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Sample records for ho-1 tg group

  1. Heme oxygenase-1 (HO-1) inhibits postmyocardial infarct remodeling and restores ventricular function.

    Liu, Xiaoli; Pachori, Alok S; Ward, Christopher A; Davis, J Paul; Gnecchi, Massimiliano; Kong, Deling; Zhang, Lunan; Murduck, Jared; Yet, Shaw-Fang; Perrella, Mark A; Pratt, Richard E; Dzau, Victor J; Melo, Luis G

    2006-02-01

    We reported previously that predelivery of the anti-oxidant gene heme oxygenase-1 (HO-1) to the heart by adeno associated virus (AAV) markedly reduces injury after acute myocardial infarction (MI). However, the effect of HO-1 gene delivery on postinfarction recovery has not been investigated. In the current study, we assessed the effect of HO-1 gene delivery on post-MI left ventricle (LV) remodeling and function using echocardiographic imaging and histomorphometric approaches. Two groups of Sprague-Dawley rats were injected with 4 x 10(11) particles of AAV-LacZ (control) or AAV-hHO-1 in the LV wall. Eight wk after gene transfer, the animals were subjected to 30 min of ischemia by ligation of left anterior descending artery (LAD) followed by reperfusion. Echocardiographic measurements were obtained in a blinded fashion prior and at 1.5 and 3 months after I/R. Ejection fraction (EF) was reduced by 13% and 40% in the HO-1 and LacZ groups, respectively at 1.5 months after MI. Three months after MI, EF recovered fully in the HO-1, but only partially in the LacZ-treated animals. Post-MI LV dimensions were markedly increased and the anterior wall was markedly thinned in the LacZ-treated animals compared with the HO-1-treated animals. Significant myocardial scarring and fibrosis were observed in the LacZ-group in association with elevated levels of interstitial collagen I and III and MMP-2 activity. Post-MI myofibroblast accumulation was reduced in the HO-1-treated animals, and retroviral overexpression of HO-1 reduced proliferation of isolated cardiac fibroblasts. Our data indicate that rAAV-HO-1 gene transfer markedly reduces fibrosis and ventricular remodeling and restores LV function and chamber dimensions after myocardial infarction.

  2. Mechanisms of HO-1 mediated attenuation of renal immune injury: a gene profiling study.

    Duann, Pu; Lianos, Elias A

    2011-10-01

    Using a mouse model of immune injury directed against the renal glomerular vasculature and resembling human forms of glomerulonephritis (GN), we assessed the effect of targeted expression of the cytoprotective enzyme heme oxygenase (HO)-1. A human (h) HO-1 complementary DNAN (cDNA) sequence was targeted to glomerular epithelial cells (GECs) using a GEC-specific murine nephrin promoter. Injury by administration of antibody against the glomerular basement membrane (anti-GBM) to transgenic (TG) mice with GEC-targeted hHO-1 was attenuated compared with wild-type (WT) controls. To explore changes in the expression of genes that could mediate this salutary effect, we performed gene expression profiling using a microarray analysis of RNA isolated from the renal cortex of WT or TG mice with or without anti-GBM antibody-induced injury. Significant increases in expression were detected in 9 major histocompatibility complex (MHC)-class II genes, 2 interferon-γ (IFN-γ)-inducible guanosine triphosphate (GTP)ases, and 3 genes of the ubiquitin-proteasome system. The increase in MHC-class II and proteasome gene expression in TG mice with injury was validated by real-time polymerase chain reaction (PCR) or Western blot analysis. The observations point to novel mechanisms underlying the cytoprotective effect of HO-1 in renal immune injury. Copyright © 2011. Published by Mosby, Inc.

  3. Embryotoxicity Caused by DON-Induced Oxidative Stress Mediated by Nrf2/HO-1 Pathway

    Miao Yu

    2017-06-01

    Full Text Available Deoxynivalenol (DON belongs to the type B group of trichothecenes family, which is composed of sesquiterpenoid metabolites produced by Fusarium and other fungi in grain. DON may cause various toxicities, such as cytotoxicity, immunotoxicity, genotoxicity as well as teratogenicity and carcinogenicity. In the present study, we focus on a hypothesis that DON alters the expressions of Nrf2/HO-1 pathway by inducing embryotoxicity in C57BL/6 mouse (5.0, 2.5, 1.0, and 0 mg/kg/day and BeWo cell lines (0 and 50 nM; 3 h, 12 h and 24 h. Our results indicate that DON treatment in mice during pregnancy leads to ROS accumulation in the placenta, which results in embryotoxicity. At the same time Nrf2/HO-1 pathway is up-regulated by ROS to protect placenta cells from oxidative damage. In DON-treated BeWo cells, the level of ROS has time–effect and dose–effect relationships with HO-1 expression. Moderate increase in HO-1 protects the cell from oxidative damage, while excessive increase in HO-1 aggravates the oxidative damage, which is called in some studies the “threshold effect”. Therefore, oxidative stress may be the critical molecular mechanism for DON-induced embryotoxicity. Besides, Nrf2/HO-1 pathway accompanied by the “threshold effect” also plays an important role against DON-induced oxidative damage in this process.

  4. Production and characterization of soluble human TNFRI-Fc and human HO-1(HMOX1) transgenic pigs by using the F2A peptide.

    Park, Sol Ji; Cho, Bumrae; Koo, Ok Jae; Kim, Hwajung; Kang, Jung Taek; Hurh, Sunghoon; Kim, Su Jin; Yeom, Hye Jung; Moon, Joonho; Lee, Eun Mi; Choi, Ji Yei; Hong, Ju Ho; Jang, Goo; Hwang, Joing-Ik; Yang, Jaeseok; Lee, Byeong Chun; Ahn, Curie

    2014-06-01

    Generation of transgenic pigs for xenotransplantation is one of the most promising technologies for resolving organ shortages. Human heme oxygenase-1 (hHO-1/HMOX1) can protect transplanted organs by its strong anti-oxidative, anti-apoptotic, and anti-inflammatory effects. Soluble human TNFRI-Fc (shTNFRI-Fc) can inhibit the binding of human TNF-α (hTNF-α) to TNF receptors on porcine cells, and thereby, prevent hTNF-α-mediated inflammation and apoptosis. Herein, we successfully generated shTNFRI-Fc-F2A-HA-hHO-1 transgenic (TG) pigs expressing both shTNFRI-Fc and hemagglutinin-tagged-human heme oxygenase-1 (HA-hHO-1) by using an F2A self-cleaving peptide. shTNFRI-Fc and HA-hHO-1 transgenes containing the F2A peptide were constructed under the control of the CAG promoter. Transgene insertion and copy number in the genome of transgenic pigs was confirmed by polymerase chain reaction (PCR) and Southern blot analysis. Expressions of shTNFRI-Fc and HA-hHO-1 in TG pigs were confirmed using PCR, RT-PCR, western blot, ELISA, and immunohistochemistry. shTNFRI-Fc and HA-hHO-1 were expressed in various organs, including the heart, lung, and spleen. ELISA assays detected shTNFRI-Fc in the sera of TG pigs. For functional analysis, fibroblasts isolated from a shTNFRI-Fc-F2A-HA-hHO-1 TG pig (i.e., #14; 1 × 10(5) cells) were cultured with hTNF-α (20 ng/mL) and cycloheximide (10 μg/mL). The viability of shTNFRI-Fc-F2A-HA-hHO-1 TG pig fibroblasts was significantly higher than that of the wild type (wild type vs. shTNFRI-Fc-F2A-HA-hHO-1 TG at 24 h, 31.6 ± 3.2 vs. 60.4 ± 8.3 %, respectively; p hHO-1 TG pig fibroblasts was lower than that of the wild type pig fibroblasts (wild type vs. shTNFRI-Fc-F2A-HA-hHO-1 TG at 12 h, 812,452 ± 113,078 RLU vs. 88,240 ± 10,438 RLU, respectively; p hHO-1 TG pigs generated by the F2A self-cleaving peptide express both shTNFRI-Fc and HA-hHO-1 molecules, which provides protection against oxidative and inflammatory injury

  5. hHO-1 combined with GATA-4 transduction promotes myocardial transdifferentiation and anti- apoptosis of rat mesenchymal stem cells

    Ning-bo DENG

    2017-06-01

    Full Text Available Objectives To explore if the rat bone marrow mesenchymal stem cells (BMSCs modified by human heme oxygenase 1 (hHO-1 gene combined with GATA-4 gene may promote the ability of anti-apoptosis and myocardial transdifferentiation in vitro in hypoxia ischemic environment. Methods The rat BMSCs were isolated and cultured by whole bone marrow adherence and identified in vitro, and then were transfected with recombinant adenovirus; Western blotting was used to determinate the optimal time of gene expression; the genetically modified BMSCs were taken to hypoxia serum-free conditions simulating ischemia hypoxia microenvironment in vivo; CCK-8 kit and trypan blue staining were performed to detect the 12, 24, 48 and 72h survival rates in hypoxia ischemia respectively; flow cytometry was used to detect the apoptosis of BMSCs in hypoxia ischemia for 24h. The cardiomyocyte-specific cardiac troponin I (cTnI was detected by Western blotting and cellular immunofluorescence. Results The 12, 24, 48 and 72h survival rates were higher in hHO-1+GATA-4 group cultured in ischemia and hypoxia condition than in hHO-1 group (P<0.05 and GATA-4 group (P<0.05. After 24h cultivation in ischemia hypoxia condition, the apoptotic rates were lower in hHO-1+GATA-4 group than in hHO-1 group (P<0.05 and GATA-4 group (P<0.05. No significant difference existed in cTnI expressions between GATA-4 group and hHO-1+GATA-4 group. Conclusion Compared with transfection of hHO-1 or GATA-4 single gene, hHO-1 combined with GATA-4 transduction can significantly increase the survival rate of BMSCs in hypoxia ischemic condition, but myocardial transdifferentiation does not increase significantly. DOI: 10.11855/j.issn.0577-7402.2017.04.08

  6. EGR-1 regulates Ho-1 expression induced by cigarette smoke

    Chen, Huaqun; Wang, Lijuan; Gong, Tao; Yu, Yang; Zhu, Chunhua; Li, Fen; Wang, Li; Li, Chaojun

    2010-01-01

    As an anti-oxidant molecule, heme oxygenase-1 (HO-1) has been implicated in the protection of lung injury by cigarette smoke (CS). The mechanisms regulating its expression have not been defined. In this report, the role of early growth response 1 (EGR-1) in the regulation of Ho-1 expression was investigated. In C57BL/6 mice with CS exposure, HO-1 was greatly increased in bronchial epithelial cells and alveolar inflammatory cells. In primary cultured mouse lung fibroblasts and RAW264.7 cells exposed to cigarette smoke water extract (CSE), an increase in HO-1 protein level was detected. In addition, CSE induced HO-1 expression was decreased in Egr-1 deficient mouse embryo fibroblasts (Egr-1 -/- MEFs). Nuclear localization of EGR-1 was examined in mouse lung fibroblasts after exposure to CSE. Luciferase reporter activity assays showed that the enhancer region of the Ho-1 gene containing a proposed EGR-1 binding site was responsible for the induction of HO-1. A higher increase of alveolar mean linear intercept (Lm) was observed in lung tissues, and a larger increase in the number of total cells and monocytes/macrophages from bronchial alveolar lavage fluid was found in CS-exposed mice by loss of function of EGR-1 treatment. In summary, the present data demonstrate that EGR-1 plays a critical role in HO-1 production induced by CS.

  7. Role and molecular mechanism of HO-1-mediated NF-κB modulation in fibrosis progression of nonalcoholic steatohepatitis

    NAN Yuemin

    2013-05-01

    Full Text Available ObjectiveTo investigate the potential effects and molecular mechanisms of heme oxygenase-1 (HO-1-mediated modulation of nuclear factor-kappa B (NF-κB, and its downstream activation of intercellular adhesion molecule 1 (ICAM-1 and platelet derived growth factor (PDGF, in fibrosis progression of non-alcoholic steatohepatitis (NASH using the methionine and choline deficient (MCD mouse model of NASH. Methods Forty C57BL/6J male mice (18-20 g were randomly divided into four groups (n=10 each: NASH model group, administered the MCD diet; HO-1 agonist group, administered the MCD diet with intraperitoneal (ip injections of hemin (30 μmol/kg every other day; HO-1 inhibitor group, administered the MCD diet with ip injections of zinc protoporphyrin (ZnPP-IX; 20 μmol/kg every other day; and control group, administered a methionine and choline sufficient (MCS diet, without agonist nor inhibitor injections. After eight weeks, the mice were sacrificed and resected liver tissues used to assess successful model establishment by histological analysis (hematoxylin-eosin and Masson staining and the differential mRNA expression of HO-1, NF-κB, ICAM-1, and PDGF by real-time quantitative PCR (GAPDH normalized and protein expression of HO-1 and PDGF by western blotting ( β-actin normalized. Significance of an intergroup difference was assessed by single-factor analysis of variance test, and the Student-Newman-Keuls test was used for pairwise comparisons. ResultsThe NASH model group showed the appropriate histologic features of hepatic steatosis, necroinflammation and fibrogenesis, while the control group showed normal lobular architecture. In addition, the NASH model group showed significantly higher expression of HO-1, NF-κB, ICAM-1 and PDGF mRNA (all P<0.05, and concomitant increases in HO-1 and PDGF protein. The group treated with HO-1 agonist showed significant down-regulation of the NASH-induced NF-κB, ICAM-1 and PDGF expressions, while the opposite

  8. HO-1 gene overexpression enhances the beneficial effects of superparamagnetic iron oxide labeled bone marrow stromal cells transplantation in swine hearts underwent ischemia/reperfusion: an MRI study.

    Jiang, Yibo; Chen, Lijuan; Tang, Yaoliang; Ma, Genshan; Shen, Chengxing; Qi, Chunmei; Zhu, Qi; Yao, Yuyu; Liu, Naifeng

    2010-05-01

    To determine the effect of intracoronary transfer of superparamagnetic iron oxide (SPIO) labeled heme oxygenase-1 (HO-1) overexpressed bone marrow stromal cells (BMSCs) in a porcine myocardial ischemia/reperfusion model. Cell apoptosis was assayed and supernatant cytokine concentrations were measured in BMSCs that underwent hypoxia/reoxygen in vitro. Female mini-swines that underwent 1 h LAD occlusion followed by 1 h reperfusion were randomly allocated to receive intracoronary saline (control), 1 x 10(7) SPIO-labeled BMSCs transfected with pcDNA3.1-Lacz plasmid (Lacz-BMSCs), pcDNA3.1-human HO-1 (HO-1-BMSCs), pcDNA3.1-hHO-1 pretreated with a HO inhibitor, tin protoporphyrin (SnPP, n = 10 each). MRI and postmortem histological analysis were made at 1 week or 3 months thereafter. Post hypoxia/reoxygen in vitro, apoptosis was significantly reduced, supernatant VEGF significantly increased while TNF-alpha and IL-6 significantly reduced in HO-1-BMSCs group compared with Lacz-BMSCs group (all p < 0.05). Myocardial expression of VEGF was significantly higher in HO-1-BMSCs than in Lacz-BMSCs group at 1 week post transplantation (all p < 0.05). Signal voids induced by the SPIO were detected in the peri-infarction region in all BMSC groups at 1 week but not at 3 months post transplantation and the extent of the hypointense signal was the highest in HO-1-BMSCs group, and histological analysis showed that signal voids represented cardiac macrophages that engulfed the SPIO-labeled BMSCs. Pretreatment with SnPP significantly attenuated the beneficial effects of HO-1-BMSCs. Transplantation of HO-1-overexpressed BMSCs significantly enhanced the beneficial effects of BMSCs on improving cardiac function in this model.

  9. The effects of lead exposure on the expression of HMGB1 and HO-1 in rats and PC12 cells.

    Yang, Meiyuan; Li, Yaobin; Wang, Ying; Cheng, Nuo; Zhang, Yi; Pang, Shimin; Shen, Qiwei; Zhao, Lijuan; Li, Guilin; Zhu, Gaochun

    2018-05-15

    Lead (Pb) is an environmental neurotoxic metal. Chronic exposure to Pb causes deficits of learning and memory in children and spatial learning deficits in developing rats. In this study we investigated the effects of Pb exposure on the expression of HMGB1 and HO-1 in rats and PC12 cells. The animals were randomly divided to three groups: control group; low lead exposure group; high lead exposure group; PC12 cells were divided into 3 groups: 0 μM (control group), 1 μM and 100 μM Pb acetate. The results showed that Pb levels in blood and brain of Pb exposed groups were significantly higher than that of the control group (p < 0.05). The expression of HMGB1 and HO-1 were increased in Pb exposed groups than that of the control group (p < 0.05). Moreover, we found that the up-regulation of HO-1 in Pb exposure environment inhibited the expression of HMGB1. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. [hHO-1 structure prediction and its mutant construct, expression, purification and activity analysis].

    Xia, Zhen Wei; Cui, Wen Jun; Zhou, Wen Pu; Zhang, Xue Hong; Shen, Qing Xiang; Li, Yun Zhu; Yu, Shan Chang

    2004-10-01

    Human Heme Oxygenase-1 (hHO-1) is the rate-limiting enzyme in the catabolism reaction of heme, which directly regulates the concentration of bilirubin in human body. The mutant structure was simulated by Swiss-pdbviewer procedure, which showed that the structure of active pocket was changed distinctly after Ala25 substituted for His25 in active domain, but the mutated enzyme still binded with heme. On the basis of the results, the expression vectors, pBHO-1 and pBHO-1(M), were constructed, induced by IPTG and expressed in E. coli DH5alpha strain. The expression products were purified with 30%-60% saturation (NH4)2SO4 and Q-Sepharose Fast Flow column chromatography. The concentration of hHO-1 in 30%-60% saturation (NH4)2SO4 components and in fractions through twice column chromatography was 3.6-fold and 30-fold higher than that in initial product, respectively. The activity of wild hHO-1 (whHO-1) and mutant hHO-1 (deltahHO-1) showed that the activity of deltahHO-1 was reduced 91.21% compared with that of whHO-1. The study shows that His25 is of importance for the mechanism of hHO-1, and provides the possibility for effectively regulating the activity to exert biological function.

  11. Extratumoral Heme Oxygenase-1 (HO-1 Expressing Macrophages Likely Promote Primary and Metastatic Prostate Tumor Growth.

    Sofia Halin Bergström

    Full Text Available Aggressive tumors induce tumor-supporting changes in the benign parts of the prostate. One factor that has increased expression outside prostate tumors is hemoxygenase-1 (HO-1. To investigate HO-1 expression in more detail, we analyzed samples of tumor tissue and peritumoral normal prostate tissue from rats carrying cancers with different metastatic capacity, and human prostate cancer tissue samples from primary tumors and bone metastases. In rat prostate tumor samples, immunohistochemistry and quantitative RT-PCR showed that the main site of HO-1 synthesis was HO-1+ macrophages that accumulated in the tumor-bearing organ, and at the tumor-invasive front. Small metastatic tumors were considerably more effective in attracting HO-1+ macrophages than larger non-metastatic ones. In clinical samples, accumulation of HO-1+ macrophages was seen at the tumor invasive front, almost exclusively in high-grade tumors, and it correlated with the presence of bone metastases. HO-1+ macrophages, located at the tumor invasive front, were more abundant in bone metastases than in primary tumors. HO-1 expression in bone metastases was variable, and positively correlated with the expression of macrophage markers but negatively correlated with androgen receptor expression, suggesting that elevated HO-1 could be a marker for a subgroup of bone metastases. Together with another recent observation showing that selective knockout of HO-1 in macrophages reduced prostate tumor growth and metastatic capacity in animals, the results of this study suggest that extratumoral HO-1+ macrophages may have an important role in prostate cancer.

  12. HO-1-mediated macroautophagy: a mechanism for unregulated iron deposition in aging and degenerating neural tissues.

    Zukor, Hillel; Song, Wei; Liberman, Adrienne; Mui, Jeannie; Vali, Hojatollah; Fillebeen, Carine; Pantopoulos, Kostas; Wu, Ting-Di; Guerquin-Kern, Jean-Luc; Schipper, Hyman M

    2009-05-01

    Oxidative stress, deposition of non-transferrin iron, and mitochondrial insufficiency occur in the brains of patients with Alzheimer disease (AD) and Parkinson disease (PD). We previously demonstrated that heme oxygenase-1 (HO-1) is up-regulated in AD and PD brain and promotes the accumulation of non-transferrin iron in astroglial mitochondria. Herein, dynamic secondary ion mass spectrometry (SIMS) and other techniques were employed to ascertain (i) the impact of HO-1 over-expression on astroglial mitochondrial morphology in vitro, (ii) the topography of aberrant iron sequestration in astrocytes over-expressing HO-1, and (iii) the role of iron regulatory proteins (IRP) in HO-1-mediated iron deposition. Astroglial hHO-1 over-expression induced cytoplasmic vacuolation, mitochondrial membrane damage, and macroautophagy. HO-1 promoted trapping of redox-active iron and sulfur within many cytopathological profiles without impacting ferroportin, transferrin receptor, ferritin, and IRP2 protein levels or IRP1 activity. Thus, HO-1 activity promotes mitochondrial macroautophagy and sequestration of redox-active iron in astroglia independently of classical iron mobilization pathways. Glial HO-1 may be a rational therapeutic target in AD, PD, and other human CNS conditions characterized by the unregulated deposition of brain iron.

  13. Paracrine action of HO-1-modified mesenchymal stem cells mediates cardiac protection and functional improvement.

    Zeng, Bin; Ren, Xiaofeng; Lin, Guosheng; Zhu, Chengang; Chen, Honglei; Yin, Jiechao; Jiang, Hong; Yang, Bo; Ding, Danhua

    2008-10-01

    The aim has been to determine whether the supernatants of mesenchymal stem cells (MSCs) transfected with adenovirus carrying human heme oxygenase-1 (hHO-1) gene protect cardiomyocytes from ischemic injury. We have found that hHO-1 infected MSCs (hHO-1-MSCs) increased expression of hHO-1 protein. Apoptosis of cultured hHO-1-MSCs exposed to hypoxia was suppressed. Several cytokines, including HGF, bFGF, TGF-beta, VEGF and IL-1beta, were produced by hHO-1-MSCs, some being significantly enhanced under hypoxia stimulation. Meanwhile, those cytokines reduced caspase-3 level and activity in cultured adult rat ventricular cardiomyocytes (ARVCs) exposed to hypoxia. Supernatants obtained from hHO-1-MSCs improved left ventricular function, limited myocardial infarct size, increased microvessel density, and inhibited apoptosis of cardiomyocytes in rat myocardial infarction. It can be concluded hHO-1-modified MSCs prevent myocardial cell injury via secretion of paracrine-acting mediators.

  14. HO-1 Upregulation Attenuates Adipocyte Dysfunction, Obesity, and Isoprostane Levels in Mice Fed High Fructose Diets

    Zeid Khitan

    2014-01-01

    Full Text Available Background. Fructose metabolism is an unregulated metabolic pathway and excessive fructose consumption is known to activate ROS. HO-1 is a potent antioxidant gene that plays a key role in decreasing ROS and isoprostanes. We examined whether the fructose-mediated increase in adipocyte dysfunction involves an increase in isoprostanes and that pharmacological induction of HO-1 would decrease both isoprostane levels and adipogenesis. Methods and Results. We examined the effect of fructose, on adipogenesis in human MSCs in the presence and absence of CoPP, an inducer of HO-1. Fructose increased adipogenesis and the number of large lipid droplets while decreasing the number of small lipid droplets (P<0.05. Levels of heme and isoprostane in fructose treated MSC-derived adipocytes were increased. CoPP reversed these effects and markedly increased HO-1 and the Wnt signaling pathway. The high fructose diet increased heme levels in adipose tissue and increased circulating isoprostane levels (P<0.05 versus control. Fructose diets decreased HO-1 and adiponectin levels in adipose tissue. Induction of HO-1 by CoPP decreased isoprostane synthesis (P<0.05 versus fructose. Conclusion. Fructose treatment resulted in increased isoprostane production and adipocyte dysfunction, which was reversed by the increased expression of HO-1.

  15. GEC-targeted HO-1 expression reduces proteinuria in glomerular immune injury.

    Duann, Pu; Lianos, Elias A

    2009-09-01

    Induction of heme oxygenase (HO)-1 is a key defense mechanism against oxidative stress. Compared with tubules, glomeruli are refractory to HO-1 upregulation in response to injury. This can be a disadvantage as it may be associated with insufficient production of cytoprotective heme-degradation metabolites. We, therefore, explored whether 1) targeted HO-1 expression can be achieved in glomeruli without altering their physiological integrity and 2) this expression reduces proteinuria in immune injury induced by an anti-glomerular basement membrane (GBM) antibody (Ab). We employed a 4.125-kb fragment of a mouse nephrin promoter downstream to which a FLAG-tagged hHO-1 cDNA sequence was inserted and subsequently generated transgenic mice from the FVB/N parental strain. There was a 16-fold higher transgene expression in the kidney than nonspecific background (liver) while the transprotein immunolocalized in glomerular epithelial cells (GEC). There was no change in urinary protein excretion, indicating that GEC-targeted HO-1 expression had no effect on glomerular protein permeability. Urinary protein excretion in transgenic mice with anti-GBM Ab injury (days 3 and 6) was significantly lower compared with wild-type controls. There was no significant change in renal expression levels of profibrotic (TGF-beta1) or anti-inflammatory (IL-10) cytokines in transgenic mice with anti-GBM Ab injury. These observations indicate that GEC-targeted HO-1 expression does not alter glomerular physiological integrity and reduces proteinuria in glomerular immune injury.

  16. Cordycepin alleviates lipopolysaccharide-induced acute lung injury via Nrf2/HO-1 pathway.

    Qing, Rui; Huang, Zezhi; Tang, Yufei; Xiang, Qingke; Yang, Fan

    2018-04-24

    The present study is to investigate the protective effect of cordycepin on inflammatory reactions in rats with acute lung injury (ALI) induced by lipopolysaccharide (LPS), as well as the underlying mechanism. Wistar rat model of ALI was induced by intravenous injection of LPS (30 mg/kg body weight). One hour later, intravenous injection of cordycepin (1, 10 or 30 mg/kg body weight) was administered. The wet-to-dry weight ratio of lung tissues and myeloperoxidase activity in the lung tissues were measured. The contents of nitrite and nitrate were measured by reduction method, while chemiluminescence was used to determine the content of superoxide. Quantitative real-time polymerase chain reaction and Western blotting were used to determine the expression of mRNA and protein, respectively. Colorimetry was performed to determine the enzymatic activity of heme oxygenase-1 (HO-1). Nuclear translocation of Nrf2 was identified by Western blotting. The plasma contents of cytokines were measured by enzyme-linked immunosorbent assay. Cordycepin enhanced the expression and enzymatic activity of HO-1 in ALI rats, and activated Nrf2 by inducing the translocation of Nrf2 from cytoplasm to nucleus. In addition, cordycepin regulated the secretion of TNF-α, IL-6 and IL-10 via HO-1, and suppressed inflammation in lung tissues of ALI rats by inducing the expression of HO-1. HO-1 played important roles in the down-regulation of superoxide levels in lung tissues by cordycepin, and HO-1 expression induced by cordycepin affected nitrite and nitrate concentrations in plasma and iNOS protein expression in lung tissues. Cordycepin showed protective effect on injuries in lung tissues. The present study demonstrates that cordycepin alleviates inflammation induced by LPS via the activation of Nrf2 and up-regulation of HO-1 expression. Copyright © 2018. Published by Elsevier B.V.

  17. Expression and characterization of truncated human heme oxygenase (hHO-1) and a fusion protein of hHO-1 with human cytochrome P450 reductase.

    Wilks, A; Black, S M; Miller, W L; Ortiz de Montellano, P R

    1995-04-04

    A human heme oxygenase (hHO-1) gene without the sequence coding for the last 23 amino acids has been expressed in Escherichia coli behind the pho A promoter. The truncated enzyme is obtained in high yields as a soluble, catalytically-active protein, making it available for the first time for detailed mechanistic studies. The purified, truncated hHO-1/heme complex is spectroscopically indistinguishable from that of the rat enzyme and converts heme to biliverdin when reconstituted with rat liver cytochrome P450 reductase. A self-sufficient heme oxygenase system has been obtained by fusing the truncated hHO-1 gene to the gene for human cytochrome P450 reductase without the sequence coding for the 20 amino acid membrane binding domain. Expression of the fusion protein in pCWori+ yields a protein that only requires NADPH for catalytic turnover. The failure of exogenous cytochrome P450 reductase to stimulate turnover and the insensitivity of the catalytic rate toward changes in ionic strength establish that electrons are transferred intramolecularly between the reductase and heme oxygenase domains of the fusion protein. The Vmax for the fusion protein is 2.5 times higher than that for the reconstituted system. Therefore, either the covalent tether does not interfere with normal docking and electron transfer between the flavin and heme domains or alternative but equally efficient electron transfer pathways are available that do not require specific docking.

  18. Curcumin attenuates quinocetone induced apoptosis and inflammation via the opposite modulation of Nrf2/HO-1 and NF-kB pathway in human hepatocyte L02 cells.

    Dai, Chongshan; Li, Bin; Zhou, Yan; Li, Daowen; Zhang, Shen; Li, Hui; Xiao, Xilong; Tang, Shusheng

    2016-09-01

    The potential toxicity of quinocetone (QCT) has raised widely concern, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on QCT induced apoptosis and the underlying mechanism in human hepatocyte L02 cells. The results showed that QCT treatment significantly decreased the cell viability of L02 cell and increased the release of lactate dehydrogenase (LDH), which was attenuated by curcumin pre-treatment at 1.25, 2.5 and 5 μM. Compared to the QCT alone group, curcumin pre-treatment significantly attenuated QCT induced oxidative stress, mitochondrial dysfunction and apoptosis. In addition, curcumin pretreatment markedly attenuated QCT-induced increase of iNOS activity and NO production in a dose-dependent manner. Meanwhile, curcumin pretreatment markedly down-regulated the expression of nuclear factor -kB (NF-kB) and iNOS mRNAs, but up-regulated the expressions of Nrf2 and HO-1 mRNAs, compared to the QCT alone group. Zinc protoporphyrin IX, a HO-1 inhibitor, markedly partly abolished the cytoprotective effect of curcumin against QCT-induced caspase activation, NF-kB mRNA expression. These results indicate that curcumin could effectively inhibit QCT induced apoptosis and inflammatory response in L02 cells, which may involve the activation of Nrf2/HO-1 and inhibition of NF-kB pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Edaravone Improves Septic Cardiac Function by Inducing an HIF-1α/HO-1 Pathway

    Chao He

    2018-01-01

    Full Text Available Septic myocardial dysfunction remains prevalent and raises mortality rate in patients with sepsis. During sepsis, tissues undergo tremendous oxidative stress which contributes critically to organ dysfunction. Edaravone, a potent radical scavenger, has been proved beneficial in ischemic injuries involving hypoxia-inducible factor- (HIF- 1, a key regulator of a prominent antioxidative protein heme oxygenase- (HO- 1. However, its effect in septic myocardial dysfunction remains unclarified. We hypothesized that edaravone may prevent septic myocardial dysfunction by inducing the HIF-1/HO-1 pathway. Rats were subjected to cecal ligation and puncture (CLP with or without edaravone infusion at three doses (50, 100, or 200 mg/kg, resp. before CLP and intraperitoneal injection of the HIF-1α antagonist, ME (15 mg/kg, after CLP. After CLP, rats had cardiac dysfunction, which was associated with deformed myocardium, augmented lipid peroxidation, and increased myocardial apoptosis and inflammation, along with decreased activities of catalase, HIF-1α, and HO-1 in the myocardium. Edaravone pretreatment dose-dependently reversed the changes, of which high dose most effectively improved cardiac function and survival rate of septic rats. However, inhibition of HIF-1α by ME demolished the beneficial effects of edaravone at high dose, reducing the survival rate of the septic rats without treatments. Taken together, edaravone, by inducing the HIF-1α/HO-1 pathway, suppressed oxidative stress and protected the heart against septic myocardial injury and dysfunction.

  20. Protectin DX suppresses hepatic gluconeogenesis through AMPK-HO-1-mediated inhibition of ER stress.

    Jung, Tae Woo; Kim, Hyung-Chun; Abd El-Aty, A M; Jeong, Ji Hoon

    2017-06-01

    Several studies have shown that protectins, which are ω-3 fatty acid-derived proresolution mediators, may improve insulin resistance. Recently, protectin DX (PDX) was documented to attenuate insulin resistance by stimulating IL-6 expression in skeletal muscle, thereby regulating hepatic gluconeogenesis. These findings made us investigate the direct effects of PDX on hepatic glucose metabolism in the context of diabetes. In the current study, we show that PDX regulates hepatic gluconeogenesis in a manner distinct from its indirect glucoregulatory activity via IL-6. We found that PDX stimulated AMP-activated protein kinase (AMPK) phosphorylation, thereby inducing heme oxygenase 1 (HO-1) expression. This induction blocked hepatic gluconeogenesis by suppressing endoplasmic reticulum (ER) stress in hepatocytes under hyperlipidemic conditions. These effects were significantly dampened by silencing AMPK or HO-1 expression with small interfering RNA (siRNA). We also demonstrated that administration of PDX to high fat diet (HFD)-fed mice resulted in increased hepatic AMPK phosphorylation and HO-1 expression, whereas hepatic ER stress was substantially attenuated. Furthermore, PDX treatment suppressed the expression of gluconeogenic genes, thereby decreasing blood glucose levels in HFD-fed mice. In conclusion, our findings suggest that PDX inhibits hepatic gluconeogenesis via AMPK-HO-1-dependent suppression of ER stress. Thus, PDX may be an effective therapeutic target for the treatment of insulin resistance and type 2 diabetes through the regulation of hepatic gluconeogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Neutron diffraction studies of Ho1-xYxNi2B2C compounds

    Chang, L.J.; Tomy, C.V.; Paul, D.M.K.

    1996-01-01

    Neutron diffraction measurements have been carried out to investigate the nature of magnetic ordering in Ho(1-x)Y(x)Ni(2)B(2)C (x = 0, 0.1 and 0.2) compounds. HoNi(2)B(2)C shows a complex type of magnetic ordering below the superconducting transition, with a commensurate antiferromagnetic ordering...

  2. Heme oxygenase-1 (HO-1 expression in prostate cancer cells modulates the oxidative response in bone cells.

    Mercedes Ferrando

    Full Text Available Prostate cancer (PCa is a leading cause of death among males. It is currently estimated that inflammatory responses are linked to 15-20% of all deaths from cancer worldwide. PCa is dominated by complications arising from metastasis to the bone where the tumor cells interact with the bone microenvironment impairing the balance between bone formation and degradation. However, the molecular nature of this interaction is not completely understood. Heme oxygenase-1 (HO-1 counteracts oxidative damage and inflammation. Previous studies from our laboratory showed that HO-1 is implicated in PCa, demonstrating that endogenous HO-1 inhibits bone derived-prostate cancer cells proliferation, invasion and migration and decreases tumor growth and angiogenesis in vivo. The aim of this work was to analyze the impact of HO-1 modulated PCa cells on osteoblasts proliferation in vitro and on bone remodeling in vivo. Using a co-culture system of PC3 cells with primary mice osteoblasts (PMOs, we demonstrated that HO-1 pharmacological induction (hemin treatment abrogated the diminution of PMOs proliferation induced by PCa cells and decreased the expression of osteoclast-modulating factors in osteoblasts. No changes were detected in the expression of genes involved in osteoblasts differentiation. However, co-culture of hemin pre-treated PC3 cells (PC3 Hem with PMOs provoked an oxidative status and activated FoxO signaling in osteoblasts. The percentage of active osteoblasts positive for HO-1 increased in calvarias explants co-cultured with PC3 Hem cells. Nuclear HO-1 expression was detected in tumors generated by in vivo bone injection of HO-1 stable transfected PC3 (PC3HO-1 cells in the femur of SCID mice. These results suggest that HO-1 has the potential to modify the bone microenvironment impacting on PCa bone metastasis.

  3. Thyroglobulin (Tg) Testing Revisited: Tg Assays, TgAb Assays, and Correlation of Results With Clinical Outcomes.

    Netzel, Brian C; Grebe, Stefan K G; Carranza Leon, B Gisella; Castro, M Regina; Clark, Penelope M; Hoofnagle, Andrew N; Spencer, Carole A; Turcu, Adina F; Algeciras-Schimnich, Alicia

    2015-08-01

    Measurement of thyroglobulin (Tg) by mass spectrometry (Tg-MS) is emerging as a tool for accurate Tg quantification in patients with anti-Tg autoantibodies (TgAbs). The objective of the study was to perform analytical and clinical evaluations of two Tg-MS assays in comparison with immunometric Tg assays (Tg-IAs) and Tg RIAs (Tg-RIAs) in a cohort of thyroid cancer patients. A total of 589 samples from 495 patients, 243 TgAb-/252 TgAb+, were tested by Beckman, Roche, Siemens-Immulite, and Thermo-Brahms Tg and TgAb assays, two Tg-RIAs, and two Tg-MS assays. The frequency of TgAb+ was 58%, 41%, 27%, and 39% for Roche, Beckman, Siemens-Immulite, and Thermo-Brahms, respectively. In TgAb- samples, clinical sensitivities and specificities of 100% and 74%-100%, respectively, were observed across all assays. In TgAb+ samples, all Tg-IAs demonstrated assay-dependent Tg underestimation, ranging from 41% to 86%. In TgAb+ samples, the use of a common cutoff (0.5 ng/mL) for the Tg-MS, three Tg-IAs, and the USC-RIA improved the sensitivity for the Tg-MSs and Tg-RIAs when compared with the Tg-IAs. In up to 20% of TgAb+ cases, Tg-IAs failed to detect Tg that was detectable by Tg-MS. In Tg-RIAs false-high biases were observed in TgAb+ samples containing low Tg concentrations. Tg-IAs remain the method of choice for Tg quantitation in TgAb- patients. In TgAb+ patients with undetectable Tg by immunometric assay, the Tg-MS will detect Tg in up to 20% additional cases. The Tg-RIA will detect Tg in approximately 35% cases, but a significant proportion of these will be clinical false-positive results. The undetectable Tg-MS seen in approximately 40% of TgAb+ cases in patients with disease need further evaluation.

  4. Modulation of cGMP by human HO-1 retrovirus gene transfer in pulmonary microvessel endothelial cells.

    Abraham, Nader G; Quan, Shuo; Mieyal, Paul A; Yang, Liming; Burke-Wolin, Theresa; Mingone, Christopher J; Goodman, Alvin I; Nasjletti, Alberto; Wolin, Michael S

    2002-11-01

    Carbon monoxide (CO) stimulates guanylate cyclase (GC) and increases guanosine 3',5'-cyclic monophosphate (cGMP) levels. We transfected rat-lung pulmonary endothelial cells with a retrovirus-mediated human heme oxygenase (hHO)-1 gene. Pulmonary cells that expressed hHO-1 exhibited a fourfold increase in HO activity associated with decreases in the steady-state levels of heme and cGMP without changes in soluble GC (sGC) and endothelial nitric oxide synthase (NOS) proteins or basal nitrite production. Heme elicited significant increases in CO production and intracellular cGMP levels in both pulmonary endothelial and pulmonary hHO-1-expressing cells. N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS, significantly decreased cGMP levels in heme-treated pulmonary endothelial cells but not heme-treated hHO-1-expressing cells. In the presence of exogenous heme, CO and cGMP levels in hHO-1-expressing cells exceeded the corresponding levels in pulmonary endothelial cells. Acute exposure of endothelial cells to SnCl2, which is an inducer of HO-1, increased cGMP levels, whereas chronic exposure decreased heme and cGMP levels. These results indicate that prolonged overexpression of HO-1 ultimately decreases sGC activity by limiting the availability of cellular heme. Heme activates sGC and enhances cGMP levels via a mechanism that is largely insensitive to NOS inhibition.

  5. Induction of HO-1 in tissue macrophages and monocytes in fatal falciparum malaria and sepsis

    Liomba N

    2003-11-01

    Full Text Available Abstract Background As well as being inducible by haem, haemoxygenase -1 (HO-1 is also induced by interleukin-10 and an anti-inflammatory prostaglandin, 15d PGJ2, the carbon monoxide thus produced mediating the anti-inflammatory effects of these molecules. The cellular distribution of HO-1, by immunohistochemistry, in brain, lung and liver in fatal falciparum malaria, and in sepsis, is reported. Methods Wax sections were stained, at a 1:1000 dilution of primary antibody, for HO-1 in tissues collected during paediatric autopsies in Blantyre, Malawi. These comprised 37 acutely ill comatose patients, 32 of whom were diagnosed clinically as cerebral malaria and the other 5 as bacterial diseases with coma. Another 3 died unexpectedly from an alert state. Other control tissues were from Australian adults. Results Apart from its presence in splenic red pulp macrophages and microhaemorrhages, staining for HO-1 was confined to intravascular monocytes and certain tissue macrophages. Of the 32 clinically diagnosed cerebral malaria cases, 11 (category A cases had negligible histological change in the brain and absence of or scanty intravascular sequestration of parasitized erythrocytes. Of these 11 cases, eight proved at autopsy to have other pathological changes as well, and none of these eight showed HO-1 staining within the brain apart from isolated moderate staining in one case. Two of the three without another pathological diagnosis showed moderate staining of scattered monocytes in brain vessels. Six of these 11 (category A cases exhibited strong lung staining, and the Kupffer cells of nine of them were intensely stained. Of the seven (category B cases with no histological changes in the brain, but appreciable sequestered parasitised erythrocytes present, one was without staining, and the other six showed strongly staining, rare or scattered monocytes in cerebral vessels. All six lung sections not obscured by neutrophils showed strong staining of

  6. Activation of the complement cascade enhances motility of leukemic cells by downregulating expression of HO-1.

    Abdelbaset-Ismail, A; Borkowska-Rzeszotek, S; Kubis, E; Bujko, K; Brzeźniakiewicz-Janus, K; Bolkun, L; Kloczko, J; Moniuszko, M; Basak, G W; Wiktor-Jedrzejczak, W; Ratajczak, M Z

    2017-02-01

    As a crucial arm of innate immunity, the complement cascade (ComC) is involved both in mobilization of normal hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM) into peripheral blood and in their homing to BM. Despite the fact that ComC cleavage fragments alone do not chemoattract normal HSPCs, we found that leukemia cell lines as well as clonogenic blasts from chronic myeloid leukemia and acute myeloid leukemia patients respond robustly to C3 and C5 cleavage fragments by chemotaxis and increased adhesion. This finding was supported by the detection of C3a and C5a receptors in cells from human malignant hematopoietic cell lines and patient blasts at the mRNA (reverse transcriptase-polymerase chain reaction) and protein level (fluorescence-activated cell sorting), and by the demonstration that these receptors respond to stimulation by C3a and C5a by phosphorylation of p42/44 and p38 mitogen-activated protein kinases (MAPK), and protein kinase B (PKB/AKT). We also found that inducible heme oxygenase 1 (HO-1) is a negative regulator of ComC-mediated trafficking of leukemic cells, and that stimulation of leukemic cells by C3 or C5 cleavage fragments activates p38 MAPK, which downregulates HO-1 expression, rendering cells more mobile. We conclude that activation of the ComC in leukemia/lymphoma patients (for example, as a result of accompanying infections) enhances the motility of malignant cells and contributes to their spread in a p38 MAPK-HO-1-dependent manner. Therefore, inhibition of p38 MAPK or upregulation of HO-1 by small-molecule modulators would have a beneficial effect on ameliorating cell migration-mediated expansion of leukemia/lymphoma cells when the ComC becomes activated.

  7. Activation of the complement cascade enhances motility of leukemic cells by downregulating expression of HO-1

    Abdelbaset-Ismail, A; Borkowska-Rzeszotek, S; Kubis, E; Bujko, K; Brzeźniakiewicz-Janus, K; Bolkun, L; Kloczko, J; Moniuszko, M; Basak, G W; Wiktor-Jedrzejczak, W; Ratajczak, M Z

    2017-01-01

    As a crucial arm of innate immunity, the complement cascade (ComC) is involved both in mobilization of normal hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM) into peripheral blood and in their homing to BM. Despite the fact that ComC cleavage fragments alone do not chemoattract normal HSPCs, we found that leukemia cell lines as well as clonogenic blasts from chronic myeloid leukemia and acute myeloid leukemia patients respond robustly to C3 and C5 cleavage fragments by chemotaxis and increased adhesion. This finding was supported by the detection of C3a and C5a receptors in cells from human malignant hematopoietic cell lines and patient blasts at the mRNA (reverse transcriptase-polymerase chain reaction) and protein level (fluorescence-activated cell sorting), and by the demonstration that these receptors respond to stimulation by C3a and C5a by phosphorylation of p42/44 and p38 mitogen-activated protein kinases (MAPK), and protein kinase B (PKB/AKT). We also found that inducible heme oxygenase 1 (HO-1) is a negative regulator of ComC-mediated trafficking of leukemic cells, and that stimulation of leukemic cells by C3 or C5 cleavage fragments activates p38 MAPK, which downregulates HO-1 expression, rendering cells more mobile. We conclude that activation of the ComC in leukemia/lymphoma patients (for example, as a result of accompanying infections) enhances the motility of malignant cells and contributes to their spread in a p38 MAPK–HO-1-dependent manner. Therefore, inhibition of p38 MAPK or upregulation of HO-1 by small-molecule modulators would have a beneficial effect on ameliorating cell migration-mediated expansion of leukemia/lymphoma cells when the ComC becomes activated. PMID:27451975

  8. MAT, a Novel Polyherbal Aphrodisiac Formulation, Enhances Sexual Function and Nrf2/HO-1 Pathway While Reducing Oxidative Damage in Male Rats

    Kazim Sahin

    2018-01-01

    Full Text Available Mucuna pruriens, Ashwagandha, and Tribulus terrestris are known as the enhancers for sexual health, functional activities, vitality, and longevity. These herbs had been widely used in the Ayurveda medicine as aphrodisiacs through the ages, and their efficacy was also verified separately in our previous publication. Therefore, the aim of this study was to determine the effects of Mucuna, Ashwagandha, and Tribulus complexes on sexual function in rats. Twenty-eight male rats allocated to four groups as follows: (i negative control (C; (ii positive control or sildenafil citrate treated group (5 mg/kg (S; (iii MAT1 (combination of 10 mg Mucuna (M + 10 mg Ashwagandha (A + 10 mg Tribulus (T/kg BW; (iv MAT 2 (20 mg Mucuna + 20 mg Ashwagandha + 20 mg Tribulus/kg BW. There was no significant difference found between the MAT1 and MAT2 groups while they showed significantly increased testosterone, follicle-stimulating hormone (FSH, and luteinizing hormone (LH levels when compared to the negative control. Significant increases in Nrf2/HO1 levels and decreases in NF-κB were detected in MAT groups similar to the decrease in serum and testis malondialdehyde (MDA levels as compared to both controls. The sperm motility, count, and rate also significantly improved in both MAT groups, while ALT, AST, creatinine, ALP, and urea levels did not change in any of the groups. Oral consumption of MATs combination in male rats resulted in inhibition of NF-κB and MDA and also increased sex hormones with Nrf2-mediated HO-1 induction. MAT combinations may improve sexual functions by increasing levels of sexual hormones and regulation of NF-κB and Nrf2/HO-1 signaling pathways.

  9. MAT, a Novel Polyherbal Aphrodisiac Formulation, Enhances Sexual Function and Nrf2/HO-1 Pathway While Reducing Oxidative Damage in Male Rats

    Tuzcu, Mehmet; Orhan, Cemal; Sahin, Nurhan; Akdemir, Fatih; Yilmaz, Ismet

    2018-01-01

    Mucuna pruriens, Ashwagandha, and Tribulus terrestris are known as the enhancers for sexual health, functional activities, vitality, and longevity. These herbs had been widely used in the Ayurveda medicine as aphrodisiacs through the ages, and their efficacy was also verified separately in our previous publication. Therefore, the aim of this study was to determine the effects of Mucuna, Ashwagandha, and Tribulus complexes on sexual function in rats. Twenty-eight male rats allocated to four groups as follows: (i) negative control (C); (ii) positive control or sildenafil citrate treated group (5 mg/kg) (S); (iii) MAT1 (combination of 10 mg Mucuna (M) + 10 mg Ashwagandha (A) + 10 mg Tribulus (T)/kg BW); (iv) MAT 2 (20 mg Mucuna + 20 mg Ashwagandha + 20 mg Tribulus/kg BW). There was no significant difference found between the MAT1 and MAT2 groups while they showed significantly increased testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels when compared to the negative control. Significant increases in Nrf2/HO1 levels and decreases in NF-κB were detected in MAT groups similar to the decrease in serum and testis malondialdehyde (MDA) levels as compared to both controls. The sperm motility, count, and rate also significantly improved in both MAT groups, while ALT, AST, creatinine, ALP, and urea levels did not change in any of the groups. Oral consumption of MATs combination in male rats resulted in inhibition of NF-κB and MDA and also increased sex hormones with Nrf2-mediated HO-1 induction. MAT combinations may improve sexual functions by increasing levels of sexual hormones and regulation of NF-κB and Nrf2/HO-1 signaling pathways. PMID:29853975

  10. NRF2 activation is involved in ozonated human serum upregulation of HO-1 in endothelial cells

    Pecorelli, Alessandra; Bocci, Velio; Acquaviva, Alessandra; Belmonte, Giuseppe; Gardi, Concetta; Virgili, Fabio; Ciccoli, Lucia; Valacchi, Giuseppe

    2013-01-01

    During the last decade, it has been shown that the activation of NRF2 and the binding to electrophile-responsive element (EpREs), stimulates the expression of a great number of genes responsible for the synthesis of phase I and phase II proteins, including antioxidants enzymes and heme oxygenase-1 (HO-1). This critical cell response occurs in cardiovascular, degenerative and chronic infective diseases aggravated by a chronic oxidative stress. In our previous reports we have shown that ozonated plasma is able to up-regulate HO-1 expression in endothelial cells. In the present work we investigated a candidate mechanism involved in this process. After treatment with increasing doses of ozonated serum (20, 40 and 80 μg/mL O 3 per mL of serum), a clear dose dependent activation of NRF2 and the subsequent induction of HO-1 and NAD(P)H quinone oxidoreductase 1(NQO1) was observed. This effect was also present when cells were treated with serum and hydrogen peroxide (H 2 O 2 ) or serum and 4-hydroxynonenal (4HNE). Moreover, the treatment with ozonated serum was associated with a dose-dependent activation of extracellular-signal-regulated kinases (ERK1/2) and p38 MAP kinases (p38), not directly involved in NRF2 activation. These data, provide a new insight on the mechanism responsible for the induction of HO-1 expression by ozonated serum in the endothelium, and have a practical importance as an expedient approach to the treatment of patients with both effective orthodox drugs and ozonated autohemotherapy, targeted to the restoration of redox homeostasis. - Highlights: ► Endothelial HO1 is upregulated by ozonated plasma ► This activation is induced by NRF2 and it is ERK independent. ► 4HNE and H 2 O 2 are the main molecules involved in this process. ► Ozonated plasma induced a hormetic effect ► Combination of orthodox medicine and ozonated plasma can be a useful treatment

  11. NRF2 activation is involved in ozonated human serum upregulation of HO-1 in endothelial cells

    Pecorelli, Alessandra [Department of Molecular and Developmental Medicine, University of Siena (Italy); Child Neuropsychiatry Unit, University Hospital, AOUS, Siena (Italy); Bocci, Velio [Department of Physiology, University of Siena (Italy); Acquaviva, Alessandra [Department of Molecular and Developmental Medicine, University of Siena (Italy); Belmonte, Giuseppe [Department of Biomedical Sciences, University of Siena (Italy); Gardi, Concetta [Department of Molecular and Developmental Medicine, University of Siena (Italy); Virgili, Fabio [INRAN, Rome (Italy); Ciccoli, Lucia [Department of Molecular and Developmental Medicine, University of Siena (Italy); Valacchi, Giuseppe, E-mail: giuseppe.valacchi@unife.it [Department of Life Sciences and Biotechnology, University of Ferrara (Italy); Department of Food and Nutrition, Kyung Hee University, Seoul (Korea, Republic of)

    2013-02-15

    During the last decade, it has been shown that the activation of NRF2 and the binding to electrophile-responsive element (EpREs), stimulates the expression of a great number of genes responsible for the synthesis of phase I and phase II proteins, including antioxidants enzymes and heme oxygenase-1 (HO-1). This critical cell response occurs in cardiovascular, degenerative and chronic infective diseases aggravated by a chronic oxidative stress. In our previous reports we have shown that ozonated plasma is able to up-regulate HO-1 expression in endothelial cells. In the present work we investigated a candidate mechanism involved in this process. After treatment with increasing doses of ozonated serum (20, 40 and 80 μg/mL O{sub 3} per mL of serum), a clear dose dependent activation of NRF2 and the subsequent induction of HO-1 and NAD(P)H quinone oxidoreductase 1(NQO1) was observed. This effect was also present when cells were treated with serum and hydrogen peroxide (H{sub 2}O{sub 2}) or serum and 4-hydroxynonenal (4HNE). Moreover, the treatment with ozonated serum was associated with a dose-dependent activation of extracellular-signal-regulated kinases (ERK1/2) and p38 MAP kinases (p38), not directly involved in NRF2 activation. These data, provide a new insight on the mechanism responsible for the induction of HO-1 expression by ozonated serum in the endothelium, and have a practical importance as an expedient approach to the treatment of patients with both effective orthodox drugs and ozonated autohemotherapy, targeted to the restoration of redox homeostasis. - Highlights: ► Endothelial HO1 is upregulated by ozonated plasma ► This activation is induced by NRF2 and it is ERK independent. ► 4HNE and H{sub 2}O{sub 2} are the main molecules involved in this process. ► Ozonated plasma induced a hormetic effect ► Combination of orthodox medicine and ozonated plasma can be a useful treatment.

  12. Thyroglobulin (Tg) recovery testing with quantitative Tg antibody measurement for determining interference in serum Tg assays in differentiated thyroid carcinoma

    Persoon, ACM; Links, TP; Wilde, J; Sluiter, WJ; Wolffenbuttel, BHR; van den Ouweland, JMW

    Background: Thyroglobulin (Tg) measurements are complicated by interference from Tg autoantibodies (TgAbs) or heterophilic antibodies (HAMAs). We used a new automated immunochemiluminometric assay (ICMA) with Tg recovery (TgR) on the Nichols Advantage (R) platform to reassess the clinical utility of

  13. The HO-1/CO system regulates mitochondrial-capillary density relationships in human skeletal muscle.

    Pecorella, Shelly R H; Potter, Jennifer V F; Cherry, Anne D; Peacher, Dionne F; Welty-Wolf, Karen E; Moon, Richard E; Piantadosi, Claude A; Suliman, Hagir B

    2015-10-15

    The heme oxygenase-1 (HO-1)/carbon monoxide (CO) system induces mitochondrial biogenesis, but its biological impact in human skeletal muscle is uncertain. The enzyme system generates CO, which stimulates mitochondrial proliferation in normal muscle. Here we examined whether CO breathing can be used to produce a coordinated metabolic and vascular response in human skeletal muscle. In 19 healthy subjects, we performed vastus lateralis muscle biopsies and tested one-legged maximal O2 uptake (V̇o2max) before and after breathing air or CO (200 ppm) for 1 h daily for 5 days. In response to CO, there was robust HO-1 induction along with increased mRNA levels for nuclear-encoded mitochondrial transcription factor A (Tfam), cytochrome c, cytochrome oxidase subunit IV (COX IV), and mitochondrial-encoded COX I and NADH dehydrogenase subunit 1 (NDI). CO breathing did not increase V̇o2max (1.96 ± 0.51 pre-CO, 1.87 ± 0.50 post-CO l/min; P = not significant) but did increase muscle citrate synthase, mitochondrial density (139.0 ± 34.9 pre-CO, 219.0 ± 36.2 post-CO; no. of mitochondrial profiles/field), myoglobin content and glucose transporter (GLUT4) protein level and led to GLUT4 localization to the myocyte membrane, all consistent with expansion of the tissue O2 transport system. These responses were attended by increased cluster of differentiation 31 (CD31)-positive muscle capillaries (1.78 ± 0.16 pre-CO, 2.37 ± 0.59 post-CO; capillaries/muscle fiber), implying the enrichment of microvascular O2 reserve. The findings support that induction of the HO-1/CO system by CO not only improves muscle mitochondrial density, but regulates myoglobin content, GLUT4 localization, and capillarity in accordance with current concepts of skeletal muscle plasticity. Copyright © 2015 the American Physiological Society.

  14. 3D nuclear organization of telomeres in the Hodgkin cell lines U-HO1 and U-HO1-PTPN1: PTPN1 expression prevents the formation of very short telomeres including "t-stumps"

    Lemieux Bruno

    2010-12-01

    Full Text Available Abstract Background In cancer cells the three-dimensional (3D telomere organization of interphase nuclei into a telomeric disk is heavily distorted and aggregates are found. In Hodgkin's lymphoma quantitative FISH (3D Q-FISH reveals a major impact of nuclear telomere dynamics during the transition form mononuclear Hodgkin (H to diagnostic multinuclear Reed-Sternberg (RS cells. In vitro and in vivo formation of RS-cells is associated with the increase of very short telomeres including "t-stumps", telomere loss, telomeric aggregate formation and the generation of "ghost nuclei". Results Here we analyze the 3D telomere dynamics by Q-FISH in the novel Hodgkin cell line U-HO1 and its non-receptor protein-tyrosine phosphatase N1 (PTPN1 stable transfectant U-HO1-PTPN1, derived from a primary refractory Hodgkin's lymphoma. Both cell lines show equally high telomerase activity but U-HO1-PTPN differs from U-HO1 by a three times longer doubling time, low STAT5A expression, accumulation of RS-cells (p As expected, multinuclear U-HO1-RS-cells and multinuclear U-HO1-PTPN1-RS-cells differ from their mononuclear H-precursors by their nuclear volume (p Conclusion Abundant RS-cells without additional very short telomeres including "t-stumps", high rate of apoptosis, but low STAT5A expression, are hallmarks of the U-HO1-PTPN1 cell line. These characteristics are independent of telomerase activity. Thus, PTPN1 induced dephosphorylation of STAT5 with consecutive lack of Akt/PKB activation and cellular arrest in G2, promoting induction of apoptosis, appears as a possible pathogenetic mechanism deserving further experimental investigation.

  15. Potential Ameliorative Effects of Qing Ye Dan Against Cadmium Induced Prostatic Deficits via Regulating Nrf-2/HO-1 and TGF-β1/Smad Pathways.

    Du, Lifen; Lei, Yongfang; Chen, Jinglou; Song, Hongping; Wu, Xinying

    2017-01-01

    Cadmium (Cd) is an environmental pollutant with reproductive toxicity. Swertia mileensis is used in Chinese medicine for the treatment of prostatic deficits and named as Qing Ye Dan (QYD). This study was undertaken to investigate the potential protective effects of QYD against Cd-induced prostatic deficits. Rat model of prostatic deficits was induced by 0.2 mg/kg/d CdCl2 subcutaneous injection for 15 days. The prostatic oxidative stress was evaluated by detecting the levels of malondialdehyde, nitric oxide, reduced/ oxidized glutathione, total sulfhydryl groups and enzymatic antioxidant status. The prostatic inflammation was estimated by testing the levels of pro-inflammatory cytokines. The levels of epithelial-mesenchymal transition (EMT) markers E-cadherin, fibronectin, vimentin and α-smooth muscle actin were measured by qPCR analysis. Additionally, the prostatic expressions of transforming growth factor-β1 (TGF-β1), type I TGF-β receptor (TGF-βRI), Smad2, phosphorylation-Smad2 (p-Smad2), Smad3, p-Smad3, Smad7, nuclear related factor-2 (Nrf-2), heme oxygenase-1 (HO-1), B-cell CLL/lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax) were measured by western blot assay. It was found that QYD ameliorated the Cd-induced prostatic oxidative stress and inflammation, attenuated prostatic EMT, inhibited the TGF-β1/Smad pathway, increased Bcl-2/Bax ratio and enhanced the activity of Nrf-2/HO-1 pathway. These results showed that QYD could ameliorate Cd-induced prostatic deficits via modulating Nrf-2/HO-1 and TGF-β1/Smad pathways. © 2017 The Author(s). Published by S. Karger AG, Basel.

  16. Antrodia camphorata Potentiates Neuroprotection against Cerebral Ischemia in Rats via Downregulation of iNOS/HO-1/Bax and Activated Caspase-3 and Inhibition of Hydroxyl Radical Formation

    Po-Sheng Yang

    2015-01-01

    Full Text Available Antrodia camphorata (A. camphorata is a fungus generally used in Chinese folk medicine for treatment of viral hepatitis and cancer. Our previous study found A. camphorata has neuroprotective properties and could reduce stroke injury in cerebral ischemia animal models. In this study, we sought to investigate the molecular mechanisms of neuroprotective effects of A. camphorata in middle cerebral artery occlusion (MCAO rats. A selective occlusion of the middle cerebral artery (MCA with whole blood clots was used to induce ischemic stroke in rats and they were orally treated with A. camphorata (0.25 and 0.75 g/kg/day alone or combined with aspirin (5 mg/kg/day. To provide insight into the functions of A. camphorata mediated neuroprotection, the expression of Bax, inducible nitric oxide synthase (iNOS, haem oxygenase-1 (HO-1, and activated caspase-3 was determined by Western blot assay. Treatment of aspirin alone significantly reduced the expressions of HO-1 (P<0.001, iNOS (P<0.001, and Bax (P<0.01 in ischemic regions. The reduction of these expressions was more potentiated when rats treated by aspirin combined with A. camphorata (0.75 g/kg/day. Combination treatment also reduced apoptosis as measured by a significant reduction in active caspase-3 expression in the ischemic brain compared to MCAO group (P<0.01. Moreover, treatment of A. camphorata significantly (P<0.05 reduced fenton reaction-induced hydroxyl radical (OH• formation at a dose of 40 mg/mL. Taken together, A. camphorata has shown neuroprotective effects in embolic rats, and the molecular mechanisms may correlate with the downregulation of Bax, iNOS, HO-1, and activated caspase-3 and the inhibition of OH• signals.

  17. 50 Hz electric field effects on protein carbonyl (PCO), heme oxygenase-1 (HO-1) and hydroxyproline levels

    Ozgur, Elcin; Goknur, Guler; Seyhan, Nesrin

    2008-01-01

    Full text: Non-ionizing electromagnetic field (EMF) radiation sources, such as power lines and other Extremely Low Frequency (ELF) sources have become one of the most ubiquitous components of the spectrum of the human environment, and the possibility that they may have hazardous effects on human health is a major a public concern. Although it is well documented that EMFs have biological effects, the degree to which these exposures constitute a human health hazard is not clear yet. Today relation between production of oxidative stress resulted by reactive oxygen species and electrical stimulus, also the protective effects of antioxidant treatments are mentioned in many researches. In this study, it was aimed to determine both oxidation of proteins and protein collagen levels under 50 Hz 12 kV/m vertical Electric (E) Field exposure and the N-Acetylcysteine (NAC) administration which is a well-known antioxidant. To this end, protein carbonyl levels (PCO) as bio-markers of oxidative stress and Heme oxygenase-1 (HO-1), an enzyme that catalyzes the degradation of heme analyzed to figure out the protein oxidation. Hydroxyproline level, a major component of the protein collagen was measured in order to express the level of collagen in lung tissue. Guinea pigs, weighted 250-300 g, were used in the study. A total forty male guinea pigs were randomly divided into four groups which are composed of 10 guinea pigs each for groups: 1) Group I (Sham); 2) Group II (NAC-administrated group); 3) Group III (E Field Exposure group); 4) Group IV (NAC administrated + E Field exposed group). One week exposure period for 8 hours per daily was conducted for each exposure groups (Group III, Group IV ). The electric field exposure period was from 9 a.m. to 5 p.m. After the last exposure day, the guinea pigs were anesthetized by the injection of ketamine and xylazine. The guinea pigs were killed by decapitation. Statistical analyses were carried out using SPSS software (SPSS 11.5 for windows

  18. Edaravone attenuates hippocampal damage in an infant mouse model of pneumococcal meningitis by reducing HMGB1 and iNOS expression via the Nrf2/HO-1 pathway.

    Li, Zheng; Ma, Qian-Qian; Yan, Yan; Xu, Feng-Dan; Zhang, Xiao-Ying; Zhou, Wei-Qin; Feng, Zhi-Chun

    2016-09-01

    Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a free radical scavenger that has shown potent antioxidant, anti-inflammatory and neuroprotective effects in variety of disease models. In this study, we investigated whether edaravone produced neuroprotective actions in an infant mouse model of pneumococcal meningitis. C57BL/6 mice were infected on postnatal d 11 by intracisternal injection of a certain inoculum of Streptococcus pneumoniae. The mice received intracisternal injection of 10 μL of saline containing edaravone (3 mg/kg) once a day for 7 d. The severity of pneumococcal meningitis was assessed with a clinical score. In mice with severe meningitis, the survival rate from the time of infection to d 8 after infection was analyzed using Kaplan-Meier curves. In mice with mild meningitis, the CSF inflammation and cytokine levels in the hippocampus were analyzed d 7 after infection, and the clinical neurological deficit score was evaluated using a neurological scoring system d 14 after infection. The nuclear factor (erythroid-derived 2)-like 2 knockout (Nrf2 KO) mice and heme oxygenase-1 knockout (HO-1 KO) mice were used to confirm the involvement of Nrf2/HO-1 pathway in the neuroprotective actions of edaravone. In mice with severe meningitis, edaravone treatment significantly increased the survival rate (76.4%) compared with the meningitis model group (32.2%). In mice with mild meningitis, edaravone treatment significantly decreased the number of leukocytes and TNF- levels in CSF, as well as the neuronal apoptosis and protein levels of HMGB1 and iNOS in the hippocampus, but did not affect the high levels of IL-10 and IL-6 in the hippocampus. Moreover, edaravone treatment significantly improved the neurological function of mice with mild meningitis. In Nrf2 KO or HO-1 KO mice with the meningitis, edaravone treatment was no longer effective in improving the survival rate of the mice with severe meningitis (20.2% and 53.6%, respectively), nor it affected the

  19. Soybean-Derived Phytoalexins Improve Cognitive Function through Activation of Nrf2/HO-1 Signaling Pathway

    Ji Yeon Seo

    2018-01-01

    Full Text Available As soy-derived glyceollins are known to induce antioxidant enzymes in various types of cells and tissues, we hypothesized that the compounds could protect neurons from damage due to reactive oxygen species (ROS. In order to examine the neuroprotective effect of glyceollins, primary cortical neurons collected from mice and mouse hippocampal HT22 cells were challenged with glutamate. Glyceollins attenuated glutamate-induced cytotoxicity in primary cortical neuron isolated from mice carrying wild-type nuclear factor (erythroid-derived 2-like 2 (Nrf2, but the compounds were ineffective in those isolated from Nrf2 knockout mice, suggesting the involvement of the Nrf2 signaling pathway in glyceollin-mediated neuroprotection. Furthermore, the inhibition of heme oxygenase-1 (HO-1, a major downstream enzyme of Nrf2, abolished the suppressive effect of glyceollins against glutamate-induced ROS production and cytotoxicity, confirming that activation of HO-1 by glyceollins is responsible for the neuroprotection. To examine whether glyceollins also improve cognitive ability, mice pretreated with glyceollins were challenged with scopolamine and subjected to behavioral tests. Glyceollins attenuated scopolamine-induced cognitive impairment of mice, but failed to enhance memory in Nrf2 knockout mice, suggesting that the memory-enhancing effect is also mediated by the Nrf2 signaling pathway. Overall, glyceollins showed neuroprotection against glutamate-induced damage, and attenuated scopolamine-induced memory deficits in an Nrf2-dependent manner.

  20. HO-1 inhibits IL-13-induced goblet cell hyperplasia associated with CLCA1 suppression in normal human bronchial epithelial cells.

    Mishina, Kei; Shinkai, Masaharu; Shimokawaji, Tadasuke; Nagashima, Akimichi; Hashimoto, Yusuke; Inoue, Yoriko; Inayama, Yoshiaki; Rubin, Bruce K; Ishigatsubo, Yoshiaki; Kaneko, Takeshi

    2015-12-01

    Mucus hypersecretion and goblet cell hyperplasia are common features that characterize asthma. IL-13 increases mucin (MUC) 5AC, the major component of airway mucus, in airway epithelial cells. According to the literature, IL-13 receptor activation leads to STAT6 activation and consequent induction of chloride channel accessory 1 (CLCA1) gene expression, associated with the induction of MUC5AC. Heme oxygenase-1 (HO-1) is an enzyme that catalyzes oxidation of heme to biliverdin, and has anti-inflammatory and anti-oxidant properties. We examined the effects of HO-1 on mucin production and goblet cell hyperplasia induced by IL-13. Moreover, we assessed the cell signaling intermediates that appear to be responsible for mucin production. Normal human bronchial epithelial (NHBE) cells were grown at air liquid interface (ALI) in the presence or absence of IL-13 and hemin, a HO-1 inducer, for 14 days. Protein concentration was analyzed using ELISA, and mRNA expression was examined by real-time PCR. Histochemical analysis was performed using HE staining, andWestern blotting was performed to evaluate signaling transduction pathway. Hemin (4 μM) significantly increased HO-1 protein expression (p b 0.01) and HO-1 mRNA expression (p b 0.001). IL-13 significantly increased goblet cells, MUC5AC protein secretion (p b 0.01) and MUC5AC mRNA (p b 0.001), and these were decreased by hemin by way of HO-1. Tin protoporphyrin (SnPP)-IX, a HO-1 inhibitor, blocked the effect of hemin restoring MUC5AC protein secretion (p b 0.05) and goblet cell hyperplasia. Hemin decreased the expression of CLCA1 mRNA (p b 0.05) and it was reversed by SnPP-IX, but could not suppress IL-13-induced phosphorylation of STAT6 or SAM pointed domain-containing ETS transcription factor (SPDEF) and Forkhead box A2 (FOXA2) mRNA expression. In summary, HO-1 overexpression suppressed IL-13-induced goblet cell hyperplasia and MUC5AC production, and involvement of CLCA1 in the mechanism was suggested.

  1. Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction

    Gao, Yuanxue; Xu, Xiaojun; Chang, Sai; Wang, Yunjie; Xu, Yazhou; Ran, Siqi [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Huang, Zhangjian [Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009 (China); Li, Ping [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Li, Jia [National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 189 Guo Shoujing Road, Shanghai 201203 (China); Zhang, Luyong [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Saavedra, Juan M. [Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057 (United States); Liao, Hong, E-mail: liaohong56@hotmail.com [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Pang, Tao, E-mail: tpang@cpu.edu.cn [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057 (United States)

    2015-12-01

    The natural product totarol, a phenolic diterpenoid and a major constituent isolated from the sap of Podocarpus totara, has been reported to have a potent antimicrobial activity. In this study, we determined whether totarol possessed an additional neuroprotective activity in vitro and in vivo. We found that totarol prevented glutamate- and oxygen and glucose deprivation-induced neuronal death in primary rat cerebellar granule neuronal cells and cerebral cortical neurons. Totarol increased Akt and GSK-3β phosphorylation, Nrf2 and heme oxygenase-1 (HO-1) protein expressions and suppressed oxidative stress by increasing GSH and SOD activities. The PI3K/Akt inhibitor LY294002 prevented totarol neuroprotective effect by suppressing the totarol-induced changes in HO-1 expression and the activities of GSH and SOD. The HO-1 inhibitor ZnPPIX also prevented totarol-increased GSH and SOD activities. In a model of acute cerebral ischemic injury in Sprague–Dawley rats, produced by occlusion of the middle cerebral artery for 2 h followed by 22 h or 46 h of reperfusion, totarol significantly reduced infarct volume and improved the neurological deficit. In this model, totarol increased HO-1 expression and the activities of GSH and SOD. These observations suggest that totarol may be a novel activator of the Akt/HO-1 pathway protecting against ischemic stroke through reduction of oxidative stress. - Graphical abstract: It is unknown whether the natural product totarol has neuroprotective effects in vitro and in vivo. This study underscores that totarol prevents neuronal injury in vitro, not only by activating PI3K/Akt pathway, but also via induction of Nrf2, HO-1, GSH and SOD expressions. Totarol also ameliorated acute cerebral ischemic injury in a rat ischemic stroke model. The findings highlight that totarol may be exploited for protecting against ischemic stroke through Akt/HO-1 pathway. - Highlights: • Totarol protects glutamate- and OGD-induced neuronal injury in vitro.

  2. Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction

    Gao, Yuanxue; Xu, Xiaojun; Chang, Sai; Wang, Yunjie; Xu, Yazhou; Ran, Siqi; Huang, Zhangjian; Li, Ping; Li, Jia; Zhang, Luyong; Saavedra, Juan M.; Liao, Hong; Pang, Tao

    2015-01-01

    The natural product totarol, a phenolic diterpenoid and a major constituent isolated from the sap of Podocarpus totara, has been reported to have a potent antimicrobial activity. In this study, we determined whether totarol possessed an additional neuroprotective activity in vitro and in vivo. We found that totarol prevented glutamate- and oxygen and glucose deprivation-induced neuronal death in primary rat cerebellar granule neuronal cells and cerebral cortical neurons. Totarol increased Akt and GSK-3β phosphorylation, Nrf2 and heme oxygenase-1 (HO-1) protein expressions and suppressed oxidative stress by increasing GSH and SOD activities. The PI3K/Akt inhibitor LY294002 prevented totarol neuroprotective effect by suppressing the totarol-induced changes in HO-1 expression and the activities of GSH and SOD. The HO-1 inhibitor ZnPPIX also prevented totarol-increased GSH and SOD activities. In a model of acute cerebral ischemic injury in Sprague–Dawley rats, produced by occlusion of the middle cerebral artery for 2 h followed by 22 h or 46 h of reperfusion, totarol significantly reduced infarct volume and improved the neurological deficit. In this model, totarol increased HO-1 expression and the activities of GSH and SOD. These observations suggest that totarol may be a novel activator of the Akt/HO-1 pathway protecting against ischemic stroke through reduction of oxidative stress. - Graphical abstract: It is unknown whether the natural product totarol has neuroprotective effects in vitro and in vivo. This study underscores that totarol prevents neuronal injury in vitro, not only by activating PI3K/Akt pathway, but also via induction of Nrf2, HO-1, GSH and SOD expressions. Totarol also ameliorated acute cerebral ischemic injury in a rat ischemic stroke model. The findings highlight that totarol may be exploited for protecting against ischemic stroke through Akt/HO-1 pathway. - Highlights: • Totarol protects glutamate- and OGD-induced neuronal injury in vitro.

  3. Antihepatocarcinoma Effect of Portulaca oleracea L. in Mice by PI3K/Akt/mTOR and Nrf2/HO-1/NF-κB Pathway

    Guoyin, Zheng; Hao, Peng; Min, Li; Wei, Gu; Zhe, Chen

    2017-01-01

    The purpose of the present study was to evaluate the pharmacological effects of Portulaca oleracea L. (Purslane) (PL) on N-nitrosodiethylamine- (NDEA-) induced hepatocellular carcinomas (HCC) and explore its potential mechanism. Mice were randomly assigned to four groups: control group, NDEA group, NDEA + Purslane (100 mg/kg) group, and NDEA + Purslane (200 mg/kg) group. The animal of each group was given NDEA (100 ppm) in drinking water. 1 h later, Purslane dissolved in PBS was intragastrically administered for continuous seven days. The results showed that Purslane reduced the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in liver and serum. Purslane also reduced the contents of interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), and methane dicarboxylic aldehyde (MDA) and restored the activity of superoxygen dehydrogenises (SOD) in serum. Purslane could obviously attenuate the hepatic pathological alteration. Furthermore, treatment with Purslane effectively inhibited the phosphorylations of phosphatidylinositol 3 kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), nuclear factor-kappa B (NF-κB), and inhibitor of NF-κBα (IκBα) and upregulated the expressions of NF-E2-related factor 2 (Nrf2) and heme oxygenase- (HO-) 1. In conclusion, our research suggested that Purslane exhibited protective effects on NDEA-induced hepatocellular carcinomas by anti-inflammatory and antioxidative properties via the PI3K/Akt/mTOR and Nrf2/HO-1/NF-κB pathway. PMID:28659990

  4. Glutaredoxin 1 (GRX1) inhibits oxidative stress and apoptosis of chondrocytes by regulating CREB/HO-1 in osteoarthritis.

    Sun, Jie; Wei, Xuelei; Lu, Yandong; Cui, Meng; Li, Fangguo; Lu, Jie; Liu, Yunjiao; Zhang, Xi

    2017-10-01

    GRX1 (glutaredoxin1), a sulfhydryl disulfide oxidoreductase, is involved in many cellular processes, including anti-oxidation, anti-apoptosis, and regulation of cell differentiation. However, the role of GRX1 in the oxidative stress and apoptosis of osteoarthritis chondrocytes remains unclear, prompting the current study. Protein and mRNA expressions were measured by Western blot and RT-qPCR. Oxidative stress was detected by the measurement of MDA and SOD contents. Cells apoptosis were detected by Annexin V-FITC/PI and caspase-3 activity assays. We found that the mRNA and protein expressions of GRX1 were significantly down-regulated in osteoarthritis tissues and cells. GRX1 overexpression increased the mRNA and protein expression of CREB and HO-1. Meanwhile, GRX1 overexpression inhibited oxidative stress and apoptosis in osteoarthritis chondrocytes. Furthermore, we found that GRX1 overexpression regulated HO-1 by increasing CREB, and that HO-1 regulated oxidative stress and apoptosis in osteoarthritis chondrocytes. Thus, GRX1 overexpression constrains oxidative stress and apoptosis in osteoarthritis chondrocytes by regulating CREB/HO-1, providing a novel insight into the molecular mechanism and potential treatment of osteoarthritis. Copyright © 2017. Published by Elsevier Ltd.

  5. Spatiotemporal expression of heme oxygenase-1 detected by in vivo bioluminescence after hepatic ischemia in HO-1/luc mice

    Su, Huawei; van Dam, Gooitzen M.; Buis, Carlijn I.; Visser, Dorien S.; Hesselink, Jan Willem; Schuurs, Theo A.; Leuvenink, Henri G. D.; Contag, Christopher H.; Porte, Robert J.

    Upregulation of heme oxygenase-1 (HO-1) has been proposed as a critical mechanism protecting against cellular stress during liver transplantation, providing a potential target for new therapeutic interventions. We investigated the feasibility of in vivo bioluminescence imaging (BLI) to noninvasively

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

    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)

  7. Genipin inhibits TNF-α-induced vascular smooth muscle cell proliferation and migration via induction of HO-1.

    Fengrong Jiang

    Full Text Available Vascular smooth muscle cell (VSMC proliferation and migration triggered by inflammatory stimuli contributes importantly to the pathogenesis of atherosclerosis and restenosis. On the other hand, genipin, an aglycon of geniposide, exhibits diverse pharmacological functions such as antitumor and anti-inflammatory effects. The protective effects of genipin on the cardiovascular system have also been reported. However, the molecular mechanism involved remains unknown. This study aimed to elucidate the precise function of genipin in VSMCs, focusing particularly on the role of heme oxygenase-1 (HO-1, a potent anti-inflammatory enzyme. We found that pretreatment of genipin induced HO-1 mRNA and protein levels, as well as its activity in VSMCs. Genipin inhibited TNF-α-induced VSMC proliferation and migration in a dose-dependent manner. At the molecular level, genipin prevented ERK/MAPK and Akt phosphorylation while left p38 MAPK and JNK unchanged. Genipin also blocked the increase of ROS generation induced by TNF-α. More importantly, the specific HO-1 siRNA partially abolished the beneficial effects of genipin on VSMCs. These results suggest that genipin may serve as a novel drug in the treatment of these pathologies by inducing HO-1 expression/activity and subsequently decreasing VSMC proliferation and migration.

  8. Generation of CMAHKO/GTKO/shTNFRI-Fc/HO-1 quadruple gene modified pigs.

    Kim, Geon A; Lee, Eun Mi; Jin, Jun-Xue; Lee, Sanghoon; Taweechaipaisankul, Anukul; Hwang, Jong Ik; Alam, Zahid; Ahn, Curie; Lee, Byeong Chun

    2017-08-01

    As an alternative source of organs for transplantation into humans, attention has been directed to pigs due to their similarities in biological features and organ size. However, severe immune rejection has prevented successful xenotransplantation using pig organs and tissues. To overcome immune rejection, recently developed genetic engineering systems such as TALEN coupled with somatic cell nuclear transfer (SCNT) to make embryos could be used to produce pigs compatible with xenotransplantation. We used the TALEN system to target the non-Gal antigen cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) gene in pigs that is naturally deleted in humans. Gal-deleted cells expressing both soluble human tumor necrosis factor receptor I IgG 1 -Fc (shTNFRI-Fc) and human hemagglutinin -tagged-human heme oxygenase-1 (hHO-1) were transfected with a TALEN target for CMAH. Cells lacking CMAH were negatively selected using N-glyconeuraminic acid (Neu5Gc)/magnetic beads and the level of Neu5Gc expression of isolated cells were analyzed by FACS and DNA sequencing. Cloned embryos using 3 different genetically modified cell clones were respectively transferred into 3 recipients, with 55.6% (5/9) becoming pregnant and three cloned pigs were produced. Successful genetic disruption of the CMAH gene was confirmed by sequencing, showing lack of expression of CMAH in tail-derived fibroblasts of the cloned piglets. Besides decreased expression of Neu5Gc in piglets produced by SCNT, antibody-mediated complement-dependent cytotoxicity assays and natural antibody binding for examining immuno-reactivity of the quadruple gene modified pigs derived from endothelial cells and fibroblasts were reduced significantly compared to those of wild type animals. We conclude that by combining the TALEN system and transgenic cells, targeting of multiple genes could be useful for generating organs for xenotransplantation. We produced miniature pigs with quadruple modified genes CMAHKO/GTKO/shTNFRI-Fc/hHO

  9. Lycopene ameliorates atrazine-induced oxidative damage in adrenal cortex of male rats by activation of the Nrf2/HO-1 pathway.

