Bile duct ligation in developing rats: temporal progression of liver, kidney, and brain damage.
Sheen, Jiunn-Ming; Huang, Li-Tung; Hsieh, Chih-Sung; Chen, Chih-Cheng; Wang, Jia-Yi; Tain, You-Lin
2010-08-01
Cholestatic liver disease may result in progressive end-stage liver disease and other extrahepatic complications. We explored the temporal progression of bile duct ligation (BDL)-induced cholestasis in developing rats, focusing on brain cognition and liver and kidney pathology, to elucidate whether these findings were associated with asymmetric dimethylarginine and oxidative stress alterations. Three groups of young male Sprague-Dawley rats were studied: one group underwent laparotomy (sham), another group underwent laparotomy and BDL for 2 weeks (BDL2), and a third group underwent laparotomy and BDL for 4 weeks (BDL4). The effect of BDL on liver was represented by transforming growth factor beta1 levels and histology activity index scores, which were worse in the BDL4 rats than in the BDL2 rats. BDL4 rats also exhibited more severe spatial memory deficits than BDL2 rats. In addition, renal injury was more progressive in BDL4 rats than in BDL2 rats because BDL4 rats displayed higher Cr levels, elevated tubulointerstitial injury scores, neutrophil gelatinase-associated lipocalin, and symmetric dimethylarginine levels. Our findings highlight the fact that young BDL rats exhibit similar trends of progression of liver, kidney, and brain damage. Further studies are needed to better delineate the nature of progression of organ damage in young cholestatic rats. Copyright 2010 Elsevier Inc. All rights reserved.
Melatonin Alleviates Liver Apoptosis in Bile Duct Ligation Young Rats.
Sheen, Jiunn-Ming; Chen, Yu-Chieh; Hsu, Mei-Hsin; Tain, You-Lin; Huang, Ying-Hsien; Tiao, Mao-Meng; Li, Shih-Wen; Huang, Li-Tung
2016-08-20
Bile duct ligation (BDL)-treated rats display cholestasis and liver damages. The potential protective activity of melatonin in young BDL rats in terms of apoptosis, mitochondrial function, and endoplasmic reticulum (ER) homeostasis has not yet been evaluated. Three groups of young male Sprague-Dawley rats were used: one group received laparotomy (Sham), a second group received BDL for two weeks (BDL), and a third group received BDL and intraperitoneal melatonin (100 mg/day) for two weeks (BDL + M). BDL group rats showed liver apoptosis, increased pro-inflamamtory mediators, caspases alterations, anti-apoptotic factors changes, and dysfunction of ER homeostasis. Melatonin effectively reversed apoptosis, mainly through intrinsic pathway and reversed ER stress. In addition, in vitro study showed melatonin exerted its effect mainly through the melatonin 2 receptor (MT2) in HepG2 cells. In conclusion, BDL in young rats caused liver apoptosis. Melatonin rescued the apoptotic changes via the intrinsic pathway, and possibly through the MT2 receptor. Melatonin also reversed ER stress induced by BDL.
Colares, Josieli Raskopf; Schemitt, Elizângela Gonçalves; Hartmann, Renata Minuzzo; Licks, Francielli; Soares, Mariana do Couto; Bosco, Adriane Dal; Marroni, Norma Possa
2016-01-01
AIM To evaluate the effects of melatonin (Mel) on oxidative stress in an experimental model of bile duct ligation (BDL). METHODS Male Wistar rats (n = 32, weight ± 300 g) were allocated across four groups: CO (sham BDL), BDL (BDL surgery), CO + Mel (sham BDL and Mel administration) and BDL + Mel (BDL surgery and Mel administration). Mel was administered intraperitoneally for 2 wk, starting on postoperative day 15, at a dose of 20 mg/kg. RESULTS Mel was effective at the different standards, reestablishing normal liver enzyme levels, reducing the hepatosomatic and splenosomatic indices, restoring lipoperoxidation and antioxidant enzyme concentrations, reducing fibrosis and inflammation, and thereby reducing liver tissue injury in the treated animals. CONCLUSION The results of this study suggest a protective effect of Mel when administered to rats with secondary biliary cirrhosis induced by BDL. PMID:27833383
Effects of Lactobacillus plantarum on gut barrier function in experimental obstructive jaundice
Zhou, Yu-Kun; Qin, Huan-Long; Zhang, Ming; Shen, Tong-Yi; Chen, Hong-Qi; Ma, Yan-Lei; Chu, Zhao-Xin; Zhang, Peng; Liu, Zhi-Hua
2012-01-01
AIM: To investigate the mechanisms of Lactobacillus plantarum (L. plantarum) action on gut barrier in preoperative and postoperative experimental obstructive jaundice in rats. METHODS: Forty rats were randomly divided into groups of sham-operation, bile duct ligation (BDL), BDL + L. plantarum, BDL + internal biliary drainage (IBD), and BDL + IBD + L. plantarum. Ten days after L. plantarum administration, blood and ileal samples were collected from the rats for morphological examination, and intestinal barrier function, liver function, intestinal oxidative stress and protein kinase C (PKC) activity measurement. The distribution and expression of the PKC and tight junction (TJ) proteins, such as occludin, zonula occludens-1, claudin-1, claudin-4, junction adhesion molecule-A and F-actin, were examined by confocal laser scanning microscopy, immunohistochemistry, Western blotting, real-time fluorescent quantitative polymerase chain reaction assay. RESULTS: L. plantarum administration substantially restored gut barrier, decreased enterocyte apoptosis, improved intestinal oxidative stress, promoted the activity and expression of protein kinase (BDL vs BDL + L. plantarum, 0.295 ± 0.007 vs 0.349 ± 0.003, P < 0.05; BDL + IBD vs BDL + IBD + L. plantarum, 0.407 ± 0.046 vs 0.465 ± 0.135, P < 0.05), and particularly enhanced the expression and phosphorylation of TJ proteins in the experimental obstructive jaundice (BDL vs BDL + L. plantarum, 0.266 ± 0.118 vs 0.326 ± 0.009, P < 0.05). The protective effect of L. plantarum was more prominent after internal biliary drainage ( BDL + IBD vs BDL + IBD + L. plantarum, 0.415 ± 0.105 vs 0.494 ± 0.145, P < 0.05). CONCLUSION: L. plantarum can decrease intestinal epithelial cell apoptosis, reduce oxidative stress, and prevent TJ disruption in biliary obstruction by activating the PKC pathway. PMID:22912548
Effects of Lactobacillus plantarum on gut barrier function in experimental obstructive jaundice.
Zhou, Yu-Kun; Qin, Huan-Long; Zhang, Ming; Shen, Tong-Yi; Chen, Hong-Qi; Ma, Yan-Lei; Chu, Zhao-Xin; Zhang, Peng; Liu, Zhi-Hua
2012-08-14
To investigate the mechanisms of Lactobacillus plantarum (L. plantarum) action on gut barrier in preoperative and postoperative experimental obstructive jaundice in rats. Forty rats were randomly divided into groups of sham-operation, bile duct ligation (BDL), BDL + L. plantarum, BDL + internal biliary drainage (IBD), and BDL + IBD + L. plantarum. Ten days after L. plantarum administration, blood and ileal samples were collected from the rats for morphological examination, and intestinal barrier function, liver function, intestinal oxidative stress and protein kinase C (PKC) activity measurement. The distribution and expression of the PKC and tight junction (TJ) proteins, such as occludin, zonula occludens-1, claudin-1, claudin-4, junction adhesion molecule-A and F-actin, were examined by confocal laser scanning microscopy, immunohistochemistry, Western blotting, real-time fluorescent quantitative polymerase chain reaction assay. L. plantarum administration substantially restored gut barrier, decreased enterocyte apoptosis, improved intestinal oxidative stress, promoted the activity and expression of protein kinase (BDL vs BDL + L. plantarum, 0.295 ± 0.007 vs 0.349 ± 0.003, P < 0.05; BDL + IBD vs BDL + IBD + L. plantarum, 0.407 ± 0.046 vs 0.465 ± 0.135, P < 0.05), and particularly enhanced the expression and phosphorylation of TJ proteins in the experimental obstructive jaundice (BDL vs BDL + L. plantarum, 0.266 ± 0.118 vs 0.326 ± 0.009, P < 0.05). The protective effect of L. plantarum was more prominent after internal biliary drainage ( BDL + IBD vs BDL + IBD + L. plantarum, 0.415 ± 0.105 vs 0.494 ± 0.145, P < 0.05). L. plantarum can decrease intestinal epithelial cell apoptosis, reduce oxidative stress, and prevent TJ disruption in biliary obstruction by activating the PKC pathway.
Shreeram, Devesh D; Panmanee, Warunya; McDaniel, Cameron T; Daniel, Susan; Schaefer, Dale W; Hassett, Daniel J
2018-02-01
Pseudomonas aeruginosa is a metabolically voracious bacterium that is easily manipulated genetically. We have previously shown that the organism is also highly electrogenic in microbial fuel cells (MFCs). Polarization studies were performed in MFCs with wild-type strain PAO1 and three mutant strains (pilT, bdlA and pilT bdlA). The pilT mutant was hyperpiliated, while the bdlA mutant was suppressed in biofilm dispersion chemotaxis. The double pilT bdlA mutant was expected to have properties of both mutations. Polarization data indicate that the pilT mutant showed 5.0- and 3.2-fold increases in peak power compared to the wild type and the pilT bdlA mutant, respectively. The performance of the bdlA mutant was surprisingly the lowest, while the pilT bdlA electrogenic performance fell between the pilT mutant and wild-type bacteria. Measurements of biofilm thickness and bacterial viability showed equal viability among the different strains. The thickness of the bdlA mutant, however, was twice that of wild-type strain PAO1. This observation implicates the presence of dead or dormant bacteria in the bdlA mutant MFCs, which increases biofilm internal resistance as confirmed by electrochemical measurements.
Li, Shih-Wen; Chen, Yu-Chieh; Sheen, Jiunn-Ming; Hsu, Mei-Hsin; Tain, You-Lin; Chang, Kow-Aung; Huang, Li-Tung
2017-07-01
Bile duct ligation (BDL) model is used to study hepatic encephalopathy accompanied by cognitive impairment. We employed the proteomic analysis approach to evaluate cognition-related proteins in the prefrontal cortex of young BDL rats and analyzed the effect of minocycline on these proteins and spatial memory. BDL was induced in young rats at postnatal day 17. Minocycline as a slow-release pellet was implanted into the peritoneum. Morris water maze test and two-dimensional liquid chromatography-tandem mass spectrometry were used to evaluate spatial memory and prefrontal cortex protein expression, respectively. We used 2D/LC-MS/MS to analyze for affected proteins in the prefrontal cortex of young BDL rats. Results were verified with Western blotting, immunohistochemistry, and quantitative real-time PCR. The effect of minocycline in BDL rats was assessed. BDL induced spatial deficits, while minocycline rescued it. Collapsin response mediator protein 2 (CRMP2) and manganese-dependent superoxide dismutase (MnSOD) were upregulated and nucleoside diphosphate kinase B (NME2) was downregulated in young BDL rats. BDL rats exhibited decreased levels of brain-derived neurotrophic factor (BDNF) mRNA as compared with those by the control. However, minocycline treatment restored CRMP2 and NME2 protein expression, BDNF mRNA level, and MnSOD activity to control levels. We demonstrated that BDL altered the expression of CRMP2, NME2, MnSOD, and BDNF in the prefrontal cortex of young BDL rats. However, minocycline treatment restored the expression of the affected mediators that are implicated in cognition. Copyright © 2017 Elsevier Inc. All rights reserved.
Aktas, Cevat; Kanter, Mehmet; Erboga, Mustafa; Mete, Rafet; Oran, Mustafa
2014-10-01
The goal of this study was to evaluate the possible protective effects of melatonin against cholestatic oxidative stress, liver damage and hepatocyte apoptosis in the common rats with bile duct ligation (BDL). A total of 24 male Wistar albino rats were divided into three groups: control, BDL and BDL + received melatonin; each group contains eight animals. Melatonin-treated BDL rats received daily melatonin 100 mg/kg/day via intraperitoneal injection. The application of BDL clearly increased the malondialdehyde (MDA) levels and decreased the superoxide dismutase (SOD) and glutathione (GSH) activities. Melatonin treatment significantly decreased the elevated tissue MDA levels and increased the reduced SOD and GSH enzyme levels in the tissues. The changes demonstrate that the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, mononuclear cells and neutrophil infiltration into the widened portal areas as observed in the BDL group. The data indicate that melatonin attenuates BDL-induced cholestatic liver injury, bile duct proliferation and fibrosis. The α-smooth muscle actin (α-SMA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the BDL were observed to be reduced with the melatonin treatment. These results suggest that administration of melatonin is a potentially beneficial agent to reduce liver damage in BDL by decreasing oxidative stress. © The Author(s) 2012.
Díaz-Gil, Juan J; García-Monzón, Carmelo; Rúa, Carmen; Martín-Sanz, Paloma; Cereceda, Rosa M; Miquilena-Colina, María E; Machín, Celia; Fernández-Martínez, Amalia; García-Cañero, Rarael
2008-05-01
Liver growth factor (LGF), a mitogen for liver cells, behaves as an anti-fibrotic agent even in extrahepatic sites, but its mechanistic basis is unknown. We aimed to determine the intrahepatic expression pattern of key modulators of liver fibrosis in bile duct-ligated rats (BDL) after injection of LGF. BDL rats received either LGF (4.5 microg/ratXdose, two doses/week, at time 0 or 2 or 5w after operation, depending on the group (BDL+LGF groups, n=20) or saline (BDL+S groups, n=20). Groups were compared in terms of fibrosis (histomorphometry), liver function (aminopyrine breath test), matrix metalloproteinases MMP-2 and MMP-9, transforming growth factor beta 1 (TGF-beta1) and liver endoglin content (Western blotting), and serum tissue inhibitor of metalloproteinases 1 (TIMP-1) levels (ELISA). In BDL+LGF rats, the fibrotic index was significantly lower at 5w, p=0.006, and at 8w, p=0.04, than in BDL+S rats. Liver function values in BDL+LGF rats were higher than those obtained in BDL+S rats (80% at 5w and 79% at 8w, versus 38% and 29%, p<0.01, taking healthy controls as 100%). Notably, in BDL+LGF rats the intrahepatic expression levels of both MMPs were lower at 2w (MMP-2, p=0.03; MMP-9, p=0.05) and 5w (MMP-2, p=0.05, MMP-9, p=0.04). In addition, the hepatic TGF-beta1 level in BDL+LGF rats was lower at 2w (36%, p=0.008), 5w (50%) and 8wk (37%), whereas intrahepatic endoglin expression remained constant in all BDL rats studied. LGF ameliorates liver fibrosis and improves liver function in BDL rats. The LGF-induced anti-fibrotic effect is associated with a decreased hepatic level of MMP-2, MMP-9 and TGF-beta1 in fibrotic rats.
Organic Anion Transporting Polypeptide 1a1 Null Mice Are Sensitive to Cholestatic Liver Injury
Zhang, Youcai; Csanaky, Iván L.; Cheng, Xingguo; Lehman-McKeeman, Lois D.; Klaassen, Curtis D.
2012-01-01
Organic anion transporting polypeptide 1a1 (Oatp1a1) is predominantly expressed in livers of mice and is thought to transport bile acids (BAs) from blood into liver. Because Oatp1a1 expression is markedly decreased in mice after bile duct ligation (BDL). We hypothesized that Oatp1a1-null mice would be protected against liver injury during BDL-induced cholestasis due largely to reduced hepatic uptake of BAs. To evaluate this hypothesis, BDL surgeries were performed in both male wild-type (WT) and Oatp1a1-null mice. At 24 h after BDL, Oatp1a1-null mice showed higher serum alanine aminotransferase levels and more severe liver injury than WT mice, and all Oatp1a1-null mice died within 4 days after BDL, whereas all WT mice survived. At 24 h after BDL, surprisingly Oatp1a1-null mice had higher total BA concentrations in livers than WT mice, suggesting that loss of Oatp1a1 did not prevent BA accumulation in the liver. In addition, secondary BAs dramatically increased in serum of Oatp1a1-null BDL mice but not in WT BDL mice. Oatp1a1-null BDL mice had similar basolateral BA uptake (Na+-taurocholate cotransporting polypeptide and Oatp1b2) and BA-efflux (multidrug resistance–associated protein [Mrp]-3, Mrp4, and organic solute transporter α/β) transporters, as well as BA-synthetic enzyme (Cyp7a1) in livers as WT BDL mice. Hepatic expression of small heterodimer partner Cyp3a11, Cyp4a14, and Nqo1, which are target genes of farnesoid X receptor, pregnane X receptor, peroxisome proliferator-activated receptor alpha, and NF-E2-related factor 2, respectively, were increased in WT BDL mice but not in Oatp1a1-null BDL mice. These results demonstrate that loss of Oatp1a1 function exacerbates cholestatic liver injury in mice and suggest that Oatp1a1 plays a unique role in liver adaptive responses to obstructive cholestasis. PMID:22461449
Protective effect of gastrodin on bile duct ligation-induced hepatic fibrosis in rats.
Zhao, Shuangshuang; Li, Naren; Zhen, Yongzhan; Ge, Maoxu; Li, Yi; Yu, Bin; He, Hongwei; Shao, Rong-Guang
2015-12-01
Gastrodin has been showed to possess many beneficial physiological functions, including protection against inflammation and oxidation and apoptosis. Studies showed inflammation and oxidation play important roles in producing liver damage and initiating hepatic fibrogenesis. However, it has not been reported whether gastrodin has a protective effect against hepatic fibrosis or not. This is first ever made attempts to test gastrodin against liver fibrosis in bile duct ligation (BDL) rats. The aim of the present study is to evaluate the effect of gastrodin on BDL-induced hepatic fibrosis in rats. BDL rats were divided into two groups, BDL alone group, and BDL-gastrodin group treated with gastrodin (5 mg/ml in drinking water). The effects of gastrodin on BDL-induced hepatic injury and fibrosis in rats were estimated by assessing serum, urine, bile and liver tissue biochemistry followed by liver histopathology (using hematoxylin & eosin and sirius red stain) and hydroxyproline content measurement. The results showed that gastrodin treatment significantly reduced collagen content, bile duct proliferation and parenchymal necrosis after BDL. The serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) decreased with gastrodin treatment by 15.1 and 23.6 percent respectively in comparison to BDL group did not receive gastrodin. Gastrodin also significantly increased the level of serum high density lipoprotein (HDL) by 62.5 percent and down-regulated the elevated urine total bilirubin (TBIL) by 56.5 percent, but had no effect on total bile acid (TBA) in serum, bile and liver tissues. The immunohistochemical assay showed gastrodin remarkably reduced the expressions of CD68 and NF-κB in BDL rats. Hepatic SOD levels, depressed by BDL, were also increased by gastrodin by 8.4 percent. In addition, the increases of hepatic MDA and NO levels in BDL rats were attenuated by gastrodin by 31.3 and 38.7 percent separately. Our results indicate that gastrodin significantly attenuated the severity of BDL-induced hepatic injury and fibrosis by attenuating oxidative stress and inflammation. Taken together, these findings suggest that gastrodin might be an effective antifibrotic drug in cholestatic liver disease. Copyright © 2015 Elsevier Ltd. All rights reserved.
Dhanda, Saurabh; Sandhir, Rajat
2018-05-01
The present study was designed to investigate the mechanisms involved in blood-brain barrier (BBB) permeability in bile duct ligation (BDL) model of chronic hepatic encephalopathy (HE). Four weeks after BDL surgery, a significant increase was observed in serum bilirubin levels. Masson trichrome staining revealed severe hepatic fibrosis in the BDL rats. 99m Tc-mebrofenin retention was increased in the liver of BDL rats suggesting impaired hepatobiliary transport. An increase in permeability to sodium fluorescein, Evans blue, and fluorescein isothiocyanate (FITC)-dextran along with increase in water and electrolyte content was observed in brain regions of BDL rats suggesting disrupted BBB. Increased brain water content can be attributed to increase in aquaporin-4 mRNA and protein expression in BDL rats. Matrix metalloproteinase-9 (MMP-9) mRNA and protein expression was increased in brain regions of BDL rats. Additionally, mRNA and protein expression of tissue inhibitor of matrix metalloproteinases (TIMPs) was also increased in different regions of brain. A significant decrease in mRNA expression and protein levels of tight junction proteins, viz., occludin, claudin-5, and zona occluden-1 (ZO-1) was observed in different brain regions of BDL rats. VCAM-1 mRNA and protein expression was also found to be significantly upregulated in different brain regions of BDL animals. The findings from the study suggest that increased BBB permeability in HE involves activation of MMP-9 and loss of tight junction proteins.
Kabirifar, Razieh; Ghoreshi, Zohreh-Al-Sadat; Safari, Fatemeh; Karimollah, Alireza; Moradi, Ali; Eskandari-Nasab, Ebrahim
2017-02-01
Bile duct ligation (BDL) and subsequent cholestasis are correlated with oxidative stress, hepatocellular injury and fibrosis. Quercetin is a flavonoid with antifibrotic, and hepatoprotective properties. However, the molecular mechanism underlying quercetin-mediated hepatoprotection is not fully understood. The current study was to evaluate mechanisms of hepatoprotective effect of quercetin in BDL rat model. We divided male Wistar rats into 4 groups (n=8 for each): sham, sham+quercetin (30 mg/kg per day), BDL, and BDL+quercetin (30 mg/kg per day). Four weeks later, the rats were sacrificed, the blood was collected for liver enzyme measurements and liver for the measurement of Rac1, Rac1-GTP and NOX1 mRNA and protein levels by quantitative PCR and Western blotting, respectively. Quercetin significantly alleviated liver injury in BDL rats as evidenced by histology and reduced liver enzymes. Furthermore, the mRNA and protein expression of Rac1, Rac1-GTP and NOX1 were significantly increased in BDL rats compared with those in the sham group (P<0.05); quercetin treatment reversed these variables back toward normal (P<0.05). Another interesting finding was that the antioxidant markers e.g. superoxide dismutase and catalase were elevated in quercetin-treated BDL rats compared to BDL rats (P<0.05). Quercetin demonstrated hepatoprotective activity against BDL-induced liver injury through increasing antioxidant capacity of the liver tissue, while preventing the production of Rac1, Rac1-GTP and NOX1 proteins.
Saleh, Hanan; Soliman, Amel M; Mohamed, Ayman S; Marie, Mohamed-Assem S
2015-08-01
The aim of our study was to assess the complications of hepatic fibrosis associated with bile duct ligation and the potential curative role of sepia ink extract in hepatic damage induced by bile duct ligation. Rattus norvegicus rats were divided into 3 groups: Sham-operated group, model rats that underwent common bile duct ligation (BDL), and BDL rats treated orally with sepia ink extract (200 mg/kg body weight) for 7, 14, and 28 d after BDL. There was a significant reduction in hepatic enzymes, ALP, GGT, bilirubin levels, and oxidative stress in the BDL group after treatment with sepia ink extract. Collagen deposition reduced after sepia ink extract treatment as compared to BDL groups, suggesting that the liver was repaired. Histopathological examination of liver treated with sepia ink extract showed moderate degeneration in the hepatic architecture and mild degeneration in hepatocytes as compared to BDL groups. Sepia ink extract provides a curative effect and an antioxidant capacity on BDL rats and could ameliorate the complications of liver cholestasis. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.
Hong, Ji-Young; F. Sato, Eisuke; Nishikawa, Tomoko; Hiramoto, Keiichi; Inoue, Masayasu
2009-01-01
We previously reported that the plasma level of endotoxin and colonic expression of IgA in the mouse increased with obstructive jaundice induced by bile duct ligation (BDL). To elucidate the mechanism of the BDL-induced increase, we analyzed the effect of BDL on intestinal flora in wild type and inducible nitric oxide synthase (iNOS)-deficient mice (iNOS−/−) using the terminal restriction fragment length polymorphism analysis (T-RFLP) and 16S rDNA clone libraries. The amounts of bacterial DNA detected in fecal samples from both animal groups pretreated with antibiotics were extremely low as compared with untreated groups. We found that the profiles of enteric bacteria changed markedly after BDL. The bacterial composition is significantly different between not only wild type and iNOS−/− mice but also those before and after BDL, respectively. Among enteric bacteria examined, Lactobacillus murinus was found to increase markedly after BDL in rectum of both animal groups. However, Escherichia coli markedly increased after BDL in the iNOS−/− mice. These findings suggest that profiles of enteric flora change markedly in animals during obstructive jaundice by some mechanism that is affected by bile constituents and iNOS-derived NO. PMID:19308270
Grape seed extract reduces oxidative stress and fibrosis in experimental biliary obstruction.
Dulundu, Ender; Ozel, Yahya; Topaloglu, Umit; Toklu, Hale; Ercan, Feriha; Gedik, Nursal; Sener, Goksel
2007-06-01
The aim of this study was to assess the protective effect of grape seed extract (GSE) against oxidative liver injury and fibrosis induced by biliary obstruction in rats. Wistar albino rats were divided into four groups; control (C), GSE-treated, bile duct ligated (BDL), and BDL and GSE-treated (BDL + GSE) groups. GSE was administered at a dose of 50 mg/kg a day orally for 28 days. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels were determined to assess liver function and tissue damage, respectively. Tumor necrosis factor-alpha (TNF-alpha) and antioxidant capacity (AOC) were assayed in plasma samples. Liver tissues were taken for determination of the hepatic malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content. Production of reactive oxidants was monitored by chemiluminescence (CL) assay. Serum AST, ALT, LDH and plasma TNF-alpha were elevated in the BDL group as compared to the control group and were significantly decreased with GSE treatment. Plasma AOC and hepatic GSH level, depressed by BDL, was elevated back to the control level in the GSE-treated BDL group. Increases in tissue MDA level, MPO activity and collagen content due to BDL were also attenuated by GSE treatment. Furthermore, luminol and lucigenin CL values in the BDL group increased dramatically compared to the control and were reduced by GSE treatment. These results suggest that GSE protects the liver from oxidative damage following bile duct ligation in rats. This effect possibly involves the inhibition of neutrophil infiltration and lipid peroxidation; thus, restoration of oxidant and antioxidant status in the tissue.
Protective effect of Urtica dioica on liver damage induced by biliary obstruction in rats.
Oguz, Serhat; Kanter, Mehmet; Erboga, Mustafa; Ibis, Cem
2013-10-01
The aim of this study was to evaluate the possible protective effects of Urtica dioica (UD) against liver damage in the common bile duct-ligated rats. A total of 24 male Sprague Dawley rats were divided into three groups, namely, control, bile duct ligation (BDL) and BDL + received UD groups, containing eight animals in each group. The rats in UD-treated groups were given UD oils (2 ml/kg) once a day intraperitoneally for 2 weeks starting 3 days prior to BDL operation. The change demonstrating the bile duct proliferation and fibrosis in expanded portal tracts includes the extension of proliferated bile ducts into the lobules; inflammatory cell infiltration into the widened portal areas were observed in BDL group. Treatment of BDL with UD attenuated alterations in liver histology. The α-smooth muscle actin, cytokeratin-positive ductular proliferation and the activity of terminal deoxynucleotidyl transferase dUTP nick end labeling in the BDL were observed to be reduced with the UD treatment. The data indicate that UD attenuates BDL-induced cholestatic liver injury, bile duct proliferation and fibrosis.
Expression of renal Oat5 and NaDC1 transporters in rats with acute biliary obstruction
Brandoni, Anabel; Torres, Adriana Mónica
2015-01-01
AIM: To examine renal expression of organic anion transporter 5 (Oat5) and sodium-dicarboxylate cotransporter 1 (NaDC1), and excretion of citrate in rats with acute extrahepatic cholestasis. METHODS: Obstructive jaundice was induced in rats by double ligation and division of the common bile duct (BDL group). Controls underwent sham operation that consisted of exposure, but not ligation, of the common bile duct (Sham group). Studies were performed 21 h after surgery. During this period, animals were maintained in metabolic cages in order to collect urine. The urinary volume was determined by gravimetry. The day of the experiment, blood samples were withdrawn and used to measure total and direct bilirubin as indicative parameters of hepatic function. Serum and urine samples were used for biochemical determinations. Immunoblotting for Oat5 and NaDC1 were performed in renal homogenates and brush border membranes from Sham and BDL rats. Immunohistochemistry studies were performed in kidneys from both experimental groups. Total RNA was extracted from rat renal tissue in order to perform reverse transcription polymerase chain reaction. Another set of experimental animals were used to evaluate medullar renal blood flow (mRBF) using fluorescent microspheres. RESULTS: Total and direct bilirubin levels were significantly higher in BDL animals, attesting to the adequacy of biliary obstruction. An important increase in mRBF was determined in BDL group (Sham: 0.53 ± 0.12 mL/min per 100 g body weight vs BDL: 1.58 ± 0.24 mL/min per 100 g body weight, P < 0.05). An increase in the urinary volume was observed in BDL animals. An important decrease in urinary levels of citrate was seen in BDL group. Besides, a decrease in urinary citrate excretion (Sham: 0.53 ± 0.11 g/g creatinine vs BDL: 0.07 ± 0.02 g/g creatinine, P < 0.05) and an increase in urinary excretion of H+ (Sham: 0.082 ± 0.03 μmol/g creatinine vs BDL: 0.21 ± 0.04 μmol/g creatinine, P < 0.05) were observed in BDL animals. We found upregulations of both proteins Oat5 and NaDC1 in brush border membranes where they are functional. Immunohistochemistry technique corroborated these results for both proteins. No modifications were observed in Oat5 mRNA and in NaDC1 mRNA levels in kidney from BDL group as compared with Sham ones. CONCLUSION: Citrate excretion is decreased in BDL rats, at least in part, because of the higher NaDC1 expression. Using the outward gradient of citrate generated by NaDC1, Oat5 can reabsorb/eliminate different organic anions of pathophysiological importance. PMID:26269671
Lim, Seol-Wa; Lee, Dong-Ryung; Choi, Bong-Keun; Kim, Hong-Suk; Yang, Seung Hwan; Suh, Joo-Won; Kim, Kyung Soo
2016-12-01
To evaluate the possible protective effect of Citrus aurantium peel extract (CAE) against apoptosis in cholestatic liver fibrosis induced by bile duct ligation in mice. Male ICR mice were divided to 5 groups: 1) Control group (Sham-operated mice), 2) Cholestatic liver injury group induced by bile duct ligation (BDL), 3) BDL mice treated with silymarin (200 mg/kg) for 4 weeks, 4) BDL mice treated with 50 mg/kg CAE for 4 weeks, 5) BDL mice treated with 200 mg/kg CAE for 4 weeks. Mice were sacrificed and liver fibrosis was evaluated by serum and hepatic tissue biochemistry tests and liver histopathological examination. Effects of CAE on inflammation and apoptosis gene regulation were investigated through real-time PCR. CAE effect on lipid metabolism related signaling was determined by western blot analysis. In BDL mice, administration of CAE for 4 weeks markedly attenuated liver fibrosis based on histopathological alteration. Serum and hepatic tissue biochemistry results revealed that CAE (50 and 200 mg/kg) decreased the levels of alanine transaminase, aspartate transaminase, gamma-glutamyl transferase, total bilirubin, nitric oxide, and thiobarbituric acid reactive substances. Real-time PCR and western blot analysis showed that CAE regulated inflammation, apoptosis, and lipid metabolism factors increased by BDL. Interleukin family, tumor necrosis factor α, and related apoptosis factors mRNA levels were increased by BDL treatment. However, these increases were suppressed by CAE administration. In addition, CAE effectively increased phosphorylation of AMP-activated protein kinase, nuclear factor E2-related factor 2, and related cytoprotective proteins. CAE can efficiently regulate BDL-induced liver injury with antioxidant, anti-inflammatory, and anti-apoptotic activities. Copyright © 2016 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.
Activation of necroptosis in human and experimental cholestasis.
Afonso, Marta B; Rodrigues, Pedro M; Simão, André L; Ofengeim, Dimitry; Carvalho, Tânia; Amaral, Joana D; Gaspar, Maria M; Cortez-Pinto, Helena; Castro, Rui E; Yuan, Junying; Rodrigues, Cecília M P
2016-09-29
Cholestasis encompasses liver injury and inflammation. Necroptosis, a necrotic cell death pathway regulated by receptor-interacting protein (RIP) 3, may mediate cell death and inflammation in the liver. We aimed to investigate the role of necroptosis in mediating deleterious processes associated with cholestatic liver disease. Hallmarks of necroptosis were evaluated in liver biopsies of primary biliary cholangitis (PBC) patients and in wild-type and RIP3-deficient (RIP3 -/- ) mice subjected to common bile duct ligation (BDL). The functional link between RIP3, heme oxygenase-1 (HO-1) and antioxidant response was investigated in vivo after BDL and in vitro. We demonstrate increased RIP3 expression and mixed lineage kinase domain-like protein (MLKL) phosphorylation in liver samples of human PBC patients, coincident with thioflavin T labeling, suggesting activation of necroptosis. BDL resulted in evident hallmarks of necroptosis, concomitant with progressive bile duct hyperplasia, multifocal necrosis, fibrosis and inflammation. MLKL phosphorylation was increased and insoluble aggregates of RIP3, MLKL and RIP1 formed in BLD liver tissue samples. Furthermore, RIP3 deficiency blocked BDL-induced necroinflammation at 3 and 14 days post-BDL. Serum hepatic enzymes, fibrogenic liver gene expression and oxidative stress decreased in RIP3 -/- mice at 3 days after BDL. However, at 14 days, cholestasis aggravated and fibrosis was not halted. RIP3 deficiency further associated with increased hepatic expression of HO-1 and accumulation of iron in BDL mice. The functional link between HO-1 activity and bile acid toxicity was established in RIP3-deficient primary hepatocytes. Necroptosis is triggered in PBC patients and mediates hepatic necroinflammation in BDL-induced acute cholestasis. Targeting necroptosis may represent a therapeutic strategy for acute cholestasis, although complementary approaches may be required to control progression of chronic cholestatic liver disease.
Biecker, Erwin; De Gottardi, Andrea; Neef, Markus; Unternährer, Matthias; Schneider, Vreni; Ledermann, Monika; Sägesser, Hans; Shaw, Sidney; Reichen, Jürg
2005-06-01
Rapamycin is an immunosuppressant with antiproliferative properties. We investigated whether rapamycin treatment of bile duct-ligated (BDL) rats is capable of inhibiting liver fibrosis and thereby affecting hemodynamics. Following BDL, rats were treated for 28 days with rapamycin (BDL SIR). BDL animals without drug treatment (BDL CTR) and sham-operated animals served as controls. After 28 days, hemodynamics were measured, and livers were harvested for histology/immunohistochemistry. Liver mRNA levels of transforming growth factor (TGF)-beta1, connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF)-beta, cyclin-dependent kinase inhibitor p27(kip) (p27), and cyclin-dependent kinase inhibitor p21(WAF1/CIP1) (p21) were quantified by real-time polymerase chain reaction. Liver protein levels of p27, p21, p70 S6 kinase (p70(s6k)), phosphorylated p70(s6k) (p-p70(s6k)), eukaryotic initiation factor 4E-binding protein (4E-BP1), p-4E-BP1 (Thr37/46), and p-4E-BP1 (Ser65/Thr70) were determined by Western blotting. Portal vein pressure was lower in BDL SIR than in BDL CTR animals. Volume fractions of connective tissue, bile duct epithelial, and desmin- and actin-positive cells were lower in BDL SIR than in BDL CTR rats. On the mRNA level, TGF-beta1, CTGF, and PDGF were decreased by rapamycin. p27 and p21 mRNA did not differ. On the protein level, rapamycin increased p27 and decreased p21 levels. Levels of nonphosphorylated p70(s6k) and 4E-BP1 did not vary between groups, but levels of p-p70(s6k) were decreased by rapamycin. Rapamycin had no effect on p-4E-BP1 (Thr37/46) and p-4E-BP1 (Ser65/Thr70) levels. In BDL rats, rapamycin inhibits liver fibrosis and ameliorates portal hypertension. This is paralleled by decreased levels of TGF-beta1, CTGF, and PDGF. Rapamycin influences the cell cycle by up-regulation of p27, down-regulation of p21, and inhibition of p70(s6k) phosphorylation.
Li, Ting; Yu, Dian; Xian, Qiming; Li, Aimin; Sun, Cheng
2015-08-01
We surveyed the occurrence of nine N-nitrosamine species in ten bottled drinking waters from supermarket and other water samples including raw waters, finished waters, and distribution system waters from nine municipal drinking water treatment plants in eight cities of Jiangsu Province, East China. N-nitrosodimethylamine (NDMA) was detected in one of ten bottled drinking water samples at concentration of 4.8 ng/L and N-nitrosomorpholine (NMor) was detected in four of the ten bottles with an average concentration and a standard deviation of 16 ± 15 ng/L. The levels of nitrosamines in the distribution system water samples collected during summer season ranged from below detection limit (BDL) to 5.4 ng/L for NDMA, BDL to 9.5 ng/L for N-nitrosomethylethylamine (NMEA), BDL to 2.7 ng/L for N-nitrosodiethylamine (NDEA) and BDL to 8.5 ng/L for N-nitrosopyrrolidine (NPyr). Samples of distribution system waters collected in winter season had levels of nitrosamines ranged from BDL to 45 ng/L for NDMA, BDL to 5.2 ng/L for NPyr, and BDL to 309 ng/L for N-nitrosopiperidine (NPip). A positive correlation of the concentration of NDMA as well as the total nine N-nitrosamines between finished waters and distribution system waters was observed. Both dissolved organic carbon and nitrite were found to correlate linearly with N-nitrosamine levels in raw waters.
Sabuncuoglu, Mehmet Zafer; Kismet, Kemal; Kilicoglu, Sibel Serin; Kilicoglu, Bulent; Erel, Serap; Muratoglu, Sabahattin; Sunay, Asli Elif; Erdemli, Esra; Akkus, Mehmet Ali
2007-01-01
AIM: To investigate the effects of propolis on bacterial translocation and ultrastructure of intestinal morphology in experimental obstructive jaundice. METHODS: Thirty Wistar-Albino male rats were randomly divided into three groups, each including 10 animals: groupI, sham-operated; group II, ligation and division of the common bile duct (BDL); group III, BDL followed by oral supplementation of propolis 100 mg/kg per day. Liver, blood, spleen, mesenteric lymph nodes, and ileal samples were taken for microbiological, light and transmission electron microscopic examination on postoperative 7th d after sacrification. RESULTS: The mean number of villi per centimeter and mean mucosal height of the propolis group were significantly different in the BDL group (P = 0.001 and 0.012, respectively). The electron microscopic changes were also different between these groups. Sham and BDL + propolis groups had similar incidence of bacterial translocation (BT). The BDL group had significantly higher rates of BT as compared with sham and BDL + propolis groups. BT was predominantly detected in MLNs and the most commonly isolated bacteria was Escherichia coli. CONCLUSION: Propolis showed a significant protective effect on ileal mucosa and reduced bacterial translocation in the experimental obstructive jaundice model. Further studies should be carried out to explain the mechanisms of these effects. PMID:17876893
Walch, Joseph D; Carreño, Flávia Regina; Cunningham, J. Thomas
2013-01-01
Bile duct ligation (BDL) causes congestive liver failure that initiates hemodynamic changes including peripheral vasodilation and generalized edema. Peripheral vasodilation is hypothesized to then activate compensatory mechanisms including increased drinking behavior and neurohumoral activation. This study tested the hypothesis that changes in the expression of AT1R mRNA and protein in the lamina terminalis is associated with BDL induced hypoosmolality in the rat. All rats received either BDL or sham ligation surgery. The rats were housed in metabolic chambers for measurement of fluid and food intake and urine output. Angiotensin type 1 receptor (AT1R) expression in the lamina terminalis was assessed by western blot and quantitative real-time PCR (RT-qPCR). Average baseline water intake significantly increased in BDL rats compared to sham and upregulation of AT1R protein and AT1aR mRNA were observed in the subfornical organ (SFO) of BDL rats. Separate groups of BDL and sham ligated rats were instrumented with minipumps filled with either losartan (2.0 µg/µl) or 0.9% saline for chronic intracerebroventricular (ICV) or subcutaneous (SC) chronic infusion. Chronic ICV losartan infusion attenuated the increased drinking behavior and prevented the increased abundance of AT1R protein in the SFO in BDL rats. Chronic SC did not affect water intake or AT1R abundance in the SFO. The data presented here indicate a possible role of increased central AT1R expression in the regulation of drinking behavior during congestive cirrhosis. PMID:23243146
Effect of Rifaximin on Hepatic Fibrosis in Bile Duct-ligated Rat Model.
Shin, Seung Kak; Kwon, Oh Sang; Lee, Jong Joon; Park, Yeon Ho; Choi, Cheol Soo; Jeong, Sung Hwan; Choi, Duck Joo; Kim, Yun Soo; Kim, Ju Hyun
2017-11-25
The translocation of bacteria and their lipopolysaccharides from the gut can promote fibrosis in cirrhotic patients. The aim of this study was to investigate the effects of rifaximin on hepatic fibrosis in a bile duct-ligated rat model. The bile duct ligation (BDL) was carried out for eight days (acute injury model: sham-operated rats [G1], BDL rats [G2], and BDL rats treated with rifaximin [G3]) or 22 days (chronic injury model: sham-operated rats [G4], BDL rats [G5], and BDL rats treated with rifaximin [G6]). Rifaximin (50 mg/kg/day) was administered daily via gavage after BDL. Liver function, serum tumor necrosis factor-alpha (TNF-α), and hepatic hydroxyproline levels were measured. Moreover, a histological analysis of fibrosis contents was performed using sirius red stain. In the acute injury model, the liver function and TNF-α level were not improved after the rifaximin treatment. The hydroxyproline levels (µg/g liver tissue) in G1, G2, and G3 were 236.4±103.1, 444.8±114.4, and 312.5±131.6, respectively; and fibrosis contents (%) were 0.22±0.04, 1.64±0.53, and 1.66±0.44, respectively. The rifaximin treatment did not ameliorate acute BDL-induced fibrosis. In the chronic injury model, the hydroxyproline levels in G4, G5, and G6 were 311.5±72.9, 1,110.3±357.9, and 944.3±209.3, respectively; and fibrosis contents (%) were 0.19±0.03, 5.04±0.18, and 4.42±0.68, respectively (G5 vs. G6, p=0.059). The rifaximin treatment marginally ameliorated chronic BDL-induced fibrosis. Rifaximin did not reduce inflammation and fibrosis in bile duct-ligated rat model.
Doustimotlagh, Amir Hossein; Dehpour, Ahmad Reza; Etemad-Moghadam, Shahroo; Alaeddini, Mojgan; Ostadhadi, Sattar; Golestani, Abolfazl
2018-06-01
Chronic liver disease (CLD) affects millions of people and its impact on bone loss has become a subject of interest. Nitric oxide and endogenous opioids are suggested to increase during cholestasis/cirrhosis and may impact bone resorption by different mechanisms. The receptor activator of nuclear factor-κB (RANK)/RANK-ligand (RANKL)/osteoprotegerin (OPG) signaling pathway regulates bone resorption, but its role in metabolic bone disease subsequent to CLD is unknown. We aimed to investigate the involvement of nitrergic and opioidergic systems in bone loss relative to the RANK/RANKL/OPG pathway, in bile duct-ligated (BDL) rats. Eighty BDL/sham-operated (SO) rats received injections of 3 mg/kg/day Nω-Nitro-L-arginine methyl ester ± naltrexone (10 mg/kg/day) or saline for 28 days. Plasma bone turnover markers, OPG, RANK, and RANKL along with mRNA expression levels of the latter three were assessed. Plasma bone turnover markers and OPG level increased, but RANKL decreased in the BDL group compared with their SO controls (both: P ≤ 0.05). Administration of naltrexone reduced bone turnover markers and OPG level while increased RANKL content in comparison to BDL rats ( P ≤ 0.05). As compared to untreated BDL rats, nitric oxide inhibition showed no effect on bone turnover marker i.e. OPG, RANK, and RANKL levels. BDL significantly increased RANK mRNA, but had no significant effect on RANKL and OPG mRNA expression. The lack of association between plasma levels and quantitative gene expression of RANKL and OPG suggests an indirect function of these markers in BDL rats. Considering that opioid receptor blockage by naltrexone in BDL animals caused a significant decrease in OPG and an increase in RANKL plasma contents, it could be postulated that the opioidergic system may have a regulatory effect on these bone markers.
Dysbiosis contributes to fibrogenesis in the course of chronic liver injury in mice.
De Minicis, Samuele; Rychlicki, Chiara; Agostinelli, Laura; Saccomanno, Stefania; Candelaresi, Cinzia; Trozzi, Luciano; Mingarelli, Eleonora; Facinelli, Bruna; Magi, Gloria; Palmieri, Claudio; Marzioni, Marco; Benedetti, Antonio; Svegliati-Baroni, Gianluca
2014-05-01
Nonalcoholic fatty liver disease (NAFLD) may lead to hepatic fibrosis. Dietary habits affect gut microbiota composition, whereas endotoxins produced by Gram-negative bacteria stimulate hepatic fibrogenesis. However, the mechanisms of action and the potential effect of microbiota in the liver are still unknown. Thus, we sought to analyze whether microbiota may interfere with liver fibrogenesis. Mice fed control (CTRL) or high-fat diet (HFD) were subjected to either bile duct ligation (BDL) or CCl4 treatment. Previously gut-sterilized mice were subjected to microbiota transplantation by oral gavage of cecum content obtained from donor CTRL- or HFD-treated mice. Fibrosis, intestinal permeability, bacterial translocation, and serum endotoxemia were measured. Inflammasome components were evaluated in gut and liver. Microbiota composition (dysbiosis) was evaluated by Pyrosequencing. Fibrosis degree was increased in HFD+BDL versus CTRL+BDL mice, whereas no differences were observed between CTRL+CCl4 and HFD+CCl4 mice. Culture of mesenteric lymph nodes showed higher density of infection in HFD+BDL mice versus CTRL+BDL mice, suggesting higher bacterial translocation rate. Pyrosequencing revealed an increase in percentage of Gram-negative versus Gram-postive bacteria, a reduced ratio between Bacteroidetes and Firmicutes, as well as a dramatic increase of Gram-negative Proteobacteria in HFD+BDL versus CTRL+BDL mice. Inflammasome expression was increased in liver of fibrotic mice, but significantly reduced in gut. Furthermore, microbiota transplantation revealed more liver damage in chimeric mice fed CTRL diet, but receiving the microbiota of HFD-treated mice; liver damage was further enhanced by transplantation of selected Gram-negative bacteria obtained from cecum content of HFD+BDL-treated mice. Dietary habits, by increasing the percentage of intestinal Gram-negative endotoxin producers, may accelerate liver fibrogenesis, introducing dysbiosis as a cofactor contributing to chronic liver injury in NAFLD. © 2014 by the American Association for the Study of Liver Diseases.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hunn, B. D.; Diamond, S. C.; Bennett, G. A.
1977-10-01
A set of computer programs, called Cal-ERDA, is described that is capable of rapid and detailed analysis of energy consumption in buildings. A new user-oriented input language, named the Building Design Language (BDL), has been written to allow simplified manipulation of the many variables used to describe a building and its operation. This manual provides the user with information necessary to understand in detail the Cal-ERDA set of computer programs. The new computer programs described include: an EXECUTIVE Processor to create computer system control commands; a BDL Processor to analyze input instructions, execute computer system control commands, perform assignments andmore » data retrieval, and control the operation of the LOADS, SYSTEMS, PLANT, ECONOMICS, and REPORT programs; a LOADS analysis program that calculates peak (design) zone and hourly loads and the effect of the ambient weather conditions, the internal occupancy, lighting, and equipment within the building, as well as variations in the size, location, orientation, construction, walls, roofs, floors, fenestrations, attachments (awnings, balconies), and shape of a building; a Heating, Ventilating, and Air-Conditioning (HVAC) SYSTEMS analysis program capable of modeling the operation of HVAC components including fans, coils, economizers, humidifiers, etc.; 16 standard configurations and operated according to various temperature and humidity control schedules. A plant equipment program models the operation of boilers, chillers, electrical generation equipment (diesel or turbines), heat storage apparatus (chilled or heated water), and solar heating and/or cooling systems. An ECONOMIC analysis program calculates life-cycle costs. A REPORT program produces tables of user-selected variables and arranges them according to user-specified formats. A set of WEATHER ANALYSIS programs manipulates, summarizes and plots weather data. Libraries of weather data, schedule data, and building data were prepared.« less
Walch, Joseph D; Nedungadi, T Prashant; Cunningham, J Thomas
2014-09-15
Bile duct ligation (BDL) causes congestive liver failure that initiates hemodynamic changes, resulting in dilutional hyponatremia due to increased water intake and vasopressin release. This project tested the hypothesis that angiotensin signaling at the subfornical organ (SFO) augments drinking behavior in BDL rats. A genetically modified adeno-associated virus containing short hairpin RNA (shRNA) for ANG II receptor subtype 1a (AT1aR) gene was microinjected into the SFO of rats to knock down expression. Two weeks later, BDL or sham surgery was performed. Rats were housed in metabolic chambers for measurement of fluid and food intake and urine output. The rats were euthanized 28 days after BDL surgery for analysis. A group of rats was perfused for immunohistochemistry, and a second group was used for laser-capture microdissection for analysis of SFO AT1aR gene expression. BDL rats showed increased water intake that was attenuated in rats that received SFO microinjection of AT1aR shRNA. Among BDL rats treated with scrambled (control) and AT1aR shRNA, we observed an increased number of vasopressin-positive cells in the supraoptic nucleus that colocalized with ΔFosB staining, suggesting increased vasopressin release in both groups. These results indicate that angiotensin signaling through the SFO contributes to increased water intake, but not dilutional hyponatremia, during congestive liver failure. Copyright © 2014 the American Physiological Society.
Lee, Jing-Yi; Huo, Teh-Ia; Wang, Sun-Sang; Lin, Han-Chieh; Chuang, Chiao-Lin; Lee, Shou-Dong
2013-01-01
Liver cirrhosis may lead to portal-systemic collateral formation and bleeding. The hemostatic effect is influenced by the response of collateral vessels to vasoconstrictors. Diabetes and glucose also influence vasoresponsiveness, but their net effect on collaterals remains unexplored. This study investigated the impact of diabetes or glucose application on portal-systemic collateral vasoresponsiveness to arginine vasopressin (AVP) in cirrhosis. Spraque-Dawley rats with bile duct ligation (BDL)-induced cirrhosis received vehicle (citrate buffer) or streptozotocin (diabetic, BDL/STZ). The in situ collateral perfusion was done after hemodynamic measurements: Both were perfused with Krebs solution, D-glucose, or D-glucose and NaF, with additional OPC-31260 for the BDL/STZ group. Splenorenal shunt vasopressin receptors and Gα proteins mRNA expressions were evaluated. The survival rate of cirrhotic rats was decreased by STZ injection. The collateral perfusion pressure changes to AVP were lower in STZ-injected groups, which were reversed by OPC-31260 (a V2R antagonist) and overcome by NaF (a G protein activator). The splenorenal shunt V2R mRNA expression was increased while Gα proteins mRNA expressions were decreased in BDL/STZ rats compared to BDL rats. The Gαq and Gα11 mRNA expressions also correlated with the maximal perfusion pressure changes to AVP. Diabetes diminished the portal-systemic collateral vascular response to AVP in rats with BDL-induced cirrhosis, probably via V2 receptor up-regulation and Gα proteins down-regulation. PMID:23874439
Lee, Jing-Yi; Huo, Teh-Ia; Wang, Sun-Sang; Huang, Hui-Chun; Lee, Fa-Yauh; Lin, Han-Chieh; Chuang, Chiao-Lin; Lee, Shou-Dong
2013-01-01
Liver cirrhosis may lead to portal-systemic collateral formation and bleeding. The hemostatic effect is influenced by the response of collateral vessels to vasoconstrictors. Diabetes and glucose also influence vasoresponsiveness, but their net effect on collaterals remains unexplored. This study investigated the impact of diabetes or glucose application on portal-systemic collateral vasoresponsiveness to arginine vasopressin (AVP) in cirrhosis. Spraque-Dawley rats with bile duct ligation (BDL)-induced cirrhosis received vehicle (citrate buffer) or streptozotocin (diabetic, BDL/STZ). The in situ collateral perfusion was done after hemodynamic measurements: Both were perfused with Krebs solution, D-glucose, or D-glucose and NaF, with additional OPC-31260 for the BDL/STZ group. Splenorenal shunt vasopressin receptors and Gα proteins mRNA expressions were evaluated. The survival rate of cirrhotic rats was decreased by STZ injection. The collateral perfusion pressure changes to AVP were lower in STZ-injected groups, which were reversed by OPC-31260 (a V2R antagonist) and overcome by NaF (a G protein activator). The splenorenal shunt V2R mRNA expression was increased while Gα proteins mRNA expressions were decreased in BDL/STZ rats compared to BDL rats. The Gαq and Gα11 mRNA expressions also correlated with the maximal perfusion pressure changes to AVP. Diabetes diminished the portal-systemic collateral vascular response to AVP in rats with BDL-induced cirrhosis, probably via V2 receptor up-regulation and Gα proteins down-regulation.
A disposition kinetic study of Tramadol in bile duct ligated rats in perfused rat liver model.
Esmaeili, Zohre; Mohammadi, Saeid; Nezami, Alireza; Rouini, Mohammad Reza; Ardakani, Yalda Hosseinzadeh; Lavasani, Hoda; Ghazi-Khansari, Mahmoud
2017-07-01
Tramadol hydrochloride is a centrally acting synthetic opioid analgesic drug and is used to treat chronic pain. In this study, the effects of Bile Duct Ligation (BDL) on the pharmacokinetics of tramadol in a liver recirculating perfusion system of male rats were used. Twenty-four Wistar male rats were randomly divided into four groups: control, sham and two weeks BDL and four weeks BDL. Serum levels of liver enzymes were measured before perfusion and the pharmacokinetics of tramadol was evaluated by using liver recirculating perfusion system. Tramadol and metabolites concentrations were determined by HPLC-FL. The sharp increase in liver enzymes level in both BDL groups was observed and significant changes were also observed in liver weight and volume. Tramadol metabolites concentration significantly decreased compared with the control and sham group (P<0.05). The decrease in the hepatic metabolism of tramadol and increase in the half-life of the elimination of tramadol in rats with BDL suggests that personalized treatment and the therapeutic drug monitoring (TDM) data examination are necessary for patients with bile duct diseases and the dose of tramadol should be accordingly adjusted. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Jiang, Xi; Xu, Lexing; Tang, Lin; Liu, Fuhe; Chen, Ziwei; Zhang, Jiajia; Chen, Lei; Pang, Cong; Yu, Xuefeng
2018-01-04
This study aims to explore the role of indoleamine-2,3-dioxygenase (IDO)/kynurenine (KYN) pathway of tryptophan (TRY) metabolism in behavioral alterations observed in hepatic encephalopathy (HE) rats. Expression levels of proinflammatory cytokines were tested by QT-PCR and ELISA, levels of IDOs were tested by QT-PCR and Western blot, and levels of 5-hydroxytryptamine (5-HT), KYN, TRY, 3-hydroxykynurenine (3-HK), and kynurenic acid (KA) in different brain regions were estimated using HPLC. Effects of the IDO direct inhibitor 1-methyl-L-tryptophan (1-MT) on cognitive, anxiety, and depressive-like behavior were evaluated in bile duct ligation (BDL) rats. Increased serum TNF-α, IL-1β, and IL-6 levels were shown in rats 7 days after BDL, and these increases were observed earlier than those in the brain, indicating peripheral immune activation may result in central upregulation of proinflammatory cytokines. Moreover, BDL rats showed a progressive decline in memory formation, as well as anxiety and depressive-like behavior. Further study revealed that IDO expression increased after BDL, accompanied by a decrease of 5-HT and an increase of KYN, as well as abnormal expression of 3-HK and KA. The above results affected by BDL surgery were reversed by IDO inhibitor 1-MT treatment. Taken together, these findings indicate that (1) behavioral impairment in BDL rats is correlated with proinflammatory cytokines; (2) TRY pathway of KYN metabolism, activated by inflammation, may play an important role in HE development; and (3) 1-MT may serve as a therapeutic agent for HE.
