosis factor α and interleukin 1β), increased accumulation of NF-κB in nuclear fraction, p53 induction, and apoptotic cell death (caspase 3 activity and DNA fragmentation). Treatment of mice with EGCG markedly attenuated cisplatin induced mitochondrial oxidative/nitrative stress, mitochondrial damages to electron transport chain activities and antioxidant defense enzyme activities in mitochondria. These mitochondrial modulations by EGCG led to protection mechanism against cisplatin induced inflammation and apoptotic cell death in mice kidney. As a result, EGCG improved renal function in cisplatin mediated kidney damage. In addition to that, EGCG attenuated cisplatin induced apoptotic cell death and mitochondrial reactive oxygen species (ROS) generation in human kidney tubular cell line HK-2. Thus, our data suggest that EGCG may represent new promising adjunct candidate for

  16. Comparative Evaluation of Different Co-Antioxidants on the Photochemical- and Functional-Stability of Epigallocatechin-3-gallate in Topical Creams Exposed to Simulated Sunlight

    Directory of Open Access Journals (Sweden)

    Santo Scalia

    2013-01-01

    Full Text Available The catechin (−-epigallocatechin-3-gallate (EGCG exhibits high antioxidant activity and it has been reported to provide protection of the skin against damage induced by solar UV radiation. However, EGCG is highly unstable under sunlight. The present study aimed to compare the effectiveness of the co-antioxidant agents vitamin E, butylated hydroxytoluene, vitamin C and a-lipoic acid for their potential to protect the catechin from photochemical degradation. Model creams (oil-in-water emulsions containing EGCG (1%, w/w alone or combined with equimolar concentrations of co-antioxidant were exposed to a solar simulator at an irradiance corresponding to natural sunlight. Photodegradation was evaluated by HPLC-UV and HPLC-ESI-MS/MS. Addition of the co-antioxidants vitamin C and a-lipoic acid to the formulation significantly reduced the light-induced decomposition of EGCG from 76.9 ± 4.6% to 20.4 ± 2.7% and 12.6 ± 1.6%, respectively. Conversely, butylated hydroxytoluene had no effect (EGCG loss, 78.1 ± 4.6% and vitamin E enhanced the EGCG photolysis to 84.5 ± 3.4%. The functional stability of the catechin in the creams exposed to the solar simulator was also evaluated by measuring the in vitro antioxidant activity. Following irradiation, the reduction of the EGCG formulation antioxidant power was lower (21.8% than the extent of degradation (76.9%, suggesting the formation of photoproducts with antioxidant properties. The influence of the examined co-antioxidants on the functional stability of the catechin under simulated sunlight paralleled that measured for the EGCG photodecomposition, a-lipoic acid exerting the greatest stabilising effect (antioxidant activity decrease, 1.4%. These results demonstrated that a-lipoic acid is an effective co-antioxidant agent for the stabilization of EGCG in dermatological products for skin photoprotection.

  17. Green tea polyphenol (−)-epigallocatechin-3-gallate triggered hepatotoxicity in mice: Responses of major antioxidant enzymes and the Nrf2 rescue pathway

    International Nuclear Information System (INIS)

    Wang, Dongxu; Wang, Yijun; Wan, Xiaochun; Yang, Chung S.; Zhang, Jinsong

    2015-01-01

    (−)-Epigallocatechin-3-gallate (EGCG), a constituent of green tea, has been suggested to have numerous health-promoting effects. On the other hand, high-dose EGCG is able to evoke hepatotoxicity. In the present study, we elucidated the responses of hepatic major antioxidant enzymes and nuclear factor erythroid 2-related factor 2 (Nrf2) rescue pathway to high-dose levels of EGCG in Kunming mice. At a non-lethal toxic dose (75 mg/kg, i.p.), repeated EGCG treatments markedly decreased the levels of superoxide dismutase, catalase, and glutathione peroxidase. As a rescue response, the nuclear distribution of Nrf2 was significantly increased; a battery of Nrf2-target genes, including heme oxygenase 1 (HO1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase (GST), and those involved in glutathione and thioredoxin systems, were all up-regulated. At the maximum tolerated dose (45 mg/kg, i.p.), repeated EGCG treatments did not disturb the major antioxidant defense. Among the above-mentioned genes, only HO1, NQO1, and GST genes were significantly but modestly up-regulated, suggesting a comprehensive and extensive activation of Nrf2-target genes principally occurs at toxic levels of EGCG. At a lethal dose (200 mg/kg, i.p.), a single EGCG treatment dramatically decreased not only the major antioxidant defense but also the Nrf2-target genes, demonstrating that toxic levels of EGCG are able to cause a biphasic response of Nrf2. Overall, the mechanism of EGCG-triggered hepatotoxicity involves suppression of major antioxidant enzymes, and the Nrf2 rescue pathway plays a vital role for counteracting EGCG toxicity. - Highlights: • EGCG at maximum tolerated dose does not disturb hepatic major antioxidant defense. • EGCG at maximum tolerated dose modestly upregulates hepatic Nrf2 target genes. • EGCG at toxic dose suppresses hepatic major antioxidant enzymes. • EGCG at non-lethal toxic dose pronouncedly activates hepatic Nrf2 rescue response. • EGCG at

  18. Green tea polyphenol (−)-epigallocatechin-3-gallate triggered hepatotoxicity in mice: Responses of major antioxidant enzymes and the Nrf2 rescue pathway

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Dongxu; Wang, Yijun; Wan, Xiaochun [Key Laboratory of Tea Biochemistry & Biotechnology, School of Tea & Food Science, Anhui Agricultural University, Hefei, Anhui 230036 (China); Yang, Chung S. [Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (United States); Zhang, Jinsong, E-mail: zjs@ahau.edu.cn [Key Laboratory of Tea Biochemistry & Biotechnology, School of Tea & Food Science, Anhui Agricultural University, Hefei, Anhui 230036 (China)

    2015-02-15

    (−)-Epigallocatechin-3-gallate (EGCG), a constituent of green tea, has been suggested to have numerous health-promoting effects. On the other hand, high-dose EGCG is able to evoke hepatotoxicity. In the present study, we elucidated the responses of hepatic major antioxidant enzymes and nuclear factor erythroid 2-related factor 2 (Nrf2) rescue pathway to high-dose levels of EGCG in Kunming mice. At a non-lethal toxic dose (75 mg/kg, i.p.), repeated EGCG treatments markedly decreased the levels of superoxide dismutase, catalase, and glutathione peroxidase. As a rescue response, the nuclear distribution of Nrf2 was significantly increased; a battery of Nrf2-target genes, including heme oxygenase 1 (HO1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase (GST), and those involved in glutathione and thioredoxin systems, were all up-regulated. At the maximum tolerated dose (45 mg/kg, i.p.), repeated EGCG treatments did not disturb the major antioxidant defense. Among the above-mentioned genes, only HO1, NQO1, and GST genes were significantly but modestly up-regulated, suggesting a comprehensive and extensive activation of Nrf2-target genes principally occurs at toxic levels of EGCG. At a lethal dose (200 mg/kg, i.p.), a single EGCG treatment dramatically decreased not only the major antioxidant defense but also the Nrf2-target genes, demonstrating that toxic levels of EGCG are able to cause a biphasic response of Nrf2. Overall, the mechanism of EGCG-triggered hepatotoxicity involves suppression of major antioxidant enzymes, and the Nrf2 rescue pathway plays a vital role for counteracting EGCG toxicity. - Highlights: • EGCG at maximum tolerated dose does not disturb hepatic major antioxidant defense. • EGCG at maximum tolerated dose modestly upregulates hepatic Nrf2 target genes. • EGCG at toxic dose suppresses hepatic major antioxidant enzymes. • EGCG at non-lethal toxic dose pronouncedly activates hepatic Nrf2 rescue response. • EGCG at

  19. Recent advances on tea polyphenols

    Science.gov (United States)

    Kanwar, Jyoti; Taskeen, Mujtaba; Mohammad, Imthiyaz; Huo, Congde; Chan, Tak Hang; Dou, Qing Ping

    2012-01-01

    Over the past decade many scientific and medical studies have focused on green tea for its long-purported health benefits. There is convincing evidence that tea is a cup of life. It has multiple preventive and therapeutic effects. This review thus focuses on the recent advances of tea polyphenols and their applications in the prevention and treatment of human cancers. Of the various polyphenols in tea, (−)-Epigallocatechin-3-gallate (EGCG) is the most abundant, and active compound studied in tea research. EGCG inhibits several molecular targets to inhibit cancer initiation and modulates several essential survival pathways to block cancer progression. Herein, we describe the various mechanisms of action of EGCG and also discuss previous and current ongoing clinical trials of EGCG and green tea polyphenols in different cancer types. PMID:22201858

  20. Epigallocatechin-3-gallate enhances key enzymatic activities of hepatic thioredoxin and glutathione systems in selenium-optimal mice but activates hepatic Nrf2 responses in selenium-deficient mice

    Directory of Open Access Journals (Sweden)

    Ruixia Dong

    2016-12-01

    Full Text Available Selenium participates in the antioxidant defense mainly through a class of selenoproteins, including thioredoxin reductase. Epigallocatechin-3-gallate (EGCG is the most abundant and biologically active catechin in green tea. Depending upon the dose and biological systems, EGCG may function either as an antioxidant or as an inducer of antioxidant defense via its pro-oxidant action or other unidentified mechanisms. By manipulating the selenium status, the present study investigated the interactions of EGCG with antioxidant defense systems including the thioredoxin system comprising of thioredoxin and thioredoxin reductase, the glutathione system comprising of glutathione and glutathione reductase coupled with glutaredoxin, and the Nrf2 system. In selenium-optimal mice, EGCG increased hepatic activities of thioredoxin reductase, glutathione reductase and glutaredoxin. These effects of EGCG appeared to be not due to overt pro-oxidant action because melatonin, a powerful antioxidant, did not influence the increase. However, in selenium-deficient mice, with low basal levels of thioredoxin reductase 1, the same dose of EGCG did not elevate the above-mentioned enzymes; intriguingly EGCG in turn activated hepatic Nrf2 response, leading to increased heme oxygenase 1 and NAD(PH:quinone oxidoreductase 1 protein levels and thioredoxin activity. Overall, the present work reveals that EGCG is a robust inducer of the Nrf2 system only in selenium-deficient conditions. Under normal physiological conditions, in selenium-optimal mice, thioredoxin and glutathione systems serve as the first line defense systems against the stress induced by high doses of EGCG, sparing the activation of the Nrf2 system.

  1. The Green Tea Component (--Epigallocatechin-3-Gallate Sensitizes Primary Endothelial Cells to Arsenite-Induced Apoptosis by Decreasing c-Jun N-Terminal Kinase-Mediated Catalase Activity.

    Directory of Open Access Journals (Sweden)

    Jee-Youn Kim

    Full Text Available The green tea component (--epigallocatechin-3-gallate (EGCG has been shown to sensitize many different types of cancer cells to anticancer drug-induced apoptosis, although it protects against non-cancerous primary cells against toxicity from certain conditions such as exposure to arsenic (As or ultraviolet irradiation. Here, we found that EGCG promotes As-induced toxicity of primary-cultured bovine aortic endothelial cells (BAEC at doses in which treatment with each chemical alone had no such effect. Increased cell toxicity was accompanied by an increased condensed chromatin pattern and fragmented nuclei, cleaved poly(ADP-ribose polymerase (PARP, activity of the pro-apoptotic enzymes caspases 3, 8 and 9, and Bax translocation into mitochondria, suggesting the involvement of an apoptotic signaling pathway. Fluorescence activated cell sorting analysis revealed that compared with EGCG or As alone, combined EGCG and As (EGCG/As treatment significantly induced production of reactive oxygen species (ROS, which was accompanied by decreased catalase activity and increased lipid peroxidation. Pretreatment with N-acetyl-L-cysteine or catalase reversed EGCG/As-induced caspase activation and EC toxicity. EGCG/As also increased the phosphorylation of c-Jun N-terminal kinase (JNK, which was not reversed by catalase. However, pretreatment with the JNK inhibitor SP600125 reversed all of the observed effects of EGCG/As, suggesting that JNK may be the most upstream protein examined in this study. Finally, we also found that all the observed effects by EGCG/As are true for other types of EC tested. In conclusion, this is firstly to show that EGCG sensitizes non-cancerous EC to As-induced toxicity through ROS-mediated apoptosis, which was attributed at least in part to a JNK-activated decrease in catalase activity.

  2. The Green Tea Component (-)-Epigallocatechin-3-Gallate Sensitizes Primary Endothelial Cells to Arsenite-Induced Apoptosis by Decreasing c-Jun N-Terminal Kinase-Mediated Catalase Activity.

    Science.gov (United States)

    Kim, Jee-Youn; Choi, Ji-Young; Lee, Hyeon-Ju; Byun, Catherine Jeonghae; Park, Jung-Hyun; Park, Jae Hoon; Cho, Ho-Seong; Cho, Sung-Jin; Jo, Sangmee Ahn; Jo, Inho

    2015-01-01

    The green tea component (-)-epigallocatechin-3-gallate (EGCG) has been shown to sensitize many different types of cancer cells to anticancer drug-induced apoptosis, although it protects against non-cancerous primary cells against toxicity from certain conditions such as exposure to arsenic (As) or ultraviolet irradiation. Here, we found that EGCG promotes As-induced toxicity of primary-cultured bovine aortic endothelial cells (BAEC) at doses in which treatment with each chemical alone had no such effect. Increased cell toxicity was accompanied by an increased condensed chromatin pattern and fragmented nuclei, cleaved poly(ADP-ribose) polymerase (PARP), activity of the pro-apoptotic enzymes caspases 3, 8 and 9, and Bax translocation into mitochondria, suggesting the involvement of an apoptotic signaling pathway. Fluorescence activated cell sorting analysis revealed that compared with EGCG or As alone, combined EGCG and As (EGCG/As) treatment significantly induced production of reactive oxygen species (ROS), which was accompanied by decreased catalase activity and increased lipid peroxidation. Pretreatment with N-acetyl-L-cysteine or catalase reversed EGCG/As-induced caspase activation and EC toxicity. EGCG/As also increased the phosphorylation of c-Jun N-terminal kinase (JNK), which was not reversed by catalase. However, pretreatment with the JNK inhibitor SP600125 reversed all of the observed effects of EGCG/As, suggesting that JNK may be the most upstream protein examined in this study. Finally, we also found that all the observed effects by EGCG/As are true for other types of EC tested. In conclusion, this is firstly to show that EGCG sensitizes non-cancerous EC to As-induced toxicity through ROS-mediated apoptosis, which was attributed at least in part to a JNK-activated decrease in catalase activity.

  3. Green Tea Extract Ameliorates Learning and Memory Deficits in Ischemic Rats via Its Active Component Polyphenol Epigallocatechin-3-gallate by Modulation of Oxidative Stress and Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Kuo-Jen Wu

    2012-01-01

    Full Text Available Ischemic stroke results in brain damage and behavioral deficits including memory impairment. Protective effects of green tea extract (GTex and its major functional polyphenol (−-epigallocatechin gallate (EGCG on memory were examined in cerebral ischemic rats. GTex and EGCG were administered 1 hr before middle cerebral artery ligation in rats. GTex, EGCG, and pentoxifylline (PTX significantly improved ishemic-induced memory impairment in a Morris water maze test. Malondialdehyde (MDA levels, glutathione (GSH, and superoxide dismutase (SOD activity in the cerebral cortex and hippocampus were increased by long-term treatment with GTex and EGCG. Both compounds were also associated with reduced cerebral infraction breakdown of MDA and GSH in the hippocampus. In in vitro experiments, EGCG had anti-inflammatory effects in BV-2 microglia cells. EGCG inhibited lipopolysaccharide- (LPS- induced nitric oxide production and reduced cyclooxygenase-2 and inducible nitric oxide synthase expression in BV-2 cells. GTex and its active polyphenol EGCG improved learning and memory deficits in a cerebral ischemia animal model and such protection may be due to the reduction of oxidative stress and neuroinflammation.

  4. Biophysical characteristics of proteins and living cells exposed to the green tea polyphenol epigallocatechin-3-gallate (EGCg): review of recent advances from molecular mechanisms to nanomedicine and clinical trials.

    Science.gov (United States)

    Peter, Beatrix; Bosze, Szilvia; Horvath, Robert

    2017-01-01

    Herbs and traditional medicines have been applied for thousands of years, but researchers started to study their mode of action at the molecular, cellular and tissue levels only recently. Nowadays, just like in ancient times, natural compounds are still determining factors in remedies. To support this statement, the recently won Nobel Prize for an anti-malaria agent from the plant sweet wormwood, which had been used to effectively treat the disease, could be mentioned. Among natural compounds and traditional Chinese medicines, the green tea polyphenol epigallocatechin gallate (EGCg) is one of the most studied active substances. In the present review, we summarize the molecular scale interactions of proteins and EGCg with special focus on its limited stability and antioxidant properties. We outline the observed biophysical effects of EGCg on various cell lines and cultures. The alteration of cell adhesion, motility, migration, stiffness, apoptosis, proliferation as well as the different impacts on normal and cancer cells are all reviewed. We also handle the works performed using animal models, microbes and clinical trials. Novel ways to develop its utilization for therapeutic purposes in the future are discussed too, for instance, using nanoparticles and green tea polyphenols together to cure illnesses and the combination of EGCg and anticancer compounds to intensify their effects. The limitations of the employed experimental models and criticisms of the interpretation of the obtained experimental data are summarized as well.

  5. A component of green tea (-)-epigallocatechin-3-gallate, promotes apoptosis in T24 human bladder cancer cells via modulation of the PI3K/Akt pathway and Bcl-2 family proteins

    International Nuclear Information System (INIS)

    Qin Jie; Xie Liping; Zheng Xiangyi; Wang Yunbin; Bai Yu; Shen Huafeng; Li Longcheng; Dahiya, Rajvir

    2007-01-01

    Bladder cancer is the fourth most common cancer in men and ninth most common in women. It has a protracted course of progression and is thus an ideal candidate for chemoprevention strategies and trials. This study was conducted to evaluate the chemopreventive/antiproliferative potential of (-)-epigallocatechin gallate (EGCG, the major phytochemical in green tea) against bladder cancer and its mechanism of action. Using the T24 human bladder cancer cell line, we found that EGCG treatment caused dose- and time-dependent inhibition of cellular proliferation and cell viability, and induced apoptosis. Mechanistically, EGCG inhibits phosphatidylinositol 3'-kinase/Akt activation that, in turn, results in modulation of Bcl-2 family proteins, leading to enhanced apoptosis of T24 cells. These findings suggest that EGCG may be an important chemoprevention agent for the management of bladder cancer

  6. Epigallocatechin-3-gallate on Melanogenesis in Ultraviolet A ...

    African Journals Online (AJOL)

    compared to blank (control) which was neither treated by UVA nor by EGCG. TEM showed that UVA induced the formation of ... Biological Engineering Technology Co., Ltd,. (Shanghai, China). PA102 Bradford protein assay kit ..... Sliney DH. Estimating the solar ultraviolet radiation exposure to an intraocular eye implant.

  7. Green-Tea and Epigallocatechin-3-Gallate are Bactericidal against Bacillus anthracis

    Science.gov (United States)

    2017-06-13

    strategies against B. anthracis (3). 60 After water, tea is the most consumed beverage in the world. Although containing little 61 caloric value, teas...Civilian B. 2002. Anthrax as a biological weapon, 2002: updated 270 recommendations for management . JAMA 287:2236-52. 271 4. Cabrera C, Artacho R...Sharma A, Gupta S, Sarethy IP, Dang S, Gabrani R. 2012. Green tea extract: possible mechanism 285 and antibacterial activity on skin pathogens. Food

  8. The regulation of steroid receptors by epigallocatechin-3-gallate in breast cancer cells

    Directory of Open Access Journals (Sweden)

    Hallman K

    2017-05-01

    Full Text Available Kelly Hallman,* Katie Aleck,* Meghan Quigley, Brigitte Dwyer, Victoria Lloyd, Monica Szmyd, Sumi Dinda Biomedical Diagnostic and Therapeutic Sciences, School of Health Sciences, Center for Biomedical Research, Oakland University, Rochester, MI, USA *These authors contributed equally to this work Abstract: It has been reported that phytoestrogen epigallocatechin gallate (EGCG suppresses cancer cell proliferation and may have antitumor properties. In this study, we analyzed the effects of EGCG on estrogen receptor α (ERα and progesterone receptor in hormone-dependent T-47D breast cancer cells. Western blot analysis revealed EGCG induced a concentration-dependent decrease in ERα protein levels, with a 56% reduction occurring with 60 µM EGCG when compared to controls. Downregulation of ERα protein levels was observed after 24-hour co-treatment of T-47D cells with 60 µM EGCG and 10 nM 17β-estradiol (E2. The proliferative effect of E2 on cell viability was reversed when treated in combination with EGCG. In contrast, the combination of EGCG with the pure ER antagonist, ICI 182, 780, showed no further reduction in cell number as only 5% of the cells were viable after 6 days of treatment. These studies may provide further understanding of the interactions among flavonoids and steroid receptors in breast cancer cells. Keywords: phytoestrogen, ER, PR, T-47D, antiestrogens

  9. Direct interaction of natural and synthetic catechins with signal transducer activator of transcription 1 affects both its phosphorylation and activity

    KAUST Repository

    Menegazzi, Marta; Mariotto, Sofia; Dal Bosco, Martina; Darra, Elena; Vaiana, Nadia; Shoji, Kazuo; Safwat, Abdel Azeim; Marechal, Jean Didier; Perahia, David; Suzuki, Hisanori; Romeo, Sergio

    2013-01-01

    Our previous studies showed that (-)-epigallocatechin-3-gallate (EGCG) inhibits signal transducer activator of transcription 1 (STAT1) activation. Since EGCG may be a promising lead compound for new anti-STAT1 drug design, 15 synthetic catechins

  10. A green tea polyphenol epigallocatechin-3-gallate enhances neuroregeneration after spinal cord injury by altering levels of inflammatory cytokines.

    Czech Academy of Sciences Publication Activity Database

    Machová-Urdzíková, Lucia; Růžička, Jiří; Kárová, Kristýna; Kloudová, Anna; Svobodová, Barbora; Anubhav, A.; Dubišová, Jana; Schmidt, M.; Kubinová, Šárka; Jhanwar Uniyal, M.; Jendelová, Pavla

    2017-01-01

    Roč. 126, nov. (2017), s. 213-223 ISSN 0028-3908 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) EF15_003/0000419; GA MŠk(CZ) LM2015064; GA MŠk LTAUSA17120 Institutional support: RVO:68378041 Keywords : cytokines * EGCG * green tea Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 5.012, year: 2016

  11. Chronic epigallocatechin-3-gallate ameliorates learning and memory deficits in diabetic rats via modulation of nitric oxide and oxidative stress.

    Science.gov (United States)

    Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad

    2011-10-31

    Due to anti-diabetic and antioxidant activity of green tea epigallocatechin gallate (EGCG) and the existence of evidence for its beneficial effect on cognition and memory, this research study was conducted to evaluate, for the first time, the efficacy of chronic EGCG on alleviation of learning and memory deficits in streptozotocin (STZ)-diabetic rats. Male Wistar rats were divided into control, diabetic, EGCG-treated-control and -diabetic groups. EGCG was administered at a dose of 20 and 40 mg/kg/day for 7 weeks. Learning and memory was evaluated using Y maze, passive avoidance, and radial 8-arm maze (RAM) tests. Oxidative stress markers and involvement of nitric oxide system were also evaluated. Alternation score of the diabetic rats in Y maze was lower than that of control and a significant impairment was observed in retention and recall in passive avoidance test (pRAM task and EGCG (40 mg/kg) significantly ameliorated these changes (pmemory respectively. Meanwhile, increased levels of malondialdehyde (MDA) and nitrite in diabetic rats significantly reduced due to EGCG treatment (pmemory deficits in STZ-diabetic rats through attenuation of oxidative stress and modulation of NO. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Preventive effects of a major component of green tea, epigallocathechin-3-gallate, on hepatitis-B virus DNA replication.

    Science.gov (United States)

    Karamese, Murat; Aydogdu, Sabiha; Karamese, Selina Aksak; Altoparlak, Ulku; Gundogdu, Cemal

    2015-01-01

    Hepatitis B virus infection is one of the major world health problems. Epigallocatechin-3 gallate is the major component of the polyphenolic fraction of green tea and it has an anti-viral, anti-mutagenic, anti- tumorigenic, anti-angiogenic, anti-proliferative, and/or pro-apoptotic effects on mammalian cells. In this study, our aim was to investigate the inhibition of HBV replication by epigallocatechin-3 gallate in the Hep3B2.1-7 hepatocellular carcinoma cell line. HBV-replicating Hep3B2.1-7 cells were used to investigate the preventive effects of epigallocatechin-3 gallate on HBV DNA replication. The expression levels of HBsAg and HBeAg were determined using ELISA. Quantitative real-time-PCR was applied for the determination of the expression level of HBV DNA. Cytotoxicity of epigallocathechin-3-gallate was not observed in the hepatic carcinoma cell line when the dose was lower than 100 μM. The ELISA method demonstrated that epigallocatechin-3 gallate have strong effects on HBsAg and HBeAg levels. Also it was detected by real-time PCR that epigallocatechin-3 gallate could prevent HBV DNA replication. The obtained data pointed out that although the exact mechanism of HBV DNA replication and related diseases remains unclear, epigallocatechin-3 gallate has a potential as an effective anti-HBV agent with low toxicity.

  13. EGCG Inhibits Proliferation, Invasiveness and Tumor Growth by Up-Regulation of Adhesion Molecules, Suppression of Gelatinases Activity, and Induction of Apoptosis in Nasopharyngeal Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Chih-Yeu Fang

    2015-01-01

    Full Text Available (−-Epigallocatechin-3-gallate (EGCG, a major green tea polyphenol, has been shown to inhibit the proliferation of a variety of tumor cells. Epidemiological studies have shown that drinking green tea can reduce the incidence of nasopharyngeal carcinoma (NPC, yet the underlying mechanism is not well understood. In this study, the inhibitory effect of EGCG was tested on a set of Epstein Barr virus-negative and -positive NPC cell lines. Treatment with EGCG inhibited the proliferation of NPC cells but did not affect the growth of a non-malignant nasopharyngeal cell line, NP460hTert. Moreover, EGCG treated cells had reduced migration and invasive properties. The expression of the cell adhesion molecules E-cadherin and β-catenin was found to be up-regulated by EGCG treatment, while the down-regulation of matrix metalloproteinases (MMP-2 and MMP-9 were found to be mediated by suppression of extracellular signal-regulated kinase (ERK phosphorylation and AP-1 and Sp1 transactivation. Spheroid formation by NPC cells in suspension was significantly inhibited by EGCG. Oral administration of EGCG was capable of suppressing tumor growth in xenografted mice bearing NPC tumors. Treatment with EGCG was found to elevate the expression of p53 and p21, and eventually led to apoptosis of NPC cells via caspase 3 activation. The nuclear translocation of NF-κB and β-catenin was also suppressed by EGCG treatment. These results indicate that EGCG can inhibit the proliferation and invasiveness, and induce apoptosis, of NPC cells, making it a promising agent for chemoprevention or adjuvant therapy of NPC.

  14. Skin delivery of epigallocatechin-3-gallate (EGCG) and hyaluronic acid loaded nano-transfersomes for antioxidant and anti-aging effects in UV radiation induced skin damage.

    Science.gov (United States)

    Avadhani, Kiran S; Manikkath, Jyothsna; Tiwari, Mradul; Chandrasekhar, Misra; Godavarthi, Ashok; Vidya, Shimoga M; Hariharapura, Raghu C; Kalthur, Guruprasad; Udupa, Nayanabhirama; Mutalik, Srinivas

    2017-11-01

    The present work attempts to develop and statistically optimize transfersomes containing EGCG and hyaluronic acid to synergize the UV radiation-protective ability of both compounds, along with imparting antioxidant and anti-aging effects. Transfersomes were prepared by thin film hydration technique, using soy phosphatidylcholine and sodium cholate, combined with high-pressure homogenization. They were characterized with respect to size, polydispersity index, zeta potential, morphology, entrapment efficiency, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), in vitro antioxidant activity and ex vivo skin permeation studies. Cell viability, lipid peroxidation, intracellular ROS levels and expression of MMPs (2 and 9) were determined in human keratinocyte cell lines (HaCaT). The composition of the transfersomes was statistically optimized by Design of Experiments using Box-Behnken design with four factors at three levels. The optimized transfersome formulation showed vesicle size, polydispersity index and zeta potential of 101.2 ± 6.0 nm, 0.245 ± 0.069 and -44.8 ± 5.24 mV, respectively. FTIR and DSC showed no interaction between EGCG and the selected excipients. XRD results revealed no form conversion of EGCG in its transfersomal form. The optimized transfersomes were found to increase the cell viability and reduce the lipid peroxidation, intracellular ROS and expression of MMPs in HaCaT cells. The optimized transfersomal formulation of EGCG and HA exhibited considerably higher skin permeation and deposition of EGCG than that observed with plain EGCG. The results underline the potential application of the developed transfersomes in sunscreen cream/lotions for improvement of UV radiation-protection along with deriving antioxidant and anti-aging effects.

  15. Epigallocatechin-3-gallate combined with cognitive training in young adults with Down syndrome Phase II clinical trial: Important considerations for treatment- efficacy evaluation on cognitive and functional improvement

    OpenAIRE

    del Hoyo Soriano, Laura

    2016-01-01

    Introducción: El síndrome de Down es un trastorno del neurodesarrollo causado por la trisomía 21 que conduce a una serie de déficits cognitivos y funcionales, un alto riesgo de desarrollo precoz de la enfermedad de Alzheimer y deterioro cognitivo en edades tempranas. Debido a un aumento de la esperanza de vida en el síndrome de Down y a la gran variabilidad a nivel cognitivo existente en esta población, es imprescindible evaluar que posibles factores explicarían estas diferencias. Este conoci...

  16. Application of non-invasive low strength pulsed electric field to EGCG treatment synergistically enhanced the inhibition effect on PANC-1 cells.

    Science.gov (United States)

    Hsieh, Chih-Hsiung; Lu, Chueh-Hsuan; Chen, Wei-Ting; Ma, Bo-Lun; Chao, Chih-Yu

    2017-01-01

    Traditional therapies for pancreatic cancer are usually expensive and likely to cause side effects, and most patients have the risk of recurrence and suffering pain. Here, we investigated combination treatment of epigallocatechin-3-gallate (EGCG) and non-invasive low strength pulsed electric field (PEF) on the human pancreatic cell line PANC-1. Cells were cultured in various concentrations of EGCG and exposed to trains of PEF. The results showed that the low strength PEF alone or single treatment with low concentration of EGCG did not obviously affect the cell proliferation and migration in PANC-1. However, the EGCG-induced inhibitions of cell viability and migration ability in PANC-1 were dramatically enhanced by the further exposure of low strength PEF (60 V/cm). In particular, the same combination treatment caused less inhibition of cell viability in non-malignant HEK293 cells. We also found the combination treatment significantly decreased the ratio of Bcl-2/Bax protein and increased caspase activity in PANC-1 cells, resulting in the promotion of apoptotic responses, evidenced by chromatin condensation. The findings of the present study reveal the synergistic reactions in the combination treatment may severely disturb mitochondria, enhance the intrinsic pathway transduction, and effectively induce apoptosis; moreover, the migration and invasion of PANC-1 cancer cells were also significantly suppressed. Since normal cells are less sensitive to this combination treatment, and the non-invasive PEF could be modified to focus on a specific location, this treatment may serve as a promising method for anti-cancer therapy.

  17. Coptis chinensis Polysaccharides Inhibit Advanced Glycation End Product Formation.

    Science.gov (United States)

    Yang, Ye; Li, Yun; Yin, Dengke; Chen, Song; Gao, Xiangdong

    2016-06-01

    Coptis chinensis Franch (Huanglian) is commonly used to treat diabetes in China. In this study, the effects of the C. chinensis Franch polysaccharides (CCP) on advanced glycation end product (AGE) formation in vitro and in streptozotocin-induced diabetic mice were investigated. CCP significantly inhibited all the three periods of nonenzymatic protein glycation in vitro, including Amadori product, dicarbonyl compound, and AGE formation (P < .01). In diabetic mice, the administration of CCP not only improved both bodyweight and serum insulin and decreased fasting blood glucose and glycated serum protein concentrations but also decreased the AGE accumulations and morphological abnormalities in pancreas and liver. The inhibitory effects of CCP on AGE formation afford a potential therapeutic use in the prevention and treatment of diabetes.

  18. Inhibition of protein glycation and advanced glycation end products ...

    African Journals Online (AJOL)

    Advanced glycation end products (AGEs) formation is increased in diabetes mellitus, leading to microvascular and macrovascular complications. Recently, much attention has been focused on natural and synthetic inhibitors to delay the onset or progression of diabetes and its comorbidities. Ascorbic acid (AA) can react with ...

  19. Advanced Glycation End Products Inhibit the Proliferation of Human Umbilical Vein Endothelial Cells by Inhibiting Cathepsin D

    Directory of Open Access Journals (Sweden)

    Yuan Li

    2017-02-01

    Full Text Available We aimed to investigate the effect of advanced glycation end products (AGEs on the proliferation and migration ability of human umbilical vein endothelial cells (HUVECs. Cell proliferation was detected by methyl thiazolyl tetrazolium (MTT assay, real-time cell analyzer and 5-Ethynyl-2′-deoxyuridine (EdU staining. Cell migration was detected by wound-healing and transwell assay. AGEs significantly inhibited the proliferation and migration of HUVECs in a time-and dose-dependent way. Western blotting revealed that AGEs dramatically increased the expression of microtubule-associated protein 1 light chain 3 (LC3 II/I and p62. Immunofluorescence of p62 and acridine orange staining revealed that AGEs significantly increased the expression of p62 and the accumulation of autophagic vacuoles, respectively. Chloroquine (CQ could further promote the expression of LC3 II/I and p62, increase the accumulation of autophagic vacuoles and promote cell injury induced by AGEs. In addition, AGEs reduced cathepsin D (CTSD expression in a time-dependent way. Overexpression of wild-type CTSD significantly decreased the ratio of LC 3 II/I as well as p62 accumulation induced by AGEs, but overexpression of catalytically inactive mutant CTSD had no such effects. Only overexpression of wild-type CTSD could restore the proliferation of HUVECs inhibited by AGEs. However, overexpression of both wild-type CTSD and catalytically inactive mutant CTSD could promote the migration of HUVECs inhibited by AGEs. Collectively, our study found that AGEs inhibited the proliferation and migration in HUVECs and promoted autophagic flux, which in turn played a protective role against AGEs-induced cell injury. CTSD, in need of its catalytic activity, may promote proliferation in AGEs-treated HUVECs independent of the autophagy-lysosome pathway. Meanwhile, CTSD could improve the migration of AGEs-treated HUVECs regardless of its enzymatic activity.

  20. Advanced Glycation End Products Inhibit the Proliferation of Human Umbilical Vein Endothelial Cells by Inhibiting Cathepsin D.

    Science.gov (United States)

    Li, Yuan; Chang, Ye; Ye, Ning; Dai, Dongxue; Chen, Yintao; Zhang, Naijin; Sun, Guozhe; Sun, Yingxian

    2017-02-17

    We aimed to investigate the effect of advanced glycation end products (AGEs) on the proliferation and migration ability of human umbilical vein endothelial cells (HUVECs). Cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) assay, real-time cell analyzer and 5-Ethynyl-2'-deoxyuridine (EdU) staining. Cell migration was detected by wound-healing and transwell assay. AGEs significantly inhibited the proliferation and migration of HUVECs in a time-and dose-dependent way. Western blotting revealed that AGEs dramatically increased the expression of microtubule-associated protein 1 light chain 3 (LC3) II/I and p62. Immunofluorescence of p62 and acridine orange staining revealed that AGEs significantly increased the expression of p62 and the accumulation of autophagic vacuoles, respectively. Chloroquine (CQ) could further promote the expression of LC3 II/I and p62, increase the accumulation of autophagic vacuoles and promote cell injury induced by AGEs. In addition, AGEs reduced cathepsin D (CTSD) expression in a time-dependent way. Overexpression of wild-type CTSD significantly decreased the ratio of LC 3 II/I as well as p62 accumulation induced by AGEs, but overexpression of catalytically inactive mutant CTSD had no such effects. Only overexpression of wild-type CTSD could restore the proliferation of HUVECs inhibited by AGEs. However, overexpression of both wild-type CTSD and catalytically inactive mutant CTSD could promote the migration of HUVECs inhibited by AGEs. Collectively, our study found that AGEs inhibited the proliferation and migration in HUVECs and promoted autophagic flux, which in turn played a protective role against AGEs-induced cell injury. CTSD, in need of its catalytic activity, may promote proliferation in AGEs-treated HUVECs independent of the autophagy-lysosome pathway. Meanwhile, CTSD could improve the migration of AGEs-treated HUVECs regardless of its enzymatic activity.

  1. EGCG-targeted p57/KIP2 reduces tumorigenicity of oral carcinoma cells: Role of c-Jun N-terminal kinase

    International Nuclear Information System (INIS)

    Yamamoto, Tetsuya; Digumarthi, Hari; Aranbayeva, Zina; Wataha, John; Lewis, Jill; Messer, Regina; Qin, Haiyan; Dickinson, Douglas; Osaki, Tokio; Schuster, George S.; Hsu, Stephen

    2007-01-01

    The green tea polyphenol epigallocatechin-3-gallate (EGCG) regulates gene expression differentially in tumor and normal cells. In normal human primary epidermal keratinocytes (NHEK), one of the key mediators of EGCG action is p57/KIP2, a cyclin-dependent kinase (CDK) inhibitor. EGCG potently induces p57 in NHEK, but not in epithelial cancer cells. In humans, reduced expression of p57 often is associated with advanced tumors, and tumor cells with inactivated p57 undergo apoptosis when exposed to EGCG. The mechanism of p57 induction by EGCG is not well understood. Here, we show that in NHEK, EGCG-induces p57 via the p38 mitogen-activated protein kinase (MAPK) signaling pathway. In p57-negative tumor cells, JNK signaling mediates EGCG-induced apoptosis, and exogenous expression of p57 suppresses EGCG-induced apoptosis via inhibition of c-Jun N-terminal kinase (JNK). We also found that restoration of p57 expression in tumor cells significantly reduced tumorigenicity in athymic mice. These results suggest that p57 expression may be an useful indicator for the clinical course of cancers, and could be potentially useful as a target for cancer therapies

  2. Nanoencapsulation of polyphenols for protective effect against colon-rectal cancer.

    Science.gov (United States)

    Santos, Isis S; Ponte, Bruno M; Boonme, Prapaporn; Silva, Amélia M; Souto, Eliana B

    2013-01-01

    The human population at large is exposed to many critical factors (e.g. bad food habits, chemical substances, and stress) leading to the development of serious diseases. Colon or colorectal cancer is one of the most prevalent types of cancer in many countries. Despite being a multi-factorial chronic disease, resulting from the interaction of multiple genetic and environmental factors, the critical factor is mostly a poor diet regimen. Therefore, an accumulation of constant mutations leads to a complex arrangement of events during tumor initiation, development and propagation. It is well known that many plants are rich in polyphenols with anti-oxidant, anti-atherogenic, anti-diabetic, anti-cancer, anti-viral, and anti-inflammatory properties. These compounds are secondary metabolites with the ability to donate electrons to free radicals through different mechanisms. In recent years, a large number of studies have attributed a protective effect to polyphenols and foods containing these compounds (e.g. plants, vegetables, cereals, tea, coffee or chocolate). Polyphenolic compounds have been described to inhibit cancer development and propagation, being used as chemopreventive agents. Some polyphenols reported a preventive action against colon cancer, e.g. curcumin, gallic acid, ellagic acid, and epigallocatechin-3-gallate. The present article focuses on the properties of these molecules as chemopreventive agents and the recent advances on their formulation in nanoparticulate systems for targeted therapy and increased bioavailability. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Platyphylloside Isolated From Betula platyphylla Inhibit Adipocyte Differentiation and Induce Lipolysis Via Regulating Adipokines Including PPARγ in 3T3-L1 Cells

    Science.gov (United States)

    Lee, Mina; Sung, Sang Hyun

    2016-01-01

    -regulation of HSL, perilipin, PPARγ, PDE3B, and Gia1.BPP is a novel potential agent in the prevention and treatment of obesity through its anti-adipogenic activities and lipolysis. Abbreviations used: DMEM: Dulbecco's modified Eagle's medium, FBS: fetal bovine serum, ORO: Oil Red O, PBS: phosphate buffered saline, RT: room temperature, PPAR: peroxisome proliferator-activated receptor, C/EBP: CCAAT/enhancer-binding protein, SREBP1: sterol regulatory element binding protein 1, SCD-1: steroyl-coenzyme A desaturase 1, LPL: lipoprotein lipase, aP2: adipocyte fatty acid binding protein, FAS: fatty acid synthase, HSL: hormone sensitive lipase, Giα1: GPT binding protein, PDE3B: phosphodiesterase 3B, TNFα: tumor necrosis factor α, GAPDH: glyceraldehyde 3-phosphate dehydrogenase, SD: standard deviation, EGCG: epigallocatechin-3-gallate, TZD: thiazolidinediones PMID:27867269

  4. Targeting receptor for advanced glycation end products (RAGE) expression induces apoptosis and inhibits prostate tumor growth

    International Nuclear Information System (INIS)

    Elangovan, Indira; Thirugnanam, Sivasakthivel; Chen, Aoshuang; Zheng, Guoxing; Bosland, Maarten C.; Kajdacsy-Balla, André; Gnanasekar, Munirathinam

    2012-01-01

    Highlights: ► Targeting RAGE by RNAi induces apoptosis in prostate cancer cells. ► Silencing RAGE expression abrogates rHMGB1 mediated cell proliferation. ► Down regulation of RAGE by RNAi inhibits PSA secretion of prostate cancer cells. ► Knock down of RAGE abrogates prostate tumor growth in vivo. ► Disruption of RAGE expression in prostate tumor activates death receptors. -- Abstract: Expression of receptor for advanced glycation end products (RAGE) plays a key role in the progression of prostate cancer. However, the therapeutic potential of targeting RAGE expression in prostate cancer is not yet evaluated. Therefore in this study, we have investigated the effects of silencing the expression of RAGE by RNAi approach both in vitro and in vivo. The results of this study showed that down regulation of RAGE expression by RNAi inhibited the cell proliferation of androgen-dependent (LNCaP) and androgen-independent (DU-145) prostate cancer cells. Furthermore, targeting RAGE expression resulted in apoptotic elimination of these prostate cancer cells by activation of caspase-8 and caspase-3 death signaling. Of note, the levels of prostate specific antigen (PSA) were also reduced in LNCaP cells transfected with RAGE RNAi constructs. Importantly, the RAGE RNAi constructs when administered in nude mice bearing prostate tumors, inhibited the tumor growth by targeting the expression of RAGE, and its physiological ligand, HMGB1 and by up regulating death receptors DR4 and DR5 expression. Collectively, the results of this study for the first time show that targeting RAGE by RNAi may be a promising alternative therapeutic strategy for treating prostate cancer.

  5. Advanced glycation endproducts form during ovalbumin digestion in the presence of fructose: Inhibition by chlorogenic acid.

    Science.gov (United States)

    Bains, Yasmin; Gugliucci, Alejandro; Caccavello, Russell

    2017-07-01

    One mechanism by which fructose could exert deleterious effects is through intestinal formation and absorption of pro-inflammatory advanced glycation endproducts via the Maillard reaction. We employed simulated stomach and duodenum digestion of ovalbumin (OVA) to test the hypothesis that advanced glycation endproducts (AGEs) are formed by fructose during simulated digestion of a ubiquitous food protein under model physiological conditions. OVA was subjected to simulated gastric and intestinal digestion using standard models, in presence of fructose or glucose (0-100mM). Peptide fractions were analyzed by fluorescence spectroscopy and intensity at Excitation: λ370nm, Emission: λ 440nm. AGE adducts formed between fructose and OVA, evidenced by the peptide fractions (fructose-AGE formation on a ubiquitous dietary protein under model physiological conditions. Our study also suggests ways to decrease the damage: enteral fructose-AGE formation may be partially inhibited by co-intake of beverages, fruits and vegetables with concentrations of phenolics high enough to serve as anti-glycation agents. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Emerging role of epidermal growth factor receptor inhibition in therapy for advanced malignancy: focus on NSCLC

    International Nuclear Information System (INIS)

    Langer, Corey J.

    2004-01-01

    Combination chemotherapy regimens have emerged as the standard approach in advanced non-small-cell lung cancer. Meta-analyses have demonstrated a 2-month increase in median survival after platinum-based therapy vs. best supportive care, and an absolute 10% improvement in the 1-year survival rate. Just as importantly, cytotoxic therapy has produced benefits in symptom control and quality of life. Newer agents, including the taxanes, vinorelbine, gemcitabine, and irinotecan, have expanded our therapeutic options in the treatment of advanced non-small-cell lung cancer. Despite their contributions, we have reached a therapeutic plateau, with response rates seldom exceeding 30-40% in cooperative group studies and 1-year survival rates stable between 30% and 40%. It is doubtful that substituting one agent for another in various combinations will lead to any further improvement in these rates. The thrust of current research has focused on targeted therapy, and epidermal growth factor receptor inhibition is one of the most promising clinical strategies. Epidermal growth factor receptor inhibitors currently under investigation include the small molecules gefitinib (Iressa, ZD1839) and erlotinib (Tarceva, OSI-774), as well as monoclonal antibodies such as cetuximab (IMC-225, Erbitux). Agents that have only begun to undergo clinical evaluation include CI-1033, an irreversible pan-erbB tyrosine kinase inhibitor, and PKI166 and GW572016, both examples of dual kinase inhibitors (inhibiting epidermal growth factor receptor and Her2). Preclinical models have demonstrated synergy for all these agents in combination with either chemotherapy or radiotherapy, leading to great enthusiasm regarding their ultimate contribution to lung cancer therapy. However, serious clinical challenges persist. These include the identification of the optimal dose(s); the proper integration of these agents into popular, established cytotoxic regimens; and the selection of the optimal setting(s) in which

  7. Receptor for advanced glycation end products inhibits proliferation in osteoblast through suppression of Wnt, PI3K and ERK signaling

    International Nuclear Information System (INIS)

    Li, Guofeng; Xu, Jingren; Li, Zengchun

    2012-01-01

    Highlights: ► RAGE overexpression suppresses cell proliferation in MC3T3-E1 cells. ► RAGE overexpression decreases Wnt/β-catenin signaling. ► RAGE overexpression decreases ERK and PI3K signaling. ► Inhibition of Wnt signaling abolishes PI3K signaling restored by RAGE blockade. ► Inhibition of Wnt signaling abolishes ERK signaling restored by RAGE blockade. -- Abstract: Expression of receptor for advanced glycation end products (RAGE) plays a crucial role in bone metabolism. However, the role of RAGE in the control of osteoblast proliferation is not yet evaluated. In the present study, we demonstrate that RAGE overexpression inhibits osteoblast proliferation in vitro. The negative regulation of RAGE on cell proliferation results from suppression of Wnt, PI3K and ERK signaling, and is restored by RAGE neutralizing antibody. Prevention of Wnt signaling using Sfrp1 or DKK1 rescues RAGE-decreased PI3K and ERK signaling and cell proliferation, indicating that the altered cell growth in RAGE overexpressing cells is in part secondary to alterations in Wnt signaling. Consistently, RAGE overexpression inhibits the expression of Wnt targets cyclin D1 and c-myc, which is partially reversed by RAGE blockade. Overall, these results suggest that RAGE inhibits osteoblast proliferation via suppression of Wnt, PI3K and ERK signaling, which provides novel mechanisms by which RAGE regulates osteoblast growth.

  8. Receptor for advanced glycation end products inhibits proliferation in osteoblast through suppression of Wnt, PI3K and ERK signaling

    Energy Technology Data Exchange (ETDEWEB)

    Li, Guofeng [Department of Emergency Surgery, East Hospital, Tongji University School of Medicine, Shanghai 200120 (China); Xu, Jingren [Department of Traditional Chinese Orthopaedics, East Hospital, Tongji University School of Medicine, Shanghai 200120 (China); Li, Zengchun, E-mail: lizc.2007@yahoo.com.cn [Department of Emergency Surgery, East Hospital, Tongji University School of Medicine, Shanghai 200120 (China)

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer RAGE overexpression suppresses cell proliferation in MC3T3-E1 cells. Black-Right-Pointing-Pointer RAGE overexpression decreases Wnt/{beta}-catenin signaling. Black-Right-Pointing-Pointer RAGE overexpression decreases ERK and PI3K signaling. Black-Right-Pointing-Pointer Inhibition of Wnt signaling abolishes PI3K signaling restored by RAGE blockade. Black-Right-Pointing-Pointer Inhibition of Wnt signaling abolishes ERK signaling restored by RAGE blockade. -- Abstract: Expression of receptor for advanced glycation end products (RAGE) plays a crucial role in bone metabolism. However, the role of RAGE in the control of osteoblast proliferation is not yet evaluated. In the present study, we demonstrate that RAGE overexpression inhibits osteoblast proliferation in vitro. The negative regulation of RAGE on cell proliferation results from suppression of Wnt, PI3K and ERK signaling, and is restored by RAGE neutralizing antibody. Prevention of Wnt signaling using Sfrp1 or DKK1 rescues RAGE-decreased PI3K and ERK signaling and cell proliferation, indicating that the altered cell growth in RAGE overexpressing cells is in part secondary to alterations in Wnt signaling. Consistently, RAGE overexpression inhibits the expression of Wnt targets cyclin D1 and c-myc, which is partially reversed by RAGE blockade. Overall, these results suggest that RAGE inhibits osteoblast proliferation via suppression of Wnt, PI3K and ERK signaling, which provides novel mechanisms by which RAGE regulates osteoblast growth.

  9. The role of inhibition by phosphocitrate and its analogue in chondrocyte differentiation and subchondral bone advance in Hartley guinea pigs.

