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.

Effect of impaired twitching motility and biofilm dispersion on performance of Pseudomonas aeruginosa-powered microbial fuel cells.

PubMed

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.

Minocycline restores cognitive-relative altered proteins in young bile duct-ligated rat prefrontal cortex.

PubMed

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.

Melatonin attenuates oxidative stress, liver damage and hepatocyte apoptosis after bile-duct ligation in rats.

PubMed

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.

The anti-fibrotic effect of liver growth factor is associated with decreased intrahepatic levels of matrix metalloproteinases 2 and 9 and transforming growth factor beta 1 in bile duct-ligated rats.

PubMed

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

PubMed Central

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.

PubMed

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.

Blood-Brain Barrier Permeability Is Exacerbated in Experimental Model of Hepatic Encephalopathy via MMP-9 Activation and Downregulation of Tight Junction Proteins.

PubMed

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.

Quercetin protects liver injury induced by bile duct ligation via attenuation of Rac1 and NADPH oxidase1 expression in rats.

PubMed

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.

Antioxidant Effect of Sepia Ink Extract on Extrahepatic Cholestasis Induced by Bile Duct Ligation in Rats.

PubMed

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.

Assessment of metal contents in spices and herbs from Saudi Arabia.

PubMed

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.

Acute carbon tetrachloride feeding induces damage of large but not small cholangiocytes from BDL rat liver.

PubMed

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.

Grape seed extract reduces oxidative stress and fibrosis in experimental biliary obstruction.

PubMed

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.

PubMed

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

PubMed Central

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

Prominent contribution of portal mesenchymal cells to liver fibrosis in ischemic and obstructive cholestatic injuries.

PubMed

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.

Protective effects of a polymethoxy flavonoids-rich Citrus aurantium peel extract on liver fibrosis induced by bile duct ligation in mice.

PubMed

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.

PubMed

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.

Long-term treatment of bile duct-ligated rats with rapamycin (sirolimus) significantly attenuates liver fibrosis: analysis of the underlying mechanisms.

PubMed

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.

Radioactivity measurements in moss (Hypnum cupressiforme) and lichen (Cladonia rangiformis) samples collected from Marmara region of Turkey.

PubMed

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.

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.

INTRACEREBROVENTRICULAR LOSARTAN INFUSION MODULATES ANGIOTENSIN TYPE 1 RECEPTOR EXPRESSION IN THE SUBFORNICAL ORGAN AND DRINKING BEHAVIOUR IN BILE DUCT LIGATED RATS

PubMed Central

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.

PubMed

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.

A study on OPG/RANK/RANKL axis in osteoporotic bile duct-ligated rats and the involvement of nitrergic and opioidergic systems.

PubMed

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.

PubMed

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.

Sildenafil protects against bile duct ligation induced hepatic fibrosis in rats: Potential role for silent information regulator 1 (SIRT1).

PubMed

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.

ANG II receptor subtype 1a gene knockdown in the subfornical organ prevents increased drinking behavior in bile duct-ligated rats.

PubMed

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.

Diabetes Diminishes the Portal-Systemic Collateral Vascular Response to Vasopressin via Vasopressin Receptor and Gα Proteins Regulations in Cirrhotic Rats

PubMed Central

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

Diabetes diminishes the portal-systemic collateral vascular response to vasopressin via vasopressin receptor and Gα proteins regulations in cirrhotic rats.

PubMed

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.

PubMed

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.

Role of the indoleamine-2,3-dioxygenase/kynurenine pathway of tryptophan metabolism in behavioral alterations in a hepatic encephalopathy rat model.

PubMed

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

PubMed Central

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

A BRCA1 deficient-like signature is enriched in breast cancer brain metastases and predicts DNA damage-induced poly (ADP-ribose) polymerase inhibitor sensitivity.

PubMed

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.

A BRCA1 deficient-like signature is enriched in breast cancer brain metastases and predicts DNA damage-induced poly (ADP-ribose) polymerase inhibitor sensitivity

PubMed Central

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

Breast Reference Set Application: Karen Anderson-ASU (2014) — EDRN Public Portal

Cancer.gov

In order to increase the predictive value of tumor-specific antibodies for use as immunodiagnostics, our EDRN BDL has developed a novel protein microarray technology, termed Nucleic Acid Protein Programmable Array (NAPPA), which circumvents many of the limitations of traditional protein microarrays. NAPPA arrays are generated by printing full-length cDNAs encoding the target proteins at each feature of the array. The proteins are then transcribed and translated by a cell-free system and immobilized in situ using epitope tags fused to the proteins. Sera are added, and bound IgG is detected by standard secondary reagents. Using a sequential screening strategy to select AAb from 4,988 candidate tumor antigens, we have identified 28 potential AAb biomarkers for the early detection of breast cancer, and here we propose to evaluate these biomarkers using the EDRN Breast Cancer Reference Set.

Development of resistance to serotonin-induced itch in bile duct ligated mice.

PubMed

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.

Swertianlarin, an Herbal Agent Derived from Swertia mussotii Franch, Attenuates Liver Injury, Inflammation, and Cholestasis in Common Bile Duct-Ligated Rats

PubMed Central

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.

PubMed

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.

Cholinergic system modulates growth, apoptosis, and secretion of cholangiocytes from bile duct-ligated rats.

PubMed

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.

Characterization of pressure-mediated vascular tone in resistance arteries from bile duct-ligated rats

PubMed Central

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

Cross-activating invariant NKT cells and kupffer cells suppress cholestatic liver injury in a mouse model of biliary obstruction.

PubMed

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.

Cross-Activating Invariant NKT Cells and Kupffer Cells Suppress Cholestatic Liver Injury in a Mouse Model of Biliary Obstruction

PubMed Central

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

Plasma biomarkers of liver injury and inflammation demonstrate a lack of apoptosis during obstructive cholestasis in mice

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

Protective effect of bicyclol against bile duct ligation-induced hepatic fibrosis in rats.

PubMed

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.

Metabolomics changes in a rat model of obstructive jaundice: mapping to metabolism of amino acids, carbohydrates and lipids as well as oxidative stress.

PubMed

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.

Hedgehog-mediated mesenchymal-epithelial interactions modulate hepatic response to bile duct ligation.

PubMed

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.

Mechanisms of TNFalpha-induced cardiac dysfunction in cholestatic bile duct-ligated mice: interaction between TNFalpha and endocannabinoids.

PubMed

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.

Sortilin 1 Loss-of-Function Protects Against Cholestatic Liver Injury by Attenuating Hepatic Bile Acid Accumulation in Bile Duct Ligated Mice.

PubMed

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.

PubMed

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.

Measurement of the branching fractions of B-->D**(l) nu(l) decays in events tagged by a fully reconstructed B meson.

PubMed

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.

Inhalation Dose and Source Term Studies in a Tribal Area of Wayanad, Kerala, India

PubMed Central

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

Role of dopaminergic and serotonergic neurotransmitters in behavioral alterations observed in rodent model of hepatic encephalopathy.

PubMed

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.

Liver fibrosis in bile duct-ligated rats correlates with increased hepatic IL-17 and TGF-β2 expression.

PubMed

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

PubMed Central

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

Droxidopa, an oral norepinephrine precursor, improves hemodynamic and renal alterations of portal hypertensive rats.

PubMed

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.

Modulation of transport and metabolism of bile acids and bilirubin by chlorogenic acid against hepatotoxicity and cholestasis in bile duct ligation rats: involvement of SIRT1-mediated deacetylation of FXR and PGC-1α.

PubMed

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.

Increased brain lactate is central to the development of brain edema in rats with chronic liver disease.

PubMed

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.

Coffee consumption prevents fibrosis in a rat model that mimics secondary biliary cirrhosis in humans.

PubMed

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.

Low-dose oral rapamycin treatment reduces fibrogenesis, improves liver function, and prolongs survival in rats with established liver cirrhosis.

PubMed

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.

PubMed

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.

Ammonia produces pathological changes in human hepatic stellate cells and is a target for therapy of portal hypertension.

PubMed

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.

Automated evaluation of liver fibrosis in thioacetamide, carbon tetrachloride, and bile duct ligation rodent models using second-harmonic generation/two-photon excited fluorescence microscopy.

PubMed

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.

Simultaneous determination of theobromine, (+)-catechin, caffeine, and (-)-epicatechin in standard reference material baking chocolate 2384, cocoa, cocoa beans, and cocoa butter.

PubMed

Risner, Charles H

2008-01-01

A reverse-phase liquid chromatography analysis is used to access the quantity of theobromine, (+)-catechin, caffeine, and (-)-epicatechin in Standard Reference Material 2384 Baking Chocolate, cocoa, cocoa beans, and cocoa butter using water or a portion of the mobile phase as the extract. The procedure requires minimal sample preparation. Theobromine, (+)-catechin, caffeine, and (-)-epicatechin are detected by UV absorption at 273 nm after separation using a 0.3% acetic acid-methanol gradient (volume fractions) and quantified using external standards. The limit of detection for theobromine, (+)-catechin, caffeine, and (-)-epicatechin averages 0.08, 0.06, 0.06, and 0.06 microg/mL, respectively. The method when applied to Standard Reference Material 2384 Baking Chocolate; baking chocolate reference material yields results that compare to two different, separate procedures. Theobromine ranges from 26000 mg/kg in cocoa to 140 mg/kg in cocoa butter; (+)-catechin from 1800 mg/kg in cocoa to below detection limits of < 32 mg/kg in cocoa butter; caffeine from 2400 mg/kg in cocoa to 400 mg/kg in cocoa butter, and (-)-epicatechin from 3200 mg/kg in cocoa to BDL, < 27 mg/kg, in cocoa butter. The mean recoveries from cocoa are 102.4 +/- 0.6% for theobromine, 100.0 +/- 0.6 for (+)-catechin, 96.2 +/- 2.1 for caffeine, and 106.2 +/- 1.7 for (-)-epicatechin.

incurvata13, a Novel Allele of AUXIN RESISTANT6, Reveals a Specific Role for Auxin and the SCF Complex in Arabidopsis Embryogenesis, Vascular Specification, and Leaf Flatness1[W][OA

PubMed Central

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

Effects of asymmetric dimethylarginine on renal arteries in portal hypertension and cirrhosis

PubMed Central

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.

PubMed

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.

MicroRNA-29a mitigation of endoplasmic reticulum and autophagy aberrance counteracts in obstructive jaundice-induced fibrosis in mice.

PubMed

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.

Collapsed Reticular Network and its Possible Mechanism during the Initiation and/or Progression of Hepatic Fibrosis

PubMed Central

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

POPCORN functions in the auxin pathway to regulate embryonic body plan and meristem organization in Arabidopsis.

PubMed

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.

POPCORN Functions in the Auxin Pathway to Regulate Embryonic Body Plan and Meristem Organization in Arabidopsis[W][OA

PubMed Central

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

Increased Renal Clearance of Rocuronium Compensates for Chronic Loss of Bile Excretion, via upregulation of Oatp2.

PubMed

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.

The pathophysiology of human obstructive cholestasis is mimicked in cholestatic Gold Syrian hamsters.

PubMed

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.

Substance P increases liver fibrosis by differential changes in senescence of cholangiocytes and hepatic stellate cells.

PubMed

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.

PubMed

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.

Intestinal decontamination inhibits TLR4 dependent fibronectin mediated crosstalk between stellate cells and endothelial cells in liver fibrosis in mice

PubMed Central

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

Liver Cell-Derived Microparticles Activate Hedgehog Signaling and Alter Gene Expression in Hepatic Endothelial Cells

PubMed Central

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

Liver cell-derived microparticles activate hedgehog signaling and alter gene expression in hepatic endothelial cells.

PubMed

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.

PubMed

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.

The natural radioactivity measurements in coastal sediment samples along the East Coast of Tamilnadu using gamma spectrometry technique

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

Extrahepatic angiogenesis hinders recovery of portal hypertension and collaterals in rats with cirrhosis resolution.

PubMed

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.

Pleiotrophin regulates the ductular reaction by controlling the migration of cells in liver progenitor niches.

PubMed

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/

Nuclear factor-E2-related factor 2 is a major determinant of bile acid homeostasis in the liver and intestine

PubMed Central

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

The role of S1PR2 in bile acid-induced cholangiocyte proliferation and cholestasis-induced liver injury in mice

PubMed Central

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

α7-nAChR Knockout Mice Decreases Biliary Hyperplasia and Liver Fibrosis in Cholestatic Bile-Duct Ligated Mice.

PubMed

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

PubMed Central

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

The effects of proton pump inhibitor on hepatic vascular responsiveness and hemodynamics in cirrhotic rats.

PubMed

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.

Treatment with milk thistle extract (Silybum marianum), ursodeoxycholic acid, or their combination attenuates cholestatic liver injury in rats: Role of the hepatic stem cells.

PubMed

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.

Installation Restoration Program. Phase 2. Confirmation/Quantification, Stage 2 for Seymour Johnson Air Force Base, North Carolina. Volume 4

DTIC Science & Technology

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

Delivering biodefense continuing education to military medical providers by allowing a biodefense educational curriculum to unfold in practice.

PubMed

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.

Zinc supplementation suppresses the progression of bile duct ligation-induced liver fibrosis in mice.

PubMed

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.

Diversity-oriented combinatorial biosynthesis of benzenediol lactone scaffolds by subunit shuffling of fungal polyketide synthases.

PubMed

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.

Evaluation of laser photobiomodulation on healing of bone defects grafted with bovine bone in diabetic rats

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.

Oral administration of oleanolic acid, isolated from Swertia mussotii Franch, attenuates liver injury, inflammation, and cholestasis in bile duct-ligated rats

PubMed Central

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

Impacts of climate-induced changes on the distribution of pesticides residues in water and sediment of Lake Naivasha, Kenya.

PubMed

Otieno, Peter O; Owuor, P Okinda; Lalah, Joseph O; Pfister, Gerd; Schramm, Karl-Werner

2013-03-01

This study reports evidence of increased chlorpyrifos contamination in sediment and water in Lake Naivasha following its intensive application in the horticultural farms in the catchment area. Analytical results show that levels of chlorpyrifos residues were influenced by climate-induced rainfall pattern with higher levels reported during period of heavy precipitation with significant decrease during low rainfall. On average, the levels ranged between 14.8 and 32.8 ng g(-1) in sediment during rainy season compared to a range of 8.5-16.6 ng g(-1) in the dry season. Additionally, the mean concentration of chlorpyrifos in water ranged between 8.61 and 22.4 μg L(-1) during rainy season and below detection limit (bdl) -13.6 μg L(-1) in dry season as quantified by enzyme-linked immunosorbent assay. Meanwhile, independent t test analysis indicated that there was significant difference in concentration at p ≤ 0.05 between the seasons with respect to sediment and water samples. This demonstrated that climate-induced variations had considerable influence on contamination. While diazinon and carbofuran were equally applied intensively, their levels were below the detection limit in the all the samples analyzed. ELISA results were validated by the capillary-HPLC photodiode-array detector instrument analysis, and statistical comparison showed no significant difference between them. It was evident that chlorpyrifos residues determination in water and sediment by ELISA can be a useful strategy in environmental management and monitoring program, and a complimentary analytical tool to high performance liquid chromatography. Levels of chlorpyrifos detected in sediment and water were found to exceed recommended criteria for protection of aquatic life and preservation of water quality and may be hazardous if not regularly monitored.

Ultrastructural Characteristics of Rat Hepatic Oval Cells and Their Intercellular Contacts in the Model of Biliary Fibrosis: New Insights into Experimental Liver Fibrogenesis

PubMed Central

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.

PubMed

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.

The linear accumulation of atmospheric mercury by vegetable and grass leaves: Potential biomonitors for atmospheric mercury pollution.