    Abass, Marwa Ahmed; Elkhateeb, Shereen Ahmed; Abd El-Baset, Samia Adel; Kattaia, Asmaa Alhosiny; Mohamed, Eman Mosallam; Atteia, Hebatallah Husseini

    2016-08-01

    Atrazine (ATZ) is one of the most commonly used herbicides contaminating plants, soil and water resources. Several strategies have been used to counteract ATZ toxicity. Here, we tested the hypothesis that lycopene could ameliorate ATZ-induced toxicity in the adrenal cortex. For this purpose, 35 adult male albino rats were randomized into five equal groups: untreated control, vehicle control (received 0.5 mL corn oil/day), lycopene (treated with lycopene dissolved in 0.5 mL corn oil, 10 mg/kg b.w./day), ATZ (received ATZ dissolved in 0.5 mL corn oil 300 mg/kg b.w./day), and ATZ + lycopene (treated with ATZ and lycopene at the same previously mentioned doses). All treatments were given by oral gavage for 4 weeks. We found that ATZ exposure significantly increased relative adrenal weight, plasma ACTH levels, and adrenal oxidative stress as manifested by elevated malondialdehyde levels, decreased reduced glutathione content and depressed antioxidant enzyme activities in adrenal cortex tissues with respect to control groups. Furthermore, the transcription of adrenal cortex nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), nuclear factor kappa B, and caspase-3 genes was increased significantly compared with the control groups. This was accompanied with DNA fragmentation and structural and ultrastructural changes in zona glomerulosa and zona fasiculata of the adrenal cortex. Notably, all these changes were partially ameliorated in rats treated concomitantly with ATZ and lycopene. Our results showed that lycopene exerts protective effects against ATZ-induced toxicity in rat adrenal cortex. These effects may be attributed to the antioxidative property of lycopene and its ability to activate the Nrf2/HO-1 pathway.

  10. Trimetazidine protects retinal ganglion cells from acute glaucoma via the Nrf2/Ho-1 pathway.

    Wan, Peixing; Su, Wenru; Zhang, Yingying; Li, Zhidong; Deng, Caibin; Zhuo, Yehong

    2017-09-15

    Acute glaucoma is one of the leading causes of irreversible vision impairment characterized by the rapid elevation of intraocular pressure (IOP) and consequent retinal ganglion cell (RGC) death. Oxidative stress and neuroinflammation have been considered critical for the pathogenesis of RGC death in acute glaucoma. Trimetazidine (TMZ), an anti-ischemic drug, possesses antioxidative and anti-inflammatory properties, contributing to its therapeutic potential in tissue damage. However, the role of TMZ in acute glaucoma and the underlying molecular mechanisms remain elusive. Here, we report that treatment with TMZ significantly attenuated retinal damage and RGC death in mice with acute glaucoma, with a significant decrease in reactive oxygen species (ROS) and inflammatory cytokine production in the retina. Furthermore, TMZ treatment directly decreased ROS production and rebalanced the intracellular redox state, thus contributing to the survival of RGCs in vitro TMZ treatment also reduced the production of inflammatory cytokines in vitro Mechanistically, the TMZ-mediated inhibition of apoptosis and inflammatory cytokine production in RGCs occurred via the regulation of the nuclear factor erythroid 2-related factor 2/heme oxygenase 1/caspase-8 pathway. Moreover, the TMZ-mediated neuroprotection in acute glaucoma was abrogated when an HO-1 inhibitor, SnPP, was used. Our findings identify potential mechanisms of RGC apoptosis and propose a novel therapeutic agent, TMZ, which exerts a precise neuroprotective effect against acute glaucoma. © 2017 The Author(s).

  11. Involvement of PKA and HO-1 signaling in anti-inflammatory effects of surfactin in BV-2 microglial cells

    Park, Sun Young; Kim, Ji-Hee [Department of Molecular Biology, College of Natural Sciences, Pusan National University, Jangjeon-dong, Keumjeong-gu, Busan 609-735 (Korea, Republic of); Lee, Sang Joon [Department of Microbiology, College of Natural Sciences, Pusan National University, Jangjeon-dong, Keumjeong-gu, Busan 609-735 (Korea, Republic of); Kim, YoungHee, E-mail: yheekim@pusan.ac.kr [Department of Molecular Biology, College of Natural Sciences, Pusan National University, Jangjeon-dong, Keumjeong-gu, Busan 609-735 (Korea, Republic of)

    2013-04-01

    Surfactin, one of the most powerful biosurfactants, is a bacterial cyclic lipopeptide. Here, we investigated the anti-neuroinflammatory properties of surfactin in lipoteichoic acid (LTA)-stimulated BV-2 microglial cells. Surfactin significantly inhibited excessive production of the pro-inflammatory mediators TNF-α, IL-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1), prostaglandin E{sub 2} (PGE{sub 2}), nitric oxide (NO) and reactive oxygen species (ROS), and suppressed the expression of matrix metalloproteinase-9 (MMP-9), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). Subsequent mechanistic studies revealed that surfactin inhibited LTA-induced nuclear factor-kappaB (NF-κB) and signal transducer and activator of transcription-1 (STAT-1) activation. However, surfactin increases the phosphorylation of the STAT-3, a component of the homeostatic mechanism causing anti-inflammatory events. We also demonstrated that surfactin induces heme oxygenase-1 (HO-1) expression and nuclear factor-regulated factor-2 (Nrf-2) activation, and that the anti-inflammatory effects of surfactin are abrogated by small interfering RNA-mediated knock-down of HO-1 or Nrf-2. Interestingly, we found that surfactin increased the level of cAMP and induced phosphorylation of cAMP responsive element binding protein (CREB) in microglial cells. Furthermore, treatment with the protein kinase A (PKA) inhibitor, H-89, blocked HO-1 induction by surfactin and abolished surfactin's suppressive effects on ROS and NO production. These results indicate that HO-1 and its upstream effector, PKA, play a pivotal role in the anti-neuroinflammatory response of surfactin in LTA-stimulated microglia. Therefore, surfactin might have therapeutic potential for neuroprotective agents to treat inflammatory and neurodegenerative diseases. - Highlights: ► Surfactin inhibits proinflammatory mediator synthesis in LTA-activated BV-2 cells. ► Surfactin suppresses NF-κB and STAT-1, but potentiates

  12. Involvement of PKA and HO-1 signaling in anti-inflammatory effects of surfactin in BV-2 microglial cells

    Park, Sun Young; Kim, Ji-Hee; Lee, Sang Joon; Kim, YoungHee

    2013-01-01

    Surfactin, one of the most powerful biosurfactants, is a bacterial cyclic lipopeptide. Here, we investigated the anti-neuroinflammatory properties of surfactin in lipoteichoic acid (LTA)-stimulated BV-2 microglial cells. Surfactin significantly inhibited excessive production of the pro-inflammatory mediators TNF-α, IL-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1), prostaglandin E 2 (PGE 2 ), nitric oxide (NO) and reactive oxygen species (ROS), and suppressed the expression of matrix metalloproteinase-9 (MMP-9), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). Subsequent mechanistic studies revealed that surfactin inhibited LTA-induced nuclear factor-kappaB (NF-κB) and signal transducer and activator of transcription-1 (STAT-1) activation. However, surfactin increases the phosphorylation of the STAT-3, a component of the homeostatic mechanism causing anti-inflammatory events. We also demonstrated that surfactin induces heme oxygenase-1 (HO-1) expression and nuclear factor-regulated factor-2 (Nrf-2) activation, and that the anti-inflammatory effects of surfactin are abrogated by small interfering RNA-mediated knock-down of HO-1 or Nrf-2. Interestingly, we found that surfactin increased the level of cAMP and induced phosphorylation of cAMP responsive element binding protein (CREB) in microglial cells. Furthermore, treatment with the protein kinase A (PKA) inhibitor, H-89, blocked HO-1 induction by surfactin and abolished surfactin's suppressive effects on ROS and NO production. These results indicate that HO-1 and its upstream effector, PKA, play a pivotal role in the anti-neuroinflammatory response of surfactin in LTA-stimulated microglia. Therefore, surfactin might have therapeutic potential for neuroprotective agents to treat inflammatory and neurodegenerative diseases. - Highlights: ► Surfactin inhibits proinflammatory mediator synthesis in LTA-activated BV-2 cells. ► Surfactin suppresses NF-κB and STAT-1, but potentiates phosphorylation

  13. Induction of HO-1 by carbon monoxide releasing molecule-2 attenuates thrombin-induced COX-2 expression and hypertrophy in primary human cardiomyocytes

    Chien, Peter Tzu-Yu; Lin, Chih-Chung; Hsiao, Li-Der; Yang, Chuen-Mao

    2015-01-01

    Carbon monoxide (CO) is one of the cytoprotective byproducts of heme oxygenase (HO)-1 and exerts anti-inflammatory action in various models. However, the detailed mechanisms underlying CO-induced HO-1 expression in primary human cardiomyocytes remain largely unidentified. We used primary left ventricle myocytes as a model and applied CO releasing molecule (CORM)-2 to investigate the relationship of CO and HO-1 expression. We herein used Western blot, real-time PCR, promoter activity and EIA to investigate the role of HO-1 expression protecting against thrombin-mediated responses. We found that thrombin-induced COX-2 expression, PGE 2 release and cardiomyocyte hypertrophy markers (increase in ANF/BNP, α-actin expression and cell surface area) was attenuated by pretreatment with CORM-2 which was partially reversed by hemoglobin (Hb) or ZnPP (an inhibitor of HO-1 activity), suggesting that HO-1/CO system may be of clinical importance to ameliorate heart failure through inhibition of inflammatory responses. CORM-2-induced HO-1 protein expression, mRNA and promoter was attenuated by pretreatment with the inhibitors of Pyk2 (PF431396), PDGFR (AG1296), PI3K (LY294002), Akt (SH-5), p38 (SB202530), JNK1/2 (SP600125), FoxO1 (AS1842856) and Sp1 (mithramycin A). The involvement of these signaling components was further confirmed by transfection with respective siRNAs, consistent with those of pharmacological inhibitors. These results suggested that CORM-2-induced HO-1 expression is mediated through a Pyk2/PDGFR/PI3K/Akt/FoxO1/Sp1-dependent manner and exerts a cytoprotective effect in human cardiomyocytes. - Graphical abstract: In summary, CORM-2 treatment induces Pyk2 transactivated PDGFR, which induces PI3K/Akt/MAPK activation, and then recruits Sp1/Foxo1 transcriptional factors to regulate HO-1 gene expression in primary human cardiomyocytes. - Highlights: • CORM-2 induces HO-1 expression. • Pyk2-dependent PDGFR activates PI3K/Akt/MAPK pathway in CORM-2-induced HO-1

  14. Induction of HO-1 by carbon monoxide releasing molecule-2 attenuates thrombin-induced COX-2 expression and hypertrophy in primary human cardiomyocytes

    Chien, Peter Tzu-Yu [Department of Physiology and Pharmacology and Health Ageing Research Center, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan (China); Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan (China); Lin, Chih-Chung; Hsiao, Li-Der [Department of Anesthetics, Chang Gung Memorial Hospital at Lin-Kou and College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan (China); Yang, Chuen-Mao, E-mail: chuenmao@mail.cgu.edu.tw [Department of Physiology and Pharmacology and Health Ageing Research Center, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan (China); Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan (China); Research Center for Industry of Human Ecology and Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Tao-Yuan, Taiwan (China)

    2015-12-01

    Carbon monoxide (CO) is one of the cytoprotective byproducts of heme oxygenase (HO)-1 and exerts anti-inflammatory action in various models. However, the detailed mechanisms underlying CO-induced HO-1 expression in primary human cardiomyocytes remain largely unidentified. We used primary left ventricle myocytes as a model and applied CO releasing molecule (CORM)-2 to investigate the relationship of CO and HO-1 expression. We herein used Western blot, real-time PCR, promoter activity and EIA to investigate the role of HO-1 expression protecting against thrombin-mediated responses. We found that thrombin-induced COX-2 expression, PGE{sub 2} release and cardiomyocyte hypertrophy markers (increase in ANF/BNP, α-actin expression and cell surface area) was attenuated by pretreatment with CORM-2 which was partially reversed by hemoglobin (Hb) or ZnPP (an inhibitor of HO-1 activity), suggesting that HO-1/CO system may be of clinical importance to ameliorate heart failure through inhibition of inflammatory responses. CORM-2-induced HO-1 protein expression, mRNA and promoter was attenuated by pretreatment with the inhibitors of Pyk2 (PF431396), PDGFR (AG1296), PI3K (LY294002), Akt (SH-5), p38 (SB202530), JNK1/2 (SP600125), FoxO1 (AS1842856) and Sp1 (mithramycin A). The involvement of these signaling components was further confirmed by transfection with respective siRNAs, consistent with those of pharmacological inhibitors. These results suggested that CORM-2-induced HO-1 expression is mediated through a Pyk2/PDGFR/PI3K/Akt/FoxO1/Sp1-dependent manner and exerts a cytoprotective effect in human cardiomyocytes. - Graphical abstract: In summary, CORM-2 treatment induces Pyk2 transactivated PDGFR, which induces PI3K/Akt/MAPK activation, and then recruits Sp1/Foxo1 transcriptional factors to regulate HO-1 gene expression in primary human cardiomyocytes. - Highlights: • CORM-2 induces HO-1 expression. • Pyk2-dependent PDGFR activates PI3K/Akt/MAPK pathway in CORM-2-induced HO

  15. Small molecule activators of the Nrf2-HO-1 antioxidant axis modulate heme metabolism and inflammation in BV2 microglia cells.

    Foresti, Roberta; Bains, Sandip K; Pitchumony, Tamil Selvi; de Castro Brás, Lisandra E; Drago, Filippo; Dubois-Randé, Jean-Luc; Bucolo, Claudio; Motterlini, Roberto

    2013-10-01

    The nuclear factor erythroid derived 2-related factor 2 (Nrf2) and the antioxidant protein heme oxygenase-1 (HO-1) are crucial components of the cellular stress response. These two systems work together to combat oxidative stress and inflammation and are attractive drug targets for counteracting different pathologies, including neuroinflammation. We aimed to identify the most effective Nrf2/HO-1 activators that modulate the inflammatory response in microglia cells. In the present study, we searched the literature and selected 56 compounds reported to activate Nrf2 or HO-1 and analyzed them for HO-1 induction at 6 and 24h and cytotoxicity in BV2 microglial cells in vitro. Approximately 20 compounds up-regulated HO-1 at the concentrations tested (5-20 μM) with carnosol, supercurcumin, cobalt protoporphyrin-IX and dimethyl fumarate exhibiting the best induction/low cytotoxicity profile. Up-regulation of HO-1 by some compounds resulted in increased cellular bilirubin levels but did not augment the expression of proteins involved in heme synthesis (ALAS 1) or biliverdin reductase. Bilirubin production by HO-1 inducers correlated with their potency in inhibiting nitrite production after challenge with interferon-γ (INF-γ) or lipopolysaccharide (LPS). The compounds down-regulated the inflammatory response (TNF-α, PGE2 and nitrite) more strongly in cells challenged with INF-γ than LPS, and silencing HO-1 or Nrf2 with shRNA differentially affected the levels of inflammatory markers. These findings indicate that some small activators of Nrf2/HO-1 are effective modulators of microglia inflammation and highlight the chemical scaffolds that can serve for the synthesis of potent new derivatives to counteract neuroinflammation and neurodegeneration. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Selenolate complexes of CYP101 and the heme-bound hHO-1/H25A proximal cavity mutant.

    Jiang, Yongying; Ortiz de Montellano, Paul R

    2008-05-05

    Thiolate and selenolate complexes of CYP101 (P450cam) and the H25A proximal cavity mutant of heme-bound human heme oxygenase-1 (hHO-1) have been examined by UV-vis spectroscopy. Both thiolate and selenolate ligands bound to the heme distal side in CYP101 and gave rise to characteristic hyperporphyrin spectra. Thiolate ligands also bound to the proximal side of the heme in the cavity created by the H25A mutation in hHO-1, giving a Soret absorption similar to that of the H25C hHO-1 mutant. Selenolate ligands also bound to this cavity mutant under anaerobic conditions but reduced the heme iron to the ferrous state, as shown by the formation of a ferrous CO complex. Under aerobic conditions, the selenolate ligand but not the thiolate ligand was rapidly oxidized. These results indicate that selenocysteine-coordinated heme proteins will not be stable species in the absence of a redox potential stabilizing effect.

  17. Quercetin Protects Primary Human Osteoblasts Exposed to Cigarette Smoke through Activation of the Antioxidative Enzymes HO-1 and SOD-1

    Karl F. Braun

    2011-01-01

    Full Text Available Smokers frequently suffer from impaired fracture healing often due to poor bone quality and stability. Cigarette smoking harms bone cells and their homeostasis by increased formation of reactive oxygen species (ROS. The aim of this study was to investigate whether Quercetin, a naturally occurring antioxidant, can protect osteoblasts from the toxic effects of smoking. Human osteoblasts exposed to cigarette smoke medium (CSM rapidly produced ROS and their viability decreased concentration- and time-dependently. Co-, pre- and postincubation with Quercetin dose-dependently improved their viability. Quercetin increased the expression of the anti-oxidative enzymes heme-oxygenase- (HO- 1 and superoxide-dismutase- (SOD- 1. Inhibiting HO-1 activity abolished the protective effect of Quercetin. Our results demonstrate that CSM damages human osteoblasts by accumulation of ROS. Quercetin can diminish this damage by scavenging the radicals and by upregulating the expression of HO-1 and SOD-1. Thus, a dietary supplementation with Quercetin could improve bone matter, stability and even fracture healing in smokers.

  18. Sulforaphane protects rodent retinas against ischemia-reperfusion injury through the activation of the Nrf2/HO-1 antioxidant pathway.

    Hong Pan

    Full Text Available Retinal ischemia-reperfusion (I/R injury induces oxidative stress, leukocyte infiltration, and neuronal cell death. Sulforaphane (SF, which can be obtained in cruciferous vegetables such as broccoli, exerts protective effects in response to oxidative stress in various tissues. These effects can be initiated through nuclear factor E2-related factor 2 (Nrf2-mediated induction of heme oxygenase-1 (HO-1. This investigation was designed to elucidate the neural protective mechanisms of SF in the retinal I/R rat model. Animals were intraperitoneally (i.p. injected with SF (12.5 mg/kg or vehicle (corn oil once a day for 7 consecutive days. Then, retinal I/R was made by elevating the intraocular pressure (IOP to 130 mmHg for 1 h. To determine if HO-1 was involved in the Nrf2 antioxidant pathway, rats were subjected to protoporphyrin IX zinc (II (ZnPP, 30 mg/kg, i.p. treatments at 24 h before retinal ischemia. The neuroprotective effects of SF were assessed by determining the morphology of the retina, counting the infiltrating inflammatory cells and the surviving retinal ganglion cells (RGCs and amacrine cells, and measuring apoptosis in the retinal layers. The expression of Nrf2 and HO-1 was studied by immunofluorescence analysis and western blotting. I/R induced a marked increase of ROS generation, caused pronounced inflammation, increased the apoptosis of RGCs and amacrine cells and caused the thinning of the inner retinal layer (IRL, and these effects were diminished or abolished by SF pretreatment. Meanwhile, SF pretreatment significantly elevated the nuclear accumulation of Nrf2 and the level of HO-1 expression in the I/R retinas; however, ZnPP reversed the protective effects of SF on I/R retinas. Together, we offer direct evidence that SF had protective effects on I/R retinas, which could be attributed, at least in part, to the activation of the Nrf2/HO-1 antioxidant pathway.

  19. Diagnosis of Xeroderma Pigmentosum Groups A and C by Detection of Two Prevalent Mutations in West Algerian Population: A Rapid Genotyping Tool for the Frequent XPC Mutation c.1643_1644delTG.

    Bensenouci, Salima; Louhibi, Lotfi; De Verneuil, Hubert; Mahmoudi, Khadidja; Saidi-Mehtar, Nadhira

    2016-01-01

    Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder. Considering that XP patients have a defect of the nucleotide excision repair (NER) pathway which enables them to repair DNA damage caused by UV light, they have an increased risk of developing skin and eyes cancers. In the present study, we investigated the involvement of the prevalent XPA and XPC genes mutations-nonsense mutation (c.682C>T, p.Arg228X) and a two-base-pair (2 bp) deletion (c.1643_1644delTG or p.Val548Ala fsX25), respectively-in 19 index cases from 19 unrelated families in the West of Algeria. For the genetic diagnosis of XPA gene, we proceeded to PCR-RFLP. For the XPC gene, we validated a routine analysis which includes a specific amplification of a short region surrounding the 2 bp deletion using a fluorescent primer and fragment sizing (GeneScan size) on a sequencing gel. Among the 19 index cases, there were 17 homozygous patients for the 2 bp deletion in the XPC gene and 2 homozygous patients carrying the nonsense XPA mutation. Finally, XPC appears to be the major disease-causing gene concerning xeroderma pigmentosum in North Africa. The use of fragment sizing is the simplest method to analyze this 2 bp deletion for the DNA samples coming from countries where the mutation c.1643_1644delTG of XPC gene is prevalent.

  20. Activation of the Nrf2/HO-1 Antioxidant Pathway Contributes to the Protective Effects of Lycium Barbarum Polysaccharides in the Rodent Retina after Ischemia-Reperfusion-Induced Damage

    Chang, Raymond Chuen-Chung; So, Kwok-Fai; Brecha, Nicholas C.; Pu, Mingliang

    2014-01-01

    Lycium barbarum polysaccharides (LBP), extracts from the wolfberries, are protective to retina after ischemia-reperfusion (I/R). The antioxidant response element (ARE)–mediated antioxidant pathway plays an important role in maintaining the redox status of the retina. Heme oxygenase-1 (HO-1), combined with potent AREs in its promoter, is a highly effective therapeutic target for the protection against neurodegenerative diseases, including I/R-induced retinal damage. The aim of our present study was to investigate whether the protective effect of LBP after I/R damage was mediated via activation of the Nrf2/HO-1-antioxidant pathway in the retina. Retinal I/R was induced by an increase in intraocular pressure to 130 mm Hg for 60 minutes. Prior to the induction of ischemia, rats were orally treated with either vehicle (PBS) or LBP (1 mg/kg) once a day for 1 week. For specific experiments, zinc protoporphyrin (ZnPP, 20 mg/kg), an HO-1 inhibitor, was intraperitoneally administered at 24 h prior to ischemia. The protective effects of LBP were evaluated by quantifying ganglion cell and amacrine cell survival, and by measuring cell apoptosis in the retinal layers. In addition, HO-1 expression was examined using Western blotting and immunofluorescence analyses. Cytosolic and nuclear Nrf2 was measured using immunofluorescent staining. LBP treatment significantly increased Nrf2 nuclear accumulation and HO-1 expression in the retina after I/R injury. Increased apoptosis and a decrease in the number of viable cells were observed in the ganglion cell layer (GCL) and inner nuclear layer (INL) in the I/R retina, which were reversed by LBP treatment. The HO-1 inhibitor, ZnPP, diminished the LBP treatment-induced protective effects in the retina after I/R. Taken together, these results suggested that LBP partially exerted its beneficial neuroprotective effects via the activation of Nrf2 and an increase in HO-1 protein expression. PMID:24400114

  1. Arctigenin Protects against Lipopolysaccharide-Induced Pulmonary Oxidative Stress and Inflammation in a Mouse Model via Suppression of MAPK, HO-1, and iNOS Signaling.

    Zhang, Wen-zhou; Jiang, Zheng-kui; He, Bao-xia; Liu, Xian-ben

    2015-08-01

    Arctigenin, a bioactive component of Arctium lappa (Nubang), has anti-inflammatory activity. Here, we investigated the effects of arctigenin on lipopolysaccharide (LPS)-induced acute lung injury. Mice were divided into four groups: control, LPS, LPS + DMSO, and LPS + Arctigenin. Mice in the LPS + Arctigenin group were injected intraperitoneally with 50 mg/kg of arctigenin 1 h before an intratracheal administration of LPS (5 mg/kg). Lung tissues and bronchoalveolar lavage fluids (BALFs) were collected. Histological changes of the lung were analyzed by hematoxylin and eosin staining. Arctigenin decreased LPS-induced acute lung inflammation, infiltration of inflammatory cells into BALF, and production of pro-inflammatory cytokines. Moreover, arctigenin pretreatment reduced the malondialdehyde level and increased superoxide dismutase and catalase activities and glutathione peroxidase/glutathione disulfide ratio in the lung. Mechanically, arctigenin significantly reduced the production of nitric oxygen and inducible nitric oxygen synthase (iNOS) expression, enhanced the expression of heme oxygenase-1, and decreased the phosphorylation of mitogen-activated protein kinases (MAPKs). Arctigenin has anti-inflammatory and antioxidative effects on LPS-induced acute lung injury, which are associated with modulation of MAPK, HO-1, and iNOS signaling.

  2. Prunella vulgaris Suppresses HG-Induced Vascular Inflammation via Nrf2/HO-1/eNOS Activation

    Ho Sub Lee

    2012-01-01

    Full Text Available Vascular inflammation is an important factor which can promote diabetic complications. In this study, the inhibitory effects of aqueous extract from Prunella vulgaris (APV on high glucose (HG-induced expression of cell adhesion molecules in human umbilical vein endothelial cells (HUVEC are reported. APV decreased HG-induced expression of intercellular adhesion molecule-1 (ICAM-1, vascular cell adhesion molecule-1 (VCAM-1, and E-selectin. APV also dose-dependently inhibited HG-induced adhesion of HL-60 monocytic cells. APV suppressed p65 NF-κB activation in HG-treated cells. APV significantly inhibited the formation of intracellular reactive oxygen species (ROS. HG-stimulated HUVEC secreted gelatinases, however, APV inhibited it. APV induced Akt phosphorylation as well as activation of heme oxygenase-1 (HO-1, eNOS, and nuclear factor E2-related factor 2 (Nrf2, which may protect vascular inflammation caused by HG. In conclusion, APV exerts anti-inflammatory effect via inhibition of ROS/NF-κB pathway by inducing HO-1 and eNOS expression mediated by Nrf2, thereby suggesting that Prunella vulgaris may be a possible therapeutic approach to the inhibition of diabetic vascular diseases.

  3. Cytoprotective effect exerted by geraniin in HepG2 cells is through microRNA mediated regulation of BACH-1 and HO-1.

    Aayadi, Hoda; Mittal, Smriti P K; Deshpande, Anjali; Gore, Makarand; Ghaskadbi, Saroj S

    2017-11-01

    Geraniin, a hydrolysable tannin, used in traditional medicine in Southeast Asia, is known to exhibit various biological activities. As an antioxidant it is known to up-regulate phase II enzyme Heme oxygenase-1 (HO-1). However its mechanism is not clearly understood. Nuclear factor erythroid-derived 2 related factor 2 (Nrf-2) is transcriptionally up-regulated by Extracellular signal-regulated kinase (ERK) 1/2 and retained in nucleus due to inactivated Glycogen synthase kinase 3 beta (GSK-3β). Geraniin additionally down-regulates expression of microRNA 217 and 377 (miR-217 and miR-377) which target HO-1 mRNA. Expression of BTB and CNC homolog 1 (BACH-1), another regulator of HO-1, is also down-regulated by up-regulating microRNA 98 (miR-98), a negative regulator of BACH-1. Thus, geraniin up-regulates HO-1 expression both through activating its positive regulator Nrf-2 and by down-regulating its negative regulator BACH-1. Up-regulation of HO-1 also confers protection to HepG2 cells from tertiary butyl hydroperoxide (TBH) induced cytotoxicity. [BMB Reports 2017; 50(11): 560-565].

  4. Omega-3 polyunsaturated fatty acid has an anti-oxidant effect via the Nrf-2/HO-1 pathway in 3T3-L1 adipocytes

    Kusunoki, Chisato, E-mail: yosizaki@belle.shiga-med.ac.jp [Department of Medicine, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu, Shiga 520-2192 (Japan); Yang, Liu; Yoshizaki, Takeshi; Nakagawa, Fumiyuki; Ishikado, Atsushi; Kondo, Motoyuki; Morino, Katsutaro; Sekine, Osamu; Ugi, Satoshi [Department of Medicine, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu, Shiga 520-2192 (Japan); Nishio, Yoshihiko [Division of Diabetes, Metabolism and Endocrinology, Department of Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Kashiwagi, Atsunori; Maegawa, Hiroshi [Department of Medicine, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu, Shiga 520-2192 (Japan)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer Omega-3 PUFA has a direct anti-oxidant effect in adipocytes. Black-Right-Pointing-Pointer EPA and DHA induce HO-1 expression in 3T3-L1 adipocytes. Black-Right-Pointing-Pointer Omega-3 PUFA and its end-product, 4-HHE, activates the Nrf-2/HO-1 pathway. Black-Right-Pointing-Pointer Omega-3 PUFA protects against oxidative stress-induced cytotoxicity. -- Abstract: Oxidative stress is produced in adipose tissue of obese subjects and has been associated with obesity-related disorders. Recent studies have shown that omega-3 polyunsaturated fatty acid ({omega}3-PUFA) has beneficial effects in preventing atherosclerotic diseases and insulin resistance in adipose tissue. However, the role of {omega}3-PUFA on adipocytes has not been elucidated. In this study, 3T3-L1 adipocytes were treated with {omega}3-PUFA and its metabolites, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or 4-hydroxy hexenal (4-HHE). {omega}3-PUFA and its metabolites dose-dependently increased mRNA and protein levels of the anti-oxidative enzyme, heme oxygenase-1 (HO-1); whereas no changes in the well-known anti-oxidant molecules, superoxide dismutase, catalase, and glutathione peroxidase, were observed. Knockdown of nuclear factor erythroid 2-related factor 2 (Nrf-2) significantly reduced EPA, DHA or 4-HHE-induced HO-1 mRNA and protein expression. Also, pretreatment with {omega}3-PUFA prevented H{sub 2}O{sub 2}-induced cytotoxicity in a HO-1 dependent manner. In conclusion, treatment with EPA and DHA induced HO-1 through the activation of Nrf-2 and prevented oxidative stress in 3T3-L1 adipocytes. This anti-oxidant defense may be of high therapeutic value for clinical conditions associated with systemic oxidative stress.

  5. Omega-3 polyunsaturated fatty acid has an anti-oxidant effect via the Nrf-2/HO-1 pathway in 3T3-L1 adipocytes

    Kusunoki, Chisato; Yang, Liu; Yoshizaki, Takeshi; Nakagawa, Fumiyuki; Ishikado, Atsushi; Kondo, Motoyuki; Morino, Katsutaro; Sekine, Osamu; Ugi, Satoshi; Nishio, Yoshihiko; Kashiwagi, Atsunori; Maegawa, Hiroshi

    2013-01-01

    Highlights: ► Omega-3 PUFA has a direct anti-oxidant effect in adipocytes. ► EPA and DHA induce HO-1 expression in 3T3-L1 adipocytes. ► Omega-3 PUFA and its end-product, 4-HHE, activates the Nrf-2/HO-1 pathway. ► Omega-3 PUFA protects against oxidative stress-induced cytotoxicity. -- Abstract: Oxidative stress is produced in adipose tissue of obese subjects and has been associated with obesity-related disorders. Recent studies have shown that omega-3 polyunsaturated fatty acid (ω3-PUFA) has beneficial effects in preventing atherosclerotic diseases and insulin resistance in adipose tissue. However, the role of ω3-PUFA on adipocytes has not been elucidated. In this study, 3T3-L1 adipocytes were treated with ω3-PUFA and its metabolites, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or 4-hydroxy hexenal (4-HHE). ω3-PUFA and its metabolites dose-dependently increased mRNA and protein levels of the anti-oxidative enzyme, heme oxygenase-1 (HO-1); whereas no changes in the well-known anti-oxidant molecules, superoxide dismutase, catalase, and glutathione peroxidase, were observed. Knockdown of nuclear factor erythroid 2-related factor 2 (Nrf-2) significantly reduced EPA, DHA or 4-HHE-induced HO-1 mRNA and protein expression. Also, pretreatment with ω3-PUFA prevented H 2 O 2 -induced cytotoxicity in a HO-1 dependent manner. In conclusion, treatment with EPA and DHA induced HO-1 through the activation of Nrf-2 and prevented oxidative stress in 3T3-L1 adipocytes. This anti-oxidant defense may be of high therapeutic value for clinical conditions associated with systemic oxidative stress.

  6. Mechanism of estrogen-mediated attenuation of hepatic injury following trauma-hemorrhage: Akt-dependent HO-1 up-regulation.

    Hsu, Jun-Te; Kan, Wen-Hong; Hsieh, Chi-Hsun; Choudhry, Mashkoor A; Schwacha, Martin G; Bland, Kirby I; Chaudry, Irshad H

    2007-10-01

    Protein kinase B (Akt) is known to be involved in proinflammatory and chemotactic events in response to injury. Akt activation also leads to the induction of heme oxygenase (HO)-1. Up-regulation of HO-1 mediates potent, anti-inflammatory effects and attenuates organ injury. Although studies have shown that 17beta-estradiol (E2) prevents organ damage following trauma-hemorrhage, it remains unknown whether Akt/HO-1 plays any role in E2-mediated attenuation of hepatic injury following trauma-hemorrhage. To study this, male rats underwent trauma-hemorrhage (mean blood pressure, approximately 40 mmHg for 90 min), followed by fluid resuscitation. At the onset of resuscitation, rats were treated with vehicle, E2 (1 mg/kg body weight), E2 plus the PI-3K inhibitor (Wortmannin), or the estrogen receptor (ER) antagonist (ICI 182,780). At 2 h after sham operation or trauma-hemorrhage, plasma alpha-GST and hepatic tissue myeloperoxidase (MPO) activity, IL-6, TNF-alpha, ICAM-1, cytokine-induced neutrophil chemoattractant-1, and MIP-2 levels were measured. Hepatic Akt and HO-1 protein levels were also determined. Trauma-hemorrhage increased hepatic injury markers (alpha-GST and MPO activity), cytokines, ICAM-1, and chemokine levels. These parameters were markedly improved in the E2-treated rats following trauma-hemorrhage. E2 treatment also increased hepatic Akt activation and HO-1 expression compared with vehicle-treated, trauma-hemorrhage rats, which were abolished by coadministration of Wortmannin or ICI 182,780. These results suggest that the salutary effects of E2 on hepatic injury following trauma-hemorrhage are in part mediated via an ER-related, Akt-dependent up-regulation of HO-1.

  7. Fructose Mediated Non-Alcoholic Fatty Liver Is Attenuated by HO-1-SIRT1 Module in Murine Hepatocytes and Mice Fed a High Fructose Diet.

    Komal Sodhi

    Full Text Available Oxidative stress underlies the etiopathogenesis of nonalcoholic fatty liver disease (NAFLD, obesity and cardiovascular disease (CVD. Heme Oxygenase-1 (HO-1 is a potent endogenous antioxidant gene that plays a key role in decreasing oxidative stress. Sirtuin1 (SIRT1 belongs to the family of NAD-dependent de-acyetylases and is modulated by cellular redox.We hypothesize that fructose-induced obesity creates an inflammatory and oxidative environment conducive to the development of NAFLD and metabolic syndrome. The aim of this study is to determine whether HO-1 acts through SIRT1 to form a functional module within hepatocytes to attenuate steatohepatitis, hepatic fibrosis and cardiovascular dysfunction.We examined the effect of fructose, on hepatocyte lipid accumulation and fibrosis in murine hepatocytes and in mice fed a high fructose diet in the presence and absence of CoPP, an inducer of HO-1, and SnMP, an inhibitor of HO activity. Fructose increased oxidative stress markers and decreased HO-1 and SIRT1 levels in hepatocytes (p<0.05. Further fructose supplementation increased FAS, PPARα, pAMPK and triglycerides levels; CoPP negated this increase. Concurrent treatment with CoPP and SIRT1 siRNA in hepatocytes increased FAS, PPARα, pAMPK and triglycerides levels suggesting that HO-1 is upstream of SIRT1 and suppression of SIRT1 attenuates the beneficial effects of HO-1. A high fructose diet increased insulin resistance, blood pressure, markers of oxidative stress and lipogenesis along with fibrotic markers in mice (p<0.05. Increased levels of HO-1 increased SIRT1 levels and ameliorated fructose-mediated lipid accumulation and fibrosis in liver along with decreasing vascular dysfunction (p<0.05 vs. fructose. These beneficial effects of CoPP were reversed by SnMP.Taken together, our study demonstrates, for the first time, that HO-1 induction attenuates fructose-induced hepatic lipid deposition, prevents the development of hepatic fibrosis and abates

  8. Report of AAPM TG 135: quality assurance for robotic radiosurgery.

    Dieterich, Sonja; Cavedon, Carlo; Chuang, Cynthia F; Cohen, Alan B; Garrett, Jeffrey A; Lee, Charles L; Lowenstein, Jessica R; d'Souza, Maximian F; Taylor, David D; Wu, Xiaodong; Yu, Cheng

    2011-06-01

    The task group (TG) for quality assurance for robotic radiosurgery was formed by the American Association of Physicists in Medicine's Science Council under the direction of the Radiation Therapy Committee and the Quality Assurance (QA) Subcommittee. The task group (TG-135) had three main charges: (1) To make recommendations on a code of practice for Robotic Radiosurgery QA; (2) To make recommendations on quality assurance and dosimetric verification techniques, especially in regard to real-time respiratory motion tracking software; (3) To make recommendations on issues which require further research and development. This report provides a general functional overview of the only clinically implemented robotic radiosurgery device, the CyberKnife. This report includes sections on device components and their individual component QA recommendations, followed by a section on the QA requirements for integrated systems. Examples of checklists for daily, monthly, annual, and upgrade QA are given as guidance for medical physicists. Areas in which QA procedures are still under development are discussed.

  9. Relationship of Heme Oxygenase-1 (HO-1 Level with Onset and Severity in Normotensive Pregnancy and Severe Preeclampsia

    John Johannes Wantania

    2016-08-01

    Full Text Available Background: Preeclampsia still becomes a major problem in pregnancies. Various evidences showed that heme oxygenase-1 (HO-1 is very important in pregnancy. This study aims to understand the relationship of heme oxygenase-1 level with onset and severity in normotensive pregnancy and severe preeclampsia. Methods: This is a cross sectional analytic comparative study, the subjects consisted of 26 patients with normotensive pregnancies and 26 patients with severe preeclampsia. Blood samples from women with < 34 / ≥ 34 weeks’ normotensive pregnancies and women with severe preeclampsia were taken. HO-1 ELISA kit used to quantitate heme oxygenase-1 level in samples. Results: The level of heme oxygenase-1 in normotensive pregnant women < 34 weeks lower than severe preeclampsia pregnant women < 34 weeks (3.28 ± 0.46 ng/mL vs 4.20 ± 0.64 ng/mL, p=0.003, respectively. The median level of heme oxygenase-1 in normotensive pregnant women ≥ 34 weeks was 2.96 (2.41–4.39 ng/mL, while severe preeclampsia pregnant women ≥ 34 weeks was 3.52 (2.88–5.43 ng/mL, (p=0.040. The median level of heme oxygenase-1 in normotensive pregnant women was 3.04 (2.41–4.39 ng/mL, while severe preeclampsia pregnant women was 3.68 (2.88–5.67 ng/mL, (p=0.001. Conclusions: There is correlation between the incidence of severe preeclampsia with heme oxygenase-1 level in < 34 and ≥ 34 weeks of pregnancy. There is a significant difference between the level of heme oxygenase-1 in pregnant women with severe preeclampsia and in women with normotensive pregnancy. 

  10. Atractylenolide I restores HO-1 expression and inhibits Ox-LDL-induced VSMCs proliferation, migration and inflammatory responses in vitro

    Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn; Zhi, Wenbing; Liu, Fang; He, Zehong; Wang, Xiuei; Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn

    2017-04-01

    Pathogenesis of atherosclerosis is characterized by the proliferation and migration of vascular smooth muscle cells (VSMCs) and inflammatory lesions. The aim of this study is to elucidate the effect of atractylenolide I (AO-I) on smooth muscle cell inflammation, proliferation and migration induced by oxidized modified low density lipoprotein (Ox-LDL). Here, We found that atractylenolide I inhibited Ox-LDL-induced VSMCs proliferation and migration in a dose-dependent manner, and decreased the production of inflammatory cytokines and the expression of monocyte chemoattractant protein-1 (MCP-1) in VSMCs. The study also identified that AO-I prominently inhibited p38-MAPK and NF-κB activation. More importantly, the specific heme oxygenase-1 (HO-1) inhibitor zinc protoporphyrin (ZnPP) IX partially abolished the beneficial effects of atractylenolide I on Ox-LDL-induced VSMCs. Furthermore, atractylenolide I blocked the foam cell formation in macrophages induced by Ox-LDL. In summary, inhibitory roles of AO-I in VSMCs proliferation and migration, lipid peroxidation and subsequent inflammatory responses might contribute to the anti-atherosclerotic property of AO-I. - Highlights: • AO-I inhibited Ox-LDL-induced VSMCs proliferation and migration. • AO-I alleviated inflammatory response via inhibiting TNF-α, IL-6 and NO production. • AO-I restored HO-1 expression and down-regulated PCNA expression. • MCP-1 overexpression is potentially regulated by NF-κB and p38 MAPK pathway. • AO-I possesses strong anti-lipid peroxidation effect.

  11. Taurine Protects Mouse Spermatocytes from Ionizing Radiation-Induced Damage Through Activation of Nrf2/HO-1 Signaling.

    Yang, Wenjun; Huang, Jinfeng; Xiao, Bang; Liu, Yan; Zhu, Yiqing; Wang, Fang; Sun, Shuhan

    2017-01-01

    The increasing prevalence of ionizing radiation exposure has inevitably raised public concern over the potential detrimental effects of ionizing radiation on male reproductive system function. The detection of drug candidates to prevent reproductive system from damage caused by ionizing radiation is urgent. We aimed to investigate the protective role of taurine on the injury of mouse spermatocyte-derived cells (GC-2) subjected to ionizing radiation. mouse spermatocytes (GC-2 cells) were exposed to ionizing radiation with or without treatment of Taurine. The effect of ionizing radiation and Taurine treatment on GC-2 cells were evaluated by cell viability assay (CCK8), cell cycle and apoptosis. The relative protein abundance change was determined by Western blotting. The siRNA was used to explore whether Nrf2 signaling was involved in the cytoprotection of Taurine. Taurine significantly inhibited the decrease of cell viability, percentage of apoptotic cells and cell cycle arrest induced by ionizing radiation. Western blot analysis showed that taurine significantly limited the ionizing radiation-induced down-regulation of CyclinB1 and CDK1, and suppressed activation of Fas/FasL system pathway. In addition, taurine treatment significantly increased the expression of Nrf2 and HO-1 in GC-2 cells exposed to ionizing radiation, two components in antioxidant pathway. The above cytoprotection of Taurine was blocked by siNrf2. Our results demonstrate that taurine has the potential to effectively protect GC-2 cells from ionizing radiation- triggered damage via upregulation of Nrf2/HO-1 signaling. © 2017 The Author(s). Published by S. Karger AG, Basel.

  12. A new VME timing module: TG8

    Beetham, C.G.; Daems, G.; Lewis, J.; Puccio, B.

    1992-01-01

    The two accelerator divisions of CERN, namely PS and SL, are defining a new common control system based on PC, VME and Workstations. This has provided an opportunity to review both central timing systems and to come up with common solutions. The result was, amongst others, the design of a unique timing module, called TG8. The TG8 is a multipurpose VME module, which receives messages distributed over a timing network. These messages include timing information, clock plus calendar and telegrams instructing the CERN accelerators on the characteristics of the next beam to be produced. The TG8 compares incoming messages with up to 256 programmed actions. An action consists of two parts, a trigger which matches an incoming message and what to do when the match occurs. The latter part may optionally create an output pulse on one of the eight output channels and/or a bus interrupt, both with programmable delay and telegram conditioning. (author)

  13. Transglutaminase (TG) involvement in early embryogenesis

    Maccioni, R.B.; Arechaga, J.

    1986-01-01

    Transglutaminase (TG) has been examined in different stages of preimplantation mouse embryogenesis. The specific activity of this enzyme in the soluble cellular fraction increases 2-fold from 2-cell embryos to 8-cell morulae and 4-fold from 2-cell embryos to blastocyst. The same developmental profile was seen when either N,N-dimethylcasein or endogenous substrates were used in the TG assay. Using high-speed supernatants from different stage embryos as a source of enzyme and [ 3 H]putrescine as acyl acceptor, the major acyl donor components were tubulin and a high molecular weight (HMW) cross-linkage product, as assessed by electrophoresis and immunoblotting. When either assembled or monomeric cytoskeleton proteins were compared as subtrates, microtubules were the best acyl donors. These studies indicate that TG activity is modulated during the changing demands of blastomeres for microtubule cytoskeleton in early embryogenesis

  14. Characterization of docosahexaenoic acid (DHA)-induced heme oxygenase-1 (HO-1) expression in human cancer cells: the importance of enhanced BTB and CNC homology 1 (Bach1) degradation.

    Wang, Shuai; Hannafon, Bethany N; Wolf, Roman F; Zhou, Jundong; Avery, Jori E; Wu, Jinchang; Lind, Stuart E; Ding, Wei-Qun

    2014-05-01

    The effect of docosahexaenoic acid (DHA) on heme oxygenase-1 (HO-1) expression in cancer cells has never been characterized. This study examines DHA-induced HO-1 expression in human cancer cell model systems. DHA enhanced HO-1 gene expression in a time- and concentration-dependent manner, with maximal induction at 21 h of treatment. This induction of HO-1 expression was confirmed in vivo using a xenograft nude mouse model fed a fish-oil-enriched diet. The increase in HO-1 gene transcription induced by DHA was significantly attenuated by the antioxidant N-acetyl cysteine, suggesting the involvement of oxidative stress. This was supported by direct measurement of lipid peroxide levels after DHA treatment. Using a human HO-1 gene promoter reporter construct, we identified two antioxidant response elements (AREs) that mediate the DHA-induced increase in HO-1 gene transcription. Knockdown of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression compromised the DHA-induced increase in HO-1 gene transcription, indicating the importance of the Nrf2 pathway in this event. However, the nuclear protein levels of Nrf2 remained unchanged upon DHA treatment. Further studies demonstrated that DHA reduces nuclear Bach1 protein expression by promoting its degradation and attenuates Bach1 binding to the AREs in the HO-1 gene promoter. In contrast, DHA enhanced Nrf2 binding to the AREs without affecting nuclear Nrf2 expression levels, indicating a new cellular mechanism that mediates DHA's induction of HO-1 gene transcription. To our knowledge, this is the first characterization of DHA-induced HO-1 expression in human malignant cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Maresin 1 Ameliorates Lung Ischemia/Reperfusion Injury by Suppressing Oxidative Stress via Activation of the Nrf-2-Mediated HO-1 Signaling Pathway

    Quanchao Sun

    2017-01-01

    Full Text Available Lung ischemia/reperfusion (I/R injury occurs in various clinical conditions and heavily damaged lung function. Oxidative stress reaction and antioxidant enzymes play a pivotal role in the etiopathogenesis of lung I/R injury. In the current study, we investigated the impact of Maresin 1 on lung I/R injury and explored the possible mechanism involved in this process. MaR 1 ameliorated I/R-induced lung injury score, wet/dry weight ratio, myeloperoxidase, tumor necrosis factor, bronchoalveolar lavage fluid (BALF leukocyte count, BALF neutrophil ratio, and pulmonary permeability index levels in lung tissue. MaR 1 significantly reduced ROS, methane dicarboxylic aldehyde, and 15-F2t-isoprostane generation and restored antioxidative enzyme (superoxide dismutase, glutathione peroxidase, and catalase activities. Administration of MaR 1 improved the expression of nuclear Nrf-2 and cytosolic HO-1 in I/R-treated lung tissue. Furthermore, we also found that the protective effects of MaR 1 on lung tissue injury and oxidative stress were reversed by HO-1 activity inhibitor, Znpp-IX. Nrf-2 transcription factor inhibitor, brusatol, significantly decreased MaR 1-induced nuclear Nrf-2 and cytosolic HO-1 expression. In conclusion, these results indicate that MaR 1 protects against lung I/R injury through suppressing oxidative stress. The mechanism is partially explained by activation of the Nrf-2-mediated HO-1 signaling pathway.

  16. Aging of Dielectric Properties below Tg

    Olsen, Niels Boye; Dyre, Jeppe; Christensen, Tage Emil

    The dielectric loss at 1Hz in TPP is studied during a temperature step from one equilibrium state to another. In the applied cryostate the temperature can be equilibrated on a timescale of 1 second. The aging time dependence of the dielectric loss is studied below Tg applying temperature steps...

  17. Andrographolide protects liver cells from H2O2 induced cell death by upregulation of Nrf-2/HO-1 mediated via adenosine A2a receptor signalling.

    Mittal, Smriti P K; Khole, Swati; Jagadish, Nidhi; Ghosh, Debjani; Gadgil, Vijay; Sinkar, Vilas; Ghaskadbi, Saroj S

    2016-11-01

    Andrographolide, principle constituent of Andrographis paniculata Nees is used in traditional medicine in Southeast Asia and is known to exhibit various biological activities. Its antioxidant activity is due to its ability to activate one of the antioxidant enzymes, heme oxygenase-1 (HO-1) which is regulated transcriptionally through Nrf-2. However, molecular mechanism underlying activation of Nrf-2/HO-1 has not yet been clearly understood. Protective effect of andrographolide against H2O2 induced cell death, reactive oxygen species and lipid peroxidation was observed in HepG2 cells. Ability of andrographolide to modulate G-protein coupled receptor (GPCR) mediated signalling was determined using in silico docking and gene expression was analyzed by qRT-PCR, confocal microscopy and western blot analysis. We clearly show that andrographolide via adenosine A2A receptor signalling leads to activation of p38 MAP kinase, resulting in upregulation of Nrf-2, its translocation to nucleus and activation of HO-1. Additionally, it activates adenylate cyclase resulting in cAMP formation which in turn activates protein kinase A leading to inhibition of GSK-3β by phosphorylation. Inactivated GSK-3β leads to retention of Nrf-2 in the nucleus leading to sustained expression of HO-1 by binding to its antioxidant response element (ARE). Thus, andrographolide probably by binding to adenosine A2a receptor activates Nrf-2 transcription and also inhibits its exclusion from the nucleus by inactivating GSK-3β, together resulting in activation of HO-1. We speculate that andrographolide can be used as a therapeutic drug to combat oxidative stress implicated in pathogenesis of various diseases such as diabetes, osteoporosis, neurodegenerative diseases etc. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Agmatine Reduces Lipopolysaccharide-Mediated Oxidant Response via Activating PI3K/Akt Pathway and Up-Regulating Nrf2 and HO-1 Expression in Macrophages.

    Jianshen Chai

    Full Text Available Macrophages are key responders of inflammation and are closely related with oxidative stress. Activated macrophages can enhance oxygen depletion, which causes an overproduction of reactive oxygen species (ROS and leads to further excessive inflammatory response and tissue damage. Agmatine, an endogenous metabolite of L-arginine, has recently been shown to have neuroprotective effects based on its antioxidant properties. However, the antioxidant effects of agmatine in peripheral tissues and cells, especially macrophages, remain unclear. In this study we explored the role of agmatine in mediating antioxidant effects in RAW 264.7 cells and studied its antioxidant mechanism. Our data demonstrate that agmatine is an activator of Nrf2 signaling that markedly enhances Nrf2 nuclear translocation, increases nuclear Nrf2 protein level, up-regulates the expression of the Nrf2 downstream effector HO-1, and attenuates ROS generation induced by Lipopolysaccharide (LPS. We further demonstrated that the agmatine-induced activation of Nrf2 is likely through the PI3K/Akt pathway. LY294002, a specific PI3K/Akt inhibitor, abolished agmatine-induced HO-1 up-regulation and ROS suppression significantly. Inhibiting HO-1 pathway significantly attenuated the antioxidant effect of agmatine which the products of HO-1 enzymatic activity contributed to. Furthermore, the common membrane receptors of agmatine were evaluated, revealing that α2-adrenoceptor, I1-imidazoline receptor or I2-imidazoline receptor are not required by the antioxidant properties of agmatine. Taken together, our findings revealed that agmatine has antioxidant activity against LPS-induced ROS accumulation in RAW 264.7 cells involving HO-1 expression induced by Nrf2 via PI3K/Akt pathway activation.

  19. Electroacupuncture Ameliorates Acute Renal Injury in Lipopolysaccharide-Stimulated Rabbits via Induction of HO-1 through the PI3K/Akt/Nrf2 Pathways.

    Yu, Jian-Bo; Shi, Jia; Zhang, Yuan; Gong, Li-Rong; Dong, Shu-An; Cao, Xin-Shun; Wu, Li-Li; Wu, Li-Na

    2015-01-01

    Electroacupuncture at select acupoints have been verified to protect against organ dysfunctions during endotoxic shock. And, heme oxygenase (HO)-1 as a phase II enzyme and antioxidant contributed to the protection of kidney in septic shock rats. The phosphatidylinositol 3-kinase (PI3K)-Akt pathway mediated the activation of NF-E2 related factor-2 (Nrf2), which was involved in HO-1 induction. To understand the efficacy of electroacupuncture stimulation in ameliorating acute kidney injury (AKI) through the PI3K/Akt/Nrf2 pathway and subsequent HO-1 upregulation, a dose of LPS 5mg/kg was administered intravenously to replicate the rabbit model of AKI induced by endotoxic shock. Electroacupuncture pretreatment was handled bilaterally at Zusanli and Neiguan acupoints for five consecutive days while sham electroacupuncture at non-acupoints as control. Results displayed that electroacupuncture stimulation significantly alleviated the morphologic renal damage, attenuated renal tubular apoptosis, suppressed the elevated biochemical indicators of AKI caused by LPS, enhanced the expressions of phospho-Akt, HO-1protein, Nrf2 total and nucleoprotein, and highlighted the proportions of Nrf2 nucleoprotein as a parallel. Furthermore, partial protective effects of elecroacupuncture were counteracted by preconditioning with wortmannin (the selective PI3K inhibitor), indicating a direct involvement of PI3K/Akt pathway. Inconsistently, wortmannin pretreatment made little difference to the expressions of HO-1, Nrf2 nucleoprotein and total protein, which indicated that PI3K/Akt may be not the only pathway responsible for electroacupuncture-afforded protection against LPS-induced AKI. These findings provide new insights into the potential future clinical applications of electroacupuncture for AKI induced by endotoxic shock instead of traditional remedies.

  20. Tanshinol ameliorates CCl4-induced liver fibrosis in rats through the regulation of Nrf2/HO-1 and NF-κB/IκBα signaling pathway

    Wang R

    2018-05-01

    Full Text Available Rong Wang,* Jing Wang,* Fuxing Song, Shengnan Li, Yongfang Yuan Department of Pharmacy, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China *These authors contributed equally to this work Abstract: Tanshinol, a water-soluble component isolated from Salvia miltiorrhiza Bunge, has a variety of biological activities involving anti-fibrotic effect. However, the exact role and the underlying mechanisms remain largely unclear. This study mainly focused on the anti-hepatic fibrotic activities and mechanisms of tanshinol on carbon tetrachloride (CCl4-induced liver fibrosis in rats via anti-oxidative and anti-inflammation pathways. The rats were divided into 4 groups as follows: control, model, tanshinol 20 mg/kg, and tanshinol 40 mg/kg. Except for the control group, CCl4 was used to induce liver fibrosis processing for 8 weeks, meanwhile rats in tanshinol groups were intraperitoneally injected with additional tanshinol. Control group simultaneously received the same volumes of olive oil and saline. The potentially protective effect and mechanisms of tanshinol on liver fibrosis in rats were evaluated. The serum levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin were obviously lower in the tanshinol treatment groups related to model group. Compared with the model group, the levels of hyaluronic acid, type IV collagen, Laminin (LN, and procollagen III peptide (PIIIP in serum were significantly decreased after tanshinol treatment. Furthermore, tanshinol could regulate Nrf2/HO-1 signaling pathway and increase the level of superoxide dismutase (SOD and glutathione peroxidase (GSH-Px, and also decrease the level of malondialdehyde (MDA to against damage induced by oxidative stress. Simultaneously tanshinol could regulate nuclear factor kappa B signaling pathway to inhibit expression of inflammation factors, including transforming growth factor-β, tumor necrosis factor-α, Cox-2

  1. Intermittent hypoxia simulating obstructive sleep apnea causes pulmonary inflammation and activates the Nrf2/HO-1 pathway.

    Wang, Yeying; Chai, Yanling; He, Xiaojie; Ai, Li; Sun, Xia; Huang, Yiling; Li, Yongxia

    2017-10-01

    Obstructive sleep apnea (OSA) is a disorder with high morbidity in adults. OSA damages multiple organs and tissues, including the cardiovascular and cerebrovascular systems, the metabolism system, the lungs, liver and heart. OSA-induced damage is earliest and greatest to the pulmonary tissue. The present study established a rat OSA model of differing severity by inducing intermittent hypoxia with different concentrations of O 2 and it was determined that OSA caused a severe oxidative stress response and pulmonary inflammation in a dose-dependent manner. OSA increased serum levels of C-reactive protein and 8-isoprostane and elevated the expression of malondialdehyde, tumor necrosis factor α, interleukin (IL)-1β and IL-6 in the pulmonary tissue. Furthermore, the expression of two important antioxidants, superoxide dismutase and glutathione, was downregulated following intermittent hypoxia. By contrast, levels of cylooxygenase 2 and inducible nitric oxide synthase, which are crucial in the antioxidative response, increased. In addition, OSA activates the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase (OH)-1 antioxidative signaling pathway. Finally, all increases and decreases in levels of inflammatory and antioxidative substances were dependent on oxygen concentrations. Therefore, the present study demonstrated that OSA, simulated by intermittent hypoxia, caused an oxidative stress response and pulmonary inflammation, and activated the canonical antioxidative Nrf2/HO-1 signaling pathway in a dose-dependent manner. These results may facilitate the development of clinical therapies to treat pulmonary diseases caused by OSA.

  2. TG 220 MW hydraulic control system diagnostics

    Svabcik, A.

    1996-01-01

    The TG power output control system comprises a hydraulic and an electronic part. TG speed, power output or the main steam header pressure (HPK) depend on the steam flow at the turbine inlet. The steam admission into the turbine is controlled by four control valves and one by-pass valve in case of the HP part and by four capture flap valves in case of the LP part. The task of the SKODA K-220 MW turbine protection and control systems is to provide both the turbine speed and power output control to the setpoint value. Diagnostic measurements were aimed at getting an overview of both technical and functional states of all power output control elements. Principally, it can be stated that some deficiencies of a design nature originating from the manufacturer's factory were revealed and some other deficiencies related to hydraulic control elements functionality were identified more closely by the new method. 5 figs

  3. TG 220 MW hydraulic control system diagnostics

    Svabcik, A [Atomova Elektraren Bohunice, Jaslovske Bohunice (Slovakia)

    1997-12-31

    The TG power output control system comprises a hydraulic and an electronic part. TG speed, power output or the main steam header pressure (HPK) depend on the steam flow at the turbine inlet. The steam admission into the turbine is controlled by four control valves and one by-pass valve in case of the HP part and by four capture flap valves in case of the LP part. The task of the SKODA K-220 MW turbine protection and control systems is to provide both the turbine speed and power output control to the setpoint value. Diagnostic measurements were aimed at getting an overview of both technical and functional states of all power output control elements. Principally, it can be stated that some deficiencies of a design nature originating from the manufacturer`s factory were revealed and some other deficiencies related to hydraulic control elements functionality were identified more closely by the new method. 5 figs.

  4. TG-FTIR analysis of biomass pyrolysis

    Bassilakis, R.; Carangelo, R.M.; Wojtowicz, M.A. [Advanced Fuel Research Inc., Hartford, CT (United States)

    2001-10-09

    A great need exists for comprehensive biomass-pyrolysis models that could predict yields and evolution patterns of selected volatile products as a function of feedstock characteristics and process conditions. A thermogravimetric analyzer coupled with Fourier transform infrared analysis of evolving products (TG-FTIR) can provide useful input to such models in the form of kinetic information obtained under low heating rate conditions. In this work, robust TG-FTIR quantification routes were developed for infrared analysis of volatile products relevant to biomass pyrolysis. The analysis was applied to wheat straw, three types of tobacco (Burley, Oriental, and Bright) and three biomass model compounds (xylan, chlorogenic acid, and D-glucose). Product yields were compared with literature data, and species potentially quantifiable by FT-IR are reviewed. Product-evolution patterns are reported for all seven biomass samples. 41 refs., 7 figs., 2 tabs.

  5. Clinical electron beam dosimetry: transition from AAPM TG-25 to AAPM TG-70

    Mihailidis, Dimitris

    2017-01-01

    The absolute calibration of clinical electron beams is increasingly based on TG-51 protocol. In addition, recently published dosimetry data on electrons beams bring up the question of how would one need to modify the widely used TG-25 that originally was based on TG-21 calibration protocol? The answer to the question is given by the recently published TG-70. This new protocol operates as supplement and update to TG-25 on issues that need to be modified because of TG-51 approach to electron dosimetry and because of newer data on clinical electron beams. It describes in detail the procedure of converting measured depth-ionization curves with ion chambers into depth-dose curves, making use of recently published stopping-power ratios and other conversion factors. It also describes the use of water equivalent phantoms to perform relative electron dosimetry based on recently published conversions factors. The report discusses small and irregularly shaped electron field dosimetry using the concept of lateral buildup ratio (LBR) as an avenue to evaluate electronic equilibrium and compute dose per MU for those fields. Finally, it gives some common clinical examples where electron beam dosimetry are applied

  6. TG/FT-IR characterization of additives typically employed in EPDM formulations

    Natália Beck Sanches

    2015-06-01

    Full Text Available AbstractThermogravimetric analysis coupled to Fourier transform infrared spectroscopy (TG/FT-IR is a very popular technique for rubbers characterization. It involves analyses of the base polymer and additives. Ethylene–propylene–diene (EPDM rubbers are frequently investigated by TG/FT-IR; however, the focus has been the degradation temperature range of the polymer. In this study, unvulcanized and vulcanized EPDM rubber and its additives were investigated by TG/FT-IR, without solvent extraction, and in a wide temperature range. Initially, the additives were individually characterized. TG/FT-IR identified the characteristic groups of all the additives analyzed and distinguished them from each other. Afterwards, unvulcanized and vulcanized EPDM rubbers were investigated without prior extraction.TG/FT-IR detected absorptions due to the additives tetramethylthiuram monosulfide and 2-mercaptobenzothiazole. Both of these sulfur-containing additives were present in the EPDM formulation at concentrations of 0.7 phr (0.63 wt %. The TG/FT-IR technique had some limitations, because not all the additives in EPDM rubber were detected. Paraffin oil, stearic acid and 2,2,4-trimethyl-1,2-dihydroquinoline functional groups were not observed in either the unvulcanized or vulcanized EPDM. Nevertheless, in addition to the ability of this method to detect sulfur-containing groups, the lack of a pre-extraction reduces the time and effort required for additive analysis in rubbers.

  7. Glaucocalyxin B Alleviates Lipopolysaccharide-Induced Parkinson’s Disease by Inhibiting TLR/NF-κB and Activating Nrf2/HO-1 Pathway

    Wei Xu

    2017-12-01

    Full Text Available Background/Aims: Parkinson’s disease (PD is a common neurodegenerative disease in the old population, characterized by dopaminergic neuron loss, inflammation and oxidative stress injury in the substantia nigra. Glaucocalyxin B (GLB, an ent-kauranoid diterpenoid isolated from Rabdosia japonica, has anti-inflammation and anti-tumor effects. However, its effects on PD remain unclear. Methods: PD was introduced in rats via injection of lipopolysaccharide (LPS into cerebral corpus striatum, and GLB was given intracerebroventricularly to these rats. Their walking, climbing and sensory states were detected by Stepping, Whisker and Cylinder Tests. The expression of tyrosine hydroxylase (TH, glial fibrillary acidic protein (GFAP, CD11b and ionized calcium binding adaptor molecule (IBA-1 were detected by immunohischemical staining. The levels of a series of inflammatory factors, oxidative stress-related factors and apoptosis-related factors were measured by real-time PCR, immunoblotting and ELISA. In addition, Toll-like receptor (TLR/nuclear factor kappa B (NF-κB and nuclear factor erythroid 2-related factor 2 (Nrf2/heme oxygenase (HO-1 pathways were investigated to illustrate the underlying mechanism. In vitro, microglial cells exposed to LPS were treated with GLB. Results: The injection of LPS caused walking, climbing and sensory disturbances in rats, induced inflammation, oxidative stress response and apoptosis, and activated TLR/NF-κB and Nrf2/ HO-1 pathways in the cerebral tissue. GLB administration attenuated LPS-induced alterations. The TLR/NF-κB pathway was deactivated and Nrf2/HO-1 was activated after application of GLB. In vitro, cytotoxic effects induced by the conditioned medium derived from microglial cells exposed to LPS in PC12 cells were attenuated by GLB. Conclusion: GLB suppresses LPS-induced PD symptoms by modification of TLR/NF-κB and Nrf2/HO-1 pathways in vivo and in vitro.

  8. Differential expression patterns of Nqo1, AKR1B8 and Ho-1 in the liver and small intestine of C57BL/6 mice treated with sulforaphane

    Lin Luo

    2015-12-01

    Full Text Available This data article contains complementary figures and results related to the research article entitled “butylated hydroxyanisole induces distinct expression patterns of Nrf2 and detoxification enzymes in the liver and small intestine of C57BL/6 mice” (Luo et al., 2015 [1], which defined the basal and butylated hydroxyanisole (BHA-induced expression patterns of Phase II enzymes Nqo1, AKR1B8, and Ho-1 in the liver and small intestine of C57BL/6 mice. Sulforaphane [1-isothiocyanato-4-(methylsulfinylbutane] (SFN, a naturally occurring isothiocyanate derived from cruciferous vegetables, is a highly potent inducer of phase II cytoprotective enzymes. This dataset reports the histological changes of Nqo1, AKR1B8, and Ho-1 in wild-type (WT and Nrf2-/- mice induced by SFN. The mice were given a 25 mg/kg single oral dose of SFN for 24 h and 48 h. Immunohistochemistry revealed that, in the liver from WT mice, SFN increased Nqo1 staining in hepatocytes with slight higher staining in the pericentral region. The induction of AKR1B8 appeared mostly in hepatocytes in the periportal region. The basal and inducible Ho-1 was located predominately in Kupffer cells. In the small intestine from WT mice, the inducible expression of Nqo1 and AKR1B8 appeared more obvious in the villus than that in the crypt.

  9. Andrographolide Activates Keap1/Nrf2/ARE/HO-1 Pathway in HT22 Cells and Suppresses Microglial Activation by Aβ42 through Nrf2-Related Inflammatory Response.

    Seo, Ji Yeon; Pyo, Euisun; An, Jin-Pyo; Kim, Jinwoong; Sung, Sang Hyun; Oh, Won Keun

    2017-01-01

    Therapeutic approach of Alzheimer's disease (AD) has been gradually diversified. We examined the therapeutic and preventive potential of andrographolide, which is a lactone diterpenoid from Andrographis paniculata , and focused on the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated heme oxygenase (HO)-1-inducing effects and the inhibitory activity of amyloid beta (A β ) 42 -induced microglial activation related to Nrf2 and nuclear factor κ B (NF- κ B)-mediated inflammatory responses. Andrographolide induced the expression and translocation of Nrf2 from the cytoplasm to the nucleus, thereby activating antioxidant response element (ARE) gene transcription and HO-1 expression in murine hippocampal HT22 cells. Andrographolide eliminated intracellular A β 42 in BV-2 cells and decreased the production of interleukin (IL)-6, IL-1 β , prostaglandin (PG)E 2 , and nitric oxide (NO) because of artificial phagocytic A β 42 . It decreased pNF- κ B accumulation in the nucleus and the expression of inducible nitric oxide synthase (i-NOS) and cyclooxygenase II (COX-II) in the microglial BV-2 cell line. In summary, andrographolide activates Nrf2-mediated HO-1 expression and inhibits A β 42 -overexpressed microglial BV-2 cell activation. These results suggested that andrographolide might have the potential for further examination of the therapeutics of AD.

  10. Andrographolide Activates Keap1/Nrf2/ARE/HO-1 Pathway in HT22 Cells and Suppresses Microglial Activation by Aβ42 through Nrf2-Related Inflammatory Response

    Ji Yeon Seo

    2017-01-01

    Full Text Available Therapeutic approach of Alzheimer’s disease (AD has been gradually diversified. We examined the therapeutic and preventive potential of andrographolide, which is a lactone diterpenoid from Andrographis paniculata, and focused on the Kelch-like ECH-associated protein 1 (Keap1/nuclear factor (erythroid-derived 2-like 2 (Nrf2-mediated heme oxygenase (HO-1-inducing effects and the inhibitory activity of amyloid beta (Aβ42-induced microglial activation related to Nrf2 and nuclear factor κB (NF-κB-mediated inflammatory responses. Andrographolide induced the expression and translocation of Nrf2 from the cytoplasm to the nucleus, thereby activating antioxidant response element (ARE gene transcription and HO-1 expression in murine hippocampal HT22 cells. Andrographolide eliminated intracellular Aβ42 in BV-2 cells and decreased the production of interleukin (IL-6, IL-1β, prostaglandin (PGE2, and nitric oxide (NO because of artificial phagocytic Aβ42. It decreased pNF-κB accumulation in the nucleus and the expression of inducible nitric oxide synthase (i-NOS and cyclooxygenase II (COX-II in the microglial BV-2 cell line. In summary, andrographolide activates Nrf2-mediated HO-1 expression and inhibits Aβ42-overexpressed microglial BV-2 cell activation. These results suggested that andrographolide might have the potential for further examination of the therapeutics of AD.

  11. Curcumin Attenuates on Carbon Tetrachloride-Induced Acute Liver Injury in Mice via Modulation of the Nrf2/HO-1 and TGF-β1/Smad3 Pathway

    Xinyan Peng

    2018-01-01

    Full Text Available This study aimed to investigate the protective effect of curcumin against carbon tetrachloride (CCl4-induced acute liver injury in a mouse model, and to explain the underlying mechanism. Curcumin at doses of 50, 100 and 200 mg/kg/day were administered orally once daily for seven days prior to CCl4 exposure. At 24 h, curcumin-attenuated CCl4 induced elevated serum transaminase activities and histopathological damage in the mouse’s liver. Curcumin pre-treatment at 50, 100 and 200 mg/kg significantly ameliorated CCl4-induced oxidative stress, characterized by decreased malondialdehyde (MDA formations, and increased superoxide dismutase (SOD, catalase (CAT activities and glutathione (GSH content, followed by a decrease in caspase-9 and -3 activities. Curcumin pre-treatment significantly decreased CCl4-induced inflammation. Furthermore, curcumin pre-treatment significantly down-regulated the expression of TGF-β1 and Smad3 mRNAs (both p < 0.01, and up-regulated the expression of nuclear-factor erythroid 2-related factor 2 (Nrf2 and HO-1 mRNA (both p < 0.01 in the liver. Inhibition of HO-1 attenuated the protective effect of curcumin on CCl4-induced acute liver injury. Given these outcomes, curcumin could protect against CCl4-induced acute liver injury by inhibiting oxidative stress and inflammation, which may partly involve the activation of Nrf2/HO-1 and inhibition of TGF-β1/Smad3 pathways.

  12. Casein Glycomacropeptide Hydrolysates Exert Cytoprotective Effect against Cellular Oxidative Stress by Up-Regulating HO-1 Expression in HepG2 Cells

    Tiange Li

    2017-01-01

    Full Text Available Oxidative stress is considered as an important mediator in the progression of metabolic disorders. The objective of this study was to investigate the potential hepatoprotective effects and mechanisms of bovine casein glycomacropeptide hydrolysates (GHP on hydrogen peroxide (H2O2-induced oxidative damage in HepG2 cells. Results showed that GHP significantly blocked H2O2-induced intracellular reactive oxygen species (ROS generation and cell viability reduction in a dose-dependent manner. Further, GHP concentration-dependently induced heme oxygenase-1 (HO-1 expression and increased nuclear factor-erythroid 2-related factor 2 (Nrf2 nuclear translocation. Moreover, pretreatment of GHP increased the activation of p38 mitogen-activated protein kinase (p38 MAPK and extracellular signal-regulated protein kinase 1/2 (ERK1/2, which were shown to contribute to Nrf2-mediated HO-1 expression. Taken together, GHP protected HepG2 cells from oxidative stress by activation of Nrf2 and HO-1 via p38 MAPK and ERK1/2 signaling pathways. Our findings indicate that bovine casein glycomacropeptide hydrolysates might be a potential ingredient in the treatment of oxidative stress-related disorders and further studies are needed to investigate the protective effects in vivo.

  13. TH-EF-BRC-00: TG-100 Workshop

    NONE

    2016-06-15

    This Hands-on Workshop will be focused on providing participants with experience with the principal tools of TG 100 and hence start to build both competence and confidence in the use of risk-based quality management techniques. The three principal tools forming the basis of TG 100’s risk analysis: Process mapping, Failure-Modes and Effects Analysis and fault-tree analysis will be introduced with a 5 minute refresher presentation and each presentation will be followed by a 30 minute small group exercise. An exercise on developing QM from the risk analysis follows. During the exercise periods, participants will apply the principles in 2 different clinical scenarios. At the conclusion of each exercise there will be ample time for participants to discuss with each other and the faculty their experience and any challenges encountered. Learning Objectives: To review the principles of Process Mapping, Failure Modes and Effects Analysis and Fault Tree Analysis. To gain familiarity with these three techniques in a small group setting. To share and discuss experiences with the three techniques with faculty and participants. Director, TreatSafely, LLC. Director, Center for the Assessment of Radiological Sciences. Occasional Consultant to the IAEA and Varian.

  14. TH-EF-BRC-00: TG-100 Workshop

    2016-01-01

    This Hands-on Workshop will be focused on providing participants with experience with the principal tools of TG 100 and hence start to build both competence and confidence in the use of risk-based quality management techniques. The three principal tools forming the basis of TG 100’s risk analysis: Process mapping, Failure-Modes and Effects Analysis and fault-tree analysis will be introduced with a 5 minute refresher presentation and each presentation will be followed by a 30 minute small group exercise. An exercise on developing QM from the risk analysis follows. During the exercise periods, participants will apply the principles in 2 different clinical scenarios. At the conclusion of each exercise there will be ample time for participants to discuss with each other and the faculty their experience and any challenges encountered. Learning Objectives: To review the principles of Process Mapping, Failure Modes and Effects Analysis and Fault Tree Analysis. To gain familiarity with these three techniques in a small group setting. To share and discuss experiences with the three techniques with faculty and participants. Director, TreatSafely, LLC. Director, Center for the Assessment of Radiological Sciences. Occasional Consultant to the IAEA and Varian.

  15. GLUT4 expression in human muscle fibres is not correlated with intracellular triglyceride (TG) content. Is TG a maker or a marker of insulin resistance?

    Gaster, M; Ottosen, P D; Vach, W

    2003-01-01

    diabetic subjects, and young lean controls. TG density was significantly higher in slow compared to fast fibres in all studied subjects (pslow twitch fibres of obese diabetic subjects compared to obese (p...We have recently reported a progressive decline in the expression of glucose transporter isoform 4 (GLUT4) from control subjects through obese non-diabetics to obese type 2 diabetic subjects, indicating that the reduced GLUT4 in slow twitch fibres could be secondary to obesity. In this study we...... densities in slow and fast fibres did not correlate with the corresponding GLUT4 density in the same fibres in our study groups (p>0.05). Plasma TG and FFA did not correlate with GLUT4 expression in slow or fast fibres (p>0.05). In conclusion, TG content was increased in diabetic slow fibres with a reduced...

  16. Relationship TG/HDL-C and insulin resistance in adult women by nutritional status

    Lorena Belén

    2014-04-01

    Full Text Available Introduction: The ratio assessment TG/HDL-C is an indicator of LDL size, facilitating the detection of individuals with increased atherogenic risk. Estimating the size of the LDL becomes important, especially in patients with TG values near the upper limit of normal values of reference and HDL-C. The objective of the study is to estimate the association between TG/HDL-C and insulin resistance (IR by nutritional status in adult women attending the Foundation for Endocrine Metabolic Diseases Research and Applied Clinical Research (FIEEM.Material and methods: Design Cross-sectional, non-pregnant adult women, apparently healthy, older than 30 years old, attending FIEEM in the Autonomous City of Buenos Aires. Dependent variable: TG/HDL-C ≥ 3.0 considered high value. Independent variables: IR by homeostatic model index HOMA-IR ≥ 2.5 categorizing the sample into two groups: with and without IR, and controlled by nutritional status using body mass index (BMI and waist circumference (CC. SPSS Statistics 15.0, calculating X2 or Fisher exact test, OR with confidence intervals of 95% and establishing logistic regression p value < 0.05.Results: We evaluated a purposive sample of 104 women (31.4% and 26% IR with TG/HDL-C high. 84.6% were overweight or obese and 88.5% increased CC. Women with BMI had significantly increased 0.15-fold increased risk (95% CI = 0.01 to 1.26 for TG/HDL-C high (p = 0.04 than the control women. There was no significance with increased CC. The ratio TG/HDL-C high IR was significantly correlated (r = 0.30 p = 0.002.Conclusions: Body weight was significantly associated with IR and the ratio TG/HDL-C increased. This ratio correlated significantly with IR in apparently healthy women.

  17. Punicalagin, a PTP1B inhibitor, induces M2c phenotype polarization via up-regulation of HO-1 in murine macrophages.

    Xu, Xiaolong; Guo, Yuhong; Zhao, Jingxia; He, Shasha; Wang, Yan; Lin, Yan; Wang, Ning; Liu, Qingquan

    2017-09-01

    Current data have shown that punicalagin (PUN), an ellagitannin isolated from pomegranate, possesses anti-inflammatory and anti-oxidant properties; however, its direct targets have not yet been reported. This is the first report that PTP1B serves as a direct target of PUN, with IC 50 value of 1.04μM. Results from NPOI further showed that the K on and K off of PUN-PTP1B complex were 3.38e2M -1 s -1 and 4.13e-3s -1 , respectively. The active site Arg24 of PTP1B was identified as a key binding site of PUN by computation simulation and point mutation. Moreover, inhibition of PTP1B by PUN promoted an M2c-like macrophage polarization and enhanced anti-inflammatory cytokines expression, including IL-10 and M-CSF. Based on gene expression profile, we elucidated that PUN treatment significantly up-regulated 275 genes and down-regulated 1059 genes. M1-like macrophage marker genes, such as Tlr4, Irf1/2, Hmgb1, and Stat1 were down-regulated, while M2 marker genes, including Tmem171, Gpr35, Csf1, Il1rn, Cebpb, Fos, Vegfα, Slc11a1, and Bhlhe40 were up-regulated in PUN-treated macrophages. Hmox-1, a gene encoding HO-1 protein, was preferentially expressed with 16-fold change. Inhibition of HO-1 obviously restored PUN-induced M2 polarization and IL-10 secretion. In addition, phosphorylation of both Akt and STAT3 contributed to PUN-induced HO-1 expression. This study provided new insights into the mechanisms of PUN-mediated anti-inflammatory and anti-oxidant activities and provided new therapeutic strategies for inflammatory diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Pinocembrin Suppresses H2O2-Induced Mitochondrial Dysfunction by a Mechanism Dependent on the Nrf2/HO-1 Axis in SH-SY5Y Cells.

    de Oliveira, Marcos Roberto; da Costa Ferreira, Gustavo; Brasil, Flávia Bittencourt; Peres, Alessandra

    2018-02-01

    Mitochondria are susceptible to redox impairment, which has been associated with neurodegeneration. These organelles are both a source and target of reactive species. In that context, there is increasing interest in finding natural compounds that modulate mitochondrial function and mitochondria-related signaling in order to prevent or to treat diseases involving mitochondrial impairment. Herein, we investigated whether and how pinocembrin (PB) would prevent mitochondrial dysfunction elicited by the exposure of human neuroblastoma SH-SY5Y cells to hydrogen peroxide (H 2 O 2 ). PB (25 μM) was administrated for 4 h before H 2 O 2 treatment (300 μM for 24 h). PB prevented H 2 O 2 -induced loss of cell viability mitochondrial depolarization in SH-SY5Y cells. PB also attenuated redox impairment in mitochondrial membranes. The production of superoxide anion radical (O 2 -• ) and nitric oxide (NO • ) was alleviated by PB in cells exposed to H 2 O 2 . PB suppressed the H 2 O 2 -induced inhibition of the tricarboxylic acid (TCA) cycle enzymes aconitase, α-ketoglutarate dehydrogenase, and succinate dehydrogenase. Furthermore, PB induced anti-inflammatory effects by abolishing the H 2 O 2 -dependent activation of the nuclear factor-κB (NF-κB) and upregulation of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). The PB-induced antioxidant and anti-inflammatory effects are dependent on the heme oxygenate-1 (HO-1) enzyme and on the activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), since HO-1 inhibition (with 0.5 μM ZnPP IX) or Nrf2 silencing (with small interfering RNA (siRNA)) abolished the effects of PB. Overall, PB afforded cytoprotection by the Nrf2/HO-1 axis in H 2 O 2 -treated SH-SY5Y cells.

  19. Assessment of display performance for medical imaging systems: Executive summary of AAPM TG18 report

    Samei, Ehsan; Badano, Aldo; Chakraborty, Dev

    2005-01-01

    Digital imaging provides an effective means to electronically acquire, archive, distribute, and view medical images. Medical imaging display stations are an integral part of these operations. Therefore, it is vitally important to assure that electronic display devices do not compromise image quality and ultimately patient care. The AAPM Task Group 18 (TG18) recently published guidelines and acceptance criteria for acceptance testing and quality control of medical display devices. This paper is an executive summary of the TG18 report. TG18 guidelines include visual, quantitative, and advanced testing methodologies for primary and secondary class display devices. The characteristics, tested in conjunction with specially designed test patterns (i.e., TG18 patterns), include reflection, geometric distortion, luminance, the spatial and angular dependencies of luminance, resolution, noise, glare, chromaticity, and display artifacts. Geometric distortions are evaluated by linear measurements of the TG18-QC test pattern, which should render distortion coefficients less than 2%/5% for primary/secondary displays, respectively. Reflection measurements include specular and diffuse reflection coefficients from which the maximum allowable ambient lighting is determined such that contrast degradation due to display reflection remains below a 20% limit and the level of ambient luminance (L amb ) does not unduly compromise luminance ratio (LR) and contrast at low luminance levels. Luminance evaluation relies on visual assessment of low contrast features in the TG18-CT and TG18-MP test patterns, or quantitative measurements at 18 distinct luminance levels of the TG18-LN test patterns. The major acceptable criteria for primary/secondary displays are maximum luminance of greater than 170/100 cd/m 2 , LR of greater than 250/100, and contrast conformance to that of the grayscale standard display function (GSDF) of better than 10%/20%, respectively. The angular response is tested to

  20. Baicalein inhibition of oxidative-stress-induced apoptosis via modulation of ERKs activation and induction of HO-1 gene expression in rat glioma cells C6

    Chen, Y.-C.; Chow, J.-M.; Lin, C.-W.; Wu, C.-Y.; Shen, S.-C.