    Science.gov (United States)

    Sun, Yubo; Kiraly, Alex J; Cox, Michael; Mauerhan, David R; Hanley, Edward N

    2018-04-01

    Phosphocitrate (PC) and its analogue, PC-β ethyl ester, inhibit articular cartilage degeneration in Hartley guinea pigs. However, the underlying molecular mechanisms remain unclear. The present study aimed to investigate the hypothesis that PC exerted its disease-modifying effect on osteoarthritis (OA), in part, by inhibiting a molecular program similar to that in the endochondral pathway of ossification. The results demonstrated that severe proteoglycan loss occurred in the superficial and middle zones, as well as in the calcified zone of articular cartilage in the Hartley guinea pigs. Subchondral bone advance was greater in the control Hartley guinea pigs compared with PC- or PC analogue-treated guinea pigs. Resorption of cartilage bars or islands and vascular invasion in the growth plate were also greater in the control guinea pigs compared with the PC- or PC analogue-treated guinea pigs. The levels of matrix metalloproteinase-13 and type X collagen within the articular cartilage and growth plate were significantly increased in the control guinea pigs compared with PC-treated guinea pigs (Pguinea pigs exhibited a hypertrophic phenotype and recapitulated a developmental molecular program similar to the endochondral pathway of ossification. Activation of this molecular program resulted in resorption of calcified articular cartilage and subchondral bone advance. This suggests that PC and PC analogues exerted their OA disease-modifying activity, in part, by inhibiting this molecular program.

  10. Recent Advances in Electrochemical Biosensors Based on Enzyme Inhibition for Clinical and Pharmaceutical Applications.

    Science.gov (United States)

    El Harrad, Loubna; Bourais, Ilhame; Mohammadi, Hasna; Amine, Aziz

    2018-01-09

    A large number of enzyme inhibitors are used as drugs to treat several diseases such as gout, diabetes, AIDS, depression, Parkinson's and Alzheimer's diseases. Electrochemical biosensors based on enzyme inhibition are useful devices for an easy, fast and environment friendly monitoring of inhibitors like drugs. In the last decades, electrochemical biosensors have shown great potentials in the detection of different drugs like neostigmine, ketoconazole, donepezil, allopurinol and many others. They attracted increasing attention due to the advantage of being high sensitive and accurate analytical tools, able to reach low detection limits and the possibility to be performed on real samples. This review will spotlight the research conducted in the past 10 years (2007-2017) on inhibition based enzymatic electrochemical biosensors for the analysis of different drugs. New assays based on novel bio-devices will be debated. Moreover, the exploration of the recent graphical approach in diagnosis of reversible and irreversible inhibition mechanism will be discussed. The accurate and the fast diagnosis of inhibition type will help researchers in further drug design improvements and the identification of new molecules that will serve as new enzyme targets.

  11. Recent Advances in Electrochemical Biosensors Based on Enzyme Inhibition for Clinical and Pharmaceutical Applications

    Directory of Open Access Journals (Sweden)

    Loubna El Harrad

    2018-01-01

    Full Text Available A large number of enzyme inhibitors are used as drugs to treat several diseases such as gout, diabetes, AIDS, depression, Parkinson’s and Alzheimer’s diseases. Electrochemical biosensors based on enzyme inhibition are useful devices for an easy, fast and environment friendly monitoring of inhibitors like drugs. In the last decades, electrochemical biosensors have shown great potentials in the detection of different drugs like neostigmine, ketoconazole, donepezil, allopurinol and many others. They attracted increasing attention due to the advantage of being high sensitive and accurate analytical tools, able to reach low detection limits and the possibility to be performed on real samples. This review will spotlight the research conducted in the past 10 years (2007–2017 on inhibition based enzymatic electrochemical biosensors for the analysis of different drugs. New assays based on novel bio-devices will be debated. Moreover, the exploration of the recent graphical approach in diagnosis of reversible and irreversible inhibition mechanism will be discussed. The accurate and the fast diagnosis of inhibition type will help researchers in further drug design improvements and the identification of new molecules that will serve as new enzyme targets.

  12. Inhibition of macrophage oxidative stress prevents the reduction of ABCA-1 transporter induced by advanced glycated albumin.

    Science.gov (United States)

    de Souza Pinto, Raphael; Castilho, Gabriela; Paim, Bruno Alves; Machado-Lima, Adriana; Inada, Natalia M; Nakandakare, Edna Regina; Vercesi, Aníbal Eugênio; Passarelli, Marisa

    2012-05-01

    We investigated the role of aminoguanidine and benfotiamine on the inhibition of reactive oxygen species (ROS) generation in macrophages induced by advanced glycated albumin (AGE-albumin) and its relationship with cell cholesterol homeostasis, emphasizing the expression of the ATP binding cassette transporter A-1 (ABCA-1). AGE-albumin was made by incubating fatty acid-free albumin with 10 mM glycolaldehyde. ROS production and ABCA-1 protein level were determined by flow cytometry in J774 macrophages treated along time with control (C) or AGE-albumin alone or in the presence of aminoguanidine or benfotiamine. Mitochondrial function was evaluated by oxygraphy. Compared to C-albumin, AGE-albumin increased ROS production in macrophages, which was ascribed to the activities of NADPH oxidase and of the mitochondrial system. Mitochondrial respiratory chain activity was reduced in cells incubated with AGE-albumin. ROS generation along time was associated with the reduction in macrophage ABCA-1 protein level. Aminoguanidine prevented ROS elevation and restored the ABCA-1 content in macrophages; on the other hand, benfotiamine that promoted a lesser reduction in ROS generation was not able to restore ABCA-1 levels. Inhibition of oxidative stress induced by AGE-albumin prevents disturbances in reverse cholesterol transport by curbing the reduction of ABCA-1 elicited by advanced glycation in macrophages and therefore may contribute to the prevention of atherosclerosis in diabetes mellitus.

  13. Aspartic acid functions as carbonyl trapper to inhibit the formation of advanced glycation end products by chemical chaperone activity.

    Science.gov (United States)

    Prasanna, Govindarajan; Saraswathi, N T

    2016-05-01

    Advanced glycation end products (AGEs) were implicated in pathology of numerous diseases. In this study, we present the bioactivity of aspartic acid (Asp) to inhibit the AGEs. Hemoglobin and bovine serum albumin (BSA) were glycated with glucose, fructose, and ribose in the presence and absence of Asp (100-200 μM). HbA1c inhibition was investigated using human blood and characterized by micro-column ion exchange chromatography. The effect of methyl glyoxal (MG) on hemoglobin and BSA was evaluated by fluorescence spectroscopy and gel electrophoresis. The effect of MG on red blood cells morphology was characterized by scanning electron micrographs. Molecular docking was performed on BSA with Asp. Asp is capable of inhibiting the formation of fluorescent AGEs by reacting with the reducing sugars. The presence of Asp as supplement in whole blood reduced the HbA1c% from 8.8 to 6.1. The presence of MG showed an increase in fluorescence and the presence of Asp inhibited the glycation thereby the fluorescence was quenched. MG also affected the electrophoretic mobility of hemoglobin and BSA by forming high molecular weight aggregates. Normal RBCs showed typical biconcave shape. MG modified RBCs showed twisted and elongated shape whereas the presence of ASP tends to protect RBC from twisting. Asp interacted with arginine residues of bovine serum albumin particularly ARG 194, ARG 198, and ARG 217 thereby stabilized the protein complex. We conclude that Asp has dual functions as a chemical chaperone to stabilize protein and as a dicarbonyl trapper, and thereby it can prevent the complications caused by glycation.

  14. Effects of advanced glycation end-product inhibition and cross-link breakage in diabetic rats

    DEFF Research Database (Denmark)

    Oturai, P S; Christensen, M; Rolin, B

    2000-01-01

    ), and a breaker of already formed AGE cross-links, N-phenacylthiazolium bromide (PTB), were investigated in streptozotocin-diabetic female Wistar rats. Diabetes for 24 weeks resulted in decreased tail collagen pepsin solubility, reflecting the formation of AGE cross-linking. Collagen solubility was significantly...... ameliorated by treatment with NNC39-0028, whereas PTB had no effect. Increased urinary albumin excretion (UAE) in diabetic rats was observed in serial measurements throughout the study period, and was not reduced by any treatment. Vascular dysfunction in the eye, measured as increased clearance of 125I......-albumin, was induced by diabetes. NNC39-0028 did not affect this abnormality. This study demonstrated a pharmacological inhibition of collagen solubility alterations in diabetic rats without affecting diabetes-induced pathophysiology such as the increase in UAE or albumin clearance. Treatment with PTB, a specific...

  15. Recent Advances in the Inhibition of p38 MAPK as a Potential Strategy for the Treatment of Alzheimer's Disease.

    Science.gov (United States)

    Lee, Jong Kil; Kim, Nam-Jung

    2017-08-02

    P38 mitogen-activated protein kinase (MAPK) is a crucial target for chronic inflammatory diseases. Alzheimer's disease (AD) is characterized by the presence of amyloid plaques and neurofibrillary tangles in the brain, as well as neurodegeneration, and there is no known cure. Recent studies on the underlying biology of AD in cellular and animal models have indicated that p38 MAPK is capable of orchestrating diverse events related to AD, such as tau phosphorylation, neurotoxicity, neuroinflammation and synaptic dysfunction. Thus, the inhibition of p38 MAPK is considered a promising strategy for the treatment of AD. In this review, we summarize recent advances in the targeting of p38 MAPK as a potential strategy for the treatment of AD and envision possibilities of p38 MAPK inhibitors as a fundamental therapeutics for AD.

  16. Targeting multiple cannabinoid anti-tumour pathways with a resorcinol derivative leads to inhibition of advanced stages of breast cancer.

    Science.gov (United States)

    Murase, Ryuichi; Kawamura, Rumi; Singer, Eric; Pakdel, Arash; Sarma, Pranamee; Judkins, Jonathon; Elwakeel, Eiman; Dayal, Sonali; Martinez-Martinez, Esther; Amere, Mukkanti; Gujjar, Ramesh; Mahadevan, Anu; Desprez, Pierre-Yves; McAllister, Sean D

    2014-10-01

    The psychoactive cannabinoid Δ(9) -tetrahydrocannabinol (THC) and the non-psychoactive cannabinoid cannabidiol (CBD) can both reduce cancer progression, each through distinct anti-tumour pathways. Our goal was to discover a compound that could efficiently target both cannabinoid anti-tumour pathways. To measure breast cancer cell proliferation/viability and invasion, MTT and Boyden chamber assays were used. Modulation of reactive oxygen species (ROS) and apoptosis was measured using dichlorodihydrofluorescein and annexin/propidium iodide, respectively, in combination with cell flow cytometry. Changes in protein levels were evaluated using Western analysis. Orthotopic and i.v. mouse models of breast cancer metastasis were used to test the activity of cannabinoids in vivo. CBD reduced breast cancer metastasis in advanced stages of the disease as the direct result of down-regulating the transcriptional regulator Id1. However, this was associated with moderate increases in survival. We therefore screened for analogues that could co-target cannabinoid anti-tumour pathways (CBD- and THC-associated) and discovered the compound O-1663. This analogue inhibited Id1, produced a marked stimulation of ROS, up-regulated autophagy and induced apoptosis. Of all the compounds tested, it was the most potent at inhibiting breast cancer cell proliferation and invasion in culture and metastasis in vivo. O-1663 prolonged survival in advanced stages of breast cancer metastasis. Developing compounds that can simultaneously target multiple cannabinoid anti-tumour pathways efficiently may provide a novel approach for the treatment of patients with metastatic breast cancer. © 2014 The British Pharmacological Society.

  17. Inhibition of advanced glycation endproduct (AGE) rescues against streptozotocin-induced diabetic cardiomyopathy: Role of autophagy and ER stress.

    Science.gov (United States)

    Pei, Zhaohui; Deng, Qinqin; Babcock, Sara A; He, Emily Y; Ren, Jun; Zhang, Yingmei

    2018-03-01

    Diabetes mellitus leads to oxidative stress and contractile dysfunction in the heart. Although several rationales have been speculated, the precise mechanism behind diabetic cardiomyopathy remains elusive. This study was designed to assess the role of inhibition of advanced glycation endproducts (AGE) in streptozotocin (STZ)-induced diabetic cardiac dysfunction. Cardiac contractile function was assessed in normal C57BL/6 and STZ (200mg/kg, single injection and maintained for 2 wks)-induced diabetic mice treated with or without the AGE inhibitor aminoguanidine (50mg/kg/d in drinking water) for 2 weeks using echocardiography and IonOptix MyoCam techniques. Diabetes compromised cardiac contractile function shown as reduced fractional shortening and ejection fraction, enlarged left ventricular end systolic/diastolic diameters, decreased peak shortening, maximal velocity of shortening/relengthening, prolonged shortening and relengthening duration as well as impaired intracellular Ca 2+ homeostasis, the effects of which were alleviated or reversed by aminoguanidine treatment. Diabetes also inhibited autophagy, increased ER stress and phosphorylation of pro-hypertrophic signaling molecules Akt and mTOR, the effect of which was reversed by aminoguanidine. In vitro study revealed that methylglyoxal-derived AGE (MG-AGE) incubation in isolated cardiomyocytes promoted oxidation of sarco(endo)plasmic reticulum Ca 2+ -ATPase (SERCA2a) and production of superoxide, the effects of which were negated by the autophagy inducer rapamycin, the ER stress chaperone TUDCA or the antioxidant N-acetylcysteine. Taken together, these data revealed that inhibition of AGE formation rescues against experimental diabetes-induced cardiac remodeling and contractile dysfunction possible through regulation of autophagy and ER stress. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Advanced glycation end-products inhibition improves endothelial dysfunction in rheumatoid arthritis.

    Science.gov (United States)

    Syngle, Ashit; Vohra, Kanchan; Garg, Nidhi; Kaur, Ladbans; Chand, Prem

    2012-02-01

    Chronic inflammation in rheumatoid arthritis is associated with vascular endothelial dysfunction. The objective was to study the efficacy and safety of advanced glycation end products (AGEs) inhibitor (benfotiamine 50 mg + pyridoxamine 50 mg + methylcobalamin 500 μg, Vonder(®) (ACME Lifescience, Baddi, Himachal Pradesh, India)) on endothelial function in rheumatoid arthritis (RA). Twenty-four patients with established active RA with high disease activity (Disease Activity Score of 28 joints [DAS28 score] > 5.1) despite treatment with stable doses of conventional disease-modifying antirheumatic drugs were investigated. Inflammatory disease activity (DAS28 and Health Assessment Questionnaire-Disability Index [HAQ-DI] scores, erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]), markers of endothelial dysfunction, serum nitrite concentration and endothelium-dependent and -independent vasodilation of the brachial artery were measured before and after 12 weeks therapy with twice a day oral AGEs inhibitor. After treatment, flow-mediated vasodilation improved from 9.64 ± 0.65% to 15.82 ± 1.02% (P < 0.01), whereas there was no significant change in endothelium-independent vasodilation with nitroglycerin and baseline diameter; serum nitrite concentration significantly reduced from 5.6 ± 0.13 to 5.1 ± 0.14 μmol/L (P = 0.004), ESR from 63.00 ± 3.5 to 28.08 ± 1.5 mm in the first h (P < 0.01) and CRP levels from 16.7 ± 4.1 to 10.74 ± 2.9 mg/dL (P < 0.01). DAS28 and HAQ-DI scores were significantly reduced, from 5.9 ± 0.17 to 3.9 ± 0.17 (P < 0.01) and 4.6 ± 0.17 to 1.7 ± 0.22 (P < 0.01), respectively. Advanced glycation end products inhibitor improves endothelial dysfunction and inflammatory disease activity in RA. In RA, endothelial dysfunction is part of the disease process and is mediated by AGEs-induced inflammation. © 2011 The Authors. International Journal of Rheumatic Diseases © 2011 Asia Pacific League of Associations for Rheumatology and

  19. Increased topoisomerase IIalpha expression in colorectal cancer is associated with advanced disease and chemotherapeutic resistance via inhibition of apoptosis.

    LENUS (Irish Health Repository)

    Coss, Alan

    2012-02-01

    Topoisomerase IIalpha is a nuclear enzyme that regulates the tertiary structure of DNA. The influence of topoisomerase IIalpha gene (TOP2A) or protein alterations on disease progression and treatment response in colorectal cancer (CRC) is unknown. The study investigated the clinical relevance of topoisomerase IIalpha in CRC using in vivo and in vitro models. Differentially expressed genes in early and late-stage CRC were identified by array comparative genomic hybridization (CGH). Cellular location of gene amplifications was determined by fluorescence in situ hybridization (FISH). Topoisomerase IIalpha levels, proliferation index, and HER2 expression were examined in 228 colorectal tumors by immunohistochemistry. Overexpression of topoisomerase IIalpha in vitro was achieved by liposome-based transfection. Cell growth inhibition and apoptosis were quantified using the crystal violet assay and flow cytometry, respectively, in response to drug treatment. Amplification of TOP2A was identified in 3 (7.7%) tumors using array CGH and confirmed using FISH. At the protein level, topoisomerase IIalpha staining was observed in 157 (69%) tumors, and both staining and intensity levels were associated with an aggressive tumor phenotype (p values 0.04 and 0.005, respectively). Using logistic regression analysis, topoisomerase IIalpha remained significantly associated with advanced tumor stage when corrected for tumor proliferation (p=0.007) and differentiation (p=0.001). No association was identified between topoisomerase IIalpha and HER2. In vitro, overexpression of topoisomerase IIalpha was associated with resistance to irinotecan (p=0.001) and etoposide chemotherapy (p=0.03), an effect mediated by inhibition of apoptosis. Topoisomerase IIalpha overexpression is significantly associated with alterations in tumor behavior and response to drug treatment in CRC. Our results suggest that gene amplification may represent an important mechanism underlying these changes.

  20. Combined MTOR and autophagy inhibition: phase I trial of hydroxychloroquine and temsirolimus in patients with advanced solid tumors and melanoma.

    Science.gov (United States)

    Rangwala, Reshma; Chang, Yunyoung C; Hu, Janice; Algazy, Kenneth M; Evans, Tracey L; Fecher, Leslie A; Schuchter, Lynn M; Torigian, Drew A; Panosian, Jeffrey T; Troxel, Andrea B; Tan, Kay-See; Heitjan, Daniel F; DeMichele, Angela M; Vaughn, David J; Redlinger, Maryann; Alavi, Abass; Kaiser, Jonathon; Pontiggia, Laura; Davis, Lisa E; O'Dwyer, Peter J; Amaravadi, Ravi K

    2014-08-01

    The combination of temsirolimus (TEM), an MTOR inhibitor, and hydroxychloroquine (HCQ), an autophagy inhibitor, augments cell death in preclinical models. This phase 1 dose-escalation study evaluated the maximum tolerated dose (MTD), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of HCQ in combination with TEM in cancer patients. In the dose escalation portion, 27 patients with advanced solid malignancies were enrolled, followed by a cohort expansion at the top dose level in 12 patients with metastatic melanoma. The combination of HCQ and TEM was well tolerated, and grade 3 or 4 toxicity was limited to anorexia (7%), fatigue (7%), and nausea (7%). An MTD was not reached for HCQ, and the recommended phase II dose was HCQ 600 mg twice daily in combination with TEM 25 mg weekly. Other common grade 1 or 2 toxicities included fatigue, anorexia, nausea, stomatitis, rash, and weight loss. No responses were observed; however, 14/21 (67%) patients in the dose escalation and 14/19 (74%) patients with melanoma achieved stable disease. The median progression-free survival in 13 melanoma patients treated with HCQ 1200mg/d in combination with TEM was 3.5 mo. Novel 18-fluorodeoxyglucose positron emission tomography (FDG-PET) measurements predicted clinical outcome and provided further evidence that the addition of HCQ to TEM produced metabolic stress on tumors in patients that experienced clinical benefit. Pharmacodynamic evidence of autophagy inhibition was evident in serial PBMC and tumor biopsies only in patients treated with 1200 mg daily HCQ. This study indicates that TEM and HCQ is safe and tolerable, modulates autophagy in patients, and has significant antitumor activity. Further studies combining MTOR and autophagy inhibitors in cancer patients are warranted.

  1. Synergy between scientific advancement and technological innovation, illustrated by a mechanism-based model characterizing sodium-glucose cotransporter-2 inhibition.

    Science.gov (United States)

    Zhang, Liping; Ng, Chee M; List, James F; Pfister, Marc

    2010-09-01

    Advances in experimental medicine and technological innovation during the past century have brought tremendous progress in modern medicine and generated an ever-increasing amount of data from bench and bedside. The desire to extend scientific knowledge motivates effective data integration. Technological innovation makes this possible, which in turn accelerates the advancement in science. This mutually beneficial interaction is illustrated by the development of an expanded mechanism-based model for understanding a novel mechanism, sodium-glucose cotransporter-2 SGLT2 inhibition for potential treatment of type 2 diabetes mellitus.

  2. Addition of Everolimus Post VEGFR Inhibition Treatment Failure in Advanced Sarcoma Patients Who Previously Benefited from VEGFR Inhibition: A Case Series

    OpenAIRE

    ElNaggar, Adam C.; Hays, John L.; Chen, James L.

    2016-01-01

    Background Patients with metastatic sarcoma who progress on vascular endothelial growth factor receptor inhibitors (VEGFRi) have limited treatment options. Upregulation of the mTOR pathway has been demonstrated to be a means of resistance to targeted VEGFRi in metastatic sarcoma. Patients and methods Retrospective cohort study to evaluate the clinical benefit at four months of combining mTOR inhibition (mTORi) via everolimus with VEGFRi in patients who have derived benefit from single-agent V...

  3. Torin1-mediated TOR kinase inhibition reduces Wee1 levels and advances mitotic commitment in fission yeast and HeLa cells.

    Science.gov (United States)

    Atkin, Jane; Halova, Lenka; Ferguson, Jennifer; Hitchin, James R; Lichawska-Cieslar, Agata; Jordan, Allan M; Pines, Jonathon; Wellbrock, Claudia; Petersen, Janni

    2014-03-15

    The target of rapamycin (TOR) kinase regulates cell growth and division. Rapamycin only inhibits a subset of TOR activities. Here we show that in contrast to the mild impact of rapamycin on cell division, blocking the catalytic site of TOR with the Torin1 inhibitor completely arrests growth without cell death in Schizosaccharomyces pombe. A mutation of the Tor2 glycine residue (G2040D) that lies adjacent to the key Torin-interacting tryptophan provides Torin1 resistance, confirming the specificity of Torin1 for TOR. Using this mutation, we show that Torin1 advanced mitotic onset before inducing growth arrest. In contrast to TOR inhibition with rapamycin, regulation by either Wee1 or Cdc25 was sufficient for this Torin1-induced advanced mitosis. Torin1 promoted a Polo and Cdr2 kinase-controlled drop in Wee1 levels. Experiments in human cell lines recapitulated these yeast observations: mammalian TOR (mTOR) was inhibited by Torin1, Wee1 levels declined and mitotic commitment was advanced in HeLa cells. Thus, the regulation of the mitotic inhibitor Wee1 by TOR signalling is a conserved mechanism that helps to couple cell cycle and growth controls.

  4. Catechins activate muscle stem cells by Myf5 induction and stimulate muscle regeneration.

    Science.gov (United States)

    Kim, A Rum; Kim, Kyung Min; Byun, Mi Ran; Hwang, Jun-Ha; Park, Jung Il; Oh, Ho Taek; Kim, Hyo Kyeong; Jeong, Mi Gyeong; Hwang, Eun Sook; Hong, Jeong-Ho

    2017-07-22

    Muscle weakness is one of the most common symptoms in aged individuals and increases risk of mortality. Thus, maintenance of muscle mass is important for inhibiting aging. In this study, we investigated the effect of catechins, polyphenol compounds in green tea, on muscle regeneration. We found that (-)-epicatechin gallate (ECG) and (-)-epigallocatechin-3-gallate (EGCG) activate satellite cells by induction of Myf5 transcription factors. For satellite cell activation, Akt kinase was significantly induced after ECG treatment and ECG-induced satellite cell activation was blocked in the presence of Akt inhibitor. ECG also promotes myogenic differentiation through the induction of myogenic markers, including Myogenin and Muscle creatine kinase (MCK), in satellite and C2C12 myoblast cells. Finally, EGCG administration to mice significantly increased muscle fiber size for regeneration. Taken together, the results suggest that catechins stimulate muscle stem cell activation and differentiation for muscle regeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Epigallocatechin gallate (EGCG), a major component of green tea, is a dual phosphoinositide-3-kinase/mTOR inhibitor

    International Nuclear Information System (INIS)

    Van Aller, Glenn S.; Carson, Jeff D.; Tang, Wei; Peng, Hao; Zhao, Lin; Copeland, Robert A.; Tummino, Peter J.; Luo, Lusong

    2011-01-01

    Research highlights: → Epigallocatechin-3-gallate (EGCG) is an ATP-competitive inhibitor of PI3K and mTOR with Ki values around 300 nM. → EGCG inhibits cell proliferation and AKT phosphorylation at Ser473 in MDA-MB-231and A549 cells. → Molecular docking studies show that EGCG binds well to the PI3K kinase domain active site. → These results suggest another important molecular mechanism for the anticancer activities of EGCG. -- Abstract: The PI3K signaling pathway is activated in a broad spectrum of human cancers, either directly by genetic mutation or indirectly via activation of receptor tyrosine kinases or inactivation of the PTEN tumor suppressor. The key nodes of this pathway have emerged as important therapeutic targets for the treatment of cancer. In this study, we show that (-)-epigallocatechin-3-gallate (EGCG), a major component of green tea, is an ATP-competitive inhibitor of both phosphoinositide-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) with K i values of 380 and 320 nM respectively. The potency of EGCG against PI3K and mTOR is within physiologically relevant concentrations. In addition, EGCG inhibits cell proliferation and AKT phosphorylation at Ser473 in MDA-MB-231 and A549 cells. Molecular docking studies show that EGCG binds well to the PI3K kinase domain active site, agreeing with the finding that EGCG competes for ATP binding. Our results suggest another important molecular mechanism for the anticancer activities of EGCG.

  6. Quantitative (q)AOP for aromatase inhibition as case study to advance qAOP development practices

    Science.gov (United States)

    Here we describe how “read across” of a quantitative adverse outcome pathway (qAOP) developed with data for one chemical can be used to screen impacts of other chemicals. We developed a qAOP starting with inhibition of CYP19A (aromatase) in fathead minnows (FHM) as th...

  7. Nifedipine inhibits advanced glycation end products (AGEs) and their receptor (RAGE) interaction-mediated proximal tubular cell injury via peroxisome proliferator-activated receptor-gamma activation

    International Nuclear Information System (INIS)

    Matsui, Takanori; Yamagishi, Sho-ichi; Takeuchi, Masayoshi; Ueda, Seiji; Fukami, Kei; Okuda, Seiya

    2010-01-01

    Research highlights: → Nifedipine inhibited the AGE-induced up-regulation of RAGE mRNA levels in tubular cells, which was prevented by GW9662, an inhibitor of peroxisome proliferator-activated receptor-γ. → GW9662 treatment alone increased RAGE mRNA levels in tubular cells. → Nifedipine inhibited the AGE-induced reactive oxygen species generation, NF-κB activation and increases in intercellular adhesion molecule-1 and transforming growth factor-β gene expression in tubular cells, all of which were blocked by GW9662. -- Abstract: There is a growing body of evidence that advanced glycation end products (AGEs) and their receptor (RAGE) interaction evokes oxidative stress generation and subsequently elicits inflammatory and fibrogenic reactions, thereby contributing to the development and progression of diabetic nephropathy. We have previously found that nifedipine, a calcium-channel blocker (CCB), inhibits the AGE-induced mesangial cell damage in vitro. However, effects of nifedipine on proximal tubular cell injury remain unknown. We examined here whether and how nifedipine blocked the AGE-induced tubular cell damage. Nifedipine, but not amlodipine, a control CCB, inhibited the AGE-induced up-regulation of RAGE mRNA levels in tubular cells, which was prevented by the simultaneous treatment of GW9662, an inhibitor of peroxisome proliferator-activated receptor-γ (PPARγ). GW9662 treatment alone was found to increase RAGE mRNA levels in tubular cells. Further, nifedipine inhibited the AGE-induced reactive oxygen species generation, NF-κB activation and increases in intercellular adhesion molecule-1 and transforming growth factor-beta gene expression in tubular cells, all of which were blocked by GW9662. Our present study provides a unique beneficial aspect of nifedipine on diabetic nephropathy; it could work as an anti-oxidative and anti-inflammatory agent against AGEs in tubular cells by suppressing RAGE expression via PPARγ activation.

  8. Nifedipine inhibits advanced glycation end products (AGEs) and their receptor (RAGE) interaction-mediated proximal tubular cell injury via peroxisome proliferator-activated receptor-gamma activation

    Energy Technology Data Exchange (ETDEWEB)

    Matsui, Takanori [Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume (Japan); Yamagishi, Sho-ichi, E-mail: shoichi@med.kurume-u.ac.jp [Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume (Japan); Takeuchi, Masayoshi [Department of Pathophysiological Science, Faculty of Pharmaceutical Science, Hokuriku University, Kanazawa (Japan); Ueda, Seiji; Fukami, Kei; Okuda, Seiya [Department of Medicine, Kurume University School of Medicine, Kurume (Japan)

    2010-07-23

    Research highlights: {yields} Nifedipine inhibited the AGE-induced up-regulation of RAGE mRNA levels in tubular cells, which was prevented by GW9662, an inhibitor of peroxisome proliferator-activated receptor-{gamma}. {yields} GW9662 treatment alone increased RAGE mRNA levels in tubular cells. {yields} Nifedipine inhibited the AGE-induced reactive oxygen species generation, NF-{kappa}B activation and increases in intercellular adhesion molecule-1 and transforming growth factor-{beta} gene expression in tubular cells, all of which were blocked by GW9662. -- Abstract: There is a growing body of evidence that advanced glycation end products (AGEs) and their receptor (RAGE) interaction evokes oxidative stress generation and subsequently elicits inflammatory and fibrogenic reactions, thereby contributing to the development and progression of diabetic nephropathy. We have previously found that nifedipine, a calcium-channel blocker (CCB), inhibits the AGE-induced mesangial cell damage in vitro. However, effects of nifedipine on proximal tubular cell injury remain unknown. We examined here whether and how nifedipine blocked the AGE-induced tubular cell damage. Nifedipine, but not amlodipine, a control CCB, inhibited the AGE-induced up-regulation of RAGE mRNA levels in tubular cells, which was prevented by the simultaneous treatment of GW9662, an inhibitor of peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}). GW9662 treatment alone was found to increase RAGE mRNA levels in tubular cells. Further, nifedipine inhibited the AGE-induced reactive oxygen species generation, NF-{kappa}B activation and increases in intercellular adhesion molecule-1 and transforming growth factor-beta gene expression in tubular cells, all of which were blocked by GW9662. Our present study provides a unique beneficial aspect of nifedipine on diabetic nephropathy; it could work as an anti-oxidative and anti-inflammatory agent against AGEs in tubular cells by suppressing RAGE expression

  9. Growth-inhibiting effect of tumor necrosis factor on human umbilical vein endothelial cells is enhanced with advancing age in vitro

    International Nuclear Information System (INIS)

    Shimada, Y.; Kaji, K.; Ito, H.; Noda, K.; Matsuo, M.

    1990-01-01

    We have examined the effects of in vitro aging on the growth capacity of human umbilical vein endothelial cells (HUVECs) under the influence of tumor necrosis factor (TNF) with or without interferon-gamma (IFN-gamma). The growth and colony-forming abilities of control cells were impaired with advancing age in vitro, especially at later stages (more than 70-80% of life span completed). It was found that treatment with TNF inhibited growth and colony-forming efficiency at any in vitro age. The effects of TNF were shown to increase with increasing in vitro age, as reflected by a more pronounced increase in doubling times, a decrease in saturation density, and a reduction in colony-forming efficiency. However, the characteristics of TNF receptors, including the dissociation constant, and the number of TNF-binding sites per cell-surface area remained rather constant. The effect of TNF was augmented by IFN-gamma at a dose that alone affected growth and colony formation only slightly. The augmentation by IFN-gamma was also found to depend on in vitro age; the synergy with TNF in the deterioration of colony-forming ability was observed only in aged cells. These results suggest that the intrinsic responsiveness of HUVECs to growth-inhibiting factors, as well as to growth-stimulating factors, changes during aging in vitro

  10. The Extract of Litsea japonica Reduced the Development of Diabetic Nephropathy via the Inhibition of Advanced Glycation End Products Accumulation in db/db Mice

    Directory of Open Access Journals (Sweden)

    Eunjin Sohn

    2013-01-01

    Full Text Available Increasing evidence indicates that advanced glycation end products (AGEs contribute to the pathogenesis of diabetic nephropathy. The aim of this study was to investigate the protective effect of L. japonica extract (LJE against renal damage in the db/db mouse. LJE (100 or 250 mg/kg per day was given to diabetic mice for 12 weeks. Body weight, blood glucose levels, glycated hemoglobin (HbA1c levels, and proteinuria were examined. In in vitro assay of the inhibition of AGE formation, immunohistochemical analysis of podocyte loss and AGE accumulations were performed. In 20-week-old db/db mice, severe hyperglycemia developed, and proteinuria was significantly increased. Diabetes induced markedly morphological alterations to the renal glomerular cells. AGE accumulations and podocyte loss were detected in renal glomeruli. LJE treatment significantly reduced proteinuria and AGE accumulations in diabetic mice. Moreover, the loss of nephrin, an important slit diaphragm component in the kidneys, was restored by LJE treatment. Our studies suggest that LJE might be beneficial for the treatment of diabetic nephropathy. The ability of LJE to attenuate proteinuria and podocyte dysfunction may be mediated by the inhibition of AGE accumulation in the context of diabetic nephropathy in db/db mice.

  11. Advanced glycation end product-induced astrocytic differentiation of cultured neurospheres through inhibition of Notch-Hes1 pathway-mediated neurogenesis.

    Science.gov (United States)

    Guo, Yijing; Wang, Pin; Sun, Haixia; Cai, Rongrong; Xia, Wenqing; Wang, Shaohua

    2013-12-23

    This study aims to investigate the roles of the Notch-Hes1 pathway in the advanced glycation end product (AGE)-mediated differentiation of neural stem cells (NSCs). We prepared pLentiLox3.7 lentiviral vectors that express short hairpin RNA (shRNA) against Notch1 and transfected it into NSCs. Cell differentiation was analyzed under confocal laser-scanning microscopy. The percentage of neurons and astrocytes was quantified by normalizing the total number of TUJ1+ (Neuron-specific class III β-tubulin) and GFAP+ (Glial fibrillary acidic protein) cells to the total number of Hoechst 33342-labeled cell nuclei. The protein and gene expression of Notch-Hes1 pathway components was examined via western blot analysis and real-time PCR. After 1 week of incubation, we found that AGE-bovine serum albumin (BSA) (400 μg/mL) induced the astrocytic differentiation of cultured neurospheres and inhibited neuronal formation. The expression of Notch-Hes1 pathway components was upregulated in the cells in the AGE-BSA culture medium. Immunoblot analysis indicated that shRNA silencing of Notch1 expression in NSCs significantly increases neurogenesis and suppresses astrocytic differentiation in NSCs incubated with AGE-BSA. AGEs promote the astrocytic differentiation of cultured neurospheres by inhibiting neurogenesis through the Notch-Hes1 pathway, providing a potential therapeutic target for hyperglycemia-related cognitive deficits.

  12. Advanced glycosylation end product promotes forkhead box O1 and inhibits Wnt pathway to suppress capacities of epidermal stem cells.

    Science.gov (United States)

    Zhu, Jie; Wang, Peng; Yu, Zhimin; Lai, Wei; Cao, Yi; Huang, Pinbo; Xu, Qiaodong; Yu, Menglei; Xu, Junyao; Huang, Zitong; Zeng, Bing

    2016-01-01

    Diabetes mellitus is frequently accompanied by chronic complications like delayed wound healing, which is consider to be attributed to the accumulation of advanced glycosylation end product (AGE). However, the impacts of AGE on epidermal stem cells (ESCs) are largely unknown. This study aims to address the influence and mechanism of AGE on ESCs. ESCs isolated from rats were cultured in AGE-modified bovine serum albumin and transfected with small interfering RNA to knock down AGE-specific receptor (AGER). Expression of stem cell markers integrin β1 (ITGB1) and keratin 19 (KRT19), cell viability, apoptosis and reactive oxygen species (ROS) were examined. Wnt pathway-related factors Wnt family member 1 (WNT1), WNT3A, β-catenin, v-myc avian myelocytomatosis viral oncogene homolog (MYC), cyclin D1 (CCND1) and matrix metallopeptidase 7 (MMP7) were quantified. The interaction between forkhead box O1 (FOXO1) and β-catenin was assessed by co-immunoprecipitation. Results indicated that AGE down-regulated ITGB1 and KRT19 expression, suppressed ESC viability and promoted apoptosis, and ROS level ( P factor 1 to interact with β-catenin, which might help to elucidate the mechanism of AGE repressing ESCs. This study helps to understand the mechanism of accumulated AGE in affecting ESC capacities, and provides potential therapeutic targets to meliorate diabetic wound healing.

  13. Inhibition of the receptor for advanced glycation end-products (RAGE) protects from secondhand smoke (SHS)-induced intrauterine growth restriction IUGR in mice.

    Science.gov (United States)

    Lewis, Joshua B; Mejia, Camilo; Jordan, Clinton; Monson, Troy D; Bodine, Jared S; Dunaway, Todd M; Egbert, Kaleb M; Lewis, Adam L; Wright, Tanner J; Ogden, K Connor; Broberg, Dallin S; Hall, Parker D; Nelson, Shawn M; Hirschi, Kelsey M; Reynolds, Paul R; Arroyo, Juan A

    2017-12-01

    Intrauterine growth restriction (IUGR) is a disease affecting 10% of all pregnancies. IUGR is associated with maternal, fetal, or placental abnormalities. Studies investigating the effects of secondhand smoke (SHS) exposure and IUGR are limited. The receptor for advanced glycation end-products (RAGE) is a pro-inflammatory transmembrane receptor increased by SHS in the placenta. We tested the hypothesis that inhibition of RAGE during SHS exposure protects from smoke-induced IUGR. C57BL/6 mice were exposed to SHS or SHS + semi-synthetic glycosaminoglycan ethers (SAGEs) known to inhibit RAGE signaling. Trophoblast cells were treated with cigarette smoke extract (CSE) with or without SAGEs in order to address the effects of RAGE inhibition during trophoblast invasion in vitro. SHS-treated mice demonstrated a significant reduction in fetal weight (7.35-fold, P ≤ 0.0001) and placental weight (1.13-fold, P ≤ 0.0001) compared with controls. Mice co-treated with SHS and SAGEs were protected from SHS-induced fetal weights decreases. SHS treatment of C57BL/6 mice activated placental extracellular signal-regulated kinase (ERK) (3.0-fold, P ≤ 0.05), JNK (2.4-fold, P ≤ 0.05) and p38 (2.1-fold, P ≤ 0.05) and the expression of inflammatory mediators including TNF-α (1.34-fold, P ≤ 0.05) and IL-1β (1.03-fold, P ≤ 0.05). SHS-mediated activation of these molecules was reduced to basal levels when SAGE was co-administered. Invasion of trophoblast cells decreased 92% (P < 0.002) when treated with CSE and CSE-mediated invasion was completely reversed by SAGEs. We conclude that RAGE inhibition protects against fetal weight loss during SHS-induced IUGR. These studies provide insight into tobacco-mediated IUGR development and clarify avenues that may be helpful in the alleviation of placental complications.

  14. Phenolic acids inhibit the formation of advanced glycation end products in food simulation systems depending on their reducing powers and structures.

    Science.gov (United States)

    Chen, Hengye; Virk, Muhammad Safiullah; Chen, Fusheng

    2016-06-01

    The concentration of advanced glycation end products (AGEs) in foods, which are formed by Maillard reaction, has demonstrated as risk factors associated with many chronic diseases. The AGEs inhibitory activities of five common phenolic acids (protocatechuic acid, dihydroferulic acid, p-coumaric acid, p-hydroxybenzoic acid and salicylic acid) with different chemical properties had been investigated in two food simulation systems (glucose-bovine serum albumin (BSA) and oleic acid-BSA). The results substantiated that the AGEs inhibitory abilities of phenolic acids in the oleic acid BSA system were much better than the glucose-BSA system for their strong reducing powers and structures. Among them, dihydrogenferulic acid showed strong inhibition of AGEs formation in oleic acid-BSA system at 0.01 mg/mL compared to nonsignificant AGEs inhibitory effect in oleic acid-BSA system at 10-fold higher concentration (0.1 mg/mL). This study suggests that edible plants rich in phenolic acids may be used as AGEs inhibitor during high-fat cooking.

  15. (R)-α-Lipoic acid inhibits fructose-induced myoglobin fructation and the formation of advanced glycation end products (AGEs) in vitro.

    Science.gov (United States)

    Ghelani, Hardik; Razmovski-Naumovski, Valentina; Pragada, Rajeswara Rao; Nammi, Srinivas

    2018-01-15

    Fructose-mediated protein glycation (fructation) has been linked to an increase in diabetic and cardiovascular complications due to over consumption of high-fructose containing diets in recent times. The objective of the present study is to evaluate the protective effect of (R)-α-lipoic acid (ALA) against fructose-induced myoglobin fructation and the formation of advanced glycation end products (AGEs) in vitro. The anti-glycation activity of ALA was determined using the formation of AGEs fluorescence intensity, iron released from the heme moiety of myoglobin and the level of fructosamine. The fructation-induced myoglobin oxidation was examined using the level of protein carbonyl content and thiol group estimation. The results showed that co-incubation of myoglobin (1 mg/mL), fructose (1 M) and ALA (1, 2 and 4 mM) significantly inhibited the formation of AGEs during the 30 day study period. ALA markedly decreased the levels of fructosamine, which is directly associated with the reduction of AGEs formation. Furthermore, ALA significantly reduced free iron release from myoglobin which is attributed to the protection of myoglobin from fructose-induced glycation. The results also demonstrated a significant protective effect of ALA on myoglobin oxidative damages, as seen from decreased protein carbonyl content and increased protein thiols. These findings provide new insights into the anti-glycation properties of ALA and emphasize that ALA supplementation is beneficial in the prevention of AGEs-mediated diabetic and cardiovascular complications.

  16. Benazepril, an angiotensin-converting enzyme inhibitor, alleviates renal injury in spontaneously hypertensive rats by inhibiting advanced glycation end-product-mediated pathways.

    Science.gov (United States)

    Liu, Xue-Ping; Pang, Yue-Jiu; Zhu, Wei-Wei; Zhao, Ting-Ting; Zheng, Min; Wang, Yi-Bing; Sun, Zhi-Jian; Sun, Siao-Jing

    2009-03-01

    1. Advanced glycation end-products (AGE) and their receptors (RAGE) have been implicated in renal damage in diabetes. The aim of the present study was to investigate the effects of benazepril, an angiotensin-converting enzyme inhibitor (ACEI), on the formation of AGE, the expression RAGE and other associated components in the oxidative stress pathway in spontaneously hypertensive rats (SHR). 2. Groups of SHR were treated with or without 10 mg/kg per day benazepril for 12 weeks. Systolic blood pressure (SBP) and angiotensin (Ang) II levels were evaluated in SHR and control Wistar-Kyoto (WKY) rats. Renal function was investigated by determining levels of proteinuria and glomerulosclerosis. Furthermore, reactive oxygen species (ROS) in the rat renal cortex were analysed using an H(2)O(2)-based hydroxyl radical-detection assay and the renal content of AGE, RAGE, NADPH oxidase p47phox, nuclear factor (NF)-kappaB p65, phosphorylated (p-) NF-kappaB p65, vascular cell adhesion molecule (VCAM)-1 and transforming growth factor (TGF)-beta1 was determined by immunohistochemistry, quantitative real-time polymerase chain reaction and western blot analysis. 3. Treatment with benazepril inhibited the formation of AngII, reduced SBP and alleviated renal lesions in SHR compared with both untreated SHR and control WKY rats. Benazepril treatment significantly suppressed the accumulation of AGE and expression of RAGE in the kidney of SHR. In addition, benazepril treatment reduced the upregulation of NADPH oxidase p47phox, ROS generation and NF-kappaB p65, p-NF-kappaB p65, VCAM-1 and TGF-beta1 expression in the kidney of SHR compared with both untreated SHR and control WKY rats. 4. The results of the present study provide new insights into the regulation by the renin-angiotensin system of AGE-RAGE, oxidative stress and nephropathy, increasing our understanding of the role of the RAS in nephropathy.

  17. SL-401 and SL-501, Targeted Therapeutics Directed at the Interleukin-3 Receptor, Inhibit the Growth of Leukaemic Cells and Stem Cells in Advanced Phase Chronic Myeloid Leukaemia

    Science.gov (United States)

    Frolova, Olga; Benito, Juliana; Brooks, Chris; Wang, Rui-Yu; Korchin, Borys; Rowinsky, Eric K.; Cortes, Jorge; Kantarjian, Hagop; Andreeff, Michael; Frankel, Arthur E.; Konopleva, Marina

    2014-01-01

    SUMMARY While imatinib and other tyrosine kinase inhibitors (TKIs) are highly efficacious in the treatment of chronic myeloid leukaemia (CML), some patients become refractory to these therapies. After confirming that interleukin-3 receptor (IL3R, CD123) is highly expressed on CD34+/CD38− BCR-ABL1+ CML stem cells, we investigated whether targeting IL3R with diphtheria toxin (DT)-IL3 fusion proteins SL-401 (DT388-IL3) and SL-501 (DT388-IL3[K116W]) could eradicate these stem cells. SL-401 and SL-501 inhibited cell growth and induced apoptosis in the KBM5 cell line and its TKI-resistant KBM5-STI subline. Combinations of imatinib with these agents increased apoptosis in KBM5 and in primary CML cells. In six primary CML samples, including CML cells harbouring the ABL1 T315I mutation, SL-401 and SL-501 decreased the absolute numbers of viable CD34+/CD38−/CD123+ CML progenitor cells by inducing apoptosis. IL3-targeting agents reduced clonogenic growth and diminished the fraction of primitive long-term culture-initiating cells in samples from patients with advanced phase CML that were resistant to TKIs or harboured an ABL1 mutation. Survival was also extended in a mouse model of primary TKI-resistant CML blast crisis. These data suggest that the DT-IL3 fusion proteins, SL-401 and SL-501, deplete CML stem cells and may increase the effectiveness of current CML treatment, which principally targets tumour bulk. PMID:24942980

  18. Ilex paraguariensis and its main component chlorogenic acid inhibit fructose formation of advanced glycation endproducts with amino acids at conditions compatible with those in the digestive system.

    Science.gov (United States)

    Bains, Yasmin; Gugliucci, Alejandro

    2017-03-01

    We have previously shown that Ilex paraguariensis extracts have potent antiglycation actions. Associations of excess free fructose consumption with inflammatory diseases have been proposed to be mediated through in situ enteral formation of fructose AGEs, which, after being absorbed may contribute to inflammatory diseases via engagement of RAGE. In this proof of principle investigation we show fluorescent AGE formation between amino acids (Arg, Lys, Gly at 10-50mM) and fructose (10-50mM) under time, temperature, pH and concentrations compatible with the digestive system lumen and its inhibition by Ilex paraguariensis extracts. Incubation of amino acids with fructose (but not glucose) leads to a time dependent formation of AGE fluorescence, already apparent after just 1h incubation, a time frame well compatible with the digestive process. Ilex paraguariensis (mate tea) inhibited AGE formation by 83% at 50μl/ml (pfructose and amino acids at times and concentrations plausibly found in the intestines. The reaction is inhibited by mate tea and its individual phenolics (caffeic acid and chlorogenic acids). The study provides the first evidence for the proposed mechanism to explain epidemiological correlations between excess fructose consumption and inflammatory diseases. Enteral fructose-AGE formation would be inhibited by co-intake of Ilex paraguariensis, and potentially other beverages, fruits and vegetables that contain comparable concentrations of phenolics as in IP (mate tea). Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Identification of Hepatoprotective Constituents in Limonium tetragonum and Development of Simultaneous Analysis Method using High-performance Liquid Chromatography

    Science.gov (United States)

    Lee, Jae Sun; Kim, Yun Na; Kim, Na-Hyun; Heo, Jeong-Doo; Yang, Min Hye; Rho, Jung-Rae; Jeong, Eun Ju

    2017-01-01

    Background: Limonium tetragonum, a naturally salt-tolerant halophyte, has been studied recently and is of much interest to researchers due to its potent antioxidant and hepatoprotective activities. Objective: In the present study, we attempted to elucidate bioactive compounds from ethyl acetate (EtOAc) soluble fraction of L. tetragonum extract. Furthermore, the simultaneous analysis method of bioactive EtOAc fraction of L. tetragonum has been developed using high-performance liquid chromatography (HPLC). Materials and Methods: Thirteen compounds have been successfully isolated from EtOAc fraction of L. tetragonum, and the structures of 1–13 were elucidated by extensive one-dimensional and two-dimensional spectroscopic methods including 1H-NMR, 13C-NMR, 1H-1H COSY, heteronuclear single quantum coherence, heteronuclear multiple bond correlation, and nuclear Overhauser effect spectroscopy. Hepatoprotection of the isolated compounds against liver fibrosis was evaluated by measuring inhibition on hepatic stellate cells (HSCs) undergoing proliferation. Results: Compounds 1–13 were identified as gallincin (1), apigenin-3-O-β-D-galactopyranoside (2), quercetin (3), quercetin-3-O-β-D-galactopyranoside (4), (−)-epigallocatechin (5), (−)-epigallocatechin-3-gallate (6), (−)-epigallocatechin-3-(3″-O-methyl) gallate (7), myricetin-3-O-β-D-galactopyranoside (8), myricetin-3-O-(6″-O-galloyl)-β-D-galactopyranoside (9), myricetin-3-O-α-L-rhamnopyranoside (10), myricetin-3-O-(2″-O-galloyl)-α-L-rhamnopyranoside (11), myricetin-3-O-(3″-O-galloyl)-α-L-rhamnopyranoside (12), and myricetin-3-O-α-L-arabinopyranoside (13), respectively. All compounds except for 4, 8, and 10 are reported for the first time from this plant. Conclusion: Myricetin glycosides which possess galloyl substituent (9, 11, and 12) showed most potent inhibitory effects on the proliferation of HSCs. SUMMARY In the present study, we have successfully isolated 13 compounds from bioactive fraction

  20. The DHEA-sulfate depot following P450c17 inhibition supports the case for AKR1C3 inhibition in high risk localized and advanced castration resistant prostate cancer.