Deleterious effect of oltipraz on extrahepatic cholestasis in bile duct-ligated mice
Weerachayaphorn, Jittima; Luo, Yuhuan; Mennone, Albert; Soroka, Carol J.; Harry, Kathy; Boyer, James L.
2014-01-01
Background & Aims Oltipraz (4-methyl-5(pyrazinyl-2)-1-2-dithiole-3-thione), a promising cancer preventive agent, has an anti-oxidative activity and ability to enhance glutathione biosynthesis, phase II detoxification enzymes and multidrug resistance-associated protein-mediated efflux transporters. Oltipraz can protect against hepatotoxicity caused by carbon tetrachloride, acetaminophen and alpha-naphthylisothiocyanate. Whether oltipraz has hepato-protective effects on obstructive cholestasis is unknown. Methods We administered oltipraz to mice for 5 days prior to bile duct ligation (BDL) for 3 days. Liver histology, liver function markers, bile flow rates and hepatic expression of profibrogenic genes were evaluated. Results Mice pretreated with oltipraz prior to BDL demonstrated higher levels of serum aminotransferases and more severe liver damage than in control mice. Higher bile flow and glutathione secretion rates were observed in unoperated mice treated with oltipraz than in control mice, suggesting that liver necrosis in oltipraz-treated BDL mice may be related partially to increased bile-acid independent flow and biliary pressure. Oltipraz treatment in BDL mice enhanced -smooth muscle actin expression, consistent with activation of hepatic stellate cells and portal fibroblasts. Matrix metalloproteinases (MMP) 9 and 13 and tissue inhibitors of metalloproteinases (TIMP) 1 and 2 levels were increased in the oltipraz -treated BDL group, suggesting that the secondary phase of liver injury induced by oltipraz might be due to excessive MMP and TIMP secretions which induce remodeling of the extracellular matrix. Conclusions Oltipraz treatment exacerbates the severity of liver injury following BDL and should be avoided as therapy for extrahepatic cholestatic disorders due to bile duct obstruction. PMID:23978715
McMullin, Ryan P; Wittner, Ben S; Yang, Chuanwei; Denton-Schneider, Benjamin R; Hicks, Daniel; Singavarapu, Raj; Moulis, Sharon; Lee, Jeongeun; Akbari, Mohammad R; Narod, Steven A; Aldape, Kenneth D; Steeg, Patricia S; Ramaswamy, Sridhar; Sgroi, Dennis C
2014-03-14
There is an unmet clinical need for biomarkers to identify breast cancer patients at an increased risk of developing brain metastases. The objective is to identify gene signatures and biological pathways associated with human epidermal growth factor receptor 2-positive (HER2+) brain metastasis. We combined laser capture microdissection and gene expression microarrays to analyze malignant epithelium from HER2+ breast cancer brain metastases with that from HER2+ nonmetastatic primary tumors. Differential gene expression was performed including gene set enrichment analysis (GSEA) using publicly available breast cancer gene expression data sets. In a cohort of HER2+ breast cancer brain metastases, we identified a gene expression signature that anti-correlates with overexpression of BRCA1. Sequence analysis of the HER2+ brain metastases revealed no pathogenic mutations of BRCA1, and therefore the aforementioned signature was designated BRCA1 Deficient-Like (BD-L). Evaluation of an independent cohort of breast cancer metastases demonstrated that BD-L values are significantly higher in brain metastases as compared to other metastatic sites. Although the BD-L signature is present in all subtypes of breast cancer, it is significantly higher in BRCA1 mutant primary tumors as compared with sporadic breast tumors. Additionally, BD-L signature values are significantly higher in HER2-/ER- primary tumors as compared with HER2+/ER + and HER2-/ER + tumors. The BD-L signature correlates with breast cancer cell line pharmacologic response to a combination of poly (ADP-ribose) polymerase (PARP) inhibitor and temozolomide, and the signature outperformed four published gene signatures of BRCA1/2 deficiency. A BD-L signature is enriched in HER2+ breast cancer brain metastases without pathogenic BRCA1 mutations. Unexpectedly, elevated BD-L values are found in a subset of primary tumors across all breast cancer subtypes. Evaluation of pharmacological sensitivity in breast cancer cell lines representing all breast cancer subtypes suggests the BD-L signature may serve as a biomarker to identify sporadic breast cancer patients who might benefit from a therapeutic combination of PARP inhibitor and temozolomide and may be indicative of a dysfunctional BRCA1-associated pathway.
2014-01-01
Introduction There is an unmet clinical need for biomarkers to identify breast cancer patients at an increased risk of developing brain metastases. The objective is to identify gene signatures and biological pathways associated with human epidermal growth factor receptor 2-positive (HER2+) brain metastasis. Methods We combined laser capture microdissection and gene expression microarrays to analyze malignant epithelium from HER2+ breast cancer brain metastases with that from HER2+ nonmetastatic primary tumors. Differential gene expression was performed including gene set enrichment analysis (GSEA) using publicly available breast cancer gene expression data sets. Results In a cohort of HER2+ breast cancer brain metastases, we identified a gene expression signature that anti-correlates with overexpression of BRCA1. Sequence analysis of the HER2+ brain metastases revealed no pathogenic mutations of BRCA1, and therefore the aforementioned signature was designated BRCA1 Deficient-Like (BD-L). Evaluation of an independent cohort of breast cancer metastases demonstrated that BD-L values are significantly higher in brain metastases as compared to other metastatic sites. Although the BD-L signature is present in all subtypes of breast cancer, it is significantly higher in BRCA1 mutant primary tumors as compared with sporadic breast tumors. Additionally, BD-L signature values are significantly higher in HER2-/ER- primary tumors as compared with HER2+/ER + and HER2-/ER + tumors. The BD-L signature correlates with breast cancer cell line pharmacologic response to a combination of poly (ADP-ribose) polymerase (PARP) inhibitor and temozolomide, and the signature outperformed four published gene signatures of BRCA1/2 deficiency. Conclusions A BD-L signature is enriched in HER2+ breast cancer brain metastases without pathogenic BRCA1 mutations. Unexpectedly, elevated BD-L values are found in a subset of primary tumors across all breast cancer subtypes. Evaluation of pharmacological sensitivity in breast cancer cell lines representing all breast cancer subtypes suggests the BD-L signature may serve as a biomarker to identify sporadic breast cancer patients who might benefit from a therapeutic combination of PARP inhibitor and temozolomide and may be indicative of a dysfunctional BRCA1-associated pathway. PMID:24625110
Development of resistance to serotonin-induced itch in bile duct ligated mice.
Ostadhadi, Sattar; Haddadi, Nazgol-Sadat; Foroutan, Arash; Azimi, Ehsan; Elmariah, Sarina; Dehpour, Ahmad-Reza
2017-06-01
Cholestatic itch can be severe and significantly impair the quality of life of patients. The serotonin system is implicated in cholestatic itch; however, the pruritogenic properties of serotonin have not been evaluated in cholestatic mice. Here, we investigated the serotonin-induced itch in cholestatic mice which was induced by bile duct ligation (BDL). Serotonin, sertraline or saline were administered intradermally to the rostral back area in BDL and sham operated (SHAM) mice, and the scratching behaviour was videotaped for 1 hour. Bile duct ligated mice had significantly increased scratching responses to saline injection on the seventh day after surgery. Additionally, serotonin or sertraline significantly induced scratching behaviour in BDL mice compared to saline at day 7 after surgery, while it did not induce itch at day 5. The scratching behaviour induced by serotonin or sertraline was significantly less in BDL mice compared to SHAM mice. Likewise, the locomotor activity of BDL or SHAM mice was not significantly different from unoperated (UNOP) mice on the fifth and seventh day, suggesting that the scratching behaviour was not affected by motor dysfunctions. Our data suggest that despite the potentiation of evoked itch, a resistance to serotonin-induced itch is developed in cholestatic mice. © 2017 John Wiley & Sons Australia, Ltd.
Zhang, Liangjun; Cheng, Ying; Du, Xiaohuang; Chen, Sheng; Feng, Xinchan; Gao, Yu; Li, Shaoxue; Liu, Li; Yang, Mei; Chen, Lei; Peng, Zhihong; Yang, Yong; Luo, Weizao; Wang, Rongquan; Chen, Wensheng
2015-01-01
Swertianlarin is an herbal agent abundantly distributed in Swertia mussotii Franch, a Chinese traditional herb used for treatment of jaundice. To study the therapeutic effect of swertianlarin on cholestasis, liver injury, serum proinflammatory cytokines, and bile salt concentrations were measured by comparing rats treated with swertianlarin 100 mg/kg/d or saline for 3, 7, or 14 days after bile duct ligation (BDL). Serum alanine aminotransferase (ATL) and aspartate aminotransferase (AST) levels were significantly decreased in BDL rats treated with swertianlarin for 14 days (P < 0.05). The reduced liver injury in BDL rats by swertianlarin treatment for 14 days was further confirmed by liver histopathology. Levels of serum tumor necrosis factor alpha (TNFα) were decreased by swertianlarin in BDL rats for 3 and 7 days (P < 0.05). Moreover, reductions in serum interleukins IL-1β and IL-6 levels were also observed in BDL rats treated with swertianlarin (P < 0.05). In addition, most of serum toxic bile salt concentrations (e.g., chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA)) in cholestatic rats were decreased by swertianlarin (P < 0.05). In conclusion, the data suggest that swertianlarin derived from Swertia mussotii Franch attenuates liver injury, inflammation, and cholestasis in bile duct-ligated rats. PMID:26273316
Ketorolac pharmacokinetics in experimental cirrhosis by bile duct ligation in the rat.
Rivera-Espinosa, Liliana; Muriel, Pablo; Ordaz Gallo, Mónica; Pérez-Urizar, José; Palma-Aguirre, Antonio; Castañeda-Hernández, Gilberto
2003-01-01
The purpose of the present work was to study the pharmacokinetics of ketorolac, a poorly metabolized drug, in experimental cirrhosis. Cirrhosis was induced by bile duct ligation (BDL) for four weeks in male Wistar rats. Ketorolac was given intravenously (1 mg/kg ) or orally (3.2 mg/kg) to control (sham-operated) and BDL-rats. Determination of ketorolac in plasma was carried out by HPLC and estimation of pharmacokinetic parameters was performed by non-compartmental analysis. Indicators of liver damage and liver fibrosis were significantly increased (p < 0.05) in BDL compared to control rats. Experimental cirrhosis did not induce any significant alteration in intravenous ketorolac pharmacokinetics. Volume of distribution, clearance, AUC and t1/2 were similar in BDL and control animals. Notwithstanding, oral ketorolac bioavailability was significantly altered in BDL rats. AUC and Cmax were reduced, while tmax was prolonged, suggesting that both, the extent and the rate of ketorolac absorption were decreased. Results show that liver cirrhosis may result in significant pharmacokinetic alterations, even for poorly bio-transformed drugs, but that alterations may vary with the route of administration. In conclusion, uncritical generalizations on the effect of liver damage on drug kinetics should be avoided and systematic studies for every drug and every route of administration are thus recommended.
Effect of honey on bacterial translocation and intestinal morphology in obstructive jaundice
Gencay, Cem; Kilicoglu, Sibel Serin; Kismet, Kemal; Kilicoglu, Bulent; Erel, Serap; Muratoglu, Sabahattin; Sunay, Asli Elif; Erdemli, Esra; Akkus, Mehmet Ali
2008-01-01
AIM: To evaluate the effects of honey on bacterial translocation and intestinal villus histopathology in experimental obstructive jaundice. METHODS: Thirty Wistar-Albino rats were randomly divided into three groups each including 10 animals: group I, sham-operated; group II, ligation and section of the common bile duct (BDL); group III, bile duct ligation followed by oral supplementation of honey (BDL + honey) 10 g/kg per day. Liver, blood, spleen, mesenteric lymph nodes, and ileal samples were taken for microbiological, light and transmission electrone microscopic examination. RESULTS: Although the number of villi per centimeter and the height of the mucosa were higher in sham group, there was no statistically significant difference between sham and BDL + honey groups (P > 0.05). On the other hand, there was a statistically significant difference between BDL group and other groups (P < 0.05). The electron microscopic changes were also different between these groups. Sham and honey groups had similar incidence of bacterial translocation (P > 0.05). BDL group had significantly higher rates of bacterial translocation as compared with sham and honey groups. Bacterial translocation was predominantly detected in mesenteric lymph nodes. CONCLUSION: Supplementation of honey in presence of obstructive jaundice ameliorates bacterial translocation and improves ileal morphology. PMID:18528939
LeSagE, G; Alvaro, D; Benedetti, A; Glaser, S; Marucci, L; Baiocchi, L; Eisel, W; Caligiuri, A; Phinizy, J L; Rodgers, R; Francis, H; Alpini, G
1999-07-01
To investigate the role of the cholinergic system in regulation of cholangiocyte functions, we evaluated the effects of vagotomy on cholangiocyte proliferation and secretion in rats that underwent bile duct ligation (BDL rats). After bile duct ligation (BDL), the vagus nerve was resected; 7 days later, expression of M3 acetylcholine receptor was evaluated. Cholangiocyte proliferation was assessed by morphometry and measurement of DNA synthesis. Apoptosis was evaluated by light microscopy and annexin-V staining. Ductal secretion was evaluated by measurement of secretin-induced choleresis, secretin receptor (SR) gene expression, and cyclic adenosine 3',5'-monophosphate (cAMP) levels. Vagotomy decreased the expression of M3 acetylcholine receptors in cholangiocytes. DNA synthesis and ductal mass were markedly decreased, whereas cholangiocyte apoptosis was increased by vagotomy. Vagotomy decreased ductal secretion. Forskolin treatment prevented the decrease in cAMP levels induced by vagotomy, maintained cholangiocyte proliferation, and decreased cholangiocyte apoptosis caused by vagotomy in BDL rats. Cholangiocyte secretion was also maintained by forskolin. Vagotomy impairs cholangiocyte proliferation and enhances apoptosis, leading to decreased ductal mass in response to BDL. Secretin-induced choleresis of BDL rats was virtually eliminated by vagotomy in association with decreased cholangiocyte cAMP levels. Maintenance of cAMP levels by forskolin administration prevents the effects of vagotomy on cholangiocyte proliferation, apoptosis, and secretion.
Jadeja, Ravirajsinh N.; Thounaojam, Menaka C.; Khurana, Sandeep
2017-01-01
In cirrhosis, changes in pressure-mediated vascular tone, a key determinant of systemic vascular resistance (SVR), are unknown. To address this gap in knowledge, we assessed ex vivo dynamics of pressurized mesenteric resistance arteries (diameter ~ 260 μm) from bile duct-ligated (BDL) and sham-operated (SHAM) rats and determined the underlying mechanisms. At isobaric intraluminal pressure (70 mmHg) as well as with step-wise increase in pressure (10-110 mmHg), arteries from SHAM-rats constricted more than BDL-rats, and had reduced luminal area. In both groups, incubation with LNAME (a NOS inhibitor) had no effect on pressure-mediated tone, and expression of NOS isoforms were similar. TEA, which enhances Ca2+ influx, augmented arterial tone only in SHAM-rats, with minimal effect in those from BDL-rats that was associated with reduced expression of Ca2+ channel TRPC6. In permeabilized arteries, high-dose Ca2+ and γGTP enhanced the vascular tone, which remained lower in BDL-rats that was associated with reduced ROCK2 and pMLC expression. Further, compared to SHAM-rats, in BDL-rats, arteries had reduced collagen expression which was associated with increased expression and activity of MMP-9. BDL-rats also had increased plasma reactive oxygen species (ROS). In vascular smooth muscle cells in vitro, peroxynitrite enhanced MMP-9 activity and reduced ROCK2 expression. These data provide evidence that in cirrhosis, pressure-mediated tone is reduced in resistance arteries, and suggest that circulating ROS play a role in reducing Ca2+ sensitivity and enhancing elasticity to induce arterial adaptations. These findings provide insights into mechanisms underlying attenuated SVR in cirrhosis. PMID:28430609
Duwaerts, Caroline C; Sun, Eric P; Cheng, Chao-Wen; van Rooijen, Nico; Gregory, Stephen H
2013-01-01
Both Kupffer cells and invariant natural killer T (iNKT) cells suppress neutrophil-dependent liver injury in a mouse model of biliary obstruction. We hypothesize that these roles are interdependent and require iNKT cell-Kupffer cell cross-activation. Female, wild-type and iNKT cell-deficient C57Bl/6 mice were injected with magnetic beads 3 days prior to bile duct ligation (BDL) in order to facilitate subsequent Kupffer cell isolation. On day three post-BDL, the animals were euthanized and the livers dissected. Necrosis was scored; Kupffer cells were isolated and cell surface marker expression (flow cytometry), mRNA expression (qtPCR), nitric oxide (NO (.) ) production (Griess reaction), and protein secretion (cytometric bead-array or ELISAs) were determined. To address the potential role of NO (.) in suppressing neutrophil accumulation, a group of WT mice received 1400W, a specific inducible nitric oxide synthase (iNOS) inhibitor, prior to BDL. To clarify the mechanisms underlying Kupffer cell-iNKT cell cross-activation, WT animals were administered anti-IFN-γ or anti-lymphocyte function-associated antigen (LFA)-1 antibody prior to BDL. Compared to their WT counterparts, Kupffer cells obtained from BDL iNKT cell-deficient mice expressed lower iNOS mRNA levels, produced less NO (.) , and secreted more neutrophil chemoattractants. Both iNOS inhibition and IFN-γ neutralization increased neutrophil accumulation in the livers of BDL WT mice. Anti-LFA-1 pre-treatment reduced iNKT cell accumulation in these same animals. These data indicate that the LFA-1-dependent cross-activation of iNKT cells and Kupffer cells inhibits neutrophil accumulation and cholestatic liver injury.
Duwaerts, Caroline C.; Sun, Eric P.; Cheng, Chao-Wen; van Rooijen, Nico; Gregory, Stephen H.
2013-01-01
Both Kupffer cells and invariant natural killer T (iNKT) cells suppress neutrophil-dependent liver injury in a mouse model of biliary obstruction. We hypothesize that these roles are interdependent and require iNKT cell-Kupffer cell cross-activation. Female, wild-type and iNKT cell-deficient C57Bl/6 mice were injected with magnetic beads 3 days prior to bile duct ligation (BDL) in order to facilitate subsequent Kupffer cell isolation. On day three post-BDL, the animals were euthanized and the livers dissected. Necrosis was scored; Kupffer cells were isolated and cell surface marker expression (flow cytometry), mRNA expression (qtPCR), nitric oxide (NO.) production (Griess reaction), and protein secretion (cytometric bead-array or ELISAs) were determined. To address the potential role of NO. in suppressing neutrophil accumulation, a group of WT mice received 1400W, a specific inducible nitric oxide synthase (iNOS) inhibitor, prior to BDL. To clarify the mechanisms underlying Kupffer cell-iNKT cell cross-activation, WT animals were administered anti-IFN-γ or anti-lymphocyte function-associated antigen (LFA)-1 antibody prior to BDL. Compared to their WT counterparts, Kupffer cells obtained from BDL iNKT cell-deficient mice expressed lower iNOS mRNA levels, produced less NO., and secreted more neutrophil chemoattractants. Both iNOS inhibition and IFN-γ neutralization increased neutrophil accumulation in the livers of BDL WT mice. Anti-LFA-1 pre-treatment reduced iNKT cell accumulation in these same animals. These data indicate that the LFA-1-dependent cross-activation of iNKT cells and Kupffer cells inhibits neutrophil accumulation and cholestatic liver injury. PMID:24260285
DOE Office of Scientific and Technical Information (OSTI.GOV)
Woolbright, Benjamin L.; Antoine, Daniel J.; Jenkins, Rosalind E.
Cholestasis is a pathological common component of numerous liver diseases that results in hepatotoxicity, inflammation, and cirrhosis when untreated. While the predominant hypothesis in cholestatic liver injury remains hepatocyte apoptosis due to direct toxicity of hydrophobic bile acid exposure, recent work suggests that the injury occurs through inflammatory necrosis. In order to resolve this controversy, we used novel plasma biomarkers to assess the mechanisms of cell death during early cholestatic liver injury. C57Bl/6 mice underwent bile duct ligation (BDL) for 6–72 h, or sham operation. Another group of mice were given D-galactosamine and endotoxin as a positive control for apoptosismore » and inflammatory necrosis. Plasma levels of full length cytokeratin-18 (FL-K18), microRNA-122 (miR-122) and high mobility group box-1 protein (HMGB1) increased progressively after BDL with peak levels observed after 48 h. These results indicate extensive cell necrosis after BDL, which is supported by the time course of plasma alanine aminotransferase activities and histology. In contrast, plasma caspase-3 activity, cleaved caspase-3 protein and caspase-cleaved cytokeratin-18 fragments (cK18) were not elevated at any time during BDL suggesting the absence of apoptosis. In contrast, all plasma biomarkers of necrosis and apoptosis were elevated 6 h after Gal/End treatment. In addition, acetylated HMGB1, a marker for macrophage and monocyte activation, was increased as early as 12 h but mainly at 48–72 h. However, progressive neutrophil accumulation in the area of necrosis started at 6 h after BDL. In conclusion, these data indicate that early cholestatic liver injury in mice is an inflammatory event, and occurs through necrosis with little evidence for apoptosis. - Highlights: • The mechanism of cell death during cholestasis remains a controversial topic. • Plasma biomarkers offer new insight into cell death after bile duct ligation. • Cytokeratin-18, microRNA-122 and HMGB1 levels implicate necrosis. • Acetylated HMGB1 levels rise late after BDL confirming inflammation. • BDL-induced liver injury involves mainly inflammation and necrosis but no apoptosis.« less
NASA Astrophysics Data System (ADS)
Lin, Jian; Lu, Fake; Zheng, Wei; Xu, Shuoyu; Tai, Dean; Yu, Hanry; Huang, Zhiwei
2011-11-01
We report the implementation of a unique integrated coherent anti-Stokes Raman scattering (CARS), second-harmonic generation (SHG), and two-photon excitation fluorescence (TPEF) microscopy imaging technique developed for label-free monitoring of the progression of liver steatosis and fibrosis generated in a bile duct ligation (BDL) rat model. Among the 21 adult rats used in this study, 18 rats were performed with BDL surgery and sacrificed each week from weeks 1 to 6 (n = 3 per week), respectively; whereas 3 rats as control were sacrificed at week 0. Colocalized imaging of the aggregated hepatic fats, collagen fibrils, and hepatocyte morphologies in liver tissue is realized by using the integrated CARS, SHG, and TPEF technique. The results show that there are significant accumulations of hepatic lipid droplets and collagen fibrils associated with severe hepatocyte necrosis in BDL rat liver as compared to a normal liver tissue. The volume of normal hepatocytes keeps decreasing and the fiber collagen content in BDL rat liver follows a growing trend until week 6; whereas the hepatic fat content reaches a maximum in week 4 and then appears to stop growing in week 6, indicating that liver steatosis and fibrosis induced in a BDL rat liver model may develop at different rates. This work demonstrates that the integrated CARS and multiphoton microscopy imaging technique has the potential to provide an effective means for early diagnosis and detection of liver steatosis and fibrosis without labeling.
Protective effect of bicyclol against bile duct ligation-induced hepatic fibrosis in rats.
Zhen, Yong-Zhan; Li, Na-Ren; He, Hong-Wei; Zhao, Shuang-Shuang; Zhang, Guang-Ling; Hao, Xiao-Fang; Shao, Rong-Guang
2015-06-21
To evaluate the protective effect of bicyclol against bile duct ligation (BDL)-induced hepatic fibrosis in rats. Sprague-Dawley male rats underwent BDL and sham-operated animals were used as healthy controls. The BDL rats were divided into two groups which received sterilized PBS or bicyclol (100 mg/kg per day) orally for two consecutive weeks. Serum, urine and bile were collected for biochemical determinations. Liver tissues were collected for histological analysis and a whole genome oligonucleotide microarray assay. Reverse transcription-polymerase chain reaction and Western blotting were used to verify the expression of liver fibrosis-related genes. Treatment with bicyclol significantly reduced liver fibrosis and bile duct proliferation after BDL. The levels of alanine aminotransferase (127.7 ± 72.3 vs 230.4 ± 69.6, P < 0.05) and aspartate aminotransferase (696.8 ± 232.6 vs 1032.6 ± 165.8, P < 0.05) were also decreased by treatment with bicyclol in comparison to PBS. The expression changes of 45 fibrogenic genes and several fibrogenesis-related pathways were reversed by bicyclol in the microarray assay. Bicyclol significantly reduced liver mRNA and/or protein expression levels of collagen 1a1, matrix metalloproteinase 2, tumor necrosis factor, tissue inhibitors of metalloproteinases 2, transforming growth factor-β1 and α-smooth muscle actin. Bicyclol significantly attenuates BDL-induced liver fibrosis by reversing fibrogenic gene expression. These findings suggest that bicyclol might be an effective anti-fibrotic drug for the treatment of cholestatic liver disease.
Long, Yue; Dong, Xin; Yuan, Yawei; Huang, Jinqiang; Song, Jiangang; Sun, Yumin; Lu, Zhijie; Yang, Liqun; Yu, Weifeng
2015-07-01
The study examined the global metabolic and some biochemical changes in rats with cholestasis induced by bile duct ligation (BDL). Serum samples were collected in male Wistar rats with BDL (n = 8) and sham surgery (n = 8) at day 3 after surgery for metabolomics analysis using a combination of reversed phase chromatography and hydrophilic interaction chromatography (HILIC) and quadrupole-time-of-flight mass spectrometry (Q-TOF MS). The serum levels of malondialdehyde (MDA), total antioxidative capacity (T-AOC), glutathione (GSH) and glutathione disulfide (GSSG), the activities of superoxide dismutase (SOD) and glutathion peroxidase (GSH-Px) were measured to estimate the oxidative stress state. Key changes after BDL included increased levels of l-phenylalanine, l-glutamate, l-tyrosine, kynurenine, l-lactic acid, LysoPC(c) (14:0), glycine and succinic acid and decreased levels of l-valine, PC(b) (19:0/0:0), taurine, palmitic acid, l-isoleucine and citric acid metabolism products. And treatment with BDL significantly decreased the levels of GSH, T-AOC as well as SOD, GSH-Px activities, and upregulated MDA levels. The changes could be mapped to metabolism of amino acids and lipids, Krebs cycle and glycolysis, as well as increased oxidative stress and decreased antioxidant capability. Our study indicated that BDL induces major changes in the metabolism of all 3 major energy substances, as well as oxidative stress.
Lin, Jian; Lu, Fake; Zheng, Wei; Xu, Shuoyu; Tai, Dean; Yu, Hanry; Huang, Zhiwei
2011-11-01
We report the implementation of a unique integrated coherent anti-Stokes Raman scattering (CARS), second-harmonic generation (SHG), and two-photon excitation fluorescence (TPEF) microscopy imaging technique developed for label-free monitoring of the progression of liver steatosis and fibrosis generated in a bile duct ligation (BDL) rat model. Among the 21 adult rats used in this study, 18 rats were performed with BDL surgery and sacrificed each week from weeks 1 to 6 (n = 3 per week), respectively; whereas 3 rats as control were sacrificed at week 0. Colocalized imaging of the aggregated hepatic fats, collagen fibrils, and hepatocyte morphologies in liver tissue is realized by using the integrated CARS, SHG, and TPEF technique. The results show that there are significant accumulations of hepatic lipid droplets and collagen fibrils associated with severe hepatocyte necrosis in BDL rat liver as compared to a normal liver tissue. The volume of normal hepatocytes keeps decreasing and the fiber collagen content in BDL rat liver follows a growing trend until week 6; whereas the hepatic fat content reaches a maximum in week 4 and then appears to stop growing in week 6, indicating that liver steatosis and fibrosis induced in a BDL rat liver model may develop at different rates. This work demonstrates that the integrated CARS and multiphoton microscopy imaging technique has the potential to provide an effective means for early diagnosis and detection of liver steatosis and fibrosis without labeling.
Omenetti, Alessia; Yang, Liu; Li, Yin-Xiong; McCall, Shannon J; Jung, Youngmi; Sicklick, Jason K; Huang, Jiawen; Choi, Steve; Suzuki, Ayako; Diehl, Anna Mae
2007-05-01
In bile duct-ligated (BDL) rodents, as in humans with chronic cholangiopathies, biliary obstruction triggers proliferation of bile ductular cells that are surrounded by fibrosis produced by adjacent myofibroblastic cells in the hepatic mesenchyme. The proximity of the myofibroblasts and cholangiocytes suggests that mesenchymal-epithelial crosstalk promotes the fibroproliferative response to cholestatic liver injury. Studying BDL mice, we found that bile duct obstruction induces activity of the Hedgehog (Hh) pathway, a system that regulates the viability and differentiation of various progenitors during embryogenesis. After BDL, many bile ductular cells and fibroblastic-appearing cells in the portal stroma express Hh ligands, receptor and/or target genes. Transwell cocultures of an immature cholangiocyte line that expresses the Hh receptor, Patched (Ptc), with liver myofibroblastic cells demonstrated that both cell types produced Hh ligands that enhanced each other's viability and proliferation. Further support for the concept that Hh signaling modulates the response to BDL was generated by studying PtcLacZ mice, which have an impaired ability to constrain Hh signaling due to a heterozygous deficiency of Ptc. After BDL, PtcLacZ mice upregulated fibrosis gene expression earlier than wild-type controls and manifested an unusually intense ductular reaction, more expanded fibrotic portal areas, and a greater number of lobular necrotic foci. Our findings reveal that adult livers resurrect developmental signaling systems, such as the Hh pathway, to guide remodeling of the biliary epithelia and stroma after cholestatic injury.
Yang, Ying-Ying; Liu, Hongqun; Nam, Soon Woo; Kunos, George; Lee, Samuel S
2010-08-01
Chronic liver disease is associated with endotoxemia, oxidative stress, increased endocannabinoids and decreased cardiac responsiveness. Endocannabinoids activate the tumor necrosis factor-alpha (TNFalpha)-nuclear factor kappaB (NFkappaB) pathway. However, how they interact with each other remains obscure. We therefore aimed to clarify the relationship between the TNFalpha-NFkappaB pathway and endocannabinoids in the pathogenesis of cardiodepression of cholestatic bile duct ligated (BDL) mice. BDL mice with TNFalpha knockout (TNFalpha-/-) and infusion of anti-TNFalpha antibody were used. Cardiac mRNA and protein expression of NFkappaBp65, c-Jun-N-terminal kinases (JNK), p38 mitogen-activated protein kinase (p38MAPK), extracelullar-signal- regulated kinase (ERK), inducible nitric oxide synthase (iNOS), Copper/Zinc and Magnesium-superoxide dismutase (Cu/ Zn- and Mn-SOD), cardiac anandamide, 2-arachidonoylglycerol (2-AG), nitric oxide (NOx) and glutathione, and plasma TNFalpha were measured. The effects of TNFalpha, cannabinoid receptor (CB1) antagonist AM251 and the endocannabinoid reuptake inhibitor UCM707, on the contractility of isolated cardiomyocytes, were assessed. In BDL mice, cardiac mRNA and protein expression of NFkappaBp65, p38MAPK, iNOS, NOx, anandamide, and plasma TNFa were increased, whereas glutathione, Cu/Zn-SOD, and Mn-SOD were decreased. Cardiac contractility was blunted in BDL mice. Anti-TNFa treatment in BDL mice decreased cardiac anandamide and NOx, reduced expression of NFkappaBp65, p38MAPK, and iNOS, enhanced expression of Cu/Zn-SOD and Mn-SOD, increased reductive glutathione and restored cardiomyocyte contractility. TNFa-depressed contractility was worsened by UCM707, whereas AM251 improved contractility. Increased TNFalpha, acting via NFkappaB-iNOS and p38MAPK signaling pathways, plays an important role in the pathogenesis of cardiodepression in BDL mice. TNFalpha also suppressed contractility by increasing oxidative stress and endocannabinoid activity.
Li, Jibiao; Woolbright, Benjamin L; Zhao, Wen; Wang, Yifeng; Matye, David; Hagenbuch, Bruno; Jaeschke, Hartmut; Li, Tiangang
2018-01-01
Sortilin 1 (Sort1) is an intracellular trafficking receptor that mediates protein sorting in the endocytic or secretory pathways. Recent studies revealed a role of Sort1 in the regulation of cholesterol and bile acid (BA) metabolism. This study further investigated the role of Sort1 in modulating BA detoxification and cholestatic liver injury in bile duct ligated mice. We found that Sort1 knockout (KO) mice had attenuated liver injury 24 h after bile duct ligation (BDL), which was mainly attributed to less bile infarct formation. Sham-operated Sort1 KO mice had about 20% larger BA pool size than sham-operated wildtype (WT) mice, but 24 h after BDL Sort1 KO mice had significantly attenuated hepatic BA accumulation and smaller BA pool size. After 14 days BDL, Sort1 KO mice showed significantly lower hepatic BA concentration and reduced expression of inflammatory and fibrotic marker genes, but similar degree of liver fibrosis compared with WT mice. Unbiased quantitative proteomics revealed that Sort1 KO mice had increased hepatic BA sulfotransferase 2A1, but unaltered phase-I BA metabolizing cytochrome P450s or phase-III BA efflux transporters. Consistently, Sort1 KO mice showed elevated plasma sulfated taurocholate after BDL. Finally, we found that liver Sort1 was repressed after BDL, which may be due to BA activation of farnesoid x receptor. In conclusion, we report a role of Sort1 in the regulation of hepatic BA detoxification and cholestatic liver injury in mice. The mechanisms underlying increased hepatic BA elimination in Sort1 KO mice after BDL require further investigation. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Cholangiocytes and blood supply.
Gaudio, Eugenio; Franchitto, Antonio; Pannarale, Luigi; Carpino, Guido; Alpini, Gianfranco; Francis, Heather; Glaser, Shannon; Alvaro, Domenico; Onori, Paolo
2006-06-14
The microvascular supply of the biliary tree, the peribiliary plexus (PBP), stems from the hepatic artery branches and flows into the hepatic sinusoids. A detailed three-dimensional study of the PBP has been performed by using the Scanning Electron Microscopy vascular corrosion casts (SEMvcc) technique. Considering that the PBP plays a fundamental role in supporting the secretory and absorptive functions of the biliary epithelium, their organization in either normalcy and pathology is explored. The normal liver shows the PBP arranged around extra- and intrahepatic biliary tree. In the small portal tract PBP was characterized by a single layer of capillaries which progressively continued with the extrahepatic PBP where it showed a more complex vascular network. After common duct ligation (BDL), progressive modifications of bile duct and PBP proliferation are observed. The PBP presents a three-dimensional network arranged around many bile ducts and appears as bundles of vessels, composed by capillaries of homogeneous diameter with a typical round mesh structure. The PBP network is easily distinguishable from the sinusoidal network which appears normal. Considering the enormous extension of the PBP during BDL, the possible role played by the Vascular Endothelial Growth Factor (VEGF) is evaluated. VEGF-A, VEGF-C and their related receptors appeared highly immunopositive in proliferating cholangiocytes of BDL rats. The administration of anti-VEGF-A or anti-VEGF-C antibodies to BDL rats as well as hepatic artery ligation induced a reduced bile duct mass. The administration of rVEGF-A to BDL hepatic artery ligated rats prevented the decrease of cholangiocyte proliferation and VEGF-A expression as compared to BDL control rats. These data suggest the role of arterial blood supply of the biliary tree in conditions of cholangiocyte proliferation, such as it occurs during chronic cholestasis. On the other hand, the role played by VEGF as a tool of cross-talk between cholangiocytes and PBP endothelial cells suggests that manipulation of VEGF release and function could represent a therapeutic strategy for human pathological conditions characterized by damage of hepatic artery or the biliary tree.
Aubert, B; Bona, M; Karyotakis, Y; Lees, J P; Poireau, V; Prencipe, E; Prudent, X; Tisserand, V; Garra Tico, J; Grauges, E; Lopez, L; Palano, A; Pappagallo, M; Eigen, G; Stugu, B; Sun, L; Abrams, G S; Battaglia, M; Brown, D N; Cahn, R N; Jacobsen, R G; Kerth, L T; Kolomensky, Yu G; Lynch, G; Osipenkov, I L; Ronan, M T; Tackmann, K; Tanabe, T; Hawkes, C M; Soni, N; Watson, A T; Koch, H; Schroeder, T; Walker, D; Asgeirsson, D J; Fulsom, B G; Hearty, C; Mattison, T S; Mckenna, J A; Barrett, M; Khan, A; Blinov, V E; Bukin, A D; Buzykaev, A R; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Bondioli, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Martin, E C; Stoker, D P; Abachi, S; Buchanan, C; Gary, J W; Liu, F; Long, O; Shen, B C; Vitug, G M; Yasin, Z; Zhang, L; Sharma, V; Campagnari, C; Hong, T M; Kovalskyi, D; Mazur, M A; Richman, J D; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Schalk, T; Schumm, B A; Seiden, A; Wang, L; Wilson, M G; Winstrom, L O; Cheng, C H; Doll, D A; Echenard, B; Fang, F; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Andreassen, R; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Bloom, P C; Ford, W T; Gaz, A; Hirschauer, J F; Nagel, M; Nauenberg, U; Smith, J G; Ulmer, K A; Wagner, S R; Ayad, R; Soffer, A; Toki, W H; Wilson, R J; Altenburg, D D; Feltresi, E; Hauke, A; Jasper, H; Karbach, M; Merkel, J; Petzold, A; Spaan, B; Wacker, K; Kobel, M J; Mader, W F; Nogowski, R; Schubert, K R; Schwierz, R; Sundermann, J E; Volk, A; Bernard, D; Bonneaud, G R; Latour, E; Thiebaux, Ch; Verderi, M; Clark, P J; Gradl, W; Playfer, S; Watson, J E; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cecchi, A; Cibinetto, G; Franchini, P; Luppi, E; Negrini, M; Petrella, A; Piemontese, L; Santoro, V; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Buzzo, A; Contri, R; Lo Vetere, M; Macri, M M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Chaisanguanthum, K S; Morii, M; Marks, J; Schenk, S; Uwer, U; Klose, V; Lacker, H M; Bard, D J; Dauncey, P D; Nash, J A; Panduro Vazquez, W; Tibbetts, M; Behera, P K; Chai, X; Charles, M J; Mallik, U; Cochran, J; Crawley, H B; Dong, L; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gao, Y Y; Gritsan, A V; Guo, Z J; Lae, C K; Denig, A G; Fritsch, M; Schott, G; Arnaud, N; Béquilleux, J; D'Orazio, A; Davier, M; Firmino da Costa, J; Grosdidier, G; Höcker, A; Lepeltier, V; Le Diberder, F; Lutz, A M; Pruvot, S; Roudeau, P; Schune, M H; Serrano, J; Sordini, V; Stocchi, A; Wormser, G; Lange, D J; Wright, D M; Bingham, I; Burke, J P; Chavez, C A; Fry, J R; Gabathuler, E; Gamet, R; Hutchcroft, D E; Payne, D J; Touramanis, C; Bevan, A J; Clarke, C K; George, K A; Di Lodovico, F; Sacco, R; Sigamani, M; Cowan, G; Flaecher, H U; Hopkins, D A; Paramesvaran, S; Salvatore, F; Wren, A C; Brown, D N; Davis, C L; Alwyn, K E; Bailey, D; Barlow, R J; Chia, Y M; Edgar, C L; Jackson, G; Lafferty, G D; West, T J; Yi, J I; Anderson, J; Chen, C; Jawahery, A; Roberts, D A; Simi, G; Tuggle, J M; Dallapiccola, C; Li, X; Salvati, E; Saremi, S; Cowan, R; Dujmic, D; Fisher, P H; Koeneke, K; Sciolla, G; Spitznagel, M; Taylor, F; Yamamoto, R K; Zhao, M; Patel, P M; Robertson, S H; Lazzaro, A; Lombardo, V; Palombo, E; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Sanders, D A; Summers, D J; Zhao, H W; Simard, M; Taras, P; Viaud, F B; Nicholson, H; De Nardo, G; Lista, L; Monorchio, D; Onorato, G; Sciacca, C; Raven, G; Snoek, H L; Jessop, C P; Knoepfel, K J; Lo Secco, J M; Wang, W F; Benelli, G; Corwin, L A; Honscheid, K; Kagan, H; Kass, R; Morris, J P; Rahimi, A M; Regensburger, J J; Sekula, S J; Wong, Q K; Blount, N L; Brau, J; Frey, R; Igonkina, O; Kolb, J A; Lu, M; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Castelli, G; Gagliardi, N; Margoni, M; Morandin, M; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; del Amo Sanchez, P; Ben-Haim, E; Briand, H; Calderini, G; Chauveau, J; David, P; Del Buono, L; Hamon, O; Leruste, Ph; Ocariz, J; Perez, A; Prendki, J; Sitt, S; Gladney, L; Biasini, M; Covarelli, R; Manoni, E; Angelini, C; Batignani, G; Bettarini, S; Carpinelli, M; Cervelli, A; Forti, E; Giorgi, M A; Lusiani, A; Marchiori, G; Morganti, M; Neri, N; Paoloni, E; Rizzo, G; Walsh, J J; Lopes Pegna, D; Lu, C; Olsen, J; Smith, A J S; Telnov, A V; Anulli, F; Baracchini, E; Cavoto, G; del Re, D; Di Marco, E; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Jackson, P D; Li Gioi, L; Mazzoni, M A; Morganti, S; Piredda, G; Polci, F; Renga, F; Voena, C; Ebert, M; Hartmann, T; Schröder, H; Waldi, R; Adye, T; Franek, B; Olaiya, E O; Wilson, F F; Emery, S; Escalier, M; Esteve, L; Ganzhur, S F; Hamel de Monchenault, G; Kozanecki, W; Vasseur, G; Yèche, Ch; Zito, M; Chen, X R; Liu, H; Park, W; Purohit, M V; White, R M; Wilson, J R; Allen, M T; Aston, D; Bartoldus, R; Bechtle, P; Benitez, J F; Cenci, R; Coleman, J P; Convery, M R; Dingfelder, J C; Dorfan, J; Dubois-Felsmann, G P; Dunwoodie, W; Field, R C; Gabareen, A M; Gowdy, S J; Graham, M T; Grenier, P; Hast, C; Innes, W R; Kaminski, J; Kelsey, M H; Kim, H; Kim, P; Kocian, M L; Leith, D W G S; Li, S; Lindquist, B; Luitz, S; Luth, V; Lynch, H L; MacFarlane, D B; Marsiske, H; Messner, R; Muller, D R; Neal, H; Nelson, S; O'Grady, C P; Ofte, I; Perazzo, A; Perl, M; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Snyder, A; Su, D; sullivan, M K; Suzuki, K; Swain, S K; Thompson, J M; Va'vra, J; Wagner, A P; Weaver, M; West, C A; Wisniewski, W J; Wittgen, M; Wright, D H; Wulsin, H W; Yarritu, A K; Yi, K; Young, C C; Ziegler, V; Burchat, P R; Edwards, A J; Majewski, S A; Miyashita, T S; Petersen, B A; Wilden, L; Ahmed, S; Alam, M S; Ernst, J A; Pan, B; Saeed, M A; Zain, S B; Spanier, S M; Wogsland, B J; Eckmann, R; Ritchie, J L; Ruland, A M; Schilling, C J; Schwitters, R F; Drummond, B W; Izen, J M; Lou, X C; Bianchi, F; Gamba, D; Pelliccioni, M; Bomben, M; Bosisio, L; Cartaro, C; Della Ricca, G; Lanceri, L; Vitale, L; Azzolini, V; Lopez-March, N; Martinez-Vidal, F; Milanes, D A; Oyanguren, A; Albert, J; Banerjee, Sw; Bhuyan, B; Choi, H H F; Hamano, K; Kowalewski, R; Lewczuk, M J; Nugent, I M; Roney, J M; Sobie, R J; Gershon, T J; Harrison, P F; Ilic, J; Latham, T E; Mohanty, G B; Band, H R; Chen, X; Dasu, S; Flood, K T; Pan, Y; Pierini, M; Prepost, R; Vuosalo, C O; Wu, S L
2008-12-31
We report a measurement of the branching fractions of B-->D**(l) nu(l), decays based on 417 fb(-1) of data collected at the Y(4S) resonance with the BABAR detector at the PEP-II e+e- storage rings. Events are selected by full reconstructing one of the B mesons in a hadronic decay mode. A fit to the invariant mass differences m(D(*) pi)- m(D(*)) is performed to extract the signal yields of the different D** states. We observe the B-->D**l(-1)nu(l) decay modes corresponding to the four D states predicted by heavy quark symmetry with a significance greater than 5 standard deviations including systematic uncertainties.
Dhanda, Saurabh; Sandhir, Rajat
2015-06-01
The present study was designed to evaluate the role of biogenic amines in behavioral alterations observed in rat model of hepatic encephalopathy (HE) following bile duct ligation (BDL). Male Wistar rats subjected to BDL developed biliary fibrosis after four weeks which was supported by altered liver function tests, increased ammonia levels and histological staining (Sirius red). Animals were assessed for their behavioral performance in terms of cognitive, anxiety and motor functions. The levels of dopamine (DA), serotonin (5-HT), epinephrine and norepinephrine (NE) were estimated in different regions of brain viz. cortex, hippocampus, striatum and cerebellum using HPLC along with activity of monoamine oxidase (MAO). Cognitive assessment of BDL rats revealed a progressive decline in learning, memory formation, retrieval, exploration of novel environment and spontaneous locomotor activity along with decrease in 5-HT and NE levels. This was accompanied by an increase in MAO activity. Motor functions of BDL rats were also altered which were evident from decrease in the time spent on the rotating rod and higher foot faults assessed using narrow beam walk task. A global decrease was observed in the DA content along with an increase in MAO activity. Histopathological studies using hematoxylin-eosin (H&E) and cresyl violet exhibited marked neuronal degeneration, wherein neurons appeared more pyknotic, condensed and damaged. The results reveal that dopaminergic and serotonergic pathways are disturbed in chronic liver failure post-BDL which may be responsible for behavioral impairments observed in HE. Copyright © 2015 Elsevier B.V. All rights reserved.
Zepeda-Morales, Adelaida Sara M; Del Toro-Arreola, Susana; García-Benavides, Leonel; Bastidas-Ramírez, Blanca E; Fafutis-Morris, Mary; Pereira-Suárez, Ana L; Bueno-Topete, Miriam R
2016-01-01
BACKGROUND AND RATIONALE FOR THE STUDY: IL-17, TGF-β1/2 are cytokines involved in the development of kidney, pulmonary and liver fibrosis. However, their expression kinetics in the pathogenesis of cholestatic liver fibrosis have not yet been fully explored. The aim of the study was to analyze the expression of IL-17, RORγt, NKp46, TGF-β1, and TGF-β2 in the liver of rats with bile duct ligation (BDL). Hepatic IL-17A gene expression analyzed by qRT-PCR showed a dramatic increase of 350 and 10 fold, at 8 and 30 days post BDL, respectively. TGFβ1 and TGFβ2 gene expression significantly increased throughout the whole fibrotic process. At the protein level in liver homogenates, IL-17, TGF-β1, and RORγt significantly increased at 8 and 30 days after BDL. Interestingly, a significant increase in the protein levels of TGF-β2 and decrease of NKp46 was observed only 30 days after BDL. Unexpectedly, TGF-β2 exhibited stronger signals than TGF-β1 at the gene expression and protein levels. Histological analysis showed bile duct proliferation and collagen deposition. Our results suggest that pro-fibrogenic cytokines IL-17, TGF-β1 and, strikingly, TGF-β2 might be important players of liver damage in the pathogenesis of early and advanced experimental cholestatic fibrosis. Th17 cells might represent an important source of IL-17, while NK cell depletion may account for the perpetuation of liver damage in the BDL model.
Protective effect of bicyclol against bile duct ligation-induced hepatic fibrosis in rats
Zhen, Yong-Zhan; Li, Na-Ren; He, Hong-Wei; Zhao, Shuang-Shuang; Zhang, Guang-Ling; Hao, Xiao-Fang; Shao, Rong-Guang
2015-01-01
AIM: To evaluate the protective effect of bicyclol against bile duct ligation (BDL)-induced hepatic fibrosis in rats. METHODS: Sprague-Dawley male rats underwent BDL and sham-operated animals were used as healthy controls. The BDL rats were divided into two groups which received sterilized PBS or bicyclol (100 mg/kg per day) orally for two consecutive weeks. Serum, urine and bile were collected for biochemical determinations. Liver tissues were collected for histological analysis and a whole genome oligonucleotide microarray assay. Reverse transcription-polymerase chain reaction and Western blotting were used to verify the expression of liver fibrosis-related genes. RESULTS: Treatment with bicyclol significantly reduced liver fibrosis and bile duct proliferation after BDL. The levels of alanine aminotransferase (127.7 ± 72.3 vs 230.4 ± 69.6, P < 0.05) and aspartate aminotransferase (696.8 ± 232.6 vs 1032.6 ± 165.8, P < 0.05) were also decreased by treatment with bicyclol in comparison to PBS. The expression changes of 45 fibrogenic genes and several fibrogenesis-related pathways were reversed by bicyclol in the microarray assay. Bicyclol significantly reduced liver mRNA and/or protein expression levels of collagen 1a1, matrix metalloproteinase 2, tumor necrosis factor, tissue inhibitors of metalloproteinases 2, transforming growth factor-β1 and α-smooth muscle actin. CONCLUSION: Bicyclol significantly attenuates BDL-induced liver fibrosis by reversing fibrogenic gene expression. These findings suggest that bicyclol might be an effective anti-fibrotic drug for the treatment of cholestatic liver disease. PMID:26109801
Coll, Mar; Rodriguez, Sarai; Raurell, Imma; Ezkurdia, Nahia; Brull, Astrid; Augustin, Salvador; Guardia, Jaime; Esteban, Rafael; Martell, María; Genescà, Joan
2012-11-01
We aimed to evaluate the effects of droxidopa (an oral synthetic precursor of norepinephrine) on the hemodynamic and renal alterations of portal hypertensive rats. Sham, portal vein-ligated (PVL), and 4-week biliary duct-ligated (BDL) rats received a single oral dose of droxidopa (25-50 mg/kg) or vehicle and hemodynamic parameters were monitored for 2 hours. Two groups of BDL and cirrhotic rats induced by carbon tetrachloride (CCl(4) ) were treated for 5 days with droxidopa (15 mg/kg, twice daily, orally); hemodynamic parameters and blood and urinary parameters were assessed. The droxidopa effect on the Rho kinase (RhoK) / protein kinase B (AKT) / endothelial nitric oxide synthase (eNOS) pathways was analyzed by western blot in superior mesenteric artery (SMA). The acute administration of droxidopa in PVL and BDL rats caused a significant and maintained increase in arterial pressure and mesenteric arterial resistance, with a significant decrease of mesenteric arterial and portal blood flow, without changing portal pressure and renal blood flow. Two-hour diuresis greatly increased. Carbidopa (DOPA decarboxylase inhibitor) blunted all effects of droxidopa. Chronic droxidopa therapy in BDL rats produced the same beneficial hemodynamic effects observed in the acute study, did not alter liver function parameters, and caused a 50% increase in 24-hour diuresis volume (7.4 ± 0.9 mL/100g in BDL vehicle versus 11.8 ± 2.5 mL/100g in BDL droxidopa; P = 0.01). Droxidopa-treated rats also showed a decreased ratio of p-eNOS/eNOS and p-AKT/AKT and increased activity of RhoK in SMA. The same chronic treatment in CCl(4) rats caused similar hemodynamic effects and produced significant increases in diuresis volume and 24-hour natriuresis (0.08 ± 0.02 mmol/100g in CCl(4) vehicle versus 0.23 ± 0.03 mmol/100g in CCl(4) droxidopa; P = 0.014). Droxidopa might be an effective therapeutic agent for hemodynamic and renal alterations of liver cirrhosis and should be tested in cirrhosis patients. Copyright © 2012 American Association for the Study of Liver Diseases.
Wang, Weijie; Yan, Jiqi; Wang, Huakai; Shi, Minmin; Zhang, Mingjun; Yang, Weiping; Peng, Chenghong; Li, Hongwei
2014-01-01
Objective Hepatic stellate cells (HSCs) transdifferentiation and subsequent inflammation are important pathological processes involved in the formation of cirrhotic portal hypertension. This study characterizes the pathogenetic mechanisms leading to cholestatic liver fibrosis and portal hypertension, and focuses on mammalian target of rapamycin (mTOR) pathway as a potential modulator in the early phase of cirrhotic portal hypertension. Methods Early cirrhotic portal hypertension was induced by bile duct ligation (BDL) for three weeks. One week after operation, sham-operated (SHAM) and BDL rats received rapamycin (2 mg/kg/day) by intraperitoneal injection for fourteen days. Vehicle-treated SHAM and BDL rats served as controls. Fibrosis, inflammation, and portal pressure were evaluated by histology, morphometry, and hemodynamics. Expressions of pro-fibrogenic and pro-inflammatory genes in liver were measured by RT-PCR; alpha smooth muscle actin (α-SMA) and antigen Ki67 were detected by immunohistochemistry; expressions of AKT/mTOR signaling molecules, extracellular-signal-regulated kinase 1/2 (ERK1/2), p-ERK1/2, and interleukin-1 beta (IL-1β) were assessed by western blot. Results The AKT/mTOR signaling pathway was markedly activated in the early phase of cirrhotic portal hypertension induced by BDL in rats. mTOR blockade by rapamycin profoundly improved liver function by limiting inflammation, fibrosis and portal pressure. Rapamycin significantly inhibited the expressions of phosphorylated 70KD ribosomal protein S6 kinase (p-P70S6K) and phosphorylated ribosomal protein S6 (p-S6) but not p-AKT Ser473 relative to their total proteins in BDL-Ra rats. Those results suggested that mTOR Complex 1 (mTORC1) rather than mTORC2 was inhibited by rapamycin. Interestingly, we also found that the level of p-ERK1/2 to ERK1/2 was significantly increased in BDL rats, which was little affected by rapamycin. Conclusions The AKT/mTOR signaling pathway played an important role in the early phase of cirrhotic portal hypertension in rats, which could be a potential target for therapeutic intervention in the early phase of such pathophysiological progress. PMID:24404143
Wang, Weijie; Yan, Jiqi; Wang, Huakai; Shi, Minmin; Zhang, Mingjun; Yang, Weiping; Peng, Chenghong; Li, Hongwei
2014-01-01
Hepatic stellate cells (HSCs) transdifferentiation and subsequent inflammation are important pathological processes involved in the formation of cirrhotic portal hypertension. This study characterizes the pathogenetic mechanisms leading to cholestatic liver fibrosis and portal hypertension, and focuses on mammalian target of rapamycin (mTOR) pathway as a potential modulator in the early phase of cirrhotic portal hypertension. Early cirrhotic portal hypertension was induced by bile duct ligation (BDL) for three weeks. One week after operation, sham-operated (SHAM) and BDL rats received rapamycin (2 mg/kg/day) by intraperitoneal injection for fourteen days. Vehicle-treated SHAM and BDL rats served as controls. Fibrosis, inflammation, and portal pressure were evaluated by histology, morphometry, and hemodynamics. Expressions of pro-fibrogenic and pro-inflammatory genes in liver were measured by RT-PCR; alpha smooth muscle actin (α-SMA) and antigen Ki67 were detected by immunohistochemistry; expressions of AKT/mTOR signaling molecules, extracellular-signal-regulated kinase 1/2 (ERK1/2), p-ERK1/2, and interleukin-1 beta (IL-1β) were assessed by western blot. The AKT/mTOR signaling pathway was markedly activated in the early phase of cirrhotic portal hypertension induced by BDL in rats. mTOR blockade by rapamycin profoundly improved liver function by limiting inflammation, fibrosis and portal pressure. Rapamycin significantly inhibited the expressions of phosphorylated 70KD ribosomal protein S6 kinase (p-P70S6K) and phosphorylated ribosomal protein S6 (p-S6) but not p-AKT Ser473 relative to their total proteins in BDL-Ra rats. Those results suggested that mTOR Complex 1 (mTORC1) rather than mTORC2 was inhibited by rapamycin. Interestingly, we also found that the level of p-ERK1/2 to ERK1/2 was significantly increased in BDL rats, which was little affected by rapamycin. The AKT/mTOR signaling pathway played an important role in the early phase of cirrhotic portal hypertension in rats, which could be a potential target for therapeutic intervention in the early phase of such pathophysiological progress.
van den Brand, Marre; van den Dungen, Frank A M; Bos, Martine P; van Weissenbruch, Mirjam M; van Furth, A Marceline; de Lange, Annemieke; Rubenjan, Anna; Peters, Remco P H; Savelkoul, Paul H M
2018-04-22
Rapid and accurate diagnosis of neonatal sepsis is highly warranted because of high associated morbidity and mortality. The aim of this study was to evaluate the performance of a novel multiplex PCR assay for diagnosis of late-onset sepsis and to investigate the value of bacterial DNA load (BDL) determination as a measure of infection severity. This cross-sectional study was conducted in a neonatal intensive care unit. Preterm and/or very low birth weight infants suspected for late-onset sepsis were included. Upon suspicion of sepsis, a whole blood sample was drawn for multiplex PCR to detect the eight most common bacteria causing neonatal sepsis, as well as for blood culture. BDL was determined in episodes with a positive multiplex PCR. In total, 91 episodes of suspected sepsis were investigated, and PCR was positive in 53 (58%) and blood culture in 60 (66%) episodes, yielding no significant difference in detection rate (p = 0.17). Multiplex PCR showed a sensitivity of 77%, specificity of 81%, positive predictive value of 87%, and negative predictive value of 68% compared with blood culture. Episodes with discordant results of PCR and blood culture included mainly detection of coagulase-negative staphylococci (CoNS). C-reactive protein (CRP) level and immature to total neutrophil (I/T) ratio were lower in these episodes, indicating less severe disease or even contamination. Median BDL was high (4.1 log 10 cfu Eq/ml) with a wide range, and was it higher in episodes with a positive blood culture than in those with a negative blood culture (4.5 versus 2.5 log 10 cfu Eq/ml; p < 0.0001). For CoNS infection episodes BDL and CRP were positively associated (p = 0.004), and for Staphylococcus aureus infection episodes there was a positive association between BDL and I/T ratio (p = 0.049). Multiplex PCR provides a powerful assay to enhance rapid identification of the causative pathogen in late-onset sepsis. BDL measurement may be a useful indicator of severity of infection.