    2006-01-01

    In the present study, we examined the protective mechanism of baicalein (BE) and its glycoside, baicalin (BI), on hydrogen-peroxide (H 2 O 2 )-induced cell death in rat glioma C6 cells. Results of the MTT assay, LDH release assay, and morphological observation showed that H 2 O 2 addition reduced the viability of C6 cells, and this was prevented by the addition of BE but not BI. Incubation of C6 cells with BE significantly decreased the intracellular peroxide level induced by H 2 O 2 according to flow cytometric analysis using DCHF-DA as a fluorescent substrate. Suppression of H 2 O 2 -induced apoptotic events including DNA ladders, hypodiploid cells, and activation of caspases 3, 8, and, 9 by BE but not BI was identified in C6 cells. The cytotoxicity and phosphorylation of ERK proteins induced by H 2 O 2 were blocked by the ERK inhibitor PD98059. Catalase addition prevented H 2 O 2 -induced ROS production, ERKs protein phosphorylation, and cell death, and BE dose-dependently inhibited H 2 O 2 -induced ERK protein phosphorylation in C6 cells. These data suggest that ROS-scavenging activity is involved in BE prevention of H 2 O 2 -induced cell death via blocking ERKs activation. Additionally, BE but not BI induced heat shock protein 32 (HSP32; HO-1) protein expression in both time- and dose-dependent manners, but not heme oxygenase 2 (HO-2), heat shock protein 70 (HSP70), or heat shock protein 90 (HSP90) protein expression. In the absence of H 2 O 2 , BE induces ERKs protein phosphorylation, and HO-1 protein expression induced by BE was blocked by the addition of cycloheximide, actinomycin D, and the ERK inhibitor PD98059. The addition of the HO inhibitor ZnPP inhibited the protective effect of BE against H 2 O 2 -induced cytotoxicity in C6 cells according to the MTT assay and apoptotic morphology under microscopic observation, accompanied by blocking the ROS-scavenging activity of BE in C6 cells. However, BE treatment was unable to protect C6 cells from C2-ceramide

  1. Antioxidant and Antifibrotic Effect of a Herbal Formulation In Vitro and in the Experimental Andropause via Nrf2/HO-1 Signaling Pathway

    Woong Jin Bae

    2017-01-01

    Full Text Available The Korean herbal formulation Ojayeonjonghwan is used for improving late-onset hypogonadism (LOH symptoms such as erectile dysfunction (ED. A previous research suggested that a modified Ojayeonjonghwan (KH-204 could be used as an alternative to the treatment for ED. The pharmacological effects were examined in different conditions, including in vitro and in vivo. We measured the survival rate of TM3 Leydig cells under the oxidative stress condition. The s.c. injection of leuprorelin was used to induce androgen deprivation. We measured serum testosterone levels, oxidative stress, and apoptosis. The results of the treatment by KH-204 (1 preserved TM3 cells from oxidative stress by improving the expression of nuclear factor erythroid 2-related factor 2 (Nrf2/heme oxygenase-1 (HO-1; (2 lowered the expression of transforming growth factor-beta (TGF-β 1/SMAD; (3 increased the average of serum testosterone in androgen-deprived male rats; (4 kept the activation of spermatogenesis; (5 upgraded the contents of 8-hydroxy-20-deoxyguanosine (8-OHdG and degraded the contents of superoxide dismutase (SOD; and (6 reduced apoptosis. We studied that KH-204 improved testicular dysfunction in LOH. It is likely, at least in part, to degrade oxidative stress through the Nrf2/HO-1 pathway. These findings may offer credible evidences for the use of new alternative therapies to treat LOH.

  2. TG Grammar's Implications for the Foreign Language Teaching

    殷彩

    2009-01-01

    Chomsky's Transformational-Generative (TG) grammar is another revolution to linguistics after Saussure's strueturalism, and it plays an important role in the modem linguistics. Introducing the research perspective and method of TG grammar, this paper analyses its implications for the foreign language teaching.

  3. The follow-up of patients with differentiated thyroid cancer and undetectable thyroglobulin (Tg) and Tg antibodies during ablation

    Phan, Ha T. T.; Jager, Pieter L.; van der Wal, Jacqueline E.; Sluiter, Wim J.; Plukker, John T. M.; Dierckx, Rudi A. J. O.; Wolffenbuttel, Bruce H. R.; Links, Thera P.

    Objective: This retrospective study describes the rote of serum thyroglobulin (Tg) in relation to tumor characteristics in the prediction of persistent/recurrent disease in patients with differentiated thyroid cancer (DTC) with negative Tg at the time of ablation. Design: Between 1989 and 2006, 94

  4. Preconditioning with Gua Lou Gui Zhi decoction enhances H2O2-induced Nrf2/HO-1 activation in PC12 cells

    MAO, JINGJIE; LI, ZUANFANG; LIN, RUHUI; ZHU, XIAOQIN; LIN, JIUMAO; PENG, JUN; CHEN, LIDIAN

    2015-01-01

    Spasticity is common in various central neurological conditions, including after a stroke. Such spasticity may cause additional problems, and often becomes a primary concern for afflicted individuals. A number of studies have identified nuclear factor (erythroid-derived 2)-like 2 (Nrf2) as a key regulator in the adaptive survival response to oxidative stress. Elevated expression of Nrf2, combined with heme oxygenase 1 (HO-1) resistance, in the central nervous system is known to elicit key internal and external oxidation protection. Gua Lou Gui Zhi decoction (GLGZD) is a popular traditional Chinese formula with a long history of clinical use in China for the treatment of muscular spasticity following a stroke, epilepsy or a spinal cord injury. However, the mechanism underlying the efficacy of the medicine remains unclear. In the present study, the antioxidative effects of GLGZD were evaluated and the underlying molecular mechanisms were investigated, using hydrogen peroxide (H2O2)-induced rat pheochromocytoma cells (PC12 cells) as an in vitro oxidative stress model of neural cells. Upon application of different concentrations of GLGZD, a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay and ATP measurement were conducted to assess the impact on PC12 cell proliferation. In addition, inverted microscopy observations, and the MTT and ATP assessments, revealed that GLGZD attenuated H2O2-induced oxidative damage and signaling repression in PC12 cells. Furthermore, the mRNA and protein expression levels of Nrf2 and HO-1, which are associated with oxidative stress, were analyzed using reverse transcription quantitative polymerase chain reaction (PCR) and confocal microscopy. Confocal microscopy observations, as well as the quantitative PCR assay, revealed that GLGZD exerted a neuroprotective function against H2O2-induced oxidative damage in PC12 cells. Therefore, the results demonstrated that GLGZD protected PC12 cells injured by H2O2, which may be

  5. Non-shoring construction for T/G pedestal beams

    Abe, T.

    1992-01-01

    The T/G pedestal construction work has been the critical path within the T/B construction work of BWR type nuclear power plant. In order to meet the requirement of shortening the construction period and improved in safety on a Turbine Building (T/B) construction work, Non-soring construction for T/G Pedestal Beams was developed. By applying this method to T/G pedestal construction work, we succeeded in shortening the T/B construction period and improvement in safety significantly. (author)

  6. Comparison of TG-43 and TG-186 in breast irradiation using a low energy electronic brachytherapy source

    White, Shane A.; Landry, Guillaume; Reniers, Brigitte; Fonseca, Gabriel Paiva; Holt, Randy; Rusch, Thomas; Beaulieu, Luc; Verhaegen, Frank

    2014-01-01

    Purpose: The recently updated guidelines for dosimetry in brachytherapy in TG-186 have recommended the use of model-based dosimetry calculations as a replacement for TG-43. TG-186 highlights shortcomings in the water-based approach in TG-43, particularly for low energy brachytherapy sources. The Xoft Axxent is a low energy ( w,m ) and dose to medium (D m,m ), for the heterogeneous simulations. All results were compared against TG-43-based dose distributions and evaluated using dose ratio maps and DVH metrics. Changes in skin and PTV dose were highlighted. Results: All simulated heterogeneous models showed a reduced dose to the DVH metrics that is dependent on the method of dose reporting and patient geometry. Based on a prescription dose of 34 Gy, the average D 90 to PTV was reduced by between ∼4% and ∼40%, depending on the scoring method, compared to the TG-43 result. Peak skin dose is also reduced by 10%–15% due to the absence of backscatter not accounted for in TG-43. The balloon applicator also contributed to the reduced dose. Other ROIs showed a difference depending on the method of dose reporting. Conclusions: TG-186-based calculations produce results that are different from TG-43 for the Axxent source. The differences depend strongly on the method of dose reporting. This study highlights the importance of backscatter to peak skin dose. Tissue heterogeneities, applicator, and patient geometries demonstrate the need for a more robust dose calculation method for low energy brachytherapy sources

  7. A Sensitive Tg Assay or rhTSH Stimulated Tg : What's the Best in the Long-Term Follow-Up of Patients with Differentiated Thyroid Carcinoma?

    Persoon, Adrienne C. M.; Jager, Pieter L.; Sluiter, Wim J.; Plukker, John T. M.; Wolffenbuttel, Bruce H. R.; Links, Thera P.

    2007-01-01

    Sensitivity of thyroglobulin (Tg) measurement in the follow-up of differentiated thyroid carcinoma (DTC) can be optimized by using a sensitive Tg assay and rhTSH stimulation. We evaluated the diagnostic yield of a sensitive Tg assay and rhTSH stimulated Tg in the detection of recurrences in the

  8. Diagnostic value of Tg and TgAb for metastasis following ablation in patients with differentiated thyroid carcinoma coexistent with Hashimoto thyroiditis.

    Chai, Hong; Zhu, Zhao-Jin; Chen, Ze-Quan; Yu, Yong-Li

    2016-08-01

    This study was designed to investigate the clinical value of serum thyroglobulin (Tg) and antithyroglobulin antibody (TgAb) measurements and the cutoff value after ablation in differentiated thyroid carcinoma (DTC) complicated by Hashimoto thyroiditis (HT) with metastasis. We measured serum Tg and TgAb levels and evaluated the disease status in 164 cases of DTC coexistent with HT in pathologically confirmed patients after surgery and post-remnant ablation during a 3-year follow-up. All Tg and TgAb levels were assessed by chemiluminescent immunoassay (IMA). Receiver operating characteristic (ROC) curve analysis was used to evaluate the prognostic value of Tg and TgAb for disease metastasis. The relationship between Tg and TgAb was analyzed using the scatter diagram distribution method. We found that the cutoff values of Tg and TgAb were 1.48 µg/L and 45 kIU/L, respectively. The area under the ROC curve (AUC) of Tg and TgAb was 0.907 and 0.650, respectively. In DTC coexistent with HT patients, the optimal cutoff value correlated with metastasis in Tg and TgAb was 1.48 µg/L and 45 kIU/L, respectively.

  9. IMRT Commissioning: application of the AAPM's TG-119; Comissionamento de IMRT: aplicacao do TG-119 da AAPM

    Zeppellini, Caroline; Furnari, Laura, E-mail: laurafurnari@hotmail.com [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Fac. de Medicina. Inst. de Radiologia

    2013-08-15

    In order to verify the commissioning of the planning of intensity-modulated radiation therapy system (IMRT), the TG-119 of the American Association of Physicists in Medicine (AAPM) was applied. Using pre defined targets and normal structures, plans were realized, absolute and relative dose were measured with an ionizing chamber and films, and the results were compared with planned values. The maximum deviation of the measurements with the ionization chamber was 3,6%, but, in the total eleven measurements, only two were bigger than the tolerance limit of 3%, recommended by TG-119. The number of points which passed criteria gamma 3% to 3 mm ranged between 96.36% and 99.92%, all measurements were within the recommended 95%. The confidence limits found for both film and for chamber were lower than those achieved in the TG-119. Our results showed a good concordance with TG-119, what means that the system is adequate for clinical applications. (author)

  10. The Cytoprotective Effects of E-α-(4-Methoxyphenyl-2',3,4,4'-Tetramethoxychalcone (E-α-p-OMe-C6H4-TMC--A Novel and Non-Cytotoxic HO-1 Inducer.

    Kai B Kaufmann

    Full Text Available Cell protection against different noxious stimuli like oxidative stress or chemical toxins plays a central role in the treatment of many diseases. The inducible heme oxygenase isoform, heme oxygenase-1 (HO-1, is known to protect cells against a variety of harmful conditions including apoptosis. Because a number of medium strong electrophiles from a series of α-X-substituted 2',3,4,4'-tetramethoxychalcones (α-X-TMCs, X = H, F, Cl, Br, I, CN, Me, p-NO2-C6H4, Ph, p-OMe-C6H4, NO2, CF3, COOEt, COOH had proven to activate Nrf2 resulting in HO-1 induction and inhibit NF-κB downstream target genes, their protective effect against staurosporine induced apoptosis and reactive oxygen species (ROS production was investigated. RAW264.7 macrophages treated with 19 different chalcones (15 α-X-TMCs, chalcone, 2'-hydroxychalcone, calythropsin and 2'-hydroxy-3,4,4'-trimethoxychalcone prior to staurosporine treatment were analyzed for apoptosis and ROS production, as well as HO-1 protein expression and enzyme activity. Additionally, Nrf2 and NF-κB activity was assessed. We found that amongst all tested chalcones only E-α-(4-methoxyphenyl-2',3,4,4'-tetramethoxychalcone (E-α-p-OMe-C6H4-TMC demonstrated a distinct, statistically significant antiapoptotic effect in a dose dependent manner, showing no toxic effects, while its double bond isomer Z-α-p-OMe-C6H4-TMC displayed no significant activity. Also, E-α-p-OMe-C6H4-TMC induced HO-1 protein expression and increased HO-1 activity, whilst inhibition of HO-1 by SnPP-IX abolished its antiapoptotic effect. The only weakly electrophilic chalcone E-α-p-OMe-C6H4-TMC reduced the staurosporine triggered formation of ROS, while inducing the translocation of Nrf2 into the nucleus. Furthermore, staurosporine induced NF-κB activity was attenuated following E-α-p-OMe-C6H4-TMC treatment. Overall, E-α-p-OMe-C6H4-TMC demonstrated its effective cytoprotective potential via a non-toxic induction of HO-1 in RAW264

  11. Increased hippocampal excitability in the 3xTgAD mouse model for Alzheimer's disease in vivo.

    Katherine E Davis

    Full Text Available Mouse Alzheimer's disease (AD models develop age- and region-specific pathology throughout the hippocampal formation. One recently established pathological correlate is an increase in hippocampal excitability in vivo. Hippocampal pathology also produces episodic memory decline in human AD and we have shown a similar episodic deficit in 3xTg AD model mice aged 3-6 months. Here, we tested whether hippocampal synaptic dysfunction accompanies this cognitive deficit by probing dorsal CA1 and DG synaptic responses in anaesthetized, 4-6 month-old 3xTgAD mice. As our previous reports highlighted a decline in episodic performance in aged control mice, we included aged cohorts for comparison. CA1 and DG responses to low-frequency perforant path stimulation were comparable between 3xTgAD and controls at both age ranges. As expected, DG recordings in controls showed paired-pulse depression; however, paired-pulse facilitation was observed in DG and CA1 of young and old 3xTgAD mice. During stimulus trains both short-latency (presumably monosynaptic: 'direct' and long-latency (presumably polysynaptic: 're-entrant' responses were observed. Facilitation of direct responses was modest in 3xTgAD animals. However, re-entrant responses in DG and CA1 of young 3xTgAD mice developed earlier in the stimulus train and with larger amplitude when compared to controls. Old mice showed less DG paired-pulse depression and no evidence for re-entrance. In summary, DG and CA1 responses to low-frequency stimulation in all groups were comparable, suggesting no loss of synaptic connectivity in 3xTgAD mice. However, higher-frequency activation revealed complex change in synaptic excitability in DG and CA1 of 3xTgAD mice. In particular, short-term plasticity in DG and CA1 was facilitated in 3xTgAD mice, most evidently in younger animals. In addition, re-entrance was facilitated in young 3xTgAD mice. Overall, these data suggest that the episodic-like memory deficit in 3xTgAD mice

  12. Local confidence limits for IMRT and VMAT techniques: a study based on TG119 test suite

    Thomas, M.; Chandroth, M.

    2014-01-01

    The aim of this study was to generate a local confidence limit (CL) for intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques used at Waikato Regional Cancer Centre. This work was carried out based on the American Association of Physicists in Medicine (AAPM) Task Group (TG) 119 report. The AAPM TG 119 report recommends CLs as a bench mark for IMRT commissioning and delivery based on its multiple institutions planning and dosimetry comparisons. In this study the locally obtained CLs were compared to TG119 benchmarks. Furthermore, the same bench mark was used to test the capabilities and quality of the VMAT technique in our clinic. The TG 119 test suite consists of two primary and four clinical tests for evaluating the accuracy of IMRT planning and dose delivery systems. Pre defined structure sets contoured on computed tomography images were downloaded from AAPM website and were transferred to a locally designed phantom. For each test case two plans were generated using IMRT and VMAT optimisation. Dose prescriptions and planning objectives recommended by TG119 report were followed to generate the test plans in Eclipse Treatment Planning System. For each plan the point dose measurements were done using an ion chamber at high dose and low dose regions. The planar dose distribution was analysed for percentage of points passing the gamma criteria of 3 %/3 mm, for both the composite plan and individual fields of each plan. The CLs were generated based on the results from the gamma analysis and point dose measurements. For IMRT plans, the CLs obtained were (1) from point dose measurements: 2.49 % at high dose region and 2.95 % for the low dose region (2) from gamma analysis: 2.12 % for individual fields and 5.9 % for the composite plan. For VMAT plans, the CLs obtained were (1) from point dose measurements: 2.56 % at high dose region and 2.6 % for the low dose region (2) from gamma analysis: 1.46 % for individual fields and 0

  13. Comparison of TG-43 and TG-186 in breast irradiation using a low energy electronic brachytherapy source

    White, Shane A.; Landry, Guillaume; Reniers, Brigitte, E-mail: brigitte.reniers@maastro.nl [Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center (MUMC), Maastricht 6201 BN (Netherlands); Fonseca, Gabriel Paiva [Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center (MUMC), Maastricht 6201 BN, The Netherlands and Instituto de Pesquisas Energéticas e Nucleares – IPEN-CNEN/SP, São Paulo CP 11049, 05422-970 (Brazil); Holt, Randy; Rusch, Thomas [Xoft, A Subsidiary of iCAD, Sunnyvale, California 94085-4115 (United States); Beaulieu, Luc [Centre Hospitalier Universitaire de Québec Université Laval, Radio-Oncologie et Centre de Recherche en Cancérologie de l’Université Laval, Québec, Québec G1R 2J6 Canada (Canada); Verhaegen, Frank [Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center (MUMC), Maastricht 6201 BN, The Netherlands and Department of Oncology, McGill University, Montreal, Quebec H3G 1A4 (Canada)

    2014-06-15

    Purpose: The recently updated guidelines for dosimetry in brachytherapy in TG-186 have recommended the use of model-based dosimetry calculations as a replacement for TG-43. TG-186 highlights shortcomings in the water-based approach in TG-43, particularly for low energy brachytherapy sources. The Xoft Axxent is a low energy (<50 kV) brachytherapy system used in accelerated partial breast irradiation (APBI). Breast tissue is a heterogeneous tissue in terms of density and composition. Dosimetric calculations of seven APBI patients treated with Axxent were made using a model-based Monte Carlo platform for a number of tissue models and dose reporting methods and compared to TG-43 based plans. Methods: A model of the Axxent source, the S700, was created and validated against experimental data. CT scans of the patients were used to create realistic multi-tissue/heterogeneous models with breast tissue segmented using a published technique. Alternative water models were used to isolate the influence of tissue heterogeneity and backscatter on the dose distribution. Dose calculations were performed using Geant4 according to the original treatment parameters. The effect of the Axxent balloon applicator used in APBI which could not be modeled in the CT-based model, was modeled using a novel technique that utilizes CAD-based geometries. These techniques were validated experimentally. Results were calculated using two dose reporting methods, dose to water (D{sub w,m}) and dose to medium (D{sub m,m}), for the heterogeneous simulations. All results were compared against TG-43-based dose distributions and evaluated using dose ratio maps and DVH metrics. Changes in skin and PTV dose were highlighted. Results: All simulated heterogeneous models showed a reduced dose to the DVH metrics that is dependent on the method of dose reporting and patient geometry. Based on a prescription dose of 34 Gy, the average D{sub 90} to PTV was reduced by between ∼4% and ∼40%, depending on the

  14. Comparison of TG-43 and TG-186 in breast irradiation using a low energy electronic brachytherapy source.

    White, Shane A; Landry, Guillaume; Fonseca, Gabriel Paiva; Holt, Randy; Rusch, Thomas; Beaulieu, Luc; Verhaegen, Frank; Reniers, Brigitte

    2014-06-01

    The recently updated guidelines for dosimetry in brachytherapy in TG-186 have recommended the use of model-based dosimetry calculations as a replacement for TG-43. TG-186 highlights shortcomings in the water-based approach in TG-43, particularly for low energy brachytherapy sources. The Xoft Axxent is a low energy (S700, was created and validated against experimental data. CT scans of the patients were used to create realistic multi-tissue/heterogeneous models with breast tissue segmented using a published technique. Alternative water models were used to isolate the influence of tissue heterogeneity and backscatter on the dose distribution. Dose calculations were performed using Geant4 according to the original treatment parameters. The effect of the Axxent balloon applicator used in APBI which could not be modeled in the CT-based model, was modeled using a novel technique that utilizes CAD-based geometries. These techniques were validated experimentally. Results were calculated using two dose reporting methods, dose to water (Dw,m) and dose to medium (Dm,m), for the heterogeneous simulations. All results were compared against TG-43-based dose distributions and evaluated using dose ratio maps and DVH metrics. Changes in skin and PTV dose were highlighted. All simulated heterogeneous models showed a reduced dose to the DVH metrics that is dependent on the method of dose reporting and patient geometry. Based on a prescription dose of 34 Gy, the average D90 to PTV was reduced by between ~4% and ~40%, depending on the scoring method, compared to the TG-43 result. Peak skin dose is also reduced by 10%-15% due to the absence of backscatter not accounted for in TG-43. The balloon applicator also contributed to the reduced dose. Other ROIs showed a difference depending on the method of dose reporting. TG-186-based calculations produce results that are different from TG-43 for the Axxent source. The differences depend strongly on the method of dose reporting. This study

  15. In vivo determination of triglyceride (TG) secretion in rats fed different dietary saturated fats using [2-3H]-glycerol

    Lai, H.C.; Yang, H.; Lasekan, J.; Clayton, M.; Ney, D.M.

    1990-01-01

    Male, Sprague-Dawley rats (154±1 g) were fed diets containing 2% corn oil (CO) + 14% butterfat (BF), beef tallow (BT), olive oil (OO) or coconut oil (CN) vs a 16% CO control diet for 5 weeks. Changes in plasma TG specific activity (dpm/mg TG) were determined in individual unanesthetized rats after injection of 100 μCi [2- 3 H]-glycerol via a carotid cannula. Fractional rate constants were obtained using a 2-compartment model and nonlinear regression analysis. Results demonstrated no difference in the fractional rate constants among dietary groups; but, differences in the rates of hepatic TG secretion were noted. Rats fed BT showed a higher rate of hepatic TG secretion than rats fed CO. Rats fed BF, OO or CN showed somewhat higher rates of hepatic TG secretion than CO. VLDL TG, phospholipid, and apolipoprotein B and E levels were higher with saturated fats vs CO. The data suggest that the higher plasma TG levels noted in response to feeding saturated fats vs corn oil can be explained, in part, by an increased flux of hepatic TG secretion

  16. Evaluation of TG-43 recommended 2D-anisotropy function for elongated brachytherapy sources

    Awan, Shahid B.; Meigooni, Ali S.; Mokhberiosgouei, Ramin; Hussain, Manzoor

    2006-01-01

    The original and updated protocols recommended by Task Group 43 from the American Association of Physicists in Medicine (i.e., TG-43 and TG-43U1, respectively), have been introduced to unify brachytherapy source dosimetry around the world. Both of these protocols are based on experiences with sources less than 1.0 cm in length. TG-43U1 recommends that for 103 Pd sources, 2D anisotropy function F(r,θ), should be tabulated at a minimum for radial distances of 0.5, 1.0, 2.0, 3.0, and 5.0 cm. Anisotropy functions defined in these protocols are only valid when the point of calculation does not fall on the active length of the source. However, for elongated brachytherapy sources (active length >1 cm), some of the calculation points with r 103 Pd source at radial distances of 2.5, 3.0, and 4.0 cm were 2.95, 1.74, and 1.19, respectively, with differences up to about a factor of 3. Therefore, the validity of the linear interpolation technique for an elongated brachytherapy source with such a large variation in F(r,θ) needs to be investigated. In this project, application of the TG-43U1 formalism for dose calculation around an elongated RadioCoil trade mark sign 103 Pd brachytherapy source has been investigated. In addition, the linear interpolation techniques as described in TG-43U1 for seed type sources have been evaluated for a 5.0 cm long RadioCoil trade mark sign 103 Pd brachytherapy source. Application of a polynomial fit to F(r,θ) has also been investigated as an alternate approach to the linear interpolation technique. The results of these investigations indicate that the TG-43U1 formalism can be extended for elongated brachytherapy sources, if the two-dimensional (2D) anisotropy function is tabulated at a minimum for radial distances of 0.2, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0 cm, L/2, and L/2±0.2 cm. Moreover, with the addition of recommended radial distances for 2D anisotropy functions, the linear interpolation technique more closely replicates

  17. TH-A-BRC-01: AAPM TG-135U1 QA for Robotic Radiosurgery

    Dieterich, S.

    2016-01-01

    AAPM TG-135U1 QA for Robotic Radiosurgery - Sonja Dieterich Since the publication of AAPM TG-135 in 2011, the technology of robotic radiosurgery has rapidly developed. AAPM TG-135U1 will provide recommendations on the clinical practice for using the IRIS collimator, fiducial-less real-time motion tracking, and Monte Carlo based treatment planning. In addition, it will summarize currently available literature about uncertainties. Learning Objectives: Understand the progression of technology since the first TG publication Learn which new QA procedures should be implemented for new technologies Be familiar with updates to clinical practice guidelines AAPM TG-178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance - Steven Goetsch Purpose: AAPM Task Group 178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance was formed in August, 2008. The Task Group has 12 medical physicists, two physicians and two consultants. Methods: A round robin dosimetry intercomparison of proposed ionization chambers, electrometer and dosimetry phantoms was conducted over a 15 month period in 2011 and 2012 (Med Phys 42, 11, Nov, 2015). The data obtained at 9 institutions (with ten different Elekta Gamma Knife units) was analyzed by the lead author using several protocols. Results: The most consistent results were obtained using the Elekta ABS 16cm diameter phantom, with the TG-51 protocol modified as recommended by Alfonso et al (Med Phys 35, 11, Nov 2008). A key white paper (Med Phys, in press) sponsored by Elekta Corporation, was used to obtain correction factors for the ionization chambers and phantoms used in this intercomparison. Consistent results were obtained for both Elekta Gamma Knife Model 4C and Gamma Knife Perfexion units as measured with each of two miniature ionization chambers. Conclusion: The full report gives clinical history and background of gamma stereotactic radiosurgery, clinical examples and history, quality assurance recommendations and outline

  18. TH-A-BRC-01: AAPM TG-135U1 QA for Robotic Radiosurgery

    Dieterich, S. [UC Davis Medical Center (United States)

    2016-06-15

    AAPM TG-135U1 QA for Robotic Radiosurgery - Sonja Dieterich Since the publication of AAPM TG-135 in 2011, the technology of robotic radiosurgery has rapidly developed. AAPM TG-135U1 will provide recommendations on the clinical practice for using the IRIS collimator, fiducial-less real-time motion tracking, and Monte Carlo based treatment planning. In addition, it will summarize currently available literature about uncertainties. Learning Objectives: Understand the progression of technology since the first TG publication Learn which new QA procedures should be implemented for new technologies Be familiar with updates to clinical practice guidelines AAPM TG-178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance - Steven Goetsch Purpose: AAPM Task Group 178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance was formed in August, 2008. The Task Group has 12 medical physicists, two physicians and two consultants. Methods: A round robin dosimetry intercomparison of proposed ionization chambers, electrometer and dosimetry phantoms was conducted over a 15 month period in 2011 and 2012 (Med Phys 42, 11, Nov, 2015). The data obtained at 9 institutions (with ten different Elekta Gamma Knife units) was analyzed by the lead author using several protocols. Results: The most consistent results were obtained using the Elekta ABS 16cm diameter phantom, with the TG-51 protocol modified as recommended by Alfonso et al (Med Phys 35, 11, Nov 2008). A key white paper (Med Phys, in press) sponsored by Elekta Corporation, was used to obtain correction factors for the ionization chambers and phantoms used in this intercomparison. Consistent results were obtained for both Elekta Gamma Knife Model 4C and Gamma Knife Perfexion units as measured with each of two miniature ionization chambers. Conclusion: The full report gives clinical history and background of gamma stereotactic radiosurgery, clinical examples and history, quality assurance recommendations and outline

  19. TH-A-BRC-02: AAPM TG-178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance

    Goetsch, S. [San Diego Medical Physics (United States)

    2016-06-15

    AAPM TG-135U1 QA for Robotic Radiosurgery - Sonja Dieterich Since the publication of AAPM TG-135 in 2011, the technology of robotic radiosurgery has rapidly developed. AAPM TG-135U1 will provide recommendations on the clinical practice for using the IRIS collimator, fiducial-less real-time motion tracking, and Monte Carlo based treatment planning. In addition, it will summarize currently available literature about uncertainties. Learning Objectives: Understand the progression of technology since the first TG publication Learn which new QA procedures should be implemented for new technologies Be familiar with updates to clinical practice guidelines AAPM TG-178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance - Steven Goetsch Purpose: AAPM Task Group 178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance was formed in August, 2008. The Task Group has 12 medical physicists, two physicians and two consultants. Methods: A round robin dosimetry intercomparison of proposed ionization chambers, electrometer and dosimetry phantoms was conducted over a 15 month period in 2011 and 2012 (Med Phys 42, 11, Nov, 2015). The data obtained at 9 institutions (with ten different Elekta Gamma Knife units) was analyzed by the lead author using several protocols. Results: The most consistent results were obtained using the Elekta ABS 16cm diameter phantom, with the TG-51 protocol modified as recommended by Alfonso et al (Med Phys 35, 11, Nov 2008). A key white paper (Med Phys, in press) sponsored by Elekta Corporation, was used to obtain correction factors for the ionization chambers and phantoms used in this intercomparison. Consistent results were obtained for both Elekta Gamma Knife Model 4C and Gamma Knife Perfexion units as measured with each of two miniature ionization chambers. Conclusion: The full report gives clinical history and background of gamma stereotactic radiosurgery, clinical examples and history, quality assurance recommendations and outline

  20. TH-A-BRC-02: AAPM TG-178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance

    Goetsch, S.

    2016-01-01

    AAPM TG-135U1 QA for Robotic Radiosurgery - Sonja Dieterich Since the publication of AAPM TG-135 in 2011, the technology of robotic radiosurgery has rapidly developed. AAPM TG-135U1 will provide recommendations on the clinical practice for using the IRIS collimator, fiducial-less real-time motion tracking, and Monte Carlo based treatment planning. In addition, it will summarize currently available literature about uncertainties. Learning Objectives: Understand the progression of technology since the first TG publication Learn which new QA procedures should be implemented for new technologies Be familiar with updates to clinical practice guidelines AAPM TG-178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance - Steven Goetsch Purpose: AAPM Task Group 178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance was formed in August, 2008. The Task Group has 12 medical physicists, two physicians and two consultants. Methods: A round robin dosimetry intercomparison of proposed ionization chambers, electrometer and dosimetry phantoms was conducted over a 15 month period in 2011 and 2012 (Med Phys 42, 11, Nov, 2015). The data obtained at 9 institutions (with ten different Elekta Gamma Knife units) was analyzed by the lead author using several protocols. Results: The most consistent results were obtained using the Elekta ABS 16cm diameter phantom, with the TG-51 protocol modified as recommended by Alfonso et al (Med Phys 35, 11, Nov 2008). A key white paper (Med Phys, in press) sponsored by Elekta Corporation, was used to obtain correction factors for the ionization chambers and phantoms used in this intercomparison. Consistent results were obtained for both Elekta Gamma Knife Model 4C and Gamma Knife Perfexion units as measured with each of two miniature ionization chambers. Conclusion: The full report gives clinical history and background of gamma stereotactic radiosurgery, clinical examples and history, quality assurance recommendations and outline

  1. Implicación de las vías Nrf2/HO-1 y NADPH oxidasa en los modelos experimentales de artritis y osteoporosis postmenópausicas.

    Ibáñez Torres, Lidia

    2012-01-01

    Hemos puesto a punto y caracterizado el modelo de artritis postmenopáusica mediante ovariectomía (OVX) y artritis inducida por colágeno (CIA). Además, hemos estudiado la influencia de la vía HO-1 en este modelo animal mediante la administración de tin protoporfirina IX (SnPP) (inhibidor reversible de HO-1) y de CORM-3 (molécula liberadora de CO), así como la influencia de la vía NADPH oxidasa mediante el empleo de ratones con una modificación genética en Ncf1 de manera que no producen especie...

  2. Anti-Fibrotic Effect of Losartan, an Angiotensin II Receptor Blocker, Is Mediated through Inhibition of ER Stress via Up-Regulation of SIRT1, Followed by Induction of HO-1 and Thioredoxin

    Hyosang Kim

    2017-01-01

    Full Text Available Endoplasmic reticulum (ER stress is increasingly identified as modulator of fibrosis. Losartan, an angiotensin II receptor blocker, has been widely used as the first choice of treatment in chronic renal diseases. We postulated that anti-fibrotic effect of losartan is mediated through inhibition of ER stress via SIRT1 (silent mating type information regulation 2 homolog 1 hemeoxygenase-1 (HO-1/thioredoxin pathway. Renal tubular cells, tunicamycin (TM-induced ER stress, and unilateral ureteral obstruction (UUO mouse model were used. Expression of ER stress was assessed by Western blot analysis and immunohistochemical stain. ER stress was induced by chemical ER stress inducer, tunicamycin, and non-chemical inducers such as TGF-β, angiotensin II, high glucose, and albumin. Losartan suppressed the TM-induced ER stress, as shown by inhibition of TM-induced expression of GRP78 (glucose related protein 78 and p-eIF2α (phosphospecific-eukaryotic translation initiation factor-2α, through up-regulation of SIRT1 via HO-1 and thioredoxin. Losartan also suppressed the ER stress by non-chemical inducers. In both animal models, losartan reduced the tubular expression of GRP78, which were abolished by pretreatment with sirtinol (SIRT1 inhibitor. Sirtinol also blocked the inhibitory effect of losartan on the UUO-induced renal fibrosis. These findings provide new insights into renoprotective effects of losartan and suggest that SIRT1, HO-1, and thioredoxin may be potential pharmacological targets in kidney diseases under excessive ER stress condition.

  3. Thought about ICRP TG84 report. What beyond it

    Niwa, Ohtsura

    2013-01-01

    Explained was the ICRP TG84 Report (Report of ICRP Task Group 84 on Initial Lessons Learned from the Nuclear Power Plant Accident in Japan vis-a-vis the ICRP System of Radiological Protection: Issues Identified from the NPP Accident in Japan and Recommendations to Improve the System of Radiation Protection; presented in October, 2012), together with author's thought about it. The Report contained 18 items and their related proposals: Inferring radiation risks (and the misunderstanding of nominal risk coefficients), Attributing radiation effects from low dose exposures, Quantifying radiation exposure, Assessing the importance of internal exposures, Managing emergency crisis, Protecting rescuers and volunteers, Responding with medical aid, Justifying necessary but disruptive protective actions, Transiting from an emergency to an existing situation, Rehabilitating evacuated areas, Categorizing public exposures due to an accident, Restricting individual doses of members of the public, Caring for infants and children, Considering pregnant women and their foetuses and embryos, Monitoring public protection, Dealing with 'contamination' of territories, rubble and residues, and consumer products, Recognizing the importance of psychological consequences, and Fostering the sharing of information. The Report also contained 11 Recommendations of actions for the Commission to take. The author had been installed as the Chair of Radiation Council in February, 2011, just before the Accident in March, and had had to concern the definition of various post-Accident dose limits in Japan, having had often faced the inefficiency of measures. He thought the ICRP protecting system was difficult to understand due to 2 reasons: one was that the system had been written aiming at experts of radiological protection and the other, that the system had been composed not only from science but also from an incorporated standard of social values, which resulted in inconsiderateness to the general

  4. Thermal behaviors of mechanically activated pyrites by thermogravimetry (TG)

    Hu Huiping; Chen Qiyuan; Yin Zhoulan; Zhang Pingmin

    2003-01-01

    The thermal decompositions of mechanically activated and non-activated pyrites were studied by thermogravimetry (TG) at the heating rate of 10 K min -1 in argon. Results indicate that the initial temperature of thermal decomposition (T di ) in TG curves for mechanically activated pyrites decreases gradually with increasing the grinding time. The specific granulometric surface area (S G ), the structural disorder of mechanically activated pyrites were analyzed by X-ray diffraction laser particle size analyzer, and X-ray powder diffraction analysis (XRD), respectively. The results show that the S G of mechanically activated pyrites remains almost constant after a certain grinding time, and lattice distortions (ε) rise but the crystallite sizes (D) decrease with increasing the grinding time. All these results imply that the decrease of T di in TG curves of mechanically activated pyrites is mainly caused by the increase of lattice distortions ε and the decrease of the crystallite sizes D of mechanically activated pyrite with increasing the grinding time. The differences in the reactivity between non-activated and mechanically activated pyrites were observed using characterization of the products obtained from 1 h treatment of non-activated and mechanically activated pyrites at 713 K under inert atmosphere and characterization of non-activated and mechanically activated pyrites exposed to ambient air for a certain period

  5. Long term aging of selenide glasses: evidence of sub-Tg endotherms and pre-Tg exotherms

    Chen, Ping; Boolchand, P.; Georgiev, D. G.

    2010-02-01

    Long term aging, extending from months to several years, is studied on several families of chalcogenide glasses including the Ge-Se, As-Se, and Ge-As-Se systems. Special attention is given to the As-Se binary, a system that displays a rich variety of aging behavior intimately tied to sample synthesis conditions and the ambient environment in which samples are aged. Calorimetric (modulated DSC) and Raman scattering experiments are undertaken. Our results show all samples display a sub-Tg endotherm typically 10-70 °C below Tg in glassy networks possessing a mean coordination number r in the 2.25 < r < 2.45 range. Two sets of AsxSe100-x samples aged for eight years were compared, set A consisted of slow cooled samples aged in the dark, and set B consisted of melt-quenched samples aged at laboratory environment. Samples of set B in the As concentration range, 35% < x < 60%, display a pre-Tg exotherm, but the feature is not observed in samples of set A. The aging behavior of set A presumably represents intrinsic aging in these glasses, while that of set B is extrinsic due to the presence of light. The reversibility window persists in both sets of samples, but is less well defined in set B. These findings contrast with a recent study by Golovchak et al (2008 Phys. Rev. B 78 014202), which finds the onset of the reversibility window moved up to the stoichiometric composition (x = 40%). Here we show that the up-shifted window is better understood as resulting due to demixing of As4Se4 and As4Se3 molecules from the backbone, i.e., nanoscale phase separation (NSPS). We attribute sub-Tg endotherms to compaction of the flexible part of the networks upon long term aging, while the pre-Tg exotherm is to NSPS. The narrowing and sharpening of the reversibility window upon aging is interpreted as the slow 'self-organizing' stress relaxation of the phases just outside the intermediate phase, which itself is stress free and displays little aging.

  6. SU-F-P-15: Report On AAPM TG 178 Gamma Knife Dosimetry and Quality Assurance

    Goetsch, S [San Diego Medical Physics, Solana Beach, CA (United States)

    2016-06-15

    Purpose: AAPM Task Group 178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance was formed in August, 2008. The Task Group has 12 medical physicists, two physicians and two consultants. Methods: A round robin dosimetry intercomparison of proposed ionization chambers, electrometer and dosimetry phantoms was conducted over a 15 month period in 2011 and 2012 (Med Phys 42, 11, Nov, 2015). The data obtained at 9 institutions (with ten different Elekta Gamma Knife units) was analyzed by the lead author using several protocols. Results: The most consistent results were obtained using the Elekta ABS 16cm diameter phantom, with the TG-51 protocol modified as recommended by Alfonso et al (Med Phys 35, 11, Nov 2008). A key white paper (Med Phys, in press) sponsored by Elekta Corporation, was used to obtain correction factors for the ionization chambers and phantoms used in this intercomparison. Consistent results were obtained for both Elekta Gamma Knife Model 4C and Gamma Knife Perfexion units as measured with each of two miniature ionization chambers Conclusion: The full TG 178 report gives clinical history and background of gamma stereotactic radiosurgery, clinical examples and history, quality assurance recommendations and outline of possible dosimetry protocols. The report will be reviewed by the AAPM Working Group on Recommendations for Radiotherapy External Beam Quality Assurance and then by the AAPM Science Council before publication in Medical Physics. Consultant to Elekta, Inc.

  7. SU-F-P-15: Report On AAPM TG 178 Gamma Knife Dosimetry and Quality Assurance

    Goetsch, S

    2016-01-01

    Purpose: AAPM Task Group 178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance was formed in August, 2008. The Task Group has 12 medical physicists, two physicians and two consultants. Methods: A round robin dosimetry intercomparison of proposed ionization chambers, electrometer and dosimetry phantoms was conducted over a 15 month period in 2011 and 2012 (Med Phys 42, 11, Nov, 2015). The data obtained at 9 institutions (with ten different Elekta Gamma Knife units) was analyzed by the lead author using several protocols. Results: The most consistent results were obtained using the Elekta ABS 16cm diameter phantom, with the TG-51 protocol modified as recommended by Alfonso et al (Med Phys 35, 11, Nov 2008). A key white paper (Med Phys, in press) sponsored by Elekta Corporation, was used to obtain correction factors for the ionization chambers and phantoms used in this intercomparison. Consistent results were obtained for both Elekta Gamma Knife Model 4C and Gamma Knife Perfexion units as measured with each of two miniature ionization chambers Conclusion: The full TG 178 report gives clinical history and background of gamma stereotactic radiosurgery, clinical examples and history, quality assurance recommendations and outline of possible dosimetry protocols. The report will be reviewed by the AAPM Working Group on Recommendations for Radiotherapy External Beam Quality Assurance and then by the AAPM Science Council before publication in Medical Physics. Consultant to Elekta, Inc

  8. AIR QUALITY IN THE CITY OF TG JIU

    Adina TĂTAR

    2014-05-01

    Full Text Available One of the most important problems of the modern age is the air pollution. Within this work I realized a description of Tgjiu City: geographic location, climate, hydrographical network, variations in temperature, terrain, sources of pollution. On the basis of registered values for the air quality indicator, sedimentable powders, and interpretation of results on the basis of the provisions of the standards in force, the comments were made in relation to particulate air pollution in the city area of sedimentableTg Jiu, identifying the polluters in the area, the proposed solutions for the reduction of pollution.

  9. TU-E-BRB-03: Overview of Proposed TG-132 Recommendations

    Brock, K. [University of Michigan (United States)

    2015-06-15

    Deformable image registration (DIR) is developing rapidly and is poised to substantially improve dose fusion accuracy for adaptive and retreatment planning and motion management and PET fusion to enhance contour delineation for treatment planning. However, DIR dose warping accuracy is difficult to quantify, in general, and particularly difficult to do so on a patient-specific basis. As clinical DIR options become more widely available, there is an increased need to understand the implications of incorporating DIR into clinical workflow. Several groups have assessed DIR accuracy in clinically relevant scenarios, but no comprehensive review material is yet available. This session will also discuss aspects of the AAPM Task Group 132 on the Use of Image Registration and Data Fusion Algorithms and Techniques in Radiotherapy Treatment Planning official report, which provides recommendations for DIR clinical use. We will summarize and compare various commercial DIR software options, outline successful clinical techniques, show specific examples with discussion of appropriate and inappropriate applications of DIR, discuss the clinical implications of DIR, provide an overview of current DIR error analysis research, review QA options and research phantom development and present TG-132 recommendations. Learning Objectives: Compare/contrast commercial DIR software and QA options Overview clinical DIR workflow for retreatment To understand uncertainties introduced by DIR Review TG-132 proposed recommendations.

  10. Open TG-GATEs: a large-scale toxicogenomics database

    Igarashi, Yoshinobu; Nakatsu, Noriyuki; Yamashita, Tomoya; Ono, Atsushi; Ohno, Yasuo; Urushidani, Tetsuro; Yamada, Hiroshi

    2015-01-01

    Toxicogenomics focuses on assessing the safety of compounds using gene expression profiles. Gene expression signatures from large toxicogenomics databases are expected to perform better than small databases in identifying biomarkers for the prediction and evaluation of drug safety based on a compound's toxicological mechanisms in animal target organs. Over the past 10 years, the Japanese Toxicogenomics Project consortium (TGP) has been developing a large-scale toxicogenomics database consisting of data from 170 compounds (mostly drugs) with the aim of improving and enhancing drug safety assessment. Most of the data generated by the project (e.g. gene expression, pathology, lot number) are freely available to the public via Open TG-GATEs (Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System). Here, we provide a comprehensive overview of the database, including both gene expression data and metadata, with a description of experimental conditions and procedures used to generate the database. Open TG-GATEs is available from http://toxico.nibio.go.jp/english/index.html. PMID:25313160

  11. TU-B-304-00: The Aftermath of TG-142

    NONE

    2015-06-15

    Although published in 2009, the AAPM TG-142 report on accelerator quality assurance still proves a challenge for full clinical implementation. The choice of methodologies to satisfy TG-142 requirements is critical to a successful application. Understanding the philosophy of TG-142 can help in creating an institution-specific QA practice that is both efficient and effective. The concept of maintaining commissioned beam profiles is still found confusing. The physicist must also consider technologies not covered by TG-142 (i.e. arc therapy techniques). On the horizon is TG-198 report on implementing TG-142. Although the community still lacks a final TG-100 report, performing a failure-mode -and-effects analysis and statistical process control analysis to determine the institution-specific clinical impact of each TG-142 test may be useful for identifying trends for pro-active surveillance. Learning Objectives: To better understand the confusing and controversial aspects of TG-142. To understand what is still missing from TG-142 and how to account for these tests in clinical practice To describe which QA tests in TG-142 yield the largest potential clinical result if not discovered.

  12. TU-B-304-01: The Aftermath of TG-142

    Klein, E. [Washington University (United States)

    2015-06-15

    Although published in 2009, the AAPM TG-142 report on accelerator quality assurance still proves a challenge for full clinical implementation. The choice of methodologies to satisfy TG-142 requirements is critical to a successful application. Understanding the philosophy of TG-142 can help in creating an institution-specific QA practice that is both efficient and effective. The concept of maintaining commissioned beam profiles is still found confusing. The physicist must also consider technologies not covered by TG-142 (i.e. arc therapy techniques). On the horizon is TG-198 report on implementing TG-142. Although the community still lacks a final TG-100 report, performing a failure-mode -and-effects analysis and statistical process control analysis to determine the institution-specific clinical impact of each TG-142 test may be useful for identifying trends for pro-active surveillance. Learning Objectives: To better understand the confusing and controversial aspects of TG-142. To understand what is still missing from TG-142 and how to account for these tests in clinical practice To describe which QA tests in TG-142 yield the largest potential clinical result if not discovered.

  13. TU-B-304-02: Quantitative FMEA of TG-142

    O’Daniel, J. [Duke University Medical Center (United States)

    2015-06-15

    Although published in 2009, the AAPM TG-142 report on accelerator quality assurance still proves a challenge for full clinical implementation. The choice of methodologies to satisfy TG-142 requirements is critical to a successful application. Understanding the philosophy of TG-142 can help in creating an institution-specific QA practice that is both efficient and effective. The concept of maintaining commissioned beam profiles is still found confusing. The physicist must also consider technologies not covered by TG-142 (i.e. arc therapy techniques). On the horizon is TG-198 report on implementing TG-142. Although the community still lacks a final TG-100 report, performing a failure-mode -and-effects analysis and statistical process control analysis to determine the institution-specific clinical impact of each TG-142 test may be useful for identifying trends for pro-active surveillance. Learning Objectives: To better understand the confusing and controversial aspects of TG-142. To understand what is still missing from TG-142 and how to account for these tests in clinical practice To describe which QA tests in TG-142 yield the largest potential clinical result if not discovered.

  14. Comparison of Thyroglobulin Measurements Using Three Different Immunoassay Kits: A BRAMHS Tg-Plus RIA Kit, a BRAMHS hTg Sensitive Kryptor Kit, and a Beckman Coulter ACCESS Immunoassay Kit

    Mijin Kim

    2016-09-01

    Full Text Available BackgroundSecond-generation thyroglobulin immunometric assays (Tg-IMAs have been developed with improved sensitivity. Our aim was to compare the diagnostic value of Tg-IMA measurements using a Kryptor (BRAHMS AG kit (Tg-K and an ACCESS (Beckman Coulter kit (Tg-A with that of the first-generation Tg measurement using a Tg-plus (BRAHMS AG kit (Tg+.MethodsWe enrolled 82 differentiated thyroid cancer patients who underwent total thyroidectomy with radioactive iodine remnant ablation and who underwent diagnostic whole body scan using recombinant human thyroid stimulating hormone (rhTSH. The Tg+, Tg-K, and Tg-A were measured before rhTSH administration during levothyroxine treatment (suppressed Tg from the same sample. Serum Tg+ was measured after rhTSH stimulation (stimulated Tg.ResultsSuppressed Tg+ was more significantly correlated with suppressed Tg-K (R2=0.919, P<0.001 than with suppressed Tg-A (R2=0.536, P<0.001. The optimal cut-off values of suppressed Tg+, Tg-K, and Tg-A for predicting stimulated Tg+ of 1 ng/mL were 0.3, 0.2, and 0.2 ng/mL, respectively. The sensitivity, specificity, and accuracy of suppressed Tg+ were 67%, 100%, and 90%, respectively; those of suppressed Tg-K were 83%, 90%, and 88%; those of suppressed Tg-A were 96%, 82%, and 87%, respectively. The positive predictive and negative predictive values of Tg+ were 100% and 87%, respectively; those of Tg-K were 79% and 92%; and those of Tg-A were 73% and 98%.ConclusionWe could not clearly demonstrate which kit had better diagnostic performance after comparison of first-generation Tg measurements with Tg-IMA measurements. Also, there were kit-to-kit variations between Tg-IMA kits. Suppressed Tg measured by Tg-IMA was insufficient to completely substitute for a stimulated Tg measurement.

  15. SU-E-J-52: Decreasing Frequency of Performing TG-142 Imaging QA – 5 Year Experience

    Lin, T; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States)

    2015-06-15

    Purpose This study is an update to check if the frequency of imaging QA suggested by AAPM Task Group Report 142 (TG142) is necessary with our 5 year experience. TG142 presents recommendations for QA criteria of IGRT treatment. ACR has adopted it to be the requirements for any radiatiotherapy practices; however, we propose to reduce the frequency on image quality QA according to this 5 year study.Method and Materials: This study uses VarianIX2100 and Siemens Artiste Linacs to perform QAs on KV, MV, CBCT modalities. The QA was designed following under the recommendations of TG142. This study reports the daily imaging positioning/repositioning and imaging and treatment coordinate coincidence. QA results on kV, MV and CBCT from 4/7/2010∼3/11/15 are analyzed. KV, MV, CBCT images are taken with the Varian isocube localized at the isocenter. Digital graticule is used in the software to verify the isocenter position. CBCT images are taken with the cube placed at 1cm superior, lateral and anterior of the isocenter. In-line fusion software is used to verify the contrived shift. Digital ruler provided at the on-board-imaging software or adaptive-targeting software was used to measure the position differences. The position differences were recorded at AP,LR,SI directions. Results 5 year records on kV, MV, CBCT show the shifts in all three directions are within the tolerance of 1mm suggested in TG142 for stereotactic radiation treatment(SRS/SRT). There is no occasion where shifts are outside 1mm tolerance. Conclusions The daily imaging QA suggested in TG142 is useful in ensuring the accuracy needed for SRS/SRT in IGRT. 5 year measurements presented suggest that decreasing the frequency of imaging QA may be acceptable, in particular for institutions reporting no violation of tolerance over periods of few years.

  16. SU-E-J-52: Decreasing Frequency of Performing TG-142 Imaging QA – 5 Year Experience

    Lin, T; Ma, C

    2015-01-01

    Purpose This study is an update to check if the frequency of imaging QA suggested by AAPM Task Group Report 142 (TG142) is necessary with our 5 year experience. TG142 presents recommendations for QA criteria of IGRT treatment. ACR has adopted it to be the requirements for any radiatiotherapy practices; however, we propose to reduce the frequency on image quality QA according to this 5 year study.Method and Materials: This study uses VarianIX2100 and Siemens Artiste Linacs to perform QAs on KV, MV, CBCT modalities. The QA was designed following under the recommendations of TG142. This study reports the daily imaging positioning/repositioning and imaging and treatment coordinate coincidence. QA results on kV, MV and CBCT from 4/7/2010∼3/11/15 are analyzed. KV, MV, CBCT images are taken with the Varian isocube localized at the isocenter. Digital graticule is used in the software to verify the isocenter position. CBCT images are taken with the cube placed at 1cm superior, lateral and anterior of the isocenter. In-line fusion software is used to verify the contrived shift. Digital ruler provided at the on-board-imaging software or adaptive-targeting software was used to measure the position differences. The position differences were recorded at AP,LR,SI directions. Results 5 year records on kV, MV, CBCT show the shifts in all three directions are within the tolerance of 1mm suggested in TG142 for stereotactic radiation treatment(SRS/SRT). There is no occasion where shifts are outside 1mm tolerance. Conclusions The daily imaging QA suggested in TG142 is useful in ensuring the accuracy needed for SRS/SRT in IGRT. 5 year measurements presented suggest that decreasing the frequency of imaging QA may be acceptable, in particular for institutions reporting no violation of tolerance over periods of few years

  17. Roles of TgAb and TPOAb in the development of hypothyroidism after 131I treatment in hyperthyroid patients with Graves' disease

    Han Yunfeng; Tong Liangqian; Lan Qiong; Zhu Xiaohua; Chen Jing; Zhao Ming

    2012-01-01

    To evaluate the roles of antithyroid peroxidase antibodies (TPOAb) and antithyroglobulin antibodies (TbAb) in the development of hypothyroidism after 131 I treatment in hyperthyroid patients with Graves' disease (GD), data were collected from 160 GD patients who were treated with 131 I in the department of nuclear medicine of Tongji Hospital between January 2008 and February 2011. Patients were divided into four groups: group A (TgAb 131 I. The incidence of hypothyroidism after 131 I treatment was different for each group(P=0.034 131 I treatment. In conclusion, because TgAb and TPOAb play important roles in the occurrence of hypothyroidism after 131 I therapy, in patients with positive levels of TgAb and TPOAb, lower doses of 131 I might prevent hypothyroidism. (authors)

  18. Inhibition of microRNA-153 protects neurons against ischemia/reperfusion injury in an oxygen-glucose deprivation and reoxygenation cellular model by regulating Nrf2/HO-1 signaling.

    Ji, Qiong; Gao, Jianbo; Zheng, Yan; Liu, Xueli; Zhou, Qiangqiang; Shi, Canxia; Yao, Meng; Chen, Xia

    2017-07-01

    MicroRNAs are emerging as critical regulators in cerebral ischemia/reperfusion injury; however, their exact roles remain poorly understood. miR-153 is reported to be a neuron-related miRNA involved in neuroprotection. In this study, we aimed to investigate the precise role of miR-153 in regulating neuron survival during cerebral ischemia/reperfusion injury using an oxygen-glucose deprivation and reoxygenation (OGD/R) cellular model. We found that miR-153 was significantly upregulated in neurons subjected to OGD/R treatment. Inhibition of miR-153 significantly attenuated OGD/R-induced injury and oxidative stress in neurons. Nuclear factor erythroid 2-related factor 2 (Nrf2) was identified as a target gene of miR-153. Inhibition of miR-153 significantly promoted the expression of Nrf2 and heme oxygenase-1 (HO-1). However, silencing of Nrf2 significantly blocked the protective effects of miR-153 inhibition. Our study indicates that the inhibition of miR-153 protects neurons against OGD/R-induced injury by regulating Nrf2/HO-1 signaling and suggests a potential therapeutic target for cerebral ischemia/reperfusion injury. © 2017 Wiley Periodicals, Inc.

  19. Making the Tg-Confinement Effect Disappear in Thin Polystyrene Films: Good Physics vs. Inappropriate Analysis

    Torkelson, John; Chen, Lawrence

    2013-03-01

    The Tg-confinement effect in polymers was first characterized in supported polystyrene (PS) films by Keddie et al. in 1994. Since then, many researchers have shown that (pseudo-)thermodynamic Tg measurements of supported PS films taken on cooling consistently yield the same qualitative results, with a decrease from bulk Tg beginning at 40-60 nm thickness and becoming very strong below 20 nm thickness. Some quantitative differences have been noted between studies, which may be ascribed to measurement method or the analysis employed. In 2004, we showed that the Tg-confinement effect in PS may be suppressed by adding several wt% of small-molecule diluents such as dioctyl phthalate. Recently, Kremer and co-workers (Macromolecules 2010, 43, 9937) reported that there was no Tg-confinement in supported PS films based on an analysis of the second derivative of ellipsometry data and use of a ninth order polynomial fit. Here, we demonstrate a new method for suppressing the Tg-confinement effect. In particular, PS made by emulsion polymerization yields no Tg-confinement effect as measured by ellipsometry or fluorescence, while PS made by anionic or conventional free radical polymerization yield strong Tg-confinement effects. The difference is hypothesized to result from surfactant in the emulsion polymerized PS. We also show that the absence of the Tg-confinement effect reported by Kremer is due to inappropriate analysis of ellipsometry data and that correct analysis yields Tg-confinement effects.

  20. TU-D-201-03: Results of a Survey On the Implementation of the TG-51 Protocol and Associated Addendum On Reference Dosimetry of External Beams

    Kim, G [University of California, San Diego, La Jolla, CA (United States); Muir, B [National Research Council, Ottawa, AB (Canada); Culberson, W [University of Wisconsin Madison, Madison, WI (United States); Davis, S [McGill University Health Center, Montreal, QC (Canada); Huang, Y [Henry Ford Health System, West Bloomfield, MI (United States); Lee, S [University of Maryland School of Medicine, Columbia, MD (United States); Lowenstein, J [UT MD Anderson Cancer Center, Houston, TX (United States); Sarfehnia, A [Sunnybrook Health Science Center, Toronto, ON (Canada); Tolani, N [Michael E. DeBakey VA Medical Center, Sugarland (United States); Siebers, J [University of Virginia Health System, Charlottesville, VA (United States)

    2016-06-15

    Purpose: The working group on the review and extension of the TG-51 protocol (WGTG51) collected data from American Association of Physicists in Medicine (AAPM) members with respect to their current TG-51 and associated addendum usage in the interest of considering future protocol addenda and guidance on reference dosimetry best practices. This study reports an overview of this survey on dosimetry of external beams. Methods: Fourteen survey questions were developed by WGTG51 and released in November 2015. The questions collected information on reference dosimetry, beam quality specification, and ancillary calibration equipment. Results: Of the 190 submissions completed worldwide (U.S. 70%), 83% were AAPM members. Of the respondents, 33.5% implemented the TG-51 addendum, with the maximum calibration difference for any photon beam, with respect to the original TG-51 protocol, being <1% for 97.4% of responses. One major finding is that 81.8% of respondents used the same cylindrical ionization chamber for photon and electron dosimetry, implying that many clinics are foregoing the use of parallel-plate chambers. Other evidence suggests equivalent dosimetric results can be obtained with both cylindrical and parallel-plate chambers in electron beams. This, combined with users comfort with cylindrical chambers for electrons will likely impact recommendations put forward in an upcoming electron beam addendum to the TG-51 protocol. Data collected on ancillary equipment showed 58.2% (45.0%) of the thermometers (barometers) in use for beam calibration had NIST traceable calibration certificates, but 48.4% (42.7%) were never recalibrated. Conclusion: This survey provides a snapshot of TG-51 external beam reference dosimetry practice in radiotherapy centers. Findings demonstrate the rapid take-up of the TG-51 photon beam addendum and raise issues for the WGTG51 to focus on going forward, including guidelines on ancillary equipment and the choice of chamber for electron beam

  1. Comparative study by TG and DSC Of membranes polyamide66/bentonite clay nanocomposite; Estudo comparativo por TG e DSC de membranas de nanocompositos poliamida66/argila bentonitica

    Medeiros, K.M. de; Kojuch, L R; Araujo, E M; Lira, H.L., E-mail: keilamm@ig.com.b [Universidade Federal de Campina Grande (UFCG), PB (Brazil). Unidade Academica de Engenharia de Materiais; Lima, F [Universidade Estadual da Paraiba (UEPB), Campina Grande, PB (Brazil). Dept. de Quimica

    2010-07-01

    In this study, it was obtained membranes of nanocomposites polyamide66 with 3 and 5% bentonite clay consists of silicates in layers from the interior of Paraiba. The clay was treated with a quaternary ammonium salt in order to make it organophilic. The membranes were prepared by phase inversion technique from the nanocomposites in solution. The clays were characterized by X-ray diffraction (XRD) and thermogravimetry (TG). Also the membranes were characterized by differential scanning calorimetry (DSC) and TG. The XRD and TG confirmed the presence of salt in the clay and thermal stability of the treated clay. For DSC, it was observed that there was no change in melting temperature of the membranes of nanocomposites compared to membrane pure polyamide66. By TG, it was found that the decomposition of the membranes of polyamide66 with treated clay were higher compared with the untreated clay. (author)

  2. TH-A-BRC-03: AAPM TG218: Measurement Methods and Tolerance Levels for Patient-Specific IMRT Verification QA

    Miften, M. [University of Colorado School of Medicine (United States)

    2016-06-15

    AAPM TG-135U1 QA for Robotic Radiosurgery - Sonja Dieterich Since the publication of AAPM TG-135 in 2011, the technology of robotic radiosurgery has rapidly developed. AAPM TG-135U1 will provide recommendations on the clinical practice for using the IRIS collimator, fiducial-less real-time motion tracking, and Monte Carlo based treatment planning. In addition, it will summarize currently available literature about uncertainties. Learning Objectives: Understand the progression of technology since the first TG publication Learn which new QA procedures should be implemented for new technologies Be familiar with updates to clinical practice guidelines AAPM TG-178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance - Steven Goetsch Purpose: AAPM Task Group 178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance was formed in August, 2008. The Task Group has 12 medical physicists, two physicians and two consultants. Methods: A round robin dosimetry intercomparison of proposed ionization chambers, electrometer and dosimetry phantoms was conducted over a 15 month period in 2011 and 2012 (Med Phys 42, 11, Nov, 2015). The data obtained at 9 institutions (with ten different Elekta Gamma Knife units) was analyzed by the lead author using several protocols. Results: The most consistent results were obtained using the Elekta ABS 16cm diameter phantom, with the TG-51 protocol modified as recommended by Alfonso et al (Med Phys 35, 11, Nov 2008). A key white paper (Med Phys, in press) sponsored by Elekta Corporation, was used to obtain correction factors for the ionization chambers and phantoms used in this intercomparison. Consistent results were obtained for both Elekta Gamma Knife Model 4C and Gamma Knife Perfexion units as measured with each of two miniature ionization chambers. Conclusion: The full report gives clinical history and background of gamma stereotactic radiosurgery, clinical examples and history, quality assurance recommendations and outline

  3. TH-A-BRC-03: AAPM TG218: Measurement Methods and Tolerance Levels for Patient-Specific IMRT Verification QA

    Miften, M.

    2016-01-01

    AAPM TG-135U1 QA for Robotic Radiosurgery - Sonja Dieterich Since the publication of AAPM TG-135 in 2011, the technology of robotic radiosurgery has rapidly developed. AAPM TG-135U1 will provide recommendations on the clinical practice for using the IRIS collimator, fiducial-less real-time motion tracking, and Monte Carlo based treatment planning. In addition, it will summarize currently available literature about uncertainties. Learning Objectives: Understand the progression of technology since the first TG publication Learn which new QA procedures should be implemented for new technologies Be familiar with updates to clinical practice guidelines AAPM TG-178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance - Steven Goetsch Purpose: AAPM Task Group 178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance was formed in August, 2008. The Task Group has 12 medical physicists, two physicians and two consultants. Methods: A round robin dosimetry intercomparison of proposed ionization chambers, electrometer and dosimetry phantoms was conducted over a 15 month period in 2011 and 2012 (Med Phys 42, 11, Nov, 2015). The data obtained at 9 institutions (with ten different Elekta Gamma Knife units) was analyzed by the lead author using several protocols. Results: The most consistent results were obtained using the Elekta ABS 16cm diameter phantom, with the TG-51 protocol modified as recommended by Alfonso et al (Med Phys 35, 11, Nov 2008). A key white paper (Med Phys, in press) sponsored by Elekta Corporation, was used to obtain correction factors for the ionization chambers and phantoms used in this intercomparison. Consistent results were obtained for both Elekta Gamma Knife Model 4C and Gamma Knife Perfexion units as measured with each of two miniature ionization chambers. Conclusion: The full report gives clinical history and background of gamma stereotactic radiosurgery, clinical examples and history, quality assurance recommendations and outline

  4. Trend analysis of body weight parameters, mortality, and incidence of spontaneous tumors in Tg.rasH2 mice.

    Paranjpe, Madhav G; Denton, Melissa D; Vidmar, Tom; Elbekai, Reem H

    2014-01-01

    Carcinogenicity studies have been performed in conventional 2-year rodent studies for at least 3 decades, whereas the short-term carcinogenicity studies in transgenic mice, such as Tg.rasH2, have only been performed over the last decade. In the 2-year conventional rodent studies, interlinked problems, such as increasing trends in the initial body weights, increased body weight gains, high incidence of spontaneous tumors, and low survival, that complicate the interpretation of findings have been well established. However, these end points have not been evaluated in the short-term carcinogenicity studies involving the Tg.rasH2 mice. In this article, we present retrospective analysis of data obtained from control groups in 26-week carcinogenicity studies conducted in Tg.rasH2 mice since 2004. Our analysis showed statistically significant decreasing trends in initial body weights of both sexes. Although the terminal body weights did not show any significant trends, there was a statistically significant increasing trend toward body weight gains, more so in males than in females, which correlated with increasing trends in the food consumption. There were no statistically significant alterations in mortality trends. In addition, the incidence of all common spontaneous tumors remained fairly constant with no statistically significant differences in trends. © The Author(s) 2014.

  5. Primary motor cortex alterations in Alzheimer disease: A study in the 3xTg-AD model.

    Orta-Salazar, E; Feria-Velasco, A I; Díaz-Cintra, S

    2017-04-19

    In humans and animal models, Alzheimer disease (AD) is characterised by accumulation of amyloid-β peptide (Aβ) and hyperphosphorylated tau protein, neuronal degeneration, and astrocytic gliosis, especially in vulnerable brain regions (hippocampus and cortex). These alterations are associated with cognitive impairment (loss of memory) and non-cognitive impairment (motor impairment). The purpose of this study was to identify cell changes (neurons and glial cells) and aggregation of Aβ and hyperphosphorylated tau protein in the primary motor cortex (M1) in 3xTg-AD mouse models at an intermediate stage of AD. We used female 3xTg-AD mice aged 11 months and compared them to non-transgenic mice of the same age. In both groups, we assessed motor performance (open field test) and neuronal damage in M1 using specific markers: BAM10 (extracellular Aβ aggregates), tau 499 (hyperphosphorylated tau protein), GFAP (astrocytes), and Klüver-Barrera staining (neurons). Female 3xTg-AD mice in intermediate stages of the disease displayed motor and cellular alterations associated with Aβ and hyperphosphorylated tau protein deposition in M1. Patients with AD display signs and symptoms of functional impairment from early stages. According to our results, M1 cell damage in intermediate-stage AD affects motor function, which is linked to progression of the disease. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Peracetylated hydroxytyrosol, a new hydroxytyrosol derivate, attenuates LPS-induced inflammatory response in murine peritoneal macrophages via regulation of non-canonical inflammasome, Nrf2/HO1 and JAK/STAT signaling pathways.

    Montoya, Tatiana; Aparicio-Soto, Marina; Castejón, María Luisa; Rosillo, María Ángeles; Sánchez-Hidalgo, Marina; Begines, Paloma; Fernández-Bolaños, José G; Alarcón-de-la-Lastra, Catalina

    2018-03-18

    The present study was designed to investigate the anti-inflammatory effects of a new derivative of hydroxytyrosol (HTy), peracetylated hydroxytyrosol (Per-HTy), compared with its parent, HTy, on lipopolysaccharide (LPS)-stimulated murine macrophages as well as potential signaling pathways involved. In particular, we attempted to characterize the role of the inflammasome underlying Per-HTy possible anti-inflammatory effects. Isolated murine peritoneal macrophages were treated with HTy or its derivative in the presence or absence of LPS (5 μg/ml) for 18 h. Cell viability was determined using sulforhodamine B (SRB) assay. Nitric oxide (NO) production was analyzed by Griess method. Production of pro-inflammatory cytokines was evaluated by enzyme-linked immunosorbent assay (ELISA) and inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway (STAT3), haem oxigenase 1 (HO1), nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression and mitogen-activated protein kinases (MAPKs) activation was determined by Western blot. Per-HTy significantly reduced the levels of NO and pro-inflammatory cytokines as well as both COX-2 and iNOS expressions. Furthermore, Per-HTy treatment inhibited STAT3 and increased Nrf2 and HO1 protein levels in murine macrophages exposed to LPS. In addition, Per-HTy anti-inflammatory activity was related with an inhibition of non-canonical nucleotide binding domain (NOD)-like receptor (NLRP3) inflammasome pathways by decreasing pro-inflammatory interleukin (IL)-1β and IL-18 cytokine levels as consequence of regulation of cleaved caspase-11 enzyme. These results support that this new HTy derivative may offer a new promising nutraceutical therapeutic strategy in the management of inflammatory-related pathologies. Copyright © 2018. Published by Elsevier Inc.

  7. Re-examining TG-142 recommendations in light of modern techniques for linear accelerator based radiosurgery.

    Faught, Austin M; Trager, Michael; Yin, Fang-Fang; Kirkpatrick, John; Adamson, Justus

    2016-10-01

    The recent development of multifocal stereotactic radiosurgery (SRS) using a single isocenter volumetric modulated arc theory (VMAT) technique warrants a re-examination of the quality assurance (QA) tolerances for routine mechanical QA recommended by the American Association of Physicists in Medicine Task Group Report Number 142. Multifocal SRS can result in targets with small volumes being at a large off-axis distance from the treatment isocenter. Consequently, angular errors in the collimator, patient support assembly (PSA), or gantry could have an increased impact on target coverage. The authors performed a retrospective analysis of dose deviations caused by systematic errors in PSA, collimator, and gantry angle at the tolerance level for routine linear accelerator QA as recommended by TG-142. Dosimetric deviations from multifocal SRS plans (N = 10) were compared to traditional single target SRS using dynamic conformal arcs (N = 10). The chief dosimetric quantities used in determining clinical impact were V 100% and D 99% of the individual planning target volumes and V 12Gy of the healthy brain. Induced errors at tolerance levels showed the greatest change in multifocal SRS target coverage for collimator rotations (±1.0°) with the average changes to V 100% and D 99% being 5% and 6%, respectively, with maximum changes of 33% and 20%. A reduction in the induced error to half the TG-142 tolerance (±0.5°) demonstrated similar changes in coverage loss to traditional single target SRS assessed at the recommended tolerance level. The observed change in coverage for multifocal SRS was reduced for gantry errors (±1.0°) at 2% and 4.5% for V 100% and D 99% , respectively, with maximum changes of 18% and 12%. Minimal change in coverage was noted for errors in PSA rotation. This study indicates that institutions utilizing a single isocenter VMAT technique for multifocal disease should pay careful attention to the angular mechanical tolerances in designing a robust and

  8. Tissue transglutaminase (TG2 activity regulates osteoblast differentiation and mineralization in the SAOS-2 cell line

    Xiaoxue Yin

    2012-08-01

    Full Text Available Tissue transglutaminase (type II, TG2 has long been postulated to directly promote skeletal matrix calcification and play an important role in ossification. However, limited information is available on the expression, function and modulating mechanism of TG2 during osteoblast differentiation and mineralization. To address these issues, we cultured the well-established human osteosarcoma cell line SAOS-2 with osteo-inductive conditioned medium and set up three time points (culture days 4, 7, and 14 to represent different stages of SAOS-2 differentiation. Osteoblast markers, mineralization, as well as TG2 expression and activity, were then assayed in each stage. Furthermore, we inhibited TG activity with cystamine and then checked SAOS-2 differentiation and mineralization in each stage. The results showed that during the progression of osteoblast differentiation SAOS-2 cells presented significantly high levels of osteocalcin (OC mRNA, bone morphogenetic protein-2 (BMP-2 and collagen I, significantly high alkaline phosphatase (ALP activity, and the increased formation of calcified matrix. With the same tendency, TG2 expression and activity were up-regulated. Furthermore, inhibition of TG activity resulted in a significant decrease of OC, collagen I, and BMP-2 mRNA and of ALP activity and mineralization. This study demonstrated that TG2 is involved in osteoblast differentiation and may play a role in the initiation and regulation of the mineralization processes. Moreover, the modulating effects of TG2 on osteoblasts may be related to BMP-2.

  9. Endogenous murine tau promotes neurofibrillary tangles in 3xTg-AD mice without affecting cognition.

    Baglietto-Vargas, David; Kitazawa, Masashi; Le, Elaine J; Estrada-Hernandez, Tatiana; Rodriguez-Ortiz, Carlos J; Medeiros, Rodrigo; Green, Kim N; LaFerla, Frank M

    2014-02-01

    Recent studies on tauopathy animal models suggest that the concomitant expression of the endogenous murine tau delays the pathological accumulation of human tau, and interferes with the disease progression. To elucidate the role of endogenous murine tau in a model with both plaques and tangles, we developed a novel transgenic mouse model by crossing 3xTg-AD with mtauKO mice (referred to as 3xTg-AD/mtauKO mice). Therefore, this new model allows us to determine the pathological consequences of the murine tau. Here, we show that 3xTg-AD/mtauKO mice have lower tau loads in both soluble and insoluble fractions, and lower tau hyperphosphorylation level in the soluble fraction relative to 3xTg-AD mice. In the 3xTg-AD model endogenous mouse tau is hyperphosphorylated and significantly co-aggregates with human tau. Despite the deletion of the endogenous tau gene in 3xTg-AD/mtauKO mice, cognitive dysfunction was equivalent to 3xTg-AD mice, as there was no additional impairment on a spatial memory task, and thus despite increased tau phosphorylation, accumulation and NFTs in 3xTg-AD mice no further effects on cognition are seen. These findings provide better understanding about the role of endogenous tau to Alzheimer's disease (AD) pathology and for developing new AD models. © 2013.

  10. SU-E-I-20: Comprehensive Quality Assurance Test of Second Generation Toshiba Aquilion Large Bore CT Simulator Based On AAPM TG-66 Recommendations

    Zhang, D [Toshiba America Medical Systems, Tustin, CA (United States)

    2015-06-15

    Purpose: AAPM radiation therapy committee task group No. 66 (TG-66) published a report which described a general approach to CT simulator QA. The report outlines the testing procedures and specifications for the evaluation of patient dose, radiation safety, electromechanical components, and image quality for a CT simulator. The purpose of this study is to thoroughly evaluate the performance of a second generation Toshiba Aquilion Large Bore CT simulator with 90 cm bore size (Toshiba, Nasu, JP) based on the TG-66 criteria. The testing procedures and results from this study provide baselines for a routine QA program. Methods: Different measurements and analysis were performed including CTDIvol measurements, alignment and orientation of gantry lasers, orientation of the tabletop with respect to the imaging plane, table movement and indexing accuracy, Scanogram location accuracy, high contrast spatial resolution, low contrast resolution, field uniformity, CT number accuracy, mA linearity and mA reproducibility using a number of different phantoms and measuring devices, such as CTDI phantom, ACR image quality phantom, TG-66 laser QA phantom, pencil ion chamber (Fluke Victoreen) and electrometer (RTI Solidose 400). Results: The CTDI measurements were within 20% of the console displayed values. The alignment and orientation for both gantry laser and tabletop, as well as the table movement and indexing and scanogram location accuracy were within 2mm as specified in TG66. The spatial resolution, low contrast resolution, field uniformity and CT number accuracy were all within ACR’s recommended limits. The mA linearity and reproducibility were both well below the TG66 threshold. Conclusion: The 90 cm bore size second generation Toshiba Aquilion Large Bore CT simulator that comes with 70 cm true FOV can consistently meet various clinical needs. The results demonstrated that this simulator complies with the TG-66 protocol in all aspects including electromechanical component

  11. Influence of the Zeolite ZSM-5 on Catalytic Pyrolysis of Biomass via TG-FTIR

    Ze Wang

    2015-06-01

    Full Text Available Bio-oil from the pyrolysis of biomass is an important renewable source for liquid fuel. However, the application of bio-oil has been severely restricted due to its high viscosity, acidity, and low heating value. Thus, it has been necessary to upgrade bio-oil for automobile fuel via catalytic deoxygenation reactions. Herein, the effects of the zeolite ZSM-5 on the pyrolysis of four biomass materials (corn cob, corn straw, pine powder, and cellulose were investigated via TG-FTIR (thermogravimetric analyzer coupled with a Fourier transform infrared spectrometer to better understand the working mechanism of ZSM-5. The contents of the products of H2O, CO, CO2, and the C-O, C=O, and OH groups evolved with increasing pyrolytic temperature were monitored by FTIR. It was found that the relative contents of the C-O and C=O groups were decreased under the catalysis of ZSM-5, while the formations of CO, H2O, and the OH containing compounds were promoted. To explain the regulations, reaction routes were speculated and the catalytic conversion mechanisms were deduced.

  12. Hydrogen bonding analysis of hydroxyl groups in glucose aqueous solutions by a molecular dynamics simulation study

    Chen, Cong; Li, Wei Zhong; Song, Yong Chen; Weng, Lin Dong; Zhang, Ning

    2012-01-01

    Molecular dynamics simulations have been performed to investigate hydrogen bonding characteristics of hydroxyl groups in glucose aqueous solutions with different concentrations. The hydrogen bonding abilities and strength of different O and H atom types have been calculated and compared. The acceptor/donor efficiencies have been predicted and it has been found that: (1) O2-HO2 and O3-HO3 are more efficient intramolecular hydrogen bonding acceptors than donors; (2) O1-HO1, O4-HO4 and O6-HO6 are more efficient intramolecular hydrogen bonding donors than acceptors; (5) O1-HO1 and O6-HO6 are more efficient intermolecular hydrogen bonding acceptors than donors while hydroxyl groups O2-HO2 and O4-HO4 are more efficient intermolecular hydrogen bonding donors than acceptors. The hydrogen bonding abilities of hydroxyl groups revealed that: (1) the hydrogen bonding ability of OH2-H w is larger than that of hydroxyl groups in glucose; (2) among the hydroxyl groups in glucose, the hydrogen bonding ability of O6-HO6 is the largest and the hydrogen bonding ability of O4-HO4 is the smallest; (3) the intermolecular hydrogen bonding ability of O6-HO6 is the largest; (4) the order for intramolecular hydrogen bonding abilities (from large to small) is O2-HO2, O1-HO1, O3-HO3, O6-HO6 and O4-HO4

  13. Differences Between Tg2576 and Wild Type Mice in the NMDA Receptor-Nitric Oxide Pathway After Prolonged Application of a Diet High in Advanced Glycation End Products.

    Kristofikova, Zdena; Ricny, Jan; Sirova, Jana; Ripova, Daniela; Lubitz, Irit; Schnaider-Beeri, Michal

    2015-08-01

    It has been suggested that advanced glycation end (AGE) products, via cognate receptor activation, are implicated in several diseases, including Alzheimer's disease. The NMDA receptor-nitric oxide pathway appears to be influenced by AGE products and involved in the pathogenesis of this type of dementia. In this study, C57BL/6J (WT) and transgenic (Tg2576) mice expressing human mutant amyloid precursor protein were kept on prolonged (8 months) diets containing regular or high amounts of AGE products. After the decapitation of 11-months old mice, brain tissue analyses were performed [expressions of the NR1, NR2A and NR2B subunits of NMDA receptors, activities of neuronal, endothelial and inducible nitric oxide synthase (nNOS, eNOS and iNOS)]. Moreover, levels of malondialdehyde and of human amyloid β 1-42 were estimated. We found increased activity of nNOS in WT mice maintained on a high compared to regular AGE diet; however, no similar differences were found in Tg2576 mice. In addition, we observed an increase in NR1 expression in Tg2576 compared to WT mice, both kept on a diet high in AGE products. Correlation analyses performed on mice kept on the regular AGE diet supported close links between particular subunits (NR2A-NR2B, in WT as well as in Tg2576 mice), between subunits and synthase (NR2A/NR2B-nNOS, only in WT mice) or between particular synthases (nNOS-iNOS, only in WT). Correlation analysis also revealed differences between WT mice kept on both diets (changed correlations between NR2A/NR2B-nNOS, between nNOS-eNOS and between eNOS-iNOS). Malondialdehyde levels were increased in both Tg2576 groups when compared to the corresponding WT mice, but no effects of the diets were observed. Analogously, no significant effects of diets were found in the levels of soluble or insoluble amyloid β 1-42 in Tg2576 mice. Our results demonstrate that prolonged ingestion of AGE products can influence the NMDA receptor-nitric oxide pathway in the brain and that only WT mice

  14. Andrographolide inhibits hypoxia-induced HIF-1α-driven endothelin 1 secretion by activating Nrf2/HO-1 and promoting the expression of prolyl hydroxylases 2/3 in human endothelial cells.