PubMed

Niu, Zhenchuan; Zhang, Xiaoshan; Wang, Sen; Ci, Zhijia; Kong, Xiangrui; Wang, Zhangwei

2013-09-01

One question in the use of plants as biomonitors for atmospheric mercury (Hg) is to confirm the linear relationships of Hg concentrations between air and leaves. To explore the origin of Hg in the vegetable and grass leaves, open top chambers (OTCs) experiment was conducted to study the relationships of Hg concentrations between air and leaves of lettuce (Lactuca sativa L.), radish (Raphanus sativus L.), alfalfa (Medicago sativa L.) and ryegrass (Lolium perenne L.). The influence of Hg in soil on Hg accumulation in leaves was studied simultaneously by soil Hg-enriched experiment. Hg concentrations in grass and vegetable leaves and roots were measured in both experiments. Results from OTCs experiment showed that Hg concentrations in leaves of the four species were significantly positively correlated with those in air during the growth time (p < 0.05), while results from soil Hg-enriched experiment indicated that soil-borne Hg had significant influence on Hg accumulation in the roots of each plant (p < 0.05), and some influence on vegetable leaves (p < 0.05), but no significant influence on Hg accumulation in grass leaves (p > 0.05). Thus, Hg in grass leaves is mainly originated from the atmosphere, and grass leaves are more suitable as potential biomonitors for atmospheric Hg pollution. The effect detection limits (EDLs) for the leaves of alfalfa and ryegrass were 15.1 and 22.2 ng g(-1), respectively, and the biological detection limit (BDL) for alfalfa and ryegrass was 3.4 ng m(-3).

Occurrence of antibiotics in water, sediments, aquatic plants, and animals from Baiyangdian Lake in North China.

PubMed

Li, Wenhui; Shi, Yali; Gao, Lihong; Liu, Jiemin; Cai, Yaqi

2012-11-01

This study investigated the presence and distribution of 22 antibiotics, including eight quinolones, nine sulfonamides and five macrolides, in the water, sediments, and biota samples from Baiyangdian Lake, China. A total of 132 samples were collected in 2008 and 2010, and laboratory analyses revealed that antibiotics were widely distributed in the lake. Sulfonamides were the dominant antibiotics in the water (0.86-1563 ng L(-1)), while quinolones were prominent in sediments (65.5-1166 μg kg(-1)) and aquatic plants (8.37-6532 μg kg(-1)). Quinolones (17.8-167 μg kg(-1)) and macrolides [from below detection limit (BDL) to 182 μg kg(-1)] were often found in aquatic animals and birds. Salvinia natans exhibited the highest bioaccumulation capability for quinolones among three species of aquatic plants. Geographical differences of antibiotic concentrations were greatly due to anthropogenic activities. Sewage discharged from Baoding City was likely the main source of antibiotics in the lake. Risk assessment of antibiotics on aquatic organisms suggested that algae and aquatic plants might be at risk in surface water, while animals were likely not at risk. Copyright © 2012 Elsevier Ltd. All rights reserved.

Polarization-resolved second-harmonic generation imaging for liver fibrosis assessment without labeling

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.

Insights into the Biosynthesis of 12-Membered Resorcylic Acid Lactones from Heterologous Production in Saccharomyces cerevisiae

PubMed Central

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

Dioscin alleviates BDL- and DMN-induced hepatic fibrosis via Sirt1/Nrf2-mediated inhibition of p38 MAPK pathway

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

PubMed Central

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

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.

PubMed

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.

Silymarin-loaded Eudragit(®) RS100 nanoparticles improved the ability of silymarin to resolve hepatic fibrosis in bile duct ligated rats.

PubMed

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.

Evaluation of the 13C-octanoate breath test as a surrogate marker of liver damage in animal models.

PubMed

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.

[Notch signaling pathway participates in the differentiation of hepatic progenitor cells into bile duct epithelial cells and progression of hepatic fibrosis in cholestatic liver fibrosis rat].

PubMed

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.

Carnosic Acid Alleviates BDL-Induced Liver Fibrosis through miR-29b-3p-Mediated Inhibition of the High-Mobility Group Box 1/Toll-Like Receptor 4 Signaling Pathway in Rats

PubMed Central

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

Pleiotrophin regulates the ductular reaction by controlling the migration of cells in liver progenitor niches

PubMed Central

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

Contrasting Responses of Kupffer Cells and Inflammatory Mononuclear Phagocytes to Biliary Obstruction in a Mouse Model of Cholestatic Liver Injury

PubMed Central

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

Micronutrients (B, Co, Cu, Fe, Mn, Mo, and Zn) content in made tea (Camellia sinensis L.) and tea infusion with health prospect: A critical review.

PubMed

Karak, Tanmoy; Kutu, Funso Raphael; Nath, Jyoti Rani; Sonar, Indira; Paul, Ranjit Kumar; Boruah, Romesh Kumar; Sanyal, Sandip; Sabhapondit, Santanu; Dutta, Amrit Kumar

2017-09-22

Tea (Camellia sinensis L.) is a perennial acidophilic crop, and known to be a nonalcoholic stimulating beverage that is most widely consumed after water. The aim of this review paper is to provide a detailed documentation of selected micronutrient contents, viz. boron (B), cobalt (Co), copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo), and zinc (Zn) in made tea and tea infusion. Available data from the literature were used to calculate human health aspect associated with the consumption of tea infusion. A wide range of micronutrients reported in both made tea and tea infusion could be the major sources of micronutrients for human. The content of B, Co, Cu, Fe, Mn, Mo, and Zn in made tea are ranged from 3.04 to 58.44 μg g -1 , below detectable limit (BDL) to 122.4 μg g -1 , BDL to 602 μg g -1 , 0.275 to 13,040 μg g -1 , 0.004 to 15,866 μg g -1 , 0.04 to 570.80 μg g -1 and 0.01 to 1120 μg g -1 , respectively. Only 3.2 μg L -1 to 7.25 mg L -1 , 0.01 μg L -1 to 7 mg L -1 , 3.80 μg L -1 to 6.13 mg L -1 , 135.59 μg L -1 -11.05 mg L -1 , 0.05 μg L -1 to 1980.34 mg L -1 , 0.012 to 3.78 μg L -1 , and 1.12 μg L -1 to 2.32 μg L -1 of B, Co, Cu, Fe, Mn, Mo, and Zn, respectively, are found in tea infusion which are lower than the prescribed limit of micronutrients in drinking water by World Health Organization. Furthermore, micronutrient contents in tea infusion depend on infusion procedure as well as on the instrument used for analysis. The proportion of micronutrients found in different tea types are 1.0-88.9% for B, 10-60% for Co, 2.0-97.8% for Cu, 67.8-89.9% for Fe, 71.0-87.4% for Mn, 13.3-34% for Mo, and 34.9-83% for Zn. From the results, it can also be concluded that consumption of three cups of tea infusion per day does not have any adverse effect on human health with respect to the referred micronutrients rather got beneficial effects to human.

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.

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

Incidences of mortality of Indian peafowl Pavo cristatus due to pesticide poisoning in India and accumulation pattern of chlorinated pesticides in tissues of the same species collected from Ahmedabad and Coimbatore.

PubMed

Nambirajan, Kanthan; Muralidharan, Subramanian; Manonmani, Subbian; Kirubhanandhini, Venkatachalam; Ganesan, Kitusamy

2018-06-01

Incidences of mortality of Indian peafowl Pavo cristatus, the national bird (Schedule I Indian Wild Life Protection Act 1972), are rampant in India. Between January 2011 and March 2017, around 550 peafowl in 35 incidences were reported dead across the country. Due to the non-availability of fresh carcases, poisoning could not be confirmed. Birds which died due to kite string injuries in Ahmedabad (15) and accidents in Coimbatore (5) were tested for residues of chlorinated pesticides, namely hexachlorocyclohexane (HCH), dichloro-diphenyl-trichloroethane (DDT), endosulfan, heptachlor, dicofol, dieldrin and cholipyrifos. The liver, kidney and muscle were the tissues considered to document pesticide load. Total load ranged from BDL to 388.2 ng/g. DDT (95%) and HCH (80%) were detected more frequently. DDT (40%) and endosulfan (26%) contributed maximum to the total pesticide load followed by HCH (21%). Pesticide accumulation pattern among the organs was in the order of liver (123.9 ng/g) > kidney (91.9 ng/g) > muscle (19.5 ng/g) with significant difference (p < 0.05). Peafowl from Ahmedabad had significantly (p < 0.05) higher level of total pesticide (149.0 ng/g) than birds from Coimbatore (47.8 ng/g). Although varying levels of chlorinated pesticide were detected, they were below reported toxic limits. Nevertheless, persistence of chlorinated pesticides and poisoning due to modern pesticides across the entire distribution range of Peafowl in India is a cause for concern.

Residues of acephate and its metabolite methamidophos in/on mango fruit (Mangifera indica L.).

PubMed

Mohapatra, Soudamini; Ahuja, A K; Deepa, M; Sharma, Debi

2011-01-01

Mango, the major fruit crop of India is affected by stone weevil, which can cause serious damage to the fruits. Acephate gives good control of mango stone weevil. Residues of acephate and its major metabolite, methamidophos were evaluated on mango fruits following repeated spray applications at the recommended dose (0.75 kg a.i. ha⁻¹) and double the recommended dose (1.5 kg a.i. ha⁻¹). Acephate residues mostly remained on the fruit peel which persisted up to 30 days. Movement of residues to the fruit pulp was detected after 1 day of application, increased to maximum of 0.14 and 0.26 mg kg⁻¹ after 3 days and reached to below detectable level (BDL) after 20 days. Methamidophos, a metabolite of acephate, was detected from 3rd day onwards in both peel and pulp and persisted up to 15 days. The residues (acephate + methamidophos) dissipated with the half-life of 5 days in peel and pulp. A safe pre-harvest interval of 30 days is recommended for consumption of mango fruits following treatment of acephate at the recommended dose of 0.75 kg a.i. ha⁻¹.

Glechoma hederacea extracts attenuate cholestatic liver injury in a bile duct-ligated rat model.

PubMed

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.

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...

Inhibitory effect of dietary capsaicin on liver fibrosis in mice.

PubMed

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.

Biochemical and morphological changes in the liver after hepatic artery ligation in the presence or absence of extrahepatic cholestasis.

PubMed Central

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

[Distributions and seasonal variations of total dissolved inorganic arsenic in the estuaries and coastal area of eastern Hainan].

PubMed

Cao, Xiu-Hong; Ren, Jing-Ling; Zhang, Gui-Ling; Zhang, Jin-E; Du, Jin-Zhou; Zhu, De-Di

2012-03-01

The concentrations of total dissolved inorganic arsenic (TDIAs) were measured by Hydride Generation-Atomic Fluorescence Spectrometry (HG-AFS). Two cruises were carried out in the river, estuary, coastal area and groundwater of eastern Hainan in December 2006 and August 2007. The concentrations of TDIAs in the Wanquan and Wenchang/Wenjiao rivers and their estuaries, coastal area in December 2006 were 4.0-9.4, 1.3-13.3, 13.3-17.3 nmol x L(-1), respectively. The concentrations of TDIAs in the Wanquan and Wenchang/Wenjiao rivers and their estuaries, coastal area in August 2007 were 1.6-15.5, 2.4-15.9, 10.8-17.6 nmol x L(-1), respectively. There was no significantly seasonal variation of TDIAs in the rivers and estuaries during the dry and wet seasons. Compared with other areas in the world, the concentration of TDIAs in the Eastern Hainan remained at pristine levels. TDIAs showed conservatively mixing in the both estuaries. The concentration of TDIAs of groundwater was below detection limit (BDL)-41.7 nmol x L(-1). The submarine groundwater discharge (SGD) to the coastal area was estimated in the drainage basin of Wenchang/Wenjiao river based on the average concentration of TDIAs in the groundwater and SGD water discharge, with the value of 1 153 mol x a(-1). Budget estimation indicated that the SGD discharge is one of the important sources of arsenic in the coastal area.

77 FR 74458 - Enterysys Corporation, with Last Known Addresses of: 1307 Muench Court, San Jose, CA 95131 and...

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...

Promising toxicological biomarkers for the diagnosis of liver injury types: Bile acid metabolic profiles and oxidative stress marker as screening tools in drug development.

PubMed

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.

PubMed

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.

Hazardous waste characterization among various thermal processes in South Korea: a comparative analysis.

PubMed

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.

Pharmacokinetic analysis of modified-release metoprolol formulations: An interspecies comparison.

PubMed

De Thaye, Elien; Vervaeck, Anouk; Marostica, Eleonora; Remon, Jean Paul; Van Bocxlaer, Jan; Vervaet, Chris; Vermeulen, An

2017-01-15

In the current study, we investigated the metoprolol absorption kinetics of an in-house produced oral sustained-release formulation, matrices manufactured via prilling, and two commercially available formulations, ZOK-ZID ® (reservoir) and Slow-Lopresor ® (matrix) in both New Zealand White rabbits and Beagle dogs, using a population pharmacokinetic analysis approach. The aim of this study was to compare the in vivo pharmacokinetic (PK) profiles of different formulations based on metoprolol, a selective adrenergic β 1 -receptor antagonist, in dogs and rabbits and to contrast the observed differences. To that end, metoprolol (50 to 200mg) was administered to 6 Beagle dogs and 6 New Zealand White rabbits as a single intravenous (IV) bolus injection and to 8 dogs and 6 rabbits as an oral modified release formulation. To derive pharmacokinetic parameters from the data, a non-linear mixed-effects model was developed using NONMEM ® where the contribution of observations below the limit of detection (BDL, below detection limit) to the parameter estimates was taken into account in the parameter estimation procedure. In both species and for the three modified release formulations, different absorption models were tested to describe the PK of metoprolol following oral dosing. In Beagle dogs, plasma concentration-time profiles were best described using a sequential zero- and first-order absorption model. In rabbits though, the absorption phase was best described using a first-order process only. In both species, the reservoir formulation ZOK-ZID ® was behaving quite similarly. In contrast, the absorption properties of both matrix formulations were rather different between species. This study indicates that the PK of the reservoir formulation is similar in both species, even after accounting for the almost completely missed absorption phase in rabbits. The insights gained further illustrate that rabbits are not very well suited to study the PK of the current matrix formulations in view of their less optimal prolonged release characteristics and the resulting fast decline in metoprolol plasma levels. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of an analytical method for analysis of flubendiamide, des-iodo flubendiamide and study of their residue persistence in tomato and soil.

PubMed

Mohapatra, S; Ahuja, A K; Deepa, M; Jagadish, G K; Rashmi, N; Sharma, D

2011-01-01

Flubendiamide is a new insecticide that has been found to give excellent control of lepidopterous pests of tomato. This study has been undertaken to develop an improved method for analysis of flubendiamide and its metabolite des-iodo flubendiamide and determine residue retention in tomato and soil. The analytical method developed involved extraction of flubendiamide and its metabolite des-iodo flubendiamide with acetonitrile, liquid-liquid partitioning into hexane-ethyl acetate mixture (6:4, v v⁻¹) and cleanup with activated neutral alumina. Finally the residues were dissolved in gradient high pressure liquid chromatography (HPLC) grade acetonitrile for analysis by HPLC. The mobile phase, acetonitrile-water at 60:40 (v v⁻¹) proportion and the wavelength of 235 nm gave maximum peak resolution. Using the above method and HPLC parameters described, nearly 100 % recovery of both insecticides were obtained. There was no matrix interference and the limit of quantification (LOQ) of the method was 0.01 mg kg⁻¹. Initial residue deposits of flubendiamide on field-treated tomato from treatments @ 48 and 96 g active ingredient hectare⁻¹ were 0.83 and 1.68 mg kg⁻¹, respectively. The residues of flubendiamide dissipated at the half-life of 3.9 and 4.4 days from treatments @ 48 and 96 g a.i. ha⁻¹, respectively and persisted for 15 days from both the treatments. Des-iodo flubendiamide was not detected in tomato fruits at any time during the study period. Residues of flubendiamide and des-iodo flubendiamide in soil from treatment @ 48 and 96 g a.i. ha⁻¹ were below detectable level (BDL, < 0.01 mg kg⁻¹) after 20 days. Flubendiamide completely dissipated from tomato within 20 days when the 480 SC formulation was applied at doses recommended for protection against lepidopterous pests.

Estimation of annual effective dose due to natural radioactive elements in ingestion of foodstuffs in tin mining area of Jos-Plateau, Nigeria.

PubMed

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.

PubMed

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.

Authenticating Secure Tokens Using Slow Memory Access

DTIC Science & Technology

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

Natural radionuclide dose and lifetime cancer risk due to ingestion of fish and water from fresh water reservoirs near the proposed uranium mining site.