Zhu, Lili; Wang, Lei; Cao, Fei; Liu, Peng; Bao, Haidong; Yan, Yumei; Dong, Xin; Wang, Dong; Wang, Zhongyu; Gong, Peng
2018-03-01
The purpose of the present study was to investigate the effect and potential mechanism of chlorogenic acid (CA) on liver injury induced by cholestasis in a rat model of bile duct ligation (BDL). Rats received vehicle or CA (20, 50, or 100 mg/kg per day) orally for 3 days. On the 4th day, the rats underwent sham or BDL surgery, and were orally administrated vehicle or CA for 3 or 7 days. mRNA and protein expression levels were evaluated by qRT-PCR and western blot. After BDL, plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and total bile acids (TBA) were increased and typical pathological changes were observed in liver morphology. Hepatic uptake transporters (Ntcp, Oatp 1a4, and Oatp 1b2) were downregulated, while efflux transporters (Bsep and Mrp 2/3/4) were upregulated. BDL inhibited the expressions of Cyp7a1, Cyp8b1, and Cyp27a1 and induced Ugt1a1. CA treatment decreased ALT, AST, TBIL, and TBA (P < 0.05) and alleviated the liver pathological changes. The degree of expression changes in the transporters and enzymes was extended by CA (P < 0.05). SIRT1 protein was induced after CA treatment in BDL rats. Chlorogenic acid attenuated hepatotoxicity and cholestasis by decreasing the uptake and synthesis of bilirubin and bile acids and accelerating the metabolism and efflux of bilirubin and bile acids. © 2018 Japanese Society of Hepato-Biliary-Pancreatic Surgery.
Bosoi, Cristina R; Zwingmann, Claudia; Marin, Helen; Parent-Robitaille, Christian; Huynh, Jimmy; Tremblay, Mélanie; Rose, Christopher F
2014-03-01
The pathogenesis of brain edema in patients with chronic liver disease (CLD) and minimal hepatic encephalopathy (HE) remains undefined. This study evaluated the role of brain lactate, glutamine and organic osmolytes, including myo-inositol and taurine, in the development of brain edema in a rat model of cirrhosis. Six-week bile-duct ligated (BDL) rats were injected with (13)C-glucose and de novo synthesis of lactate, and glutamine in the brain was quantified using (13)C nuclear magnetic resonance spectroscopy (NMR). Total brain lactate, glutamine, and osmolytes were measured using (1)H NMR or high performance liquid chromatography. To further define the interplay between lactate, glutamine and brain edema, BDL rats were treated with AST-120 (engineered activated carbon microspheres) and dichloroacetate (DCA: lactate synthesis inhibitor). Significant increases in de novo synthesis of lactate (1.6-fold, p<0.001) and glutamine (2.2-fold, p<0.01) were demonstrated in the brains of BDL rats vs. SHAM-operated controls. Moreover, a decrease in cerebral myo-inositol (p<0.001), with no change in taurine, was found in the presence of brain edema in BDL rats vs. controls. BDL rats treated with either AST-120 or DCA showed attenuation in brain edema and brain lactate. These two treatments did not lead to similar reductions in brain glutamine. Increased brain lactate, and not glutamine, is a primary player in the pathogenesis of brain edema in CLD. In addition, alterations in the osmoregulatory response may also be contributing factors. Our results suggest that inhibiting lactate synthesis is a new potential target for the treatment of HE. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Arauz, Jonathan; Zarco, Natanael; Hernández-Aquino, Erika; Galicia-Moreno, Marina; Favari, Liliana; Segovia, José; Muriel, Pablo
2017-04-01
Investigations demonstrated that oxidative stress plays an important role in injury promotion in cholestatic liver disease. We hypothesized that coffee attenuates cholestasis-induced hepatic necrosis and fibrosis via its antioxidant, anti-inflammatory, and antifibrotic properties. The major aim of this study was to evaluate the hepatoprotective properties of coffee and caffeine in a model of chronic bile duct ligation (BDL) in male Wistar rats. Liver injury was induced by 28-day BDL, and conventional coffee, decaffeinated coffee, or caffeine was administered daily. After treatment, the hepatic oxidative status was estimated by measuring lipid peroxidation, the reduced to oxidized glutathione ratio, and glutathione peroxidase. Fibrosis was assessed by measuring the liver hydroxyproline content. The transforming growth factor-β, connective tissue growth factor, α-smooth muscle actin, collagen 1, and interleukin-10 proteins and mRNAs were measured by Western blot and polymerase chain reaction, respectively. Conventional coffee suppressed most of the changes produced by BDL; however, caffeine showed better antifibrotic effects. Coffee demonstrated antioxidant properties by restoring the redox equilibrium, and it also prevented the elevation of liver enzymes as well as hepatic glycogen depletion. Interestingly, coffee and caffeine administration prevented collagen increases. Western blot assays showed decreased expression levels of transforming growth factor-β, connective tissue growth factor, α-smooth muscle actin, and collagen 1 in the coffee- and caffeine-treated BDL groups. Similarly, coffee decreased the mRNA levels of these proteins. We conclude that coffee prevents liver cirrhosis induced by BDL by attenuating the oxidant processes, blocking hepatic stellate cell activation, and downregulating the main profibrotic molecules involved in extracellular matrix deposition. Copyright © 2017 Elsevier Inc. All rights reserved.
Neef, Markus; Ledermann, Monika; Saegesser, Hans; Schneider, Vreni; Reichen, Juerg
2006-12-01
Mammalian target of rapamycin (mTOR) signalling is central in the activation of hepatic stellate cells (HSCs), the key source of extracellular matrix (ECM) in fibrotic liver. We tested the therapeutic potential of the mTOR inhibitor rapamycin in advanced cirrhosis. Cirrhosis was induced by bile duct-ligation (BDL) or thioacetamide injections (TAA). Rats received oral rapamycin (0.5 mg/kg/day) for either 14 or 28 days. Untreated BDL and TAA-rats served as controls. Liver function was quantified by aminopyrine breath test. ECM and ECM-producing cells were quantified by morphometry. MMP-2 activity was measured by zymography. mRNA expression of procollagen-alpha1, transforming growth factor-beta1 (TGF-beta1) and beta2 was quantified by RT-PCR. Fourteen days of rapamycin improved liver function. Accumulation of ECM was decreased together with numbers of activated HSCs and MMP-2 activity in both animal models. TGF-beta1 mRNA was downregulated in TAA, TGF-beta2 mRNA was downregulated in BDL. 28 days of rapamycin treatment entailed a survival advantage of long-term treated BDL-rats. Low-dose rapamycin treatment is effectively antifibrotic and attenuates disease progression in advanced fibrosis. Our results warrant the clinical evaluation of rapamycin as an antifibrotic drug.
The ultrastructural research of liver in experimental obstructive jaundice and effect of honey.
Kilicoglu, Bulent; Gencay, Cem; Kismet, Kemal; Serin Kilicoglu, Sibel; Erguder, Imge; Erel, Serap; Sunay, Asli Elif; Erdemli, Esra; Durak, Ilker; Akkus, Mehmet Ali
2008-02-01
To examine the effects of honey on oxidative stress and apoptosis in experimental obstructive jaundice model. Thirty rats were divided into 3 groups: group I, sham-operated; group II, ligation and division of the common bile duct (BDL); group III, BDL followed by oral supplementation of honey 10 g/kg/d. Liver samples were examined under light microscope and transmission electron microscope. Hepatocyte apoptosis was quantitated using the terminal deoxy-nucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Plasma and blood malondialdehyde (MDA) and glutation activities were measured for determining the oxidative stress. The liver levels of MDA and GSH were significantly different between the honey and BDL groups (P = .006 and .001, respectively). However, there was no significant difference between the plasma MDA and GSH levels of these groups (P > .05). In group III, significant reductions in the size of enlarged hepatocytes and the edema were demonstrated. The dilatation of the bile canaliculi dramatically turned to original dimention. By TUNEL assay, it was shown that administration of honey decreased the number of apoptotic cells. In the present study, we found that honey diminished the negative effects of BDL on the hepatic ultrastructure. We conclude that this effect might be due to its antioxidant and anti-inflammatory activities.
Deciphering the environmental and landscape evolution of Sierra Nevada (S Iberia) from bog archives
NASA Astrophysics Data System (ADS)
Garcia Alix, Antonio; Toney, Jaime L.; Jiménez-Moreno, Gonzalo; Ramos-Román, Maria J.; Anderson, R. Scott; Jiménez-Espejo, Francisco; Delgado Huertas, Antonio; Ruano, Patricia
2016-04-01
Sierra Nevada is the southernmost mountain range in the Iberian Peninsula and one of the highest in Europe. Its geomorphology was the result of Pleistocene glaciations that carved out depressions, valleys and cirques at high elevations in the metamorphic basement. Depressions gave rise to lakes and wetlands during the Holocene. Geophysical and organic geochemical analyses of biomarkers (n-alkanes) and bulk sediment (C and N ratio and isotopes) from two high elevation bogs (locally called "Borreguiles"): Borreguiles de la Virgen (BdlV) and Borreguiles de la Caldera (BdlC), have allowed us to track the hydrological evolution of the area and its relationship to climatic fluctuations of the western Mediterranean during the Holocene. Most of the bogs of this area resulted from the natural evolution of former small lakes. The records are 56 cm and 169 cm long, respectively. Geophysical data suggest that we recovered the whole sedimentary record from BdlC; however, there are some post-glacial sediments remaining below the BdlV core that we could not recover due to hard-ground conditions. During the early and middle Holocene, aquatic conditions predominated in BdlV compared to the most recent part of the record (low C/N values and high proportion of aquatic plants (Paq) deduced from the n-alkanes) suggesting a lake environment whose water level gradually decreased until ˜5.5 cal ky BP. This aridity trend is also observed in nearby records such as at Laguna de Río Seco (LdRS), a result of the African Humid Period demise. Carbon and nitrogen isotopes were higher during this interval, which might suggest more algae activity, in agreement with the highest concentrations of the algae Pediastrum in the area. There is an important development of terrestrial plants, a real bog stage (C/N higher than 20, high TOC, lower Paq) in both records from ˜5.5 to 3.5-3.0 cal ky BP. Those hydrological changes in the landscape might be related to a possible change in the source of precipitation, detected by n-alkane deuterium data in the nearby LdRS record, and boosted by a dominant NAO positive phase. The record from BdlV shows really low sedimentation rates from 3.5 to ˜0.7 cal ky BP. The same period in BdlC does not show drastic changes in the sedimentation rate or in the geochemical data, suggesting local factors as an explanation for the differences between the records. Important environmental changes are identified during the latest part of both records agreeing with the transition between the Medieval Climate Anomaly (MCA) and the Little Ice Age (LIA). Although the main pattern during the LIA is humid at the beginning ˜600-500 cal yr BP and drier afterwards, surprisingly, the high-resolution BdlC record suggests fluctuating humidity conditions during the LIA. There is an increase in aquatic environments in both bogs during the last decades, which might be related to ice melting during summer time due to the rise of global temperatures.
Dhananjayan, V
2012-07-01
In order to understand whether organochlorine pesticides and polychlorinated biphenyls (PCBs) are responsible for the mortality of waterbirds in Nalaban bird sanctuary in Chilika Lake, the current investigation was carried out in tissues of 11 individuals comprising 7 species of birds. One or more residues were detected in all the tissues of birds analysed. Concentration of ∑HCH, ∑DDT, and ∑PCBs were ranged from below detectable level (BDL)-811 ng/g, BDL-1,987 ng/g and BDL-1,027 ng/g respectively. PCBs levels were less than the food and drug administration's (FDA) action limits. Although varying levels of residues were detected among tissues, they do not appear to be responsible for the mass mortality of waterfowl. However, the need for additional research is heightened when considering that some of the birds are classified as a globally protected species by the international bodies.
Jalan, Rajiv; De Chiara, Francesco; Balasubramaniyan, Vairappan; Andreola, Fausto; Khetan, Varun; Malago, Massimo; Pinzani, Massimo; Mookerjee, Rajeshwar P; Rombouts, Krista
2016-04-01
Hepatic stellate cells (HSCs) are vital to hepatocellular function and the liver response to injury. They share a phenotypic homology with astrocytes that are central in the pathogenesis of hepatic encephalopathy, a condition in which hyperammonemia plays a pathogenic role. This study tested the hypothesis that ammonia modulates human HSC activation in vitro and in vivo, and evaluated whether ammonia lowering, by using l-ornithine phenylacetate (OP), modifies HSC activation in vivo and reduces portal pressure in a bile duct ligation (BDL) model. Primary human HSCs were isolated and cultured. Proliferation (BrdU), metabolic activity (MTS), morphology (transmission electron, light and immunofluorescence microscopy), HSC activation markers, ability to contract, changes in oxidative status (ROS) and endoplasmic reticulum (ER) were evaluated to identify effects of ammonia challenge (50 μM, 100 μM, 300 μM) over 24-72 h. Changes in plasma ammonia levels, markers of HSC activation, portal pressure and hepatic eNOS activity were quantified in hyperammonemic BDL animals, and after OP treatment. Pathophysiological ammonia concentrations caused significant and reversible changes in cell proliferation, metabolic activity and activation markers of hHSC in vitro. Ammonia also induced significant alterations in cellular morphology, characterised by cytoplasmic vacuolisation, ER enlargement, ROS production, hHSC contraction and changes in pro-inflammatory gene expression together with HSC-related activation markers such as α-SMA, myosin IIa, IIb, and PDGF-Rβ. Treatment with OP significantly reduced plasma ammonia (BDL 199.1 μmol/L±43.65 vs. BDL+OP 149.27 μmol/L±51.1, p<0.05) and portal pressure (BDL 14±0.6 vs. BDL+OP 11±0.3 mmHg, p<0.01), which was associated with increased eNOS activity and abrogation of HSC activation markers. The results show for the first time that ammonia produces deleterious morphological and functional effects on HSCs in vitro. Targeting ammonia with the ammonia lowering drug OP reduces portal pressure and deactivates hHSC in vivo, highlighting the opportunity for evaluating ammonia lowering as a potential therapy in cirrhotic patients with portal hypertension. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Liu, Feng; Chen, Long; Rao, Hui-Ying; Teng, Xiao; Ren, Ya-Yun; Lu, Yan-Qiang; Zhang, Wei; Wu, Nan; Liu, Fang-Fang; Wei, Lai
2017-01-01
Animal models provide a useful platform for developing and testing new drugs to treat liver fibrosis. Accordingly, we developed a novel automated system to evaluate liver fibrosis in rodent models. This system uses second-harmonic generation (SHG)/two-photon excited fluorescence (TPEF) microscopy to assess a total of four mouse and rat models, using chemical treatment with either thioacetamide (TAA) or carbon tetrachloride (CCl 4 ), and a surgical method, bile duct ligation (BDL). The results obtained by the new technique were compared with that using Ishak fibrosis scores and two currently used quantitative methods for determining liver fibrosis: the collagen proportionate area (CPA) and measurement of hydroxyproline (HYP) content. We show that 11 shared morphological parameters faithfully recapitulate Ishak fibrosis scores in the models, with high area under the receiver operating characteristic (ROC) curve (AUC) performance. The AUC values of 11 shared parameters were greater than that of the CPA (TAA: 0.758-0.922 vs 0.752-0.908; BDL: 0.874-0.989 vs 0.678-0.966) in the TAA mice and BDL rat models and similar to that of the CPA in the TAA rat and CCl 4 mouse models. Similarly, based on the trends in these parameters at different time points, 9, 10, 7, and 2 model-specific parameters were selected for the TAA rats, TAA mice, CCl 4 mice, and BDL rats, respectively. These parameters identified differences among the time points in the four models, with high AUC accuracy, and the corresponding AUC values of these parameters were greater compared with those of the CPA in the TAA rat and mouse models (rats: 0.769-0.894 vs 0.64-0.799; mice: 0.87-0.93 vs 0.739-0.836) and similar to those of the CPA in the CCl 4 mouse and BDL rat models. Similarly, the AUC values of 11 shared parameters and model-specific parameters were greater than those of HYP in the TAA rats, TAA mice, and CCl 4 mouse models and were similar to those of HYP in the BDL rat models. The automated evaluation system, combined with 11 shared parameters and model-specific parameters, could specifically, accurately, and quantitatively stage liver fibrosis in animal models.
Esteve-Bruna, David; Pérez-Pérez, José Manuel; Ponce, María Rosa; Micol, José Luis
2013-01-01
Auxin plays a pivotal role in plant development by modulating the activity of SCF ubiquitin ligase complexes. Here, we positionally cloned Arabidopsis (Arabidopsis thaliana) incurvata13 (icu13), a mutation that causes leaf hyponasty and reduces leaf venation pattern complexity and auxin responsiveness. We found that icu13 is a novel recessive allele of AUXIN RESISTANT6 (AXR6), which encodes CULLIN1, an invariable component of the SCF complex. Consistent with a role for auxin in vascular specification, the vascular defects in the icu13 mutant were accompanied by reduced expression of auxin transport and auxin perception markers in provascular cells. This observation is consistent with the expression pattern of AXR6, which we found to be restricted to vascular precursors and hydathodes in wild-type leaf primordia. AXR1, RELATED TO UBIQUITIN1-CONJUGATING ENZYME1, CONSTITUTIVE PHOTOMORPHOGENIC9 SIGNALOSOME5A, and CULLIN-ASSOCIATED NEDD8-DISSOCIATED1 participate in the covalent modification of CULLIN1 by RELATED TO UBIQUITIN. Hypomorphic alleles of these genes also display simple venation patterns, and their double mutant combinations with icu13 exhibited a synergistic, rootless phenotype reminiscent of that caused by loss of function of MONOPTEROS (MP), which forms an auxin-signaling module with BODENLOS (BDL). The phenotypes of double mutant combinations of icu13 with either a gain-of-function allele of BDL or a loss-of-function allele of MP were synergistic. In addition, a BDL:green fluorescent protein fusion protein accumulated in icu13, and BDL loss of function or MP overexpression suppressed the phenotype of icu13. Our results demonstrate that the MP-BDL module is required not only for root specification in embryogenesis and vascular postembryonic development but also for leaf flatness. PMID:23319550
Beaussier, Marc; Wendum, Dominique; Schiffer, Eduardo; Dumont, Sylvie; Rey, Colette; Lienhart, André; Housset, Chantal
2007-03-01
Liver fibrosis is produced by myofibroblasts of different origins. In culture models, rat myofibroblasts derived from hepatic stellate cells (HSCs) and from periductal portal mesenchymal cells, show distinct proliferative and immunophenotypic evolutive profiles, in particular regarding desmin microfilament (overexpressed vs shut-down, respectively). Here, we examined the contributions of both cell types, in two rat models of cholestatic injury, arterial liver ischemia and bile duct ligation (BDL). Serum and (immuno)histochemical hepatic analyses were performed at different time points (2 days, 1, 2 and 6 weeks) after injury induction. Cholestatic liver injury, as attested by serum biochemical tests, was moderate/resolutive in ischemia vs severe and sustained in BDL. Spatio-temporal and morphometric analyses of cytokeratin-19 and Sirius red stainings showed that in both models, fibrosis accumulated around reactive bile ductules, with a significant correlation between the progression rates of fibrosis and of the ductular reaction (both higher in BDL). After 6 weeks, fibrosis was stabilized and did not exceed F2 (METAVIR) in arterial ischemia, whereas micronodular cirrhosis (F4) was established in BDL. Immuno-analyses of alpha-smooth muscle actin and desmin expression profiles showed that intralobular HSCs underwent early phenotypic changes marked by desmin overexpression in both models and that the accumulation of fibrosis coincided with that of alpha-SMA-labeled myofibroblasts around portal/septal ductular structures. With the exception of desmin-positive myofibroblasts located at the portal/septal-lobular interface at early stages, and of myofibroblastic HSCs detected together with fine lobular septa in BDL cirrhotic liver, the vast majority of myofibroblasts were desmin-negative. These findings suggest that both in resolutive and sustained cholestatic injury, fibrosis is produced by myofibroblasts that derive predominantly from portal/periportal mesenchymal cells. While HSCs massively undergo phenotypic changes marked by desmin overexpression, a minority fully converts into matrix-producing myofibroblasts, at sites, which however may be important in the healing process that circumscribes wounded hepatocytes.
Effects of asymmetric dimethylarginine on renal arteries in portal hypertension and cirrhosis
Segarra, Gloria; Cortina, Belén; Mauricio, María Dolores; Novella, Susana; Lluch, Paloma; Navarrete-Navarro, Javier; Noguera, Inmaculada; Medina, Pascual
2016-01-01
AIM To evaluate the effects of asymmetric dimethylarginine (ADMA) in renal arteries from portal hypertensive and cirrhotic rats. METHODS Rat renal arteries from Sham (n = 15), pre-hepatic portal hypertension (PPVL; n = 15) and bile duct ligation and excision-induced cirrhosis (BDL; n = 15) were precontracted with norepinephrine, and additional contractions were induced with ADMA (10-6-10-3 mol/L), an endogenous inhibitor of nitric oxide (NO) synthase. Concentration-response curves to acetylcholine (1 × 10-9-3 × 10-6 mol/L) were determined in precontracted renal artery segments with norepinephrine in the absence and in the presence of ADMA. Kidneys were collected to determine the protein expression and activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that catabolizes ADMA. RESULTS In renal arteries precontracted with norepinephrine, ADMA caused endothelium-dependent contractions. The pD2 values to ADMA were similar in the Sham and PPVL groups (4.20 ± 0.08 and 4.11 ± 0.09, P > 0.05, respectively), but were lower than those of the BDL group (4.79 ± 0.16, P < 0.05). Acetylcholine-induced endothelium-dependent relaxation that did not differ, in terms of pD2 and maximal relaxation, among the 3 groups studied. Treatment with ADMA (3 × 10-4 mol/L) inhibited acetylcholine-induced relaxation in the 3 groups, but the inhibition was higher (P < 0.05) in the BDL group compared with that for the Sham and PPVL groups. The mRNA and protein expression of DDAH-1 were similar in kidneys from the three groups. Conversely, DDAH-2 expression was increased (P < 0.05) in PPVL and further enhanced (P < 0.05) in the BDL group. However, renal DDAH activity was significantly decreased in the BDL group. CONCLUSION Cirrhosis increased the inhibitory effect of ADMA on basal- and induced-release of NO in renal arteries, and decreased DDAH activity in the kidney. PMID:28082806
Effects of asymmetric dimethylarginine on renal arteries in portal hypertension and cirrhosis.
Segarra, Gloria; Cortina, Belén; Mauricio, María Dolores; Novella, Susana; Lluch, Paloma; Navarrete-Navarro, Javier; Noguera, Inmaculada; Medina, Pascual
2016-12-28
To evaluate the effects of asymmetric dimethylarginine (ADMA) in renal arteries from portal hypertensive and cirrhotic rats. Rat renal arteries from Sham ( n = 15), pre-hepatic portal hypertension (PPVL; n = 15) and bile duct ligation and excision-induced cirrhosis (BDL; n = 15) were precontracted with norepinephrine, and additional contractions were induced with ADMA (10 -6 -10 -3 mol/L), an endogenous inhibitor of nitric oxide (NO) synthase. Concentration-response curves to acetylcholine (1 × 10 -9 -3 × 10 -6 mol/L) were determined in precontracted renal artery segments with norepinephrine in the absence and in the presence of ADMA. Kidneys were collected to determine the protein expression and activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that catabolizes ADMA. In renal arteries precontracted with norepinephrine, ADMA caused endothelium-dependent contractions. The pD 2 values to ADMA were similar in the Sham and PPVL groups (4.20 ± 0.08 and 4.11 ± 0.09, P > 0.05, respectively), but were lower than those of the BDL group (4.79 ± 0.16, P < 0.05). Acetylcholine-induced endothelium-dependent relaxation that did not differ, in terms of pD 2 and maximal relaxation, among the 3 groups studied. Treatment with ADMA (3 × 10 -4 mol/L) inhibited acetylcholine-induced relaxation in the 3 groups, but the inhibition was higher ( P < 0.05) in the BDL group compared with that for the Sham and PPVL groups. The mRNA and protein expression of DDAH-1 were similar in kidneys from the three groups. Conversely, DDAH-2 expression was increased ( P < 0.05) in PPVL and further enhanced ( P < 0.05) in the BDL group. However, renal DDAH activity was significantly decreased in the BDL group. Cirrhosis increased the inhibitory effect of ADMA on basal- and induced-release of NO in renal arteries, and decreased DDAH activity in the kidney.
Huang, Ying-Hsien; Yang, Ya-Ling; Huang, Fu-Chen; Tiao, Mao-Meng; Lin, Yen-Cheng; Tsai, Ming-Horng; Wang, Feng-Sheng
2018-01-01
Hepatic fibrosis was caused by a number of signaling pathways that damage liver integrity. We have previously shown that microRNA-29a (miR-29a) protects against liver fibrosis. Aberrant endoplasmic reticulum (ER) and autophagy function reportedly exaggerate hepatic disorders. The aim of this study was to characterize the biological influence of miR-29a on ER function in injured livers with bile duct ligation (BDL). We performed BDL on miR-29a transgenic mice (miR-29aTg) and wild-type mice to induce cholestatic liver injury. Rat T6 cells were transfected with miR-29a mimic and tunicamycin. Compared to the wild-type mice, the BDL deterioration of liver function in terms of total bilirubin, alanine transaminase, and aspartate transaminase activity in the miR-29aTg mice was significantly reduced. Affected livers in the miR-29aTg mice demonstrated a slight fibrotic matrix formation. miR-29a over-expression reduced the BDL disturbance of the expressions of inositol-requiring kinase 1alpha, double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase, spliced-X-box binding protein 1 (sXBP1), CCAAT/enhancer-binding protein homologous protein (CHOP), ULK, LC3BII, p62, and cleaved caspase-8, 9 and 3. In vitro, T6 cells exposed to tunicamycin by increasing abundances of CHOP, sXBP1, cleaved caspase-3, and LC3BII were diminished in the cell cultures transfected with the miR-29a mimic. On the other hand, we observed that miR-29a signaling protected liver tissues from BDL-mediated metabolic dysfunction and excessive fibrosis histopathology. This study provides new molecular insight into the miR-29a stabilization of ER integrity that slows the progression of cholestatic liver deterioration. Impact statement Long-term hepatic damage caused by hepatitis and cholestasis can accelerate fibrosis matrix over-production, which is a harmful process attributed to the dysregulation of a number of cellular and molecular events. The purpose of this study is to characterize the biological influence of miR-29a on endoplasmic reticulum (ER) function in bile duct ligation (BDL)-injured livers. To the best of our knowledge, this report is the first demonstration that miR-29a over-expression diminishes BDL provocation of ER stress (unfolded protein response, UPR) effector protein expression. This work also demonstrates that miR-29a decreased caspases protein expression in cholestatic livers, while an increase in miR-29a function reduced sXBP1 and CHOP expressions in T6 cells in mice. Analyses of this study highlight that controlling miR-29a signaling can serve as an innovative strategy in the future for microRNA regulation of ER homeostasis to combat cholestasis induction hepatic disorders.
Xiang, Daoquan; Yang, Hui; Venglat, Prakash; Cao, Yongguo; Wen, Rui; Ren, Maozhi; Stone, Sandra; Wang, Edwin; Wang, Hong; Xiao, Wei; Weijers, Dolf; Berleth, Thomas; Laux, Thomas; Selvaraj, Gopalan; Datla, Raju
2011-12-01
The shoot and root apical meristems (SAM and RAM) formed during embryogenesis are crucial for postembryonic plant development. We report the identification of POPCORN (PCN), a gene required for embryo development and meristem organization in Arabidopsis thaliana. Map-based cloning revealed that PCN encodes a WD-40 protein expressed both during embryo development and postembryonically in the SAM and RAM. The two pcn alleles identified in this study are temperature sensitive, showing defective embryo development when grown at 22°C that is rescued when grown at 29°C. In pcn mutants, meristem-specific expression of WUSCHEL (WUS), CLAVATA3, and WUSCHEL-RELATED HOMEOBOX5 is not maintained; SHOOTMERISTEMLESS, BODENLOS (BDL) and MONOPTEROS (MP) are misexpressed. Several findings link PCN to auxin signaling and meristem function: ectopic expression of DR5(rev):green fluorescent protein (GFP), pBDL:BDL-GFP, and pMP:MP-β-glucuronidase in the meristem; altered polarity and expression of pPIN1:PIN1-GFP in the apical domain of the developing embryo; and resistance to auxin in the pcn mutants. The bdl mutation rescued embryo lethality of pcn, suggesting that improper auxin response is involved in pcn defects. Furthermore, WUS, PINFORMED1, PINOID, and TOPLESS are dosage sensitive in pcn, suggesting functional interaction. Together, our results suggest that PCN functions in the auxin pathway, integrating auxin signaling in the organization and maintenance of the SAM and RAM.
Xiang, Daoquan; Yang, Hui; Venglat, Prakash; Cao, Yongguo; Wen, Rui; Ren, Maozhi; Stone, Sandra; Wang, Edwin; Wang, Hong; Xiao, Wei; Weijers, Dolf; Berleth, Thomas; Laux, Thomas; Selvaraj, Gopalan; Datla, Raju
2011-01-01
The shoot and root apical meristems (SAM and RAM) formed during embryogenesis are crucial for postembryonic plant development. We report the identification of POPCORN (PCN), a gene required for embryo development and meristem organization in Arabidopsis thaliana. Map-based cloning revealed that PCN encodes a WD-40 protein expressed both during embryo development and postembryonically in the SAM and RAM. The two pcn alleles identified in this study are temperature sensitive, showing defective embryo development when grown at 22°C that is rescued when grown at 29°C. In pcn mutants, meristem-specific expression of WUSCHEL (WUS), CLAVATA3, and WUSCHEL-RELATED HOMEOBOX5 is not maintained; SHOOTMERISTEMLESS, BODENLOS (BDL) and MONOPTEROS (MP) are misexpressed. Several findings link PCN to auxin signaling and meristem function: ectopic expression of DR5rev:green fluorescent protein (GFP), pBDL:BDL-GFP, and pMP:MP-β-glucuronidase in the meristem; altered polarity and expression of pPIN1:PIN1-GFP in the apical domain of the developing embryo; and resistance to auxin in the pcn mutants. The bdl mutation rescued embryo lethality of pcn, suggesting that improper auxin response is involved in pcn defects. Furthermore, WUS, PINFORMED1, PINOID, and TOPLESS are dosage sensitive in pcn, suggesting functional interaction. Together, our results suggest that PCN functions in the auxin pathway, integrating auxin signaling in the organization and maintenance of the SAM and RAM. PMID:22158464
Wang, Long; Zhou, Mai-Tao; Chen, Cai-Yang; Yin, Wen; Wen, Da-Xiang; Cheung, Chi-Wai; Yang, Li-Qun; Yu, Wei-Feng
2017-01-13
Requirement for rocuronium upon surgery changes only minimally in patients with end-stage liver diseases. Our study consisted of both human and rat studies to explore the reason. The reduction rate of rocuronium infusion required to maintain neuromuscular blockade during the anhepatic phase (relative to paleohepatic phase) was examined in 16 children with congenital biliary atresia receiving orthotopic liver transplantation. Pharmacodynamics and pharmacokinetics of rocuronium were studied based on BDL rats. The role of increased Oatp2 and decrease Oatp1 expressions in renal compensation were explored. The reduction of rocuronium requirements significantly decreased in obstructively jaundiced children (24 ± 9 vs. 39 ± 11%). TOF50 in BDL rats was increased by functional removal of the kidneys but not the liver, and the percentage of rocuronium excretion through urine increased (20.3 ± 6.9 vs. 8.6 ± 1.8%), while that decreased through bile in 28d-BDL compared with control group. However, this enhanced renal secretion for rocuronium was eliminated by Oatp2 knock-down, rather than Oatp1 overexpression (28-d BDL vs. Oatp1-ShRNA or Oatp2-ShRNA, 20.3 ± 6.9 vs. 17.0 ± 6.6 or 9.3 ± 3.2%). Upon chronic/sub-chronic loss of bile excretion, rocuronium clearance via the kidneys is enhanced, by Oatp2 up-regulation.
Wan, Ying; Meng, Fanyin; Wu, Nan; Zhou, Tianhao; Venter, Julie; Francis, Heather; Kennedy, Lindsey; Glaser, Trenton; Bernuzzi, Francesca; Invernizzi, Pietro; Glaser, Shannon; Huang, Qiaobing; Alpini, Gianfranco
2017-08-01
Substance P (SP) is involved in the proliferation of cholangiocytes in bile duct-ligated (BDL) mice and human cholangiocarcinoma growth by interacting with the neurokinin-1 receptor (NK-1R). To identify whether SP regulates liver fibrosis during cholestasis, wild-type or NK-1R knockout (NK-1R -/- ) mice that received BDL or sham surgery and multidrug resistance protein 2 knockout (Mdr2 -/- ) mice treated with either an NK-1R antagonist (L-733,060) or saline were used. Additionally, wild-type mice were treated with SP or saline intraperitoneally. In vivo, there was increased expression of tachykinin precursor 1 (coding SP) and NK-1R in both BDL and Mdr2 -/- mice compared to wild-type mice. Expression of tachykinin precursor 1 and NK-1R was significantly higher in liver samples from primary sclerosing cholangitis patients compared to healthy controls. Knockout of NK-1R decreased BDL-induced liver fibrosis, and treatment with L-733,060 resulted in decreased liver fibrosis in Mdr2 -/- mice, which was shown by decreased sirius red staining, fibrosis gene and protein expression, and reduced transforming growth factor-β1 levels in serum and cholangiocyte supernatants. Furthermore, we observed that reduced liver fibrosis in NK-1R -/- mice with BDL surgery or Mdr2 -/- mice treated with L-733,060 was associated with enhanced cellular senescence of hepatic stellate cells and decreased senescence of cholangiocytes. In vitro, L-733,060 inhibited SP-induced expression of fibrotic genes in hepatic stellate cells and cholangiocytes; treatment with L-733,060 partially reversed the SP-induced decrease of senescence gene expression in cultured hepatic stellate cells and the SP-induced increase of senescence-related gene expression in cultured cholangiocytes. Collectively, our results demonstrate the regulatory effects of the SP/NK-1R axis on liver fibrosis through changes in cellular senescence during cholestatic liver injury. (Hepatology 2017;66:528-541). © 2017 by the American Association for the Study of Liver Diseases. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
HIF-1 α as a Key Factor in Bile Duct Ligation-Induced Liver Fibrosis in Rats.
Moczydlowska, Joanna; Miltyk, Wojciech; Hermanowicz, Adam; Lebensztejn, Dariusz M; Palka, Jerzy A; Debek, Wojciech
2017-02-01
Although several studies suggested hypoxia as an important microenvironmental factor contributing to inflammation and fibrosis in chronic liver diseases, the mechanism of this process is not fully understood. We considered hypoxia inducible factor (HIF-1α) as a key transcription factor in liver fibrosis. The aim of the study was to evaluate the mechanisms of signaling pathway during bile duct ligation (BDL)-induced liver fibrosis in rats. BDL animal model of liver fibrosis was used in the study. Male Wistar rats were divided randomly into two experimental groups: sham group (n = 15), BDL group (n = 30). Hydroxyproline (Hyp) content as a marker of collagen accumulation in liver of rats subjected to BDL was evaluated according to the method described by Gerling B et al. Expression of signaling proteins [integrin β 1 receptor, HIF-1α, nuclear factor kappa B (NF-κB), and transforming growth factor (TGF-β)] was evaluated applying Western-immunoblot analysis. In all experiments, the mean values for six assays ± standard deviations (SD) were calculated. The results were submitted to the statistical analysis using the Student's "t" test, accepting p < 0.05 as significant. Ligation of bile ducts was found to increase Hyp content in rat liver, accompanied by increase of HIF-1α expression during 10 weeks after BDL. The Hyp level was time dependent. There was not such a difference in control group (p < 0.001). Simultaneously expression of NF-κB, TGF-β, β 1 -integrin receptor was significantly elevated starting from sixth week after ligation. Activity of metalloproteinases 2 and 9 in the livers were increased 1 week after surgery and remained increased until the end of the experiment. The mechanism of development of liver fibrosis involves activation of Matrix metalloproteinase-2 (MMP-2) and Matrix metalloproteinase-9 (MMP-9), upregulation of HIF-1α transcriptional activity and its related factors, NF-κB and TGF-β. It suggests that they may represent targets for the treatment of the disease.
Zhu, Qiang; Zou, Li; Jagavelu, Kumaravelu; Simonetto, Douglas A.; Huebert, Robert C.; Jiang, Zhi-Dong; DuPont, Herbert L.; Shah, Vijay H.
2012-01-01
Background/Aims Liver fibrosis is associated with angiogenesis and leads to portal hypertension. Certain antibiotics reduce complications of liver failure in humans, however, effect of antibiotics on the pathologic alterations of the disease are not fully understood. The aim of this study was to test whether the non-absorbable antibiotic rifaximin could attenuate fibrosis progression and portal hypertension in vivo, and explore potential mechanisms in vitro. Methods Effect of rifaximin on portal pressure, fibrosis, and angiogenesis was examined in wild type and toll like receptor 4 (TLR4) mutant mice after bile duct ligation (BDL). In vitro studies were carried out to evaluate the effect of the bacterial product and TLR agonist, lipopolysaccharide (LPS) on paracrine interactions between hepatic stellate cells (HSC) and liver endothelial cells (LEC) that lead to fibrosis and portal hypertension. Results Portal pressure, fibrosis, and angiogenesis were significantly lower in BDL mice receiving rifaximin compared to BDL mice receiving vehicle. Studies in TLR4 mutant mice confirmed that the effect of rifaximin was dependent on LPS/TLR4 pathway. Fibronectin (FN) was increased in BDL liver and was reduced by rifaximin administration and thus was explored further in vitro as a potential mediator of paracrine interactions of HSC and LEC. In vitro, LPS promoted FN production from HSC. Furthermore, HSC-derived FN promoted LEC migration and angiogenesis. Conclusion These studies expand our understanding of the relationship of intestinal microbiota with fibrosis development by identifying FN as a TLR4 dependent mediator of the matrix and vascular changes that characterize cirrhosis. PMID:22173161
Pesticide residue analysis of soil, water, and grain of IPM basmati rice.
Arora, Sumitra; Mukherji, Irani; Kumar, Aman; Tanwar, R K
2014-12-01
The main aim of the present investigations was to compare the pesticide load in integrated pest management (IPM) with non-IPM crops of rice fields. The harvest samples of Basmati rice grain, soil, and irrigation water, from IPM and non-IPM field trials, at villages in northern India, were analyzed using multi-pesticide residue method. The field experiments were conducted for three consecutive years (2008-2011) for the successful validation of the modules, synthesized for Basmati rice, at these locations. Residues of tricyclazole, propiconazole, hexconazole, lambda cyhalothrin, pretilachlor chlorpyrifos, DDVP, carbendazim, and imidacloprid were analyzed from two locations, Dudhli village of Dehradun, Uttrakhand and Saboli and Aterna village of Sonepat, Haryana. The pesticide residues were observed below detectable limit (BDL) (<0.001-0.05 μg/g) in all 24 samples of rice grains and soil under IPM and non-IPM trials. Residues were below detection level (<0.001-0.05 μg/L) in irrigation water samples (2008-09). Residues of tricyclazole and carbendazim, analyzed from same locations, revealed pesticide residues as BDL (<0.001-0.05 μg/g) in all 40 samples of Basmati rice grains and soil. It was also observed as BDL (<0.001-0.05 μg/L) for 12 water samples (2009-2010). The residues of tricyclazole, propioconazole, chlorpyrifos, hexaconazole, pretilachlor, and λ-cyhalothrin were also found as BDL (<0.001-0.05 μg/g) in 40 samples of Basmati rice grains and soil and 12 water samples (<0.001-0.05 μg/L) (2010-2011).
Witek, Rafal P.; Yang, Liu; Liu, Renshui; Jung, Youngmi; Omenetti, Alessia; Syn, Wing-Kin; Choi, Steve S.; Cheong, Yeiwon; Fearing, Caitlin M.; Agboola, Kolade M.; Chen, Wei; Diehl, Anna Mae
2013-01-01
Background & Aims Angiogenesis contributes to vascular remodeling during cirrhosis. In cirrhotic livers, cholangiocytes and myofibroblastic hepatic stellate cells (MF-HSC) produce Hedgehog (Hh) ligands. During embryogenesis Hh ligands are released from ligand-producing cells in microparticles and activate Hh signaling in endothelial cells. We studied whether adult liver cell-derived microparticles contain Hh ligands that alter hepatic sinusoidal endothelial cells (SEC). Methods MF-HSCs and cholangiocytes were exposed to platelet-derived growth factor (PDGF) to induce Hh ligands; microparticles were isolated from medium, analyzed by transmission electron microscopy (TEM) and immunoblots, and applied to Hh-reporter containing cells. Microparticles were also obtained from serum and bile of rats after bile duct ligation (BDL) or sham surgery and applied to normal primary liver SEC with or without cyclopamine, a Hh signaling inhibitor. Effects on SEC gene expression were evaluated by QRT-PCR and immunoblotting. Finally, Hh target gene expression and SEC activation markers were compared in primary SEC and in liver sections from healthy and BDL rats. Results PDGF-treated MF-HSC and cholangiocytes released exosome-enriched microparticles containing biologically active Hh ligands. BDL also increased release of Hh-containing exosome-enriched microparticles into plasma and bile. TEM and immunoblots revealed similarities among microparticles from all sources; all microparticles induced similar Hh-dependent changes in SEC gene expression. SEC from healthy livers did not express Hh target genes or activation markers, but both were up-regulated in SEC after BDL. Conclusions Hh-containing exosome-enriched microparticles released from liver cells alter hepatic SEC gene expression, suggesting a novel mechanism for cirrhotic vasculopathy. PMID:19013163
Witek, Rafal P; Yang, Liu; Liu, Renshui; Jung, Youngmi; Omenetti, Alessia; Syn, Wing-Kin; Choi, Steve S; Cheong, Yeiwon; Fearing, Caitlin M; Agboola, Kolade M; Chen, Wei; Diehl, Anna Mae
2009-01-01
Angiogenesis contributes to vascular remodeling during cirrhosis. In cirrhotic livers, cholangiocytes, and myofibroblastic hepatic stellate cells (MF-HSC) produce Hedgehog (Hh) ligands. During embryogenesis Hh ligands are released from ligand-producing cells in microparticles and activate Hh signaling in endothelial cells. We studied whether adult liver cell-derived microparticles contain Hh ligands that alter hepatic sinusoidal endothelial cells (SEC). MF-HSC and cholangiocytes were exposed to platelet-derived growth factor to induce Hh ligands; microparticles were isolated from medium, analyzed by transmission electron microscopy and immunoblots, and applied to Hh-reporter-containing cells. Microparticles were obtained from serum and bile of rats after bile duct ligation (BDL) or sham surgery and applied to normal primary liver SEC with or without cyclopamine, an Hh signaling inhibitor. Effects on SEC gene expression were evaluated by quantitative reverse-transcription polymerase chain reaction and immunoblotting. Hh target gene expression and SEC activation markers were compared in primary SEC and in liver sections from healthy and BDL rats. Platelet-derived growth factor-treated MF-HSC and cholangiocytes released exosome-enriched microparticles containing biologically-active Hh ligands. BDL increased release of Hh-containing exosome-enriched microparticles into plasma and bile. Transmission electron microscopy and immunoblots revealed similarities among microparticles from all sources; all microparticles induced similar Hh-dependent changes in SEC gene expression. SEC from healthy livers did not express Hh target genes or activation markers, but both were up-regulated in SEC after BDL. Hh-containing exosome-enriched microparticles released from liver cells alter hepatic SEC gene expression, suggesting a novel mechanism for cirrhotic vasculopathy.
Use of the sea hare (Aplysia fasciata) in marine pollution biomonitoring of harbors and bays.
Dirrigl, Frank J; Badaoui, Zachariah; Tamez, Carlos; Vitek, Christopher J; Parsons, Jason G
2018-04-01
Our study evaluated heavy metal concentrations in soft tissues of sea hare, Aplysia fasciata, from the Lower Laguna Madre, Texas. Heavy metals in tissues followed Se>As>Pb>Cd. Concentrations ranged As (BDL-28.08), Cd (BDL-5.50), Pb (BDL-12.85) and Se (4.25-93.43ppm). Median As, Cd, Pb, and Se tissue levels exceeded exposure levels. Significant relationships occurred in metal-metal (AsCd, AsPb, CdPb, CdSe, and PbSe), metal-tissue (significant Se uptake by inhalant and exhalant siphons and As in the hepatopancreas), and metal-metal within tissue (AsPb in the hepatopancreas and CdPb in the digestive cecum) analyses (p<0.05). Bioaccumulation factors (BAF) suggested the inhalant siphon, hepatopancreas, and digestive cecum function as macroconcentrators of Cd, hepatopancreas and digestive cecum as macroconcentrators of Pb, and all tissues were deconcentrators for As and Se. As a bioaccumulator of heavy metals, Aplysia was evaluated as a bioindicator of marine pollution in harbors and bays. Copyright © 2017 Elsevier Ltd. All rights reserved.
Abd El Motteleb, Dalia M; Ibrahim, Islam A A E-H; Elshazly, Shimaa M
2017-11-15
Hepatic fibrosis is a potential health problem that may end with life-threatening cirrhosis and primary liver cancer. Recent studies point out to the protective effects of silent information regulator1 (SIRT1), against different models of organs fibrosis. This work aimed to investigate the possible protective effect of sildenafil (SIRT1 activator) against hepatic fibrosis induced by bile duct ligation (BDL). Firstly, three different doses of sildenafil (5, 10, 20mg/kg/day) were investigated; to detect the most protective one against BDL induced liver dysfunction and hepatic fibrosis. The most protective dose is then used; to study its effect on BDL induced SIRT1 downregulation, imbalance of oxidant/antioxidant status, increased inflammatory cytokines and fibrosis. Sildenafil (20mg/kg/day) was the most protective one, it caused upregulation of SIRT1, reduction of hepatic malondialdehyde (MDA) content, increase in expression of nuclear factor erythroid 2-related factor 2 (Nrf2), hemeoxygenease (HO)-1, reduced glutathione (GSH) content and superoxide dismutase (SOD) activity. Hepatic content of tumor necrosis factor-α (TNF-α) and nuclear factor κB (NFκB) expression & content displayed significant reductions with sildenafil treatment, Furthermore, sildenafil caused marked reductions of transforming growth factor (TGF)-β content, expression of plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), α-smooth muscle actin (α-SMA), fibronectin, collagen I (α1) and hydroxyproline content. However, sildenafil protective effects were significantly reduced by co-administration of EX527 (SIRT1 inhibitor). Our work showed, for the first time that, sildenafil has promising protective effects against BDL induced liver dysfunction and hepatic fibrosis. These effects may be, in part, mediated by up regulation of SIRT1. Copyright © 2017. Published by Elsevier Inc.
Weerachayaphorn, Jittima; Mennone, Albert; Soroka, Carol J.; Harry, Kathy; Hagey, Lee R.; Kensler, Thomas W.
2012-01-01
The transcription factor nuclear factor-E2-related factor 2 (Nrf2) is a key regulator for induction of hepatic detoxification and antioxidant mechanisms, as well as for certain hepatobiliary transporters. To examine the role of Nrf2 in bile acid homeostasis and cholestasis, we assessed the determinants of bile secretion and bile acid synthesis and transport before and after bile duct ligation (BDL) in Nrf2−/− mice. Our findings indicate reduced rates of biliary bile acid and GSH excretion, higher levels of intrahepatic bile acids, and decreased expression of regulators of bile acid synthesis, Cyp7a1 and Cyp8b1, in Nrf2−/− compared with wild-type control mice. The mRNA expression of the bile acid transporters bile salt export pump (Bsep) and organic solute transporter (Ostα) were increased in the face of impaired expression of the multidrug resistance-associated proteins Mrp3 and Mrp4. Deletion of Nrf2 also decreased ileal apical sodium-dependent bile acid transporter (Asbt) expression, leading to reduced bile acid reabsorption and increased loss of bile acid in feces. Finally, when cholestasis is induced by BDL, liver injury was not different from that in wild-type BDL mice. These Nrf2−/− mice also had increased pregnane X receptor (Pxr) and Cyp3a11 mRNA expression in association with enhanced hepatic bile acid hydroxylation. In conclusion, this study finds that Nrf2 plays a major role in the regulation of bile acid homeostasis in the liver and intestine. Deletion of Nrf2 results in a cholestatic phenotype but does not augment liver injury following BDL. PMID:22345550
Wang, Yongqing; Aoki, Hiroaki; Yang, Jing; Peng, Kesong; Liu, Runping; Li, Xiaojiaoyang; Qiang, Xiaoyan; Sun, Lixin; Gurley, Emily C; Lai, Guanhua; Zhang, Luyong; Liang, Guang; Nagahashi, Masayuki; Takabe, Kazuaki; Pandak, William M; Hylemon, Phillip B.; Zhou, Huiping
2017-01-01
Bile duct obstruction is a potent stimulus for cholangiocyte proliferation, especially for large cholangiocytes. Our previous studies reported that conjugated bile acids (CBAs) activate the AKT and ERK1/2 signaling pathways via the sphingosine 1-phosphate receptor 2 (S1PR2) in hepatocytes and cholangiocarcinoma cells. It also has been reported that taurocholate (TCA) promotes large cholangiocyte proliferation and protects cholangiocytes from bile duct ligation (BDL)-induced apoptosis. However, the role of S1PR2 in bile acid-mediated cholangiocyte proliferation and cholestatic liver injury has not been elucidated. Here we report that S1PR2 is the predominant S1PR expressed in cholangiocytes. Both TCA- and S1P-induced activation of ERK1/2 and AKT were inhibited by JTE-013, a specific antagonist of S1PR2, in cholangiocytes. In addition, TCA- and S1P-induced cell proliferation and migration were inhibited by JTE-013 and a specific shRNA of S1PR2 as well as chemical inhibitors of ERK1/2 and AKT in mouse cholangiocytes. In BDL mice, the expression of S1PR2 was upregulated in whole liver and cholangiocytes. S1PR2 deficiency significantly reduced BDL-induced cholangiocyte proliferation and cholestatic injury as indicated by significant reduction of inflammation and liver fibrosis in S1PR2−/− mice. Treatment of BDL mice with JTE-013 significantly reduced total bile acid levels in the serum and cholestatic liver injury. This study suggests that the CBA-induced activation of S1PR2-mediated signaling pathways plays a critical role in obstructive cholestasis and may represent a novel therapeutic target for cholestatic liver diseases. PMID:28120434
Ehrlich, Laurent; O'Brien, April; Hall, Chad; White, Tori; Chen, Lixian; Wu, Nan; Venter, Julie; Scrushy, Marinda; Mubarak, Muhammad; Meng, Fanyin; Dostal, David; Wu, Chaodong; Lairmore, Terry C; Alpini, Gianfranco; Glaser, Shannon
2018-03-26
α7-nAChR is a nicotinic acetylcholine receptor (specifically expressed on hepatic stellate cells, Kupffer cells, and cholangiocytes) that regulates inflammation and apoptosis in the liver. Thus, targeting α7-nAChR may be therapeutic in biliary diseases. Bile-duct ligation (BDL) was performed on wild-type (WT) and α7-nAChR-/- mice. We first evaluated the expression of α7-nAChR by immunohistochemistry (IHC) in liver sections. IHC was also performed to assess intrahepatic bile-duct mass (IBDM), and Sirius Red staining was performed to quantify the amount of collagen deposition. Immunofluorescence was performed to assess co-localization of α7-nAChR with bile ducts (co-stained with CK-19) and hepatic stellate cells (HSCs) (co-stained with desmin). The mRNA expression of α7-nAChR, Ki67/PCNA (proliferation), fibrosis genes (TGF-β1, Fibronectin-1, Col1α1, and α-SMA), and inflammatory markers (IL-6, IL-1β, and TNFα) was measured by real-time PCR. Biliary TGF-β1 and hepatic CD68 (Kupffer cell marker) expression was assessed using IHC. α7-nAChR immunoreactivity was observed in both bile ducts and HSCs and increased following BDL. α7-nAChR-/- BDL mice exhibited decreased: (i) bile duct mass, liver fibrosis, and inflammation; and (ii) immunoreactivity of TGF-1 as well as expression of fibrosis genes compared to WT BDL mice. α7-nAChR activation triggers biliary proliferation and liver fibrosis and may be a therapeutic target in managing extra-hepatic biliary obstruction.