    Science.gov (United States)

    Tamae, Daniel; Mostaghel, Elahe; Montgomery, Bruce; Nelson, Peter S; Balk, Steven P; Kantoff, Philip W; Taplin, Mary-Ellen; Penning, Trevor M

    2015-06-05

    Prostate cancer is the second leading cause of cancer death in the United States. Treatment of localized high-risk disease and de novo metastatic disease frequently leads to relapse. These metastatic castration resistant prostate cancers (mCRPC) claim a high mortality rate, despite the extended survival afforded by the growing armamentarium of androgen deprivation, radiation and immunotherapies. Here, we review two studies of neoadjuvant treatment of high-risk localized prostate cancer prior to prostatectomy, the total androgen pathway suppression (TAPS) trial and the neoadjuvant abiraterone acetate (AA) trial. These two trials assessed the efficacy of the non-specific P450c17 inhibitor, ketoconazole and the specific P450c17 inhibitor, AA, to inhibit tissue and serum androgen levels. Furthermore, a novel and validated stable isotope dilution liquid chromatography electrospray ionization selected reaction monitoring mass spectrometry assay was used to accurately quantify adrenal and gonadal androgens in circulation during the course of these trials. The adrenal androgens, Δ(4)-androstene-3,17-dione, dehydroepiandrosterone and dehydroepiandrosterone sulfate were significantly reduced in the patients receiving ketoconazole or AA compared to those who did not. However, in both trials, a significant amount of DHEA-S (∼20 μg/dL) persists and thus may serve as a depot for intratumoral conversion to the potent androgen receptor ligands, testosterone (T) and 5α-dihydrotestosterone (DHT). The final step in conversion of Δ(4)-androstene-3,17-dione and 5α-androstanedione to T and DHT, respectively, is catalyzed by AKR1C3. We therefore present the case that in the context of the DHEA-S depot, P450c17 and AKR1C3 inhibition may be an effective combinatorial treatment strategy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Combination of erlotinib and EGCG induces apoptosis of head and neck cancers through posttranscriptional regulation of Bim and Bcl-2.

    Science.gov (United States)

    Haque, Abedul; Rahman, Mohammad Aminur; Chen, Zhuo Georgia; Saba, Nabil F; Khuri, Fadlo R; Shin, Dong M; Ruhul Amin, A R M

    2015-07-01

    Combinatorial approaches using two or more compounds are gaining increasing attention for cancer therapy. We have previously reported that the combination of the EGFR-TKI erlotinib and epigallocatechin-3-gallate (EGCG) exhibited synergistic chemopreventive effects in head and neck cancers by inducing the expression of Bim, p21, p27, and by inhibiting the phosphorylation of ERK and AKT and expression of Bcl-2. In the current study, we further investigated the mechanism of regulation of Bim, Bcl-2, p21 and p27, and their role in apoptosis. shRNA-mediated silencing of Bim significantly inhibited apoptosis induced by the combination of erlotinib and EGCG (p = 0.005). On the other hand, overexpression of Bcl-2 markedly protected cells from apoptosis (p = 0.003), whereas overexpression of constitutively active AKT only minimally protected cells from apoptosis induced by the combination of the two compounds. Analysis of mRNA expression by RT-PCR revealed that erlotinib, EGCG and their combination had no significant effects on the mRNA expression of Bim, p21, p27 or Bcl-2 suggesting the post-transcriptional regulation of these molecules. Furthermore, we found that erlotinib or the combination of EGCG and erlotinib inhibited the phosphorylation of Bim and stabilized Bim after inhibition of protein translation by cycloheximide. Taken together, our results strongly suggest that the combination of erlotinib and EGCG induces apoptosis of SCCHN cells by regulating Bim and Bcl-2 at the posttranscriptional level.

  2. Encapsulated nanoepigallocatechin-3-gallate and elemental selenium nanoparticles as paradigms for nanochemoprevention

    Directory of Open Access Journals (Sweden)

    Wang D

    2012-03-01

    Full Text Available Dongxu Wang1, Ethan Will Taylor2, Yijun Wang1, Xiaochun Wan1, Jinsong Zhang11Key Laboratory of Tea Biochemistry and Biotechnology, School of Tea and Food Science, Anhui Agricultural University, Hefei, Anhui, People’s Republic of China; 2Department of Nanoscience, Joint School of Nanoscience and Nanoengineering, University of North Carolina at Greensboro, Greensboro, NC, USAAbstract: Chemoprevention that impedes one or more steps in carcinogenesis, via long-term administration of naturally occurring or synthetic compounds, is widely considered to be a crucial strategy for cancer control. Selenium (Se has chemopreventive effects, but its application is limited due to a low therapeutic index as shown in numerous animal experiments. In contrast to Se, which was known for its toxicity prior to the discovery of its beneficial effects, the natural compound epigallocatechin-3-gallate (EGCG was originally considered to be nontoxic. Due to its preventive effects on many types of cancer in various animal models, EGCG has been regarded as a prime example of a promising chemopreventive agent without major toxicity concerns. However, very recently, evidence has accumulated showing that efficacious doses of EGCG used in health promotion may not be far from its toxic dose level. Therefore, both Se and EGCG need to be modified by novel pharmaceutical technologies to attain enhanced efficacy and/or reduced toxicity. Nanotechnology may be one of these technologies. In support of this hypothesis, the characteristics of polylactic acid and polyethylene glycol-encapsulated nano-EGCG and elemental Se nanoparticles dispersed by bovine serum albumin are reviewed in this article. Encapsulation of EGCG to form nano-EGCG leads to its enhanced stability in plasma and remarkably superior chemopreventive effects, with more than tenfold dose advantages in inducing apoptosis and inhibition of both angiogenesis and tumor growth. Se at nanoparticle size (“Nano-Se”, compared

  3. Advanced glycation end products induce chemokine/cytokine production via activation of p38 pathway and inhibit proliferation and migration of bone marrow mesenchymal stem cells

    OpenAIRE

    Yang, Ke; Wang, Xiao Qun; He, Yu Song; Lu, Lin; Chen, Qiu Jing; Liu, Jing; Shen, Wei Feng

    2010-01-01

    Abstract Background Advanced glycation products (AGEs), as endogenous inflammatory mediator, compromise the physiological function of mesenchymal stem cells (MSCs). MSCs have a potential role in cell replacement therapy in acute myocardial infarction and ischemic cardiomyopathy. However, mechanisms of AGEs on MSCs are still not unveiled. Methods Reactive oxygen species (ROS), genes regulation, cell proliferation and migration have been detected by AGE-BSA stimulated MSCs. Results We found tha...

  4. A comprehensive assessment of memory, delay aversion, timing, inhibition, decision making and variability in attention deficit hyperactivity disorder: advancing beyond the three-pathway models.

    Science.gov (United States)

    Coghill, D R; Seth, S; Matthews, K

    2014-07-01

    Although attention deficit hyperactivity disorder (ADHD) has been associated with a broad range of deficits across various neuropsychological domains, most studies have assessed only a narrow range of neuropsychological functions. Direct cross-domain comparisons are rare, with almost all studies restricted to less than four domains. Therefore, the relationships between these various domains remain undefined. In addition, almost all studies included previously medicated participants, limiting the conclusions that can be drawn. We present the first study to compare a large cohort of medication-naive boys with ADHD with healthy controls on a broad battery of neuropsychological tasks, assessing six key domains of neuropsychological functioning. The neuropsychological functioning of 83 medication-naive boys with well-characterized ADHD (mean age 8.9 years) was compared with that of 66 typically developing (TYP) boys (mean age 9.0 years) on a broad battery of validated neuropsychological tasks. Data reduction using complementary factor analysis (CFA) confirmed six distinct neuropsychological domains: working memory, inhibition, delay aversion, decision making, timing and response variability. Boys with ADHD performed less well across all six domains although, for each domain, only a minority of boys with ADHD had a deficit [effect size (% with deficit) ADHD versus TYP: working memory 0.95 (30.1), inhibition 0.61 (22.9), delay aversion 0.82 (36.1), decision making 0.55 (20.5), timing 0.71 (31.3), response variability 0.37 (18.1)]. The clinical syndrome of ADHD is neuropsychologically heterogeneous. These data highlight the complexity of the relationships between the different neuropsychological profiles associated with ADHD and the clinical symptoms and functional impairment.

  5. Evaluation of Asteraceae herbal extracts in the management of diabetes and obesity. Contribution of caffeoylquinic acids on the inhibition of digestive enzymes activity and formation of advanced glycation end-products (in vitro).

    Science.gov (United States)

    Spínola, Vítor; Castilho, Paula C

    2017-11-01

    The study was performed to assess, for the first time, the in vitro anti-diabetic potential of ten Asteraceae plant extracts to inhibit the activity of digestive enzymes (α-amylase, α-, β-glucosidases and lipase) responsible for hydrolysis/digestion of sugar and lipids. Prevention of advanced glycation end-products (AGEs) formation was evaluated in bovine serum albumin/ribose glycation reaction model. The phytochemical profiles and caffeoylquinic acids (CQAs) contents were determined for the methanolic extract of each plant. Analyzed plant extracts exhibited significant inhibitory activity against key digestive enzymes linked to type II diabetes and obesity. A strong inhibition was observed for glucosidases and mild activity towards amylase and lipase (compared to reference compounds). Moreover, some extracts exhibited potent ability to prevent formation of AGEs, implicated in some diabetic complications. Caffeoylquinic acids were dominant in all plant extracts and findings demonstrate that these compounds are the most relevant hypoglycemic and anti-glycation agents. From the obtained results, Argyranthemum pinnatifidum, Helichrysum melaleucum, and Phagnalon lowei are good candidates for further development of phyto-pharmaceutical preparations as complementary therapy for diabetes and obesity control. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Receptor for advanced glycation end products (RAGE) functions as receptor for specific sulfated glycosaminoglycans, and anti-RAGE antibody or sulfated glycosaminoglycans delivered in vivo inhibit pulmonary metastasis of tumor cells.

    Science.gov (United States)

    Mizumoto, Shuji; Takahashi, Jun; Sugahara, Kazuyuki

    2012-06-01

    Altered expression of chondroitin sulfate (CS) and heparan sulfate (HS) at the surfaces of tumor cells plays a key role in malignant transformation and tumor metastasis. Previously we demonstrated that a Lewis lung carcinoma (LLC)-derived tumor cell line with high metastatic potential had a higher proportion of E-disaccharide units, GlcUA-GalNAc(4,6-O-disulfate), in CS chains than low metastatic LLC cells and that such CS chains are involved in the metastatic process. The metastasis was markedly inhibited by the pre-administration of CS-E from squid cartilage rich in E units or by preincubation with a phage display antibody specific for CS-E. However, the molecular mechanism of the inhibition remains to be investigated. In this study the receptor molecule for CS chains containing E-disaccharides expressed on LLC cells was revealed to be receptor for advanced glycation end products (RAGE), which is a member of the immunoglobulin superfamily predominantly expressed in the lung. Interestingly, RAGE bound strongly to not only E-disaccharide, but also HS-expressing LLC cells. Furthermore, the colonization of the lungs by LLC cells was effectively inhibited by the blocking of CS or HS chains at the tumor cell surface with an anti-RAGE antibody through intravenous injections in a dose-dependent manner. These results provide the clear evidence that RAGE is at least one of the critical receptors for CS and HS chains expressed at the tumor cell surface and involved in experimental lung metastasis and that CS/HS and RAGE are potential molecular targets in the treatment of pulmonary metastasis.

  7. A bibliometric study of scientific literature in Scopus on botanicals for treatment of androgenetic alopecia.

    Science.gov (United States)

    Rondanelli, Mariangela; Perna, Simone; Peroni, Gabriella; Guido, Davide

    2016-06-01

    In androgenetic alopecia, a number of botanicals are available that can effectively slow or reduce hair loss and inflammation or stimulate partial hair regrowth. The aim of this study was to provide a descriptive overview of the impact and production of literature on botanicals used for androgenetic alopecia and to perform a citation analysis of the related research articles. We searched for "alopecia" OR "androgenetic alopecia" OR "hair loss" AND "Camelia sinensis" OR (and other 15 botanicals) in ARTICLE (Title/Abstract/Keyword) in Scopus database. A total of 29 references, that is, research articles, were retrieved by SCOPUS search, and 93.1% had been published since 2000. The majority (48.3%) describe applications of hair grow stimulants, followed by inhibitors of 5-alpha-reductase applications (27.6%), and studies concerning inhibitors of inflammation (24.1%). The citation analysis revealed a growing interest for this topic and the papers on hair grow stimulants are most cited. Citation trend of inhibition of 5-alpha-reductase articles is growing in the last years. This study has highlighted three important aspects: (1) growing interest for this topic; (2) evidences mainly in hair grow stimulants and recently in the inhibition of 5-alpha-reductase, as demonstrated by article and citation counts across years; (3) in addition, all major studies have been focused on green tea epigallocatechin-3-gallate, Serenoa repens, Citrullus colocynthis and Cuscuta reflexa. © 2015 Wiley Periodicals, Inc.

  8. Computational and Biochemical Discovery of RSK2 as a Novel Target for Epigallocatechin Gallate (EGCG.

    Directory of Open Access Journals (Sweden)

    Hanyong Chen

    Full Text Available The most active anticancer component in green tea is epigallocatechin-3-gallate (EGCG. Protein interaction with EGCG is a critical step for mediating the effects of EGCG on the regulation of various key molecules involved in signal transduction. By using computational docking screening methods for protein identification, we identified a serine/threonine kinase, 90-kDa ribosomal S6 kinase (RSK2, as a novel molecular target of EGCG. RSK2 includes two kinase catalytic domains in the N-terminal (NTD and the C-terminal (CTD and RSK2 full activation requires phosphorylation of both terminals. The computer prediction was confirmed by an in vitro kinase assay in which EGCG inhibited RSK2 activity in a dose-dependent manner. Pull-down assay results showed that EGCG could bind with RSK2 at both kinase catalytic domains in vitro and ex vivo. Furthermore, results of an ATP competition assay and a computer-docking model showed that EGCG binds with RSK2 in an ATP-dependent manner. In RSK2+/+ and RSK2-/- murine embryonic fibroblasts, EGCG decreased viability only in the presence of RSK2. EGCG also suppressed epidermal growth factor-induced neoplastic cell transformation by inhibiting phosphorylation of histone H3 at Ser10. Overall, these results indicate that RSK2 is a novel molecular target of EGCG.

  9. Plant Polyphenols and Oxidative Metabolites of the Herbal Alkenylbenzene Methyleugenol Suppress Histone Deacetylase Activity in Human Colon Carcinoma Cells

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    Isabel Anna Maria Groh

    2013-01-01

    Full Text Available Evidence has been provided that diet and environmental factors directly influence epigenetic mechanisms associated with cancer development in humans. The inhibition of histone deacetylase (HDAC activity and the disruption of the HDAC complex have been recognized as a potent strategy for cancer therapy and chemoprevention. In the present study, we investigated whether selected plant constituents affect HDAC activity or HDAC1 protein status in the human colon carcinoma cell line HT29. The polyphenols (−-epigallocatechin-3-gallate (EGCG and genistein (GEN as well as two oxidative methyleugenol (ME metabolites were shown to inhibit HDAC activity in intact HT29 cells. Concomitantly, a significant decrease of the HDAC1 protein level was observed after incubation with EGCG and GEN, whereas the investigated ME metabolites did not affect HDAC1 protein status. In conclusion, dietary compounds were found to possess promising HDAC-inhibitory properties, contributing to epigenetic alterations in colon tumor cells, which should be taken into account in further risk/benefit assessments of polyphenols and alkenylbenzenes.

  10. High throughput virtual screening and in silico ADMET analysis for rapid and efficient identification of potential PAP248-286 aggregation inhibitors as anti-HIV agents

    Science.gov (United States)

    Malik, Ruchi; Bunkar, Devendra; Choudhary, Bhanwar Singh; Srivastava, Shubham; Mehta, Pakhuri; Sharma, Manish

    2016-10-01

    Human semen is principal vehicle for transmission of HIV-1 and other enveloped viruses. Several endogenous peptides present in semen, including a 39-amino acid fragments of prostatic acid phosphatase (PAP248-286) assemble into amyloid fibrils named as semen-derived enhancer of viral infection (SEVI) that promote virion attachment to target cells which dramatically enhance HIV virus infection by up to 105-fold. Epigallocatechin-3-gallate (EGCG), a polyphenolic compound, is the major catechin found in green tea which disaggregates existing SEVI fibers, and inhibits the formation of SEVI fibers. The aim of this study was to screen a number of relevant polyphenols to develop a rational approach for designing PAP248-286 aggregation inhibitors as potential anti-HIV agents. The molecular docking based virtual screening results showed that polyphenolic compounds 2-6 possessed good docking score and interacted well with the active site residues of PAP248-286. Amino acid residues of binding site namely; Lys255, Ser256, Leu258 and Asn265 are involved in binding of these compounds. In silico ADMET prediction studies on these hits were also found to be promising. Polyphenolic compounds 2-6 identified as hits may act as novel leads for inhibiting aggregation of PAP248-286 into SEVI.

  11. Epigallocatechin Gallate Attenuates Proliferation and Oxidative Stress in Human Vascular Smooth Muscle Cells Induced by Interleukin-1β via Heme Oxygenase-1

    Directory of Open Access Journals (Sweden)

    Po-Len Liu

    2014-01-01

    Full Text Available Proliferation of vascular smooth muscle cells (VSMCs triggered by inflammatory stimuli and oxidative stress contributes importantly to atherogenesis. The association of green tea consumption with cardiovascular protection has been well documented in epidemiological observations, however, the underlying mechanisms remain unclear. This study aimed to elucidate the effects of the most active green tea catechin derivative, (−-epigallocatechin-3-gallate (EGCG, in human aortic smooth muscle cells (HASMCs, focusing particularly on the role of a potent anti-inflammatory and antioxidative enzyme heme oxygenase-1 (HO-1. We found that pretreatment of EGCG dose- and time-dependently induced HO-1 protein levels in HASMCs. EGCG inhibited interleukin- (IL-1β-induced HASMC proliferation and oxidative stress in a dose-dependent manner. The HO-1 inducer CoPPIX decreased IL-1β-induced cell proliferation, whereas the HO-1 enzyme inhibitor ZnPPIX significantly reversed EGCG-caused growth inhibition in IL-1β-treated HASMCs. At the molecular level, EGCG treatment significantly activated nuclear factor erythroid-2-related factor (Nrf2 transcription activities. These results suggest that EGCG might serve as a complementary and alternative medicine in the treatment of these pathologies by inducing HO-1 expression and subsequently decreasing VSMC proliferation.

  12. Nutraceuticals in Parkinson's Disease.

    Science.gov (United States)

    Hang, Liting; Basil, Adeline Henry; Lim, Kah-Leong

    2016-09-01

    Current pharmacological strategies for Parkinson's disease (PD), the most common neurological movement disorder worldwide, are predominantly symptom relieving and are often plagued with undesirable side effects after prolonged treatment. Despite this, they remain as the mainstay treatment for PD due to the lack of better alternatives. Nutraceuticals are compounds derived from natural food sources that have certain therapeutic value and the advent of which has opened doors to the use of alternative strategies to tackle neurodegenerative diseases such as PD. Notably, nutraceuticals are able to position themselves as a "safer" strategy due to the fact that they are naturally derived compounds, therefore possibly having less side effects. Significant efforts have been put into better comprehending the role of nutraceuticals in PD, and we will look at some of them in this review. Broadly speaking, these compounds execute their positive effects via modulating signalling pathways, inhibiting oxidative stress, inflammation and apoptosis, as well as regulating mitochondrial homoeostasis. Importantly, we will highlight how a component of green tea, epigallocatechin-3-gallate (EGCG), confers neuroprotection in PD via its ability to activate AMP kinase and articulate how its beneficial effects in PD are possibly due to enhancing mitochondrial quality control.

  13. Regulation of Sirtuin-Mediated Protein Deacetylation by Cardioprotective Phytochemicals

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    Niria Treviño-Saldaña

    2017-01-01

    Full Text Available Modulation of posttranslational modifications (PTMs, such as protein acetylation, is considered a novel therapeutic strategy to combat the development and progression of cardiovascular diseases. Protein hyperacetylation is associated with the development of numerous cardiovascular diseases, including atherosclerosis, hypertension, cardiac hypertrophy, and heart failure. In addition, decreased expression and activity of the deacetylases Sirt1, Sirt3, and Sirt6 have been linked to the development and progression of cardiac dysfunction. Several phytochemicals exert cardioprotective effects by regulating protein acetylation levels. These effects are mainly exerted via activation of Sirt1 and Sirt3 and inhibition of acetyltransferases. Numerous studies support a cardioprotective role for sirtuin activators (e.g., resveratrol, as well as other emerging modulators of protein acetylation, including curcumin, honokiol, oroxilyn A, quercetin, epigallocatechin-3-gallate, bakuchiol, tyrosol, and berberine. Studies also point to a cardioprotective role for various nonaromatic molecules, such as docosahexaenoic acid, alpha-lipoic acid, sulforaphane, and caffeic acid ethanolamide. Here, we review the vast evidence from the bench to the clinical setting for the potential cardioprotective roles of various phytochemicals in the modulation of sirtuin-mediated deacetylation.

  14. Regulation of Sirtuin-Mediated Protein Deacetylation by Cardioprotective Phytochemicals

    Science.gov (United States)

    2017-01-01

    Modulation of posttranslational modifications (PTMs), such as protein acetylation, is considered a novel therapeutic strategy to combat the development and progression of cardiovascular diseases. Protein hyperacetylation is associated with the development of numerous cardiovascular diseases, including atherosclerosis, hypertension, cardiac hypertrophy, and heart failure. In addition, decreased expression and activity of the deacetylases Sirt1, Sirt3, and Sirt6 have been linked to the development and progression of cardiac dysfunction. Several phytochemicals exert cardioprotective effects by regulating protein acetylation levels. These effects are mainly exerted via activation of Sirt1 and Sirt3 and inhibition of acetyltransferases. Numerous studies support a cardioprotective role for sirtuin activators (e.g., resveratrol), as well as other emerging modulators of protein acetylation, including curcumin, honokiol, oroxilyn A, quercetin, epigallocatechin-3-gallate, bakuchiol, tyrosol, and berberine. Studies also point to a cardioprotective role for various nonaromatic molecules, such as docosahexaenoic acid, alpha-lipoic acid, sulforaphane, and caffeic acid ethanolamide. Here, we review the vast evidence from the bench to the clinical setting for the potential cardioprotective roles of various phytochemicals in the modulation of sirtuin-mediated deacetylation. PMID:29234485

  15. EFFECT OF NATURAL PLANT EXTRACTS ON PORCINE OVARIAN FUNCTIONS

    Directory of Open Access Journals (Sweden)

    Attila Kádasi

    2015-02-01

    Full Text Available This report provides information about the impact of chosen natural plant extracts on basic ovarian functions. This article summarizes our results concerning the effect of selected plant extracts on proliferation, apoptosis and hormone secretion – release of progesterone (P4, testosterone (T and leptin (L on porcine granulosa cells (GC, We analyzed effects of ginkgo (GB, rooibos (RB, flaxseed (FL, green tea polyphenols (GTPP, green tea - epigallocatechin-3-gallate (EGCG, resveratrol (RSV and curcumin (CURC (0; 1; 10 and 100 μg.ml-1 on markers of proliferation, apoptosis and secretory activity of porcine ovarian granulosa cells by using immunocytochemistry and EIA. It was demonstrated, that all these natural plants and plant molecules inhibited the accumulation of proliferation-related peptide (PCNA and apoptosis-associated peptide (Bax in cultured. Furthermore, it was observed that natural plant extracts altered progesterone, testosterone and leptin release in porcine ovarian cells. It is concluded, that GB, RB, FL, RSV, CURC, GTPP and EGCG can directly affect ovarian cells and therefore they could potentially influence ovarian functions.

  16. Potential role of green tea catechins in the management of oxidative stress-associated infertility.

    Science.gov (United States)

    Roychoudhury, Shubhadeep; Agarwal, Ashok; Virk, Gurpriya; Cho, Chak-Lam

    2017-05-01

    Reactive oxygen species (ROS) are present in low concentrations in the genital tracts of males and females. Excessive ROS lead to oxidative stress, which damages DNA, lipids and proteins. Such molecular changes result in compromised vitality, increased morphological defects and decreased sperm motility in the male. In the female, oxidative stress interferes with oocyte maturation, and may inhibit in-vitro maturation of the oocyte. Recently, green tea supplementation has been reported to possess properties that may improve the quality of male and female gametes largely due to the ability of catechin polyphenols to quench ROS. Epigallocatechin-3-gallate (EGCG) is considered the most promising bioactive compound in green tea due to its strong antioxidant activity. The unique property of green tea catechins may potentially improve reproductive health and pose an important research area. We present a comprehensive overview on the effects and potential roles of green tea catechins on oxidative stress in male and female reproduction and fertility. In this review, possible mechanisms of action are highlighted to better understand the potential use of green tea catechins in the reduction of oxidative stress and its associated beneficial effects in the clinical setting. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  17. Effects of herbal mixture extracts on obesity in rats fed a high-fat diet

    Directory of Open Access Journals (Sweden)

    Mei-Yin Chien

    2016-07-01

    Full Text Available The aim of this study was to investigate and compare the effects of three herbal mixture extracts on obesity induced by high-fat diet (HFD in rats. The prescriptions—Pericarpium citri reticulatae and Fructus crataegi—were used as matrix components and mixed with Ampelopsis grossedentata, Salvia miltiorrhiza, and epigallocatechin-3-gallate (EGCG to form T1, T2, and T3 complexes, respectively. Results revealed that HFD feeding significantly increased body weight gain, fat deposition, plasma lipid profiles, hepatic lipid accumulation, and hepatic vacuoles formation, but decreased plasma levels of adiponectin in rats. Only the T1 complex showed the tendency, although not significantly so, for decreased HFD-induced body weight gain. T1 and T3 complexes significantly reduced HFD-induced fat deposition, and plasma levels of triglyceride, total cholesterol, and low-density lipoprotein cholesterol. Only the T1 complex significantly increased HFD-reduced adiponectin levels in plasma, but decreased HFD-increased triglyceride content in liver tissues. All complexes effectively inhibited HFD-induced vacuoles formation. The content of dihydromyricetin, salvianolic acid B, and EGCG in T1, T2, and T3 complexes was 18.25 ± 0.07%, 22.20 ± 0.10%, and 18.86 ± 0.04%, respectively. In summary, we demonstrated that herbal mixture extracts, especially T1 complex, exhibit antiobesity activity in HFD-fed rats.

  18. EGCG Enhances Cisplatin Sensitivity by Regulating Expression of the Copper and Cisplatin Influx Transporter CTR1 in Ovary Cancer.

    Directory of Open Access Journals (Sweden)

    Xuemin Wang

    Full Text Available Cisplatin is one of the first-line platinum-based chemotherapeutic agents for treatment of many types of cancer, including ovary cancer. CTR1 (copper transporter 1, a transmembrane solute carrier transporter, has previously been shown to increase the cellular uptake and sensitivity of cisplatin. It is hypothesized that increased CTR1 expression would enhance the sensitivity of cancer cells to cisplatin (cDDP. The present study demonstrates for the first time that (--epigallocatechin-3-gallate (EGCG, a major polyphenol from green tea, can enhance CTR1 mRNA and protein expression in ovarian cancer cells and xenograft mice. EGCG inhibits the rapid degradation of CTR1 induced by cDDP. The combination of EGCG and cDDP increases the accumulation of cDDP and DNA-Pt adducts, and subsequently enhances the sensitivity of ovarian cancer SKOV3 and OVCAR3 cells to the chemotherapeutic agent. In the OVCAR3 ovarian cancer xenograft nude mice model, the combination of the lower concentration of cDDP and EGCG strongly repressed the tumor growth and exhibited protective effect on the nephrotoxicity induced by cisplatin. Overall, these findings uncover a novel chemotherapy mechanism of EGCG as an adjuvant for the treatment of ovarian cancer.

  19. Tea: age-old beverage as an effective cancer chemopreventive agent

    Directory of Open Access Journals (Sweden)

    Jasmine George

    2011-12-01

    Full Text Available Cancer is the major public health problem, causing approximately 7 million deaths every year worldwide. The existing treatment approaches and surgical techniques have not been able to cope effectively with this dreaded disease. Because of this, the concept of chemoprevention is now considered a valid approach to reduce the incidence of cancer. There is convincing epidemiological and experimental evidence to show that dietary polyphenolic plant-derived compounds have cancer preventive properties. Based on evidence from in vitro, in vivo data and epidemiological studies, tea has received considerable attention over recent years for reducing the risk of several cancers. Much of the cancer preventive effects of tea, and in particular green tea, appear to be mediated by the polyphenols they contain. In addition to inhibiting mutagenesis and proliferation, tea is relatively non-toxic, is low cost, and can be taken orally or as a part of the daily diet. Therefore it is logical that future clinical studies should focus on examining the efficacy of tea and its active constituents, such as epigallocatechin- 3-gallate (EGCG and theaflavins (TFs, in chemoprevention as an alternative to pharmacological agents. In this review, we address the use of tea and its constituents for the prevention and treatment of cancer. Further mechanistic and dose-response studies will help us to understand the effects of tea consumption on human carcinogenesis.

  20. Combined autophagy and HDAC inhibition: a phase I safety, tolerability, pharmacokinetic, and pharmacodynamic analysis of hydroxychloroquine in combination with the HDAC inhibitor vorinostat in patients with advanced solid tumors.

    Science.gov (United States)

    Mahalingam, Devalingam; Mita, Monica; Sarantopoulos, John; Wood, Leslie; Amaravadi, Ravi K; Davis, Lisa E; Mita, Alain C; Curiel, Tyler J; Espitia, Claudia M; Nawrocki, Steffan T; Giles, Francis J; Carew, Jennifer S

    2014-08-01

    We previously reported that inhibition of autophagy significantly augmented the anticancer activity of the histone deacetylase (HDAC) inhibitor vorinostat (VOR) through a cathepsin D-mediated mechanism. We thus conducted a first-in-human study to investigate the safety, preliminary efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of the combination of the autophagy inhibitor hydroxychloroquine (HCQ) and VOR in patients with advanced solid tumors. Of 27 patients treated in the study, 24 were considered fully evaluable for study assessments and toxicity. Patients were treated orally with escalating doses of HCQ daily (QD) (d 2 to 21 of a 21-d cycle) in combination with 400 mg VOR QD (d one to 21). Treatment-related adverse events (AE) included grade 1 to 2 nausea, diarrhea, fatigue, weight loss, anemia, and elevated creatinine. Grade 3 fatigue and/or myelosuppression were observed in a minority of patients. Fatigue and gastrointestinal AE were dose-limiting toxicities. Six-hundred milligrams HCQ and 400 mg VOR was established as the maximum tolerated dose and recommended phase II regimen. One patient with renal cell carcinoma had a confirmed durable partial response and 2 patients with colorectal cancer had prolonged stable disease. The addition of HCQ did not significantly impact the PK profile of VOR. Treatment-related increases in the expression of CDKN1A and CTSD were more pronounced in tumor biopsies than peripheral blood mononuclear cells. Based on the safety and preliminary efficacy of this combination, additional clinical studies are currently being planned to further investigate autophagy inhibition as a new approach to increase the efficacy of HDAC inhibitors.

  1. Corrosion inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, A O

    1965-12-29

    An acid corrosion-inhibiting composition consists essentially of a sugar, and an alkali metal salt selected from the group consisting of iodides and bromides. The weight ratio of the sugar to the alkali metal salt is between 2:1 and about 20,000:1. Also, a corrosion- inhibited phosphoric acid composition comprising at least about 20 wt% of phosphoric acid and between about 0.1 wt% and about 10 wt% of molasses, and between about 0.0005 wt% and about 1 wt% of potassium iodide. The weight ratio of molasses to iodide is greater than about 2:1. (11 claims)

  2. Suppression of growth and invasive behavior of human prostate cancer cells by ProstaCaid™: mechanism of activity.

    Science.gov (United States)

    Jiang, Jiahua; Eliaz, Isaac; Sliva, Daniel

    2011-06-01

    Since the use of dietary supplements as alternative treatments or adjuvant therapies in cancer treatment is growing, a scientific verification of their biological activity and the detailed mechanisms of their action are necessary for the acceptance of dietary supplements in conventional cancer treatments. In the present study we have evaluated the anti-cancer effects of dietary supplement ProstaCaid™ (PC) which contains mycelium from medicinal mushrooms (Ganoderma lucidum, Coriolus versicolor, Phellinus linteus), saw palmetto berry, pomegranate, pumpkin seed, green tea [40% epigallocatechin-3-gallate (EGCG)], Japanese knotweed (50% resveratrol), extracts of turmeric root (BCM-95®), grape skin, pygeum bark, sarsaparilla root, Scutellaria barbata, eleuthero root, Job's tears, astragalus root, skullcap, dandelion, coptis root, broccoli, and stinging nettle, with purified vitamin C, vitamin D3, selenium, quercetin, citrus bioflavonoid complex, β sitosterolzinc, lycopene, α lipoic acid, boron, berberine and 3.3'-diinodolymethane (DIM). We show that PC treatment resulted in the inhibition of cell proliferation of the highly invasive human hormone refractory (independent) PC-3 prostate cancer cells in a dose- and time-dependent manner with IC50 56.0, 45.6 and 39.0 µg/ml for 24, 48 and 72 h, respectively. DNA-microarray analysis demonstrated that PC inhibits proliferation through the modulation of expression of CCND1, CDK4, CDKN1A, E2F1, MAPK6 and PCNA genes. In addition, PC also suppresses metastatic behavior of PC-3 by the inhibition of cell adhesion, cell migration and cell invasion, which was associated with the down-regulation of expression of CAV1, IGF2, NR2F1, and PLAU genes and suppressed secretion of the urokinase plasminogen activator (uPA) from PC-3 cells. In conclusion, the dietary supplement PC is a promising natural complex with the potency to inhibit invasive human prostate cancer.

  3. Direct interaction of natural and synthetic catechins with signal transducer activator of transcription 1 affects both its phosphorylation and activity

    KAUST Repository

    Menegazzi, Marta

    2013-12-10

    Our previous studies showed that (-)-epigallocatechin-3-gallate (EGCG) inhibits signal transducer activator of transcription 1 (STAT1) activation. Since EGCG may be a promising lead compound for new anti-STAT1 drug design, 15 synthetic catechins, characterized by the (-)-gallocatechin-3-gallate stereochemistry, were studied in the human mammary MDA-MB-231 cell line to identify the minimal structural features that preserve the anti-STAT1 activity. We demonstrate that the presence of three hydroxyl groups of B ring and one hydroxyl group in D ring is essential to preserve their inhibitory action. Moreover, a possible molecular target of these compounds in the STAT1 pathway was investigated. Our results demonstrate a direct interaction between STAT1 protein and catechins displaying anti-STAT1 activity. In particular, surface plasmon resonance (SPR) analysis and molecular modeling indicate the presence of two putative binding sites (a and b) with different affinity. Based on docking data, site-directed mutagenesis was performed, and interaction of the most active catechins with STAT1 was studied with SPR to test whether Gln518 on site a and His568 on site b could be important for the catechin-STAT1 interaction. Data indicate that site b has higher affinity for catechins than site a as the highest affinity constant disappears in the H568ASTAT1 mutant. Furthermore, Janus kinase 2 (JAK2) kinase assay data suggest that the contemporary presence in vitro of STAT1 and catechins inhibits JAK2-elicited STAT1 phosphorylation. The very tight catechin-STAT1 interaction prevents STAT1 phosphorylation and represents a novel, specific and efficient molecular mechanism for the inhibition of STAT1 activation. © Copyright 2014 Federation of European Biochemical Societies. All rights reserved.

  4. FREQUENT SUBCLINICAL MACULAR CHANGES IN COMBINED BRAF/MEK INHIBITION WITH HIGH-DOSE HYDROXYCHLOROQUINE AS TREATMENT FOR ADVANCED METASTATIC BRAF MUTANT MELANOMA: Preliminary Results From a Phase I/II Clinical Treatment Trial.

    Science.gov (United States)

    Nti, Akosua A; Serrano, Leona W; Sandhu, Harpal S; Uyhazi, Katherine E; Edelstein, Ilaina D; Zhou, Elaine J; Bowman, Scott; Song, Delu; Gangadhar, Tara C; Schuchter, Lynn M; Mitnick, Sheryl; Huang, Alexander; Nichols, Charles W; Amaravadi, Ravi K; Kim, Benjamin J; Aleman, Tomas S

    2018-01-10

    To assess the potential ocular toxicity of a combined BRAF inhibition (BRAFi) + MEK inhibition (MEKi) + hydroxychloroquine (HCQ) regime used to treat metastatic BRAF mutant melanoma. Patients with stage IV metastatic melanoma and BRAF V600E mutations (n = 11, 31-68 years of age) were included. Treatment was with oral dabrafenib, 150 mg bid, trametinib, 2 mg/day, and HCQ, 400 mg to 600 mg bid. An ophthalmic examination, spectral domain optical coherence tomography, near-infrared and short-wavelength fundus autofluorescence, and static perimetry were performed at baseline, 1 month, and q/6 months after treatment. There were no clinically significant ocular events; there was no ocular inflammation. The only medication-related change was a separation of the photoreceptor outer segment tip from the apical retinal pigment epithelium that could be traced from the fovea to the perifoveal retina noted in 9/11 (82%) of the patients. There were no changes in retinal pigment epithelium melanization or lipofuscin content by near-infrared fundus autofluorescence and short-wavelength fundus autofluorescence, respectively. There were no inner retinal or outer nuclear layer changes. Visual acuities and sensitivities were unchanged. BRAFi (trametinib) + MEKi (dabrafenib) + HCQ causes very frequent, subclinical separation of the photoreceptor outer segment from the apical retinal pigment epithelium without inner retinal changes or signs of inflammation. The changes suggest interference with the maintenance of the outer retinal barrier and/or phagocytic/pump functions of the retinal pigment epithelium by effective MEK inhibition.

  5. Functional amyloid formation by Streptococcus mutans

    Science.gov (United States)

    Oli, M. W.; Otoo, H. N.; Crowley, P. J.; Heim, K. P.; Nascimento, M. M.; Ramsook, C. B.; Lipke, P. N.

    2012-01-01

    Dental caries is a common infectious disease associated with acidogenic and aciduric bacteria, including Streptococcus mutans. Organisms that cause cavities form recalcitrant biofilms, generate acids from dietary sugars and tolerate acid end products. It has recently been recognized that micro-organisms can produce functional amyloids that are integral to biofilm development. We now show that the S. mutans cell-surface-localized adhesin P1 (antigen I/II, PAc) is an amyloid-forming protein. This conclusion is based on the defining properties of amyloids, including binding by the amyloidophilic dyes Congo red (CR) and Thioflavin T (ThT), visualization of amyloid fibres by transmission electron microscopy and the green birefringent properties of CR-stained protein aggregates when viewed under cross-polarized light. We provide evidence that amyloid is present in human dental plaque and is produced by both laboratory strains and clinical isolates of S. mutans. We provide further evidence that amyloid formation is not limited to P1, since bacterial colonies without this adhesin demonstrate residual green birefringence. However, S. mutans lacking sortase, the transpeptidase enzyme that mediates the covalent linkage of its substrates to the cell-wall peptidoglycan, including P1 and five other proteins, is not birefringent when stained with CR and does not form biofilms. Biofilm formation is inhibited when S. mutans is cultured in the presence of known inhibitors of amyloid fibrillization, including CR, Thioflavin S and epigallocatechin-3-gallate, which also inhibited ThT uptake by S. mutans extracellular proteins. Taken together, these results indicate that S. mutans is an amyloid-forming organism and suggest that amyloidogenesis contributes to biofilm formation by this oral microbe. PMID:23082034

  6. Y-27632 Increases Sensitivity of PANC-1 Cells to EGCG in Regulating Cell Proliferation and Migration.

    Science.gov (United States)

    Liu, Xing; Bi, Yongyi

    2016-10-03

    BACKGROUND The study aimed to investigate the inhibitory effect of (1R,4r)-4-((R)-1-aminoethyl)-N-(pyridin-4-yl) cyclohexanecarboxamide (Y-27632) and (-)-epigallocatechin-3-gallate (EGCG) on the proliferation and migration of PANC-1 cells. EGCG, found in green tea, has been previously shown to be one of the most abundant and powerful catechins in cancer prevention and treatment. Y-27632, a selective inhibitor of rho-associated protein kinase 1, is widely used in treating cardiovascular disease, inflammation, and cancer. MATERIAL AND METHODS PANC-1 cells, maintained in Dulbecco's Modified Eagle's Medium, were treated with dimethyl sulfoxide (control) as well as different concentrations (20, 40, 60, and 80 μg/mL) of EGCG for 48 h. In addition, PANC-1 cells were treated separately with 60 μg/mL EGCG, 20 μM Y-27632, and EGCG combined with Y-27632 (60 μg/mL EGCG + 20 μM Y-27632) for 48 h. The effect of EGCG and Y-27632 on the proliferation and migration of PANC-1 cells was evaluated using Cell Counting Kit-8 and transwell migration assays. The expression of peroxisome proliferator-activated receptor alpha (PPARα) and Caspase-3 mRNA was determined by Quantitative real-time polymerase chain reaction (RT-qPCR). RESULTS EGCG (20-80 μg/mL) inhibited cell viability in a dose-dependent manner. Y-27632 enhanced the sensitivity of PANC-1 cells to EGCG (by increasing the expression of PPARa and Caspase-3 mRNA) and suppressed cell proliferation. PANC-1 cell migration was inhibited by treatment with a combination of EGCG and Y-27632. CONCLUSIONS Y-27632 increases the sensitivity of PANC-1 cells to EGCG in regulating cell proliferation and migration, which is likely to be related to the expression of PPARa mRNA and Caspase-3 mRNA.

  7. Y-27632 Increases Sensitivity of PANC-1 Cells to Epigallocatechin Gallate (EGCG) in Regulating Cell Proliferation and Migration

    Science.gov (United States)

    Liu, Xing; Bi, Yongyi

    2016-01-01

    Background The study aimed to investigate the inhibitory effect of (1R,4r)-4-((R)-1-aminoethyl)-N-(pyridin-4-yl) cyclohexanecarboxamide (Y-27632) and (−)-epigallocatechin-3-gallate (EGCG) on the proliferation and migration of PANC-1 cells. EGCG, found in green tea, has been previously shown to be one of the most abundant and powerful catechins in cancer prevention and treatment. Y-27632, a selective inhibitor of rho-associated protein kinase 1, is widely used in treating cardiovascular disease, inflammation, and cancer. Material/Methods PANC-1 cells, maintained in Dulbecco’s Modified Eagle’s Medium, were treated with dimethyl sulfoxide (control) as well as different concentrations (20, 40, 60, and 80 μg/mL) of EGCG for 48 h. In addition, PANC-1 cells were treated separately with 60 μg/mL EGCG, 20 μM Y-27632, and EGCG combined with Y-27632 (60 μg/mL EGCG + 20 μM Y-27632) for 48 h. The effect of EGCG and Y-27632 on the proliferation and migration of PANC-1 cells was evaluated using Cell Counting Kit-8 and transwell migration assays. The expression of peroxisome proliferator–activated receptor alpha (PPARα) and Caspase-3 mRNA was determined by Quantitative real-time polymerase chain reaction (RT-qPCR). Results EGCG (20–80 μg/mL) inhibited cell viability in a dose-dependent manner. Y-27632 enhanced the sensitivity of PANC-1 cells to EGCG (by increasing the expression of PPARα and Caspase-3 mRNA) and suppressed cell proliferation. PANC-1 cell migration was inhibited by treatment with a combination of EGCG and Y-27632. Conclusions Y-27632 increases the sensitivity of PANC-1 cells to EGCG in regulating cell proliferation and migration, which is likely to be related to the expression of PPARα mRNA and Caspase-3 mRNA. PMID:27694793

  8. Keratinocyte proliferation, differentiation, and apoptosis-Differential mechanisms of regulation by curcumin, EGCG and apigenin

    International Nuclear Information System (INIS)

    Balasubramanian, Sivaprakasam; Eckert, Richard L.

    2007-01-01

    We have proposed that it is important to examine the impact of chemopreventive agents on the function of normal human epidermal keratinocytes since these cells comprise the barrier that protects the body from a range of environmental insults. In this context, it is widely appreciated that cancer may be retarded by consumption or topical application of naturally occurring food-derived chemopreventive agents. Our studies show that (-)-epigallocatechin-3-gallate (EGCG), a green tea-derived polyphenol, acts to enhance the differentiation of normal human keratinocytes as evidenced by its ability to increase involucrin (hINV), transglutaminase type 1 (TG1) and caspase-14 gene expression. EGCG also stimulates keratinocyte morphological differentiation. These actions of EGCG are mediated via activation of a nPKC, Ras, MEKK1, MEK3, p38δ-ERK1/2 signaling cascade which leads to increased activator protein 1 (AP1) and CAATT enhancer binding protein (C/EBP) transcription factor expression, increased binding of these factors to DNA, and increased gene transcription. In contrast, apigenin, a dietary flavonoid derived from plants and vegetables, and curcumin, an agent derived from turmeric, inhibit differentiation by suppressing MAPK signal transduction and reducing API transcription factor level. Curcumin also acts to enhance apoptosis, although EGCG and apigenin do not stimulate apoptosis. In addition, all of these agents inhibit keratinocyte proliferation. These findings indicate that each of these diet-derived chemopreventive agents has a profound impact on normal human keratinocyte function and that they operate via distinct and sometimes opposing mechanisms. However, all are expected to act as chemopreventive agents

  9. Green tea and its anti-angiogenesis effects.

    Science.gov (United States)

    Rashidi, Bahman; Malekzadeh, Mehrnoush; Goodarzi, Mohammad; Masoudifar, Aria; Mirzaei, Hamed

    2017-05-01

    The development of new blood vessels from a pre-existing vasculature (also known as angiogenesis) is required for many physiological processes including embryogenesis and post-natal growth. However, pathological angiogenesis is also a hallmark of cancer and many ischaemic and inflammatory diseases. The pro-angiogenic members of the VEGF family (vascular endothelial growth factor family), VEGF-A, VEGF-B, VEGF-C, VEGF-D and placental growth factor (PlGF), and the related receptors, VEGFR-1, VEGFR-2 and VEGFR-3 have a central and decisive role in angiogenesis. Indeed, they are the targets for anti-angiogenic drugs currently approved. Green tea (from the Camellia sinensis plant) is one of the most popular beverages in the world. It is able to inhibit angiogenesis by different mechanisms such as microRNAs (miRNAs). Green tea and its polyphenolic substances (like catechins) show chemo-preventive and chemotherapeutic features in various types of cancer and experimental models for human cancers. The tea catechins, including (-)-epigallocatechin-3-gallate (EGCG), have multiple effects on the cellular proteome and signalome. Note that the polyphenolic compounds from green tea are able to change the miRNA expression profile associated with angiogenesis in various cancer types. This review focuses on the ability of the green tea constituents to suppress angiogenesis signaling and it summarizes the mechanisms by which EGCG might inhibit the VEGF family. We also highlighted the miRNAs affected by green tea which are involved in anti-angiogenesis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Advanced Ceramics

    International Nuclear Information System (INIS)

    1989-01-01

    The First Florida-Brazil Seminar on Materials and the Second State Meeting about new materials in Rio de Janeiro State show the specific technical contribution in advanced ceramic sector. The others main topics discussed for the development of the country are the advanced ceramic programs the market, the national technic-scientific capacitation, the advanced ceramic patents, etc. (C.G.C.) [pt

  11. Inhibiting cancer cell hallmark features through nuclear export inhibition.

    Science.gov (United States)

    Sun, Qingxiang; Chen, Xueqin; Zhou, Qiao; Burstein, Ezra; Yang, Shengyong; Jia, Da

    2016-01-01

    Treating cancer through inhibition of nuclear export is one of the best examples of basic research translation into clinical application. Nuclear export factor chromosomal region maintenance 1 (CRM1; Xpo1 and exportin-1) controls cellular localization and function of numerous proteins that are critical for the development of many cancer hallmarks. The diverse actions of CRM1 are likely to explain the broad ranging anti-cancer potency of CRM1 inhibitors observed in pre-clinical studies and/or clinical trials (phase I-III) on both advanced-stage solid and hematological tumors. In this review, we compare and contrast the mechanisms of action of different CRM1 inhibitors, and discuss the potential benefit of unexplored non-covalent CRM1 inhibitors. This emerging field has uncovered that nuclear export inhibition is well poised as an attractive target towards low-toxicity broad-spectrum potent anti-cancer therapy.

  12. EGCG Suppresses ERK5 Activation to Reverse Tobacco Smoke-Triggered Gastric Epithelial-Mesenchymal Transition in BALB/c Mice

    Directory of Open Access Journals (Sweden)

    Ling Lu

    2016-07-01

    Full Text Available Tobacco smoke is an important risk factor of gastric cancer. Epithelial-mesenchymal transition is a crucial pathophysiological process in cancer development. ERK5 regulation of epithelial-mesenchymal transition may be sensitive to cell types and/or the cellular microenvironment and its role in the epithelial-mesenchymal transition process remain elusive. Epigallocatechin-3-gallate (EGCG is a promising chemopreventive agent for several types of cancers. In the present study we investigated the regulatory role of ERK5 in tobacco smoke-induced epithelial-mesenchymal transition in the stomach of mice and the preventive effect of EGCG. Exposure of mice to tobacco smoke for 12 weeks reduced expression of epithelial markers E-cadherin, ZO-1, and CK5, while the expression of mesenchymal markers Snail-1, Vimentin, and N-cadherin were increased. Importantly, we demonstrated that ERK5 modulated tobacco smoke-mediated epithelial-mesenchymal transition in mice stomach, as evidenced by the findings that tobacco smoke elevated ERK5 activation, and that tobacco smoke-triggered epithelial-mesenchymal transition was reversed by ERK5 inhibition. Treatment of EGCG (100 mg/kg BW effectively attenuated tobacco smoke-triggered activation of ERK5 and epithelial-mesenchymal transition alterations in mice stomach. Collectively, these data suggested that ERK5 was required for tobacco smoke-triggered gastric epithelial-mesenchymal transition and that EGCG suppressed ERK5 activation to reverse tobacco smoke-triggered gastric epithelial-mesenchymal transition in BALB/c mice. These findings provide new insights into the mechanism of tobacco smoke-associated gastric tumorigenesis and the chemoprevention of tobacco smoke-associated gastric cancer.