    Lin, Hung-Chih; Su, Shih-Li; Lu, Chia-Yang; Lin, Ai-Hsuan; Lin, Wan-Chun; Liu, Chin-San; Yang, Ya-Chen; Wang, Hsiu-Miao; Lii, Chong-Kuei; Chen, Haw-Wen

    2017-03-01

    Andrographolide, the main bioactive component of the medicinal plant Andrographis paniculata, has been shown to possess potent anti-inflammatory activity. Endothelin 1 (ET-1), a potent vasoconstrictor peptide produced by vascular endothelial cells, displays proinflammatory property. Hypoxia-inducible factor 1α (HIF-1α), the regulatory member of the transcription factor heterodimer HIF-1α/β, is one of the most important molecules that responds to hypoxia. Changes in cellular HIF-1α protein level are the result of altered gene transcription and protein stability, with the latter being dependent on prolyl hydroxylases (PHDs). In this study, inhibition of pro-inflammatory ET-1 expression and changes of HIF-1α gene transcription and protein stability under hypoxia by andrographolide in EA.hy926 endothelial-like cells were investigated. Hypoxic conditions were created using the hypoxia-mimetic agent CoCl 2. We found that hypoxia stimulated the production of reactive oxygen species (ROS), the expression of HIF-1α mRNA and protein, and the expression and secretion of ET-1. These effects, however, were attenuated by co-exposure to andrographolide, bilirubin, and RuCO. Silencing Nrf2 and heme oxygenase 1 (HO-1) reversed the inhibitory effects of andrographolide on hypxoia-induced HIF-1α mRNA and protein expression. Moreover, andrographolide increased the expression of prolyl hydroxylases (PHD) 2/3, which hydroxylate HIF-1α and promotes HIF-1α proteasome degradation, with an increase in HIF-1α hydroxylation was noted under hypoxia. Inhibition of p38 MAPK abrogated the hypoxia-induced increases in HIF-1α mRNA and protein expression as well as ET-1 mRNA expression and secretion. Taken together, these results suggest that andrographolide suppresses hypoxia-induced pro-inflammatory ET-1 expression by activating Nrf2/HO-1, inhibiting p38 MAPK signaling, and promoting PHD2/3 expression. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 918-930, 2017. © 2016 Wiley

  15. Download - Open TG-GATEs | LSDB Archive [Life Science Database Archive metadata

    Full Text Available switchLanguage; BLAST Search Image Search Home About Archive Update History Data ...Download License Update History of This Database Site Policy | Contact Us Download - Open TG-GATEs | LSDB Archive ...

  16. Database Description - Open TG-GATEs | LSDB Archive [Life Science Database Archive metadata

    Full Text Available ne expression data and predict the safety of candidate chemicals has been develop...ears of the project, more than 30 safety biomarkers were develped by using TG-GATEs. In addition, data acqui

  17. Notes on the implementation of the TG-43 formalism in high-rate brachytherapy; Notas sobre la implementacion del formalismo TG-43 en braquiterapia de lata tasa

    Sendon del Rio, J. R.; Gonzalez Ruiz, C.; Garcia Marcos, R.; Jimenez Rojas, R.; Lopez Bote, M. A.

    2011-07-01

    The TG-43 formalism is based on dosimetric parameters depend on the specific font design extracted from dose distributions calculated by Monte Carlo in water. Relatively easy to implement, yet provides a degree of uncertainty, making it necessary to verify the calculation algorithm in the planning system to assess its behavior.

  18. Aged Tg2576 mice are impaired on social memory and open field habituation tests.

    Deacon, R M J; Koros, E; Bornemann, K D; Rawlins, J N P

    2009-02-11

    In a previous publication [Deacon RMJ, Cholerton LL, Talbot K, Nair-Roberts RG, Sanderson DJ, Romberg C, et al. Age-dependent and -independent behavioral deficits in Tg2576 mice. Behav Brain Res 2008;189:126-38] we found that very few cognitive tests were suitable for demonstrating deficits in Tg2576 mice, an amyloid over-expression model of Alzheimer's disease, even at 23 months of age. However, in a retrospective analysis of a separate project on these mice, tests of social memory and open field habituation revealed large cognitive impairments. Controls showed good open field habituation, but Tg2576 mice were hyperactive and failed to habituate. In the test of social memory for a juvenile mouse, controls showed considerably less social investigation on the second meeting, indicating memory of the juvenile, whereas Tg2576 mice did not show this decrement.As a control for olfactory sensitivity, on which social memory relies, the ability to find a food pellet hidden under wood chip bedding was assessed. Tg2576 mice found the pellet as quickly as controls. As this test requires digging ability, this was independently assessed in tests of burrowing and directly observed digging. In line with previous results and the hippocampal dysfunction characteristic of aged Tg2576 mice, they both burrowed and dug less than controls.

  19. SU-E-T-393: Using TG119 to Assess RapidArc at Hamad Medical Corporation.

    Nobah, A; El-Kaissi, T; Hammoud, R; Al-Hammadi, N

    2012-06-01

    To provide a confidence level within our clinic relating to the implementation and administration of RapidArc, the AAPM TG1 19 has been implemented. This task group provides a sound and relatively simple methodology for determining the accuracy of the overall IMRT process administered in the day-to-day clinicMethods: Six different test plans, of varying complexity, were created on mock structure sets, downloaded from AAPM, and delivered. The treatment planning system results were then compared with the delivered results. Plans were created and delivered on a solid water phantom, using 25×25cm water equivalent slabs of varying thicknesses. Delivered point and planar dose measurements were obtained using an ionization chamber and film, respectively. The confidence limit (CL), averaged for all test plans, was calculated for the high dose point in the PTV and for the low dose point in the avoidance structure. This was used as an indicator of the uncertainty of the average difference between measured and planned dose. Where the precision of the delivery is based on how small the CL value is.For both the high and low dose points, the local CL's were determined to be 0.036 and 0.011, respectively. The range of results for the CL presented in TG1 19 varies from 0.015 to 0.098 for the high dose point, and from 0.014 to 0.086 for the low dose point. Our results indicate the accurate implementation of RapidArc within our clinic, especially when compared to the results of other institutions, published in TG1 19. Furthermore, the CL value for the low dose measurements is lower than any of the results published in TG119. We recommend that any clinic conducting IMRT should implement this task group. This will not only provide a greater understanding of the delivery and its limitations, but will also give the overall accuracy and consistency of the technique as it applies to the various treatment sites. © 2012 American Association of Physicists in Medicine.

  20. MO-A-BRB-00: TG191: Clinical Use of Luminescent Dosimeters

    NONE

    2016-06-15

    This presentation will highlight the upcoming TG-191 report: Clinical Use of Luminescent Dosimeters. Luminescent dosimetry based on TLD and OSLD is a practical, accurate, and precise technique for point dosimetry in medical physics applications. The charges of Task Group 191 were to detail the methodologies for practical and optimal luminescent dosimetry in a clinical setting. This includes (1) To review the variety of TLD/OSL materials available, including features and limitations of each. (2) To outline the optimal steps to achieve accurate and precise dosimetry with luminescent detectors and to evaluate the uncertainty induced when less rigorous procedures are used. (3) To develop consensus guidelines on the optimal use of luminescent dosimeters for clinical practice. (4) To develop guidelines for special medically relevant uses of TLDs/OSLs (e.g., mixed field i.e. photon/neutron dosimetry, particle beam dosimetry, skin dosimetry). While this report provides general guidelines for arbitrary TLD and OSLD processes, the report, and therefore this presentation, provide specific guidance for TLD-100 (LiF:Ti,Mg) and nanoDot (Al2O3:C) dosimeters because of their prevalence in clinical practice. Learning Objectives: Understand the available dosimetry systems, and basic theory of their operation Understand the range of dose determination methodologies and the uncertainties associated with them Become familiar with special considerations for TLD/OSLD relevant for special clinical situations Learn recommended commissioning and QA procedures for these dosimetry systems.

  1. MO-A-BRB-01: TG191: Clinical Use of Luminescent Dosimeters

    Kry, S. [UT MD Anderson Cancer Center (United States)

    2016-06-15

    This presentation will highlight the upcoming TG-191 report: Clinical Use of Luminescent Dosimeters. Luminescent dosimetry based on TLD and OSLD is a practical, accurate, and precise technique for point dosimetry in medical physics applications. The charges of Task Group 191 were to detail the methodologies for practical and optimal luminescent dosimetry in a clinical setting. This includes (1) To review the variety of TLD/OSL materials available, including features and limitations of each. (2) To outline the optimal steps to achieve accurate and precise dosimetry with luminescent detectors and to evaluate the uncertainty induced when less rigorous procedures are used. (3) To develop consensus guidelines on the optimal use of luminescent dosimeters for clinical practice. (4) To develop guidelines for special medically relevant uses of TLDs/OSLs (e.g., mixed field i.e. photon/neutron dosimetry, particle beam dosimetry, skin dosimetry). While this report provides general guidelines for arbitrary TLD and OSLD processes, the report, and therefore this presentation, provide specific guidance for TLD-100 (LiF:Ti,Mg) and nanoDot (Al2O3:C) dosimeters because of their prevalence in clinical practice. Learning Objectives: Understand the available dosimetry systems, and basic theory of their operation Understand the range of dose determination methodologies and the uncertainties associated with them Become familiar with special considerations for TLD/OSLD relevant for special clinical situations Learn recommended commissioning and QA procedures for these dosimetry systems.

  2. MO-A-BRB-01: TG191: Clinical Use of Luminescent Dosimeters

    Kry, S.

    2016-01-01

    This presentation will highlight the upcoming TG-191 report: Clinical Use of Luminescent Dosimeters. Luminescent dosimetry based on TLD and OSLD is a practical, accurate, and precise technique for point dosimetry in medical physics applications. The charges of Task Group 191 were to detail the methodologies for practical and optimal luminescent dosimetry in a clinical setting. This includes (1) To review the variety of TLD/OSL materials available, including features and limitations of each. (2) To outline the optimal steps to achieve accurate and precise dosimetry with luminescent detectors and to evaluate the uncertainty induced when less rigorous procedures are used. (3) To develop consensus guidelines on the optimal use of luminescent dosimeters for clinical practice. (4) To develop guidelines for special medically relevant uses of TLDs/OSLs (e.g., mixed field i.e. photon/neutron dosimetry, particle beam dosimetry, skin dosimetry). While this report provides general guidelines for arbitrary TLD and OSLD processes, the report, and therefore this presentation, provide specific guidance for TLD-100 (LiF:Ti,Mg) and nanoDot (Al2O3:C) dosimeters because of their prevalence in clinical practice. Learning Objectives: Understand the available dosimetry systems, and basic theory of their operation Understand the range of dose determination methodologies and the uncertainties associated with them Become familiar with special considerations for TLD/OSLD relevant for special clinical situations Learn recommended commissioning and QA procedures for these dosimetry systems.

  3. MO-A-BRB-00: TG191: Clinical Use of Luminescent Dosimeters

    2016-01-01

    This presentation will highlight the upcoming TG-191 report: Clinical Use of Luminescent Dosimeters. Luminescent dosimetry based on TLD and OSLD is a practical, accurate, and precise technique for point dosimetry in medical physics applications. The charges of Task Group 191 were to detail the methodologies for practical and optimal luminescent dosimetry in a clinical setting. This includes (1) To review the variety of TLD/OSL materials available, including features and limitations of each. (2) To outline the optimal steps to achieve accurate and precise dosimetry with luminescent detectors and to evaluate the uncertainty induced when less rigorous procedures are used. (3) To develop consensus guidelines on the optimal use of luminescent dosimeters for clinical practice. (4) To develop guidelines for special medically relevant uses of TLDs/OSLs (e.g., mixed field i.e. photon/neutron dosimetry, particle beam dosimetry, skin dosimetry). While this report provides general guidelines for arbitrary TLD and OSLD processes, the report, and therefore this presentation, provide specific guidance for TLD-100 (LiF:Ti,Mg) and nanoDot (Al2O3:C) dosimeters because of their prevalence in clinical practice. Learning Objectives: Understand the available dosimetry systems, and basic theory of their operation Understand the range of dose determination methodologies and the uncertainties associated with them Become familiar with special considerations for TLD/OSLD relevant for special clinical situations Learn recommended commissioning and QA procedures for these dosimetry systems.

  4. Tail-flick test response in 3×Tg-AD mice at early and advanced stages of disease.

    Baeta-Corral, Raquel; Defrin, Ruti; Pick, Chagi G; Giménez-Llort, Lydia

    2015-07-23

    Despite the impact of pain in cognitive dysfunctions and affective disorders has been largely studied, the research that examines pain dimensions in cognitive impairment or dementia is still scarce. In patients with Alzheimer's disease (AD) and related dementias, management of pain is challenging. While the sensory-discriminative dimension of pain is preserved, the cognitive-evaluative and the affective-motivational pain dimensions are affected. Due to the complexity of the disease and the poor self-reports, pain is underdiagnosed and undertreated. In confluence with an impaired thermoregulatory behavior, the patients' ability to confront environmental stressors such as cold temperature can put them at risk of fatal accidental hypothermia. Here, 3xTg-AD mice demonstrate that the sensorial-discriminative threshold to a noxious cold stimulus, as measured by the latency of tail-flicking, was preserved at early and advances stages of disease (7 and 11 month-old, respectively) as compared to age-matched (adulthood and middle aged, respectively) non-transgenic mice (NTg). In both genotypes, the sensory deterioration and poor thermoregulatory behavior associated to age was observed as an increase of tail-flick response and poor sensorimotor performance. At both stages studied, 3xTg-AD mice exhibited BPSD (Behavioral and Psychological Symptoms of Dementia)-like alterations in the corner, open-field, dark-light box and the T-maze tests. In the adult NTg mice, this nociceptive withdrawal response was correlated with copying with stress-related behaviors. This integrative behavioral profile was lost in both groups of 3xTg-AD mice and middle aged controls, suggesting derangements in their subjacent networks and the complex interplay between the pain dimensions in the elderly with dementia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Tissue transglutaminase (TG-2) modified amniotic membrane: a novel scaffold for biomedical applications

    Chau, David Y S; Brown, Sheridan V; Ghaemmaghami, Amir M; Mather, Melissa L; Hutter, Victoria; Tint, Naing L; Rose, Felicity R A J; Dua, Harminder S

    2012-01-01

    The amniotic membrane (AM) is considered as a natural cell culture substrate and has occasionally been exploited in regenerative medicine especially for ocular surface reconstruction and dermal wound healing applications. However, its use is limited by its relatively weak mechanical strength, difficulty during manual handling and susceptibility to proteolytic degradation in vivo. Therefore, in this study we aimed to enhance the mechanical and biological characteristics of the AM by enzymatically cross-linking it using tissue transglutaminase (TG)—a calcium-dependent enzyme capable of forming stable ε(γ-glutamyl)lysine cross-linkages. Using a biological catalyst such as TG does not only prevent denaturation during sample preparation but also minimizes the potential of residual chemical cross-linking agents compared to alternative methodologies. Human AM, sourced from elective caesarean sectioning, were treated with TG, bovine serum albumin and/or a no-treatment control. Samples were then compared in terms of their physical and (scanning electron microscopy (SEM), transparency, mechanical strength, susceptibility to proteolytic degradation) biological characteristics (in vitro cell culture, activation of dendritic cells (DC)) and their in vivo biocompatibility/angiogenic capacity (chick chorioallantoic membrane assay). TG-treated AM exhibited enhanced mechanical strength and greater resistance to proteolytic/collagenase degradation compared to the control(s). SEM imaging of the TG-treated membrane summarized a significantly closer association and greater interconnectivity of individual collagen fibres yet it had no effect on the overall transparency of the AM. In vitro cell culture demonstrated no detrimental effect of TG-treatment on the AM in terms of cell attachment, spreading, proliferation and differentiation. Moreover, an ‘immune response’ was not elicited based on extended in vitro culture with human-monocyte-derived DC. Interestingly, the TG

  6. Ocular changes in TgF344-AD rat model of Alzheimer's disease.

    Tsai, Yuchun; Lu, Bin; Ljubimov, Alexander V; Girman, Sergey; Ross-Cisneros, Fred N; Sadun, Alfredo A; Svendsen, Clive N; Cohen, Robert M; Wang, Shaomei

    2014-01-29

    Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by progressive decline in learning, memory, and executive functions. In addition to cognitive and behavioral deficits, vision disturbances have been reported in early stage of AD, well before the diagnosis is clearly established. To further investigate ocular abnormalities, a novel AD transgenic rat model was analyzed. Transgenic (Tg) rats (TgF344-AD) heterozygous for human mutant APPswe/PS1ΔE9 and age-matched wild type (WT) rats, as well as 20 human postmortem retinal samples from both AD and healthy donors were used. Visual function in the rodent was analyzed using the optokinetic response and luminance threshold recording from the superior colliculus. Immunohistochemistry on retinal and brain sections was used to detect various markers including amyloid-β (Aβ) plaques. As expected, Aβ plaques were detected in the hippocampus, cortex, and retina of Tg rats. Plaque-like structures were also found in two AD human whole-mount retinas. The choroidal thickness was significantly reduced in both Tg rat and in AD human eyes when compared with age-matched controls. Tg rat eyes also showed hypertrophic retinal pigment epithelial cells, inflammatory cells, and upregulation of complement factor C3. Although visual acuity was lower in Tg than in WT rats, there was no significant difference in the retinal ganglion cell number and retinal vasculature. In this study, we observed pathological changes in the choroid and in RPE cells in the TgF344-AD rat model; choroidal thinning was observed further in human AD retina. Along with Ab deposition, the inflammatory response was manifested by microglial recruitment and complement activation. Further studies are needed to elucidate the significance and mechanisms of these pathological changes [corrected].

  7. Spaceflight influences both mucosal and peripheral cytokine production in PTN-Tg and wild type mice.

    Justin L McCarville

    Full Text Available Spaceflight is associated with several health issues including diminished immune efficiency. Effects of long-term spaceflight on selected immune parameters of wild type (Wt and transgenic mice over-expressing pleiotrophin under the human bone-specific osteocalcin promoter (PTN-Tg were examined using the novel Mouse Drawer System (MDS aboard the International Space Station (ISS over a 91 day period. Effects of this long duration flight on PTN-Tg and Wt mice were determined in comparison to ground controls and vivarium-housed PTN-Tg and Wt mice. Levels of interleukin-2 (IL-2 and transforming growth factor-beta1 (TGF-β1 were measured in mucosal and systemic tissues of Wt and PTN-Tg mice. Colonic contents were also analyzed to assess potential effects on the gut microbiota, although no firm conclusions could be made due to constraints imposed by the MDS payload and the time of sampling. Spaceflight-associated differences were observed in colonic tissue and systemic lymph node levels of IL-2 and TGF-β1 relative to ground controls. Total colonic TGF-β1 levels were lower in Wt and PTN-Tg flight mice in comparison to ground controls. The Wt flight mouse had lower levels of IL-2 and TGF-β1 compared to the Wt ground control in both the inguinal and brachial lymph nodes, however this pattern was not consistently observed in PTN-Tg mice. Vivarium-housed Wt controls had higher levels of active TGF-β1 and IL-2 in inguinal lymph nodes relative to PTN-Tg mice. The results of this study suggest compartmentalized effects of spaceflight and on immune parameters in mice.

  8. A Novel Form of Compensation in the Tg2576 Amyloid Mouse Model of Alzheimer's Disease.

    Somogyi, Attila; Katonai, Zoltán; Alpár, Alán; Wolf, Ervin

    2016-01-01

    One century after its first description, pathology of Alzheimer's disease (AD) is still poorly understood. Amyloid-related dendritic atrophy and membrane alterations of susceptible brain neurons in AD, and in animal models of AD are widely recognized. However, little effort has been made to study the potential effects of combined morphological and membrane alterations on signal transfer and synaptic integration in neurons that build up affected neural networks in AD. In this study spatial reconstructions and electrophysiological measurements of layer II/III pyramidal neurons of the somatosensory cortex from wild-type (WT) and transgenic (TG) human amyloid precursor protein (hAPP) overexpressing Tg2576 mice were used to build faithful segmental cable models of these neurons. Local synaptic activities were simulated in various points of the dendritic arbors and properties of subthreshold dendritic impulse propagation and predictors of synaptic input pattern recognition ability were quantified and compared in modeled WT and TG neurons. Despite the widespread dendritic degeneration and membrane alterations in mutant mouse neurons, surprisingly little, or no change was detected in steady-state and 50 Hz sinusoidal voltage transfers, current transfers, and local and propagation delays of PSPs traveling along dendrites of TG neurons. Synaptic input pattern recognition ability was also predicted to be unaltered in TG neurons in two different soma-dendritic membrane models investigated. Our simulations predict the way how subthreshold dendritic signaling and pattern recognition are preserved in TG neurons: amyloid-related membrane alterations compensate for the pathological effects that dendritic atrophy has on subthreshold dendritic signal transfer and integration in layer II/III somatosensory neurons of this hAPP mouse model for AD. Since neither propagation of single PSPs nor integration of multiple PSPs (pattern recognition) changes in TG neurons, we conclude that AD

  9. Implementation of a Quality Assurance Program in a new Radiotherapy Center taking as base the TG-40; Implementacion del programa de Garantia de Calidad en un Centro nuevo de Radioterapia tomando como base el TG-40

    Marles, A.; Besa, P.; Hecht, P.; Arriagada, L.; Ruz, A.; Garay, C. [Pontificia Universidad Catolica de Chile, Centro de Cancer. Diagonal Paraguay, 319. Santiago (Chile)

    1998-12-31

    The recommended principles in the `Comprehensive QA for radiation oncology: Report of AAPM Radiation Therapy Committee Task Group 40`, TG-40, have been the base for implementation of the Quality Assurance Program of a modern Radiotherapy service. During its application has been necessary: to initiate its implementation before the equipment installation, assuming the costs of the contracts of the qualified personnel, realizing an initial investment adequate for equipment acquisition necessary for acceptation, commissioning and routinary control, the experienced formation of the personnel in the protocol philosophy, establishing procedures for day by day process which would allow the retrofeeding, the elaboration of templates and opening to changes and adjustments according to the necessities. The experience of two years had been demonstrated that the TG-40: a) It is feasible to be implemented but sometimes no strict totally and it is essential to have qualified personnel and the necessary material resources; b) It does not contains all the necessary for its practical implementation and must be completing with procedures and routine formats which facilitate their application; c) It allows the detection and opportune failure correction in the process; d) It is a continuous process that does not finishes. (Author)

  10. Implementation of a Quality Assurance Program in a new Radiotherapy Center taking as base the TG-40

    Marles, A.; Besa, P.; Hecht, P.; Arriagada, L.; Ruz, A.; Garay, C.

    1998-01-01

    The recommended principles in the 'Comprehensive QA for radiation oncology: Report of AAPM Radiation Therapy Committee Task Group 40', TG-40, have been the base for implementation of the Quality Assurance Program of a modern Radiotherapy service. During its application has been necessary: to initiate its implementation before the equipment installation, assuming the costs of the contracts of the qualified personnel, realizing an initial investment adequate for equipment acquisition necessary for acceptation, commissioning and routinary control, the experienced formation of the personnel in the protocol philosophy, establishing procedures for day by day process which would allow the retrofeeding, the elaboration of templates and opening to changes and adjustments according to the necessities. The experience of two years had been demonstrated that the TG-40: a) It is feasible to be implemented but sometimes no strict totally and it is essential to have qualified personnel and the necessary material resources; b) It does not contains all the necessary for its practical implementation and must be completing with procedures and routine formats which facilitate their application; c) It allows the detection and opportune failure correction in the process; d) It is a continuous process that does not finishes. (Author)

  11. The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio as a predictor of insulin resistance but not of β cell function in a Chinese population with different glucose tolerance status.

    Zhou, Meicen; Zhu, Lixin; Cui, Xiangli; Feng, Linbo; Zhao, Xuefeng; He, Shuli; Ping, Fan; Li, Wei; Li, Yuxiu

    2016-06-07

    Triglyceride/high-density lipoprotein-cholesterol (TG/HDL-C) ratio was a surrogate marker of IR; however, the relationship of TG/HDL-C with IR might vary by ethnicity. This study aims to investigate whether lipid ratios-TG/HDL-C, cholesterol/high-density lipoprotein-cholesterol (TC/HDL-C) ratio, low-density lipoprotein-cholesterol/high-density lipoprotein-cholesterol (LDL-C/HDL-C)) could be potential clinical markers of insulin resistance (IR) and β cell function and further to explore the optimal cut-offs in a Chinese population with different levels of glucose tolerance. Four hundred seventy-nine subjects without a history of diabetes underwent a 75 g 2 h Oral Glucose Tolerance Test (OGTT). New-onset diabetes (n = 101), pre-diabetes (n = 186), and normal glucose tolerance (n = 192) were screened. IR was defined by HOMA-IR > 2.69. Based on indices (HOMA-β, early-phase disposition index [DI30], (ΔIns30/ΔGlu30)/HOMA-IR and total-phase index [DI120]) that indicated different phases of insulin secretion, the subjects were divided into two groups, and the lower group was defined as having inadequate β cell compensation. Logistic regression models and accurate estimates of the areas under receiver operating characteristic curves (AUROC) were obtained. In all of the subjects, TG/HDL, TC/HDL-C, LDL-C/HDL-C, and TG were significantly associated with IR. The AUROCs of TG/HDL-C and TG were 0.71 (95 % CI: 0.66-0.75) and 0.71 (95 % CI: 0.65-0.75), respectively. The optimal cut-offs of TG/HDL-C and TG for IR diagnosis were 1.11 and 1.33 mmol/L, respectively. The AUROCs of TC/HDL-C and LDL-C/HDL-C were 0.66 and 0.65, respectively, but they were not acceptable for IR diagnosis. TG/HDL-C,LDL-C/HDL-C and TG were significantly associated with HOMA-β, but AUROCs were less than 0.50; therefore, the lipid ratios could not be predictors of basal β cell dysfunction. None of the lipid ratios was associated with early-phase insulin secretion. Only TG/HDL-C and

  12. Andrographolide inhibits TNFα-induced ICAM-1 expression via suppression of NADPH oxidase activation and induction of HO-1 and GCLM expression through the PI3K/Akt/Nrf2 and PI3K/Akt/AP-1 pathways in human endothelial cells.

    Lu, Chia-Yang; Yang, Ya-Chen; Li, Chien-Chun; Liu, Kai-Li; Lii, Chong-Kuei; Chen, Haw-Wen

    2014-09-01

    Andrographolide, the major bioactive component of Andrographis paniculata, has been demonstrated to have various biological properties including anti-inflammation, antioxidation, and anti-hepatotoxicity. Oxidative stress is considered a major risk factor in aging, inflammation, cancer, atherosclerosis, and diabetes mellitus. NADPH oxidase is a major source of endogenous reactive oxygen species (ROS). In this study, we used EA.hy926 endothelial-like cells to explore the anti-inflammatory activity of andrographolide. Andrographolide attenuated TNFα-induced ROS generation, Src phosphorylation, membrane translocation of the NADPH oxidase subunits p47(phox) and p67(phox), and ICAM-1 gene expression. In the small hairpin RNA interference assay, shp47(phox) abolished TNFα-induced p65 nuclear translocation, ICAM-1 gene expression, and adhesion of HL-60 cells. Andrographolide induced the gene expression of heme oxygenase 1 (HO-1) and glutamate cysteine ligase modifier subunit (GCLM) in a time-dependent manner. Cellular glutathione (GSH) content was increased by andrographolide. shGCLM attenuated the andrographolide-induced increase in GSH content and reversed the andrographolide inhibition of HL-60 adhesion. shHO-1 showed a similar effect on andrographolide inhibition of HL-60 adhesion to shGCLM. The mechanism underlying the up-regulation of HO-1 and GCLM by andrographolide was dependent on the PI3K/Akt pathway, and both the Nrf2 and AP-1 transcriptional factors were involved. Our results suggest that andrographolide attenuates TNFα-induced ICAM-1 expression at least partially through suppression of NADPH oxidase activation and induction of HO-1 and GCLM expression, which is PI3K/Akt pathway-dependent. Copyright © 2014. Published by Elsevier Inc.

  13. Anti-neuroinflammatory Activity of Elephantopus scaber L. via Activation of Nrf2/HO-1 Signaling and Inhibition of p38 MAPK Pathway in LPS-Induced Microglia BV-2 Cells

    Chim-Kei Chan

    2017-06-01

    Full Text Available Elephantopus scaber L. (family: Asteraceae has been traditionally utilized as a folkloric medicine and scientifically shown to exhibit anti-inflammatory activities in various in vivo inflammatory models. Given the lack of study on the effect of E. scaber in neuroinflammation, this study aimed to investigate the anti-neuroinflammatory effect and the underlying mechanisms of ethyl acetate fraction from the leaves of E. scaber (ESEAF on the release of pro-inflammatory mediators in lipopolysaccharide (LPS-induced microglia cells (BV-2. Present findings showed that ESEAF markedly attenuated the translocation of NF-κB to nucleus concomitantly with the significant mitigation on the LPS-induced production of NO, iNOS, COX-2, PGE2, IL-1β, and TNF-α. These inflammatory responses were reduced via the inhibition of p38. Besides, ESEAF was shown to possess antioxidant activities evident by the DPPH and SOD scavenging activities. The intracellular catalase enzyme activity was enhanced by ESEAF in the LPS-stimulated BV-2 cells. Furthermore, the formation of ROS induced by LPS in BV-2 cells was reduced upon the exposure to ESEAF. Intriguingly, the reduction of ROS was found in concerted with the activation of Nrf2 and HO-1. It is conceivable that the activation promotes the scavenging power of antioxidant enzymes as well as to ameliorate the inflammatory response in LPS-stimulated BV-2 cells. Finally, the safety profile analysis through oral administration of ESEAF at 2000 mg/kg did not result in any mortalities, adverse effects nor histopathologic abnormalities of organs in mice. Taken altogether, the cumulative findings suggested that ESEAF holds the potential to develop as nutraceutical for the intervention of neuroinflammatory disorders.

  14. Local lymph node assay: how testing laboratories apply OECD TG 429 for REACH purposes.

    Rovida, Costanza

    2011-01-01

    The Local Lymph Node Assay (LLNA) is the official method for assessing the allergic contact dermatitis potential of chemicals for the purposes of REACH regulation. The LLNA went through a validation process that allowed the delineation of a robust protocol for performing new tests. The OECD accepted this method in 2002 and published OECD TG 429. The European Chemical Agency (ECHA) recently published data that were submitted in the registration dossiers of chemicals. This database was analysed to determine how testing laboratories apply OECD TG 429. This analysis comes after a detailed analysis of four full study reports that were also prepared for REACH purposes. Although the majority of the tests are fully compliant with OECD TG 429, some showed major deviations, and a number of others used more animals than necessary. This suggests that in vivo tests need to be planned more carefully and consciously to obtain meaningful results with the minimum animal number necessary.

  15. Tissue transglutaminase (TG2) is involved in the resistance of cancer cells to the histone deacetylase (HDAC) inhibitor vorinostat.

    Carbone, Carmine; Di Gennaro, Elena; Piro, Geny; Milone, Maria Rita; Pucci, Biagio; Caraglia, Michele; Budillon, Alfredo

    2017-03-01

    Vorinostat demonstrated preclinical and clinical efficacy in human cancers and is the first histone deacetylase inhibitor (HDACi) approved for cancer treatment. Tissue transglutaminase (TG2) is a multifunctional enzyme that catalyzes a Ca 2+ dependent transamidating reaction resulting in covalent cross-links between proteins. TG2 acts also as G-protein in trans-membrane signaling and as a cell surface adhesion mediator. TG2 up-regulation has been demonstrated in several cancers and its expression levels correlate with resistance to chemotherapy and metastatic potential. We demonstrated that the anti-proliferative effect of the HDACi vorinostat is paralleled by the induction of TG2 mRNA and protein expression in cancer cells but not in ex vivo treated peripheral blood lymphocytes. This effect was also shared by other pan-HDACi and resulted in increased TG2 transamidating activity. Notably, high TG2 basal levels in a panel of cancer cell lines correlated with lower vorinostat antiproliferative activity. Notably, in TG2-knockdown cancer cells vorinostat anti-proliferative and pro-apoptotic effects were enhanced, whereas in TG2-full-length transfected cells were impaired, suggesting that TG2 could represent a mechanism of intrinsic or acquired resistance to vorinostat. In fact, co-treatment of tumor cells with inhibitors of TG2 transamidating activity potentiated the antitumor effect of vorinostat. Moreover, vorinostat-resistant MCF7 cells selected by stepwise increasing concentrations of the drug, significantly overexpressed TG2 protein compared to parental cells, and co-treatment of these cells with TG2 inhibitors reversed vorinostat-resistance. Taken together, our data demonstrated that TG2 is involved in the resistance of cancer cells to vorinostat, as well as to other HDACi.

  16. High-Tg TOPAS mPOF strain sensing at 110 degrees

    Nielsen, Kristian; Markos, Christos; Stefani, Alessio

    2013-01-01

    We demonstrate a mPOF made of high-Tg TOPAS grade 5013 with Tg = 135°C. We inscribe FBGs into the fiber and demonstrate strain sensing of 2.5% strain at 98°C, further we also demonstrate strain sensing at a record high temperature of 110°C. The Bragg wavelengths of the FBGs are around 860 nm, whe...... the propagation loss is 5.1dB/m, close to the fiber loss minimum of 3.67dB/m at 787nm....

  17. FPGA Implementation of Burst-Mode Synchronization for SOQSPK-TG

    2014-06-01

    is normalized to π. The proposed burst-mode architecture is written in VHDL and verified using Modelsim. The VHDL design is implemented on a Xilinx...Document Number: SET 2014-0043 412TW-PA-14298 FPGA Implementation of Burst-Mode Synchronization for SOQSPK-TG June 2014 Final Report Test...To) 9/11 -- 8/14 4. TITLE AND SUBTITLE FPGA Implementation of Burst-Mode Synchronization for SOQSPK-TG 5a. CONTRACT NUMBER: W900KK-11-C-0032 5b

  18. Database Description - Open TG-GATEs Pathological Image Database | LSDB Archive [Life Science Database Archive metadata

    Full Text Available List Contact us Open TG-GATEs Pathological Image Database Database Description General information of database Database... name Open TG-GATEs Pathological Image Database Alternative name - DOI 10.18908/lsdba.nbdc00954-0...iomedical Innovation 7-6-8, Saito-asagi, Ibaraki-city, Osaka 567-0085, Japan TEL:81-72-641-9826 Email: Database... classification Toxicogenomics Database Organism Taxonomy Name: Rattus norvegi... Article title: Author name(s): Journal: External Links: Original website information Database

  19. Sub-Tg enthalpy relaxation in an extremely unstable oxide glass and its implication for structural heterogeneity

    Zhang, Yanfei; Hu, L.N.; Liu, S.J.

    2013-01-01

    We study the sub-Tg relaxation in an extremely unstable glass former, i.e., 65SiO2-35Al2O3, and its relation to structural heterogeneity (e.g., structurally ordered domains in glass matrix). This is done by hyperquenching (~106 K/s) the liquid, then annealing the hyperquenched glass below Tg...... and subsequently scanning the annealed hyperquenched glass in a differential scanning calorimeter. The results show that structural ordering can take place even below Tg. An endothermic pre-peak is observed when the hyperquenched sample is annealed at 0.75Tg for sufficiently long time, which is, however, much...... weaker compared to that of stable glass formers subjected to same annealing conditions. We also investigate the effect of the sub-Tg annealing on crystallization above Tg. The results imply that some structurally ordered domains exist already in the liquid state. The ordered domains lower the activation...

  20. Long-chain fatty acid triglyceride (TG) metabolism disorder impairs male fertility: a study using adipose triglyceride lipase deficient mice.

    Masaki, Hidetake; Kim, Namhyo; Nakamura, Hitomi; Kumasawa, Keiichi; Kamata, Eriko; Hirano, Ken-Ichi; Kimura, Tadashi

    2017-07-01

    Does the deletion of adipose triglyceride lipase (Atgl) gene impair male fertility? The deletion of Atgl gene impaired male fertility but the effect was partially reversed by a low long-chain triglyceride (TG) diet. ATGL specifically hydrolyses long-chain fatty acid TG to diacylglycerol and a high level of expression of ATGL in testes has been reported. However, the role of ATGL in male fertility is unknown. To investigate the effect of deletion of Atgl gene on male fertility, cauda epididymides and testes were collected from wild-type, heterozygous and homozygous Atgl-deficient mice at 10 weeks of age and epididymal sperm analysis and histological analysis of the testes were performed. To investigate whether a medium-chain triglycerides (MCTs) replacement diet mitigated the impaired male fertility by deletion of Atgl gene, homozygous Atgl-deficient mice were fed a MCT replacement diet, or a standard diet including long-chain triglycerides (LCTs) in a control group, for 6 weeks from 5 weeks of age (n = 22). The systematic and local effects of the MCT replacement diet on spermatogenesis and sperm maturation in the epididymis were analyzed at 10 weeks of age. Hematoxylin and eosin staining in paraffin-embedded sections of testes and Oil Red O staining in frozen sections of testes were performed. The epididymal sperm concentrations were analyzed. Statistical analyses were performed using the Student's t-test or Mann-Whitney U test with Shapiro-Wilk Normality test. Although heterozygous mice were fertile and showed a similar number of epididymal total and motile sperm concentrations to wild-type mice, the deletion of Atgl gene in homozygous mice led to accumulation of TG deposits in testes and impaired spermatogenesis. The deletion of Atgl gene also impaired the sperm maturation process required for sperm to acquire the ability to move forward in the epididymis. The MCT replacement diet for 6 weeks increased the plasma level of non-esterified fatty acid (NEFA) (1

  1. TG/DTG, FT-ICR Mass Spectrometry, and NMR Spectroscopy Study of Heavy Fuel Oil

    Elbaz, Ayman M.

    2015-11-12

    There is an increasing interest in the comprehensive study of heavy fuel oil (HFO) due to its growing use in furnaces, boilers, marines, and recently in gas turbines. In this work, the thermal combustion characteristics and chemical composition of HFO were investigated using a range of techniques. Thermogravimetric analysis (TGA) was conducted to study the nonisothermal HFO combustion behavior. Chemical characterization of HFO was accomplished using various standard methods in addition to direct infusion atmospheric pressure chemical ionization Fourier transform ion cyclotron resonance mass spectrometry (APCI-FTICR MS), high resolution 1H nuclear magnetic resonance (NMR), 13C NMR, and two-dimensional heteronuclear multiple bond correlation (HMBC) spectroscopy. By analyzing thermogravimetry and differential thermogravimetry (TG/DTG) results, three different reaction regions were identified in the combustion of HFO with air, specifically, low temperature oxidation region (LTO), fuel deposition (FD), and high temperature oxidation (HTO) region. At the high end of the LTO region, a mass transfer resistance (skin effect) was evident. Kinetic analysis in LTO and HTO regions was conducted using two different kinetic models to calculate the apparent activation energy. In both models, HTO activation energies are higher than those for LTO. The FT-ICR MS technique resolved thousands of aromatic and sulfur containing compounds in the HFO sample and provided compositional details for individual molecules of three major class species. The major classes of compounds included species with one sulfur atom (S1), with two sulfur atoms (S2), and purely hydrocarbons (HC). The DBE (double bond equivalent) abundance plots established for S1 and HC provided additional information on their distributions in the HFO sample. The 1H NMR and 13C NMR results revealed that nearly 59% of the 1H nuclei were distributed as paraffinic CH2 and 5% were in aromatic groups. Nearly 21% of 13C nuclei were

  2. Fragility of chalcogenide glass in relation to characteristic temperature T0/Tg

    Shaker, A. M.; Shanker Rao, T.; Lilly Shanker Rao, T.; Venkataraman, K.

    2018-03-01

    The present study reports the mutual relationship between the fragility index m and the characteristic temperature T0/Tg. The fragility of the chalcogenide amorphous glass of Ge10Se50Te40 is calculated by utilizing glass transition temperature (Tg) measured by DSC (Differential Scanning Calorimetry) at different heating rates (β) in the range 5 to 20 K/min. Vogel-Fulcher-Tammann (VFT) equation is fitted to the data of Tg. In addition to the VFT method, three other methods are also used to evaluate m. The fragility index m of the Ge10Se50Te40 system showed the trend of decrease with increasing heating rate but remained stable around 22 for the heating rate 10 K/min. The value of m for the glass is near the lower limit (m ≈ 16) this indicates the alloy is a strong glass forming material in accordance of Angell’s interpretation of fragility. The calculated values of characteristic temperature T0/Tg is very close to 1 which also indicates that clearly the system is most fragile.

  3. TG13 current terminology, etiology, and epidemiology of acute cholangitis and cholecystitis

    Kimura, Yasutoshi; Takada, Tadahiro; Strasberg, Steven M.; Pitt, Henry A.; Gouma, Dirk J.; Garden, O. James; Büchler, Markus W.; Windsor, John A.; Mayumi, Toshihiko; Yoshida, Masahiro; Miura, Fumihiko; Higuchi, Ryota; Gabata, Toshifumi; Hata, Jiro; Gomi, Harumi; Dervenis, Christos; Lau, Wan-Yee; Belli, Giulio; Kim, Myung-Hwan; Hilvano, Serafin C.; Yamashita, Yuichi

    2013-01-01

    While referring to the evidence adopted in the Tokyo Guidelines 2007 (TG07) as well as subsequently obtained evidence, further discussion took place on terminology, etiology, and epidemiological data. In particular, new findings have accumulated on the occurrence of symptoms in patients with

  4. Comparison between TG-51 and TRS-398: electron contamination effect on photon beam-quality specification

    Medina, Antonio Lopez; Teijeiro, Antonio; Salvador, Francisco; Medal, Daniela; Vazquez, Julio; Salgado, Manuel; Carrion, MarIa C

    2004-01-01

    Two dosimetry protocols based on absorbed dose to water have recently been implemented: TG-51 and TRS-398. These protocols use different beam-quality indices. The effect of electron contamination in measurements of %dd(10) x has been proposed as a disadvantage of the TG-51. For actual measurements of %dd(10) x in five clinical beams ) a purging magnet was employed to remove the electron contamination. Also, %dd(10) x was measured in the different ways described in TG-51 for high-energy beams: with a lead foil at 50 cm from the phantom surface, at 30 cm, and for open beam. Moreover, TPR 20,10 was determined. Also, periodic quality-control measurements were used for comparing both quality indices and variation over time, but D 20,10 was used instead of TPR 20,10 and measurements in open beam for the %dd(10) x determination. Considering both protocols, S w,air and k Q were calculated in order to compare the results with the experimental data. Significant differences (0.3% for k Q ) were only found for the two high-energy beams, but when the electron contamination is underestimated by TG-51, the difference in k Q is lower. Differences in the other cases and variations over time were less than 0.1%

  5. Ocular Changes in TgF344-AD Rat Model of Alzheimer's Disease

    Tsai, Yuchun; Lu, Bin; Ljubimov, Alexander V.; Girman, Sergey; Ross-Cisneros, Fred N.; Sadun, Alfredo A.; Svendsen, Clive N.; Cohen, Robert M.; Wang, Shaomei

    2014-01-01

    In this study, we observed pathological changes in the choroid and in RPE cells in the TgF344-AD rat model; choroidal thinning was further observed in human AD retina. Along with Aβ deposition, the inflammatory response was manifested by microglial recruitment and complement activation.

  6. TG-FTIR Study of the Influence of potassium Chloride on Wheat Straw Pyrolysis

    Jensen, Anker; Dam-Johansen, Kim; Wójtowicz, M.A.

    1998-01-01

    of products into char, tar and gas. In this work, a combination of thermogravimetry and evolved gas analysis by Fourier transform infrared analysis (TG-FTIR) has been applied to study the influence of potassium chloride (KCl) on wheat straw pyrolysis. Raw straw, washed straw and washed straw impregnated...

  7. Body weight - Open TG-GATEs | LSDB Archive [Life Science Database Archive metadata

    Full Text Available switchLanguage; BLAST Search Image Search Home About Archive Update History Data ...le URL: ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/open_tggates_body_...atabase Description Download License Update History of This Database Site Policy | Contact Us Body weight - Open TG-GATEs | LSDB Archive ...

  8. Thermal behavior of biflorin by beans TG and a DSC photovisual system

    C. F. S. Aragão

    Full Text Available This work proposes thermal characterization, of the biflorine, orto-quinon of Capraria biflora L., through the TG and DSC photovisual data. The thermogravimetric results showed that the decomposition reaction biflorine occurs three steps under air atmosphere, The DSC of biflorin presented five peaks relating to phase transitions. The DSC photovisual system demonstrated changes in biflorin.

  9. Detecting spatial memory deficits beyond blindness in tg2576 Alzheimer mice.

    Yassine, Nour; Lazaris, Anelise; Dorner-Ciossek, Cornelia; Després, Olivier; Meyer, Laurence; Maitre, Michel; Mensah-Nyagan, Ayikoe Guy; Cassel, Jean-Christophe; Mathis, Chantal

    2013-03-01

    The retinal degeneration Pde6b(rd1) (rd) mutation can be a major pitfall in behavioral studies using tg2576 mice bred on a B6:SJL genetic background, 1 of the most widely used models of Alzheimer's disease. After a pilot study in wild type mice, performance of 8- and 16-month-old tg2576 mice were assessed in several behavioral tasks with the challenge of selecting 1 or more task(s) showing robust memory deficits on this genetic background. Water maze acquisition was impossible in rd homozygotes, whereas Y-maze alternation, object recognition, and olfactory discrimination were unaffected by both the transgene and the rd mutation. Spatial memory retention of 8- and 16-month-old tg2576 mice, however, was dramatically affected independently of the rd mutation when mice had to recognize a spatial configuration of objects or to perform the Barnes maze. Thus, the latter tasks appear extremely useful to evaluate spatial memory deficits and to test cognitive therapies in tg2576 mice and other mouse models bred on a background susceptible to visual impairment. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. SU-F-T-22: Clinical Implications When Using TG-186 (ACE) Heterogeneity Software

    Likhacheva, A; Grade, E; Sadeghi, A; Sokolowski, T [Arizona Cancer Specialists, Mesa, AZ (United States)

    2016-06-15

    Purpose: The purpose of this study is to compare dosimetric calculations using traditional TG-43 formalism and Oncentra Brachy Advanced Collapsed cone Engine (ACE) TG-186 calculation algorithm in clinical setting. Methods: We analyzed dosimetry of four patients treated with accelerated partial breast irradiation using a multi-channel intracavitary device (SAVI). All patients were treated to 34 Gy in 10 fractions using a high-dose-rate (192) Ir source. The plans were designed and treated using the TG-43 model. ACE was used to assess the effect heterogeneity correction on various dosimetric parameters. Mass density was estimated using Hounsfield units. Results: Compared to TG-43 formalism, ACE estimated lower doses to targets and organs at risk. The mean difference was 19.8% (range 15.3–24.1%) for PTV-eval V200, 12.0% (range 9.7–17.7%) for PTV-eval V150, 4.3% (range 3.3–6.5%) for PTV-eval D95, 3.3% (range 1.4–5.4%) for PTV-eval D90, 5.4% (range 2.9–9.9%) for maximum rib dose, and 5.7% (2.4–7.4%) for maximum skin dose. There was no correlation between the magnitude of the difference and the PTV-eval volume, air volume, or tissue-applicator conformance. Conclusion: Based on our preliminary study, the TG-43 algorithm appears to overestimate the dose to targets and organs at risk when compared to the ACE TG-186 software. We hypothesize that air adjacent to the SAVI struts contributes to lack of scatter thereby contributing a significant difference in dose calculation when using ACE. We believe that ACE calculation provides a more realistic isodose distribution than TG-43. We plan to further investigate the impact of heterogeneity correction on brachytherapy planning for a wide variety of clinical scenarios, include skin, cervix/uterus, prostate, and lung.

  11. Análises de protocolos de braquiterapia, por alta taxa de dose, do controle de qualidade de alguns serviços locais, baseados no TG40, TG56 e ARCAL XXX Analysis of the high dose rate brachytherapy protocols of quality assurance programs of some local services, based on TG40, TG56 and ARCAL XXX.

    Carmen S. Guzmán Calcina

    2001-08-01

    Full Text Available A braquiterapia por alta taxa de dose está recebendo atenção considerável na maioria dos países. Por isso, nos serviços que utilizam este equipamento exige-se que o desenvolvimento de um programa de controle de qualidade seja cada vez mais rigoroso, para garantir não apenas a segurança aos pacientes, mas também aos operadores e demais envolvidos. Este trabalho tem por objetivos fazer um levantamento dos tipos de testes para um equipamento de braquiterapia por alta taxa de dose, propostos pelos protocolos oficiais publicados (TG40, TG56 e ARCAL XXX e avaliar os tipos de testes que atualmente são realizados por alguns serviços de radioterapia, comparando-os com aqueles apresentados nos protocolos citados. Das análises feitas, observou-se que: a quanto aos protocolos oficiais, o TG56 é mais completo que o TG40 e o ARCAL XXX; b quanto às instituições analisadas, estas em geral se basearam no TG56 para elaborar seus próprios protocolos, os quais demonstraram ter também concordância com os outros já citados. Nestes protocolos, a inexistência dos testes anuais foi notada, o que pode ser explicado por sua aparição nas freqüências trimestral e semestral. Do produto deste estudo são apresentadas tabelas dos tipos de testes com suas respectivas freqüências de utilização, das quais um protocolo pode ser inferido para auxiliar na implementação, pelo menos, dos tipos de testes de controle de qualidade básicos e indispensáveis para o equipamento, garantindo, assim, um tratamento adequado aos pacientes e uma melhor segurança ao pessoal envolvido e, conseqüentemente, assegurando a garantia de qualidade na braquiterapia por alta taxa de dose.High dose rate brachytherapy has been increasingly recognized in most countries, and radiotherapy services using this equipment are encouraged to have a very efficient quality assurance program to ensure protection for patients, workers and other personnel involved. The objective of this

  12. MO-D-BRD-02: In Memoriam of Bengt Bjarngard: SBRT II: Small Field Dosimetry - TG155

    Das, I; Reft, C

    2014-01-01

    formalism for reference dosimetry of small and nonstandard fields,” Med Phys 35, 5179–5186 (2008).2 I. J. Das, P. Francescon, A. Ahnesjo, M. M. Aspradakis, C. W. Cheng, G. X. Ding, G. S. Ibbott, M. Oldham, M. S. Huq, C. S. Reft and S. O.A., “Task Group 155 report: Small fields and non-equilibrium condition photon beam dosimetry,” Med Phys (under review). Learning Objectives: Physics of cavity theory for non-equilibrium condition and definition of small fields Description of absolute and relative dosimetry in the context of TG-155 Choice of detector in small field dosimetry, perturbations and corrections (K(fmsr, fclin)) for accurate dosimetry Understand the advantages and limitations of commercially available detectors for small field dosimetry

  13. WE-PIS-Exhibit Hall-01: Tools for TG-142 Linac Imaging QA II

    Childress, N; Murray, B

    2014-01-01

    Partners in Solutions is an exciting new program in which AAPM partners with our vendors to present practical “hands-on” information about the equipment and software systems that we use in our clinics. The therapy topic this year is solutions for TG-142 recommendations for linear accelerator imaging QA. Note that the sessions are being held in a special purpose room built on the Exhibit Hall Floor, to encourage further interaction with the vendors. Using DoseLab to Perform TG-142 Imaging QA The goals of this session will be to present a clinical overview of acquiring images for TG-142 Imaging QA, as well as analyzing and evaluating results using DoseLab software. DoseLab supports planar imaging QA analysis using almost any QA phantom provided by numerous vendors. General advantages and disadvantages of selecting each of these phantoms will be briefly summarized. Best practices for selecting image acquisition parameters will be presented. A demonstration of using DoseLab software to perform a series of TG-142 tests will be performed. We will disuss why DoseLab uses its own set of imaging QA formulas, and why imaging QA measurement values of the same nominal properties will vary between TG- 142 software packages. Because TG-142 does not specify baseline and tolerance values for imaging QA, the presentation will recommend performing the manufacturer's acceptance test procedure to validate the equipment is functioning correctly. Afterwards, results can be obtained using the clinic's selected set of phantoms, image acquisition parameters, and TG-142 software to set proper baseline values. This presentation will highlight the reasons why comparing imaging QA results can be trickier than comparing linear accelerator treatment results and what physicists should keep in mind when comparing imaging QA results for different machines. Physicists are often unsure of the next step when there is an issue discovered during Imaging QA. Therefore, a few common examples

  14. WE-PIS-Exhibit Hall-01: Tools for TG-142 Linac Imaging QA II

    Childress, N [Mobius Medical Management, LLC,, Houston, TX (United States); Murray, B [ZapIT Medical, Dublin, OH (Ireland)

    2014-06-15

    Partners in Solutions is an exciting new program in which AAPM partners with our vendors to present practical “hands-on” information about the equipment and software systems that we use in our clinics. The therapy topic this year is solutions for TG-142 recommendations for linear accelerator imaging QA. Note that the sessions are being held in a special purpose room built on the Exhibit Hall Floor, to encourage further interaction with the vendors. Using DoseLab to Perform TG-142 Imaging QA The goals of this session will be to present a clinical overview of acquiring images for TG-142 Imaging QA, as well as analyzing and evaluating results using DoseLab software. DoseLab supports planar imaging QA analysis using almost any QA phantom provided by numerous vendors. General advantages and disadvantages of selecting each of these phantoms will be briefly summarized. Best practices for selecting image acquisition parameters will be presented. A demonstration of using DoseLab software to perform a series of TG-142 tests will be performed. We will disuss why DoseLab uses its own set of imaging QA formulas, and why imaging QA measurement values of the same nominal properties will vary between TG- 142 software packages. Because TG-142 does not specify baseline and tolerance values for imaging QA, the presentation will recommend performing the manufacturer's acceptance test procedure to validate the equipment is functioning correctly. Afterwards, results can be obtained using the clinic's selected set of phantoms, image acquisition parameters, and TG-142 software to set proper baseline values. This presentation will highlight the reasons why comparing imaging QA results can be trickier than comparing linear accelerator treatment results and what physicists should keep in mind when comparing imaging QA results for different machines. Physicists are often unsure of the next step when there is an issue discovered during Imaging QA. Therefore, a few common examples

  15. Accelerator beam data commissioning equipment and procedures: Report of the TG-106 of the Therapy Physics Committee of the AAPM

    Das, Indra J.; Cheng, C.-W.; Watts, Ronald J.; Ahnesjoe, Anders; Gibbons, John; Li, X. Allen; Lowenstein, Jessica; Mitra, Raj K.; Simon, William E.; Zhu, Timothy C.

    2008-01-01

    For commissioning a linear accelerator for clinical use, medical physicists are faced with many challenges including the need for precision, a variety of testing methods, data validation, the lack of standards, and time constraints. Since commissioning beam data are treated as a reference and ultimately used by treatment planning systems, it is vitally important that the collected data are of the highest quality to avoid dosimetric and patient treatment errors that may subsequently lead to a poor radiation outcome. Beam data commissioning should be performed with appropriate knowledge and proper tools and should be independent of the person collecting the data. To achieve this goal, Task Group 106 (TG-106) of the Therapy Physics Committee of the American Association of Physicists in Medicine was formed to review the practical aspects as well as the physics of linear accelerator commissioning. The report provides guidelines and recommendations on the proper selection of phantoms and detectors, setting up of a phantom for data acquisition (both scanning and no-scanning data), procedures for acquiring specific photon and electron beam parameters and methods to reduce measurement errors (<1%), beam data processing and detector size convolution for accurate profiles. The TG-106 also provides a brief discussion on the emerging trend in Monte Carlo simulation techniques in photon and electron beam commissioning. The procedures described in this report should assist a qualified medical physicist in either measuring a complete set of beam data, or in verifying a subset of data before initial use or for periodic quality assurance measurements. By combining practical experience with theoretical discussion, this document sets a new standard for beam data commissioning

  16. MO-PIS-Exhibit Hall-01: Tools for TG-142 Linac Imaging QA I

    Clements, M [RAD Image, Colorado Springs, CO (United States); Wiesmeyer, M [Standard Imaging, Inc., Middleton, WI (United States)

    2014-06-15

    Partners in Solutions is an exciting new program in which AAPM partners with our vendors to present practical “hands-on” information about the equipment and software systems that we use in our clinics. The therapy topic this year is solutions for TG-142 recommendations for linear accelerator imaging QA. Note that the sessions are being held in a special purpose room built on the Exhibit Hall Floor, to encourage further interaction with the vendors. Automated Imaging QA for TG-142 with RIT Presentation Time: 2:45 – 3:15 PM This presentation will discuss software tools for automated imaging QA and phantom analysis for TG-142. All modalities used in radiation oncology will be discussed, including CBCT, planar kV imaging, planar MV imaging, and imaging and treatment coordinate coincidence. Vendor supplied phantoms as well as a variety of third-party phantoms will be shown, along with appropriate analyses, proper phantom setup procedures and scanning settings, and a discussion of image quality metrics. Tools for process automation will be discussed which include: RIT Cognition (machine learning for phantom image identification), RIT Cerberus (automated file system monitoring and searching), and RunQueueC (batch processing of multiple images). In addition to phantom analysis, tools for statistical tracking, trending, and reporting will be discussed. This discussion will include an introduction to statistical process control, a valuable tool in analyzing data and determining appropriate tolerances. An Introduction to TG-142 Imaging QA Using Standard Imaging Products Presentation Time: 3:15 – 3:45 PM Medical Physicists want to understand the logic behind TG-142 Imaging QA. What is often missing is a firm understanding of the connections between the EPID and OBI phantom imaging, the software “algorithms” that calculate the QA metrics, the establishment of baselines, and the analysis and interpretation of the results. The goal of our brief presentation will be to

  17. MO-PIS-Exhibit Hall-01: Tools for TG-142 Linac Imaging QA I

    Clements, M; Wiesmeyer, M

    2014-01-01

    Partners in Solutions is an exciting new program in which AAPM partners with our vendors to present practical “hands-on” information about the equipment and software systems that we use in our clinics. The therapy topic this year is solutions for TG-142 recommendations for linear accelerator imaging QA. Note that the sessions are being held in a special purpose room built on the Exhibit Hall Floor, to encourage further interaction with the vendors. Automated Imaging QA for TG-142 with RIT Presentation Time: 2:45 – 3:15 PM This presentation will discuss software tools for automated imaging QA and phantom analysis for TG-142. All modalities used in radiation oncology will be discussed, including CBCT, planar kV imaging, planar MV imaging, and imaging and treatment coordinate coincidence. Vendor supplied phantoms as well as a variety of third-party phantoms will be shown, along with appropriate analyses, proper phantom setup procedures and scanning settings, and a discussion of image quality metrics. Tools for process automation will be discussed which include: RIT Cognition (machine learning for phantom image identification), RIT Cerberus (automated file system monitoring and searching), and RunQueueC (batch processing of multiple images). In addition to phantom analysis, tools for statistical tracking, trending, and reporting will be discussed. This discussion will include an introduction to statistical process control, a valuable tool in analyzing data and determining appropriate tolerances. An Introduction to TG-142 Imaging QA Using Standard Imaging Products Presentation Time: 3:15 – 3:45 PM Medical Physicists want to understand the logic behind TG-142 Imaging QA. What is often missing is a firm understanding of the connections between the EPID and OBI phantom imaging, the software “algorithms” that calculate the QA metrics, the establishment of baselines, and the analysis and interpretation of the results. The goal of our brief presentation will be to

  18. Impaired hippocampal acetylcholine release parallels spatial memory deficits in Tg2576 mice subjected to basal forebrain cholinergic degeneration

    Laursen, Bettina; Mørk, Arne; Plath, Niels

    2013-01-01

    (BFCD) in 3 months old male Tg2576 mice to co-express cholinergic degeneration with Aβ overexpression as these characteristics constitutes key hallmarks of AD. At 9 months, SAP lesioned Tg2576 mice were cognitively impaired in two spatial paradigms addressing working memory and mid to long-term memory...

  19. MO-E-9A-01: Risk Based Quality Management: TG100 In Action

    Huq, M [University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Palta, J [Virginia Commonwealth University, Richmond, VA (United States); Dunscombe, P [Tom Baker Cancer Centre, Calgary, AB (Canada); Thomadsen, B [University of Wisconsin, Madison, WI (United States)

    2014-06-15

    One of the goals of quality management in radiation therapy is to gain high confidence that patients will receive the prescribed treatment correctly. To accomplish these goals professional societies such as the American Association of Physicists in Medicine (AAPM) has published many quality assurance (QA), quality control (QC), and quality management (QM) guidance documents. In general, the recommendations provided in these documents have emphasized on performing device-specific QA at the expense of process flow and protection of the patient against catastrophic errors. Analyses of radiation therapy incidents find that they are most often caused by flaws in the overall therapy process, from initial consult through final treatment, than by isolated hardware or computer failures detectable by traditional physics QA. This challenge is shared by many intrinsically hazardous industries. Risk assessment tools and analysis techniques have been developed to define, identify, and eliminate known and/or potential failures, problems, or errors, from a system, process and/or service before they reach the customer. These include, but are not limited to, process mapping, failure modes and effects analysis (FMEA), fault tree analysis (FTA), and establishment of a quality management program that best avoids the faults and risks that have been identified in the overall process. These tools can be easily adapted to radiation therapy practices because of their simplicity and effectiveness to provide efficient ways to enhance the safety and quality of treatment processes. Task group 100 (TG100) of AAPM has developed a risk-based quality management program that uses these tools. This session will be devoted to a discussion of these tools and how these tools can be used in a given radiotherapy clinic to develop a risk based QM program. Learning Objectives: Learn how to design a process map for a radiotherapy process. Learn how to perform a FMEA analysis for a given process. Learn what

  20. MO-AB-206-02: Testing Gamma Cameras Based On TG177 WG Report

    Halama, J. [Loyola Univ. Medical Center (United States)

    2016-06-15

    This education session will cover the physics and operation principles of gamma cameras and PET scanners. The first talk will focus on PET imaging. An overview of the principles of PET imaging will be provided, including positron decay physics, and the transition from 2D to 3D imaging. More recent advances in hardware and software will be discussed, such as time-of-flight imaging, and improvements in reconstruction algorithms that provide for options such as depth-of-interaction corrections. Quantitative applications of PET will be discussed, as well as the requirements for doing accurate quantitation. Relevant performance tests will also be described. Learning Objectives: Be able to describe basic physics principles of PET and operation of PET scanners. Learn about recent advances in PET scanner hardware technology. Be able to describe advances in reconstruction techniques and improvements Be able to list relevant performance tests. The second talk will focus on gamma cameras. The Nuclear Medicine subcommittee has charged a task group (TG177) to develop a report on the current state of physics testing of gamma cameras, SPECT, and SPECT/CT systems. The report makes recommendations for performance tests to be done for routine quality assurance, annual physics testing, and acceptance tests, and identifies those needed satisfy the ACR accreditation program and The Joint Commission imaging standards. The report is also intended to be used as a manual with detailed instructions on how to perform tests under widely varying conditions. Learning Objectives: At the end of the presentation members of the audience will: Be familiar with the tests recommended for routine quality assurance, annual physics testing, and acceptance tests of gamma cameras for planar imaging. Be familiar with the tests recommended for routine quality assurance, annual physics testing, and acceptance tests of SPECT systems. Be familiar with the tests of a SPECT/CT system that include the CT images

  1. MO-AB-206-02: Testing Gamma Cameras Based On TG177 WG Report

    Halama, J.

    2016-01-01

    This education session will cover the physics and operation principles of gamma cameras and PET scanners. The first talk will focus on PET imaging. An overview of the principles of PET imaging will be provided, including positron decay physics, and the transition from 2D to 3D imaging. More recent advances in hardware and software will be discussed, such as time-of-flight imaging, and improvements in reconstruction algorithms that provide for options such as depth-of-interaction corrections. Quantitative applications of PET will be discussed, as well as the requirements for doing accurate quantitation. Relevant performance tests will also be described. Learning Objectives: Be able to describe basic physics principles of PET and operation of PET scanners. Learn about recent advances in PET scanner hardware technology. Be able to describe advances in reconstruction techniques and improvements Be able to list relevant performance tests. The second talk will focus on gamma cameras. The Nuclear Medicine subcommittee has charged a task group (TG177) to develop a report on the current state of physics testing of gamma cameras, SPECT, and SPECT/CT systems. The report makes recommendations for performance tests to be done for routine quality assurance, annual physics testing, and acceptance tests, and identifies those needed satisfy the ACR accreditation program and The Joint Commission imaging standards. The report is also intended to be used as a manual with detailed instructions on how to perform tests under widely varying conditions. Learning Objectives: At the end of the presentation members of the audience will: Be familiar with the tests recommended for routine quality assurance, annual physics testing, and acceptance tests of gamma cameras for planar imaging. Be familiar with the tests recommended for routine quality assurance, annual physics testing, and acceptance tests of SPECT systems. Be familiar with the tests of a SPECT/CT system that include the CT images

  2. MO-E-9A-01: Risk Based Quality Management: TG100 In Action

    Huq, M; Palta, J; Dunscombe, P; Thomadsen, B

    2014-01-01

    One of the goals of quality management in radiation therapy is to gain high confidence that patients will receive the prescribed treatment correctly. To accomplish these goals professional societies such as the American Association of Physicists in Medicine (AAPM) has published many quality assurance (QA), quality control (QC), and quality management (QM) guidance documents. In general, the recommendations provided in these documents have emphasized on performing device-specific QA at the expense of process flow and protection of the patient against catastrophic errors. Analyses of radiation therapy incidents find that they are most often caused by flaws in the overall therapy process, from initial consult through final treatment, than by isolated hardware or computer failures detectable by traditional physics QA. This challenge is shared by many intrinsically hazardous industries. Risk assessment tools and analysis techniques have been developed to define, identify, and eliminate known and/or potential failures, problems, or errors, from a system, process and/or service before they reach the customer. These include, but are not limited to, process mapping, failure modes and effects analysis (FMEA), fault tree analysis (FTA), and establishment of a quality management program that best avoids the faults and risks that have been identified in the overall process. These tools can be easily adapted to radiation therapy practices because of their simplicity and effectiveness to provide efficient ways to enhance the safety and quality of treatment processes. Task group 100 (TG100) of AAPM has developed a risk-based quality management program that uses these tools. This session will be devoted to a discussion of these tools and how these tools can be used in a given radiotherapy clinic to develop a risk based QM program. Learning Objectives: Learn how to design a process map for a radiotherapy process. Learn how to perform a FMEA analysis for a given process. Learn what

  3. Observation of changes of serum leptin and lipid (TG and TC) levels in patients with graves' disease

    Wang Zhaobao; Cheng Guanghua

    2008-01-01

    Objective: To investigate the clinical significance of changes of serum leptin (with RIA) and lipid (TG and TC) (with biochemistry) levels in patients with Graves' disease. Methods: Serum Leptin, TG and TC levels were determined in 29 patients with Graves' disease both before and after treatment as well as in 30 controls. Results: Before treatment, serum Leptin, TG and TC levels in the patients were significantly lower than those in the controls. After treatment, serum Leptin, TG and TC levels increased and were significantly higher than those before treatment and were not much different from those in controls. Conclusion: The changes of serum Leptin, TG and TC levels may be of value for outcome prediction in patients with Graves' disease. (authors)

  4. Sub-Tg enthalpy relaxation in an unstable oxide glass former: insights into the structural heterogeneity

    Yue, Yuanzheng; Zhang, Yanfei

    Structural heterogeneity plays a crucial role in determining functionality of glasses. In this work we have found that the sub-Tg enthalpy relaxation pattern in a hyperquenched glass is highly sensitive to structural heterogeneity. As a consequence, the former can be used as an effective approach...... to detect and quantify the structural heterogeneity in glass-forming liquids. However, the chemical nature of structural heterogeneity should be revealed by other means such as high resolution microscopic and spectroscopic methods. To study the impact of the structural heterogeneity on the sub-Tg relaxation...... chemical features and degrees of structural heterogeneity in glass-forming liquids. This finding contributes to the microscopic origin of both the primary and secondary relaxation in terms of structural heterogeneity. Finally the results provide insights into the relation between structural heterogeneity...

  5. Compositional characterization of carbon electrode material: A study using simultaneous TG-DTA-FTIR

    Raje, Naina; Aacherekar, Darshana A.; Reddy, A.V.R.

    2009-01-01

    Present work describes the application of thermal methods, especially the evolved gas analysis (EGA) for the compositional characterization of carbon electrode material with respect to its organic, amorphous and graphitic carbon content. Trace levels of organic carbon present in the amorphous carbon samples were determined qualitatively by using FTIR absorption spectroscopy. Amorphous and graphitic carbon content in synthetic mixture samples were determined quantitatively using simultaneous TG-DTA-FTIR measurements. FTIR system was calibrated using the measured absorption signal of the evolved carbon dioxide due to the decomposition of cadmium carbonate. Inter-comparison studies using TG-FTIR measurements show that simultaneous FTIR spectroscopy is an effective complementary quantitative measurement technique for thermogravimetric analysis involving the complex decomposition reaction processes.

  6. Characteristic Study of Some Different Kinds of Coal Particles Combustion with Online TG-MS-FTIR

    Pan, Guanfu

    2018-01-01

    Four kinds of pulverized coal samples from China and Indonesia were studied by thermogravimetry coupled with mass spectrometry and fourier transform infrared spectroscopy (TG-MS-FTIR). The thermal behaviors and gaseous emissions of these coals were analyzed in this work. The results indicate that the relative lower values of H/C ratios, which normally represent the degree of aromatization and ring condensation in coal samples, could lead to the relative more intense thermal reaction. The time-evolved profiles of some typical gas products (i.e., CO, SO2, CH4, NO, NO2, NH3 and etc.) were provided by TG-MS-FTIR, and their variations are different. For all the samples, the releases of SO2 and COS can be found at lower temperature than those of NO and CO. As the temperature increases, the possible conversion of NO2 and NH3 to NO is deduced in this work.

  7. Abnormal three-steplike sub-Tg enthalpy relaxation pattern in hyperquenched metallic glasses

    Hu, Lina; Yue, Yuanzheng

    Our recent work observed a quite different relaxation pattern, i.e., the abnormal three-steplike sub-Tg relaxation in CuZrAl GRs[1]. However, the generality and the origin of this remarkable thermodynamic anomaly remain enigmatic. By hyperquenching strategy, the present work investigated the depe......Our recent work observed a quite different relaxation pattern, i.e., the abnormal three-steplike sub-Tg relaxation in CuZrAl GRs[1]. However, the generality and the origin of this remarkable thermodynamic anomaly remain enigmatic. By hyperquenching strategy, the present work investigated...... in La55Al25Ni20 GRs. However, the correlation between Tf and the activation energy for initiating the energy releasing during thermal scanning is three-steplike for La55Al25Ni20, revealing the similar phenomenon with the abnormal ERP of Cu46Zr46Al8. These unexpected phenomena have been well explained...

  8. Role of humidity and other correction factors in the AAPM TG-21 dosimetry protocol

    Rogers, D.W.; Ross, C.K.

    1988-01-01

    A detailed derivation is presented of the formulas required to determine Ngas and Dmed in the AAPM TG-21 dosimetry protocol. This protocol specifies how to determine the absorbed dose in an electron or photon beam when using exposure or absorbed dose calibrated ion chambers. It is shown that the expression given in TG-21's recent letter of clarification is incorrect. Accounting for humidity correctly increases, by 0.4%, all absorbed dose determinations using an exposure calibrated ion chamber. Taking into account other correction factors in the equation for exposure could also have varying, but significant effects (possibly over 1%). These are the stem scatter correction, the axial nonuniformity correction and the electrode correction for electrodes made of different materials from the wall. Attention is drawn to differences in the definitions of the exposure and absorbed dose calibration factors, Nx and ND, respectively, as supplied by the NBS and the NRCC

  9. A Monte Carlo derived TG-51 equivalent calibration for helical tomotherapy

    Thomas, S.D.; Mackenzie, M.; Rogers, D.W.O.; Fallone, B.G.

    2005-01-01

    Helical tomotherapy (HT) requires a method of accurately determining the absorbed dose under reference conditions. In the AAPM's TG-51 external beam dosimetry protocol, the quality conversion factor, k Q , is presented as a function of the photon component of the percentage depth-dose at 10 cm depth, %dd(10) x , measured under the reference conditions of a 10x10 cm 2 field size and a source-to-surface distance (SSD) of 100 cm. The value of %dd(10) x from HT cannot be used for the determination of k Q because the design of the HT does not meet the following TG-51 reference conditions: (i) the field size and the practical SSD required by TG-51 are not obtainable and (ii) the absence of the flattening filter changes the beam quality thus affecting some components of k Q . The stopping power ratio is not affected because of its direct relationship to %dd(10) x . We derive a relationship for the Exradin A1SL ion chamber converting the %dd(10) x measured under HT 'reference conditions' of SSD=85 cm and a 5x10 cm 2 field-size [%dd(10) x[HTRef] ], to the dosimetric equivalent value under for TG-51 reference conditions [%dd(10) x[HTTG-51] ] for HT. This allows the determination of k Q under the HT reference conditions. The conversion results in changes of 0.1% in the value of k Q for our particular unit. The conversion relationship should also apply to other ion chambers with possible errors on the order of 0.1%

  10. Helhetsorienterad utvärdering av kollektivtrafikåtgärder

    Hiselius, Lena Winslott; Barfod, Michael Bruhn; Leleur, Steen

    Under hösten 2008 och våren 2009 har forskare vid Avd. Trafik och väg vid Lunds Tekniska Högskola, DTU Transport vid Danmarks Tekniska Universitet samt National-ekonomiska institutionen vid Lunds Universitet genomfört ett forskningsprojekt med syfte att studera tillämpningen av en sammansatt...... (helhetsorienterad) analys av kollektiv-trafikåtgärder....

  11. TgICMAP1 is a novel microtubule binding protein in Toxoplasma gondii.

    Aoife T Heaslip

    Full Text Available The microtubule cytoskeleton provides essential structural support for all eukaryotic cells and can be assembled into various higher order structures that perform drastically different functions. Understanding how microtubule-containing assemblies are built in a spatially and temporally controlled manner is therefore fundamental to understanding cell physiology. Toxoplasma gondii, a protozoan parasite, contains at least five distinct tubulin-containing structures, the spindle pole, centrioles, cortical microtubules, the conoid, and the intra-conoid microtubules. How these five structurally and functionally distinct sets of tubulin containing structures are constructed and maintained in the same cell is an intriguing problem. Previously, we performed a proteomic analysis of the T. gondii apical complex, a cytoskeletal complex located at the apical end of the parasite that is composed of the conoid, three ring-like structures, and the two short intra-conoid microtubules. Here we report the characterization of one of the proteins identified in that analysis, TgICMAP1. We show that TgICMAP1 is a novel microtubule binding protein that can directly bind to microtubules in vitro and stabilizes microtubules when ectopically expressed in mammalian cells. Interestingly, in T. gondii, TgICMAP1 preferentially binds to the intra-conoid microtubules, providing us the first molecular tool to investigate the intra-conoid microtubule assembly process during daughter construction.

  12. Cotinine improves visual recognition memory and decreases cortical Tau phosphorylation in the Tg6799 mice.

    Grizzell, J Alex; Patel, Sagar; Barreto, George E; Echeverria, Valentina

    2017-08-01

    Alzheimer's disease (AD) is associated with the progressive aggregation of hyperphosphorylated forms of the microtubule associated protein Tau in the central nervous system. Cotinine, the main metabolite of nicotine, reduced working memory deficits, synaptic loss, and amyloid β peptide aggregation into oligomers and plaques as well as inhibited the cerebral Tau kinase, glycogen synthase 3β (GSK3β) in the transgenic (Tg)6799 (5XFAD) mice. In this study, the effect of cotinine on visual recognition memory and cortical Tau phosphorylation at the GSK3β sites Serine (Ser)-396/Ser-404 and phospho-CREB were investigated in the Tg6799 and non-transgenic (NT) littermate mice. Tg mice showed short-term visual recognition memory impairment in the novel object recognition test, and higher levels of Tau phosphorylation when compared to NT mice. Cotinine significantly improved visual recognition memory performance increased CREB phosphorylation and reduced cortical Tau phosphorylation. Potential mechanisms underlying theses beneficial effects are discussed. Copyright © 2017. Published by Elsevier Inc.

  13. Textural properties of low-fat set-type yoghurt depending on mTG addition

    Lívia Darnay

    2016-07-01

    Full Text Available Our aim was to determine how 0.5-2 U/g non-inactivated mTG affects the pH development and apparent viscosity during fermentation. Furthermore we wished to examine how the enzyme addition could change protein structure, gel strength and sensory characteristics by healthy low-fat set-type yoghurt product. Therefore commercial mTG enzyme preparation was added in different concentrations (0.5-2.0 U/g, in 0.5 U/g steps to 1.5 % bovine milk simultaneously with DVS starter culture. Our study revealed that enzyme dosage (0.5-2 U/g protein had no impact on pH development and apparent viscosity during fermentation when manufacturing low-fat (1.5 % set-type yoghurt. The addition of mTG contributed to 38 % more whey retention with incorporation of β-casein, and caused 44 % higher gel strength up to a level of 1 U/g protein.

  14. Recombinant TgHSP70 Immunization Protects against Toxoplasma gondii Brain Cyst Formation by Enhancing Inducible Nitric Oxide Expression

    Neide M. Silva

    2017-04-01

    Full Text Available Toxoplasma gondii is known to cause congenital infection in humans and animals and severe disease in immunocompromised individuals; consequently development of vaccines against the parasite is highly necessary. Under stress conditions, T. gondii expresses the highly immunogenic heat shock protein 70 (TgHSP70. Here, we assessed the protective efficacy of rTgHSP70 immunization combined with Alum in oral ME-49 T. gondii infection and the mechanisms involved on it. It was observed that immunized mice with rTgHSP70 or rTgHSP70 adsorbed in Alum presented a significantly reduced number of cysts in the brain that was associated with increased iNOS+ cell numbers in the organ, irrespective the use of the adjuvant. Indeed, ex vivo experiments showed that peritoneal macrophages pre-stimulated with rTgHSP70 presented increased NO production and enhanced parasite killing, and the protein was able to directly stimulate B cells toward antibody producing profile. In addition, rTgHSP70 immunization leads to high specific antibody titters systemically and a mixed IgG1/IgG2a response, with predominance of IgG1 production. Nonetheless, it was observed that the pretreatment of the parasite with rTgHSP70 immune sera was not able to control T. gondii internalization and replication by NIH fibroblast neither peritoneal murine macrophages, nor anti-rTgHSP70 antibodies were able to kill T. gondii by complement-mediated lysis, suggesting that these mechanisms are not crucial to resistance. Interestingly, when in combination with Alum, rTgHSP70 immunization was able to reduce inflammation in the brain of infected mice and in parallel anti-rTgHSP70 immune complexes in the serum. In conclusion, immunization with rTgHSP70 induces massive amounts of iNOS expression and reduced brain parasitism, suggesting that iNOS expression and consequently NO production in the brain is a protective mechanism induced by TgHSP70 immunization, therefore rTgHSP70 can be a good candidate for

  15. Clinical reevaluation of radioimmunological thyroglobulin (hTg) determination in follow-up of differentiated thyroid carcinoma

    Boettger, I.; Kanitz, W.; Pabst, W.H.

    1985-01-01

    A reevaluation of the clinical value of radioimmunological thyroglobulin (hTg) determination during follow-up of differentiated thyroid carcinoma, in general, confirms our previous results already published in 1980 and 1981. A total of 163 patients with differentiated thyroid carcinoma, 53 with papillary and 110 with follicular carcinoma, was studied up to January 1984. 586 sera are included in this study. The differentiation of suspicious from nonsuspicious findings was found to be based upon a cut-off concentration of 10 μg/l. Pathological findings were associated with hTg concentrations above 20 μg/l. Diagnostic accuracy was calculated to be between 95 and 97%, sensitivity of the method in comparison to be radioiodine whole-body scan was 98 versus 83%, respectively, and specificity 94%. At first 5 false negative and 6 false positive hTg findings have been obtained. 7.6% of the patients demonstrated endogeneous hTg antibodies by Boyden test. 7.7% of Boyden test negative sera showed an unacceptable hTg recovery of worse than +- 50%, which was possibly due to endogeneous antibodies. Again, endogenous TSH was able to stimulate hTg secretion in the form of elevated levels, yet did not affect the clinical diagnosis. Examples of the behaviour of hTg levels during follow-up are demonstrated. Specifically, the cases with false hTg findings are discussed. Basically, the conclusions are the same as in 1980 and 1981: hTg determination is able to replace the routinely performed radioiodine whole-body scan during follow-up, if once residual thyroid tissue and metastases have been excluded by means of radioiodine and an optimal follow-up program is used. (orig.) [de

  16. Cerebrospinal fluid neurofilament light chain as a biomarker of neurodegeneration in the Tg4510 and MitoPark mouse models

    Clement, Amalie; Mitchelmore, Cathy; Andersson, Daniel

    2017-01-01

    examined whether changes in NF-L levels in brain, plasma, and CSF reflect the changing disease status of preclinical models of neurodegeneration. Using Western Blot and ELISA we characterized NF-L and disease-related proteins in brain, CSF and plasma samples from Tg4510 mice (tauopathy/AD), MitoPark mice...... (PD), and their age-matched control littermates. We found that CSF NF-L clearly discriminates Tg4510 from control littermates, which was not observed for the MitoPark model. However, both Tg4510 and MitoPark showed altered expression and solubilization of NFs compared to control littermates. We found...