Cholestasis‐induced adaptive remodeling of interlobular bile ducts
Damle‐Vartak, Amruta; Richter, Beate; Dirsch, Olaf; Dahmen, Uta; Hammad, Seddik
2016-01-01
Cholestasis is a common complication in liver diseases that triggers a proliferative response of the biliary tree. Bile duct ligation (BDL) is a frequently used model of cholestasis in rodents. To determine which changes occur in the three‐dimensional (3D) architecture of the interlobular bile duct during cholestasis, we used 3D confocal imaging, surface reconstructions, and automated image quantification covering a period up to 28 days after BDL. We show a highly reproducible sequence of interlobular duct remodeling, where cholangiocyte proliferation initially causes corrugation of the luminal duct surface, leading to an approximately five‐fold increase in surface area. This is analogous to the function of villi in the intestine or sulci in the brain, where an expansion of area is achieved within a restricted volume. The increase in surface area is further enhanced by duct branching, branch elongation, and loop formation through self‐joining, whereby an initially relatively sparse mesh surrounding the portal vein becomes five‐fold denser through elongation, corrugation, and ramification. The number of connections between the bile duct and the lobular bile canalicular network by the canals of Hering decreases proportionally to the increase in bile duct length, suggesting that no novel connections are established. The diameter of the interlobular bile duct remains constant after BDL, a response that is qualitatively distinct from that of large bile ducts, which tend to enlarge their diameters. Therefore, volume enhancement is only due to net elongation of the ducts. Because curvature and tortuosity of the bile duct are unaltered, this enlargement of the biliary tree is caused by branching and not by convolution. Conclusion: BDL causes adaptive remodeling that aims at optimizing the intraluminal surface area by way of corrugation and branching. (Hepatology 2016;63:951–964) PMID:26610202
Hsin, I-Fang; Hsu, Shao-Jung; Chuang, Chiao-Lin; Huo, Teh-Ia; Huang, Hui-Chun; Lee, Fa-Yauh; Ho, Hsin-Ling; Chang, Shu-Yu; Lee, Shou-Dong
2018-05-17
Liver cirrhosis is associated with increased intrahepatic resistance due to hepatic fibrosis and exaggerated vasoconstriction. Recent studies have indicated that proton pump inhibitors (PPIs), in addition to acid suppression, modulate vasoactive substances and vasoresponsiveness. PPIs are frequently prescribed in patients with cirrhosis due to a higher prevalence of peptic ulcers, however other impacts are unknown. Liver cirrhosis was induced in Sprague-Dawley rats with common bile duct ligation (BDL). On the 29th day after BDL and after hemodynamic measurements, the intrahepatic vascular responsiveness to high concentrations of endothelin-1 (ET-1) was evaluated after preincubation with (1) Krebs solution (vehicle), (2) esomeprazole (30 μM), or (3) esomeprazole plus N ω -nitro l-arginine (NNA, a non-selective NO synthase (NOS) inhibitor, 10 -4 M). After perfusion, the hepatic protein expressions of endothelial NOS (eNOS), inducible NOS (iNOS), cyclooxygenase (COX)-1, COX-2, endothelin-1, DDAH-1 (dimethylarginine dimethylaminohydrolase-1, ADMA inhibitor), DDAH-2, ADMA (asymmetrical dimethyl arginine, NOS inhibitor) were evaluated. In the chronic model, the BDL rats received (1) vehicle; or (2) esomeprazole (3.6 mg/kg/day, oral gavage) from the 1st to 28th day after BDL. On the 29th day and after hemodynamic measurements, plasma liver biochemistry and liver fibrosis were evaluated. Esomeprazole did not affect hepatic ET-1 vasoresponsiveness. The hepatic protein expressions of the aforementioned factors were not significantly different among the groups. There were no significant differences in hemodynamics, liver biochemistry and hepatic fibrosis after chronic esomeprazole administration. PPIs did not affect hepatic vasoresponsiveness or the release of vasoactive substances. Furthermore, they did not influence hemodynamics, liver biochemistry or severity of hepatic fibrosis in the cirrhotic rats. Copyright © 2018. Published by Elsevier Taiwan LLC.
Alaca, Nuray; Özbeyli, Dilek; Uslu, Serap; Şahin, Hasan Hüseyin; Yiğittürk, Gürkan; Kurtel, Hızır; Öktem, Gülperi; Çağlayan Yeğen, Berrak
2017-11-01
Cholestasis, which results in hepatic cell death, fibrosis, cirrhosis, and eventually liver failure, is associated with oxidative stress. The aim of this study was to evaluate the effects of milk thistle (MT, Silybum marianum) and ursodeoxycholic acid (UDCA) or their combination on the activation of hepatic stem cells and on the severity of cholestasis liver injury in rats. Under anesthesia, bile ducts of female Sprague Dawley rats were ligated (BDL) or had sham operation. BDL rats were administered saline, UDCA (15 mg/kg/d), MT (600 mg/kg/d), or UDCA+MT by gavage for 10 days. On the 11th day, rats were sacrificed and blood and liver samples were obtained. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic malondialdehyde (MDA) levels, and myeloperoxidase (MPO) activity were measured. Hepatic injury, a-smooth muscle actin expression, and stem cell markers c-kit, c-Myc, Oct3/4, and SSEA-1 were histologically determined. Histological scores, serum ALT, and hepatic MDA levels were higher in BDL group than in the sham rats, while all treatments significantly reduced these levels. The reduction in ALT was significantly greater in UCDA+MT-treated group than in other treatment groups. c-Kit, c-Myc, Oct3/4, and SSEA-1 were increased in saline-treated BDL group with respect to sham-operated control group, and these markers were significantly reduced in all treatment groups. In addition to a modulatory effect on the stem cell-induced regenerative response of the liver, UDCA, MT, and their combination demonstrated similar anti-inflammatory and antiproliferative effects on cholestasis-induced hepatic injury.
Farrar, Christian T; DePeralta, Danielle K; Day, Helen; Rietz, Tyson A; Wei, Lan; Lauwers, Gregory Y; Keil, Boris; Subramaniam, Arun; Sinskey, Anthony J; Tanabe, Kenneth K; Fuchs, Bryan C; Caravan, Peter
2015-09-01
Liver biopsy, the gold standard for assessing liver fibrosis, suffers from limitations due to sampling error and invasiveness. There is therefore a critical need for methods to non-invasively quantify fibrosis throughout the entire liver. The goal of this study was to use molecular Magnetic Resonance Imaging (MRI) of Type I collagen to non-invasively image liver fibrosis and assess response to rapamycin therapy. Liver fibrosis was induced in rats by bile duct ligation (BDL). MRI was performed 4, 10, or 18 days following BDL. Some BDL rats were treated daily with rapamycin starting on day 4 and imaged on day 18. A three-dimensional (3D) inversion recovery MRI sequence was used to quantify the change in liver longitudinal relaxation rate (ΔR1) induced by the collagen-targeted probe EP-3533. Liver tissue was subjected to pathologic scoring of fibrosis and analyzed for Sirius Red staining and hydroxyproline content. ΔR1 increased significantly with time following BDL compared to controls in agreement with ex vivo measures of increasing fibrosis. Receiver operating characteristic curve analysis demonstrated the ability of ΔR1 to detect liver fibrosis and distinguish intermediate and late stages of fibrosis. EP-3533 MRI correctly characterized the response to rapamycin in 11 out of 12 treated rats compared to the standard of collagen proportional area (CPA). 3D MRI enabled characterization of disease heterogeneity throughout the whole liver. EP-3533 allowed for staging of liver fibrosis, assessment of response to rapamycin therapy, and demonstrated the ability to detect heterogeneity in liver fibrosis. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
1988-11-01
BENZIDINE 400 81)1 5 BENZO (a) ANTHRACENE 400 ODL 6 BENZ0 (a) PYRENE 400 61 )1 7 BENZO (b) FLUORANTHENE 400 61 )1 a BENZO (ghl) PERYLENE 1003 61 )1 9...BENZO (k) FLUIORANTHENE 400 61 )1 10 815 (2-CHOROEThOXY) METHANE 400 81)1 11 815 (2-CHOROETIIYL) ETHER 400 BDL 12 8(5 (2-CHLOROISOPROPYL) ETHER 400 BDL 13...CHOROPHENYL PHENYL ETHER 400 61 )1 18 CHRYSENE 400 B1)L - 19 DIBEIQO (ah) ANTHRACENE 400 81)1 20 1,2-DICHOROBENZENE 400 81)1 21 1 ,3-DICHLOROBENZENE
D'Alessandro, Donna M; D'Alessandro, Michael P
2007-12-01
A challenge today is how to deliver initial and continuing education on biodefense to military medical providers in a manner that can be integrated into their workflow and lifestyle. A summative evaluation of a prototypical biodefense digital library (BDL) and learning collaboratory was performed. The BDL posted daily links to biodefense news stories from January 2004 to December 2005. Four evaluations were completed, that is, content evaluation, curriculum comparison with a biodefense graduate program, usage evaluation, and impact factor analysis. News stories (N = 678) came from a broad range of authoritative national and international news sources (N = 178). News stories covered all of the categories in the required and elective formal biodefense graduate program courses. The BDL was consistently displayed on the first page of the top three Internet search engines, meaning that it was among the top 10 authoritative Internet sites on biodefense. Presenting biodefense news stories to busy military medical providers in an organized chronological fashion produces an unstructured biodefense educational curriculum that unfolds in practice and becomes an educational resource that is ultimately well regarded and may be efficient to use.
Shi, Fang; Sheng, Qin; Xu, Xinhua; Huang, Wenli; Kang, Y James
2015-09-01
Metallothionein (MT) gene therapy leads to resolution of liver fibrosis in mouse model, in which the activation of collagenases is involved in the regression of liver fibrosis. MT plays a critical role in zinc sequestration in the liver suggesting its therapeutic effect would be mediated by zinc. The present study was undertaken to test the hypothesis that zinc supplementation suppresses liver fibrosis. Male Kunming mice subjected to bile duct ligation (BDL) resulted in liver fibrosis as assessed by increased α-smooth muscle actin (α-SMA) and collagen I production/deposition in the liver. Zinc supplementation was introduced 4 weeks after BDL surgery via intragastric administration once daily for 2 weeks resulting in a significant reduction in the collagen deposition in the liver and an increase in the survival rate. Furthermore, zinc suppressed gene expression of α-SMA and collagen I and enhanced the capacity of collagen degradation, as determined by the increased activity of total collagenases and elevated mRNA and protein levels of MMP13. Therefore, the results demonstrate that zinc supplementation suppresses BDL-induced liver fibrosis through both inhibiting collagen production and enhancing collagen degradation. © 2014 by the Society for Experimental Biology and Medicine.
Xu, Yuquan; Zhou, Tong; Zhang, Shuwei; Espinosa-Artiles, Patricia; Wang, Luoyi; Zhang, Wei; Lin, Min; Gunatilaka, A A Leslie; Zhan, Jixun; Molnár, István
2014-08-26
Combinatorial biosynthesis aspires to exploit the promiscuity of microbial anabolic pathways to engineer the synthesis of new chemical entities. Fungal benzenediol lactone (BDL) polyketides are important pharmacophores with wide-ranging bioactivities, including heat shock response and immune system modulatory effects. Their biosynthesis on a pair of sequentially acting iterative polyketide synthases (iPKSs) offers a test case for the modularization of secondary metabolic pathways into "build-couple-pair" combinatorial synthetic schemes. Expression of random pairs of iPKS subunits from four BDL model systems in a yeast heterologous host created a diverse library of BDL congeners, including a polyketide with an unnatural skeleton and heat shock response-inducing activity. Pairwise heterocombinations of the iPKS subunits also helped to illuminate the innate, idiosyncratic programming of these enzymes. Even in combinatorial contexts, these biosynthetic programs remained largely unchanged, so that the iPKSs built their cognate biosynthons, coupled these building blocks into chimeric polyketide intermediates, and catalyzed intramolecular pairing to release macrocycles or α-pyrones. However, some heterocombinations also provoked stuttering, i.e., the relaxation of iPKSs chain length control to assemble larger homologous products. The success of such a plug and play approach to biosynthesize novel chemical diversity bodes well for bioprospecting unnatural polyketides for drug discovery.
NASA Astrophysics Data System (ADS)
Paraguassú, Gardênia Matos; da Costa Lino, Maíra Doria Martinez; de Carvalho, Fabíola Bastos; Cangussu, Maria Cristina; Pinheiro, Antônio Luiz Barbosa; Ramalho, Luciana Maria Pedreira
2012-09-01
Previous studies have shown positive effects of Low Level Laser Therapy (LLLT) on the repair of bone defects, but there is a few that associates bone healing in the presence of a metabolic disorder such as Diabetes Mellitus, a systemic disorder associated to impair of the repair of different tissues. The aim of this study was to assess, histologically, the repair of surgical defects created in the femur of diabetic and non-diabetic rats treated or not with LLLT (λ780nm, 70mW, CW, o/˜0.4mm, 16J/cm2 per session) associated or not to the use of a biomaterial. Surgical tibial bone defects were created in 60 animals that were divided into 4 groups: Group B (non-diabetic + biomaterial); Group BL (non-diabetic + biomaterial + LLLT); Group BD (diabetic + biomaterial); Group BDL (diabetic + biomaterial + LLLT). The irradiated group received 16 J/cm2 per session divided into 4 points around the defect, being the first irradiation carried out immediately after surgery and repeated every 48h for 14 days. The animals were killed 15, 21 and 30 days after surgery. The specimens underwent a semi-quantitative analysis. The results showed inflammation more intense in the BD and BDL groups than in the B and BL groups in the period of 15 days (p = 0.02), however the cortical repair in the BDL group was below 25% in more than half of the specimens, while in the BD group, the repair was more than to 25% in all specimens. At 30 days, both osteoblastic activity and collagen deposition were significantly higher in the B group when compared to the BD group (p=0.04). Bone deposition was significantly higher in the BL group (p=0.023) than in BDL group. It is concluded that LLLT has a positive biomodulative effect in the early stages of the healing process of bone defects grafted with biomaterial in diabetic and non-diabetic rats.
Chai, Jin; Du, Xiaohuang; Chen, Sheng; Feng, XinChan; Cheng, Ying; Zhang, Liangjun; Gao, Yu; Li, Shaoxue; He, Xiaochong; Wang, Rongquan; Zhou, Xiangdong; Yang, Yong; Luo, Weizao; Chen, Wensheng
2015-01-01
Background & aims: Oleanolic acid is abundantly distributed in Swertia mussotii Franch, a Chinese traditional herb for the treatment of jaundice. However, the hepatoprotective role of oleanolic acid in obstructive cholestasis and its underlying molecular mechanism are unclear. Methods: Normal rats and bile duct-ligated (BDL) rats were given oleanolic acid and serum biochemistry, bile salts, and pro-inflammatory factors were measured, as well as the expression levels of liver bile acid synthesis and detoxification enzymes, membrane transporters, nuclear receptors, and transcriptional factors. Results: Oral administration of oleanolic acid at 100 mg/kg did not cause rat liver injury. However, it significantly reduced the serum levels of alanine aminotransferase (ALT) on days 7 and 14, aspartate aminotransferase (AST) and TNF-α on day 14, and alkaline phosphatase (ALP) and IL-1β on days 3, 7, and 14 in the BDL rats. Furthermore, the serum levels of total bile acid (TBA) and bile acids, including CDCA, CA, DCA, and Tα/βMCA were significantly reduced by oleanolic acid on day 3 in the BDL rats. In addition, the expression levels of detoxification enzymes Cyp3a, Ugt2b, Sult2a1, Gsta1-2, and Gstm1-3, membrane transporters Mrp3, Mrp4, Ostβ, Mdr1, Mdr2, and Bsep, nuclear receptors Pxr, Vdr, Hnf4α, Rxrα, Rarα, Lxr, and Lrh-1, and transcriptional factors Nrf2, Hnf3β, and Ahr were significantly increased in oleanolic acid-treated rats. Conclusion: We demonstrated that the oral administration of oleanolic acid attenuates liver injury, inflammation, and cholestasis in BDL rats. The anti-cholestatic effect may be associated with the induction of hepatic detoxification enzymes and efflux transporters mediated by nuclear receptors and transcriptional factors. PMID:25932098
Nanogeochemistry of hydrothermal magnetite
NASA Astrophysics Data System (ADS)
Deditius, Artur P.; Reich, Martin; Simon, Adam C.; Suvorova, Alexandra; Knipping, Jaayke; Roberts, Malcolm P.; Rubanov, Sergey; Dodd, Aaron; Saunders, Martin
2018-06-01
Magnetite from hydrothermal ore deposits can contain up to tens of thousands of parts per million (ppm) of elements such as Ti, Si, V, Al, Ca, Mg, Na, which tend to either structurally incorporate into growth and sector zones or form mineral micro- to nano-sized particles. Here, we report micro- to nano-structural and chemical data of hydrothermal magnetite from the Los Colorados iron oxide-apatite deposit in Chile, where magnetite displays both types of trace element incorporation. Three generations of magnetites (X-Z) were identified with concentrations of minor and trace elements that vary significantly: SiO2, from below detection limit (bdl) to 3.1 wt%; Al2O3, 0.3-2.3 wt%; CaO, bdl-0.9 wt%; MgO, 0.02-2.5 wt%; TiO2, 0.1-0.4 wt%; MnO, 0.04-0.2 wt%; Na2O, bdl-0.4 wt%; and K2O, bdl-0.4 wt%. An exception is V2O3, which is remarkably constant, ranging from 0.3 to 0.4 wt%. Six types of crystalline nanoparticles (NPs) were identified by means of transmission electron microscopy in the trace element-rich zones, which are each a few micrometres wide: (1) diopside, (2) clinoenstatite; (3) amphibole, (4) mica, (5) ulvöspinel, and (6) Ti-rich magnetite. In addition, Al-rich nanodomains, which contain 2-3 wt% of Al, occur within a single crystal of magnetite. The accumulation of NPs in the trace element-rich zones suggest that they form owing to supersaturation from a hydrothermal fluid, followed by entrapment during continuous growth of the magnetite surface. It is also concluded that mineral NPs promote exsolution of new phases from the mineral host, otherwise preserved as structurally bound trace elements. The presence of abundant mineral NPs in magnetite points to a complex incorporation of trace elements during growth, and provides a cautionary note on the interpretation of micron-scale chemical data of magnetite.
Corpus-Based Approaches to Language Description for Specialized Academic Writing
ERIC Educational Resources Information Center
Flowerdew, John
2017-01-01
Language description is a fundamental requirement for second language (L2) syllabus design. The greatest advances in language description in recent decades have been done with the help of electronic corpora. Such language description is the theme of this article. The article first introduces some basic concepts and principles in corpus research.…
Lebensztejn, Dariusz Marek; Daniluk, Urszula; Sobaniec, Piotr; Sendrowski, Krzysztof; Daniluk, Jaroslaw; Debek, Wojciech
2017-01-01
Purpose Recently, it has been emphasized that hepatic progenitor/oval cells (HPCs) are significantly involved in liver fibrogenesis. We evaluated the multipotential population of HPCs by transmission electron microscope (TEM), including relations with adherent hepatic nonparenchymal cells (NPCs) in rats with biliary fibrosis induced by bile duct ligation (BDL). Methods The study used 6-week-old Wistar Crl: WI(Han) rats after BDL for 1, 6, and 8 weeks. Results Current ultrastructural analysis showed considerable proliferation of HPCs in experimental intensive biliary fibrosis. HPCs formed proliferating bile ductules and were scattered in periportal connective tissue. We distinguished 4 main types of HPCs: 0, I, II (bile duct-like cells; most common), and III (hepatocyte-like cells). We observed, very seldom presented in literature, cellular interactions between HPCs and adjacent NPCs, especially commonly found transitional hepatic stellate cells (T-HSCs) and Kupffer cells/macrophages. We showed the phenomenon of penetration of the basement membrane of proliferating bile ductules by cytoplasmic processes sent by T-HSCs and the formation of direct cell-cell contact with ductular epithelial cells related to HPCs. Conclusions HPC proliferation induced by BDL evidently promotes portal fibrogenesis. Better understanding of the complex cellular interactions between HPCs and adjacent NPCs, especially T-HSCs, may help develop antifibrotic therapies in the future. PMID:28769978
A study on polypropylene encapsulation and solidification of textile sludge.
Kumari, V Krishna; Kanmani, S
2011-10-01
The textile sludge is an inevitable solid waste from the textile wastewater process and is categorised under toxic substances by statutory authorities. In this study, an attempt has been made to encapsulate and solidify heavy metals and dyes present in textile sludge using polypropylene and Portland cement. Sludge samples (2 Nos.) were characterized for pH (8.5, 9.5), moisture content (1.5%, 1.96%) and chlorides (245mg/L, 425.4mg/L). Sludge samples were encapsulated into polypropylene with calcium carbonate (additive) and solidified with cement at four different proportions (20, 30, 40, 50%) of sludge. Encapsulated and solidified cubes were made and then tested for compressive strength. Maximum compressive strength of cubes (size, 7.06cm) containing sludge (50%) for encapsulation (16.72 N/mm2) and solidification (18.84 N/mm2) was more than that of standard M15 mortar cubes. The leachability of copper, nickel and chromium has been effectively reduced from 0.58 mg/L, 0.53 mg/L and 0.07 mg/L to 0.28mg/L, 0.26mg/L and BDL respectively in encapsulated products and to 0.24mg/L, BDL and BDL respectively in solidified products. This study has shown that the solidification process is slightly more effective than encapsulation process. Both the products were recommended for use in the construction of non-load bearing walls.
Hardware description languages
NASA Technical Reports Server (NTRS)
Tucker, Jerry H.
1994-01-01
Hardware description languages are special purpose programming languages. They are primarily used to specify the behavior of digital systems and are rapidly replacing traditional digital system design techniques. This is because they allow the designer to concentrate on how the system should operate rather than on implementation details. Hardware description languages allow a digital system to be described with a wide range of abstraction, and they support top down design techniques. A key feature of any hardware description language environment is its ability to simulate the modeled system. The two most important hardware description languages are Verilog and VHDL. Verilog has been the dominant language for the design of application specific integrated circuits (ASIC's). However, VHDL is rapidly gaining in popularity.
Structured Natural-Language Descriptions for Semantic Content Retrieval of Visual Materials.
ERIC Educational Resources Information Center
Tam, A. M.; Leung, C. H. C.
2001-01-01
Proposes a structure for natural language descriptions of the semantic content of visual materials that requires descriptions to be (modified) keywords, phrases, or simple sentences, with components that are grammatical relations common to many languages. This structure makes it easy to implement a collection's descriptions as a relational…
NASA Astrophysics Data System (ADS)
Lin, Jian; Pan, Shiying; Zheng, Wei; Huang, Zhiwei
2013-10-01
We apply the polarization-resolved second-harmonic generation (PR-SHG) microscopy to investigate the changes of collagen typings (type I vs type III) and collagen fibril orientations of liver tissue in bile-duct-ligation (BDL) rat models. The PR-SHG results show that the second-order susceptibility tensor ratios (χ31/χ15 and χ33/χ15) of collagen fibers increase with liver fibrotic progression after BDL surgery, reflecting an increase of the type III collagen component with the severity of liver fibrosis; and the square root of the collagen type III to type I ratio linearly correlates (R2 = 0.98) with histopathological scores. Furthermore, the collagen fibril orientations become more random with liver fibrosis transformation as compared to normal liver tissue. This work demonstrates that PR-SHG microscopy has the potential for label-free diagnosis and characterization of liver fibrosis based on quantitative analysis of collagen typings and fibril orientations.
Assessment of fibrotic liver disease with multimodal nonlinear optical microscopy
NASA Astrophysics Data System (ADS)
Lu, Fake; Zheng, Wei; Tai, Dean C. S.; Lin, Jian; Yu, Hanry; Huang, Zhiwei
2010-02-01
Liver fibrosis is the excessive accumulation of extracellular matrix proteins such as collagens, which may result in cirrhosis, liver failure, and portal hypertension. In this study, we apply a multimodal nonlinear optical microscopy platform developed to investigate the fibrotic liver diseases in rat models established by performing bile duct ligation (BDL) surgery. The three nonlinear microscopy imaging modalities are implemented on the same sectioned tissues of diseased model sequentially: i.e., second harmonic generation (SHG) imaging quantifies the contents of the collagens, the two-photon excitation fluorescence (TPEF) imaging reveals the morphology of hepatic cells, while coherent anti-Stokes Raman scattering (CARS) imaging maps the distributions of fats or lipids quantitatively across the tissue. Our imaging results show that during the development of liver fibrosis (collagens) in BDL model, fatty liver disease also occurs. The aggregated concentrations of collagen and fat constituents in liver fibrosis model show a certain correlationship between each other.
2015-01-01
The phytotoxic fungal polyketides lasiodiplodin and resorcylide inhibit human blood coagulation factor XIIIa, mineralocorticoid receptors, and prostaglandin biosynthesis. These secondary metabolites belong to the 12-membered resorcylic acid lactone (RAL12) subclass of the benzenediol lactone (BDL) family. Identification of genomic loci for the biosynthesis of lasiodiplodin from Lasiodiplodia theobromae and resorcylide from Acremonium zeae revealed collaborating iterative polyketide synthase (iPKS) pairs whose efficient heterologous expression in Saccharomyces cerevisiae provided a convenient access to the RAL12 scaffolds desmethyl-lasiodiplodin and trans-resorcylide, respectively. Lasiodiplodin production was reconstituted in the heterologous host by co-expressing an O-methyltransferase also encoded in the lasiodiplodin cluster, while a glutathione-S-transferase was found not to be necessary for heterologous production. Clarification of the biogenesis of known resorcylide congeners in the heterologous host helped to disentangle the roles that biosynthetic irregularities and chemical interconversions play in generating chemical diversity. Observation of 14-membered RAL homologues during in vivo heterologous biosynthesis of RAL12 metabolites revealed “stuttering” by fungal iPKSs. The close global and domain-level sequence similarities of the orthologous BDL synthases across different structural subclasses implicate repeated horizontal gene transfers and/or cluster losses in different fungal lineages. The absence of straightforward correlations between enzyme sequences and product structural features (the size of the macrocycle, the conformation of the exocyclic methyl group, or the extent of reduction by the hrPKS) suggest that BDL structural variety is the result of a select few mutations in key active site cavity positions. PMID:24597618
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gu, Lina; Tao, Xufeng; Xu, Youwei
Oxidative stress is involved in hepatic stellate cells (HSCs) activation and extracellular matrix overproduction. We previously reported the promising effects of dioscin against CCl{sub 4}-induced liver fibrosis, but its effects and mechanisms on BDL- and DMN-induced liver fibrosis remain unknown. The results in the present study indicated that dioscin significantly inhibited HSCs activation and attenuated hepatic fibrosis in rats. Furthermore, dioscin markedly up-regulated the levels of sirtuin 1 (Sirt1), HO-1, GST, GCLC and GCLM via increasing the nuclear translocation of nuclear erythroid factor 2-related factor 2 (Nrf2), which in turn inhibited mitogen-activated protein kinase 14 (p38 MAPK) phosphorylation and reducedmore » the levels of COL1A1, COL3A1, α-SMA and fibronectin. These results were further validated by knockdown of Sirt1 and Nrf2 using siRNAs silencing, and abrogation of p38 MAPK using SB-203580 (a p38 MAPK inhibitor) in HSC-T6 and LX-2 cells. Collectively, our findings confirmed the potent effects of dioscin against liver fibrosis and also provided novel insights into the mechanisms of this compound as a candidate for the prevention of liver fibrosis in the future. - Highlights: • Dioscin showed potent effects against BDL- and DMN-induced liver fibrosis in rats. • Dioscin significantly suppressed oxidative stress. • Dioscin triggered Sirt1/Nrf2-mediated inhibition of p38 MAPK pathway. • Dioscin should be developed as a novel candidate to treat liver fibrosis.« less
Vasopressin regulates the growth of the biliary epithelium in polycystic liver disease
Mancinelli, Romina; Franchitto, Antonio; Glaser, Shannon; Vetuschi, Antonella; Venter, Julie; Sferra, Roberta; Pannarale, Luigi; Olivero, Francesca; Carpino, Guido; Alpini, Gianfranco; Onori, Paolo; Gaudio, Eugenio
2017-01-01
The neurohypophysial hormone arginine vasopressin (AVP) acts by three distinct receptor subtypes: V1a, V1b, and V2. In the liver, AVP is involved in ureogenesis, glycogenolysis, neoglucogenesis and regeneration. No data exist about the presence of AVP in the biliary epithelium. Cholangiocytes are the target cells in a number of animal models of cholestasis, including bile duct ligation (BDL), and in several human pathologies, such as polycystic liver disease characterized by the presence of cysts that bud from the biliary epithelium. In vivo, liver fragments from normal and BDL mice and rats as well as liver samples from normal and ADPKD patients were collected to evaluate: (i) intrahepatic bile duct mass by immunohistochemistry for cytokeratin-19; and (ii) expression of V1a, V1b and V2 by immunohistochemistry, immunofluorescence and real-time PCR. In vitro, small and large mouse cholangiocytes, H69 (non-malignant human cholangiocytes) and LCDE (human cholangiocytes from the cystic epithelium) were stimulated with vasopressin in the absence/presence of AVP antagonists such as OPC-31260 and Tolvaptan, before assessing cellular growth by MTT assay and cAMP levels. Cholangiocytes express V2 receptor that was upregulated following BDL and in ADPKD liver samples. Administration of AVP increased proliferation and cAMP levels of small cholangiocytes and LCDE cells. We found no effect in the proliferation of large mouse cholangiocytes and H69 cells. Increases were blocked by preincubation with the AVP antagonists. These results showed that AVP and its receptors may be important in the modulation of the proliferation rate of the biliary epithelium. PMID:27571215
Kobeissi, M A; El-Samad, O; Rachidi, I
2013-03-01
Measurements of specific activities (Bq kg(-1)) of gamma-emissions from radioactive nuclides, (238)U, (226)Ra, (214)Bi, (232)Th, (212)Pb and (40)K, contained in 28 granite types, used as building materials in indoors in Lebanon, were performed on the powdered granites. The concentration of the nuclides, (226)Ra, (232)Th and (40)K, in the granites varied from below detection level (BDL) to 494 Bq kg(-1), BDL to 157.2 Bq kg(-1) and BDL to 1776 Bq kg(-1), respectively. (226)Ra concentration equivalents, C(Raeq), were obtained and ranged between 37 and 591 Bq kg(-1), with certain values above the allowed limit of 370 Bq kg(-1). Calculated annual gamma-absorbed dose in air, D(aR), varied from 17.7 to 274.5 (nGy h(-1)). Annual effective dose, E (mSv y(-1)), of gamma radiations related to the studied granites and absorbed by the inhabitants was evaluated. E (mSv y(-1)) ranged from 0.09 to 1.35 mSv y(-1). Some granite types produced E above the allowed limit of 1 mSv y(-1) set by ICRP. Values of (222)Rn mass exhalation rate, E(M) (mBq kg(-1)h(-1))(,) in granite powder were obtained using the CR-39 detector technique. Diffusion factors, f, in 23 granite types were calculated with f ranging between (0.1 ± 0.02)×10(-2) and (6.6 ± 1.01)×10(-2).
DOE Office of Scientific and Technical Information (OSTI.GOV)
Takemura, Takayo; Yoshida, Yuichi; Kiso, Shinichi, E-mail: kiso@gh.med.osaka-u.ac.jp
Highlights: •HB-EGF expression was increased during the development of liver fibrosis. •Conditional HB-EGF knockout mouse showed enhanced experimental liver fibrosis. •HB-EGF antagonized TGF-β-induced activation of hepatic stellate cells. •We report a possible protective role of HB-EGF in cholestatic liver fibrosis. -- Abstract: Our aims were to evaluate the involvement of heparin-binding EGF-like growth factor (HB-EGF) in liver fibrogenesis of humans and mice and to elucidate the effect of HB-EGF deficiency on cholestatic liver fibrosis using conditional HB-EGF knockout (KO) mice. We first demonstrated that gene expression of HB-EGF had a positive significant correlation with that of collagen in human fibroticmore » livers, and was increased in bile duct ligation (BDL)-induced fibrotic livers in mouse. We then generated conditional HB-EGF knockout (KO) mice using the interferon inducible Mx-1 promoter driven Cre recombinase transgene and wild type (WT) and KO mice were subjected to BDL. After BDL, KO mice exhibited enhanced liver fibrosis with increased expression of collagen, compared with WT mice. Finally, we used mouse hepatic stellate cells (HSCs) to examine the role of HB-EGF in the activation of these cells and showed that HB-EGF antagonized TGF-β-induced gene expression of collagen in mouse primary HSCs. Interestingly, HB-EGF did not prevent the TGF-β-induced nuclear accumulation of Smad3, but did lead to stabilization of the Smad transcriptional co-repressor TG-interacting factor. In conclusion, our data suggest a possible protective role of HB-EGF in cholestatic liver fibrosis.« less
Vasopressin regulates the growth of the biliary epithelium in polycystic liver disease.
Mancinelli, Romina; Franchitto, Antonio; Glaser, Shannon; Vetuschi, Antonella; Venter, Julie; Sferra, Roberta; Pannarale, Luigi; Olivero, Francesca; Carpino, Guido; Alpini, Gianfranco; Onori, Paolo; Gaudio, Eugenio
2016-11-01
The neurohypophysial hormone arginine vasopressin (AVP) acts by three distinct receptor subtypes: V1a, V1b, and V2. In the liver, AVP is involved in ureogenesis, glycogenolysis, neoglucogenesis and regeneration. No data exist about the presence of AVP in the biliary epithelium. Cholangiocytes are the target cells in a number of animal models of cholestasis, including bile duct ligation (BDL), and in several human pathologies, such as polycystic liver disease characterized by the presence of cysts that bud from the biliary epithelium. In vivo, liver fragments from normal and BDL mice and rats as well as liver samples from normal and ADPKD patients were collected to evaluate: (i) intrahepatic bile duct mass by immunohistochemistry for cytokeratin-19; and (ii) expression of V1a, V1b and V2 by immunohistochemistry, immunofluorescence and real-time PCR. In vitro, small and large mouse cholangiocytes, H69 (non-malignant human cholangiocytes) and LCDE (human cholangiocytes from the cystic epithelium) were stimulated with vasopressin in the absence/presence of AVP antagonists such as OPC-31260 and Tolvaptan, before assessing cellular growth by MTT assay and cAMP levels. Cholangiocytes express V2 receptor that was upregulated following BDL and in ADPKD liver samples. Administration of AVP increased proliferation and cAMP levels of small cholangiocytes and LCDE cells. We found no effect in the proliferation of large mouse cholangiocytes and H69 cells. Increases were blocked by preincubation with the AVP antagonists. These results showed that AVP and its receptors may be important in the modulation of the proliferation rate of the biliary epithelium.
What Is Grammar and Why Teach It?
ERIC Educational Resources Information Center
Greenbaum, Sidney
The word "grammar" can be used in many ways: a general theory of language description; a theory for describing one language; a description of a particular language, either in the form of a book (an "English grammar") or the contents of that book; an ideal as opposed to actual description of a language; the properties and processes of a language…
Younis, N; Shaheen, Mohamed A; Abdallah, Marwa H
2016-07-01
Some nano-formulations of silymarin (SM), a drug commonly used for liver diseases, were developed to overcome its poor solubility and poor bioavailability; antifibrotic effect of these formulations has not been tested yet. In this study we aimed to formulate and evaluate silymarin-loaded Eudragit(®) RS100 nanoparticles (SMnps) and to test the capability of SMnps to reverse an established fibrosis model. SMnps were prepared by solvent evaporation and nano-precipitation techniques. The influence of drug:polymer ratio, concentration of surfactant in the aqueous phase on particle size, drug entrapment efficiency (EE) % and in vitro drug releases were investigated. For in vivo evaluation, bile duct ligated (BDL)-rats were treated with either SM or SMnps every other day (125mg/kg) orally for 3 weeks started 3 weeks after BDL. Liver function tests, oxidative stress and fibrosis/fibrogenesis process were evaluated using biochemical and histopathological techniques. The formulation No (F4) of SMnps showed an average particle size of 632.28±12.15nm, a drug EE% of 89.47±1.65% and released the drug in a prolonged manner over 24h. The prepared SMnps were nearly spherical with smooth surfaces. In BDL-rats, treatments with either SM or SMnps corrected liver function and oxidative stress. Only SMnps was able to reverse the induced fibrosis; SMnps significantly decreased serum tumor necrosis factor- α (TNF-α), serum transforming growth factor- β1 (TGF-β1), hepatic hydroxyproline and downregulated the hepatic expression of tissue inhibitor metalloproteinase-1 (TIMP-1) and cytokeratin-19 (CK-19), whilst increased hepatic hepatocytes growth factor (HGF) and upregulated the hepatic expression of matrix metalloproteinase-2 (MMP-2) and increased MMP-2/TIMP-1 ratio at mRNA level. Livers of rats treated with SMnps showed very little collagen in ECM and restored hepatic architecture as compared to either BDL rats or rats treated with SM. Formulation of silymarin as nanoparticles improved its ability to resolve cholestasis-induced liver fibrosis by restoring hepatic regenerative capabilities. Therefore, formulation of SMnps may represent a step forward in the field of anti-fibrotic drug development. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
The language parallel Pascal and other aspects of the massively parallel processor
NASA Technical Reports Server (NTRS)
Reeves, A. P.; Bruner, J. D.
1982-01-01
A high level language for the Massively Parallel Processor (MPP) was designed. This language, called Parallel Pascal, is described in detail. A description of the language design, a description of the intermediate language, Parallel P-Code, and details for the MPP implementation are included. Formal descriptions of Parallel Pascal and Parallel P-Code are given. A compiler was developed which converts programs in Parallel Pascal into the intermediate Parallel P-Code language. The code generator to complete the compiler for the MPP is being developed independently. A Parallel Pascal to Pascal translator was also developed. The architecture design for a VLSI version of the MPP was completed with a description of fault tolerant interconnection networks. The memory arrangement aspects of the MPP are discussed and a survey of other high level languages is given.
Evaluation of the 13C-octanoate breath test as a surrogate marker of liver damage in animal models.
Shalev, Tamar; Aeed, Hussein; Sorin, Vladimir; Shahmurov, Mark; Didkovsky, Elena; Ilan, Yaron; Avni, Yona; Shirin, Haim
2010-06-01
Octanoate (also known as sodium octanoate), a medium-chain fatty acid metabolized in the liver, is a potential substrate for non-invasive breath testing of hepatic mitochondrial beta-oxidation. We evaluated the 13C-octanoate breath test (OBT) for assessing injury in acute hepatitis and two rat models of liver cirrhosis, first testing octanoate absorption (per os or intraperitoneally (i.p.)) in normal rats. We then induced acute hepatitis with thioacetamide (300 mg/kg/i.p., 24-h intervals). Liver injury end points were serum aminotransferase levels and 13C-OBT (24 and 48 h following initial injection). Thioacetamide (200 mg/kg/i.p., twice per week, 12 weeks) was used to induce liver cirrhosis. OBT and liver histological assessment were performed every 4 weeks. Bile duct ligation (BDL) was used to induce cholestatic liver injury. We completed breath tests with 13C-OBT and 13C-methacetin (MBID), liver biochemistry, and liver histology in BDL and sham-operated rats (baseline, 6, 14, 20 days post-BDL). Octanoate absorbs well by either route. Peak amplitudes and cumulative percentage dose recovered at 30 and 60 min (CPDR30/60), but not peak time, correlated with acute hepatitis. Fibrosis stage 3 at week 8 significantly correlated with each OBT parameter. Cholestatic liver injury (serum bilirubin, ALP, gamma-GT, liver histology) was associated with significant suppression of the maximal peak values and CPDR30/60, respectively (P<0.05),using MBID but not 13C-octanoate. OBT is sensitive for potentially evaluating liver function in rat models of acute hepatitis and thioacetamide-induced liver cirrhosis but not in cholestatic liver injury. The MBID test may be better for evaluation of cholestatic liver disease in this model.
Mu, Y P; Zhang, X; Xu, Y; Fan, W W; Li, X W; Chen, J M; Chen, G F; Liu, P
2017-06-08
Objective: To investigate differentiation direction of hepatic progenitor cells (HPCs) in cholestatic liver fibrosis (CLF), and the role of Notch signaling pathway in the differentiation of HPCs. Methods: A CLF rat model was established by bile duct ligation (BDL) followed by monitoring changes of Notch signal pathway and the cellular origin of proliferating cholangiocytes. After intraperitoneal injection of DAPT (a Notch signaling inhibitor) after bile duct ligation, the progress of liver fibrosis and the proliferation of cholangiocytes after inhibition of the Notch pathway were analyzed. Results: Data showed that bile duct proliferation gradually increased along with inflammatory cell infiltration and proliferating bile duct cells surrounded by abundant collagen in the BDL group. Immunostaining confirmed markedly increased expression of CK19, OV6, Sox9 and EpCAM. In addition, RT-PCR results showed that Notch signaling pathway was activated significantly. Once the Notch signaling pathway was inhibited by DAPT, bile duct proliferation markedly suppressed along with significantly decreased the mRNA expression of CK19, OV6, Sox9 and EpCAM, compared with BDL group [(10.2±0.7) vs . (22.3±0.8), (7.6±1.5) vs . (18.1±3.7), (1.4±0.4) vs . (4.1±1.1), (1.3±0.3) vs . (5.0±1.4), respectively, P <0.01]. Moreover, liver fibrosis was also reduced significantly. Conclusion: Notch signaling activation is required for HPCs differentiation into cholangiocytes in CLF and inhibition of the Notch signaling pathway may offer a therapeutic option for treating CLF.
Zhang, Shuai; Wang, Zhecheng; Zhu, Jie; Xu, Ting; Zhao, Yan; Zhao, Huanyu; Tang, Fan; Li, Zhenlu; Zhou, Junjun; Gao, Dongyan; Tian, Xiaofeng; Yao, Jihong
2018-01-01
Fibrosis reflects a progression to liver cancer or cirrhosis of the liver. Recent studies have shown that high-mobility group box-1 (HMGB1) plays a major role in hepatic injury and fibrosis. Carnosic acid (CA), a compound extracted from rosemary, has been reported to alleviate alcoholic and non-alcoholic fatty liver injury. CA can also alleviate renal fibrosis. We hypothesized that CA might exert anti-liver fibrosis properties through an HMGB1-related pathway, and the results of the present study showed that CA treatment significantly protected against hepatic fibrosis in a bile duct ligation (BDL) rat model. CA reduced the liver expression of α-smooth muscle actin (α-SMA) and collagen 1 (Col-1). Importantly, we found that CA ameliorated the increase in HMGB1 and Toll-like receptor 4 (TLR4) caused by BDL, and inhibited NF-κB p65 nuclear translocation in fibrotic livers. In vitro, CA inhibited LX2 cell activation by inhibiting HMGB1/TLR4 signaling pathway. Furthermore, miR-29b-3p decreased HMGB1 expression, and a dual-luciferase assay validated these results. Moreover, CA down-regulated HMGB1 and inhibited LX2 cell activation, and these effects were significantly counteracted by antago-miR-29b-3p, indicating that the CA-mediated inhibition of HMGB1 expression might be miR-29b-3p dependent. Collectively, the results demonstrate that a miR-29b-3p/HMGB1/TLR4/NF-κB signaling pathway, which can be modulated by CA, is important in liver fibrosis, and indicate that CA might be a prospective therapeutic drug for liver fibrosis. PMID:29403377
Michelotti, Gregory A; Tucker, Anikia; Swiderska-Syn, Marzena; Machado, Mariana Verdelho; Choi, Steve S; Kruger, Leandi; Soderblom, Erik; Thompson, J Will; Mayer-Salman, Meredith; Himburg, Heather A; Moylan, Cynthia A; Guy, Cynthia D; Garman, Katherine S; Premont, Richard T; Chute, John P; Diehl, Anna Mae
2016-01-01
Objective The ductular reaction (DR) involves mobilisation of reactive-appearing duct-like cells (RDC) along canals of Hering, and myofibroblastic (MF) differentiation of hepatic stellate cells (HSC) in the space of Disse. Perivascular cells in stem cell niches produce pleiotrophin (PTN) to inactivate the PTN receptor, protein tyrosine phosphatase receptor zeta-1 (PTPRZ1), thereby augmenting phosphoprotein-dependent signalling. We hypothesised that the DR is regulated by PTN/PTPRZ1 signalling. Design PTN-GFP, PTN-knockout (KO), PTPRZ1-KO, and wild type (WT) mice were examined before and after bile duct ligation (BDL) for PTN, PTPRZ1 and the DR. RDC and HSC from WT, PTN-KO, and PTPRZ1-KO mice were also treated with PTN to determine effects on downstream signaling phosphoproteins, gene expression, growth, and migration. Liver biopsies from patients with DRs were also interrogated. Results Although quiescent HSC and RDC lines expressed PTN and PTPRZ1 mRNAs, neither PTN nor PTPRZ1 protein was demonstrated in healthy liver. BDL induced PTN in MF-HSC and increased PTPRZ1 in MF-HSC and RDC. In WT mice, BDL triggered a DR characterised by periportal accumulation of collagen, RDC and MF-HSC. All aspects of this DR were increased in PTN-KO mice and suppressed in PTPRZ1-KO mice. In vitro studies revealed PTN-dependent accumulation of phosphoproteins that control cell-cell adhesion and migration, with resultant inhibition of cell migration. PTPRZ1-positive cells were prominent in the DRs of patients with ductal plate defects and adult cholestatic diseases. Conclusions PTN, and its receptor, PTPRZ1, regulate the DR to liver injury by controlling the migration of resident cells in adult liver progenitor niches. PMID:25596181
Duwaerts, Caroline C.; Gehring, Stephan; Cheng, Chao-Wen; van Rooijen, Nico; Gregory, Stephen H.
2012-01-01
Background Biliary obstruction and cholestasis are serious complications of many liver diseases. While resident hepatic macrophages (Kupffer cells) are frequently implicated in disease progression, most studies fail to differentiate the contribution of Kupffer cells and inflammatory mononuclear phagocytes (iMNPs) that infiltrate the liver subsequent to obstruction. Aim This study was undertaken to examine the roles and potential interactions of these two disparate mononuclear phagocyte populations in hepatic injury attending cholestasis. Methods Female, C57Bl/6 mice were injected with magnetic beads on day three prior to sham operation or bile duct ligation (BDL) in order to facilitate subsequent Kupffer cell isolation. Three days post surgery, animals were euthanized, and bead-containing Kupffer cells and iMNPs were separated, purified, and analyzed. To examine the ability of Kupffer cells to modulate iMNP activity, iMNPs were isolated from the livers of intact and Kupffer cell-depleted mice on day 3 post-surgery and compared. Results Purified Kupffer cells and iMNP populations obtained from BDL mice exhibited heterogeneous morphologies rendering them visually indistinguishable. iMNPs, however, were characterized by the increased expression of Ly-6C and CD11b and the elevated production of chemokines/cytokines characteristic of inflammatory cells. In the absence of Kupffer cells, iMNPs immigrating to the liver following BDL exhibited significant decreases in CD11b and Ly-6C expression, and in pro-inflammatory chemokine/cytokine production. Conclusions Kupffer cells and iMNPs exhibit disparate biological responses to biliary obstruction and cholestasis. Kupffer cells play a key role in regulating iMNP influx and activity. PMID:23240869
Digital systems design language
NASA Technical Reports Server (NTRS)
Shiva, S. G.
1979-01-01
Digital Systems Design Language (DDL) is implemented on the SEL-32 Computer Systems. The detaileds of the language, the translator, and the simulator, and the smulator programs are given. Several example descriptions and a tutorial on hardware description languages are provided, to guide the user.
Digital systems design language. Design synthesis of digital systems
NASA Technical Reports Server (NTRS)
Shiva, S. G.
1979-01-01
The Digital Systems Design Language (DDL) is implemented on the SEL-32 computer systems. The details of the language, translator and simulator programs are included. Several example descriptions and a tutorial on hardware description languages are provided, to guide the user.
The Loyal Opposition Comments on Plan Domain Description Languages
NASA Technical Reports Server (NTRS)
Frank, Jeremy; Golden, Keith; Jonsson, Ari
2003-01-01
In this paper we take a critical look at PDDL 2.1 as designers and users of plan domain description languages. We describe planning domains that have features which are hard to model using PDDL 2.1. We then offer some suggestions on domain description language design, and describe how these suggestions make modeling our chosen domains easier.
The Manu-Facturing of a Language.
ERIC Educational Resources Information Center
Washabaugh, William
1980-01-01
Discusses Providence Island Sign Language (PSL), an autochthonous and relatively immature language of about 20 speakers. It is a nascent and evolving language whose description can produce rich results for linguistic theory. Such a description will also be an explanation of the phylogeny of a linguistic system. (Author/PJM)
106-17 Telemetry Standards Metadata Configuration Chapter 23
2017-07-01
23-1 23.2 Metadata Description Language ...Chapter 23, July 2017 iii Acronyms HTML Hypertext Markup Language MDL Metadata Description Language PCM pulse code modulation TMATS Telemetry...Attributes Transfer Standard W3C World Wide Web Consortium XML eXtensible Markup Language XSD XML schema document Telemetry Network Standard
Truth and probability in evolutionary games
NASA Astrophysics Data System (ADS)
Barrett, Jeffrey A.
2017-01-01
This paper concerns two composite Lewis-Skyrms signalling games. Each consists in a base game that evolves a language descriptive of nature and a metagame that coevolves a language descriptive of the base game and its evolving language. The first composite game shows how a pragmatic notion of truth might coevolve with a simple descriptive language. The second shows how a pragmatic notion of probability might similarly coevolve. Each of these pragmatic notions is characterised by the particular game and role that it comes to play in the game.
Multimedia data from two probability-based exposure studies were investigated in terms of how censoring of non-detects affected estimation of population parameters and associations. Appropriate methods for handling censored below-detection-limit (BDL) values in this context were...
A Domain Description Language for Data Processing
NASA Technical Reports Server (NTRS)
Golden, Keith
2003-01-01
We discuss an application of planning to data processing, a planning problem which poses unique challenges for domain description languages. We discuss these challenges and why the current PDDL standard does not meet them. We discuss DPADL (Data Processing Action Description Language), a language for describing planning domains that involve data processing. DPADL is a declarative, object-oriented language that supports constraints and embedded Java code, object creation and copying, explicit inputs and outputs for actions, and metadata descriptions of existing and desired data. DPADL is supported by the IMAGEbot system, which we are using to provide automation for an ecological forecasting application. We compare DPADL to PDDL and discuss changes that could be made to PDDL to make it more suitable for representing planning domains that involve data processing actions.
Descriptive Metadata: Emerging Standards.
ERIC Educational Resources Information Center
Ahronheim, Judith R.
1998-01-01
Discusses metadata, digital resources, cross-disciplinary activity, and standards. Highlights include Standard Generalized Markup Language (SGML); Extensible Markup Language (XML); Dublin Core; Resource Description Framework (RDF); Text Encoding Initiative (TEI); Encoded Archival Description (EAD); art and cultural-heritage metadata initiatives;…
Instrumentation Hardware Abstraction Language (IHAL) Handbook
2017-01-01
1-1 1.1 The Range Commanders Council (RCC) and IHAL ....................................................... 1-1 1.2 Problem Description ...1-5 1.3.1 IHAL as a Description Language...Figure 2-6. Generic IHAL Device Schema Diagram ............................................................. 2-7 Figure 2-7. Device Description Schema
NASA Astrophysics Data System (ADS)
Hachaj, Tomasz; Ogiela, Marek R.
2014-09-01
Gesture Description Language (GDL) is a classifier that enables syntactic description and real time recognition of full-body gestures and movements. Gestures are described in dedicated computer language named Gesture Description Language script (GDLs). In this paper we will introduce new GDLs formalisms that enable recognition of selected classes of movement trajectories. The second novelty is new unsupervised learning method with which it is possible to automatically generate GDLs descriptions. We have initially evaluated both proposed extensions of GDL and we have obtained very promising results. Both the novel methodology and evaluation results will be described in this paper.
ERIC Educational Resources Information Center
Fuentes, Mariana; Tolchinsky, Liliana
2004-01-01
Linguistic descriptions of sign languages are important to the recognition of their linguistic status. These languages are an essential part of the cultural heritage of the communities that create and use them and vital in the education of deaf children. They are also the reference point in language acquisition studies. Ours is exploratory…
Nondetect (ND) or below detection limit (BDL) results cannot be measured accurately, and, therefore, are reported as less than certain detection limit (DL) values. However, since the presence of some contaminants (e.g., dioxin) in environmental media may pose a threat to human he...
Variation and Linguistic Theory.
ERIC Educational Resources Information Center
Bailey, Charles-James N.
This volume presents principles and models for describing language variation, and introduces a time-based, dynamic framework for linguistic description. The book first summarizes some of the problems of grammatical description encountered from Saussure through the present and then outlines possibilities for new descriptions of language which take…
Glechoma hederacea extracts attenuate cholestatic liver injury in a bile duct-ligated rat model.
Wang, Ya-Yu; Lin, Shih-Yi; Chen, Wen-Ying; Liao, Su-Lan; Wu, Chih-Cheng; Pan, Pin-Ho; Chou, Su-Tze; Chen, Chun-Jung
2017-05-23
In traditional Chinese medicine, Glechoma hederacea is frequently prescribed to patients with cholelithiasis, dropsy, abscess, diabetes, inflammation, and jaundice. Polyphenolic compounds are main bioactive components of Glechoma hederacea. This study was aimed to investigate the hepatoprotective potential of hot water extract of Glechoma hederacea against cholestatic liver injury in rats. Cholestatic liver injury was produced by ligating common bile ducts in Sprague-Dawley rats. Saline and hot water extract of Glechoma hederacea were orally administrated using gastric gavages. Liver tissues and bloods were collected and subjected to evaluation using histological, molecular, and biochemical approaches. Using a rat model of cholestasis caused by bile duct ligation (BDL), daily oral administration of Glechoma hederacea hot water extracts showed protective effects against cholestatic liver injury, as evidenced by the improvement of serum biochemicals, ductular reaction, oxidative stress, inflammation, and fibrosis. Glechoma hederacea extracts alleviated BDL-induced transforming growth factor beta-1 (TGF-β1), connective tissue growth factor, and collagen expression, and the anti-fibrotic effects were accompanied by reductions in α-smooth muscle actin-positive matrix-producing cells and Smad2/3 activity. Glechoma hederacea extracts attenuated BDL-induced inflammatory cell infiltration/accumulation, NF-κB and AP-1 activation, and inflammatory cytokine production. Further studies demonstrated an inhibitory effect of Glechoma hederacea extracts on the axis of high mobility group box-1 (HMGB1)/toll-like receptor-4 (TLR4) intracellular signaling pathways. The hepatoprotective, anti-oxidative, anti-inflammatory, and anti-fibrotic effects of Glechoma hederacea extracts seem to be multifactorial. The beneficial effects of daily Glechoma hederacea extracts supplementation were associated with anti-oxidative, anti-inflammatory, and anti-fibrotic potential, as well as down-regulation of NF-κB, AP-1, and TGF-β/Smad signaling, probably via interference with the HMGB1/TLR4 axis. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.