  13. The preparation and characterization of gold-conjugated polyphenol nanoparticles as a novel delivery system

    Directory of Open Access Journals (Sweden)

    Hsieh DS

    2012-03-01

    Full Text Available Dar-Shih Hsieh1,2, Hsiu-Chin Lu5, Cheng-Cheung Chen1,3, Chang-Jer Wu1,*, Ming-Kung Yeh4,* 1Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan; 2Division of Urology, 3Department of Pathology, Tri-Service General Hospital, 4Institute of Preventive Medicine, National Defence Medical Center, Taipei, Taiwan; 5Department of Laboratory Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan*These authors contributed equally to this workAbstract: Nanogold particles are commonly used in nanomedicine. We generated physical nanogold (pNG conjugated with different ratios of epigallocatechin-3-gallate (EGCG and evaluated its physicochemical properties, antioxidant activity, and cytotoxicity in vitro as well as anticancer activity in vivo. Results showed that the EGCG-pNG conjugates were successfully prepared at ratios between 23:1 and 23:5, with the percentage of EGCG content increasing with the EGCG:pNG ratio from 23:1 (2.0% ± 0.02% to 23:5 (28% ± 0.3%. EGCG-pNG particles at ratios of 23:1 and 23:5 demonstrated significantly decreased size from 500 to 20 nm and decreasing zeta potentials of 21 mV to –22 mV, respectively. At a ratio of 23:2.5, the EGCG-pNG particles (27% EGCG, 50 nm in size, zeta potential of –8 mV showed longer EGCG activity half-life (110 days vs 5 hours, controlled release (2 hours vs 30 minutes, and higher antioxidant activity (four times, as well as inhibition of tumor cell growth, than controls. The present study indicated that EGCG-pNG possesses promising therapeutic potential, based on its strong free-radical scavenging and anticancer activities.Keywords: EGCG, nanoparticles, antioxidant, antitumor activity, nanogold

  14. INHIBITION IN SPEAKING PERFORMANCE

    OpenAIRE

    Humaera, Isna

    2015-01-01

    The most common problem encountered by the learner in the languageacquisition process is learner inhibition. Inhibition refers to a temperamentaltendency to display wariness, fearfulness, or restrain in response tounfamiliar people, objects, and situations. There are some factors that causeinhibition, such as lack of motivation, shyness, self-confidence, self-esteem,and language ego. There are also levels of inhibition, it refers to kinds ofinhibition and caused of inhibition itself. Teacher ...

  15. ADVANCE PAYMENTS

    CERN Multimedia

    Human Resources Division

    2002-01-01

    Administrative Circular Nº 8 makes provision for the granting of advance payments, repayable in several monthly instalments, by the Organization to the members of its personnel. Members of the personnel are reminded that these advances are only authorized in exceptional circumstances and at the discretion of the Director-General. In view of the current financial situation of the Organization, and in particular the loans it will have to incur, the Directorate has decided to restrict the granting of such advances to exceptional or unforeseen circumstances entailing heavy expenditure and more specifically those pertaining to social issues. Human Resources Division Tel. 73962

  16. Advance payments

    CERN Multimedia

    Human Resources Division

    2003-01-01

    Administrative Circular N 8 makes provision for the granting of advance payments, repayable in several monthly instalments, by the Organization to the members of its personnel. Members of the personnel are reminded that these advances are only authorized in exceptional circumstances and at the discretion of the Director-General. In view of the current financial situation of the Organization, and in particular the loans it will have to incur, the Directorate has decided to restrict the granting of such advances to exceptional or unforeseen circumstances entailing heavy expenditure and more specifically those pertaining to social issues. Human Resources Division Tel. 73962

  17. Novel radiosensitizers for locally advanced epithelial tumors: inhibition of the PI3K/Akt survival pathway in tumor cells and in tumor-associated endothelial cells as a novel treatment strategy?

    International Nuclear Information System (INIS)

    Riesterer, Oliver; Tenzer, Angela; Zingg, Daniel; Hofstetter, Barbara; Vuong, Van; Pruschy, Martin; Bodis, Stephan

    2004-01-01

    In locally advanced epithelial malignancies, local control can be achieved with high doses of radiotherapy (RT). Concurrent chemoradiotherapy can improve tumor control in selected solid epithelial adult tumors; however, treatment-related toxicity is of major concern and the therapeutic window often small. Therefore, novel pharmacologic radiosensitizers with a tumor-specific molecular target and a broad therapeutic window are attractive. Because of clonal heterogeneity and the high mutation rate of these tumors, combined treatment with single molecular target radiosensitizers and RT are unlikely to improve sustained local tumor control substantially. Therefore, radiosensitizers modulating entire tumor cell survival pathways in epithelial tumors are of potential clinical use. We discuss the preclinical efficacy and the mechanism of three different, potential radiosensitizers targeting the PTEN/PI3K/Akt survival pathway. These compounds were initially thought to act as single-target agents against growth factor receptors (PKI 166 and PTK 787) or protein kinase C isoforms (PKC 412). We describe an additional target for these compounds. PKI 166 (an epidermal growth factor [EGF] receptor inhibitor) and PKC 412, target the PTEN/PI3K/Akt pathway mainly in tumor cells, and PTK 787 (a vascular endothelial growth factor [VEGF] receptor inhibitor) in endothelial cells. Even for these broader range molecular radiosensitizers, the benefit could be restricted to human epithelial tumor cell clones with a distinct molecular profile. Therefore, these potential radiosensitizers have to be carefully tested in specific model systems before introduction in early clinical trials

  18. Nifedipine, a calcium channel blocker, inhibits advanced glycation end product (AGE)-elicited mesangial cell damage by suppressing AGE receptor (RAGE) expression via peroxisome proliferator-activated receptor-gamma activation

    International Nuclear Information System (INIS)

    Matsui, Takanori; Yamagishi, Sho-ichi; Takeuchi, Masayoshi; Ueda, Seiji; Fukami, Kei; Okuda, Seiya

    2009-01-01

    The interaction between advanced glycation end products (AGE) and their receptor RAGE mediates the progressive alteration in renal architecture and loss of renal function in diabetic nephropathy. Oxidative stress generation and inflammation also play a central role in diabetic nephropathy. This study investigated whether and how nifedipine, a calcium channel blocker (CCB), blocked the AGE-elicited mesangial cell damage in vitro. Nifedipine, but not amlodipine, a control CCB, down-regulated RAGE mRNA levels and subsequently reduced reactive oxygen species (ROS) generation in AGE-exposed mesangial cells. AGE increased mRNA levels of vascular cell adhesion molecule-1 (VCAM-1) and induced monocyte chemoattractant protein-1 (MCP-1) production in mesangial cells, both of which were prevented by the treatment with nifedipine, but not amlodipine. The beneficial effects of nifedipine on AGE-exposed mesangial cells were blocked by the simultaneous treatment of GW9662, an inhibitor of peroxisome proliferator-activated receptor-γ (PPAR-γ). Although nifedipine did not affect expression levels of PPAR-γ, it increased the PPAR-γ transcriptional activity in mesangial cells. Our present study provides a unique beneficial aspect of nifedipine on diabetic nephropathy; it could work as an anti-inflammatory agent against AGE by suppressing RAGE expression in cultured mesangial cells via PPAR-γ activation.

  19. Metastatic spinal cord compression from basal cell carcinoma of the skin treated with surgical decompression and vismodegib: case report and review of Hedgehog signalling pathway inhibition in advanced basal cell carcinoma.

    Science.gov (United States)

    McGrane, J; Carswell, S; Talbot, T

    2017-01-01

    We report a case of a 66-year-old man with locally advanced and metastatic basal cell carcinoma (BCC) causing spinal cord compression, which was treated with spinal surgery and subsequent vismodegib. The patient presented with a large fungating chest wall lesion and a metastasis in T8 that was causing cord compression. He had neurosurgical decompression of the T8 lesion and fixation of the spine. Punch biopsy from the fungating chest wall lesion showed a BCC with some malignant squamous differentiation (basosquamous). Histopathological examination of the metastatic lesion in T8 at the time of surgical decompression identified features identical to the punch biopsy. The patient was referred to the oncology clinic for adjuvant treatment. In light of his metastatic disease and the large area over his chest wall that could not fully be covered by radiotherapy, he was treated with the novel oral Hedgehog signalling pathway (HHSP) inhibitor vismodegib, which led to marked improvement. © 2016 British Association of Dermatologists.

  20. Advanced Electronics

    Science.gov (United States)

    2017-07-21

    AFRL-RV-PS- AFRL-RV-PS- TR-2017-0114 TR-2017-0114 ADVANCED ELECTRONICS Ashwani Sharma 21 Jul 2017 Interim Report APPROVED FOR PUBLIC RELEASE...NUMBER Advanced Electronics 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 62601F 6. AUTHOR(S) 5d. PROJECT NUMBER 4846 Ashwani Sharma 5e. TASK NUMBER...Approved for public release; distribution is unlimited. (RDMX-17-14919 dtd 20 Mar 2018) 13. SUPPLEMENTARY NOTES 14. ABSTRACT The Space Electronics

  1. AdvancED Flex 4

    CERN Document Server

    Tiwari, Shashank; Schulze, Charlie

    2010-01-01

    AdvancED Flex 4 makes advanced Flex 4 concepts and techniques easy. Ajax, RIA, Web 2.0, mashups, mobile applications, the most sophisticated web tools, and the coolest interactive web applications are all covered with practical, visually oriented recipes. * Completely updated for the new tools in Flex 4* Demonstrates how to use Flex 4 to create robust and scalable enterprise-grade Rich Internet Applications.* Teaches you to build high-performance web applications with interactivity that really engages your users.* What you'll learn Practiced beginners and intermediate users of Flex, especially

  2. Antioxidant efficacy of crude methanol extract of ashitaba green tea against radiation induced oxidative stress in E.coli K12 bacteria

    International Nuclear Information System (INIS)

    Darshan Raj, C.G.; Sindhu Priya, E.S.; Sarojini, B.K.

    2013-01-01

    This study was undertaken to evaluate the antioxidant activity of methanol crude extract of ashitaba green tea (G). The DPPH scavenging assay was evaluated for green tea extract to determine its radical scavenging capacity. The bacteria was pretreated with ashitaba green tea extract, quercetin (Q) and (-) epigallocatechin -3-gallate (E) at below MIC level. Oxidative stress was induced at 0.4 Gy using gamma radiation. The antioxidant efficacy of ashitaba green tea was evaluated through enzyme antioxidant studies like SOD (Superoxidedismutase) and CAT (Catalase). The oxidative stress marker Thiobarbituric acid-reactive substance (TBARS) was also evaluated. Further the protective efficacy of the(G) was confirmed by colony forming units (CFU) study. Among the tested compounds the crude extract of ashitaba (G) exhibited excellent antioxidant activity in comparison with quercetin and (-) epigallocatechin -3-gallate. (abstract)

  3. Advanced calculus

    CERN Document Server

    Nickerson, HK; Steenrod, NE

    2011-01-01

    ""This book is a radical departure from all previous concepts of advanced calculus,"" declared the Bulletin of the American Mathematics Society, ""and the nature of this departure merits serious study of the book by everyone interested in undergraduate education in mathematics."" Classroom-tested in a Princeton University honors course, it offers students a unified introduction to advanced calculus. Starting with an abstract treatment of vector spaces and linear transforms, the authors introduce a single basic derivative in an invariant form. All other derivatives - gradient, divergent, curl,

  4. Crystal Structure of the Human Laminin Receptor Precursor

    Energy Technology Data Exchange (ETDEWEB)

    Jamieson,K.; Wu, J.; Hubbard, S.; Meruelo, D.

    2008-01-01

    The human laminin receptor (LamR) interacts with many ligands, including laminin, prions, Sindbis virus, and the polyphenol (-)-epigallocatechin-3-gallate (EGCG), and has been implicated in a number of diseases. LamR is overexpressed on tumor cells, and targeting LamR elicits anti-cancer effects. Here, we report the crystal structure of human LamR, which provides insights into its function and should facilitate the design of novel therapeutics targeting LamR.

  5. Effects of topical application of EGCG on testosterone-induced hair loss in a mouse model.

    Science.gov (United States)

    Kim, Yoon Young; Up No, Sun; Kim, Min Ho; Kim, Hei Sung; Kang, Hoon; Kim, Hyung Ok; Park, Young Min

    2011-12-01

    We investigated the effect of topical epigallocatechin-3-gallate (EGCG) on testosterone (T)-induced hair loss in mice. Marked hair loss was observed at the T-injected site, and topical EGCG significantly reduced the hair loss (P hair loss by apoptosis of the hair follicles rather than through the androgen metabolic pathway and also saw that T-induced apoptosis of hair follicles was reduced by topical EGCG. © 2011 John Wiley & Sons A/S.

  6. EGCG Protects against 6-OHDA-Induced Neurotoxicity in a Cell Culture Model

    OpenAIRE

    Chen, Dan; Kanthasamy, Anumantha G.; Reddy, Manju B.

    2015-01-01

    Background. Parkinson's disease (PD) is a progressive neurodegenerative disease that causes severe brain dopamine depletion. Disruption of iron metabolism may be involved in the PD progression. Objective. To test the protective effect of (?)-epigallocatechin-3-gallate (EGCG) against 6-hydroxydopamine- (6-OHDA-) induced neurotoxicity by regulating iron metabolism in N27 cells. Methods. Protection by EGCG in N27 cells was assessed by SYTOX green assay, MTT, and caspase-3 activity. Iron regulato...

  7. Sustained Release Oral Nanoformulated Green Tea for Prostate Cancer Prevention

    Science.gov (United States)

    2013-05-01

    epigallocatechin-3-gallate. Cancer Res. 2009;69:1712-6. 2. Adhami VM, Siddiqui IA, Syed DN, Lall RK, Mukhtar H. Oral infusion of pomegranate fruit ...and fungi , and is also known for its non-toxic, non-immunogenic properties (23). It has already been used as a pharmaceutical excipient, a weight loss...component EGCG and perceived toxicity associated with its long-term use affect its clinical outcome (36,37). This study suggests a different

  8. Advanced Virgo

    CERN Multimedia

    Virgo, a first-generation interferometric gravitational wave (GW) detector, located in the European Gravitational Observatory, EGO, Cascina (Pisa-Italy) and constructed by the collaboration of French and Italian institutes (CNRS and INFN) has successfully completed its long-duration data taking runs. It is now undergoing a fundamental upgrade that exploits available cutting edges technology to open an exciting new window on the universe, with the first detection of a gravitational wave signal. Advanced Virgo (AdV) is the project to upgrade the Virgo detector to a second-generation instrument. AdV will be able to scan a volume of the Universe 1000 times larger than initial Virgo. AdV will be hosted in the same infrastructures as Virgo. The Advanced VIRGO project is funded and at present carried on by a larger collaboration of institutes belonging to CNRS- France , RMKI - Hungary, INFN- Italy, Nikhef - The Netherlands Polish Academy of Science - Poland.

  9. Advanced Combustion

    Energy Technology Data Exchange (ETDEWEB)

    Holcomb, Gordon R. [NETL

    2013-03-11

    The activity reported in this presentation is to provide the mechanical and physical property information needed to allow rational design, development and/or choice of alloys, manufacturing approaches, and environmental exposure and component life models to enable oxy-fuel combustion boilers to operate at Ultra-Supercritical (up to 650{degrees}C & between 22-30 MPa) and/or Advanced Ultra-Supercritical conditions (760{degrees}C & 35 MPa).

  10. Inhibition of lactation.

    Science.gov (United States)

    Llewellyn-Jones, D

    1975-01-01

    The mechanism and hormonal regulation of lactation is explained and illustrated with a schematic representation. Circulating estrogen above a critical amount seems to be the inhibitory factor controlling lactation during pregnancy. Once delivery occurs, the level of estrogen falls, that of prolactin rises, and lactation begins. Nonsuckling can be used to inhibit lactation. Estrogens can also be used to inhibit lactation more quickly and with less pain. The reported association between estrogens and puerperal thromboembolism cannot be considered conclusive due to defects in the reporting studies. There is no reason not to use estrogens in lactation inhibition except for women over 35 who experienced a surgical delivery. Alternative therapy is available for these women. The recently-developed drug, brom-ergocryptine, may replace other methods of lactation inhibition.

  11. Inhibition of protein glycation and advanced glycation end products ...

    African Journals Online (AJOL)

    Fatima

    2012-06-26

    Jun 26, 2012 ... acid (AA) can react with proteins, including hemoglobin and possibly interfere with protein glycation process. .... 50 mM) and AA (100, 200, 300 and 400 mM) at 37°C for five weeks ... drops were removed by patting the plate over a paper towel. The .... adults participating in the Beaver Dam Eye Study. In.

  12. Advanced calculus

    CERN Document Server

    Friedman, Avner

    2007-01-01

    This rigorous two-part treatment advances from functions of one variable to those of several variables. Intended for students who have already completed a one-year course in elementary calculus, it defers the introduction of functions of several variables for as long as possible, and adds clarity and simplicity by avoiding a mixture of heuristic and rigorous arguments.The first part explores functions of one variable, including numbers and sequences, continuous functions, differentiable functions, integration, and sequences and series of functions. The second part examines functions of several

  13. Advanced calculus

    CERN Document Server

    Fitzpatrick, Patrick M

    2009-01-01

    Advanced Calculus is intended as a text for courses that furnish the backbone of the student's undergraduate education in mathematical analysis. The goal is to rigorously present the fundamental concepts within the context of illuminating examples and stimulating exercises. This book is self-contained and starts with the creation of basic tools using the completeness axiom. The continuity, differentiability, integrability, and power series representation properties of functions of a single variable are established. The next few chapters describe the topological and metric properties of Euclide

  14. Advanced trigonometry

    CERN Document Server

    Durell, C V; Robson, A

    1950-01-01

    This volume will provide a welcome resource for teachers seeking an undergraduate text on advanced trigonometry, when few are readily available. Ideal for self-study, this text offers a clear, logical presentation of topics and an extensive selection of problems with answers. Contents include the properties of the triangle and the quadrilateral; equations, sub-multiple angles, and inverse functions; hyperbolic, logarithmic, and exponential functions; and expansions in power-series. Further topics encompass the special hyperbolic functions; projection and finite series; complex numbers; de Moiv

  15. Advanced Pacemaker

    Science.gov (United States)

    1990-01-01

    Synchrony, developed by St. Jude Medical's Cardiac Rhythm Management Division (formerly known as Pacesetter Systems, Inc.) is an advanced state-of-the-art implantable pacemaker that closely matches the natural rhythm of the heart. The companion element of the Synchrony Pacemaker System is the Programmer Analyzer APS-II which allows a doctor to reprogram and fine tune the pacemaker to each user's special requirements without surgery. The two-way communications capability that allows the physician to instruct and query the pacemaker is accomplished by bidirectional telemetry. APS-II features 28 pacing functions and thousands of programming combinations to accommodate diverse lifestyles. Microprocessor unit also records and stores pertinent patient data up to a year.

  16. Enzyme inhibition by iminosugars

    DEFF Research Database (Denmark)

    López, Óscar; Qing, Feng-Ling; Pedersen, Christian Marcus

    2013-01-01

    Imino- and azasugar glycosidase inhibitors display pH dependant inhibition reflecting that both the inhibitor and the enzyme active site have groups that change protonation state with pH. With the enzyme having two acidic groups and the inhibitor one basic group, enzyme-inhibitor complexes...

  17. Quorum sensing inhibition

    DEFF Research Database (Denmark)

    Persson, T.; Givskov, Michael Christian; Nielsen, J.

    2005-01-01

    /receptor transcriptional regulator in some clinically relevant Gram-negative bacteria. The present review contains all reported compound types that are currently known to inhibit the QS transcriptional regulator in Gram-negative bacteria. These compounds are sub-divided into two main groups, one comprising structural...

  18. Cooperation for Better Inhibiting.

    Science.gov (United States)

    Novoa, Eva Maria; Ribas de Pouplana, Lluís

    2015-06-18

    Cladosporin is an antimalarial drug that acts as an ATP-mimetic to selectively inhibit Plasmodium lysyl-tRNA synthetase. Using multiple crystal structures, Fang et al. (2015) reveal in this issue of Chemistry & Biology the fascinating mechanism responsible for cladosporin selectivity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Green tea catechins potentiate the effect of antibiotics and modulate adherence and gene expression in Porphyromonas gingivalis.

    Science.gov (United States)

    Fournier-Larente, Jade; Morin, Marie-Pierre; Grenier, Daniel

    2016-05-01

    A number of studies have brought evidence that green tea catechins may contribute to periodontal health. The objective of this study was to investigate the ability of a green tea extract and its principal constituent epigallocatechin-3-gallate (EGCG) to potentiate the antibacterial effects of antibiotics (metronidazole, tetracycline) against Porphyromonas gingivalis, and to modulate the adherence to oral epithelial cells and expression of genes coding for virulence factors and the high temperature requirement A (HtrA) stress protein in P. gingivalis. A broth microdilution assay was used to determine the antibacterial activity of the green tea extract and EGCG. The synergistic effects of either compounds in association with metronidazole or tetracycline were evaluated using the checkerboard technique. A fluorescent assay was used to determine bacterial adherence to oral epithelial cells. The modulation of gene expression in P. gingivalis was evaluated by quantitative RT-PCR. The Vibrio harveyi bioassay was used for monitoring quorum sensing inhibitory activity. The MIC values of the green tea extract on P. gingivalis ranged from 250 to 1000 μg/ml, while those of EGCG ranged from 125 to 500 μg/ml. A marked synergistic effect on P. gingivalis growth was observed for the green tea extract or EGCG in combination with metronidazole. Both the green tea extract and EGCG caused a dose-dependent inhibition of P. gingivalis adherence to oral epithelial cells. On the one hand, green tea extract and EGCG dose-dependently inhibited the expression of several P. gingivalis genes involved in host colonization (fimA, hagA, hagB), tissue destruction (rgpA, kgp), and heme acquisition (hem). On the other hand, both compounds increased the expression of the stress protein htrA gene. The ability of the green tea extract and EGCG to inhibit quorum sensing may contribute to the modulation of gene expression. This study explored the preventive and therapeutic potential of green tea

  20. Plastics for corrosion inhibition

    CERN Document Server

    Goldade, Victor A; Makarevich, Anna V; Kestelman, Vladimir N

    2005-01-01

    The development of polymer composites containing inhibitors of metal corrosion is an important endeavour in modern materials science and technology. Corrosion inhibitors can be located in a polymer matrix in the solid, liquid or gaseous phase. This book details the thermodynamic principles for selecting these components, their compatibility and their effectiveness. The various mechanisms of metal protection – barrier, inhibiting and electromechanical – are considered, as are the conflicting requirements placed on the structure of the combined material. Two main classes of inhibited materials (structural and films/coatings) are described in detail. Examples are given of structural plastics used in friction units subjected to mechano-chemical wear and of polymer films/coatings for protecting metal objects against corrosion.

  1. Inhibiting the inevitable

    DEFF Research Database (Denmark)

    Shashoua, Yvonne

    2006-01-01

    conservation is to ‘buy time’ for the object. Inhibitive conservation of plastics involves the removal or reduction of factors causing or accelerating degradation including light, oxygen, acids, relative humidity and acidic breakdown products. Specific approaches to conservation have been developed......Once plastics objects are registered in museum collections, the institution becomes responsible for their long term preservation, until the end of their useful lifetime. Plastics appear to deteriorate faster than other materials in museum collections and have a useful lifetime between 5 and 25...... years. Preventive or inhibitive conservation involves controlling the environments in which objects are placed during storage and display, with the aim of slowing the major deterioration reactions. Once in progress, degradation of plastics cannot be stopped or reversed, so the aim of preventive...

  2. Anxiety and retrieval inhibition: support for an enhanced inhibition account.

    Science.gov (United States)

    Nuñez, Mia; Gregory, Josh; Zinbarg, Richard E

    2017-02-01

    Retrieval inhibition of negative associations is important for exposure therapy for anxiety, but the relationship between memory inhibition and anxiety is not well understood-anxiety could either be associated with enhanced or deficient inhibition. The present study tested these two competing hypotheses by measuring retrieval inhibition of negative stimuli by related neutral stimuli. Non-clinically anxious undergraduates completed measures of trait and state anxiety and completed a retrieval induced forgetting task. Adaptive forgetting varied with state anxiety. Low levels of state anxiety were associated with no evidence for retrieval inhibition for either threatening or non-threatening categories. Participants in the middle tertile of state anxiety scores exhibited retrieval inhibition for non-threatening categories but not for threatening categories. Participants in the highest tertile of state anxiety, however, exhibited retrieval inhibition for both threatening and non-threatening categories with the magnitude of retrieval inhibition being greater for threatening than non-threatening categories. The data are in line with the avoidance aspect of the vigilance-avoidance theory of anxiety and inhibition. Implications for cognitive behavioural therapy practices are discussed.

  3. Inhibition of polyphenoloxidase by sulfite

    International Nuclear Information System (INIS)

    Sayavedra-Soto, L.A.; Montgomery, M.W.

    1986-01-01

    When polyphenoloxidase (PPO) was exposed to sulfite prior to substrate addition, inhibition was irreversible. Trials to regenerate PPO activity, using extensive dialysis, column chromatography, and addition of copper salts were not successful. Increased concentrations of sulfite and pH levels less than 5 enhanced the inhibition of PPO by sulfite. At pH 4, concentrations greater than 0.04 mg/mL completely inhibited 1000 units of PPO activity almost instantaneously. This suggested that the HSO 3 - molecule was the main component in the sulfite system inhibiting PPO. Column chromatography, extensive dialysis, and gel electrophoresis did not demonstrate 35 SO 2 bound to purified pear PPO protein. Formation of extra protein bands of sulfite inhibited purified pear PPO fractions on gel electrophoresis was demonstrated. This and other evidence suggested that the major mode of direct irreversible inhibition of PPO was modification of the protein structure, with retention of its molecular unity

  4. The Clinical Presentation and Management of Systemic Light-Chain Amyloidosis in China.

    Science.gov (United States)

    Huang, Xiang-Hua; Liu, Zhi-Hong

    2016-04-01

    the time of diagnosis, edema is twice as frequent and the proportion of renal involvement is higher in Chinese compared to Western patients. (2) Melphalan followed by ASCT is the current standard therapy but is restricted to eligible patients. The efficacy and safety of bortezomib combined with dexamethasone were proven in Western patients and recently confirmed in a Chinese cohort. Recent studies in China and the US indicate that bortezomib induction prior to ASCT increases the response rate. Thalidomide and lenalidomide have shown benefit, but toxicity and lack of clinical evidence exclude these agents from first-line therapy. The green tea extract epigallocatechin-3-gallate is under investigation as an inhibitor of AL amyloid formation and a compound that might dissolve amyloid.

  5. Modeling intentional inhibition of actions

    NARCIS (Netherlands)

    Thilakarathne, D.J.; Treur, J.

    2015-01-01

    Inspired by cognitive and neurological literature on action ownership and action awareness, in this paper a computational cognitive model for intentional inhibition (i.e.; the capacity to voluntarily suspend or inhibit an action) is introduced. The interplay between (positive) potential selection of

  6. Can Arousal Modulate Response Inhibition?

    Science.gov (United States)

    Weinbach, Noam; Kalanthroff, Eyal; Avnit, Amir; Henik, Avishai

    2015-01-01

    The goal of the present study was to examine if and how arousal can modulate response inhibition. Two competing hypotheses can be drawn from previous literature. One holds that alerting cues that elevate arousal should result in an impulsive response and therefore impair response inhibition. The other suggests that alerting enhances processing of…

  7. Advanced Chemical Propulsion

    Science.gov (United States)

    Bai, S. Don

    2000-01-01

    Design, propellant selection, and launch assistance for advanced chemical propulsion system is discussed. Topics discussed include: rocket design, advance fuel and high energy density materials, launch assist, and criteria for fuel selection.

  8. Molecular basis of cyclooxygenase enzymes (COXs) selective inhibition

    Science.gov (United States)

    Limongelli, Vittorio; Bonomi, Massimiliano; Marinelli, Luciana; Gervasio, Francesco Luigi; Cavalli, Andrea; Novellino, Ettore; Parrinello, Michele

    2010-01-01

    The widely used nonsteroidal anti-inflammatory drugs block the cyclooxygenase enzymes (COXs) and are clinically used for the treatment of inflammation, pain, and cancers. A selective inhibition of the different isoforms, particularly COX-2, is desirable, and consequently a deeper understanding of the molecular basis of selective inhibition is of great demand. Using an advanced computational technique we have simulated the full dissociation process of a highly potent and selective inhibitor, SC-558, in both COX-1 and COX-2. We have found a previously unreported alternative binding mode in COX-2 explaining the time-dependent inhibition exhibited by this class of inhibitors and consequently their long residence time inside this isoform. Our metadynamics-based approach allows us to illuminate the highly dynamical character of the ligand/protein recognition process, thus explaining a wealth of experimental data and paving the way to an innovative strategy for designing new COX inhibitors with tuned selectivity. PMID:20215464

  9. Soluble Aβ aggregates can inhibit prion propagation.

    Science.gov (United States)

    Sarell, Claire J; Quarterman, Emma; Yip, Daniel C-M; Terry, Cassandra; Nicoll, Andrew J; Wadsworth, Jonathan D F; Farrow, Mark A; Walsh, Dominic M; Collinge, John

    2017-11-01

    Mammalian prions cause lethal neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD) and consist of multi-chain assemblies of misfolded cellular prion protein (PrP C ). Ligands that bind to PrP C can inhibit prion propagation and neurotoxicity. Extensive prior work established that certain soluble assemblies of the Alzheimer's disease (AD)-associated amyloid β-protein (Aβ) can tightly bind to PrP C , and that this interaction may be relevant to their toxicity in AD. Here, we investigated whether such soluble Aβ assemblies might, conversely, have an inhibitory effect on prion propagation. Using cellular models of prion infection and propagation and distinct Aβ preparations, we found that the form of Aβ assemblies which most avidly bound to PrP in vitro also inhibited prion infection and propagation. By contrast, forms of Aβ which exhibit little or no binding to PrP were unable to attenuate prion propagation. These data suggest that soluble aggregates of Aβ can compete with prions for binding to PrP C and emphasize the bidirectional nature of the interplay between Aβ and PrP C in Alzheimer's and prion diseases. Such inhibitory effects of Aβ on prion propagation may contribute to the apparent fall-off in the incidence of sporadic CJD at advanced age where cerebral Aβ deposition is common. © 2017 The Authors.

  10. Advanced CANDU reactors

    International Nuclear Information System (INIS)

    Dunn, J.T.; Finlay, R.B.; Olmstead, R.A.

    1988-12-01

    AECL has undertaken the design and development of a series of advanced CANDU reactors in the 700-1150 MW(e) size range. These advanced reactor designs are the product of ongoing generic research and development programs on CANDU technology and design studies for advanced CANDU reactors. The prime objective is to create a series of advanced CANDU reactors which are cost competitive with coal-fired plants in the market for large electricity generating stations. Specific plant designs in the advanced CANDU series will be ready for project commitment in the early 1990s and will be capable of further development to remain competitive well into the next century

  11. Advances in chemical Physics

    CERN Document Server

    Rice, Stuart A

    2011-01-01

    The Advances in Chemical Physics series-the cutting edge of research in chemical physics The Advances in Chemical Physics series provides the chemical physics and physical chemistry fields with a forum for critical, authoritative evaluations of advances in every area of the discipline. Filled with cutting-edge research reported in a cohesive manner not found elsewhere in the literature, each volume of the Advances in Chemical Physics series offers contributions from internationally renowned chemists and serves as the perfect supplement to any advanced graduate class devoted to the study of che

  12. Advances in chemical physics

    CERN Document Server

    Rice, Stuart A

    2012-01-01

    The Advances in Chemical Physics series-the cutting edge of research in chemical physics The Advances in Chemical Physics series provides the chemical physics field with a forum for critical, authoritative evaluations of advances in every area of the discipline. Filled with cutting-edge research reported in a cohesive manner not found elsewhere in the literature, each volume of the Advances in Chemical Physics series serves as the perfect supplement to any advanced graduate class devoted to the study of chemical physics. This volume explores: Quantum Dynamical Resonances in Ch

  13. Advances in chemical physics

    CERN Document Server

    Rice, Stuart A

    2011-01-01

    The Advances in Chemical Physics series-the cutting edge of research in chemical physics The Advances in Chemical Physics series provides the chemical physics and physical chemistry fields with a forum for critical, authoritative evaluations of advances in every area of the discipline. Filled with cutting-edge research reported in a cohesive manner not found elsewhere in the literature, each volume of the Advances in Chemical Physics series offers contributions from internationally renowned chemists and serves as the perfect supplement to any advanced graduate class devoted to the study of che

  14. ACR-700 advanced technologies

    International Nuclear Information System (INIS)

    Tapping, R.L.; Turner, C.W.; Yu, S.K.W.; Olmstead, R.; Speranzini, R.A.

    2004-01-01

    A successful advanced reactor plant will have optimized economics including reduced operating and maintenance costs, improved performance, and enhanced safety. Incorporating improvements based on advanced technologies ensures cost, safety and operational competitiveness of the ACR-700. These advanced technologies include modern configuration management; construction technologies; operational technology for the control centre and information systems for plant monitoring and analysis. This paper summarizes the advanced technologies used to achieve construction and operational improvements to enhance plant economic competitiveness, advances in the operational technology used for reactor control, and presents the development of the Smart CANDU suite of tools and its application to existing operating reactors and to the ACR-700. (author)

  15. Selective inhibition of distracting input.

    Science.gov (United States)

    Noonan, MaryAnn P; Crittenden, Ben M; Jensen, Ole; Stokes, Mark G

    2017-10-16

    We review a series of studies exploring distractor suppression. It is often assumed that preparatory distractor suppression is controlled via top-down mechanisms of attention akin to those that prepare brain areas for target enhancement. Here, we consider two alternative mechanisms: secondary inhibition and expectation suppression within a predictive coding framework. We draw on behavioural studies, evidence from neuroimaging and some animal studies. We conclude that there is very limited evidence for selective top-down control of preparatory inhibition. By contrast, we argue that distractor suppression often relies secondary inhibition of non-target items (relatively non-selective inhibition) and on statistical regularities of the environment, learned through direct experience. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  16. [Concepts of inhibition in psychiatry].

    Science.gov (United States)

    Auroux, Y; Bourrat, M M; Brun, J P

    1978-01-01

    Following a historical approach, the authors first describe the original development of the concept of inhibition in neurophysiology and then analyze the subsequent adaptations made in psychiatry around such concept including those of: -- Pavlov, Hull, Watson and the behaviorists, -- Freud and the Freudian School, -- clinicians and psychopharmacologists. The concept of inhibition has thus various meanings in psychiatry. Although some unity is achieved on the semiological level, this aspect cannot explain the extent of the process.

  17. Inhibition of MMPs by alcohols

    Science.gov (United States)

    Tezvergil-Mutluay, Arzu; Agee, Kelli A.; Hoshika, Tomohiro; Uchiyama, Toshikazu; Tjäderhane, Leo; Breschi, Lorenzo; Mazzoni, Annalisa; Thompson, Jeremy M.; McCracken, Courtney E.; Looney, Stephen W.; Tay, Franklin R.; Pashley, David H.

    2011-01-01

    Objectives While screening the activity of potential inhibitors of matrix metalloproteinases (MMPs), due to the limited water solubility of some of the compounds, they had to be solubilized in ethanol. When ethanol solvent controls were run, they were found to partially inhibit MMPs. Thus, the purpose of this study was to compare the MMP-inhibitory activity of a series of alcohols. Methods The possible inhibitory activity of a series of alcohols was measured against soluble rhMMP-9 and insoluble matrix-bound endogenous MMPs of dentin in completely demineralized dentin. Increasing concentrations (0.17, 0.86, 1.71 and 4.28 moles/L) of a homologous series of alcohols (i.e. methanol, ethanol, propanols, butanols, pentanols, hexanols, the ethanol ester of methacrylic acid, heptanols and octanol) were compared to ethanediol, and propanediol by regression analysis to calculate the molar concentration required to inhibit MMPs by 50% (i.e. the IC50). Results Using two different MMP models, alcohols were shown to inhibit rhMMP-9 and the endogenous proteases of dentin matrix in a dose-dependent manner. The degree of MMP inhibition by alcohols increased with chain length up to 4 methylene groups. Based on the molar concentration required to inhibit rhMMP-9 fifty percent, 2-hydroxyethylmethacrylate (HEMA), 3-hexanol, 3-heptanol and 1-octanol gave the strongest inhibition. Significance The results indicate that alcohols with 4 methylene groups inhibit MMPs more effectively than methanol or ethanol. MMP inhibition was inversely related to the Hoy's solubility parameter for hydrogen bonding forces of the alcohols (i.e. to their hydrophilicity). PMID:21676453

  18. Methanol Extract of Myelophycus caespitosus Inhibits the ...

    African Journals Online (AJOL)

    Methanol Extract of Myelophycus caespitosus Inhibits the Inflammatory Response in Lipopolysaccharidestimulated BV2 Microglial Cells by Downregulating NF-kB via Inhibition of the Akt Signaling Pathway.

  19. Japan's advanced medicine.

    Science.gov (United States)

    Sho, Ri; Narimatsu, Hiroto; Murakami, Masayasu

    2013-10-01

    Like health care systems in other developed countries, Japan's health care system faces significant challenges due to aging of the population and economic stagnation. Advanced medicine (Senshin Iryou) is a unique system of medical care in Japan offering highly technology-driven medical care that is not covered by public health insurance. Advanced medicine has recently developed and expanded as part of health care reform. Will it work? To answer this question, we briefly trace the historical development of advanced medicine and describe the characteristics and current state of advanced medical care in Japan. We then offer our opinions on the future of advanced medicine with careful consideration of its pros and cons. We believe that developing advanced medicine is an attempt to bring health care reform in line rather than the goal of health care reform.

  20. Advanced accumulator for PWR

    International Nuclear Information System (INIS)

    Ichimura, Taiki; Chikahata, Hideyuki

    1997-01-01

    Advanced accumulators have been incorporated into the APWR design in order to simplify the safety system configuration and to improve reliability. The advanced accumulators refill the reactor vessel with a large discharge flow rate in a large LOCA, then switch to a small flow rate to continue safety injection for core reflooding. The functions of the conventional accumulator and the low head safety injection pump are integrated into this advanced accumulator. Injection performance tests simulating LOCA conditions and visualization tests for new designs have been carried out. This paper describes the APWR ECCS configuration, the advanced accumulator design and some of the injection performance and visualization test results. It was verified that the flow resistance of the advanced accumulator is independent of the model scale. The similarity law and performance data of the advanced accumulator for applying APWR was established. (author)

  1. Advances in Applied Mechanics

    OpenAIRE

    2013-01-01

    Advances in Applied Mechanics draws together recent significant advances in various topics in applied mechanics. Published since 1948, Advances in Applied Mechanics aims to provide authoritative review articles on topics in the mechanical sciences, primarily of interest to scientists and engineers working in the various branches of mechanics, but also of interest to the many who use the results of investigations in mechanics in various application areas, such as aerospace, chemical, civil, en...

  2. Advanced fuels safety comparisons

    International Nuclear Information System (INIS)

    Grolmes, M.A.

    1977-01-01

    The safety considerations of advanced fuels are described relative to the present understanding of the safety of oxide fueled Liquid Metal Fast Breeder Reactors (LMFBR). Safety considerations important for the successful implementation of advanced fueled reactors must early on focus on the accident energetics issues of fuel coolant interactions and recriticality associated with core disruptive accidents. It is in these areas where the thermal physical property differences of the advanced fuel have the greatest significance

  3. Advanced Photon Source (APS)

    Data.gov (United States)

    Federal Laboratory Consortium — The Advanced Photon Source (APS) at the U.S. Department of Energy's Argonne National Laboratoryprovides this nation's (in fact, this hemisphere's) brightest storage...

  4. Advanced Simulation Center

    Data.gov (United States)

    Federal Laboratory Consortium — The Advanced Simulation Center consists of 10 individual facilities which provide missile and submunition hardware-in-the-loop simulation capabilities. The following...

  5. Advanced Manufacturing Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Advanced Manufacturing Laboratory at the University of Maryland provides the state of the art facilities for realizing next generation products and educating the...

  6. Advances in dental materials.

    Science.gov (United States)

    Fleming, Garry J P

    2014-05-01

    The dental market is replete with new resorative materials marketed on the basis of novel technological advances in materials chemistry, bonding capability or reduced operator time and/or technique sensitivity. This paper aims to consider advances in current materials, with an emphasis on their role in supporting contemporary clinical practice.

  7. Advanced Manufacturing Technologies

    Science.gov (United States)

    Fikes, John

    2016-01-01

    Advanced Manufacturing Technologies (AMT) is developing and maturing innovative and advanced manufacturing technologies that will enable more capable and lower-cost spacecraft, launch vehicles and infrastructure to enable exploration missions. The technologies will utilize cutting edge materials and emerging capabilities including metallic processes, additive manufacturing, composites, and digital manufacturing. The AMT project supports the National Manufacturing Initiative involving collaboration with other government agencies.

  8. Planning for Advanced Cancer

    Science.gov (United States)

    Find out what issues need to be addressed when dealing with an advanced or metastatic cancer diagnosis. Completing advance directives, looking at health insurance, organizing records and documents, and looking at the meanings in your life are some of the things to think about.

  9. Advanced uranium enrichment technologies

    International Nuclear Information System (INIS)

    Merriman, R.

    1983-01-01

    The Advanced Gas Centrifuge and Atomic Vapor Laser Isotope Separation methods are described. The status and potential of the technologies are summarized, the programs outlined, and the economic incentives are noted. How the advanced technologies, once demonstrated, might be deployed so that SWV costs in the 1990s can be significantly reduced is described

  10. Advanced research technology transfer

    International Nuclear Information System (INIS)

    Naraghi, Masud

    1977-01-01

    The importance of advanced research in the less developed countries of the world is described. Advanced research is a way of building from the top; it helps industrial development; it provides ''know-how'' economically; it enhances international understanding; it prevents the brain drain to developed countries and is of mutual benefit. The problems concerned with this type of research are pointed out

  11. Homo economicus belief inhibits trust.

    Directory of Open Access Journals (Sweden)

    Ziqiang Xin

    Full Text Available As a foundational concept in economics, the homo economicus assumption regards humans as rational and self-interested actors. In contrast, trust requires individuals to believe partners' benevolence and unselfishness. Thus, the homo economicus belief may inhibit trust. The present three experiments demonstrated that the direct exposure to homo economicus belief can weaken trust. And economic situations like profit calculation can also activate individuals' homo economicus belief and inhibit their trust. It seems that people's increasing homo economicus belief may serve as one cause of the worldwide decline of trust.

  12. Homo Economicus Belief Inhibits Trust

    Science.gov (United States)

    Xin, Ziqiang; Liu, Guofang

    2013-01-01

    As a foundational concept in economics, the homo economicus assumption regards humans as rational and self-interested actors. In contrast, trust requires individuals to believe partners’ benevolence and unselfishness. Thus, the homo economicus belief may inhibit trust. The present three experiments demonstrated that the direct exposure to homo economicus belief can weaken trust. And economic situations like profit calculation can also activate individuals’ homo economicus belief and inhibit their trust. It seems that people’s increasing homo economicus belief may serve as one cause of the worldwide decline of trust. PMID:24146907

  13. Inhibition of Retinoblastoma Protein Inactivation

    Science.gov (United States)

    2017-11-01

    CONTRACT NUMBER Inhibition of Retinoblastoma Protein Inactivation 5b. GRANT NUMBER W81XWH-14-1-0329 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Seth M...confirmed 108 compounds as giving a dose-response curve with at least 30% inhibition at 10 µM. The flowchart of hit progression is shown on the...Cancer Research Program under Award No. W81XWH-14-1-0329 to S.M.R. Opinions, interpretations, conclusions, and recommendations are those of the author

  14. Advanced Chemical Propulsion Study

    Science.gov (United States)

    Woodcock, Gordon; Byers, Dave; Alexander, Leslie A.; Krebsbach, Al

    2004-01-01

    A study was performed of advanced chemical propulsion technology application to space science (Code S) missions. The purpose was to begin the process of selecting chemical propulsion technology advancement activities that would provide greatest benefits to Code S missions. Several missions were selected from Code S planning data, and a range of advanced chemical propulsion options was analyzed to assess capabilities and benefits re these missions. Selected beneficial applications were found for higher-performing bipropellants, gelled propellants, and cryogenic propellants. Technology advancement recommendations included cryocoolers and small turbopump engines for cryogenic propellants; space storable propellants such as LOX-hydrazine; and advanced monopropellants. It was noted that fluorine-bearing oxidizers offer performance gains over more benign oxidizers. Potential benefits were observed for gelled propellants that could be allowed to freeze, then thawed for use.

  15. Is forgetting caused by inhibition?

    NARCIS (Netherlands)

    Raaijmakers, J.G.W.; Jakab, E.

    2013-01-01

    A well-known finding in memory research is the forgetting effect that occurs because of practicing some Item A on the recall of a related Item B. The traditional explanation for such interference effects is based on the notion of competition. According to the inhibition theory of forgetting,

  16. Testing of Biologically Inhibiting Surface

    DEFF Research Database (Denmark)

    Bill Madsen, Thomas; Larsen, Erup

    2003-01-01

    The main purpose of this course is to examine a newly developed biologically inhibiting material with regards to galvanic corrosion and electrochemical properties. More in detail, the concern was how the material would react when exposed to cleaning agents, here under CIP cleaning (Cleaning...

  17. Editorial: Advanced learning technologies

    Directory of Open Access Journals (Sweden)

    Yu-Ju Lan

    2012-03-01

    Full Text Available Recent rapid development of advanced information technology brings high expectations of its potential to improvement and innovations in learning. This special issue is devoted to using some of the emerging technologies issues related to the topic of education and knowledge sharing, involving several cutting edge research outcomes from recent advancement of learning technologies. Advanced learning technologies are the composition of various related technologies and concepts such as mobile technologies and social media towards learner centered learning. This editorial note provides an overview of relevant issues discussed in this special issue.

  18. Advancing Ethical Neuroscience Research.

    Science.gov (United States)

    Borah, B Rashmi; Strand, Nicolle K; Chillag, Kata L

    2016-12-01

    As neuroscience research advances, researchers, clinicians, and other stakeholders will face a host of ethical challenges. The Presidential Commission for the Study of Bioethical Issues (Bioethics Commission) has published two reports that provide recommendations on how to advance research endeavors ethically. The commission addressed, among other issues, how to prioritize different types of neuroscience research and how to include research participants who have impaired consent capacity. The Bioethics Commission's recommendations provide a foundation for ethical guidelines as neuroscience research advances and progresses. © 2016 American Medical Association. All Rights Reserved.

  19. Advanced information society(7)

    Science.gov (United States)

    Chiba, Toshihiro

    Various threats are hiding in advanced informationalized society. As we see car accident problems in motorization society light aspects necessarily accompy shady ones. Under the changing circumstances of advanced informationalization added values of information has become much higher. It causes computer crime, hacker, computer virus to come to the surface. In addition it can be said that infringement of intellectual property and privacy are threats brought by advanced information. Against these threats legal, institutional and insurance measures have been progressed, and newly security industry has been established. However, they are not adequate individually or totally. The future vision should be clarified, and countermeasures according to the visions have to be considered.

  20. Indian advanced nuclear reactors

    International Nuclear Information System (INIS)

    Saha, D.; Sinha, R.K.

    2005-01-01

    For sustainable development of nuclear energy, a number of important issues like safety, waste management, economics etc. are to be addressed. To do this, a number of advanced reactor designs as well as fuel cycle technologies are being pursued worldwide. The advanced reactors being developed in India are the AHWR and the CHTR. Both the reactors use thorium based fuel and have many passive features. This paper describes the Indian advanced reactors and gives a brief account of the international initiatives for the sustainable development of nuclear energy. (author)

  1. On the automaticity of response inhibition in individuals with alcoholism.

    Science.gov (United States)

    Noël, Xavier; Brevers, Damien; Hanak, Catherine; Kornreich, Charles; Verbanck, Paul; Verbruggen, Frederick

    2016-06-01

    Response inhibition is usually considered a hallmark of executive control. However, recent work indicates that stop performance can become associatively mediated ('automatic') over practice. This study investigated automatic response inhibition in sober and recently detoxified individuals with alcoholism.. We administered to forty recently detoxified alcoholics and forty healthy participants a modified stop-signal task that consisted of a training phase in which a subset of the stimuli was consistently associated with stopping or going, and a test phase in which this mapping was reversed. In the training phase, stop performance improved for the consistent stop stimuli, compared with control stimuli that were not associated with going or stopping. In the test phase, go performance tended to be impaired for old stop stimuli. Combined, these findings support the automatic inhibition hypothesis. Importantly, performance was similar in both groups, which indicates that automatic inhibitory control develops normally in individuals with alcoholism.. This finding is specific to individuals with alcoholism without other psychiatric disorders, which is rather atypical and prevents generalization. Personalized stimuli with a stronger affective content should be used in future studies. These results advance our understanding of behavioral inhibition in individuals with alcoholism. Furthermore, intact automatic inhibitory control may be an important element of successful cognitive remediation of addictive behaviors.. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Lactate dehydrogenase inhibition: exploring possible applications beyond cancer treatment.

    Science.gov (United States)

    Di Stefano, Giuseppina; Manerba, Marcella; Di Ianni, Lorenza; Fiume, Luigi

    2016-04-01

    Lactate dehydrogenase (LDH) inhibition is considered a worthwhile attempt in the development of innovative anticancer strategies. Unfortunately, in spite of the involvement of several research institutions and pharma-companies, the discovery of LDH inhibitors with drug-like properties seems a hardly resolvable challenge. While awaiting new advancements, in the present review we will examine other pathologic conditions characterized by increased glycolysis and LDH activity, which could potentially benefit from LDH inhibition. The rationale for targeting LDH activity in these contexts is the same justifying the LDH-based approach in anticancer therapy: because of the enzyme position at the end of glycolytic pathway, LDH inhibitors are not expected to hinder glucose metabolism of normal cells. Moreover, we will summarize the latest contributions in the discovery of enzyme inhibitors and try to glance over the reasons underlying the complexity of this research.

  3. Advanced Light Source (ALS)

    Data.gov (United States)

    Federal Laboratory Consortium — The Advanced Light Source (ALS), a world leader in soft x-ray science, generates light in the wavelengths needed for examining the atomic and electronic structure of...