  17. FXIIIA and TGF-beta over-expression produces normal musculo-skeletal phenotype in TG2-/- mice.

    Tarantino, U; Oliva, F; Taurisano, G; Orlandi, A; Pietroni, V; Candi, E; Melino, G; Maffulli, N

    2009-04-01

    Transglutaminase (TGs) enzymes and proteins crosslinking have for long time been implicated in the formation of hard tissue development, matrix maturation and mineralization. Among the TGs family members, in the context of connective tissue formation, TG2 and Factor XIII are expressed in cartilage by hypertrophic chondrocytes. Here, we analyse the morphological consequences of TG2 deficiency, during the development of skeletal elements. When TG2 is absent, there are not gross abnormalities in the development of the skeletal system, probably from compensatory mechanisms resulting in increased expression of FXIIIA and TGF-beta 1. In vivo other TGs may be involved in promoting chondrocytes and osteoblast differentiation and matrix mineralisation.

  18. Characterisation of model compounds and a synthetic coal by TG/MS/FTIR to represent the pyrolysis behaviour of coal

    Arenillas, A.; Pevida, C.; Rubiera, F.; Garcia, R.; Pis, J.J. [Instituto Nacional del Carbon, CSIC, Apartado 73, 33080 Oviedo (Spain)

    2004-06-01

    Coal pyrolysis is the initial, accompanying reaction of a number of coal conversion processes such as hydrogenation, combustion and gasification. However, because of the inherent complexity of coal composition, it is difficult to describe coal pyrolysis clearly. Single model compounds have been used before in order to provide additional insight into the complex processes that occur in the pyrolysis of coal. Yet the picture obtained is a simplified one and certain important aspects such as coal structure, interactions between different surface groups and cross-links are omitted. The approach used in this work involves the preparation of a synthetic coal, SC, with a known structure by curing a mixture of single, well-defined model compounds. By means of chemical characterisation, the SC was shown to contain the macroscopic features of a high volatile coal (proximate and ultimate analyses). FTIR characterisation revealed the presence of functional groups similar to those of coal in the structure of the SC. Temperature-programmed pyrolysis tests were performed in a thermobalance linked to a mass spectrometer and a Fourier transform infrared analyser (TG/MS/FTIR). The thermal behaviour of the synthetic coal (i.e., rate of mass loss and the evolution profiles of gaseous compounds during pyrolysis tests) is very similar to that of the high volatile bituminous coal which was used as a reference material. The great advantage of using SC lies in the fact that its composition and structure can be accurately determined and employed in subsequent applications in basic and mechanistic studies.

  19. Long-term Treatment with Low-Dose Caffeine Worsens BPSD-Like Profile in 3xTg-AD Mice Model of Alzheimer’s Disease and Affects Mice with Normal Aging

    Raquel Baeta-Corral

    2018-02-01

    Full Text Available Coffee or caffeine has recently been suggested as prophylaxis for dementia. Although memory problems are hallmarks of Alzheimer’s disease, this dementia is also characterized by neuropsychiatric symptoms called Behavioral and Psychological Symptoms of Dementia (BPSD. The impact of preventive/therapeutic strategies on both cognitive and non-cognitive symptoms can be addressed in the 3xTg-AD mice, since they exhibit cognitive but also BPSD-like profiles. Here, we studied the long-term effects of a low dose of caffeine in male 3xTg-AD mice and as compared to age-matched non-transgenic (NTg counterparts with normal aging. Animals were treated (water or caffeine in drinking water from adulthood (6 months of age until middle-aged (13 months of age, that in 3xTg-AD mice correspond to onset of cognitive impairment and advanced stages, respectively. The low caffeine dosing used (0.3 mg/ml was previously found to give a plasma concentration profile in mice roughly equivalent to that of a human coffee drinker. There were significant effects of caffeine on most behavioral variables, especially those related to neophobia and other anxiety-like behaviors, emotionality, and cognitive flexibility. The 3xTg-AD and NTg mice were differently influenced by caffeine. Overall, the increase of neophobia and other anxiety-related behaviors resulted in an exacerbation of BPSD-like profile in 3xTg-AD mice. Learning and memory, strongly influenced by anxiety in 3xTg-AD mice, got little benefit from caffeine, only shown after a detailed analysis of navigation strategies. The worsened pattern in NTg mice and the use of search strategies in 3xTg-AD mice make both groups more similar. Circadian motor activity showed genotype differences, which were found to be enhanced by caffeine. Selective effects of caffeine on NTg were found in the modulation of behaviors related to emotional profile and risk assessment. Caffeine normalized splenomegaly of 3xTg-AD mice, a physical

  20. Tg.rasH2 Mice and not CByB6F1 Mice Should Be Used for 28-Day Dose Range Finding Studies Prior to 26-Week Tg.rasH2 Carcinogenicity Studies.

    Paranjpe, Madhav G; Belich, Jessica; Vidmar, Tom J; Elbekai, Reem H; McKeon, Marie; Brown, Caren

    Our recent retrospective analysis of data, collected from 29 Tg.rasH2 mouse carcinogenicity studies, determined how successful the strategy of choosing the high dose for the 26-week studies was based on the estimated maximum tolerated dose (EMTD) derived from earlier 28-day dose range finding (DRF) studies conducted in CByB6F1 mice. Our analysis demonstrated that the high doses applied at EMTD in the 26-week Tg.rasH2 studies failed to detect carcinogenic effects. To investigate why the dose selection process failed in the 26-week carcinogenicity studies, the initial body weights, terminal body weights, body weight gains, food consumption, and mortality from the first 4 weeks of 26-week studies with Tg.rasH2 mice were compared with 28-day DRF studies conducted with CByB6F1 mice. Both the 26-week and the earlier respective 28-day studies were conducted with the exact same vehicle, test article, and similar dose levels. The analysis of our results further emphasizes that the EMTD and subsequent lower doses, determined on the basis of the 28-day studies in CByB6F1 mice, may not be an accurate strategy for selecting appropriate dose levels for the 26-week carcinogenicity studies in Tg.rasH2 mice. Based on the analysis presented in this article, we propose that the Tg.rasH2 mice and not the CByB6F1 mice should be used in future DRF studies. The Tg.rasH2 mice demonstrate more toxicity than the CByB6F1 mice, possibly because of their smaller size compared to CByB6F1 mice. Also, the Tg.rasH2 males appear to be more sensitive than the female Tg.rasH2 mice.

  1. Immunization with a DNA vaccine encoding Toxoplasma gondii Superoxide dismutase (TgSOD) induces partial immune protection against acute toxoplasmosis in BALB/c mice.

    Liu, Yuan; Cao, Aiping; Li, Yawen; Li, Xun; Cong, Hua; He, Shenyi; Zhou, Huaiyu

    2017-06-07

    Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite that infects all warm-blooded animals including humans and causes toxoplasmosis. An effective vaccine could be an ideal choice for preventing and controlling toxoplasmosis. T. gondii Superoxide dismutase (TgSOD) might participate in affecting the intracellular growth of both bradyzoite and tachyzoite forms. In the present study, the TgSOD gene was used to construct a DNA vaccine (pEGFP-SOD). TgSOD gene was amplified and inserted into eukaryotic vector pEGFP-C1 and formed the DNA vaccine pEGFP-SOD. Then the BALB/c mice were immunized intramuscularly with the DNA vaccine and those injected with pEGFP-C1, PBS or nothing were treated as controls. Four weeks after the last immunization, all mouse groups followed by challenging intraperitoneally with tachyzoites of T. gondii ME49 strain. Results showed higher levels of total IgG, IgG2α in the sera and interferon gamma (IFN-γ) in the splenocytes from pEGFP-SOD inoculated mice than those unvaccinated, or inoculated with either empty plasmid vector or PBS. The proportions of CD4 + T cells and CD8 + T cells in the spleen from pEGFP-SOD inoculated mice were significantly (p < 0.05) increased compared to control groups. In addition, the survival time of mice immunized with pEGFP-SOD was significantly prolonged as compared to the controls (p < 0.05) although all the mice died. The present study revealed that the DNA vaccine triggered strong humoral and cellular immune responses, and aroused partial protective immunity against acute T. gondii infection in BALB/c mice. The collective data suggests the SOD may be a potential vaccine candidate for further development.

  2. Influence of processing parameters on microstructure and tensile properties of TG6 titanium alloy

    Wang Tao; Guo Hongzhen; Wang Yanwei; Yao Zekun

    2010-01-01

    Research highlights: → This paper highlights the relationships among processing parameters, microstructure and tensile properties of TG6 high temperature titanium alloy. → The microstructural evolutions under different processing parameters were studied by the quantitative metallography, and the effects of microstructure on room and high temperature tensile properties of TG6 alloy were analysed by SEM and TEM. → Linear relationships of elongation vs. volume fraction of primary α phase and ultimate tensile strength vs. thickness of lamellar α phase were determined. - Abstract: Near-isothermal forging of the TG6 titanium alloy was conducted on microprocessor-controlled 630 ton hydraulic press at the deformation temperatures ranging from 850 deg. C to 1045 deg. C, the strain rates of 0.0008 s -1 , 0.003 s -1 and 0.008 s -1 and the deformation degree from 10% to 70%, and then different double heat treatments were applied to the forged specimens. The microstructural evolutions were researched by optical microscope and the microstructural features, i.e. volume fraction of primary α phase and thickness of lamellar α phase, were measured by means of the image analysis software. The room and high temperature tensile properties were obtained for all the specimens. Effects of microstructure on the properties were analysed by scanning electronic microscope. It was found that tenslie properties depended on microstructural features strongly. The plots of ultimate tensile strength vs. thickness of α lamellae and elongation vs. volume fraction of primary α phase produced straight lines. The liner equations were determined by fitting the experimental date, respectively. Compared to other parameters, heat treatment had more influence on the tensile strength and the tensile plasticity was more sensitive to the forging temperature.

  3. License - Open TG-GATEs | LSDB Archive [Life Science Database Archive metadata

    Full Text Available List Contact us Open TG-GATEs License License to Use This Database Last updated : 2012/05/24 You may use this database...scribed below. The Standard License specifies the license terms regarding the use of this database and the r...equirements you must follow in using this database. The Additional License specif...icense. Standard License The Standard License for this database is the license specified in the Creative Com...mons Attribution-Share Alike 2.1 Japan . If you use data from this database, plea

  4. Total skin high-dose-rate electron therapy dosimetry using TG-51

    Gossman, Michael S.; Sharma, Subhash C.

    2004-01-01

    An approach to dosimetry for total skin electron therapy (TSET) is discussed using the currently accepted TG-51 high-energy calibration protocol. The methodology incorporates water phantom data for absolute calibration and plastic phantom data for efficient reference dosimetry. The scheme is simplified to include the high-dose-rate mode conversion and provides support for its use, as it becomes more available on newer linear accelerators. Using a 6-field, modified Stanford technique, one may follow the process for accurate determination of absorbed dose

  5. Follow-up of patients with thyroglobulin-antibodies : Rising Tg-Ab trend is a risk factor for recurrence of differentiated thyroid cancer

    de Meer, Siegrid G A; Vorselaars, Wessel M C M; Kist, Jakob W; Stokkel, Marcel P M; de Keizer, Bart; Valk, Gerlof D; Borel Rinkes, Inne H M; Vriens, Menno R

    2017-01-01

    PURPOSE: Differentiated thyroid cancer is the most common endocrine malignancy. Recurrences (5-20%) are the main reason for follow-up. Thyroglobulin (Tg) has proven to be an excellent disease marker, but thyroglobulin-antibodies (Tg-Ab) may interfere with Tg measurement, leading to over or

  6. TG2 regulates the heat-shock response by the post-translational modification of HSF1.

    Rossin, Federica; Villella, Valeria Rachela; D'Eletto, Manuela; Farrace, Maria Grazia; Esposito, Speranza; Ferrari, Eleonora; Monzani, Romina; Occhigrossi, Luca; Pagliarini, Vittoria; Sette, Claudio; Cozza, Giorgio; Barlev, Nikolai A; Falasca, Laura; Fimia, Gian Maria; Kroemer, Guido; Raia, Valeria; Maiuri, Luigi; Piacentini, Mauro

    2018-05-11

    Heat-shock factor 1 (HSF1) is the master transcription factor that regulates the response to proteotoxic stress by controlling the transcription of many stress-responsive genes including the heat-shock proteins. Here, we show a novel molecular mechanism controlling the activation of HSF1. We demonstrate that transglutaminase type 2 (TG2), dependent on its protein disulphide isomerase activity, triggers the trimerization and activation of HSF1 regulating adaptation to stress and proteostasis impairment. In particular, we find that TG2 loss of function correlates with a defect in the nuclear translocation of HSF1 and in its DNA-binding ability to the HSP70 promoter. We show that the inhibition of TG2 restores the unbalance in HSF1-HSP70 pathway in cystic fibrosis (CF), a human disorder characterized by deregulation of proteostasis. The absence of TG2 leads to an increase of about 40% in CFTR function in a new experimental CF mouse model lacking TG2. Altogether, these results indicate that TG2 plays a key role in the regulation of cellular proteostasis under stressful cellular conditions through the modulation of the heat-shock response. © 2018 The Authors.

  7. Effect of Sodium Selenate on Hippocampal Proteome of 3×Tg-AD Mice-Exploring the Antioxidant Dogma of Selenium against Alzheimer's Disease.

    Iqbal, Javed; Zhang, Kaoyuan; Jin, Na; Zhao, Yuxi; Liu, Qiong; Ni, Jiazuan; Shen, Liming

    2018-04-19

    Selenium (Se), an antioxidant trace element, is an important nutrient for maintaining brain functions and is reported to be involved in Alzheimer's disease (AD) pathologies. The present study has been designed to elucidate the protein changes in hippocampus of 3×Tg-AD mice after supplementing sodium selenate as an inorganic source of selenium. By using iTRAQ proteomics technology, 113 differentially expressed proteins (DEPs) are found in AD/WT mice with 37 upregulated and 76 downregulated proteins. Similarly, in selenate-treated 3×Tg-AD (ADSe/AD) mice, 115 DEPs are found with 98 upregulated and 17 downregulated proteins. The third group of mice (ADSe/WT) showed 75 DEPs with 46 upregulated and 29 downregulated proteins. Among these results, 42 proteins (40 downregulated and 2 upregulated) in the diseased group showed reverse expression when treated with selenate. These DEPs are analyzed with different bioinformatics tools and are found associated with various AD pathologies and pathways. Based on their functions, selenate-reversed proteins are classified as structural proteins, metabolic proteins, calcium regulating proteins, synaptic proteins, signaling proteins, stress related proteins, and transport proteins. Six altered AD associated proteins are successfully validated by Western blot analysis. This study shows that sodium selenate has a profound effect on the hippocampus of the triple transgenic AD mice. This might be established as an effective therapeutic agent after further investigation.

  8. Long-term phenylbutyrate administration prevents memory deficits in Tg2576 mice by decreasing Abeta.

    Ricobaraza, Ana; Cuadrado-Tejedor, Mar; Garcia-Osta, Ana

    2011-06-01

    Aberrations in protein folding, processing, and/or degradation are common features of neurodegenerative diseases, such as Alzheimer's disease (AD). Sodium 4-phenylbutyrate (PBA) is a well-known histone deacetylase inhibitor, which increases gene transcription of a number of genes, and also exerts neuroprotective effects. PBA acts as a chemical chaperone reducing the load of mutant or unfolded proteins during cellular stress. Previously, we reported that 5-week administration of PBA reinstated memory loss and dendritic spine densities in the Tg2576 mouse model of AD. In this study we reported that chronic administration of PBA, starting before the onset of disease symptoms (6 month-old) prevents age-related memory deficits in Tg2576 mice. The amelioration of the memory impairment is associated to a decrease in amyloid beta pathology and the glial fibrillary acidic protein (GFAP), suggesting that inflammation was reduced in PBA-treated animals. Together, the beneficial effects of PBA make it a promising agent for the prevention of AD.

  9. Investigation on caloric requirement of biomass pyrolysis using TG-DSC analyzer

    He Fang [Institute of Utilization of Biomass, Shandong University of Technology, No. 12, Zhangzhou Road, Zibo, Shandong 255049 (China)]. E-mail: hf@sdut.edu.cn; Yi Weiming [Institute of Utilization of Biomass, Shandong University of Technology, No. 12, Zhangzhou Road, Zibo, Shandong 255049 (China); Bai Xueyuan [Institute of Utilization of Biomass, Shandong University of Technology, No. 12, Zhangzhou Road, Zibo, Shandong 255049 (China)

    2006-09-15

    The caloric requirement of biomass pyrolysis has an important influence on the course of the thermal conversion. However, precise data are difficult to achieve by the current calculation method because of the complexity of the process. A new method for achieving the caloric requirement of the process by integrating the differential scanning calorimetry (DSC) curves was proposed after the simultaneous thermal analyzer (TG-DSC) and DSC curves were investigated. Experiments were conducted for wheat straw, cotton stalk, pine and peanut shell on a Netsch STA 449C analyzer. Powder samples were put into a platinum crucible with a lid on a high accuracy DSC-cp sample holder in the furnace and then heated from ambient temperature up to the maximum temperature of 973 K at the heating rate of 10 K/min in the analyzer. The product gases were swept away by 25 ml/min nitrogen. Mass changes (TG) and calorimetric effects (DSC) were recorded and analyzed. The process was investigated in detail through comparison of the DTG (differential thermogravimetric) and DSC curves of wheat straw. After the water influence in the DSC was eliminated, the relationship of the caloric requirement with the temperature of the aforementioned dry biomass was obtained by integrating the DSC curve. The results showed that 523 kJ, 459 kJ, 646 kJ and 385 kJ were required, respectively, to increase the temperature of 1 kg of dried wheat straw, cotton stalk, pine and peanut from 303 K to 673 K.

  10. Cheese whey protein recovery by ultrafiltration through transglutaminase (TG) catalysis whey protein cross-linking.

    Wen-Qiong, Wang; Lan-Wei, Zhang; Xue, Han; Yi, Lu

    2017-01-15

    In whey ultrafiltration (UF) production, two main problems are whey protein recovery and membrane fouling. In this study, membrane coupling protein transglutaminase (TG) catalysis protein cross-linking was investigated under different conditions to find out the best treatment. We found that the optimal conditions for protein recovery involved catalyzing whey protein cross-linking with TG (40U/g whey proteins) at 40°C for 60min at pH 5.0. Under these conditions, the recovery rate was increased 15-20%, lactose rejection rate was decreased by 10%, and relative permeate flux was increase 30-40% compared to the sample without enzyme treatment (control). It was noticeable that the total resistance and cake resistance were decreased after enzyme catalysis. This was mainly due to the increased particle size and decreased zeta potential. Therefore, membrane coupling enzyme catalysis protein cross-linking is a potential means for further use. Copyright © 2016. Published by Elsevier Ltd.

  11. Tissue Transglutaminase (TG2)-Induced Inflammation in Initiation, Progression, and Pathogenesis of Pancreatic Cancer

    Mehta, Kapil, E-mail: kmehta@mdanderson.org; Han, Amy [Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 (United States); Graduate School of Biomedical Sciences, The University of Texas Health Science Center, Houston, TX 77030 (United States)

    2011-02-25

    Pancreatic cancer (PC) is among the deadliest cancers, with a median survival of six months. It is generally believed that infiltrating PC arises through the progression of early grade pancreatic intraepithelial lesions (PanINs). In one model of the disease, the K-ras mutation is an early molecular event during progression of pancreatic cancer; it is followed by the accumulation of additional genetic abnormalities. This model has been supported by animal studies in which activated K-ras and p53 mutations produced metastatic pancreatic ductal adenocarcinoma in mice. According to this model, oncogenic K-ras induces PanIN formation but fails to promote the invasive stage. However, when these mice are subjected to caerulein treatment, which induces a chronic pancreatitis-like state and inflammatory response, PanINs rapidly progress to invasive carcinoma. These results are consistent with epidemiologic studies showing that patients with chronic pancreatitis have a much higher risk of developing PC. In line with these observations, recent studies have revealed elevated expression of the pro-inflammatory protein tissue transglutaminase (TG2) in early PanINs, and its expression increases even more as the disease progresses. In this review we discuss the implications of increased TG2 expression in initiation, progression, and pathogenesis of pancreatic cancer.

  12. WE-A-18A-01: TG246 On Patient Dose From Diagnostic Radiation

    Supanich, M [Rush University Medical Center, Chicago, IL (United States); Dong, F [The Cleveland Clinic, Solon, OH (United States); Andersson, J [Umea University, Umea (Sweden); Pavlicek, W [Mayo Clinic Arizona, Scottsdale, AZ (United States); Bolch, W [University Florida, Gainesville, FL (United States); Fetterly, K [Mayo Clinic, Rochester, MN (United States)

    2014-06-15

    Radiation dose from diagnostic and interventional radiations continues to be a focus of the regulatory, accreditation and standards organizations in the US and Europe. A Joint AAPM/EFOMP effort has been underway in the past year — having the goal to assist the clinical medical physicist with communicating optional and varied approaches in estimating (and validating) patient dose. In particular, the tools provided by DICOM Radiation Dose Structured Reports, either by themselves or as part of a networked data repository of dose related information are a rich source of actionable information. The tools of the medical physicist have evolved to include using DICOM data in meaningful ways to look at patient dose with respect to imaging practices. In addition to how accurate or reproducible a dose value is (totally necessary and our traditional workspace) it is now being asked how reproducible (patient to patient, device to device) are the delivered doses (new tasking)? Clinical medical physicists are best equipped to assist our radiology and technologist colleagues with this effort. The purpose of this session is to review the efforts of TG246 - bringing forward a summary content of the TG246 Report including specific dose descriptors for CT and Fluoroscopy — particularly in a focus of leveraging the RDSR as a means for monitoring good practices ALARA. Additionally, rapidly evolving technologies for more refined dose estimates are now in use. These will be presented as they look to having highly patient specific dose estimates in automated use.

  13. High Tg and fast curing epoxy-based anisotropic conductive paste for electronic packaging

    Keeratitham, Waralee; Somwangthanaroj, Anongnat

    2016-03-01

    Herein, our main objective is to prepare the fast curing epoxy system with high glass transition temperature (Tg) by incorporating the multifunctional epoxy resin into the mixture of diglycidyl ether of bisphenol A (DGEBA) as a major epoxy component and aromatic diamine as a hardener. Furthermore, the curing behavior as well as thermal and thermomechanical properties were investigated by differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA) and thermomechanical analysis (TMA). It was found that Tg obtained from tan δ of DGEBA/aromatic diamine system increased from 100 °C to 205 °C with the presence of 30 percentage by weight of multifunctional epoxy resin. Additionally, the isothermal DSC results showed that the multifunctional epoxy resin can accelerate the curing reaction of DGEBA/aromatic diamine system. Namely, a high degree of curing (˜90%) was achieved after a few minutes of curing at low temperature of 130 °C, owing to a large number of epoxy ring of multifunctional epoxy resin towards the active hydrogen atoms of aromatic diamine.

  14. Gender-Specific Neuroimmunoendocrine Response to Treadmill Exercise in 3xTg-AD Mice

    Lydia Giménez-Llort

    2010-01-01

    Full Text Available The 3xTg-AD mouse develops a progressive Alzheimer's disease- (AD- like brain pathology that causes cognitive- and neuropsychiatric-like symptoms of dementia. Since its neuroimmunoendocrine axis is likewise impaired, this mouse is also useful for modelling complex age-related neurodegeneration. This study analyzed behavioral, physiological, neurochemical, pathological and immunoendocrine alterations in male and female 3xTg-AD mice and assayed the effects of a short therapy of forced physical exercise at the moderate pathology stage of 6 months of age. Gender effects were observed in most AD-related pathology and dysfunctions. Five weeks of treadmill training produced beneficial effects, such as the reduction of brain oxidative stress and GABA-A receptor dysfunction in males and improvement of sensorimotor function in females. In both sexes, exercise decreased the brain amyloid 42/40 ratio levels. The results highlight the importance of analyzing experimental therapies in both mouse model genders in order to improve our understanding of the disease and develop more appropriate therapies.

  15. Cystatin C, CRP, log TG/HDLc and metabolic syndrome are associated with microalbuminuria in hypertension

    Moura, Rafaela do Socorro Souza e Silva [Pós-Graduação em Ciências Médicas, Faculdade de Medicina, Universidade de Brasília, Brasília, DF (Brazil); Vasconcelos, Daniel França [Área de Cardiologia, Faculdade de Medicina, Universidade de Brasília, Brasília, DF (Brazil); Freitas, Eduardo [Departamento de Estatística, Universidade de Brasília, Brasília, DF (Brazil); Moura, Flavio José Dutra de; Rosa, Tânia Torres; Veiga, Joel Paulo Russomano, E-mail: joelprv@unb.br [Área de Clínica Médica, Nefrologia, Faculdade de Medicina, Universidade de Brasília, Brasília, DF (Brazil)

    2014-01-15

    In patients with systemic hypertension, microalbuminuria is a marker of endothelial damage and is associated with an increased risk for cardiovascular disease. To determine the factors that may lead to the occurrence of microalbuminuria in hypertensive patients with serum creatinine lower than 1.5 mg/dL. This cross-sectional study included 133 Brazilians with essential hypertension followed up at a hypertension outpatient clinic. Those with serum creatinine higher than 1.5 mg/dL, as well as those with diabetes mellitus, were excluded. Systolic and diastolic blood pressures were measured, and body mass index (BMI) and GFR estimated by using the CKD-EPI formula were calculated. The serum levels of the following were assessed: CysC, creatinine, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, C-reactive protein (CRP) and fasting glucose. Microalbuminuria was determined in 24-hour urine. Hypertensive patients were classified according to the presence of one or more criteria for metabolic syndrome. In a multiple regression analysis, the serum levels of CysC and CRP, the atherogenic index log TG/HDLc and the presence of three or more criteria for metabolic syndrome were positively correlated with microalbuminuria (r{sup 2}: 0.277, p < 0.05). CysC, CRP, log TG/HDLc, and the presence of three or more criteria for metabolic syndrome, regardless of serum creatinine, were associated with microalbuminuria, an early marker of kidney damage and cardiovascular risk in patients with essential hypertension.

  16. Cystatin C, CRP, log TG/HDLc and metabolic syndrome are associated with microalbuminuria in hypertension

    Moura, Rafaela do Socorro Souza e Silva; Vasconcelos, Daniel França; Freitas, Eduardo; Moura, Flavio José Dutra de; Rosa, Tânia Torres; Veiga, Joel Paulo Russomano

    2014-01-01

    In patients with systemic hypertension, microalbuminuria is a marker of endothelial damage and is associated with an increased risk for cardiovascular disease. To determine the factors that may lead to the occurrence of microalbuminuria in hypertensive patients with serum creatinine lower than 1.5 mg/dL. This cross-sectional study included 133 Brazilians with essential hypertension followed up at a hypertension outpatient clinic. Those with serum creatinine higher than 1.5 mg/dL, as well as those with diabetes mellitus, were excluded. Systolic and diastolic blood pressures were measured, and body mass index (BMI) and GFR estimated by using the CKD-EPI formula were calculated. The serum levels of the following were assessed: CysC, creatinine, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, C-reactive protein (CRP) and fasting glucose. Microalbuminuria was determined in 24-hour urine. Hypertensive patients were classified according to the presence of one or more criteria for metabolic syndrome. In a multiple regression analysis, the serum levels of CysC and CRP, the atherogenic index log TG/HDLc and the presence of three or more criteria for metabolic syndrome were positively correlated with microalbuminuria (r 2 : 0.277, p < 0.05). CysC, CRP, log TG/HDLc, and the presence of three or more criteria for metabolic syndrome, regardless of serum creatinine, were associated with microalbuminuria, an early marker of kidney damage and cardiovascular risk in patients with essential hypertension

  17. Thermal Phenomena in the Friction Process of the TG15 - Hard Anodic Coating Couple

    Służałek G.

    2016-09-01

    Full Text Available The paper presents a one-dimensional model of heat conduction in a couple consisting of a cylinder made of a sliding plastic material, TG15, and a cuboid made of alloy AW 6061 coated with a hard anodic coating, where the couple is heated with the heat generated during friction. TG15 is a composite material based on polytetrafluoroethylene (PTFE with a 15% graphite filler, used for piston rings in oil-free air-compressors. Measurement of temperature in the friction zone is extremely important for the understanding and analysis of the phenomena occurring therein. It is practically impossible to introduce a temperature sensor in such a place. Therefore, the interaction taking place in such a couple was modelled using numerical methods. In order to simplify and accelerate the calculations, a one-dimensional model and constant thermophysical parameters of the materials participating in friction were adopted. To solve the proposed model, the finite difference method was used (FDM. The resultant system of equations was solved by means of an explicit scheme.

  18. MO-A-BRB-01: Review of TG-262 Internal Survey of Practices in EMR for External Beam Therapy

    Mechalakos, J.

    2015-01-01

    The process of converting to an electronic chart for radiation therapy can be daunting. It requires a dedicated committee to first research and choose appropriate software, to review the entire documentation policy and flow of the clinic, to convert this system to electronic form or if necessary, redesign the system to more easily conform to the electronic process. Those making the conversion and those who already use electronic charting would benefit from the shared experience of those who have been through the process in the past. Therefore TG262 was convened to provide guidance on electronic charting for external beam radiation therapy and brachytherapy. This course will present the results of an internal survey of task group members on EMR practices in External Beam Radiation Therapy as well as discuss important issues in EMR development and structure for both EBRT and brachytherapy. Learning Objectives: Be familiarized with common practices and pitfalls in development and maintenance of an electronic chart in Radiation Oncology Be familiarized with important issues related to electronic charting in External Beam Radiation Therapy Be familiarized with important issues related to electronic charting in Brachytherapy

  19. Eplerenone ameliorates the phenotypes of metabolic syndrome with NASH in liver-specific SREBP-1c Tg mice fed high-fat and high-fructose diet.

    Wada, Tsutomu; Miyashita, Yusuke; Sasaki, Motohiro; Aruga, Yusuke; Nakamura, Yuto; Ishii, Yoko; Sasahara, Masakiyo; Kanasaki, Keizo; Kitada, Munehiro; Koya, Daisuke; Shimano, Hitoshi; Tsuneki, Hiroshi; Sasaoka, Toshiyasu

    2013-12-01

    Because the renin-angiotensin-aldosterone system has been implicated in the development of insulin resistance and promotion of fibrosis in some tissues, such as the vasculature, we examined the effect of eplerenone, a selective mineralocorticoid receptor (MR) antagonist, on nonalcoholic steatohepatitis (NASH) and metabolic phenotypes in a mouse model reflecting metabolic syndrome in humans. We adopted liver-specific transgenic (Tg) mice overexpressing the active form of sterol response element binding protein-1c (SREBP-1c) fed a high-fat and fructose diet (HFFD) as the animal model in the present study. When wild-type (WT) C57BL/6 and liver-specific SREBP-1c Tg mice grew while being fed HFFD for 12 wk, body weight and epididymal fat weight increased in both groups with an elevation in blood pressure and dyslipidemia. Glucose intolerance and insulin resistance were also observed. Adipose tissue hypertrophy and macrophage infiltration with crown-like structure formation were also noted in mice fed HFFD. Interestingly, the changes noted in both genotypes fed HFFD were significantly ameliorated with eplerenone. HFFD-fed Tg mice exhibited the histological features of NASH in the liver, including macrovesicular steatosis and fibrosis, whereas HFFD-fed WT mice had hepatic steatosis without apparent fibrotic changes. Eplerenone effectively ameliorated these histological abnormalities. Moreover, the direct suppressive effects of eplerenone on lipopolysaccharide-induced TNFα production in the presence and absence of aldosterone were observed in primary-cultured Kupffer cells and bone marrow-derived macrophages. These results indicated that eplerenone prevented the development of NASH and metabolic abnormalities in mice by inhibiting inflammatory responses in both Kupffer cells and macrophages.

  20. A generic high-dose rate {sup 192}Ir brachytherapy source for evaluation of model-based dose calculations beyond the TG-43 formalism

    Ballester, Facundo, E-mail: Facundo.Ballester@uv.es [Department of Atomic, Molecular and Nuclear Physics, University of Valencia, Burjassot 46100 (Spain); Carlsson Tedgren, Åsa [Department of Medical and Health Sciences (IMH), Radiation Physics, Faculty of Health Sciences, Linköping University, Linköping SE-581 85, Sweden and Department of Medical Physics, Karolinska University Hospital, Stockholm SE-171 76 (Sweden); Granero, Domingo [Department of Radiation Physics, ERESA, Hospital General Universitario, Valencia E-46014 (Spain); Haworth, Annette [Department of Physical Sciences, Peter MacCallum Cancer Centre and Royal Melbourne Institute of Technology, Melbourne, Victoria 3000 (Australia); Mourtada, Firas [Department of Radiation Oncology, Helen F. Graham Cancer Center, Christiana Care Health System, Newark, Delaware 19713 (United States); Fonseca, Gabriel Paiva [Instituto de Pesquisas Energéticas e Nucleares – IPEN-CNEN/SP, São Paulo 05508-000, Brazil and Department of Radiation Oncology (MAASTRO), GROW, School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht 6201 BN (Netherlands); Zourari, Kyveli; Papagiannis, Panagiotis [Medical Physics Laboratory, Medical School, University of Athens, 75 MikrasAsias, Athens 115 27 (Greece); Rivard, Mark J. [Department of Radiation Oncology, Tufts University School of Medicine, Boston, Massachusetts 02111 (United States); Siebert, Frank-André [Clinic of Radiotherapy, University Hospital of Schleswig-Holstein, Campus Kiel, Kiel 24105 (Germany); Sloboda, Ron S. [Department of Medical Physics, Cross Cancer Institute, Edmonton, Alberta T6G 1Z2, Canada and Department of Oncology, University of Alberta, Edmonton, Alberta T6G 2R3 (Canada); and others

    2015-06-15

    Purpose: In order to facilitate a smooth transition for brachytherapy dose calculations from the American Association of Physicists in Medicine (AAPM) Task Group No. 43 (TG-43) formalism to model-based dose calculation algorithms (MBDCAs), treatment planning systems (TPSs) using a MBDCA require a set of well-defined test case plans characterized by Monte Carlo (MC) methods. This also permits direct dose comparison to TG-43 reference data. Such test case plans should be made available for use in the software commissioning process performed by clinical end users. To this end, a hypothetical, generic high-dose rate (HDR) {sup 192}Ir source and a virtual water phantom were designed, which can be imported into a TPS. Methods: A hypothetical, generic HDR {sup 192}Ir source was designed based on commercially available sources as well as a virtual, cubic water phantom that can be imported into any TPS in DICOM format. The dose distribution of the generic {sup 192}Ir source when placed at the center of the cubic phantom, and away from the center under altered scatter conditions, was evaluated using two commercial MBDCAs [Oncentra{sup ®} Brachy with advanced collapsed-cone engine (ACE) and BrachyVision ACUROS{sup TM}]. Dose comparisons were performed using state-of-the-art MC codes for radiation transport, including ALGEBRA, BrachyDose, GEANT4, MCNP5, MCNP6, and PENELOPE2008. The methodologies adhered to recommendations in the AAPM TG-229 report on high-energy brachytherapy source dosimetry. TG-43 dosimetry parameters, an along-away dose-rate table, and primary and scatter separated (PSS) data were obtained. The virtual water phantom of (201){sup 3} voxels (1 mm sides) was used to evaluate the calculated dose distributions. Two test case plans involving a single position of the generic HDR {sup 192}Ir source in this phantom were prepared: (i) source centered in the phantom and (ii) source displaced 7 cm laterally from the center. Datasets were independently produced by

  1. A Novel Form of Compensation in the Tg2576 Amyloid Mouse Model of Alzheimer’s Disease

    Somogyi, Attila; Katonai, Zoltán; Alpár, Alán; Wolf, Ervin

    2016-01-01

    One century after its first description, pathology of Alzheimer’s disease (AD) is still poorly understood. Amyloid-related dendritic atrophy and membrane alterations of susceptible brain neurons in AD, and in animal models of AD are widely recognized. However, little effort has been made to study the potential effects of combined morphological and membrane alterations on signal transfer and synaptic integration in neurons that build up affected neural networks in AD. In this study spatial reconstructions and electrophysiological measurements of layer II/III pyramidal neurons of the somatosensory cortex from wild-type (WT) and transgenic (TG) human amyloid precursor protein (hAPP) overexpressing Tg2576 mice were used to build faithful segmental cable models of these neurons. Local synaptic activities were simulated in various points of the dendritic arbors and properties of subthreshold dendritic impulse propagation and predictors of synaptic input pattern recognition ability were quantified and compared in modeled WT and TG neurons. Despite the widespread dendritic degeneration and membrane alterations in mutant mouse neurons, surprisingly little, or no change was detected in steady-state and 50 Hz sinusoidal voltage transfers, current transfers, and local and propagation delays of PSPs traveling along dendrites of TG neurons. Synaptic input pattern recognition ability was also predicted to be unaltered in TG neurons in two different soma-dendritic membrane models investigated. Our simulations predict the way how subthreshold dendritic signaling and pattern recognition are preserved in TG neurons: amyloid-related membrane alterations compensate for the pathological effects that dendritic atrophy has on subthreshold dendritic signal transfer and integration in layer II/III somatosensory neurons of this hAPP mouse model for AD. Since neither propagation of single PSPs nor integration of multiple PSPs (pattern recognition) changes in TG neurons, we conclude that AD

  2. WE-G-BRB-08: TG-51 Calibration of First Commercial MRI-Guided IMRT System in the Presence of 0.35 Tesla Magnetic Field.

    Goddu, S; Green, O Pechenaya; Mutic, S

    2012-06-01

    The first real-time-MRI-guided radiotherapy system has been installed in a clinic and it is being evaluated. Presence of magnetic field (MF) during radiation output calibration may have implications on ionization measurements and there is a possibility that standard calibration protocols may not be suitable for dose measurements for such devices. In this study, we evaluated whether a standard calibration protocol (AAPM- TG-51) is appropriate for absolute dose measurement in presence of MF. Treatment delivery of the ViewRay (VR) system is via three 15,000Ci Cobalt-60 heads positioned 120-degrees apart and all calibration measurements were done in the presence of 0.35T MF. Two ADCL- calibrated ionization-chambers (Exradin A12, A16) were used for TG-51 calibration. Chambers were positioned at 5-cm depth, (SSD=105cm: VR's isocenter), and the MLC leaves were shaped to a 10.5cm × 10.5 cm field size. Percent-depth-dose (PDD) measurements were performed for 5 and 10 cm depths. Individual output of each head was measured using the AAPM- TG51 protocol. Calibration accuracy for each head was subsequently verified by Radiological Physics Center (RPC) TLD measurements. Measured ion-recombination (Pion) and polarity (Ppol) correction factors were less-than 1.002 and 1.006, respectively. Measured PDDs agreed with BJR-25 within ±0.2%. Maximum dose rates for the reference field size at VR's isocenter for heads 1, 2 and 3 were 1.445±0.005, 1.446±0.107, 1.431±0.006 Gy/minute, respectively. Our calibrations agreed with RPC- TLD measurements within ±1.3%, ±2.6% and ±2.0% for treatment-heads 1, 2 and 3, respectively. At the time of calibration, mean activity of the Co-60 sources was 10,800Ci±0.1%. This study shows that the TG- 51 calibration is feasible in the presence of 0.35T MF and the measurement agreement is within the range of results obtainable for conventional treatment machines. Drs. Green, Goddu, and Mutic served as scientific consultants for ViewRay, Inc. Dr. Mutic

  3. U.S. Army RDECOM-ARDEC's results of the TG-53 experiment and field test

    Desai, Sachi V.; Morcos, Amir

    2009-05-01

    Herein is described the U.S. Army RDECOM-ARDEC's purpose and series of activities conducted at the 2008 NATO SET-093 TG-53 experiment and field test. The overall purpose of the field test as stated by SET-093 panel was to provide a baseline test capable of providing relevant scenarios and data regarding a variety of impulsive generated acoustic events. As organized, the field experiment also allowed the room o study sensor interoperability across multiple platforms and multi-national users via the spider communication framework/reporting structure. This multinational network maintained by the host ETBS with a standardized messaging format with specific goals for each participating organization. ARDEC's role and purpose for the test was to provide situational awareness via the Spider and associated messaging format to the ETBS command center while continuing to gather unique acoustic data from various vantage points. ARDEC had several deliverables for the TG-53 field experiment derived from the mission and spirit of the field test. The most relevant deliverable was to demonstrate sensor interoperability via the Spider network and provide situational awareness by describing the said mortar/artillery events. The second purpose revolved around a relevant environment algorithm validation of the muzzle blast discrimination for future UGS transition in particular the UTAMS II. The algorithm validation information remained internal to the specific data acquisition system and not broadcasted out on the Spider network. The TG-53 field experiments provided the added opportunity to further test and refine the algorithm based on the discrete wavelet transform (DWT) and multiresolution analysis. These techniques are used to classify and reliably discriminates between launch and impact artillery and/or mortar events via acoustic signals produced during detonation. Distinct characteristics are found within the acoustic signatures since impact events emphasize concussive and

  4. Structure investigations on zirconium phosphate preparates by means of DTA, ETA, and TG

    Herbell, J.D.; Specht, S.; Born, H.J.

    1976-01-01

    The simultanous DTA, ETA and TG inorganic ion exchanger based on zirconium phosphate enables the clear interpretation of the effects occuring. In particular it can be seen that the fast transition in amorphous preparates at high temperature of a badly defined form of pyrophosphate into the cubic crystalline substances, however a measurable energy release by means of DTA is not observed due to the slight mobility of the atoms in the crystal lattice. This effect on the other hand may be seen using ETA. In addition, an exothermal reaction occuring in some preparates, especially in cation charged ones, was traced back to the forming of part-crystalline structures which could be especially fast and sensitively characterized using DTA. (orig.) [de

  5. Solid-phase microextraction for bioconcentration studies according to OECD TG 305

    Duering, Rolf-Alexander; Boehm, Leonard [Land Use and Nutrition (IFZ) Justus Liebig University Giessen, Institute of Soil Science and Soil Conservation, Research Centre for BioSystems, Giessen (Germany); Schlechtriem, Christian [Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Schmallenberg (Germany)

    2012-12-15

    An important aim of the European Community Regulation on chemicals and their safe use is the identification of (very) persistent, (very) bioaccumulative, and toxic substances. In other regulatory chemical safety assessments (pharmaceuticals, biocides, pesticides), the identification of such (very) persistent, (very) bioaccumulative, and toxic substances is of increasing importance. Solid-phase microextraction is especially capable of extracting total water concentrations as well as the freely dissolved fraction of analytes in the water phase, which is available for bioconcentration in fish. However, although already well established in environmental analyses to determine and quantify analytes mainly in aqueous matrices, solid-phase microextraction is still a rather unusual method in regulatory ecotoxicological research. Here, the potential benefits and drawbacks of solid-phase microextraction are discussed as an analytical routine approach for aquatic bioconcentration studies according to OECD TG 305, with a special focus on the testing of hydrophobic organic compounds characterized by log K{sub OW}> 5. (orig.)

  6. Synthesis, characterization and TG-DSC study of cadmium halides adducts with caffeine

    Farias, Robson F. de; Silva, Ademir O. da; Silva, Umberto G. da

    2003-11-28

    The synthesis, characterization and TG-DSC study of the compounds CdX{sub 2}{center_dot}ncaff, for which X: Cl, Br and I; n=1 and 2 and caff: caffeine is reported. It is verified that caffeine is coordinated through more than one coordination site, despite the fact that the nitrogen of the imidazole ring is the main coordination site. The following thermal stability trend is observed: Cl>Br>I and monoadducts are more stable than bisadducts. The thermal degradation (td) enthalpies have the values (kJ mol{sup -1}): 58.2 and 71.5; 74.9 and 91.4; 31.1 and 47.5 for Cl, Br and I mono and bisadducts, respectively.

  7. Investigation of hydropyrolysis behaviour of Shenmu macerals by TG-MS

    Sun, Q.; Li, W.; Chen, H.; Li, B. [Analysis and Test Center, Shandong Academy of Sciences, Jinan (China)

    2004-12-01

    The hydropyrolysis characteristics of Shenmu coal and its macerals were investigated using TG-151 thermo balance, and the evolved gases were on-line analyzed by mass spectroscopy. The results show that vitrinite has higher volatile yield, maximum weight loss rate and lower peak temperature. Vitrinite produces more C{sub 1} - C{sub 4} lighter hydrocarbons and C{sub 5} - C{sub 8} aromatic hydrocarbons than inertinite. Vitrinite has a higher water yield, which is consistent with that the vitrinite has higher phenolic-OH content. The difference in the evolved gases and water between pyrolysis and hydropyrolysis shows the effect of hydrogenation and hydrocracking during hydropyolysis. 11 refs., 4 figs., 1 tab.

  8. Dynamic traffic grooming with Spectrum Engineering (TG-SE) in flexible grid optical networks

    Yu, Xiaosong; Zhao, Yongli; Zhang, Jiawei; Wang, Jianping; Zhang, Guoying; Chen, Xue; Zhang, Jie

    2015-12-01

    Flexible grid has emerged as an evolutionary technology to satisfy the ever increasing demand for higher spectrum efficiency and operational flexibility. To optimize the spectrum resource utilization, this paper introduces the concept of Spectrum Engineering in flex-grid optical networks. The sliceable optical transponder has been proposed to offload IP traffic to the optical layer and reduce the number of IP router ports and transponders. We discuss the impact of sliceable transponder in traffic grooming and propose several traffic-grooming schemes with Spectrum Engineering (TG-SE). Our results show that there is a tradeoff among different traffic grooming policies, which should be adopted based on the network operator's objectives. The proposed traffic grooming with Spectrum Engineering schemes can reduce OPEX as well as increase spectrum efficiency by efficiently utilizing the bandwidth variability and capability of sliceable optical transponders.

  9. [Morphological analysis of the hippocampal region associated with an innate behaviour task in the transgenic mouse model (3xTg-AD) for Alzheimer disease].

    Orta-Salazar, E; Feria-Velasco, A; Medina-Aguirre, G I; Díaz-Cintra, S

    2013-10-01

    Different animal models for Alzheimer disease (AD) have been designed to support the hypothesis that the neurodegeneration (loss of neurons and synapses with reactive gliosis) associated with Aβ and tau deposition in these models is similar to that in the human brain. These alterations produce functional changes beginning with decreased ability to carry out daily and social life activities, memory loss, and neuropsychiatric disorders in general. Neuronal alteration plays an important role in early stages of the disease, especially in the CA1 area of hippocampus in both human and animal models. Two groups (WT and 3xTg-AD) of 11-month-old female mice were used in a behavioural analysis (nest building) and a morphometric analysis of the CA1 region of the dorsal hippocampus. The 3xTg-AD mice showed a 50% reduction in nest quality associated with a significant increase in damaged neurons in the CA1 hippocampal area (26%±6%, Pde Neurología. Published by Elsevier Espana. All rights reserved.

  10. A meta-analysis of adiponectin gene rs22411766 T>G polymorphism and ischemic stroke susceptibility

    Xiuju Chen

    2016-01-01

    Full Text Available Several studies have investigated the correlation between adiponectin gene rs22411766 T>G polymorphism and ischemic stroke risk. However, the results were not conclusive with each other. Therefore, to overcome this obstacle, we performed this meta-analysis to further explicate the adiponectin gene rs22411766 T>G polymorphism and ischemic stroke susceptibility. Case-control or cohort studies focused on adiponectin gene rs22411766 T>G polymorphism and ischemic stroke risk were electronic searched in the databases of Medline, Pubmed, Cochrane library, Excerpta Medica database(EMBASE and China National Knowledge Infrastructure (CNKI. All the potentially relevant studies were included in this meta-analysis. The association between adiponectin gene rs22411766 T>G polymorphism and ischemic stroke was expressed by odds ratio with its confidence interval. Publication bias has been assessed by begg’s funnel plot. All the analyses have been performed by Revman 5.1 statistical software. Finally, a total of six studies with 1,345 cases and 1,421 controls were included in this meta-analysis. Our results demonstrated that there was a significant association between adiponectin gene rs22411766 T>G polymorphism and ischemic stroke risk (p<0.05. People with G single nucleotide of adiponectin gene have the increased risk of developing ischemic stroke compared to T single nucleotide.

  11. Technical Report: TG-142 compliant and comprehensive quality assurance tests for respiratory gating

    Woods, Kyle [Department of Radiation Oncology, Ohio State University, Columbus, Ohio 43210 (United States); Rong, Yi, E-mail: yrong@ucdavis.edu [Department of Radiation Oncology, University of California Davis Comprehensive Cancer Center, Sacramento, California 95817 (United States)

    2015-11-15

    Purpose: To develop and establish a comprehensive gating commissioning and quality assurance procedure in compliance with TG-142. Methods: Eight Varian TrueBeam Linacs were used for this study. Gating commissioning included an end-to-end test and baseline establishment. The end-to-end test was performed using a CIRS dynamic thoracic phantom with a moving cylinder inside the lung, which was used for carrying both optically simulated luminescence detectors (OSLDs) and Gafchromic EBT2 films while the target is moving, for a point dose check and 2D profile check. In addition, baselines were established for beam-on temporal delay and calibration of the surrogate, for both megavoltage (MV) and kilovoltage (kV) beams. A motion simulation device (MotionSim) was used to provide periodic motion on a platform, in synchronizing with a surrogate motion. The overall accuracy and uncertainties were analyzed and compared. Results: The OSLD readings were within 5% compared to the planned dose (within measurement uncertainty) for both phase and amplitude gated deliveries. Film results showed less than 3% agreement to the predicted dose with a standard sinusoid motion. The gate-on temporal accuracy was averaged at 139 ± 10 ms for MV beams and 92 ± 11 ms for kV beams. The temporal delay of the surrogate motion depends on the motion speed and was averaged at 54.6 ± 3.1 ms for slow, 24.9 ± 2.9 ms for intermediate, and 23.0 ± 20.1 ms for fast speed. Conclusions: A comprehensive gating commissioning procedure was introduced for verifying the output accuracy and establishing the temporal accuracy baselines with respiratory gating. The baselines are needed for routine quality assurance tests, as suggested by TG-142.

  12. AbetaPP induces cdk5-dependent tau hyperphosphorylation in transgenic mice Tg2576.

    Otth, Carola; Concha, Ilona I; Arendt, Thomas; Stieler, Jens; Schliebs, Reinhard; González-Billault, Christian; Maccioni, Ricardo B

    2002-10-01

    Previous studies of Abeta-induced neuronal damage of hippocampal cells in culture have provided strong evidence that deregulation of the Cdk5/p35 kinase system is involved in the neurodegeneration pathway. Cdk5 inhibitors and antisense probes neuroprotected hippocampal cells against the neurotoxic action of Abeta. To further investigate the mechanisms underlying the participation of Cdk5 in neuronal degeneration, the transgenic mouse containing the Swedish mutations, Tg2576, was used as an animal model. Immunocytochemical studies using anti-Abeta(1-17) antibody evidenced the presence of labeled small-clustered core plaques in the hippocampus and cortex of 18-month-old transgenic mice brains. The loss of granular cells without a compressed appearance was detected in the vicinity of the cores in the dentate gyrus of the hippocampus. Immunostaining of Tg2576 brain sections with antibodies AT8, PHF1 and GFAP labeled punctuate dystrophic neurites in and around the amyloid core. Reactive astrogliosis around the plaques in the hippocampus was also observed. Studies at the molecular level showed differences in the expression of the truncated Cdk5 activator p25 in the transgenic animal, as compared with wild type controls. However no differences in Cdk5 levels were detected, thus corroborating previous cellular findings. Interestingly, hyperphosphorylated tau epitopes were substantially increased as assessed with the AT8 and PHF1 antibodies, in agreement with the observation of a p25 increase in the transgenic animal. These observations strongly suggest that the increased exposure of Alzheimer's type tau phosphoepitopes in the transgenic mice correlated with deregulation of Cdk5 leading to an increase in p25 levels. These studies also provide further evidence on the links between extraneuronal amyloid deposition and tau pathology.

  13. The polyphenol oleuropein aglycone protects TgCRND8 mice against Aß plaque pathology.

    Cristina Grossi

    Full Text Available The claimed beneficial effects of the Mediterranean diet include prevention of several age-related dysfunctions including neurodegenerative diseases and Alzheimer-like pathology. These effects have been related to the protection against cognitive decline associated with aging and disease by a number of polyphenols found in red wine and extra virgin olive oil. The double transgenic TgCRND8 mice (overexpressing the Swedish and Indiana mutations in the human amyloid precursor protein, aged 1.5 and 4, and age-matched wild type control mice were used to examine in vivo the effects of 8 weeks dietary supplementation of oleuropein aglycone (50 mg/kg of diet, the main polyphenol found in extra virgin olive oil. We report here that dietary supplementation of oleuropein aglycone strongly improves the cognitive performance of young/middle-aged TgCRND8 mice, a model of amyloid-ß deposition, respect to age-matched littermates with un-supplemented diet. Immunofluorescence analysis of cerebral tissue in oleuropein aglycone-fed transgenic mice showed remarkably reduced ß-amyloid levels and plaque deposits, which appeared less compact and "fluffy"; moreover, microglia migration to the plaques for phagocytosis and a remarkable reduction of the astrocyte reaction were evident. Finally, oleuropein aglycone-fed mice brain displayed an astonishingly intense autophagic reaction, as shown by the increase of autophagic markers expression and of lysosomal activity. Data obtained with cultured cells confirmed the latter evidence, suggesting mTOR regulation by oleuropein aglycone. Our results support, and provide mechanistic insights into, the beneficial effects against Alzheimer-associated neurodegeneration of a polyphenol enriched in the extra virgin olive oil, a major component of the Mediterranean diet.

  14. TH-B-204-03: TG-199: Implanted Markers for Radiation Treatment Verification

    Wang, Z.

    2016-01-01

    Implanted markers as target surrogates have been widely used for treatment verification, as they provide safe and reliable monitoring of the inter- and intra-fractional target motion. The rapid advancement of technology requires a critical review and recommendation for the usage of implanted surrogates in current field. The symposium, also reporting an update of AAPM TG 199 - Implanted Target Surrogates for Radiation Treatment Verification, will be focusing on all clinical aspects of using the implanted target surrogates for treatment verification and related issues. A wide variety of markers available in the market will be first reviewed, including radiopaque markers, MRI compatible makers, non-migrating coils, surgical clips and electromagnetic transponders etc. The pros and cons of each kind will be discussed. The clinical applications of implanted surrogates will be presented based on different anatomical sites. For the lung, we will discuss gated treatments and 2D or 3D real-time fiducial tracking techniques. For the prostate, we will be focusing on 2D-3D, 3D-3D matching and electromagnetic transponder based localization techniques. For the liver, we will review techniques when patients are under gating, shallow or free breathing condition. We will review techniques when treating challenging breast cancer as deformation may occur. Finally, we will summarize potential issues related to the usage of implanted target surrogates with TG 199 recommendations. A review of fiducial migration and fiducial derived target rotation in different disease sites will be provided. The issue of target deformation, especially near the diaphragm, and related suggestions will be also presented and discussed. Learning Objectives: Knowledge of a wide variety of markers Knowledge of their application for different disease sites Understand of issues related to these applications Z. Wang: Research funding support from Brainlab AG Q. Xu: Consultant for Accuray; Q. Xu, I am a consultant

  15. TH-B-204-00: Implanted Markers for Radiation Therapy and TG 199 Update

    2016-01-01

    Implanted markers as target surrogates have been widely used for treatment verification, as they provide safe and reliable monitoring of the inter- and intra-fractional target motion. The rapid advancement of technology requires a critical review and recommendation for the usage of implanted surrogates in current field. The symposium, also reporting an update of AAPM TG 199 - Implanted Target Surrogates for Radiation Treatment Verification, will be focusing on all clinical aspects of using the implanted target surrogates for treatment verification and related issues. A wide variety of markers available in the market will be first reviewed, including radiopaque markers, MRI compatible makers, non-migrating coils, surgical clips and electromagnetic transponders etc. The pros and cons of each kind will be discussed. The clinical applications of implanted surrogates will be presented based on different anatomical sites. For the lung, we will discuss gated treatments and 2D or 3D real-time fiducial tracking techniques. For the prostate, we will be focusing on 2D-3D, 3D-3D matching and electromagnetic transponder based localization techniques. For the liver, we will review techniques when patients are under gating, shallow or free breathing condition. We will review techniques when treating challenging breast cancer as deformation may occur. Finally, we will summarize potential issues related to the usage of implanted target surrogates with TG 199 recommendations. A review of fiducial migration and fiducial derived target rotation in different disease sites will be provided. The issue of target deformation, especially near the diaphragm, and related suggestions will be also presented and discussed. Learning Objectives: Knowledge of a wide variety of markers Knowledge of their application for different disease sites Understand of issues related to these applications Z. Wang: Research funding support from Brainlab AG Q. Xu: Consultant for Accuray; Q. Xu, I am a consultant

  16. Furoquinoline Alkaloids and Methoxyflavones from the Stem Bark of Melicope madagascariensis (Baker T.G. Hartley

    Vincent E. Rasamison

    2016-09-01

    Full Text Available Abstract Melicope madagascariensis (Rutaceae is an endemic plant species of Madagascar that was first classified as a member of the genus Euodia J. R. & G. Forst (Rutaceae under the scientific name Euodia madagascariensis Baker. Based on morphological characteristics, Thomas Gordon Hartley taxonomically revised E. madagascariensis Baker to be M. madagascariensis (Baker T.G. Hartley. Chemotaxonomical studies have long been used to help the identification and confirmation of taxonomical classification of plant species and botanicals. Aiming to find more evidences to support the taxonomical revision performed on E. madagascariensis, we carried out phytochemical investigation of two samples of the plant. Fractionation of the ethanol extracts prepared from two stem bark samples of M. madagascariensis (Baker T.G. Hartley led to the isolation of seven known furoquinoline alkaloids 1–7 and two known methoxyflavones 8 and 9. The presence of furoquinoline alkaloids and methoxyflavones in the title species is in agreement with its taxonomic transfer from Euodia to Melicope. Antiprotozoal evaluation of the isolated compounds showed that 6-methoxy-7-hydroxydictamnine (heliparvifoline, 3 showed weak antimalarial activity (IC50 = 35 µM against the chloroquine-resistant strain Dd2 of Plasmodium falciparum. Skimmianine (4 displayed moderate cytotoxicity with IC50 value of 1.5 µM against HT-29 colon cancer cell line whereas 3,5-dihydroxy-3′,4′,7-trimethoxyflavone (9 was weakly active in the same assay (IC50 = 13.9 µM. Graphical Abstract

  17. Technical Report: TG-142 compliant and comprehensive quality assurance tests for respiratory gating

    Woods, Kyle; Rong, Yi

    2015-01-01

    Purpose: To develop and establish a comprehensive gating commissioning and quality assurance procedure in compliance with TG-142. Methods: Eight Varian TrueBeam Linacs were used for this study. Gating commissioning included an end-to-end test and baseline establishment. The end-to-end test was performed using a CIRS dynamic thoracic phantom with a moving cylinder inside the lung, which was used for carrying both optically simulated luminescence detectors (OSLDs) and Gafchromic EBT2 films while the target is moving, for a point dose check and 2D profile check. In addition, baselines were established for beam-on temporal delay and calibration of the surrogate, for both megavoltage (MV) and kilovoltage (kV) beams. A motion simulation device (MotionSim) was used to provide periodic motion on a platform, in synchronizing with a surrogate motion. The overall accuracy and uncertainties were analyzed and compared. Results: The OSLD readings were within 5% compared to the planned dose (within measurement uncertainty) for both phase and amplitude gated deliveries. Film results showed less than 3% agreement to the predicted dose with a standard sinusoid motion. The gate-on temporal accuracy was averaged at 139 ± 10 ms for MV beams and 92 ± 11 ms for kV beams. The temporal delay of the surrogate motion depends on the motion speed and was averaged at 54.6 ± 3.1 ms for slow, 24.9 ± 2.9 ms for intermediate, and 23.0 ± 20.1 ms for fast speed. Conclusions: A comprehensive gating commissioning procedure was introduced for verifying the output accuracy and establishing the temporal accuracy baselines with respiratory gating. The baselines are needed for routine quality assurance tests, as suggested by TG-142

  18. TH-B-204-03: TG-199: Implanted Markers for Radiation Treatment Verification

    Wang, Z. [Duke University Medical Center (United States)

    2016-06-15

    Implanted markers as target surrogates have been widely used for treatment verification, as they provide safe and reliable monitoring of the inter- and intra-fractional target motion. The rapid advancement of technology requires a critical review and recommendation for the usage of implanted surrogates in current field. The symposium, also reporting an update of AAPM TG 199 - Implanted Target Surrogates for Radiation Treatment Verification, will be focusing on all clinical aspects of using the implanted target surrogates for treatment verification and related issues. A wide variety of markers available in the market will be first reviewed, including radiopaque markers, MRI compatible makers, non-migrating coils, surgical clips and electromagnetic transponders etc. The pros and cons of each kind will be discussed. The clinical applications of implanted surrogates will be presented based on different anatomical sites. For the lung, we will discuss gated treatments and 2D or 3D real-time fiducial tracking techniques. For the prostate, we will be focusing on 2D-3D, 3D-3D matching and electromagnetic transponder based localization techniques. For the liver, we will review techniques when patients are under gating, shallow or free breathing condition. We will review techniques when treating challenging breast cancer as deformation may occur. Finally, we will summarize potential issues related to the usage of implanted target surrogates with TG 199 recommendations. A review of fiducial migration and fiducial derived target rotation in different disease sites will be provided. The issue of target deformation, especially near the diaphragm, and related suggestions will be also presented and discussed. Learning Objectives: Knowledge of a wide variety of markers Knowledge of their application for different disease sites Understand of issues related to these applications Z. Wang: Research funding support from Brainlab AG Q. Xu: Consultant for Accuray; Q. Xu, I am a consultant

  19. TH-B-204-00: Implanted Markers for Radiation Therapy and TG 199 Update

    NONE

    2016-06-15

    Implanted markers as target surrogates have been widely used for treatment verification, as they provide safe and reliable monitoring of the inter- and intra-fractional target motion. The rapid advancement of technology requires a critical review and recommendation for the usage of implanted surrogates in current field. The symposium, also reporting an update of AAPM TG 199 - Implanted Target Surrogates for Radiation Treatment Verification, will be focusing on all clinical aspects of using the implanted target surrogates for treatment verification and related issues. A wide variety of markers available in the market will be first reviewed, including radiopaque markers, MRI compatible makers, non-migrating coils, surgical clips and electromagnetic transponders etc. The pros and cons of each kind will be discussed. The clinical applications of implanted surrogates will be presented based on different anatomical sites. For the lung, we will discuss gated treatments and 2D or 3D real-time fiducial tracking techniques. For the prostate, we will be focusing on 2D-3D, 3D-3D matching and electromagnetic transponder based localization techniques. For the liver, we will review techniques when patients are under gating, shallow or free breathing condition. We will review techniques when treating challenging breast cancer as deformation may occur. Finally, we will summarize potential issues related to the usage of implanted target surrogates with TG 199 recommendations. A review of fiducial migration and fiducial derived target rotation in different disease sites will be provided. The issue of target deformation, especially near the diaphragm, and related suggestions will be also presented and discussed. Learning Objectives: Knowledge of a wide variety of markers Knowledge of their application for different disease sites Understand of issues related to these applications Z. Wang: Research funding support from Brainlab AG Q. Xu: Consultant for Accuray; Q. Xu, I am a consultant

  20. Design of a PET/CT facility considering the shielding calculation in accordance with AAPM TG-108; Diseno de una instalacion PET/CT considerando el calculo de blindaje segun AAPM TG-108

    Guevara R, V. Y.; Romero C, N. [Empresa QC DOSE S. A. C., Av. Tomas Marsano 1915, Surquillo, Lima 34 (Peru); Berrocal T, M., E-mail: vguevara@qcdose.com [Universidad Nacional Mayor de San Marcos, C. German Amezaga 375, Edif. Jorge Basadre, Ciudad Universitaria, Lima 1 (Peru)

    2014-08-15

    A Positron Emission Tomography / Computed Tomography facility may require protection barriers on floor, ceiling and walls, because the patient becomes a radioactive source that emits photons of 0.511 MeV, after having received a radiopharmaceutical, usually F-18 fluorodeoxyglucose (F-18 FDG). This work has as objective to propose the design of a PET/CT facility, taking into account technical and radiation protection considerations applied internationally, and also develop the necessary shielding for such installation by applying as published by the American Association of Physicists in Medicine Task Group Report 108. A shielding spreadsheet in Excel program was developed with reference to the recommendations of the AAPM TG - 08, to determine the shielding required for the walls, floor and ceiling. For fixing the radiation levels in the shielding calculation has been considered the actual restrictions for the occupationally exposed personnel (100 μSv/week) as well as the people in general (20 μSv/ week). The radiopharmaceutical used as a reference for the shielding calculation was the F-18 FDG. With the assistance of an architectural plan were determined distances from potential sources of radiation in facility (uptake and image acquisition living rooms) to points of interest around them. Finally the thickness of the protective barriers in lead and concrete necessary to achieve the established radiation levels were calculated and these results were stored in a table. This paper shows that technical aspects considered in the design of the installation and environments distribution can improve work processes within the PET/CT facility, consequently resulting in a reduction of the dose levels for people in general. (author)

  1. Design of a PET/CT facility considering the shielding calculation in accordance with AAPM TG-108

    Guevara R, V. Y.; Romero C, N.; Berrocal T, M.

    2014-08-01

    A Positron Emission Tomography / Computed Tomography facility may require protection barriers on floor, ceiling and walls, because the patient becomes a radioactive source that emits photons of 0.511 MeV, after having received a radiopharmaceutical, usually F-18 fluorodeoxyglucose (F-18 FDG). This work has as objective to propose the design of a PET/CT facility, taking into account technical and radiation protection considerations applied internationally, and also develop the necessary shielding for such installation by applying as published by the American Association of Physicists in Medicine Task Group Report 108. A shielding spreadsheet in Excel program was developed with reference to the recommendations of the AAPM TG - 08, to determine the shielding required for the walls, floor and ceiling. For fixing the radiation levels in the shielding calculation has been considered the actual restrictions for the occupationally exposed personnel (100 μSv/week) as well as the people in general (20 μSv/ week). The radiopharmaceutical used as a reference for the shielding calculation was the F-18 FDG. With the assistance of an architectural plan were determined distances from potential sources of radiation in facility (uptake and image acquisition living rooms) to points of interest around them. Finally the thickness of the protective barriers in lead and concrete necessary to achieve the established radiation levels were calculated and these results were stored in a table. This paper shows that technical aspects considered in the design of the installation and environments distribution can improve work processes within the PET/CT facility, consequently resulting in a reduction of the dose levels for people in general. (author)

  2. Cistatina C, PCR, Log TG/HDLc e Sindrome Metabolica estao Relacionados a Microalbuminuria na Hipertensao

    Rafaela do Socorro Souza e Silva Moura

    2014-01-01

    Full Text Available Fundamento: Em pacientes com hipertensão arterial sistêmica, a microalbuminúria é um marcador de lesão endotelial e está associada a um risco aumentado de doença cardiovascular. Objetivo: O objetivo do presente estudo foi determinar os fatores que influenciam a ocorrência de microalbumiúria em pacientes hipertensos com creatinina sérica menor que 1,5 mg/dL. Métodos: Foram incluídos no estudo 133 pacientes brasileiros atendidos em um ambulatório multidisciplinar para hipertensos. Pacientes com creatinina sérica maior do que 1,5 mg/dL e aqueles com diabete mellitus foram excluídos do estudo. A pressão arterial sistólica e diastólica foi aferida. O índice de massa corporal (IMC e a taxa de filtração glomerular estimada pela fórmula CKD-EPI foram calculados. Em um estudo transversal, creatinina, cistatina C, colesterol total, HDL colesterol, LDL colesterol, triglicerídeos, proteína C-reativa (PCR e glicose foram mensurados em amostra de sangue. A microalbuminúria foi determinada na urina colhida em 24 horas. Os hipertensos foram classificados pela presença de um ou mais critérios para síndrome metabólica. Resultados: Em análise de regressão múltipla, os níveis séricos de cistatina C, PCR, o índice aterogênico log TG/HDLc e a presença de três ou mais critérios para síndrome metabólica foram positivamente correlacionados com a microalbuminuria (r2: 0,277; p < 0,05. Conclusão: Cistatina C, PCR, log TG/HDLc e presença de três ou mais critérios para síndrome metabólica, independentemente da creatinina sérica, foram associados com a microalbuminúria, um marcador precoce de lesão renal e de risco cardiovascular em pacientes com hipertensão arterial essencial.

  3. Exercise training in Tgαq*44 mice during the progression of chronic heart failure: cardiac vs. peripheral (soleus muscle) impairments to oxidative metabolism.

    Grassi, Bruno; Majerczak, Joanna; Bardi, Eleonora; Buso, Alessia; Comelli, Marina; Chlopicki, Stefan; Guzik, Magdalena; Mavelli, Irene; Nieckarz, Zenon; Salvadego, Desy; Tyrankiewicz, Urszula; Skórka, Tomasz; Bottinelli, Roberto; Zoladz, Jerzy A; Pellegrino, Maria Antonietta

    2017-08-01

    Cardiac function, skeletal (soleus) muscle oxidative metabolism, and the effects of exercise training were evaluated in a transgenic murine model (Tgα q *44) of chronic heart failure during the critical period between the occurrence of an impairment of cardiac function and the stage at which overt cardiac failure ensues (i.e., from 10 to 12 mo of age). Forty-eight Tgα q *44 mice and 43 wild-type FVB controls were randomly assigned to control groups and to groups undergoing 2 mo of intense exercise training (spontaneous running on an instrumented wheel). In mice evaluated at the beginning and at the end of training we determined: exercise performance (mean distance covered daily on the wheel); cardiac function in vivo (by magnetic resonance imaging); soleus mitochondrial respiration ex vivo (by high-resolution respirometry); muscle phenotype [myosin heavy chain (MHC) isoform content; citrate synthase (CS) activity]; and variables related to the energy status of muscle fibers [ratio of phosphorylated 5'-AMP-activated protein kinase (AMPK) to unphosphorylated AMPK] and mitochondrial biogenesis and function [peroxisome proliferative-activated receptor-γ coactivator-α (PGC-1α)]. In the untrained Tgα q *44 mice functional impairments of exercise performance, cardiac function, and soleus muscle mitochondrial respiration were observed. The impairment of mitochondrial respiration was related to the function of complex I of the respiratory chain, and it was not associated with differences in CS activity, MHC isoforms, p-AMPK/AMPK, and PGC-1α levels. Exercise training improved exercise performance and cardiac function, but it did not affect mitochondrial respiration, even in the presence of an increased percentage of type 1 MHC isoforms. Factors "upstream" of mitochondria were likely mainly responsible for the improved exercise performance. NEW & NOTEWORTHY Functional impairments in exercise performance, cardiac function, and soleus muscle mitochondrial respiration

  4. The relationship between the Tg depression and the speeding up of physical aging in polystyrene/gold nanocomposites

    Boucher, Virginie M.; Cangialosi, Daniele; Alegria, Angel; Colmenero, Juan

    2011-03-01

    The effect of gold nanoparticles on the segmental dynamics, glass transition (Tg) and physical aging of polystyrene (PS) was studied in PS/Gold nanocomposites samples containing 5 and 15 wt.% of 60 nm spherical gold nanoparticles, surface-treated with thiolated-PS. While the segmental dynamics of PS, as assessed by broadband dielectric spectroscopy (BDS), was found to be unchanged in presence of gold nanoparticles, the calorimetric Tg of PS was shown to decrease with increasing the amount of nanoparticles in the samples. Furthermore, the physical aging of PS, monitored by measuring the enthalpy relaxation below Tg by means of DSC, was shown to speed up with increasing the nanoparticles weight fraction, i.e. the amount of PS/Gold interface in the hybrid material. Thus, the main conclusion of our work is that PS molecular mobility and out-of-equilibrium dynamics are decoupled in these nanocomposites. The significant effect of the amount of PS/Gold interface on both the physical aging rate of PS and the calorimetric Tg depression are quantitatively accounted for by a model based on the diffusion of free volume holes towards polymer interfaces, with a diffusion coefficient depending only on the molecular mobility.

  5. No Effect of Resveratrol on VLDL-TG Kinetics and Insulin Sensitivity in Obese Men with Nonalcoholic Fatty Liver Disease

    Poulsen, Marianne K; Nellemann, Birgitte; Bibby, Bo Martin

    2018-01-01

    The present study assess long-term effects of high-dose Resveratrol (RSV) on basal and insulin-mediated very low-desity lipoprotein triglyceride (VLDL-TG), palmitate and glucose kinetics, and liver fat content in men with nonalcoholic fatty liver disease (NAFLD). Participants (n=16) were non...

  6. Anxiety-like behavior as an early endophenotype in the TgF344-AD rat model of Alzheimer's disease.

    Pentkowski, Nathan S; Berkowitz, Laura E; Thompson, Shannon M; Drake, Emma N; Olguin, Carlos R; Clark, Benjamin J

    2018-01-01

    Alzheimer's disease (AD) is characterized by progressive cognitive decline and the presence of aggregates of amyloid beta (plaques) and hyperphosphorylated tau (tangles). Early diagnosis through neuropsychological testing is difficult due to comorbidity of symptoms between AD and other types of dementia. As a result, there is a need to identify the range of behavioral phenotypes expressed in AD. In the present study, we utilized a transgenic rat (TgF344-AD) model that bears the mutated amyloid precursor protein as well as presenilin-1 genes, resulting in progressive plaque and tangle pathogenesis throughout the cortex. We tested young adult male and female TgF344-AD rats in a spatial memory task in the Morris water maze and for anxiety-like behavior in the elevated plus-maze. Results indicated that regardless of sex, TgF344-AD rats exhibited increased anxiety-like behavior in the elevated plus-maze, which occurred without significant deficits in the spatial memory. Together, these results indicate that enhanced anxiety-like behavior represents an early-stage behavioral marker in the TgF344-AD rat model. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Molecular structure of virgin and Tg cycled (Ag2Se)x (AsSe)1-x bulk glasses

    Wachtman, Jacob; Chen, Ping; Boochand, P.

    2009-03-01

    AsSe, the base glass (x = 0) in the titled ternary, is an interesting example of a chalcogenide that is partially de-mixed into As4Se4 molecules segregated from a connected AsSe network, with the latter determining glass network properties. Raman scattering reveals sharp modes of the Realgar molecules that are superimposed on broad modes coming from of the backbone. Upon Tg cycling virgin samples (as quenched melts), the concentration of de-mixed As4Se4 molecules decreases, suggesting that thermally induced polymerization occurs; molecules break up to form part of the connective tissue. Modulated DSC experiments reveal a broad exotherm near 140 ^oC in virgin samples, which becomes nearly extinct in Tg cycled samples. The exotherm may represent Realgar molecules nano-crystallizing as the temperature approaches Tg. Compositional trends in thermal parameters such as Tg(x), δCp(x), and the δHnr(x) as a function of Ag2Se content `x' of the glasses will be reported.

  8. TG-FTIR measurement of CO2-H2O co-adsorption for CO2 air capture sorbent screening

    Smal, I.M.; Yu, Qian; Veneman, Rens; Fränzel-Luiten, B.; Brilman, Derk Willem Frederik

    2014-01-01

    Capturing atmospheric CO2 using solid sorbents is gaining interest. As ambient air normally contains much more (up to 100 times) water than CO2, a selective sorbent is desirable as co-adsorption will most likely occur. In this study, a convenient method based on an TG-FTIR analysis system is

  9. Citalopram Ameliorates Impairments in Spatial Memory and Synaptic Plasticity in Female 3xTgAD Mice

    Zhang Wei

    2017-01-01

    Full Text Available Alzheimer’s disease (AD is the primary cause of dementia. There is no effective treatment. Amyloid-β peptide (Aβ plays an important role in the pathogenesis and thus strategies suppressing Aβ production and accumulation seem promising. Citalopram is an antidepressant drug and can decrease Aβ production and amyloid plaques in transgenic mice of AD and humans. Whether citalopram can ameliorate memory deficit was not known yet. We tested the effects of citalopram on behavioral performance and synaptic plasticity in female 3xTgAD mice, a well-characterized model of AD. Mice were treated with citalopram or water from 5 months of age for 3 months. Citalopram treatment at approximately 10 mg/kg/day significantly improved spatial memory in the Morris water maze (MWM test, while not affecting anxiety-like and depression-like behavior in 3xTgAD mice. Further, hippocampal long-term potentiation (LTP impairment in 3xTgAD mice was reversed by citalopram treatment. Citalopram treatment also significantly decreased the levels of insoluble Aβ40 in hippocampal and cortical tissues in 3xTgAD mice, accompanied with a reduced amyloid precursor protein (APP. Together, citalopram treatment may be a promising strategy for AD and further clinical trials should be conducted to verify the effect of citalopram on cognition in patients with AD or mild cognitive impairment.

  10. Characteristic Study of Shenmu Bituminous Coal Combustion with Online TG-MS-FTIR

    Pan, Guanfu

    2018-01-01

    The combustion characteristics of Shenmu bituminous pulverized coal (SBC) were comprehensively investigated with a combined TG-MS-FTIR system by considering the effect of particle size, heating rate and total flowrate. The combustion products were accurately quantified by normalization and numerical analysis of MS results. The results indicate that the decrease of the particle size, heating rate and total flowrate result in lower ignition and burnout temperatures. The activation energy tends to be lower with smaller particle size, lower heating rate and total flowrate. The MS and FTIR results demonstrate that lower concentrations of different products, such as NO, NO2, HCN, CH4 and SO2 were produced with smaller particle size, slower heating rate and lower total flowrate. The decrease of particle size would lead to more contact area with oxygen and slower heating rate could provide more sufficient time for the diffusion. High total flowrate would reduce the oxygen adsorbability on the coal particle surface and shorten the residence time of oxygen, which makes the ignition difficult to occur. This work will guide to understand the combustion kinetics of pulverized coals and be beneficial to control the formation of pollutants.

  11. STUDY ON THE CONTENT OF SEDIMENT PARTICLES IN THE AIR AROUND TG. JIU TOWN

    Ramona Violeta Cazalbașu

    2016-12-01

    Full Text Available One of the most important problems of the modern era is the air pollution. This phenomenon, highly complex, has become the focus of several international organizations since the consequences of air pollution are felt outside the country borders. By and large wecan speak of a regional pollution, which consists of atmospheric contamination by waste or by products liquids, solids gas, threatening the health of people, plants and animals or which can attack materials, reduce visibility and cause unpleasant odors. On a planetary scale, the elimination or accumulation in the atmosphere of certain products, leads to irreparable consequences on the planet's natural balance: ozone depletion and global warming of the atmosphere. This paper presents the study on the sedimentparticles in the air in Tg-Jiu. Determination of particulate matter from the air was done according to Standard no. 10195 / 75.Air purity.Determination of settled particles. In 2014 no exceeding of the maximum allowable concentration of sediment particles has been found in the four sampling points and in2015, out of a total of 60 measurements in four sampling points only one was above the maximum permissible concentration

  12. High-Tg Polynorbornene-Based Block and Random Copolymers for Butanol Pervaporation Membranes

    Register, Richard A.; Kim, Dong-Gyun; Takigawa, Tamami; Kashino, Tomomasa; Burtovyy, Oleksandr; Bell, Andrew

    Vinyl addition polymers of substituted norbornene (NB) monomers possess desirably high glass transition temperatures (Tg); however, until very recently, the lack of an applicable living polymerization chemistry has precluded the synthesis of such polymers with controlled architecture, or copolymers with controlled sequence distribution. We have recently synthesized block and random copolymers of NB monomers bearing hydroxyhexafluoroisopropyl and n-butyl substituents (HFANB and BuNB) via living vinyl addition polymerization with Pd-based catalysts. Both series of polymers were cast into the selective skin layers of thin film composite (TFC) membranes, and these organophilic membranes investigated for the isolation of n-butanol from dilute aqueous solution (model fermentation broth) via pervaporation. The block copolymers show well-defined microphase-separated morphologies, both in bulk and as the selective skin layers on TFC membranes, while the random copolymers are homogeneous. Both block and random vinyl addition copolymers are effective as n-butanol pervaporation membranes, with the block copolymers showing a better flux-selectivity balance. While polyHFANB has much higher permeability and n-butanol selectivity than polyBuNB, incorporating BuNB units into the polymer (in either a block or random sequence) limits the swelling of the polyHFANB and thereby improves the n-butanol pervaporation selectivity.

  13. A comparative Tg-Ms study of the carbonization behaviour of different pitches

    Garcia, R.; Arenillas, A.; Crespo, J.L.; Pis, J.J.; Moinelo, S.R. [CSIC, Oviedo (Spain). Inst. Nacional del Carbon

    2002-08-01

    The purpose of this work was to study the formation of mesophase spherules from a low-temperature coal tar pitch under carbonization conditions. For comparison, the carbonization of a high-temperature coal tar pitch and a petroleum pitch were also considered. Different degrees of mesophase formation and development for each pitch. The results from Fourier transform infrared spectroscopy (FT-IR), elemental analysis, and the thermogravimetric analyzer mass spectrometer (TG-MS) tests were compared with the different extents of mesophase formation, checked by optical microscopy. According to the results, several stages can be distinguished as temperature increases in the carbonization process of the pitches. In the low-temperature coal tar pitch, the devolatilization of light components, especially phenols, accounts for the most significant weight loss. Moreover, cross-linking contributes greatly to the formation and development of mesophase, resulting in the predominance of bulk mesophase in a relatively short time in the case of the low-temperature coal tar pitch. 19 refs., 10 figs., 2 tabs.

  14. Studies concerning recycling by composting organic waste in Tg-Mureş

    Florica Morar

    2011-12-01

    Full Text Available Recycling organic waste has become a matter of utmost importance for overall healthiness of the Earth, its volume largely interacting with the economic development. The problem tends to become a vital matter of survival for an entire society. In this context, recovery, recycling, physical-chemical treatment, composting or incineration are methods of waste processing, commonly used in most countries of the world. These measures are intended to both environmental protection and rational use and economically efficient. Based on the data regarding the municipal waste generated in Mures County, in previous years, and in Tg-Mures city, in 2007 were calculated the quantities expected to generate by the year 2038. Also, concerning the cleaning recovery it is proposed the pile composting method, being, from our point of view, more Beneficial in the area. In conclusion, at county level but at city level too, there is still working to do, primarily in terms of awareness, not only the population but also the relevant, local bodies, of what means the cleaning recovery of the municipal waste.