PubMed

Annamalai, Sathesh Kumar; Arunachalam, Kantha Deivi; Selvaraj, Rajaram

2017-06-01

Ten sampling locations in Nagarjuna Sagar Dam have been selected to assess the suitability of the reservoir water for human consumption. The sediment, water, and fish samples were collected and analyzed for radionuclide ( 238 U, 232 Th, 210 Po, 226 Ra, 210 Pb) and physicochemical parameters like pH, TOC, total hardness, alkalinity, DO, cation exchange capacity, and particle size. The spatial variations among the radionuclides ( 238 U, 232 Th, 210 Po, 226 Ra, 210 Pb) in water and bottom sediments of Nagarjuna Sagar Dam were determined. The uranium concentration in the sediment and water was in BDL (<0.5 ppb). The maximum permissible limits in water samples of the analyzed radionuclides are 238 U-10 Bq/l, 210 Po-0.1 Bq/l, 226 Ra-1 Bq/l, and 210 Pb-0.1 Bq/l. The radionuclides in our water samples were approximately 50 times far below the recommended limit. The ingestion of water and fish would not pose any significant radiological impact on health or cancer risk to the public, implicating that the fishes from Nagarjuna Sagar Dam reservoir are safe for human consumption except the fisherman community.

Bile acid receptor TGR5 overexpression is associated with decreased intestinal mucosal injury and epithelial cell proliferation in obstructive jaundice.

PubMed

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.

Decabrominated Diphenyl Ethers (BDE-209) in Chinese and Global Air: Levels, Gas/Particle Partitioning, and Long-Range Transport: Is Long-Range Transport of BDE-209 Really Governed by the Movement of Particles?

PubMed

Li, Yi-Fan; Qiao, Li-Na; Ren, Nan-Qi; Sverko, Ed; Mackay, Donald; Macdonald, Robie W

2017-01-17

In this paper, we report air concentrations of BDE-209 in both gas- and particle-phases across China. The annual mean concentrations of BDE-209 were from below detection limit (BDL) to 77.0 pg·m -3 in the gas-phase and 1.06-728 pg·m -3 in the particle-phase. Among the nine PBDEs measured, BDE-209 is the dominant congener in Chinese atmosphere in both gas and particle phases. We predicted the partitioning behavior of BDE-209 in air using our newly developed steady state equation, and the results matched the monitoring data worldwide very well. It was found that the logarithm of the partition quotient of BDE-209 is a constant, and equal to -1.53 under the global ambient temperature range (from -50 to +50 °C). The gaseous fractions of BDE-209 in air depends on the concentration of total suspended particle (TSP). The most important conclusion derived from this study is that, BDE-209, like other semivolatile organic compounds (SVOCs), cannot be sorbed entirely to atmospheric particles; and there is a significant amount of gaseous BDE-209 in global atmosphere, which is subject to long-range atmospheric transport (LRAT). Therefore, it is not surprising that BDE-209 can enter the Arctic through LRAT mainly by air transport rather than by particle movement. This is a significant advancement in understanding the global transport process and the pathways entering the Arctic for chemicals with low volatility and high octanol-air partition coefficients, such as BDE-209.

Going to where the users are! Making the collaborative resource management and science workspace mobile

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

Janus-kinase-2 relates directly to portal hypertension and to complications in rodent and human cirrhosis.

PubMed

Klein, Sabine; Rick, Johanna; Lehmann, Jennifer; Schierwagen, Robert; Schierwagen, Irela Gretchen; Verbeke, Len; Hittatiya, Kanishka; Uschner, Frank Erhard; Manekeller, Steffen; Strassburg, Christian P; Wagner, Kay-Uwe; Sayeski, Peter P; Wolf, Dominik; Laleman, Wim; Sauerbruch, Tilman; Trebicka, Jonel

2017-01-01

Angiotensin II (AngII) activates via angiotensin-II-type-I receptor (AT1R) Janus-kinase-2 (JAK2)/Arhgef1 pathway and subsequently RHOA/Rho-kinase (ROCK), which induces experimental and probably human liver fibrosis. This study investigated the relationship of JAK2 to experimental and human portal hypertension. The mRNA and protein levels of JAK2/ARHGEF1 signalling components were analysed in 49 human liver samples and correlated with clinical parameters of portal hypertension in these patients. Correspondingly, liver fibrosis (bile duct ligation (BDL), carbon tetrachloride (CCl 4 )) was induced in floxed-Jak2 knock-out mice with SM22-promotor (SM22 Cre+ -Jak2 f/f ). Transcription and contraction of primary myofibroblasts from healthy and fibrotic mice and rats were analysed. In two different cirrhosis models (BDL, CCl 4 ) in rats, the acute haemodynamic effect of the JAK2 inhibitor AG490 was assessed using microsphere technique and isolated liver perfusion experiments. Hepatic transcription of JAK2/ARHGEF1 pathway components was upregulated in liver cirrhosis dependent on aetiology, severity and complications of human liver cirrhosis (Model for End-stage Liver disease (MELD) score, Child score as well as ascites, high-risk varices, spontaneous bacterial peritonitis). SM22 Cre+ - Jak2 f/f mice lacking Jak2 developed less fibrosis and lower portal pressure (PP) than SM22 Cre- -Jak2 f/f upon fibrosis induction. Myofibroblasts from SM22 Cre+ -Jak2 f/f mice expressed less collagen and profibrotic markers upon activation. AG490 relaxed activated hepatic stellate cells in vitro. In cirrhotic rats, AG490 decreased hepatic vascular resistance and consequently the PP in vivo and in situ. Hepatic JAK2/ARHGEF1/ROCK expression is associated with portal hypertension and decompensation in human cirrhosis. The deletion of Jak2 in myofibroblasts attenuated experimental fibrosis and acute inhibition of JAK2 decreased PP. Thus, JAK2 inhibitors, already in clinical use for other indications, might be a new approach to treat cirrhosis with portal hypertension. 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/.

Late Holocene climate change in the western Mediterranean: centennial-scale vegetation and North Atlantic Oscillation variability

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.

Ammonia mediates cortical hemichannel dysfunction in rodent models of chronic liver disease

PubMed Central

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

A Comparison of the Optimization and Analysis of Doubly Curved Shells Using MSC/NASTRAN and ASTROS

DTIC Science & Technology

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

1H and 31P magnetic resonance spectroscopy in a rat model of chronic hepatic encephalopathy: in vivo longitudinal measurements of brain energy metabolism.

PubMed

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.

Bone marrow-derived mesenchymal stem cells effectively regenerate fibrotic liver in bile duct ligation rat model

PubMed Central

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

Caveolin 1-related autophagy initiated by aldosterone-induced oxidation promotes liver sinusoidal endothelial cells defenestration.

PubMed

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.

Decreased C-reactive protein induces abnormal vascular structure in a rat model of liver dysfunction induced by bile duct ligation.

PubMed

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.

Bone marrow-derived mesenchymal stem cells effectively regenerate fibrotic liver in bile duct ligation rat model.

PubMed

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.

PubMed

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.

MicroRNA-29a Alleviates Bile Duct Ligation Exacerbation of Hepatic Fibrosis in Mice through Epigenetic Control of Methyltransferases.

PubMed

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.

CAL--ERDA program manual. [Building Design Language; LOADS, SYSTEMS, PLANT, ECONOMICS, REPORT, EXECUTIVE, CAL-ERDA

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

Microbial biofilms control economic metal mobility in an acid-sulfate hydrothermal system

NASA Astrophysics Data System (ADS)

Phillips-Lander, C. M.; Roberts, J. A.; Hernandez, W.; Mora, M.; Fowle, D. A.

2012-12-01

Trace metal cycling in hydrothermal systems has been the subject of a variety of geochemical and economical geology studies. Typically in these settings these elements are sequestered in sulfide and oxide mineral fractions, however in near-surface low-temperature environments organic matter and microorganisms (typically in mats) have been implicated in their mobility through sorption. Here we specifically examine the role of microbial biofilms on metal partitioning in an acid-sulfate hydrothermal system. We studied the influence of microorganisms and microbial biofilms on trace metal adsorption in Pailas de Aguas I, an acid-sulfate hot spring on the southwest flank of Rincon de la Vieja, a composite stratovolcano in the Guanacaste Province, Costa Rica. Spring waters contain high suspended loads, and are characterized by high T (79.6-89.3oC), low pH (2.6-4), and high ionic strengths (I= 0.5-0.8). Waters contain high concentrations of the biogeochemically active elements Fe (4-6 mmol/l) and SO42- (38 mmol/l), but PO43- are below detection limits (bdl). Silver, Ni, and Mo concentrations are bdl; however other trace metals are present in solution in concentrations of 0.1-0.2 mg/l Cd, 0.2-0.4 mg/l Cr and V, 0.04-1 mg/l Cu,. Preliminary 16S rRNA analyses of microorganisms in sediments reveal several species of algae, including Galderia sp., Cyanidium sp, γ-proteobacteria, Acidithiobacillus caldus, Euryarcheota, and methanogens. To evaluate microbial biofilms' impact on trace metal mobility we analyzed a combination of suspended, bulk and biofilm associated sediment samples via X-ray diffraction (XRD) and trace element sequential extractions (SE). XRD analysis indicated all samples were primarily composed of Fe/Al clay minerals (nontronite, kaolinite), 2- and 6-line ferrihydrite, goethite, and hematite, quartz, and opal-α. SE showed the highest concentrations of Cu, Mo, and V were found in the suspended load. Molybdenum was found primarily in the residual and organic fractions of suspended sediments. Copper is distributed in all but the carbonate fraction of suspended sediments. Vanadium was bound primarily to the oxide and residual fractions with Si, which is probably found as opal-α. In contrast, biofilm sediments had the highest concentrations of Fe, Si, Cd, Al, Zn, Ag, and Ni. Trace metals were sequestered mainly in the organic fraction in decreasing concentrations of: Cu

Corona-directed nucleic acid delivery into hepatic stellate cells for liver fibrosis therapy.

PubMed

Zhang, Zhengping; Wang, Chunming; Zha, Yinhe; Hu, Wei; Gao, Zhongfei; Zang, Yuhui; Chen, Jiangning; Zhang, Junfeng; Dong, Lei

2015-03-24

Strategies to modify nanoparticles with biological ligands for targeted drug delivery in vivo have been widely studied but met with limited clinical success. A possible reason is that, in the blood circulation, serum proteins could rapidly form a layer of protein "corona" on the vehicle surface, which might block the modified ligands and hamper their targeting functions. We speculate that strategies for drug delivery can be designed based upon elegant control of the corona formation on the vehicle surfaces. In this study, we demonstrate a retinol-conjugated polyetherimine (RcP) nanoparticle system that selectively recruited the retinol binding protein 4 (RBP) in its corona components. RBP was found to bind retinol, and direct the antisense oligonucleotide (ASO)-laden RcP carrier to hepatic stellate cells (HSC), which play essential roles in the progression of hepatic fibrosis. In both mouse fibrosis models, induced by carbon tetrachloride (CCl4) and bile duct ligation (BDL), respectively, the ASO-laden RcP particles effectively suppressed the expression of type I collagen (collagen I), and consequently ameliorated hepatic fibrosis. Such findings suggest that this delivery system, designed to exploit the power of corona proteins, can serve as a promising tool for targeted delivery of therapeutic agents for the treatment of hepatic fibrosis.

Thermal Analysis and Design of Air Cooled Electronic Circuit Boards Using a Desktop Computer.

DTIC Science & Technology

1980-06-01

pi rameter is" 3340 PRINT "as1gneid ,hii:h cauas;.es the progran to beg’ rat ’he section which a_=! for the" 3350 PRINT "geometric parieters of the...THERMELE:.: 1030 LiNE TYPE 3 1035 LruBdl N r I LR - LENGTH OF EACH PEGIr4t4 1040 HrmBdh- Hr I HP a HEIGHT OF EiCH PEG ;ION 1045 FOR 1-1 TO Ni.r-1 1650 MOVE I...PAGEHEAD 3345 ! 3350 Errin:1 THIS SECTION ALERTS THE USER TO AN ATTEtiFT TO INPUT SAD DATA 3355 BEEP 3360 DISP "INPUT OUT OF ’RNGE ............ TRY AGAIN

Loss of cellular FLICE-inhibitory protein promotes acute cholestatic liver injury and inflammation from bile duct ligation.

PubMed

Gehrke, Nadine; Nagel, Michael; Straub, Beate K; Wörns, Marcus A; Schuchmann, Marcus; Galle, Peter R; Schattenberg, Jörn M

2018-03-01

Cholestatic liver injury results from impaired bile flow or metabolism and promotes hepatic inflammation and fibrogenesis. Toxic bile acids that accumulate in cholestasis induce apoptosis and contribute to early cholestatic liver injury, which is amplified by accompanying inflammation. The aim of the current study was to evaluate the role of the antiapoptotic caspase 8-homolog cellular FLICE-inhibitory (cFLIP) protein during acute cholestatic liver injury. Transgenic mice exhibiting hepatocyte-specific deletion of cFLIP (cFLIP -/- ) were used for in vivo and in vitro analysis of cholestatic liver injury using bile duct ligation (BDL) and the addition of bile acids ex vivo. Loss of cFLIP in hepatocytes promoted acute cholestatic liver injury early after BDL, which was characterized by a rapid release of proinflammatory and chemotactic cytokines (TNF, IL-6, IL-1β, CCL2, CXCL1, and CXCL2), an increased presence of CD68 + macrophages and an influx of neutrophils in the liver, and resulting apoptotic and necrotic hepatocyte cell death. Mechanistically, liver injury in cFLIP -/- mice was aggravated by reactive oxygen species, and sustained activation of the JNK signaling pathway. In parallel, cytoprotective NF-κB p65, A20, and the MAPK p38 were inhibited. Increased injury in cFLIP -/- mice was accompanied by activation of hepatic stellate cells and profibrogenic regulators. The antagonistic caspase 8-homolog cFLIP is a critical regulator of acute, cholestatic liver injury. NEW & NOTEWORTHY The current paper explores the role of a classical modulator of hepatocellular apoptosis in early, cholestatic liver injury. These include activation of NF-κB and MAPK signaling, production of inflammatory cytokines, and recruitment of neutrophils in response to cholestasis. Because these signaling pathways are currently exploited in clinical trials for the treatment of nonalcoholic steatohepatitis and cirrhosis, the current data will help in the development of novel pharmacological options in these indications.

Conjugated Bilirubin Triggers Anemia by Inducing Erythrocyte Death

PubMed Central

Lang, Elisabeth; Gatidis, Sergios; Freise, Noemi F; Bock, Hans; Kubitz, Ralf; Lauermann, Christian; Orth, Hans Martin; Klindt, Caroline; Schuier, Maximilian; Keitel, Verena; Reich, Maria; Liu, Guilai; Schmidt, Sebastian; Xu, Haifeng C; Qadri, Syed M; Herebian, Diran; Pandyra, Aleksandra A; Mayatepek, Ertan; Gulbins, Erich; Lang, Florian; Häussinger, Dieter; Lang, Karl S; Föller, Michael; Lang, Philipp A

2015-01-01

Hepatic failure is commonly associated with anemia, which may result from gastrointestinal bleeding, vitamin deficiency, or liver-damaging diseases, such as infection and alcohol intoxication. At least in theory, anemia during hepatic failure may result from accelerated clearance of circulating erythrocytes. Here we show that bile duct ligation (BDL) in mice leads to severe anemia despite increased reticulocyte numbers. Bilirubin stimulated suicidal death of human erythrocytes. Mechanistically, bilirubin triggered rapid Ca2+ influx, sphingomyelinase activation, formation of ceramide, and subsequent translocation of phosphatidylserine to the erythrocyte surface. Consistent with our in vitro and in vivo findings, incubation of erythrocytes in serum from patients with liver disease induced suicidal death of erythrocytes in relation to their plasma bilirubin concentration. Consistently, patients with hyperbilirubinemia had significantly lower erythrocyte and significantly higher reticulocyte counts compared to patients with low bilirubin levels. Conclusion: Bilirubin triggers suicidal erythrocyte death, thus contributing to anemia during liver disease. (Hepatology 2015;61:275–284) PMID:25065608

An assessment of geographical distribution of different plant functional types over North America simulated using the CLASS-CTEM modelling framework

NASA Astrophysics Data System (ADS)

Shrestha, Rudra K.; Arora, Vivek K.; Melton, Joe R.; Sushama, Laxmi

2017-10-01

The performance of the competition module of the CLASS-CTEM (Canadian Land Surface Scheme and Canadian Terrestrial Ecosystem Model) modelling framework is assessed at 1° spatial resolution over North America by comparing the simulated geographical distribution of its plant functional types (PFTs) with two observation-based estimates. The model successfully reproduces the broad geographical distribution of trees, grasses and bare ground although limitations remain. In particular, compared to the two observation-based estimates, the simulated fractional vegetation coverage is lower in the arid southwest North American region and higher in the Arctic region. The lower-than-observed simulated vegetation coverage in the southwest region is attributed to lack of representation of shrubs in the model and plausible errors in the observation-based data sets. The observation-based data indicate vegetation fractional coverage of more than 60 % in this arid region, despite only 200-300 mm of precipitation that the region receives annually, and observation-based leaf area index (LAI) values in the region are lower than one. The higher-than-observed vegetation fractional coverage in the Arctic is likely due to the lack of representation of moss and lichen PFTs and also likely because of inadequate representation of permafrost in the model as a result of which the C3 grass PFT performs overly well in the region. The model generally reproduces the broad spatial distribution and the total area covered by the two primary tree PFTs (needleleaf evergreen trees, NDL-EVG; and broadleaf cold deciduous trees, BDL-DCD-CLD) reasonably well. The simulated fractional coverage of tree PFTs increases after the 1960s in response to the CO2 fertilization effect and climate warming. Differences between observed and simulated PFT coverages highlight model limitations and suggest that the inclusion of shrubs, and moss and lichen PFTs, and an adequate representation of permafrost will help improve model performance.