  4. Advance Payment ACO Model

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Advance Payment Model is designed for physician-based and rural providers who have come together voluntarily to give coordinated high quality care to the...

  5. Advanced Welding Concepts

    Science.gov (United States)

    Ding, Robert J.

    2010-01-01

    Four advanced welding techniques and their use in NASA are briefly reviewed in this poster presentation. The welding techniques reviewed are: Solid State Welding, Friction Stir Welding (FSW), Thermal Stir Welding (TSW) and Ultrasonic Stir Welding.

  6. Advanced Missile Signature Center

    Data.gov (United States)

    Federal Laboratory Consortium — The Advanced Missile Signature Center (AMSC) is a national facility supporting the Missile Defense Agency (MDA) and other DoD programs and customers with analysis,...

  7. Advanced walling systems

    CSIR Research Space (South Africa)

    De Villiers, A

    2010-01-01

    Full Text Available The question addressed by this chapter is: How should advanced walling systems be planned, designed, built, refurbished, and end their useful lives, to classify as smart, sustainable, green or eco-building environments?...

  8. [Advanced resuscitation of adults

    DEFF Research Database (Denmark)

    Lippert, F.K.; Lauritsen, T.L.; Torp-Pedersen, C.

    2008-01-01

    International and European Resuscitation Council (ERC) Guidelines for Resuscitation 2005 implicate major changes in resuscitation, including new universal treatment algorithms. This brief summary of Guidelines 2005 for advanced resuscitation of adult cardiac arrest victims is based upon the ERC...

  9. Advanced Chemistry Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Description/History: Chemistry laboratoryThe Advanced Chemistry Laboratory (ACL) is a unique facility designed for working with the most super toxic compounds known...

  10. Advanced Electron Linacs

    Energy Technology Data Exchange (ETDEWEB)

    Siemann, R.

    2005-02-14

    The research into advanced acceleration concepts for electron linear accelerators being pursued at SLAC is reviewed. This research includes experiments in laser acceleration, plasma wakefield acceleration, and mmwavelength RF driven accelerators.

  11. Advanced Transportation Institute 2008.

    Science.gov (United States)

    2009-02-01

    The seventh version of the Advanced Transportation Institute (ATI-08) was conducted in 2008 to encourage high school students to pursue careers in the field of transportation engineering. The University Transportation Center for Alabama partnered wit...

  12. Advanced Transportation Institute 2009.

    Science.gov (United States)

    2009-09-01

    The eighth version of the Advanced Transportation Institute (ATI-09) was conducted in 2009 to encourage high school students to pursue careers in the field of transportation engineering. The University Transportation Center for Alabama partnered with...

  13. Advanced Microanalysis Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Advanced Microanalysis Facility fully integrates capabilities for chemical and structural analysis of electronic materials and devices for the U.S. Army and DoD....

  14. Ferumoxtran-10 advanced magnetics.

    NARCIS (Netherlands)

    Leenders, W.P.J.

    2003-01-01

    Ferumoxtran-10 (Combidex) is an ultra-small superparamagnetic iron oxide molecular resonance imaging contrast agent under development by Advanced Magnetics Ltd and Guerbet for the principal indication of lymph node imaging.

  15. Advances in Numerical Methods

    CERN Document Server

    Mastorakis, Nikos E

    2009-01-01

    Features contributions that are focused on significant aspects of current numerical methods and computational mathematics. This book carries chapters that advanced methods and various variations on known techniques that can solve difficult scientific problems efficiently.

  16. Advanced Propulsion Study

    National Research Council Canada - National Science Library

    Davis, Eric

    2004-01-01

    ... that show promise of leading to a major advance in Earth-to-orbit (ETO) propulsion. The study also reviewed and evaluated a select number of credible far-term breakthrough propulsion physics concepts pertaining...

  17. Advanced Welding Applications

    Science.gov (United States)

    Ding, Robert J.

    2010-01-01

    Some of the applications of advanced welding techniques are shown in this poster presentation. Included are brief explanations of the use on the Ares I and Ares V launch vehicle and on the Space Shuttle Launch vehicle. Also included are microstructural views from four advanced welding techniques: Variable Polarity Plasma Arc (VPPA) weld (fusion), self-reacting friction stir welding (SR-FSW), conventional FSW, and Tube Socket Weld (TSW) on aluminum.

  18. Joining of advanced materials

    CERN Document Server

    Messler, Robert W

    1993-01-01

    Provides an unusually complete and readable compilation of the primary and secondary options for joining conventional materials in non-conventional ways. Provides unique coverage of adhesive bonding using both organic and inorganic adhesives, cements and mortars. Focuses on materials issues without ignoring issues related to joint design, production processing, quality assurance, process economics, and joining performance in service.Joining of advanced materials is a unique treatment of joining of both conventional and advanced metals andalloys, intermetallics, ceramics, glasses, polymers, a

  19. Advances in atomic spectroscopy

    CERN Document Server

    Sneddon, J

    1997-01-01

    This series describes selected advances in the area of atomic spectroscopy. It is primarily intended for the reader who has a background in atmoic spectroscopy; suitable to the novice and expert. Although a widely used and accepted method for metal and non-metal analysis in a variety of complex samples, Advances in Atomic Spectroscopy covers a wide range of materials. Each Chapter will completely cover an area of atomic spectroscopy where rapid development has occurred.

  20. Advances in bistatic radar

    CERN Document Server

    Willis, Nick

    2007-01-01

    Advances in Bistatic Radar updates and extends bistatic and multistatic radar developments since publication of Willis' Bistatic Radar in 1991. New and recently declassified military applications are documented. Civil applications are detailed including commercial and scientific systems. Leading radar engineers provide expertise to each of these applications. Advances in Bistatic Radar consists of two major sections: Bistatic/Multistatic Radar Systems and Bistatic Clutter and Signal Processing. Starting with a history update, the first section documents the early and now declassified military

  1. Advanced Tokamak Stability Theory

    Science.gov (United States)

    Zheng, Linjin

    2015-03-01

    The intention of this book is to introduce advanced tokamak stability theory. We start with the derivation of the Grad-Shafranov equation and the construction of various toroidal flux coordinates. An analytical tokamak equilibrium theory is presented to demonstrate the Shafranov shift and how the toroidal hoop force can be balanced by the application of a vertical magnetic field in tokamaks. In addition to advanced theories, this book also discusses the intuitive physics pictures for various experimentally observed phenomena.

  2. Advanced TCA Backplane Tester

    CERN Document Server

    Oltean, Alexandra Dana

    2004-01-01

    At the beginning of 2003, the PICMG group adopted the AdvancedTCA (Advanced Telecom Computing Architecture) standard. The 10Gb/s backplane of the AdvancedTCA chassis is well specified in the standard but it remains however a high end product, which can be itself subject to printed circuit board manufacturing control problems that could greatly affect its quality control. In order to study the practical aspects of high speed Ethernet switching at 10Gb/s and to validate the signal integrity of the AdvancedTCA backplane, we developed a Backplane Tester. The tester system is able of running monitored PRBS traffic at 3.125Gb/s over every link on the AdvancedTCA backplane simultaneously and to monitor any possible connectivity failure immediately in terms of link and slot position inside the chassis. The present report presents the architectural hardware design, the control structure and software aspects of the AdvancedTCA Backplane Tester design.

  3. United States advanced technologies

    International Nuclear Information System (INIS)

    Longenecker, J.R.

    1985-01-01

    In the United States, the advanced technologies have been applied to uranium enrichment as a means by which it can be assured that nuclear fuel cost will remain competitive in the future. The United States is strongly committed to the development of advanced enrichment technology, and has brought both advanced gas centrifuge (AGC) and atomic vapor laser isotope separation (AVLIS) programs to a point of significant technical refinement. The ability to deploy advanced technologies is the basis for the confidence in competitive future price. Unfortunately, the development of advanced technologies is capital intensive. The year 1985 is the key year for advanced technology development in the United States, since the decision on the primary enrichment technology for the future, AGC or AVLIS, will be made shortly. The background on the technology selection process, the highlights of AGC and AVLIS programs and the way to proceed after the process selection are described. The key objective is to maximize the sales volume and minimize the operating cost. This will help the utilities in other countries supply low cost energy on a reliable, long term basis. (Kako, I.)

  4. On inhibition of dental erosion.

    Science.gov (United States)

    Rölla, Gunnar; Jonski, Grazyna; Saxegaard, Erik

    2013-11-01

    To examine the erosion-inhibiting effect of different concentrations of hydrofluoric acid. Thirty-six human molars were individually treated with 10 ml of 0.1 M citric acid for 30 min (Etch 1), acid was collected and stored until analysis. The teeth were randomly divided into six groups and then individually treated with 10 ml of one of six dilutions (from 0.1-1%) of hydrofluoric acid. The teeth were then again treated with citric acid (Etch 2). The individual acid samples from Etch 1 and 2 were analyzed for calcium by flame atomic absorption spectroscopy and difference in calcium loss was calculated. The highest erosion inhibiting effect was obtained in groups with the highest concentrations of hydrofluoric acid, where the pH was lowest, below pKa of 3.17, thus the hydrofluoric acids being mainly in an undissociated state. Diluted hydrofluoric acid is present in aqueous solution of SnF2 and TiF4 (which are known to inhibit dental erosion): SnF2 + 3H2O = Sn(OH)2 + 2HF + H2O and TiF4 + 5H2O = Ti(OH)4 + 4HF + H2O. It is also known that pure, diluted hydrofluoric acid can inhibit dental erosion. Teeth treated with hydrofluoric acid are covered by a layer of CaF2-like mineral. This mineral is acid resistant at pH acid resistant mineral, initiated by tooth enamel treatment with hydrofluoric acid. Hydrofluoric acid is different in having fluoride as a conjugated base, which provides this acid with unique properties.

  5. Entanglement and inhibited quantum evolution

    International Nuclear Information System (INIS)

    Toschek, P E; Balzer, Chr; Hannemann, Th; Wunderlich, Ch; Neuhauser, W

    2003-01-01

    The evolution of a quantum system is impeded by the system's state being observed. A test on an ensemble neither proves the causal nexus nor discloses the nature of the inhibition. Two recent experiments that make use of sequential optical or microwave-optical double resonance on an individual trapped ion disprove a dynamical effect of back action by meter or environment. They rather indicate the ionic states involved in the evolution being entangled with the potentially recorded bivalued scattered-light signal

  6. Recruit and ADVANCE

    Science.gov (United States)

    Rosser, Sue V.

    2007-04-01

    Beginning in 2001, the National Science Foundation launched the ADVANCE Initiative, which has now awarded more than 70 million to some thirty institutions for transformations to advance women. Results of studies on how to attract and retain women students and faculty underpinned our ADVANCE Institutional Transformation grant funded by the NSF for 3.7 million for five years, beginning in 2001. As co-principal investigator on this grant, I insured that this research informed the five major threads of the grant: 1) Four termed ADVANCE professors to mentor junior women faculty in each college; 2) Collection of MIT-Report-like data indicators to assess whether advancement of women really occurs during and after the institutional transformation undertaken through ADVANCE; 3) Family-friendly policies and practices to stop the tenure clock and provide active service, modified duties, lactation stations and day care; 4) Mini-retreats to facilitate access for tenure-track women faculty to male decision-makers and administrators for informal conversations and discussion on topics important to women faculty; 5) Removal of subtle gender, racial, and other biases in promotion and tenure. The dynamic changes resulting from the grant in quality of mentoring, new understanding of promotion and tenure, numbers of women retained and given endowed chairs, and emergence of new family friendly policies gave me hope for genuine diversification of leadership in science and technology. As the grant funding ends, the absence of NSF prestige and monitoring, coupled with a change in academic leadership at the top, provide new challenges for institutionalization, recruitment, and advancement of women into leadership positions in science and engineering.

  7. Advanced glycation end products in clinical nephrology.

    Science.gov (United States)

    Kalousová, M; Zima, T; Tesar, V; Stípek, S; Sulková, S

    2004-01-01

    As a result of oxidative and carbonyl stress, advanced glycation end products (AGEs) are involved in the pathogenesis of severe and frequent diseases and their fatal vascular/cardiovascular complications, i.e. diabetes mellitus and its complications (nephropathy, angiopathy, neuropathy and retinopathy, renal failure and uremic and dialysis-associated complications), atherosclerosis and dialysis-related amyloidosis, neurodegenerative diseases, and rheumatoid arthritis. They are formed via non-enzymatic glycation which is specifically enhanced through the presence of oxidative and carbonyl stress, and their ability to form glycoxidation products in peptide and protein structures finally modulating or inducing biological reactivity. Food can be another source of AGEs; however, high serum AGEs in hemodialysis patients might reflect nutritional status better. Several methods of renal replacement therapy have been studied in connection with the AGE removal, but unfortunately the possibilities are still unsatisfactory even if high flux dialysis, hemofiltration, or hemodiafiltration give better results than conventional low flux dialysis. AGEs are currently being studied in the patients on peritoneal dialysis as their precursors can be formed in the dialysis fluid. AGEs can cause damage to the peritoneum and so a loss of ultrafiltration capacity. Many compounds give promising results in AGE inhibition (inhibition of formation of AGEs, inhibition of their action or degradation of AGEs), are tested for these properties, and eventually undergo clinical studies (e.g. aminoguanidine, OPB-9195, pyridoxamine, antioxidants, N-phenacylthiazolium bromide, antihypertensive drugs, angiotensin-converting enzyme inhibitors and angiotensin II receptor-1 antagonists). Copyright 2004 S. Karger AG, Basel

  8. Advanced TCA BAckplane Tester

    CERN Document Server

    Oltean, Alexandra Dana; PGNet2005

    2005-01-01

    The “Advanced Telecom Computing Architecture” (AdvancedTCA) is a modular standard chassis based system designed to support the needs of carrier class telecommunication applications. It is defined by a set of industry standards under the direction of the PICMG group. One early deployment of the standard technology has been a 10 Gigabit Ethernet switch developed in the framework of the EU funded ESTA project. In order to study the practical aspects of high speed Ethernet switching at 10 Gigabit and above and to validate the signal integrity of the AdvancedTCA backplane, we developed a Backplane Tester. This system is able to run pseudo-random bit sequence (PRBS) traffic at 3.125 Gbps over every link on the AdvancedTCA backplane simultaneously, and to monitor any possible connectivity failure immediately in terms of the link and slot positions inside the chassis. In this paper, we describe the design and the practical architectural hardware and software aspects of the AdvancedTCA Backplane Tester. We also pr...

  9. Advanced reactor development

    International Nuclear Information System (INIS)

    Till, C.E.

    1989-01-01

    Consideration is given to what the aims of advanced reactor development have to be, if a new generation of nuclear power is really to play an important role in man's energy generation activities in a fragile environment. The background given briefly covers present atmospheric evidence, the current situation in nuclear power, how reactors work and what can go wrong with them, and the present magnitudes of world energy generation. The central part of the paper describes what is currently being done in advanced reactor development and what can be expected from various systems and various elements of it. A vigorous case is made that three elements must be present in any advanced reactor development: (1) breeding; (2) passive safety; and (3) shorter-live nuclear waste. All three are possible. In the right advanced reactor systems the ways of achieving them are known. But R and D is necessary. That is the central argument made in the paper. Not advanced reactor prototype construction at this point, but R and D itself. (author)

  10. Inhibition Performance in Children with Math Disabilities

    OpenAIRE

    Winegar, Kathryn Lileth

    2013-01-01

    This study examined the inhibition deficit hypothesis in children with math disabilities (MD). Children with and without MD were compared on two inhibition tasks that included the random generation of numbers and letters. The results addressed three hypotheses. Weak support was found for the first hypothesis which stated difficulties related to inhibition are significantly related to math performance. I found partial support for this hypothesis in that inhibition was related to math problem s...

  11. Advancement & Promotion Review: 2003

    CERN Multimedia

    2003-01-01

    Advancement, exceptional advancement and promotion decisions were made at the end of June, following the procedures published in Weekly Bulletin No. 13/2003. These decisions were included, where applicable, in the salaries for the month of July 2003. The award of the periodic step was communicated to staff by the salary shown on the July salary slip. All other decisions are communicated by separate notification. The names of staff receiving exceptional advancements or promotions are now published on the HR Division website and are accessible for consultation only at the following address: http://cern.ch/hr-div/internal/personnel/advlist_2003.asp It is recalled that change of career path proposals submitted to the Technical Engineers and Administrative Careers Committee (TEACC) or to Human Resources Division are being examined with a view to preparing the latters' recommendations by the end of September 2003. Final decisions will be applied retroactively to 1 July 2003. Human Resources Division Tel:...

  12. Advanced Hydrogen Turbine Development

    Energy Technology Data Exchange (ETDEWEB)

    Marra, John [Siemens Energy, Inc., Orlando, FL (United States)

    2015-09-30

    Under the sponsorship of the U.S. Department of Energy (DOE) National Energy Technology Laboratories, Siemens has completed the Advanced Hydrogen Turbine Development Program to develop an advanced gas turbine for incorporation into future coal-based Integrated Gasification Combined Cycle (IGCC) plants. All the scheduled DOE Milestones were completed and significant technical progress was made in the development of new technologies and concepts. Advanced computer simulations and modeling, as well as subscale, full scale laboratory, rig and engine testing were utilized to evaluate and select concepts for further development. Program Requirements of: A 3 to 5 percentage point improvement in overall plant combined cycle efficiency when compared to the reference baseline plant; 20 to 30 percent reduction in overall plant capital cost when compared to the reference baseline plant; and NOx emissions of 2 PPM out of the stack. were all met. The program was completed on schedule and within the allotted budget

  13. Advanced Magnetic Nanostructures

    CERN Document Server

    Sellmyer, David

    2006-01-01

    Advanced Magnetic Nanostructures is devoted to the fabrication, characterization, experimental investigation, theoretical understanding, and utilization of advanced magnetic nanostructures. Focus is on various types of 'bottom-up' and 'top-down' artificial nanostructures, as contrasted to naturally occurring magnetic nanostructures, such as iron-oxide inclusions in magnetic rocks, and to structures such as perfect thin films. Chapter 1 is an introduction into some basic concepts, such as the definitions of basic magnetic quantities. Chapters 2-4 are devoted to the theory of magnetic nanostructures, Chapter 5 deals with the characterization of the structures, and Chapters 6-10 are devoted to specific systems. Applications of advanced magnetic nanostructures are discussed in Chapters11-15 and, finally, the appendix lists and briefly discusses magnetic properties of typical starting materials. Industrial and academic researchers in magnetism and related areas such as nanotechnology, materials science, and theore...

  14. Advanced servomanipulator development

    International Nuclear Information System (INIS)

    Kuban, D.P.

    1985-01-01

    The Advanced Servomanipulator (ASM) System consists of three major components: the ASM slave, the dual arm master controller (DAMC) or master, and the control system. The ASM is remotely maintainable force-reflecting servomanipulator developed at the Oak Ridge National Laboratory (ORNL) as part of the Consolidated Fuel Reprocessing Program. This new manipulator addresses requirements of advanced nuclear fuel reprocessing with emphasis on force reflection, remote maintainability, reliability, radiation tolerance, and corrosion resistance. The advanced servomanipulator is uniquely subdivided into remotely replaceable modules which will permit in situ manipulator repair by spare module replacement. Manipulator modularization and increased reliability are accomplished through a force transmission system that uses gears and torque tubes. Digital control algorithms and mechanical precision are used to offset the increased backlash, friction, and inertia resulting from the gear drives. This results in the first remotely maintainable force-reflecting servomanipulator in the world

  15. Advanced Worker Protection System

    International Nuclear Information System (INIS)

    1996-04-01

    The Advanced Worker Protection System (AWPS) is a liquid-air-based, self-contained breathing and cooling system with a duration of 2 hrs. AWPS employs a patented system developed by Oceaneering Space Systems (OSS), and was demonstrated at their facility in Houston, TX as well as at Kansas State University, Manhattan. The heart of the system is the life-support backpack that uses liquid air to provide cooling as well as breathing gas to the worker. The backpack is combined with advanced protective garments, an advanced liquid cooling garment (LCG), a respirator, and communications and support equipment. The prototype unit development and testing under Phase 1 has demonstrated that AWPS has the ability to meet performance criteria. These criteria were developed with an understanding of both the AWPS capabilities and the DOE decontamination and decommissioning (D and D) activities protection needs

  16. Advances in business ICT

    CERN Document Server

    Pełech-Pilichowski, Tomasz

    2014-01-01

    Futurists and scientists alike profess the coming of a new era in the history – the knowledge era. The notion of knowledge is as old as humans’ self-consciousness, but new challenges appear. The meaning of the word “knowledge” is changing from cognitive notion to a technical term denoting a structured economic resource to be actively managed. This contributed volume is a result of vivid and extremely valuable discussions held at 3rd International Workshop on Advances in Business ICT (ABICT) in Wrocław, Poland, September 9-12, 2012. The workshop focused on Advances in Business ICT approached from a multidisciplinary perspective. It provided an international forum for scientists/experts from academia and industry to discuss and exchange current results, applications, new ideas of ongoing research and experience on all aspects of Business Intelligence. ABICT has also been an opportunity to demonstrate different ideas and tools for developing and supporting organizational creativity, as well as advances ...

  17. Advanced maintenance research programs

    International Nuclear Information System (INIS)

    Marston, T.U.; Gelhaus, F.; Burke, R.

    1985-01-01

    The purpose of this paper is to provide the reader with an idea of the advanced maintenance research program at the Electric Power Research Institute (EPRI). A brief description of the maintenance-related activities is provided as a foundation for the advanced maintenance research projects. The projects can be divided into maintenance planning, preventive maintenance program development and implementation, predictive (or conditional) maintenance, and innovative maintenance techniques. The projects include hardware and software development, human factors considerations, and technology promotion and implementation. The advanced concepts include: the incorporation of artificial intelligence into outage planning; turbine and pump maintenance; rotating equipment monitoring and diagnostics with the aid of expert systems; and the development of mobile robots for nuclear power plant maintenance

  18. Advanced flip chip packaging

    CERN Document Server

    Lai, Yi-Shao; Wong, CP

    2013-01-01

    Advanced Flip Chip Packaging presents past, present and future advances and trends in areas such as substrate technology, material development, and assembly processes. Flip chip packaging is now in widespread use in computing, communications, consumer and automotive electronics, and the demand for flip chip technology is continuing to grow in order to meet the need for products that offer better performance, are smaller, and are environmentally sustainable. This book also: Offers broad-ranging chapters with a focus on IC-package-system integration Provides viewpoints from leading industry executives and experts Details state-of-the-art achievements in process technologies and scientific research Presents a clear development history and touches on trends in the industry while also discussing up-to-date technology information Advanced Flip Chip Packaging is an ideal book for engineers, researchers, and graduate students interested in the field of flip chip packaging.

  19. ADVANCEMENT & PROMOTION REVIEW: 2002

    CERN Multimedia

    2002-01-01

    Advancement, exceptional advancement and promotion decisions were made at the beginning of July, under the new career structure scheme and following the procedures published in Weekly Bulletin No. 11/2002. These decisions were included, where applicable, in the salaries for the month of July 2002. The award of the periodic step was communicated to staff by the salary shown on the July salary slip. All other decisions are communicated by separate notification. The names of staff receiving exceptional advancements or promotions will be published this year on the HR Division website and are accessible for consultation only at the following address : http://cern.ch/hr-div/internal/personnel/advlist.asp It is recalled that change of career path proposals submitted to the Technical Engineers and Administrative Careers Committee (TEACC) or to Human Resources Division are being examined with a view to preparing the latters' recommendations by the end of September 2002. Final decisions will be applied retroactivel...

  20. Advanced number theory

    CERN Document Server

    Cohn, Harvey

    1980-01-01

    ""A very stimulating book ... in a class by itself."" - American Mathematical MonthlyAdvanced students, mathematicians and number theorists will welcome this stimulating treatment of advanced number theory, which approaches the complex topic of algebraic number theory from a historical standpoint, taking pains to show the reader how concepts, definitions and theories have evolved during the last two centuries. Moreover, the book abounds with numerical examples and more concrete, specific theorems than are found in most contemporary treatments of the subject.The book is divided into three parts

  1. Advanced router architectures

    CERN Document Server

    Kloth, Axel K

    2005-01-01

    Routers, switches, and transmission equipment form the backbone of the Internet, yet many users and service technicians do not understand how these nodes really work.Advanced Router Architectures addresses how components of advanced routers work together and how they are integrated with each other. This book provides the background behind why these building blocks perform certain functions, and how the function is implemented in general use. It offers an introduction to the subject matter that is intended to trigger deeper interest from the reader. The book explains, for example, why traffic m

  2. Advances in quantum chemistry

    CERN Document Server

    Sabin, John R

    2013-01-01

    Advances in Quantum Chemistry presents surveys of current topics in this rapidly developing field that has emerged at the cross section of the historically established areas of mathematics, physics, chemistry, and biology. It features detailed reviews written by leading international researchers. This volume focuses on the theory of heavy ion physics in medicine.Advances in Quantum Chemistry presents surveys of current topics in this rapidly developing field that has emerged at the cross section of the historically established areas of mathematics, physics, chemistry, and biology. It features

  3. Advanced Techniques in Biophysics

    CERN Document Server

    Arrondo, José Luis R

    2006-01-01

    Technical advancements are basic elements in our life. In biophysical studies, new applications and improvements in well-established techniques are being implemented every day. This book deals with advancements produced not only from a technical point of view, but also from new approaches that are being taken in the study of biophysical samples, such as nanotechniques or single-cell measurements. This book constitutes a privileged observatory for reviewing novel applications of biophysical techniques that can help the reader enter an area where the technology is progressing quickly and where a comprehensive explanation is not always to be found.

  4. Advances in catalysis

    CERN Document Server

    Gates, Bruce C

    2012-01-01

    Advances in Catalysis fills the gap between the journal papers and the textbooks across the diverse areas of catalysis research. For more than 60 years Advances in Catalysis has been dedicated to recording progress in the field of catalysis and providing the scientific community with comprehensive and authoritative reviews. This series in invaluable to chemical engineers, physical chemists, biochemists, researchers and industrial chemists working in the fields of catalysis and materials chemistry. * In-depth, critical, state-of-the-art reviews * Comprehensive, covers of all as

  5. Advances in microwaves 3

    CERN Document Server

    Young, Leo

    2013-01-01

    Advances in Microwaves, Volume 3 covers the advances and applications of microwave signal transmission and Gunn devices. This volume contains six chapters and begins with descriptions of ground-station antennas for space communications. The succeeding chapters deal with beam waveguides, which offer interesting possibilities for transmitting microwave energy, as well as with parallel or tubular beams from antenna apertures. A chapter discusses the electron transfer mechanism and the velocity-field characteristics, with a particular emphasis on the microwave properties of Gunn oscillators. The l

  6. Advanced concepts for acceleration

    International Nuclear Information System (INIS)

    Keefe, D.

    1986-07-01

    Selected examples of advanced accelerator concepts are reviewed. Such plasma accelerators as plasma beat wave accelerator, plasma wake field accelerator, and plasma grating accelerator are discussed particularly as examples of concepts for accelerating relativistic electrons or positrons. Also covered are the pulsed electron-beam, pulsed laser accelerator, inverse Cherenkov accelerator, inverse free-electron laser, switched radial-line accelerators, and two-beam accelerator. Advanced concepts for ion acceleration discussed include the electron ring accelerator, excitation of waves on intense electron beams, and two-wave combinations

  7. Advanced exhaust nozzle technology

    Energy Technology Data Exchange (ETDEWEB)

    Glidewell, R J; Warburton, R E

    1981-01-01

    Recent developments in turbine engine exhaust nozzle technology include nonaxisymmetric nozzles, thrust reversing, and thrust vectoring. Trade studies have been performed to determine the impact of these developments on the thrust-to-weight ratio and specific fuel consumption of an advanced high performance, augmented turbofan engine. Results are presented in a manner which provides an understanding of the sources and magnitudes of differences in the basic elements of nozzle internal performance and weight as they relate to conventional, axisymmetric nozzle technology. Conclusions are presented and recommendations are made with regard to future directions of advanced development and demonstration. 5 refs.

  8. Advanced Surface Technology

    DEFF Research Database (Denmark)

    Møller, Per; Nielsen, Lars Pleht

    of the components. It covers everything from biocompatible surfaces of IR absorbent or reflective surfaces to surfaces with specific properties within low friction, hardness, corrosion, colors, etc. The book includes more than 400 pages detailing virtually all analysis methods for examining at surfaces.......This new significant book on advanced modern surface technology in all its variations, is aimed at both teaching at engineering schools and practical application in industry. The work covers all the significant aspects of modern surface technology and also describes how new advanced techniques make...

  9. Advanced solid state batteries

    Energy Technology Data Exchange (ETDEWEB)

    Levasseur, A; Delmas, C; Menetrier, M; Hagenmuller, P

    1984-01-01

    Direct electrochemical storage of electricity is attractive because of its adaptability to vehicle traction as well as to stationary applications. Important advancements are necessary to improve primary or secondary batteries so far used. The aim of this study was to develop and to characterize materials for the next generation of advanced, rechargeable solid state batteries for vehicle transport and stationary storage applications. One of the best electricity storage systems was the lithium/intercalation compound secondary battery, though up to now the behavior of liquid organic electrolytes did not allow for good recycling in such systems. The research program for these batteries is described.

  10. Advances in chemical physics

    CERN Document Server

    Rice, Stuart A

    2014-01-01

    Advances in Chemical Physics is the only series of volumes available that explores the cutting edge of research in chemical physics. This is the only series of volumes available that presents the cutting edge of research in chemical physics.Includes contributions from experts in this field of research.Contains a representative cross-section of research that questions established thinking on chemical solutions.Structured with an editorial framework that makes the book an excellent supplement to an advanced graduate class in physical chemistry or chemical physics.

  11. MR Neurography: Advances

    International Nuclear Information System (INIS)

    Chhabra, A.; Carrino, J.A.; Trueblood, E.; Lianxin Zhao, L.; Koceski, S.; Shteriev, F.; Lenkinski, L.; Sinclair, Ch.D.J.; Andreisek, G.

    2013-01-01

    High resolution and high field magnetic resonance neurography (MR neurography, MRN) is shown to have excellent anatomic capability. There have been considerable advances in the technology in the last few years leading to various feasibility studies using different structural and functional imaging approaches in both clinical and research settings. This paper is intended to be a useful seminar for readers who want to gain knowledge of the advancements in the MRN pulse sequences currently used in clinical practice as well as learn about the other techniques on the horizon aimed at better depiction of nerve anatomy, pathology, and potential noninvasive evaluation of nerve degeneration or regeneration.

  12. Advancing Physics evaluated

    Science.gov (United States)

    Ogborn, Jon

    2003-07-01

    The first phase of an evaluation of the new AS/A-level course Advancing Physics, sponsored by the Institute of Physics, is now complete. It shows that the course has achieved very high satisfaction ratings from teachers of the course, and that a majority of these teachers see it as achieving its main aims. The first phase of the evaluation was designed to pinpoint aspects of Advancing Physics that offer scope for improvement. Two such aspects have been identified: course planning and use of the CD-ROM material, and arrangements for coursework in the examination.

  13. Entanglement and inhibited quantum evolution

    Energy Technology Data Exchange (ETDEWEB)

    Toschek, P E; Balzer, Chr; Hannemann, Th; Wunderlich, Ch; Neuhauser, W [Universitaet Hamburg, Institut fuer Laser-Physik, Jungiusstrasse 9, D-20355 Hamburg (Germany)

    2003-03-14

    The evolution of a quantum system is impeded by the system's state being observed. A test on an ensemble neither proves the causal nexus nor discloses the nature of the inhibition. Two recent experiments that make use of sequential optical or microwave-optical double resonance on an individual trapped ion disprove a dynamical effect of back action by meter or environment. They rather indicate the ionic states involved in the evolution being entangled with the potentially recorded bivalued scattered-light signal.

  14. Formation and Inhibition of Nε-(Carboxymethyllysine in Saccharide-Lysine Model Systems during Microwave Heating

    Directory of Open Access Journals (Sweden)

    Bing Li

    2012-10-01

    Full Text Available  Nε-(carboxymethyl lysine (CML is the most abundant advanced glycation end product (AGE, and frequently selected as an AGEs marker in laboratory studies. In this paper, the formation and inhibition of Nε-(carboxymethyllysine in saccharide-lysine model systems during microwave heating have been studied. The microwave heating treatment significantly promoted the formation of CML during Maillard reactions, which was related to the reaction temperature, time and type of saccharide. The order of CML formation for different saccharides was lactose > glucose > sucrose. Then, the inhibition effect on CML by five inhibitors was further examined. According to the results, ascorbic acid and tocopherol did not affect inhibition of CML, in contrast, thiamin, rutin and quercetin inhibited CML formation, and the inhibitory effects were concentration dependent.

  15. History and Advancements

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 15; Issue 9. Colour: History and Advancements. Vinod R Kanetkar. General Article Volume 15 Issue 9 September 2010 pp 794-803. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/015/09/0794-0803 ...

  16. Animal Production Research Advances

    African Journals Online (AJOL)

    Animal Production Research Advances is a peer-review journal established expressly to promote the production of all animal species utilized as food. The journal has an international scope and is intended for professionals in animal production and related sciences. We solicit contributions from animal production and ...

  17. Management of advanced melanoma

    International Nuclear Information System (INIS)

    Nathanson, L.

    1986-01-01

    This book presents papers on the subject of management of advanced melanoma. The topics covered are: non-investigational cytotoxic agents; high-dosage chemotherapy in antologous bone marrow transplantation; Radiotherapy of melanomas; hyperthermia; ureal melanoma; surgical treatment of recurrent a metastatic melanoma; role of interferons in management of melanoma and molecular genetics of melanoma

  18. Advanced classical thermodynamics

    International Nuclear Information System (INIS)

    Emanuel, G.

    1987-01-01

    The theoretical and mathematical foundations of thermodynamics are presented in an advanced text intended for graduate engineering students. Chapters are devoted to definitions and postulates, the fundamental equation, equilibrium, the application of Jacobian theory to thermodynamics, the Maxwell equations, stability, the theory of real gases, critical-point theory, and chemical thermodynamics. Diagrams, graphs, tables, and sample problems are provided. 38 references

  19. Advances in pediatric dentistry.

    Science.gov (United States)

    Yoon, Richard K; Best, Jed M

    2011-07-01

    This article addresses advances in 4 key areas related to pediatric dentistry: (1) caries detection tools, (2) early interventions to arrest disease progression, (3) caries-risk assessment tools, and (4) trends in pediatric procedures and dental materials. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Advances in tomographic PIV

    NARCIS (Netherlands)

    Novara, M.

    2013-01-01

    This research deals with advanced developments in 3D particle image velocimetry based on the tomographic PIV technique (Tomo-PIV). The latter is a relatively recent measurement technique introduced by Elsinga et al. in 2005, which is based on the tomographic reconstruction of particle tracers in

  1. Advanced Curvature Deformable Mirrors

    Science.gov (United States)

    2010-09-01

    ORGANIZATION NAME(S) AND ADDRESS(ES) University of Hawaii ,Institute for Astronomy,640 North A‘ohoku Place, #209 , Hilo ,HI,96720-2700 8. PERFORMING...Advanced Curvature Deformable Mirrors Christ Ftaclas1,2, Aglae Kellerer2 and Mark Chun2 Institute for Astronomy, University of Hawaii

  2. Cartoons as Advance Organizers

    Science.gov (United States)

    Kovalik, Cindy L.; Williams, Matthew A.

    2011-01-01

    This exploratory study investigated student reaction to the use of cartoons as advance organizers for online discussions in an online course. A convenience sample of 15 students participated in the study by contributing cartoons, participating in online discussions, and completing a survey. Overall, survey results indicated student reaction to the…

  3. Advanced computers and simulation

    International Nuclear Information System (INIS)

    Ryne, R.D.

    1993-01-01

    Accelerator physicists today have access to computers that are far more powerful than those available just 10 years ago. In the early 1980's, desktop workstations performed less one million floating point operations per second (Mflops), and the realized performance of vector supercomputers was at best a few hundred Mflops. Today vector processing is available on the desktop, providing researchers with performance approaching 100 Mflops at a price that is measured in thousands of dollars. Furthermore, advances in Massively Parallel Processors (MPP) have made performance of over 10 gigaflops a reality, and around mid-decade MPPs are expected to be capable of teraflops performance. Along with advances in MPP hardware, researchers have also made significant progress in developing algorithms and software for MPPS. These changes have had, and will continue to have, a significant impact on the work of computational accelerator physicists. Now, instead of running particle simulations with just a few thousand particles, we can perform desktop simulations with tens of thousands of simulation particles, and calculations with well over 1 million particles are being performed on MPPs. In the area of computational electromagnetics, simulations that used to be performed only on vector supercomputers now run in several hours on desktop workstations, and researchers are hoping to perform simulations with over one billion mesh points on future MPPs. In this paper we will discuss the latest advances, and what can be expected in the near future, in hardware, software and applications codes for advanced simulation of particle accelerators

  4. Advanced instrumentation and teleoperation

    International Nuclear Information System (INIS)

    Decreton, M.

    1998-01-01

    SCK-CEN's advanced instrumentation and teleoperation project aims at evaluating the potential of a telerobotic approach in a nuclear environment and, in particular, the use of remote-perception systems. Main achievements in 1997 in the areas of R and D on radiation tolerance for remote sensing, optical fibres and optical-fibre sensors, and computer-aided teleoperation are reported

  5. Advanced Control Engineering

    DEFF Research Database (Denmark)

    Zhou, Jianjun

    1999-01-01

    This book is developed as a textbook for the course Advanced Control Engineering. The book is intended for students in mechanical engineering and its aim is to provide an understanding of modern control theory as well as methodologies and applications for state space modeling and design...

  6. Methodological Advances in Dea

    NARCIS (Netherlands)

    L. Cherchye (Laurens); G.T. Post (Thierry)

    2001-01-01

    textabstractWe survey the methodological advances in DEA over the last 25 years and discuss the necessary conditions for a sound empirical application. We hope this survey will contribute to the further dissemination of DEA, the knowledge of its relative strengths and weaknesses, and the tools

  7. Advanced fire information system

    CSIR Research Space (South Africa)

    Frost, PE

    2007-01-01

    Full Text Available The South African Advanced Fire Information System (AFIS) is the first near real-time satellite-based fire monitoring system in Africa. It was originally developed for, and funded by, the electrical power utility Eskom, to reduce the impact of wild...

  8. Primatology: advanced ape technology.

    Science.gov (United States)

    McGrew, W C

    2004-12-29

    New findings from African rainforests show chimpanzees to have impressively advanced technology. They make tools of vegetation to harvest termites as in East and West Africa, but some apes in Central Africa show different techniques and tool sets geared for different tasks.

  9. Advanced Cruise Control (ACC).

    NARCIS (Netherlands)

    2008-01-01

    Advanced Cruise Control (ACC), also known as adaptive or intelligent cruise control, not only maintains the driver-set vehicle speed, but also adjusts the vehicle's speed to that of a preceding vehicle, and helps to maintain a pre-selected headway time to the vehicle ahead. ACC systems can have a

  10. Advanced Cruise Control (ACC).

    NARCIS (Netherlands)

    2010-01-01

    Advanced Cruise Control (ACC), ook bekend als Adaptive, Active of Intelligent Cruise Control, handhaaft niet alleen de door de bestuurder ingestelde rijsnelheid, maar stemt ook de snelheid van het voertuig af op die van de voorligger. ACC helpt op deze manier om een vooraf bepaalde volgtijd tot de

  11. Advances in Computer Entertainment.

    NARCIS (Netherlands)

    Nijholt, Antinus; Romão, T.; Reidsma, Dennis; Unknown, [Unknown

    2012-01-01

    These are the proceedings of the 9th International Conference on Advances in Computer Entertainment ACE 2012). ACE has become the leading scientific forum for dissemination of cutting-edge research results in the area of entertainment computing. Interactive entertainment is one of the most vibrant

  12. Advances in satellite communications

    CERN Document Server

    Minoli, Daniel

    2015-01-01

    Discussing advances in modulation techniques and HTS spotbeam technologiesSurveying emerging high speed aeronautical mobility services and maritime and other terrestrial mobility servicesAssessing M2M (machine-to-machine) applications, emerging Ultra HD video technologies and new space technology

  13. Advances in Opto Electronics

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Advances in Opto Electronics. Optoelectronics is where electronics was 15 years back. All Optical Amplifiers and Semiconductor Amplifiers. Fastest Semiconductor (InP) switch is at 170GHz- where is terrabit ? MEMS based switches that route traffic at wavelength level ...

  14. Advanced Cardiac Life Support.

    Science.gov (United States)

    Kirkwood Community Coll., Cedar Rapids, IA.

    This document contains materials for an advanced college course in cardiac life support developed for the State of Iowa. The course syllabus lists the course title, hours, number, description, prerequisites, learning activities, instructional units, required text, six references, evaluation criteria, course objectives by units, course…

  15. Advanced Distribution Management System

    OpenAIRE

    Avazov, Artur; Sobinova, Lubov Anatolievna

    2016-01-01

    This article describes the advisability of using advanced distribution management systems in the electricity distribution networks area and considers premises of implementing ADMS within the Smart Grid era. Also, it gives the big picture of ADMS and discusses the ADMS advantages and functionalities.

  16. Advanced Distribution Management System

    Science.gov (United States)

    Avazov, Artur R.; Sobinova, Liubov A.

    2016-02-01

    This article describes the advisability of using advanced distribution management systems in the electricity distribution networks area and considers premises of implementing ADMS within the Smart Grid era. Also, it gives the big picture of ADMS and discusses the ADMS advantages and functionalities.

  17. Advanced Distribution Management System

    Directory of Open Access Journals (Sweden)

    Avazov Artur R.

    2016-01-01

    Full Text Available This article describes the advisability of using advanced distribution management systems in the electricity distribution networks area and considers premises of implementing ADMS within the Smart Grid era. Also, it gives the big picture of ADMS and discusses the ADMS advantages and functionalities.

  18. Advances in statistics

    Science.gov (United States)

    Howard Stauffer; Nadav Nur

    2005-01-01

    The papers included in the Advances in Statistics section of the Partners in Flight (PIF) 2002 Proceedings represent a small sample of statistical topics of current importance to Partners In Flight research scientists: hierarchical modeling, estimation of detection probabilities, and Bayesian applications. Sauer et al. (this volume) examines a hierarchical model...

  19. Advanced Heart Failure

    Science.gov (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More Advanced Heart Failure Updated:May 9,2017 When heart failure (HF) ... Making This content was last reviewed May 2017. Heart Failure • Home • About Heart Failure • Causes and Risks for ...

  20. Advances in Crash Response

    Centers for Disease Control (CDC) Podcasts

    In this podcast, Dr. Richard C. Hunt, Director of CDC's Division of Injury Response, provides an overview on the benefits of using an Advanced Automatic Collision Notification system, or AACN, to help with emergency triage of people injured in vehicle crashes.

  1. Behavioral inhibition and obsessive-compulsive disorder.

    Science.gov (United States)

    Coles, Meredith E; Schofield, Casey A; Pietrefesa, Ashley S

    2006-01-01

    Behavioral inhibition is frequently cited as a vulnerability factor for development of anxiety. However, few studies have examined the unique relationship between behavioral inhibition and obsessive-compulsive disorder (OCD). Therefore, the current study addressed the relationship between behavioral inhibition and OCD in a number of ways. In a large unselected student sample, frequency of current OC symptoms was significantly correlated with retrospective self-reports of total levels of childhood behavioral inhibition. In addition, frequency of current OC symptoms was also significantly correlated with both social and nonsocial components of behavioral inhibition. Further, there was evidence for a unique relationship between behavioral inhibition and OC symptoms beyond the relationship of behavioral inhibition and social anxiety. In addition, results showed that reports of childhood levels of behavioral inhibition significantly predicted levels of OCD symptoms in adulthood. Finally, preliminary evidence suggested that behavioral inhibition may be more strongly associated with some types of OC symptoms than others, and that overprotective parenting may moderate the impact of behavioral inhibition on OC symptoms. The current findings suggest the utility of additional research examining the role of behavioral inhibition in the etiology of OCD.

  2. Precision medicine for advanced prostate cancer.

    Science.gov (United States)

    Mullane, Stephanie A; Van Allen, Eliezer M

    2016-05-01

    Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer. Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer. Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients.

  3. Self-regulation, ego depletion, and inhibition.

    Science.gov (United States)

    Baumeister, Roy F

    2014-12-01

    Inhibition is a major form of self-regulation. As such, it depends on self-awareness and comparing oneself to standards and is also susceptible to fluctuations in willpower resources. Ego depletion is the state of reduced willpower caused by prior exertion of self-control. Ego depletion undermines inhibition both because restraints are weaker and because urges are felt more intensely than usual. Conscious inhibition of desires is a pervasive feature of everyday life and may be a requirement of life in civilized, cultural society, and in that sense it goes to the evolved core of human nature. Intentional inhibition not only restrains antisocial impulses but can also facilitate optimal performance, such as during test taking. Self-regulation and ego depletion- may also affect less intentional forms of inhibition, even chronic tendencies to inhibit. Broadly stated, inhibition is necessary for human social life and nearly all societies encourage and enforce it. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Labour analgesia: Recent advances

    Science.gov (United States)

    Pandya, Sunil T

    2010-01-01

    Advances in the field of labour analgesia have tread a long journey from the days of ether and chloroform in 1847 to the present day practice of comprehensive programme of labour pain management using evidence-based medicine. Newer advances include introduction of newer techniques like combined spinal epidurals, low-dose epidurals facilitating ambulation, pharmacological advances like introduction of remifentanil for patient-controlled intravenous analgesia, introduction of newer local anaesthetics and adjuvants like ropivacaine, levobupivacaine, sufentanil, clonidine and neostigmine, use of inhalational agents like sevoflourane for patient-controlled inhalational analgesia using special vaporizers, all have revolutionized the practice of pain management in labouring parturients. Technological advances like use of ultrasound to localize epidural space in difficult cases minimizes failed epidurals and introduction of novel drug delivery modalities like patient-controlled epidural analgesia (PCEA) pumps and computer-integrated drug delivery pumps have improved the overall maternal satisfaction rate and have enabled us to customize a suitable analgesic regimen for each parturient. Recent randomized controlled trials and Cochrane studies have concluded that the association of epidurals with increased caesarean section and long-term backache remains only a myth. Studies have also shown that the newer, low-dose regimes do not have a statistically significant impact on the duration of labour and breast feeding and also that these reduce the instrumental delivery rates thus improving maternal and foetal safety. Advances in medical technology like use of ultrasound for localizing epidural space have helped the clinicians to minimize the failure rates, and many novel drug delivery modalities like PCEA and computer-integrated PCEA have contributed to the overall maternal satisfaction and safety. PMID:21189877

  5. Graphene: corrosion-inhibiting coating.

    Science.gov (United States)

    Prasai, Dhiraj; Tuberquia, Juan Carlos; Harl, Robert R; Jennings, G Kane; Rogers, Bridget R; Bolotin, Kirill I

    2012-02-28

    We report the use of atomically thin layers of graphene as a protective coating that inhibits corrosion of underlying metals. Here, we employ electrochemical methods to study the corrosion inhibition of copper and nickel by either growing graphene on these metals, or by mechanically transferring multilayer graphene onto them. Cyclic voltammetry measurements reveal that the graphene coating effectively suppresses metal oxidation and oxygen reduction. Electrochemical impedance spectroscopy measurements suggest that while graphene itself is not damaged, the metal under it is corroded at cracks in the graphene film. Finally, we use Tafel analysis to quantify the corrosion rates of samples with and without graphene coatings. These results indicate that copper films coated with graphene grown via chemical vapor deposition are corroded 7 times slower in an aerated Na(2)SO(4) solution as compared to the corrosion rate of bare copper. Tafel analysis reveals that nickel with a multilayer graphene film grown on it corrodes 20 times slower while nickel surfaces coated with four layers of mechanically transferred graphene corrode 4 times slower than bare nickel. These findings establish graphene as the thinnest known corrosion-protecting coating.

  6. Action inhibition in Tourette syndrome.

    Science.gov (United States)

    Ganos, Christos; Kühn, Simone; Kahl, Ursula; Schunke, Odette; Feldheim, Jan; Gerloff, Christian; Roessner, Veit; Bäumer, Tobias; Thomalla, Götz; Haggard, Patrick; Münchau, Alexander

    2014-10-01

    Tourette syndrome is a neuropsychiatric disorder characterized by tics. Tic generation is often linked to dysfunction of inhibitory brain networks. Some previous behavioral studies found deficiencies in inhibitory motor control in Tourette syndrome, but others suggested normal or even better-than-normal performance. Furthermore, neural correlates of action inhibition in these patients are poorly understood. We performed event-related functional magnetic resonance imaging during a stop-signal reaction-time task in 14 uncomplicated adult Tourette patients and 15 healthy controls. In patients, we correlated activations in stop-signal reaction-time task with their individual motor tic frequency. Task performance was similar in both groups. Activation of dorsal premotor cortex was stronger in the StopSuccess than in the Go condition in healthy controls. This pattern was reversed in Tourette patients. A significant positive correlation was present between motor tic frequency and activations in the supplementary motor area during StopSuccess versus Go in patients. Inhibitory brain networks differ between healthy controls and Tourette patients. In the latter the supplementary motor area is probably a key relay of inhibitory processes mediating both suppression of tics and inhibition of voluntary action. © 2014 International Parkinson and Movement Disorder Society.

  7. Cationic Polymers Inhibit the Conductance of Lysenin Channels

    Directory of Open Access Journals (Sweden)

    Daniel Fologea

    2013-01-01

    Full Text Available The pore-forming toxin lysenin self-assembles large and stable conductance channels in natural and artificial lipid membranes. The lysenin channels exhibit unique regulation capabilities, which open unexplored possibilities to control the transport of ions and molecules through artificial and natural lipid membranes. Our investigations demonstrate that the positively charged polymers polyethyleneimine and chitosan inhibit the conducting properties of lysenin channels inserted into planar lipid membranes. The preservation of the inhibitory effect following addition of charged polymers on either side of the supporting membrane suggests the presence of multiple binding sites within the channel's structure and a multistep inhibition mechanism that involves binding and trapping. Complete blockage of the binding sites with divalent cations prevents further inhibition in conductance induced by the addition of cationic polymers and supports the hypothesis that the binding sites are identical for both multivalent metal cations and charged polymers. The investigation at the single-channel level has shown distinct complete blockages of each of the inserted channels. These findings reveal key structural characteristics which may provide insight into lysenin’s functionality while opening innovative approaches for the development of applications such as transient cell permeabilization and advanced drug delivery systems.