  15. TG-FTIR, DSC and quantum chemical studies of the thermal decomposition of quaternary methylammonium halides

    Sawicka, Marlena; Storoniak, Piotr; Skurski, Piotr; Blazejowski, Jerzy; Rak, Janusz

    2006-01-01

    The thermal decomposition of quaternary methylammonium halides was studied using thermogravimetry coupled to FTIR (TG-FTIR) and differential scanning calorimetry (DSC) as well as the DFT, MP2 and G2 quantum chemical methods. There is almost perfect agreement between the experimental IR spectra and those predicted at the B3LYP/6-311G(d,p) level: this has demonstrated for the first time that an equimolar mixture of trimethylamine and a methyl halide is produced as a result of decomposition. The experimental enthalpies of dissociation are 153.4, 171.2, and 186.7 kJ/mol for chloride, bromide and iodide, respectively, values that correlate well with the calculated enthalpies of dissociation based on crystal lattice energies and quantum chemical thermodynamic barriers. The experimental activation barriers estimated from the least-squares fit of the F1 kinetic model (first-order process) to thermogravimetric traces - 283, 244 and 204 kJ/mol for chloride, bromide and iodide, respectively - agree very well with theoretically calculated values. The theoretical approach assumed in this work has been shown capable of predicting the relevant characteristics of the thermal decomposition of solids with experimental accuracy

  16. SU-E-T-468: Implementation of the TG-142 QA Process for Seven Linacs with Enhanced Beam Conformance

    Woollard, J; Ayan, A; DiCostanzo, D; Grzetic, S; Hessler, J; Gupta, N [OH State University, Columbus, OH (United States)

    2015-06-15

    Purpose: To develop a TG-142 compliant QA process for 7 Varian TrueBeam linear accelerators (linacs) with enhanced beam conformance and dosimetrically matched beam models. To ensure consistent performance of all 7 linacs, the QA process should include a common set of baseline values for use in routine QA on all linacs. Methods: The TG 142 report provides recommended tests, tolerances and frequencies for quality assurance of medical accelerators. Based on the guidance provided in the report, measurement tests were developed to evaluate each of the applicable parameters listed for daily, monthly and annual QA. These tests were then performed on each of our 7 new linacs as they came on line at our institution. Results: The tolerance values specified in TG-142 for each QA test are either absolute tolerances (i.e. ±2mm) or require a comparison to a baseline value. The results of our QA tests were first used to ensure that all 7 linacs were operating within the suggested tolerance values provided in TG −142 for those tests with absolute tolerances and that the performance of the linacs was adequately matched. The QA test results were then used to develop a set of common baseline values for those QA tests that require comparison to a baseline value at routine monthly and annual QA. The procedures and baseline values were incorporated into a spreadsheets for use in monthly and annual QA. Conclusion: We have developed a set of procedures for daily, monthly and annual QA of our linacs that are consistent with the TG-142 report. A common set of baseline values was developed for routine QA tests. The use of this common set of baseline values for comparison at monthly and annual QA will ensure consistent performance of all 7 linacs.

  17. SU-E-T-468: Implementation of the TG-142 QA Process for Seven Linacs with Enhanced Beam Conformance

    Woollard, J; Ayan, A; DiCostanzo, D; Grzetic, S; Hessler, J; Gupta, N

    2015-01-01

    Purpose: To develop a TG-142 compliant QA process for 7 Varian TrueBeam linear accelerators (linacs) with enhanced beam conformance and dosimetrically matched beam models. To ensure consistent performance of all 7 linacs, the QA process should include a common set of baseline values for use in routine QA on all linacs. Methods: The TG 142 report provides recommended tests, tolerances and frequencies for quality assurance of medical accelerators. Based on the guidance provided in the report, measurement tests were developed to evaluate each of the applicable parameters listed for daily, monthly and annual QA. These tests were then performed on each of our 7 new linacs as they came on line at our institution. Results: The tolerance values specified in TG-142 for each QA test are either absolute tolerances (i.e. ±2mm) or require a comparison to a baseline value. The results of our QA tests were first used to ensure that all 7 linacs were operating within the suggested tolerance values provided in TG −142 for those tests with absolute tolerances and that the performance of the linacs was adequately matched. The QA test results were then used to develop a set of common baseline values for those QA tests that require comparison to a baseline value at routine monthly and annual QA. The procedures and baseline values were incorporated into a spreadsheets for use in monthly and annual QA. Conclusion: We have developed a set of procedures for daily, monthly and annual QA of our linacs that are consistent with the TG-142 report. A common set of baseline values was developed for routine QA tests. The use of this common set of baseline values for comparison at monthly and annual QA will ensure consistent performance of all 7 linacs

  18. Dosimetric and radiobiological comparison of TG-43 and Monte Carlo calculations in 192Ir breast brachytherapy applications.

    Peppa, V; Pappas, E P; Karaiskos, P; Major, T; Polgár, C; Papagiannis, P

    2016-10-01

    To investigate the clinical significance of introducing model based dose calculation algorithms (MBDCAs) as an alternative to TG-43 in 192 Ir interstitial breast brachytherapy. A 57 patient cohort was used in a retrospective comparison between TG-43 based dosimetry data exported from a treatment planning system and Monte Carlo (MC) dosimetry performed using MCNP v. 6.1 with plan and anatomy information in DICOM-RT format. Comparison was performed for the target, ipsilateral lung, heart, skin, breast and ribs, using dose distributions, dose-volume histograms (DVH) and plan quality indices clinically used for plan evaluation, as well as radiobiological parameters. TG-43 overestimation of target DVH parameters is statistically significant but small (less than 2% for the target coverage indices and 4% for homogeneity indices, on average). Significant dose differences (>5%) were observed close to the skin and at relatively large distances from the implant leading to a TG-43 dose overestimation for the organs at risk. These differences correspond to low dose regions (<50% of the prescribed dose), being less than 2% of the prescribed dose. Detected dosimetric differences did not induce clinically significant differences in calculated tumor control probabilities (mean absolute difference <0.2%) and normal tissue complication probabilities. While TG-43 shows a statistically significant overestimation of most indices used for plan evaluation, differences are small and therefore not clinically significant. Improved MBDCA dosimetry could be important for re-irradiation, technique inter-comparison and/or the assessment of secondary cancer induction risk, where accurate dosimetry in the whole patient anatomy is of the essence. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  19. Correlations of serum levels of TG with leptin and other related factors (L-1, NPY adiponectin) in patients with hyperlipidaemia

    Wang Donghong; Yu Ping; Wei Jingjun

    2007-01-01

    Objective: To study the changes and correlations of serum levels of triglyeride (TG), leptin, L -1, neuropeptide Y (NPY) and adiponectin in patients with hypertriglyceridemia (HTG). Methods: Serum levels of TG, leptin, L-1, NPY and adiponectin in 54 patients with HTG and 55 controls were measured with radioimmunoassay (RIA). Results: The serum levels of TG, Leptin, L -1 and NPY in patients with HTG [ (3.46 ± 1.14) mmol/L, (10.56 ±3.79) μg/L, (0.40 ± 0.18) μg/L, (115.89 ± 24.56) μg/L, respectively] were significantly higher than those in controls [ (1.26 ± 0.30) mmol/L, (5.66 ± 2.01) μg/L, (0.22 ± 0.09) μg/L, (95.21 ± 16.85) μg/L, respectively] P < 0.01 in all. But serum levels of adiponectin in patients with HTG (8.98 ± 3.51μg/L) was significantly lower than those in controls [(13.21 ± 9.46) μg/L, P < 0.01]. There were significantly positive correlations between serum TG levels and serum levels of leptin (r = 0.576, P < 0.05). There were also significantly positive correlations between serum leptin levels and serum levels of L-1 and NPY (r = 0.582; r = 0.479, respectively, P < 0.05). Conclusion: There was close relationship between increase in serum TG level and changes of serum levels of leptin, L-1, NPY, adiponectin. Neural-endocrine-immune system participated in fatty metabolism and could result in HTG. (authors)

  20. Exercise alters the immune profile in Tg2576 Alzheimer mice toward a response coincident with improved cognitive performance and decreased amyloid

    Cribbs David H

    2008-04-01

    Full Text Available Abstract Background Inflammation is associated with Aβ pathology in Alzheimer's disease (AD and transgenic AD models. Previously, it has been demonstrated that chronic stimulation of the immune response induces pro-inflammatory cytokines IL-1β and TNF-α which contribute to neurodegeneration. However, recent evidence has shown that inducing the adaptive immune response reduces Aβ pathology and is neuroprotective. Low concentrations of IFN-γ modulate the adaptive immune response by directing microglia to differentiate to antigen presenting cells. Our objective was to determine if exercise could induce a shift from the immune profile in aged (17–19 months Tg2576 mice to a response that reduces Aβ pathology. Methods TG (n = 29 and WT (n = 27 mice were divided into sedentary (SED and exercised (RUN groups. RUN animals were provided an in-cage running wheel for 3 weeks. Tissue was harvested and hippocampus and cortex dissected out. Quantitative data was analyzed using 2 × 2 ANOVA and student's t-tests. Results IL-1β and TNF-α were significantly greater in hippocampi from sedentary Tg2576 (TGSED mice than in wildtype (WTSED (p = 0.04, p = 0.006. Immune response proteins IFN-γ and MIP-1α are lower in TGSED mice than in WTSED (p = 0.03, p = 0.07. Following three weeks of voluntary wheel running, IL-1β and TNF-α decreased to levels indistinguishable from WT. Concurrently, IFN-γ and MIP-1α increased in TGRUN. Increased CD40 and MHCII, markers of antigen presentation, were observed in TGRUN animals compared to TGSED, as well as CD11c staining in and around plaques and vasculature. Additional vascular reactivity observed in TGRUN is consistent with an alternative activation immune pathway, involving perivascular macrophages. Significant decreases in soluble Aβ40 (p = 0.01 and soluble fibrillar Aβ (p = 0.01 were observed in the exercised transgenic animals. Conclusion Exercise shifts the immune response from innate to an adaptive or

  1. Influence of metal additives on pyrolysis behavior of bituminous coal by TG-FTIR analysis

    Su, Wenjuan; Fang, Mengxiang; Cen, Jianmeng; Li, Chao; Luo, Zhongyang; Cen, Kefa [Zhejiang Univ., Hangzhou (China). State Key Lab. of Clean Energy Utilization

    2013-07-01

    To study the catalytic effects of alkali, alkaline earth and transition metal additives on coal pyrolysis behavior, bituminous coal loaded NaCl, KCl, CaCl{sub 2}, MgCl{sub 2}, FeCl{sub 3} and NiCl{sub 2} was respectively investigated using Thermogravimetry and Fourier Transform Infrared Spectroscopy (TG-FTIR). Results indicated that the maximum mass loss rate decreased under the metal additives in the primary pyrolysis stage. The total mass loss of pyrolysis was reduced in metals catalyzed pyrolysis except for Na loaded sample. Kinetic analysis was taken for all samples adopting the method of Coats-Redfern. Activation energy of raw coal in the primary pyrolysis stage was 92.15vkJ.mol{sup -1}, which was lowered to 44.59-73.42 kJ.mol{sup -1} under metal additives. The orders of catalytic effect for this bituminous coal were Mg > Fe > Ca > Ni > K > Na according to their activation energies. Several investigated volatiles including CH{sub 4}, CO{sub 2}, CO, toluene, phenol and formic acid were identified from FTIR spectra. The yields of CH{sub 4}, CO{sub 2}, toluene, phenol and formic acid were decreased, but the evolution of CO was increased. The presence of metals in the coal samples have been involved in a repeated bond-forming and bond-breaking process, which greatly hindered the release of tars during pyrolysis as the tar precursors were connected to coal/char matrix and were thermally cracked, becoming a part of char.

  2. SU-E-T-87: A TG-100 Approach for Quality Improvement of Associated Dosimetry Equipment

    Manger, R; Pawlicki, T; Kim, G [UCSD Medical Center, La Jolla, CA (United States)

    2015-06-15

    Purpose: Dosimetry protocols devote so much time to the discussion of ionization chamber choice, use and performance that is easy to forget about the importance of the associated dosimetry equipment (ADE) in radiation dosimetry - barometer, thermometer, electrometer, phantoms, triaxial cables, etc. Improper use and inaccuracy of these devices may significantly affect the accuracy of radiation dosimetry. The purpose of this study is to evaluate the risk factors in the monthly output dosimetry procedure and recommend corrective actions using a TG-100 approach. Methods: A failure mode and effects analysis (FMEA) of the monthly linac output check procedure was performed to determine which steps and failure modes carried the greatest risk. In addition, a fault tree analysis (FTA) was performed to expand the initial list of failure modes making sure that none were overlooked. After determining the failure modes with the highest risk priority numbers (RPNs), 11 physicists were asked to score corrective actions based on their ease of implementation and potential impact. The results were aggregated into an impact map to determine the implementable corrective actions. Results: Three of the top five failure modes were related to the thermometer and barometer. The two highest RPN-ranked failure modes were related to barometric pressure inaccuracy due to their high lack-of-detectability scores. Six corrective actions were proposed to address barometric pressure inaccuracy, and the survey results found the following two corrective actions to be implementable: 1) send the barometer for recalibration at a calibration laboratory and 2) check the barometer accuracy against the local airport and correct for elevation. Conclusion: An FMEA on monthly output measurements displayed the importance of ADE for accurate radiation dosimetry. When brainstorming for corrective actions, an impact map is helpful for visualizing the overall impact versus the ease of implementation.

  3. Thrombin Generating Capacity and Phenotypic Association in ABO Blood Groups.

    Kremers, Romy M W; Mohamed, Abdulrahman B O; Pelkmans, Leonie; Hindawi, Salwa; Hemker, H Coenraad; de Laat, H Bas; Huskens, Dana; Al Dieri, Raed

    2015-01-01

    Individuals with blood group O have a higher bleeding risk than non-O blood groups. This could be explained by the lower levels of FVIII and von Willebrand Factor (VWF) levels in O individuals. We investigated the relationship between blood groups, thrombin generation (TG), prothrombin activation and thrombin inactivation. Plasma levels of VWF, FVIII, antithrombin, fibrinogen, prothrombin and α2Macroglobulin (α2M) levels were determined. TG was measured in platelet rich (PRP) and platelet poor plasma (PPP) of 217 healthy donors and prothrombin conversion and thrombin inactivation were calculated. VWF and FVIII levels were lower (75% and 78%) and α2M levels were higher (125%) in the O group. TG is 10% lower in the O group in PPP and PRP. Less prothrombin was converted in the O group (86%) and the thrombin decay capacity was lower as well. In the O group, α2M plays a significantly larger role in the inhibition of thrombin (126%). In conclusion, TG is lower in the O group due to lower prothrombin conversion, and a larger contribution of α2M to thrombin inactivation. The former is unrelated to platelet function because it is similar in PRP and PPP, but can be explained by the lower levels of FVIII.

  4. Comparison between AAPM TG-51 and IAEA TRS-398 for plane parallel ionization chambers irradiated by clinical electron beams

    Mahmoud, M.A.

    2005-01-01

    We compared the results of absorbed dose determined at reference conditions according to AAPM T G-51 and IAEA TRS-398 using plane parallel ionization chambers. The study showed agreement between the two protocols for Holt ,Exradin P11, NACP, Attix RMI 449 and Roos ionization chambers. For Markus ionization chambers the absorbed dose calculated using AAPM TG-51 is higher than that calculated using IAEA TRS-398 by 1.8 % for R 5 0 =2 cm and decrease with increased R 5 0 to reach 1.2 % for R 5 0 =20 cm. For Capintec PS-033 ionization chambers the absorbed dose calculated using AAPM TG-51 is constantly higher than that calculated by IAEA TRS-398 by 1.5 %. A theoretical explanation was introduced for these results

  5. High-Tg TOPAS microstructured polymer optical fiber for fiber Bragg grating strain sensing at 110 degrees

    Markos, Christos; Stefani, Alessio; Nielsen, Kristian

    2013-01-01

    We present the fabrication and characterization of fiber Bragg gratings (FBGs) in an endlessly single-mode microstructured polymer optical fiber (mPOF) made of humidity-insensitive high-Tg TOPAS cyclic olefin copolymer. The mPOF is the first made from grade 5013 TOPAS with a glass transition...... temperature of Tg = 135°C and we experimentally demonstrate high strain operation (2.5%) of the FBG at 98°C and stable operation up to a record high temperature of 110°C. The Bragg wavelengths of the FBGs are around 860 nm, where the propagation loss is 5.1dB/m, close to the fiber loss minimum of 3.67d...

  6. Progressive impairment of directional and spatially precise trajectories by TgF344-AD Rats in the Morris Water Task

    Thompson, Shannon; Harvey, Ryan; Clark, Benjamin; Drake, Emma; Berkowitz, Laura

    2018-01-01

    Spatial navigation is impaired in early stages of Alzheimers disease (AD), and may be a defining behavioral marker of preclinical AD. Nevertheless, limitations of diagnostic criteria for AD and within animal models of AD make characterization of preclinical AD difficult. A new rat model (TgF344-AD) of AD overcomes many of these limitations, though spatial navigation has not been comprehensively assessed. Using the hidden and cued platform variants of the Morris water task, a longitudinal asse...

  7. Brief Eclectic Psychotherapy for Traumatic Grief (BEP-TG): toward integrated treatment of symptoms related to traumatic loss.

    Smid, Geert E; Kleber, Rolf J; de la Rie, Simone M; Bos, Jannetta B A; Gersons, Berthold P R; Boelen, Paul A

    2015-01-01

    Traumatic events such as disasters, accidents, war, or criminal violence are often accompanied by the loss of loved ones, and may then give rise to traumatic grief. Traumatic grief refers to a clinical diagnosis of persistent complex bereavement disorder (PCBD) with comorbid (symptoms of) posttraumatic stress disorder (PTSD) and/or major depressive disorder (MDD) following confrontation with a traumatic loss. Trauma survivors, who are frequently from different cultural backgrounds, have often experienced multiple losses and ambiguous loss (missing family members or friends). Current evidence-based treatments for PTSD do not focus on traumatic grief. To develop a treatment for traumatic grief combining treatment interventions for PTSD and PCBD that may accommodate cultural aspects of grief. To provide a rationale for treatment, we propose a cognitive stress model of traumatic grief. Based on this model and on existing evidence-based treatments for PTSD and complicated grief, we developed Brief Eclectic Psychotherapy for Traumatic Grief (BEP-TG) for the treatment of patients with traumatic grief. The treatment is presented along with a case vignette. Processes contributing to traumatic grief include inadequately integrating the memory of the traumatic loss, negative appraisal of the traumatic loss, sensitivity to matching triggers and new stressors, and attempting to avoid distress. BEP-TG targets these processes. The BEP-TG protocol consists of five parts with proven effectiveness in the treatment of PCBD, PTSD, and MDD: information and motivation, grief-focused exposure, memorabilia and writing assignments, finding meaning and activation, and a farewell ritual. Tailored to fit the needs of trauma survivors, BEP-TG can be used to address traumatic grief symptoms related to multiple losses and ambiguous loss, as well as cultural aspects of bereavement through its different components.

  8. Developing a Treatment Planning Software Based on TG-43U1 Formalism for Cs-137 LDR Brachytherapy.

    Sina, Sedigheh; Faghihi, Reza; Soleimani Meigooni, Ali; Siavashpour, Zahra; Mosleh-Shirazi, Mohammad Amin

    2013-08-01

    The old Treatment Planning Systems (TPSs) used for intracavitary brachytherapy with Cs-137 Selectron source utilize traditional dose calculation methods, considering each source as a point source. Using such methods introduces significant errors in dose estimation. As of 1995, TG-43 is used as the main dose calculation formalism in treatment TPSs. The purpose of this study is to design and establish a treatment planning software for Cs-137 Solectron brachytherapy source, based on TG-43U1 formalism by applying the effects of the applicator and dummy spacers. Two softwares used for treatment planning of Cs-137 sources in Iran (STPS and PLATO), are based on old formalisms. The purpose of this work is to establish and develop a TPS for Selectron source based on TG-43 formalism. In this planning system, the dosimetry parameters of each pellet in different places inside applicators were obtained by MCNP4c code. Then the dose distribution around every combination of active and inactive pellets was obtained by summing the doses. The accuracy of this algorithm was checked by comparing its results for special combination of active and inactive pellets with MC simulations. Finally, the uncertainty of old dose calculation formalism was investigated by comparing the results of STPS and PLATO softwares with those obtained by the new algorithm. For a typical arrangement of 10 active pellets in the applicator, the percentage difference between doses obtained by the new algorithm at 1cm distance from the tip of the applicator and those obtained by old formalisms is about 30%, while the difference between the results of MCNP and the new algorithm is less than 5%. According to the results, the old dosimetry formalisms, overestimate the dose especially towards the applicator's tip. While the TG-43U1 based software perform the calculations more accurately.

  9. Role of Tulipa gesneriana TEOSINTE BRANCHED1 (TgTB1) in the control of axillary bud outgrowth in bulbs.

    Moreno-Pachon, Natalia M; Mutimawurugo, Marie-Chantal; Heynen, Eveline; Sergeeva, Lidiya; Benders, Anne; Blilou, Ikram; Hilhorst, Henk W M; Immink, Richard G H

    2018-06-01

    Tulip vegetative reproduction. Tulips reproduce asexually by the outgrowth of their axillary meristems located in the axil of each bulb scale. The number of axillary meristems in one bulb is low, and not all of them grow out during the yearly growth cycle of the bulb. Since the degree of axillary bud outgrowth in tulip determines the success of their vegetative propagation, this study aimed at understanding the mechanism controlling the differential axillary bud activity. We used a combined physiological and "bottom-up" molecular approach to shed light on this process and found that first two inner located buds do not seem to experience dormancy during the growth cycle, while mid-located buds enter dormancy by the end of the growing season. Dormancy was assessed by weight increase and TgTB1 expression levels, a conserved TCP transcription factor and well-known master integrator of environmental and endogenous signals influencing axillary meristem outgrowth in plants. We showed that TgTB1 expression in tulip bulbs can be modulated by sucrose, cytokinin and strigolactone, just as it has been reported for other species. However, the limited growth of mid-located buds, even when their TgTB1 expression is downregulated, points at other factors, probably physical, inhibiting their growth. We conclude that the time of axillary bud initiation determines the degree of dormancy and the sink strength of the bud. Thus, development, apical dominance, sink strength, hormonal cross-talk, expression of TgTB1 and other possibly physical but unidentified players, all converge to determine the growth capacity of tulip axillary buds.

  10. SU-E-T-159: Evaluation of a Patient Specific QA Tool Based On TG119

    Ashmeg, S; Zhang, Y; O'Daniel, J; Yin, F; Ren, L

    2014-01-01

    Purpose: To evaluate the accuracy of a 3D patient specific QA tool by analysis of the results produced from associated software in homogenous phantom and heterogonous patient CT. Methods: IMRT and VMAT plans of five test suites introduced by TG119 were created in ECLIPSE on a solid water phantom. The ten plans -of increasing complexity- were delivered to Delta4 to give a 3D measurement. The Delta4's “Anatomy” software uses the measured dose to back-calculate the energy fluence of the delivered beams, which is used for dose calculation in a patient CT using a pencilbeam algorithm. The effect of the modulated beams' complexity on the accuracy of the “Anatomy” calculation was evaluated. Both measured and Anatomy doses were compared to ECLIPSE calculation using 3% - 3mm gamma criteria.We also tested the effect of heterogeneity by analyzing the results of “Anatomy” calculation on a Brain VMAT and a 3D conformal lung cases. Results: In homogenous phantom, the gamma passing rates were found to be as low as 74.75% for a complex plan with high modulation. The mean passing rates were 91.47% ± 6.35% for “Anatomy” calculation and 99.46% ± 0.62% for Delta4 measurements.As for the heterogeneous cases, the rates were 96.54%±3.67% and 83.87%±9.42% for Brain VMAT and 3D lung respectively. This increased error in the lung case could be due to the use of the pencil beam algorithm as opposed to the AAA used by ECLIPSE.Also, gamma analysis showed high discrepancy along the beam edge in the “Anatomy” calculated results. This suggests a poor beam modeling in the penumbra region. Conclusion: The results show various sources of errors in “Anatomy” calculations. These include beam modeling in the penumbra region, complexity of a modulated beam (shown in homogenous phantom and brain cases) and dose calculation algorithms (3D conformal lung case)

  11. A poliomyelitis model through mucosal infection in transgenic mice bearing human poliovirus receptor, TgPVR21

    Nagata, Noriyo; Iwasaki, Takuya; Ami, Yasushi; Sato, Yuko; Hatano, Ikuyoshi; Harashima, Ayako; Suzaki, Yuriko; Yoshii, Takao; Hashikawa, Tsutomu; Sata, Tetsutaro; Horiuchi, Yoshinobu; Koike, Satoshi; Kurata, Takeshi; Nomoto, Akio

    2004-01-01

    Transgenic mice bearing the human poliovirus receptor (TgPVR) are less susceptible to oral inoculation, although they are susceptible to parenteral inoculation. We investigated the susceptibility of TgPVR 21 line [Arch. Virol. 130 (1994) 351] to poliovirus through various mucosal routes. Intranasal inoculation of a neurovirulent Mahoney strain (OM1) caused flaccid paralysis with viral replication in the central nervous system at a dose of 10 6 cell culture infectious dose (CCID 50 ), in contrast, no paralysis following oral or intragastric inoculation of the same dose. Intranasal inoculation of a vaccine strain, Sabin 1, at 10 6 CCID 50 , resulted in no paralysis. Initial replication of poliovirus in the nasal cavity was confirmed by virus isolation and detection of negative-stranded replicative intermediates by RT-PCR and viral antigens using a high-sensitive immunohistochemistry and genome/transcripts by in situ hybridization. Poliovirus-specific IgG antibodies were elevated in the sera of surviving TgPVR21. This model can be used as a mucosal infection model and for differentiation of neurovirulent and attenuated poliovirus strains

  12. Role of protein glycosylation on the expression of muscarinic receptors of N4TG1 neuroblastoma cells

    Ahmad, A.; Chiang, P.K.

    1986-01-01

    Muscarinic acetylcholine receptors (mAChR) are glycoproteins. Experiments were conducted to determine whether active glycosylation of proteins in N4TG1 neuroblastoma cells could affect the expression of muscarinic receptors on the cell surface. The binding of radioactive N-methylscopolamine, a membrane impermeable ligand, to intact cells was used as a measure of mAChR. In the presence of the inhibitors of glycosylation, such as tunicamycin, monensin and amphomycin, N-linked glycosylation of proteins in the N4TG1 cells was inhibited, as measured by the incorporation of radioactive glucosamine or mannose in proteins. At the concentrations of tunicamycin and monensin used, the glycosylation of proteins after 3 hours were drastically reduced, but the number of mAChR in the cells was not altered. The apparent lack of effect within a short incubation period could be attributed to the presence of preformed oligosaccharide dolichol readily available for N-glycosylation. However, after 24 hours, tunicamycin (0.05 μg/ml) caused a decrease in the number of mAChR by 17% without having any effect on protein synthesis. Therefore, de novo glycosylation of proteins may be required for the expression of mAChR receptors in the N4TG1 neuroblastoma cell surface

  13. Cytokine-producing microglia have an altered beta-amyloid load in aged APP/PS1 Tg mice

    Babcock, Alicia A; Ilkjær, Laura; Clausen, Bettina H

    2015-01-01

    of CD11b, TNF, and IL-1Ra. Cytokine production and Aβ load were assessed in neocortical CD11b(+)(CD45(+)) microglia by flow cytometry. Whereas most microglia in aged mice produced IL-1Ra, relatively low proportions of microglia produced TNF, IL-1α, and IL-1β. However, microglial production......, however the inter-relationship between these processes is poorly understood. Here we show that % Aβ plaque load followed a sigmoidal trajectory with age in the neocortex of APPswe/PS1ΔE9 Tg mice, and correlated positively with soluble Aβ40 and Aβ42. Aβ measures were moderately correlated with mRNA levels...... of these latter cytokines was generally increased in APP/PS1 Tg mice. Microglia that phagocytosed endogenously-produced Aβ were only observed in APP/PS1 Tg mice. Differences in phagocytic index and total Aβ load were observed in microglia with specific cytokine profiles. Both phagocytic index and total Aβ load...

  14. Yeast three-hybrid screen identifies TgBRADIN/GRA24 as a negative regulator of Toxoplasma gondii bradyzoite differentiation.

    Anahi V Odell

    Full Text Available Differentiation of the protozoan parasite Toxoplasma gondii into its latent bradyzoite stage is a key event in the parasite's life cycle. Compound 2 is an imidazopyridine that was previously shown to inhibit the parasite lytic cycle, in part through inhibition of parasite cGMP-dependent protein kinase. We show here that Compound 2 can also enhance parasite differentiation, and we use yeast three-hybrid analysis to identify TgBRADIN/GRA24 as a parasite protein that interacts directly or indirectly with the compound. Disruption of the TgBRADIN/GRA24 gene leads to enhanced differentiation of the parasite, and the TgBRADIN/GRA24 knockout parasites show decreased susceptibility to the differentiation-enhancing effects of Compound 2. This study represents the first use of yeast three-hybrid analysis to study small-molecule mechanism of action in any pathogenic microorganism, and it identifies a previously unrecognized inhibitor of differentiation in T. gondii. A better understanding of the proteins and mechanisms regulating T. gondii differentiation will enable new approaches to preventing the establishment of chronic infection in this important human pathogen.

  15. Measurements of Gasification Characteristics of Coal and Char in CO2-Rich Gas Flow by TG-DTA

    Zhigang Li

    2013-01-01

    Full Text Available Pyrolysis, combustion, and gasification properties of pulverized coal and char in CO2-rich gas flow were investigated by using gravimetric-differential thermal analysis (TG-DTA with changing O2%, heating temperature gradient, and flow rate of CO2-rich gases provided. Together with TG-DTA, flue gas generated from the heated coal, such as CO, CO2, and hydrocarbons (HCs, was analyzed simultaneously on the heating process. The optimum O2% in CO2-rich gas for combustion and gasification of coal or char was discussed by analyzing flue gas with changing O2 from 0 to 5%. The experimental results indicate that O2% has an especially large effect on carbon oxidation at temperature less than 1100°C, and lower O2 concentration promotes gasification reaction by producing CO gas over 1100°C in temperature. The TG-DTA results with gas analyses have presented basic reference data that show the effects of O2 concentration and heating rate on coal physical and chemical behaviors for the expected technologies on coal gasification in CO2-rich gas and oxygen combustion and underground coal gasification.

  16. A novel Toxoplasma gondii nuclear factor TgNF3 is a dynamic chromatin-associated component, modulator of nucleolar architecture and parasite virulence.

    Alejandro Olguin-Lamas

    2011-03-01

    Full Text Available In Toxoplasma gondii, cis-acting elements present in promoter sequences of genes that are stage-specifically regulated have been described. However, the nuclear factors that bind to these cis-acting elements and regulate promoter activities have not been identified. In the present study, we performed affinity purification, followed by proteomic analysis, to identify nuclear factors that bind to a stage-specific promoter in T. gondii. This led to the identification of several nuclear factors in T. gondii including a novel factor, designated herein as TgNF3. The N-terminal domain of TgNF3 shares similarities with the N-terminus of yeast nuclear FK506-binding protein (FKBP, known as a histone chaperone regulating gene silencing. Using anti-TgNF3 antibodies, HA-FLAG and YFP-tagged TgNF3, we show that TgNF3 is predominantly a parasite nucleolar, chromatin-associated protein that binds specifically to T. gondii gene promoters in vivo. Genome-wide analysis using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq identified promoter occupancies by TgNF3. In addition, TgNF3 has a direct role in transcriptional control of genes involved in parasite metabolism, transcription and translation. The ectopic expression of TgNF3 in the tachyzoites revealed dynamic changes in the size of the nucleolus, leading to a severe attenuation of virulence in vivo. We demonstrate that TgNF3 physically interacts with H3, H4 and H2A/H2B assembled into bona fide core and nucleosome-associated histones. Furthermore, TgNF3 interacts specifically to histones in the context of stage-specific gene silencing of a promoter that lacks active epigenetic acetylated histone marks. In contrast to virulent tachyzoites, which express the majority of TgNF3 in the nucleolus, the protein is exclusively located in the cytoplasm of the avirulent bradyzoites. We propose a model where TgNF3 acts essentially to coordinate nucleolus and nuclear functions by modulating

  17. IEC Quality Assurance Task Group 5: UV, Temperature, and Humidity (Presentation)

    Miller, D.; Bath, J.; Kohl, M.; Shioda, T.

    2014-03-01

    Taskgroup 5 (TG5) is concerned with a comparative aging standard incorporating factors including ultraviolet radiation, temperature, and humidity. Separate experiments are being conducted in support of a test standard via the regional sub-groups in Asia, Europe, and the United States. The authors will describe the objectives and timeline for TG5 as well as providing an update on the experiments in progress.

  18. ANÁLISES DE PROTOCOLOS TELETERÁPICOS DE CONTROLE DE QUALIDADE DE ALGUNS SERVIÇOS LOCAIS, BASEADOS NO TG40 E ARCAL XXX Routine teletherapy quality control protocols based on TG40 and ARCAL XXX

    Carmen S. Guzmán Calcina

    2002-01-01

    Full Text Available Considerando a importância da garantia da qualidade nos serviços de radioterapia, este trabalho tem como primeiro objetivo fazer uma avaliação dos testes propostos pelos protocolos oficiais internacionais TG40 e ARCAL XXX para os equipamentos de cobalto, acelerador linear e simulador. O segundo objetivo consistiu em se fazer uma avaliação dos testes que atualmente são realizados por alguns serviços de radioterapia nacionais e da América Latina, comparando-os com os apresentados nos protocolos citados. Dos resultados obtidos, observou-se que embora o TG40 apresente os testes básicos necessários para um controle de qualidade adequado, o ARCAL ainda sugere testes complementares. Dos resultados e discussões, concluiu-se que é necessário que os serviços de radioterapia implementem os testes de controle de qualidade básicos e indispensáveis aos seus equipamentos, e que os demais testes sejam implementados de acordo com as suas necessidades e disponibilidades. Como produto deste estudo, sugestões de protocolos são apresentadas para o trabalho de rotina, provenientes da fusão dos protocolos analisados.In view of the great importance of quality control in radiotherapy services, this paper aimed primarily to evaluate the tests recommended by international protocols TG40 and ARCAL XXX for teletherapic equipments (cobalt, linear accelerator and simulator. A second objective was to evaluate the tests currently used in some radiotherapy services in Brazil and Latin America and to compare these tests with the ones recommended by the international protocols. Our results suggest that ARCAL is more complete than TG40, although the latter includes all the essential basic tests. We concluded that radiotherapy services should implement all basic quality control tests and that all other complementary tests should be implemented according to the need of each service. Finally, suggestions of protocols are presented, elaborated from the official and

  19. Regulatory Forum Opinion Piece*: Retrospective Evaluation of Doses in the 26-week Tg.rasH2 Mice Carcinogenicity Studies: Recommendation to Eliminate High Doses at Maximum Tolerated Dose (MTD) in Future Studies.

    Paranjpe, Madhav G; Denton, Melissa D; Vidmar, Tom J; Elbekai, Reem H

    2015-07-01

    High doses in Tg.rasH2 carcinogenicity studies are usually set at the maximum tolerated dose (MTD), although this dose selection strategy has not been critically evaluated. We analyzed the body weight gains (BWGs), mortality, and tumor response in control and treated groups of 29 Tg.rasH2 studies conducted at BioReliance. Based on our analysis, it is evident that the MTD was exceeded at the high and/or mid-doses in several studies. The incidence of tumors in high doses was lower when compared to the low and mid-doses of both sexes. Thus, we recommend that the high dose in male mice should not exceed one-half of the estimated MTD (EMTD), as it is currently chosen, and the next dose should be one-fourth of the EMTD. Because females were less sensitive to decrements in BWG, the high dose in female mice should not exceed two-third of EMTD and the next dose group should be one-third of EMTD. If needed, a third dose group should be set at one-eighth EMTD in males and one-sixth EMTD in females. In addition, for compounds that do not show toxicity in the range finding studies, a limit dose should be applied for the 26-week carcinogenicity studies. © 2014 by The Author(s).

  20. Mannan-Abeta28 conjugate prevents Abeta-plaque deposition, but increases microhemorrhages in the brains of vaccinated Tg2576 (APPsw mice

    Karapetyan Adrine

    2008-09-01

    Full Text Available Abstract Background New pre-clinical trials in AD mouse models may help to develop novel immunogen-adjuvant configurations with the potential to avoid the adverse responses that occurred during the clinical trials with AN-1792 vaccine formulation. Recently, we have pursued an alternative immunization strategy that replaces QS21 the Th1 type adjuvant used in the AN-1792 clinical trial with a molecular adjuvant, mannan that can promote a Th2-polarized immune response through interactions with mannose-binding and CD35/CD21 receptors of the innate immune system. Previously we established that immunization of wild-type mice with mannan-Aβ28 conjugate promoted Th2-mediated humoral and cellular immune responses. In the current study, we tested the efficacy of this vaccine configuration in amyloid precursor protein (APP transgenic mice (Tg2576. Methods Mannan was purified, activated and chemically conjugated to Aβ28 peptide. Humoral immune responses induced by the immunization of mice with mannan-Aβ28 conjugate were analyzed using a standard ELISA. Aβ42 and Aβ40 amyloid burden, cerebral amyloid angiopathy (CAA, astrocytosis, and microgliosis in the brain of immunized and control mice were detected using immunohistochemistry. Additionally, cored plaques and cerebral vascular microhemorrhages in the brains of vaccinated mice were detected by standard histochemistry. Results Immunizations with low doses of mannan-Aβ28 induced potent and long-lasting anti-Aβ humoral responses in Tg2576 mice. Even 11 months after the last injection, the immunized mice were still producing low levels of anti-Aβ antibodies, predominantly of the IgG1 isotype, indicative of a Th2 immune response. Vaccination with mannan-Aβ28 prevented Aβ plaque deposition, but unexpectedly increased the level of microhemorrhages in the brains of aged immunized mice compared to two groups of control animals of the same age either injected with molecular adjuvant fused with an irrelevant

  1. Insulin receptor in mouse neuroblastoma cell line N18TG2: binding properties and visualization with colloidal gold.

    Sartori, C; Stefanini, S; Bernardo, A; Augusti-Tocco, G

    1992-08-01

    Insulin function in the nervous system is still poorly understood. Possible roles as a neuromodulator and as a growth factor have been proposed (Baskin et al., 1987, Ann. Rev. Physiol. 49, 335-347). Stable cell lines may provide an appropriate experimental system for the analysis of insulin action on the various cellular components of the central nervous system. We report here a study to investigate the presence and the properties of insulin specific binding sites in the murine neuroblastoma line, N18TG2, together with insulin action on cell growth and metabolism. Also, receptor internalization has been studied. Binding experiments, carried out in standard conditions at 20 degrees C, enabled us to demonstrate that these cells bind insulin in a specific manner, thus confirming previous findings on other cell lines. Saturation curves showed the presence of two binding sites with Kd 0.3 and 9.7 nM. Competition experiments with porcine and bovine insulin showed an IC50 of 1 and 10 nM, respectively. Competition did not occur in the presence of the unrelated hormones ACTH and FSH. Dissociation experiments indicated the existence of an internalization process of the ligand-receptor complex; this was confirmed by an ultrastructural study using gold conjugated insulin. As far as the insulin action in N18TG2 cells is concerned, physiological concentrations stimulate cell proliferation, whereas no stimulation of glucose uptake was observed, indicating that insulin action in these cells is not mediated by general metabolic effects. On the basis of these data, N18TG2 line appears to be a very suitable model for further studies of the neuronal type insulin receptors, and possibly insulin specific action on the nervous system.

  2. SU-E-T-127: Application of TG-119 for Evaluation of Proton Spot Scanning Based Planning and Treatment Delivery

    Saini, J; Cao, N; Wong, T [SCCA Proton Therapy, A Procure Center, Seattle, WA (United States); Bowen, S; Bloch, C [University of Washington, School of Medicine, Seattle, WA (United States)

    2015-06-15

    Purpose: The clinical test cases presented in AAPM TG-119 are used to evaluate the accuracy of treatment planning and delivery through spot scanning proton beams. Methods: An IBA spot scanning delivery system has been commissioned to be used with the RayStation treatment planning system. Various test cases provided in TG-119 were used for planning and delivery verification. The CT dataset and structures as provided by TG-119 were imported into a mock patient. The plans were optimized using the multi field optimization (MFO) to achieve the desired goals. The planner was given the flexibility to achieve the given dose-volume goals by creating appropriate objectives and constraints. Beams were delivered to a phantom and measurements were performed at multiple depths using the MatrixxPT detector array. The analyses were performed on beam by beam basis and quantified using the gamma index. A tolerance of 3%/3 mm in 2D was used for gamma index analysis along with dose threshold of 10%. Results: The clinical goals for targets and critical structures were met or improved for all cases except the C-Shape target with difficult constraints. The minimum gamma index using the 3%/3mm as a criterion is 93.3% for one of the planes measured for C-Shape target. Using 2%/2mm as a criterion, the minimum gamma index drops to 70%. Only Prostate target has all the planes above >90% pass using the 2%/2mm criterion. Conclusion: The overall accuracy of the treatment planning and delivery is deemed clinically acceptable. The test cases with highly modulated beams can have steep gradients in the dose profiles that can reduce the gamma index pass rate. Gamma analysis based on 3D data may be needed for routine use of 2%/2mm criterion. In addition, improvements in modelling of spot profiles in dose engine may be required for further improving the gamma index pass rate.

  3. SU-F-T-248: FMEA Risk Analysis Implementation (AAPM TG-100) in Total Skin Electron Irradiation Technique

    Ibanez-Rosello, B; Bautista-Ballesteros, J; Bonaque, J [Hospital La Fe, Valencia, Valencia (Spain); Perez-Calatayud, J [Hospital La Fe, Valencia, Valencia (Spain); Clinica Benidorm, Benidorm, Alicante (Spain); Gonzalez-Sanchis, A; Lopez-Torrecilla, J; Brualla-Gonzalez, L; Garcia-Hernandez, T; Vicedo-Gonzalez, A; Granero, D; Serrano, A; Borderia, B; Solera, C [Hospital General ERESA, Valencia, Valencia (Spain); Rosello, J [Hospital General ERESA, Valencia, Valencia (Spain); Universidad de Valencia, Valencia, Valencia (Spain)

    2016-06-15

    Purpose: Total Skin Electron Irradiation (TSEI) is a radiotherapy treatment which involves irradiating the entire body surface as homogeneously as possible. It is composed of an extensive multi-step technique in which quality management requires high consumption of resources and a fluid communication between the involved staff, necessary to improve the safety of treatment. The TG-100 proposes a new perspective of quality management in radiotherapy, presenting a systematic method of risk analysis throughout the global flow of the stages through the patient. The purpose of this work has been to apply TG-100 approach to the TSEI procedure in our institution. Methods: A multidisciplinary team specifically targeting TSEI procedure was formed, that met regularly and jointly developed the process map (PM), following TG-100 guidelines of the AAPM. This PM is a visual representation of the temporal flow of steps through the patient since start until the end of his stay in the radiotherapy service. Results: This is the first stage of the full risk analysis, which is being carried out in the center. The PM provides an overview of the process and facilitates the understanding of the team members who will participate in the subsequent analysis. Currently, the team is implementing the analysis of failure modes and effects (FMEA). The failure modes of each of the steps have been identified and assessors are assigning a value of severity (S), frequency of occurrence (O) and lack of detection (D) individually. To our knowledge, this is the first PM made for the TSEI. The developed PM can be useful for those centers that intend to implement the TSEI technique. Conclusion: The PM of TSEI technique has been established, as the first stage of full risk analysis, performed in a reference center in this treatment.

  4. Association of Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Thyroglobulin (TG) Genetic Variants with Autoimmune Hypothyroidism

    Patel, Hinal; Mansuri, Mohmmad Shoab; Singh, Mala; Begum, Rasheedunnisa; Shastri, Minal; Misra, Ambikanandan

    2016-01-01

    Autoimmune hypothyroidism is known to be caused by immune responses related to the thyroid gland and its immunological feature includes presence of autoimmune antibodies. Therefore the aim was to analyze presence of anti-TPO antibodies in hypothyroidism patients in Gujarat. Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) is one of the susceptibility genes for various autoimmune diseases. Hence, exon1 +49A/G and 3’UTR CT60A/G single nucleotide polymorphisms (SNPs) in CTLA4 and its mRNA expression levels were investigated in autoimmune hypothyroidism patients. Thyroglobulin (TG) is known to be associated with autoimmune thyroid disorders and thus exon 33 (E33) SNP in TG was investigated. We analyzed the presence of anti-TPO antibodies in the plasma samples of 84 hypothyroidism patients and 62 controls by ELISA. PCR-RFLP technique was used for genotyping of polymorphisms. sCTLA4 and flCTLA4 mRNA expression levels were assessed by real time PCR. 59.52% of hypothyroid patients had anti-TPO antibodies in their circulation. The genotype and allele frequencies differed significantly for +49A/G (p = 0.0004 for +49AG, p = 0.0019 for +49GG & p = 0.0004 for allele), CT60 (p = 0.0110 for CT60AG, p = 0.0005 for CT60GG & phypothyroidism when adjusted for age and gender. Our results suggest +49A/G and CT60 polymorphism of CTLA4 and E33 polymorphism of TG may be genetic risk factors for autoimmune hypothyroidism susceptibility and down regulation of both forms of CTLA4 advocates the crucial role of CTLA4 in pathogenesis of autoimmune hypothyroidism. PMID:26963610

  5. Investigation of thermodynamic properties of magnesium chloride amines by HPDSC and TG. For application in a high-lift high-temperature chemical heat pump

    Bevers, E.R.T.; Oonk, H.A.J.; Haije, W.G.; Ekeren, P.J. van

    2007-01-01

    The formation as well as the decomposition of magnesium chloride ammonia complexes was studied by high-pressure differential scanning calorimetry (HPDSC) and thermogravimetric analysis (TG). HPDSC runs were performed under constant ammonia pressure conditions to determine the transition temperatures

  6. Tracking the conversion of nitrogen during pyrolysis of antibiotic mycelial fermentation residues using XPS and TG-FTIR-MS technology

    Zhu, Xiangdong; Yang, Shijun; Wang, Liang; Liu, Yuchen; Qian, Feng; Yao, Wenqing; Zhang, Shicheng; Chen, Jianmin

    2016-01-01

    Antibiotic mycelial fermentation residues (AMFRs), which are emerging solid pollutants, have been recognized as hazardous waste in China since 2008. Nitrogen (N), which is an environmental sensitivity element, is largely retained in AMFR samples derived from fermentation substrates. Pyrolysis is a promising technology for the treatment of solid waste. However, the outcomes of N element during the pyrolysis of AMFRs are still unknown. In this study, the conversion of N element during the pyrolysis of AMFRs was tracked using XPS (X-ray photoelectron spectroscopy) and online TG-FTIR-MS (Thermogravimetry-Fourier transform infrared-Mass spectrometry) technology. In the AMFR sample, organic amine-N, pyrrolic-N, protein-N, pyridinic-N, was the main N-containing species. XPS results indicated that pyrrolic-N and pyridinic-N were retained in the AMFR-derived pyrolysis char. More stable species, such as N-oxide and quaternary-N, were also produced in the char. TG-FTIR-MS results indicated that NH_3 and HCN were the main gaseous species, and their contents were closely related to the contents of amine-N and protein-N, and pyrrolic-N and pyridinic-N of AMFRs, respectively. Increases in heating rate enhanced the amounts of NH_3 and HCN, but had less of an effect on the degradation degree of AMFRs. N-containing organic compounds, including amine-N, nitrile-N and heterocyclic-N, were discerned from the AMFR pyrolysis process. Their release range was extended with increasing of heating rate and carbon content of AMFR sample. This work will help to take appropriate measure to reduce secondary pollution from the treatment of AMFRs. - Highlights: • Hazardous AMFR material was treated by slow pyrolysis reaction. • TG-FTIR-MS were used to study the N conversion for pyrolysis gas and bio-oil. • NH_3 and HCN were observed as the main N-containing gas species. • XPS were used to study the N conversion for pyrolysis char. • Stable species, such as N-oxide and quaternary-N, were

  7. Characterization of Two Different Clay Materials by Thermogravimetry (TG), Differential Scanning Calorimetry (DSC), Dilatometry (DIL) and Mass Spectrometry (MS) - 12215

    Post, Ekkehard [NETZSCH Geraetebau GmbH, Wittelsbacherstrasse 42, 95100 Selb (Germany); Henderson, Jack B. [NETZSCH Instruments North America, LLC, 129 Middlesex Turnpike, Burlington, MA 01803 (United States)

    2012-07-01

    An illitic clay containing higher amounts of organic materials was investigated by dilatometry, thermogravimetry and differential scanning calorimetric. The evolved gases were studied during simultaneous TG-DSC (STA) and dilatometer measurements with simultaneous mass spectrometry in inert gas and oxidizing atmosphere. The dilatometer results were compared with the STA-MS results which confirmed and explained the reactions found during heating of the clay, like dehydration, dehydroxylation, shrinkage, sintering, quartz phase transition, combustion or pyrolysis of organics and the solid state reactions forming meta-kaolinite and mullite. The high amount of organic material effects in inert gas atmosphere most probably a reduction of the oxides which leads to a higher mass loss than in oxidizing atmosphere. Due to this reduction an additional CO{sub 2} emission at around 1000 deg. C was detected which did not occur in oxidizing atmosphere. Furthermore TG-MS results of a clay containing alkali nitrates show that during heating, in addition to water and CO{sub 2}, NO and NO{sub 2} are also evolved, leading to additional mass loss steps. These types of clays showed water loss starting around 100 deg. C or even earlier. This relative small mass loss affects only less shrinkage during the expansion of the sample. The dehydroxylation and the high crystalline quartz content result in considerable shrinkage and expansion of the clay. During the usual solid state reaction where the clay structure collapses, the remaining material finally shrinks down to a so-called clinker. With the help of MS the TG steps can be better interpreted as the evolved gases are identified. With the help of the MS it is possible to distinguish between CO{sub 2} and water (carbonate decomposition, oxidation of organics or dehydration/dehydroxylation). The MS also clearly shows that mass number 44 is found during the TG step of the illitic clay at about 900 deg. C in inert gas, which was interpreted

  8. Kinetic analysis of dechlorination and oxidation of PrOCl by using a non-isothermal TG method

    Yang, H.C.; Eun, H.C.; Cho, Y.Z.; Lee, H.S.; Kim, I.T.

    2009-01-01

    Thermal dechlorination and oxidation process of praseodymium oxychloride, PrOCl, was studied from the view point of reaction kinetics. On the basis of data of thermogravimetry under different oxygen partial pressures at various heating rates, a kinetic analysis was performed using an isoconversional method and a master plot method. The results of the isoconversional method of TG data suggested that the dechlorination and oxidation of PrOCl followed a single step with activation energy of 112.6 ± 3.4 kJ mol -1 , and from master plot methods, the reaction was described by a linear-contracting phase boundary reaction

  9. Meeting of the ITPA Topical Group on Diagnostics

    Costley, A.E.; Donne, A.J.H.

    2002-01-01

    The first meeting of the International Tokamak Physics Activities (ITPA) Topical Group (TG) on diagnostics was held at the Ioffe Physical-Technical institute, St. Petersburg, Russian Federation, on 14-16 November 2001. In total 38 participants attended the meeting and all four ITPA partners (EU, JA, RF and US) were represented. This summary covers mainly the discussions at the TG meeting. The meeting immediately followed a progress meeting, held in the same location on 12-13 November 2001, on the efforts carried out in the Russian Federation on diagnostics for ITER and burning plasma experiments

  10. Age-related changes in core body temperature and activity in triple-transgenic Alzheimer’s disease (3xTgAD mice

    Elysse M. Knight

    2013-01-01

    Alzheimer’s disease (AD is characterised, not only by cognitive deficits and neuropathological changes, but also by several non-cognitive behavioural symptoms that can lead to a poorer quality of life. Circadian disturbances in core body temperature and physical activity are reported in AD patients, although the cause and consequences of these changes are unknown. We therefore characterised circadian patterns of body temperature and activity in male triple transgenic AD mice (3xTgAD and non-transgenic (Non-Tg control mice by remote radiotelemetry. At 4 months of age, daily temperature rhythms were phase advanced and by 6 months of age an increase in mean core body temperature and amplitude of temperature rhythms were observed in 3xTgAD mice. No differences in daily activity rhythms were seen in 4- to 9-month-old 3xTgAD mice, but by 10 months of age an increase in mean daily activity and the amplitude of activity profiles for 3xTgAD mice were detected. At all ages (4–10 months, 3xTgAD mice exhibited greater food intake compared with Non-Tg mice. The changes in temperature did not appear to be solely due to increased food intake and were not cyclooxygenase dependent because the temperature rise was not abolished by chronic ibuprofen treatment. No β-amyloid (Aβ plaques or neurofibrillary tangles were noted in the hypothalamus of 3xTgAD mice, a key area involved in temperature regulation, although these pathological features were observed in the hippocampus and amygdala of 3xTgAD mice from 10 months of age. These data demonstrate age-dependent changes in core body temperature and activity in 3xTgAD mice that are present before significant AD-related neuropathology and are analogous to those observed in AD patients. The 3xTgAD mouse might therefore be an appropriate model for studying the underlying mechanisms involved in non-cognitive behavioural changes in AD.

  11. Age-related changes in core body temperature and activity in triple-transgenic Alzheimer’s disease (3xTgAD) mice

    Knight, Elysse M.; Brown, Timothy M.; Gümüsgöz, Sarah; Smith, Jennifer C. M.; Waters, Elizabeth J.; Allan, Stuart M.; Lawrence, Catherine B.

    2013-01-01

    SUMMARY Alzheimer’s disease (AD) is characterised, not only by cognitive deficits and neuropathological changes, but also by several non-cognitive behavioural symptoms that can lead to a poorer quality of life. Circadian disturbances in core body temperature and physical activity are reported in AD patients, although the cause and consequences of these changes are unknown. We therefore characterised circadian patterns of body temperature and activity in male triple transgenic AD mice (3xTgAD) and non-transgenic (Non-Tg) control mice by remote radiotelemetry. At 4 months of age, daily temperature rhythms were phase advanced and by 6 months of age an increase in mean core body temperature and amplitude of temperature rhythms were observed in 3xTgAD mice. No differences in daily activity rhythms were seen in 4- to 9-month-old 3xTgAD mice, but by 10 months of age an increase in mean daily activity and the amplitude of activity profiles for 3xTgAD mice were detected. At all ages (4–10 months), 3xTgAD mice exhibited greater food intake compared with Non-Tg mice. The changes in temperature did not appear to be solely due to increased food intake and were not cyclooxygenase dependent because the temperature rise was not abolished by chronic ibuprofen treatment. No β-amyloid (Aβ) plaques or neurofibrillary tangles were noted in the hypothalamus of 3xTgAD mice, a key area involved in temperature regulation, although these pathological features were observed in the hippocampus and amygdala of 3xTgAD mice from 10 months of age. These data demonstrate age-dependent changes in core body temperature and activity in 3xTgAD mice that are present before significant AD-related neuropathology and are analogous to those observed in AD patients. The 3xTgAD mouse might therefore be an appropriate model for studying the underlying mechanisms involved in non-cognitive behavioural changes in AD. PMID:22864021

  12. Age-related changes in core body temperature and activity in triple-transgenic Alzheimer's disease (3xTgAD) mice.

    Knight, Elysse M; Brown, Timothy M; Gümüsgöz, Sarah; Smith, Jennifer C M; Waters, Elizabeth J; Allan, Stuart M; Lawrence, Catherine B

    2013-01-01

    Alzheimer's disease (AD) is characterised, not only by cognitive deficits and neuropathological changes, but also by several non-cognitive behavioural symptoms that can lead to a poorer quality of life. Circadian disturbances in core body temperature and physical activity are reported in AD patients, although the cause and consequences of these changes are unknown. We therefore characterised circadian patterns of body temperature and activity in male triple transgenic AD mice (3xTgAD) and non-transgenic (Non-Tg) control mice by remote radiotelemetry. At 4 months of age, daily temperature rhythms were phase advanced and by 6 months of age an increase in mean core body temperature and amplitude of temperature rhythms were observed in 3xTgAD mice. No differences in daily activity rhythms were seen in 4- to 9-month-old 3xTgAD mice, but by 10 months of age an increase in mean daily activity and the amplitude of activity profiles for 3xTgAD mice were detected. At all ages (4-10 months), 3xTgAD mice exhibited greater food intake compared with Non-Tg mice. The changes in temperature did not appear to be solely due to increased food intake and were not cyclooxygenase dependent because the temperature rise was not abolished by chronic ibuprofen treatment. No β-amyloid (Aβ) plaques or neurofibrillary tangles were noted in the hypothalamus of 3xTgAD mice, a key area involved in temperature regulation, although these pathological features were observed in the hippocampus and amygdala of 3xTgAD mice from 10 months of age. These data demonstrate age-dependent changes in core body temperature and activity in 3xTgAD mice that are present before significant AD-related neuropathology and are analogous to those observed in AD patients. The 3xTgAD mouse might therefore be an appropriate model for studying the underlying mechanisms involved in non-cognitive behavioural changes in AD.

  13. Heme and HO-1 inhibition of HCV, HBV, and HIV

    Warren N Schmidt

    2012-10-01

    Full Text Available Hepatitis C virus, human immunodeficiency virus, and hepatitis B virus are chronic viral infections that cause considerable morbidity and mortality throughout the world. In the decades following the identification and sequencing of these viruses, in vitro experiments demonstrated that heme oxygenase-1, its oxidative products, and related compounds of the heme oxygenase system are virucidal for all three viruses. The purpose of this review is to critically evaluate and summarize the seminal studies that described and characterized this remarkable behavior. It will also discuss more recent work that discovered the antiviral mechanisms and target sites of these unique antiviral agents. In spite of the fact that these viruses are diverse pathogens with quite profound differences in structure and life cycle, it is significant that heme and related compounds show striking similarity for viral target sites across all three species. Collectively, these findings strongly indicate that we should move forward and develop heme and related tetrapyrroles into versatile antiviral agents that could be used therapeutically in patients with single or multiple viral infections.

  14. AN ELISA ASSAY FOR HEME OXYGENASE (HO-1)

    An ELISA assay for heme oxygenase (HO-l ) Abstract A double antibody capture ELISA for the HO-l protein has been developed to separately quantitate HO-I protein. The use of 2.5% NP40 detergent greatly assists in freeing HO-l protein from membranes and/or other cel...

  15. Adaptation of the fish juvenile growth test (OECD TG 215, 2000) to the marine species Dicentrarchus labrax.

    Tornambè, A; Manfra, L; Canepa, S; Oteri, F; Martuccio, G; Cicero, A M; Magaletti, E

    2018-02-01

    The OECD TG 215 method (2000) (C.14 method of EC Regulation 440/2008) was developed on the rainbow trout (Oncorynchus mykiss) to assess chronic toxicity (28d) of chemicals on fish juveniles. It contemplates to use other well documented species identifying suitable conditions to evaluate their growth. OECD proposes the European sea bass (Dicentrarchus labrax, L. 1758) as Mediterranean species among vertebrates recommended in the OECD guidelines for the toxicity testing of chemicals. In this context, our study is aimed to proposing the adaptation of the growth test (OECD TG 215, 2000) to D. labrax. For this purpose toxicity tests were performed with sodium dodecyl sulfate, a reference toxicant commonly used in fish toxicity assays. The main aspects of the testing procedure were reviewed: fish size (weight), environmental conditions, dilution water type, experimental design, loading rate and stocking density, feeding (food type and ration), test validity criteria. The experience gained from growth tests with the sea bass allows to promote its inclusion among the species to be used for the C.14 method. Copyright © 2016. Published by Elsevier Inc.

  16. Relationship of body weight parameters with the incidence of common spontaneous tumors in Tg.rasH2 mice.

    Paranjpe, Madhav G; Denton, Melissa D; Vidmar, Tom J; Elbekai, Reem H

    2014-10-01

    The mechanistic relationship between increased food consumption, increased body weights, and increased incidence of tumors has been well established in 2-year rodent models. Body weight parameters such as initial body weights, terminal body weights, food consumption, and the body weight gains in grams and percentages were analyzed to determine whether such relationship exists between these parameters with the incidence of common spontaneous tumors in Tg.rasH2 mice. None of these body weight parameters had any statistically significant relationship with the incidence of common spontaneous tumors in Tg.rasH2 males, namely lung tumors, splenic hemangiosarcomas, nonsplenic hemangiosarcomas, combined incidence of all hemangiosarcomas, and Harderian gland tumors. These parameters also did not have any statistically significant relationship with the incidence of lung and Harderian gland tumors in females. However, in females, increased initial body weights did have a statistically significant relationship with the nonsplenic hemangiosarcomas, and increased terminal body weights did have a statistically significant relationship with the incidence of splenic hemangiosarcomas, nonsplenic hemangiosarcomas, and the combined incidence of all hemangiosarcomas. In addition, increased body weight gains in grams and percentages had a statistically significant relationship with the combined incidence of all hemangiosarcomas in females, but not separately with splenic and nonsplenic hemangiosarcomas. © 2013 by The Author(s).

  17. Efficient protein-repelling thin films regulated by chain mobility of low-Tg polymers with increased stability via crosslinking

    Zhang, Jinghui; Huang, Zhiwei; Liu, Dan

    2017-12-01

    Polymer thin films are generally employed as coatings on implants to prevent protein adsorption. Polymer chain mobility and surface softness have been found to contribute to the protein resistance, but also bring film instability in a liquid protein medium. We investigated the protein resistance ability of three low-Tg polymers, including hydrophobic polymers polyisoprene (PI), poly(n-butyl methacrylate) (PnBMA) and hydrophilic polyethylene oxide (PEO), by overcoming the instability issue with crosslinking. We found that the Tgs of PI and PEO can be increased to around 0 °C after crosslinking. The remained strong chain mobility of both films can still resist protein adsorption regardless the hydrophobicity, yet greatly increases the film stability under an aqueous circumstance. The PnBMA film increased its Tg to around room temperature after crosslinking, which deteriorated the protein-resistance ability having the surface covered by BSA molecules. Our results support that the chain mobility of a polymer film plays an important role in resisting protein adsorption due to the increased entropy associated with more mobile polymer chains. By tune the degree of crosslinking, the stability of polymer in aqueous environment can be increased while the protein resistant ability can be remained. Our results provide a new strategy to design polymer materials for effective antifouling.

  18. The role of FDG-PET/CT in differentiated thyroid cancer patients with negative iodine-131 whole-body scan and elevated anti-Tg level.

    Asa, Sertac; Aksoy, Sabire Yılmaz; Vatankulu, Betül; Aliyev, Anar; Uslu, Lebriz; Ozhan, Meftune; Sager, Sait; Halac, Metin; Sonmezoglu, Kerim

    2014-12-01

    In the follow-up of differentiated thyroid cancer (DTC) after a successful total-near total thyroidectomy and I-131 ablation therapy, anti-thyroglobulin antibodies (anti-Tg) may be persistently or progressively increased in the patients with an undetectable serum thyroglobulin (Tg) level. In these cases, further investigation was performed to search for recurrence/metastases. The aim of our study was clarifying the role of FDG-PET/CT in detecting recurrence/metastasis in patients with DTC with negative serum Tg and elevated anti-Tg level. A total of 40 patients (32 female, 8 male; mean age: 43.15 years (22-65); mean age at diagnosis: 39.08 (16-64)) with DTC who had undetectable serum Tg and elevated anti-Tg level after a successful initial therapy were included in the study. All of the patients had serum anti-Tg of >40 IU/ml and underwent FDG-PET/CT to search for recurrence/metastasis. Twenty patients (50 %) had recurrence/metastasis on FDG-PET/CT while the other 20 had no pathologic findings. Of the 20 patients who had positive FDG-PET/CT, 12 had a histopathological final diagnosis of which 11 were true positive (TP) and 1 was false positive (FP). On the other hand, 16 of the 40 patients had a histopathological final diagnosis of which 11/16 had TP, 1/16 FP, 3/16 false negative (FN) and 1/16 true negative (TN) findings by PET/CT. The final diagnosis was made by clinical follow-up in the remaining 24 patients. Of these, 8 patients were PET positive, and in 1 (12.5 %) of 8 patients a decrease in serum anti-Tg level, in 2 (25 %) patients a saw-toothed pattern and in 5 (62.5 %) a progressive increase in the serum anti-Tg level were noted during the follow-up. Of the 16 of 24 patients who were diagnosed by clinical follow-up, in 8 a (50 %) decrease in serum anti-Tg level, in 6 (37.5 %) a saw-toothed pattern, and in 2 (12.5 %) a progressively increased anti-Tg level was seen. Of the 40 patients, 14 (35 %) had a diagnosis of recurrence/metastasis finally, with

  19. SU-D-204-07: Comparison of AAPM TG150 Draft Image Receptor Tests with Vendor Automated QC Tests for Five Mobile DR Units

    Li, G; Nishino, T [UT MD Anderson Cancer Center, Houston, TX (United States); Greene, T [Radiation Services, Inc., Dover, FL (United States); Willis, C [MD Anderson Cancer Center, Bellaire, TX (United States)

    2015-06-15

    Purpose: To determine the consistency of digital detector (DR) tests recommended by AAPM TG150 and tests provided by commercially available DirectView Total Quality Tool (TQT). Methods: The DR tests recommended by the TG150 Detector Subgroup[1] were performed on 4 new Carestream DRX-Revolution and one Carestream DRX1C retrofit of a GE AMX-4 that had been in service for three years. After detector calibration, flat-field images plus images of two bar patterns oriented parallel and perpendicular to the A-C axis, were acquired at conditions recommended by TG150. Raw images were harvested and then analyzed using a MATLAB software previously validated[2,3,4]. Data were analyzed using ROIs of two different dimensions: 1) 128 x 128 ROIs matching the detector electronics; and 2) 256 x 256 ROIs, each including 4 adjacent smaller ROIs. TG150 metrics from 128 x 128 ROIs were compared to TQT metrics, which are also obtained from 128 x 128 ROIs[5]. Results: The results show that both TG150 and TQT measurements were consistent among these detectors. Differences between TG150 and TQT values appear systematic. Compared with 128 x 128 ROIs, noise and SNR non-uniformity were lower with 256 x 256 ROIs, although signal non-uniformity was similar, indicating detectors were appropriately calibrated for gain and offset. MTF of the retrofit unit remained essentially the same between 2012 and 2015, but was inferior to the new units. The older generator focal spot is smaller (0.75mm vs. 1.2mm), and the SID for acquisition is 182cm as well, so focal spot dimensions cannot explain the difference. The difference in MTF may be secondary to differences in generator X-ray spectrum or by unannounced changes in detector architecture. Further investigation is needed. Conclusion: The study shows that both TG150 and TQT tests are consistent. The numerical value of some metrics are dependent on ROI size.

  20. Immunogenicity of oncolytic vaccinia viruses JX-GFP and TG6002 in a human melanoma in vitro model: studying immunogenic cell death, dendritic cell maturation and interaction with cytotoxic T lymphocytes

    Heinrich B

    2017-05-01

    Full Text Available B Heinrich,1 J Klein,1 M Delic,1 K Goepfert,1 V Engel,1 L Geberzahn,1 M Lusky,2 P Erbs,2 X Preville,3 M Moehler1 1First Department of Internal Medicine, University Medical Center Mainz, Mainz, Germany; 2Transgene SA, Illkirch-Graffenstaden, 3Amoneta Diagnostics, Huningue, France Abstract: Oncolytic virotherapy is an emerging immunotherapeutic modality for cancer treatment. Oncolytic viruses with genetic modifications can further enhance the oncolytic effects on tumor cells and stimulate antitumor immunity. The oncolytic vaccinia viruses JX-594-GFP+/hGM-CSF (JX-GFP and TG6002 are genetically modified by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF or transforming 5-fluorocytosine (5-FC into 5-fluorouracil (5-FU. We compared their properties to kill tumor cells and induce an immunogenic type of cell death in a human melanoma cell model using SK29-MEL melanoma cells. Their influence on human immune cells, specifically regarding the activation of dendritic cells (DCs and the interaction with the autologous cytotoxic T lymphocyte (CTL clone, was investigated. Melanoma cells were infected with either JX-GFP or TG6002 alone or in combination with 5-FC and 5-FU. The influence of viral infection on cell viability followed a time- and multiplicity of infection dependent manner. Combination of virus treatment with 5-FU resulted in stronger reduction of cell viability. TG6002 in combination with 5-FC did not significantly strengthen the reduction of cell viability in this setting. Expression of calreticulin and high mobility group 1 protein (HMGB1, markers of immunogenic cell death (ICD, could be detected after viral infection. Accordingly, DC maturation was noted after viral oncolysis. DCs presented stronger expression of activation and maturation markers. The autologous CTL clone IVSB expressed the activation marker CD69, but viral treatment failed to enhance cytotoxicity marker. In summary, vaccinia viruses JX-GFP and TG6002 lyse

  1. Isohexide and Sorbitol-Derived, Enzymatically Synthesized Renewable Polyesters with Enhanced Tg.

    Gustini, Liliana; Lavilla, Cristina; de Ilarduya, Antxon Martínez; Muñoz-Guerra, Sebastián; Koning, Cor E

    2016-10-10

    Sugar-based polyesters derived from sorbitol and isohexides were obtained via solvent-free enzymatic catalysis. Pendant hydroxyl groups, coming from the sorbitol units, were present along the polyester backbone, whereas the two isohexides, namely, isomannide and isoidide dimethyl ester monomers, were selected to introduce rigidity into the polyester chains. The feasibility of incorporating isomannide as a diol compared to the isoidide dimethyl ester as acyl-donor via lipase-catalyzed polycondensation was investigated. The presence of bicyclic units resulted in enhanced T g with respect to the parent sorbitol-containing polyester lacking isohexides. The different capability of the two isohexides to boost the thermal properties confirmed the more flexible character provided by the isoidide diester derivative. Solvent-borne coatings were prepared by cross-linking the sugar-based polyester polyols with polyisocyanates. The increased rigidity of the obtained sugar-based polyester polyols led to an enhancement in hardness of the resulting coatings.

  2. Immuno-Spin Trapping-Based Detection of Oxidative Modifications in Cardiomyocytes and Coronary Endothelium in the Progression of Heart Failure in Tgαq*44 Mice

    Bartosz Proniewski

    2018-05-01

    Full Text Available Recent studies suggest both beneficial and detrimental role of increased reactive oxygen species and oxidative stress in heart failure (HF. However, it is not clear at which stage oxidative stress and oxidative modifications occur in the endothelium in relation to cardiomyocytes in non-ischemic HF. Furthermore, most methods used to date to study oxidative stress are either non-specific or require tissue homogenization. In this study, we used immuno-spin trapping (IST technique with fluorescent microscopy-based detection of DMPO nitrone adducts to localize and quantify oxidative modifications of the hearts from Tgαq*44 mice; a murine model of HF driven by cardiomyocyte-specific overexpression of Gαq* protein. Tgαq*44 mice and age-matched FVB controls at early, transition, and late stages of HF progression were injected with DMPO in vivo and analyzed ex vivo for DMPO nitrone adducts signals. Progressive oxidative modifications in cardiomyocytes, as evidenced by the elevation of DMPO nitrone adducts, were detected in hearts from 10- to 16-month-old, but not in 8-month-old Tgαq*44 mice, as compared with age-matched FVB mice. The DMPO nitrone adducts were detected in left and right ventricle, septum, and papillary muscle. Surprisingly, significant elevation of DMPO nitrone adducts was also present in the coronary endothelium both in large arteries and in microcirculation simultaneously, as in cardiomyocytes, starting from 10-month-old Tgαq*44 mice. On the other hand, superoxide production in heart homogenates was elevated already in 6-month-old Tgαq*44 mice and progressively increased to high levels in 14-month-old Tgαq*44 mice, while the enzymatic activity of catalase, glutathione reductase, and glutathione peroxidase was all elevated as early as in 4-month-old Tgαq*44 mice and stayed at a similar level in 14-month-old Tgαq*44. In summary, this study demonstrates that IST represents a unique method that allows to quantify oxidative

  3. TU-B-19A-01: Image Registration II: TG132-Quality Assurance for Image Registration

    Brock, K; Mutic, S

    2014-01-01

    AAPM Task Group 132 was charged with a review of the current approaches and solutions for image registration in radiotherapy and to provide recommendations for quality assurance and quality control of these clinical processes. As the results of image registration are always used as the input of another process for planning or delivery, it is important for the user to understand and document the uncertainty associate with the algorithm in general and the Result of a specific registration. The recommendations of this task group, which at the time of abstract submission are currently being reviewed by the AAPM, include the following components. The user should understand the basic image registration techniques and methods of visualizing image fusion. The disclosure of basic components of the image registration by commercial vendors is critical in this respect. The physicists should perform end-to-end tests of imaging, registration, and planning/treatment systems if image registration is performed on a stand-alone system. A comprehensive commissioning process should be performed and documented by the physicist prior to clinical use of the system. As documentation is important to the safe implementation of this process, a request and report system should be integrated into the clinical workflow. Finally, a patient specific QA practice should be established for efficient evaluation of image registration results. The implementation of these recommendations will be described and illustrated during this educational session. Learning Objectives: Highlight the importance of understanding the image registration techniques used in their clinic. Describe the end-to-end tests needed for stand-alone registration systems. Illustrate a comprehensive commissioning program using both phantom data and clinical images. Describe a request and report system to ensure communication and documentation. Demonstrate an clinically-efficient patient QA practice for efficient evaluation of image

  4. Tau causes synapse loss without disrupting calcium homeostasis in the rTg4510 model of tauopathy.

    Katherine J Kopeikina

    Full Text Available Neurofibrillary tangles (NFTs of tau are one of the defining hallmarks of Alzheimer's disease (AD, and are closely associated with neuronal degeneration. Although it has been suggested that calcium dysregulation is important to AD pathogenesis, few studies have probed the link between calcium homeostasis, synapse loss and pathological changes in tau. Here we test the hypothesis that pathological changes in tau are associated with changes in calcium by utilizing in vivo calcium imaging in adult rTg4510 mice that exhibit severe tau pathology due to over-expression of human mutant P301L tau. We observe prominent dendritic spine loss without disruptions in calcium homeostasis, indicating that tangles do not disrupt this fundamental feature of neuronal health, and that tau likely induces spine loss in a calcium-independent manner.

  5. The AMH genotype (rs10407022 T>G) is associated with circulating AMH levels in boys, but not in girls

    Greiber, Iben Katinka; Hagen, Casper P; Busch, Alexander Siegfried

    2018-01-01

    and girls. DESIGN AND METHODS: This study is a combined longitudinal and cross-sectional study in healthy Danish boys and girls from the general population. We included 658 boys aged 5.8-19.8 years and 320 girls aged 5.6-16.5 years. The main outcome measures were genotyping ofAMHandAMHR2, pubertal staging...... the genetic variation also had lower levels of LH (TT: 3.0 IU/L vs TG: 2.8 IU/L vs GG: 1.8 IU/L,P = 0.012). Hormone levels in girls and pubertal onset in either sex did not seem to be profoundly affected by the genotypes. CONCLUSION: Our findings support recent GWAS results in young adults and expand our...

  6. Acoustic Doppler current profiling from the JGOFS Arabian Sea cruises aboard the RV T.G. Thompson

    Kim, H.S.; Flagg, C.N.; Shi, Y. [Brookhaven National Lab., Upton, NY (United States). Oceanographic and Atmospheric Sciences Div.

    1996-12-01

    Acoustic Doppler current profiler (ADCP) data is part of the core data for the US JGOFS Arabian Sea project, along with hydrographic and nutrient data. Seventeen cruises are scheduled to take place between September 1994 and January 1996 on the R/V T.G. Thompson. Seven of the cruises follow a standard cruise track, taking hydrographic, chemical and biological measurements. The rest of the cruises, which take place generally within the standard cruise region defined by a set track, are for the deployment and recovery of moored equipment and towing of a SeaSoar. Detailed description of ADCP hardware, the AutoADCP data acquisition system, and the collection of navigation and compass data on the Thompson is documented in Section 2. Followed by data collection for each cruise together with a cruise track, Section 3 presents the processing and analysis of velocity and acoustic backscatter intensity data. Section 5 shows results of profile quality diagnosis.

  7. Análise TG-ROC de testes de imunofluorescência no diagnóstico de leishmaniose visceral canina Análisis TG-ROC de pruebas de inmunofluorescencia en el diagnóstico de leishmaniasis visceral canina TG-ROC analysis of immunofluorescence assays in canine visceral leishmaniasis diagnosis

    Rita Maria da Silva

    2009-12-01

    Full Text Available OBJETIVO: Analisar a acurácia do diagnóstico de dois protocolos de imunofluorescência indireta para leishmaniose visceral canina. MÉTODOS: Cães provenientes de inquérito soroepidemiológico realizado em área endêmica nos municípios de Araçatuba e de Andradina, na região noroeste do estado de São Paulo, em 2003, e área não endêmica da região metropolitana de São Paulo, foram utilizados para avaliar comparativamente dois protocolos da reação de imunofluorescência indireta (RIFI para leishmaniose: um utilizando antígeno heterólogo Leishmania major (RIFI-BM e outro utilizando antígeno homólogo Leishmania chagasi (RIFI-CH. Para estimar acurácia utilizou-se a análise two-graph receiver operating characteristic (TG-ROC. A análise TG-ROC comparou as leituras da diluição 1:20 do antígeno homólogo (RIFI-CH, consideradas como teste referência, com as diluições da RIFI-BM (antígeno heterólogo. RESULTADOS: A diluição 1:20 do teste RIFI-CH apresentou o melhor coeficiente de contingência (0,755 e a maior força de associação entre as duas variáveis estudadas (qui-quadrado=124,3, sendo considerada a diluição-referência do teste nas comparações com as diferentes diluições do teste RIFI-BM. Os melhores resultados do RIFI-BM foram obtidos na diluição 1:40, com melhor coeficiente de contingência (0,680 e maior força de associação (qui-quadrado=80,8. Com a mudança do ponto de corte sugerido nesta análise para a diluição 1:40 da RIFI-BM, o valor do parâmetro especificidade aumentou de 57,5% para 97,7%, embora a diluição 1:80 tivesse apresentado a melhor estimativa para sensibilidade (80,2% com o novo ponto de corte. CONCLUSÕES: A análise TG-ROC pode fornecer importantes informações sobre os testes de diagnósticos, além de apresentar sugestões sobre pontos de cortes que podem melhorar as estimativas de sensibilidade e especificidade do teste, e avaliá-los a luz do melhor custo

  8. Polymorphisms in Genes Involved in Fatty Acid β-Oxidation Interact with Dietary Fat Intakes to Modulate the Plasma TG Response to a Fish Oil Supplementation

    Bouchard-Mercier, Annie; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

    2014-01-01

    A large inter-individual variability in the plasma triglyceride (TG) response to an omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been observed. The objective was to examine gene-diet interaction effects on the plasma TG response after a fish oil supplementation, between single-nucleotide polymorphisms (SNPs) within genes involved in fatty acid β-oxidation and dietary fat intakes. Two hundred and eight (208) participants were recruited in the greater Quebec City area. The participants completed a six-week fish oil supplementation (5 g fish oil/day: 1.9–2.2 g EPA and 1.1 g DHA). Dietary fat intakes were measured using three-day food records. SNPs within RXRA, CPT1A, ACADVL, ACAA2, ABCD2, ACOX1 and ACAA1 genes were genotyped using TAQMAN methodology. Gene-diet interaction effects on the plasma TG response were observed for SNPs within RXRA (rs11185660, rs10881576 and rs12339187) and ACOX1 (rs17583163) genes. For rs11185660, fold changes in RXRA gene expression levels were different depending on SFA intakes for homozygotes T/T. Gene-diet interaction effects of SNPs within genes involved in fatty acid β-oxidation and dietary fat intakes may be important in understanding the inter-individual variability in plasma TG levels and in the plasma TG response to a fish oil supplementation. PMID:24647074

  9. Polymorphisms in Genes Involved in Fatty Acid β-Oxidation Interact with Dietary Fat Intakes to Modulate the Plasma TG Response to a Fish Oil Supplementation

    Annie Bouchard-Mercier

    2014-03-01

    Full Text Available A large inter-individual variability in the plasma triglyceride (TG response to an omega-3 polyunsaturated fatty acid (n-3 PUFA supplementation has been observed. The objective was to examine gene-diet interaction effects on the plasma TG response after a fish oil supplementation, between single-nucleotide polymorphisms (SNPs within genes involved in fatty acid β-oxidation and dietary fat intakes. Two hundred and eight (208 participants were recruited in the greater Quebec City area. The participants completed a six-week fish oil supplementation (5 g fish oil/day: 1.9–2.2 g EPA and 1.1 g DHA. Dietary fat intakes were measured using three-day food records. SNPs within RXRA, CPT1A, ACADVL, ACAA2, ABCD2, ACOX1 and ACAA1 genes were genotyped using TAQMAN methodology. Gene-diet interaction effects on the plasma TG response were observed for SNPs within RXRA (rs11185660, rs10881576 and rs12339187 and ACOX1 (rs17583163 genes. For rs11185660, fold changes in RXRA gene expression levels were different depending on SFA intakes for homozygotes T/T. Gene-diet interaction effects of SNPs within genes involved in fatty acid β-oxidation and dietary fat intakes may be important in understanding the inter-individual variability in plasma TG levels and in the plasma TG response to a fish oil supplementation.

  10. The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio as a predictor of β-cell function in African American women.

    Maturu, Amita; DeWitt, Peter; Kern, Philip A; Rasouli, Neda

    2015-05-01

    The TG/HDL-C ratio is used as a marker of insulin resistance (IR) in Caucasians. However, there are conflicting data on TG/HDL-C ratio as a predictor of IR in African Americans. Compared to Caucasians, African Americans have lower TG levels and increased insulin levels despite a greater risk for diabetes. We hypothesized that the TG/HDL-C ratio is predictive of IR and/or β-cell function in African American (AA) women. Non-diabetic AA women (n = 41) with a BMI > 25 kg/m(2) underwent frequently sampled intravenous glucose tolerance test (FSIGTT). Insulin sensitivity (SI) and the acute insulin response to glucose (AIRg) were measured using minimal model and β-cell function was determined by disposition index (DI = S I*AIRg). IR was defined as the lowest tertile of SI ( 0.70 was defined as significant discrimination. The mean (± SD) age was 38.5 ± 11.3 years, with BMI of 33.5 ± 6.7 kg/m(2) and fasting glucose of 86.5 ± 10.5 mg/dL. The AUC-ROC for the prediction of DI women. However, we did show an inverse association between the TG/HDL-C ratio and β-cell function, suggesting that this simple tool may effectively identify AA women at risk for DM2. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations.