Hsu, Shao-Jung; Tsai, Ming-Hung; Chang, Ching-Chih; Hsieh, Yu-Hsin; Huang, Hui-Chun; Lee, Fa-Yauh; Chuang, Chiao-Ling; Hou, Ming-Chih; Lee, Shou-Dong
2018-03-30
Liver cirrhosis is characterized by portal hypertension. However, the alteration of portal hypertension-related derangements during cirrhosis resolution is not well known. The present study aimed to establish animal models with cirrhosis resolution and to investigate the relevant changes during this process. Male Sprague-Dawley rats were applied. In reverse thioacetamide (rTAA) model, rats were randomly allocated into four groups with control, thioacetamide (TAA) cirrhosis and rTAA groups that discontinued TAA for 4 or 8 weeks after cirrhosis induction. In reverse bile duct ligation (rBDL) model, rats received choledochoduodenal shunt surgery upon the establishment of cirrhosis and 4, 8, or 16 weeks were allowed after the surgery. At the end, portal hypertension-related parameters were evaluated. Cirrhosis resolution was observed in rTAA groups. Portal pressure (PP) decreased after cirrhosis resolution but remained higher than control group (control, TAA, rTAA4, rTAA8 (mmHg): 5.4 ± 0.3, 12.9 ± 0.3, 8.6 ± 0.4, 7.6 ± 0.6). Further survey found the increased splanchnic blood flow did not reduce during cirrhosis resolution. The extrahepatic pathological angiogenesis was not ameliorated (% of mesenteric window area: 1.2 ± 0.3, 7.3 ± 1.1, 8.3 ± 1.0, 11.3 ± 2.7). In collateral system, the shunting degree reduced while the vessels structure remained. The vascular contractility of all systems and nitric oxide (NO) production were normalized. In rBDL series, PP decreased in rBDL16 groups but the extrahepatic angiogenesis persisted. In conclusion, cirrhosis resolution attenuates but not completely normalizes portal hypertension because of persistently high splanchnic inflow and angiogenesis. In clinical setting, vascular complications such as varices could persist after cirrhosis resolution and further investigation to define the follow-up and treatment strategies is anticipated. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
Michelotti, Gregory A; Tucker, Anikia; Swiderska-Syn, Marzena; Machado, Mariana Verdelho; Choi, Steve S; Kruger, Leandi; Soderblom, Erik; Thompson, J Will; Mayer-Salman, Meredith; Himburg, Heather A; Moylan, Cynthia A; Guy, Cynthia D; Garman, Katherine S; Premont, Richard T; Chute, John P; Diehl, Anna Mae
2016-04-01
The ductular reaction (DR) involves mobilisation of reactive-appearing duct-like cells (RDC) along canals of Hering, and myofibroblastic (MF) differentiation of hepatic stellate cells (HSC) in the space of Disse. Perivascular cells in stem cell niches produce pleiotrophin (PTN) to inactivate the PTN receptor, protein tyrosine phosphatase receptor zeta-1 (PTPRZ1), thereby augmenting phosphoprotein-dependent signalling. We hypothesised that the DR is regulated by PTN/PTPRZ1 signalling. PTN-GFP, PTN-knockout (KO), PTPRZ1-KO, and wild type (WT) mice were examined before and after bile duct ligation (BDL) for PTN, PTPRZ1 and the DR. RDC and HSC from WT, PTN-KO, and PTPRZ1-KO mice were also treated with PTN to determine effects on downstream signaling phosphoproteins, gene expression, growth, and migration. Liver biopsies from patients with DRs were also interrogated. Although quiescent HSC and RDC lines expressed PTN and PTPRZ1 mRNAs, neither PTN nor PTPRZ1 protein was demonstrated in healthy liver. BDL induced PTN in MF-HSC and increased PTPRZ1 in MF-HSC and RDC. In WT mice, BDL triggered a DR characterised by periportal accumulation of collagen, RDC and MF-HSC. All aspects of this DR were increased in PTN-KO mice and suppressed in PTPRZ1-KO mice. In vitro studies revealed PTN-dependent accumulation of phosphoproteins that control cell-cell adhesion and migration, with resultant inhibition of cell migration. PTPRZ1-positive cells were prominent in the DRs of patients with ductal plate defects and adult cholestatic diseases. PTN, and its receptor, PTPRZ1, regulate the DR to liver injury by controlling the migration of resident cells in adult liver progenitor niches. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Linguistic Corpora and Language Teaching.
ERIC Educational Resources Information Center
Murison-Bowie, Simon
1996-01-01
Examines issues raised by corpus linguistics concerning the description of language. The article argues that it is necessary to start from correct descriptions of linguistic units and the contexts in which they occur. Corpus linguistics has joined with language teaching by sharing a recognition of the importance of a larger, schematic view of…
NASA Technical Reports Server (NTRS)
Shiva, S. G.
1978-01-01
Several high level languages which evolved over the past few years for describing and simulating the structure and behavior of digital systems, on digital computers are assessed. The characteristics of the four prominent languages (CDL, DDL, AHPL, ISP) are summarized. A criterion for selecting a suitable hardware description language for use in an automatic integrated circuit design environment is provided.
ERIC Educational Resources Information Center
Ouellon, Conrad, Comp.
Presentations from a colloquium on applications of research on natural languages to computer science address the following topics: (1) analysis of complex adverbs; (2) parser use in computerized text analysis; (3) French language utilities; (4) lexicographic mapping of official language notices; (5) phonographic codification of Spanish; (6)…
DPADL: An Action Language for Data Processing Domains
NASA Technical Reports Server (NTRS)
Golden, Keith; Clancy, Daniel (Technical Monitor)
2002-01-01
This paper presents DPADL (Data Processing Action Description Language), a language for describing planning domains that involve data processing. DPADL is a declarative object-oriented language that supports constraints and embedded Java code, object creation and copying, explicit inputs and outputs for actions, and metadata descriptions of existing and desired data. DPADL is supported by the IMAGEbot system, which will provide automation for an ecosystem forecasting system called TOPS.
EDAC Test Collection Catalogue: A Description of Tests for Use in Bilingual Education Programs.
ERIC Educational Resources Information Center
Wolfsfeld, Lynn
The descriptions of 200 tests for a variety of language groups are designed for use with the test file maintained by the Evaluation, Dissemination, and Assessment Center for Bilingual Education (EDAC). The content areas covered include reading, mathematics, self-concept, language dominance, language proficiency, and intelligence. Tests are…
How the Potawatomi Language Lives: A Grammar of Potawatomi
ERIC Educational Resources Information Center
Lockwood, Hunter Thompson
2017-01-01
This dissertation is a descriptive grammar of Potawatomi, a critically endangered Algonquian language now only spoken as a first language by a handful of elders in northern Wisconsin. Throughout, the goal is to present an authoritative linguistic description of Potawatomi by drawing on direct elicitation, a corpus of new texts gathered in close…
78 FR 38294 - Order Making Denial of Export Privileges Applicable to a Related Person
Federal Register 2010, 2011, 2012, 2013, 2014
2013-06-26
...)), has continued the Regulations in effect under the International Emergency Economic Powers Act (50 U.S.... 764.2(e)--Acting with Knowledge of a Violation On or about July 11, 2007, in connection with the... from the United States to BDL in Hyderabad, India, with knowledge that a violation of the Regulations...
ERIC Educational Resources Information Center
Ward, Shelley
2017-01-01
Language must be taught with academic vocabulary that is meaningful and that can be transferred between content and context. This comparative-descriptive research study examines how academic specific instruction increases students' learning of a second language acquisition (i.e., English). The conceptual framework of the study drew research…
Putting Practice into Words: The State of Data and Methods Transparency in Grammatical Descriptions
ERIC Educational Resources Information Center
Gawne, Lauren; Kelly, Barbara F.; Berez-Kroeker, Andrea L.; Heston, Tyler
2017-01-01
Language documentation and description are closely related practices, often performed as part of the same fieldwork project on an un(der)-studied language. Research trends in recent decades have seen a great volume of publishing in regards to the methods of language documentation, however, it is not clear that linguists' awareness of the…
ERIC Educational Resources Information Center
Bavali, Mohammad; Sadighi, Firooz
2008-01-01
Recent developments in theories of language (grammars) seem to share a number of tenets which mark a drastic shift from traditional disentangled descriptions of language: emphasis on a big number of discrete grammatical rules or a corpus of structure patterns has given way to a more unitary, explanatory powerful description of language informed by…
Research: Research in Language Arts Education: Notes on How It Works.
ERIC Educational Resources Information Center
Dilworth, Collett B., Jr.
1980-01-01
Provides an overview of different types of educational research in language arts, including the quasi-experiment, the controlled methodological experiment, the controlled descriptive experiment, the non-controlled description, and textual analysis. (RL)
ERIC Educational Resources Information Center
Voronina, Marianna V.; Tretyakova, Zlata O.
2017-01-01
The article considers the peculiarities of training foreign students subject "Descriptive geometry and Engineering Graphics" in a modern engineering university of Russia. The relevance of the problem conditioned by the fact that virtually there are no special studies of teaching Descriptive Geometry and Engineering Graphics in Russian…
On the System of Person-Denoting Signs in Estonian Sign Language: Estonian Name Signs
ERIC Educational Resources Information Center
Paales, Liina
2010-01-01
This article discusses Estonian personal name signs. According to study there are four personal name sign categories in Estonian Sign Language: (1) arbitrary name signs; (2) descriptive name signs; (3) initialized-descriptive name signs; (4) loan/borrowed name signs. Mostly there are represented descriptive and borrowed personal name signs among…
Molina, Martin; Sanchez-Soriano, Javier; Corcho, Oscar
2015-07-03
Providing descriptions of isolated sensors and sensor networks in natural language, understandable by the general public, is useful to help users find relevant sensors and analyze sensor data. In this paper, we discuss the feasibility of using geographic knowledge from public databases available on the Web (such as OpenStreetMap, Geonames, or DBpedia) to automatically construct such descriptions. We present a general method that uses such information to generate sensor descriptions in natural language. The results of the evaluation of our method in a hydrologic national sensor network showed that this approach is feasible and capable of generating adequate sensor descriptions with a lower development effort compared to other approaches. In the paper we also analyze certain problems that we found in public databases (e.g., heterogeneity, non-standard use of labels, or rigid search methods) and their impact in the generation of sensor descriptions.
Molina, Martin; Sanchez-Soriano, Javier; Corcho, Oscar
2015-01-01
Providing descriptions of isolated sensors and sensor networks in natural language, understandable by the general public, is useful to help users find relevant sensors and analyze sensor data. In this paper, we discuss the feasibility of using geographic knowledge from public databases available on the Web (such as OpenStreetMap, Geonames, or DBpedia) to automatically construct such descriptions. We present a general method that uses such information to generate sensor descriptions in natural language. The results of the evaluation of our method in a hydrologic national sensor network showed that this approach is feasible and capable of generating adequate sensor descriptions with a lower development effort compared to other approaches. In the paper we also analyze certain problems that we found in public databases (e.g., heterogeneity, non-standard use of labels, or rigid search methods) and their impact in the generation of sensor descriptions. PMID:26151211
2016-12-01
C. METHODOLOGY ....................................................................................4 D. LITERATURE REVIEW... Descriptions ................................................10 Table 3. Interagency Language Roundtable Language Skill Level Table 4. Descriptions ...and cultural acquisition. METHODOLOGY D. In this project the author analyzed official documents associated with Military Information Support
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shilling, J.
1984-02-01
FRED, the friendly editor, is a screen-based structured editor. This manual is intended to serve the needs of a wide range of users of the FRED text editor. Most users will find it sufficient to read the introductory material in section 2, supplemented with the full command set description in section 3. Advanced users may wish to change the keystroke sequences which invoke editor commands. Section 4 describes how to change key bindings and how to define command macros. Some users may need to modify a language description or create an entirely new language description for use with FRED. Sectionmore » 5 describes the format of the language descriptions used by the editor, and describes how to construct a language grammar. Section 6 describes known portability problems of the FRED editor and should concern only system installation personnel. The editor points out syntax errors in the file being edited and does automatic pretty printing.« less
Inhibitory effect of dietary capsaicin on liver fibrosis in mice.
Bitencourt, Shanna; Stradiot, Leslie; Verhulst, Stefaan; Thoen, Lien; Mannaerts, Inge; van Grunsven, Leo A
2015-06-01
Virtually all chronic liver injuries result in the activation of hepatic stellate cells (HSCs). In their activated state, these cells are the main collagen-producing cells implicated in liver fibrosis. Capsaicin (CPS), the active compound of chili peppers, can modulate the activation and migration of HSCs in vitro. Here, we evaluated the potential protective and prophylactic effects of CPS related to cholestatic and hepatotoxic-induced liver fibrosis and its possible underlying mechanism of action. Male Balb/c mice received dietary CPS after 3 days of bile duct ligation (BDL) or before and during carbon tetrachloride (CCl4 ) injections. Mice receiving dietary CPS after BDL had a significant improvement of liver fibrosis accompanied by a decrease in collagen deposition and downregulation of activation markers in isolated HSCs. In the CCl4 model, dietary CPS inhibited the upregulation of profibrogenic markers. However, CPS could not attenuate the CCl4 -induced fibrosis when it was already established. Furthermore, in vitro CPS treatment inhibited the autophagic process during HSC activation. Dietary CPS has potential benefits in the therapy of cholestatic liver fibrosis and in the prophylaxis of hepatotoxic-induced liver injury. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Soares, A. F.; Castro e Silva Júnior, O.; Ceneviva, R.; Roselino, J. E.; Zucoloto, S.
1993-01-01
The present study was carried out to investigate the biochemical and morphological changes in the liver after ligation of the hepatic artery (HA) in the presence and in the absence of extrahepatic cholestasis (EHC). The study was conducted on 100 rats divided into four groups of 25 animals each: group 1, sham operation; group 2, hepatic artery ligation (HAL); group 3, bile duct ligation (BDL); and group 4, HAL plus BDL. All animals were sacrificed 7 days after surgery when total bilirubin and fractions, alkaline phosphatase (AP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured in serum and on the inner hepatocyte mitochondrial membrane (IHMM); the incidence of necrosis and the volume fractions of vessels, bile ducts and hepatocytes in the liver were also determined. HAL reduces the relative volumes of bile ducts, with no changes in levels of bilirubin and fractions, AP, ALT, AST and IHMM, but HAL associated with EHC reduces duct proliferation and the liver becomes more vulnerable to necrosis. In conclusion, the normal liver depends on HA flow and this dependence is more evident in the presence of EHC. PMID:8398809
van Golen, Rowan F; Olthof, Pim B; de Haan, Lianne R; Coelen, Robert J; Pechlivanis, Alexandros; de Keijzer, Mark J; Weijer, Ruud; de Waart, Dirk R; van Kuilenburg, André B P; Roelofsen, Jeroen; Gilijamse, Pim W; Maas, Martinus A; Lewis, Matthew R; Nicholson, Jeremy K; Verheij, Joanne; Heger, Michal
2018-03-01
Obstructive cholestasis causes liver injury via accumulation of toxic bile acids (BAs). Therapeutic options for cholestatic liver disease are limited, partially because the available murine disease models lack translational value. Profiling of time-related changes following bile duct ligation (BDL) in Gold Syrian hamsters revealed a biochemical response similar to cholestatic patients in terms of BA pool composition, alterations in hepatocyte BA transport and signaling, suppression of BA production, and adapted BA metabolism. Hamsters tolerated cholestasis well for up to 28days and progressed relatively slowly to fibrotic liver injury. Hepatocellular necrosis was absent, which coincided with preserved intrahepatic energy levels and only mild oxidative stress. The histological response to cholestasis in hamsters was similar to the changes seen in 17 patients with prolonged obstructive cholestasis caused by cholangiocarcinoma. Hamsters moreover upregulated hepatic fibroblast growth factor 15 (Fgf15) expression in response to BDL, which is a cytoprotective adaptation to cholestasis that hitherto had only been documented in cholestatic human livers. Hamster models should therefore be added to the repertoire of animal models used to study the pathophysiology of cholestatic liver disease. Copyright © 2017 Elsevier B.V. All rights reserved.
LeSage, G D; Glaser, S S; Marucci, L; Benedetti, A; Phinizy, J L; Rodgers, R; Caligiuri, A; Papa, E; Tretjak, Z; Jezequel, A M; Holcomb, L A; Alpini, G
1999-05-01
Bile duct damage and/or loss is limited to a range of duct sizes in cholangiopathies. We tested the hypothesis that CCl4 damages only large ducts. CCl4 or mineral oil was given to bile duct-ligated (BDL) rats, and 1, 2, and 7 days later small and large cholangiocytes were purified and evaluated for apoptosis, proliferation, and secretion. In situ, we measured apoptosis by morphometric and TUNEL analysis and the number of small and large ducts by morphometry. Two days after CCl4 administration, we found an increased number of small ducts and reduced number of large ducts. In vitro apoptosis was observed only in large cholangiocytes, and this was accompanied by loss of proliferation and secretion in large cholangiocytes and loss of choleretic effect of secretin. Small cholangiocytes de novo express the secretin receptor gene and secretin-induced cAMP response. Consistent with damage of large ducts, we detected cytochrome P-4502E1 (which CCl4 converts to its radicals) only in large cholangiocytes. CCl4 induces selective apoptosis of large ducts associated with loss of large cholangiocyte proliferation and secretion.
Wen, Shi-Lei; Feng, Shi; Tang, Shi-Hang; Gao, Jin-Hang; Zhang, Lin-hao; Tong, Huan; Yan, Zhao-Ping; Fang, Ding Zhi
2016-01-01
Among the researches on hepatic fibrosis, great attention was paid to both hepatocytes and extracellular matrix (ECM). However, little focus was drawn on reticular fibrous network, which is important for demarcation and support of hepatocytes. The aim of this study was to investigate the change pattern of reticular fibers in hepatic fibrosis/cirrhosis and its underlying mechanism. In this study, thioacetamide (TAA) and bile duct ligation (BDL) were utilized to induce rat hepatic fibrosis respectively, and Human liver cirrhotic microassay was analyzed with IHC to confirm the results in animal experiment and to detect the metalloproteinases (MMPs) expressions. As a result, the reticular fibers decreased markedly after 1 week in TAA and 1 day in BDL treated rats. Multiple representative regulators of MMPs and MMPs increased significantly in their expressions and activities. Further more, in human liver cirrhotic microassay, MMPs expressions also showed similar patterns as that of animal experiment. In Conclusions: Degradation or collapse of reticular fibers in hepatic sinusoid can be considered as a pathological feature during the initiation and/or progression of hepatic fibrosis. Moreover, such degradation is associated with and probably caused by the over/dysregulated expression of MMPs. PMID:27739503
ERIC Educational Resources Information Center
Caballero, Gabriela
2017-01-01
Choguita Rarámuri (Tarahumara) is a Uto-Aztecan language spoken in Northern Mexico of great typological, theoretical, and historical significance. This paper presents an overview and background of the Choguita Rarámuri language description and documentation project and provides a guide to the documentary collection emerging from this project. This…
Automatic Requirements Specification Extraction from Natural Language (ARSENAL)
2014-10-01
designers, implementers) involved in the design of software systems. However, natural language descriptions can be informal, incomplete, imprecise...communication of technical descriptions between the various stakeholders (e.g., customers, designers, imple- menters) involved in the design of software systems...the accuracy of the natural language processing stage, the degree of automation, and robustness to noise. 1 2 Introduction Software systems operate in
ERIC Educational Resources Information Center
Plastina, Anna Franca
2016-01-01
The need to teach medical students plain language for their future engagement in pain communication can no longer be underestimated. Pain education has traditionally neglected the teaching of pain language, yet patients' descriptive accounts have been acknowledged as the standard in medical care. English for Medical Purposes (EMP) can make its…
A Proposed Pattern of Enterprise Architecture
2013-02-01
consistent architecture descriptions. UPDM comprises extensions to both OMG’s Unified Modelling Language (UML) and Systems Modelling Language ( SysML ...those who use UML and SysML . These represent significant advancements that enable architecture trade-off analyses, architecture model execution...Language ( SysML ), and thus provides for architectural descriptions that contain a rich set of (formally) connected DoDAF/MoDAF viewpoints expressed
Federal Register 2010, 2011, 2012, 2013, 2014
2012-12-14
... under the International Emergency Economic Powers Act (50 U.S.C. Sec. 1701, et seq.). Charge 1 15 CFR...)--Acting With Knowledge of a Violation On or about July 11, 2007, in connection with the transaction... United States to BDL in Hyderabad, India, with knowledge that a violation of the Regulations was about to...
Masubuchi, Noriko; Nishiya, Takayoshi; Imaoka, Masako; Mizumaki, Kiyoko; Okazaki, Osamu
2016-08-05
Promising biomarkers were identified in adult male Crl:CD (SD) rats for the screening of new chemical entities for their potential to cause liver injury. We examined the serum biochemistry, liver histopathology, and bile acid profiles by LC-MS/MS, and the mRNA expression of transporters and CYPs by an RT-PCR after the following treatments to male Crl:CD (SD) rats: (a) bile duct ligation (BDL); (b) a single oral dose of 150 mg/kg α-naphthylisothiocyanate (ANIT); and (c) repeated oral doses of a novel pyrrolidinecarboxylic acid derivative (abbreviated as PCA) at 30, 300, and 1000 mg/kg. The serum total bile acid levels and bilirubin concentrations were found to be elevated in all of the groups. However, the bile acid component profiles of the PCA group differed significantly from BDL and ANIT models: deoxycholic acid, lithocholic acid, and sulfated bile acids were upregulated in a dose-dependent manner only in the PCA group. In addition, the PCA group demonstrated high levels of hepatic heme oxygenase-1 expression, whereas the profiles of the mRNA levels of the hepatic transporters and CYPs of all groups were found to be similar. The histopathological findings, for both the BDL and ANIT groups, were of bile duct hyperplasia, hepatocyte degeneration and necrosis. In contrast, only bile duct hyperplasia and hepatocyte degeneration were observed in the PCA group, even at a lethal dose. These results indicated that PCA induced a cholestatic condition and the increase of oxidative stress markers implies that this will also lead hepatocellular injury. In conclusion, the serum bile acid components and sulfated bile acid levels, and the expression of oxidative stress markers could provide information that aids in the diagnosis of liver injury type and helps to elucidate the mechanisms of hepatotoxicity. These findings can be extrapolated into our clinical investigation. The analysis of these crucial biomarkers is likely to be a useful screening tool in the lead optimization phase of drug discovery. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Plectin controls biliary tree architecture and stability in cholestasis.
Jirouskova, Marketa; Nepomucka, Katerina; Oyman-Eyrilmez, Gizem; Kalendova, Alzbeta; Havelkova, Helena; Sarnova, Lenka; Chalupsky, Karel; Schuster, Bjoern; Benada, Oldrich; Miksatkova, Petra; Kuchar, Martin; Fabian, Ondrej; Sedlacek, Radislav; Wiche, Gerhard; Gregor, Martin
2018-05-01
Plectin, a highly versatile cytolinker protein, controls intermediate filament cytoarchitecture and cellular stress response. In the present study, we investigate the role of plectin in the liver under basal conditions and in experimental cholestasis. We generated liver-specific plectin knockout (Ple Δalb ) mice and analyzed them using two cholestatic liver injury models: bile duct ligation (BDL) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) feeding. Primary hepatocytes and a cholangiocyte cell line were used to address the impact of plectin on keratin filament organization and stability in vitro. Plectin deficiency in hepatocytes and biliary epithelial cells led to aberrant keratin filament network organization, biliary tree malformations, and collapse of bile ducts and ductules. Further, plectin ablation significantly aggravated biliary damage upon cholestatic challenge. Coincidently, we observed a significant expansion of A6-positive progenitor cells in Ple Δalb livers. After BDL, plectin-deficient bile ducts were prominently dilated with more frequent ruptures corresponding to an increased number of bile infarcts. In addition, more abundant keratin aggregates indicated less stable keratin filaments in Ple Δalb hepatocytes. A transmission electron microscopy analysis revealed a compromised tight junction formation in plectin-deficient biliary epithelial cells. In addition, protein profiling showed increased expression of the adherens junction protein E-Cadherin, and inefficient upregulation of the desmosomal protein desmoplakin in response to BDL. In vitro analyses revealed a higher susceptibility of plectin-deficient keratin networks to stress-induced collapse, paralleled by elevated activation of p38 MAP kinase. Our study shows that by maintaining proper keratin network cytoarchitecture and biliary epithelial stability, plectin plays a critical role in protecting the liver from stress elicited by cholestasis. Plectin is a cytolinker protein capable of interconnecting all three cytoskeletal filament systems and linking them to plasma membrane-bound junctional complexes. In liver, the plectin-controlled cytoskeleton mechanically stabilizes epithelial cells and provides them with the capacity to adapt to increased bile pressure under cholestasis. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
NASA Technical Reports Server (NTRS)
Khovanskiy, Y. D.; Kremneva, N. I.
1975-01-01
Problems and methods are discussed of automating information retrieval operations in a data bank used for long term storage and retrieval of data from scientific experiments. Existing information retrieval languages are analyzed along with those being developed. The results of studies discussing the application of the descriptive 'Kristall' language used in the 'ASIOR' automated information retrieval system are presented. The development and use of a specialized language of the classification-descriptive type, using universal decimal classification indices as the main descriptors, is described.
Natural Language Description of Emotion
ERIC Educational Resources Information Center
Kazemzadeh, Abe
2013-01-01
This dissertation studies how people describe emotions with language and how computers can simulate this descriptive behavior. Although many non-human animals can express their current emotions as social signals, only humans can communicate about emotions symbolically. This symbolic communication of emotion allows us to talk about emotions that we…
South Korea: Language Policy and Planning in the Making
ERIC Educational Resources Information Center
Song, Jae Jung
2012-01-01
This monograph discusses South Korea's language situation in a language policy and planning context. This monograph consists of four parts. Part 1 presents a genetic, typological and sociolinguistic description of South Korea's national language, and an overview of minority languages, including English as well as other languages, recently…
FLAX: Flexible and Open Corpus-Based Language Collections Development
ERIC Educational Resources Information Center
Fitzgerald, Alannah; Wu, Shaoqun; Marín, María José
2015-01-01
In this case study we present innovative work in building open corpus-based language collections by focusing on a description of the opensource multilingual Flexible Language Acquisition (FLAX) language project, which is an ongoing example of open materials development practices for language teaching and learning. We present language-learning…
Systems Biology Graphical Notation: Process Description language Level 1 Version 1.3.
Moodie, Stuart; Le Novère, Nicolas; Demir, Emek; Mi, Huaiyu; Villéger, Alice
2015-09-04
The Systems Biological Graphical Notation (SBGN) is an international community effort for standardized graphical representations of biological pathways and networks. The goal of SBGN is to provide unambiguous pathway and network maps for readers with different scientific backgrounds as well as to support efficient and accurate exchange of biological knowledge between different research communities, industry, and other players in systems biology. Three SBGN languages, Process Description (PD), Entity Relationship (ER) and Activity Flow (AF), allow for the representation of different aspects of biological and biochemical systems at different levels of detail. The SBGN Process Description language represents biological entities and processes between these entities within a network. SBGN PD focuses on the mechanistic description and temporal dependencies of biological interactions and transformations. The nodes (elements) are split into entity nodes describing, e.g., metabolites, proteins, genes and complexes, and process nodes describing, e.g., reactions and associations. The edges (connections) provide descriptions of relationships (or influences) between the nodes, such as consumption, production, stimulation and inhibition. Among all three languages of SBGN, PD is the closest to metabolic and regulatory pathways in biological literature and textbooks, but its well-defined semantics offer a superior precision in expressing biological knowledge.
A preliminary comparison of Cantonese and American-English as taste languages.
O'Mahony, M; Tsang, T
1980-05-01
Groups of monolingual American-English speaking Americans of Chinese descent were compared with Cantonese/American-English bilingual Chinese living in America to examine their taste descriptions for a set of aqueous solutions. Cantonese, unlike other languages, did not appear to differ greatly from American-English in its general taste descriptive strategy and depth of vocabulary, although Cantonese speakers had a tendency to use 'glutamic' as a descriptive term for monosodium glutamate.
Classification and Counter-Classification of Language on Saint Barthelemy.
ERIC Educational Resources Information Center
Pressman, Jon F.
1998-01-01
Analyzes the use of metapragmatic description in the ethnoclassification of language by native speakers on the Franco-Antillean island of Saint Barthelemy. A prevalent technique for metapragmatic description based on honorific pronouns that reflects the varied geolinguistic and generational attributes of the speakers is described. (Author/MSE)
Computer hardware description languages - A tutorial
NASA Technical Reports Server (NTRS)
Shiva, S. G.
1979-01-01
The paper introduces hardware description languages (HDL) as useful tools for hardware design and documentation. The capabilities and limitations of HDLs are discussed along with the guidelines needed in selecting an appropriate HDL. The directions for future work are provided and attention is given to the implementation of HDLs in microcomputers.
Two Types of Definites in Natural Language
ERIC Educational Resources Information Center
Schwarz, Florian
2009-01-01
This thesis is concerned with the description and analysis of two semantically different types of definite articles in German. While the existence of distinct article paradigms in various Germanic dialects and other languages has been acknowledged in the descriptive literature for quite some time, the theoretical implications of their existence…
An Introduction to the Resource Description Framework.
ERIC Educational Resources Information Center
Miller, Eric
1998-01-01
Explains the Resource Description Framework (RDF), an infrastructure developed under the World Wide Web Consortium that enables the encoding, exchange, and reuse of structured metadata. It is an application of Extended Markup Language (XML), which is a subset of Standard Generalized Markup Language (SGML), and helps with expressing semantics.…
Hardware acceleration and verification of systems designed with hardware description languages (HDL)
NASA Astrophysics Data System (ADS)
Wisniewski, Remigiusz; Wegrzyn, Marek
2005-02-01
Hardware description languages (HDLs) allow creating bigger and bigger designs nowadays. The size of prototyped systems very often exceeds million gates. Therefore verification process of the designs takes several hours or even days. The solution for this problem can be solved by hardware acceleration of simulation.
Towards a Bernsteinian Language of Description for Mathematics Classroom Discourse
ERIC Educational Resources Information Center
Straehler-Pohl, Hauke; Gellert, Uwe
2013-01-01
This article aims at developing an external language of description to investigate the problem of why particular groups of students are systematically not provided access to school mathematical knowledge. Based on Basil Bernstein's conceptualisation of power in classification, we develop a three-dimensional model that operationalises the…
Composing Models of Geographic Physical Processes
NASA Astrophysics Data System (ADS)
Hofer, Barbara; Frank, Andrew U.
Processes are central for geographic information science; yet geographic information systems (GIS) lack capabilities to represent process related information. A prerequisite to including processes in GIS software is a general method to describe geographic processes independently of application disciplines. This paper presents such a method, namely a process description language. The vocabulary of the process description language is derived formally from mathematical models. Physical processes in geography can be described in two equivalent languages: partial differential equations or partial difference equations, where the latter can be shown graphically and used as a method for application specialists to enter their process models. The vocabulary of the process description language comprises components for describing the general behavior of prototypical geographic physical processes. These process components can be composed by basic models of geographic physical processes, which is shown by means of an example.
English-Language Writing Instruction in Poland
ERIC Educational Resources Information Center
Reichelt, Melinda
2005-01-01
Second language writing scholars have undertaken descriptions of English-language writing instruction in a variety of international settings, describing the role of various contextual factors in shaping English-language writing instruction. This article describes English-language writing instruction at various levels in Poland, noting how it is…
Shin, Sun Kyoung; Kim, Woo-Il; Jeon, Tae-Wan; Kang, Young-Yeul; Jeong, Seong-Kyeong; Yeon, Jin-Mo; Somasundaram, Swarnalatha
2013-09-15
Ministry of Environment, Republic of Korea (South Korea) is in progress of converting its current hazardous waste classification system to harmonize it with the international standard and to set-up the regulatory standards for toxic substances present in the hazardous waste. In the present work, the concentrations along with the trend of 13 heavy metals, F(-), CN(-) and 19 PAH present in the hazardous waste generated among various thermal processes (11 processes) in South Korea were analyzed along with their leaching characteristics. In all thermal processes, the median concentrations of Cu (3.58-209,000 mg/kg), Ni (BDL-1560 mg/kg), Pb (7.22-5132.25mg/kg) and Zn (83.02-31419 mg/kg) were comparatively higher than the other heavy metals. Iron & Steel thermal process showed the highest median value of the heavy metals Cd (14.76 mg/kg), Cr (166.15 mg/kg) and Hg (2.38 mg/kg). Low molecular weight PAH (BDL-37.59 mg/kg) was predominant in sludge & filter cake samples present in most of the thermal processes. Comparatively flue gas dust present in most of the thermal processing units resulted in the higher leaching of the heavy metals. Copyright © 2013 Elsevier B.V. All rights reserved.
Belivermiş, Murat; Cotuk, Yavuz
2010-11-01
The present study was conducted to compare the (137)Cs, (40)K, (232)Th, and (238)U activity concentrations in epigeic moss (Hypnum cupressiforme) and lichen (Cladonia rangiformis). The activity levels in 37 moss and 38 lichen samples collected from the Marmara region of Turkey were measured using a gamma spectrometer equipped with a high purity germanium (HPGe) detector. The activity concentrations of (137)Cs, (40)K, (232)Th, and (238)U in the moss samples were found to be in the range of 0.36-8.13, 17.1-181.1, 1.51-6.17, and 0.87-6.70 Bq kg(-1) respectively, while these values were below detection limit (BDL)-4.32, 16.6-240.0, 1.32-6.47, and BDL-3.57 Bq kg(-1) respectively in lichen. The average moss/lichen activity ratios of (137)Cs, (40)K, (232)Th, and (238)U were found to be 1.32 +/- 0.57, 2.79 +/- 1.67, 2.11 +/- 0.82, and 2.19 +/- 1.02, respectively. Very low (137)Cs concentrations were observed in moss and lichen samples compared to soil samples collected from the same locations in a previous study. Seasonal variations of the measured radionuclide activities were also examined in the three sampling stations.
Modular hardware synthesis using an HDL. [Hardware Description Language
NASA Technical Reports Server (NTRS)
Covington, J. A.; Shiva, S. G.
1981-01-01
Although hardware description languages (HDL) are becoming more and more necessary to automated design systems, their application is complicated due to the difficulty in translating the HDL description into an implementable format, nonfamiliarity of hardware designers with high-level language programming, nonuniform design methodologies and the time and costs involved in transfering HDL design software. Digital design language (DDL) suffers from all of the above problems and in addition can only by synthesized on a complete system and not on its subparts, making it unsuitable for synthesis using standard modules or prefabricated chips such as those required in LSI or VLSI circuits. The present paper presents a method by which the DDL translator can be made to generate modular equations that will allow the system to be synthesized as an interconnection of lower-level modules. The method involves the introduction of a new language construct called a Module which provides for the separate translation of all equations bounded by it.
The carbohydrate sequence markup language (CabosML): an XML description of carbohydrate structures.
Kikuchi, Norihiro; Kameyama, Akihiko; Nakaya, Shuuichi; Ito, Hiromi; Sato, Takashi; Shikanai, Toshihide; Takahashi, Yoriko; Narimatsu, Hisashi
2005-04-15
Bioinformatics resources for glycomics are very poor as compared with those for genomics and proteomics. The complexity of carbohydrate sequences makes it difficult to define a common language to represent them, and the development of bioinformatics tools for glycomics has not progressed. In this study, we developed a carbohydrate sequence markup language (CabosML), an XML description of carbohydrate structures. The language definition (XML Schema) and an experimental database of carbohydrate structures using an XML database management system are available at http://www.phoenix.hydra.mki.co.jp/CabosDemo.html kikuchi@hydra.mki.co.jp.
A program code generator for multiphysics biological simulation using markup languages.
Amano, Akira; Kawabata, Masanari; Yamashita, Yoshiharu; Rusty Punzalan, Florencio; Shimayoshi, Takao; Kuwabara, Hiroaki; Kunieda, Yoshitoshi
2012-01-01
To cope with the complexity of the biological function simulation models, model representation with description language is becoming popular. However, simulation software itself becomes complex in these environment, thus, it is difficult to modify the simulation conditions, target computation resources or calculation methods. In the complex biological function simulation software, there are 1) model equations, 2) boundary conditions and 3) calculation schemes. Use of description model file is useful for first point and partly second point, however, third point is difficult to handle for various calculation schemes which is required for simulation models constructed from two or more elementary models. We introduce a simulation software generation system which use description language based description of coupling calculation scheme together with cell model description file. By using this software, we can easily generate biological simulation code with variety of coupling calculation schemes. To show the efficiency of our system, example of coupling calculation scheme with three elementary models are shown.
Creating Body Shapes From Verbal Descriptions by Linking Similarity Spaces.
Hill, Matthew Q; Streuber, Stephan; Hahn, Carina A; Black, Michael J; O'Toole, Alice J
2016-11-01
Brief verbal descriptions of people's bodies (e.g., "curvy," "long-legged") can elicit vivid mental images. The ease with which these mental images are created belies the complexity of three-dimensional body shapes. We explored the relationship between body shapes and body descriptions and showed that a small number of words can be used to generate categorically accurate representations of three-dimensional bodies. The dimensions of body-shape variation that emerged in a language-based similarity space were related to major dimensions of variation computed directly from three-dimensional laser scans of 2,094 bodies. This relationship allowed us to generate three-dimensional models of people in the shape space using only their coordinates on analogous dimensions in the language-based description space. Human descriptions of photographed bodies and their corresponding models matched closely. The natural mapping between the spaces illustrates the role of language as a concise code for body shape that captures perceptually salient global and local body features. © The Author(s) 2016.
Microprocessor Design Using Hardware Description Language
ERIC Educational Resources Information Center
Mita, Rosario; Palumbo, Gaetano
2008-01-01
The following paper has been conceived to deal with the contents of some lectures aimed at enhancing courses on digital electronic, microelectronic or VLSI systems. Those lectures show how to use a hardware description language (HDL), such as the VHDL, to specify, design and verify a custom microprocessor. The general goal of this work is to teach…
ERIC Educational Resources Information Center
Chang, May
2000-01-01
Describes the development of electronic finding aids for archives at the University of Illinois, Urbana-Champaign that used XML (extensible markup language) and EAD (encoded archival description) to enable more flexible information management and retrieval than using MARC or a relational database management system. EAD template is appended.…
Object Language and the Language Subject: On the Mediating Role of Applied Linguistics.
ERIC Educational Resources Information Center
Widdowson, Henry G.
2000-01-01
Examines the extent to which linguistic descriptions can adequately account for their reality for learners and provide a reference point for the design of language courses. Special concern is focused on second language learners as a particular kind of language user. (Author/VWL)
Understanding How Babies Build Language Skills
ERIC Educational Resources Information Center
Honig, Alice Sterling
2006-01-01
Language is a great communication system. Through language, humans can express logical reasoning, grief, happiness, wishes, descriptions, and a rich array of feelings and ideas. Every baby deserves the gift of language power! In this article, the author discusses how babies build language skills and presents activities to help babies build…
Research accomplished at the Knowledge Based Systems Lab: IDEF3, version 1.0
NASA Technical Reports Server (NTRS)
Mayer, Richard J.; Menzel, Christopher P.; Mayer, Paula S. D.
1991-01-01
An overview is presented of the foundations and content of the evolving IDEF3 process flow and object state description capture method. This method is currently in beta test. Ongoing efforts in the formulation of formal semantics models for descriptions captured in the outlined form and in the actual application of this method can be expected to cause an evolution in the method language. A language is described for the representation of process and object state centered system description. IDEF3 is a scenario driven process flow modeling methodology created specifically for these types of descriptive activities.
ERIC Educational Resources Information Center
Kurt, Mustafa
2015-01-01
The present study investigated whether English language teachers were aware of the innovative language learning methodologies in language learning, how they made use of these methodologies and the learners' reactions to them. The descriptive survey method was employed to disclose the frequencies and percentages of 175 English language teachers'…
Language Contact Means Language Conflict.
ERIC Educational Resources Information Center
Nelde, Peter H.
1987-01-01
Describes the characteristics of language conflict and examines the areas of emphasis in the literature, including multilingualism and linguistic identity, glottophagia and minority/majority relations, the danger of reliance on language censuses, conflict resolution/avoidance, and the importance of ecolinguistics in conflict description and for…
The Cooperate Assistive Teamwork Environment for Software Description Languages.
Groenda, Henning; Seifermann, Stephan; Müller, Karin; Jaworek, Gerhard
2015-01-01
Versatile description languages such as the Unified Modeling Language (UML) are commonly used in software engineering across different application domains in theory and practice. They often use graphical notations and leverage visual memory for expressing complex relations. Those notations are hard to access for people with visual impairment and impede their smooth inclusion in an engineering team. Existing approaches provide textual notations but require manual synchronization between the notations. This paper presents requirements for an accessible and language-aware team work environment as well as our plan for the assistive implementation of Cooperate. An industrial software engineering team consisting of people with and without visual impairment will evaluate the implementation.
ERIC Educational Resources Information Center
Carroll, Patricia E.; Bailey, Alison L.
2016-01-01
English language proficiency assessments (ELPA) are used in the United States to measure annually the English language progress and proficiency of English-language learners (ELLs), a subgroup of language minority students who receive language acquisition support mandated and largely funded by Title III (NCLB, 2001). ELPA proficient and…
ERIC Educational Resources Information Center
Weismer, Susan Ellis; Kaushanskaya, Margarita
2010-01-01
In her Keynote Article, Paradis reviews evidence from bilingual language development to assess the claims of two opposing theoretical views of language disorders. Specifically, she examines the evidence for similarities in language profiles of typically developing (TD) sequential bilingual (second language [L2]) children and monolingual children…
Sources, Developments and Directions of Task-Based Language Teaching
ERIC Educational Resources Information Center
Bygate, Martin
2016-01-01
This paper provides an outline of the origins, the current shape and the potential directions of task-based language teaching (TBLT) as an approach to language pedagogy. It first offers a brief description of TBLT and considers its origins within language teaching methodology and second language acquisition. It then summarises the current position…
77 FR 17467 - Combined Notice of Filings #2
Federal Register 2010, 2011, 2012, 2013, 2014
2012-03-26
... Interconnection, L.L.C. Description: Admin. Filing to Re-instate Missing Language in PJM Tariff Attach Q (V-0.1.0.... Filing to Re-instate Missing Language in PJM Tariff Attach Q (V-2.1.0) to be effective 1/1/2011. Filed...-1284-002. Applicants: PJM Interconnection, L.L.C. Description: Admin. Filing to Re-instate Missing...
Teaching EFL outside the United States.
ERIC Educational Resources Information Center
Teachers of English to Speakers of Other Languages.
The guide contains profiles of the linguistic situation and English language teaching conditions, in both public and private sectors, in 48 foreign countries. Descriptions include such information as official language(s), qualifications and requirements for teaching English as a Second Language (ESL), typical class sizes and hours, accessibility…
Issues and solutions for storage, retrieval, and searching of MPEG-7 documents
NASA Astrophysics Data System (ADS)
Chang, Yuan-Chi; Lo, Ming-Ling; Smith, John R.
2000-10-01
The ongoing MPEG-7 standardization activity aims at creating a standard for describing multimedia content in order to facilitate the interpretation of the associated information content. Attempting to address a broad range of applications, MPEG-7 has defined a flexible framework consisting of Descriptors, Description Schemes, and Description Definition Language. Descriptors and Description Schemes describe features, structure and semantics of multimedia objects. They are written in the Description Definition Language (DDL). In the most recent revision, DDL applies XML (Extensible Markup Language) Schema with MPEG-7 extensions. DDL has constructs that support inclusion, inheritance, reference, enumeration, choice, sequence, and abstract type of Description Schemes and Descriptors. In order to enable multimedia systems to use MPEG-7, a number of important problems in storing, retrieving and searching MPEG-7 documents need to be solved. This paper reports on initial finding on issues and solutions of storing and accessing MPEG-7 documents. In particular, we discuss the benefits of using a virtual document management framework based on XML Access Server (XAS) in order to bridge the MPEG-7 multimedia applications and database systems. The need arises partly because MPEG-7 descriptions need customized storage schema, indexing and search engines. We also discuss issues arising in managing dependence and cross-description scheme search.
Miller, Hilary E; Simmering, Vanessa R
2018-08-01
Children's spatial language reliably predicts their spatial skills, but the nature of this relation is a source of debate. This investigation examined whether the mechanisms accounting for such relations are specific to language use or reflect a domain-general mechanism of selective attention. Experiment 1 examined whether 4-year-olds' spatial skills were predicted by their selective attention or their adaptive language use. Children completed (a) an attention task assessing attention to task-relevant color, size, and location cues; (b) a description task assessing adaptive language use to describe scenes varying in color, size, and location; and (c) three spatial tasks. There was correspondence between the cue types that children attended to and produced across description and attention tasks. Adaptive language use was predicted by both children's attention and task-related language production, suggesting that selective attention underlies skills in using language adaptively. After controlling for age, gender, receptive vocabulary, and adaptive language use, spatial skills were predicted by children's selective attention. The attention score predicted variance in spatial performance previously accounted for by adaptive language use. Experiment 2 followed up on the attention task (Experiment 2a) and description task (Experiment 2b) from Experiment 1 to assess whether performance in the tasks related to selective attention or task-specific demands. Performance in Experiments 2a and 2b paralleled that in Experiment 1, suggesting that the effects in Experiment 1 reflected children's selective attention skills. These findings show that selective attention is a central factor supporting spatial skill development that could account for many effects previously attributed to children's language use. Copyright © 2018 Elsevier Inc. All rights reserved.
Foreign Language Training in the United States Peace Corps.
ERIC Educational Resources Information Center
Kulakow, Allan
This document reports on the foreign language training offered in the Peace Corps. Following a brief introductory statement, a list of languages taught by the Peace Corps in the years 1961-67 is provided, as well as a brief description of Peace Corps language training methods. Guidelines for language coordinators are outlined, and the approach to…
ERIC Educational Resources Information Center
Heng, Chan Swee
2012-01-01
Any attempt to define English language proficiency can never be divorced from the theories that describe the nature of language, language acquisition and human cognition. By virtue of such theories being socially constructed, the descriptions are necessarily value-laden. Thus, a definition of language proficiency can only, at best, be described as…
A Grammar of Sierra Popoluca (Soteapanec, a Mixe-Zoquean Language)
ERIC Educational Resources Information Center
de Jong Boudreault, Lynda J.
2009-01-01
This dissertation is a comprehensive description of the grammar of Sierra Popoluca (SP, aka Soteapanec), a Mixe-Zoquean language spoken by approximately 28,000 people in Veracruz, Mexico. This grammar begins with an introduction to the language, its language family, a typological overview of the language, a brief history of my fieldwork, and the…
DRFM Cordic Processor and Sea Clutter Modeling for Enhancing Structured False Target Synthesis
2017-09-01
was implemented using the Verilog hardware description language. The second investigation concerns generating sea clutter to impose on the false target...to achieve accuracy at 5.625o. The resulting design was implemented using the Verilog hardware description language. The second investigation...33 3. Initialization of the Angle Accumulator ....................................34 4. Design Methodology for I/Q Phase
ERIC Educational Resources Information Center
Litman, Cindy; Marple, Stacy; Greenleaf, Cynthia; Charney-Sirott, Irisa; Bolz, Michael J.; Richardson, Lisa K.; Hall, Allison H.; George, MariAnne; Goldman, Susan R.
2017-01-01
This study presents a descriptive analysis of 71 videotaped lessons taught by 34 highly regarded secondary English language arts, history, and science teachers, collected to inform an intervention focused on evidence-based argumentation from multiple text sources. Studying the practices of highly regarded teachers is valuable for identifying…
Development of a test and flight engineering oriented language. Phase 3: Presentation
NASA Technical Reports Server (NTRS)
Kamsler, W. F.; Case, C. W.; Kinney, E. L.; Gyure, J.
1970-01-01
The format material used in an oral presentation of the phase 3 study effort is given. The material includes a description of the language ALOFT and a terminology comparison with other test languages.
NASA Technical Reports Server (NTRS)
Orlov, I. G.
1979-01-01
The BASIC algorithmic language is described, and a guide is presented for the programmer using the language interpreter. The high-level algorithm BASIC is a problem-oriented programming language intended for solution of computational and engineering problems.
SDL: A Surface Description Language
NASA Technical Reports Server (NTRS)
Maple, Raymond C.
1992-01-01
A new interpreted language specifically designed for surface grid generation is introduced. Many unique aspects of the language are discussed, including the farray, vector, curve, and surface data types and the operators used to manipulate them. Custom subroutine libraries written in the language are used to easily build surface grids for generic missile shapes.
The Sociolinguistic Model in Speech and Language Pathology.
ERIC Educational Resources Information Center
Wolfram, Walt
A discussion of the role of sociolinguistics in the treatment of communication disorders focuses on issues related to dialect and language variation. It begins with an examination of linguistic diversity and dynamic description of language, reporting on a study of speech and language pathologists' judgments of sentences in African American…
ERIC Educational Resources Information Center
Petersen, Douglas B.; Gillam, Ronald B.
2013-01-01
Sixty-three bilingual Latino children who were at risk for language impairment were administered reading-related measures in English and Spanish (letter identification, phonological awareness, rapid automatized naming, and sentence repetition) and descriptive measures including English language proficiency (ELP), language ability (LA),…
Assessment of metal contents in spices and herbs from Saudi Arabia.
Seddigi, Z S; Kandhro, G A; Shah, F; Danish, E; Soylak, Mustafa
2016-02-01
In the recent years, there has been a growing interest in monitoring heavy metal contamination of spices/herbs. Spices and herbs are sources of many bioactive compounds that can improve the tastes of food as well as influence digestion and metabolism processes. In the present study, the levels of some essential and toxic elements such as iron (Fe), zinc (Zn), copper (Cu), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), lead (Pb), and cadmium (Cd), present in common spices/herbs that were purchased from the local market in Saudi Arabia, were analyzed by atomic absorption spectroscopy after digestion with nitric acid/hydrogen peroxide mixture. Samples from the following spices/herbs were used: turmeric, cloves, black pepper, red pepper, cumin, legume, cinnamon, abazir, white pepper, ginger, and coriander. The concentration ranges for the studied elements were found as 48.8-231, 4.7-19.4, 2.5-10.5, below detection level (BDL)-1.0, 8.8-490, 1.0-2.6, and BDL-3.7 µg g(-1) for Fe, Zn, Cu, Cr, Mn, Ni, and Pb, respectively, while Cd and Co levels were below the detection limit. Consumers of these spices/herbs would not be exposed to any risk associated with the daily intake of 10 g of spices per day as far as metals Fe, Zn, Cu, Cr, Mn, Ni, and Pb are concerned. © The Author(s) 2013.
Jibiri, N N; Farai, I P; Alausa, S K
2007-01-01
Soils and food crops from a former tin mining location in a high background radiation area on the Jos-Plateau, Nigeria were collected and analyzed by gamma spectrometry to measure their contents of 40K, 238U and 232Th. As well as collecting samples, in situ dose rates on farms were measured using a precalibrated survey meter. Activity concentrations determined in food crops were compared with the local food derivatives or diets to investigate the possible removal or addition of radionuclides during food preparation by cooking or other means. Potassium-40 was found to contribute the highest activity in all the food products. The activity concentration of 40K, 238U and 232Th in local prepared diets ranged between 60 and 494 Bq kg-1, between BDL and 48 Bq kg-1 and between BDL and 17 Bq kg-1, respectively. The internal effective dose to individuals from the consumption of the food types was estimated on the basis of the measured radionuclide contents in the food crops. It ranged between 0.2 microSv y-1 (beans) and 2164 microSv y-1 (yam) while the annual external gamma effective dose in the farms due to soil radioactivity ranged between 228 microSv and 4065 microSv.
Personalized Age Progression with Bi-Level Aging Dictionary Learning.
Shu, Xiangbo; Tang, Jinhui; Li, Zechao; Lai, Hanjiang; Zhang, Liyan; Yan, Shuicheng
2018-04-01
Age progression is defined as aesthetically re-rendering the aging face at any future age for an individual face. In this work, we aim to automatically render aging faces in a personalized way. Basically, for each age group, we learn an aging dictionary to reveal its aging characteristics (e.g., wrinkles), where the dictionary bases corresponding to the same index yet from two neighboring aging dictionaries form a particular aging pattern cross these two age groups, and a linear combination of all these patterns expresses a particular personalized aging process. Moreover, two factors are taken into consideration in the dictionary learning process. First, beyond the aging dictionaries, each person may have extra personalized facial characteristics, e.g., mole, which are invariant in the aging process. Second, it is challenging or even impossible to collect faces of all age groups for a particular person, yet much easier and more practical to get face pairs from neighboring age groups. To this end, we propose a novel Bi-level Dictionary Learning based Personalized Age Progression (BDL-PAP) method. Here, bi-level dictionary learning is formulated to learn the aging dictionaries based on face pairs from neighboring age groups. Extensive experiments well demonstrate the advantages of the proposed BDL-PAP over other state-of-the-arts in term of personalized age progression, as well as the performance gain for cross-age face verification by synthesizing aging faces.
Carlson, Laura; Skubic, Marjorie; Miller, Jared; Huo, Zhiyu; Alexenko, Tatiana
2014-07-01
This contribution presents a corpus of spatial descriptions and describes the development of a human-driven spatial language robot system for their comprehension. The domain of application is an eldercare setting in which an assistive robot is asked to "fetch" an object for an elderly resident based on a natural language spatial description given by the resident. In Part One, we describe a corpus of naturally occurring descriptions elicited from a group of older adults within a virtual 3D home that simulates the eldercare setting. We contrast descriptions elicited when participants offered descriptions to a human versus robot avatar, and under instructions to tell the addressee how to find the target versus where the target is. We summarize the key features of the spatial descriptions, including their dynamic versus static nature and the perspective adopted by the speaker. In Part Two, we discuss critical cognitive and perceptual processing capabilities necessary for the robot to establish a common ground with the human user and perform the "fetch" task. Based on the collected corpus, we focus here on resolving the perspective ambiguity and recognizing furniture items used as landmarks in the descriptions. Taken together, the work presented here offers the key building blocks of a robust system that takes as input natural spatial language descriptions and produces commands that drive the robot to successfully fetch objects within our eldercare scenario. Copyright © 2014 Cognitive Science Society, Inc.
Semantic message oriented middleware for publish/subscribe networks
NASA Astrophysics Data System (ADS)
Li, Han; Jiang, Guofei
2004-09-01
The publish/subscribe paradigm of Message Oriented Middleware provides a loosely coupled communication model between distributed applications. Traditional publish/subscribe middleware uses keywords to match advertisements and subscriptions and does not support deep semantic matching. To this end, we designed and implemented a Semantic Message Oriented Middleware system to provide such capabilities for semantic description and matching. We adopted the DARPA Agent Markup Language and Ontology Inference Layer, a formal knowledge representation language for expressing sophisticated classifications and enabling automated inference, as the topic description language in our middleware system. A simple description logic inference system was implemented to handle the matching process between the subscriptions of subscribers and the advertisements of publishers. Moreover our middleware system also has a security architecture to support secure communication and user privilege control.
An amodal shared resource model of language-mediated visual attention
Smith, Alastair C.; Monaghan, Padraic; Huettig, Falk
2013-01-01
Language-mediated visual attention describes the interaction of two fundamental components of the human cognitive system, language and vision. Within this paper we present an amodal shared resource model of language-mediated visual attention that offers a description of the information and processes involved in this complex multimodal behavior and a potential explanation for how this ability is acquired. We demonstrate that the model is not only sufficient to account for the experimental effects of Visual World Paradigm studies but also that these effects are emergent properties of the architecture of the model itself, rather than requiring separate information processing channels or modular processing systems. The model provides an explicit description of the connection between the modality-specific input from language and vision and the distribution of eye gaze in language-mediated visual attention. The paper concludes by discussing future applications for the model, specifically its potential for investigating the factors driving observed individual differences in language-mediated eye gaze. PMID:23966967
Waltemath, Dagmar; Adams, Richard; Bergmann, Frank T; Hucka, Michael; Kolpakov, Fedor; Miller, Andrew K; Moraru, Ion I; Nickerson, David; Sahle, Sven; Snoep, Jacky L; Le Novère, Nicolas
2011-12-15
The increasing use of computational simulation experiments to inform modern biological research creates new challenges to annotate, archive, share and reproduce such experiments. The recently published Minimum Information About a Simulation Experiment (MIASE) proposes a minimal set of information that should be provided to allow the reproduction of simulation experiments among users and software tools. In this article, we present the Simulation Experiment Description Markup Language (SED-ML). SED-ML encodes in a computer-readable exchange format the information required by MIASE to enable reproduction of simulation experiments. It has been developed as a community project and it is defined in a detailed technical specification and additionally provides an XML schema. The version of SED-ML described in this publication is Level 1 Version 1. It covers the description of the most frequent type of simulation experiments in the area, namely time course simulations. SED-ML documents specify which models to use in an experiment, modifications to apply on the models before using them, which simulation procedures to run on each model, what analysis results to output, and how the results should be presented. These descriptions are independent of the underlying model implementation. SED-ML is a software-independent format for encoding the description of simulation experiments; it is not specific to particular simulation tools. Here, we demonstrate that with the growing software support for SED-ML we can effectively exchange executable simulation descriptions. With SED-ML, software can exchange simulation experiment descriptions, enabling the validation and reuse of simulation experiments in different tools. Authors of papers reporting simulation experiments can make their simulation protocols available for other scientists to reproduce the results. Because SED-ML is agnostic about exact modeling language(s) used, experiments covering models from different fields of research can be accurately described and combined.
LANGUAGES OF THE WORLD--INDO-PACIFIC FASCICLE FIVE.