  8. Interaction of tea polyphenols with serum albumins: A fluorescence spectroscopic analysis

    Energy Technology Data Exchange (ETDEWEB)

    Bose, Adity, E-mail: adityc17j@gmail.com

    2016-01-15

    Interactions of some tea polyphenols, namely (−) Catechin (C), (−)-epicatechin (EC), (–) epicatechin-3-gallate (ECG), (−)-epigallocatechin (EGC) and (−)-epigallocatechin-3-gallate (EGCG) are outlined with the serum albumin proteins. These interactions had all resulted in binding with the proteins with a concomitant static quenching of the protein fluorescence. A fluorescence technique has been considered as the tool to comprehend the polyphenol–protein interactions mainly and simultaneously other spectroscopic techniques used to verify the results have been discussed. In this mini review the different types of equations usually employed to calculate the binding constant values have been outlined, namely, modified Stern Volmer plot, Scatchard plot and Lineweaver Burk equation, with their corresponding results. The n values (number of binding sites) had always been close to unity suggesting a 1:1 complexation with the polyphenols and the protein. A structural change in the polyphenols has been found to alter the binding constant value and the galloyl moiety attached to the C ring of the polyphenols have been found to play a crucial role in this regard. It has been found that an increase in galloyl moiety increases binding of the catechins with proteins. - Highlights: • Review on interactions of some tea polyphenols with the serum albumin proteins. • Tea polyphenols include Catechin, epigallocatechin-3-gallate, epigallocatechin, epicatechin-3-gallate and epicatechin. • Fluorescence spectroscopic technique is mainly outlined. • Binding constant studies have been given importance. • Galloyl moiety in the C ring is crucial in increasing binding constant.

  9. The Immunomodulatory Potential of Selected Bioactive Plant-Based Compounds in Breast Cancer: A Review.

    Science.gov (United States)

    Baraya, Yushau Shuaibu; Wong, Kah Keng; Yaacob, Nik Soriani

    2017-01-01

    Breast cancer has continued to cause high cancer death rates among women worldwide. The use of plants' natural products in breast cancer treatment has received more attention in recent years due to their potentially wider safety margin and the potential to complement conventional chemotherapeutic drugs. Plantbased products have demonstrated anticancer potential through different biological pathways including modulation of the immune system. Immunomodulatory properties of medicinal plants have been shown to mitigate breast cancer cell growth. Different immune cell types participate in this process especially cytotoxic T cells and natural killer cells, and cytokines including chemokines and tumor necrosis factor-α. Medicinal plants such as Glycyrrhiza glabra, Uncaria tomentosa, Camellia sinensis, Panax ginseng, Prunus armenaica (apricot), Allium sativum, Arctium lappa and Curcuma longa were reported to hold strong potential in breast cancer treatment in various parts of the world. Interestingly, research findings have shown that these plants possess bioactive immunomodulators as their main constituents producing the anticancer effects. These immunomodulatory compounds include ajoene, arctigenin, β-carotene, curcumin, epigallocatechin-3-gallate, ginsan, glabridin and quinic acid. In this review, we discussed the ability of these eight immunomodulators in regulating the immune system potentially applicable in breast cancer treatment via anti-inflammatory (curcumin, arctigenin, glabridin and ajoene) and lymphocytes activation (β-carotene, epigallocatechin-3-gallate, quinic acid and ginsan) properties, as well as future research direction in their use for breast cancer treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. 4 Birds 1 Stone to Inhibit 5androstane-3alpha,17beta-diol Conversion to DHT

    Science.gov (United States)

    2016-09-01

    Award Number: W81XWH-15-1-0409 TITLE: 4 Birds 1 Stone to Inhibit 5androstane-3alpha,17beta-diol Conversion to DHT PRINCIPAL INVESTIGATOR...SUBTITLE 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-04094 Birds 1 Stone to Inhibit 5androstane-3alpha,17beta-diol Conversion to DHT 5c...testicular androgens, testosterone or dihydrotestosterone ( DHT ). Men diagnosed with advanced prostate cancer or failure potentially curative therapy are

  11. Advanced steel reheat furnace

    Energy Technology Data Exchange (ETDEWEB)

    Moyeda, D.; Sheldon, M.; Koppang, R. [Energy and Environmental Research Corp., Irvine, CA (United States); Lanyi, M.; Li, X.; Eleazer, B. [Air Products and Chemicals, Inc., Allentown, PA (United States)

    1997-10-01

    Energy and Environmental Research Corp. (EER) under a contract from the Department of Energy is pursuing the development and demonstration of an Advanced Steel Reheating Furnace. This paper reports the results of Phase 1, Research, which has evaluated an advanced furnace concept incorporating two proven and commercialized technologies previously applied to other high temperature combustion applications: EER`s gas reburn technology (GR) for post combustion NOx control; and Air Product`s oxy-fuel enrichment air (OEA) for improved flame heat transfer in the heating zones of the furnace. The combined technologies feature greater production throughput with associated furnace efficiency improvements; lowered NOx emissions; and better control over the furnace atmosphere, whether oxidizing or reducing, leading to better control over surface finish.

  12. [Research advances in dendrochronology].

    Science.gov (United States)

    Fang, Ke-Yan; Chen, Qiu-Yan; Liu, Chang-Zhi; Cao, Chun-Fu; Chen, Ya-Jun; Zhou, Fei-Fei

    2014-07-01

    Tree-ring studies in China have achieved great advances since the 1990s, particularly for the dendroclimatological studies which have made some influence around the world. However, because of the uneven development, limited attention has been currently paid on the other branches of dendrochronology. We herein briefly compared the advances of dendrochronology in China and of the world and presented suggestions on future dendrochronological studies. Large-scale tree-ring based climate reconstructions in China are highly needed by employing mathematical methods and a high quality tree-ring network of the ring-width, density, stable isotope and wood anatomy. Tree-ring based field climate reconstructions provide potentials on explorations of climate forcings during the reconstructed periods via climate diagnosis and process simulation.

  13. Advanced Clothing System

    Science.gov (United States)

    Broyan, James; Orndoff, Evelyne

    2014-01-01

    The goal of the Advanced Clothing System (ACS) is to use advanced commercial off-the-shelf fibers and antimicrobial treatments with the goal of directly reducing the mass and volume of a logistics item. The current clothing state-of-the-art on the International Space Station (ISS) is disposable, mostly cotton-based, clothing with no laundry provisions. Each clothing article has varying use periods and will become trash. The goal is to increase the length of wear of the clothing to reduce the logistical mass and volume. The initial focus has been exercise clothing since the use period is lower. Various ground studies and an ISS technology demonstration have been conducted to evaluate clothing preference and length of wear. The analysis indicates that use of ACS selected garments (e.g. wool, modacrylic, polyester) can increase the breakeven point for laundry to 300 days.

  14. Advanced information processing system

    Science.gov (United States)

    Lala, J. H.

    1984-01-01

    Design and performance details of the advanced information processing system (AIPS) for fault and damage tolerant data processing on aircraft and spacecraft are presented. AIPS comprises several computers distributed throughout the vehicle and linked by a damage tolerant data bus. Most I/O functions are available to all the computers, which run in a TDMA mode. Each computer performs separate specific tasks in normal operation and assumes other tasks in degraded modes. Redundant software assures that all fault monitoring, logging and reporting are automated, together with control functions. Redundant duplex links and damage-spread limitation provide the fault tolerance. Details of an advanced design of a laboratory-scale proof-of-concept system are described, including functional operations.

  15. Advanced polymers in medicine

    CERN Document Server

    Puoci, Francesco

    2014-01-01

    The book provides an up-to-date overview of the diverse medical applications of advanced polymers. The book opens by presenting important background information on polymer chemistry and physicochemical characterization of polymers. This serves as essential scientific support for the subsequent chapters, each of which is devoted to the applications of polymers in a particular medical specialty. The coverage is broad, encompassing orthopedics, ophthalmology, tissue engineering, surgery, dentistry, oncology, drug delivery, nephrology, wound dressing and healing, and cardiology. The development of polymers that enhance the biocompatibility of blood-contacting medical devices and the incorporation of polymers within biosensors are also addressed. This book is an excellent guide to the recent advances in polymeric biomaterials and bridges the gap between the research literature and standard textbooks on the applications of polymers in medicine.

  16. CANDU advanced fuel cycles

    International Nuclear Information System (INIS)

    Slater, J.B.

    1986-03-01

    This report is based on informal lectures and presentations made on CANDU Advanced Fuel Cycles over the past year or so, and discusses the future role of CANDU in the changing environment for the Canadian and international nuclear power industry. The changing perspectives of the past decade lead to the conclusion that a significant future market for a CANDU advanced thermal reactor will exist for many decades. Such a reactor could operate in a stand-alone strategy or integrate with a mixed CANDU-LWR or CANDU-FBR strategy. The consistent design focus of CANDU on enhanced efficiency of resource utilization combined with a simple technology to achieve economic targets, will provide sufficient flexibility to maintain CANDU as a viable power producer for both the medium- and long-term future

  17. Advanced transport aircraft technology

    Energy Technology Data Exchange (ETDEWEB)

    Winblade, R L

    1980-06-01

    Various elements of the NASA aircraft energy efficiency program are described. Regarding composite structures, the development of three secondary and three medium-primary components to validate structural and fabrication technology is discussed. In laminar flow control, the design of advanced airfoils having large regions of supercritical flow with features which simplify laminarization are considered. Emphasis is placed on engine performance improvement, directed at developing advanced components to reduce fuel consumption in current production engines, and engine diagnostics aimed at identifying the sources and causes of performance deterioration in high-bypass turbofan engines. In addition, the results of propeller aerodynamic and acoustic tests have substantiated the feasibility of achieving the propeller efficiency goal of 80% and confirmed that the effect of blade sweep on reducing propeller source noise was 5-6 dB.

  18. Advanced SEM imaging

    International Nuclear Information System (INIS)

    Joy, D. C.; Newbury, D. E.

    1998-01-01

    The scanning electron microscope (SEM) represents the most promising tool for metrology, defect review, and for the analysis of ULSI structures, but both fundamental problems such as electron-solid interactions, and practical considerations such as electron-optical constraints, are now setting a limit to performance. This paper examines the directions in which an advanced SEM might be developed to overcome these constraints. The SEM also offers considerable promise as a tool for the high spatial resolution X-ray microanalysis, especially for those situations where a thin cross-section is not practical and first surface analysis is required. The ways in which this capability can be incorporated in an advanced SEM are examined

  19. Advanced CCD camera developments

    Energy Technology Data Exchange (ETDEWEB)

    Condor, A. [Lawrence Livermore National Lab., CA (United States)

    1994-11-15

    Two charge coupled device (CCD) camera systems are introduced and discussed, describing briefly the hardware involved, and the data obtained in their various applications. The Advanced Development Group Defense Sciences Engineering Division has been actively designing, manufacturing, fielding state-of-the-art CCD camera systems for over a decade. These systems were originally developed for the nuclear test program to record data from underground nuclear tests. Today, new and interesting application for these systems have surfaced and development is continuing in the area of advanced CCD camera systems, with the new CCD camera that will allow experimenters to replace film for x-ray imaging at the JANUS, USP, and NOVA laser facilities.

  20. Advanced business analytics

    CERN Document Server

    Lev, Benjamin

    2015-01-01

    The book describes advanced business analytics and shows how to apply them to many different professional areas of engineering and management. Each chapter of the book is contributed by a different author and covers a different area of business analytics. The book connects the analytic principles with business practice and provides an interface between the main disciplines of engineering/technology and the organizational, administrative and planning abilities of management. It also refers to other disciplines such as economy, finance, marketing, behavioral economics and risk analysis. This book is of special interest to engineers, economists and researchers who are developing new advances in engineering management but also to practitioners working on this subject.

  1. Advances in soil dynamics

    DEFF Research Database (Denmark)

    Advances in Soil Dynamics, Volume 3, represents the culmination of the work undertaken by the Advances in Soil Dynamics Monograph Committee, PM-45-01, about 15 years ago to summarize important developments in this field over the last 35 years. When this project was initiated, the main goal...... was to abridge major strides made in the general area of soil dynamics during the sixties, seventies, and eighties. However, by about the mid-nineties soil dynamics research in the US and much of the developed world had come to a virtual standstill. Although significant progress was made prior to the mid......-nineties, we still do not have a sound fundamental knowledge of soil-machine and soil-plant interactions. It is the hope of the editors that these three volumes will provide a ready reference for much needed future research in this area....

  2. Advances in atomic spectroscopy

    CERN Document Server

    Sneddon, J

    1998-01-01

    This volume continues the series'' cutting-edge reviews on developments in this field. Since its invention in the 1920s, electrostatic precipitation has been extensively used in industrial hygiene to remove dust and particulate matter from gases before entering the atmosphere. This combination of electrostatic precipitation is reported upon in the first chapter. Following this, chapter two reviews recent advances in the area of chemical modification in electrothermal atomization. Chapter three consists of a review which deal with advances and uses of electrothermal atomization atomic absorption spectrometry. Flow injection atomic spectroscopy has developed rapidly in recent years and after a general introduction, various aspects of this technique are looked at in chapter four. Finally, in chapter five the use of various spectrometric techniques for the determination of mercury are described.

  3. Advanced far infrared detectors

    International Nuclear Information System (INIS)

    Haller, E.E.

    1993-05-01

    Recent advances in photoconductive and bolometric semiconductor detectors for wavelength 1 mm > λ > 50 μm are reviewed. Progress in detector performance in this photon energy range has been stimulated by new and stringent requirements for ground based, high altitude and space-borne telescopes for astronomical and astrophysical observations. The paper consists of chapters dealing with the various types of detectors: Be and Ga doped Ge photoconductors, stressed Ge:Ga devices and neutron transmutation doped Ge thermistors. Advances in the understanding of basic detector physics and the introduction of modern semiconductor device technology have led to predictable and reliable fabrication techniques. Integration of detectors into functional arrays has become feasible and is vigorously pursued by groups worldwide

  4. Advancing work practices

    DEFF Research Database (Denmark)

    Noesgaard, Signe Schack

    2016-01-01

    -executed instructional interventions will advance work practices. Design/methodology/approach The paper synthesizes contemporary social-psychological and educational research in the creation of a model of intervention-based change. In addition, the findings from an empirical study of online teacher professional......Purpose The paper aims to discuss the effectiveness of e-Learning in advancing work practices. The paper investigates the assumption that e-Learning is as effective as face-to-face interventions when stimulating change. It also examines the assumption that well-designed and well...... development simultaneously inspire and exemplify the model. Findings The paper suggests that increased attention to individual motivational drivers is needed, especially post intervention, to help ensure meaningful learning transfer and sustainable behavior change. The importance of individualized on...

  5. Advanced LIGO status

    International Nuclear Information System (INIS)

    Dwyer, S

    2015-01-01

    Advanced LIGO is currently in the final stages of installation and early commissioning. In the design of Advanced LIGO a key goal was the ability to detect gravitational waves from compact object binary inspirals, as these are thought to be the most likely candidates for early detections with ground based interferometers. Special emphasis has been placed on improving the low frequency sensitivity relative to the first generations of LIGO, in addition to improving the high frequency sensitivity by increasing the laser power. The interferometer in Livingston Louisiana has been locked (continuously held within the linear operating range) and noise investigations have begun, and the major installation activities for the interferometer at Hanford, Washington are completed. (paper)

  6. Materials for advanced packaging

    CERN Document Server

    Wong, CP

    2017-01-01

    This second edition continues to be the most comprehensive review on the developments in advanced electronic packaging technologies, with a focus on materials and processing. Recognized experts in the field contribute to 22 updated and new chapters that provide comprehensive coverage on various 3D package architectures, novel bonding and joining techniques, wire bonding, wafer thinning techniques, organic substrates, and novel approaches to make electrical interconnects between integrated circuit and substrates. Various chapters also address advances in several key packaging materials, including: Lead-free solders Flip chip underfills Epoxy molding compounds Conductive adhesives Die attach adhesives/films Thermal interface materials (TIMS) Materials for fabricating embedded passives including capacitors, inductors, and resistors Materials and processing aspects on wafer-level chip scale package (CSP) and MicroElectroMechanical system (MEMS) Contributors also review new and emerging technologies such as Light ...

  7. Advanced alkaline water electrolysis

    International Nuclear Information System (INIS)

    Marini, Stefania; Salvi, Paolo; Nelli, Paolo; Pesenti, Rachele; Villa, Marco; Berrettoni, Mario; Zangari, Giovanni; Kiros, Yohannes

    2012-01-01

    A short review on the fundamental and technological issues relevant to water electrolysis in alkaline and proton exchange membrane (PEM) devices is given. Due to price and limited availability of the platinum group metal (PGM) catalysts they currently employ, PEM electrolyzers have scant possibilities of being employed in large-scale hydrogen production. The importance and recent advancements in the development of catalysts without PGMs are poised to benefit more the field of alkaline electrolysis rather than that of PEM devices. This paper presents our original data which demonstrate that an advanced alkaline electrolyzer with performances rivaling those of PEM electrolyzers can be made without PGM and with catalysts of high stability and durability. Studies on the advantages/limitations of electrolyzers with different architectures do show how a judicious application of pressure differentials in a recirculating electrolyte scheme helps reduce mass transport limitations, increasing efficiency and power density.

  8. Advanced intelligent systems

    CERN Document Server

    Ryoo, Young; Jang, Moon-soo; Bae, Young-Chul

    2014-01-01

    Intelligent systems have been initiated with the attempt to imitate the human brain. People wish to let machines perform intelligent works. Many techniques of intelligent systems are based on artificial intelligence. According to changing and novel requirements, the advanced intelligent systems cover a wide spectrum: big data processing, intelligent control, advanced robotics, artificial intelligence and machine learning. This book focuses on coordinating intelligent systems with highly integrated and foundationally functional components. The book consists of 19 contributions that features social network-based recommender systems, application of fuzzy enforcement, energy visualization, ultrasonic muscular thickness measurement, regional analysis and predictive modeling, analysis of 3D polygon data, blood pressure estimation system, fuzzy human model, fuzzy ultrasonic imaging method, ultrasonic mobile smart technology, pseudo-normal image synthesis, subspace classifier, mobile object tracking, standing-up moti...

  9. Advanced SEM imaging

    International Nuclear Information System (INIS)

    Joy, D.C.; Newbury, D.E.; Newbury, D.E.

    1998-01-01

    The scanning electron microscope (SEM) represents the most promising tool for metrology, defect review, and for the analysis of ULSI structures, but both fundamental problems such as electron-solid interactions, and practical considerations such as electron-optical constraints, are now setting a limit to performance. This paper examines the directions in which an advanced SEM might be developed to overcome these constraints. The SEM also offers considerable promise as a tool for the high spatial resolution X-ray microanalysis, especially for those situations where a thin cross-section is not practical and first surface analysis is required. The ways in which this capability can be incorporated in an advanced SEM are examined. copyright 1998 American Institute of Physics

  10. Advanced Agriculture system

    Directory of Open Access Journals (Sweden)

    Shrinivas R. Zanwar

    2012-05-01

    Full Text Available This article addresses the advanced system which improves agriculture processes like cultivation on ploughed land, based on robotic platform. We have developed a robotic vehicle having four wheels and steered by DC motor. The advanced autonomous system architecture gives us the opportunity to develop a complete new range of agricultural equipment based on small smart machines. The machine will cultivate the farm by considering particular rows and specific column at fixed distance depending on crop. The obstacle detection problem will also be considered, sensed by infrared sensor. The whole algorithm, calculation, processing, monitoring are designed with motors & sensor interfaced with microcontroller. The result obtained through example activation unit is also presented. The dc motor simulation with feedforward and feedback technique shows precise output. With the help of two examples, a DC motor and a magnetic levitation system, the use of MATLAB and Simulink for modeling, analysis and control is designed.

  11. Advanced Light Source

    International Nuclear Information System (INIS)

    Sah, R.C.

    1983-03-01

    The Advanced Light Source (ALS) is a new synchrotron radiation source which has been proposed by Lawrence Berkeley Laboratory. The ALS will be a key component in a major new research facility, the National Center for Advanced Materials. The ALS will consist of an electron linear accelerator, a booster synchrotron, a 1.3-GeV electron storage ring, and a number of photon beam lines. Most or all photon beam lines will originate from wiggler and undulator magnets placed in the 12 long straight sections of the ALS. A very low electron beam emittance will provide photon beams of unsurpassed spectral brilliance from specially-designed undulators, and a high radiofrequency will produce very short pulse lengths

  12. Silicene: Recent theoretical advances

    KAUST Repository

    Lew Yan Voon, L. C.; Zhu, Jiajie; Schwingenschlö gl, Udo

    2016-01-01

    Silicene is a two-dimensional allotrope of silicon with a puckered hexagonal structure closely related to the structure of graphene and that has been predicted to be stable. To date, it has been successfully grown in solution (functionalized) and on substrates. The goal of this review is to provide a summary of recent theoretical advances in the properties of both free-standing silicene as well as in interaction with molecules and substrates, and of proposed device applications.

  13. Polarized advanced fuel reactors

    International Nuclear Information System (INIS)

    Kulsrud, R.M.

    1987-07-01

    The d- 3 He reaction has the same spin dependence as the d-t reaction. It produces no neutrons, so that if the d-d reactivity could be reduced, it would lead to a neutron-lean reactor. The current understanding of the possible suppression of the d-d reactivity by spin polarization is discussed. The question as to whether a suppression is possible is still unresolved. Other advanced fuel reactions are briefly discussed. 11 refs

  14. Advances in microwaves 8

    CERN Document Server

    Young, Leo

    2013-01-01

    Advances in Microwaves, Volume 8 covers the developments in the study of microwaves. The book discusses the circuit forms for microwave integrated circuits; the analysis of microstrip transmission lines; and the use of lumped elements in microwave integrated circuits. The text also describes the microwave properties of ferrimagnetic materials, as well as their interaction with electromagnetic waves propagating in bounded waveguiding structures. The integration techniques useful at high frequencies; material technology for microwave integrated circuits; specific requirements on technology for d

  15. The Advanced Neutron Source

    International Nuclear Information System (INIS)

    Hayter, J.B.

    1989-01-01

    The Advanced Neutron Source (ANS) is a new user experimental facility planned to be operational at Oak Ridge in the late 1990's. The centerpiece of the ANS will be a steady-state research reactor of unprecedented thermal neutron flux (φ th ∼ 9·10 19 m -2 ·s -1 ) accompanied by extensive and comprehensive equipment and facilities for neutron-based research. 5 refs., 5 figs

  16. 6 Sigma project advance

    International Nuclear Information System (INIS)

    2002-12-01

    This book deals with 6 sigma project advance which introduces 6 sigma project in Changwon special steel, how is failure accepted? CTQ selection which is starting line, definition of performance standard, measurement system check on reliability of measurement data, check of process capacity for current level, establishment of target, optimal design and performance of application, practice of management system for maintain of improved result, CTQ selection, check of measurement system and practice of management system.

  17. Advanced worker protection system

    International Nuclear Information System (INIS)

    Caldwell, B.; Duncan, P.; Myers, J.

    1995-01-01

    The Department of Energy (DOE) is in the process of defining the magnitude and diversity of Decontamination and Decommissioning (D ampersand D) obligations at its numerous sites. The DOE believes that existing technologies are inadequate to solve many challenging problems such as how to decontaminate structures and equipment cost effectively, what to do with materials and wastes generated, and how to adequately protect workers and the environment. Preliminary estimates show a tremendous need for effective use of resources over a relatively long period (over 30 years). Several technologies are being investigated which can potentially reduce D ampersand D costs while providing appropriate protection to DOE workers. The DOE recognizes that traditional methods used by the EPA in hazardous waste site clean up activities are insufficient to provide the needed protection and worker productivity demanded by DOE D ampersand D programs. As a consequence, new clothing and equipment which can adequately protect workers while providing increases in worker productivity are being sought for implementation at DOE sites. This project will result in the development of an Advanced Worker Protection System (AWPS). The AWPS will be built around a life support backpack that uses liquid air to provide cooling as well as breathing gas to the worker. The backpack will be combined with advanced protective garments, advanced liquid cooling garment, respirator, communications, and support equipment to provide improved worker protection, simplified system maintenance, and dramatically improve worker productivity through longer duration work cycles. Phase I of the project has resulted in a full scale prototype Advanced Worker Protection Ensemble (AWPE, everything the worker will wear), with sub-scale support equipment, suitable for integrated testing and preliminary evaluation. Phase II will culminate in a full scale, certified, pre-production AWPS and a site demonstration

  18. Advanced superconducting materials

    International Nuclear Information System (INIS)

    Fluekiger, R.

    1983-11-01

    The superconducting properties of various materials are reviewed in view of their use in high field magnets. The critical current densities above 12 T of conductors based on NbN or PbMo 6 S 8 are compared to those of the most advanced practical conductors based on alloyed by Nb 3 Sn. Different aspects of the mechanical reinforcement of high field conductors, rendered necessary by the strong Lorentz forces (e.g. in fusion magnets), are discussed. (orig.) [de

  19. Advancing mangrove macroecology

    Science.gov (United States)

    Rivera-Monroy, Victor H.; Osland, Michael J.; Day, John W.; Ray, Santanu; Rovai, Andre S.; Day, Richard H.; Mukherjee, Joyita; Rivera-Monroy, Victor H.; Lee, Shing Yip; Kristensen, Erik; Twilley, Robert R.

    2017-01-01

    Mangrove forests provide a wide range of ecosystem services to society, yet they are among the most anthropogenically impacted coastal ecosystems in the world. In this chapter, we discuss and provide examples for how macroecology can advance our understanding of mangrove ecosystems. Macroecology is broadly defined as a discipline that uses statistical analyses to investigate large-scale, universal patterns in the distribution, abundance, diversity, and organization of species and ecosystems, including the scaling of ecological processes and structural and functional relationships. Macroecological methods can be used to advance our understanding of how non-linear responses in natural systems can be triggered by human impacts at local, regional, and global scales. Although macroecology has the potential to gain knowledge on universal patterns and processes that govern mangrove ecosystems, the application of macroecological methods to mangroves has historically been limited by constraints in data quality and availability. Here we provide examples that include evaluations of the variation in mangrove forest ecosystem structure and function in relation to macroclimatic drivers (e.g., temperature and rainfall regimes) and climate change. Additional examples include work focused upon the continental distribution of aboveground net primary productivity and carbon storage, which are rapidly advancing research areas. These examples demonstrate the value of a macroecological perspective for the understanding of global- and regional-scale effects of both changing environmental conditions and management actions on ecosystem structure, function, and the supply of goods and services. We also present current trends in mangrove modeling approaches and their potential utility to test hypotheses about mangrove structural and functional properties. Given the gap in relevant experimental work at the regional scale, we also discuss the potential use of mangrove restoration and

  20. Silicene: Recent theoretical advances

    KAUST Repository

    Lew Yan Voon, L. C.

    2016-04-14

    Silicene is a two-dimensional allotrope of silicon with a puckered hexagonal structure closely related to the structure of graphene and that has been predicted to be stable. To date, it has been successfully grown in solution (functionalized) and on substrates. The goal of this review is to provide a summary of recent theoretical advances in the properties of both free-standing silicene as well as in interaction with molecules and substrates, and of proposed device applications.

  1. Advanced electron beam techniques

    International Nuclear Information System (INIS)

    Hirotsu, Yoshihiko; Yoshida, Yoichi

    2007-01-01

    After 100 years from the time of discovery of electron, we now have many applications of electron beam in science and technology. In this report, we review two important applications of electron beam: electron microscopy and pulsed-electron beam. Advanced electron microscopy techniques to investigate atomic and electronic structures, and pulsed-electron beam for investigating time-resolved structural change are described. (author)

  2. Advanced Environmental Monitoring Technologies

    Science.gov (United States)

    Jan, Darrell

    2004-01-01

    Viewgraphs on Advanced Environmental Monitoring Technologies are presented. The topics include: 1) Monitoring & Controlling the Environment; 2) Illustrative Example: Canary 3) Ground-based Commercial Technology; 4) High Capability & Low Mass/Power + Autonomy = Key to Future SpaceFlight; 5) Current Practice: in Flight; 6) Current Practice: Post Flight; 7) Miniature Mass Spectrometer for Planetary Exploration and Long Duration Human Flight; 8) Hardware and Data Acquisition System; 9) 16S rDNA Phylogenetic Tree; and 10) Preview of Porter.

  3. Advances in optical imaging

    International Nuclear Information System (INIS)

    Bremer, C.; Ntziachristos, V.; Mahmood, U.; Tung, C.H.; Weissleder, R.

    2001-01-01

    Different optical imaging technologies have significantly progressed over the last years. Besides advances in imaging techniques and image reconstruction, new 'smart' optical contrast agents have been developed which can be used to detect molecular targets (such as endogenous enzymes) in vivo. The combination of novel imaging technologies coupled with smart agents bears great diagnostic potential both clinically and experimentally. This overview outlines the basic principles of optical imaging and summarizes the current state of the art. (orig.) [de

  4. Advances in microwaves 7

    CERN Document Server

    Young, Leo

    2013-01-01

    Advances in Microwaves, Volume 7 covers the developments in the study of microwaves. The book discusses the effect of surface roughness on the propagation of the TEM mode, as well as the voltage breakdown of microwave antennas. The text also describes the theory and design considerations of single slotted-waveguide linear arrays and the techniques and theories that led to the achievement of wide bandwidths and ultralow noise temperatures for communication applications. The book will prove invaluable to microwave engineers.

  5. The advanced neutron source

    International Nuclear Information System (INIS)

    Raman, S.; Hayter, J.B.

    1990-01-01

    The Advanced Neutron Source (ANS) is a new user experimental facility planned to be operational at Oak Ridge in the late 1990's. The centerpiece of the ANS will be a steady-state research reactor of unprecedented thermal neutron flux (φ th ∼ 8 x 10 19 m -2 ·s -1 ) accompanied by extensive and comprehensive equipment and facilities for neutron-based research

  6. Machinability of advanced materials

    CERN Document Server

    Davim, J Paulo

    2014-01-01

    Machinability of Advanced Materials addresses the level of difficulty involved in machining a material, or multiple materials, with the appropriate tooling and cutting parameters.  A variety of factors determine a material's machinability, including tool life rate, cutting forces and power consumption, surface integrity, limiting rate of metal removal, and chip shape. These topics, among others, and multiple examples comprise this research resource for engineering students, academics, and practitioners.

  7. Advances in Crash Response

    Centers for Disease Control (CDC) Podcasts

    2009-06-29

    In this podcast, Dr. Richard C. Hunt, Director of CDC's Division of Injury Response, provides an overview on the benefits of using an Advanced Automatic Collision Notification system, or AACN, to help with emergency triage of people injured in vehicle crashes.  Created: 6/29/2009 by National Center for Injury Prevention and Control (NCIPC), Division of Injury Response (DIR).   Date Released: 6/29/2009.

  8. Advance in structural bioinformatics

    CERN Document Server

    Wei, Dongqing; Zhao, Tangzhen; Dai, Hao

    2014-01-01

    This text examines in detail mathematical and physical modeling, computational methods and systems for obtaining and analyzing biological structures, using pioneering research cases as examples. As such, it emphasizes programming and problem-solving skills. It provides information on structure bioinformatics at various levels, with individual chapters covering introductory to advanced aspects, from fundamental methods and guidelines on acquiring and analyzing genomics and proteomics sequences, the structures of protein, DNA and RNA, to the basics of physical simulations and methods for conform

  9. Advances in Computer Entertainment.

    OpenAIRE

    Nijholt, Antinus; Romão, T.; Reidsma, Dennis; Unknown, [Unknown

    2012-01-01

    These are the proceedings of the 9th International Conference on Advances in Computer Entertainment ACE 2012). ACE has become the leading scientific forum for dissemination of cutting-edge research results in the area of entertainment computing. Interactive entertainment is one of the most vibrant areas of interest in modern society and is amongst the fastest growing industries in the world. ACE 2012 will bring together leading researchers and practitioners from academia and industry to prese...

  10. Advanced composites for windmills

    Science.gov (United States)

    Bourquardez, G.

    A development status assessment is conducted for advanced composite construction techniques for windmill blade structures which, as in the case of composite helicopter rotors, promise greater reliability, longer service life, superior performance, and lower costs. Composites in wind turbine applications must bear aerodynamic, inertial and gravitational loads in complex interaction cycles. Attention is given to large Darrieus-type vertical axis windmills, to which composite construction methods may offer highly effective pitch-control mechanisms, especially in the 'umbrella' configuration.

  11. Advances in geophysics

    CERN Document Server

    Sato, Haruo

    2013-01-01

    The critically acclaimed serialized review journal for over 50 years, Advances in Geophysics is a highly respected publication in the field of geophysics. Since 1952, each volume has been eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. Now in its 54th volume, it contains much material still relevant today--truly an essential publication for researchers in all fields of geophysics.Key features: * Contributions from leading authorities * Informs and updates on all the latest developments in the field

  12. Advances in heat transfer

    CERN Document Server

    Hartnett, James P; Cho, Young I; Greene, George A

    2001-01-01

    Heat transfer is the exchange of heat energy between a system and its surrounding environment, which results from a temperature difference and takes place by means of a process of thermal conduction, mechanical convection, or electromagnetic radiation. Advances in Heat Transfer is designed to fill the information gap between regularly scheduled journals and university-level textbooks by providing in-depth review articles over a broader scope than is allowable in either journals or texts.

  13. Delirium in advanced disease

    OpenAIRE

    Harris, Dylan

    2007-01-01

    Delirium in advanced disease, while common, is often not recognised or poorly treated. The aim of management of delirium is to assess and treat reversible causes in combination with environmental, psychological and pharmacological intervention to control symptoms. Delirium presents significant distress and impedes communication between patients and their families at the end of life. A structured approach to recognise, assess and manage delirium is essential for all clinicians caring for patie...

  14. Advanced energy materials (Preface)

    Science.gov (United States)

    Titus, Elby; Ventura, João; Araújo, João Pedro; Campos Gil, João

    2017-12-01

    Advances in material science make it possible to fabricate the building blocks of an entirely new generation of hierarchical energy materials. Recent developments were focused on functionality and areas connecting macroscopic to atomic and nanoscale properties, where surfaces, defects, interfaces and metastable state of the materials played crucial roles. The idea is to combine both, the top-down and bottom-up approach as well as shape future materials with a blend of both the paradigms.

  15. Advanced broadband baffle materials

    International Nuclear Information System (INIS)

    Seals, R.D.

    1991-01-01

    In this paper broadband performance characteristics of robust, light-weight, diffuse-absorptive baffle surfaces fabricated from sputter-deposited beryllium on cross-rolled Be ingot sheet material and on Be foam, plasma sprayed beryllium, plasma sprayed boron-on-beryllium, and chemical vapor deposited boron carbide on graphite are described and compared to Martin Black. An overview of the Optics Manufacturing Operations Development and Integration Laboratory (MODIL) Advanced Optical Baffle Program will be discussed

  16. Technological Advances in Joining

    Science.gov (United States)

    1981-08-01

    joint with the progressively advancing laser beam. Surface tension forces support the molten metal and close the keyhole behind the moving be:zm. Deep... keyhole welds in much the same manner as the electron beam which it so closely resembles. Low-power lasers rated at 1000 watts or less are used for...welding, the arc penetrates through the base metal to form the keyhole . Surface tension forces close the keyhole behind the arc as it progresses along

  17. Advanced Teleprocessing Systems

    Science.gov (United States)

    1983-03-31

    Nelson and Richard Gail with equations written on napkins at lunch time. Other students of the ATS (Advanced Teleprocessing Systems) group have also been... ink Mik 2Gk (I+S,)2 Mk = (1+k/Mk) 2 - Mi k M -I- - mk -- 2Gk, Eq.(2.11) reduces to Gk - ’h (2.13) k-1 which allows throughput of G,/e for group k ( k

  18. Advanced worker protection system

    Energy Technology Data Exchange (ETDEWEB)

    Caldwell, B.; Duncan, P.; Myers, J.

    1995-12-01

    The Department of Energy (DOE) is in the process of defining the magnitude and diversity of Decontamination and Decommissioning (D&D) obligations at its numerous sites. The DOE believes that existing technologies are inadequate to solve many challenging problems such as how to decontaminate structures and equipment cost effectively, what to do with materials and wastes generated, and how to adequately protect workers and the environment. Preliminary estimates show a tremendous need for effective use of resources over a relatively long period (over 30 years). Several technologies are being investigated which can potentially reduce D&D costs while providing appropriate protection to DOE workers. The DOE recognizes that traditional methods used by the EPA in hazardous waste site clean up activities are insufficient to provide the needed protection and worker productivity demanded by DOE D&D programs. As a consequence, new clothing and equipment which can adequately protect workers while providing increases in worker productivity are being sought for implementation at DOE sites. This project will result in the development of an Advanced Worker Protection System (AWPS). The AWPS will be built around a life support backpack that uses liquid air to provide cooling as well as breathing gas to the worker. The backpack will be combined with advanced protective garments, advanced liquid cooling garment, respirator, communications, and support equipment to provide improved worker protection, simplified system maintenance, and dramatically improve worker productivity through longer duration work cycles. Phase I of the project has resulted in a full scale prototype Advanced Worker Protection Ensemble (AWPE, everything the worker will wear), with sub-scale support equipment, suitable for integrated testing and preliminary evaluation. Phase II will culminate in a full scale, certified, pre-production AWPS and a site demonstration.

  19. Advances in desalination technology

    International Nuclear Information System (INIS)

    Pankratz, T.M.

    2005-01-01

    Seawater desalination has been the cornerstone of the Middle East's water supply strategy since the mid-1950s, and most of the installed desalination capacity is still provided by multistage flash evaporators. But, desalination is changing. In fact, the term 'desalination' is no longer limited to seawater applications; desalination technologies are now routinely employed to desalinate brackish groundwater and repurify municipal effluents. Recent advances in desalination technology have simultaneously reduced costs while dramatically improving performance and reliability to the point where desalination technologies now compete with 'conventional' treatment processes in many applications. New commercial strategies and a realisation of the economies-of-scale have led to further improvements in plant economics, and an increase in the size of plants now being developed and constructed. This presentation reviews advances in membrane and membrane pretreatment systems, energy recovery devices, materials of construction, hybrid process configurations, increased unit capacities, and the use of public-private partnerships; all of which have led to reduced capital and operating costs, enabling desalination to be economically competitive with traditional treatment options. Advances in desalination technology have resulted in better performances, lower capital and operating costs, and increased application of desalination systems. In the face of increased water shortages and growing costs of 'conventional treatment', this trend will certainly continue. (author)

  20. Fusion advanced studies Torus

    International Nuclear Information System (INIS)

    2007-01-01

    The successful development of ITER and DEMO scenarios requires preparatory activities on devices that are smaller than ITER, sufficiently flexible and capable of investigating the peculiar physics of burning plasma conditions. The aim of the Fusion Advanced Studies Torus (FAST) proposal [2.1] (formerly FT3 [2.2]) is to show that the preparation of ITER scenarios and the development of new expertise for the DEMO design and RD can be effectively implemented on a new facility. FAST will a) operate with deuterium plasmas, thereby avoiding problems associated with tritium, and allow investigation of nonlinear dynamics (which are important for understanding alpha particle behaviour in burning plasmas) by using fast ions accelerated by heating and current drive systems; b) work in a dimensionless parameter range close to that of ITER; c) test technical innovative solutions, such as full-tungsten plasma-facing components and an advanced liquid metal divertor target for the first wall/divertor, directly relevant for ITER and DEMO; d) exploit advanced regimes with a much longer pulse duration than the current diffusion time; e) provide a test bed for ITER and DEMO diagnostics; f) provide an ideal framework for model and numerical code benchmarks, their verification and validation in ITER/ DEMO-relevant plasma conditions

  1. Advanced SLARette delivery machine

    International Nuclear Information System (INIS)

    Bodner, R.R.

    1995-01-01

    SLARette 1 equipment, comprising of a SLARette Delivery Machine, SLAR Tools, SLAR power supplies and SLAR Inspection Systems was designed, developed and manufactured to service fuel channels of CANDU 6 stations during the regular yearly station outages. The Mark 2 SLARette Delivery Machine uses a Push Tube system to provide the axial and rotary movements of the SLAR Tool. The Push Tubes are operated remotely but must be attached and removed manually. Since this operation is performed at the Reactor face, there is radiation dose involved for the workers. An Advanced SLARette Delivery Machine which incorporates a computer controlled telescoping Ram in the place of the Push Tubes has been recently designed and manufactured. Utilization of the Advanced SLARette Delivery Machine significantly reduces the amount of radiation dose picked up by the workers because the need to have workers at the face of the Reactor during the SLARette operation is greatly reduced. This paper describes the design, development and manufacturing process utilized to produce the Advanced SLARette Delivery Machine and the experience gained during the Gentilly-2 NGS Spring outage. (author)

  2. Advances in titanium alloys

    International Nuclear Information System (INIS)

    Seagle, S.R.; Wood, J.R.

    1993-01-01

    As described above, new developments in the aerospace market are focusing on higher temperature alloys for jet engine components and higher strength/toughness alloys for airframe applications. Conventional alloys for engines have reached their maximum useful temperature of about 1000 F (540 C) because of oxidation resistance requirements. IMI 834 and Ti-1100 advanced alloys show some improvement, however, the major improvement appears to be in gamma titanium aluminides which could extend the maximum usage temperature to about 1500 F (815 C). This puts titanium alloys in a competitive position to replace nickel-base superalloys. Advanced airframe alloys such as Ti-6-22-22S, Beta C TM , Ti-15-333 and Ti-10-2-3 with higher strength than conventional Ti-6-4 are being utilized in significantly greater quantities, both in military and commercial applications. These alloys offer improved strength with little or no sacrifice in toughness and improved formability, in some cases. Advanced industrial alloys are being developed for improved corrosion resistance in more reducing and higher temperature environments such as those encountered in sour gas wells. Efforts are focused on small precious metal additions to optimize corrosion performance for specific applications at a modest increase in cost. As these applications develop, the usage of titanium alloys for industrial markets should steadily increase to approach that for aerospace applications. (orig.)

  3. Advanced converters and reactors

    International Nuclear Information System (INIS)

    Haefele, W.; Kessler, G.

    1984-01-01

    As Western Europe and most countries of the Asia-Pacific region (except Australia) have only small natural uranium resources, they must import nuclear fuel from the major uranium supplier countries. The introduction of advanced converter and breeder reactor technology allows a fuel utilization of a factor of 4 to 100 higher than with present low converters (LWRs) and will make uranium-importing countries less vulnerable to price jumps and supply stops in the uranium market. In addition, breeder-reactor technology will open up a potential that can cover world energy requirements for several thousand years. The enormous development costs of advanced converter and breeder technologies can probably be raised only by highly industrialized countries. Those highly industrialized countries that have little or no uranium resources (Western Europe, Japan) will probably be the first to introduce this advanced reactor technology on a commercial scale. A number of small countries and islands will need only small power reactors with inherent safety capabilities, especially in the beginning of their nuclear energy programs. For economic reasons, the fuel cycle services should come from large reprocessing centers of countries having sufficiently large nuclear power programs or from international fuel cycle centers. (author)

  4. Advanced gadolinia core and Toshiba advanced reactor management system

    International Nuclear Information System (INIS)

    Miyamoto, Toshiki; Yoshioka, Ritsuo; Ebisuya, Mitsuo

    1988-01-01

    At the Hamaoka Nuclear Power Station, Unit No. 3, advanced core design and core management technology have been adopted, significantly improving plant availability, operability and reliability. The outstanding technologies are the advanced gadolinia core (AGC) which utilizes gadolinium for the axial power distribution control, and Toshiba advanced reactor management system (TARMS) which uses a three-dimensional core physics simulator to calculate the power distribution. Presented here are the effects of these advanced technologies as observed during field testing. (author)

  5. STIR: Assessing and Training Response Inhibition Abilities

    Science.gov (United States)

    2014-07-30

    Learning to stop responding to alcohol cues reduces alcohol intake via reduced affective associations rather than increased response inhibition. Addiction ...requires an abstract application of the core learning principle1,2, and viable examples are often hard to find and/or assess. If exposure to non...inhibition training that expands upon previous successful “near transfer” response inhibition training efforts—such as treating alcohol addictions by

  6. Inhibition of cortiocosteroidogenesis by delta-9-tetrahydrocannabinol.

    Science.gov (United States)

    Warner, W; Harris, L S; Carchman, R A

    1977-12-01

    ACTH, cholera toxin, cyclic AMP but not pregnenolone-induced steroidogenesis in Y-1 functional mouse adrenal tumor cells was significantly inhibited by delta-9-tetrahydrocannabinol, cannabidiol, and cannabinol. The inhibition of steroidogenesis could not be correlated with a general depression in cell function or viability. The data suggest that cannabinoids inhibit corticosteroidogenesis at a site between the synthesis of cAMP and of pregnenolone.

  7. Inhibition of apparent photosynthesis by nitrogen oxides

    Energy Technology Data Exchange (ETDEWEB)

    Hill, A C; Bennett, J H

    1970-01-01

    The nitrogen oxides (NO/sub 2/ and NO) inhibited apparent photosynthesis of oats and alfalfa at concentrations below those required to cause visible injury. There appeared to be a threshold concentration of about 0.6 ppm for each pollutant. An additive effect in depressing apparent photosynthesis occurred when the plants were exposed to a mixture of NO and NO/sub 2/. Although NO produced a more rapid effect on the plants, lower concentrations of NO/sub 2/ were required to cause a given inhibition after 2 hour of exposure. Inhibition by nitric oxide was more closely related to its partial pressure than was inhibition by NO/sub 2/.

  8. Psychiatric Advance Directives: Getting Started

    Science.gov (United States)

    ... News Legal Issues Search for: About PADs A psychiatric advance directive (PAD) is a legal document that ... decisions during a mental health crisis. Getting Started Psychiatric advance directives (PADs) are relatively new legal instruments ...

  9. Freeform electronics for advanced healthcare

    KAUST Repository

    Hussain, Muhammad Mustafa

    2017-02-16

    Freeform (physically flexible, stretchable and reconfigurable) electronics can be critical enabler for advanced personalized healthcare. With increased global population and extended average lifetime of mankind, it is more important than ever to integrate advanced electronics into our daily life for advanced personalized healthcare. In this paper, we discuss some critical criteria to design such electronics with enabling applications.

  10. Freeform electronics for advanced healthcare

    KAUST Repository

    Hussain, Muhammad Mustafa; Hussain, Aftab M.; Nassar, Joanna M.; Kutbee, Arwa T.; Gumus, Abdurrahman; Hanna, Amir

    2017-01-01

    Freeform (physically flexible, stretchable and reconfigurable) electronics can be critical enabler for advanced personalized healthcare. With increased global population and extended average lifetime of mankind, it is more important than ever to integrate advanced electronics into our daily life for advanced personalized healthcare. In this paper, we discuss some critical criteria to design such electronics with enabling applications.

  11. TIMSS Advanced 2015 Assessment Frameworks

    Science.gov (United States)

    Mullis, Ina V. S., Ed.; Martin, Michael O., Ed.

    2014-01-01

    The "TIMSS Advanced 2015 Assessment Frameworks" provides the foundation for the two international assessments to take place as part of the International Association for the Evaluation of Educational Achievement's TIMSS (Trends in International Mathematics and Science Study) Advanced 2015--Advanced Mathematics and Physics. Chapter 1 (Liv…

  12. The Net Advance of Physics

    Science.gov (United States)

    THE NET ADVANCE OF PHYSICS Review Articles and Tutorials in an Encyclopædic Format Established 1995 [Link to MIT] Computer support for The Net Advance of Physics is furnished by The Massachusetts Newest Additions SPECIAL FEATURES: Net Advance RETRO: Nineteenth Century Physics History of Science

  13. ADVANCED SULFUR CONTROL CONCEPTS

    Energy Technology Data Exchange (ETDEWEB)

    Apostolos A. Nikolopoulos; Santosh K. Gangwal; William J. McMichael; Jeffrey W. Portzer

    2003-01-01

    Conventional sulfur removal in integrated gasification combined cycle (IGCC) power plants involves numerous steps: COS (carbonyl sulfide) hydrolysis, amine scrubbing/regeneration, Claus process, and tail-gas treatment. Advanced sulfur removal in IGCC systems involves typically the use of zinc oxide-based sorbents. The sulfides sorbent is regenerated using dilute air to produce a dilute SO{sub 2} (sulfur dioxide) tail gas. Under previous contracts the highly effective first generation Direct Sulfur Recovery Process (DSRP) for catalytic reduction of this SO{sub 2} tail gas to elemental sulfur was developed. This process is currently undergoing field-testing. In this project, advanced concepts were evaluated to reduce the number of unit operations in sulfur removal and recovery. Substantial effort was directed towards developing sorbents that could be directly regenerated to elemental sulfur in an Advanced Hot Gas Process (AHGP). Development of this process has been described in detail in Appendices A-F. RTI began the development of the Single-step Sulfur Recovery Process (SSRP) to eliminate the use of sorbents and multiple reactors in sulfur removal and recovery. This process showed promising preliminary results and thus further process development of AHGP was abandoned in favor of SSRP. The SSRP is a direct Claus process that consists of injecting SO{sub 2} directly into the quenched coal gas from a coal gasifier, and reacting the H{sub 2}S-SO{sub 2} mixture over a selective catalyst to both remove and recover sulfur in a single step. The process is conducted at gasifier pressure and 125 to 160 C. The proposed commercial embodiment of the SSRP involves a liquid phase of molten sulfur with dispersed catalyst in a slurry bubble-column reactor (SBCR).

  14. Advanced reactors: A retrospective

    International Nuclear Information System (INIS)

    Starr, C.

    1989-01-01

    The objectives for nuclear power have always emphasized competitive costs, reliability, and public safety. During its initial two decades, the nuclear reactor program was enthusiastically and generously supported by the public, government, and industry. In the subsequent decades this external support was substantially eroded by the growing public fears of catastrophic accidents, poor economic performance of many nuclear plants, regulatory constraints, and a plethora of engineering issues disclosed by plant operations. The technical and institutional histories are discussed with particular relevance to their influence on the framework for future development of the several proposed advance reactors

  15. Advancing materials research

    International Nuclear Information System (INIS)

    Langford, H.D.; Psaras, P.A.