    Pardanani, A; Hood, J; Lasho, T; Levine, R L; Martin, M B; Noronha, G; Finke, C; Mak, C C; Mesa, R; Zhu, H; Soll, R; Gilliland, D G; Tefferi, A

    2007-08-01

    JAK2V617F and MPLW515L/K represent recently identified mutations in myeloproliferative disorders (MPD) that cause dysregulated JAK-STAT signaling, which is implicated in MPD pathogenesis. We developed TG101209, an orally bioavailable small molecule that potently inhibits JAK2 (IC(50)=6 nM), FLT3 (IC(50)=25 nM) and RET (IC(50)=17 nM) kinases, with significantly less activity against other tyrosine kinases including JAK3 (IC(50)=169 nM). TG101209 inhibited growth of Ba/F3 cells expressing JAK2V617F or MPLW515L mutations with an IC(50) of approximately 200 nM. In a human JAK2V617F-expressing acute myeloid leukemia cell line, TG101209-induced cell cycle arrest and apoptosis, and inhibited phosphorylation of JAK2V617F, STAT5 and STAT3. Therapeutic efficacy of TG101209 was demonstrated in a nude mouse model. Furthermore, TG101209 suppressed growth of hematopoietic colonies from primary progenitor cells harboring JAK2V617F or MPL515 mutations.

  12. Mobility of coated and uncoated TiO2 nanomaterials in soil columns--Applicability of the tests methods of OECD TG 312 and 106 for nanomaterials.

    Nickel, Carmen; Gabsch, Stephan; Hellack, Bryan; Nogowski, Andre; Babick, Frank; Stintz, Michael; Kuhlbusch, Thomas A J

    2015-07-01

    Nanomaterials are commonly used in everyday life products and during their life cycle they can be released into the environment. Soils and sediments are estimated as significant sinks for those nanomaterials. To investigate and assess the behaviour of nanomaterials in soils and sediments standardized test methods are needed. In this study the applicability of two existing international standardized test guidelines for the testing of nanomaterials, OECD TG 106 "Adsorption/Desorption using a Bath Equilibrium Method" and the OECD TG 312 "Leaching in Soil Columns", were investigated. For the study one coated and two uncoated TiO2 nanomaterials were used, respectively. The results indicate that the OECD TG 106 is not applicable for nanomaterials. However, the test method according to OECD TG 312 was found to be applicable if nano-specific adaptations are applied. The mobility investigations of the OECD TG 312 indicated a material-dependent mobility of the nanomaterials, which in some cases may lead to an accumulation in the upper soil layers. Whereas no significant transport was observed for the uncoated materials for the double-coated material (coating with dimethicone and aluminiumoxide) a significant transport was detected and attributed to the coating. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Tracking the conversion of nitrogen during pyrolysis of antibiotic mycelial fermentation residues using XPS and TG-FTIR-MS technology.

    Zhu, Xiangdong; Yang, Shijun; Wang, Liang; Liu, Yuchen; Qian, Feng; Yao, Wenqing; Zhang, Shicheng; Chen, Jianmin

    2016-04-01

    Antibiotic mycelial fermentation residues (AMFRs), which are emerging solid pollutants, have been recognized as hazardous waste in China since 2008. Nitrogen (N), which is an environmental sensitivity element, is largely retained in AMFR samples derived from fermentation substrates. Pyrolysis is a promising technology for the treatment of solid waste. However, the outcomes of N element during the pyrolysis of AMFRs are still unknown. In this study, the conversion of N element during the pyrolysis of AMFRs was tracked using XPS (X-ray photoelectron spectroscopy) and online TG-FTIR-MS (Thermogravimetry-Fourier transform infrared-Mass spectrometry) technology. In the AMFR sample, organic amine-N, pyrrolic-N, protein-N, pyridinic-N, was the main N-containing species. XPS results indicated that pyrrolic-N and pyridinic-N were retained in the AMFR-derived pyrolysis char. More stable species, such as N-oxide and quaternary-N, were also produced in the char. TG-FTIR-MS results indicated that NH3 and HCN were the main gaseous species, and their contents were closely related to the contents of amine-N and protein-N, and pyrrolic-N and pyridinic-N of AMFRs, respectively. Increases in heating rate enhanced the amounts of NH3 and HCN, but had less of an effect on the degradation degree of AMFRs. N-containing organic compounds, including amine-N, nitrile-N and heterocyclic-N, were discerned from the AMFR pyrolysis process. Their release range was extended with increasing of heating rate and carbon content of AMFR sample. This work will help to take appropriate measure to reduce secondary pollution from the treatment of AMFRs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Comparison of Dose Distributions With TG-43 and Collapsed Cone Convolution Algorithms Applied to Accelerated Partial Breast Irradiation Patient Plans

    Thrower, Sara L., E-mail: slloupot@mdanderson.org [The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Shaitelman, Simona F.; Bloom, Elizabeth [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Salehpour, Mohammad; Gifford, Kent [Department of Radiation Physics, The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2016-08-01

    Purpose: To compare the treatment plans for accelerated partial breast irradiation calculated by the new commercially available collapsed cone convolution (CCC) and current standard TG-43–based algorithms for 50 patients treated at our institution with either a Strut-Adjusted Volume Implant (SAVI) or Contura device. Methods and Materials: We recalculated target coverage, volume of highly dosed normal tissue, and dose to organs at risk (ribs, skin, and lung) with each algorithm. For 1 case an artificial air pocket was added to simulate 10% nonconformance. We performed a Wilcoxon signed rank test to determine the median differences in the clinical indices V90, V95, V100, V150, V200, and highest-dosed 0.1 cm{sup 3} and 1.0 cm{sup 3} of rib, skin, and lung between the two algorithms. Results: The CCC algorithm calculated lower values on average for all dose-volume histogram parameters. Across the entire patient cohort, the median difference in the clinical indices calculated by the 2 algorithms was <10% for dose to organs at risk, <5% for target volume coverage (V90, V95, and V100), and <4 cm{sup 3} for dose to normal breast tissue (V150 and V200). No discernable difference was seen in the nonconformance case. Conclusions: We found that on average over our patient population CCC calculated (<10%) lower doses than TG-43. These results should inform clinicians as they prepare for the transition to heterogeneous dose calculation algorithms and determine whether clinical tolerance limits warrant modification.

  15. SU-F-T-78: Minimum Data Set of Measurements for TG 71 Based Electron Monitor-Unit Calculations

    Xu, H; Guerrero, M; Prado, K; Yi, B

    2016-01-01

    Purpose: Building up a TG-71 based electron monitor-unit (MU) calculation protocol usually involves massive measurements. This work investigates a minimum data set of measurements and its calculation accuracy and measurement time. Methods: For 6, 9, 12, 16, and 20 MeV of our Varian Clinac-Series linear accelerators, the complete measurements were performed at different depth using 5 square applicators (6, 10, 15, 20 and 25 cm) with different cutouts (2, 3, 4, 6, 10, 15 and 20 cm up to applicator size) for 5 different SSD’s. For each energy, there were 8 PDD scans and 150 point measurements for applicator factors, cutout factors and effective SSDs that were then converted to air-gap factors for SSD 99–110cm. The dependence of each dosimetric quantity on field size and SSD was examined to determine the minimum data set of measurements as a subset of the complete measurements. The “missing” data excluded in the minimum data set were approximated by linear or polynomial fitting functions based on the included data. The total measurement time and the calculated electron MU using the minimum and the complete data sets were compared. Results: The minimum data set includes 4 or 5 PDD’s and 51 to 66 point measurements for each electron energy, and more PDD’s and fewer point measurements are generally needed as energy increases. Using only <50% of complete measurement time, the minimum data set generates acceptable MU calculation results compared to those with the complete data set. The PDD difference is within 1 mm and the calculated MU difference is less than 1.5%. Conclusion: Data set measurement for TG-71 electron MU calculations can be minimized based on the knowledge of how each dosimetric quantity depends on various setup parameters. The suggested minimum data set allows acceptable MU calculation accuracy and shortens measurement time by a few hours.

  16. SU-E-T-179: Clinical Impact of IMRT Failure Modes at Or Near TG-142 Tolerance Criteria Levels

    Faught, J Tonigan; Balter, P; Johnson, J; Kry, S; Court, L; Stingo, F; Followill, D [UT MD Anderson Cancer Center, Houston, TX (United States)

    2015-06-15

    Purpose: Quantitatively assess the clinical impact of 11 critical IMRT dose delivery failure modes. Methods: Eleven step-and-shoot IMRT failure modes (FMs) were introduced into twelve Pinnacle v9.8 treatment plans. One standard and one highly modulated plan on the IROC IMRT phantom and ten previous H&N patient treatment plans were used. FMs included physics components covered by basic QA near tolerance criteria levels (TG-142) such as beam energy, MLC positioning, and MLC modeling. Resultant DVHs were compared to those of failure-free plans and the severity of plan degradation was assessed considering PTV coverage and OAR and normal tissue tolerances and used for FMEA severity scoring. Six of these FMs were physically simulated and phantom irradiations performed. TLD and radiochromic film results are used for comparison to treatment planning studies. Results: Based on treatment planning studies, the largest clinical impact from the phantom cases was induced by 2 mm systematic MLC shift in one bank with the combination of a D95% target under dose near 16% and OAR overdose near 8%. Cord overdoses of 5%–11% occurred with gantry angle, collimator angle, couch angle, MLC leaf end modeling, and MLC transmission and leakage modeling FMs. PTV coverage and/or OAR sparing was compromised in all FMs introduced in phantom plans with the exception of CT number to electron density tables, MU linearity, and MLC tongue-and-groove modeling. Physical measurements did not entirely agree with treatment planning results. For example, symmetry errors resulted in the largest physically measured discrepancies of up to 3% in the PTVs while a maximum of 0.5% deviation was seen in the treatment planning studies. Patient treatment plan study results are under analysis. Conclusion: Even in the simplistic anatomy of the IROC phantom, some basic physics FMs, just outside of TG-142 tolerance criteria, appear to have the potential for large clinical implications.

  17. c.1643_1644delTG XPC mutation is more frequent in Moroccan patients with xeroderma pigmentosum.

    Senhaji, Mohamed Amine; Abidi, Omar; Nadifi, Sellama; Benchikhi, Hakima; Khadir, Khadija; Ben Rekaya, Mariem; Eloualid, Abdelmajid; Messaoud, Olfa; Abdelhak, Sonia; Barakat, Abdelhamid

    2013-01-01

    Xeroderma pigmentosum is a rare autosomal recessive disease characterized by hypersensitivity to UV light which is due to alterations of the nucleotide excision repair pathway. Eight genes (XPA to XPG and XPV) are responsible for the disease. Among them, the XPC gene is known to be the most mutated in Mediterranean patients. The aim of this study was to determine the frequency of the most common XPC mutation and describe the clinical features of Moroccan patients with xeroderma pigmentosum. Twenty four patients belonging to 21 unrelated Moroccan families and 58 healthy subjects were investigated. After clinical examination, the screening for the c.1643_1644delTG (p.Val548AlafsX25) mutation in the XPC gene was performed by PCR and automated sequencing of exon 9 in all patients and controls. The molecular analysis showed that among the 24 patients, 17 were homozygous for the c.1643_1644delTG mutation and all their tested parents were heterozygous, whereas the others (7 patients) did not carry the mutation. The frequency of this mutation was estimated to be 76.19 % (16/21 families). None of the 58 healthy individuals carried this mutation. In addition, clinical investigation showed that the majority of the patients bearing this mutation have the same clinical features. Our results revealed that the p.Val548AlafsX25 mutation is the major cause (76.19 %) of xeroderma pigmentosum in Moroccan families. This would have an important impact on improving management of patients and their relatives.

  18. SU-F-T-78: Minimum Data Set of Measurements for TG 71 Based Electron Monitor-Unit Calculations

    Xu, H; Guerrero, M; Prado, K; Yi, B [University of Maryland School of Medicine, Baltimore, MD (United States)

    2016-06-15

    Purpose: Building up a TG-71 based electron monitor-unit (MU) calculation protocol usually involves massive measurements. This work investigates a minimum data set of measurements and its calculation accuracy and measurement time. Methods: For 6, 9, 12, 16, and 20 MeV of our Varian Clinac-Series linear accelerators, the complete measurements were performed at different depth using 5 square applicators (6, 10, 15, 20 and 25 cm) with different cutouts (2, 3, 4, 6, 10, 15 and 20 cm up to applicator size) for 5 different SSD’s. For each energy, there were 8 PDD scans and 150 point measurements for applicator factors, cutout factors and effective SSDs that were then converted to air-gap factors for SSD 99–110cm. The dependence of each dosimetric quantity on field size and SSD was examined to determine the minimum data set of measurements as a subset of the complete measurements. The “missing” data excluded in the minimum data set were approximated by linear or polynomial fitting functions based on the included data. The total measurement time and the calculated electron MU using the minimum and the complete data sets were compared. Results: The minimum data set includes 4 or 5 PDD’s and 51 to 66 point measurements for each electron energy, and more PDD’s and fewer point measurements are generally needed as energy increases. Using only <50% of complete measurement time, the minimum data set generates acceptable MU calculation results compared to those with the complete data set. The PDD difference is within 1 mm and the calculated MU difference is less than 1.5%. Conclusion: Data set measurement for TG-71 electron MU calculations can be minimized based on the knowledge of how each dosimetric quantity depends on various setup parameters. The suggested minimum data set allows acceptable MU calculation accuracy and shortens measurement time by a few hours.

  19. Syringyl Methacrylate, a Hardwood Lignin-Based Monomer for High-Tg Polymeric Materials.

    Holmberg, Angela L; Reno, Kaleigh H; Nguyen, Ngoc A; Wool, Richard P; Epps, Thomas H

    2016-05-17

    As viable precursors to a diverse array of macromolecules, biomass-derived compounds must impart wide-ranging and precisely controllable properties to polymers. Herein, we report the synthesis and subsequent reversible addition-fragmentation chain-transfer polymerization of a new monomer, syringyl methacrylate (SM, 2,6-dimethoxyphenyl methacrylate), that can facilitate widespread property manipulations in macromolecules. Homopolymers and heteropolymers synthesized from SM and related monomers have broadly tunable and highly controllable glass transition temperatures ranging from 114 to 205 °C and zero-shear viscosities ranging from ∼0.2 kPa·s to ∼17,000 kPa·s at 220 °C, with consistent thermal stabilities. The tailorability of these properties is facilitated by the controlled polymerization kinetics of SM and the fact that one vs two o -methoxy groups negligibly affect monomer reactivity. Moreover, syringol, the precursor to SM, is an abundant component of depolymerized hardwood (e.g., oak) and graminaceous (e.g., switchgrass) lignins, making SM a potentially sustainable and low-cost candidate for tailoring macromolecular properties.

  20. WE-G-BRC-00: Experiences with TG100 in Clinical Use

    NONE

    2016-06-15

    Failure Mode and Effects Analysis (FMEA) originated as an industrial engineering technique used for risk management and safety improvement of complex processes. In the context of radiotherapy, the AAPM Task Group 100 advocates FMEA as the framework of choice for establishing clinical quality management protocols. However, there is concern that widespread adoption of FMEA in radiation oncology will be hampered by the perception that implementation of the tool will have a steep learning curve, be extremely time consuming and labor intensive, and require additional resources. To overcome these preconceptions and facilitate the introduction of the tool into clinical practice, the medical physics community must be educated in the use of this tool and the ease in which it can be implemented. Organizations with experience in FMEA should share their knowledge with others in order to increase the implementation, effectiveness and productivity of the tool. This session will include a brief, general introduction to FMEA followed by a focus on practical aspects of implementing FMEA for specific clinical procedures including HDR brachytherapy, physics plan review and radiosurgery. A description of common equipment and devices used in these procedures and how to characterize new devices for safe use in patient treatments will be presented. This will be followed by a discussion of how to customize FMEA techniques and templates to one’s own clinic. Finally, cases of common failure modes for specific procedures (described previously) will be shown and recommended intervention methodologies and outcomes reviewed. Learning Objectives: Understand the general concept of failure mode and effect analysis Learn how to characterize new equipment for safety Be able to identify potential failure modes for specific procedures and learn mitigation techniques Be able to customize FMEA examples and templates for use in any clinic.

  1. WE-G-BRC-00: Experiences with TG100 in Clinical Use

    2016-01-01

    Failure Mode and Effects Analysis (FMEA) originated as an industrial engineering technique used for risk management and safety improvement of complex processes. In the context of radiotherapy, the AAPM Task Group 100 advocates FMEA as the framework of choice for establishing clinical quality management protocols. However, there is concern that widespread adoption of FMEA in radiation oncology will be hampered by the perception that implementation of the tool will have a steep learning curve, be extremely time consuming and labor intensive, and require additional resources. To overcome these preconceptions and facilitate the introduction of the tool into clinical practice, the medical physics community must be educated in the use of this tool and the ease in which it can be implemented. Organizations with experience in FMEA should share their knowledge with others in order to increase the implementation, effectiveness and productivity of the tool. This session will include a brief, general introduction to FMEA followed by a focus on practical aspects of implementing FMEA for specific clinical procedures including HDR brachytherapy, physics plan review and radiosurgery. A description of common equipment and devices used in these procedures and how to characterize new devices for safe use in patient treatments will be presented. This will be followed by a discussion of how to customize FMEA techniques and templates to one’s own clinic. Finally, cases of common failure modes for specific procedures (described previously) will be shown and recommended intervention methodologies and outcomes reviewed. Learning Objectives: Understand the general concept of failure mode and effect analysis Learn how to characterize new equipment for safety Be able to identify potential failure modes for specific procedures and learn mitigation techniques Be able to customize FMEA examples and templates for use in any clinic

  2. TU-D-9A-01: TG176: Dosimetric Effects of Couch Tops and Immobilization Devices

    Olch, A

    2014-01-01

    The dosimetric impact from devices external to the patient is a complex combination of increased skin dose, reduced tumor dose, and altered dose distribution. Although small monitor unit or dose corrections are routinely made for blocking trays, ion chamber correction factors, or tissue inhomogeneities, the dose perturbation of the treatment couch top or immobilization devices are often overlooked. These devices also increase surface dose, an effect which is also often ignored or underestimated. These concerns have grown recently due to the increased use of monolithic carbon fiber couch tops which are optimal for imaging for patient position verification but cause attenuation and increased surface dose compared to the ‘tennis racket’ style couch top they often replace. Also, arc delivery techniques have replaced stationary gantry techniques which cause a greater fraction of the dose to be delivered from posterior angles. A host of immobilization devices are available and used to increase patient positioning reproducibility, and these also have attenuation and skin dose implications which are often ignored. This report of Task Group 176 serves to present a survey of published data that illustrates the magnitude of the dosimetric effects of a wide range of devices external to the patient. The report also provides methods for modeling couch tops in treatment planning systems so the physicist can accurately compute the dosimetric effects for indexed patient treatments. Both photon and proton beams are considered. A discussion on avoidance of high density structures during beam planning is also provided. An important aspect of this report are the recommendations we make to clinical physicists, treatment planning system vendors, and device vendors on how to make measurements of skin dose and attenuation, how to report these values, and for the vendors, an appeal is made to work together to provide accurate couch top models in planning systems. Learning Objectives

  3. Cotinine halts the advance of Alzheimer’s disease-like pathology and associated depressive-like behavior in Tg6799 mice

    Sagar ePatel

    2014-07-01

    Full Text Available Alzheimer’s disease (AD is associated with cognitive and non-cognitive symptoms for which there are currently no effective therapies. We have previously reported that cotinine, a natural product obtained from tobacco leaves, prevented memory loss and diminished amyloid-β (Aβ plaque pathology in the transgenic 6799 mice (Tg6799 mice when treated prior to the development of the pathology. We have also shown that cotinine reduces depressive-like behavior in normal and chronically stressed C57BL/6 mice. Here, we extend our previous studies by investigating the effects of cotinine on the progression of AD-like pathology, depressive-like behavior, and the mechanisms underlying its beneficial effects in the Tg6799 mice when left untreated until after a more advanced stage of the disease’s development. The results show that vehicle-treated Tg6799 mice displayed an accentuated loss of working memory and an abundant Aβ plaque pathology that were accompanied by higher levels of depressive-like behavior as compared to control littermates. By contrast, prolonged daily cotinine treatment, withheld until after a mid-level progression of AD-like pathology, reduced Aβ levels, Aβ plaques, and depressive-like behavior as well as dramatically improved working memory in Tg6799 mice to levels no different from control littermates. The beneficial effects of cotinine were accompanied by an increase in the expression of the active form of protein kinase B (Akt and the postsynaptic density protein 95 (PSD95 in the hippocampi and frontal cortices of Tg6799 mice. This suggests that cotinine halts the progression of AD-like pathology while reducing depressive-like behavior by stimulating signaling pathways supporting synaptic plasticity in Tg6799 mice. The potential use of cotinine to treat cognitive and non-cognitive symptoms of AD is discussed.

  4. A vacuolar iron transporter in tulip, TgVit1, is responsible for blue coloration in petal cells through iron accumulation.

    Momonoi, Kazumi; Yoshida, Kumi; Mano, Shoji; Takahashi, Hideyuki; Nakamori, Chihiro; Shoji, Kazuaki; Nitta, Akira; Nishimura, Mikio

    2009-08-01

    Blue color in flowers is due mainly to anthocyanins, and a considerable part of blue coloration can be attributed to metal-complexed anthocyanins. However, the mechanism of metal ion transport into vacuoles and subsequent flower color development has yet to be fully explored. Previously, we studied the mechanism of blue color development specifically at the bottom of the inner perianth in purple tulip petals of Tulipa gesneriana cv. Murasakizuisho. We found that differences in iron content were associated with the development of blue- and purple-colored cells. Here, we identify a vacuolar iron transporter in T. gesneriana (TgVit1), and characterize the localization and function of this transporter protein in tulip petals. The amino acid sequence of TgVit1 is 85% similar that of the Arabidopsis thaliana vacuolar iron transporter AtVIT1, and also showed similarity to the AtVIT1 homolog in yeast, Ca(2+)-sensitive cross-complementer 1 (CCC1). The gene TgVit1 was expressed exclusively in blue-colored epidermal cells, and protein levels increased with increasing mRNA expression and blue coloration. Transient expression experiments revealed that TgVit1 localizes to the vacuolar membrane, and is responsible for the development of the blue color in purple cells. Expression of TgVit1 in yeast rescued the growth defect of ccc1 mutant cells in the presence of high concentrations of FeSO(4). Our results indicate that TgVit1 plays an essential role in blue coloration as a vacuolar iron transporter in tulip petals. These results suggest a new role for involvement of a vacuolar iron transporter in blue flower color development.

  5. Estudo termoanalítico de comprimidos revestidos contendo captopril através de termogravimetria (TG e calorimetria exploratória diferencial (DSC Thermal analysis study of captopril coated tablets by thermogravimetry (TG and differential scanning calorimetry (DSC

    Giovana Carolina Bazzo

    2005-09-01

    Full Text Available No presente trabalho foram desenvolvidos comprimidos de captopril revestidos com hidroxipropilmetilcelulose (HPMC, Opadry®, polivinilpirrolidona (PVP, Eudragit® E e goma laca. Foi realizado estudo termoanalítico do fármaco e das formulações através de termogravimetria (TG e calorimetria exploratória diferencial (DSC. Através da análise das curvas DSC verificou-se que não houve a ocorrência de interação entre o fármaco e os excipientes lactose, celulose microcristalina, croscarmelose sódica, Aerosil® e talco, utilizados na formulação do comprimido. Através desta técnica detectou-se a possibilidade de interação entre captopril e estearato de magnésio. De acordo com os resultados obtidos através de DSC não foram observadas alterações na cristalinidade do fármaco decorrentes dos processos de compressão e revestimento. A termogravimetria foi utilizada para o estudo da cinética de degradação do captopril e dos comprimidos. Os parâmetros cinéticos foram determinados através do método de Ozawa. Os resultados demonstraram que não houve alteração da estabilidade térmica do captopril na forma de comprimido. A formulação revestida com HPMC foi a que apresentou maior estabilidade térmica, quando comparada às demais formulações de revestimento.In the present study, captopril coated tablets with hydroxypropylmethylcellulose (HPMC, Opadry®, polyvinylpirrolidone (PVP, Eudragit® and shellac were produced. Differential scanning calorimetry (DSC and thermogravimetry (TG were used to evaluate the thermal properties of the drug and the formulations. On the basis of DSC results, captopril was found to be compatible with lactose, microcrystalline cellulose, sodium croscarmellose, Aerosil® and talc. Some possibility of interaction between drug-excipient was observed with magnesium stearate. However, additional techniques to confirm the results obtained are needed. There was no influence of mechanical treatment (tableting

  6. Influence of prevastein (R), an isoflavone-rich soy product, on mammary gland development and Tumorigenesis in Tg.NK (MMTV/c-neu) mice

    Thomsen, Anni R.; Mortensen, Alicja; Breinholt, Vibeke

    2005-01-01

    We investigated spontaneous mammary tumor development and mammary gland morphogenesis in female Tg.NK mice postnatally exposed to dietary soy isoflavones (0, 11, 39, and 130 mg aglycones/kg diet) added to a Western-style diet. Instead of preventing mammary tumorigenesis, the highest dose of isofl......We investigated spontaneous mammary tumor development and mammary gland morphogenesis in female Tg.NK mice postnatally exposed to dietary soy isoflavones (0, 11, 39, and 130 mg aglycones/kg diet) added to a Western-style diet. Instead of preventing mammary tumorigenesis, the highest dose...

  7. Molecular docking, TG/DTA, molecular structure, harmonic vibrational frequencies, natural bond orbital and TD-DFT analysis of diphenyl carbonate by DFT approach

    Xavier, S.; Periandy, S.; Carthigayan, K.; Sebastian, S.

    2016-12-01

    Vibrational spectral analysis of Diphenyl Carbonate (DPC) is carried out by using FT-IR and FT-Raman spectroscopic techniques. It is found that all vibrational modes are in the expected region. Gaussian computational calculations were performed using B3LYP method with 6-311++G (d, p) basis set. The computed geometric parameters are in good agreement with XRD data. The observation shows that the structure of the carbonate group is unsymmetrical by ∼5° due to the attachment of the two phenyl rings. The stability of the molecule arising from hyperconjugative interaction and charge delocalization are analyzed by Natural Bond Orbital (NBO) study and the results show the lone pair transition has higher stabilization energy compared to all other. The 1H and 13C NMR chemical shifts are calculated using the Gauge-Including Atomic Orbital (GIAO) method with B3LYP/6-311++G (d, p) method. The chemical shifts computed theoretically go very closer to the experimental results. A study on the electronic and optical properties; absorption wavelengths, excitation energy, dipole moment and frontier molecular orbital energies and Molecular electrostatic potential (MEP) exhibit the high reactivity nature of the molecule. The non-linear optical property of the DPC molecule predicted theoretically found to be good candidate for NLO material. TG/DTA analysis was made and decomposition of the molecule with respect to the temperature was studied. DPC having the anthelmintic activity is docked in the Hemoglobin of Fasciola hepatica protein. The DPC has been screened to antimicrobial activity and found to exhibit antibacterial effects.

  8. Overexpressed human heme Oxygenase-1 decreases adipogenesis in pigs and porcine adipose-derived stem cells.

    Park, Eun Jung; Koo, Ok Jae; Lee, Byeong Chun

    2015-11-27

    Adipose-derived mesenchymal stem cells (ADSC) are multipotent, which means they are able to differentiate into several lineages in vivo and in vitro under proper conditions. This indicates it is possible to determine the direction of differentiation of ADSC by controlling the microenvironment. Heme oxygenase 1 (HO-1), a type of antioxidant enzyme, attenuates adipogenicity and obesity. We produced transgenic pigs overexpressing human HO-1 (hHO-1-Tg), and found that these animals have little fatty tissue when autopsied. To determine whether overexpressed human HO-1 suppresses adipogenesis in pigs, we analyzed body weight increases of hHO-1-Tg pigs and wild type (WT) pigs of the same strain, and induced adipogenic differentiation of ADSC derived from WT and hHO-1-Tg pigs. The hHO-1-Tg pigs had lower body weights than WT pigs from 16 weeks of age until they died. In addition, hHO-1-Tg ADSC showed reduced adipogenic differentiation and expression of adipogenic molecular markers such as PPARγ and C/EBPα compared to WT ADSC. These results suggest that HO-1 overexpression reduces adipogenesis both in vivo and in vitro, which could support identification of therapeutic targets of obesity and related metabolic diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. High-temperature Brillouin scattering study of haplogranitic glasses and liquids: Effects of F, K, Na and Li on Tg and elastic properties

    Manghnani, M. H.; Hushur, A.; Williams, Q. C.; Dingwell, D. B.

    2010-12-01

    The density, compressibility and viscosity of silicate melts are important in understanding the thermodynamic and fluid dynamic properties of magmatic systems. Knowledge of the compressibility of silicate melts at 1 bar is an important component in the construction of accurate pressure-volume-temperature equations of state. In light of this, the velocity (nVp, Vp, Vs) and refractive index n of four anhydrous haplogranitic glasses and liquids with similar alkali abundances, but different cations, are measured at high temperature by Brillouin scattering spectroscopy through the glass transition temperature (Tg) in both platelet and back scattering geometry. The compositions of four haplogranites are 5 wt% of the components Li2O, Na2O, K2O and F each added to a base of haplogranitic (HPG8) composition. The glass transition temperature Tg of different haplogranite samples at the GHz frequency of the Brillouin probe are determined from the change in slope of the temperature-dependent longitudinal or transverse sound velocity. HPG8-Li5 has the lowest glass transition temperature (466°C), while HPG8-K5 has the highest glass transition temperature (575°C). Our Brillouin results, when compared with DSC measurements, show lower Tg values. This raises the possibility of a role of either heating rates or a frequency dependence of the glass transition in explaining the discrepancies in Tg values derived from the two methods. The sound velocity (nVp, Vp, Vs) shows markedly different temperature dependences (including differences in sign) below Tg depending on their different alkali contents. The unrelaxed elastic moduli of three haplogranitic glasses with added Li2O, Na2O and F components have been obtained as a function of temperature. The unrelaxed bulk modulus, shear modulus and Poisson’s ratio show strong compositional dependences at ambient temperature. On heating, The K initially decreases with increasing temperature up to ~ 135°C, then increases up to Tg, and then

  10. Biomechanical assays amniotic membrane preserved in glycerol correlating with optical coherence tomography (OCT) and thermal gravimetric analysis (TG)

    Soares, Fernando Augusto N.; Santin, Stefany P.; Martino Junior, Antonio C.; Machado, Luci Diva B.; Freitas, Anderson Z.; Mathor, Monica B.

    2013-01-01

    Young's modulus, the OCT technique, to generate high-resolution images in real time being a non-destructive technique, thermogravimetry (TG) assessing the amount of water and rate of water output membranes after treatment with ionizing radiation, relating the possible changes with non-irradiated tissue. However the results of the tensile test had the same behavior compared to the values of total attenuation coefficient by OCT, in addition the dehydration rate analyzed by TG had no statistically significant variation to some radiation doses. (author)

  11. Biomechanical assays amniotic membrane preserved in glycerol correlating with optical coherence tomography (OCT) and thermal gravimetric analysis (TG)

    Soares, Fernando Augusto N.; Santin, Stefany P.; Martino Junior, Antonio C.; Machado, Luci Diva B.; Freitas, Anderson Z.; Mathor, Monica B., E-mail: fernandonevessoares@yahoo.com.br [Instituto de Pesquisas Energetias Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Young's modulus, the OCT technique, to generate high-resolution images in real time being a non-destructive technique, thermogravimetry (TG) assessing the amount of water and rate of water output membranes after treatment with ionizing radiation, relating the possible changes with non-irradiated tissue. However the results of the tensile test had the same behavior compared to the values of total attenuation coefficient by OCT, in addition the dehydration rate analyzed by TG had no statistically significant variation to some radiation doses. (author)

  12. A promoter polymorphism (rs17222919, -1316T/G of ALOX5AP gene is associated with decreased risk of ischemic stroke in two independent Chinese populations.

    Yujia Fan

    Full Text Available No coding sequence variants of the gene encoding 5-lipoxygenase-activating protein (ALOX5AP leading to amino acid substitutions have been identified. Therefore, variants in the ALOX5AP promoter region have received attention recently. The purpose of this study was to explore whether the promoter polymorphism rs17222919 is involved in the etiology of ischemic stroke (IS in the Chinese Han population. We investigated the rs17222919 polymorphism by TaqMan genotyping in two independent Chinese Han samples: the first comprised 910 IS patients and 925 healthy inhabitants from the northern Henan Province, while the second included 1003 IS patients and 889 healthy controls from the southern Henan Province. Functional characterization of rs17222919 was performed by an in vitro luciferase assay. After adjusting for conventional risk factors, the G allele frequencies in the IS groups were significantly lower than that in the control groups of the two independent Chinese cohorts (19.0% vs. 22.9%, P = 0.004, odds ratio (OR = 0.792, 95% confidence interval (CI = 0.675-0.929; 18.8% vs. 22.9%, P = 0.002, OR = 0.782, 95% CI = 0.668-0.915, respectively. This was also observed in the large-artery atherosclerosis (LAA and stroke of other undetermined etiology (SUE subtypes (P = 0.019, OR = 0.815, 95% CI = 0.687-0.967; P = 0.021, OR = 0.815, 95% CI = 0.685-0.970, respectively. Additionally, the TG genotype and G allele frequencies were significantly lower in the IS compared with the control group in two female cohorts (P<0.05. Finally, the in vitro luciferase assay demonstrated that the G allele has a significantly lower transcription activity than the T allele (P = 0.031. Our study provides evidence that the promoter single nucleotide polymorphism (SNP rs17222919 is a potential genetic protective factor for IS in the Chinese Han population.

  13. Group X

    Fields, Susannah

    2007-08-16

    This project is currently under contract for research through the Department of Homeland Security until 2011. The group I was responsible for studying has to remain confidential so as not to affect the current project. All dates, reference links and authors, and other distinguishing characteristics of the original group have been removed from this report. All references to the name of this group or the individual splinter groups has been changed to 'Group X'. I have been collecting texts from a variety of sources intended for the use of recruiting and radicalizing members for Group X splinter groups for the purpose of researching the motivation and intent of leaders of those groups and their influence over the likelihood of group radicalization. This work included visiting many Group X websites to find information on splinter group leaders and finding their statements to new and old members. This proved difficult because the splinter groups of Group X are united in beliefs, but differ in public opinion. They are eager to tear each other down, prove their superiority, and yet remain anonymous. After a few weeks of intense searching, a list of eight recruiting texts and eight radicalizing texts from a variety of Group X leaders were compiled.

  14. Regulatory Forum Opinion Piece*: Retrospective Evaluation of Doses in the 26-week Tg.rasH2 Mice Carcinogenicity Studies: Recommendation to Eliminate High Doses at Maximum Tolerated Dose in Future Studies. A Response to the Counterpoints.

    Paranjpe, Madhav G; Denton, Melissa D; Vidmar, Tom J; Elbekai, Reem H

    2016-01-01

    We recently conducted a retrospective analysis of data collected from 29 Tg.rasH2 carcinogenicity studies conducted at our facility to determine how successful was the strategy of choosing the high dose of the 26-week studies based on an estimated maximum tolerated dose (MTD). As a result of our publication, 2 counterviews were expressed. Both counterviews illustrate very valid points in their interpretation of our data. In this article, we would like to highlight clarifications based on several points and issues they have raised in their papers, namely, the dose-level selection, determining if MTD was exceeded in 26-week studies, and a discussion on the number of dose groups to be used in the studies. © The Author(s) 2015.

  15. Prevalence of iodine- and thyroglobulin-negative findings in differentiated thyroid cancer. A retrospective analysis of patients treated from 1961 to 1998 in a university hospital; Haeufigkeit lod- und hTG-negativer Befunde beim differenzierten Schilddruesenkarzinom. Eine retrospektive Analyse der von 1961 bis 1998 in einer Universitaetsklinik behandelten Patienten

    Klutmann, S.; Jenicke, L.; Geiss-Toenshoff, M.; Bohuslavizki, K.H.; Mester, J.; Clausen, M. [Universitaetskrankenhaus Eppendorf, Hamburg (Germany). Abt. fuer Nuklearmedizin

    2001-10-01

    Aim: The prevalence of iodine- and thyroglobulin-negative findings was evaluated in all patients with differentiated thyroid cancer (DTC) treated from 1961 until 1998 at the Department of Nuclear Medicine, University Hospital Hamburg-Eppendorf. Methods: A total of 490 patients with papillary thyroid cancer (PCA) and 242 patients with follicular thyroid cancer (FCA) were analyzed retrospectively. Patients were divided into four groups: 1: no recurrence, 2: recurrent disease, 3: primary metastatic/progressive disease and 4: inconclusive follow-up. Results of iodine scan, serum-TG, and additional imaging modalities as well as histology were compared in all patients. Results: 21/490 (4,3%) of patients with PCA and 16/242 (6,6%) with FCA suffered from recurrent disease. 62/490 (12,7%) of patients with PCA and 59/242 (24,4%) with FCA had primary metastatic/progressive disease. 12/21 patients with PCA and 12/16 with FCA showing up with recurrent disease had a negative iodinescan. 11/21 of patients with PCA and 4/16 with FCA and tumor recurrence had negative serum-TG levels. 14/62 patients with PCA and 14/59 with FCA presenting with primary metastatic/progressive disease had negative iodinescan. 14/62 patients with PCA and 6/59 with FCA had negative serum-TG. Conclusion: The prevalence of iodine-negative recurrent/metastatic disease is in accordance to the literature, whereas the prevalence of TG-negative recurrent/metastatic was noted higher than reported previously. Thus, the commonly used follow-up scheme of DTC is confirmed. However, iodine scan should be regularly performed in patients with high risk of recurrence. (orig.) [German] Ziel: Retrospektiv wurden alle von 1961 bis 1998 in der Abteilung fuer Nukleamedizin des Universitaetsklinikums Hamburg-Eppendorf behandelten Patienten mit einem differenzierten Schilddruesenkarzinom bezueglich des Anteils lod- und/oder hTG-negativer Rezidive analysiert. Methoden: Es wurden 490 Patienten mit einem papillaeren

  16. Group Flow and Group Genius

    Sawyer, Keith

    2015-01-01

    Keith Sawyer views the spontaneous collaboration of group creativity and improvisation actions as "group flow," which organizations can use to function at optimum levels. Sawyer establishes ideal conditions for group flow: group goals, close listening, complete concentration, being in control, blending egos, equal participation, knowing…

  17. Language Image in National Minority Language Television Idents. TG4 (Teilifís na Gaeilge, Ireland and Whakaata Māori (Māori Television, New Zealand

    Ruth Lysaght

    2009-03-01

    Full Text Available Born of community and political action, Teilifis na Gaeilge (TG4 began in 1996, and Whakaata Māori/ Māori Television Service (MTS in 2004. Despite obvious differences between the two broadcasting environments, both stations attempt to reclaim a national (but minority language (Ó Ruairc 1996; Moring 2007 and compete with other broadcasters (Horrocks and Perry 2004 to attract an audience (Smith and Abel 2008 by an appeal to identity (Cormack 2000; 2007; Delap 2007. This paper investigates idents from TG4 and MTS. What image or brand have the language and culture in these mini-advertisements? Thornley’s (2004 discussion of “transculturation” is useful in examining the often inventive approach taken to elements of the dominant culture. Indeed, the motto ‘Súil eile’ [another perspective] is the criterion for many TG4 projects, and there is a clear awareness of multiple audiences in the MTS logline, ‘mā mātou, mā rātou, mā koutou, mā tātou’ [just for us, for them, for all of you, for all of us]. In the symbiotic relationship between a minority station and other larger stations in terms of the depiction/creation of local and national identity, language is used as another marketing tool. TG4 and MTS idents respond to and celebrate current sociolinguistic changes (Romaine 2006; Ó Tuathaigh 2008, making them visible.

  18. Prolonged Running, not Fluoxetine Treatment, Increases Neurogenesis, but does not Alter Neuropathology, in the 3xTg Mouse Model of Alzheimer's Disease.

    Marlatt, M.W.; Potter, M.C.; Bayer, T.A.; van Praag, H.; Lucassen, P.J.

    2013-01-01

    Reductions in adult neurogenesis have been documented in the original 3xTg mouse model of Alzheimer's disease (AD), notably occurring at the same age when spatial memory deficits and amyloid plaque pathology appeared. As this suggested reduced neurogenesis was associated with behavioral deficits, we

  19. Estimates of epistatic and pleiotropic effects of casein alpha s1 (CSN1S1) and thyroglobulin (TG) genetic markers on beef heifer performance traits enhanced by selection

    Genetic marker effects and type of inheritance are estimated with poor precision when minor marker allele frequencies are low. A stable composite population (MARC II) was subjected to marker assisted selection for two years to equalize CSN1S1 and TG genetic marker frequencies to evaluate the epista...

  20. Structure-to-property relationships in addition cured polymers. II - Resin Tg and composite initial mechanical properties of norbornenyl cured polyimide resins

    Alston, William B.

    1986-01-01

    PRM (polymerization of monomeric reactants) methodology was used to prepare thirty different polyimide oligomeric resins. Monomeric composition as well as chain length between sites of crosslinks were varied to examine their effects on glass transition temperature (Tg) of the cured/postcured resins. An almost linear correlation of Tg versus molecular distance between the crosslinks was observed. An attempt was made to correlate Tg with initial mechanical properties (flexural strength and interlaminar shear strength) of unidirectional graphite fiber composites prepared with these resins. However, the scatter in mechanical strength data prevented obtaining as clear a correlation as was observed for the structural modification/crosslink distance versus Tg. Instead, only a range of composite mechanical properties was obtained at the test temperatures studied (room temperature, 288 and 316 C). Perhaps more importantly, what did become apparent during the attempted correlation study was: (1) that PMR methodology could be used to prepare composites from resins that contain a wide variety of monomer modifications, and (2) that these composites almost invariably provided satisfactory initial mechanical properties as long as the resins selected were melt processable.

  1. Study on the characterization and thermal decomposition of uranium compounds by thermogravimetry (TG) and differential scanning calorimetry (DSC)

    Dantas, J.M.; Abrao, A.

    1981-04-01

    A contribution to the characterization of several uranium compounds obtained at the IPEN' Uranium Pilot Plant is given. Particularly, samples of ammonium diuranate (ADU) and uranium oxides were studied. The main objective was to know the stoichiometry of the ADU and the oxides resulting from its thermal transformation. ADU samples were prepared by batchwise precipitation, stationary dewatering into stove and batchwise thermal decomposition, or, alternatively, continuous precipitation, continuous filtration, continuous drying and continuous thermal decomposition inside a temperature gradient electrical furnace. All ADU were precipitated using NH 3 gas from uranul sulfate or uranyl nitrate solutions. The thermal decomposition of ADU and uranium oxides were studied in an air atmosphere by thermogravimetry (TG) and differential scanning calorimetry (DSC). Any correlation between the parameters of precipitation, drying, calcination and the hystory of the obtaintion of the several uraniumm compounds and their initial and final composition was looked for. Heating program was established to have the U 3 O 8 oxide as the final product. Intermediary phases were tentatively identified. Temperatures at which occurred the absorption water elimination, crystallization water elimination, evolution or oxidation of NH 3 , decomposition of NO -3 ion and oxygen evolution and the exo- and endothermic process for each sample were identified. (Author) [pt

  2. Multi-Shell Hybrid Diffusion Imaging (HYDI at 7 Tesla in TgF344-AD Transgenic Alzheimer Rats.

    Madelaine Daianu

    Full Text Available Diffusion weighted imaging (DWI is widely used to study microstructural characteristics of the brain. Diffusion tensor imaging (DTI and high-angular resolution imaging (HARDI are frequently used in radiology and neuroscience research but can be limited in describing the signal behavior in composite nerve fiber structures. Here, we developed and assessed the benefit of a comprehensive diffusion encoding scheme, known as hybrid diffusion imaging (HYDI, composed of 300 DWI volumes acquired at 7-Tesla with diffusion weightings at b = 1000, 3000, 4000, 8000 and 12000 s/mm2 and applied it in transgenic Alzheimer rats (line TgF344-AD that model the full clinico-pathological spectrum of the human disease. We studied and visualized the effects of the multiple concentric "shells" when computing three distinct anisotropy maps-fractional anisotropy (FA, generalized fractional anisotropy (GFA and normalized quantitative anisotropy (NQA. We tested the added value of the multi-shell q-space sampling scheme, when reconstructing neural pathways using mathematical frameworks from DTI and q-ball imaging (QBI. We show a range of properties of HYDI, including lower apparent anisotropy when using high b-value shells in DTI-based reconstructions, and increases in apparent anisotropy in QBI-based reconstructions. Regardless of the reconstruction scheme, HYDI improves FA-, GFA- and NQA-aided tractography. HYDI may be valuable in human connectome projects and clinical research, as well as magnetic resonance research in experimental animals.

  3. Multi-Shell Hybrid Diffusion Imaging (HYDI) at 7 Tesla in TgF344-AD Transgenic Alzheimer Rats.

    Daianu, Madelaine; Jacobs, Russell E; Weitz, Tara M; Town, Terrence C; Thompson, Paul M

    2015-01-01

    Diffusion weighted imaging (DWI) is widely used to study microstructural characteristics of the brain. Diffusion tensor imaging (DTI) and high-angular resolution imaging (HARDI) are frequently used in radiology and neuroscience research but can be limited in describing the signal behavior in composite nerve fiber structures. Here, we developed and assessed the benefit of a comprehensive diffusion encoding scheme, known as hybrid diffusion imaging (HYDI), composed of 300 DWI volumes acquired at 7-Tesla with diffusion weightings at b = 1000, 3000, 4000, 8000 and 12000 s/mm2 and applied it in transgenic Alzheimer rats (line TgF344-AD) that model the full clinico-pathological spectrum of the human disease. We studied and visualized the effects of the multiple concentric "shells" when computing three distinct anisotropy maps-fractional anisotropy (FA), generalized fractional anisotropy (GFA) and normalized quantitative anisotropy (NQA). We tested the added value of the multi-shell q-space sampling scheme, when reconstructing neural pathways using mathematical frameworks from DTI and q-ball imaging (QBI). We show a range of properties of HYDI, including lower apparent anisotropy when using high b-value shells in DTI-based reconstructions, and increases in apparent anisotropy in QBI-based reconstructions. Regardless of the reconstruction scheme, HYDI improves FA-, GFA- and NQA-aided tractography. HYDI may be valuable in human connectome projects and clinical research, as well as magnetic resonance research in experimental animals.

  4. Synthesis of Co/MCM-41catalysts and characterization by XRD, EDX, DTA/TG, SEM and TEM

    Sousa, B.V.; Rodrigues, M.G.F.

    2009-01-01

    Full text: In this work, molecular sieve MCM-41 was prepared as well as the Co/MCM-41 catalyst, via humid impregnation with concentration of 5 wt.% and 10 wt.% Co/MCM- 41. The attainment of the mesoporous molecular sieve, Si-MCM-41, was confirmed by the x-ray diffractogram. It was verified that after the calcination all the bromine (Br) was removed indicating that the calcination process removed all surfactant in the mesoporous structure. XRD and EDX analyses indicated that cobalt was found in the form of Co3O2 in the Co/MCM-41 catalysts. The diffraction standards showed that the impregnation and calcination processes caused changes in the structure only for catalyst with 10 wt.% Co/MCM-41. The DTA/TG curves showed that cobalt nitrate was totally decomposed on the MCM-41. From the images of SEM, it was possible to observe that the Co/MCM-41 catalysts were composed by clusters of small crystals. The images obtained from TEM showed clearly the presence of metal cobalt particles in a well dispersed form for catalyst with 5 wt.% Co/MCM41, except for the catalyst with 10 wt.% Co/MCM41. (author)

  5. Acoustic Doppler current profiling from the JGOFS Arabian sea cruises aboard the RV T.G. Thompson

    Kim, Hyun-Sook; Flagg, C.N.; Shi, Yan

    1996-06-01

    Acoustic Doppler current profiler (ADCP) data is part of the core data for the U.S. JGOFS Arabian Sea project, along with hydrographic and nutrient data. Seventeen cruises are scheduled to take place between September 1994 and January 1996 on the R/V T.G. Thompson. They are numbered consecutively from the ship`s commissioning with the first JGOFS cruise designated TN039. Table 1 lists start and end dates of each cruise with its mission. All but the first cruise have been or will be staged from Muscat, Oman. Each cruise is scheduled for a duration of between two weeks and one month. Seven of the cruises, referred to as process cruises, follow a standard cruise track, taking hydrographic, chemical and biological measurements. The rest of the cruises, which take place generally within the standard cruise region defined by a set track, are for the deployment and recovery of moored equipments and towing of a SeaSoar. ADCP data are collected using an autonomous data acquisition system developed for ship-of-opportunity cruises, named the AutoADCP system. The system is an extension of RD instrument`s DAS version 2.48 using enhancements made possible with {open_quotes}user-exit{close_quotes} programs. It makes it possible to collect ADCP data without the constant monitoring usually necessary and insures constant data coverage and uniform data quality.

  6. Effect of heating rate on thermal cracking characteristics and kinetics of Xinjiang oil sand bitumen by TG-FTIR

    Hao, Junhui; Zhang, Jinhong; Qiao, Yingyun; Tian, Yuanyu

    2017-08-01

    This work was aimed to investigate effects of heating rate on thermal cracking behaviors, distribution of gaseous products and activation energy of the thermal cracking process of Xinjiang oil sand bitumen (OSB). The thermal cracking experiments of Xinjiang OSB were performed by using thermogravimetric analyzer (TGA) at various heating rates of 10, 20, 50, 80 and 120 K/min. The evolving characteristic of gaseous products produced from the thermal cracking process was evaluated by the Fourier transform infrared spectrometry (FTIR) connected with TG. The kinetic parameters of the thermal cracking process of Xinjiang OSB at each of heating rate were determined by the Coats-Redfern model. The result show that the temperature intervals of DE volatilization stage and main reaction stage, the ((dw/dt) max and Tmax in thermal cracking process of Xinjiang OSB all increased with the increasing heating rate. While the heating rate has not obvious effect on the coke yield of Xinjiang OSB. Furthermore, the maximum absorbance of gaseous products and corresponding temperature became larger as the heating rate increases. The activation energy of this two stage both presented increasing trend with the rising heating rate, while the increasing content of that of DE volatilization stage was weaker compared to that of main reaction stage.

  7. X11beta rescues memory and long-term potentiation deficits in Alzheimer's disease APPswe Tg2576 mice.

    Mitchell, Jacqueline C

    2009-12-01

    Increased production and deposition of amyloid beta-protein (Abeta) are believed to be key pathogenic events in Alzheimer\\'s disease. As such, routes for lowering cerebral Abeta levels represent potential therapeutic targets for Alzheimer\\'s disease. X11beta is a neuronal adaptor protein that binds to the intracellular domain of the amyloid precursor protein (APP). Overexpression of X11beta inhibits Abeta production in a number of experimental systems. However, whether these changes to APP processing and Abeta production induced by X11beta overexpression also induce beneficial effects to memory and synaptic plasticity are not known. We report here that X11beta-mediated reduction in cerebral Abeta is associated with normalization of both cognition and in vivo long-term potentiation in aged APPswe Tg2576 transgenic mice that model the amyloid pathology of Alzheimer\\'s disease. Overexpression of X11beta itself has no detectable adverse effects upon mouse behaviour. These findings support the notion that modulation of X11beta function represents a therapeutic target for Abeta-mediated neuronal dysfunction in Alzheimer\\'s disease.

  8. A 28-day oral gavage toxicity study of 3-monochloropropane-1,2-diol (3-MCPD) in CB6F1-non-Tg rasH2 mice.

    Lee, Byoung-Seok; Park, Sang-Jin; Kim, Yong-Bum; Han, Ji-Seok; Jeong, Eun-Ju; Moon, Kyoung-Sik; Son, Hwa-Young

    2015-12-01

    3-Monochloro-1,2-propanediol (3-MCPD) is a well-known contaminant of foods containing hydrolyzed vegetable protein. However, limited toxicity data are available for the risk assessment of 3-MCPD and its carcinogenic potential is controversial. To evaluate the potential toxicity and determine the dose levels for a 26-week carcinogenicity test using Tg rasH2 mice, 3-MCPD was administered once daily by oral gavage at doses of 0, 25, 50, and 100 mg/kg body weight (b.w.)/day for 28 days to male and female CB6F1-non-Tg rasH2 mice (N = 5 males and females per dose). The standard toxicological evaluations were conducted during the in-life and post-mortem phase. In the 100 mg/kg b.w./day group, 3 males and 1 female died during the study and showed clinical signs such as thin appearance and subdued behavior accompanied by significant decreases in mean b.w. Microscopy revealed tubular basophilia in the kidneys, exfoliated degenerative germ cells in the lumen of the seminiferous tubule of the testes, vacuolation in the brain, axonal degeneration of the sciatic nerve, and cardiomyopathy in the 100, ≥25, ≥50, 100, and 100 mg/kg b.w./day groups, respectively. In conclusion, 3-MCPD's target organs were the kidneys, testes, brain, sciatic nerve, and heart. The "no-observed-adverse-effect level" (NOAEL) of 3-MCPD was ≤25 and 25 mg/kg b.w./day in males and females, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Lipid Peroxidation, Nitric Oxide Metabolites, and Their Ratio in a Group of Subjects with Metabolic Syndrome

    Gregorio Caimi

    2014-01-01

    Full Text Available Our aim was to evaluate lipid peroxidation, expressed as thiobarbituric acid-reactive substances (TBARS, nitric oxide metabolites (nitrite + nitrate expressed as NOx, and TBARS/NOx ratio in a group of subjects with metabolic syndrome (MS. In this regard we enrolled 106 subjects with MS defined according to the IDF criteria, subsequently subdivided into diabetic (DMS and nondiabetic (NDMS and also into subjects with a low triglycerides/HDL-cholesterol (TG/HDL-C index or with a high TG/HDL-C index. In the entire group and in the four subgroups of MS subjects we found an increase in TBARS and NOx levels and a decrease in TBARS/NOx ratio in comparison with normal controls. Regarding all these parameters no statistical difference between DMS and NDMS was evident, but a significant increase in NOx was present in subjects with a high TG/HDL-C index in comparison with those with a low index. In MS subjects we also found a negative correlation between TBARS/NOx ratio and TG/HDL-C index. Considering the hyperactivity of the inducible NO synthase in MS, these data confirm the altered redox and inflammatory status that characterizes the MS and suggest a link between lipid peroxidation, inflammation, and insulin resistance, evaluated as TG/HDL-C index.

  10. Specific expression of the vacuolar iron transporter, TgVit, causes iron accumulation in blue-colored inner bottom segments of various tulip petals.

    Momonoi, Kazumi; Tsuji, Toshiaki; Kazuma, Kohei; Yoshida, Kumi

    2012-01-01

    Several flowers of Tulipa gesneriana exhibit a blue color in the bottom segments of the inner perianth. We have previously reported the inner-bottom tissue-specific iron accumulation and expression of the vacuolar iron transporter, TgVit1, in tulip cv. Murasakizuisho. To clarify whether the TgVit1-dependent iron accumulation and blue-color development in tulip petals are universal, we analyzed anthocyanin, its co-pigment components, iron contents and the expression of TgVit1 mRNA in 13 cultivars which show a blue color in the bottom segments of the inner perianth accompanying yellow- and white-colored inner-bottom petals. All of the blue bottom segments contained the same anthocyanin component, delphinidin 3-rutinoside. The flavonol composition varied with cultivar and tissue part. The major flavonol in the bottom segments of the inner perianth was rutin. The iron content in the upper part was less than that in the bottom segments of the inner perianth. The iron content in the yellow and white petals was higher in the bottom segment of the inner perianth than in the upper tissues. TgVit1 mRNA expression was apparent in all of the bottom tissues of the inner perianth. The result of a reproduction experiment by mixing the constituents suggests that the blue coloration in tulip petals is generally caused by iron complexation to delphinidin 3-rutinoside and that the iron complex is solubilized and stabilized by flavonol glycosides. TgVit1-dependent iron accumulation in the bottom segments of the inner perianth might be controlled by an unknown system that differentiated the upper parts and bottom segments of the inner perianth.

  11. NOG-hIL-4-Tg, a new humanized mouse model for producing tumor antigen-specific IgG antibody by peptide vaccination.

    Yoshie Kametani

    Full Text Available Immunodeficient mice transplanted with human peripheral blood mononuclear cells (PBMCs are promising tools to evaluate human immune responses to vaccines. However, these mice usually develop severe graft-versus-host disease (GVHD, which makes estimation of antigen-specific IgG production after antigen immunization difficult. To evaluate antigen-specific IgG responses in PBMC-transplanted immunodeficient mice, we developed a novel NOD/Shi-scid-IL2rγnull (NOG mouse strain that systemically expresses the human IL-4 gene (NOG-hIL-4-Tg. After human PBMC transplantation, GVHD symptoms were significantly suppressed in NOG-hIL-4-Tg compared to conventional NOG mice. In kinetic analyses of human leukocytes, long-term engraftment of human T cells has been observed in peripheral blood of NOG-hIL-4-Tg, followed by dominant CD4+ T rather than CD8+ T cell proliferation. Furthermore, these CD4+ T cells shifted to type 2 helper (Th2 cells, resulting in long-term suppression of GVHD. Most of the human B cells detected in the transplanted mice had a plasmablast phenotype. Vaccination with HER2 multiple antigen peptide (CH401MAP or keyhole limpet hemocyanin (KLH successfully induced antigen-specific IgG production in PBMC-transplanted NOG-hIL-4-Tg. The HLA haplotype of donor PBMCs might not be relevant to the antibody secretion ability after immunization. These results suggest that the human PBMC-transplanted NOG-hIL-4-Tg mouse is an effective tool to evaluate the production of antigen-specific IgG antibodies.

  12. Permutation groups

    Passman, Donald S

    2012-01-01

    This volume by a prominent authority on permutation groups consists of lecture notes that provide a self-contained account of distinct classification theorems. A ready source of frequently quoted but usually inaccessible theorems, it is ideally suited for professional group theorists as well as students with a solid background in modern algebra.The three-part treatment begins with an introductory chapter and advances to an economical development of the tools of basic group theory, including group extensions, transfer theorems, and group representations and characters. The final chapter feature

  13. An analysis of confidence limit calculations used in AAPM Task Group No. 119

    Knill, Cory; Snyder, Michael

    2011-01-01

    Purpose: The report issued by AAPM Task Group No. 119 outlined a procedure for evaluating the effectiveness of IMRT commissioning. The procedure involves measuring gamma pass-rate indices for IMRT plans of standard phantoms and determining if the results fall within a confidence limit set by assuming normally distributed data. As stated in the TG report, the assumption of normally distributed gamma pass rates is a convenient approximation for commissioning purposes, but may not accurately describe the data. Here the authors attempt to better describe gamma pass-rate data by fitting it to different distributions. The authors then calculate updated confidence limits using those distributions and compare them to those derived using TG No. 119 method. Methods: Gamma pass-rate data from 111 head and neck patients are fitted using the TG No. 119 normal distribution, a truncated normal distribution, and a Weibull distribution. Confidence limits to 95% are calculated for each and compared. A more general analysis of the expected differences between the TG No. 119 method of determining confidence limits and a more time-consuming curve fitting method is performed. Results: The TG No. 119 standard normal distribution does not fit the measured data. However, due to the small range of measured data points, the inaccuracy of the fit has only a small effect on the final value of the confidence limits. The confidence limits for the 111 patient plans are within 0.1% of each other for all distributions. The maximum expected difference in confidence limits, calculated using TG No. 119's approximation and a truncated distribution, is 1.2%. Conclusions: A three-parameter Weibull probability distribution more accurately fits the clinical gamma index pass-rate data than the normal distribution adopted by TG No. 119. However, the sensitivity of the confidence limit on distribution fit is low outside of exceptional circumstances.

  14. Group devaluation and group identification

    Leach, C.W.; Rodriguez Mosquera, P.M.; Vliek, M.L.W.; Hirt, E.

    2010-01-01

    In three studies, we showed that increased in-group identification after (perceived or actual) group devaluation is an assertion of a (preexisting) positive social identity that counters the negative social identity implied in societal devaluation. Two studies with real-world groups used order

  15. Lie groups and algebraic groups

    We give an exposition of certain topics in Lie groups and algebraic groups. This is not a complete ... of a polynomial equation is equivalent to the solva- bility of the equation ..... to a subgroup of the group of roots of unity in k (in particular, it is a ...

  16. Histone deacetylase inhibitor trichostatin A resensitizes gemcitabine resistant urothelial carcinoma cells via suppression of TG-interacting factor

    Yeh, Bi-Wen; Li, Wei-Ming; Li, Ching-Chia; Kang, Wan-Yi; Huang, Chun-Nung; Hour, Tzyh-Chyuan; Liu, Zi-Miao

    2016-01-01

    Gemcitabine and cisplatin (GC) has been widely used for advanced and metastatic urothelial carcinoma (UC). However, resistance to this remedy has been noticed. We have demonstrated that increase of TG-interacting factor (TGIF) in specimens is associated with worse prognosis of upper tract UC (UTUC) patients. The roles of TGIF in the gemcitabine resistance of UC were explored. Specimens of 23 locally advanced/advanced stage UTUC patients who received GC systemic chemotherapy after radical nephroureterectomy were collected to evaluate the alterations of TGIF in the resistance to the remedy by using immunohistochemistry. In vitro characterizations of mechanisms mediating TGIF in gemcitabine resistance were conducted by analyzing NTUB1 cells and their gemcitabine-resistant subline, NGR cells. Our results show that increased TGIF is significantly associated with chemo-resistance, poor progression-free survival, and higher cancer-related deaths of UTUC patients. Higher increases of TGIF, p-AKT Ser473 and invasive ability were demonstrated in NGR cells. Overexpression of TGIF in NTUB1 cells upregulated p-AKT Ser473 activation, enhanced migration ability, and attenuated cellular sensitivity to gemcitabine. Knockdown of TGIF in NGR cells downregulated p-AKT Ser473 activation, declined migration ability, and enhanced cellular sensitivity to gemcitabine. In addition, histone deacetylases inhibitor trichostatin A (TSA) inhibited TGIF, p-AKT Ser473 expression and migration ability. Synergistic effects of gemcitabine and TSA on NGR cells were also demonstrated. Collectively, TGIF contributes to the gemcitabine resistance of UC via AKT activation. Combined treatment with gemcitabine and TSA might be a promising therapeutic remedy to improve the gemcitabine resistance of UC. - Highlights: • TGIF expression in UC cells is associated with chemoresistance to gemcitabine. • TGIF-regulated AKT activation contributes to the gemcitabine resistance. • Increased TGIF is significantly

  17. Histone deacetylase inhibitor trichostatin A resensitizes gemcitabine resistant urothelial carcinoma cells via suppression of TG-interacting factor

    Yeh, Bi-Wen [Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China); Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Li, Wei-Ming [Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Li, Ching-Chia [Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Kang, Wan-Yi [Department of Pathology, Kuo General Hospital, Tainan 701, Taiwan (China); Huang, Chun-Nung [Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Hour, Tzyh-Chyuan [Institute of Biochemistry, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Liu, Zi-Miao [Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China); and others

    2016-01-01

    Gemcitabine and cisplatin (GC) has been widely used for advanced and metastatic urothelial carcinoma (UC). However, resistance to this remedy has been noticed. We have demonstrated that increase of TG-interacting factor (TGIF) in specimens is associated with worse prognosis of upper tract UC (UTUC) patients. The roles of TGIF in the gemcitabine resistance of UC were explored. Specimens of 23 locally advanced/advanced stage UTUC patients who received GC systemic chemotherapy after radical nephroureterectomy were collected to evaluate the alterations of TGIF in the resistance to the remedy by using immunohistochemistry. In vitro characterizations of mechanisms mediating TGIF in gemcitabine resistance were conducted by analyzing NTUB1 cells and their gemcitabine-resistant subline, NGR cells. Our results show that increased TGIF is significantly associated with chemo-resistance, poor progression-free survival, and higher cancer-related deaths of UTUC patients. Higher increases of TGIF, p-AKT{sup Ser473} and invasive ability were demonstrated in NGR cells. Overexpression of TGIF in NTUB1 cells upregulated p-AKT{sup Ser473} activation, enhanced migration ability, and attenuated cellular sensitivity to gemcitabine. Knockdown of TGIF in NGR cells downregulated p-AKT{sup Ser473} activation, declined migration ability, and enhanced cellular sensitivity to gemcitabine. In addition, histone deacetylases inhibitor trichostatin A (TSA) inhibited TGIF, p-AKT{sup Ser473} expression and migration ability. Synergistic effects of gemcitabine and TSA on NGR cells were also demonstrated. Collectively, TGIF contributes to the gemcitabine resistance of UC via AKT activation. Combined treatment with gemcitabine and TSA might be a promising therapeutic remedy to improve the gemcitabine resistance of UC. - Highlights: • TGIF expression in UC cells is associated with chemoresistance to gemcitabine. • TGIF-regulated AKT activation contributes to the gemcitabine resistance. • Increased

  18. Group Work

    Wilson, Kristy J.; Brickman, Peggy; Brame, Cynthia J.

    2018-01-01

    Science, technology, engineering, and mathematics faculty are increasingly incorporating both formal and informal group work in their courses. Implementing group work can be improved by an understanding of the extensive body of educational research studies on this topic. This essay describes an online, evidence-based teaching guide published by…

  19. Reflection groups

    Eggermont, G.

    2006-01-01

    In 2005, PISA organised proactive meetings of reflection groups on involvement in decision making, expert culture and ethical aspects of radiation protection.All reflection group meetings address particular targeted audiences while the output publication in book form is put forward

  20. Short-term modern life-like stress exacerbates Aβ-pathology and synapse loss in 3xTg-AD mice.

    Baglietto-Vargas, David; Chen, Yuncai; Suh, Dongjin; Ager, Rahasson R; Rodriguez-Ortiz, Carlos J; Medeiros, Rodrigo; Myczek, Kristoffer; Green, Kim N; Baram, Tallie Z; LaFerla, Frank M

    2015-09-01

    Alzheimer's disease (AD) is a progressive neurological disorder that impairs memory and other cognitive functions in the elderly. The social and financial impacts of AD are overwhelming and are escalating exponentially as a result of population aging. Therefore, identifying AD-related risk factors and the development of more efficacious therapeutic approaches are critical to cure this neurological disorder. Current epidemiological evidence indicates that life experiences, including chronic stress, are a risk for AD. However, it is unknown if short-term stress, lasting for hours, influences the onset or progression of AD. Here, we determined the effect of short-term, multi-modal 'modern life-like' stress on AD pathogenesis and synaptic plasticity in mice bearing three AD mutations (the 3xTg-AD mouse model). We found that combined emotional and physical stress lasting 5 h severely impaired memory in wild-type mice and tended to impact it in already low-performing 3xTg-AD mice. This stress reduced the number of synapse-bearing dendritic spines in 3xTg-AD mice and increased Aβ levels by augmenting AβPP processing. Thus, short-term stress simulating modern-life conditions may exacerbate cognitive deficits in preclinical AD by accelerating amyloid pathology and reducing synapse numbers. Epidemiological evidence indicates that life experiences, including chronic stress, are a risk for Alzheimer disease (AD). However, it is unknown if short stress in the range of hours influences the onset or progression of AD. Here, we determined the effect of short, multi-modal 'modern-lifelike'stress on AD pathogenesis and synaptic plasticity in mice bearing three AD mutations (the 3xTg-AD mouse model). We found that combined emotional and physical stress lasting 5 h severely impaired memory in wild-type mice and tended to impact it in already low-performing 3xTg-AD mice. This stress reduced the number of synapse-bearing dendritic spines in 3xTg-AD mice and increased Aβ levels by

  1. Age-dependent modifications of AMPA receptor subunit expression levels and related cognitive effects in 3xTg-AD mice

    Pamela eCantanelli

    2014-08-01

    Full Text Available GluA1, GluA2, GluA3, and GluA4 are the constitutive subunits of AMPA receptors (AMPARs, the major mediators of fast excitatory transmission in the mammalian central nervous system. Most AMPARs are Ca2+-impermeable because of the presence of the GluA2 subunit. GluA2 mRNA undergoes an editing process that results in a Q to R substitution, a key factor in the regulation of AMPAR Ca2+-permeability. AMPARs lacking GluA2 or containing the unedited subunit are permeable to Ca2+ and Zn2+. The phenomenon physiologically modulates synaptic plasticity while, in pathologic conditions, leads to increased vulnerability to excitotoxic neuronal death. Given the importance of these subunits, we have therefore evaluated possible associations between changes in expression levels of AMPAR subunits and development of cognitive deficits in 3xTg-AD mice, a widely investigated transgenic mouse model of Alzheimer’s disease. With qRT-PCR, we assayed hippocampal mRNA expression levels of GluA1-4 subunits occurring in young [3 months of age (m.o.a.] and old (12 m.o.a Tg-AD mice and made comparisons with levels found in age-matched wild type (WT mice. Efficiency of GluA2 RNA editing was also analyzed. All animals were cognitively tested for short- and long-term spatial memory with the Morris Water Maze (MWM navigation task. 3xTg-AD mice showed age-dependent decreases of mRNA levels for all the AMPAR subunits, with the exception of GluA2. Editing remained fully efficient with aging in 3xTg-AD and WT mice. A one-to-one correlation analysis between MWM performances and GluA1-4 mRNA expression profiles showed negative correlations between GluA2 levels and MWM performances in young 3xTg-AD mice. On the contrary, positive correlations between GluA2 mRNA and MWM performances were found in young WT mice. Our data suggest that increases of AMPARs that contain GluA1, GluA3, and GluA4 subunits may help in maintaining cognition in pre-symptomatic 3xTg-AD mice.

  2. SU-F-T-485: Independent Remote Audits for TG51 NonCompliant Photon Beams Performed by the IROC Houston QA Center

    Alvarez, P; Molineu, A; Lowenstein, J; Taylor, P; Kry, S; Followill, D [UT MD Anderson Cancer Center, Houston, TX (United States)

    2016-06-15

    Purpose: IROC-H conducts external audits for output check verification of photon and electron beams. Many of these beams can meet the geometric requirements of the TG 51 calibration protocol. For those photon beams that are non TG 51 compliant like Elekta GammaKnife, Accuray CyberKnife and TomoTherapy, IROC-H has specific audit tools to monitor the reference calibration. Methods: IROC-H used its TLD and OSLD remote monitoring systems to verify the output of machines with TG 51 non compliant beams. Acrylic OSLD miniphantoms are used for the CyberKnife. Special TLD phantoms are used for TomoTherapy and GammaKnife machines to accommodate the specific geometry of each machine. These remote audit tools are sent to institutions to be irradiated and returned to IROC-H for analysis. Results: The average IROC-H/institution ratios for 480 GammaKnife, 660 CyberKnife and 907 rotational TomoTherapy beams are 1.000±0.021, 1.008±0.019, 0.974±0.023, respectively. In the particular case of TomoTherapy, the overall ratio is 0.977±0.022 for HD units. The standard deviations of all results are consistent with values determined for TG 51 compliant photon beams. These ratios have shown some changes compared to values presented in 2008. The GammaKnife results were corrected by an experimentally determined scatter factor of 1.025 in 2013. The TomoTherapy helical beam results are now from a rotational beam whereas in 2008 the results were from a static beam. The decision to change modality was based on recommendations from the users. Conclusion: External audits of beam outputs is a valuable tool to confirm the calibrations of photon beams regardless of whether the machine is TG 51 or TG 51 non compliant. The difference found for TomoTherapy units is under investigation. This investigation was supported by IROC grant CA180803 awarded by the NCI.

  3. SU-F-T-485: Independent Remote Audits for TG51 NonCompliant Photon Beams Performed by the IROC Houston QA Center

    Alvarez, P; Molineu, A; Lowenstein, J; Taylor, P; Kry, S; Followill, D

    2016-01-01

    Purpose: IROC-H conducts external audits for output check verification of photon and electron beams. Many of these beams can meet the geometric requirements of the TG 51 calibration protocol. For those photon beams that are non TG 51 compliant like Elekta GammaKnife, Accuray CyberKnife and TomoTherapy, IROC-H has specific audit tools to monitor the reference calibration. Methods: IROC-H used its TLD and OSLD remote monitoring systems to verify the output of machines with TG 51 non compliant beams. Acrylic OSLD miniphantoms are used for the CyberKnife. Special TLD phantoms are used for TomoTherapy and GammaKnife machines to accommodate the specific geometry of each machine. These remote audit tools are sent to institutions to be irradiated and returned to IROC-H for analysis. Results: The average IROC-H/institution ratios for 480 GammaKnife, 660 CyberKnife and 907 rotational TomoTherapy beams are 1.000±0.021, 1.008±0.019, 0.974±0.023, respectively. In the particular case of TomoTherapy, the overall ratio is 0.977±0.022 for HD units. The standard deviations of all results are consistent with values determined for TG 51 compliant photon beams. These ratios have shown some changes compared to values presented in 2008. The GammaKnife results were corrected by an experimentally determined scatter factor of 1.025 in 2013. The TomoTherapy helical beam results are now from a rotational beam whereas in 2008 the results were from a static beam. The decision to change modality was based on recommendations from the users. Conclusion: External audits of beam outputs is a valuable tool to confirm the calibrations of photon beams regardless of whether the machine is TG 51 or TG 51 non compliant. The difference found for TomoTherapy units is under investigation. This investigation was supported by IROC grant CA180803 awarded by the NCI

  4. Group theory

    Scott, W R

    2010-01-01

    Here is a clear, well-organized coverage of the most standard theorems, including isomorphism theorems, transformations and subgroups, direct sums, abelian groups, and more. This undergraduate-level text features more than 500 exercises.

  5. Group Grammar

    Adams, Karen

    2015-01-01

    In this article Karen Adams demonstrates how to incorporate group grammar techniques into a classroom activity. In the activity, students practice using the target grammar to do something they naturally enjoy: learning about each other.

  6. Computer group

    Bauer, H.; Black, I.; Heusler, A.; Hoeptner, G.; Krafft, F.; Lang, R.; Moellenkamp, R.; Mueller, W.; Mueller, W.F.; Schati, C.; Schmidt, A.; Schwind, D.; Weber, G.

    1983-01-01

    The computer groups has been reorganized to take charge for the general purpose computers DEC10 and VAX and the computer network (Dataswitch, DECnet, IBM - connections to GSI and IPP, preparation for Datex-P). (orig.)

  7. Group learning

    Pimentel, Ricardo; Noguira, Eloy Eros da Silva; Elkjær, Bente

    The article presents a study that aims at the apprehension of the group learning in a top management team composed by teachers in a Brazilian Waldorf school whose management is collective. After deciding to extend the school, they had problems recruiting teachers who were already trained based...... on the Steiner´s ideas, which created practical problems for conducting management activities. The research seeks to understand how that group of teachers collectively manage the school, facing the lack of resources, a significant heterogeneity in the relationships, and the conflicts and contradictions......, and they are interrelated to the group learning as the construction, maintenance and reconstruction of the intelligibility of practices. From this perspective, it can be said that learning is a practice and not an exceptional phenomenon. Building, maintaining and rebuilding the intelligibility is the group learning...

  8. Multi-valued logic circuits using hybrid circuit consisting of three gates single-electron transistors (TG-SETs) and MOSFETs.

    Shin, SeungJun; Yu, YunSeop; Choi, JungBum

    2008-10-01

    New multi-valued logic (MVL) families using the hybrid circuits consisting of three gates single-electron transistors (TG-SETs) and a metal-oxide-semiconductor field-effect transistor (MOSFET) are proposed. The use of SETs offers periodic literal characteristics due to Coulomb oscillation of SET, which allows a realization of binary logic (BL) circuits as well as multi-valued logic (MVL) circuits. The basic operations of the proposed MVL families are successfully confirmed through SPICE circuit simulation based on the physical device model of a TG-SET. The proposed MVL circuits are found to be much faster, but much larger power consumption than a previously reported MVL, and they have a trade-off between speed and power consumption. As an example to apply the newly developed MVL families, a half-adder is introduced.

  9. Molybdenum(V, germanium(IV, aluminum(III and nickel(II adducts with ethyleneurea, ethylenethiourea and propyleneurea: some empirical correlations involving TG and IR data

    ROBSON F. DE FARIAS

    2006-03-01

    Full Text Available The adducts MoCl5·2eu, MoCl5·2pu, GeCl4·2etu, AlCl3·2pu, AlCl3·3pu, NiCl2·2etu and NiCl2·4etu (eu = ethyleneurea, etu = ethylenethiourea and pu =propyleneurea were synthesized and characterized by elemental analysis (C, H, N, infrared spectroscopy (IR and thermogravimetry (TG. IR Results show that eu and pu coordinate through oxygen, whereas etu coordinates through nitrogen. For all investigated adducts, a single mass loss step associated with the release of ligand molecules is observed. Empirical correlations involving TG and IR data are established.

  10. Group technology

    Rome, C.P.

    1976-01-01

    Group Technology has been conceptually applied to the manufacture of batch-lots of 554 machined electromechanical parts which now require 79 different types of metal-removal tools. The products have been grouped into 7 distinct families which require from 8 to 22 machines in each machine-cell. Throughput time can be significantly reduced and savings can be realized from tooling, direct-labor, and indirect-labor costs

  11. Abelian groups

    Fuchs, László

    2015-01-01

    Written by one of the subject’s foremost experts, this book focuses on the central developments and modern methods of the advanced theory of abelian groups, while remaining accessible, as an introduction and reference, to the non-specialist. It provides a coherent source for results scattered throughout the research literature with lots of new proofs. The presentation highlights major trends that have radically changed the modern character of the subject, in particular, the use of homological methods in the structure theory of various classes of abelian groups, and the use of advanced set-theoretical methods in the study of undecidability problems. The treatment of the latter trend includes Shelah’s seminal work on the undecidability in ZFC of Whitehead’s Problem; while the treatment of the former trend includes an extensive (but non-exhaustive) study of p-groups, torsion-free groups, mixed groups, and important classes of groups arising from ring theory. To prepare the reader to tackle these topics, th...

  12. Thioredoxin-1 attenuates sepsis-induced cardiomyopathy after cecal ligation and puncture in mice.

    Wilson, Rickesha L; Selvaraju, Vaithinathan; Lakshmanan, Rajesh; Thirunavukkarasu, Mahesh; Campbell, Jacob; McFadden, David W; Maulik, Nilanjana

    2017-12-01

    Sepsis is a leading cause of mortality among patients in intensive care units across the USA. Thioredoxin-1 (Trx-1) is an essential 12 kDa cytosolic protein that, apart from maintaining the cellular redox state, possesses multifunctional properties. In this study, we explored the possibility of controlling adverse myocardial depression by overexpression of Trx-1 in a mouse model of severe sepsis. Adult C57BL/6J and Trx-1 Tg/+ mice were divided into wild-type sham (WTS), wild-type cecal ligation and puncture (WTCLP), Trx-1 Tg/+ sham (Trx-1 Tg/+ S), and Trx-1 Tg/+ CLP groups. Cardiac function was evaluated before surgery, 6 and 24 hours after CLP surgery. Immunohistochemical and Western blot analysis were performed after 24 hours in heart tissue sections. Echocardiography analysis showed preserved cardiac function in the Trx-1 Tg/+ CLP group compared with the WTCLP group. Similarly, Western blot analysis revealed increased expression of Trx-1, heme oxygenase-1 (HO-1), survivin (an inhibitor of apoptosis [IAP] protein family), and decreased expression of thioredoxin-interacting protein (TXNIP), caspase-3, and 3- nitrotyrosine in the Trx-1 Tg/+ CLP group compared with the WTCLP group. Immunohistochemical analysis showed reduced 4-hydroxynonenal, apoptosis, and vascular leakage in the cardiac tissue of Trx-1 Tg/+ CLP mice compared with mice in the WTCLP group. Our results indicate that overexpression of Trx-1 attenuates cardiac dysfunction during CLP. The mechanism of action may involve reduction of oxidative stress, apoptosis, and vascular permeability through activation of Trx-1/HO-1 and anti-apoptotic protein survivin. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Characterization of pH dependent Mn(II) oxidation strategies and formation of a bixbyite-like phase by Mesorhizobium australicum T-G1

    Bohu, Tsing; Santelli, Cara M; Akob, Denise M.; Neu, Thomas R; Ciobota, Valerian; Rösch, Petra; Popp, Jürgen; Nietzsche, Sándor; Küsel, Kirsten

    2015-01-01

    Despite the ubiquity of Mn oxides in natural environments, there are only a few observations of biological Mn(II) oxidation at pH < 6. The lack of low pH Mn-oxidizing bacteria (MOB) isolates limits our understanding of how pH influences biological Mn(II) oxidation in extreme environments. Here, we report that a novel MOB isolate, Mesorhizobium australicum strain T-G1, isolated from an acidic and metalliferous uranium mining area, can oxidize Mn(II) at both acidic and neutral pH using different enzymatic pathways. X-ray diffraction, Raman spectroscopy, and scanning electron microscopy with energy dispersive X-ray spectroscopy revealed that T-G1 initiated bixbyite-like Mn oxide formation at pH 5.5 which coincided with multi-copper oxidase expression from early exponential phase to late stationary phase. In contrast, reactive oxygen species (ROS), particularly superoxide, appeared to be more important for T-G1 mediated Mn(II) oxidation at neutral pH. ROS was produced in parallel with the occurrence of Mn(II) oxidation at pH 7.2 from early stationary phase. Solid phase Mn oxides did not precipitate, which is consistent with the presence of a high amount of H2O2 and lower activity of catalase in the liquid culture at pH 7.2. Our results show that M. australicum T-G1, an acid tolerant MOB, can initiate Mn(II) oxidation by varying its oxidation mechanisms depending on the pH and may play an important role in low pH manganese biogeochemical cycling.

  14. Rozmanitost projevů heteroplazmické mtDNA mutace 8993 T>G ve dvou rodinách

    Tesařová, M.; Hansíková, H.; Hlavatá, A.; Klement, P.; Houšťková, H.; Houštěk, Josef; Zeman, J.