ERIC Educational Resources Information Center
VOEGELIN, C. F.; AND OTHERS
THIS REPORT CONTAINS A HISTORY OF RESEARCH CONCERNED WITH THE AUSTRALIAN LANGUAGES, AND DESCRIPTIONS OF THE 228 LANGUAGES IN THE AUSTRALIAN MACRO-PHYLUM. (THE REPORT IS PART OF A SERIES, ED 010 350 TO ED 010 367.) (JK)
ERIC Educational Resources Information Center
Dollerup, Cay
This is a descriptive outline of the language situation in the Danish education system. The introductory material discusses the reason for foreign language study. A major reason is that Denmark is a small country with a difficult native language for speakers of other languages to learn. Therefore, the Danish population is exposed to foreign…
ERIC Educational Resources Information Center
Saito, Kazuya
2017-01-01
This study examines the relationship between different types of language learning aptitude (measured via the LLAMA test) and adult second language (L2) learners' attainment in speech production in English-as-a-foreign-language (EFL) classrooms. Picture descriptions elicited from 50 Japanese EFL learners from varied proficiency levels were analyzed…
Thick Descriptions: A Language for Articulating Ethnographic Media Technology.
ERIC Educational Resources Information Center
Goldman-Segall, Ricki
"Thick descriptions" are descriptions that are layered enough to draw conclusions and uncover the intentions of a given act, event, or process. In a video environment, thick descriptions are images, gestures, or sequences that convey meaning. Neither the quantity nor the resolution of the images makes the descriptions thick. Thickness is…
ERIC Educational Resources Information Center
POPPE, NICHOLAS
THIS MANUAL PRESENTS A COMPREHENSIVE GRAMMAR OF TATAR, ONE OF THE TURKIC LANGUAGES BELONGING TO THE NORTH-WESTERN (KIPCHAK) BRANCH. IT IS SPOKEN BY NEARLY FIVE MILLION PEOPLE IN THE AUTONOMOUS TATAR SOVIET REPUBLIC OF THE USSR. A BRIEF DESCRIPTION OF THE LANGUAGE AND ITS MAIN DIALECTS IS GIVEN IN THE INTRODUCTION, WHICH ALSO INCLUDES A SELECTED…
A UML model for the description of different brain-computer interface systems.
Quitadamo, Lucia Rita; Abbafati, Manuel; Saggio, Giovanni; Marciani, Maria Grazia; Cardarilli, Gian Carlo; Bianchi, Luigi
2008-01-01
BCI research lacks a universal descriptive language among labs and a unique standard model for the description of BCI systems. This results in a serious problem in comparing performances of different BCI processes and in unifying tools and resources. In such a view we implemented a Unified Modeling Language (UML) model for the description virtually of any BCI protocol and we demonstrated that it can be successfully applied to the most common ones such as P300, mu-rhythms, SCP, SSVEP, fMRI. Finally we illustrated the advantages in utilizing a standard terminology for BCIs and how the same basic structure can be successfully adopted for the implementation of new systems.
Assilaméhou, Yvette; Lepastourel, Nadia; Testé, Benoit
2013-01-01
The present research investigated whether the impact of the Linguistic Intergroup Bias (LIB; Maass, 1999) is related to the effects of linguistic abstraction on social attribution (Yzerbyt & Rogier, 2001). We did this by assessing the impact of abstract descriptions versus concrete descriptions on the generalization of a group member's behaviors to the whole group. A target's behaviors were more attributed to the group when the description was abstract than when it was concrete, and this effect of language abstraction was stronger when the description was positive than when it was negative. Our results provide an insight into how the LIB is involved in the perpetuation of intergroup bias.
Berber Dialects. Materials Status Report.
ERIC Educational Resources Information Center
Center for Applied Linguistics, Washington, DC. Language/Area Reference Center.
The materials status report for the Berber languages, minority languages spoken in northern Africa, is one of a series intended to provide the nonspecialist with a picture of the availability and quality of texts for teaching various languages to English speakers. The report consists of: (1) a brief narrative description of the Berber language,…
Language and Ageing--Exploring Propositional Density in Written Language--Stability over Time
ERIC Educational Resources Information Center
Spencer, Elizabeth; Craig, Hugh; Ferguson, Alison; Colyvas, Kim
2012-01-01
This study investigated the stability of propositional density (PD) in written texts, as this aspect of language shows promise as an indicator and as a predictor of language decline with ageing. This descriptive longitudinal study analysed written texts obtained from the Australian Longitudinal Study of Women's Health in which participants were…
ERIC Educational Resources Information Center
Le Page, R. B.
A discussion on the nature of language argues the following: (1) the concept of a closed and finite rule system is inadequate for the description of natural languages; (2) as a consequence, the writing of variable rules to modify such rule systems so as to accommodate the properties of natural language is inappropriate; (3) the concept of such…
Legal Language: What Is It and What Can We Do About It?
ERIC Educational Resources Information Center
Charrow, Veda R.; Crandall, Jo Ann
The simplification of legal language is required by President Carter's Executive Order requiring "clear and simple English" in government regulations. A major problem in the simplification process is the absence of any adequate description or classification of legal language. This paper defines some specific features of legal language,…
Curriculum Guide, English as a Second Language, Kindergarten through Grade Twelve.
ERIC Educational Resources Information Center
Berrios, Ana Teresa; And Others
This curriculum guide provides a detailed description of the program in English as a second language (ESL) in the Newark Public Schools. After an introduction that describes the audiolingual method of teaching foreign languages and that defines briefly the cognitive approach to language instruction and the "silent way," the guide…
Anthropology and Language Science in Educational Development Newsletter, No. 2/3.
ERIC Educational Resources Information Center
United Nations Educational, Scientific, and Cultural Organization, Paris (France). Div. of Structures and Content of Life-Long Education.
This issue of the ALSED newsletter contains: (1) a description of the Anthropology and Language Science in Educational Development (ALSED) program; (2) information on the meeting of experts on diversification of methods and techniques for teaching a second language or foreign languages (Paris, Unesco, 15-20 September, 1975), which discussed such…
Classroom Management in Foreign Language Education: An Exploratory Review
ERIC Educational Resources Information Center
Macías, Diego Fernando
2018-01-01
This review examines studies in the area of classroom management in foreign language education. It is organized into three large areas: The first area focuses on the distinctive characteristics of foreign language instruction that are more likely to impact classroom management in foreign language classes. The second area provides a description of…
Foreign Language Week: A Successful Public Relations Model.
ERIC Educational Resources Information Center
Reschke, Claus
A detailed description is presented of a foreign language (FL) week project that was organized and executed by the Houston Area Teachers of Foreign Languages (HATFL) during the 1979-80 academic year. The document describes the preparation activities of the organizing committee, the pre-foreign language week advertising campaigns, the design of…
Student Centered WebCT Instruction for African Language.
ERIC Educational Resources Information Center
Moshi, Lioba; Ojo, Akinloye
2000-01-01
Explores theoretical issues concerning instructional technology for African language instruction, gives a brief description of WebCT (a web-based instruction framework), and describes its practicality in the instruction of African languages with special focus on Swahili and Yoruba. (Author/VWL)
Hadl: HUMS Architectural Description Language
NASA Technical Reports Server (NTRS)
Mukkamala, R.; Adavi, V.; Agarwal, N.; Gullapalli, S.; Kumar, P.; Sundaram, P.
2004-01-01
Specification of architectures is an important prerequisite for evaluation of architectures. With the increase m the growth of health usage and monitoring systems (HUMS) in commercial and military domains, the need far the design and evaluation of HUMS architectures has also been on the increase. In this paper, we describe HADL, HUMS Architectural Description Language, that we have designed for this purpose. In particular, we describe the features of the language, illustrate them with examples, and show how we use it in designing domain-specific HUMS architectures. A companion paper contains details on our design methodology of HUMS architectures.
Hardware synthesis from DDL. [Digital Design Language for computer aided design and test of LSI
NASA Technical Reports Server (NTRS)
Shah, A. M.; Shiva, S. G.
1981-01-01
The details of the digital systems can be conveniently input into the design automation system by means of Hardware Description Languages (HDL). The Computer Aided Design and Test (CADAT) system at NASA MSFC is used for the LSI design. The Digital Design Language (DDL) has been selected as HDL for the CADAT System. DDL translator output can be used for the hardware implementation of the digital design. This paper addresses problems of selecting the standard cells from the CADAT standard cell library to realize the logic implied by the DDL description of the system.
ERIC Educational Resources Information Center
Gocer, Ali
2014-01-01
The purpose of this study is to assess the anxiety connected with target language of the high school students learning Turkish as a foreign language. In this study, descriptive relational screening model was used. Two scales were used for collecting data. First scale was FLCAS-Foreign Language Classroom Anxiety Scale; it was developed by Horwitz…
Does language guide event perception? Evidence from eye movements
Papafragou, Anna; Hulbert, Justin; Trueswell, John
2008-01-01
Languages differ in how they encode motion. When describing bounded motion, English speakers typically use verbs that convey information about manner (e.g., slide, skip, walk) rather than path (e.g., approach, ascend), whereas Greek speakers do the opposite. We investigated whether this strong cross-language difference influences how people allocate attention during motion perception. We compared eye movements from Greek and English speakers as they viewed motion events while (a) preparing verbal descriptions, or (b) memorizing the events. During the verbal description task, speakers’ eyes rapidly focused on the event components typically encoded in their native language, generating significant cross-language differences even during the first second of motion onset. However, when freely inspecting ongoing events, as in the memorization task, people allocated attention similarly regardless of the language they speak. Differences between language groups arose only after the motion stopped, such that participants spontaneously studied those aspects of the scene that their language does not routinely encode in verbs. These findings offer a novel perspective on the relation between language and perceptual/cognitive processes. They indicate that attention allocation during event perception is not affected by the perceiver’s native language; effects of language arise only when linguistic forms are recruited to achieve the task, such as when committing facts to memory. PMID:18395705
Design Language for Digital Systems
NASA Technical Reports Server (NTRS)
Shiva, S. G.
1985-01-01
Digital Systems Design Language (DDL) is convenient hardware description language for developing and testing digital designs and for inputting design details into design automation system. Describes digital systems at gate, register transfer, and combinational block levels. DDL-based programs written in FORTRAN IV for batch execution.
Authenticating Secure Tokens Using Slow Memory Access
1999-01-01
Cryptology— CRYPTO ’97 Proceedings, Springer- Verlag, 1997, pp. 513–525. [CP93] D . Chaum and T. Pederson, “Wallet Databases with Observers,” Advances in...96 Proceedings, Springer-Verlag, 1996, pp. 1–15. [BDL97] D . Boneh, R.A. Demillo, R.J. Lip- ton, “On the Importance of Check- ing Cryptographic...Protocols for Faults,” Advances in Cryptology—EUROCRYPT ’97 Proceedings, Springer-Verlag, 1997, pp. 37–51. [BGW98] M. Briceno, I. Goldberg, D . Wagner
NASA Technical Reports Server (NTRS)
Shiva, S. G.; Shah, A. M.
1980-01-01
The details of digital systems can be conveniently input into the design automation system by means of hardware description language (HDL). The computer aided design and test (CADAT) system at NASA MSFC is used for the LSI design. The digital design language (DDL) was selected as HDL for the CADAT System. DDL translator output can be used for the hardware implementation of the digital design. Problems of selecting the standard cells from the CADAT standard cell library to realize the logic implied by the DDL description of the system are addressed.
ERIC Educational Resources Information Center
Lavalle, Pamela I.; Briesmaster, Mark
2017-01-01
Teachers of English as a foreign language (EFL) encourage students to take a more active role in the oral activities in the classroom through different strategies. This study examines the use of picture descriptions as a strategy to develop and enhance communication skills among the eighth-grade students attending a private English school in…
Automatic Digital Hardware Synthesis
1990-09-01
VHDL to PALASM, a hardware synthesis language. The PALASM description is then directly implemented into a field programmable gate array (FPGAI using...process of translating VHDL to PALASM, a hardware synthesis language. The PALASM description is then directly implemented into a field programmable gate...allows the engineer to use VHDL to create and validate a design, and then to implement it in a gate array. The development of software o translate VHDL
Grande, Marion; Meffert, Elisabeth; Schoenberger, Eva; Jung, Stefanie; Frauenrath, Tobias; Huber, Walter; Hussmann, Katja; Moormann, Mareike; Heim, Stefan
2012-07-02
Spontaneous language has rarely been subjected to neuroimaging studies. This study therefore introduces a newly developed method for the analysis of linguistic phenomena observed in continuous language production during fMRI. Most neuroimaging studies investigating language have so far focussed on single word or - to a smaller extent - sentence processing, mostly due to methodological considerations. Natural language production, however, is far more than the mere combination of words to larger units. Therefore, the present study aimed at relating brain activation to linguistic phenomena like word-finding difficulties or syntactic completeness in a continuous language fMRI paradigm. A picture description task with special constraints was used to provoke hesitation phenomena and speech errors. The transcribed speech sample was segmented into events of one second and each event was assigned to one category of a complex schema especially developed for this purpose. The main results were: conceptual planning engages bilateral activation of the precuneus. Successful lexical retrieval is accompanied - particularly in comparison to unsolved word-finding difficulties - by the left middle and superior temporal gyrus. Syntactic completeness is reflected in activation of the left inferior frontal gyrus (IFG) (area 44). In sum, the method has proven to be useful for investigating the neural correlates of lexical and syntactic phenomena in an overt picture description task. This opens up new prospects for the analysis of spontaneous language production during fMRI. Copyright © 2012 Elsevier Inc. All rights reserved.
ERIC Educational Resources Information Center
Barbour, Ross; Ostler, Catherine; Templeman, Elizabeth; West, Elizabeth
2007-01-01
The British Columbia (BC) English as a Second Language (ESL) Articulation Committee's Canadian Language Benchmarks project was precipitated by ESL instructors' desire to address transfer difficulties of ESL students within the BC transfer system and to respond to the recognition that the Canadian Language Benchmarks, a descriptive scale of ESL…
Moving beyond Communicative Language Teaching: A Situated Pedagogy for Japanese EFL Classrooms
ERIC Educational Resources Information Center
Lochland, Paul W.
2013-01-01
This article questions the appropriateness of communicative language teaching (CLT) in classrooms teaching English as a foreign language (EFL) to Japanese students. The four main criticisms of CLT are the ambiguity of its description, the benefits of CLT for language learning, the amalgamation of CLT methods with local classroom practices, and the…
ERIC Educational Resources Information Center
Tuncer, Murat; Dogan, Yunus
2015-01-01
This study was carried out in order to identify to what extent the Turkish students' English classroom anxiety affects their academic achievement in English language. In this quantitative descriptive study, a correlational survey model was employed, and the convenience sampling was done. In order to collect data, the Foreign Language Classroom…
ERIC Educational Resources Information Center
Travers, Claudia S.; Reilly, Joseph T. M.
A foreign travel program for eighth grade French language students from Shoreham, New York was developed to provide language speaking practice in Quebec, Canada. The program was designed to allow students to spend as much time as possible speaking the language and interacting with the people. The following "survival through speaking"…
ERIC Educational Resources Information Center
Stansfield, Charles W.; Kenyon, Dorry Mann
The report of the Interagency Language Roundtable's invitational symposium on language aptitude testing consists of a description of the project and appendixes which include the following: (1) the symposium program and abstracts of papers; (2) a list of participants; and (3) summaries of the discussions of three working groups (on applications,…
First Steps to Endangered Language Documentation: The Kalasha Language, a Case Study
ERIC Educational Resources Information Center
Mela-Athanasopoulou, Elizabeth
2011-01-01
The present paper based on extensive fieldwork D conducted on Kalasha, an endangered language spoken in the three small valleys in Chitral District of Northwestern Pakistan, exposes a spontaneous dialogue-based elicitation of linguistic material used for the description and documentation of the language. After a brief display of the basic typology…
Philippine and North Bornean Languages: Issues in Description, Subgrouping, and Reconstruction
ERIC Educational Resources Information Center
Lobel, Jason William
2013-01-01
The Philippines, northern Sulawesi, and northern Borneo are home to two or three hundred languages that can be described as Philippine-type. In spite of nearly five hundred years of language documentation in the Philippines, and at least a century of work in Borneo and Sulawesi, the majority of these languages remain grossly underdocumented, and…
ERIC Educational Resources Information Center
Okoth, Teresa A.
2016-01-01
This study investigated the challenges Form III English language teachers face when implementing the revised integrated English language curriculum. A mixed-method descriptive design was used in Eldoret East SubCounty in Kenya. Data was collected through questionnaires, interviews and reflective conversations. Cluster, purposive and random…
Issues of Identity in Minority Language Media Production in Colombia and Wales
ERIC Educational Resources Information Center
Uribe-Jongbloed, Enrique
2016-01-01
This paper addresses how different media production teams negotiate the use of their minority languages in their practice. After a brief discussion of the concepts of language and description of a linguistic minority, a short review of similar research in the area of Minority Language Media is presented. Within this area, radio producers from…
Teacher Language Competence Description: Towards a New Framework of Evaluation
ERIC Educational Resources Information Center
Sokolova, Nataliya
2012-01-01
The article is centred around the concept of "language competence of a foreign language (FL) teacher" and the ways it can be evaluated. Though the definition of teacher language competence might sound obvious it has not yet been clearly structured and, therefore, no component has been thoroughly described. I use this fact as a starting…
The Multifaceted Ecology of Language Play in an Elementary School EFL Classroom
ERIC Educational Resources Information Center
Kang, Dae-Min
2017-01-01
Language play (LP) in second language (L2) classrooms has attracted increasing attention in recent years, but descriptions and explanations of LP construction in English as a foreign language (EFL) settings remain insufficient. This paper reports the discursive processes of LP construction in an elementary school EFL classroom in Korea. I found…
ERIC Educational Resources Information Center
POLOME, EDGAR C.
THIS INTRODUCTION TO THE STRUCTURE AND BACKGROUND OF THE SWAHILI LANGUAGE WAS WRITTEN FOR THE NON-SPECIALIST. ALTHOUGH THE LINGUISTIC TERMINOLOGY USED IN THE DESCRIPTION OF THE LANGUAGE ASSUMES THE READER HAS HAD SOME TRAINING IN LINGUISTICS, THIS HANDBOOK PROVIDES BASIC LINGUISTIC AND SOCIOLINGUISTIC INFORMATION FOR STUDENTS OF AFRICAN CULTURE…
The Language of Qualitative Issues. AIR Forum 1982 Paper.
ERIC Educational Resources Information Center
Duckwall, Julia M.; Johnson, F. Craig
The communication of research findings among collegiate institutional researchers is considered in relation to the contribution of qualitative language in general, and catastrophe theory in particular. The qualitative language of catastrophe theory may help reduce the arbitrariness of description, through identification of qualitative features…
Descriptions of Selected Career-Related College Language Courses
ERIC Educational Resources Information Center
Knodel, Arthur J.; And Others
1977-01-01
Seven courses or programs at different colleges emphasizing specific career applications of languages are described. They include: Technical French; Spanish for Law Enforcement and Correctional Personnel; Executive German; Proyecto Desarrollo Economico; Spanish for Medical Professions; Elements of Foreign Language, and Business French and Business…
LANGUAGES OF THE WORLD--INDO-PACIFIC FASCICLE FOUR.
ERIC Educational Resources Information Center
VOEGELIN, C. F.; VOEGELIN, FLORENCE M.
THIS REPORT CONTAINS A LIST AND DESCRIPTIONS OF THE AUSTRONESIAN FAMILY OF LANGUAGES WHICH INCLUDE THE LANGUAGES OF INDONESIA, FORMOSA, MADAGASCAR, THE PHILIPPINE ISLANDS, AND PART OF SOUTHEAST ASIA. (THE REPORT IS PART OF A SERIES, ED 010 350 TO ED 010 367.) (JK)
ERIC Educational Resources Information Center
Hyslop, Gwendolyn
2011-01-01
Kurtop is a Tibeto-Burman language spoken by approximately 15,000 people in Northeastern Bhutan. This dissertation is the first descriptive grammar of the language, based on extensive fieldwork and community-driven language documentation in Bhutan. When possible, analyses are presented in typological and historical/comparative perspectives and…
The Sizing and Optimization Language, (SOL): Computer language for design problems
NASA Technical Reports Server (NTRS)
Lucas, Stephen H.; Scotti, Stephen J.
1988-01-01
The Sizing and Optimization Language, (SOL), a new high level, special purpose computer language was developed to expedite application of numerical optimization to design problems and to make the process less error prone. SOL utilizes the ADS optimization software and provides a clear, concise syntax for describing an optimization problem, the OPTIMIZE description, which closely parallels the mathematical description of the problem. SOL offers language statements which can be used to model a design mathematically, with subroutines or code logic, and with existing FORTRAN routines. In addition, SOL provides error checking and clear output of the optimization results. Because of these language features, SOL is best suited to model and optimize a design concept when the model consits of mathematical expressions written in SOL. For such cases, SOL's unique syntax and error checking can be fully utilized. SOL is presently available for DEC VAX/VMS systems. A SOL package is available which includes the SOL compiler, runtime library routines, and a SOL reference manual.
Endara, Lorena; Cui, Hong; Burleigh, J Gordon
2018-03-01
Phenotypic data sets are necessary to elucidate the genealogy of life, but assembling phenotypic data for taxa across the tree of life can be technically challenging and prohibitively time consuming. We describe a semi-automated protocol to facilitate and expedite the assembly of phenotypic character matrices of plants from formal taxonomic descriptions. This pipeline uses new natural language processing (NLP) techniques and a glossary of over 9000 botanical terms. Our protocol includes the Explorer of Taxon Concepts (ETC), an online application that assembles taxon-by-character matrices from taxonomic descriptions, and MatrixConverter, a Java application that enables users to evaluate and discretize the characters extracted by ETC. We demonstrate this protocol using descriptions from Araucariaceae. The NLP pipeline unlocks the phenotypic data found in taxonomic descriptions and makes them usable for evolutionary analyses.
Schmitt, J F; Meline, T J
1990-12-01
We reviewed the 1983-1988 issues of six journals that frequently publish papers including specifically language-impaired (LI) subjects. A total of 92 research reports provided data for our review. The research reports included experimental studies, ex post facto studies, and intervention studies. These studies represent a broad spectrum of the theoretical and empirical foundations of knowledge regarding LI children. The analysis of the published research centered on subject descriptions and the use of control groups. A descriptive analysis of the data showed few consistent trends among the studies with respect to subject selection, subject description, and the number and types of control groups. We discuss the importance of more complete subject descriptions in studies of LI children as well as the importance of the choice of matching criteria for control groups in between-subjects designs.
Can Nomenclature for the Body be Explained by Embodiment Theories?
Majid, Asifa; van Staden, Miriam
2015-10-01
According to widespread opinion, the meaning of body part terms is determined by salient discontinuities in the visual image; such that hands, feet, arms, and legs, are natural parts. If so, one would expect these parts to have distinct names which correspond in meaning across languages. To test this proposal, we compared three unrelated languages-Dutch, Japanese, and Indonesian-and found both naming systems and boundaries of even basic body part terms display variation across languages. Bottom-up cues alone cannot explain natural language semantic systems; there simply is not a one-to-one mapping of the body semantic system to the body structural description. Although body parts are flexibly construed across languages, body parts semantics are, nevertheless, constrained by non-linguistic representations in the body structural description, suggesting these are necessary, although not sufficient, in accounting for aspects of the body lexicon. Copyright © 2015 Cognitive Science Society, Inc.
Just a preference: racialised language in the sex-seeking profiles of gay and bisexual men.
Callander, Denton; Holt, Martin; Newman, Christy E
2012-10-01
Racialised language is a salient and contested aspect of contemporary sexual cultures, particularly in the online domain. This paper explores the ways in which gay men in Australia employ race-related language when using online sex/dating websites. Using inductive content analysis, descriptive categories were developed to identify recurrent patterns in the racialised language employed by website users. A coding framework was then constructed to identify the 'subject' (self, other or concept) of each piece of race-related content, its 'purpose' (marketing, negative or positive discrimination, commentary) and the 'position' adopted (defensive, normalised or critical). Descriptive and comparative analyses revealed differences in the ways in which members of racial groups employed racialised language online. These differences are reviewed in relation to broader discourses on Whiteness and race in Australia, as well as recent community-produced anti-racism campaigns.
Summary report for the Engineering Script Language (ESL)
NASA Technical Reports Server (NTRS)
1990-01-01
The following subject areas are covered: ESL methodology concept; ESL specification; user interface description; engineering scripting language command statements specification; and recommendations for further research and development.
A Counterexample Guided Abstraction Refinement Framework for Verifying Concurrent C Programs
2005-05-24
source code are routinely executed. The source code is written in languages ranging from C/C++/Java to ML/ Ocaml . These languages differ not only in...from the difficulty to model computer programs—due to the complexity of programming languages as compared to hardware description languages —to...intermediate specification language lying between high-level Statechart- like formalisms and transition systems. Actions are encoded as changes in
BioSWR – Semantic Web Services Registry for Bioinformatics
Repchevsky, Dmitry; Gelpi, Josep Ll.
2014-01-01
Despite of the variety of available Web services registries specially aimed at Life Sciences, their scope is usually restricted to a limited set of well-defined types of services. While dedicated registries are generally tied to a particular format, general-purpose ones are more adherent to standards and usually rely on Web Service Definition Language (WSDL). Although WSDL is quite flexible to support common Web services types, its lack of semantic expressiveness led to various initiatives to describe Web services via ontology languages. Nevertheless, WSDL 2.0 descriptions gained a standard representation based on Web Ontology Language (OWL). BioSWR is a novel Web services registry that provides standard Resource Description Framework (RDF) based Web services descriptions along with the traditional WSDL based ones. The registry provides Web-based interface for Web services registration, querying and annotation, and is also accessible programmatically via Representational State Transfer (REST) API or using a SPARQL Protocol and RDF Query Language. BioSWR server is located at http://inb.bsc.es/BioSWR/and its code is available at https://sourceforge.net/projects/bioswr/under the LGPL license. PMID:25233118
BioSWR--semantic web services registry for bioinformatics.
Repchevsky, Dmitry; Gelpi, Josep Ll
2014-01-01
Despite of the variety of available Web services registries specially aimed at Life Sciences, their scope is usually restricted to a limited set of well-defined types of services. While dedicated registries are generally tied to a particular format, general-purpose ones are more adherent to standards and usually rely on Web Service Definition Language (WSDL). Although WSDL is quite flexible to support common Web services types, its lack of semantic expressiveness led to various initiatives to describe Web services via ontology languages. Nevertheless, WSDL 2.0 descriptions gained a standard representation based on Web Ontology Language (OWL). BioSWR is a novel Web services registry that provides standard Resource Description Framework (RDF) based Web services descriptions along with the traditional WSDL based ones. The registry provides Web-based interface for Web services registration, querying and annotation, and is also accessible programmatically via Representational State Transfer (REST) API or using a SPARQL Protocol and RDF Query Language. BioSWR server is located at http://inb.bsc.es/BioSWR/and its code is available at https://sourceforge.net/projects/bioswr/under the LGPL license.
Applications of Quality Management in Language Education
ERIC Educational Resources Information Center
Heyworth, Frank
2013-01-01
This review examines applications of quality management (QM) in language education. QM approaches have been adapted from methodologies developed in industrial and commercial settings, and these are briefly described. Key aspects of QM in language education are the definition of purpose, descriptions of principles and practice, including various…
LANGUAGES OF THE WORLD--SINO-TIBETAN FASCICLE THREE.
ERIC Educational Resources Information Center
VOEGELIN, C. F.; VOEGELIN, FLORENCE M.
THIS REPORT CONTAINS A LIST AND DESCRIPTION OF THE LANGUAGES OF THE CHINA-TIBET-BURMA REGION OF ASIA, WITH PARTICULAR REFERENCE TO THE MIAO-YAO LANGUAGE FAMILY AND THE CHINESE DIALECTS. (THE REPORT IS PART OF A SERIES, ED 010 350 TO ED 010 367.) (JK)
TESOL Technology Standards: Description, Implementation, Integration
ERIC Educational Resources Information Center
Teachers of English to Speakers of Other Languages, Inc. (TESOL), 2011
2011-01-01
The "TESOL Technology Standards" are applicable in a wide range of contexts: foreign language, second language, child, teen, adult, higher education, vocational education, language for specific purposes, and fully online programs; and in settings with low, medium, or high resources and access to communication technologies. Students, teachers,…
Syntactic Markedness and Language Acquisition.
ERIC Educational Resources Information Center
Mazurkewich, Irene
1985-01-01
Argues that Chomsky's theory of generative grammar provides a model for second language acquisition that meets the criteria of descriptive and exploratory adequacy in accounting for the language learning process. Illustrates this by presenting data on the acquisition of dative complements and dative questions in a passive context by second…
Britain's South Asian Languages.
ERIC Educational Resources Information Center
Mobbs, Michael
This book focuses on the languages spoken by people of South Asian origin living in Britain and is intended to assist individuals in Britain whose work involves them with speakers of these languages. The approach taken is descriptive and practical, offering linguistic, geographic, and historical background information leading to appreciation of…
Urban Elementary Teachers' Perspectives on Teaching Science to English Language Learners
ERIC Educational Resources Information Center
Lee, Okhee; Maerten-Rivera, Jaime; Buxton, Cory; Penfield, Randall; Secada, Walter G.
2009-01-01
This descriptive study examined urban elementary school teachers' perceptions of their science content knowledge, science teaching practices, and support for language development of English language learners. Also examined were teachers' perceptions of organizational supports and barriers associated with teaching science to nonmainstream students.…
Denials of Racism in Canadian English Language Textbooks
ERIC Educational Resources Information Center
Gulliver, Trevor; Thurrell, Kristy
2016-01-01
This critical discourse analysis examines denials of racism in descriptions of Canada and Canadians from English language textbooks. Denials of racism often accompany racist and nationalist discourse, preempting observations of racism. The study finds that in representations of Canada or Canadians, English language texts minimize and downplay…
ERIC Educational Resources Information Center
Nguyen, Tam Thi Minh
2013-01-01
Bih is a Chamic (Austronesian) language spoken by approximately 500 people in the Southern highlands of Vietnam. This dissertation is the first descriptive grammar of the language, based on extensive fieldwork and community-based language documentation in Vietnam and written from a functional/typological perspective. The analysis in this work is…
[The language disorders in schizophrenia in neurolinguistic and psycholinguistic perspectives].
Piovan, Cristiano
2012-01-01
The descriptive psychopathology has classically equated the language with the formal aspects of thought. Recent developments in experimental and clinical research have emphasized the study of the language as a specific communicative ability. Within the framework of cognitive neuropsychology, the development of innovative research models, such as those based on the mentalizing ability, has allowed to formulate new hypotheses on the pathogenetic aspects of schizophrenia. Furthermore, mentalizing ability appears to be a basic skill for the pragmatic dimension of language. The author, after a brief description of the methods of investigation of neurolinguistics and psycholinguistics, presents a review of recent studies obtained by consulting the PubMed and PsycINFO databases. Finally, he focuses on the relationship between research findings and issues related to clinical practice.
NASA Technical Reports Server (NTRS)
Simmons, Reid; Apfelbaum, David
2005-01-01
Task Description Language (TDL) is an extension of the C++ programming language that enables programmers to quickly and easily write complex, concurrent computer programs for controlling real-time autonomous systems, including robots and spacecraft. TDL is based on earlier work (circa 1984 through 1989) on the Task Control Architecture (TCA). TDL provides syntactic support for hierarchical task-level control functions, including task decomposition, synchronization, execution monitoring, and exception handling. A Java-language-based compiler transforms TDL programs into pure C++ code that includes calls to a platform-independent task-control-management (TCM) library. TDL has been used to control and coordinate multiple heterogeneous robots in projects sponsored by NASA and the Defense Advanced Research Projects Agency (DARPA). It has also been used in Brazil to control an autonomous airship and in Canada to control a robotic manipulator.
ERIC Educational Resources Information Center
Muhammad, Anas Sa'idu; Nair, Subadrah Madhawa
2017-01-01
This study investigates the level of pragmatic competence for ESL writing skills among Nigerian undergraduates. Methodologically, it adopts descriptive research design within the explanatory framework of the QUAN-Qual model. The instruments used are descriptive essay text and focus group interview questions. In writing the descriptive essays, a…
NASA Astrophysics Data System (ADS)
Arenas, Marcelo; Gutierrez, Claudio; Pérez, Jorge
The Resource Description Framework (RDF) is the standard data model for representing information about World Wide Web resources. In January 2008, it was released the recommendation of the W3C for querying RDF data, a query language called SPARQL. In this chapter, we give a detailed description of the semantics of this language. We start by focusing on the definition of a formal semantics for the core part of SPARQL, and then move to the definition for the entire language, including all the features in the specification of SPARQL by the W3C such as blank nodes in graph patterns and bag semantics for solutions.
ERIC Educational Resources Information Center
McCarus, Ernest N.
This study is a description of the Kurdish of the city of Sulaimaniya, Iraq. Kurdish dialects cover an area embracing parts of eastern Turkey, Soviet Armenia, northern Syria, western Iran, and Khorasan in Iran. The language is described in terms of (1) phonology, (2) morphology, (3) morphophonemics, (4) word formation, and (5) syntax. An appendix,…
O'Mahony, M; Ishii, R
1986-05-01
Everyday taste descriptions for a range of stimuli were obtained from selected groups of American and Japanese subjects, using a variety of stimuli, stimulus presentation procedures and response conditions. In English there was a tendency to use a quadrapartite classification system: 'sweet', 'sour', 'salty' and 'bitter'. The Japanese had a different strategy, adding a fifth label: 'Ajinomoto', referring to the taste of monosodium glutamate. This label was generally replaced by umami--the scientific term--by Japanese who were workers or trained tasters involved with glutamate manufacture. Cultural differences in taste language have consequences for taste psychophysicists who impose a quadrapartite restriction on allowable taste descriptions. Stimulus presentation by filter-paper or aqueous solution elicited the same response trends. Language codability was only an indicator of degree of taste mixedness/singularity if used statistically with samples of sufficient size; it had little value as an indicator for individual subjects.
ERIC Educational Resources Information Center
Grayshon, Matthew C.
Different languages code messages in different ways and use different channels for sending messages; thus there are many places for misinterpreting and mishearing messages in an intercultural context. To move from one language to another requires a description of the total language communication system, one that has its universals in social and…
ERIC Educational Resources Information Center
Charrow, Veda R.
This paper studies legal language from three perspectives. First, legal language is defined as the variety of English that lawyers, judges, and other members of the legal community use in the course of their work. In a second section, it reviews descriptions of legal language by lawyers, linguists, and social scientists. These studies indicate…
Dialogue as a Constituent Resource for Dramatic Discourse: Language, Person and Culture
ERIC Educational Resources Information Center
Zheltukhina, Marina R.; Zinkovskaya, Anastasia V.; Katermina, Veronika V.; Shershneva, Natalia B.
2016-01-01
The article is devoted to the description of peculiarities of a person, language and culture. The offered approach of studying the human factor in the language singles out implicit connotations and makes it possible to see the differences in the perception of the reality by the members of the nation. The idea of the language as an environment of…
ERIC Educational Resources Information Center
Courtin, C.; Herve, P. -Y.; Petit, L.; Zago, L.; Vigneau, M.; Beaucousin, V.; Jobard, G.; Mazoyer, B.; Mellet, E.; Tzourio-Mazoyer, N.
2010-01-01
"Highly iconic" structures in Sign Language enable a narrator to act, switch characters, describe objects, or report actions in four-dimensions. This group of linguistic structures has no real spoken-language equivalent. Topographical descriptions are also achieved in a sign-language specific manner via the use of signing-space and…
Caught in the Middle: Child Language Brokering as a Form of Unrecognised Language Service
ERIC Educational Resources Information Center
Antonini, Rachele
2016-01-01
This paper will present the findings of a wide-scale research aimed at studying the phenomenon of Child Language Brokering (henceforth CLB) in Italy. After providing a description of recent immigration patterns and the provision of language services in Italy, and an overview of current research in this field, this study will discuss narrative data…
Data-driven approach to human motion modeling with Lua and gesture description language
NASA Astrophysics Data System (ADS)
Hachaj, Tomasz; Koptyra, Katarzyna; Ogiela, Marek R.
2017-03-01
The aim of this paper is to present the novel proposition of the human motion modelling and recognition approach that enables real time MoCap signal evaluation. By motions (actions) recognition we mean classification. The role of this approach is to propose the syntactic description procedure that can be easily understood, learnt and used in various motion modelling and recognition tasks in all MoCap systems no matter if they are vision or wearable sensor based. To do so we have prepared extension of Gesture Description Language (GDL) methodology that enables movements description and real-time recognition so that it can use not only positional coordinates of body joints but virtually any type of discreetly measured output MoCap signals like accelerometer, magnetometer or gyroscope. We have also prepared and evaluated the cross-platform implementation of this approach using Lua scripting language and JAVA technology. This implementation is called Data Driven GDL (DD-GDL). In tested scenarios the average execution speed is above 100 frames per second which is an acquisition time of many popular MoCap solutions.
Ji, Chen-Guang; Xie, Xiao-Li; Yin, Jie; Qi, Wei; Chen, Lei; Bai, Yun; Wang, Na; Zhao, Dong-Qiang; Jiang, Xiao-Yu; Jiang, Hui-Qing
2017-04-01
Bile acids stimulate intestinal epithelial proliferation in vitro. We sought to investigate the role of the bile acid receptor TGR5 in the protection of intestinal epithelial proliferation in obstructive jaundice. Intestinal tissues and serum samples were obtained from patients with malignant obstructive jaundice and from bile duct ligation (BDL) rats. Intestinal permeability and morphological changes in the intestinal mucosa were observed. The functions of TGR5 in cell proliferation in intestinal epithelial injury were determined by overexpression or knockdown studies in Caco-2 and FHs 74 Int cells pretreated with lipopolysaccharide (LPS). Internal biliary drainage was superior to external biliary drainage in recovering intestinal permeability and mucosal histology in patients with obstructive jaundice. In BDL rats, feeding of chenodeoxycholic acid (CDCA) decreased intestinal mucosa injury. The levels of PCNA, a marker of proliferation, increased in response to CDCA feeding and were paralleled by elevated TGR5 expression. CDCA upregulated TGR5 expression and promoted proliferation in Caco-2 and FHs 74 Int cells pretreated with LPS. Overexpression of TGR5 resulted in increased PCNA, cell viability, EdU incorporation, and the proportion of cells in S phase, whereas knockdown of TGR5 had the opposite effect. Our data indicate that bile acids promote intestinal epithelial cell proliferation and decrease mucosal injury by upregulating TGR5 expression in obstructive jaundice. Copyright © 2016 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chandramohan, J.; Tholkappian, M.; Harikrishnan, N.
2015-08-28
The natural radioactivity concentration in beach sediment samples collected from Pattipulam to Devanampattinam of East Coast of Tamilnadu have been determined by NaI (TI) gamma ray spectrometer. The specific activity concentrations range from ≤ 2.21 (BDL) to 37.02 Bq kg{sup −1} with a mean of 3.79 Bqkg{sup −1} for {sup 238}U, ≤ 2.11 (BDL) to 643.77 Bqkg{sup −1} with a mean of 49.60 Bqkg{sup −1} for {sup 232}Th and 300.34 Bqkg{sup −1} to 449.08 Bqkg{sup −1} with a mean of 360.23 Bqkg{sup −1} for {sup 40}K. The potential radiological hazards due to natural radionuclides content such as Radium Equivalent activitymore » (Ra{sub eq}), Representative level index (RLI), External hazard index (H{sub ex}), absorbed gamma does rate (D{sub R}), and Annual effective dose rate (AEDR) are estimated to assess the radiation hazard associated with the sediments. The obtained data are compared with the recommended safety limits and international approved values. All the values are well below the recommended safety limits indicating that radiation levels do not poses any significant health hazard to the public in the area as a result of the natural radioactivity of beach sediments. This study may help the baseline data for more extensive works in the same subjects of future studies.« less
NASA Technical Reports Server (NTRS)
Mathur, F. P.
1972-01-01
Several common higher level program languages are described. FORTRAN, ALGOL, COBOL, PL/1, and LISP 1.5 are summarized and compared. FORTRAN is the most widely used scientific programming language. ALGOL is a more powerful language for scientific programming. COBOL is used for most commercial programming applications. LISP 1.5 is primarily a list-processing language. PL/1 attempts to combine the desirable features of FORTRAN, ALGOL, and COBOL into a single language.
Understanding and Forecasting Ethnolinguistic Vitality
ERIC Educational Resources Information Center
Karan, Mark E.
2011-01-01
Forecasting of ethnolinguistic vitality can only be done within a well-functioning descriptive and explanatory model of the dynamics of language stability and shift. It is proposed that the Perceived Benefit Model of Language Shift, used with a taxonomy of language shift motivations, provides that model. The model, based on individual language…
Child Language Research: Building on the Past, Looking to the Future.
ERIC Educational Resources Information Center
Perera, Katharine
1994-01-01
Outlines descriptive, theoretical, and methodological advances in child language research since the first volume of the "Journal of Child Language" was published. Papers in this volume build on earlier research, point the way to new research avenues, and open new lines of inquiry. (Contains 36 references.) (JP)
Information Retrieval and the Philosophy of Language.
ERIC Educational Resources Information Center
Blair, David C.
2003-01-01
Provides an overview of some of the main ideas in the philosophy of language that have relevance to the issues of information retrieval, focusing on the description of the intellectual content. Highlights include retrieval problems; recall and precision; words and meanings; context; externalism and the philosophy of language; and scaffolding and…
Task-Induced Variability in FL Composition: Language-Specific Perspectives.
ERIC Educational Resources Information Center
Koda, Keiko
1993-01-01
Investigated ways in which different writing tasks influence quality and quantity of foreign language composition, as well as writing strategies used by American college students when composing in Japanese as a foreign language. Study proposed to compare qualitative and quantitative differences between descriptive and narrative writing tasks; to…
DESIGN FOR THINKING, A FIRST BOOK IN SEMANTICS.
ERIC Educational Resources Information Center
UPTON, ALBERT
THIS BOOK ABOUT THE FUNCTIONS OF LANGUAGE IN HUMAN LIFE EMPHASIZES LEARNING HOW TO CLASSIFY, DEFINE, AND ANALYZE. FOLLOWING AN EXPLANATION OF THE PHYSIOLOGICAL AND PSYCHOLOGICAL ROOTS OF LANGUAGE, CHAPTERS ON ANALYSIS, MEANING, SIGNS, AMBIGUITY, SEMANTIC GROWTH, AND METAPHOR LEAD TO A DESCRIPTION OF THE COMMUNICATIVE FUNCTION OF LANGUAGE,…
End-User Use of Data Base Query Language: Pros and Cons.
ERIC Educational Resources Information Center
Nicholes, Walter
1988-01-01
Man-machine interface, the concept of a computer "query," a review of database technology, and a description of the use of query languages at Brigham Young University are discussed. The pros and cons of end-user use of database query languages are explored. (Author/MLW)
Across the Threshold: A Call for ILR Proficiency Descriptor Banks
ERIC Educational Resources Information Center
Holman, Don
2017-01-01
Whereas the Interagency Language Roundtable Language Skill Level Descriptions broke new ground for assessing proficiency in foreign languages, the need for user-oriented (rather than assessment-oriented) proficiency scales has led, especially in Europe, to the creation of scales consisting of positively formulated "can-do" statements,…
Mississippi Language Arts Framework with the Process of Instructional Intervention, 2000.
ERIC Educational Resources Information Center
Mississippi State Dept. of Education, Jackson.
This Language Arts Framework provides a description of what students should know and do in English, language arts, and reading classrooms, kindergarten through twelfth grade. The framework addresses the interrelatedness of reading, writing, speaking, listening, and viewing. The intent is to raise expectations for student performance, provide…
ERIC Educational Resources Information Center
Koffi, Yao
2010-01-01
(Purpose) The purpose of this article is to provide a detailed description of the pronouns in Akebu. Akebu is a language spoken in South-West Togo and in the neighboring towns in Ghana. Akebu belongs to a group of languages formerly called "Togo Remnant Languages", now (Ghana Togo Mountains, GTM). The native Akebu speakers call their…
Competency: The Language of the Behavioral Objectives Movement.
ERIC Educational Resources Information Center
Craig, Samuel B., Jr.
Several external and internal factors combine to hinder optimal communication in "Competency," the language of behavior modification. As a language, Competency a) is spoken with varying degrees of fluency and facility, b) is difficult to translate into English because the common vocabulary is used descriptively in English while it is…
A Strategy for Language Assessment of Young Children: A Combination of Two Approaches.
ERIC Educational Resources Information Center
Kelly, Donna J.; Rice, Mabel L.
1986-01-01
A proposed strategy for language assessment advocates a combination of descriptive and formal assessment measures. This approach involves a parent-clinician interview, parent-child observations, clinician-directed formal and nonformal assessment procedures, and a parent-clinician interpretation. An elaborated sample of language assessment is…
ERIC Educational Resources Information Center
Marascuilo, Leonard A.; Loban, Walter
To determine whether language behavior represents an early conditioned verbal response or whether it changes with age and experience was the purpose of this study which attempted to define unique isolates of language on the basis of actual language produced by young children. Tape recorded data were collected for 12 years from 211 children in…
Functional test generation for digital circuits described with a declarative language: LUSTRE
NASA Astrophysics Data System (ADS)
Almahrous, Mazen
1990-08-01
A functional approach to the test generation problem starting from a high level description is proposed. The circuit tested is modeled, using the LUSTRE high level data flow description language. The different LUSTRE primitives are translated to a SATAN format graph in order to evaluate the testability of the circuit and to generate test sequences. Another method of testing the complex circuits comprising an operative part and a control part is defined. It consists of checking experiments for the control part observed through the operative part. It was applied to the automata generated from a LUSTRE description of the circuit.
2011-01-01
Background The increasing use of computational simulation experiments to inform modern biological research creates new challenges to annotate, archive, share and reproduce such experiments. The recently published Minimum Information About a Simulation Experiment (MIASE) proposes a minimal set of information that should be provided to allow the reproduction of simulation experiments among users and software tools. Results In this article, we present the Simulation Experiment Description Markup Language (SED-ML). SED-ML encodes in a computer-readable exchange format the information required by MIASE to enable reproduction of simulation experiments. It has been developed as a community project and it is defined in a detailed technical specification and additionally provides an XML schema. The version of SED-ML described in this publication is Level 1 Version 1. It covers the description of the most frequent type of simulation experiments in the area, namely time course simulations. SED-ML documents specify which models to use in an experiment, modifications to apply on the models before using them, which simulation procedures to run on each model, what analysis results to output, and how the results should be presented. These descriptions are independent of the underlying model implementation. SED-ML is a software-independent format for encoding the description of simulation experiments; it is not specific to particular simulation tools. Here, we demonstrate that with the growing software support for SED-ML we can effectively exchange executable simulation descriptions. Conclusions With SED-ML, software can exchange simulation experiment descriptions, enabling the validation and reuse of simulation experiments in different tools. Authors of papers reporting simulation experiments can make their simulation protocols available for other scientists to reproduce the results. Because SED-ML is agnostic about exact modeling language(s) used, experiments covering models from different fields of research can be accurately described and combined. PMID:22172142
NASA Astrophysics Data System (ADS)
Osti, D.; Osti, A.
2013-12-01
People are very busy today and getting stakeholders the information they need is an important part of our jobs. The BDL application is the mobile extension of the California collaborative resource management portal www.baydeltalive.com. BDL has been visited by more than 250,000 unique visitors this past year from various areas of water use and management including state and federal agencies, agriculture, scientists, policy makers, water consumers, voters, operations management and more. The audience is a qualified user group of more than 15,000 individuals participating in California hydrological ecosystem science, water management and policy. This is an important effort aimed to improve how scientists and policy makers are working together to understand this complicated and divisive system and how they are becoming better managers of that system. The BayDetaLive mobile application gives California watershed management stakeholders and water user community unprecedented access to real time natural resource management information. The application provides user with the following: 1. Access to Real Time Environmental Conditions from the more than the 600 California Data Exchange Sensors including hydrodynamic, water quality and meteorological data. Save important stations as favorites for easy access later. 2. Daily Delta Operations Data including estimated hydrology, daily exports, status of infrastructure operations, reservoir storage, salvage data, major stations, drinking water quality reports, weather forecasts and more. 3. Photos/Videos/Documents: Browse and share from the more than 1000 current documents in the BDL library. Relevant images, videos, science journals, presentations and articles. 4. Science: Access the latest science articles, news, projects and journals. 5. Data Visualizations: View recently published real time data interpolations of Delta Conditions. From 30-day turbidity models to daily forecasts. This service is published as conditions produce scientifically relevant visuals including winter conditions, first flush archives and fish migration seasons. 5. Maps: Access the entire Delta Atlas from anywhere! The atlas includes Delta levees, soils, islands and waterways, diversions, infrastructure, urban areas, land use, salinity, tidal flows, managed lands, protected lands and more. 6. Projects: Discover the latest project summaries currently underway in the Delta. Project Categories include restoration, operations, infrastructure to name a few. Share your discovery for more depth access on the BayDeltaLive.com website. 7. News: Current Delta Science topics. App Keywords: California Delta, Water Management, Natural Resource Management, Real Time Data, Water Operations, Water Supply, Water Quality, Collaboration
1987-12-01
1985:55; Nash, 1984:18). Because of this, the Department of Defense began a program , VHDL, to standardize a hardware description language for VHSIC... Deitel , 1984:507-508). This operating system (or environment) is in general use in the commercial world. Universities, given the responsibility to ...though not necessarily exhaustive) test suite designed to exercise each VHDL grammar rule and associated program modules as thor- oughly as possible. The
ERIC Educational Resources Information Center
Akmese, Pelin Pistav
2016-01-01
Being hearing impaired limits one's ability to communicate in that it affects all areas of development, particularly speech. One of the methods the hearing impaired use to communicate is sign language. This study, a descriptive study, intends to examine the opinions of individuals who had enrolled in a sign language certification program by using…
Linguistic and Cultural Variations as Barriers to the TEFL Settings in Papua
ERIC Educational Resources Information Center
Yembise, Yohana Susana
2011-01-01
The article aims at presenting a description of languages and cultures and the effect on the teaching of English as a Foreign Language in schools in Papua. It starts with a general picture of the uniqueness of languages and cultures in Papua: its geography, the originality of the people, and the languages and cultures of both NAN and AN. The word…
ERIC Educational Resources Information Center
Huisman, Rosemary
2016-01-01
Poetry is the art shaped through language; to talk about a poem we need at least to talk about its language--but what can be said will depend on the particular linguistic theory, with its particular modelling of language, which we bring to the description. This paper outlines the approach of SFL (Systemic Functional Linguistics), describing in…
DOE Office of Scientific and Technical Information (OSTI.GOV)
Woodruff, David; Hackebeil, Gabe; Laird, Carl Damon
Pyomo supports the formulation and analysis of mathematical models for complex optimization applications. This capability is commonly associated with algebraic modeling languages (AMLs), which support the description and analysis of mathematical models with a high-level language. Although most AMLs are implemented in custom modeling languages, Pyomo's modeling objects are embedded within Python, a full- featured high-level programming language that contains a rich set of supporting libraries.
Psycholinguistic Descriptions and Their Relevance to Education
ERIC Educational Resources Information Center
Vejleskov, Hans
1976-01-01
Article deals with the Osgood model of sign learning...and the Chomskian approach. Both...approaches are discussed in terms of their appropriateness with respect to teachers' questions about language development and language stimulation. (Author)
Beres, Anna M
2017-12-01
The discovery of electroencephalography (EEG) over a century ago has changed the way we understand brain structure and function, in terms of both clinical and research applications. This paper starts with a short description of EEG and then focuses on the event-related brain potentials (ERPs), and their use in experimental settings. It describes the typical set-up of an ERP experiment. A description of a number of ERP components typically involved in language research is presented. Finally, the advantages and disadvantages of using ERPs in language research are discussed. EEG has an extensive use in today's world, including medical, psychology, or linguistic research. The excellent temporal resolution of EEG information allows one to track a brain response in milliseconds and therefore makes it uniquely suited to research concerning language processing.
Using bio.tools to generate and annotate workbench tool descriptions
Hillion, Kenzo-Hugo; Kuzmin, Ivan; Khodak, Anton; Rasche, Eric; Crusoe, Michael; Peterson, Hedi; Ison, Jon; Ménager, Hervé
2017-01-01
Workbench and workflow systems such as Galaxy, Taverna, Chipster, or Common Workflow Language (CWL)-based frameworks, facilitate the access to bioinformatics tools in a user-friendly, scalable and reproducible way. Still, the integration of tools in such environments remains a cumbersome, time consuming and error-prone process. A major consequence is the incomplete or outdated description of tools that are often missing important information, including parameters and metadata such as publication or links to documentation. ToolDog (Tool DescriptiOn Generator) facilitates the integration of tools - which have been registered in the ELIXIR tools registry (https://bio.tools) - into workbench environments by generating tool description templates. ToolDog includes two modules. The first module analyses the source code of the bioinformatics software with language-specific plugins, and generates a skeleton for a Galaxy XML or CWL tool description. The second module is dedicated to the enrichment of the generated tool description, using metadata provided by bio.tools. This last module can also be used on its own to complete or correct existing tool descriptions with missing metadata. PMID:29333231
Paradigms of Evaluation in Natural Language Processing: Field Linguistics for Glass Box Testing
ERIC Educational Resources Information Center
Cohen, Kevin Bretonnel
2010-01-01
Although software testing has been well-studied in computer science, it has received little attention in natural language processing. Nonetheless, a fully developed methodology for glass box evaluation and testing of language processing applications already exists in the field methods of descriptive linguistics. This work lays out a number of…
Organizations of Language among Adolescents in Superdiverse Copenhagen
ERIC Educational Resources Information Center
Møller, Janus Spindler; Jørgensen, Jens Normann
2013-01-01
In this paper we analyze how adolescents in a Copenhagen school classify and systematically organize the different types of language they come across in their linguistic everyday. Furthermore, we analyse descriptions of how this metapragmatic system affect the adolescents' language use in their daily life. Our primary data consist of 74 essays on…
Indigenous Minority Languages of Russia: A Bibliographical Guide.
ERIC Educational Resources Information Center
Matsumura, Kazuto, Ed.
This publication is a printed version of 54 Web documents as they were at the end of March 2002. It includes selected lists of school textbooks, dictionaries, grammars, grammatical descriptions, and folklore collections in and on 54 indigenous minority languages of Russia, many of which are endangered. The 54 languages are arranged in the…
Great-Grandfather, Please Teach Me My Language!
ERIC Educational Resources Information Center
Ka'ai, Tania M.
2017-01-01
Inspired by Joshua Fishman's lifetime dedication to the revitalisation of minority languages, especially Yiddish, this paper presents my personal story of the loss of the Maori language in my family in New Zealand/Aotearoa and our attempts to reverse this decline over several generations. The paper includes a description of several policy reforms…
"Scissors, Paper, Stone": Perceptual Foundations of Noun Classifier Systems.
ERIC Educational Resources Information Center
Erbaugh, Mary S.
While all languages use shape to classify unfamiliar objects, some languages as diverse as Mandarin, Thai, Japanese, Mohawk, and American Sign Language lexicalize these and other types of description as noun classifiers. Classification does not develop from a fixed set of features in the object, but is discourse-sensitive and invoked when it would…
Lexical Properties of Slovene Sign Language: A Corpus-Based Study
ERIC Educational Resources Information Center
Vintar, Špela
2015-01-01
Slovene Sign Language (SZJ) has as yet received little attention from linguists. This article presents some basic facts about SZJ, its history, current status, and a description of the Slovene Sign Language Corpus and Pilot Grammar (SIGNOR) project, which compiled and annotated a representative corpus of SZJ. Finally, selected quantitative data…
A Comparison of Verbal and Written Language in Alzheimer's Disease
ERIC Educational Resources Information Center
Groves-Wright, Kathy; Neils-Strunjas, Jean; Burnett, Rebecca; O'Neill, Mary Jane
2004-01-01
Few studies have examined characteristics of both verbal and written language of individuals with Alzheimer's disease (AD). This study used parallel measures (picture description, word fluency, spelling to dictation, and confrontational naming) to compare verbal and written language of individuals with mild AD, moderate AD, and normal controls (14…
ERIC Educational Resources Information Center
Szabo Wankoff, Lorain
2005-01-01
This much-needed text presents detailed descriptions of current treatment methodologies for children with language impairments. Professionals in the fields of special education, speech language pathology, psychology, psychiatry, and occupational therapy as well as audiologists who deal with central auditory processing disorders will find this book…
Research on the Language of the English Classroom: A Disconnected Dream.