    1987-01-01

    The topics discussed in this volume include historical perspectives in the fields of materials research and development, the status of selected scientific and technical areas, and current topics in materials research. Papers are presentd on progress and prospects in metallurgical research, microstructure and mechanical properties of metals, condensed-matter physics and materials research, quasi-periodic crystals, and new and artifically structured electronic and magnetic materials. Consideration is also given to materials research in catalysis, advanced ceramics, organic polymers, new ways of looking at surfaces, and materials synthesis and processing

  16. Advanced Nuclear Magnetic Resonance

    OpenAIRE

    Alonso, Diego A.

    2014-01-01

    Transparencias en inglés de la asignatura "Resonancia Magnética Nuclear Avanzada" (Advanced Nuclear Magnetic Resonance) (36643) que se imparte en el Máster de Química Médica como asignatura optativa de 3 créditos ECTS. En esta asignatura se completa el estudio iniciado en la asignatura de quinto curso de la licenciatura en Química "Determinación estructural" (7448) y en la del Grado de Química de tercer curso "Determinación estructural de los compuestos orgánicos" (26030) en lo referente a té...

  17. Advances in microwaves

    CERN Document Server

    Young, Leo

    1967-01-01

    Advances in Microwaves, Volume 2 focuses on the developments in microwave solid-state devices and circuits. This volume contains six chapters that also describe the design and applications of diplexers and multiplexers. The first chapter deals with the parameters of the tunnel diode, oscillators, amplifiers and frequency converter, followed by a simple physical description and the basic operating principles of the solid state devices currently capable of generating coherent microwave power, including transistors, harmonic generators, and tunnel, avalanche transit time, and diodes. The next ch

  18. Electrical installation calculations advanced

    CERN Document Server

    Kitcher, Christopher

    2013-01-01

    All the essential calculations required for advanced electrical installation workThe Electrical Installation Calculations series has proved an invaluable reference for over forty years, for both apprentices and professional electrical installation engineers alike. The book provides a step-by-step guide to the successful application of electrical installation calculations required in day-to-day electrical engineering practiceA step-by-step guide to everyday calculations used on the job An essential aid to the City & Guilds certificates at Levels 2 and 3For apprentices and electrical installatio

  19. Advanced energy materials

    CERN Document Server

    Tiwari, Ashutosh

    2014-01-01

    An essential resource for scientists designing new energy materials for the vast landscape of solar energy conversion as well as materials processing and characterization Based on the new and fundamental research on novel energy materials with tailor-made photonic properties, the role of materials engineering has been to provide much needed support in the development of photovoltaic devices. Advanced Energy Materials offers a unique, state-of-the-art look at the new world of novel energy materials science, shedding light on the subject's vast multi-disciplinary approach The book focuses p

  20. Advances in Modal Logic

    DEFF Research Database (Denmark)

    Modal logic is a subject with ancient roots in the western logical tradition. Up until the last few generations, it was pursued mainly as a branch of philosophy. But in recent years, the subject has taken new directions with connections to topics in computer science and mathematics. This volume...... is the proceedings of the conference of record in its fi eld, Advances in Modal Logic. Its contributions are state-of-the-art papers. The topics include decidability and complexity results for specifi c modal logics, proof theory of modal logic, logics for reasoning about time and space, provability logic, dynamic...... epistemic logic, and the logic of evidence....

  1. Advances in biomedical engineering

    CERN Document Server

    Brown, J H U

    1973-01-01

    Advances in Biomedical Engineering, Volume 2, is a collection of papers that discusses the basic sciences, the applied sciences of engineering, the medical sciences, and the delivery of health services. One paper discusses the models of adrenal cortical control, including the secretion and metabolism of cortisol (the controlled process), as well as the initiation and modulation of secretion of ACTH (the controller). Another paper discusses hospital computer systems-application problems, objective evaluation of technology, and multiple pathways for future hospital computer applications. The pos

  2. THE ADVANCED STELLAR COMPASS

    DEFF Research Database (Denmark)

    Jørgensen, John Leif; Liebe, Carl Christian

    1997-01-01

    The science objective of the Danish Geomagnetic Research Satellite "Ørsted" is to map the magnetic field of the Earth, with a vector precision of a fraction of a nanotesla. This necessitates an attitude reference instrument with a precision of a few arcseconds onboard the satellite. To meet...... this demand the Advanced Stellar Compass (ASC), a fully autonomous miniature star tracker, was developed. This ASC is capable of both solving the "lost in space" problem and determine the attitude with arcseconds precision. The development, principles of operation and instrument autonomy of the ASC...

  3. Scapholunate advanced collapse

    International Nuclear Information System (INIS)

    Chen, C.; Haller, J.; Resnick, D.

    1989-01-01

    Scapholunate advanced collapse 9SLAC) is a pattern of wrist malalignment (characterized mainly by radiocarpal abnormalities) that has been attributed to osteoarthritis. In order to determine the frequency of SLAC in calcium pyrophosphate dihydrate (CPPD) disease, the authors have reviewed wrist radiographs in 190 cases of this disorder. Forty-two (22%) of these cases reveal wrist abnormalities typical of SLAC. Associated findings include bilateral alterations (63%), abnormal calcification (70%), scapholunate dissociation (70%), and additional compartmental arthropathies. The authors' results confirm that CPPD crystal deposition disease is a major cause of SLAC. They believe, therefore, that this pattern of malalignment is not specific for posttraumatic or spontaneous osteoarthritis of the wrist

  4. Advances in biomedical engineering

    CERN Document Server

    Brown, J H U

    1976-01-01

    Advances in Biomedical Engineering, Volume 6, is a collection of papers that discusses the role of integrated electronics in medical systems and the usage of biological mathematical models in biological systems. Other papers deal with the health care systems, the problems and methods of approach toward rehabilitation, as well as the future of biomedical engineering. One paper discusses the use of system identification as it applies to biological systems to estimate the values of a number of parameters (for example, resistance, diffusion coefficients) by indirect means. More particularly, the i

  5. Advanced calculus problem solver

    CERN Document Server

    REA, Editors of

    2012-01-01

    Each Problem Solver is an insightful and essential study and solution guide chock-full of clear, concise problem-solving gems. All your questions can be found in one convenient source from one of the most trusted names in reference solution guides. More useful, more practical, and more informative, these study aids are the best review books and textbook companions available. Nothing remotely as comprehensive or as helpful exists in their subject anywhere. Perfect for undergraduate and graduate studies.Here in this highly useful reference is the finest overview of advanced calculus currently av

  6. Advances in quantum electronics

    CERN Document Server

    Goodwin, D W

    1974-01-01

    Advances in Quantum Electronics, Volume 2 deals with the effects of quantum mechanics on the behavior of electrons in matter. This book is divided into three chapters. Chapter 1 reviews the statistical properties of optical fields and spectral processing techniques, including the use of photon correlation techniques to measure scattering effects in a number of different media. The use of optical E.P.R. and excitation spectroscopic techniques and techniques for establishing the location of impurity ions in the chalcogenides are describe in Chapter 2. The last chapter surveys the field of mode l

  7. Advances in diaper technology

    Directory of Open Access Journals (Sweden)

    Sahana M Srinivas

    2016-01-01

    Full Text Available Diapering practices vary among different countries from the use of cloth diapers to the modern disposable diaper. In the last few decades, diaper technology has advanced significantly thus decreasing the prevalence of diaper dermatitis. Recent innovative techniques used in the manufacturing of diapers include incorporation of superabsorbent polymer gel that can absorb 30 times its weight in liquid. Recently, smart diapers have been developed which not only prevents diaper dermatitis but significantly has reduced the burden on parents. This article reviews how changes in disposable diaper technology have improved diapering practices.

  8. Advanced uranium enrichment processes

    International Nuclear Information System (INIS)

    Clerc, M.; Plurien, P.

    1986-01-01

    Three advanced Uranium enrichment processes are dealt with in the report: AVLIS (Atomic Vapour LASER Isotope Separation), MLIS (Molecular LASER Isotope Separation) and PSP (Plasma Separation Process). The description of the physical and technical features of the processes constitutes a major part of the report. If further presents comparisons with existing industrially used enrichment technologies, gives information on actual development programmes and budgets and ends with a chapter on perspectives and conclusions. An extensive bibliography of the relevant open literature is added to the different subjects discussed. The report was drawn up by the nuclear research Centre (CEA) Saclay on behalf of the Commission of the European Communities

  9. Advanced backend optimization

    CERN Document Server

    Touati, Sid

    2014-01-01

    This book is a summary of more than a decade of research in the area of backend optimization. It contains the latest fundamental research results in this field. While existing books are often more oriented toward Masters students, this book is aimed more towards professors and researchers as it contains more advanced subjects.It is unique in the sense that it contains information that has not previously been covered by other books in the field, with chapters on phase ordering in optimizing compilation; register saturation in instruction level parallelism; code size reduction for software pipe

  10. Advanced Polymer Processing Facility

    Energy Technology Data Exchange (ETDEWEB)

    Muenchausen, Ross E. [Los Alamos National Laboratory

    2012-07-25

    Some conclusions of this presentation are: (1) Radiation-assisted nanotechnology applications will continue to grow; (2) The APPF will provide a unique focus for radiolytic processing of nanomaterials in support of DOE-DP, other DOE and advanced manufacturing initiatives; (3) {gamma}, X-ray, e-beam and ion beam processing will increasingly be applied for 'green' manufacturing of nanomaterials and nanocomposites; and (4) Biomedical science and engineering may ultimately be the biggest application area for radiation-assisted nanotechnology development.

  11. Advanced structural wind engineering

    CERN Document Server

    Kareem, Ahsan

    2013-01-01

    This book serves as a textbook for advanced courses as it introduces state-of-the-art information and the latest research results on diverse problems in the structural wind engineering field. The topics include wind climates, design wind speed estimation, bluff body aerodynamics and applications, wind-induced building responses, wind, gust factor approach, wind loads on components and cladding, debris impacts, wind loading codes and standards, computational tools and computational fluid dynamics techniques, habitability to building vibrations, damping in buildings, and suppression of wind-induced vibrations. Graduate students and expert engineers will find the book especially interesting and relevant to their research and work.

  12. Advances in electronic materials

    CERN Document Server

    Kasper, Erich; Grimmeiss, Hermann G

    2008-01-01

    This special-topic volume, Advances in Electronic Materials, covers various fields of materials research such as silicon, silicon-germanium hetero-structures, high-k materials, III-V semiconductor alloys and organic materials, as well as nano-structures for spintronics and photovoltaics. It begins with a brief summary of the formative years of microelectronics; now the keystone of information technology. The latter remains one of the most important global technologies, and is an extremely complex subject-area. Although electronic materials are primarily associated with computers, the internet

  13. Advances in radiation epidemiology

    International Nuclear Information System (INIS)

    Boice, J.

    1997-01-01

    The 1994 UNSCEAR report provides an informative review of radiation epidemiology. During the past 2 years there have been several major advances in our understanding of radiation effects based on new studies of atomic bomb survivors in Japan, of patients given diagnostic and therapeutic radiation (including iodine-131), of workers occupationally exposed, and of general populations exposed to residential radon. Laboratory approaches are also being incorporated into epidemiological investigations to learn more about the biological mechanism by which radiation causes cancer in man. (author)

  14. Advances in fingerprint analysis.

    Science.gov (United States)

    Hazarika, Pompi; Russell, David A

    2012-04-10

    Fingerprints have been used in forensic investigations for the identification of individuals since the late 19th century. However, it is now clear that fingerprints can provide significantly more information about an individual. Here, we highlight the considerable advances in fingerprinting technology that can simultaneously provide chemical information regarding the drugs ingested and the explosives and drugs handled by a person as well as the identity of that individual. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Advanced information society (10)

    Science.gov (United States)

    Masuyama, Keiichi

    Informationalization in Japan has spread among various fields of industrial and social life in wide and depth by drastic advancement in technology and networking. Looking at the change in industrial structure as well as international trend in information the Japanese Government regards the role of information and communication technology as infrastructure to be important, and is under the way of constructing various measures with ministries and agencies concerned with them. This paper describes how administrative agencies involved in information and communication such as Ministry of Postal Services, Ministry of International Trade and Industry cope with informationalization, and mentions future direction in information policies.

  16. Advances in Solidification Processing

    Directory of Open Access Journals (Sweden)

    Hugo F. Lopez

    2015-08-01

    Full Text Available Melt solidification is the shortest and most viable route to obtain components, starting from the design to the finished products. Hence, a sound knowledge of the solidification of metallic materials is essential for the development of advanced structural metallic components that drive modern technological societies. As a result, there have been innumerable efforts and full conferences dedicated to this important subject [1–6]. In addition, there are various scientific journals fully devoted to investigating the various aspects which give rise to various solidification microstructures [7–9]. [...

  17. Advanced Industrial Materials Program

    Science.gov (United States)

    Stooksbury, F.

    1994-06-01

    The mission of the Advanced Industrial Materials (AIM) program is to commercialize new/improved materials and materials processing methods that will improve energy efficiency, productivity, and competitiveness. Program investigators in the DOE national laboratories are working with about 100 companies, including 15 partners in CRDA's. Work is being done on intermetallic alloys, ceramic composites, metal composites, polymers, engineered porous materials, and surface modification. The program supports other efforts in the Office of Industrial Technologies to assist the energy-consuming process industries. The aim of the AIM program is to bring materials from basic research to industrial application to strengthen the competitive position of US industry and save energy.

  18. Advances in DUV spectroscopy

    DEFF Research Database (Denmark)

    Buchhave, Preben; Tidemand-Lichtenberg, Peter; Mogensen, Claus Tilsted

    The would-be advantages of deep UV (DUV) spectroscopy are well known, but the potential applications have so far not been fully realized due to technological limitations and, perhaps, lack of bright ideas. However, new components and new knowledge about DUV spectra and spectroscopic methods...... combined with increasing needs for solutions to practical problems in environmental protection, medicine and pollution monitoring promise a new era in DUV spectroscopy. Here we shall review the basis for DUV spectroscopy, both DUV fluorescence and DUV Raman spectroscopy, and describe recent advances...

  19. Advanced thermal management materials

    CERN Document Server

    Jiang, Guosheng; Kuang, Ken

    2012-01-01

    ""Advanced Thermal Management Materials"" provides a comprehensive and hands-on treatise on the importance of thermal packaging in high performance systems. These systems, ranging from active electronically-scanned radar arrays to web servers, require components that can dissipate heat efficiently. This requires materials capable of dissipating heat and maintaining compatibility with the packaging and dye. Its coverage includes all aspects of thermal management materials, both traditional and non-traditional, with an emphasis on metal based materials. An in-depth discussion of properties and m

  20. Advances in microwaves 4

    CERN Document Server

    Young, Leo

    2013-01-01

    Advances in Microwaves, Volume 4 covers some innovations in the devices and applications of microwaves. This volume contains three chapters and begins with a discussion of the application of microwave phasers and time delay elements as beam steering elements in array radars. The next chapter provides first an overview of the technical aspects and different types of millimeter waveguides, followed by a survey of their application to railroads. The last chapter examines the general mode of conversion properties of nonuniform waveguides, such as waveguide tapers, using converted Maxwell's equatio

  1. Advances in biomedical engineering

    CERN Document Server

    Brown, J H U

    1976-01-01

    Advances in Biomedical Engineering, Volume 5, is a collection of papers that deals with application of the principles and practices of engineering to basic and applied biomedical research, development, and the delivery of health care. The papers also describe breakthroughs in health improvements, as well as basic research that have been accomplished through clinical applications. One paper examines engineering principles and practices that can be applied in developing therapeutic systems by a controlled delivery system in drug dosage. Another paper examines the physiological and materials vari

  2. Advances in radiotherapy

    International Nuclear Information System (INIS)

    Arnott, S.J.

    1978-01-01

    Advances during the last 20 years are illustrated by a comparison of 5-year survival rates of cancer patients treated in 1955 and in 1970. The lecture deals with the problem of radio resistant tumour cells, fast neutron therapy, hypoxic cell radiosensitizers, the application of whole-body irradiation particularly for the treatment of lymphomas and chronic lymphatic leukaemia, and whole-body irradiation which has been used recently for the management of metastatic cancer. The advantages of whole- and half-body irradiation over chemotherapy are discussed. (author)

  3. Inhibition of photosynthesis by carbon monoxide and suspension of the carbon monoxide inhibition by light

    Energy Technology Data Exchange (ETDEWEB)

    Gewitz, H S; Voelker, W

    1963-08-01

    The experimental subject was the autotroph Chlorella pyrenoidosa. It was found that growth conditions determine whether the alga is inhibited by carbon monoxide or not. Respiration and photosynthesis are inhibited by carbon monoxide if the cells have grown rapidly under high light intensities. The inhibition of respiration and photosynthesis found in such cells is completely reversible. The inhibition depends not only on carbon monoxide pressure, but also on the oxygen pressure prevailing at the same time. 5 references, 1 figure, 3 tables.

  4. Inhibition of GLO1 in Glioblastoma Multiforme Increases DNA-AGEs, Stimulates RAGE Expression, and Inhibits Brain Tumor Growth in Orthotopic Mouse Models

    Directory of Open Access Journals (Sweden)

    Rahul Jandial

    2018-01-01

    Full Text Available Cancers that exhibit the Warburg effect may elevate expression of glyoxylase 1 (GLO1 to detoxify the toxic glycolytic byproduct methylglyoxal (MG and inhibit the formation of pro-apoptotic advanced glycation endproducts (AGEs. Inhibition of GLO1 in cancers that up-regulate glycolysis has been proposed as a therapeutic targeting strategy, but this approach has not been evaluated for glioblastoma multiforme (GBM, the most aggressive and difficult to treat malignancy of the brain. Elevated GLO1 expression in GBM was established in patient tumors and cell lines using bioinformatics tools and biochemical approaches. GLO1 inhibition in GBM cell lines and in an orthotopic xenograft GBM mouse model was examined using both small molecule and short hairpin RNA (shRNA approaches. Inhibition of GLO1 with S-(p-bromobenzyl glutathione dicyclopentyl ester (p-BrBzGSH(Cp2 increased levels of the DNA-AGE N2-1-(carboxyethyl-2′-deoxyguanosine (CEdG, a surrogate biomarker for nuclear MG exposure; substantially elevated expression of the immunoglobulin-like receptor for AGEs (RAGE; and induced apoptosis in GBM cell lines. Targeting GLO1 with shRNA similarly increased CEdG levels and RAGE expression, and was cytotoxic to glioma cells. Mice bearing orthotopic GBM xenografts treated systemically with p-BrBzGSH(Cp2 exhibited tumor regression without significant off-target effects suggesting that GLO1 inhibition may have value in the therapeutic management of these drug-resistant tumors.

  5. Inhibition of GLO1 in Glioblastoma Multiforme Increases DNA-AGEs, Stimulates RAGE Expression, and Inhibits Brain Tumor Growth in Orthotopic Mouse Models.

    Science.gov (United States)

    Jandial, Rahul; Neman, Josh; Lim, Punnajit P; Tamae, Daniel; Kowolik, Claudia M; Wuenschell, Gerald E; Shuck, Sarah C; Ciminera, Alexandra K; De Jesus, Luis R; Ouyang, Ching; Chen, Mike Y; Termini, John

    2018-01-30

    Cancers that exhibit the Warburg effect may elevate expression of glyoxylase 1 (GLO1) to detoxify the toxic glycolytic byproduct methylglyoxal (MG) and inhibit the formation of pro-apoptotic advanced glycation endproducts (AGEs). Inhibition of GLO1 in cancers that up-regulate glycolysis has been proposed as a therapeutic targeting strategy, but this approach has not been evaluated for glioblastoma multiforme (GBM), the most aggressive and difficult to treat malignancy of the brain. Elevated GLO1 expression in GBM was established in patient tumors and cell lines using bioinformatics tools and biochemical approaches. GLO1 inhibition in GBM cell lines and in an orthotopic xenograft GBM mouse model was examined using both small molecule and short hairpin RNA (shRNA) approaches. Inhibition of GLO1 with S -( p -bromobenzyl) glutathione dicyclopentyl ester ( p- BrBzGSH(Cp)₂) increased levels of the DNA-AGE N ²-1-(carboxyethyl)-2'-deoxyguanosine (CEdG), a surrogate biomarker for nuclear MG exposure; substantially elevated expression of the immunoglobulin-like receptor for AGEs (RAGE); and induced apoptosis in GBM cell lines. Targeting GLO1 with shRNA similarly increased CEdG levels and RAGE expression, and was cytotoxic to glioma cells. Mice bearing orthotopic GBM xenografts treated systemically with p -BrBzGSH(Cp)₂ exhibited tumor regression without significant off-target effects suggesting that GLO1 inhibition may have value in the therapeutic management of these drug-resistant tumors.

  6. Recent advances in radiopharmaceuticals

    International Nuclear Information System (INIS)

    Smith, S.

    2000-01-01

    Full text: Radiopharmaceuticals in Nuclear Medicine may be divided into diagnostic and therapeutic agents. The diagnostic area is perceived to be mature, while the therapeutic side of nuclear medicine is still evolving. There are over 100 diagnostic radiopharmaceutical products available, the greatest number applied in cardiology followed by oncology and neurology. The greatest success in therapeutic nuclear medicine has been achieved in thyroid cancer, hyperthyroidism and bone pain palliation. Those in the field believe the future of nuclear medicine resides in the growth potential of the emerging therapeutic market, hence much of the recent research has been focussed in the development of therapeutic agents for targeting cancers. Radiopharmaceuticals under development or in clinical trials involve the use of radionuclides such as Y-90, Pd-103, Ir-192, Re-188, I-131, Sm-153, Sn-114, Sr-90, Cu-64 and In-111. Advances in cyclotron and camera technology as well as automation has enhanced and widened the potential use of positron emitting radiopharmaceuticals such as F-18 Fluorodeoxyglucose (FDG). However the relationship between FDG uptake and glucose consumption in normal and diseased tissue is still to be defined. Many challenges remain for the nuclear medicine community to apply new knowledge of human biochemistry in the development of new radiopharmaceuticals. A better understanding of effects of radiation and its role in the design of therapeutic agents is undoubtedly pivotal for advancing therapeutic Nuclear Medicine into the future

  7. Advanced Liquid Feed Experiment

    Science.gov (United States)

    Distefano, E.; Noll, C.

    1993-06-01

    The Advanced Liquid Feed Experiment (ALFE) is a Hitchhiker experiment flown on board the Shuttle of STS-39 as part of the Space Test Payload-1 (STP-1). The purpose of ALFE is to evaluate new propellant management components and operations under the low gravity flight environment of the Space Shuttle for eventual use in an advanced spacecraft feed system. These components and operations include an electronic pressure regulator, an ultrasonic flowmeter, an ultrasonic point sensor gage, and on-orbit refill of an auxiliary propellant tank. The tests are performed with two transparent tanks with dyed Freon 113, observed by a camera and controlled by ground commands and an on-board computer. Results show that the electronic pressure regulator provides smooth pressure ramp-up, sustained pressure control, and the flexibility to change pressure settings in flight. The ultrasonic flowmeter accurately measures flow and detects gas ingestion. The ultrasonic point sensors function well in space, but not as a gage during sustained low-gravity conditions, as they, like other point gages, are subject to the uncertainties of propellant geometry in a given tank. Propellant transfer operations can be performed with liquid-free ullage equalization at a 20 percent fill level, gas-free liquid transfer from 20-65 percent fill level, minimal slosh, and can be automated.

  8. Advanced Stirling Convertor Update

    Science.gov (United States)

    Wood, J. Gary; Carroll, Cliff; Matejczyk, Dan; Penswick, L. B.; Soendker, E.

    2006-01-01

    This paper reports on the 88 We Advanced Stirling Convertor (ASC) currently being developed under Phase II of a NASA NRA program for possible use in advanced high specific power radioisotope space power systems. An early developmental unit, the Frequency Test Bed (FTB) which was built and tested in Phase I demonstrated 36% efficiency. The ASC-1 currently being developed under Phase II, uses a high temperature heater head to allow for operation at 850 °C and is expected to have an efficiency approaching 40% (based on AC electrical out) at a temperature ratio of 3.1. The final lightweight ASC-2 convertor to be developed in Phase III is expected to have a mass of approximately 1 kg. The implementation of the ASC would allow for much higher specific power radioisotope power systems, requiring significantly less radioisotope fuel than current systems. The first run of the ASC-1 occurred in September 2005, and full temperature operation was achieved in early October 2005. Presented is an update on progress on the ASC program as well as the plans for future development. Also presented are efforts being performed to ensure the ASC has the required long life already demonstrated in free-piston Stirling cryocoolers.

  9. Advances in osteoporosis imaging

    International Nuclear Information System (INIS)

    Bauer, Jan S.; Link, Thomas M.

    2009-01-01

    In the assessment of osteoporosis, the measurement of bone mineral density (BMD a ) obtained from dual energy X-ray absorptiometry (DXA; g/cm 2 ) is the most widely used parameter. However, bone strength and fracture risk are also influenced by parameters of bone quality such as micro-architecture and tissue properties. This article reviews the radiological techniques currently available for imaging and quantifying bone structure, as well as advanced techniques to image bone quality. With the recent developments in magnetic resonance (MR) techniques, including the availability of clinical 3 T scanners, and advances in computed tomography (CT) technology (e.g. clinical Micro-CT), in-vivo imaging of the trabecular bone architecture is becoming more feasible. Several in-vitro studies have demonstrated that bone architecture, measured by MR or CT, was a BMD-independent determinant of bone strength. In-vivo studies showed that patients with, and without, osteoporotic fractures could better be separated with parameters of bone architecture than with BMD. Parameters of trabecular architecture were more sensitive to treatment effects than BMD. Besides the 3D tomographic techniques, projection radiography has been used in the peripheral skeleton as an additional tool to better predict fracture risk than BMD alone. The quantification of the trabecular architecture included parameters of scale, shape, anisotropy and connectivity. Finite element analyses required highest resolution, but best predicted the biomechanical properties of the bone. MR diffusion and perfusion imaging and MR spectroscopy may provide measures of bone quality beyond trabecular micro-architecture.

  10. Advancements in meat packaging.

    Science.gov (United States)

    McMillin, Kenneth W

    2017-10-01

    Packaging of meat provides the same or similar benefits for raw chilled and processed meats as other types of food packaging. Although air-permeable packaging is most prevalent for raw chilled red meat, vacuum and modified atmosphere packaging offer longer shelf life. The major advancements in meat packaging have been in the widely used plastic polymers while biobased materials and their integration into composite packaging are receiving much attention for functionality and sustainability. At this time, active and intelligent packaging are not widely used for antioxidant, antimicrobial, and other functions to stabilize and enhance meat properties although many options are being developed and investigated. The advances being made in nanotechnology will be incorporated into food packaging and presumably into meat packaging when appropriate and useful. Intelligent packaging using sensors for transmission of desired information and prompting of subsequent changes in packaging materials, environments or the products to maintain safety and quality are still in developmental stages. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Advanced directives: open issues

    Directory of Open Access Journals (Sweden)

    Gabriella Negrini

    2013-05-01

    Full Text Available BACKGROUND In Italy Advanced directives have not been regulated by law yet. Moreover, there is a confusion of concepts: advanced directives, refusal of treatment, medical futility and euthanasia are not synonymous.DISCUSSION The following aspects are then discussed: object of directives; elapse of time between their expression and their application; knowledge of the directives and their obligatory nature. The refusal of a treatment that can save a person’s life is a critical subject. There are different ethical points of view: according to lay ethics, the patient’s self-determination prevails; the religious viewpoint, instead, says that life is a gift which we cannot dispose of. In any case, the patient will be confronted with the professional autonomy of the doctor. Should the doctor save a patient’s life in any case or should he achieve best clinical practice, in respect of his will? The doctor should interpret the patient’s will but with caution and judgment. An exemption from responsibility should be provided by law for doctors who respect patient’s living will.

  12. 7-Piperazinethylchrysin inhibits melanoma cell proliferation by ...

    African Journals Online (AJOL)

    In B16F10 and A375 cells, treatment with PEC caused the inhibition ... Conclusion: PEC inhibited melanoma cell proliferation, apparently by blocking the cell cycle at G0/G1 .... all statistical analyses. .... Financial support from the Department of.

  13. A Qualitative Approach to Enzyme Inhibition

    Science.gov (United States)

    Waldrop, Grover L.

    2009-01-01

    Most general biochemistry textbooks present enzyme inhibition by showing how the basic Michaelis-Menten parameters K[subscript m] and V[subscript max] are affected mathematically by a particular type of inhibitor. This approach, while mathematically rigorous, does not lend itself to understanding how inhibition patterns are used to determine the…

  14. Inhibition: Mental Control Process or Mental Resource?

    Science.gov (United States)

    Im-Bolter, Nancie; Johnson, Janice; Ling, Daphne; Pascual-Leone, Juan

    2015-01-01

    The current study tested 2 models of inhibition in 45 children with language impairment and 45 children with normally developing language; children were aged 7 to 12 years. Of interest was whether a model of inhibition as a mental-control process (i.e., executive function) or as a mental resource would more accurately reflect the relations among…

  15. The pharmacology of visuospatial attention and inhibition

    NARCIS (Netherlands)

    Logemann, H.N.A.

    2013-01-01

    Attention and inhibition are of vital importance in everyday functioning. Problems of attention and inhibition are central to disorders such as Attention Deficit/Hyperactivity Disorder (ADHD). Both bias and disengagement key components of visuospatial attention. Bias refers to neuronal signals that

  16. Olaratumab for advanced soft tissue sarcoma.

    Science.gov (United States)

    Tobias, Alexander; O'brien, Michael P; Agulnik, Mark

    2017-07-01

    Olaratumab is a humanized IgG1 monoclonal antibody that blocks the platelet-derived growth factor receptor alpha (PDGFRα). Its antagonistic behavior inhibits the receptor's tyrosine kinase activity, thereby, turning off the downstream signaling cascades responsible for soft tissue sarcoma tumorigenesis. In October 2016, olaratumab received Food and Drug Administration (FDA) approval for its use in combination with doxorubicin for treatment of advanced soft tissue sarcoma. Areas covered: This drug profile takes a comprehensive look at the clinical studies leading to FDA approval of olaratumab as well as its safety and efficacy as a front-line treatment option for sarcoma patients. The literature search was primarily conducted using PubMed. Expert commentary: The combination of olaratumab plus doxorubicin has provided a new front-line therapeutic option for soft tissue sarcoma patients. An open-label phase Ib and randomized phase II trial in patients with advanced soft tissue sarcoma demonstrated that the addition of olaratumab to doxorubicin prolonged progression-free survival by 2.5 months and overall survival by 11.8 months when compared to doxorubicin alone. Of importance, this clinically meaningful increase in overall survival did not come at the expense of a significantly greater number of toxicities. A phase III confirmatory trial (ClinicalTrials.gov Identifier NCT02451943) will be completed in 2020.

  17. Advances in Cancer Immunotherapy in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Smitha Menon

    2016-11-01

    Full Text Available Immunotherapy is heralded as one of the most important advances in oncology. Until recently, only limited immunotherapeutic options were available in selected immunogenic cancers like melanoma and renal cell carcinomas. Nowadays, there is an improved understanding that anti-tumor immunity is controlled by a delicate balance in the tumor microenvironment between immune stimulatory and immune inhibitory pathways. Either by blocking the inhibitory pathways or stimulating the activating pathways that regulate cytotoxic lymphocytes, anti-tumor immunity can be enhanced leading to durable anti-tumor responses. Drugs which block the immune regulatory checkpoints namely the PD-1/PDL1 and CTLA 4 pathway have shown tremendous promise in a wide spectrum of solid and hematological malignancies, significantly improving overall survival in newly diagnosed and heavily pretreated patients alike. Hence there is renewed enthusiasm in the field of immune oncology with current research focused on augmenting responses to checkpoint inhibitors by combination therapy as well as studies looking at other immune modulators and adoptive T cell therapy. In this article, we highlight the key clinical advances and concepts in immunotherapy with particular emphasis on checkpoint inhibition as well as the future direction in this field.

  18. Advances in the management of diabetic neuropathy.

    Science.gov (United States)

    Várkonyi, Tamás; Körei, Anna; Putz, Zsuzsanna; Martos, Tímea; Keresztes, Katalin; Lengyel, Csaba; Nyiraty, Szabolcs; Stirban, Alin; Jermendy, György; Kempler, Péter

    2017-10-01

    The authors review current advances in the therapy of diabetic neuropathy. The role of glycemic control and management of cardiovascular risk factors in the prevention and treatment of neuropathic complications are discussed. As further options of pathogenetically oriented treatment, recent knowledge on benfotiamine and alpha-lipoic acid is comprehensively reviewed. Alpha-lipoic acid is a powerful antioxidant and clinical trials have proven its efficacy in ameliorating neuropathic signs and symptoms. Benfotiamine acts via the activation of transketolase and thereby inhibits alternative pathways triggered by uncontrolled glucose influx in the cells comprising polyol, hexosamine, protein-kinase-C pathways and formation of advanced glycation end products. Beyond additional forms of causal treatment, choices of symptomatic treatment will be summarized. The latter is mostly represented by the anticonvulsive agents pregabalin and gabapentin as well as duloxetine widely acknowledged as antidepressant. Finally, non-pharmacological therapeutic alternatives are summarized. The authors conclude that combination therapy should be more often suggested to our patients; especially the combination of pathogenetic and symptomatic agents.

  19. Inhibition of ethylene production by cobaltous ion

    International Nuclear Information System (INIS)

    Lau, O.L; Yang, S.F.

    1976-01-01

    The effect of Co 2+ on ethylene production by mung bean (Phaseolus aureus Roxb.) and by apple tissues was studied. Co 2+ , depending on concentrations applied, effectively inhibited ethylene production by both tissues. It also strongly inhibited the ethylene production induced by IAA, kinetin, IAA plus kinetin, Ca 2+ , kinetin plus Ca 2+ , or Cu 2+ treatments in mung bean hypocotyl segments. While Co 2+ greatly inhibited ethylene production, it had little effect on the respiration of apple tissue, indicating that Co 2+ does not exert its inhibitory effect as a general metabolic inhibitor. Ni 2+ , which belongs to the same group as Co 2+ in the periodic table, also markedly curtailed both the basal and the induced ethylene production by apple and mung bean hypocotyl tissues. In a system in which kinetin and Ca 2+ were applied together, kinetin greatly enhanced Ca 2+ uptake, thus enhancing ethylene production. Co 2+ , however, slightly inhibited the uptake of Ca 2+ but appreciably inhibited ethylene production, either in the presence or in the absence of kinetin. Tracer experiments using apple tissue indicated that Co 2+ strongly inhibited the in vivo conversion of L-[U-- 14 C]methionine to 14 C-ethylene. These data suggested that Co 2+ inhibited ethylene production by inhibiting the conversion of methionine to ethylene, a common step which is required for ethylene formation by higher plants. Co 2+ is known to promote elongation, leaf expansion, and hook opening in excised plant parts in response to applied auxins or cytokinins.Since ethylene is known to inhibit those growth phenomena, it is suggested that Co 2+ exerts its promotive effect, at least in part, by inhibiting ethylene formation

  20. ADVANCED TURBINE SYSTEMS PROGRAM

    Energy Technology Data Exchange (ETDEWEB)

    Gregory Gaul

    2004-04-21

    Natural gas combustion turbines are rapidly becoming the primary technology of choice for generating electricity. At least half of the new generating capacity added in the US over the next twenty years will be combustion turbine systems. The Department of Energy has cosponsored with Siemens Westinghouse, a program to maintain the technology lead in gas turbine systems. The very ambitious eight year program was designed to demonstrate a highly efficient and commercially acceptable power plant, with the ability to fire a wide range of fuels. The main goal of the Advanced Turbine Systems (ATS) Program was to develop ultra-high efficiency, environmentally superior and cost effective competitive gas turbine systems for base load application in utility, independent power producer and industrial markets. Performance targets were focused on natural gas as a fuel and included: System efficiency that exceeds 60% (lower heating value basis); Less than 10 ppmv NO{sub x} emissions without the use of post combustion controls; Busbar electricity that are less than 10% of state of the art systems; Reliability-Availability-Maintainability (RAM) equivalent to current systems; Water consumption minimized to levels consistent with cost and efficiency goals; and Commercial systems by the year 2000. In a parallel effort, the program was to focus on adapting the ATS engine to coal-derived or biomass fuels. In Phase 1 of the ATS Program, preliminary investigators on different gas turbine cycles demonstrated that net plant LHV based efficiency greater than 60% was achievable. In Phase 2 the more promising cycles were evaluated in greater detail and the closed-loop steam-cooled combined cycle was selected for development because it offered the best solution with least risk for achieving the ATS Program goals for plant efficiency, emissions, cost of electricity and RAM. Phase 2 also involved conceptual ATS engine and plant design and technology developments in aerodynamics, sealing

  1. Lysophospholipase inhibition by organophosphorus toxicants

    International Nuclear Information System (INIS)

    Quistad, Gary B.; Casida, John E.

    2004-01-01

    Lysophospholipases (LysoPLAs) are a large family of enzymes for removing lysophospholipids from cell membranes. Potent inhibitors are needed to define the importance of LysoPLAs as targets for toxicants and potential therapeutics. This study considers organophosphorus (OP) inhibitors with emphasis on mouse brain total LysoPLA activity relative to the mipafox-sensitive neuropathy target esterase (NTE)-LysoPLA recently established as 17% of the total activity and important in the action of OP delayed toxicants. The most potent inhibitors of total LysoPLA in mouse brain are isopropyl dodecylphosphonofluoridate (also for LysoPLA of Vibrio bacteria), ethyl octylphosphonofluoridate (EOPF), and two alkyl-benzodioxaphosphorin 2-oxides (BDPOs)[(S)-octyl and dodecyl] (IC50 2-8 nM). OP inhibitors acting in vitro and in vivo differentiate a more sensitive portion but not a distinct NTE-LysoPLA compared with total LysoPLA activity. For 10 active inhibitors, NTE-LysoPLA is 17-fold more sensitive than total LysoPLA, but structure-activity comparisons give a good correlation (r 2 = 0.94) of IC50 values, suggesting active site structural similarity or identity. In mice 4 h after intraperitoneal treatment with discriminating doses, EOPF, tribufos (a plant defoliant), and dodecanesulfonyl fluoride inhibit 41-57% of the total brain LysoPLA and 85-99% of the NTE-LysoPLA activity. Total LysoPLA as well as NTE-LysoPLA is decreased in activity in Nte +/- -haploinsufficient mice compared to their Nte +/+ littermates. The lysolecithin level of spinal cord but not brain is elevated significantly following EOPF treatment (3 mg/kg), thereby focusing attention on localized rather than general alterations in lysophospholipid metabolism in OP-induced hyperactivity and toxicity

  2. Advances in lung ultrasound

    International Nuclear Information System (INIS)

    Francisco Neto, Miguel Jose; Rahal Junior, Antonio; Vieira, Fabio Augusto Cardillo; Silva, Paulo Savoia Dias da; Funari, Marcelo Buarque de Gusmao

    2016-01-01

    Ultrasound examination of the chest has advanced in recent decades. This imaging modality is currently used to diagnose several pathological conditions and provides qualitative and quantitative information. Acoustic barriers represented by the aerated lungs and the bony framework of the chest generate well-described sonographic artifacts that can be used as diagnostic aids. The normal pleural line and A, B, C, E and Z lines (also known as false B lines) are artifacts with specific characteristics. Lung consolidation and pneumothorax sonographic patterns are also well established. Some scanning protocols have been used in patient management. The Blue, FALLS and C.A.U.S.E. protocols are examples of algorithms using artifact combinations to achieve accurate diagnoses. Combined chest ultrasonography and radiography are often sufficient to diagnose and manage lung and chest wall conditions. Chest ultrasonography is a highly valuable diagnostic tool for radiologists, emergency and intensive care physicians. (author)

  3. Advances in atomic spectroscopy

    CERN Document Server

    Sneddon, J

    2000-01-01

    This fifth volume of the successful series Advances in Atomic Spectroscopy continues to discuss and investigate the area of atomic spectroscopy.It begins with a description of the use of various atomic spectroscopic methods and applications of speciation studies in atomic spectroscopy. The emphasis is on combining atomic spectroscopy with gas and liquid chromatography. In chapter two the authors describe new developments in tunable lasers and the impact they will have on atomic spectroscopy. The traditional methods of detection, such as photography and the photomultiplier, and how they are being replaced by new detectors is discussed in chapter three. The very active area of glow discharge atomic spectrometry is presented in chapter four where, after a brief introduction and historical review, the use of glow discharge lamps for atomic spectroscopy and mass spectrometry are discussed. Included in this discussion is geometry and radiofrequency power. The future of this source in atomic spectroscopy is also dis...

  4. Advanced Visual Quantum Mechanics

    CERN Document Server

    Thaller, Bernd

    2005-01-01

    Advanced Visual Quantum Mechanics is a systematic effort to investigate and to teach quantum mechanics with the aid of computer-generated animations. It is a self-contained textbook that combines selected topics from atomic physics (spherical symmetry, the hydrogen atom, and particles with spin) with an introduction to quantum information theory (qubits, EPR paradox, teleportation, quantum computers). It explores relativistic quantum mechanics and the strange behavior of Dirac equation solutions. A series of appendices covers important topics from perturbation and scattering theory. The book places an emphasis on ideas and concepts, with a fair to moderate amount of mathematical rigor. Though this book stands alone, it can also be paired with Thaller Visual Quantum Mechanics to form a comprehensive course in quantum mechanics. The software for the first book earned the European Academic Software Award 2000 for outstanding innovation in its field.

  5. Advanced alarm management system

    International Nuclear Information System (INIS)

    Easter, J.R.

    1995-01-01

    The Westinghouse Advanced Alarm Management System (AWARE) is one of the Man-Machine Design Interfaces (MMI) which has great flexibility with regard to hardware type and configuration, alarm system concept, plant scope, engineering scope and installation. The AWARE System provides the capability to better manage the quantity prioritization and presentation of real-time process alarm messages in the control room. The messages are specific, precise and dynamic. The AWARE System can provide a large reduction in the number of messages that the control room staff must address at any one time, thus making the alarm message system a useful tool for the operators during situations that normally produce a high volume of messages as well as improving the clarity of the presentation of process abnormalities during small disturbances. The operating staff is now provided with the basis for a better understanding of the current plant state and for taking the appropriate control actions. (2 refs., 3 figs.)

  6. Advances in facial reanimation.

    Science.gov (United States)

    Tate, James R; Tollefson, Travis T

    2006-08-01

    Facial paralysis often has a significant emotional impact on patients. Along with the myriad of new surgical techniques in managing facial paralysis comes the challenge of selecting the most effective procedure for the patient. This review delineates common surgical techniques and reviews state-of-the-art techniques. The options for dynamic reanimation of the paralyzed face must be examined in the context of several patient factors, including age, overall health, and patient desires. The best functional results are obtained with direct facial nerve anastomosis and interpositional nerve grafts. In long-standing facial paralysis, temporalis muscle transfer gives a dependable and quick result. Microvascular free tissue transfer is a reliable technique with reanimation potential whose results continue to improve as microsurgical expertise increases. Postoperative results can be improved with ancillary soft tissue procedures, as well as botulinum toxin. The paper provides an overview of recent advances in facial reanimation, including preoperative assessment, surgical reconstruction options, and postoperative management.

  7. Advanced differential quadrature methods

    CERN Document Server

    Zong, Zhi

    2009-01-01

    Modern Tools to Perform Numerical DifferentiationThe original direct differential quadrature (DQ) method has been known to fail for problems with strong nonlinearity and material discontinuity as well as for problems involving singularity, irregularity, and multiple scales. But now researchers in applied mathematics, computational mechanics, and engineering have developed a range of innovative DQ-based methods to overcome these shortcomings. Advanced Differential Quadrature Methods explores new DQ methods and uses these methods to solve problems beyond the capabilities of the direct DQ method.After a basic introduction to the direct DQ method, the book presents a number of DQ methods, including complex DQ, triangular DQ, multi-scale DQ, variable order DQ, multi-domain DQ, and localized DQ. It also provides a mathematical compendium that summarizes Gauss elimination, the Runge-Kutta method, complex analysis, and more. The final chapter contains three codes written in the FORTRAN language, enabling readers to q...

  8. Polarons in advanced materials

    CERN Document Server

    Alexandrov, Alexandre Sergeevich

    2008-01-01

    Polarons in Advanced Materials will lead the reader from single-polaron problems to multi-polaron systems and finally to a description of many interesting phenomena in high-temperature superconductors, ferromagnetic oxides, conducting polymers and molecular nanowires. The book divides naturally into four parts. Part I introduces a single polaron and describes recent achievements in analytical and numerical studies of polaron properties in different electron-phonon models. Part II and Part III describe multi-polaron physics, and Part IV describes many key physical properties of high-temperature superconductors, colossal magnetoresistance oxides, conducting polymers and molecular nanowires, which were understood with polarons and bipolarons. The book is written in the form of self-consistent reviews authored by well-established researchers actively working in the field and will benefit scientists and postgraduate students with a background in condensed matter physics and materials sciences.

  9. Advanced engineering mathematics

    CERN Document Server

    Jeffrey, Alan

    2001-01-01

    Advanced Engineering Mathematics provides comprehensive and contemporary coverage of key mathematical ideas, techniques, and their widespread applications, for students majoring in engineering, computer science, mathematics and physics. Using a wide range of examples throughout the book, Jeffrey illustrates how to construct simple mathematical models, how to apply mathematical reasoning to select a particular solution from a range of possible alternatives, and how to determine which solution has physical significance. Jeffrey includes material that is not found in works of a similar nature, such as the use of the matrix exponential when solving systems of ordinary differential equations. The text provides many detailed, worked examples following the introduction of each new idea, and large problem sets provide both routine practice, and, in many cases, greater challenge and insight for students. Most chapters end with a set of computer projects that require the use of any CAS (such as Maple or Mathematica) th...

  10. Buildings for advanced technology

    CERN Document Server

    Teague, E; Murday, James

    2015-01-01

    This book deals with the design and construction of buildings for nanoscale science and engineering research. The information provided in this book is useful for designing and constructing buildings for such advanced technologies as nanotechnology, nanoelectronics and biotechnology. The book outlines the technology challenges unique to each of the building environmental challenges outlined below and provides best practices and examples of engineering approaches to address them: • Establishing and maintaining critical environments: temperature, humidity, and pressure • Structural vibration isolation • Airborne vibration isolation (acoustic noise) • Isolation of mechanical equipment-generated vibration/acoustic noise • Cost-effective power conditioning • Grounding facilities for low electrical interference • Electromagnetic interference (EMI)/Radio frequency interference (RFI) isolation • Airborne particulate contamination • Airborne organic and chemical contamination • Environment, safety a...

  11. Advances in Biosensing Methods

    Directory of Open Access Journals (Sweden)

    Reema Taneja

    2007-02-01

    Full Text Available A fractal analysis is presented for the binding and dissociation (if applicable kinetics of analyte-receptor reactions occurring on biosensor surfaces. The applications of the biosensors have appeared in the recent literature. The examples provided together provide the reader with a perspective of the advances in biosensors that are being used to detect analytes of interest. This should also stimulate interest in applying biosensors to other areas of application. The fractal analysis limits the evaluation of the rate constants for binding and dissociation (if applicable for the analyte-receptor reactions occurring in biosensor surfaces. The fractal dimension provides a quantitative measure of the degree of heterogeneity on the biosensor surface. Predictive relations are presented that relate the binding co-efficient with the degree of heterogeneity or the fractal dimension on the biosensor surface

  12. Advances Afoot in Microbiology.

    Science.gov (United States)

    Patel, Robin; Karon, Brad S

    2017-07-01

    In 2016, the American Academy of Microbiology convened a colloquium to examine point-of-care (POC) microbiology testing and to evaluate its effects on clinical microbiology. Colloquium participants included representatives from clinical microbiology laboratories, industry, and the government, who together made recommendations regarding the implementation, oversight, and evaluation of POC microbiology testing. The colloquium report is timely and well written (V. Dolen et al., Changing Diagnostic Paradigms for Microbiology , 2017, https://www.asm.org/index.php/colloquium-reports/item/6421-changing-diagnostic-paradigms-for-microbiology?utm_source=Commentary&utm_medium=referral&utm_campaign=diagnostics). Emerging POC microbiology tests, especially nucleic acid amplification tests, have the potential to advance medical care. Copyright © 2017 American Society for Microbiology.

  13. Advanced air distribution

    DEFF Research Database (Denmark)

    Melikov, Arsen Krikor

    2011-01-01

    The aim of total volume air distribution (TVAD) involves achieving uniform temperature and velocity in the occupied zone and environment designed for an average occupant. The supply of large amounts of clean and cool air are needed to maintain temperature and pollution concentration at acceptable...... levels in the entire space, leading to increased energy consumption and the use of large and costly HVAC and duct systems. The performance of desk installed PV combined with background TVAD used for room temperature control has been studied in an office building located in a hot and humid climate....... Ventilation in hospitals is essential to decrease the risk of airborne cross-infection. At present, mixing air distribution at a minimum of 12 ach is used in infection wards. Advanced air distribution has the potential to aid in achieving healthy, comfortable and productive indoor environments at levels...

  14. Advances in silicon nanophotonics

    DEFF Research Database (Denmark)

    Hvam, Jørn Märcher; Pu, Minhao

    Silicon has long been established as an ideal material for passive integrated optical circuitry due to its high refractive index, with corresponding strong optical confinement ability, and its low-cost CMOS-compatible manufacturability. However, the inversion symmetry of the silicon crystal lattice.......g. in high-bit-rate optical communication circuits and networks, it is vital that the nonlinear optical effects of silicon are being strongly enhanced. This can among others be achieved in photonic-crystal slow-light waveguides and in nano-engineered photonic-wires (Fig. 1). In this talk I shall present some...... recent advances in this direction. The efficient coupling of light between optical fibers and the planar silicon devices and circuits is of crucial importance. Both end-coupling (Fig. 1) and grating-coupling solutions will be discussed along with polarization issues. A new scheme for a hybrid III...