    2002-01-01

    Roč. 141, č. 17 (2002), s. 551-554 ISSN 0008-7335 R&D Projects: GA MZd(CZ) NE6533; GA MZd(CZ) NE6555; GA MŠk(CZ) LN00A079 Institutional research plan: CEZ:AV0Z5011922 Keywords : NARP syndrome * mtDNA mutation 8993 T>G Subject RIV: EB - Genetics ; Molecular Biology

  15. Characterization of pH dependent Mn(II oxidation strategies and formation of a bixbyite-like phase by Mesorhizobium australicum T-G1

    Tsing eBohu

    2015-07-01

    Full Text Available Despite the ubiquity of Mn oxides in natural environments, there are only a few observations of biological Mn(II oxidation at pH < 6. The lack of low pH Mn-oxidizing bacteria (MOB isolates limits our understanding of how pH influences biological Mn(II oxidation in extreme environments. Here, we report that a novel MOB isolate, Mesorhizobium australicum strain T-G1, isolated from an acidic and metalliferous uranium mining area, can oxidize Mn(II at both acidic and neutral pH using different enzymatic pathways. X-ray diffraction (XRD, Raman spectroscopy, and scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDS revealed that T-G1 initiated bixbyite-like Mn oxide formation at pH 5.5 which coincided with multi-copper oxidase (MCO expression from early exponential phase to late stationary phase. In contrast, reactive oxygen species (ROS, particularly superoxide, appeared to be more important for T-G1 mediated Mn(II oxidation at neutral pH. ROS was produced in parallel with the occurrence of Mn(II oxidation at pH 7.2 from early stationary phase. Solid phase Mn oxides did not precipitate, which is consistent with the presence of a high amount of H2O2 and lower activity of catalase in the liquid culture at pH 7.2. Our results show that M. australicum T-G1, an acid tolerant MOB, can initiate Mn(II oxidation by varying its oxidation mechanisms depending on the pH and may play an important role in low pH manganese biogeochemical cycling.

  16. Characterization of pH dependent Mn(II) oxidation strategies and formation of a bixbyite-like phase by Mesorhizobium australicum T-G1

    Bohu, Tsing; Santelli, Cara M; Akob, Denise M.; Neu, Thomas R; Ciobota, Valerian; Rösch, Petra; Popp, Jürgen; Nietzsche, Sándor; Küsel, Kirsten

    2015-01-01

    Despite the ubiquity of Mn oxides in natural environments, there are only a few observations of biological Mn(II) oxidation at pH MOB) isolates limits our understanding of how pH influences biological Mn(II) oxidation in extreme environments. Here, we report that a novel MOB isolate, Mesorhizobium australicum strain T-G1, isolated from an acidic and metalliferous uranium mining area, can oxidize Mn(II) at both acidic and neutral pH using different enzymatic pathways. X-ray diffraction, Raman spectroscopy, and scanning electron microscopy with energy dispersive X-ray spectroscopy revealed that T-G1 initiated bixbyite-like Mn oxide formation at pH 5.5 which coincided with multi-copper oxidase expression from early exponential phase to late stationary phase. In contrast, reactive oxygen species (ROS), particularly superoxide, appeared to be more important for T-G1 mediated Mn(II) oxidation at neutral pH. ROS was produced in parallel with the occurrence of Mn(II) oxidation at pH 7.2 from early stationary phase. Solid phase Mn oxides did not precipitate, which is consistent with the presence of a high amount of H2O2 and lower activity of catalase in the liquid culture at pH 7.2. Our results show that M. australicum T-G1, an acid tolerant MOB, can initiate Mn(II) oxidation by varying its oxidation mechanisms depending on the pH and may play an important role in low pH manganese biogeochemical cycling.

  17. Highly Stabilized Curcumin Nanoparticles Tested in an In Vitro Blood–Brain Barrier Model and in Alzheimer’s Disease Tg2576 Mice

    Cheng, Kwok Kin; Yeung, Chin Fung; Ho, Shuk Wai; Chow, Shing Fung; Chow, Albert H. L.; Baum, Larry

    2012-01-01

    The therapeutic effects of curcumin in treating Alzheimer’s disease (AD) depend on the ability to penetrate the blood–brain barrier. The latest nanoparticle technology can help to improve the bioavailability of curcumin, which is affected by the final particle size and stability. We developed a stable curcumin nanoparticle formulation to test in vitro and in AD model Tg2576 mice. Flash nanoprecipitation of curcumin, polyethylene glycol-polylactic acid co-block polymer, and polyvinylpyrrolidon...

  18. Atherogenic Impact of Lecithin-Cholesterol Acyltransferase and Its Relation to Cholesterol Esterification Rate in HDL (FERHDL) and AIP [log(TG/HDL-C)] Biomarkers: The Butterfly Effect?

    Dobiášová, Milada

    2017-01-01

    Roč. 66, č. 2 (2017), s. 193-203 ISSN 0862-8408 Institutional support: RVO:67985823 Keywords : lecithin-cholesterol acyltransferase (LCAT) * atherosclerosis * FERHDL (fractional esterification rate in HDL) * AIP (atherogenic index of plasma, log(TG/HDL-C) * biomarkers of cardiometabolic risk * lipoprotein particle size Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery OBOR OECD: Endocrinology and metabolism (including diabetes, hormones) Impact factor: 1.461, year: 2016

  19. Adiponectin gene polymorphism rs2241766 T/G is associated with response to pioglitazone treatment in type 2 diabetic patients from southern China.

    Hong Yang

    Full Text Available INTRODUCTION: Insulin sensitizing drugs such as pioglitazone are not uniformly treatment effective among individual type 2 diabetic patients. Here, the relationship of pioglitazone efficacy to single nucleotide polymorphisms (SNP of the adiponectin gene, a critical gene directly regulated by the drug, was examined in a cohort of Chinese Han type 2 diabetic patients. METHODS: Eighty type 2 diabetic patients were treated with pioglitazone (15 mg/day for 12 weeks without interruption of their current therapeutic regimen. Fasting plasma glucose, fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR, and glycated hemoglobin (HbA1c% were collected both prior to and following pioglitazone treatment. Response to pioglitazone was defined as a decrease of at least 15% in HbA1c% levels. Three regions of the adiponectin gene containing SNPs (promoter, intron 2 and exon 2, and exon 3 were amplified and sequenced to determine genotype. RESULTS: Serum adiponectin levels were significantly increased (p<0.001 whereas fasting plasma glucose, fasting insulin, HOMA-IR, and HbA1c% values were significantly decreased relative to baseline measurements (p<0.001. Response of patients with TG and TT genotypes at rs2241766 (exon2; 52.9% vs. 12.7%, respectively p = 0.001 was statistically significant relative to all other patients. Amongst rs2241766 TG and TT patients, the mean decrease in HbA1c% levels was greater where the genotype was TG (1.15±0.80 vs. 0.52±0.64, p = 0.001. CONCLUSIONS: The adiponectin gene polymorphism rs2241766 T/G is associated with pioglitazone efficacy in type 2 diabetic patients, and status of the polymorphism may be an important clinical factor to consider prior to pioglitazone treatment.

  20. In silico analysis and gene expression of TgNAC01 transcription factor involved in xylogenesis and abiotic stress in Tectona grandis.

    Vladimir Camel Paucar

    2017-09-01

    Full Text Available Secondary xylem is the most abundant component of plant biomass. Therefore, knowing the genes that regulate its formation would help to design strategies for wood genetic improvement. Thus, the objective of this work was to perform computational analysis of the primary and secondary structure of the TgNAC01 transcription factor (FT of Tectona grandis, and to evaluate its evolutionary history, conserved domains and gene expression in lignified tissues of 12 and 60 years. For this, an ion-electron interaction potential (IEP was evaluated using the information-spectrum method (IEM using the R-Project and SFAPS library, followed by structural modeling using the MODELLER software and visualized by PyMol program. In addition, the analysis of multiple sequence alignment and phylogeny was performed using Bioedit and MrBayes software, respectively. We also evaluated the qRT-PCR levels of TgNAC01. As results, it was found that TgNAC01 maintains a twisted antiparallel β-sheet structure, which is compacted against an α-helix in the N-terminal region, having three α-helix domains and seven folded β-domains. Also, through the IEM, it was demonstrated that it has about five biological functions, and mutations on amino acids with higher IEP, which leads to evolutions on genetic regulation networks. Finally, the FT TgNAC01 plays an esential role in the organization and development of the parts that make up the sapwood, such as the radial cells of the cambial zone, the vessels, fibers and the growth rings.

  1. Role of 5'TG3'-interacting factors (TGIFs) in Vorinostat (HDAC inhibitor)-mediated Corneal Fibrosis Inhibition.

    Sharma, Ajay; Sinha, Nishant R; Siddiqui, Saad; Mohan, Rajiv R

    2015-01-01

    We have previously reported that vorinostat, an FDA-approved, clinically used histone deacetylase (HDAC) inhibitor, attenuates corneal fibrosis in vivo in rabbits by blocking transforming growth factor β (TGFβ). The 5'TG3'-interacting factors (TGIFs) are transcriptional repressors of TGFβ1 signaling via the Smad pathway. The present study was designed to explore the expression of TGIFs in human corneal fibroblasts and to investigate their role in mediating the antifibrotic effect of vorinostat. Human corneal fibroblast cultures were generated from donor corneas. RNA isolation, cDNA preparation, and PCR were performed to detect the presence of TGIF1 and TGIF2 transcripts. The cultures were exposed to vorinostat (2.5 µM) to test its effect on TGIF mRNA and protein levels using qPCR and immunoblotting. Myofibroblast formation was induced with TGFβ1 (5 ng/ml) treatment under serum-free conditions. The changes in fibrosis parameters were quantified by measuring fibrosis marker α-smooth muscle actin (αSMA) mRNA and protein levels with qPCR, immunostaining, and immunoblotting. Smad2/3/4 and TGIF knockdowns were performed using pre-validated RNAi/siRNAs and a commercially available transfection reagent. Human corneal fibroblasts showed the expression of TGIF1 and TGIF2. Vorinostat (2.5 µM) caused a 2.8-3.3-fold increase in TGIF1 and TGIF2 mRNA levels and a 1.4-1.8-fold increase in TGIF1 and TGIF2 protein levels. Vorinostat treatment also caused a significant increase in acetylhistone H3 and acetylhistone H4. Vorinostat-induced increases in TGIF1 and TGIF2 were accompanied by a concurrent decrease in corneal fibrosis, as indicated by a decrease in αSMA mRNA by 83±7.7% and protein levels by 97±5%. The RNAi-mediated knockdown of Smad2, Smad3, and Smad4 markedly attenuated TGFβ1-evoked transdifferentiation of fibroblasts to myofibroblasts. The siRNA-mediated knockdown of TGIF1 and TGIF2 neutralized vorinostat-evoked decreases in αSMA mRNA by 31%-45% and protein

  2. Celiac Disease-Specific TG2-Targeted Autoantibodies Inhibit Angiogenesis Ex Vivo and In Vivo in Mice by Interfering with Endothelial Cell Dynamics.

    Suvi Kalliokoski

    Full Text Available A characteristic feature of celiac disease is the presence of circulating autoantibodies targeted against transglutaminase 2 (TG2, reputed to have a function in angiogenesis. In this study we investigated whether TG2-specific autoantibodies derived from celiac patients inhibit angiogenesis in both ex vivo and in vivo models and sought to clarify the mechanism behind this phenomenon. We used the ex vivo murine aorta-ring and the in vivo mouse matrigel-plug assays to address aforementioned issues. We found angiogenesis to be impaired as a result of celiac disease antibody supplementation in both systems. Our results also showed the dynamics of endothelial cells was affected in the presence of celiac antibodies. In the in vivo angiogenesis assays, the vessels formed were able to transport blood despite impairment of functionality after treatment with celiac autoantibodies, as revealed by positron emission tomography. We conclude that celiac autoantibodies inhibit angiogenesis ex vivo and in vivo and impair vascular functionality. Our data suggest that the anti-angiogenic mechanism of the celiac disease-specific autoantibodies involves extracellular TG2 and inhibited endothelial cell mobility.

  3. [Correlation of SNP of IL-2-330T/G Gene with Genetic Susceptibility and Efficacy of Immunosuppressive Therapy in Patients with Aplastic Anemia].

    Zeng, Qiang; Chang, Hong

    2016-10-01

    To investigate the correlation of single nucleotide polymorphism (SNP) of Interleukin-2(IL-2)-330T/G with genetic susceptibility and the efficacy of immunosuppressive therapy in patients with aplastic anemia. The peripheral blood samples from 103 patients with aplastic anemia in our hospital were collected. Out of 103 patients 46 received immuosuppressive therapy and were observed for 4 months, and 100 healthy adults were selected as control. The electrophoresis and DNA sequence were performed. The polymerase chain reaction(PCR) was used to amplify the polymorphic gene segment of IL-2 -330T/G from 103 aplastic anemia patients and 100 healthy adults. The frequencis of IL-2-330 GG genotype and G allele were a little higher in patients with aplastic anemia than that in the healthy adults(12.6% vs 12.0%, P>0.05; 27.7% vs 33.5%, P>0.05), but not statistically significant(P>0.05); in the 103 patients with aplastic anemia, 46 received immunosuppressive therapy, whereas 29 patients showed response, no significant difference was found between the responders and non-responders in the IL-2-330 GG genotype and G allele (31.0% vs 48.3%, P>0.05; 64.8% vs 61.8%, P>0.05). IL-2 -330T/G gene polymorphism may not correlate with the susceptibility of aplastic anemia or the efficacy of immunosuppressive therapy.

  4. TG-MS analysis and kinetic study for thermal decomposition of six representative components of municipal solid waste under steam atmosphere.

    Zhang, Jinzhi; Chen, Tianju; Wu, Jingli; Wu, Jinhu

    2015-09-01

    Thermal decomposition of six representative components of municipal solid waste (MSW, including lignin, printing paper, cotton, rubber, polyvinyl chloride (PVC) and cabbage) was investigated by thermogravimetric-mass spectroscopy (TG-MS) under steam atmosphere. Compared with TG and derivative thermogravimetric (DTG) curves under N2 atmosphere, thermal decomposition of MSW components under steam atmosphere was divided into pyrolysis and gasification stages. In the pyrolysis stage, the shapes of TG and DTG curves under steam atmosphere were almost the same with those under N2 atmosphere. In the gasification stage, the presence of steam led to a greater mass loss because of the steam partial oxidation of char residue. The evolution profiles of H2, CH4, CO and CO2 were well consistent with DTG curves in terms of appearance of peaks and relevant stages in the whole temperature range, and the steam partial oxidation of char residue promoted the generation of more gas products in high temperature range. The multi-Gaussian distributed activation energy model (DAEM) was proved plausible to describe thermal decomposition behaviours of MSW components under steam atmosphere. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Celiac Disease–Specific TG2-Targeted Autoantibodies Inhibit Angiogenesis Ex Vivo and In Vivo in Mice by Interfering with Endothelial Cell Dynamics

    Kalliokoski, Suvi; Sulic, Ana-Marija; Korponay-Szabó, Ilma R.; Szondy, Zsuzsa; Frias, Rafael; Perez, Mileidys Alea; Martucciello, Stefania; Roivainen, Anne; Pelliniemi, Lauri J.; Esposito, Carla; Griffin, Martin; Sblattero, Daniele; Mäki, Markku; Kaukinen, Katri; Lindfors, Katri; Caja, Sergio

    2013-01-01

    A characteristic feature of celiac disease is the presence of circulating autoantibodies targeted against transglutaminase 2 (TG2), reputed to have a function in angiogenesis. In this study we investigated whether TG2-specific autoantibodies derived from celiac patients inhibit angiogenesis in both ex vivo and in vivo models and sought to clarify the mechanism behind this phenomenon. We used the ex vivo murine aorta-ring and the in vivo mouse matrigel-plug assays to address aforementioned issues. We found angiogenesis to be impaired as a result of celiac disease antibody supplementation in both systems. Our results also showed the dynamics of endothelial cells was affected in the presence of celiac antibodies. In the in vivo angiogenesis assays, the vessels formed were able to transport blood despite impairment of functionality after treatment with celiac autoantibodies, as revealed by positron emission tomography. We conclude that celiac autoantibodies inhibit angiogenesis ex vivo and in vivo and impair vascular functionality. Our data suggest that the anti-angiogenic mechanism of the celiac disease-specific autoantibodies involves extracellular TG2 and inhibited endothelial cell mobility. PMID:23824706

  6. Primary fatty acid amide metabolism: conversion of fatty acids and an ethanolamine in N18TG2 and SCP cells1[S

    Farrell, Emma K.; Chen, Yuden; Barazanji, Muna; Jeffries, Kristen A.; Cameroamortegui, Felipe; Merkler, David J.

    2012-01-01

    Primary fatty acid amides (PFAM) are important signaling molecules in the mammalian nervous system, binding to many drug receptors and demonstrating control over sleep, locomotion, angiogenesis, and many other processes. Oleamide is the best-studied of the primary fatty acid amides, whereas the other known PFAMs are significantly less studied. Herein, quantitative assays were used to examine the endogenous amounts of a panel of PFAMs, as well as the amounts produced after incubation of mouse neuroblastoma N18TG2 and sheep choroid plexus (SCP) cells with the corresponding fatty acids or N-tridecanoylethanolamine. Although five endogenous primary amides were discovered in the N18TG2 and SCP cells, a different pattern of relative amounts were found between the two cell lines. Higher amounts of primary amides were found in SCP cells, and the conversion of N-tridecanoylethanolamine to tridecanamide was observed in the two cell lines. The data reported here show that the N18TG2 and SCP cells are excellent model systems for the study of PFAM metabolism. Furthermore, the data support a role for the N-acylethanolamines as precursors for the PFAMs and provide valuable new kinetic results useful in modeling the metabolic flux through the pathways for PFAM biosynthesis and degradation. PMID:22095832

  7. Reversal of autophagy dysfunction in the TgCRND8 mouse model of Alzheimer's disease ameliorates amyloid pathologies and memory deficits.

    Yang, Dun-Sheng; Stavrides, Philip; Mohan, Panaiyur S; Kaushik, Susmita; Kumar, Asok; Ohno, Masuo; Schmidt, Stephen D; Wesson, Daniel; Bandyopadhyay, Urmi; Jiang, Ying; Pawlik, Monika; Peterhoff, Corrinne M; Yang, Austin J; Wilson, Donald A; St George-Hyslop, Peter; Westaway, David; Mathews, Paul M; Levy, Efrat; Cuervo, Ana M; Nixon, Ralph A

    2011-01-01

    Autophagy, a major degradative pathway for proteins and organelles, is essential for survival of mature neurons. Extensive autophagic-lysosomal pathology in Alzheimer's disease brain contributes to Alzheimer's disease pathogenesis, although the underlying mechanisms are not well understood. Here, we identified and characterized marked intraneuronal amyloid-β peptide/amyloid and lysosomal system pathology in the Alzheimer's disease mouse model TgCRND8 similar to that previously described in Alzheimer's disease brains. We further establish that the basis for these pathologies involves defective proteolytic clearance of neuronal autophagic substrates including amyloid-β peptide. To establish the pathogenic significance of these abnormalities, we enhanced lysosomal cathepsin activities and rates of autophagic protein turnover in TgCRND8 mice by genetically deleting cystatin B, an endogenous inhibitor of lysosomal cysteine proteases. Cystatin B deletion rescued autophagic-lysosomal pathology, reduced abnormal accumulations of amyloid-β peptide, ubiquitinated proteins and other autophagic substrates within autolysosomes/lysosomes and reduced intraneuronal amyloid-β peptide. The amelioration of lysosomal function in TgCRND8 markedly decreased extracellular amyloid deposition and total brain amyloid-β peptide 40 and 42 levels, and prevented the development of deficits of learning and memory in fear conditioning and olfactory habituation tests. Our findings support the pathogenic significance of autophagic-lysosomal dysfunction in Alzheimer's disease and indicate the potential value of restoring normal autophagy as an innovative therapeutic strategy for Alzheimer's disease.

  8. Deducting the temperature dependence of the structural relaxation time in equilibrium far below the nominal Tg by aging the decoupled conductivity relaxation to equilibrium.

    Wojnarowska, Z; Ngai, K L; Paluch, M

    2014-05-07

    Using broadband dielectric spectroscopy we investigate the changes in the conductivity relaxation times τσ observed during the physical aging of the protic ionic conductor carvedilol dihydrogen phosphate (CP). Due to the large decoupling of ion diffusion from host molecule reorientation, the ion conductivity relaxation time τσ(Tage,tage) can be directly measured at temperatures Tage below Tg for exceedingly long aging times tage till τσ(Tage,tage) has reached the equilibrium value τσ(eq)(Tage). The dependence of τσ(Tage,tage) on tage is well described by the stretched exponential function, τσ(Tage, tage) = Aexp[-((tage)/(τage(Tage)))(β)] + τσ(eq)(Tage), where β is a constant and τage(Tage) can be taken as the structural α-relaxation time of the equilibrium liquid at T = Tage. The value of τσ(eq)(Tage) obtained after 63 days long annealing of CP, deviates from the Vogel-Fulcher-Tammann-Hesse (VFTHσ) dependence of τσ(T) determined from data taken above Tg and extrapolated down to Tage. Concurrently, τage(Tage) also deviates from the Vogel-Fulcher-Tammann-Hesse (VFTHα) dependence. The results help to answer the longstanding question of whether the VFTH dependence of τσ(T) as well as the structural α-relaxation time τα(T) holds or not in the equilibrium liquid state far below Tg.

  9. Toxoplasma gondii: humoral and cellular immune response of BALB/c mice immunized via intranasal route with rTgROP2 Toxoplasma gondii: avaliação da resposta imune humoral e celular de camundongos BALB/c imunizados pela via nasal com rTgROP2

    Michelle Igarashi

    2010-12-01

    Full Text Available TgROP2 is an intracellular protein associated with rhoptries of Toxoplama gondii and an antigen component of a candidate vaccine for toxoplasmosis. The purpose of the present study was to evaluate the efficacy of rTgROP2 to stimulate humoral and cellular immune responses in BALB/c mice via intranasal injection. TgROP2 partial coding sequence was (196-561 amplified by PCR from genomic T. gondii RH strain DNA and cloned into the pTrcHis expression vector. Escherichia coli Rosetta 2 cells transformed with pTrcHis-TgROP2 showed high levels (~1 mg.mL-1 of recombinant protein after 4 hours of IPTG induction. Recombinant TgROP2 exhibited an apparent Mr equal to 54 kDa. In order to test immunogenicity of the recombinant protein, 10 BALB/c mice received 10 µg of rROP2 protein + 10 µg of Quil-A via intranasal injection. Doses were administered at days 0, 21, and 42. Three animals were euthanized and used to evaluate cell-ular immune response on day 62. Five (50% and two (20% out of ten animals produced IgG (DO mean = 0.307; cut-off = 0.240 and IgA (DO mean = 0.133, cut-off = 0.101, respectively, by ELISA on day 62. The proliferation of splenocytes revealed high stimulation index (SI when co-cultured with 5, 10 and 15 µg.mL-1 of rTgROP2. These results indicate that intranasal immunization with recombinant protein ROP2 plus Quil-A can elicit both cellular and humoral immune responses in BALB/c mice.TgROP2 é uma proteína localizada nas roptrias do Toxoplasma gondii, sendo um antígeno candidato a componente de uma vacina contra a toxoplasmose. O objetivo do presente estudo foi avaliar a eficácia da TgROP2 recombinante em estimular a resposta imune celular e humoral de camundongos BALB/c após estímulo intranasal. A sequência da TgROP2 foi amplificada pela PCR a partir da cepa RH e clonada em vetor de expressão pTrc-His. Após a transformação em Escherichia coli- Rosetta 2, a pTrcHis-TgROP2 exibiu alto nível de expressão após 4 horas de indu

  10. Group dynamics.

    Scandiffio, A L

    1990-12-01

    Group dynamics play a significant role within any organization, culture, or unit. The important thing to remember with any of these structures is that they are made up of people--people with different ideas, motivations, background, and sometimes different agendas. Most groups, formal or informal, look for a leader in an effort to maintain cohesiveness of the unit. At times, that cultural bond must be developed; once developed, it must be nurtured. There are also times that one of the group no longer finds the culture comfortable and begins to act out behaviorally. It is these times that become trying for the leader as she or he attempts to remain objective when that which was once in the building phase of group cohesiveness starts to fall apart. At all times, the manager must continue to view the employee creating the disturbance as an integral part of the group. It is at this time that it is beneficial to perceive the employee exhibiting problem behaviors as a special employee, as one who needs the benefit of your experience and skills, as one who is still part of the group. It is also during this time that the manager should focus upon her or his own views in the area of power, communication, and the corporate culture of the unit that one has established before attempting to understand another's point of view. Once we understand our own motivation and accept ourselves, it is then that we may move on to offer assistance to another. Once we understand our insecurities recognizing staff dysfunction as a symptom of system dysfunction will not be so threatening to the concept of the manager that we perceive ourselves to be. It takes a secure person to admit that she or he favors staff before deciding to do something to change things. The important thing to know is that it can be done. The favored staff can find a new way of relating to others, the special employee can find new modes of behavior (and even find self-esteem in the process), the group can find new ways

  11. A global inventory of aircraft NO{sub x} emissions (ANCAT/EC 2). A revised inventory (1996) by the ECAC/ANCAT and EC working group

    Gardner, R M [Great Minister House, London (United Kingdom). Dept. of Transfert London

    1998-12-31

    Results of the ANCAT/EC 2 inventory produced by the European ANCAT/EC emissions inventory group is reported. The base year inventory has been completed and is currently being written up for report publication. The ANCAT/EC 2 inventory in the base year, 1991/92, has accounted for a total fuel burn of 132.5 Tg/yr and a NO{sub x} mass of 1.82 Tg/yr. The civil subsonic fleet average emissions index is EI NO{sub x} 13.9. The inventory has accounted for 80% of the IEA refined jet fuel total for 1992. The forecast 2015 inventory accounts for 289.4 Tg/yr fuel and 3.48 Tg/yr NO{sub x}, increases of 118% and 91% respectively. Both datasets will be reported fully in the next few months. (author) 5 refs.

  12. A global inventory of aircraft NO{sub x} emissions (ANCAT/EC 2). A revised inventory (1996) by the ECAC/ANCAT and EC working group

    Gardner, R.M. [Great Minister House, London (United Kingdom). Dept. of Transfert London

    1997-12-31

    Results of the ANCAT/EC 2 inventory produced by the European ANCAT/EC emissions inventory group is reported. The base year inventory has been completed and is currently being written up for report publication. The ANCAT/EC 2 inventory in the base year, 1991/92, has accounted for a total fuel burn of 132.5 Tg/yr and a NO{sub x} mass of 1.82 Tg/yr. The civil subsonic fleet average emissions index is EI NO{sub x} 13.9. The inventory has accounted for 80% of the IEA refined jet fuel total for 1992. The forecast 2015 inventory accounts for 289.4 Tg/yr fuel and 3.48 Tg/yr NO{sub x}, increases of 118% and 91% respectively. Both datasets will be reported fully in the next few months. (author) 5 refs.

  13. Group representations

    Karpilovsky, G

    1994-01-01

    This third volume can be roughly divided into two parts. The first part is devoted to the investigation of various properties of projective characters. Special attention is drawn to spin representations and their character tables and to various correspondences for projective characters. Among other topics, projective Schur index and projective representations of abelian groups are covered. The last topic is investigated by introducing a symplectic geometry on finite abelian groups. The second part is devoted to Clifford theory for graded algebras and its application to the corresponding theory

  14. Lego Group

    Møller Larsen, Marcus; Pedersen, Torben; Slepniov, Dmitrij

    2010-01-01

    The last years’ rather adventurous journey from 2004 to 2009 had taught the fifth-largest toy-maker in the world - the LEGO Group - the importance of managing the global supply chain effectively. In order to survive the largest internal financial crisis in its roughly 70 years of existence......, the management had, among many initiatives, decided to offshore and outsource a major chunk of its production to Flextronics. In this pursuit of rapid cost-cutting sourcing advantages, the LEGO Group planned to license out as much as 80 per cent of its production besides closing down major parts...

  15. Informal groups

    E. van den Berg; P. van Houwelingen; J. de Hart

    2011-01-01

    Original title: Informele groepen Going out running with a group of friends, rather than joining an official sports club. Individuals who decide to take action themselves rather than giving money to good causes. Maintaining contact with others not as a member of an association, but through an

  16. COMMUNICATIONS GROUP

    L. Taylor

    2011-01-01

    The CMS Communications Group, established at the start of 2010, has been busy in all three areas of its responsibility: (1) Communications Infrastructure, (2) Information Systems, and (3) Outreach and Education. Communications Infrastructure There are now 55 CMS Centres worldwide that are well used by physicists working on remote CMS shifts, Computing operations, data quality monitoring, data analysis and outreach. The CMS Centre@CERN in Meyrin, is the centre of the CMS offline and computing operations, hosting dedicated analysis efforts such as during the CMS Heavy Ion lead-lead running. With a majority of CMS sub-detectors now operating in a “shifterless” mode, many monitoring operations are now routinely performed from there, rather than in the main Control Room at P5. The CMS Communications Group, CERN IT and the EVO team are providing excellent videoconferencing support for the rapidly-increasing number of CMS meetings. In parallel, CERN IT and ...

  17. Group therapy

    Anon.

    1993-01-01

    Full text: In his review 'Genesis of Unified Gauge Theories' at the symposium in Honour of Abdus Salam (June, page 23), Tom Kibble of Imperial College, London, looked back to the physics events around Salam from 1959-67. He described how, in the early 1960s, people were pushing to enlarge the symmetry of strong interactions beyond the SU(2) of isospin and incorporate the additional strangeness quantum number. Kibble wrote - 'Salam had students working on every conceivable symmetry group. One of these was Yuval Ne'eman, who had the good fortune and/or prescience to work on SU(3). From that work, and of course from the independent work of Murray Gell- Mann, stemmed the Eightfold Way, with its triumphant vindication in the discovery of the omega-minus in 1964.' Yuval Ne'eman writes - 'I was the Defence Attaché at the Israeli Embassy in London and was admitted by Salam as a part-time graduate student when I arrived in 1958. I started research after resigning from the Embassy in May 1960. Salam suggested a problem: provide vector mesons with mass - the problem which was eventually solved by Higgs, Guralnik, Kibble,.... (as described by Kibble in his article). I explained to Salam that I had become interested in symmetry. Nobody at Imperial College at the time, other than Salam himself, was doing anything in groups, and attention further afield was focused on the rotation - SO(N) - groups. Reacting to my own half-baked schemes, Salam told me to forget about the rotation groups he taught us, and study group theory in depth, directing me to Eugene Dynkin's classification of Lie subalgebras, about which he had heard from Morton Hamermesh. I found Dynkin incomprehensible without first learning about Lie algebras from Henri Cartan's thesis, which luckily had been reproduced by Dynkin in his 1946 thesis, using his diagram method. From a copy of a translation of Dynkin's thesis which I found in the British Museum Library, I

  18. COMMUNICATIONS GROUP

    L. Taylor

    2010-01-01

    The CMS Communications Group, established at the start of 2010, has been strengthening the activities in all three areas of its responsibility: (1) Communications Infrastructure, (2) Information Systems, and (3) Outreach and Education. Communications Infrastructure The Communications Group has invested a lot of effort to support the operations needs of CMS. Hence, the CMS Centres where physicists work on remote CMS shifts, Data Quality Monitoring, and Data Analysis are running very smoothly. There are now 55 CMS Centres worldwide, up from just 16 at the start of CMS data-taking. The latest to join are Imperial College London, the University of Iowa, and the Università di Napoli. The CMS Centre@CERN in Meyrin, which is now full repaired after the major flooding at the beginning of the year, has been at the centre of CMS offline and computing operations, most recently hosting a large fraction of the CMS Heavy Ion community during the lead-lead run. A number of sub-detector shifts can now take pla...

  19. Group play

    Tychsen, Anders; Hitchens, Michael; Brolund, Thea

    2008-01-01

    Role-playing games (RPGs) are a well-known game form, existing in a number of formats, including tabletop, live action, and various digital forms. Despite their popularity, empirical studies of these games are relatively rare. In particular there have been few examinations of the effects of the v......Role-playing games (RPGs) are a well-known game form, existing in a number of formats, including tabletop, live action, and various digital forms. Despite their popularity, empirical studies of these games are relatively rare. In particular there have been few examinations of the effects...... of the various formats used by RPGs on the gaming experience. This article presents the results of an empirical study, examining how multi-player tabletop RPGs are affected as they are ported to the digital medium. Issues examined include the use of disposition assessments to predict play experience, the effect...... of group dynamics, the influence of the fictional game characters and the comparative play experience between the two formats. The results indicate that group dynamics and the relationship between the players and their digital characters, are integral to the quality of the gaming experience in multiplayer...

  20. COMMUNICATIONS GROUP

    L. Taylor

    2011-01-01

    The CMS Communications Group has been busy in all three areas of its responsibility: (1) Communications Infrastructure, (2) Information Systems, and (3) Outreach and Education. Communications Infrastructure The 55 CMS Centres worldwide are well used by physicists working on remote CMS shifts, Computing operations, data quality monitoring, data analysis and outreach. The CMS Centre@CERN in Meyrin, is the centre of the CMS Offline and Computing operations, and a number of subdetector shifts can now take place there, rather than in the main Control Room at P5. A new CMS meeting room has been equipped for videoconferencing in building 42, next to building 40. Our building 28 meeting room and the facilities at P5 will be refurbished soon and plans are underway to steadily upgrade the ageing equipment in all 15 CMS meeting rooms at CERN. The CMS evaluation of the Vidyo tool indicates that it is not yet ready to be considered as a potential replacement for EVO. The Communications Group provides the CMS-TV (web) cha...

  1. Antibody-Mediated Rejection in a Blood Group A-Transgenic Mouse Model of ABO-Incompatible Heart Transplantation.

    Motyka, Bruce; Fisicaro, Nella; Wang, Szu-I; Kratochvil, Annetta; Labonte, Katrina; Tao, Kesheng; Pearcey, Jean; Marshall, Thuraya; Mengel, Michael; Sis, Banu; Fan, Xiaohu; dʼApice, Anthony J F; Cowan, Peter J; West, Lori J

    2016-06-01

    ABO-incompatible (ABOi) organ transplantation is performed owing to unremitting donor shortages. Defining mechanisms of antibody-mediated rejection, accommodation, and tolerance of ABOi grafts is limited by lack of a suitable animal model. We report generation and characterization of a murine model to enable study of immunobiology in the setting of ABOi transplantation. Transgenesis of a construct containing human A1- and H-transferases under control of the ICAM-2 promoter was performed in C57BL/6 (B6) mice. A-transgenic (A-Tg) mice were assessed for A-antigen expression by histology and flow cytometry. B6 wild-type (WT) mice were sensitized with blood group A-human erythrocytes; others received passive anti-A monoclonal antibody and complement after heart transplant. Serum anti-A antibodies were assessed by hemagglutination. "A-into-O" transplantation (major histocompatibility complex syngeneic) was modeled by transplanting hearts from A-Tg mice into sensitized or nonsensitized WT mice. Antibody-mediated rejection was assessed by morphology/immunohistochemistry. A-Tg mice expressed A-antigen on vascular endothelium and other cells including erythrocytes. Antibody-mediated rejection was evident in 15/17 A-Tg grafts in sensitized WT recipients (median titer, 1:512), with 2 showing hyperacute rejection and rapid cessation of graft pulsation. Hyperacute rejection was observed in 8/8 A-Tg grafts after passive transfer of anti-A antibody and complement into nonsensitized recipients. Antibody-mediated rejection was not observed in A-Tg grafts transplanted into nonsensitized mice. A-Tg heart grafts transplanted into WT mice with abundant anti-A antibody manifests characteristic features of antibody-mediated rejection. These findings demonstrate an effective murine model to facilitate study of immunologic features of ABOi transplantation and to improve potential diagnostic and therapeutic strategies.

  2. Rapid detection of SNP (c.309T>G in the MDM2 gene by the Duplex SmartAmp method.

    Yasuaki Enokida

    Full Text Available BACKGROUND: Genetic polymorphisms in the human MDM2 gene are suggested to be a tumor susceptibility marker and a prognostic factor for cancer. It has been reported that a single nucleotide polymorphism (SNP c.309T>G in the MDM2 gene attenuates the tumor suppressor activity of p53 and accelerates tumor formation in humans. METHODOLOGY: In this study, to detect the SNP c.309T>G in the MDM2 gene, we have developed a new SNP detection method, named "Duplex SmartAmp," which enabled us to simultaneously detect both 309T and 309G alleles in one tube. To develop this new method, we introduced new primers i.e., nBP and oBPs, as well as two different fluorescent dyes that separately detect those genetic polymorphisms. RESULTS AND CONCLUSIONS: By the Duplex SmartAmp method, the genetic polymorphisms of the MDM2 gene were detected directly from a small amount of genomic DNA or blood samples. We used 96 genomic DNA and 24 blood samples to validate the Duplex SmartAmp by comparison with results of the conventional PCR-RFLP method; consequently, the Duplex SmartAmp results agreed totally with those of the PCR-RFLP method. Thus, the new SNP detection method is considered useful for detecting the SNP c.309T>G in the MDM2 gene so as to judge cancer susceptibility against some cellular stress in the clinical setting, and also to handle a large number of samples and enable rapid clinical diagnosis.

  3. Value of IgA tTG in Predicting Mucosal Recovery in Children with Celiac Disease on a Gluten Free Diet

    Leonard, Maureen M.; Weir, Dascha C.; DeGroote, Maya; Mitchell, Paul D.; Singh, Prashant; Silvester, Jocelyn A.; Leichtner, Alan M.; Fasano, Alessio

    2017-01-01

    Objective Our objective was to determine the rate of mucosal recovery in pediatric patients with celiac disease on a gluten free diet. We also sought to determine whether IgA tissue transglutaminase (tTG) correlates with mucosal damage at the time of a repeat endoscopy with duodenal biopsy in these patients. Methods We performed a retrospective chart review of one-hundred and three pediatric patients, under 21 years of age, with a diagnosis of celiac disease defined as Marsh 3 histology, and who underwent a repeat endoscopy with duodenal biopsy at least twelve months after initiating a gluten free diet. Results We found that 19% of pediatric patients treated with a gluten free diet had persistent enteropathy. At the time of the repeat biopsy, tTG was elevated in 43% of cases with persistent enteropathy and 32% of cases in which there was mucosal recovery. Overall the positive predictive value of the autoantibody tissue transglutaminase was 25% and the negative predictive value was 83% in patients on a gluten free diet for a median of 2.4 years. Conclusions Nearly one in five children with celiac disease in our population had persistent enteropathy despite maintaining a gluten free diet and IgA tTG was not an accurate marker of mucosal recovery. Neither the presence of symptoms nor positive serology were predictive of a patient’s histology at the time of repeat biopsy. These findings suggest a revisitation of monitoring and management criteria of celiac disease in childhood. PMID:28112686

  4. Sci-Sat AM(2): Brachy-05: Dosimetry effects of the TG-43 approximations for two iodine seeds in LDR brachytherapy.

    Furstoss, C; Bertrand, M J; Poon, E; Reniers, B; Pignol, J P; Carrier, J F; Beaulieu, L; Verhaegen, F

    2008-07-01

    This work consists of studying the interseed and tissue composition effects for two model iodine seeds: the IBt Interseed-125 and the 6711 model seed. Three seeds were modeled with the MCNP MC code in a water sphere to evaluate the interseed effect. The dose calculated at different distances from the centre was compared to the dose summed when the seeds were simulated separately. The tissue composition effect was studied calculating the radial dose function for different tissues. Before carrying out post-implant studies, the absolute dose calculated by MC was compared to experiment results: with LiF TLDs in an acrylic breast phantom and with an EBT Gafchromic film placed in a water tank. Afterwards, the TG-43 approximation effects were studied for a prostate and breast post-implant. The interseed effect study shows that this effect is more important for model 6711 (15%) than for IBt (10%) due to the silver rod in 6711. For both seed models the variations of the radial dose function as a function of the tissue composition are quasi similar. The absolute dose comparisons between MC calculations and experiments give good agreement (inferior to 3% in general). For the prostate and breast post-implant studies, a 10% difference between MC calculations and the TG-43 is found for both models of seeds. This study shows that the differences in dose distributions between TG43 and MC are quite similar for the two models of seeds and are about 10% for the studied post-implant treatments. © 2008 American Association of Physicists in Medicine.

  5. Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD).

    Balasubramaniam, Shanti; Lewis, B; Mock, D M; Said, H M; Tarailo-Graovac, M; Mattman, A; van Karnebeek, C D; Thorburn, D R; Rodenburg, R J; Christodoulou, J

    2017-01-01

    Leigh syndrome (LS), or subacute necrotizing encephalomyelopathy, is a genetically heterogeneous, relentlessly progressive, devastating neurodegenerative disorder that usually presents in infancy or early childhood. A diagnosis of Leigh-like syndrome may be considered in individuals who do not fulfil the stringent diagnostic criteria but have features resembling Leigh syndrome.We describe a unique presentation of Leigh-like syndrome in a 3-year-old boy with elevated 3-hydroxyisovalerylcarnitine (C5-OH) on newborn screening (NBS). Subsequent persistent plasma elevations of C5-OH and propionylcarnitine (C3) as well as fluctuating urinary markers were suggestive of multiple carboxylase deficiency (MCD). Normal enzymology and mutational analysis of genes encoding holocarboxylase synthetase (HLCS) and biotinidase (BTD) excluded MCD. Biotin uptake studies were normal excluding biotin transporter deficiency. His clinical features at 13 months of age comprised psychomotor delay, central hypotonia, myopathy, failure to thrive, hypocitrullinemia, recurrent episodes of decompensation with metabolic keto-lactic acidosis and an episode of hyperammonemia. Biotin treatment from 13 months of age was associated with increased patient activity, alertness, and attainment of new developmental milestones, despite lack of biochemical improvements. Whole exome sequencing (WES) analysis failed to identify any other variants which could likely contribute to the observed phenotype, apart from the homoplasmic (100%) m.8993T>G variant initially detected by mitochondrial DNA (mtDNA) sequencing.Hypocitrullinemia has been reported in patients with the m.8993T>G variant and other mitochondrial disorders. However, persistent plasma elevations of C3 and C5-OH have previously only been reported in one other patient with this homoplasmic mutation. We suggest considering the m.8993T>G variant early in the diagnostic evaluation of MCD-like biochemical disturbances, particularly when associated with

  6. SU-F-T-54: Determination of the AAPM TG-43 Brachytherapy Dosimetry Parameters for A New Titanium-Encapsulated Yb-169 Source by Monte Carlo Calculations

    Reynoso, F [UT MD Anderson Cancer Center, Houston, TX (United States); Washington University School of Medicine, St. Louis, MO (United States); Munro, J [Source Production & Equipment Co., Inc., St. Rose, LA (United States); Cho, S [UT MD Anderson Cancer Center, Houston, TX (United States)

    2016-06-15

    Purpose: To determine the AAPM TG-43 brachytherapy dosimetry parameters of a new titanium-encapsulated Yb-169 source designed to maximize the dose enhancement during gold nanoparticle-aided radiation therapy (GNRT). Methods: An existing Monte Carlo (MC) model of the titanium-encapsulated Yb-169 source, which was described in the current investigators’ published MC optimization study, was modified based on the source manufacturer’s detailed specifications, resulting in an accurate model of the titanium-encapsulated Yb-169 source that was actually manufactured. MC calculations were then performed using the MCNP5 code system and the modified source model, in order to obtain a complete set of the AAPM TG-43 parameters for the new Yb-169 source. Results: The MC-calculated dose rate constant for the new titanium-encapsulated Yb-169 source was 1.05 ± 0.03 cGy per hr U, indicating about 10% decrease from the values reported for the conventional stainless steel-encapsulated Yb-169 sources. The source anisotropy and radial dose function for the new source were found similar to those reported for the conventional Yb-169 sources. Conclusion: In this study, the AAPM TG-43 brachytherapy dosimetry parameters of a new titanium-encapsulated Yb-169 source were determined by MC calculations. The current results suggested that the use of titanium, instead of stainless steel, to encapsulate the Yb-169 core would not lead to any major change in the dosimetric characteristics of the Yb-169 source, while it would allow more low energy photons being transmitted through the source filter thereby leading to an increased dose enhancement during GNRT. Supported by DOD/PCRP grant W81XWH-12-1-0198 This investigation was supported by DOD/PCRP grant W81XWH-12-1- 0198.

  7. SU-F-T-458: Tracking Trends of TG-142 Parameters Via Analysis of Data Recorded by 2D Chamber Array

    Alexandrian, A; Kabat, C; Defoor, D; Saenz, D; Rasmussen, K; Kirby, N; Gutierrez, A; Papanikolaou, N; Stathakis, S [University of Texas HSC SA, San Antonio, TX (United States)

    2016-06-15

    Purpose: With increasing QA demands of medical physicists in clinical radiation oncology, the need for an effective method of tracking clinical data has become paramount. A tool was produced which scans through data automatically recorded by a 2D chamber array and extracts relevant information recommended by TG-142. Using this extracted information a timely and comprehensive analysis of QA parameters can be easily performed enabling efficient monthly checks on multiple linear accelerators simultaneously. Methods: A PTW STARCHECK chamber array was used to record several months of beam outputs from two Varian 2100 series linear accelerators and a Varian NovalisTx−. In conjunction with the chamber array, a beam quality phantom was used to simultaneously to determine beam quality. A minimalist GUI was created in MatLab that allows a user to set the file path of the data for each modality to be analyzed. These file paths are recorded to a MatLab structure and then subsequently accessed by a script written in Python (version 3.5.1) which then extracts values required to perform monthly checks as outlined by recommendations from TG-142. The script incorporates calculations to determine if the values recorded by the chamber array fall within an acceptable threshold. Results: Values obtained by the script are written to a spreadsheet where results can be easily viewed and annotated with a “pass” or “fail” and saved for further analysis. In addition to creating a new scheme for reviewing monthly checks, this application allows for able to succinctly store data for follow up analysis. Conclusion: By utilizing this tool, parameters recommended by TG-142 for multiple linear accelerators can be rapidly obtained and analyzed which can be used for evaluation of monthly checks.

  8. Her Excellency Ms Monique T.G. van Daalen Ambassador Extraordinary and Plenipotentiary Permanent Representative of the Kingdom of the Netherlands to the United Nations Office and other international organisations in Geneva

    Bennett, Sophia Elizabeth

    2017-01-01

    Her Excellency Ms Monique T.G. van Daalen Ambassador Extraordinary and Plenipotentiary Permanent Representative of the Kingdom of the Netherlands to the United Nations Office and other international organisations in Geneva

  9. Chromosomal localisation of the CD4cre transgene in B6·Cg-Tg(Cd4-cre)1Cwi mice.

    Westendorf, Kerstin; Durek, Pawel; Ayew, Samia; Mashreghi, Mir-Farzin; Radbruch, Andreas

    2016-09-01

    The B6·Cg-Tg(Cd4-cre)1Cwi line expresses CRE recombinase under the control of the promoter and regulatory elements of the Cd4 gene. Here we show that CRE recombinase expression reduces the number and frequencies of CD4 positive subsets in a dose-dependent manner and localize the integration site of the transgenic construct to position 60335693-60341285 (qD) of chromosome 3. The insert contains at least 15 complete sequential copies of the transgenic construct. Based on this information we describe a novel PCR assay for genetic typing of transgenic mice. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Association of ADIPOQ +45T>G polymorphism with body fat mass and blood levels of soluble adiponectin and inflammation markers in a Mexican-Mestizo population

    Guzman-Ornelas MO

    2012-10-01

    Full Text Available Milton-Omar Guzman-Ornelas,1 Efrain Chavarria-Avila,1 Jose-Francisco Munoz-Valle,1,2 Laura-Elizabeth Armas-Ramos,3 Jorge Castro-Albarran,3,4 Maria Elena Aguilar Aldrete,1,5 Edith Oregon-Romero,2 Monica Vazquez-Del Mercado,2 Rosa-Elena Navarro-Hernandez1–31Biomedical Sciences Doctorate Program, 2Department of Molecular Biology and Genomics, 3Master of Human Nutrition Program, University of Guadalajara, Guadalajara, Jalisco, México; 4HMIELM, Secretaria de Salud Jalisco, Guadalajara, Jalisco, Mexico; 5Department of Public Health, University of Guadalajara, Jalisco, MéxicoPurpose: Obesity is a disease with genetic susceptibility characterized by an increase in storage and irregular distribution of body fat. In obese patients, the decrease in the Adiponectin gene (ADIPOQ expression has been associated with a systemic low-grade inflammatory state. Our aim was to investigate the relationship between ADIPOQ +45T>G gene simple nucleotide polymorphism (SNP rs2241766 with serum adiponectin (sAdiponectin, distribution of body fat storage, and inflammation markers.Subjects and methods: In this cross-sectional study, 242 individuals from Western Mexico characterized as Mexican-Mestizo and classified by body mass index (BMI, were included. Anthropometrics, body composition, body fat distribution, and inflammation markers were measured by routine methods. Genotypes were characterized using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP technique and sAdiponectin by the ELISA method. A P-value <0.05 was considered the statistically significant threshold.Results: sAdiponectin is associated with BMI (P < 0.001 and the genotypes (P < 0.001 to 0.0046 GG (8169 ± 1162 ng/mL, TG (5189 ± 501 ng/mL, and TT (3741 ± 323 ng/mL, but the SNP ADIPOQ +45T.G is not associated with BMI. However, the detailed analysis showed association of this SNP with a pattern of fat distribution and correlations (P < 0.05 with inflammation markers and

  11. COMMUNICATIONS GROUP

    L. Taylor

    2010-01-01

    The recently established CMS Communications Group, led by Lucas Taylor, has been busy in all three of its main are areas of responsibility: Communications Infrastructure, Information Systems, and Outreach and Education Communications Infrastructure The damage caused by the flooding of the CMS Centre@CERN on 21st December has been completely repaired and all systems are back in operation. Major repairs were made to the roofs, ceilings and one third of the floor had to be completely replaced. Throughout these works, the CMS Centre was kept operating and even hosted a major press event for first 7 TeV collisions, as described below. Incremental work behind the scenes is steadily improving the quality of the CMS communications infrastructure, particularly Webcasting, video conferencing, and meeting rooms at CERN. CERN/IT is also deploying a pilot service of a new videoconference tool called Vidyo, to assess whether it might provide an enhanced service at a lower cost, compared to the EVO tool currently in w...

  12. COMMUNICATIONS GROUP

    L. Taylor

    2011-01-01

    Communications Infrastructure The 55 CMS Centres worldwide are well used by physicists working on remote CMS shifts, Computing operations, data quality monitoring, data analysis and outreach. The CMS Centre@CERN in Meyrin is particularly busy at the moment, hosting about 50 physicists taking part in the heavy-ion data-taking and analysis. Three new CMS meeting room will be equipped for videoconferencing in early 2012: 40/5B-08, 42/R-031, and 28/S-029. The CMS-TV service showing LHC Page 1, CMS Page 1, etc. (http://cmsdoc.cern.ch/cmscc/projector/index.jsp) is now also available for mobile devices: http://cern.ch/mcmstv. Figure 12: Screenshots of CMS-TV for mobile devices Information Systems CMS has a new web site: (http://cern.ch/cms) using a modern web Content Management System to ensure content and links are managed and updated easily and coherently. It covers all CMS sub-projects and groups, replacing the iCMS internal pages. It also incorporates the existing CMS public web site (http:/...

  13. COMMUNICATIONS GROUP

    L. Taylor

    2012-01-01

      Outreach and Education We are fortunate that our research has captured the public imagination, even though this inevitably puts us under the global media spotlight, as we saw with the Higgs seminar at CERN in December, which had 110,000 distinct webcast viewers. The media interest was huge with 71 media organisations registering to come to CERN to cover the Higgs seminar, which was followed by a press briefing with the DG and Spokespersons. This event resulted in about 2,000 generally positive stories in the global media. For this seminar, the CMS Communications Group prepared up-to-date news and public material, including links to the CMS results, animations and event displays [http://cern.ch/go/Ch8thttp://cern.ch/go/Ch8t]. There were 44,000 page-views on the CMS public website, with the Higgs news article being by far the most popular item. CMS event displays from iSpy are fast becoming the iconic media images, featuring on numerous major news outlets (BBC, CNN, MSN...) as well as in the sci...

  14. Long-term Ameliorative Effects of the Antidepressant Fluoxetine Exposure on Cognitive Deficits in 3 × TgAD Mice.

    Jin, Li; Gao, Li-Feng; Sun, Dong-Sheng; Wu, Hao; Wang, Qun; Ke, Dan; Lei, Hao; Wang, Jian-Zhi; Liu, Gong-Ping

    2017-08-01

    Fluoxetine, a selective serotonin reuptake inhibitor, is neuroprotective; therefore, it has been applied to treat some neurodegenerative disorders. For instance, chronic fluoxetine exposure has short-term effects on Alzheimer's disease (AD). However, the long-term ameliorative effects of fluoxetine exposure on AD have not been reported. In the present study, 6-month-old 3 × TgAD mice were treated with fluoxetine for 15 days, and then the influence of fluoxetine was detected at 20 days after the drug withdrawal. We found that chronic fluoxetine treatment ameliorated cognitive deficits of 3 × TgAD mice and increased the volume of the hippocampal CA1 and dentate gyrus (DG) with increased neuron number and dendritic spine density. Meanwhile, fluoxetine exposure also stimulated the long-term potentiation (LTP) in hippocampal DG. The synaptic-related protein expression increased via activation of the cyclic AMP response element binding (CREB) protein/brain-derived neurotrophic factor (BDNF) signaling pathway induced by fluoxetine exposure. Lastly, we found that fluoxetine treatment decreased beta-amyloid (Aβ) levels. These results further certified that fluoxetine may be a potent effective drug for AD.

  15. Comparison of time-gated surface-enhanced Raman spectroscopy (TG-SERS) and classical SERS based monitoring of Escherichia coli cultivation samples.

    Kögler, Martin; Paul, Andrea; Anane, Emmanuel; Birkholz, Mario; Bunker, Alex; Viitala, Tapani; Maiwald, Michael; Junne, Stefan; Neubauer, Peter

    2018-06-08

    The application of Raman spectroscopy as a monitoring technique for bioprocesses is severely limited by a large background signal originating from fluorescing compounds in the culture media. Here we compare time-gated Raman (TG-Raman)-, continuous wave NIR-process Raman (NIR-Raman) and continuous wave micro-Raman (micro-Raman) approaches in combination with surface enhanced Raman spectroscopy (SERS) for their potential to overcome this limit. For that purpose, we monitored metabolite concentrations of Escherichia coli bioreactor cultivations in cell-free supernatant samples. We investigated concentration transients of glucose, acetate, AMP and cAMP at alternating substrate availability, from deficiency to excess. Raman and SERS signals were compared to off-line metabolite analysis of carbohydrates, carboxylic acids and nucleotides. Results demonstrate that SERS, in almost all cases, led to a higher number of identifiable signals and better resolved spectra. Spectra derived from the TG-Raman were comparable to those of micro-Raman resulting in well-discernable Raman peaks, which allowed for the identification of a higher number of compounds. In contrast, NIR-Raman provided a superior performance for the quantitative evaluation of analytes, both with and without SERS nanoparticles when using multivariate data analysis. This article is protected by copyright. All rights reserved. © 2018 American Institute of Chemical Engineers.

  16. The selective positive allosteric M1 muscarinic receptor modulator PQCA attenuates learning and memory deficits in the Tg2576 Alzheimer's disease mouse model.

    Puri, Vanita; Wang, Xiaohai; Vardigan, Joshua D; Kuduk, Scott D; Uslaner, Jason M

    2015-01-01

    We have recently shown that the M1 muscarinic receptor positive allosteric modulator, PQCA, improves cognitive performance in rodents and non-human primates administered the muscarinic receptor antagonist scopolamine. The purpose of the present experiments was to characterize the effects of PQCA in a model more relevant to the disease pathology of Alzheimer's disease. Tg2576 transgenic mice that have elevated Aβ were tested in the novel object recognition task to characterize recognition memory as a function of age and treatment with the PQCA. The effects of PQCA were compared to the acetylcholinesterase inhibitor donepezil, the standard of care for Alzheimer's disease. In addition, the effect of co-administering PQCA and donepezil was evaluated. Aged Tg2576 mice demonstrated a deficit in recognition memory that was significantly attenuated by PQCA. The positive control donepezil also reversed the deficit. Furthermore, doses of PQCA and donepezil that were inactive on their own were found to improve recognition memory when given together. These studies suggest that M1 muscarinic receptor positive allosteric modulation can ameliorate memory deficits in disease relevant models of Alzheimer's disease. These data, combined with our previous findings demonstrating PQCA improves scopolamine-induced cognitive deficits in both rodents and non-human primates, suggest that M1 positive allosteric modulators have therapeutic potential for the treatment of Alzheimer's disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Amitriptyline-mediated cognitive enhancement in aged 3×Tg Alzheimer's disease mice is associated with neurogenesis and neurotrophic activity.

    Wayne Chadwick

    Full Text Available Approximately 35 million people worldwide suffer from Alzheimer's disease (AD. Existing therapeutics, while moderately effective, are currently unable to stem the widespread rise in AD prevalence. AD is associated with an increase in amyloid beta (Aβ oligomers and hyperphosphorylated tau, along with cognitive impairment and neurodegeneration. Several antidepressants have shown promise in improving cognition and alleviating oxidative stress in AD but have failed as long-term therapeutics. In this study, amitriptyline, an FDA-approved tricyclic antidepressant, was administered orally to aged and cognitively impaired transgenic AD mice (3×TgAD. After amitriptyline treatment, cognitive behavior testing demonstrated that there was a significant improvement in both long- and short-term memory retention. Amitriptyline treatment also caused a significant potentiation of non-toxic Aβ monomer with a concomitant decrease in cytotoxic dimer Aβ load, compared to vehicle-treated 3×TgAD controls. In addition, amitriptyline administration caused a significant increase in dentate gyrus neurogenesis as well as increases in expression of neurosynaptic marker proteins. Amitriptyline treatment resulted in increases in hippocampal brain-derived neurotrophic factor protein as well as increased tyrosine phosphorylation of its cognate receptor (TrkB. These results indicate that amitriptyline has significant beneficial actions in aged and damaged AD brains and that it shows promise as a tolerable novel therapeutic for the treatment of AD.

  18. TH-B-12A-01: TG124 “A Guide for Establishing a Credentialing and Privileging Program for Users of Fluoroscopic Equipment in Healthcare Organizations”

    Moore, M [Philadelphia VA Medical Ctr., Philadelphia, PA (United States)

    2014-06-15

    Fluoroscopy credentialing and privileging programs are being instituted because of recorded patient injuries and the widespread growth in fluoroscopy use by operators whose medical education did not include formal fluoroscopy training. This lack of training is recognized as a patient safety deficiency, and medical physicists and health physicists are finding themselves responsible for helping to establish fluoroscopy credentialing programs. While physicians are very knowledgeable about clinical credentials review and the privileging process, medical physicists and health physicists are not as familiar with the process and associated requirements. To assist the qualified medical physicist (QMP) and the radiation safety officer (RSO) with these new responsibilities, TG 124 provides an overview of the credentialing process, guidance for policy development and incorporating trained fluoroscopy users into a facility's established process, as well as recommendations for developing and maintaining a risk-based fluoroscopy safety training program. This lecture will review the major topics addressed in TG124 and relate them to practical situations. Learning Objectives: Understand the difference between credentialing and privileging. Understand the responsibilities, interaction and coordination among key individuals and committees. Understand options for integrating the QMP and/or RSO and Radiation Safety Committee into the credentialing and privileging process. Understand issues related to implementing the fluoroscopy safety training recommendations and with verifying and documenting successful completion.

  19. TH-B-12A-01: TG124 “A Guide for Establishing a Credentialing and Privileging Program for Users of Fluoroscopic Equipment in Healthcare Organizations”

    Moore, M

    2014-01-01

    Fluoroscopy credentialing and privileging programs are being instituted because of recorded patient injuries and the widespread growth in fluoroscopy use by operators whose medical education did not include formal fluoroscopy training. This lack of training is recognized as a patient safety deficiency, and medical physicists and health physicists are finding themselves responsible for helping to establish fluoroscopy credentialing programs. While physicians are very knowledgeable about clinical credentials review and the privileging process, medical physicists and health physicists are not as familiar with the process and associated requirements. To assist the qualified medical physicist (QMP) and the radiation safety officer (RSO) with these new responsibilities, TG 124 provides an overview of the credentialing process, guidance for policy development and incorporating trained fluoroscopy users into a facility's established process, as well as recommendations for developing and maintaining a risk-based fluoroscopy safety training program. This lecture will review the major topics addressed in TG124 and relate them to practical situations. Learning Objectives: Understand the difference between credentialing and privileging. Understand the responsibilities, interaction and coordination among key individuals and committees. Understand options for integrating the QMP and/or RSO and Radiation Safety Committee into the credentialing and privileging process. Understand issues related to implementing the fluoroscopy safety training recommendations and with verifying and documenting successful completion

  20. Distinct transmissibility features of TSE sources derived from ruminant prion diseases by the oral route in a transgenic mouse model (TgOvPrP4 overexpressing the ovine prion protein.

    Jean-Noël Arsac

    Full Text Available Transmissible spongiform encephalopathies (TSEs are a group of fatal neurodegenerative diseases associated with a misfolded form of host-encoded prion protein (PrP. Some of them, such as classical bovine spongiform encephalopathy in cattle (BSE, transmissible mink encephalopathy (TME, kuru and variant Creutzfeldt-Jakob disease in humans, are acquired by the oral route exposure to infected tissues. We investigated the possible transmission by the oral route of a panel of strains derived from ruminant prion diseases in a transgenic mouse model (TgOvPrP4 overexpressing the ovine prion protein (A136R154Q171 under the control of the neuron-specific enolase promoter. Sources derived from Nor98, CH1641 or 87V scrapie sources, as well as sources derived from L-type BSE or cattle-passaged TME, failed to transmit by the oral route, whereas those derived from classical BSE and classical scrapie were successfully transmitted. Apart from a possible effect of passage history of the TSE agent in the inocula, this implied the occurrence of subtle molecular changes in the protease-resistant prion protein (PrPres following oral transmission that can raises concerns about our ability to correctly identify sheep that might be orally infected by the BSE agent in the field. Our results provide proof of principle that transgenic mouse models can be used to examine the transmissibility of TSE agents by the oral route, providing novel insights regarding the pathogenesis of prion diseases.

  1. Heme oxygenase-1 prevents cardiac dysfunction in streptozotocin-diabetic mice by reducing inflammation, oxidative stress, apoptosis and enhancing autophagy.

    Yanli Zhao

    Full Text Available Heme oxygenase-1 (HO-1 has been implicated in cardiac dysfunction, oxidative stress, inflammation, apoptosis and autophagy associated with heart failure, and atherosclerosis, in addition to its recognized role in metabolic syndrome and diabetes. Numerous studies have presented contradictory findings about the role of HO-1 in diabetic cardiomyopathy (DCM. In this study, we explored the role of HO-1 in myocardial dysfunction, myofibril structure, oxidative stress, inflammation, apoptosis and autophagy using a streptozotocin (STZ-induced diabetes model in mice systemically overexpressing HO-1 (Tg-HO-1 or mutant HO-1 (Tg-mutHO-1. The diabetic mouse model was induced by multiple peritoneal injections of STZ. Two months after injection, left ventricular (LV function was measured by echocardiography. In addition, molecular biomarkers related to oxidative stress, inflammation, apoptosis and autophagy were evaluated using classical molecular biological/biochemical techniques. Mice with DCM exhibited severe LV dysfunction, myofibril structure disarray, aberrant cardiac oxidative stress, inflammation, apoptosis, autophagy and increased levels of HO-1. In addition, we determined that systemic overexpression of HO-1 ameliorated left ventricular dysfunction, myofibril structure disarray, oxidative stress, inflammation, apoptosis and autophagy in DCM mice. Furthermore, serine/threonine-specific protein kinase (Akt and AMP-activated protein kinase (AMPK phosphorylation is normally inhibited in DCM, but overexpression of the HO-1 gene restored the phosphorylation of these kinases to normal levels. In contrast, the functions of HO-1 in DCM were significantly reversed by overexpression of mutant HO-1. This study underlines the unique roles of HO-1, including the inhibition of oxidative stress, inflammation and apoptosis and the enhancement of autophagy, in the pathogenesis of DCM.

  2. A meta-analysis of the antiviral activity of the HBV-specific immunotherapeutic TG1050 confirms its value over a wide range of HBsAg levels in a persistent HBV pre-clinical model.

    Kratzer, Roland; Sansas, Benoît; Lélu, Karine; Evlachev, Alexei; Schmitt, Doris; Silvestre, Nathalie; Inchauspé, Geneviève; Martin, Perrine

    2018-02-01

    Pre-clinical models mimicking persistent hepatitis B virus (HBV) expression are seldom, do not capture all features of a human chronic infection and due to their complexity, are subject to variability. We report a meta-analysis of seven experiments performed with TG1050, an HBV-targeted immunotherapeutic, 1 in an HBV-persistent mouse model based on the transduction of mice by an adeno-associated virus coding for an infectious HBV genome (AAV-HBV). To mimic the clinical diversity seen in HBV chronically infected patients, AAV-HBV transduced mice displaying variable HBsAg levels were treated with TG1050. Overall mean percentages of responder mice, displaying decrease in important clinical parameters i.e. HBV-DNA (viremia) and HBsAg levels, were 52% and 51% in TG1050 treated mice, compared with 8% and 22%, respectively, in untreated mice. No significant impact of HBsAg level at baseline on response to TG1050 treatment was found. TG1050-treated mice displayed a significant shorter Time to Response (decline in viral parameters) with an Hazard Ratio (HR) of 8.3 for viremia and 2.6 for serum HBsAg. The mean predicted decrease for TG1050-treated mice was 0.5 log for viremia and 0.8 log for HBsAg, at the end of mice follow-up, compared to no decrease for viremia and 0.3 log HBsAg decrease for untreated mice. For mice receiving TG1050, a higher decline of circulating viremia and serum HBsAg level over time was detected by interaction term meta-analysis with a significant treatment effect (p = 0.002 and pHBV-persistent model mimicking clinical situations.

  3. Thermochemical study of 2,4-, 2,6- and 3,4-dihydroxybenzoic acids in the liquid phase using a TG apparatus

    Vecchio, Stefano; Brunetti, Bruno

    2011-01-01

    Research highlights: → Vapor pressures of solid and liquid 2,4- 2,6- and 3,4-dihydroxybenzoic acids, that don't decompose appreciably in the temperature range considered, were determined by torsion-effusion technique and thermogravimetry, respectively. → Agreement between the experimental sublimation vapor pressures and literature data recently published is good for all the three isomers. → From the temperature dependence of vapor pressure the molar enthalpies of sublimation and vaporization were determined at the middle of the respective experimental temperature intervals. → For validation of TG pressure data, the TG vapor pressures of solid ferrocene and 1,2-dihydroxybenzoic acid were successfully compared with the corresponding literature values. → The following increasing-order of volatility can be established: 2,6-dihydroxybenzoic acid l g H m o ( ) were determined, respectively, at the middle of the respective temperature intervals. The melting temperatures and the molar enthalpies of fusion of these compounds were measured by d.s.c. The vapor pressures of these compounds in the solid state, measured by torsion-effusion technique, were compared with recently published data, while the corresponding molar sublimation enthalpies were determined. In order to validate the vapor pressure results determined by TG, the experimental vapor pressure data regarding solid ferrocene and 1,2-dihydroxybenzoic acid were successfully compared with literature values in the range 20-200 Pa. In addition, the experimental molar enthalpies of fusion were compared with those calculated by subtracting the molar vaporization enthalpies to the sublimation ones, both adjusted to their respective melting temperatures. Finally, the standard (p o = 0.1 MPa) molar enthalpies, entropies and Gibbs energies of sublimation, corrected at the reference temperature of 298.15 K, have been calculated using the estimated heat capacity differences between gas and liquid for vaporization

  4. Association between MDM2 SNP309 T>G polymorphism and the risk of bladder cancer: new data in a Chinese population and an updated meta-analysis

    Xie LG

    2015-12-01

    Full Text Available Linguo Xie,1,2,* Yan Sun,2,* Tao Chen,1,2,* Dawei Tian,1,2 Yujuan Li,3 Yu Zhang,1,2 Na Ding,2 Zhonghua Shen,1,2 Hao Xu,1,2 Xuewu Nian,4 Nan Sha,1,2 Ruifa Han,1,2 Hailong Hu,1,2 Changli Wu1,2 Objective: Human murine double minute 2 protein (MDM2 is mainly a negative regulator of p53 tumor suppressor pathway. We aimed to investigate the association between MDM2 SNP309 polymorphism and bladder cancer risk. Methods: A total of 535 bladder cancer patients and 649 health controls were recruited for our study. MDM2 SNP309 T>G polymorphism was genotyped by polymerase chain reaction-ligase detection reaction method. Logistic regression was used to analyze the relationship between the genotype and susceptibility of bladder cancer. Kaplan–Meier estimates and log-rank test were obtained to analyze the association between the genotype and risk of recrudesce in nonmuscle-invasive bladder cancer patients. A multivariable Cox proportional hazards model was fitted to identify independent prognostic factors. To further investigate the association, we conducted a meta-analysis including six studies. Results: The frequency of the MDM2 SNP309 T>G polymorphism showed no significant difference between cases and controls (all P>0.05. In the stratification analysis, the results showed that G allele carriers were prone to have a significant decrease in risk of low-grade bladder cancer (adjusted odds ratio: 0.613, 95% confidence interval: 0.427–0.881, and G variant was associated with a significantly reduced risk of recurrence in nonmuscle-invasive bladder cancer patients with or without chemotherapy (P<0.05. The results of the meta-analysis showed that G allele and GG genotype of MDM2 SNP309 polymorphism were significantly associated with increased risk of bladder cancer in Caucasians (both P<0.05, and no association was observed in total populations and Asians (P>0.05. Conclusion: MDM2 SNP309 T>G polymorphism has no influence on bladder cancer risk in Asians, but

  5. SU-G-201-06: Directional Low-Dose Rate Brachytherapy: Determination of the TG-43 Dose-Rate Constant Analog for a New Pd-103 Source

    Aima, M; Culberson, W; Hammer, C; Micka, J; DeWerd, L [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI (United States)

    2016-06-15

    Purpose: The aim of this work is to determine the TG-43 dose-rate constant analog for a new directional low-dose rate brachytherapy source based on experimental methods and comparison to Monte Carlo simulations. The CivaSheet™ is a new commercially available planar source array comprised of a variable number of discrete directional source elements called “CivaDots”. Given the directional nature and non-conventional design of the source, modifications to the AAPM TG-43 protocol for dosimetry are required. As a result, various parameters of the TG-43 dosimetric formalism have to be adapted to accommodate this source. This work focuses on the dose-rate constant analog determination for a CivaDot. Methods: Dose to water measurements of the CivaDot were performed in a polymethyl methacrylate phantom (20×20×12 cm{sup 3}) using thermoluminescent dosimeters (TLDs) and Gafchromic EBT3 film. The source was placed in the center of the phantom, and nine TLD micro-cubes were irradiated along its central axis at a distance of 1 cm. For the film measurements, the TLDs were substituted by a (3×3) cm{sup 2} EBT3 film. Primary air-kerma strength measurements of the source were performed using a variable-aperture free-air chamber. Finally, the source was modeled using the Monte Carlo N-Particle Transport Code 6. Results: Dose-rate constant analog observed for a total of eight CivaDots using TLDs and five CivaDots using EBT3 film was within ±7.0% and ±2.9% of the Monte Carlo predicted value respectively. The average difference observed was −4.8% and −0.1% with a standard deviation of 1.7% and 2.1% for the TLD and the film measurements respectively, which are both within the comparison uncertainty. Conclusion: A preliminary investigation to determine the doserate constant analog for a CivaDot was conducted successfully with good agreement between experimental and Monte Carlo based methods. This work will aid in the eventual realization of a clinically-viable dosimetric

  6. Heme oxygenase-1 regulates the progression of K/BxN serum transfer arthritis.

    Rita Brines

    Full Text Available Heme oxygenase-1 (HO-1 is induced in many cell types as a defense mechanism against stress. We have investigated the possible role of endogenous HO-1 in the effector phase of arthritis using the K/BxN serum transfer model of arthritis in HO-1 heterozygous and homozygous knock-out mice.Arthritis was induced in C57/Black-6 xFVB (HO-1(+/+, HO-1(+/- and HO-1(-/- mice by intraperitoneal injection of 150 µl serum from arthritic K/BxN mice at days 0 and 2. Blood was collected and animals were sacrificed at day 10. Histological analysis was performed in ankle sections. The levels of inflammatory mediators were measured in serum and paw homogenates by enzyme-linked immunosorbent assay or Multiplex technology. The incidence of arthritis was higher in HO-1(+/- and HO-1(-/- groups compared with HO-1(+/+. The inflammatory response was aggravated in HO-1(+/- mice as shown by arthritic score and the migration of inflammatory cells that could be related to the enhancement of CXCL-1 production. In addition, the HO-1(+/- group showed proteoglycan depletion significantly higher than HO-1(+/+ mice. Serum levels of matrix metalloproteinase-3, monocyte chemotactic protein-1, plasminogen activator inhibitor-1, E-selectin and intercellular adhesion molecule-1 were increased in arthritic HO-1(-/- mice, whereas vascular endothelial growth factor and some cytokines such as interferon-γ showed a reduction compared to HO-1(+/+ or HO-1(+/- mice. In addition, down-regulated gene expression of ferritin, glutathione S-reductase A1 and superoxide dismutase-2 was observed in the livers of arthritic HO-1(+/- animals.Endogenous HO-1 regulates the production of systemic and local inflammatory mediators and plays a protective role in K/BxN serum transfer arthritis.

  7. MDM2 gene SNP309 T/G and p53 gene SNP72 G/C do not influence diffuse large B-cell non-Hodgkin lymphoma onset or survival in central European Caucasians

    Landt Olfert

    2008-04-01

    Full Text Available Abstract Background SNP309 T/G (rs2279744 causes higher levels of MDM2, the most important negative regulator of the p53 tumor suppressor. SNP72 G/C (rs1042522 gives rise to a p53 protein with a greatly reduced capacity to induce apoptosis. Both polymorphisms have been implicated in cancer. The SNP309 G-allele has recently been reported to accelerate diffuse large B-cell lymphoma (DLBCL formation in pre-menopausal women and suggested to constitute a genetic basis for estrogen affecting human tumorigenesis. Here we asked whether SNP309 and SNP72 are associated with DLBCL in women and are correlated with age of onset, diagnosis, or patient's survival. Methods SNP309 and SNP72 were PCR-genotyped in a case-control study that included 512 controls and 311 patients diagnosed with aggressive NHL. Of these, 205 were diagnosed with DLBCL. Results The age of onset was similar in men and women. The control and patients group showed similar SNP309 and SNP72 genotype frequencies. Importantly and in contrast to the previous findings, similar genotype frequencies were observed in female patients diagnosed by 51 years of age and those diagnosed later. Specifically, 3/20 female DLBCL patients diagnosed by 51 years of age were homozygous for SNP309 G and 2/20 DLBCL females in that age group were homozygous for SNP72 C. Neither SNP309 nor SNP72 had a significant influence on event-free and overall survival in multivariate analyses. Conclusion In contrast to the previous study on Ashkenazi Jewish Caucasians, DLBCL in pre-menopausal women of central European Caucasian ethnicity was not associated with SNP309 G. Neither SNP309 nor SNP72 seem to be correlated with age of onset, diagnosis, or survival of patients.

  8. Characteristics of miniature electronic brachytherapy x-ray sources based on TG-43U1 formalism using Monte Carlo simulation techniques

    Safigholi, Habib; Faghihi, Reza; Jashni, Somaye Karimi; Meigooni, Ali S.

    2012-01-01

    Purpose: The goal of this study is to determine a method for Monte Carlo (MC) characterization of the miniature electronic brachytherapy x-ray sources (MEBXS) and to set dosimetric parameters according to TG-43U1 formalism. TG-43U1 parameters were used to get optimal designs of MEBXS. Parameters that affect the dose distribution such as anode shapes, target thickness, target angles, and electron beam source characteristics were evaluated. Optimized MEBXS designs were obtained and used to determine radial dose functions and 2D anisotropy functions in the electron energy range of 25-80 keV. Methods: Tungsten anode material was considered in two different geometries, hemispherical and conical-hemisphere. These configurations were analyzed by the 4C MC code with several different optimization techniques. The first optimization compared target thickness layers versus electron energy. These optimized thicknesses were compared with published results by Ihsan et al.[Nucl. Instrum. Methods Phys. Res. B 264, 371-377 (2007)]. The second optimization evaluated electron source characteristics by changing the cathode shapes and electron energies. Electron sources studied included; (1) point sources, (2) uniform cylinders, and (3) nonuniform cylindrical shell geometries. The third optimization was used to assess the apex angle of the conical-hemisphere target. The goal of these optimizations was to produce 2D-dose anisotropy functions closer to unity. An overall optimized MEBXS was developed from this analysis. The results obtained from this model were compared to known characteristics of HDR 125 I, LDR 103 Pd, and Xoft Axxent electronic brachytherapy source (XAEBS) [Med. Phys. 33, 4020-4032 (2006)]. Results: The optimized anode thicknesses as a function of electron energy is fitted by the linear equation Y (μm) = 0.0459X (keV)-0.7342. The optimized electron source geometry is obtained for a disk-shaped parallel beam (uniform cylinder) with 0.9 mm radius. The TG-43 distribution

  9. Characteristics of miniature electronic brachytherapy x-ray sources based on TG-43U1 formalism using Monte Carlo simulation techniques

    Safigholi, Habib; Faghihi, Reza; Jashni, Somaye Karimi; Meigooni, Ali S. [Faculty of Engineering, Science and Research Branch, Islamic Azad University, Fars, 73481-13111, Persepolis (Iran, Islamic Republic of); Department of Nuclear Engineering and Radiation Research Center, Shiraz University, 71936-16548, Shiraz (Iran, Islamic Republic of); Shiraz University of Medical Sciences, 71348-14336, Shiraz (Iran, Islamic Republic of); Department of Radiation therapy, Comprehensive Cancer Center of Nevada, 3730 South Eastern Avenue, Las Vegas, Nevada 89169 (United States)

    2012-04-15

    Purpose: The goal of this study is to determine a method for Monte Carlo (MC) characterization of the miniature electronic brachytherapy x-ray sources (MEBXS) and to set dosimetric parameters according to TG-43U1 formalism. TG-43U1 parameters were used to get optimal designs of MEBXS. Parameters that affect the dose distribution such as anode shapes, target thickness, target angles, and electron beam source characteristics were evaluated. Optimized MEBXS designs were obtained and used to determine radial dose functions and 2D anisotropy functions in the electron energy range of 25-80 keV. Methods: Tungsten anode material was considered in two different geometries, hemispherical and conical-hemisphere. These configurations were analyzed by the 4C MC code with several different optimization techniques. The first optimization compared target thickness layers versus electron energy. These optimized thicknesses were compared with published results by Ihsan et al.[Nucl. Instrum. Methods Phys. Res. B 264, 371-377 (2007)]. The second optimization evaluated electron source characteristics by changing the cathode shapes and electron energies. Electron sources studied included; (1) point sources, (2) uniform cylinders, and (3) nonuniform cylindrical shell geometries. The third optimization was used to assess the apex angle of the conical-hemisphere target. The goal of these optimizations was to produce 2D-dose anisotropy functions closer to unity. An overall optimized MEBXS was developed from this analysis. The results obtained from this model were compared to known characteristics of HDR {sup 125}I, LDR {sup 103}Pd, and Xoft Axxent electronic brachytherapy source (XAEBS) [Med. Phys. 33, 4020-4032 (2006)]. Results: The optimized anode thicknesses as a function of electron energy is fitted by the linear equation Y ({mu}m) = 0.0459X (keV)-0.7342. The optimized electron source geometry is obtained for a disk-shaped parallel beam (uniform cylinder) with 0.9 mm radius. The TG-43

  10. Transgenic fluorescent zebrafish Tg(fli1:EGFP)y¹ for the identification of vasotoxicity within the zFET.

    Delov, Vera; Muth-Köhne, Elke; Schäfers, Christoph; Fenske, Martina

    2014-05-01

    The fish embryo toxicity test (FET) is currently one of the most advocated animal alternative tests in ecotoxicology. To date, the application of the FET with zebrafish (zFET) has focused on acute toxicity assessment, where only lethal morphological effects are accounted for. An application of the zFET beyond acute toxicity, however, necessitates the establishment of more refined and quantifiable toxicological endpoints. A valuable tool in this context is the use of gene expression-dependent fluorescent markers that can even be measured in vivo. We investigated the application of embryos of Tg(fli1:EGFP)(y1) for the identification of vasotoxic substances within the zFET. Tg(fli1:EGFP)(y1) fish express enhanced GFP in the entire vasculature under the control of the fli1 promoter, and thus enable the visualization of vascular defects in live zebrafish embryos. We assessed the fli1 driven EGFP-expression in the intersegmental blood vessels (ISVs) qualitatively and quantitatively, and found an exposure concentration related increase in vascular damage for chemicals like triclosan, cartap and genistein. The fluorescence endpoint ISV-length allowed an earlier and more sensitive detection of vasotoxins than the bright field assessment method. In combination with the standard bright field morphological effect assessment, an increase in significance and value of the zFET for a mechanism-specific toxicity evaluation was achieved. This study highlights the benefits of using transgenic zebrafish as convenient tools for identifying toxicity in vivo and to increase sensitivity and specificity of the zFET. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Tg(Th-Cre)FI172Gsat (Th-Cre) defines neurons that are required for full hypercapnic and hypoxic reflexes.

    Sun, Jenny J; Ray, Russell S

    2017-08-15

    The catecholaminergic (CA) system has been implicated in many facets of breathing control and offers an important target to better comprehend the underlying etiologies of both developmental and adult respiratory pathophysiologies. Here, we used a noninvasive DREADD-based pharmacogenetic approach to acutely perturb Tg(Th-Cre)FI172Gsat ( Th-Cre )-defined neurons in awake and unrestrained mice in an attempt to characterize CA function in breathing. We report that clozapine-N-oxide (CNO)-DREAD