ERIC Educational Resources Information Center
Kluwin, Thomas N.
Methods used in studies of the classroom language of the English teacher are described in this paper and some results of the research are reported. The paper first describes three methods traditionally employed in the description of the language of the English classroom--live observation systems, coding systems based on transcripts, and…
A Computer Assisted Language Analysis System.
ERIC Educational Resources Information Center
Rush, J. E.; And Others
A description is presented of a computer-assisted language analysis system (CALAS) which can serve as a method for isolating and displaying language utterances found in conversation. The purpose of CALAS is stated as being to deal with the question of whether it is possible to detect, isolate, and display information indicative of what is…
A Descriptive Study on EFL Learners' Perceptions of Facebook
ERIC Educational Resources Information Center
Aydin, Selami
2017-01-01
There is a strong need to investigate English as a foreign language (EFL) learners' perceptions of Facebook as a language-learning environment, as their perceptions that directly influence their language development and achievement have not been examined within the EFL learning context. Thus, this study aims to investigate EFL learners'…
Spatial Language, Visual Attention, and Perceptual Simulation
ERIC Educational Resources Information Center
Coventry, Kenny R.; Lynott, Dermot; Cangelosi, Angelo; Monrouxe, Lynn; Joyce, Dan; Richardson, Daniel C.
2010-01-01
Spatial language descriptions, such as "The bottle is over the glass", direct the attention of the hearer to particular aspects of the visual world. This paper asks how they do so, and what brain mechanisms underlie this process. In two experiments employing behavioural and eye tracking methodologies we examined the effects of spatial language on…
Critical Thinking Dispositions of Pre-Service Turkish Language Teachers and Primary Teachers
ERIC Educational Resources Information Center
Maltepe, Sadet
2016-01-01
The present study aimed to determine critical thinking dispositions of pre-service Turkish language and primary teachers in terms of several variables by employing descriptive survey design. The study group consisted of 215 senior students attending Turkish Language Teaching and Primary Education Departments of Necatibey Faculty of Education at…
A Study of Learning Strategies in Foreign Language Instruction: Findings of the Longitudinal Study.
ERIC Educational Resources Information Center
Chamot, Anna Uhl; And Others
Part of a larger research project, this longitudinal study analyzed differences between effective and ineffective high school and college language learners and changes in strategy uses over time. Related studies include a descriptive study, which identified learning strategies used in studying foreign languages, and a course development study, in…
The Production of Complement Clauses in Children with Language Impairment
ERIC Educational Resources Information Center
Steel, Gillian; Rose, Miranda; Eadie, Patricia
2016-01-01
Purpose: The purpose of this research was to provide a comprehensive description of complement-clause production in children with language impairment. Complement clauses were examined with respect to types of complement structure produced, verb use, and both semantic and syntactic accuracy. Method: A group of 17 children with language impairment…
Sex Differences in L2 Vocabulary Learning Strategies.
ERIC Educational Resources Information Center
Catalan, Rosa Maria Jimenez
2003-01-01
Reports the results of a descriptive study on sex differences in the use of a second language. A questionnaire was administered to 581 Spanish-speaking students learning Basque and English as second language to answer the following question: Do male and female second language learners differ in the number and the range of vocabulary strategies…
REPORT ON THE INTENSIVE LANGUAGE COURSES FOR THE BLIND, 1960-1966.
ERIC Educational Resources Information Center
MACDONALD, R. ROSS
A DETAILED DESCRIPTION IS GIVEN OF AN EXPERIMENT CONDUCTED AT GEORGETOWN UNIVERSITY FROM 1960 TO 1966 IN WHICH SELECTED BLIND STUDENTS, THROUGH INTENSIVE AUDIOLINGUAL LANGUAGE INSTRUCTION, WERE TRAINED TO BROADEN THEIR EMPLOYMENT POTENTIAL. ALTHOUGH ONLY RUSSIAN AND THE TRANSCRIPTION OF ORAL FOREIGN LANGUAGE MATERIALS WERE TAUGHT IN THE PILOT…
Investigation of Pre-Service Teachers' Communication Skills
ERIC Educational Resources Information Center
Kana, Fatih
2015-01-01
The purpose of this study is to determine the levels of Turkish language pre-service teachers' communication skills. Descriptive survey model was used in this study. 218 pre-service Turkish language teachers, who are studying at Department of Turkish Language Teaching at a university in the west of Turkey, participated in the study. Criterion…
Automated database design from natural language input
NASA Technical Reports Server (NTRS)
Gomez, Fernando; Segami, Carlos; Delaune, Carl
1995-01-01
Users and programmers of small systems typically do not have the skills needed to design a database schema from an English description of a problem. This paper describes a system that automatically designs databases for such small applications from English descriptions provided by end-users. Although the system has been motivated by the space applications at Kennedy Space Center, and portions of it have been designed with that idea in mind, it can be applied to different situations. The system consists of two major components: a natural language understander and a problem-solver. The paper describes briefly the knowledge representation structures constructed by the natural language understander, and, then, explains the problem-solver in detail.
Symbiotic symbolization by hand and mouth in sign language*
Sandler, Wendy
2010-01-01
Current conceptions of human language include a gestural component in the communicative event. However, determining how the linguistic and gestural signals are distinguished, how each is structured, and how they interact still poses a challenge for the construction of a comprehensive model of language. This study attempts to advance our understanding of these issues with evidence from sign language. The study adopts McNeill’s criteria for distinguishing gestures from the linguistically organized signal, and provides a brief description of the linguistic organization of sign languages. Focusing on the subcategory of iconic gestures, the paper shows that signers create iconic gestures with the mouth, an articulator that acts symbiotically with the hands to complement the linguistic description of objects and events. A new distinction between the mimetic replica and the iconic symbol accounts for the nature and distribution of iconic mouth gestures and distinguishes them from mimetic uses of the mouth. Symbiotic symbolization by hand and mouth is a salient feature of human language, regardless of whether the primary linguistic modality is oral or manual. Speakers gesture with their hands, and signers gesture with their mouths. PMID:20445832
A Data Definition Language for GLAD (Graphic Language for Databases).
1986-06-20
basic premises. These principles state that a DBMS interface must be descriptive, powerful, easy-to use and easy to learn . This thesis proposes a data...basic premises. These principles state that a DBMS interface must be descriptive, powerful, easy to use and easy to learn . This thesis proposes a data...criteria will be the most successful. 9 If a system is hard to learn , of those capable of mastering the system few may be willing to expend the time and
2014-12-01
appears that UML is becoming the de facto MBD language. OMG® states the following on the MDA® FAQ page: “Although not formally required [for MBD], UML...a known limitation [42], so UML users should plan accordingly, especially for safety-critical programs. For example, “models are not used to...description of the MBD tool chain can be produced. That description could be resident in a Plan for Software Aspects of Certification (PSAC) or Software
A Note on Intelligence Assessment within Studies of Specific Language Impairment.
ERIC Educational Resources Information Center
Camarata, Stephen; Swisher, Linda
1990-01-01
Research procedures used to evaluate the intelligence of children with specific language impairment are reviewed. Almost half of the 167 studies did not include adequate descriptions of intelligence assessment. (Author/JDD)
ERIC Educational Resources Information Center
Center for Applied Linguistics, Arlington, VA.
The purpose of this guide is to provide Americans working with the Hmongs with: (1) some practical information on the Hmongs, their origins and language; (2) a detailed description of the sounds of the Hmong language; and (3) a discussion on Hmong as an unwritten language. This is the first of three guides to be published on the Hmongs, a people…
Use of data description languages in the interchange of data
NASA Technical Reports Server (NTRS)
Pignede, M.; Real-Planells, B.; Smith, S. R.
1994-01-01
The Consultative Committee for Space Data Systems (CCSDS) is developing Standards for the interchange of information between systems, including those operating under different environments. The objective is to perform the interchange automatically, i.e. in a computer interpretable manner. One aspect of the concept developed by CCSDS is the use of a separate data description to specify the data being transferred. Using the description, data can then be automatically parsed by the receiving computer. With a suitably expressive Data Description Language (DDL), data formats of arbitrary complexity can be handled. The advantages of this approach are: (1) that the description need only be written and distributed once to all users, and (2) new software does not need to be written for each new format, provided generic tools are available to support writing and interpretation of descriptions and the associated data instances. Consequently, the effort of 'hard coding' each new format is avoided and problems of integrating multiple implementations of a given format by different users are avoided. The approach is applicable in any context where computer parsable description of data could enhance efficiency (e.g. within a spacecraft control system, a data delivery system or an archive). The CCSDS have identified several candidate DDL's: EAST (Extended Ada Subset), TSDN (Transfer Syntax Data Notation) and MADEL (Modified ASN.1 as a Data Description Language -- a DDL based on the Abstract Syntax Notation One - ASN.1 - specified in the ISO/IEC 8824). This paper concentrates on ESA's development of MADEL. ESA have also developed a 'proof of concept' prototype of the required support tools, implemented on a PC under MS-DOS, which has successfully demonstrated the feasibility of the approach, including the capability within an application of retrieving and displaying particular data elements, given its MADEL description (i.e. a data description written in MADEL). This paper outlines the work done to date and assesses the applicability of this modified ASN.1 as a DDL. The feasibility of the approach is illustrated with several examples.
Dynamic mapping of EDDL device descriptions to OPC UA
NASA Astrophysics Data System (ADS)
Atta Nsiah, Kofi; Schappacher, Manuel; Sikora, Axel
2017-07-01
OPC UA (Open Platform Communications Unified Architecture) is already a well-known concept used widely in the automation industry. In the area of factory automation, OPC UA models the underlying field devices such as sensors and actuators in an OPC UA server to allow connecting OPC UA clients to access device-specific information via a standardized information model. One of the requirements of the OPC UA server to represent field device data using its information model is to have advanced knowledge about the properties of the field devices in the form of device descriptions. The international standard IEC 61804 specifies EDDL (Electronic Device Description Language) as a generic language for describing the properties of field devices. In this paper, the authors describe a possibility to dynamically map and integrate field device descriptions based on EDDL into OPCUA.
Brown, Ramsay A; Swanson, Larry W
2013-09-01
Systematic description and the unambiguous communication of findings and models remain among the unresolved fundamental challenges in systems neuroscience. No common descriptive frameworks exist to describe systematically the connective architecture of the nervous system, even at the grossest level of observation. Furthermore, the accelerating volume of novel data generated on neural connectivity outpaces the rate at which this data is curated into neuroinformatics databases to synthesize digitally systems-level insights from disjointed reports and observations. To help address these challenges, we propose the Neural Systems Language (NSyL). NSyL is a modeling language to be used by investigators to encode and communicate systematically reports of neural connectivity from neuroanatomy and brain imaging. NSyL engenders systematic description and communication of connectivity irrespective of the animal taxon described, experimental or observational technique implemented, or nomenclature referenced. As a language, NSyL is internally consistent, concise, and comprehensible to both humans and computers. NSyL is a promising development for systematizing the representation of neural architecture, effectively managing the increasing volume of data on neural connectivity and streamlining systems neuroscience research. Here we present similar precedent systems, how NSyL extends existing frameworks, and the reasoning behind NSyL's development. We explore NSyL's potential for balancing robustness and consistency in representation by encoding previously reported assertions of connectivity from the literature as examples. Finally, we propose and discuss the implications of a framework for how NSyL will be digitally implemented in the future to streamline curation of experimental results and bridge the gaps among anatomists, imagers, and neuroinformatics databases. Copyright © 2013 Wiley Periodicals, Inc.
Teaching Computer Languages and Elementary Theory for Mixed Audiences at University Level
NASA Astrophysics Data System (ADS)
Christiansen, Henning
2004-09-01
Theoretical issues of computer science are traditionally taught in a way that presupposes a solid mathematical background and are usually considered more or less inaccessible for students without this. An effective methodology is described which has been developed for a target group of university students with different backgrounds such as natural science or humanities. It has been developed for a course that integrates theoretical material on computer languages and abstract machines with practical programming techniques. Prolog used as meta-language for describing language issues is the central instrument in the approach: Formal descriptions become running prototypes that are easy and appealing to test and modify, and can be extended into analyzers, interpreters, and tools such as tracers and debuggers. Experience shows a high learning curve, especially when the principles are extended into a learning-by-doing approach having the students to develop such descriptions themselves from an informal introduction.
ERIC Educational Resources Information Center
Mills, Nancy; Ovando, Carlos, Ed.
1988-01-01
Reviews a volume of descriptive and evaluative information on 47 commercially available English language proficiency tests used in North America, Great Britain, and Australia. The book includes discussions of uses and misuses of tests, and overviews of English as second language testing in North America and Great Britain. (SV)
ERIC Educational Resources Information Center
Harvey, T. Edward
1987-01-01
A national survey of full-time instructional faculty (N=208) at universities, 2-year colleges, and high schools regarding attitudes toward using computers in second-language composition instruction revealed a predomination of Apple and IBM-PC computers used, a major frustration in lack of foreign character support, and mixed opinions about real…
ERIC Educational Resources Information Center
Hayati, Noor
2015-01-01
This research aimed to investigate; students' English academic achievement, beliefs about English language learning, English language learning strategies, and the relationship of them. Descriptive and correlational design, quantitative methods were applied in this research. The students' final English scores of the first year, BALLI, and SILL were…
English as a Second Language (ESL) in Alberta Schools. Parent Handbook.
ERIC Educational Resources Information Center
Alberta Dept. of Education, Edmonton.
Schools in Alberta provide English-as-a-Second-Language (ESL) program support to immigrant students while they are adjusting to Canadian culture and learning the English language. This booklet is for parents who are new to Alberta, whose children are learning ESL and/or who need more information about ESL program support. A description of the…
THE GBAYA LANGUAGE, GRAMMAR, TEXTS, AND VOCABULARIES.
ERIC Educational Resources Information Center
SAMARIN, WILLIAM J.
A DESCRIPTION OF THE GBAYA PEOPLES LIVING IN THE DISTRICT OF BOSSANGOA IN THE NORTHWESTERN PART OF THE CENTRAL AFRICAN REPUBLIC IS PRESENTED IN THE INTRODUCTION TO THIS COMPREHENSIVE STUDY OF THE GBAYA LANGUAGE. (THE LANGUAGE IS SPELLED VARIOUSLY BEA, GBEA, AND GBAYA.) IN THREE SECTIONS, THE FIRST PART OF THE TEXT DEALS WITH THE PHONOLOGY AND…
ERIC Educational Resources Information Center
Di Biase, Bruno; And Others
The status of the Italian language in Australia, particularly in the educational system at all levels, in Australian society in general, and in trade, technology, and tourism is discussed in this report. It begins with a description of the teaching of Italian in elementary, secondary, higher, adult/continuing, and teacher education. Trends are…
An Insight into Secondary School Students' Beliefs Regarding Learning English Language
ERIC Educational Resources Information Center
Aziz, Fakhra; Quraishi, Uzma
2017-01-01
The present descriptive study aimed to get an insight into secondary school students' beliefs regarding English language learning. The survey method was employed for obtaining data from the secondary school students (N = 664). A modified version of "beliefs about language learning inventory" was used to collect data. Five out of nine…
The Impact of Task Type on Oral Performance of English Language Preparatory School Students
ERIC Educational Resources Information Center
Baturay, Meltem Huri; Sancar Tokmak, Hatice; Dogusoy, Berrin; Daloglu, Aysegul
2011-01-01
In this study, the effects of narrative, descriptive and prediction-personal reaction task types with visuals on the oral performance of intermediate level English language learners were compared. The study was carried out at Gazi University Preparatory School, Research and Application Center for the Instruction of Foreign Languages with the…
ERIC Educational Resources Information Center
Hsieh, Hsiu-Wei
2012-01-01
The proliferation of information and communication technologies and the prevalence of online social networks have facilitated the opportunities for informal learning of foreign languages. However, little educational research has been conducted on how individuals utilize those social networks to take part in self-initiated language learning without…
Inferring heuristic classification hierarchies from natural language input
NASA Technical Reports Server (NTRS)
Hull, Richard; Gomez, Fernando
1993-01-01
A methodology for inferring hierarchies representing heuristic knowledge about the check out, control, and monitoring sub-system (CCMS) of the space shuttle launch processing system from natural language input is explained. Our method identifies failures explicitly and implicitly described in natural language by domain experts and uses those descriptions to recommend classifications for inclusion in the experts' heuristic hierarchies.
Historical Development of Hong Kong Sign Language
ERIC Educational Resources Information Center
Sze, Felix; Lo, Connie; Lo, Lisa; Chu, Kenny
2013-01-01
This article traces the origins of Hong Kong Sign Language (hereafter HKSL) and its subsequent development in relation to the establishment of Deaf education in Hong Kong after World War II. We begin with a detailed description of the history of Deaf education with a particular focus on the role of sign language in such development. We then…
ERIC Educational Resources Information Center
Chacon, Thiago Costa
2012-01-01
This dissertation offers a detailed account of the phonology, morphophonology and elements of the morphosyntax of Kubeo, a language from the Eastern Tukanoan family, spoken in the Northwest Amazon. The dissertation is itself an experiment of how language documentation and empowering of the native speaker community can be combined with academic…
ERIC Educational Resources Information Center
Gaile, Jacqueline; Adams, Catherine
2018-01-01
Background: Metacognition is a significant component of complex interventions for children who have developmental language disorders. Research into how metacognition operates in the content or process of developmental language therapy delivery is limited. Identification and description of proposed active therapy components, such as metacognition,…
Web Delivery of Adaptive and Interactive Language Tutoring: Revisited
ERIC Educational Resources Information Center
Heift, Trude
2016-01-01
This commentary reconsiders the description and assessment of the design and implementation of "German Tutor," an Intelligent Language Tutoring System (ILTS) for learners of German as a foreign language, published in 2001. Based on our experience over the past 15 years with the design and real classroom use of an ILTS, we address a…
More than "Hello" and "Bye-Bye": Opening and Closing the Online Chats in Mandarin Chinese
ERIC Educational Resources Information Center
Zhang, De
2014-01-01
Reporting on a descriptive study on the first semester Chinese language learners' openings and closings in online chats with age-peer native speakers of Chinese, this paper demonstrates the great promise that telecollaboration holds for foreign language education, and argues for an increasing role of pragmatics in Chinese language instruction, and…
YURAK CHRESTOMATHY. URALIC AND ALTAIC SERIES, VOLUME 50.
ERIC Educational Resources Information Center
DECSY, GYULA
THE YURAK LANGUAGE, THE MOST IMPORTANT OF THE SAMOYED LANGUAGE GROUP, IS SPOKEN BY ABOUT 25,000 YURAKS IN AN AREA WHICH EXTENDS FROM ARKHANGEL TO THE YENISEY RIVER IN NORTHWESTERN SIBERIA. THIS CHRESTOMATHY PRESENTS A GENERAL INTRODUCTION TO THE LANGUAGE AND ITS MAIN DIALECTS. PART ONE, DESCRIPTIVE GRAMMAR, IS PREFACED BY AN EXPLANATION OF THE…
ERIC Educational Resources Information Center
Elaldi, Senel
2015-01-01
This study aims to determine lifelong learning dispositions of English Language and Literature students in terms of gender, grade levels, and age variables. Descriptive research design was used. The study group consisted of 402 students studying English Language and Literature at Cumhuriyet University in Sivas, Turkey. Research data were collected…
A Guide to Internet Resources in Language Arts.
ERIC Educational Resources Information Center
Homme, John, Comp.; And Others
This paper presents a list of 154 Internet resources (listservs, freenets, telnet sites, gophers, etc.) dealing with language arts. Each entry in the list includes the name of the resource, and subscription and electronic mail addresses. Some of the entries in the list include a brief description of the resource. The paper lists 17 language arts…
Task-Based Language Teaching with Smartphones: A Case Study in Pakistan
ERIC Educational Resources Information Center
Rashid, Shaista; Cunningham, Una; Watson, Kevin
2017-01-01
Integration of technology in task-based language teaching (TBLT) has long been a source of attraction for language teachers (Pierson, 2015). In the case of developing countries, such as Pakistan, mobile phones are the modern form of technology commonly available at low cost to individuals as well as institutions. The present descriptive case study…
ERIC Educational Resources Information Center
Lin, Joshua; Hughes, Rosemary; Long, Daniel; Kim, Dae
2016-01-01
As a group, English Language Learners (ELLs) are diverse and come from a variety of home languages, cultures, educational backgrounds, and educational needs. This brief focuses on descriptive characteristics of the ELL students served by the School District of Philadelphia in 2014-2015. Specifically, this brief highlights the diversity of the ELL…
ERIC Educational Resources Information Center
Barjesteh, Hamed; Mukundan, Jayakaran; Vaseghi, Reza
2014-01-01
The current paper presented theoretical assumptions behind language learning strategies (LLS) and an overview of methods used to identify learners' strategies, first, and then summarized what have been reported from large number of descriptive studies of strategies by language learners. Moreover, the paper tried to present the variety of…
On Selected Morphemes in Saudi Arabian Sign Language
ERIC Educational Resources Information Center
Morris, Carla; Schneider, Erin
2012-01-01
Following a year of study of Saudi Arabian Sign Language (SASL), we are documenting our findings to provide a grammatical sketch of the language. This paper represents one part of that endeavor and focuses on a description of selected morphemes, both manual and non-manual, that have appeared in the course of data collection. While some of the…
Cultural Studies and Foreign Language Teaching in Denmark. ROLIG-papir 41.
ERIC Educational Resources Information Center
Risager, Karen
A description is provided of foreign language and related cultural education (English, French, and German) in Denmark since the 1950s. The first section gives an overview of the development of Danish society in general since the second world war, and more specifically, of developments in foreign language teaching. The second section briefly…
Pluricentric Views towards English and Implications for ELT in China
ERIC Educational Resources Information Center
Jianli, Liang
2015-01-01
Descriptions of the classifications or models of English language have been proposed by a number of scholars who attempt to explain the differences in the ways English is used in different localities. This paper reviews three models of classification of English language, with an aim of drawing implications on how English Language Teaching (ELT) in…
Language Assessment and the Inseparability of Lexis and Grammar: Focus on the Construct of Speaking
ERIC Educational Resources Information Center
Römer, Ute
2017-01-01
This paper aims to connect recent corpus research on phraseology with current language testing practice. It discusses how corpora and corpus-analytic techniques can illuminate central aspects of speech and help in conceptualizing the notion of lexicogrammar in second language speaking assessment. The description of speech and some of its core…
The Foreign Language Classroom: Current Perspectives and Future Considerations
ERIC Educational Resources Information Center
Collins, Laura; Muñoz, Carmen
2016-01-01
"The Modern Language Journal" has long been an important venue for the publication of research and reflection on the teaching and learning of foreign languages (FL) in classroom contexts. In this article, we offer a perspective on the contemporary FL classroom, informed by a descriptive survey of all studies that took place in FL classes…
ERIC Educational Resources Information Center
Chidi-Ehiem, Ugochi Ijeoma
2015-01-01
This descriptive survey was carried out in order to determine the conditions handicapping the teaching of major Nigerian languages in secondary schools in Ebonyi State, Nigeria. A random sample of 953 students and 602 language teachers completed a corresponding copies of questionnaire designed for the study. Out of 1555 copies of questionnaire…
ERIC Educational Resources Information Center
Kayi-Aydar, Hayriye
2014-01-01
Guided by positioning theory and poststructural views of second language learning, the two descriptive case studies presented in this article explored the links between social positioning and the language learning experiences of two talkative students in an academic ESL classroom. Focusing on the macro- and micro-level contexts of communication,…
Current Issues in LPP Research and Their Impact on Society
ERIC Educational Resources Information Center
Darquennes, Jeroen
2013-01-01
After a very broad description of what language policy and planning is about this paper presents an overview of some of the current preoccupations of researchers focusing on language policy and planning as one of the blooming fields of applied linguistics. The current issues in language policy and planning research that are dealt with include…
What Do Learners Make of Teachers' Gestures in the Language Classroom?
ERIC Educational Resources Information Center
Sime, Daniela
2006-01-01
This study explores the meanings that learners of English as a foreign language give to teachers' gestures. It is a qualitative, descriptive study of the perceived functions that gestures perform in the EFL classroom, viewed mainly from the language learners' perspective. The data for the study was collected through interviews with twenty-two…
ERIC Educational Resources Information Center
Elega, Adeola Abdulateef; Özad, Bahire Efe
2017-01-01
This study sought to investigate how Nigerian students in Northern Cyprus cope with language barrier and increase interactions with people of the host community beyond the classroom via utilizing technological adaptive strategies. In order to complete this study, a descriptive design based on a survey conducted among 238 Nigerian students studying…
Cognitive, cultural, and linguistic sources of a handshape distinction expressing agentivity.
Brentari, Diane; Di Renzo, Alessio; Keane, Jonathan; Volterra, Virginia
2015-01-01
In this paper the cognitive, cultural, and linguistic bases for a pattern of conventionalization of two types of iconic handshapes are described. Work on sign languages has shown that handling handshapes (H-HSs: those that represent how objects are handled or manipulated) and object handshapes (O-HSs: those that represent the class, size, or shape of objects) express an agentive/non-agentive semantic distinction in many sign languages. H-HSs are used in agentive event descriptions and O-HSs are used in non-agentive event descriptions. In this work, American Sign Language (ASL) and Italian Sign Language (LIS) productions are compared (adults and children) as well as the corresponding groups of gesturers in each country using "silent gesture." While the gesture groups, in general, did not employ an H-HS/O-HS distinction, all participants (signers and gesturers) used iconic handshapes (H-HSs and O-HSs together) more often in agentive than in no-agent event descriptions; moreover, none of the subjects produced an opposite pattern than the expected one (i.e., H-HSs associated with no-agent descriptions and O-HSs associated with agentive ones). These effects are argued to be grounded in cognition. In addition, some individual gesturers were observed to produce the H-HS/O-HS opposition for agentive and non-agentive event descriptions-that is, more Italian than American adult gesturers. This effect is argued to be grounded in culture. Finally, the agentive/non-agentive handshape opposition is confirmed for signers of ASL and LIS, but previously unreported cross-linguistic differences were also found across both adult and child sign groups. It is, therefore, concluded that cognitive, cultural, and linguistic factors contribute to the conventionalization of this distinction of handshape type. Copyright © 2014 Cognitive Science Society, Inc.
Social media enhances languages differentiation: a mathematical description.
Vidal-Franco, Ignacio; Guiu-Souto, Jacobo; Muñuzuri, Alberto P
2017-05-01
Understanding and predicting the evolution of competing languages is a topic of high interest in a world with more than 6000 languages competing in a highly connected environment. We consider a reasonable mathematical model describing a situation of competition between two languages and analyse the effect of the speakers' connectivity (i.e. social networks). Surprisingly, instead of homogenizing the system, a high degree of connectivity helps to introduce differentiation for the appropriate parameters.
Systematic review: conservative treatments for secondary lymphedema
2012-01-01
Background Several conservative (i.e., nonpharmacologic, nonsurgical) treatments exist for secondary lymphedema. The optimal treatment is unknown. We examined the effectiveness of conservative treatments for secondary lymphedema, as well as harms related to these treatments. Methods We searched MEDLINE®, EMBASE®, Cochrane Central Register of Controlled Trials®, AMED, and CINAHL from 1990 to January 19, 2010. We obtained English- and non-English-language randomized controlled trials or observational studies (with comparison groups) that reported primary effectiveness data on conservative treatments for secondary lymphedema. For English-language studies, we extracted data in tabular form and summarized the tables descriptively. For non-English-language studies, we summarized the results descriptively and discussed similarities with the English-language studies. Results Thirty-six English-language and eight non-English-language studies were included in the review. Most of these studies involved upper-limb lymphedema secondary to breast cancer. Despite lymphedema's chronicity, lengths of follow-up in most studies were under 6 months. Many trial reports contained inadequate descriptions of randomization, blinding, and methods to assess harms. Most observational studies did not control for confounding. Many studies showed that active treatments reduced the size of lymphatic limbs, although extensive between-study heterogeneity in areas such as treatment comparisons and protocols, and outcome measures, prevented us from assessing whether any one treatment was superior. This heterogeneity also precluded us from statistically pooling results. Harms were rare (< 1% incidence) and mostly minor (e.g., headache, arm pain). Conclusions The literature contains no evidence to suggest the most effective treatment for secondary lymphedema. Harms are few and unlikely to cause major clinical problems. PMID:22216837
Barrès, Victor; Lee, Jinyong
2014-01-01
How does the language system coordinate with our visual system to yield flexible integration of linguistic, perceptual, and world-knowledge information when we communicate about the world we perceive? Schema theory is a computational framework that allows the simulation of perceptuo-motor coordination programs on the basis of known brain operating principles such as cooperative computation and distributed processing. We present first its application to a model of language production, SemRep/TCG, which combines a semantic representation of visual scenes (SemRep) with Template Construction Grammar (TCG) as a means to generate verbal descriptions of a scene from its associated SemRep graph. SemRep/TCG combines the neurocomputational framework of schema theory with the representational format of construction grammar in a model linking eye-tracking data to visual scene descriptions. We then offer a conceptual extension of TCG to include language comprehension and address data on the role of both world knowledge and grammatical semantics in the comprehension performances of agrammatic aphasic patients. This extension introduces a distinction between heavy and light semantics. The TCG model of language comprehension offers a computational framework to quantitatively analyze the distributed dynamics of language processes, focusing on the interactions between grammatical, world knowledge, and visual information. In particular, it reveals interesting implications for the understanding of the various patterns of comprehension performances of agrammatic aphasics measured using sentence-picture matching tasks. This new step in the life cycle of the model serves as a basis for exploring the specific challenges that neurolinguistic computational modeling poses to the neuroinformatics community.
Algorithms and programming tools for image processing on the MPP
NASA Technical Reports Server (NTRS)
Reeves, A. P.
1985-01-01
Topics addressed include: data mapping and rotational algorithms for the Massively Parallel Processor (MPP); Parallel Pascal language; documentation for the Parallel Pascal Development system; and a description of the Parallel Pascal language used on the MPP.
NASA Astrophysics Data System (ADS)
Ramos Román, M. J.; Jimenez-Moreno, G.; Anderson, R. S.; García-Alix, A.; Toney, J. L.; Jiménez-Espejo, F. J. J.; Carrión, J. S.
2015-12-01
Sediments from alpine peat bogs and lakes from the Sierra Nevada in southeastern Spain (western Mediterranean area) have been very informative in terms of how vegetation and wetland environments were impacted by past climate change. Recently, many studies try to find out the relationship between solar activity, atmosphere and ocean dynamics and changes in the terrestrial environments. The Mediterranean is a very sensitive area with respect to atmospheric dynamics due to (1) its location, right in the boundary between subtropical and temperate climate systems and (2) the North Atlantic Oscillation (NAO) is one of the main mechanism that influence present climate in this area. Here we present a multi-proxy high-resolution study from Borreguil de la Caldera (BdlC), a peat bog that records the last ca. 4500 cal yr BP of vegetation, fire, human impact and climate history from the Sierra Nevada. The pollen, charcoal and non-pollen palynomorphs (NPPs) reconstruction in the BdlC-01 record evidence relative humidity changes in the last millennia interrupting the late Holocene aridification trend. This study shows a relative arid period between ca. 4000 and 3100 cal yr BP; the Iberian Roman humid period (ca. 2600 to 1600 cal yr BP); a relative arid period during the Dark Ages (from ca. AD 500 to AD 900) and Medieval Climate Anomaly (from ca. AD 900 to ca. AD 1300) and predominantly wetter conditions corresponding with The Little Ice Age period (from ca. AD 1300 to AD 1850). This climate variability could be explained by centennial scale changes in the NAO and solar activity.
Inhalation Dose and Source Term Studies in a Tribal Area of Wayanad, Kerala, India
Damodaran, Ravikumar C.; Kumar, Visnuprasad Ashok; Panakal John, Jojo; Bangaru, Danalakshmi; Natarajan, Chitra; Sathiamurthy, Bala Sundar; Mundiyanikal Thomas, Jose; Mishra, Rosaline
2017-01-01
Among radiation exposure pathways to human beings, inhalation dose is the most prominent one. Radon, thoron, and their progeny contribute more than 50 per cent to the annual effective dose due to natural radioactivity. South west coast of India is classified as a High Natural Background Radioactivity Area and large scale data on natural radioactivity and dosimetry are available from these coastal regions including the Neendakara-Chavara belt in the south of Kerala. However, similar studies and reports from the northern part of Kerala are scarce. The present study involves the data collection and analysis of radon, thoron, and progeny concentration in the Wayanad district of Kerala. The radon concentration was found to be within a range of 12–378 Bq/m3. The thoron concentration varied from 15 to 621 Bq/m3. Progeny concentration of radon and thoron and the diurnal variation of radon were also studied. In order to assess source term, wall and floor exhalation studies have been done for the houses showing elevated concentration of radon and thoron. The average values of radon, thoron, and their progeny are found to be above the Indian average as well as the average values reported from the High Natural Background Radioactivity Areas of Kerala. Exhalation studies of the soil samples collected from the vicinity of the houses show that radon mass exhalation rate varied from below detectable limit (BDL) to a maximum of 80 mBq/kg/h. The thoron surface exhalation rate ranged from BDL to 17470 Bq/m2/h. PMID:28611847
Ammonia mediates cortical hemichannel dysfunction in rodent models of chronic liver disease
Hadjihambi, Anna; De Chiara, Francesco; Hosford, Patrick S.; Habtetion, Abeba; Karagiannis, Anastassios; Davies, Nathan
2017-01-01
The pathogenesis of hepatic encephalopathy (HE) in cirrhosis is multifactorial and ammonia is thought to play a key role. Astroglial dysfunction is known to be present in HE. Astrocytes are extensively connected by gap junctions formed of connexins, which also exist as functional hemichannels allowing exchange of molecules between the cytoplasm and the extracellular milieu. The astrocyte‐neuron lactate shuttle hypothesis suggests that neuronal activity is fueled (at least in part) by lactate provided by neighboring astrocytes. We hypothesized that in HE, astroglial dysfunction could impair metabolic communication between astrocytes and neurons. In this study, we determined whether hyperammonemia leads to hemichannel dysfunction and impairs lactate transport in the cerebral cortex using rat models of HE (bile duct ligation [BDL] and induced hyperammonemia) and also evaluated the effect of ammonia‐lowering treatment (ornithine phenylacetate [OP]). Plasma ammonia concentration in BDL rats was significantly reduced by OP treatment. Biosensor recordings demonstrated that HE is associated with a significant reduction in both tonic and hypoxia‐induced lactate release in the cerebral cortex, which was normalized by OP treatment. Cortical dye loading experiments revealed hemichannel dysfunction in HE with improvement following OP treatment, while the expression of key connexins was unaffected. Conclusion: The results of the present study demonstrate that HE is associated with central nervous system hemichannel dysfunction, with ammonia playing a key role. The data provide evidence of a potential neuronal energy deficit due to impaired hemichannel‐mediated lactate transport between astrocytes and neurons as a possible mechanism underlying pathogenesis of HE. (Hepatology 2017;65:1306‐1318) PMID:28066916
TumorML: Concept and requirements of an in silico cancer modelling markup language.
Johnson, David; Cooper, Jonathan; McKeever, Steve
2011-01-01
This paper describes the initial groundwork carried out as part of the European Commission funded Transatlantic Tumor Model Repositories project, to develop a new markup language for computational cancer modelling, TumorML. In this paper we describe the motivations for such a language, arguing that current state-of-the-art biomodelling languages are not suited to the cancer modelling domain. We go on to describe the work that needs to be done to develop TumorML, the conceptual design, and a description of what existing markup languages will be used to compose the language specification.
Strategic Control Algorithm Development : Volume 3. Strategic Algorithm Report.
DOT National Transportation Integrated Search
1974-08-01
The strategic algorithm report presents a detailed description of the functional basic strategic control arrival algorithm. This description is independent of a particular computer or language. Contained in this discussion are the geometrical and env...
ERIC Educational Resources Information Center
Broeder, Peter; And Others
This paper addresses the potential value of language-related criteria for use in identifying ethnic minorities in the Netherlands. A description of the way the Dutch government defines ethnic minority groups is followed by a comparative outline of the use of language-related criteria in countries with a longer tradition of immigration (Australia,…
Glossary of Terms Relating to Languages of the Middle East.
ERIC Educational Resources Information Center
Ferguson, Charles A.
This glossary gives brief, non-technical explanations of the following kinds of terms: (1) names of all important languages now spoken in the Middle East, or known to have been spoken in the area; (2) names of language families represented in the area; (3) descriptive terms used with reference to the writing systems of the area; (4) names of…
ERIC Educational Resources Information Center
New York City Board of Education, Brooklyn, NY.
The format of this report is similar to that of other reports on The Language Development Project. See AL 002 352 and 354 for descriptions of the project and the format of the reports. [Not available in hard copy due to marginal legibility of the original document.] (DO)
Effect of "Tell Me More" on EFL Undergraduate Students' English Language Achievement
ERIC Educational Resources Information Center
Gyamfi, George; Sukseemuang, Panida
2017-01-01
This descriptive study aimed at finding the impact of Tell Me More (TMM), an online language-learning program, on English as a foreign language (EFL) undergraduate learners' achievement in a University in Thailand. The study also looked at whether the time of use of TMM had an effect on learners' achievement. Data was collected from the scores of…
ChalkBoard: Mapping Functions to Polygons
NASA Astrophysics Data System (ADS)
Matlage, Kevin; Gill, Andy
ChalkBoard is a domain specific language for describing images. The ChalkBoard language is uncompromisingly functional and encourages the use of modern functional idioms. ChalkBoard uses off-the-shelf graphics cards to speed up rendering of functional descriptions. In this paper, we describe the design of the core ChalkBoard language, and the architecture of our static image generation accelerator.
The Evolution of Foreign Language AP Exam Candidates: A 36-Year Descriptive Study
ERIC Educational Resources Information Center
Brown, Alan V.; Thompson, Gregory L.
2016-01-01
Using a data set exclusively prepared for and licensed to them by the College Board, the authors examined the growth of the Advanced Placement program in foreign languages and overall trends in regard to the number of candidates who sat for the foreign language exams, their gender, their scores, and their ethnicity over the 36-year period covering…
Bibliography of Research in Natural Language Generation
1993-11-01
on 1397] Barbara J. Gross Focuing and description in Artifcial Intelligence (GWAI-88), Geseke, West natural language dialogues, In Joshi et al. (557...Proceedings of the Fifth Canadian Conference from information in a frame structure. Data and on Artificial Intelligence , pages Ŕ-24, London, Knowledge...generation workshops (IWNLGS, ENLGWS), natural language processing conferences (ANLP, TINLAP, SPEECH), artificial intelligence conferences (AAAI, SCA
Peterson's Summer Study Abroad: A Guide to Summer Academic and Language Programs. First Edition.
ERIC Educational Resources Information Center
Peterson's Guides, Inc., Princeton, NJ.
This guide provides descriptions of over 900 summer academic and language study-abroad programs in 80 countries that range from 1-week language study courses to full-summer university programs. An introductory section provides general information on study abroad programs and the use of the guide. The bulk of the guide consists of individual…
Digging for the Roots of Language Death in Eastern Indonesia: The Cases of Kayeli and Hukumina.
ERIC Educational Resources Information Center
Grimes, Charles E.
Looking at descriptive, comparative social and historical evidence, this study explored factors contributing to language death for two languages formerly spoken on the Indonesian island of Buru. Field data were gathered from the last remaining speaker of Hukumina and from the last four speakers of Kayeli. A significant historical event that set in…
A Report on Two Views of the Deficit Theory of Language.
ERIC Educational Resources Information Center
Yellin, David
The views of proponents and opponents of the language deficit theory--the theory that nonstandard dialect is a deficient form of language--are presented in this paper. Following a description of the work of Basil Bernstein, a British educator who is considered the key figure among proponents of the theory, the paper presents an overview of the…
A Longitudinal Study of Motivation in Foreign and Second Language Learning Context
ERIC Educational Resources Information Center
Ordem, Eser
2017-01-01
Although motivation has been one of the most commonly studied subjects in second and foreign language learning in recent decades, it still remains an enigma for learners and teachers. This longitudinal study aimed to follow a student (N = 1) studying German in both second and foreign language environment for three years. The study was descriptive,…
ERIC Educational Resources Information Center
Nagle, Charles
2018-01-01
This study examined relationships between language learning motivation and the longitudinal development of second language (L2) pronunciation. Twenty-six English-speaking learners of Spanish recorded a simplified picture description task 5 times over a year-long period spanning their 2nd, 3rd, and 4th semesters of Spanish language instruction.…
How Do Utterance Measures Predict Raters' Perceptions of Fluency in French as a Second Language?
ERIC Educational Resources Information Center
Préfontaine, Yvonne; Kormos, Judit; Johnson, Daniel Ezra
2016-01-01
While the research literature on second language (L2) fluency is replete with descriptions of fluency and its influence with regard to English as an additional language, little is known about what fluency features influence judgments of fluency in L2 French. This study reports the results of an investigation that analyzed the relationship between…
A software framework for pipelined arithmetic algorithms in field programmable gate arrays
NASA Astrophysics Data System (ADS)
Kim, J. B.; Won, E.
2018-03-01
Pipelined algorithms implemented in field programmable gate arrays are extensively used for hardware triggers in the modern experimental high energy physics field and the complexity of such algorithms increases rapidly. For development of such hardware triggers, algorithms are developed in C++, ported to hardware description language for synthesizing firmware, and then ported back to C++ for simulating the firmware response down to the single bit level. We present a C++ software framework which automatically simulates and generates hardware description language code for pipelined arithmetic algorithms.
PDDL4J: a planning domain description library for java
NASA Astrophysics Data System (ADS)
Pellier, D.; Fiorino, H.
2018-01-01
PDDL4J (Planning Domain Description Library for Java) is an open source toolkit for Java cross-platform developers meant (1) to provide state-of-the-art planners based on the Pddl language, and (2) to facilitate research works on new planners. In this article, we present an overview of the Automated Planning concepts and languages. We present some planning systems and their most significant applications. Then, we detail the Pddl4j toolkit with an emphasis on the available informative structures, heuristics and search algorithms.
ERIC Educational Resources Information Center
King, Anny, Ed.
This book provides a description and synthesis of a range of relevant practice and offers a framework for making language learning more relevant for new generations of practice. It is intended as a contribution to the debate about the purposes of language studies in higher education in the 21st century. The book is divided into five parts and 15…
An overview of the Opus language and runtime system
NASA Technical Reports Server (NTRS)
Mehrotra, Piyush; Haines, Matthew
1994-01-01
We have recently introduced a new language, called Opus, which provides a set of Fortran language extensions that allow for integrated support of task and data parallelism. lt also provides shared data abstractions (SDA's) as a method for communication and synchronization among these tasks. In this paper, we first provide a brief description of the language features and then focus on both the language-dependent and language-independent parts of the runtime system that support the language. The language-independent portion of the runtime system supports lightweight threads across multiple address spaces, and is built upon existing lightweight thread and communication systems. The language-dependent portion of the runtime system supports conditional invocation of SDA methods and distributed SDA argument handling.
Lesion localization of speech comprehension deficits in chronic aphasia
Binder, Jeffrey R.; Humphries, Colin; Gross, William L.; Book, Diane S.
2017-01-01
Objective: Voxel-based lesion-symptom mapping (VLSM) was used to localize impairments specific to multiword (phrase and sentence) spoken language comprehension. Methods: Participants were 51 right-handed patients with chronic left hemisphere stroke. They performed an auditory description naming (ADN) task requiring comprehension of a verbal description, an auditory sentence comprehension (ASC) task, and a picture naming (PN) task. Lesions were mapped using high-resolution MRI. VLSM analyses identified the lesion correlates of ADN and ASC impairment, first with no control measures, then adding PN impairment as a covariate to control for cognitive and language processes not specific to spoken language. Results: ADN and ASC deficits were associated with lesions in a distributed frontal-temporal parietal language network. When PN impairment was included as a covariate, both ADN and ASC deficits were specifically correlated with damage localized to the mid-to-posterior portion of the middle temporal gyrus (MTG). Conclusions: Damage to the mid-to-posterior MTG is associated with an inability to integrate multiword utterances during comprehension of spoken language. Impairment of this integration process likely underlies the speech comprehension deficits characteristic of Wernicke aphasia. PMID:28179469
Lesion localization of speech comprehension deficits in chronic aphasia.
Pillay, Sara B; Binder, Jeffrey R; Humphries, Colin; Gross, William L; Book, Diane S
2017-03-07
Voxel-based lesion-symptom mapping (VLSM) was used to localize impairments specific to multiword (phrase and sentence) spoken language comprehension. Participants were 51 right-handed patients with chronic left hemisphere stroke. They performed an auditory description naming (ADN) task requiring comprehension of a verbal description, an auditory sentence comprehension (ASC) task, and a picture naming (PN) task. Lesions were mapped using high-resolution MRI. VLSM analyses identified the lesion correlates of ADN and ASC impairment, first with no control measures, then adding PN impairment as a covariate to control for cognitive and language processes not specific to spoken language. ADN and ASC deficits were associated with lesions in a distributed frontal-temporal parietal language network. When PN impairment was included as a covariate, both ADN and ASC deficits were specifically correlated with damage localized to the mid-to-posterior portion of the middle temporal gyrus (MTG). Damage to the mid-to-posterior MTG is associated with an inability to integrate multiword utterances during comprehension of spoken language. Impairment of this integration process likely underlies the speech comprehension deficits characteristic of Wernicke aphasia. © 2017 American Academy of Neurology.
ERIC Educational Resources Information Center
Fletcher, Paul
1989-01-01
Discusses the role of linguistics in the investigation of language disorders, focusing on the application of phonetics, descriptive grammatic frameworks, grammatical theory, and concepts from semantics and pragmatics to a variety of disorders and their remediation. Some trends and examples from the field of clinical linguistics are discussed. (GLR)
An Object Description Language for Distributed Discrete Event Simulations
2001-05-24
some tremendous improvements in simulation speed and fidelity. This dissertation describes a new programming language that is useful in creating...104 CHAPTER 8. GLUT- BASED USER INTERFACE....................................il 8. 1. OUTPUT CONCERNS...143 9.3. GLUT BASED DEMONSTRATIONS ......................................................... 145 9.3
NASA Technical Reports Server (NTRS)
Al Hassan, Mohammad; Britton, Paul; Hatfield, Glen Spencer; Novack, Steven D.
2017-01-01
Today's launch vehicles complex electronic and avionics systems heavily utilize Field Programmable Gate Array (FPGA) integrated circuits (IC) for their superb speed and reconfiguration capabilities. Consequently, FPGAs are prevalent ICs in communication protocols such as MILSTD- 1553B and in control signal commands such as in solenoid valve actuations. This paper will identify reliability concerns and high level guidelines to estimate FPGA total failure rates in a launch vehicle application. The paper will discuss hardware, hardware description language, and radiation induced failures. The hardware contribution of the approach accounts for physical failures of the IC. The hardware description language portion will discuss the high level FPGA programming languages and software/code reliability growth. The radiation portion will discuss FPGA susceptibility to space environment radiation.
A Comparison of the Optimization and Analysis of Doubly Curved Shells Using MSC/NASTRAN and ASTROS
1990-12-01
BMC(7,5)=I.OD+00 CALL BMAT (X1,RI,X2,R2,0.OD+00,B,DL) CALL EMAT(DNU,E,T,G) C C DO BMC*E*B C DO 100 J1=1,7 DO 100 J2=1,5 DO 100 J3=1,5 DO 100 J4=1,6...ELEMENT LENGTH. C SUBROUTINE BMAT (XI,RI,X2,R2,DKSI,B,DL) DOUBLE PRECISION XI,RI,X2,R2,DKSI,B(S,6),DL,R,PHI,CPR,SPR,R, &DKMDKP, DLINV C C EXPLANATION OF
ERIC Educational Resources Information Center
Roedding, Amy L.
2013-01-01
In an effort to understand Christian college professors' levels of awareness to the needs of English Language Learners (ELLs) in content-based classrooms and to identify effective practices for language learning that are being implemented, a quantitative study using descriptive research was carried out. A survey was used to collect data to…
ERIC Educational Resources Information Center
Plester, B.; Lerkkanen, M.-K.; Linjama, L. J.; Rasku-Puttonen, H.; Littleton, K.
2011-01-01
The aim of the study was to demonstrate the style of text language used by Finnish pre-teen texters (n = 65) and determine how their text language related to their traditional literacy skills, and compare descriptively these results with earlier results from work with young English texters. Three kinds of text messages (natural texts, elicited…
ERIC Educational Resources Information Center
Bortolini, Umberta; Arfe, Barbara; Caselli, Cristina M.; Degasperi, Luisa; Deevy, Patricia; Leonard, Laurence B.
2006-01-01
Background: The discovery of clinical markers for specific language impairment (SLI) in children can assist in the accurate identification of children with this disorder, and in a description of the disorder's phenotype for genetic study. One challenge to this type of research is the fact that languages vary in the most salient symptoms of SLI.…
ERIC Educational Resources Information Center
Andersen, Elaine S., Comp.
Thirty-one papers and reports dealing with recent work on language input to children are listed in this annotated bibliography. The annotations, which are descriptive rather than evaluative, summarize the design of each study, the nature of the data, and some of the results and conclusions. Entries by P. Broen, J. Bynon, L. Cherry, J. M. Crawford,…
[Aphasia--a new as well as old problem].
Hadano, Kazuo
2013-01-01
Alajouanine (1956) established a concept of jargon as a speech symptom of aphasia and gave clinical descriptions of three types of jargon-undifferentiated, asemantic (neologistic) and paraphasic (semantic) jargon. Several case-reports of undifferentiated jargon in Japanese language have been published in clinical aphasiology. On the other hand language development of jargon-type in normal children was reprorted in developmental psychology. We point out a phenomenological similarity of clinical language symptoms of jargon with language development of jargon-type considering its neuropsychological implications.
ERIC Educational Resources Information Center
Beller, Charley
2013-01-01
The study of definite descriptions has been a central part of research in linguistics and philosophy of language since Russell's seminal work "On Denoting" (Russell 1905). In that work Russell quickly dispatches analyses of denoting expressions with forms like "no man," "some man," "a man," and "every…
Toledo, Cíntia Matsuda; Cunha, Andre; Scarton, Carolina; Aluísio, Sandra
2014-01-01
Discourse production is an important aspect in the evaluation of brain-injured individuals. We believe that studies comparing the performance of brain-injured subjects with that of healthy controls must use groups with compatible education. A pioneering application of machine learning methods using Brazilian Portuguese for clinical purposes is described, highlighting education as an important variable in the Brazilian scenario. The aims were to describe how to:(i) develop machine learning classifiers using features generated by natural language processing tools to distinguish descriptions produced by healthy individuals into classes based on their years of education; and(ii) automatically identify the features that best distinguish the groups. The approach proposed here extracts linguistic features automatically from the written descriptions with the aid of two Natural Language Processing tools: Coh-Metrix-Port and AIC. It also includes nine task-specific features (three new ones, two extracted manually, besides description time; type of scene described - simple or complex; presentation order - which type of picture was described first; and age). In this study, the descriptions by 144 of the subjects studied in Toledo 18 were used,which included 200 healthy Brazilians of both genders. A Support Vector Machine (SVM) with a radial basis function (RBF) kernel is the most recommended approach for the binary classification of our data, classifying three of the four initial classes. CfsSubsetEval (CFS) is a strong candidate to replace manual feature selection methods.
GSFC Systems Test and Operation Language (STOL) functional requirements and language description
NASA Technical Reports Server (NTRS)
Desjardins, R.; Hall, G.; Mcguire, J.; Merwarth, P.; Mocarsky, W.; Truszkowski, W.; Villasenor, A.; Brosi, F.; Burch, P.; Carey, D.
1978-01-01
The Systems Tests and Operation Language (STOL) provides the means for user communication with payloads, applications programs, and other ground system elements. It is a systems operation language that enables an operator or user to communicate a command to a computer system. The system interprets each high level language directive from the user and performs the indicated action, such as executing a program, printing out a snapshot, or sending a payload command. This document presents the following: (1) required language features and implementation considerations; (2) basic capabilities; (3) telemetry, command, and input/output directives; (4) procedure definition and control; (5) listing, extension, and STOL nucleus capabilities.
An Abstract Plan Preparation Language
NASA Technical Reports Server (NTRS)
Butler, Ricky W.; Munoz, Cesar A.
2006-01-01
This paper presents a new planning language that is more abstract than most existing planning languages such as the Planning Domain Definition Language (PDDL) or the New Domain Description Language (NDDL). The goal of this language is to simplify the formal analysis and specification of planning problems that are intended for safety-critical applications such as power management or automated rendezvous in future manned spacecraft. The new language has been named the Abstract Plan Preparation Language (APPL). A translator from APPL to NDDL has been developed in support of the Spacecraft Autonomy for Vehicles and Habitats Project (SAVH) sponsored by the Explorations Technology Development Program, which is seeking to mature autonomy technology for application to the new Crew Exploration Vehicle (CEV) that will replace the Space Shuttle.
Are You Listening to Your Computer?
ERIC Educational Resources Information Center
Shugg, Alan
1992-01-01
Accepting the great motivational value of computers in second-language learning, this article describes ways to use authentic language recorded on a computer with HyperCard. Graphics, sound, and hardware/software requirements are noted, along with brief descriptions of programing with sound and specific programs. (LB)
ERIC Educational Resources Information Center
Mirzayan, Armik
2010-01-01
This thesis provides a comprehensive account of the intonational phonology of Lakota, an indigenous North American language of the Siouan family. Lakota is predominantly a verb final language, characterized by complex verbal morphology. The phonological description of Lakota intonation and prosody presented here is based on acoustic analysis of…
Asian-Pacific Papers. Occasional Papers Number 10.
ERIC Educational Resources Information Center
McCarthy, Brian, Ed.
Sixteen papers are presented. Topics covered include language teaching, discourse analysis, code switching, phonetics, language and cultural identity, and descriptive and comparative studies. All presenters were from the Asia-Pacific area of the world. Papers include: "The Baba Malay Lexicon: Hokkien Loanwords in Baba Malay" (Anne…
DDL:Digital systems design language
NASA Technical Reports Server (NTRS)
Shival, S. G.
1980-01-01
Hardware description languages are valuable tools in such applications as hardware design, system documentation, and logic design training. DDL is convenient medium for inputting design details into hardware-design automation system. It is suitable for describing digital systems at gate, register transfer, and major combinational block level.
Are Prospective English Teachers Linguistically Intelligent?
ERIC Educational Resources Information Center
Tezel, Kadir Vefa
2017-01-01
Language is normally associated with linguistic capabilities of individuals. In the theory of multiple intelligences, language is considered to be related primarily to linguistic intelligence. Using the theory of Multiple Intelligences as its starting point, this descriptive survey study investigated to what extent prospective English teachers'…
A description of the verbal behavior of students during two reading instruction methods
Daly, Patricia M.