  15. Advances in solar sailing

    CERN Document Server

    Third International Symposium on Solar Sailing

    2014-01-01

    Hosted by the Advanced Space Concepts Laboratory within the department of Mechanical and Aerospace Engineering of the University of Strathclyde, the third International Symposium on Solar Sailing was held in McCance Building at 16 Richmond Street, Glasgow, between 11 and 13 June 2013. The symposium attracted over 90 delegates from19 different counties, bringing together international experts from across the globe to discuss funded solar sail flight programs alongside on-going technology development and testing programs. The symposium also provided a forum for the discussion of enabling technologies, new application concepts, materials and structural concepts, space environmental effects, dynamics, navigation, control, and much more. This volume contains the unabridged symposium proceedings, in the gathered experts own words. As symposium chair, I thank our partners at Scottish Enterprise and L’Garde, Inc., the symposium’s gold sponsor, for their support in realising this symposium.

  16. Advances in Patellofemoral Arthroplasty.

    Science.gov (United States)

    Strickland, Sabrina M; Bird, Mackenzie L; Christ, Alexander B

    2018-06-01

    To describe current indications, implants, economic benefits, comparison to TKA, and functional and patient-reported outcomes of patellofemoral arthroplasty. Modern onlay implants and improved patient selection have allowed for recent improvements in short- and long-term outcomes after patellofemoral joint replacement surgery. Patellofemoral arthroplasty has become an increasingly utilized technique for the successful treatment of isolated patellofemoral arthritis. Advances in patient selection, implant design, and surgical technique have resulted in improved performance and longevity of these implants. Although short- and mid-term data for modern patellofemoral arthroplasties appear promising, further long-term clinical studies are needed to evaluate how new designs and technologies will affect patient outcomes and long-term implant performance.

  17. Advanced Containment System

    Science.gov (United States)

    Kostelnik, Kevin M.; Kawamura, Hideki; Richardson, John G.; Noda, Masaru

    2004-10-12

    An advanced containment system for containing buried waste and associated leachate. A trench is dug on either side of the zone of interest containing the buried waste so as to accommodate a micro tunnel boring machine. A series of small diameter tunnels are serially excavated underneath the buried waste. The tunnels are excavated by the micro tunnel boring machine at a consistent depth and are substantially parallel to each other. As tunneling progresses, steel casing sections are connected end to end in the excavated portion of the tunnel so that a steel tube is formed. Each casing section has complementary interlocking structure running its length that interlocks with complementary interlocking structure on the adjacent casing section. Thus, once the first tube is emplaced, placement of subsequent tubes is facilitated by the complementary interlocking structure on the adjacent, previously placed, casing sections.

  18. The Advanced Light Source

    International Nuclear Information System (INIS)

    Jackson, A.

    1991-05-01

    The Advanced Light Source (ALS), a national user facility currently under construction at the Lawrence Berkeley Laboratory (LBL), is a third-generation synchrotron light source designed to produce extremely bright beams of synchrotron radiation in the energy range from a few eV to 10 keV. The design is based on a 1--1.9-GeV electron storage ring (optimized at 1.5 GeV), and utilizes special magnets, known as undulators and wigglers (collectively referred to as insertion devices), to generate the radiation. The facility is scheduled to begin operating in April 1993. In this paper we describe the progress in the design, construction, and commissioning of the accelerator systems, insertion devices, and beamlines. Companion presentations at this conference give more detail of specific components in the ALS, and describe the activities towards establishing an exciting user program. 3 figs., 2 tabs

  19. Advances in integrated optics

    CERN Document Server

    Chester, A; Bertolotti, M

    1994-01-01

    This volwne contains the Proceedings of a two-week summer conference titled "Advances in Integrated Optics" held June 1-9, 1993, in Erice, Sicily. This was the 18th annual course organized by the International School of Quantum Electronics, under the auspices of the "Ettore Majorana" Centre for Scientific Culture. The term Integrated Optics signifies guided-wave optical circuits consisting of two or more devices on a single substrate. Since its inception in the late 1960's, Integrated Optics has evolved from a specialized research topic into a broad field of work, ranging from basic research through commercial applications. Today many devices are available on market while a big effort is devolved to research on integrated nonlinear optical devices. This conference was organized to provide a comprehensive survey of the frontiers of this technology, including fundamental concepts, nonlinear optical materials, devices both in the linear and nonlinear regimes, and selected applications. These Proceedings update a...

  20. Advancing family psychology.

    Science.gov (United States)

    Fiese, Barbara H

    2016-02-01

    To realize the broad and complex nature of the field of family psychology, I have slightly revised the mission statement of the Journal of Family Psychology (JFP) to capture contemporary scholarship in family psychology and to advance systems perspectives in this top-tier scientific journal. Over the next 6 years, I hope that authors will consider JFP as an outlet for their best work in the following areas: (1) JFP addresses societal challenges faced by families today; (2) JFP publishes important studies on what makes couple and family relationships work; (3) JFP is a leader in publishing reports that use cutting-edge sophisticated approaches to research design and data analysis; and (4) JFP imparts knowledge about effective therapy and prevention programs relevant to couples and families. The journal is also expanding its publication rate to eight issues per year. (c) 2016 APA, all rights reserved).

  1. Advances in nanosized zeolites

    Science.gov (United States)

    Mintova, Svetlana; Gilson, Jean-Pierre; Valtchev, Valentin

    2013-07-01

    This review highlights recent developments in the synthesis of nanosized zeolites. The strategies available for their preparation (organic-template assisted, organic-template free, and alternative procedures) are discussed. Major breakthroughs achieved by the so-called zeolite crystal engineering and encompass items such as mastering and using the physicochemical properties of the precursor synthesis gel/suspension, optimizing the use of silicon and aluminium precursor sources, the rational use of organic templates and structure-directing inorganic cations, and careful adjustment of synthesis conditions (temperature, pressure, time, heating processes from conventional to microwave and sonication) are addressed. An on-going broad and deep fundamental understanding of the crystallization process, explaining the influence of all variables of this complex set of reactions, underpins an even more rational design of nanosized zeolites with exceptional properties. Finally, the advantages and limitations of these methods are addressed with particular attention to their industrial prospects and utilization in existing and advanced applications.

  2. Dietary advanced glycation endproducts

    DEFF Research Database (Denmark)

    Poulsen, Malene Wibe

    High heat cooking induces flavor, aroma, and color of food, but leads to formation of advanced glycation endproducts (AGEs) by the Maillard reaction. In addition to the formation in food, AGEs are also formed in vivo, and increased endogenous formation of AGEs has been linked to diabetic...... on postprandial subjective appetite sensations, appetite hormones, and markers of inflammation of two cooking methods that respectively induce or limit AGE formation were investigated in healthy overweight individuals. It was concluded that the meals affected subjective appetite sensations similarly, but the high...... sensitivity of cooking methods that induce or limit AGE formation were investigated in healthy overweight women. It was concluded that insulin sensitivity was improved with use of low heat cooking methods, compared with high heat cooking methods. In a rat study, effects on expression of AGE receptors, insulin...

  3. Advanced biomaterials and biodevices

    CERN Document Server

    Tiwari, Ashutosh

    2014-01-01

    Biomaterials are the fastest-growing emerging field of  biodevices. Design and development of biomaterials play a significant role in the diagnosis, treatment, and prevention of diseases. Recently, a variety of scaffolds/carriers have been evaluated for tissue regeneration, drug delivery, sensing and imaging.  Liposomes and microspheres have been developed for sustained delivery. Several anti-cancer drugs have been successfully formulated using biomaterial. The targeting of drugs to certain physiological sites has emerged as a promising tool in the treatment with improved drug bioavailability and reduction of dosing frequency. Biodevices-based targeting of drugs may improve the therapeutic success by limiting the adverse drug effects and resulting in more patient compliance and attaining a higher adherence level. Advanced biodevices hold merit as a drug carrier with high carrier capacity, feasibility of incorporation of both hydrophilic and hydrophobic substances, high stability, as well as the feasibility...

  4. The advanced photon source

    International Nuclear Information System (INIS)

    Galayda, J.N.

    1995-01-01

    The Advanced Photon Source (APS) is a 7-GeV third-generation synchrotron radiation storage ring and full-energy positron injector. Construction project funding began in 1989, and ground breaking took place on 5 May 1990. Construction of all accelerator facilities was completed in January 1995 and storage ring commissioning is underway. First observation of x-rays from a bending magnet source took place on 26 March 1995. Nearly all performance specifications of the injector have been reached, and first observations indicate that the reliability, dynamic aperture, emittance, and orbit stability in the storage ring are satisfactory. Observation of radiation from the first of 20 insertion device beamlines is scheduled for October 1995. Start of regular operations is expected to take place well before the APS Project target date of December 1996

  5. Advances in electrostatic accelerators

    International Nuclear Information System (INIS)

    Wegner, H.E.

    1975-01-01

    Advances in the design and performance of electrostatic accelerators since 1969 are reviewed with special emphasis on the ''forefront'' accelerators that are currently leading in voltage capability. A comparison of the acceleration tube design offered by the National Electrostatics Corporation and the High Voltage Engineering Corporation is also made. Other methods of increasing heavy ion energy by means of dual foil stripping are discussed as well as the performance of a newly developed sputter ion source for the production of negative heavy ions with reliability and flexibility that greatly exceeds all other present systems. Finally, new developments in terms of both booster systems and very high voltage electrostatic accelerators (25 to 60 MV) are discussed. (U.S.)

  6. Immune evasion mechanisms and immune checkpoint inhibition in advanced merkel cell carcinoma.

    Science.gov (United States)

    Schadendorf, Dirk; Nghiem, Paul; Bhatia, Shailender; Hauschild, Axel; Saiag, Philippe; Mahnke, Lisa; Hariharan, Subramanian; Kaufman, Howard L

    2017-01-01

    Merkel cell carcinoma (MCC) is a rare skin cancer caused by Merkel cell polyomavirus (MCPyV) infection and/or ultraviolet radiation-induced somatic mutations. The presence of tumor-infiltrating lymphocytes is evidence that an active immune response to MCPyV and tumor-associated neoantigens occurs in some patients. However, inhibitory immune molecules, including programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1), within the MCC tumor microenvironment aid in tumor evasion of T-cell-mediated clearance. Unlike chemotherapy, treatment with anti-PD-L1 (avelumab) or anti-PD-1 (pembrolizumab) antibodies leads to durable responses in MCC, in both virus-positive and virus-negative tumors. As many tumors are established through the evasion of infiltrating immune-cell clearance, the lessons learned in MCC may be broadly relevant to many cancers.

  7. YAP Inhibition Restores Hepatocyte Differentiation in Advanced HCC, Leading to Tumor Regression

    Directory of Open Access Journals (Sweden)

    Julien Fitamant

    2015-03-01

    Full Text Available Defective Hippo/YAP signaling in the liver results in tissue overgrowth and development of hepatocellular carcinoma (HCC. Here, we uncover mechanisms of YAP-mediated hepatocyte reprogramming and HCC pathogenesis. YAP functions as a rheostat in maintaining metabolic specialization, differentiation, and quiescence within the hepatocyte compartment. Increased or decreased YAP activity reprograms subsets of hepatocytes to different fates associated with deregulation of the HNF4A, CTNNB1, and E2F transcriptional programs that control hepatocyte quiescence and differentiation. Importantly, treatment with small interfering RNA-lipid nanoparticles (siRNA-LNPs targeting YAP restores hepatocyte differentiation and causes pronounced tumor regression in a genetically engineered mouse HCC model. Furthermore, YAP targets are enriched in an aggressive human HCC subtype characterized by a proliferative signature and absence of CTNNB1 mutations. Thus, our work reveals Hippo signaling as a key regulator of the positional identity of hepatocytes, supports targeting of YAP using siRNA-LNPs as a paradigm of differentiation-based therapy, and identifies an HCC subtype that is potentially responsive to this approach.

  8. Omics Advances in Ecotoxicology.

    Science.gov (United States)

    Zhang, Xiaowei; Xia, Pu; Wang, Pingping; Yang, Jianghu; Baird, Donald J

    2018-04-03

    Toxic substances in the environment generate adverse effects at all levels of biological organization from the molecular level to community and ecosystem. Given this complexity, it is not surprising that ecotoxicologists have struggled to address the full consequences of toxic substance release at ecosystem level, due to the limits of observational and experimental tools to reveal the changes in deep structure at different levels of organization. -Omics technologies, consisting of genomics and ecogenomics, have the power to reveal, in unprecedented detail, the cellular processes of an individual or biodiversity of a community in response to environmental change with high sample/observation throughput. This represents a historic opportunity to transform the way we study toxic substances in ecosystems, through direct linkage of ecological effects with the systems biology of organisms. Three recent examples of -omics advance in the assessment of toxic substances are explored here: (1) the use of functional genomics in the discovery of novel molecular mechanisms of toxicity of chemicals in the environment; (2) the development of laboratory pipelines of dose-dependent, reduced transcriptomics to support high-throughput chemical testing at the biological pathway level; and (3) the use of eDNA metabarcoding approaches for assessing chemical effects on biological communities in mesocosm experiments and through direct observation in field monitoring. -Omics advances in ecotoxicological studies not only generate new knowledge regarding mechanisms of toxicity and environmental effect, improving the relevance and immediacy of laboratory toxicological assessment, but can provide a wholly new paradigm for ecotoxicology by linking ecological models to mechanism-based, systems biology approaches.

  9. Advanced materials processing

    International Nuclear Information System (INIS)

    Giamei, A.F.

    1993-01-01

    Advanced materials will require improved processing methods due to high melting points, low toughness or ductility values, high reactivity with air or ceramics and typically complex crystal structures with significant anisotropy in flow and/or fracture stress. Materials for structural applications at elevated temperature in critical systems will require processing with a high degree of control. This requires an improved understanding of the relationship between process variables and microstructure to enable control systems to achieve consistently high quality. One avenue to the required level of understanding is computer simulation. Past attempts to do process modeling have been hampered by incomplete data regarding thermophysical or mechanical material behavior. Some of the required data can be calculated. Due to the advances in software and hardware, accuracy and costs are in the realm of acquiring experimental data. Such calculations can, for example, be done at an atomic level to compute lattice energy, fault energies, density of states and charge densities. These can lead to fundamental information about the competition between slip and fracture, anisotropy of bond strength (and therefore cleavage strength), cohesive strength, adhesive strength, elastic modulus, thermal expansion and possibly other quantities which are difficult (and therefore expensive to measure). Some of these quantities can be fed into a process model. It is probable that temperature dependencies can be derived numerically as well. Examples are given of the beginnings of such an approach for Ni 3 Al and MoSi 2 . Solidification problems are examples of the state-of-the-art process modeling and adequately demonstrate the need for extensive input data. Such processes can be monitored in terms of interfacial position vs. time, cooling rate and thermal gradient

  10. Telehealth on advanced networks.

    Science.gov (United States)

    Wilson, Laurence S; Stevenson, Duncan R; Cregan, Patrick

    2010-01-01

    We address advanced Internet for complex telehealth applications by reviewing four hospital-based broadband telehealth projects and identifying common threads. These projects were conducted in Australia under a 6-year research project on broadband Internet applications. Each project addressed specific clinical needs and its development was guided by the clinicians involved. Each project was trialed in the field and evaluated against the initial requirements. The four projects covered remote management of a resuscitation team in a district hospital, remote guidance and interpretation of echocardiography, virtual-reality-based instructor-student surgical training, and postoperative outpatient consultations following pediatric surgery. Each was characterized by a high level of interpersonal communication, a high level of clinical expertise, and multiple participants. Each made use of multiple high-quality video and audio links and shared real-time access to clinical data. Four common threads were observed. Each application provided a high level of usability and task focus because the design and use of broadband capability was aimed directly to meet the clinicians' needs. Each used the media quality available over broadband to convey words, gestures, body movements, and facial expressions to support communication and a sense of presence among the participants. Each required a complex information space shared among the participants, including real-time access to stored patient data and real-time interactive access to the patients themselves. Finally, each application supported the social and organizational aspects of their healthcare focus, creating and maintaining relationships between the various participants, and this was done by placing the telehealth application into a wider functioning clinical context. These findings provide evidence for a significantly enhanced role for appropriate telemedicine systems running on advanced networks, in a wider range of clinical

  11. Advances in Male Contraception

    Science.gov (United States)

    Page, Stephanie T.; Amory, John K.; Bremner, William J.

    2008-01-01

    Despite significant advances in contraceptive options for women over the last 50 yr, world population continues to grow rapidly. Scientists and activists alike point to the devastating environmental impacts that population pressures have caused, including global warming from the developed world and hunger and disease in less developed areas. Moreover, almost half of all pregnancies are still unwanted or unplanned. Clearly, there is a need for expanded, reversible, contraceptive options. Multicultural surveys demonstrate the willingness of men to participate in contraception and their female partners to trust them to do so. Notwithstanding their paucity of options, male methods including vasectomy and condoms account for almost one third of contraceptive use in the United States and other countries. Recent international clinical research efforts have demonstrated high efficacy rates (90–95%) for hormonally based male contraceptives. Current barriers to expanded use include limited delivery methods and perceived regulatory obstacles, which stymie introduction to the marketplace. However, advances in oral and injectable androgen delivery are cause for optimism that these hurdles may be overcome. Nonhormonal methods, such as compounds that target sperm motility, are attractive in their theoretical promise of specificity for the reproductive tract. Gene and protein array technologies continue to identify potential targets for this approach. Such nonhormonal agents will likely reach clinical trials in the near future. Great strides have been made in understanding male reproductive physiology; the combined efforts of scientists, clinicians, industry and governmental funding agencies could make an effective, reversible, male contraceptive an option for family planning over the next decade. PMID:18436704

  12. Advanced isotope separation

    International Nuclear Information System (INIS)

    1982-01-01

    The Study Group briefly reviewed the technical status of the three Advanced Isotope Separation (AIS) processes. It also reviewed the evaluation work that has been carried out by DOE's Process Evaluation Board (PEB) and the Union Carbide Corporation-Nuclear Division (UCCND). The Study Group briefly reviewed a recent draft assessment made for DOE staff of the nonproliferation implications of the AIS technologies. The staff also very briefly summarized the status of GCEP and Advanced Centrifuge development. The Study Group concluded that: (1) there has not been sufficient progress to provide a firm scientific, technical or economic basis on which to select one of the three competing AIS processes for full-scale engineering development at this time; and (2) however, should budgetary restraints or other factors force such a selection, we believe that the evaluation process that is being carried out by the PEB provides the best basis available for making a decision. The Study Group recommended that: (1) any decisions on AIS processes should include a comparison with gas centrifuge processes, and should not be made independently from the plutonium isotope program; (2) in evaluating the various enrichment processes, all applicable costs (including R and D and sales overhead) and an appropriate discounting approach should be included in order to make comparisons on a private industry basis; (3) if the three AIS programs continue with limited resources, the work should be reoriented to focus only on the most pressing technical problems; and (4) if a decision is made to develop the Atomic Vapor Laser Isotope Separation process, the solid collector option should be pursued in parallel to alleviate the potential program impact of liquid collector thermal control problems

  13. Inhibition of Nonenzymatic Protein Glycation by Pomegranate and Other Fruit Juices

    Science.gov (United States)

    Dorsey, Pamela Garner; Greenspan, Phillip

    2014-01-01

    Abstract The nonenzymatic glycation of proteins and the formation of advanced glycation endproducts in diabetes leads to the crosslinking of proteins and disease complications. Our study sought to demonstrate the effect of commonly consumed juices (pomegranate, cranberry, black cherry, pineapple, apple, and Concord grape) on the fructose-mediated glycation of albumin. Albumin glycation decreased by 98% in the presence of 10 μL of pomegranate juice/mL; other juices inhibited glycation by only 20%. Pomegranate juice produced the greatest inhibition on protein glycation when incubated at both the same phenolic concentration and the same antioxidant potential. Both punicalagin and ellagic acid significantly inhibited the glycation of albumin by ∼90% at 5 μg/mL. Sodium dodecyl sulfate–polyacrylamide gel electrophoresis revealed that pomegranate, but not apple juice, protected albumin from modification. These results demonstrate that pomegranate juice and two of its major constituents are potent inhibitors of fructose-mediated protein glycation. PMID:24433074

  14. Identification of breast cancer cell subtypes sensitive to ATG4B inhibition

    OpenAIRE

    Bortnik, Svetlana; Choutka, Courtney; Horlings, Hugo M.; Leung, Samuel; Baker, Jennifer H.; Lebovitz, Chandra; Dragowska, Wieslawa H.; Go, Nancy E.; Bally, Marcel B.; Minchinton, Andrew I.; Gelmon, Karen A.; Gorski, Sharon M.

    2016-01-01

    Autophagy, a lysosome-mediated degradation and recycling process, functions in advanced malignancies to promote cancer cell survival and contribute to cancer progression and drug resistance. While various autophagy inhibition strategies are under investigation for cancer treatment, corresponding patient selection criteria for these autophagy inhibitors need to be developed. Due to its central roles in the autophagy process, the cysteine protease ATG4B is one of the autophagy proteins being pu...

  15. Hedgehog Pathway Inhibition Radiosensitizes Non-Small Cell Lung Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Jing; Aziz, Khaled; Chettiar, Sivarajan T. [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Aftab, Blake T. [Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Armour, Michael; Gajula, Rajendra; Gandhi, Nishant; Salih, Tarek; Herman, Joseph M.; Wong, John [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Rudin, Charles M. [Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Tran, Phuoc T. [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Hales, Russell K., E-mail: rhales1@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2013-05-01

    Purpose: Despite improvements in chemoradiation, local control remains a major clinical problem in locally advanced non-small cell lung cancer. The Hedgehog pathway has been implicated in tumor recurrence by promoting survival of tumorigenic precursors and through effects on tumor-associated stroma. Whether Hedgehog inhibition can affect radiation efficacy in vivo has not been reported. Methods and Materials: We evaluated the effects of a targeted Hedgehog inhibitor (HhAntag) and radiation on clonogenic survival of human non-small cell lung cancer lines in vitro. Using an A549 cell line xenograft model, we examined tumor growth, proliferation, apoptosis, and gene expression changes after concomitant HhAntag and radiation. In a transgenic mouse model of Kras{sup G12D}-induced and Twist1-induced lung adenocarcinoma, we assessed tumor response to radiation and HhAntag by serial micro-computed tomography (CT) scanning. Results: In 4 human lung cancer lines in vitro, HhAntag showed little or no effect on radiosensitivity. By contrast, in both the human tumor xenograft and murine inducible transgenic models, HhAntag enhanced radiation efficacy and delayed tumor growth. By use of the human xenograft model to differentiate tumor and stromal effects, mouse stromal cells, but not human tumor cells, showed significant and consistent downregulation of Hedgehog pathway gene expression. This was associated with increased tumor cell apoptosis. Conclusions: Targeted Hedgehog pathway inhibition can increase in vivo radiation efficacy in lung cancer preclinical models. This effect is associated with pathway suppression in tumor-associated stroma. These data support clinical testing of Hedgehog inhibitors as a component of multimodality therapy for locally advanced non-small cell lung cancer.

  16. Quercetin-induced downregulation of phospholipase D1 inhibits proliferation and invasion in U87 glioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Park, Mi Hee [Department of Molecular Biology, College of Natural Science, Pusan National University, 30 Jangjeon dong, Geumjeong gu, Busan 609-735 (Korea, Republic of); Min, Do Sik, E-mail: minds@pusan.ac.kr [Department of Molecular Biology, College of Natural Science, Pusan National University, 30 Jangjeon dong, Geumjeong gu, Busan 609-735 (Korea, Republic of)

    2011-09-09

    Highlights: {yields} Quercetin, a bioactive flavonoid, suppresses expression and enzymatic activity of phospholipase D1. {yields} Quercetin abolishes NFkB-induced phospholipase D1 expression via inhibition of NFkB transactivation. {yields} Quercetin-induced suppression of phospholipase D1 inhibits invasion and proliferation of human glioma cells. -- Abstract: Phospholipase D (PLD) has been recognized as a regulator of cell proliferation and tumorigenesis, but little is known about the molecules regulating PLD expression. Thus, the identification of small molecules inhibiting PLD expression would be an important advance in PLD-mediated physiology. Quercetin, a ubiquitous bioactive flavonoid, is known to inhibit proliferation and induce apoptosis in a variety of cancer cells. In the present study, we examined the effect of quercetin on the expression of PLD in U87 glioma cells. Quercetin significantly suppressed the expression of PLD1 at the transcriptional level. Moreover, quercetin abolished the protein expression of PLD1 in a time and dose-dependent manner, as well as inhibited PLD activity. Quercetin suppressed NF{kappa}B-induced PLD1 expression via inhibition of NFkB transactivation. Furthermore, quercetin inhibited activation and invasion of metalloproteinase-2 (MMP-2), a key modulator of glioma cell invasion, induced by phosphatidic acid (PA), a product of PLD activity. Taken together these data demonstrate that quercetin abolishes PLD1 expression and subsequently inhibits invasion and proliferation of glioma cells.

  17. Regulation of spatial selectivity by crossover inhibition.

    Science.gov (United States)

    Cafaro, Jon; Rieke, Fred

    2013-04-10

    Signals throughout the nervous system diverge into parallel excitatory and inhibitory pathways that later converge on downstream neurons to control their spike output. Converging excitatory and inhibitory synaptic inputs can exhibit a variety of temporal relationships. A common motif is feedforward inhibition, in which an increase (decrease) in excitatory input precedes a corresponding increase (decrease) in inhibitory input. The delay of inhibitory input relative to excitatory input originates from an extra synapse in the circuit shaping inhibitory input. Another common motif is push-pull or "crossover" inhibition, in which increases (decreases) in excitatory input occur together with decreases (increases) in inhibitory input. Primate On midget ganglion cells receive primarily feedforward inhibition and On parasol cells receive primarily crossover inhibition; this difference provides an opportunity to study how each motif shapes the light responses of cell types that play a key role in visual perception. For full-field stimuli, feedforward inhibition abbreviated and attenuated responses of On midget cells, while crossover inhibition, though plentiful, had surprisingly little impact on the responses of On parasol cells. Spatially structured stimuli, however, could cause excitatory and inhibitory inputs to On parasol cells to increase together, adopting a temporal relation very much like that for feedforward inhibition. In this case, inhibitory inputs substantially abbreviated a cell's spike output. Thus inhibitory input shapes the temporal stimulus selectivity of both midget and parasol ganglion cells, but its impact on responses of parasol cells depends strongly on the spatial structure of the light inputs.

  18. Fear inhibition in high trait anxiety.

    Directory of Open Access Journals (Sweden)

    Merel Kindt

    Full Text Available Trait anxiety is recognized as an individual risk factor for the development of anxiety disorders but the neurobiological mechanisms remain unknown. Here we test whether trait anxiety is associated with impaired fear inhibition utilizing the AX+/BX- conditional discrimination procedure that allows for the independent evaluation of startle fear potentiation and inhibition of fear. Sixty undergraduate students participated in the study--High Trait Anxious: n = 28 and Low Trait Anxious: n = 32. We replicated earlier findings that a transfer of conditioned inhibition for startle responses requires contingency awareness. However, contrary to the fear inhibition hypothesis, our data suggest that high trait anxious individuals show a normal fear inhibition of conditioned startle responding. Only at the cognitive level the high trait anxious individuals showed evidence for impaired inhibitory learning of the threat cue. Together with other findings where impaired fear inhibition was only observed in those PTSD patients who were either high on hyperarousal symptoms or with current anxiety symptoms, we question whether impaired fear inhibition is a biomarker for the development of anxiety disorders.

  19. Histone Deacetylase Inhibition Restores Retinal Pigment Epithelium Function in Hyperglycemia.

    Directory of Open Access Journals (Sweden)

    Danielle Desjardins

    Full Text Available In diabetic individuals, macular edema is a major cause of vision loss. This condition is refractory to insulin therapy and has been attributed to metabolic memory. The retinal pigment epithelium (RPE is central to maintaining fluid balance in the retina, and this function is compromised by the activation of advanced glycation end-product receptors (RAGE. Here we provide evidence that acute administration of the RAGE agonist, glycated-albumin (gAlb or vascular endothelial growth factor (VEGF, increased histone deacetylase (HDAC activity in RPE cells. The administration of the class I/II HDAC inhibitor, trichostatin-A (TSA, suppressed gAlb-induced reductions in RPE transepithelial resistance (in vitro and fluid transport (in vivo. Systemic TSA also restored normal RPE fluid transport in rats with subchronic hyperglycemia. Both gAlb and VEGF increased HDAC activity and reduced acetyl-α-tubulin levels. Tubastatin-A, a relatively specific antagonist of HDAC6, inhibited gAlb-induced changes in RPE cell resistance. These data are consistent with the idea that RPE dysfunction following exposure to gAlb, VEGF, or hyperglycemia is associated with increased HDAC6 activity and decreased acetyl-α-tubulin. Therefore, we propose inhibiting HDAC6 in the RPE as a potential therapy for preserving normal fluid homeostasis in the hyperglycemic retina.

  20. Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity.

    Science.gov (United States)

    Hamilton, Gerhard; Rath, Barbara

    2017-04-01

    Immune checkpoint inhibition holds great promise for selected tumors. The human monoclonal antibody (mAB) avelumab is directed to programmed death ligand-1 (PD-L1) and is supposed to inhibit the immunosuppressive PD-L1/PD-1 interaction and, furthermore, effect antibody-dependent cytotoxicity (ADCC) lysis of tumor cells. Areas covered: This article presents an overview of the current means to activate the antitumor immune defense by targeting PD-1 or PD-L1 with mABs and their possible role in ADCC-mediated tumor cell elimination. Expert opinion: Avelumab contains a Fc region which can bind cognate receptors on immune effector cells and induce ADCC-mediated tumor cell lysis, in contrast to other mABs directed to PD-1/PD-L1 which lack the ability to trigger ADCC due to belonging to the IgG4 subclass or possessing a mutated Fc region. Preclinical and clinical data indicate that avelumab can be safely administered to cancer patients with a toxicity profile comparable to other mABs and without lysis of PD-L1-positive activated immune cells. This antibody yielded durable responses in a phase II trial in advanced Merkel cell carcinoma patients. Tumor cell lysis by avelumab prevents cells from resorting to alternative checkpoints as shown by targeting PD-1 and the upregulation of TIM-3.

  1. Simultaneous inhibition of aberrant cancer kinome using rationally designed polymer-protein core-shell nanomedicine.

    Science.gov (United States)

    Chandran, Parwathy; Gupta, Neha; Retnakumari, Archana Payickattu; Malarvizhi, Giridharan Loghanathan; Keechilat, Pavithran; Nair, Shantikumar; Koyakutty, Manzoor

    2013-11-01

    Simultaneous inhibition of deregulated cancer kinome using rationally designed nanomedicine is an advanced therapeutic approach. Herein, we have developed a polymer-protein core-shell nanomedicine to inhibit critically aberrant pro-survival kinases (mTOR, MAPK and STAT5) in primitive (CD34(+)/CD38(-)) Acute Myeloid Leukemia (AML) cells. The nanomedicine consists of poly-lactide-co-glycolide core (~250 nm) loaded with mTOR inhibitor, everolimus, and albumin shell (~25 nm thick) loaded with MAPK/STAT5 inhibitor, sorafenib and the whole construct was surface conjugated with monoclonal antibody against CD33 receptor overexpressed in AML. Electron microscopy confirmed formation of core-shell nanostructure (~290 nm) and flow cytometry and confocal studies showed enhanced cellular uptake of targeted nanomedicine. Simultaneous inhibition of critical kinases causing synergistic lethality against leukemic cells, without affecting healthy blood cells, was demonstrated using immunoblotting, cytotoxicity and apoptosis assays. This cell receptor plus multi-kinase targeted core-shell nanomedicine was found better specific and tolerable compared to current clinical regime of cytarabine and daunorubicin. These authors demonstrate simultaneous inhibition of critical kinases causing synergistic lethality against leukemic cells, without affecting healthy blood cells by using rationally designed polymer-protein core-shell nanomedicine, provoding an advanced method to eliminate cancer cells, with the hope of future therapeutic use. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Handbook of Advanced Magnetic Materials

    CERN Document Server

    Liu, Yi; Shindo, Daisuke

    2006-01-01

    From high-capacity, inexpensive hard drives to mag-lev trains, recent achievements in magnetic materials research have made the dreams of a few decades ago reality. The objective of Handbook of Advanced Magnetic Materials is to provide a timely, comprehensive review of recent progress in magnetic materials research. This broad yet detailed reference consists of four volumes: 1.) Nanostructured advanced magnetic materials, 2.) Characterization and simulation of advanced magnetic materials, 3.) Processing of advanced magnetic materials, and 4.) Properties and applications of advanced magnetic materials The first volume documents and explains recent development of nanostructured magnetic materials, emphasizing size effects. The second volume provides a comprehensive review of both experimental methods and simulation techniques for the characterization of magnetic materials. The third volume comprehensively reviews recent developments in the processing and manufacturing of advanced magnetic materials. With the co...

  3. Technical advances in radiation therapy

    International Nuclear Information System (INIS)

    Sause, W.T.

    1986-01-01

    Substantial advances have been made in radiation therapy. Many of these advances can be applied in most radiation therapy departments without expensive improvements in equipment. Changes in radiation fractionation, chemotherapeutic sensitization, intraoperative radiation, and interstitial implants can be performed with experience and improved physician training in most medium-sized departments. Advances that require investments in expensive equipment such as particle radiation and hyperthermia will need to be evaluated at designated treatment centers. 106 references

  4. Advanced action in classical electrodynamics

    OpenAIRE

    Boozer, A. D.

    2008-01-01

    The time evolution of a charged point particle is governed by a second-order integro-differential equation that exhibits advanced effects, in which the particle responds to an external force before the force is applied. In this paper we give a simple physical argument that clarifies the origin and physical meaning of these advanced effects, and we compare ordinary electrodynamics with a toy model of electrodynamics in which advanced effects do not occur.

  5. Advanced Concepts. Chapter 21

    Science.gov (United States)

    Johnson, Les; Mulqueen, Jack

    2013-01-01

    Before there is a funded space mission, there must be a present need for the mission. Space science and exploration are expensive, and without a well-defined and justifiable need, no one is going to commit significant funding for any space endeavor. However, as discussed in Chapter 1, applications of space technology and many and broad, hence there are many ways to determine and establish a mission need. Robotic science missions are justified by their science return. To be selected for flight, questions like these must be addressed: What is the science question that needs answering, and will the proposed mission be the most cost-effective way to answer it? Why does answering the question require an expensive space flight, instead of some ground-based alternative? If the question can only be answered by flying in space, then why is this approach better than other potential approaches? How much will it cost? And is the technology required to answer the question in hand and ready to use? If not, then how much will it cost and how long will it take to mature the technology to a usable level? There are also many ways to justify human exploration missions, including science return, technology advancement, as well as intangible reasons, such as national pride. Nonetheless, many of the questions that need answering, are similar to those for robotic science missions: Where are the people going, why, and will the proposed mission be the most cost-effective way to get there? What is the safest method to achieve the goal? How much will it cost? And is the technology required to get there and keep the crew alive in hand and ready to use? If not, then how much will it cost and how long will it take to mature the technology to a usable level? Another reason for some groups sending spacecraft into space is for profit. Telecommunications, geospatial imaging, and tourism are examples of proven, market-driven space missions and applications. For this specific set of users, the

  6. Advanced reactor experimental facilities

    International Nuclear Information System (INIS)

    Amri, A.; Papin, J.; Uhle, J.; Vitanza, C.

    2010-01-01

    For many years, the NEA has been examining advanced reactor issues and disseminating information of use to regulators, designers and researchers on safety issues and research needed. Following the recommendation of participants at an NEA workshop, a Task Group on Advanced Reactor Experimental Facilities (TAREF) was initiated with the aim of providing an overview of facilities suitable for carrying out the safety research considered necessary for gas-cooled reactors (GCRs) and sodium fast reactors (SFRs), with other reactor systems possibly being considered in a subsequent phase. The TAREF was thus created in 2008 with the following participating countries: Canada, the Czech Republic, Finland, France, Germany, Hungary, Italy, Japan, Korea and the United States. In a second stage, India provided valuable information on its experimental facilities related to SFR safety research. The study method adopted entailed first identifying high-priority safety issues that require research and then categorizing the available facilities in terms of their ability to address the safety issues. For each of the technical areas, the task members agreed on a set of safety issues requiring research and established a ranking with regard to safety relevance (high, medium, low) and the status of knowledge based on the following scale relative to full knowledge: high (100%-75%), medium (75 - 25%) and low (25-0%). Only the issues identified as being of high safety relevance and for which the state of knowledge is low or medium were included in the discussion, as these issues would likely warrant further study. For each of the safety issues, the TAREF members identified appropriate facilities, providing relevant information such as operating conditions (in- or out-of reactor), operating range, description of the test section, type of testing, instrumentation, current status and availability, and uniqueness. Based on the information collected, the task members assessed prospects and priorities

  7. Advanced intelligence and mechanism approach

    Institute of Scientific and Technical Information of China (English)

    ZHONG Yixin

    2007-01-01

    Advanced intelligence will feature the intelligence research in next 50 years.An understanding of the concept of advanced intelligence as well as its importance will be provided first,and detailed analysis on an approach,the mechanism approach.suitable to the advanced intelligence research will then be flolowed.And the mutual relationship among mechanism approach,traditional approaches existed in artificial intelligence research,and the cognitive informatics will be discussed.It is interesting to discover that mechanism approach is a good one to the Advanced Intelligence research and a tmified form of the existed approaches to artificial intelligence.

  8. Should we stop thinking about inhibition? Searching for individual and age differences in inhibition ability.

    Science.gov (United States)

    Rey-Mermet, Alodie; Gade, Miriam; Oberauer, Klaus

    2018-04-01

    Inhibition is often conceptualized as a unitary construct reflecting the ability to ignore and suppress irrelevant information. At the same time, it has been subdivided into inhibition of prepotent responses (i.e., the ability to stop dominant responses) and resistance to distracter interference (i.e., the ability to ignore distracting information). The present study investigated the unity and diversity of inhibition as a psychometric construct, and tested the hypothesis of an inhibition deficit in older age. We measured inhibition in young and old adults with 11 established laboratory tasks: antisaccade, stop-signal, color Stroop, number Stroop, arrow flanker, letter flanker, Simon, global-local, positive and negative compatibility tasks, and n-2 repetition costs in task switching. In both age groups, the inhibition measures from individual tasks had good reliabilities, but correlated only weakly among each other. Structural equation modeling identified a 2-factor model with factors for inhibition of prepotent responses and resistance to distracter interference. Older adults scored worse in the inhibition of prepotent response, but better in the resistance to distracter interference. However, the model had low explanatory power. Together, these findings call into question inhibition as a psychometric construct and the hypothesis of an inhibition deficit in older age. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  9. Advanced manufacturing technologies modern machining, advanced joining, sustainable manufacturing

    CERN Document Server

    2017-01-01

    This book provides details and collective information on working principle, process mechanism, salient features, and unique applications of various advanced manufacturing techniques and processes belong. The book is divided in three sessions covering modern machining methods, advanced repair and joining techniques and, finally, sustainable manufacturing. The latest trends and research aspects of those fields are highlighted.

  10. Advances in chemical physics advances in liquid crystals

    CERN Document Server

    Prigogine, Ilya; Vij, Jagdish K

    2009-01-01

    Prigogine and Rice's highly acclaimed series, Advances in Chemical Physics, provides a forum for critical, authoritative reviews of current topics in every area of chemical physics. Edited by J.K. Vij, this volume focuses on recent advances in liquid crystals with significant, up-to-date chapters authored by internationally recognized researchers in the field.

  11. Inhibition of urinary calculi -- a spectroscopic study

    Science.gov (United States)

    Manciu, Felicia; Govani, Jayesh; Durrer, William; Reza, Layra; Pinales, Luis

    2008-10-01

    Although a considerable number of investigations have already been undertaken and many causes such as life habits, metabolic disorders, and genetic factors have been noted as sources that accelerate calculi depositions and aggregations, there are still plenty of unanswered questions regarding efficient inhibition and treatment mechanisms. Thus, in an attempt to acquire more insights, we propose here a detailed scientific study of kidney stone formation and growth inhibition based on a traditional medicine approach with Rotula Aquatica Lour (RAL) herbal extracts. A simplified single diffusion gel growth technique was used for synthesizing the samples for the present study. The unexpected Zn presence in the sample with RAL inhibitor, as revealed by XPS measurements, explains the inhibition process and the dramatic reflectance of the incident light observed in the infrared transmission studies. Raman data demonstrate potential binding of the inhibitor with the oxygen of the kidney stone. Photoluminescence results corroborate to provide additional evidence of Zn-related inhibition.

  12. Exogenously triggered response inhibition in developmental stuttering.

    Science.gov (United States)

    Eggers, Kurt; De Nil, Luc F; Van den Bergh, Bea R H

    2018-06-01

    The purpose of the present study was to examine relations between children's exogenously triggered response inhibition and stuttering. Participants were 18 children who stutter (CWS; mean age = 9;01 years) and 18 children who not stutter (CWNS; mean age = 9;01 years). Participants were matched on age (±3 months) and gender. Response inhibition was assessed by a stop signal task (Verbruggen, Logan, & Stevens, 2008). Results suggest that CWS, compared to CWNS, perform comparable to CWNS in a task where response control is externally triggered. Our findings seem to indicate that previous questionnaire-based findings (Eggers, De Nil, & Van den Bergh, 2010) of a decreased efficiency of response inhibition cannot be generalized to all types of response inhibition. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Hypnotic suggestibility, cognitive inhibition, and dissociation.

    Science.gov (United States)

    Dienes, Zoltán; Brown, Elizabeth; Hutton, Sam; Kirsch, Irving; Mazzoni, Giuliana; Wright, Daniel B

    2009-12-01

    We examined two potential correlates of hypnotic suggestibility: dissociation and cognitive inhibition. Dissociation is the foundation of two of the major theories of hypnosis and other theories commonly postulate that hypnotic responding is a result of attentional abilities (including inhibition). Participants were administered the Waterloo-Stanford Group Scale of Hypnotic Susceptibility, Form C. Under the guise of an unrelated study, 180 of these participants also completed: a version of the Dissociative Experiences Scale that is normally distributed in non-clinical populations; a latent inhibition task, a spatial negative priming task, and a memory task designed to measure negative priming. The data ruled out even moderate correlations between hypnotic suggestibility and all the measures of dissociation and cognitive inhibition overall, though they also indicated gender differences. The results are a challenge for existing theories of hypnosis.

  14. Corrosion inhibition by lithium zinc phosphate pigment

    International Nuclear Information System (INIS)

    Alibakhshi, E.; Ghasemi, E.; Mahdavian, M.

    2013-01-01

    Highlights: •Synthesis of lithium zinc phosphate (LZP) by chemical co-precipitation method. •Corrosion inhibition activity of pigments compare with zinc phosphate (ZP). •LZP showed superior corrosion inhibition effect in EIS measurements. •Evaluation of adhesion strength and dispersion stability. -- Abstract: Lithium zinc phosphate (LZP) has been synthesized through a co-precipitation process and characterized by XRD and IR spectroscopy. The inhibitive performances of this pigment for corrosion of mild steel have been discussed in comparison with the zinc phosphate (ZP) in the pigment extract solution by means of EIS and in the epoxy coating by means of salt spray. The EIS and salt spray results revealed the superior corrosion inhibitive effect of LZP compared to ZP. Moreover, adhesion strength and dispersion stability of the pigmented epoxy coating showed the advantage of LZP compared to ZP

  15. Advances in transplantation immunology.

    Science.gov (United States)

    Morris, P J

    1987-09-01

    Although there have been dramatic advances in clinical organ transplantation over the past 20 years, rejection, both acute and chronic, and the complications of immunosuppression remain major problems. Nevertheless as our understanding of the immune response to a vascularized organ allograft develops, so too will our ability to develop more specific immunosuppression. In any strategy for more specific immunosuppression compatibility for the major histocompatibility complex of antigens (HLA in man) is likely to be important. Monoclonal antibodies to T cell subpopulations, or even to T cells specifically activated by the graft, provide methods of suppressing the immune response at a more specific level. The recognition that stable grafts are maintained, at least in experimental rodent models, by T suppressor cells may allow development of precise methods of inducing the generation of such cells in clinical practice. The induction of tolerance in the adult animal can be achieved in a number of ways, the most promising of which for clinical application, is antigen pretreatment. If tolerance could be achieved in clinical practice within the not too distant future, then this would represent the attainment of the ultimate goal of transplantation.

  16. Advanced microwave processing concepts

    Energy Technology Data Exchange (ETDEWEB)

    Lauf, R.J.; McMillan, A.D.; Paulauskas, F.L. [Oak Ridge National Laboratory, TN (United States)

    1995-05-01

    The purpose of this work is to explore the feasibility of several advanced microwave processing concepts to develop new energy-efficient materials and processes. The project includes two tasks: (1) commercialization of the variable-frequency microwave furnace; and (2) microwave curing of polymer composites. The variable frequency microwave furnace, whose initial conception and design was funded by the AIC Materials Program, will allow us, for the first time, to conduct microwave processing studies over a wide frequency range. This novel design uses a high-power traveling wave tube (TWT) originally developed for electronic warfare. By using this microwave source, one can not only select individual microwave frequencies for particular experiments, but also achieve uniform power densities over a large area by the superposition of many different frequencies. Microwave curing of thermoset resins will be studied because it hold the potential of in-situ curing of continuous-fiber composites for strong, lightweight components. Microwave heating can shorten curing times, provided issues of scaleup, uniformity, and thermal management can be adequately addressed.

  17. Advanced Manufacture of Reflectors

    Energy Technology Data Exchange (ETDEWEB)

    Angel, Roger [Univ. of Arizona, Tucson, AZ (United States)

    2014-12-17

    The main project objective has been to develop an advanced gravity sag method for molding large glass solar reflectors with either line or point focus, and with long or short focal length. The method involves taking standard sized squares of glass, 1.65 m x 1.65 m, and shaping them by gravity sag into precision steel molds. The method is designed for high volume manufacture when incorporated into a production line with separate pre-heating and cooling. The performance objectives for the self-supporting glass mirrors made by this project include mirror optical accuracy of 2 mrad root mean square (RMS), requiring surface slope errors less than 1 mrad rms, a target not met by current production of solar reflectors. Our objective also included development of new methods for rapidly shaping glass mirrors and coating them for higher reflectivity and soil resistance. Reflectivity of 95% for a glass mirror with anti-soil coating was targeted, compared to the present ~94% with no anti-soil coating. Our mirror cost objective is ~$20/m2 in 2020, a significant reduction compared to the present ~$35/m2 for solar trough mirrors produced for trough solar plants.

  18. Advanced Solar Panel Designs

    Science.gov (United States)

    Ralph, E. L.; Linder, E. B.

    1995-01-01

    Solar panel designs that utilize new high-efficiency solar cells and lightweight rigid panel technologies are described. The resulting designs increase the specific power (W/kg) achievable in the near-term and are well suited to meet the demands of higher performance small satellites (smallsats). Advanced solar panel designs have been developed and demonstrated on two NASA SBIR contracts at Applied Solar. The first used 19% efficient, large area (5.5 cm x 6.5 cm) GaAs/Ge solar cells with a lightweight rigid graphite epoxy isogrid substrate configuration. A 1,445 sq cm coupon was fabricated and tested to demonstrate 60 W/kg with a high potential of achieving 80 W/kg. The second panel design used new 22% efficiency, dual-junction GaInP2/GaAs/Ge solar cells combined with a lightweight aluminum core/graphite fiber mesh facesheet substrate. A 1,445 sq cm coupon was fabricated and tested to demonstrate 105 W/kg with the potential of achieving 115 W/kg.

  19. The advanced composition explorer

    International Nuclear Information System (INIS)

    Stone, E.C.; Burlaga, L.F.; Cummings, A.C.; Feldman, W.C.; Frain, W.E.; Geiss, J.; Gloeckler, G.; Gold, R.E.; Hovestadt, D.; Krimigis, S.M.; Mason, G.M.; McComas, D.; Mewaldt, R.A.; Simpson, J.A.; von Rosenvinge, T.T.; Wiedenbeck, M.E.

    1990-01-01

    The Advanced Composition Explorer (ACE) was recently selected as one of two new Explorer-class missions to be developed for launch during the mid-1990's ACE will observe particles of solar, interplanetary, interstellar, and galactic origins, spanning the energy range from that of the solar wind (∼1 keV/nucleon) to galactic cosmic ray energies (several hundred MeV/nucleon). Definitive studies will be made of the abundance of nearly all isotopes from H to Zn (1≤Z≤30), with exploratory isotope studies extending to Zr(Z=40). To accomplish this, the ACE payload includes six high-resolution spectrometers, each designed to provide the optimum charge, mass, or charge-state resolution in its particular energy range, and each having a geometry factor optimized for the expected flux levels, so as to provide a collecting power a factor of 10 to 1000 times greater than previous or planned experiments. The payload also includes several instruments of standard design that will monitor solar wind and magnetic field conditions and energetic H, He, and electron fluxes. We summarize here the scientific objectives, instrumentation, spacecraft, and mission approach that were defined for ACE during the Phase-A study period

  20. Advanced Hydrogen Turbine Development

    Energy Technology Data Exchange (ETDEWEB)

    Joesph Fadok

    2008-01-01

    advanced hydrogen turbine that meets the aggressive targets set forth for the advanced hydrogen turbine, including increased rotor inlet temperature (RIT), lower total cooling and leakage air (TCLA) flow, higher pressure ratio, and higher mass flow through the turbine compared to the baseline. Maintaining efficiency with high mass flow Syngas combustion is achieved using a large high AN2 blade 4, which has been identified as a significant advancement beyond the current state-of-the-art. Preliminary results showed feasibility of a rotor system capable of increased power output and operating conditions above the baseline. In addition, several concepts were developed for casing components to address higher operating conditions. Rare earth modified bond coat for the purpose of reducing oxidation and TBC spallation demonstrated an increase in TBC spallation life of almost 40%. The results from Phase 1 identified two TBC compositions which satisfy the thermal conductivity requirements and have demonstrated phase stability up to temperatures of 1850 C. The potential to join alloys using a bonding process has been demonstrated and initial HVOF spray deposition trials were promising. The qualitative ranking of alloys and coatings in environmental conditions was also performed using isothermal tests where significant variations in alloy degradation were observed as a function of gas composition. Initial basic system configuration schematics and working system descriptions have been produced to define key boundary data and support estimation of costs. Review of existing materials in use for hydrogen transportation show benefits or tradeoffs for materials that could be used in this type of applications. Hydrogen safety will become a larger risk than when using natural gas fuel as the work done to date in other areas has shown direct implications for this type of use. Studies were conducted which showed reduced CO{sub 2} and NOx emissions with increased plant efficiency. An approach to