The P2X4 purinergic receptor regulates hepatic myofibroblast activation during liver fibrogenesis.

PubMed

Le Guilcher, Camille; Garcin, Isabelle; Dellis, Olivier; Cauchois, Florent; Tebbi, Ali; Doignon, Isabelle; Guettier, Catherine; Julien, Boris; Tordjmann, Thierry

2018-05-23

Liver fibrosis is characterized by the accumulation of extracellular matrix produced by hepatic myofibroblasts (hMF), the activation of which is critical to the fibrogenic process. Extracellular adenosine triphosphate, released by dying or stressed cells, and its purinergic receptors, constitute a powerful signaling network after injury. Although the P2X4 purinergic receptor (P2X4) is highly expressed in the liver, its functions in hMF had never been investigated during liver fibrogenesis. In vivo, bile duct ligation (BDL) and methionine- and choline-deficient (MCD) diet were performed in WT and P2X4 knock-out (P2X4-KO) mice. In vitro, hMF were isolated from mouse (WT and P2X4-KO) and human liver. P2X4 pharmacological inhibition (in vitro and in vivo) and P2X4 siRNAs (in vitro) were used. Histological, biochemical and cell culture analysis allowed us to study P2X4 expression and its involvement in the regulation of fibrogenic and fibrolytic factors, as well as of hMF activation markers and properties. P2X4 genetic invalidation or pharmacological inhibition protected mice from liver fibrosis and hMF accumulation after BDL or MCD diet. Human and mouse hMF expressed P2X4, mainly in lysosomes. Invalidation of P2X4 in human and mouse hMF blunted their activation marker expression and their fibrogenic properties. We finally showed that P2X4 regulates calcium entry and lysosomal exocytosis in hMF, with impact on ATP release, pro-fibrogenic secretory profile, and on transcription factor activation. P2X4 expression and activation is critical for hMF to sustain their activated and fibrogenic phenotype. Therefore, the inactivation of P2X4 may be of therapeutic interest during liver fibrotic diseases. During chronic injury, the liver often repairs with fibrotic tissue for which there is currently no treatment. We found that a previously unexplored pathway involving the purinergic receptor "P2X4", can modulate fibrotic liver repair, and could be considered for future translational investigations. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Body Fluids as a Source of Diagnostic Biomarkers: Prostate — EDRN Public Portal

Cancer.gov

Recent advances in high-throughput protein expression profiling of bodily fluids has generated great enthusiasm and hope for this approach as a potent diagnostic tool. At the center of these efforts is the application of SELDI-TOF-MS and artificial intelligence algorithms by the EDRN BDL site at Eastern Virginia Medical School and the DMCC respectively. When the expression profiling process was applied to sera from individuals with prostate cancer (N=197), BPH (N=92) or from otherwise healthy donors (N=97) we achieved an overall misclassification rate of 90% sensitivity. Since this represents a noticeable improvement in current clinical approach we are proposing to embark upon a validation process. The described studies are designed to address validation issues and include three phases. Phase 1; Synchronization of SELDI Output within the EDRN-Prostate-SELDI Investigational Collaboration (EPSIC); addressing portability (A) Synchronize SELDI instrumentation and robotic sample processing across the EPSIC using pooled serum(QC); (B) Establish the portability and reproducibility of the SELDI protein profiling approach within the EPSIC using normal and prostate cancer patient’s serum from a single site; (C) Establish robustness of the approach toward geographic, sample collection and processing differences within EPSIC using case and control serum from five different sites. Phase 2; Population Validation Establish geographic variability and robustness in a large cross-sectional study among different sample population. Phase 3; Clinical Validation; validate the serum protein expression profiling coupled with a learning algorithm as a means for early detection of prostate cancer using longitudinal PCPT samples. We have assembled a cohesive multi-institutional team for completing these studies in a timely and efficient manner. The team consists of five EDRN laboratories, DMCC and CBI and the proposed budget reflects the total involvement.

Assessment of groundwater quality from Bankura I and II Blocks, Bankura District, West Bengal, India

NASA Astrophysics Data System (ADS)

Nag, S. K.; Das, Shreya

2017-10-01

Hydrochemical evaluation of groundwater has been conducted in Bankura I and II Blocks to analyze and determining groundwater quality in the area. Thirty-six groundwater samples were analyzed for their physical and chemical properties using standard laboratory methods. The constituents have the following ranges in the water: pH 6.4-8.6, electrical conductivity 80-1900 μS/cm, total hardness 30-730 mg/l, TDS 48-1001 mg/l, Ca2+ 4.2-222.6 mg/l, Na+ 2.33-103.33 mg/l, Mg2+ 1.56-115.36 mg/l, K+ 0.67-14 mg/l and Fe BDL-2.53 mg/l, {HCO}3^{ - } 48.8-1000.4 mg/l, Cl- 5.6-459.86 mg/l and {SO}4^{ = } BDL-99.03 mg/l. Results also show that bicarbonate ions ( {HCO}3^{ - } ) dominate the other anions (Cl- and {SO}4^{2 - } ). Sodium adsorption ratio (SAR), soluble sodium percentage (SSP), residual sodium carbonate (RSC), magnesium adsorption ratio (MAR), total hardness (TH), and permeability index (PI) were calculated as derived parameters, to investigate the ionic toxicity. Concerned chemical parameters when plotted in the U.S. Salinity diagram indicate that waters are of C1-S1, C2-S1 and C3-S1 types, i.e., low salinity and low sodium which is good for irrigation. The values of Sodium Adsorption Ratio indicate that the groundwater of the area falls under the category of low sodium hazard. So, there is neither salinity nor toxicity problem of irrigation water, and hence the ground water can safely be used for long-term irrigation. The chemical parameters when plotted in Piper's trilinear diagram are found to concentrate in the central and west central part of the diamond-shaped field. Based on the analytical results, groundwater in the area is found to be generally fresh and hard to very hard. The abundance of the major ions is as follows: HCO3 > Cl > SO4 and Ca > Na > Mg > K > Fe. Results also show that bicarbonate ions ( {HCO}3^{ - } ) dominate the other anions (Cl- and {SO}4^{2 - } ). According to Gibbs diagrams samples fall in the rock dominance field and the chemical quality of groundwater is related to the lithology of the area. The alkaline earth elements (Ca and Mg) occur in greater abundance than alkaline elements (Na and K). A comparative study of our analytical results with the WHO standards of drinking water indicate that the present waters are also good for drinking purposes.

Saturnian satellite observations made in Brazil during the 1995 opposition with an astrometric analysis

NASA Astrophysics Data System (ADS)

Vienne, A.; Thuillot, W.; Veiga, C. H.; Arlot, J.-E.; Vieira Martins, R.

2001-12-01

This paper provides an analysis of astrometric measurements of the main Saturnian satellites made thanks to CCD observations performed in 1995 at the Laboratório Nacional de Astrofísica at Itajubá in Brazil. The astrometric reduction is discussed especially the small corrections done here, but most of time neglected elsewhere. A catalog of 6006 differential positions has been obtained. They have been compared to different ephemerides, the Vienne & Duriez ephemerides (TASS 1.7), the Harper & Taylor ephemerides and the Dourneau ephemerides. These observations provide a large set of modern observations, and appear to be of good precision. This accuracy is needed for future use of these data to improve the dynamical models. These positions are included in the data base NSDC dedicated to the natural satellites (ftp://ftp.bdl.fr/pub/NSDC/saturn/raw_data/position/). They are also available at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/380/727

40 CFR Appendix B to Part 136 - Definition and Procedure for the Determination of the Method Detection Limit-Revision 1.11

Code of Federal Regulations, 2010 CFR

2010-07-01

... calculated method detection limit. To insure that the estimate of the method detection limit is a good...) where: MDL = the method detection limit t(n-1,1- α=.99) = the students' t value appropriate for a 99... Determination of the Method Detection Limit-Revision 1.11 B Appendix B to Part 136 Protection of Environment...

Material limitations on the detection limit in refractometry.

PubMed

Skafte-Pedersen, Peder; Nunes, Pedro S; Xiao, Sanshui; Mortensen, Niels Asger

2009-01-01

We discuss the detection limit for refractometric sensors relying on high-Q optical cavities and show that the ultimate classical detection limit is given by min {Δn} ≳ η, with n + iη being the complex refractive index of the material under refractometric investigation. Taking finite Q factors and filling fractions into account, the detection limit declines. As an example we discuss the fundamental limits of silicon-based high-Q resonators, such as photonic crystal resonators, for sensing in a bio-liquid environment, such as a water buffer. In the transparency window (λ ≳ 1100 nm) of silicon the detection limit becomes almost independent on the filling fraction, while in the visible, the detection limit depends strongly on the filling fraction because the silicon absorbs strongly.

Material Limitations on the Detection Limit in Refractometry

PubMed Central

Skafte-Pedersen, Peder; Nunes, Pedro S.; Xiao, Sanshui; Mortensen, Niels Asger

2009-01-01

We discuss the detection limit for refractometric sensors relying on high-Q optical cavities and show that the ultimate classical detection limit is given by min {Δn} ≳ η, with n + iη being the complex refractive index of the material under refractometric investigation. Taking finite Q factors and filling fractions into account, the detection limit declines. As an example we discuss the fundamental limits of silicon-based high-Q resonators, such as photonic crystal resonators, for sensing in a bio-liquid environment, such as a water buffer. In the transparency window (λ ≳ 1100 nm) of silicon the detection limit becomes almost independent on the filling fraction, while in the visible, the detection limit depends strongly on the filling fraction because the silicon absorbs strongly. PMID:22291513

Laser Diagnostics for Reacting Flows

DTIC Science & Technology

2010-01-11

noise characteristics of the diagnostic will be in the shot - noise limit , a fundamental limit of the LIF signal intensity... noise related to the discrete nature of photons. In the shot - noise limit , the fluctuation detection limit can be predicted using nVP B S f f  1...detection limit was shot - noise limited . Figure 2.2.3 illustrates the fluctuation detection limits for line LIF imaging. Figure 2.2.3a

Calculation of the detection limits for radionuclides identified in gamma-ray spectra based on post-processing peak analysis results.

PubMed

Korun, M; Vodenik, B; Zorko, B

2018-03-01

A new method for calculating the detection limits of gamma-ray spectrometry measurements is presented. The method is applicable for gamma-ray emitters, irrespective of the influences of the peaked background, the origin of the background and the overlap with other peaks. It offers the opportunity for multi-gamma-ray emitters to calculate the common detection limit, corresponding to more peaks. The detection limit is calculated by approximating the dependence of the uncertainty in the indication on its value with a second-order polynomial. In this approach the relation between the input quantities and the detection limit are described by an explicit expression and can be easy investigated. The detection limit is calculated from the data usually provided by the reports of peak-analyzing programs: the peak areas and their uncertainties. As a result, the need to use individual channel contents for calculating the detection limit is bypassed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Limits of detection and decision. Part 4

NASA Astrophysics Data System (ADS)

Voigtman, E.

2008-02-01

Probability density functions (PDFs) have been derived for a number of commonly used limit of detection definitions, including several variants of the Relative Standard Deviation of the Background-Background Equivalent Concentration (RSDB-BEC) method, for a simple linear chemical measurement system (CMS) having homoscedastic, Gaussian measurement noise and using ordinary least squares (OLS) processing. All of these detection limit definitions serve as both decision and detection limits, thereby implicitly resulting in 50% rates of Type 2 errors. It has been demonstrated that these are closely related to Currie decision limits, if the coverage factor, k, is properly defined, and that all of the PDFs are scaled reciprocals of noncentral t variates. All of the detection limits have well-defined upper and lower limits, thereby resulting in finite moments and confidence limits, and the problem of estimating the noncentrality parameter has been addressed. As in Parts 1-3, extensive Monte Carlo simulations were performed and all the simulation results were found to be in excellent agreement with the derived theoretical expressions. Specific recommendations for harmonization of detection limit methodology have also been made.

Search times and probability of detection in time-limited search

NASA Astrophysics Data System (ADS)

Wilson, David; Devitt, Nicole; Maurer, Tana

2005-05-01

When modeling the search and target acquisition process, probability of detection as a function of time is important to war games and physical entity simulations. Recent US Army RDECOM CERDEC Night Vision and Electronics Sensor Directorate modeling of search and detection has focused on time-limited search. Developing the relationship between detection probability and time of search as a differential equation is explored. One of the parameters in the current formula for probability of detection in time-limited search corresponds to the mean time to detect in time-unlimited search. However, the mean time to detect in time-limited search is shorter than the mean time to detect in time-unlimited search and the relationship between them is a mathematical relationship between these two mean times. This simple relationship is derived.

Shot noise limited detection of OH using the technique of laser induced fluorescence

NASA Technical Reports Server (NTRS)

Bakalyar, D. M.; Davis, L. I., Jr.; Guo, C.; James, J. V.; Kakos, S.; Morris, P. T.; Wang, C. C.

1984-01-01

Nearly shot-noise limited detection of OH using the technique of laser-induced fluorescence is reported. A LIDAR configuration is used to excite fluorescence in a large volume and a narrow-bandwidth interference filter provides spectral discrimination. This arrangement alleviates the effect of ozone interference and facilitates image processing at relatively close distances. The detection limit is determined mainly by the shot-noise of the solar background. Ground-based measurements in Dearborn indicate a detection limit of better than 1 x 10 to the 6th power OH/cubic cm over a forty-minute acquisition period. Under favorable conditions, a comparable detection limit was also observed for airborne measurements.

Shot noise limited detection of OH using the technique of laser-induced fluorescence

NASA Technical Reports Server (NTRS)

Bakalyar, D. M.; Davis, L. I., Jr.; Guo, C.; James, J. V.; Wang, C. C.; Kakos, S.; Morris, P. T.

1984-01-01

Nearly shot-noise limited detection of OH using the technique of laser-induced fluorescence is reported. A LIDAR configuration is used to excite fluoresence in a large volume and a narrow-bandwidth interference filter provides spectral discrimination. This arrangement alleviates the effect of ozone interference and facilitates image processing at relatively close distances. The detection limit is determined mainly by the short-noise of the solar background. Ground-based measurements in Dearborn indicate a detection limit of better than 1 x 10 to the 6th power OH/cubic cm over a forty-minute acquisition period. Under favorable conditions, a comparable detection limit was also observed for airborne measurements.

Re-evaluation of groundwater monitoring data for glyphosate and bentazone by taking detection limits into account.