1987-01-01
The responses of students during two reading methods, the language experience approach and two Mastery Learning programs, were analyzed using verbal operants. A description of student responding was generated for these methods. The purpose of the study was to answer the questions: What are the major controlling variables determining student reading behavior during the language experience approach and two Mastery Learning programs, and how do these controlling variables change across story reading sessions and across stories in the first method? Student responses by verbal operant were compared for both reading methods. Findings indicated higher frequencies of textual operants occurred in responses during the Mastery Learning programs. A greater reliance on intraverbal control was evident in responses during the language experience approach. It is suggested that students who can generate strong intraverbal responses and who may have visual discrimination problems during early reading instruction may benefit from use of the language experience approach at this stage. ImagesFigure 2Figure 3 PMID:22477535
From General Game Descriptions to a Market Specification Language for General Trading Agents
NASA Astrophysics Data System (ADS)
Thielscher, Michael; Zhang, Dongmo
The idea behind General Game Playing is to build systems that, instead of being programmed for one specific task, are intelligent and flexible enough to negotiate an unknown environment solely on the basis of the rules which govern it. In this paper, we argue that this principle has the great potential to bring to a new level artificially intelligent systems in other application areas as well. Our specific interest lies in General Trading Agents, which are able to understand the rules of unknown markets and then to actively participate in them without human intervention. To this end, we extend the general Game Description Language into a language that allows to formally describe arbitrary markets in such a way that these specifications can be automatically processed by a computer. We present both syntax and a transition-based semantics for this Market Specification Language and illustrate its expressive power by presenting axiomatizations of several well-known auction types.
Applying Standard Interfaces to a Process-Control Language
NASA Technical Reports Server (NTRS)
Berthold, Richard T.
2005-01-01
A method of applying open-operating-system standard interfaces to the NASA User Interface Language (UIL) has been devised. UIL is a computing language that can be used in monitoring and controlling automated processes: for example, the Timeliner computer program, written in UIL, is a general-purpose software system for monitoring and controlling sequences of automated tasks in a target system. In providing the major elements of connectivity between UIL and the target system, the present method offers advantages over the prior method. Most notably, unlike in the prior method, the software description of the target system can be made independent of the applicable compiler software and need not be linked to the applicable executable compiler image. Also unlike in the prior method, it is not necessary to recompile the source code and relink the source code to a new executable compiler image. Abstraction of the description of the target system to a data file can be defined easily, with intuitive syntax, and knowledge of the source-code language is not needed for the definition.
Equation-oriented specification of neural models for simulations
Stimberg, Marcel; Goodman, Dan F. M.; Benichoux, Victor; Brette, Romain
2013-01-01
Simulating biological neuronal networks is a core method of research in computational neuroscience. A full specification of such a network model includes a description of the dynamics and state changes of neurons and synapses, as well as the synaptic connectivity patterns and the initial values of all parameters. A standard approach in neuronal modeling software is to build network models based on a library of pre-defined components and mechanisms; if a model component does not yet exist, it has to be defined in a special-purpose or general low-level language and potentially be compiled and linked with the simulator. Here we propose an alternative approach that allows flexible definition of models by writing textual descriptions based on mathematical notation. We demonstrate that this approach allows the definition of a wide range of models with minimal syntax. Furthermore, such explicit model descriptions allow the generation of executable code for various target languages and devices, since the description is not tied to an implementation. Finally, this approach also has advantages for readability and reproducibility, because the model description is fully explicit, and because it can be automatically parsed and transformed into formatted descriptions. The presented approach has been implemented in the Brian2 simulator. PMID:24550820
Saadatnia, Mahmood; Ketabi, Saeed; Tavakoli, Mansoor
2016-12-01
The purpose of this study was to investigate the relationship between text structure and two levels of reading comprehension, namely literal and inferential, in Iranian EFL learners. Studies have generally found that learners perform differently after they have read different text structures (Amiri et al. in Proc Soc Behav Sci 66:402-409, 2012). The text structures in focus were descriptive and enumerative expository texts. One hundred eighty upper-intermediate EFL learners were assigned four reading passages, two including descriptive and the other two enumerative text structure, followed by both literal and inferential multiple-choice items. A number of paired-samples t tests were run to provide answers to the research questions of this study. The results indicated that the participants meaningfully outperformed on the descriptive texts at both levels of literal and inferential comprehension. The findings also revealed that in both text structures of description and enumeration, literal comprehension significantly outweighed inferential comprehension. Implications were made for L2 materials developers, language teachers, and language testers regarding the consideration of text typical features in their practice.
Successful communication does not drive language development: Evidence from adult homesign.
Carrigan, Emily M; Coppola, Marie
2017-01-01
Constructivist accounts of language acquisition maintain that the language learner aims to match a target provided by mature users. Communicative problem solving in the context of social interaction and matching a linguistic target or model are presented as primary mechanisms driving the language development process. However, research on the development of homesign gesture systems by deaf individuals who have no access to a linguistic model suggests that aspects of language can develop even when typical input is unavailable. In four studies, we examined the role of communication in the genesis of homesign systems by assessing how well homesigners' family members comprehend homesign productions. In Study 1, homesigners' mothers showed poorer comprehension of homesign descriptions produced by their now-adult deaf child than of spoken Spanish descriptions of the same events produced by one of their adult hearing children. Study 2 found that the younger a family member was when they first interacted with their deaf relative, the better they understood the homesigner. Despite this, no family member comprehended homesign productions at levels that would be expected if family members co-generated homesign systems with their deaf relative via communicative interactions. Study 3 found that mothers' poor or incomplete comprehension of homesign was not a result of incomplete homesign descriptions. In Study 4 we demonstrated that Deaf native users of American Sign Language, who had no previous experience with the homesigners or their homesign systems, nevertheless comprehended homesign productions out of context better than the homesigners' mothers. This suggests that homesign has comprehensible structure, to which mothers and other family members are not fully sensitive. Taken together, these studies show that communicative problem solving is not responsible for the development of structure in homesign systems. The role of this mechanism must therefore be re-evaluated in constructivist theories of language development. Copyright © 2016 Elsevier B.V. All rights reserved.
Florida Journal of Communication Disorders, 2000.
ERIC Educational Resources Information Center
Rosa-Lugo, Linda I., Ed.
2000-01-01
This volume of the Florida Journal of Communication Disorders contains the following featured articles: (1) Using Descriptive Language Assessment Procedure with African-American English Preschool Child Speakers: Advantages and Limitations (Kenyatta O. Rivers and Linda J. Lombardino), which discusses best practices for using descriptive language…
MHDL CAD tool with fault circuit handling
NASA Astrophysics Data System (ADS)
Espinosa Flores-Verdad, Guillermo; Altamirano Robles, Leopoldo; Osorio Roque, Leticia
2003-04-01
Behavioral modeling and simulation, with Analog Hardware and Mixed Signal Description High Level Languages (MHDLs), have generated the development of diverse simulation tools that allow handling the requirements of the modern designs. These systems have million of transistors embedded and they are radically diverse between them. This tendency of simulation tools is exemplified by the development of languages for modeling and simulation, whose applications are the re-use of complete systems, construction of virtual prototypes, realization of test and synthesis. This paper presents the general architecture of a Mixed Hardware Description Language, based on the standard 1076.1-1999 IEEE VHDL Analog and Mixed-Signal Extensions known as VHDL-AMS. This architecture is novel by consider the modeling and simulation of faults. The main modules of the CAD tool are briefly described in order to establish the information flow and its transformations, starting from the description of a circuit model, going throw the lexical analysis, mathematical models generation and the simulation core, ending at the collection of the circuit behavior as simulation"s data. In addition, the incorporated mechanisms to the simulation core are explained in order to realize the handling of faults into the circuit models. Currently, the CAD tool works with algebraic and differential descriptions for the circuit models, nevertheless the language design is open to be able to handle different model types: Fuzzy Models, Differentials Equations, Transfer Functions and Tables. This applies for fault models too, in this sense the CAD tool considers the inclusion of mutants and saboteurs. To exemplified the results obtained until now, the simulated behavior of a circuit is shown when it is fault free and when it has been modified by the inclusion of a fault as a mutant or a saboteur. The obtained results allow the realization of a virtual diagnosis for mixed circuits. This language works in a UNIX system; it was developed with an object-oriented methodology and programmed in C++.
Improving accessibility to mathematical formulas: the Wikipedia Math Accessor
NASA Astrophysics Data System (ADS)
Fuentes Sepúlveda, J.; Ferres, L.
2012-09-01
Mathematics accessibility is an important topic for inclusive education. In this paper, we make Wikipedia's repository of mathematical formulas accessible by providing a natural language description of its more than 420,000 formulas using a well-researched sub-language. We also contribute by targeting Spanish speakers, for whom assistive technologies, particularly domain-specific technologies like the one described here, are scarce. Our focus on the semantics of formulas (rather than their visual appearance) allowed us to generate verbalizations with a precision of approximately 80% of understandable descriptions, as shown in an evaluation with sighted users.
ERIC Educational Resources Information Center
Edgerton, Mills F., Jr., Ed.
Included in this volume are the reports dealing with the effective use of audiovisual media in foreign language instruction and developed by the working committees of the sixteenth annual Northeast Conference on the Teaching of Foreign Languages. Six individuals prepared the media descriptions and selected the demonstrations described in the…
Content Questions In American Sign Language: An RRG Analysis
2004-12-08
a temporal framework, someone might sign (29) DURING FIVE YEAR YONDER GALLAUDET … During my five years at Gallaudet …. Until a new topic is...Language: A Teacher’s Resource on Grammar and Culture. Washington, D.C.: Gallaudet University Press. BATTISON, ROBBIN. 1978. Loan Signs from...Typology and Syntactic Description, ed. by Timothy Shopen. Cambridge, MA: Cambridge University Press. —. In press b. Clause Types. Language Typology
ERIC Educational Resources Information Center
Cruz, Emily; Woodbury, Anthony C.
2014-01-01
We give a narrative description of our ten-year path into the elaborate tonal systems of the Chatino languages (Otomanguean; Oaxaca, Mexico), and of some of the methods we have used and recommend, illustrated with specific examples. The work, ongoing at the time of writing, began when one of us (Cruz), a native speaker of San Juan Quiahije…
A W-Grammar Description for ADA.
1986-12-01
7 2. A Type 2 Grammar for Ada Identifiers . . . . . . .... 8 3. The Chomsky erarchy......... ...... 10 4. Some Hypernotions Used in...Ada Language Reference Manual. The Chomsky Hierarchy (4:9-20, 7:217-232). In the 1950s, Noam Chomsky defined five classes of phrase structure grammars ...describing valid language tokens. For example a Type 3 grammar for Ada identifiers is shown in Figure 1. Type 2 Chomsky Languages are the Context-free
Dash, Tanya; Kar, Bhoomika R.
2014-01-01
Background. Bilingualism results in an added advantage with respect to cognitive control. The interaction between bilingual language control and general purpose cognitive control systems can also be understood by studying executive control among individuals with bilingual aphasia. Objectives. The current study examined the subcomponents of cognitive control in bilingual aphasia. A case study approach was used to investigate whether cognitive control and language control are two separate systems and how factors related to bilingualism interact with control processes. Methods. Four individuals with bilingual aphasia performed a language background questionnaire, picture description task, and two experimental tasks (nonlinguistic negative priming task and linguistic and nonlinguistic versions of flanker task). Results. A descriptive approach was used to analyse the data using reaction time and accuracy measures. The cumulative distribution function plots were used to visualize the variations in performance across conditions. The results highlight the distinction between general purpose cognitive control and bilingual language control mechanisms. Conclusion. All participants showed predominant use of the reactive control mechanism to compensate for the limited resources system. Independent yet interactive systems for bilingual language control and general purpose cognitive control were postulated based on the experimental data derived from individuals with bilingual aphasia. PMID:24982591
The Threshold Level--For Schools?
ERIC Educational Resources Information Center
Lauerbach, Gerda
1979-01-01
Comments on the document "Threshold Level for Modern Language Learning Schools" (J. A. Van Ek, Strasbourg, 1976) and its appropriateness as a description of learning goals for the first years of foreign language teaching. Criticizes particularly the "reduced learning" concept, on which the threshold projects are based. (IFS/WGA)
Effectiveness of Facebook in English Language Learning: A Case Study
ERIC Educational Resources Information Center
Faryadi, Qais
2017-01-01
The prime objective of this research was to investigate whether Facebook helped undergraduate students of Universiti Sains Islam Malaysia (USIM) improve their English language proficiency, critical thinking, comprehension skills, and motivation. A triangulation method (quantitative, qualitative, and descriptive) was employed in the investigation.…
Argument Structure of Tsou: Simplex and Complex Predicates
ERIC Educational Resources Information Center
Lin, Gujing
2010-01-01
This thesis investigates the argument structure of Tsou, a Formosan language within the Austronesian family. The investigation studies both simplex and complex predicates as well as describes the valency groupings and alignment patterns emerging from various clausal configurations. Assuming the stance that language description should respect…
Methods in Elementary School Foreign Language Teaching.
ERIC Educational Resources Information Center
Curtain, Helena
1991-01-01
A brief overview of the importance of the use of appropriate methodologies for elementary school foreign language instruction precedes a description of several strategies involving total physical response, story telling, games and songs, props, small-group work, role-play, content-based instruction, cultural and global awareness, language…
Culture and Language Learning in Higher Education.
ERIC Educational Resources Information Center
Byram, Michael, Ed.
A collection of papers concerning cultural studies within college and university second language programs, particularly for foreign students, includes program descriptions from a variety of countries and discussions of cultural education and cultural conflict. Themes include the nature of cultural teaching, cultural education as a discipline,…
Enhancing Students' Responses to Art through Qualitative Language
ERIC Educational Resources Information Center
Tollifson, Jerry
2011-01-01
A teacher's communication choices can spark student understanding. By harnessing and modeling the power that qualitative language provides when characterizing artworks, these choices support a student's evolving capabilities from simple description to a deeper embodiment of art criticism. This article is aimed at helping teachers understand how…
The Supervisory Process of EFL Teachers: A Case Study
ERIC Educational Resources Information Center
Chen, Cheryl Wei-Yu; Cheng, Yuh-show
2013-01-01
Supervision is an essential part of language teachers' professional experiences. The literature on language teacher supervision from the past few decades consists largely of descriptions of supervisory approaches (Bailey, 2009) and analysis of the supervisory discourse (Hooton, 2008; Wajnryb, 1994; 1995; 1998; Wallace & Woolger, 1991). This…
Using XML and Java for Astronomical Instrument Control
NASA Astrophysics Data System (ADS)
Koons, L.; Ames, T.; Evans, R.; Warsaw, C.; Sall, K.
1999-12-01
Traditionally, instrument command and control systems have been highly specialized, consisting mostly of custom code that is difficult to develop, maintain, and extend. Such solutions are initially very costly and are inflexible to subsequent engineering change requests. Instrument description is too tightly coupled with details of implementation. NASA/Goddard Space Flight Center and AppNet, Inc. are developing a very general and highly extensible framework that applies to virtually any kind of instrument that can be controlled by a computer (e.g., telescopes, microscopes and printers). A key aspect of the object-oriented architecture, implemented in Java, involves software that is driven by an instrument description. The Astronomical Instrument Markup Language (AIML) is a domain-specific implementation of the more generalized Instrument Markup Language (IML). The software architecture combines the platform-independent processing capabilities of Java with the vendor-independent data description syntax of Extensible Markup Language (XML), a human-readable and machine-understandable way to describe structured data. IML is used to describe command sets (including parameters, datatypes, and constraints) and their associated formats, telemetry, and communication mechanisms. The software uses this description to present graphical user interfaces to control and monitor the instrument. Recent efforts have extended to command procedures (scripting) and representation of data pipeline inputs, outputs, and connections. Near future efforts are likely to include an XML description of data visualizations, as well as the potential use of XSL (Extensible Stylesheet Language) to permit astronomers to customize the user interface on several levels: per user, instrument, subsystem, or observatory-wide. Our initial prototyping effort was targeted for HAWC (High-resolution Airborne Wideband Camera), a first-light instrument of SOFIA (the Stratospheric Observatory for Infrared Astronomy). A production-level application of this technology is for one of the three candidate detectors of SPIRE (Spectral and Photometric Imaging REceiver), a focal plane instrument proposed for the European Space Agency's Far Infrared Space Telescope. The detectors are being developed by the Infrared Astrophysics Branch of NASA/GSFC.
NASA Technical Reports Server (NTRS)
Al Hassan, Mohammad; Britton, Paul; Hatfield, Glen Spencer; Novack, Steven D.
2017-01-01
Field Programmable Gate Arrays (FPGAs) integrated circuits (IC) are one of the key electronic components in today's sophisticated launch and space vehicle complex avionic systems, largely due to their superb reprogrammable and reconfigurable capabilities combined with relatively low non-recurring engineering costs (NRE) and short design cycle. Consequently, FPGAs are prevalent ICs in communication protocols and control signal commands. This paper will identify reliability concerns and high level guidelines to estimate FPGA total failure rates in a launch vehicle application. The paper will discuss hardware, hardware description language, and radiation induced failures. The hardware contribution of the approach accounts for physical failures of the IC. The hardware description language portion will discuss the high level FPGA programming languages and software/code reliability growth. The radiation portion will discuss FPGA susceptibility to space environment radiation.
Rackayova, Veronika; Braissant, Olivier; McLin, Valérie A; Berset, Corina; Lanz, Bernard; Cudalbu, Cristina
2016-12-01
Chronic liver disease (CLD) leads to a spectrum of neuropsychiatric disorders named hepatic encephalopathy (HE). Even though brain energy metabolism is believed to be altered in chronic HE, few studies have explored energy metabolism in CLD-induced HE, and their findings were inconsistent. The aim of this study was to characterize for the first time in vivo and longitudinally brain metabolic changes in a rat model of CLD-induced HE with a focus on energy metabolism, using the methodological advantages of high field proton and phosphorus Magnetic Resonance Spectroscopy ( 1 H- and 31 P-MRS). Wistar rats were bile duct ligated (BDL) and studied before BDL and at post-operative weeks 4 and 8. Glutamine increased linearly over time (+146 %) together with plasma ammonium (+159 %). As a compensatory effect, other brain osmolytes decreased: myo-inositol (-36 %), followed by total choline and creatine. A decrease in the neurotransmitters glutamate (-17 %) and aspartate (-28 %) was measured only at week 8, while no significant changes were observed for lactate and phosphocreatine. Among the other energy metabolites measured by 31 P-MRS, we observed a non-significant decrease in ATP together with a significant decrease in ADP (-28 %), but only at week 8 after ligation. Finally, brain glutamine showed the strongest correlations with changes in other brain metabolites, indicating its importance in type C HE. In conclusion, mild alterations in some metabolites involved in energy metabolism were observed but only at the end stage of the disease when edema and neurological changes are already present. Therefore, our data indicate that impaired energy metabolism is not one of the major causes of early HE symptoms in the established model of type C HE.
Isoprene emission from Indian trees
NASA Astrophysics Data System (ADS)
Varshney, C. K.; Singh, Abhai Pratap
2003-12-01
Isoprene is the most dominant non-methane volatile organic compound (NMVOC) emitted by plants. NMVOCs play an important role in regulating the composition of atmospheric trace gases including global concentration of tropospheric ozone. Our present knowledge about NMVOCs emission is mainly from studies on temperate tree species. So far information on biogenic NMVOCs emission from tropical tree species is limited. In this study, isoprene emission rates from 40 tropical Indian tree species belonging to 33 genera and 17 families were measured for the first time using a dynamic flow through enclosure chamber technique. The isoprene emission rate from plants (30°C and PAR 1000 μmolm-2s-1) ranged from undetectable to 81.5 μg g-1 h-1 and values were found to be comparable with other studies on tropical tree species. Tree species screened for isoprene emission in the present study may be grouped into the four categories, proposed by [2001], namely, 18 species were negligible or BDL isoprene emitting (<1 μg g-1 h-1), 6 species were low emitting (1 ≤ to <10 μg g-1 h-1), 5 species were moderate emitting (10≤ to <25 μg g-1 h-1), and 11 species were high isoprene emitting (≥25 μg g-1 h-1). Maximum isoprene emission rate (81.5 μg g-1 h-1) was observed in the case of Dalbergia sissoo Linn. It was interesting to find that Citrus limon Linn., Citrus reticulata Linn., Citrus sinensis Linn., Grevillea robusta A. Cunn., and Morus alba Linn., which were earlier reported as BDL or non isoprene emitters in US [, 1998; , 2001] were found to be appreciably high isoprene emitters (0.61-21.60 μg g-1 h-1) in the present study.
Elswefy, Sahar E; Rashed, Laila A; Younis, Nahla N; Shaheen, Mohamed A; Ghanim, Amal MH
2016-01-01
Mesenchymal stem cells (MSCs) have attracted lots of attention for the treatment of acute liver failure and end-stage liver diseases. This study aimed at investigating the fundamental mechanism by which bone marrow-derived MSCs (BM-MSCs) induce liver regeneration of fibrotic liver in rats. Rats underwent bile duct ligation (BDL) surgery and four weeks later they were treated with either BM-MSCs (3 × 106 cells /rat, once, tail vein injection) or silymarin (100 mg/kg, daily, orally) for four weeks. Liver function tests and hepatic oxidative stress were determined. Hepatic injury and fibrosis were assessed by H and E, Sirus red staining and immunohistochemical expression of α-smooth muscle actin (α-SMA). Hepatocyte growth factor (HGF) and the gene expression of cytokeratin-19 (CK-19) and matrix metalloproteinase-2 (MMP-2) in liver tissue were determined. BDL induced cholestatic liver injury characterized by elevated ALT and AST activities, bilirubin and decreased albumin. The architecture damage was staged as Metavir score: F3, A3. Fibrosis increased around proliferating bile duct as indicated by sirus red staining and α-SMA immunostaining. Fibrogenesis was favored over fibrolysis and confirmed by decreased HGF with increased expression of CK-19, but decreased MMP-2 expression. BM-MSCs treatment restored deteriorated liver functions and restored the histological changes, resolved fibrosis by improving liver regenerative capabilities (P < 0.001), increases in HGF and MMP-2 mRNA and downregulating CK-19 mRNA. Sliymarin, however, induced similar but less prominent effects compared to BM-MSCs. In conclusion, liver regenerative capabilities can be stimulated by BM-MSCs via augmentation of HGF that subsequently up-regulate MMP-2 mRNA while downregulating CK-19 mRNA. PMID:26811102
Luo, Xiaoying; Dan Wang; Luo, Xuan; Zhu, Xintao; Wang, Guozhen; Ning, Zuowei; Li, Yang; Ma, Xiaoxin; Yang, Renqiang; Jin, Siyi; Huang, Yun; Meng, Ying; Li, Xu
2017-10-01
Aldosterone, with pro-oxidation and pro-autophagy capabilities, plays a key role in liver fibrosis. However, the mechanisms underlying aldosterone-promoted liver sinusoidal endothelial cells (LSECs) defenestration remain unknown. Caveolin 1 (Cav1) displays close links with autophagy and fenestration. Hence, we aim to investigate the role of Cav1-related autophagy in LSECs defenestration. We found the increase of aldosterone/MR (mineralocorticoid receptor) level, oxidation, autophagy, and defenestration in LSECs in the human fibrotic liver, BDL or hyperaldosteronism models; while antagonizing aldosterone or inhibiting autophagy relieved LSECs defenestration in BDL-induced fibrosis or hyperaldosteronism models. In vitro, fenestrae of primary LSECs gradually shrank, along with the down-regulation of the NO-dependent pathway and the augment of the AMPK-dependent autophagy; these effects were aggravated by rapamycin (an autophagy activator) or aldosterone treatment. Additionally, aldosterone increased oxidation mediated by Cav1, reduced ATP generation, and subsequently induced the AMPK-dependent autophagy, leading to the down-regulation of the NO-dependent pathway and LSECs defenestration. These effects were reversed by MR antagonist spironolactone, antioxidants or autophagy inhibitors. Besides, aldosterone enhanced the co-immunoprecipitation of Cav1 with p62 and ubiquitin, and induced Cav1 co-immunofluorescence staining with LC3, ubiquitin, and F-actin in the perinuclear area of LSECs. Furthermore, aldosterone treatment increased the membrane protein level of Cav1, whereas decrease the cytoplasmic protein level of Cav1, indicating that aldosterone induced Cav1-related selective autophagy and F-actin remodeling to promote defenestration. Consequently, Cav1-related selective autophagy initiated by aldosterone-induced oxidation promotes LSECs defenestration via activating the AMPK-ULK1 pathway and inhibiting the NO-dependent pathway. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Jun, Ji Hye; Choi, Jong Ho; Bae, Si Hyun; Oh, Seh Hoon; Kim, Gi Jin
2016-09-01
Chronic liver disease leads to liver fibrosis, and although the liver does have a certain regenerative capacity, this disease is associated with dysfunction of the liver vessels. C-reactive protein (CRP) is produced in the liver and circulated from there for metabolism. CRP was recently shown to inhibit angiogenesis by inducing endothelial cell dysfunction. The objective of this study was to determine the effect of CRP levels on angiogenesis in a rat model of liver dysfunction induced by bile duct ligation (BDL). The diameter of the hepatic vein was analyzed in rat liver tissues using hematoxylin and eosin (H&E) staining. The expression levels of angiogenic factors, albumin, and CRP were analyzed by real-time PCR and Western blotting. A tube formation assay was performed to confirm the effect of CRP on angiogenesis in human umbilical vein endothelial cells (HUVECs) treated with lithocholic acid (LCA) and siRNA-CRP. The diameter of the hepatic portal vein increased significantly with the progression of cirrhosis. The expression levels of angiogenic factors were increased in the cirrhotic liver. In contrast, the expression levels of albumin and CRP were significantly lower in the liver tissue obtained from the BDL rat model than in the normal liver. The CRP level was correlated with the expression of albumin in hepatocytes treated with LCA and siRNA-CRP. Tube formation was significantly decreased in HUVECs when they were treated with LCA or a combination of LCA and siRNA-CRP. CRP seems to be involved in the abnormal formation of vessels in hepatic disease, and so it could be a useful diagnostic marker for hepatic disease.
Mohamed, Hoda E; Elswefy, Sahar E; Rashed, Laila A; Younis, Nahla N; Shaheen, Mohamed A; Ghanim, Amal M H
2016-03-01
Mesenchymal stem cells (MSCs) have attracted lots of attention for the treatment of acute liver failure and end-stage liver diseases. This study aimed at investigating the fundamental mechanism by which bone marrow-derived MSCs (BM-MSCs) induce liver regeneration of fibrotic liver in rats. Rats underwent bile duct ligation (BDL) surgery and four weeks later they were treated with either BM-MSCs (3 × 10(6) cells /rat, once, tail vein injection) or silymarin (100 mg/kg, daily, orally) for four weeks. Liver function tests and hepatic oxidative stress were determined. Hepatic injury and fibrosis were assessed by H and E, Sirus red staining and immunohistochemical expression of α-smooth muscle actin (α-SMA). Hepatocyte growth factor (HGF) and the gene expression of cytokeratin-19 (CK-19) and matrix metalloproteinase-2 (MMP-2) in liver tissue were determined. BDL induced cholestatic liver injury characterized by elevated ALT and AST activities, bilirubin and decreased albumin. The architecture damage was staged as Metavir score: F3, A3. Fibrosis increased around proliferating bile duct as indicated by sirus red staining and α-SMA immunostaining. Fibrogenesis was favored over fibrolysis and confirmed by decreased HGF with increased expression of CK-19, but decreased MMP-2 expression. BM-MSCs treatment restored deteriorated liver functions and restored the histological changes, resolved fibrosis by improving liver regenerative capabilities (P < 0.001), increases in HGF and MMP-2 mRNA and downregulating CK-19 mRNA. Sliymarin, however, induced similar but less prominent effects compared to BM-MSCs. In conclusion, liver regenerative capabilities can be stimulated by BM-MSCs via augmentation of HGF that subsequently up-regulate MMP-2 mRNA while downregulating CK-19 mRNA. © 2016 by the Society for Experimental Biology and Medicine.
Effects of raloxifene on portal hypertension and hepatic encephalopathy in cirrhotic rats.
Chang, Ching-Chih; Lee, Wen-Shin; Chuang, Chiao-Lin; Hsin, I-Fang; Hsu, Shao-Jung; Chang, Ting; Huang, Hui-Chun; Lee, Fa-Yauh; Lee, Shou-Dong
2017-05-05
Raloxifene, a selective estrogen receptor modulator, has been used extensively for osteoporosis. In addition to the effect of osteoporosis treatment, emerging evidences show that raloxifene affects the vascular function in different tissues. Cirrhosis is characterized with portal hypertension and complicated with hepatic encephalopathy. Portal hypertension affects portal-systemic shunt which leads to hepatic encephalopathy that the vascular modulation might influence severity of hepatic encephalopathy. Herein, we evaluated the impact of raloxifene on bile duct ligation (BDL)-induced cirrhotic rats. The female Sprague-Dawley rats received BDL plus ovariectomy or sham-operation. Four weeks later, rats were divided into 2 subgroups respectively to receive of raloxifene (10mg/kg/day) or saline (vehicle) for 14 days. On the 43th day, motor activities and hemodynamic parameters were measured. Hepatic and vascular mRNA and protein expressions were determined. The histopathological change of liver was examined. We found that the liver biochemistry, ammonia level and motor activity were similar between cirrhotic rats with or without raloxifene administration. The hemodynamic parameters were not significantly different except that raloxifene reduced portal venous inflow. Raloxifene exacerbated hepatic fibrosis and up-regulated hepatic endothelin-1 and cyclooxygenase 2 protein expressions. In addition, raloxifene modulated the mRNA expressions of endothelial nitric oxide synthase, cyclooxygenase and endothelin-1 in the superior mesenteric artery and collateral vessel. In conclusion, raloxifene aggravates hepatic fibrosis and decreases portal venous inflow in cirrhotic rats without adversely affecting portal hypertension and hepatic encephalopathy. The modulation of hepatic and vascular endothelin-1, endothelial nitric oxide synthase and cyclooxygenase expressions may play a role in the mechanism. Copyright © 2017 Elsevier B.V. All rights reserved.
Yang, Ya-Ling; Wang, Feng-Sheng; Li, Sung-Chou; Tiao, Mao-Meng; Huang, Ying-Hsien
2017-01-18
MicroRNA-29 (miR-29) is found to modulate hepatic stellate cells' (HSCs) activation and, thereby, reduces liver fibrosis pathogenesis. Histone methyltransferase regulation of epigenetic reactions reportedly participates in hepatic fibrosis. This study is undertaken to investigate the miR-29a regulation of the methyltransferase signaling and epigenetic program in hepatic fibrosis progression. miR-29a transgenic mice (miR-29aTg mice) and wild-type littermates were subjected to bile duct-ligation (BDL) to develop cholestatic liver fibrosis. Primary HSCs were transfected with a miR-29a mimic and antisense inhibitor. Profibrogenic gene expression, histone methyltransferases and global genetic methylation were probed with real-time quantitative RT-PCR, immunohistochemical stain, Western blot and ELISA. Hepatic tissue in miR-29aTg mice displayed weak fibrotic matrix as evidenced by Sirius Red staining concomitant with low fibrotic matrix collagen 1α1 expression within affected tissues compared to the wild-type mice. miR-29a overexpression reduced the BDL exaggeration of methyltransferases, DNMT1, DNMT3b and SET domain containing 1A (SET1A) expression. It also elevated phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signaling within liver tissue. In vitro, miR-29a mimic transfection lowered collagen 1α1, DNMT1, DNMT3b and SET1A expression in HSCs. Gain of miR-29a signaling resulted in DNA hypomethylation and high PTEN expression. This study shines a new light on miR-29a inhibition of methyltransferase, a protective effect to maintain the DNA hypomethylation state that decreases fibrogenic activities in HSC. These robust analyses also highlight the miR-29a regulation of epigenetic actions to ameliorate excessive fibrosis during cholestatic liver fibrosis development.
Small-x Physics: From HERA to LHC and beyond
DOE Office of Scientific and Technical Information (OSTI.GOV)
Leonid Frankfurt; Mark Strikman; Christian Weiss
2005-07-01
We summarize the lessons learned from studies of hard scattering processes in high-energy electron-proton collisions at HERA and antiproton-proton collisions at the Tevatron, with the aim of predicting new strong interaction phenomena observable in next-generation experiments at the Large Hadron Collider (LHC). Processes reviewed include inclusive deep-inelastic scattering (DIS) at small x exclusive and diffractive processes in DIS and hadron-hadron scattering, as well as color transparency and nuclear shadowing effects. A unified treatment of these processes is outlined, based on factorization theorems of quantum chromodynamics, and using the correspondence between the ''parton'' picture in the infinite-momentum frame and the 'dipole''more » picture of high-energy processes in the target rest frame. The crucial role of the three-dimensional quark and gluon structure of the nucleon is emphasized. A new dynamical effect predicted at high energies is the unitarity, or black disk, limit (BDL) in the interaction of small dipoles with hadronic matter, due to the increase of the gluon density at small x. This effect is marginally visible in diffractive DIS at HERA and will lead to the complete disappearance of Bjorken scaling at higher energies. In hadron-hadron scattering at LHC energies and beyond (cosmic ray physics), the BDL will be a standard feature of the dynamics, with implications for (a) hadron production at forward and central rapidities in central proton-proton and proton-nucleus collisions, in particular events with heavy particle production (Higgs), (b) proton-proton elastic scattering, (c) heavy-ion collisions. We also outline the possibilities for studies of diffractive processes and photon-induced reactions (ultraperipheral collisions) at LHC, as well as possible measurements with a future electron-ion collider.« less
Metalinguistic Negation in English and Arabic
ERIC Educational Resources Information Center
Nedwick, Kelly M.
2014-01-01
Negation is a unique and fascinating property of human language which has been given extensive theoretical and typological treatment. One categorization divides negation use into metalinguistic negation and descriptive negation (Horn, 1985). Descriptive negation (DN) is the truth-functional semantic operator which has received the most attention…
ERIC Educational Resources Information Center
LoCoco, Veronica Gonzalez-Mena
Three methods for second language data collection are compared: free composition, picture description and translation. The comparison is based on percentage of errors in a grammatical category and in a source category. Most results obtained from the free compositions and picture descriptions tended to be similar. Greater variation was found for…
Spatial language and converseness.
Burigo, Michele; Coventry, Kenny R; Cangelosi, Angelo; Lynott, Dermot
2016-12-01
Typical spatial language sentences consist of describing the location of an object (the located object) in relation to another object (the reference object) as in "The book is above the vase". While it has been suggested that the properties of the located object (the book) are not translated into language because they are irrelevant when exchanging location information, it has been shown that the orientation of the located object affects the production and comprehension of spatial descriptions. In line with the claim that spatial language apprehension involves inferences about relations that hold between objects it has been suggested that during spatial language apprehension people use the orientation of the located object to evaluate whether the logical property of converseness (e.g., if "the book is above the vase" is true, then also "the vase is below the book" must be true) holds across the objects' spatial relation. In three experiments using sentence acceptability rating tasks we tested this hypothesis and demonstrated that when converseness is violated people's acceptability ratings of a scene's description are reduced indicating that people do take into account geometric properties of the located object and use it to infer logical spatial relations.
[Big data, medical language and biomedical terminology systems].
Schulz, Stefan; López-García, Pablo
2015-08-01
A variety of rich terminology systems, such as thesauri, classifications, nomenclatures and ontologies support information and knowledge processing in health care and biomedical research. Nevertheless, human language, manifested as individually written texts, persists as the primary carrier of information, in the description of disease courses or treatment episodes in electronic medical records, and in the description of biomedical research in scientific publications. In the context of the discussion about big data in biomedicine, we hypothesize that the abstraction of the individuality of natural language utterances into structured and semantically normalized information facilitates the use of statistical data analytics to distil new knowledge out of textual data from biomedical research and clinical routine. Computerized human language technologies are constantly evolving and are increasingly ready to annotate narratives with codes from biomedical terminology. However, this depends heavily on linguistic and terminological resources. The creation and maintenance of such resources is labor-intensive. Nevertheless, it is sensible to assume that big data methods can be used to support this process. Examples include the learning of hierarchical relationships, the grouping of synonymous terms into concepts and the disambiguation of homonyms. Although clear evidence is still lacking, the combination of natural language technologies, semantic resources, and big data analytics is promising.
Teachers' Grading Decision Making: Multiple Influencing Factors and Methods
ERIC Educational Resources Information Center
Cheng, Liying; Sun, Youyi
2015-01-01
This study investigated Chinese secondary school English language teachers' grading decision making, focusing on the factors they considered and types of assessment they used for grading. A questionnaire was issued to 350 secondary school English language teachers in China. Descriptive analyses of the questionnaire data showed that these teachers…
Handbook of Middle American Indians. Volume 5, Linguistics.
ERIC Educational Resources Information Center
Wauchope, Robert, Ed.; McQuown, Norman A., Ed.
This volume presents a summary of work accomplished since the Spanish conquest in the contemporary description and historical reconstruction of the indigenous languages and language families of Mexico and Central America. Contents are (1) "History of Studies in Middle American Linguistics" by N.A. McQuown; (2) "Inventory of…
Computer-Assisted Learning in Language Arts
ERIC Educational Resources Information Center
Serwer, Blanche L.; Stolurow, Lawrence M.
1970-01-01
A description of computer program segments in the feasibility and development phase of Operationally Relevant Activities for Children's Language Experience (Project ORACLE); original form of this paper was prepared by Serwer for presentation to annual meeting of New England Research Association (1st, Boston College, June 5-6, 1969). (Authors/RD)
A Neurobehavioral Model of Flexible Spatial Language Behaviors
ERIC Educational Resources Information Center
Lipinski, John; Schneegans, Sebastian; Sandamirskaya, Yulia; Spencer, John P.; Schoner, Gregor
2012-01-01
We propose a neural dynamic model that specifies how low-level visual processes can be integrated with higher level cognition to achieve flexible spatial language behaviors. This model uses real-word visual input that is linked to relational spatial descriptions through a neural mechanism for reference frame transformations. We demonstrate that…
Reading: Cognitive Input and Output.
ERIC Educational Resources Information Center
Kopp, Harriet Green
Descriptions of language learning and reading behaviors are presented, in this paper, within the context of a model of cognitive processing that reflects a continuum for the logical procession of language skills in human maturation and learning. Portions of the paper differentiate silent and oral reading in terms of cognitive load, which is a…
ERIC Educational Resources Information Center
Bautista, Romiro G.
2015-01-01
This study ascertains that the students' affordance of teleologic explanations and anthropomorphic language in eliciting concepts in Physics is influenced by their age and learning exposure and experience. Using Explicative-Reductive Method of Descriptive Research, this study focused on the determinants of students' affordance of…
Problem-Based Learning: An Experiential Strategy for English Language Teacher Education in Chile
ERIC Educational Resources Information Center
Muñoz Campos, Diego
2017-01-01
The Chilean education system requires English language teachers to be equipped with non-conventional teaching strategies that can foster meaningful learning and assure successful learners' performances in diverse and complex settings. This exploratory, descriptive, research study aimed at discovering the perceptions of 54 pre-service teachers…
Anxiety among Engineering Students in a Graduate EFL Classroom
ERIC Educational Resources Information Center
Samoilova, Valeriia; Thanh, Vo Duy; Wilang, Jeffrey Dawala
2017-01-01
This article reports the descriptive results of foreign language anxiety experiences of engineering students in a top-ranked research university in Thailand. Although numerous studies have been conducted in the past years about English language anxiety, few studies have reported anxiety situations specific to Thai engineering graduate students in…
Socioeconomic Status and Parent-Child Relationships Predict Metacognitive Questions to Preschoolers
ERIC Educational Resources Information Center
Thompson, R. Bruce; Foster, Brandon J.
2014-01-01
The importance of metacognitive language exposure to early educational achievement is widely recognized in the development literature. However, few studies have explored parents' metacognitive language, while accounting for family SES and stress within the parent-child relationship. This is a preliminary descriptive study to explore…
ERIC Educational Resources Information Center
Harris, Bryn; Sullivan, Amanda L.; Oades-Sese, Geraldine V.; Sotelo-Dynega, Marlene
2015-01-01
Past researchers suggested there are a number of shortcomings in the psychoeducational evaluation process and practices used with English language learners (ELLs). In the present exploratory study, the authors descriptively examined the assessment practices used in the special education eligibility determination process for ELLs as documented in…
Cross-Language Communication in Heliodorus' "Aethiopica"
ERIC Educational Resources Information Center
Groves, Robert William, IV
2012-01-01
This dissertation analyzes why Heliodorus pays so much attention to foreign languages in the Aethiopica and how his description of these linguistic phenomena colors the work. It demonstrates that Heliodorus is very careful to attribute linguistic abilities to characters in a sensible way that is in line with real-world expectations. Characters…
Chomsky's 'Ideal' Native Speaker: Sexism in Synchronic Linguistics.
ERIC Educational Resources Information Center
Stanley, Julia Penelope
Drawing on recent research on sexism in English and the ways in which social forces affect language structure, this paper shows how prescriptive statements about English have been incorporated into linguistic grammars as descriptions of language. It is claimed that Chomsky's "universal grammar" is masculinist and that it is contradicted…
Simulation Higher Order Language Requirements Study.
ERIC Educational Resources Information Center
Goodenough, John B.; Braun, Christine L.
The definitions provided for high order language (HOL) requirements for programming flight training simulators are based on the analysis of programs written for a variety of simulators. Examples drawn from these programs are used to justify the need for certain HOL capabilities. A description of the general structure and organization of the…
Development of the Prosodic Features of Infants' Vocalizing.
ERIC Educational Resources Information Center
Lane, Harlan; Sheppard, William
Traditional research methods of recording infant verbal behavior, namely, descriptions by a single observer transcribing the utterances of a single infant in a naturalistic setting, have been inadequate to provide data necessary for modern linguistic analyses. The Center for Research on Language and Language Behavior has undertaken to correct this…
ERIC Educational Resources Information Center
Twaddell, Freeman
A brief analysis and definition of general linguistics focuses on distinct areas of study within the science, including descriptive, historical, comparative, and computational linguistics. Other branches of the science discussed are psycholinguistics, sociolinguistics, and dialectology. Technical concepts encountered in the literature are also…
Communicative Competence of the Fourth Year Students: Basis for Proposed English Language Program
ERIC Educational Resources Information Center
Tuan, Vu Van
2017-01-01
This study on level of communicative competence covering linguistic/grammatical and discourse has aimed at constructing a proposed English language program for 5 key universities in Vietnam. The descriptive method utilized was scientifically employed with comparative techniques and correlational analysis. The researcher treated the surveyed data…
The SKI-HI Program: A Descriptive Update, 1986.
ERIC Educational Resources Information Center
Bruce, Sandy; And Others
This document provides updated information on the SKI-HI program model which presently serves over 2000 young hearing impaired children in 35 states and Canada. The program focuses on training parents in the skills needed to maximize language stimulation and minimize language deprivation. Among 14 educational and philosophical underpinnings of the…
Federal Register 2010, 2011, 2012, 2013, 2014
2011-10-28
... agency, and requirements to enhance descriptive materials distributed to families. This rule finalizes... design. The rule added language reflecting the statutory requirement that any communication with... in student households through the Home Language Survey. FNS will promote providing NSLP application...
Parameter Requirements for Description of Alternative LINC Systems. Final Report.
ERIC Educational Resources Information Center
Center for Applied Linguistics, Washington, DC. Language Information Network and Clearinghouse System.
This study was undertaken for the Center for Applied Linguistics to survey and analyze its information system program for the language sciences. The study identifies and defines the generalized sets of parameters required for subsequent quantitative analysis of proposed alternative Language Information Network and Clearinghouse Systems by means of…
Swedish: The Swedish Language in Education in Finland. Regional Dossiers Series.
ERIC Educational Resources Information Center
Ostern, Anna Lena
This regional dossier aims to provide concise, descriptive information and basic educational statistics about minority language education in a specific country of the European Union--Finland. Details are provided about the features of the educational system, recent educational policies, divisions of responsibilities, main actors, legal…
ERIC Educational Resources Information Center
Sheepway, Lyndal; Lincoln, Michelle; McAllister, Sue
2014-01-01
Background: Speech-language pathology students gain experience and clinical competency through clinical education placements. However, currently little empirical information exists regarding how competency develops. Existing research about the effectiveness of placement types and models in developing competency is generally descriptive and based…
Occitan: The Occitan Language in Education in France. Regional Dossiers Series.
ERIC Educational Resources Information Center
Berthoumieux, Michel; Willemsma, Adalgard
This regional dossier aims to provide concise, descriptive information and basic educational statistics about minority language education in a specific region of the European Union--the South of France. Details are provided about the features of the educational system, recent educational policies, divisions of responsibilities, main actors, legal…
Hupa Natural Resources Dictionary.
ERIC Educational Resources Information Center
Bennett, Ruth, Ed.; And Others
Created by children in grades 5-8 who were enrolled in a year-long Hupa language class, this computer-generated, bilingual book contains descriptions and illustrations of local animals, birds, and fish. The introduction explains that students worked on a Macintosh computer able to print the Unifon alphabet used in writing the Hupa language.…
Topics in Mocho' Phonology and Morphology
ERIC Educational Resources Information Center
Palosaari, Naomi Elizabeth
2011-01-01
This dissertation is a grammatical description of several features of the morphology and phonology of the Mocho' language. Mocho' (Motozintleco) is a moribund Mayan language spoken in the Chiapas region of Mexico near the border of Guatemala. This dissertation, based on data collected during several field trips and supplemented with unpublished…
Teaching Conversations with the XDS Sigma 7. Systems Description.
ERIC Educational Resources Information Center
Bork, Alfred M.; Mosmann, Charles
Some computers permit conventional programing languages to be extended by the use of macro-instructions, a sophisticated programing tool which is especially useful in writing instructional dialogs. Macro-instructions (or "macro's") are complex commands defined in terms of the machine language or other macro-instructions. Like terms in…
Essentials of Asheninka Perene Grammar
ERIC Educational Resources Information Center
Mihas, Elena
2010-01-01
The objective of this dissertation is to present a preliminary grammatical account of Asheninka Perene an endangered Arawak language of Southeastern Peru. The description and analysis of the language is based on the 29-week field research conducted in an area of the Southwest Amazonian high jungle. Interesting issues of Asheninka Perene grammar…
ERIC Educational Resources Information Center
Lovegren, Jesse Stuart James
2013-01-01
This dissertation is an attempt to state what is known at present about the grammar of Mungbam (ISO 693-3 [mij]). Mungbam is a Niger-Congo language spoken in the Northwest Region of Cameroon. The dissertation is a descriptive grammar, covering the phonetics, phonology morphology and syntax of the language. Source data are texts and elicited data…
FGRAAL: FORTRAN extended graph algorithmic language
NASA Technical Reports Server (NTRS)
Basili, V. R.; Mesztenyi, C. K.; Rheinboldt, W. C.
1972-01-01
The FORTRAN version FGRAAL of the graph algorithmic language GRAAL as it has been implemented for the Univac 1108 is described. FBRAAL is an extension of FORTRAN 5 and is intended for describing and implementing graph algorithms of the type primarily arising in applications. The formal description contained in this report represents a supplement to the FORTRAN 5 manual for the Univac 1108 (UP-4060), that is, only the new features of the language are described. Several typical graph algorithms, written in FGRAAL, are included to illustrate various features of the language and to show its applicability.
STAR - A computer language for hybrid AI applications
NASA Technical Reports Server (NTRS)
Borchardt, G. C.
1986-01-01
Constructing Artificial Intelligence application systems which rely on both symbolic and non-symbolic processing places heavy demands on the communication of data between dissimilar languages. This paper describes STAR (Simple Tool for Automated Reasoning), a computer language for the development of AI application systems which supports the transfer of data structures between a symbolic level and a non-symbolic level defined in languages such as FORTRAN, C and PASCAL. The organization of STAR is presented, followed by the description of an application involving STAR in the interpretation of airborne imaging spectrometer data.
Instrument Remote Control Application Framework
NASA Technical Reports Server (NTRS)
Ames, Troy; Hostetter, Carl F.
2006-01-01
The Instrument Remote Control (IRC) architecture is a flexible, platform-independent application framework that is well suited for the control and monitoring of remote devices and sensors. IRC enables significant savings in development costs by utilizing extensible Markup Language (XML) descriptions to configure the framework for a specific application. The Instrument Markup Language (IML) is used to describe the commands used by an instrument, the data streams produced, the rules for formatting commands and parsing the data, and the method of communication. Often no custom code is needed to communicate with a new instrument or device. An IRC instance can advertise and publish a description about a device or subscribe to another device's description on a network. This simple capability of dynamically publishing and subscribing to interfaces enables a very flexible, self-adapting architecture for monitoring and control of complex instruments in diverse environments.
Scalable and Accurate SMT-based Model Checking of Data Flow Systems
2013-10-30
guided by the semantics of the description language . In this project we developed instead a complementary and novel approach based on a somewhat brute...believe that our approach could help considerably in expanding the reach of abstract interpretation techniques to a variety of tar- get languages , as...project. We worked on developing a framework for compositional verification that capitalizes on the fact that data-flow languages , such as Lustre, have
ERIC Educational Resources Information Center
Applegate, Joseph R.
Shilha, which is spoken in southwest Morocco, is one of the most widely distributed of the Berber languages. The dialect described in the work is found in the area extending from Agadir to Ifni and as far east as Taroudant. This study provides a general description of the structure of the language by examing the phonology, morphology, major form…
C3I and Modelling and Simulation (M&S) Interoperability
2004-03-01
customised Open Source products. The technical implementation is based on the use of the eXtendend Markup Language (XML) and Python . XML is developed...to structure, store and send information. The language is focus on the description of data. Python is a portable, interpreted, object-oriented...programming language. A huge variety of usable Open Source Projects were issued by the Python Community. 3.1 Phase 1: Feasibility Studies Phase 1 was
A Framework for Building and Reasoning with Adaptive and Interoperable PMESII Models
2007-11-01
Description Logic SOA Service Oriented Architecture SPARQL Simple Protocol And RDF Query Language SQL Standard Query Language SROM Stability and...another by providing a more expressive ontological structure for one of the models, e.g., semantic networks can be mapped to first- order logical...Pellet is an open-source reasoner that works with OWL-DL. It accepts the SPARQL protocol and RDF query language ( SPARQL ) and provides a Java API to
Improving Method-in-Use through Classroom Observation
ERIC Educational Resources Information Center
Nunn, Roger
2011-01-01
Method-in-use (Nunn, Describing classroom interaction in intercultural curricular research and development, University of Reading, 1996, International Review of Applied Linguistics in Language Teaching 37: 23-42, 1999) is a description of the method actually being enacted through classroom interaction in a particular context. The description is…
Annual Review of Information Science and Technology. Volume Eight.
ERIC Educational Resources Information Center
Cuadra, Carlos A., Ed.; Luke, Ann W., Ed.
Descriptions and appraisals of significant recent trends and developments in the field of information science are presented. The eleven individual chapters deal, respectively, with the following topics: 1) the economics of information, 2) document description and representation, 3) automated language processing, 4) microform technology, 5) library…
Toledo, Cíntia Matsuda; Cunha, Andre; Scarton, Carolina; Aluísio, Sandra
2014-01-01
Discourse production is an important aspect in the evaluation of brain-injured individuals. We believe that studies comparing the performance of brain-injured subjects with that of healthy controls must use groups with compatible education. A pioneering application of machine learning methods using Brazilian Portuguese for clinical purposes is described, highlighting education as an important variable in the Brazilian scenario. Objective The aims were to describe how to: (i) develop machine learning classifiers using features generated by natural language processing tools to distinguish descriptions produced by healthy individuals into classes based on their years of education; and (ii) automatically identify the features that best distinguish the groups. Methods The approach proposed here extracts linguistic features automatically from the written descriptions with the aid of two Natural Language Processing tools: Coh-Metrix-Port and AIC. It also includes nine task-specific features (three new ones, two extracted manually, besides description time; type of scene described – simple or complex; presentation order – which type of picture was described first; and age). In this study, the descriptions by 144 of the subjects studied in Toledo18 were used,which included 200 healthy Brazilians of both genders. Results and Conclusion A Support Vector Machine (SVM) with a radial basis function (RBF) kernel is the most recommended approach for the binary classification of our data, classifying three of the four initial classes. CfsSubsetEval (CFS) is a strong candidate to replace manual feature selection methods. PMID:29213908
The language of violence in mental health: shifting the paradigm to the language of peace.
Alex, Marion; Whitty-Rogers, Joanne; Panagopoulos, Wendy
2013-01-01
Language used in health care, particularly with vulnerable populations such as those with mental illness, is often violent, rising from historical prejudices and politics of power over others. This creates disharmony and distrust between health care providers and patients and families. Peace involves relationships that nurture ongoing harmony, trust, and constructive solutions. In this descriptive philosophical article, we discuss connections between and among the concepts of peace, health, relational ethics, in relation to nurses' responsibilities, current health care realities, and the language of nursing. We propose a shift in discourse within nurse-patient relationships from oppressive and stigmatizing language to the discourse of peace.
Trigeminal Neuralgia and Multiple Sclerosis: A Historical Perspective.
Burkholder, David B; Koehler, Peter J; Boes, Christopher J
2017-09-01
Trigeminal neuralgia (TN) associated with multiple sclerosis (MS) was first described in Lehrbuch der Nervenkrankheiten für Ärzte und Studirende in 1894 by Hermann Oppenheim, including a pathologic description of trigeminal root entry zone demyelination. Early English-language translations in 1900 and 1904 did not so explicitly state this association compared with the German editions. The 1911 English-language translation described a more direct association. Other later descriptions were clinical with few pathologic reports, often referencing Oppenheim but citing the 1905 German or 1911 English editions of Lehrbuch. This discrepancy in part may be due to the translation differences of the original text.
The CADSS design automation system. [computerized design language for small digital systems
NASA Technical Reports Server (NTRS)
Franke, E. A.
1973-01-01
This research was designed to implement and extend a previously defined design automation system for the design of small digital structures. A description is included of the higher level language developed to describe systems as a sequence of register transfer operations. The system simulator which is used to determine if the original description is correct is also discussed. The design automation system produces tables describing the state transistions of the system and the operation of all registers. In addition all Boolean equations specifying system operation are minimized and converted to NAND gate structures. Suggestions for further extensions to the system are also given.
Simulation Experiment Description Markup Language (SED-ML) Level 1 Version 2.
Bergmann, Frank T; Cooper, Jonathan; Le Novère, Nicolas; Nickerson, David; Waltemath, Dagmar
2015-09-04
The number, size and complexity of computational models of biological systems are growing at an ever increasing pace. It is imperative to build on existing studies by reusing and adapting existing models and parts thereof. The description of the structure of models is not sufficient to enable the reproduction of simulation results. One also needs to describe the procedures the models are subjected to, as recommended by the Minimum Information About a Simulation Experiment (MIASE) guidelines. This document presents Level 1 Version 2 of the Simulation Experiment Description Markup Language (SED-ML), a computer-readable format for encoding simulation and analysis experiments to apply to computational models. SED-ML files are encoded in the Extensible Markup Language (XML) and can be used in conjunction with any XML-based model encoding format, such as CellML or SBML. A SED-ML file includes details of which models to use, how to modify them prior to executing a simulation, which simulation and analysis procedures to apply, which results to extract and how to present them. Level 1 Version 2 extends the format by allowing the encoding of repeated and chained procedures.
Simulation Experiment Description Markup Language (SED-ML) Level 1 Version 2.
Bergmann, Frank T; Cooper, Jonathan; Le Novère, Nicolas; Nickerson, David; Waltemath, Dagmar
2015-06-01
The number, size and complexity of computational models of biological systems are growing at an ever increasing pace. It is imperative to build on existing studies by reusing and adapting existing models and parts thereof. The description of the structure of models is not sufficient to enable the reproduction of simulation results. One also needs to describe the procedures the models are subjected to, as recommended by the Minimum Information About a Simulation Experiment (MIASE) guidelines. This document presents Level 1 Version 2 of the Simulation Experiment Description Markup Language (SED-ML), a computer-readable format for encoding simulation and analysis experiments to apply to computational models. SED-ML files are encoded in the Extensible Markup Language (XML) and can be used in conjunction with any XML-based model encoding format, such as CellML or SBML. A SED-ML file includes details of which models to use, how to modify them prior to executing a simulation, which simulation and analysis procedures to apply, which results to extract and how to present them. Level 1 Version 2 extends the format by allowing the encoding of repeated and chained procedures.