PubMed

Hansen, Claus Toni; Ritz, Christian; Gerhard, Daniel; Jensen, Jens Erik; Streibig, Jens Carl

2015-12-01

Current regulatory assessment of pesticide contamination of Danish groundwater is exclusively based on samples with pesticide concentrations above detection limit. Here we demonstrate that a realistic quantification of pesticide contamination requires the inclusion of "non-detect" samples i.e. samples with concentrations below the detection limit, as left-censored observations. The median calculated pesticide concentrations are shown to be reduced 10(4) to 10(5) fold for two representative herbicides (glyphosate and bentazone) relative to the median concentrations based upon observations above detection limits alone. Copyright © 2015 Elsevier B.V. All rights reserved.

The thalidomide analog 3-phthalimido-3-(3,4-dimethoxyphenyl)-propanoic acid improves the biliary cirrhosis in the rat.

PubMed

Fernández-Martínez, Eduardo; Pérez-Hernández, Nury; Muriel, Pablo; Pérez-Alvarez, Víctor; Shibayama, Mineko; Tsutsumi, Víctor

2009-09-01

Chronic cholestasis and cholangitis may lead to the last phase known as biliary cirrhosis, characterized by cellular necrosis, apoptosis, tissue damage, local regeneration, inflammation and fibrosis. Such events are mediated by cytokines. Thalidomide and its analogs have shown to be effective immunomodulatory and hepatoprotective agents. The aim of this work was to evaluate the hepatoprotective properties of a thalidomide analog, the 3-phthalimido-3-(3,4-dimethoxyphenyl)-propanoic acid (PDA), on bile duct obstruction-induced cirrhosis. Vehicle or PDA (67 mg/kg) was orally administered twice a day to sham (Sham) or bile duct-ligated (BDL) male Wistar rats. The animals were sacrificed 28 days after treatments. Alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGTP) and alanine aminotransferase (ALT) enzyme activities as well as direct and total bilirubins concentration were determined in plasma. Lipid peroxidation (LP), glycogen and collagen were quantified in liver; in addition, histopathology was performed. PDA improved cholestasis, necrosis and fibrosis by significantly diminishing most of liver injury markers (P<0.05). Histopathology also showed remarkable liver damage amelioration. PDA effectiveness may be due to its water-solubility, stability, phosphodiesterase-4 inhibitory and immunomodulatory actions. Thalidomide and its analogs seem to be promising drugs for further treatment of biliary cirrhosis.

Protective Effect of Astaxanthin on Liver Fibrosis through Modulation of TGF-β1 Expression and Autophagy

PubMed Central

Shen, Miao; Chen, Kan; Lu, Jie; Cheng, Ping; Xu, Ling; Dai, Weiqi; Wang, Fan; He, Lei; Zhang, Yan; Chengfen, Wang; Li, Jingjing; Yang, Jing; Zhu, Rong; Zhang, Huawei; Zheng, Yuanyuan; Zhou, Yingqun; Guo, Chuanyong

2014-01-01

Liver fibrosis is a common pathway leading to cirrhosis and a worldwide clinical issue. Astaxanthin is a red carotenoid pigment with antioxidant, anticancer, and anti-inflammatory properties. The aim of this study was to investigate the effect of astaxanthin on liver fibrosis and its potential protective mechanisms. Liver fibrosis was induced in a mouse model using CCL4 (intraperitoneal injection, three times a week for 8 weeks), and astaxanthin was administered everyday at three doses (20, 40, and 80 mg/kg). Pathological results indicated that astaxanthin significantly improved the pathological lesions of liver fibrosis. The levels of alanine aminotransferase aspartate aminotransferase and hydroxyproline were also significantly decreased by astaxanthin. The same results were confirmed in bile duct liagtion, (BDL) model. In addition, astaxanthin inhibited hepatic stellate cells (HSCs) activation and formation of extracellular matrix (ECM) by decreasing the expression of NF-κB and TGF-β1 and maintaining the balance between MMP2 and TIMP1. In addition, astaxanthin reduced energy production in HSCs by downregulating the level of autophagy. These results were simultaneously confirmed in vivo and in vitro. In conclusion, our study showed that 80 mg/kg astaxanthin had a significant protective effect on liver fibrosis by suppressing multiple profibrogenic factors. PMID:24860243

Three-dimensional visualization of the microvasculature of bile duct ligation-induced liver fibrosis in rats by x-ray phase-contrast imaging computed tomography

NASA Astrophysics Data System (ADS)

Xuan, Ruijiao; Zhao, Xinyan; Hu, Doudou; Jian, Jianbo; Wang, Tailing; Hu, Chunhong

2015-07-01

X-ray phase-contrast imaging (PCI) can substantially enhance contrast, and is particularly useful in differentiating biological soft tissues with small density differences. Combined with computed tomography (CT), PCI-CT enables the acquisition of accurate microstructures inside biological samples. In this study, liver microvasculature was visualized without contrast agents in vitro with PCI-CT using liver fibrosis samples induced by bile duct ligation (BDL) in rats. The histological section examination confirmed the correspondence of CT images with the microvascular morphology of the samples. By means of the PCI-CT and three-dimensional (3D) visualization technique, 3D microvascular structures in samples from different stages of liver fibrosis were clearly revealed. Different types of blood vessels, including portal veins and hepatic veins, in addition to ductular proliferation and bile ducts, could be distinguished with good sensitivity, excellent specificity and excellent accuracy. The study showed that PCI-CT could assess the morphological changes in liver microvasculature that result from fibrosis and allow characterization of the anatomical and pathological features of the microvasculature. With further development of PCI-CT technique, it may become a novel noninvasive imaging technique for the auxiliary analysis of liver fibrosis.

Radiation dose in the high background radiation area in Kerala, India.

PubMed

Christa, E P; Jojo, P J; Vaidyan, V K; Anilkumar, S; Eappen, K P

2012-03-01

A systematic radiological survey has been carried out in the region of high-background radiation area in Kollam district of Kerala to define the natural gamma-radiation levels. One hundred and forty seven soil samples from high-background radiation areas and five samples from normal background region were collected as per standard sampling procedures and were analysed for (238)U, (232)Th and (40)K by gamma-ray spectroscopy. External gamma dose rates at all sampling locations were also measured using a survey meter. The activities of (238)U, (232)Th and (40)K was found to vary from 17 to 3081 Bq kg(-1), 54 to 11976 Bq kg(-1) and BDL (67.4 Bq kg(-1)) to 216 Bq kg(-1), respectively, in the study area. Such heterogeneous distribution of radionuclides in the region may be attributed to the deposition phenomenon of beach sand soil in the region. Radium equivalent activities were found high in several locations. External gamma dose rates estimated from the levels of radionuclides in soil had a range from 49 to 9244 nGy h(-1). The result of gamma dose rate measured at the sampling sites using survey meter showed an excellent correlation with dose rates computed from the natural radionuclides estimated from the soil samples.

Assessment of body fat composition in crossbred Angus × Nellore using biometric measurements.

PubMed

Fonseca, M A; Tedeschi, L O; Filho, S C Valadares; De Paula, N F; Villadiego, F A C; Junior, J M Silva; Abreu, D C; Chizzotti, M L

2017-12-01

This study was conducted to assess the body and empty body fat physical and chemical composition through biometric measurements (BM) as well as postmortem measurements taken in 40 F Angus × Nellore bulls and steers. The animals used were 12.5 ± 0.51 mo of age, with an average shrunk BW of 233 ± 23.5 and 238 ± 24.6 kg for bulls and steers, respectively. Animals were fed 60:40 ratio of corn silage to concentrate diets. Eight animals (4 bulls and 4 steers) were slaughtered at the beginning of the trial, and the remaining animals were randomly assigned to a 1 + 2 × 3 factorial arrangement (1 reference group, 2 sexes, and 3 slaughter weights). The remaining animals were slaughtered when the average BW of the group reached 380 ± 19.5 (6 bulls and 5 steers), 440 ± 19.2 (6 bulls and 5 steers), and 500 ± 19.5 kg (5 bulls and 5 steers). Before the slaughter, the animals were led through a squeeze chute in which BM were taken, including hook bone width (HBW), pin bone width, abdomen width (AW), body length (BL), rump height, height at the withers, pelvic girdle length (PGL), rib depth (RD), girth circumference (GC), rump depth, body diagonal length (BDL), and thorax width. Additionally, the following postmortem measurements were obtained: total body surface (TBS), body volume (BV), subcutaneous fat (SF), internal physical fat (InF), intermuscular fat, carcass physical fat (CF), empty body physically separable fat (EBF), carcass chemical fat (CFch), empty body chemical fat (EBFch), fat thickness in the 12th rib, and 9th to 11th rib section fat. The equations were developed using a stepwise procedure to select the variables that should enter into the model. The and root mean square error (RMSE) were used to account for precision and accuracy. The ranges for and RMSE were 0.852 to 0.946 and 0.0625 to 0.103 m, respectively for TBS; 0.942 to 0.998 and 0.004 to 0.022 m, respectively, for BV; 0.767 to 0.967 and 2.70 to 3.24 kg, respectively, for SF; 0.816 to 0.900 and 3.04 to 4.12 kg, respectively, for InF; 0.830 to 0.988 and 3.44 to 8.39 kg, respectively, for CF; 0.861 to 0.998 and 1.51 to 10.98 kg, respectively, for EBF; 0.825 to 0.985 and 5.96 to 8.46 kg, respectively, for CFch; and 0.862 to 0.992 and 5.54 to 12.19 kg, respectively, for EBFch. Our results indicated that BM that could accurately and precisely be used as alternatives to predict different fat depots of F Angus × Nellore bulls and steers are AW, GC, or PGL for CF estimation; HBW and RD for CFch estimation; and body lengths such as BL and BDL for InF and SF estimation, respectively.

Atmospheric organochlorine pesticides and polychlorinated biphenyls in urban areas of Nepal: spatial variation, sources, temporal trends, and long-range transport potential

NASA Astrophysics Data System (ADS)

Pokhrel, Balram; Gong, Ping; Wang, Xiaoping; Nath Khanal, Sanjay; Ren, Jiao; Wang, Chuanfei; Gao, Shaopeng; Yao, Tandong

2018-02-01

The study of persistent organic pollutants (POPs) in low-latitude tropical and subtropical urban cities is necessary to assess their local and global impacts on ecosystems and human health. Despite studies on levels of POPs in water, soils, and sediments, analysis of the distribution patterns, seasonality, and sources of POPs in urban regions of Nepal remain limited. Polyurethane foam (PUF)-based passive air samplers were deployed in three major cities in Nepal: Kathmandu (the capital city), Pokhara, and Hetauda (agricultural cities). Dichlorodiphenyltrichloroethane (DDT) and hexachlorocyclohexane (HCH) were the dominant organochlorine pesticides in the atmosphere at all sites. The average concentrations of POPs were ∑ DDTs, 8.7-1.0 × 103 pg m-3; ∑ HCHs, 5.3-3.3 × 103 pg m-3; HCB, 5.8-3.4 × 102 pg m-3; ∑ endosulfan, BDL-51 pg m-3; and ∑ 6PCBs, 1.4-47 pg m-3. Isomer and metabolite ratio analyses suggested that the concentrations present were from both new and historical applications of the POPs. Vegetable production sites and their market places appeared to be the major DDT and HCH source areas. Higher atmospheric concentrations of DDT and HCH occurred during the pre-monsoon and monsoon seasons, and winter, respectively, closely associated with their local application for soil preparation and vegetable spraying. The estimated travel distances of the POPs (HCB, α-HCH, γ-HCH, and p, p'-DDT) under the Nepalese tropical climate were all above 1000 km, suggesting that high precipitation levels in the tropical climate were not enough to scavenge the POPs and that Nepal could be an important source region for POPs. Due to their close proximity and cold trapping (driven by low temperatures), the high Himalayas and the Tibetan Plateau are likely the key receptors of POPs emitted in Nepal. These results add to the information available on POPs from tropical developing countries.

Thermal background noise limitations

NASA Technical Reports Server (NTRS)

Gulkis, S.

1982-01-01

Modern detection systems are increasingly limited in sensitivity by the background thermal photons which enter the receiving system. Expressions for the fluctuations of detected thermal radiation are derived. Incoherent and heterodyne detection processes are considered. References to the subject of photon detection statistics are given.

Epidemiologic Evaluation of Measurement Data in the Presence of Detection Limits

PubMed Central

Lubin, Jay H.; Colt, Joanne S.; Camann, David; Davis, Scott; Cerhan, James R.; Severson, Richard K.; Bernstein, Leslie; Hartge, Patricia

2004-01-01

Quantitative measurements of environmental factors greatly improve the quality of epidemiologic studies but can pose challenges because of the presence of upper or lower detection limits or interfering compounds, which do not allow for precise measured values. We consider the regression of an environmental measurement (dependent variable) on several covariates (independent variables). Various strategies are commonly employed to impute values for interval-measured data, including assignment of one-half the detection limit to nondetected values or of “fill-in” values randomly selected from an appropriate distribution. On the basis of a limited simulation study, we found that the former approach can be biased unless the percentage of measurements below detection limits is small (5–10%). The fill-in approach generally produces unbiased parameter estimates but may produce biased variance estimates and thereby distort inference when 30% or more of the data are below detection limits. Truncated data methods (e.g., Tobit regression) and multiple imputation offer two unbiased approaches for analyzing measurement data with detection limits. If interest resides solely on regression parameters, then Tobit regression can be used. If individualized values for measurements below detection limits are needed for additional analysis, such as relative risk regression or graphical display, then multiple imputation produces unbiased estimates and nominal confidence intervals unless the proportion of missing data is extreme. We illustrate various approaches using measurements of pesticide residues in carpet dust in control subjects from a case–control study of non-Hodgkin lymphoma. PMID:15579415

Censoring: a new approach for detection limits in total-reflection X-ray fluorescence

NASA Astrophysics Data System (ADS)

Pajek, M.; Kubala-Kukuś, A.; Braziewicz, J.

2004-08-01

It is shown that the detection limits in the total-reflection X-ray fluorescence (TXRF), which restrict quantification of very low concentrations of trace elements in the samples, can be accounted for using the statistical concept of censoring. We demonstrate that the incomplete TXRF measurements containing the so-called "nondetects", i.e. the non-measured concentrations falling below the detection limits and represented by the estimated detection limit values, can be viewed as the left random-censored data, which can be further analyzed using the Kaplan-Meier (KM) method correcting for nondetects. Within this approach, which uses the Kaplan-Meier product-limit estimator to obtain the cumulative distribution function corrected for the nondetects, the mean value and median of the detection limit censored concentrations can be estimated in a non-parametric way. The Monte Carlo simulations performed show that the Kaplan-Meier approach yields highly accurate estimates for the mean and median concentrations, being within a few percent with respect to the simulated, uncensored data. This means that the uncertainties of KM estimated mean value and median are limited in fact only by the number of studied samples and not by the applied correction procedure for nondetects itself. On the other hand, it is observed that, in case when the concentration of a given element is not measured in all the samples, simple approaches to estimate a mean concentration value from the data yield erroneous, systematically biased results. The discussed random-left censoring approach was applied to analyze the TXRF detection-limit-censored concentration measurements of trace elements in biomedical samples. We emphasize that the Kaplan-Meier approach allows one to estimate the mean concentrations being substantially below the mean level of detection limits. Consequently, this approach gives a new access to lower the effective detection limits for TXRF method, which is of prime interest for investigation of metallic impurities on the silicon wafers.

Ultrasensitive Detection of Shigella Species in Blood and Stool.

PubMed

Luo, Jieling; Wang, Jiapeng; Mathew, Anup S; Yau, Siu-Tung

2016-02-16

A modified immunosensing system with voltage-controlled signal amplification was used to detect Shigella in stool and blood matrixes at the single-digit CFU level. Inactivated Shigella was spiked in these matrixes and detected directly. The detection was completed in 78 min. Detection limits of 21 CFU/mL and 18 CFU/mL were achieved in stool and blood, respectively, corresponding to 2-7 CFUs immobilized on the detecting electrode. The outcome of the detection of extremely low bacterium concentration, i.e., below 100 CFU/mL, blood samples show a random nature. An analysis of the detection probabilities indicates the correlation between the sample volume and the success of detection and suggests that sample volume is critical for ultrasensitive detection of bacteria. The calculated detection limit is qualitatively in agreement with the empirically determined detection limit. The demonstrated ultrasensitive detection of Shigella on the single-digit CFU level suggests the feasibility of the direct detection of the bacterium in the samples without performing a culture.

[Data distribution and transformation in population based sampling survey of viral load in HIV positive men who have sex with men in China].

PubMed

Dou, Z; Chen, J; Jiang, Z; Song, W L; Xu, J; Wu, Z Y

2017-11-10

Objective: To understand the distribution of population viral load (PVL) data in HIV infected men who have sex with men (MSM), fit distribution function and explore the appropriate estimating parameter of PVL. Methods: The detection limit of viral load (VL) was ≤ 50 copies/ml. Box-Cox transformation and normal distribution tests were used to describe the general distribution characteristics of the original and transformed data of PVL, then the stable distribution function was fitted with test of goodness of fit. Results: The original PVL data fitted a skewed distribution with the variation coefficient of 622.24%, and had a multimodal distribution after Box-Cox transformation with optimal parameter ( λ ) of-0.11. The distribution of PVL data over the detection limit was skewed and heavy tailed when transformed by Box-Cox with optimal λ =0. By fitting the distribution function of the transformed data over the detection limit, it matched the stable distribution (SD) function ( α =1.70, β =-1.00, γ =0.78, δ =4.03). Conclusions: The original PVL data had some censored data below the detection limit, and the data over the detection limit had abnormal distribution with large degree of variation. When proportion of the censored data was large, it was inappropriate to use half-value of detection limit to replace the censored ones. The log-transformed data over the detection limit fitted the SD. The median ( M ) and inter-quartile ranger ( IQR ) of log-transformed data can be used to describe the centralized tendency and dispersion tendency of the data over the detection limit.

Procedures for determination of detection limits: application to high-performance liquid chromatography analysis of fat-soluble vitamins in human serum.

PubMed

Browne, Richard W; Whitcomb, Brian W

2010-07-01

Problems in the analysis of laboratory data commonly arise in epidemiologic studies in which biomarkers subject to lower detection thresholds are used. Various thresholds exist including limit of detection (LOD), limit of quantification (LOQ), and limit of blank (LOB). Choosing appropriate strategies for dealing with data affected by such limits relies on proper understanding of the nature of the detection limit and its determination. In this paper, we demonstrate experimental and statistical procedures generally used for estimating different detection limits according to standard procedures in the context of analysis of fat-soluble vitamins and micronutrients in human serum. Fat-soluble vitamins and micronutrients were analyzed by high-performance liquid chromatography with diode array detection. A simulated serum matrix blank was repeatedly analyzed for determination of LOB parametrically by using the observed blank distribution as well as nonparametrically by using ranks. The LOD was determined by combining information regarding the LOB with data from repeated analysis of standard reference materials (SRMs), diluted to low levels; from LOB to 2-3 times LOB. The LOQ was determined experimentally by plotting the observed relative standard deviation (RSD) of SRM replicates compared with the concentration, where the LOQ is the concentration at an RSD of 20%. Experimental approaches and example statistical procedures are given for determination of LOB, LOD, and LOQ. These quantities are reported for each measured analyte. For many analyses, there is considerable information available below the LOQ. Epidemiologic studies must understand the nature of these detection limits and how they have been estimated for appropriate treatment of affected data.

Detectability limit and uncertainty considerations for laser induced fluorescence spectroscopy in flames

NASA Technical Reports Server (NTRS)

Daily, J. W.

1978-01-01

Laser induced fluorescence spectroscopy of flames is discussed, and derived uncertainty relations are used to calculate detectability limits due to statistical errors. Interferences due to Rayleigh scattering from molecules as well as Mie scattering and incandescence from particles have been examined for their effect on detectability limits. Fluorescence trapping is studied, and some methods for reducing the effect are considered. Fluorescence trapping places an upper limit on the number density of the fluorescing species that can be measured without signal loss.

Improvements in an in vivo neutron activation analysis (NAA) method for the measurement of fluorine in human bone.

PubMed

Mostafaei, F; McNeill, F E; Chettle, D R; Prestwich, W V

2013-10-01

We previously published a method for the in vivo measurement of bone fluoride using neutron activation analysis (NAA) and demonstrated the utility of the technique in a pilot study of environmentally exposed people. The method involved activation of the hand in an irradiation cavity at the McMaster University Accelerator Laboratory and acquisition of the resultant γ-ray signals in a '4π' NaI(Tl) detector array of nine detectors. In this paper we describe a series of improvements to the method. This was investigated via measurement of hand simulating phantoms doped with varying levels of fluorine and fixed amounts of sodium, chlorine and calcium. Four improvements to the technique were tested since our first publication. The previously published detection limit for phantom measurements using this system was 0.66 mg F/g Ca. The accelerator irradiation and detection facilities were relocated to a new section of the laboratory and one more detector was added to the detection system. This was found to reduce the detection limit (possibly because of better detection shielding and additional detector) to 0.59 mg F/g Ca, a factor of 1.12. A new set of phantoms was developed and in this work we show that they improved the minimum detectable limit for fluoride in phantoms irradiated using neutrons produced by 2.15 MeV protons on lithium by a factor of 1.55. We compared the detection limits previously obtained using a summed signal from the nine detectors with the detection limit obtained by acquiring the spectra in anticoincidence mode for reduction of the disturbing signal from chlorine in bone. This was found to improve the ratio of the detection of fluorine to chlorine (an interfering signal) by a factor of 2.8 and the resultant minimum detection limit was found to be reduced by a factor of 1.2. We studied the effects of changing the timing of γ-ray acquisition. Our previously published data used a series of three 10 s acquisitions followed by a 300 s count. Changing the acquisition to a series of six 5 s acquisitions was found to further improve the detection limit by a factor of 1.4. We also present data showing that if the neutron dose is delivered to the phantom in a shorter time period, i.e. the dose rate is increased and irradiation shortened then the detection limit can be reduced by a further factor of 1.35.The overall improvement in detection limit by employing all of these changes was found to be a factor of 3.9. The technique now has an in phantom detection limit of 0.17 mg F/g Ca compared to a previous detection limit of 0.66 mg F/g Ca. The system can now be tested on human volunteers to see if individuals with diagnosed fluorosis can be distinguished from the general Canadian population using this technique.

Statistical behavior of ten million experimental detection limits

NASA Astrophysics Data System (ADS)

Voigtman, Edward; Abraham, Kevin T.

2011-02-01

Using a lab-constructed laser-excited fluorimeter, together with bootstrapping methodology, the authors have generated many millions of experimental linear calibration curves for the detection of rhodamine 6G tetrafluoroborate in ethanol solutions. The detection limits computed from them are in excellent agreement with both previously published theory and with comprehensive Monte Carlo computer simulations. Currie decision levels and Currie detection limits, each in the theoretical, chemical content domain, were found to be simply scaled reciprocals of the non-centrality parameter of the non-central t distribution that characterizes univariate linear calibration curves that have homoscedastic, additive Gaussian white noise. Accurate and precise estimates of the theoretical, content domain Currie detection limit for the experimental system, with 5% (each) probabilities of false positives and false negatives, are presented.

ON COMPUTING UPPER LIMITS TO SOURCE INTENSITIES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kashyap, Vinay L.; Siemiginowska, Aneta; Van Dyk, David A.

2010-08-10

A common problem in astrophysics is determining how bright a source could be and still not be detected in an observation. Despite the simplicity with which the problem can be stated, the solution involves complicated statistical issues that require careful analysis. In contrast to the more familiar confidence bound, this concept has never been formally analyzed, leading to a great variety of often ad hoc solutions. Here we formulate and describe the problem in a self-consistent manner. Detection significance is usually defined by the acceptable proportion of false positives (background fluctuations that are claimed as detections, or Type I error),more » and we invoke the complementary concept of false negatives (real sources that go undetected, or Type II error), based on the statistical power of a test, to compute an upper limit to the detectable source intensity. To determine the minimum intensity that a source must have for it to be detected, we first define a detection threshold and then compute the probabilities of detecting sources of various intensities at the given threshold. The intensity that corresponds to the specified Type II error probability defines that minimum intensity and is identified as the upper limit. Thus, an upper limit is a characteristic of the detection procedure rather than the strength of any particular source. It should not be confused with confidence intervals or other estimates of source intensity. This is particularly important given the large number of catalogs that are being generated from increasingly sensitive surveys. We discuss, with examples, the differences between these upper limits and confidence bounds. Both measures are useful quantities that should be reported in order to extract the most science from catalogs, though they answer different statistical questions: an upper bound describes an inference range on the source intensity, while an upper limit calibrates the detection process. We provide a recipe for computing upper limits that applies to all detection algorithms.« less

On the Determination of Uncertainty and Limit of Detection in Label-Free Biosensors.

PubMed

Lavín, Álvaro; Vicente, Jesús de; Holgado, Miguel; Laguna, María F; Casquel, Rafael; Santamaría, Beatriz; Maigler, María Victoria; Hernández, Ana L; Ramírez, Yolanda

2018-06-26

A significant amount of noteworthy articles reviewing different label-free biosensors are being published in the last years. Most of the times, the comparison among the different biosensors is limited by the procedure used of calculating the limit of detection and the measurement uncertainty. This article clarifies and establishes a simple procedure to determine the calibration function and the uncertainty of the concentration measured at any point of the measuring interval of a generic label-free biosensor. The value of the limit of detection arises naturally from this model as the limit at which uncertainty tends when the concentration tends to zero. The need to provide additional information, such as the measurement interval and its linearity, among others, on the analytical systems and biosensor in addition to the detection limit is pointed out. Finally, the model is applied to curves that are typically obtained in immunoassays and a discussion is made on the application validity of the model and its limitations.

Usefulness of real-time elastography strain ratio in the assessment of bile duct ligation-induced liver injury and the hepatoprotective effect of chitosan: an experimental animal study.

PubMed

Dudea, Marina; Clichici, Simona; Olteanu, Diana Elena; Nagy, Andras; Cucoş, Maria; Dudea, Sorin

2015-01-01

The purpose of the study described here was to evaluate the usefulness of the elastographic strain ratio in the assessment of liver changes in an experimental animal setting and the hepatoprotective effects of chitosan. Ultrasonography and Strain Ratio calculation were performed before and after bile duct ligation (BDL) in three groups of Wistar albino rats (n = 10 animals per group): (i) rats subjected to bile duct ligation only; (ii) rats subjected to bile duct ligation and administered chitosan for 14 d; (iii) rats subjected to bile duct ligation and administered chitosan for 7 d. The results were compared with the laboratory data and pathologic findings. Strain ratios revealed an increase in liver stiffness after bile duct ligation (p < 0.05), except in the group with chitosan administered for 7 d, and agreed with laboratory and pathology data. In conclusion, strain ratio can be used as an experimental research instrument in the assessment of liver response to injury. To the best of our knowledge, this is the first study reporting on the usefulness of the sonoelastographic liver-to-kidney strain ratio in assessing the effects of experimentally induced liver lesions. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Baicalin Ameliorates Experimental Liver Cholestasis in Mice by Modulation of Oxidative Stress, Inflammation, and NRF2 Transcription Factor

PubMed Central

Feng, Xiaowen; Zhang, Feng; Xie, Haiyang

2017-01-01

Experimental cholestatic liver fibrosis was performed by bile duct ligation (BDL) in mice, and significant liver injury was observed in 15 days. Administration of baicalin in mice significantly ameliorates liver fibrosis. Experimental cholestatic liver fibrosis was associated with induced gene expression of fibrotic markers such as collagen I, fibronectin, alpha smooth muscle actin (SMA), and connective tissue growth factor (CTGF); increased inflammatory cytokines (TNFα, MIP1α, IL1β, and MIP2); increased oxidative stress and reactive oxygen species- (ROS-) inducing enzymes (NOX2 and iNOS); dysfunctional mitochondrial electron chain complexes; and apoptotic/necrotic cell death markers (DNA fragmentation, caspase 3 activity, and PARP activity). Baicalin administration on alternate day reduced fibrosis along with profibrotic gene expression, proinflammatory cytokines, oxidative stress, and cell death whereas improving the function of mitochondrial electron transport chain. We observed baicalin enhanced NRF2 activation by nuclear translocation and induced its target genes HO-1 and GCLM, thus enhancing antioxidant defense. Interplay of oxidative stress/inflammation and NRF2 were key players for baicalin-mediated protection. Stellate cell activation is crucial for initiation of fibrosis. Baicalin alleviated stellate cell activation and modulated TIMP1, SMA, collagen 1, and fibronectin in vitro. This study indicates that baicalin might be beneficial for reducing inflammation and fibrosis in liver injury models. PMID:28757911

Quantum Limits of Space-to-Ground Optical Communications

NASA Technical Reports Server (NTRS)

Hemmati, H.; Dolinar, S.

2012-01-01

For a pure loss channel, the ultimate capacity can be achieved with classical coherent states (i.e., ideal laser light): (1) Capacity-achieving receiver (measurement) is yet to be determined. (2) Heterodyne detection approaches the ultimate capacity at high mean photon numbers. (3) Photon-counting approaches the ultimate capacity at low mean photon numbers. A number of current technology limits drive the achievable performance of free-space communication links. Approaching fundamental limits in the bandwidth-limited regime: (1) Heterodyne detection with high-order coherent-state modulation approaches ultimate limits. SOA improvements to laser phase noise, adaptive optics systems for atmospheric transmission would help. (2) High-order intensity modulation and photon-counting can approach heterodyne detection within approximately a factor of 2. This may have advantages over coherent detection in the presence of turbulence. Approaching fundamental limits in the photon-limited regime (1) Low-duty cycle binary coherent-state modulation (OOK, PPM) approaches ultimate limits. SOA improvements to laser extinction ratio, receiver dark noise, jitter, and blocking would help. (2) In some link geometries (near field links) number-state transmission could improve over coherent-state transmission

Detection of Nuclear Explosions Using Infrasound Techniques

DTIC Science & Technology

2007-12-01

signal correlation between array elements in these arrays can seriously limit the reliable detection of infrasound generated ...goals of this investigation are to identify problems with the detection of explosion- generated infrasonic signals at stations in the global infrasound ...restricted to a thermospheric waveguide. The second part is focused on the limitations imposed on array detection of explosion- generated infrasound

Man vs. Machine: A Junior-level Laboratory Exercise Comparing Human and Instrumental Detection Limits

ERIC Educational Resources Information Center

Elias, Ryan J.; Hopfer, Helene; Hofstaedter, Amanda N.; Hayes, John E.

2017-01-01

The human nose is a very sensitive detector and is able to detect potent aroma compounds down to low ng/L levels. These levels are often below detection limits of analytical instrumentation. The following laboratory exercise is designed to compare instrumental and human methods for the detection of volatile odor active compounds. Reference…

USE OF METHOD DETECTION LIMITS IN ENVIRONMENTAL MEASUREMENTS

EPA Science Inventory

Environmental measurements often produce values below the method detection limit (MDL). Because low or zero values may be used in determining compliance with regulatory limits, in determining emission factors (typical concentrations emitted by a given type of source), or in model...

Using personal glucose meters and functional DNA sensors to quantify a variety of analytical targets

PubMed Central

Xiang, Yu; Lu, Yi

2012-01-01

Portable, low-cost and quantitative detection of a broad range of targets at home and in the field has the potential to revolutionize medical diagnostics and environmental monitoring. Despite many years of research, very few such devices are commercially available. Taking advantage of the wide availability and low cost of the pocket-sized personal glucose meter—used worldwide by diabetes sufferers—we demonstrate a method to use such meters to quantify non-glucose targets, ranging from a recreational drug (cocaine, 3.4 μM detection limit) to an important biological cofactor (adenosine, 18 μM detection limit), to a disease marker (interferon-gamma of tuberculosis, 2.6 nM detection limit) and a toxic metal ion (uranium, 9.1 nM detection limit). The method is based on the target-induced release of invertase from a functional-DNA–invertase conjugate. The released invertase converts sucrose into glucose, which is detectable using the meter. The approach should be easily applicable to the detection of many other targets through the use of suitable functional-DNA partners (aptamers DNAzymes or aptazymes). PMID:21860458

Using personal glucose meters and functional DNA sensors to quantify a variety of analytical targets

NASA Astrophysics Data System (ADS)

Xiang, Yu; Lu, Yi

2011-09-01

Portable, low-cost and quantitative detection of a broad range of targets at home and in the field has the potential to revolutionize medical diagnostics and environmental monitoring. Despite many years of research, very few such devices are commercially available. Taking advantage of the wide availability and low cost of the pocket-sized personal glucose meter—used worldwide by diabetes sufferers—we demonstrate a method to use such meters to quantify non-glucose targets, ranging from a recreational drug (cocaine, 3.4 µM detection limit) to an important biological cofactor (adenosine, 18 µM detection limit), to a disease marker (interferon-gamma of tuberculosis, 2.6 nM detection limit) and a toxic metal ion (uranium, 9.1 nM detection limit). The method is based on the target-induced release of invertase from a functional-DNA-invertase conjugate. The released invertase converts sucrose into glucose, which is detectable using the meter. The approach should be easily applicable to the detection of many other targets through the use of suitable functional-DNA partners (aptamers, DNAzymes or aptazymes).

Detection limits of antimicrobials in ewe milk by delvotest photometric measurements.

PubMed

Althaus, R L; Torres, A; Montero, A; Balasch, S; Molina, M P

2003-02-01

The Delvotest method detection limits per manufacturer's instructions at a fixed reading time of 3 h for 24 antimicrobial agents were determined in ewe milk by photometric measurement. For each drug, eight concentrations were tested on 20 ewe milk samples from individual ewes. Detection limits, determined by means of logistic regression models, were (microg/kg): 3, amoxycillin; 2, ampicillin; 18, cloxacillin; 1, penicillin "G"; 34, cefadroxil; 430, cephalosporin "C"; 40, cephalexin; 20, cefoperazone; 33, Ceftiofur; 18, cefuroxime; 6100, streptomycin; 1200, gentamycin; 2600, neomycin; 830, erythromycin; 100, tylosin; 180, doxycycline; 320, oxytetracycline; 590, tetracycline; 88, sulfadiazine; 44, sulfamethoxazole; 140, sulfametoxypyridazine; 48, sulfaquinoxaline; 12,000, chloramphenicol; and 290, trimethoprim. Whereas the beta-lactam antibiotics, sulphonamides, and tylosin were detected by Delvotest method at levels equal to those of maximum residue limits, its sensitivity needs to be enhanced to detect aminoglycosides, tetracyclines, streptomycin, chloramphenicol, and trimethoprim residues in ewe milk or to develop an integrated residue detection system for ewe milk with different sensitive microorganisms for each group of antiinfectious agents.

40 CFR 63.7833 - How do I demonstrate continuous compliance with the emission limitations that apply to me?

Code of Federal Regulations, 2010 CFR

2010-07-01

... baghouse equipped with a bag leak detection system, operating and maintaining each bag leak detection... requirements. If you increase or decrease the sensitivity of the bag leak detection system beyond the limits... event of a bag leak detection system alarm or when the hourly average opacity exceeded 5 percent, the...

Censoring approach to the detection limits in X-ray fluorescence analysis

NASA Astrophysics Data System (ADS)

Pajek, M.; Kubala-Kukuś, A.

2004-10-01

We demonstrate that the effect of detection limits in the X-ray fluorescence analysis (XRF), which limits the determination of very low concentrations of trace elements and results in appearance of the so-called "nondetects", can be accounted for using the statistical concept of censoring. More precisely, the results of such measurements can be viewed as the left random censored data, which can further be analyzed using the Kaplan-Meier method correcting the data for the presence of nondetects. Using this approach, the results of measured, detection limit censored concentrations can be interpreted in a nonparametric manner including the correction for the nondetects, i.e. the measurements in which the concentrations were found to be below the actual detection limits. Moreover, using the Monte Carlo simulation technique we show that by using the Kaplan-Meier approach the corrected mean concentrations for a population of the samples can be estimated within a few percent uncertainties with respect of the simulated, uncensored data. This practically means that the final uncertainties of estimated mean values are limited in fact by the number of studied samples and not by the correction procedure itself. The discussed random-left censoring approach was applied to analyze the XRF detection-limit-censored concentration measurements of trace elements in biomedical samples.

True detection limits in an experimental linearly heteroscedastic system.. Part 2

NASA Astrophysics Data System (ADS)

Voigtman, Edward; Abraham, Kevin T.

2011-11-01

Despite much different processing of the experimental fluorescence detection data presented in Part 1, essentially the same estimates were obtained for the true theoretical Currie decision levels ( YC and XC) and true Currie detection limits ( YD and XD). The obtained experimental values, for 5% probability of false positives and 5% probability of false negatives, were YC = 56.0 mV, YD = 125. mV, XC = 0.132 μg/mL and XD = 0.293 μg/mL. For 5% probability of false positives and 1% probability of false negatives, the obtained detection limits were YD = 158 . mV and XD = 0.371 μg/mL. Furthermore, by using bootstrapping methodology on the experimental data for the standards and the analytical blank, it was possible to validate previously published experimental domain expressions for the decision levels ( yC and xC) and detection limits ( yD and xD). This was demonstrated by testing the generated decision levels and detection limits for their performance in regard to false positives and false negatives. In every case, the obtained numbers of false negatives and false positives were as specified a priori.

METHODS OF DEALING WITH VALUES BELOW THE LIMIT OF DETECTION USING SAS

EPA Science Inventory

Due to limitations of chemical analysis procedures, small concentrations cannot be precisely measured. These concentrations are said to be below the limit of detection (LOD). In statistical analyses, these values are often censored and substituted with a constant value, such ...

Detection limit used for early warning in public health surveillance.

PubMed

Kobari, Tsuyoshi; Iwaki, Kazuo; Nagashima, Tomomi; Ishii, Fumiyoshi; Hayashi, Yuzuru; Yajima, Takehiko

2009-06-01

A theory of detection limit, developed in analytical chemistry, is applied to public health surveillance to detect an outbreak of national emergencies such as natural disaster and bioterrorism. In this investigation, the influenza epidemic around the Tokyo area from 2003 to 2006 is taken as a model of normal and large-scale epidemics. The detection limit of the normal epidemic is used as a threshold with a specified level of significance to identify a sign of the abnormal epidemic among the daily variation in anti-influenza drug sales at community pharmacies. While auto-correlation of data is often an obstacle to an unbiased estimator of standard deviation involved in the detection limit, the analytical theory (FUMI) can successfully treat the auto-correlation of the drug sales in the same way as the auto-correlation appearing as 1/f noise in many analytical instruments.

Strategies and limitations for fluorescence detection of XAFS at high flux beamlines

DOE PAGES

Heald, Steve M.

2015-02-17

The issue of detecting the XAFS signal from dilute samples is discussed in detail with the aim of making best use of high flux beamlines that provide up to 10 13 photons -1. Various detection methods are compared, including filters with slits, solid state detectors, crystal analyzers and combinations of these. These comparisons rely on simulations that use experimentally determined parameters. It is found that inelastic scattering places a fundamental limit on detection, and that it is important to take proper account of the polarization dependence of the signals. The combination of a filter–slit system with a solid state detectormore » is a promising approach. With an optimized system good performance can be obtained even if the total count rate is limited to 10 7 Hz. Detection schemes with better energy resolution can help at the largest dilutions if their collection efficiency and count rate limits can be improved.« less

Strategies and limitations for fluorescence detection of XAFS at high flux beamlines

PubMed Central

Heald, Steve M.

2015-01-01

The issue of detecting the XAFS signal from dilute samples is discussed in detail with the aim of making best use of high flux beamlines that provide up to 1013 photons s−1. Various detection methods are compared, including filters with slits, solid state detectors, crystal analyzers and combinations of these. These comparisons rely on simulations that use experimentally determined parameters. It is found that inelastic scattering places a fundamental limit on detection, and that it is important to take proper account of the polarization dependence of the signals. The combination of a filter–slit system with a solid state detector is a promising approach. With an optimized system good performance can be obtained even if the total count rate is limited to 107 Hz. Detection schemes with better energy resolution can help at the largest dilutions if their collection efficiency and count rate limits can be improved. PMID:25723945

Quantum sensing of weak radio-frequency signals by pulsed Mollow absorption spectroscopy.

PubMed

Joas, T; Waeber, A M; Braunbeck, G; Reinhard, F

2017-10-17

Quantum sensors-qubits sensitive to external fields-have become powerful detectors for various small acoustic and electromagnetic fields. A major key to their success have been dynamical decoupling protocols which enhance sensitivity to weak oscillating (AC) signals. Currently, those methods are limited to signal frequencies below a few MHz. Here we harness a quantum-optical effect, the Mollow triplet splitting of a strongly driven two-level system, to overcome this limitation. We microscopically understand this effect as a pulsed dynamical decoupling protocol and find that it enables sensitive detection of fields close to the driven transition. Employing a nitrogen-vacancy center, we detect GHz microwave fields with a signal strength (Rabi frequency) below the current detection limit, which is set by the center's spectral linewidth [Formula: see text]. Pushing detection sensitivity to the much lower 1/T 2 limit, this scheme could enable various applications, most prominently coherent coupling to single phonons and microwave photons.Dynamical decoupling protocols can enhance the sensitivity of quantum sensors but this is limited to signal frequencies below a few MHz. Here, Joas et al. use the Mollow triplet splitting in a nitrogen-vacancy centre to overcome this limitation, enabling sensitive detection of signals in the GHz range.

Probabilistic pipe fracture evaluations for leak-rate-detection applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rahman, S.; Ghadiali, N.; Paul, D.

1995-04-01

Regulatory Guide 1.45, {open_quotes}Reactor Coolant Pressure Boundary Leakage Detection Systems,{close_quotes} was published by the U.S. Nuclear Regulatory Commission (NRC) in May 1973, and provides guidance on leak detection methods and system requirements for Light Water Reactors. Additionally, leak detection limits are specified in plant Technical Specifications and are different for Boiling Water Reactors (BWRs) and Pressurized Water Reactors (PWRs). These leak detection limits are also used in leak-before-break evaluations performed in accordance with Draft Standard Review Plan, Section 3.6.3, {open_quotes}Leak Before Break Evaluation Procedures{close_quotes} where a margin of 10 on the leak detection limit is used in determining the crackmore » size considered in subsequent fracture analyses. This study was requested by the NRC to: (1) evaluate the conditional failure probability for BWR and PWR piping for pipes that were leaking at the allowable leak detection limit, and (2) evaluate the margin of 10 to determine if it was unnecessarily large. A probabilistic approach was undertaken to conduct fracture evaluations of circumferentially cracked pipes for leak-rate-detection applications. Sixteen nuclear piping systems in BWR and PWR plants were analyzed to evaluate conditional failure probability and effects of crack-morphology variability on the current margins used in leak rate detection for leak-before-break.« less

A Nanocoaxial-Based Electrochemical Sensor for the Detection of Cholera Toxin

NASA Astrophysics Data System (ADS)

Archibald, Michelle M.; Rizal, Binod; Connolly, Timothy; Burns, Michael J.; Naughton, Michael J.; Chiles, Thomas C.

2015-03-01

Sensitive, real-time detection of biomarkers is of critical importance for rapid and accurate diagnosis of disease for point of care (POC) technologies. Current methods do not allow for POC applications due to several limitations, including sophisticated instrumentation, high reagent consumption, limited multiplexing capability, and cost. Here, we report a nanocoaxial-based electrochemical sensor for the detection of bacterial toxins using an electrochemical enzyme-linked immunosorbent assay (ELISA) and differential pulse voltammetry (DPV). Proof-of-concept was demonstrated for the detection of cholera toxin (CT). The linear dynamic range of detection was 10 ng/ml - 1 μg/ml, and the limit of detection (LOD) was found to be 2 ng/ml. This level of sensitivity is comparable to the standard optical ELISA used widely in clinical applications. In addition to matching the detection profile of the standard ELISA, the nanocoaxial array provides a simple electrochemical readout and a miniaturized platform with multiplexing capabilities for the simultaneous detection of multiple biomarkers, giving the nanocoax a desirable advantage over the standard method towards POC applications. Sensitive, real-time detection of biomarkers is of critical importance for rapid and accurate diagnosis of disease for point of care (POC) technologies. Current methods do not allow for POC applications due to several limitations, including sophisticated instrumentation, high reagent consumption, limited multiplexing capability, and cost. Here, we report a nanocoaxial-based electrochemical sensor for the detection of bacterial toxins using an electrochemical enzyme-linked immunosorbent assay (ELISA) and differential pulse voltammetry (DPV). Proof-of-concept was demonstrated for the detection of cholera toxin (CT). The linear dynamic range of detection was 10 ng/ml - 1 μg/ml, and the limit of detection (LOD) was found to be 2 ng/ml. This level of sensitivity is comparable to the standard optical ELISA used widely in clinical applications. In addition to matching the detection profile of the standard ELISA, the nanocoaxial array provides a simple electrochemical readout and a miniaturized platform with multiplexing capabilities for the simultaneous detection of multiple biomarkers, giving the nanocoax a desirable advantage over the standard method towards POC applications. This work was supported by the National Institutes of Health (National Cancer Institute award No. CA137681 and National Institute of Allergy and Infectious Diseases Award No. AI100216).

Theoretical detection limit of PIXE analysis using 20 MeV proton beams

NASA Astrophysics Data System (ADS)

Ishii, Keizo; Hitomi, Keitaro

2018-02-01

Particle-induced X-ray emission (PIXE) analysis is usually performed using proton beams with energies in the range 2∼3 MeV because at these energies, the detection limit is low. The detection limit of PIXE analysis depends on the X-ray production cross-section, the continuous background of the PIXE spectrum and the experimental parameters such as the beam currents and the solid angle and detector efficiency of X-ray detector. Though the continuous background increases as the projectile energy increases, the cross-section of the X-ray increases as well. Therefore, the detection limit of high energy proton PIXE is not expected to increase significantly. We calculated the cross sections of continuous X-rays produced in several bremsstrahlung processes and estimated the detection limit of a 20 MeV proton PIXE analysis by modelling the Compton tail of the γ-rays produced in the nuclear reactions, and the escape effect on the secondary electron bremsstrahlung. We found that the Compton tail does not affect the detection limit when a thin X-ray detector is used, but the secondary electron bremsstrahlung escape effect does have an impact. We also confirmed that the detection limit of the PIXE analysis, when used with 4 μm polyethylene backing film and an integrated beam current of 1 μC, is 0.4∼2.0 ppm for proton energies in the range 10∼30 MeV and elements with Z = 16-90. This result demonstrates the usefulness of several 10 MeV cyclotrons for performing PIXE analysis. Cyclotrons with these properties are currently installed in positron emission tomography (PET) centers.

Parametric Amplification For Detecting Weak Optical Signals

NASA Technical Reports Server (NTRS)

Hemmati, Hamid; Chen, Chien; Chakravarthi, Prakash

1996-01-01

Optical-communication receivers of proposed type implement high-sensitivity scheme of optical parametric amplification followed by direct detection for reception of extremely weak signals. Incorporates both optical parametric amplification and direct detection into optimized design enhancing effective signal-to-noise ratios during reception in photon-starved (photon-counting) regime. Eliminates need for complexity of heterodyne detection scheme and partly overcomes limitations imposed on older direct-detection schemes by noise generated in receivers and by limits on quantum efficiencies of photodetectors.

DEVELOPMENT OF AN INTEGRATED CELL CULTURE/RT-PCR METHOD FOR THE DETECTION OF ENTEROVIRUS IN WATER

EPA Science Inventory

Virus contamination in environmental samples is believed to be underestimated due to the limitations in the methods available for detection. A major detection method is based upon the formation of cytopathic effect (CPE) in cell culture. The main limitations to this method are ...

The limit of detection for explosives in spectroscopic differential reflectometry

NASA Astrophysics Data System (ADS)

Dubroca, Thierry; Vishwanathan, Karthik; Hummel, Rolf E.

2011-05-01

In the wake of recent terrorist attacks, such as the 2008 Mumbai hotel explosion or the December 25th 2009 "underwear bomber", our group has developed a technique (US patent #7368292) to apply differential reflection spectroscopy to detect traces of explosives. Briefly, light (200-500 nm) is shone on a surface such as a piece of luggage at an airport. Upon reflection, the light is collected with a spectrometer combined with a CCD camera. A computer processes the data and produces in turn a differential reflection spectrum involving two adjacent areas of the surface. This differential technique is highly sensitive and provides spectroscopic data of explosives. As an example, 2,4,6, trinitrotoluene (TNT) displays strong and distinct features in differential reflectograms near 420 nm. Similar, but distinctly different features are observed for other explosives. One of the most important criteria for explosive detection techniques is the limit of detection. This limit is defined as the amount of explosive material necessary to produce a signal to noise ratio of three. We present here, a method to evaluate the limit of detection of our technique. Finally, we present our sample preparation method and experimental set-up specifically developed to measure the limit of detection for our technology. This results in a limit ranging from 100 nano-grams to 50 micro-grams depending on the method and the set-up parameters used, such as the detector-sample distance.

Studying the effect of microwave heating on the digestion process and identification of proteins.

PubMed

Devi, Shobha; Wu, Bo-Hung; Chu, Pei-Yu; Liu, Yue-Pei; Wu, Hsin-Lin; Ho, Yen-Peng

2017-02-01

The impact of microwave irradiation on the in-solution digestion processes and the detection limit of proteins are systematically studied. Kinetic processes of many peptides produced through the trypsin digestion of various proteins under microwave heating at 50°C were investigated with MALDI-MS. This study also examines the detection limits and digestion completeness of individual proteins under microwave heating at 50°C and at different time intervals (1, 5 and 30 min) using LC-MS. We conclude that if the peptides without missed cleavage dictate the detection limit, conventional digestion will lead to a better detection limit. The detection limit may not differ between the microwave and conventional heating if the peptides with missed cleavage sites and strong intensity are formed at the very early stage (i.e., less than 1 min) and are not further digested throughout the entire digestion process. The digestion of Escherichia coli lysate was compared under conventional and short time (microwave) conditions. The number of proteins identified under conventional heating exceeded that obtained from microwave heating over heating periods less than 5 min. The overall results show that the microwave-assisted digestion is not complete. Although the sequence coverage might be better, the detection limit might be worse than that under conventional heating. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nonparametric rank regression for analyzing water quality concentration data with multiple detection limits.

PubMed

Fu, Liya; Wang, You-Gan

2011-02-15

Environmental data usually include measurements, such as water quality data, which fall below detection limits, because of limitations of the instruments or of certain analytical methods used. The fact that some responses are not detected needs to be properly taken into account in statistical analysis of such data. However, it is well-known that it is challenging to analyze a data set with detection limits, and we often have to rely on the traditional parametric methods or simple imputation methods. Distributional assumptions can lead to biased inference and justification of distributions is often not possible when the data are correlated and there is a large proportion of data below detection limits. The extent of bias is usually unknown. To draw valid conclusions and hence provide useful advice for environmental management authorities, it is essential to develop and apply an appropriate statistical methodology. This paper proposes rank-based procedures for analyzing non-normally distributed data collected at different sites over a period of time in the presence of multiple detection limits. To take account of temporal correlations within each site, we propose an optimal linear combination of estimating functions and apply the induced smoothing method to reduce the computational burden. Finally, we apply the proposed method to the water quality data collected at Susquehanna River Basin in United States of America, which clearly demonstrates the advantages of the rank regression models.

Calculation of the detection limit in radiation measurements with systematic uncertainties

NASA Astrophysics Data System (ADS)

Kirkpatrick, J. M.; Russ, W.; Venkataraman, R.; Young, B. M.

2015-06-01

The detection limit (LD) or Minimum Detectable Activity (MDA) is an a priori evaluation of assay sensitivity intended to quantify the suitability of an instrument or measurement arrangement for the needs of a given application. Traditional approaches as pioneered by Currie rely on Gaussian approximations to yield simple, closed-form solutions, and neglect the effects of systematic uncertainties in the instrument calibration. These approximations are applicable over a wide range of applications, but are of limited use in low-count applications, when high confidence values are required, or when systematic uncertainties are significant. One proposed modification to the Currie formulation attempts account for systematic uncertainties within a Gaussian framework. We have previously shown that this approach results in an approximation formula that works best only for small values of the relative systematic uncertainty, for which the modification of Currie's method is the least necessary, and that it significantly overestimates the detection limit or gives infinite or otherwise non-physical results for larger systematic uncertainties where such a correction would be the most useful. We have developed an alternative approach for calculating detection limits based on realistic statistical modeling of the counting distributions which accurately represents statistical and systematic uncertainties. Instead of a closed form solution, numerical and iterative methods are used to evaluate the result. Accurate detection limits can be obtained by this method for the general case.

Automatic rectum limit detection by anatomical markers correlation.

PubMed

Namías, R; D'Amato, J P; del Fresno, M; Vénere, M

2014-06-01

Several diseases take place at the end of the digestive system. Many of them can be diagnosed by means of different medical imaging modalities together with computer aided detection (CAD) systems. These CAD systems mainly focus on the complete segmentation of the digestive tube. However, the detection of limits between different sections could provide important information to these systems. In this paper we present an automatic method for detecting the rectum and sigmoid colon limit using a novel global curvature analysis over the centerline of the segmented digestive tube in different imaging modalities. The results are compared with the gold standard rectum upper limit through a validation scheme comprising two different anatomical markers: the third sacral vertebra and the average rectum length. Experimental results in both magnetic resonance imaging (MRI) and computed tomography colonography (CTC) acquisitions show the efficacy of the proposed strategy in automatic detection of rectum limits. The method is intended for application to the rectum segmentation in MRI for geometrical modeling and as contextual information source in virtual colonoscopies and CAD systems. Copyright © 2014 Elsevier Ltd. All rights reserved.

The detection limits of antimicrobial agents in cow's milk by a simple Yoghurt Culture Test.

PubMed

Mohsenzadeh, M; Bahrainipour, A

2008-09-15

The aim of this study was to study performance of Yoghurt Culture Test (YCT) in the detection of antimicrobial residues in milk. For this purpose, the sensitivity of YCT for 15 antibiotics were determined. For each drug, 8 concentrations were tested. The detection limits of YCT at 2.5 h and 4 h incubation were determined (microg kg(-1)): 15 and 37.5, penicillin G; 4 and 5, ampicillin; 5 and 7.5, amoxycillin; 100 and 200, cephalexin; 80 and 100, cefazoline; 100 and 200, oxytetracycline; 500 and 100, chlortetracycline; 100 and 200, tetracycline; 150 and 200, doxycycline; 200 and 400, sulphadimidine; 500 and 1000, gentamycin; 1000 and 1500, spectinomycin; 400 and 500, erythromycin; 50 and 100, tylosin; 5000 and 10000, chloramphenicol. The YCT detection limits at 2.5 h incubation for ampicillin, cephalexin, tetracycline, oxytetracycline and tylosin are similar to those obtained as Maximum Residue Limit (MRL) according to Regulation 2377/90 EEC as set out by the European Union. In addition the detection limits of YCT for some antibiotics were lower than some of microbial inhibitor test.

Magnetic bead-quantum dot assay for detection of a biomarker for traumatic brain injury

NASA Astrophysics Data System (ADS)

Kim, Chloe; Searson, Peter C.

2015-10-01

Current diagnostic methods for traumatic brain injury (TBI), which accounts for 15% of all emergency room visits, are limited to neuroimaging modalities. The challenges of accurate diagnosis and monitoring of TBI have created the need for a simple and sensitive blood test to detect brain-specific biomarkers. Here we report on an assay for detection of S100B, a putative biomarker for TBI, using antibody-conjugated magnetic beads for capture of the protein, and antibody-conjugated quantum dots for optical detection. From Western Blot, we show efficient antigen capture and concentration by the magnetic beads. Using magnetic bead capture and quantum dot detection in serum samples, we show a wide detection range and detection limit below the clinical cut-off level.Current diagnostic methods for traumatic brain injury (TBI), which accounts for 15% of all emergency room visits, are limited to neuroimaging modalities. The challenges of accurate diagnosis and monitoring of TBI have created the need for a simple and sensitive blood test to detect brain-specific biomarkers. Here we report on an assay for detection of S100B, a putative biomarker for TBI, using antibody-conjugated magnetic beads for capture of the protein, and antibody-conjugated quantum dots for optical detection. From Western Blot, we show efficient antigen capture and concentration by the magnetic beads. Using magnetic bead capture and quantum dot detection in serum samples, we show a wide detection range and detection limit below the clinical cut-off level. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr05608j

Estimating the resolution limit of the map equation in community detection

NASA Astrophysics Data System (ADS)

Kawamoto, Tatsuro; Rosvall, Martin

2015-01-01

A community detection algorithm is considered to have a resolution limit if the scale of the smallest modules that can be resolved depends on the size of the analyzed subnetwork. The resolution limit is known to prevent some community detection algorithms from accurately identifying the modular structure of a network. In fact, any global objective function for measuring the quality of a two-level assignment of nodes into modules must have some sort of resolution limit or an external resolution parameter. However, it is yet unknown how the resolution limit affects the so-called map equation, which is known to be an efficient objective function for community detection. We derive an analytical estimate and conclude that the resolution limit of the map equation is set by the total number of links between modules instead of the total number of links in the full network as for modularity. This mechanism makes the resolution limit much less restrictive for the map equation than for modularity; in practice, it is orders of magnitudes smaller. Furthermore, we argue that the effect of the resolution limit often results from shoehorning multilevel modular structures into two-level descriptions. As we show, the hierarchical map equation effectively eliminates the resolution limit for networks with nested multilevel modular structures.

METHODS OF DEALING WITH VALUES BELOW THE LIMIT OF DETECTION USING SAS

EPA Science Inventory

Due to limitations of chemical analysis procedures, small values cannot be precisely measured. These values are said to be below the limit of detection (LOD). In statistical analyses, these values are often censored and substituted with a constant value, such as half the LOD,...

Fundamentals of Counting Statistics in Digital PCR: I Just Measured Two Target Copies-What Does It Mean?

PubMed

Tzonev, Svilen

2018-01-01

Current commercially available digital PCR (dPCR) systems and assays are capable of detecting individual target molecules with considerable reliability. As tests are developed and validated for use on clinical samples, the need to understand and develop robust statistical analysis routines increases. This chapter covers the fundamental processes and limitations of detecting and reporting on single molecule detection. We cover the basics of quantification of targets and sources of imprecision. We describe the basic test concepts: sensitivity, specificity, limit of blank, limit of detection, and limit of quantification in the context of dPCR. We provide basic guidelines how to determine those, how to choose and interpret the operating point, and what factors may influence overall test performance in practice.

Prediction of the limit of detection of an optical resonant reflection biosensor.

PubMed

Hong, Jongcheol; Kim, Kyung-Hyun; Shin, Jae-Heon; Huh, Chul; Sung, Gun Yong

2007-07-09

A prediction of the limit of detection of an optical resonant reflection biosensor is presented. An optical resonant reflection biosensor using a guided-mode resonance filter is one of the most promising label-free optical immunosensors due to a sharp reflectance peak and a high sensitivity to the changes of optical path length. We have simulated this type of biosensor using rigorous coupled wave theory to calculate the limit of detection of the thickness of the target protein layer. Theoretically, our biosensor has an estimated ability to detect thickness change approximately the size of typical antigen proteins. We have also investigated the effects of the absorption and divergence of the incident light on the detection ability of the biosensor.

A Comprehensive Assessment of Biologicals Contained Within Commercial Airliner Cabin Air

NASA Technical Reports Server (NTRS)

LaDuc, Myron T.; Osman, Shariff; Dekas, Anne; Stuecker, Tara; Newcombe, Dave; Piceno, Yvette; Fuhrman, J.; Andersen, Gary; Venkateswaran, Kasthuri; Bearman, Greg

2006-01-01

Both culture-based and culture-independent, biomarker-targeted microbial enumeration and identification technologies were employed to estimate total microbial and viral burden and diversity within the cabin air of commercial airliners. Samples from each of twenty flights spanning three commercial carriers were collected via air-impingement. When the total viable microbial population was estimated by assaying relative concentrations of the universal energy carrier ATP, values ranged from below detection limits (BDL) to 4.1 x 106 cells/cubic m of air. The total viable microbial population was extremely low in both of Airline A (approximately 10% samples) and C (approximately 18% samples) compared to the samples collected aboard flights on Airline A and B (approximately 70% samples). When samples were collected as a function of time over the course of flights, a gradual accumulation of microbes was observed from the time of passenger boarding through mid-flight, followed by a sharp decline in microbial abundance and viability from the initiation of descent through landing. It is concluded in this study that only 10% of the viable microbes of the cabin air were cultivable and suggested a need to employ state-of-the art molecular assay that measures both cultivable and viable-but-non-cultivable microbes. Among the cultivable bacteria, colonies of Acinetobacter sp. were by far the most profuse in Phase I, and Gram-positive bacteria of the genera Staphylococcus and Bacillus were the most abundant during Phase II. The isolation of the human pathogens Acinetobacter johnsonii, A. calcoaceticus, Janibacter melonis, Microbacterium trichotecenolyticum, Massilia timonae, Staphylococcus saprophyticus, Corynebacterium lipophiloflavum is concerning, as these bacteria can cause meningitis, septicemia, and a handful of sometimes fatal diseases and infections. Molecular microbial community analyses exhibited presence of the alpha-, beta-, gamma-, and delta- proteobacteria, as well as Gram-positive bacteria, Fusobacteria, Cyanobacteria, Deinococci, Bacterioidetes, Spirochetes, and Planctomyces in varying abundance. Neisseria meningitidis rDNA sequences were retrieved in great abundance from Airline A followed by Streptococcus oralis/mitis sequences. Pseudomonas synxantha sequences dominated Airline B clone libraries, followed by those of N. meningitidis and S. oralis/mitis. In Phase II, Airline C, sequences representative of more than 113 species, enveloping 12 classes of bacteria, were retrieved. Proteobacterial sequences were retrieved in greatest frequency (58% of all clone sequences), followed in short order by those stemming from Gram-positives bacteria (31% of all clone sequences). As for overall phylogenetic breadth, Gram-positive and alpha-proteobacteria seem to have a higher affinity for international flights, whereas beta-and gamma-proteobacteria are far more common about domestic cabin air parcels in Airline C samples. Ultimately, the majority of microbial species circulating throughout the cabin airs of commercial airliners are commensal, infrequently pathogenic normal flora of the human nasopharynx and respiratory system. Many of these microbes likely originate from the oral and nasal cavities, and lungs of passengers and flight crew and are disseminated unknowingly via routine conversation, coughing, sneezing, and stochastic passing of fomites. The data documented in this study will be useful to generate a baseline microbial population database and can be utilized to develop biosensor instrumentation for monitoring microbial quality of cabin or urban air.

Theoretical limitations of quantification for noncompetitive sandwich immunoassays.

PubMed

Woolley, Christine F; Hayes, Mark A; Mahanti, Prasun; Douglass Gilman, S; Taylor, Tom

2015-11-01

Immunoassays exploit the highly selective interaction between antibodies and antigens to provide a vital method for biomolecule detection at low concentrations. Developers and practitioners of immunoassays have long known that non-specific binding often restricts immunoassay limits of quantification (LOQs). Aside from non-specific binding, most efforts by analytical chemists to reduce the LOQ for these techniques have focused on improving the signal amplification methods and minimizing the limitations of the detection system. However, with detection technology now capable of sensing single-fluorescence molecules, this approach is unlikely to lead to dramatic improvements in the future. Here, fundamental interactions based on the law of mass action are analytically connected to signal generation, replacing the four- and five-parameter fittings commercially used to approximate sigmoidal immunoassay curves and allowing quantitative consideration of non-specific binding and statistical limitations in order to understand the ultimate detection capabilities of immunoassays. The restrictions imposed on limits of quantification by instrumental noise, non-specific binding, and counting statistics are discussed based on equilibrium relations for a sandwich immunoassay. Understanding the maximal capabilities of immunoassays for each of these regimes can greatly assist in the development and evaluation of immunoassay platforms. While many studies suggest that single molecule detection is possible through immunoassay techniques, here, it is demonstrated that the fundamental limit of quantification (precision of 10 % or better) for an immunoassay is approximately 131 molecules and this limit is based on fundamental and unavoidable statistical limitations.

Stripping analysis of nanomolar perchlorate in drinking water with a voltammetric ion-selective electrode based on thin-layer liquid membrane.

PubMed

Kim, Yushin; Amemiya, Shigeru

2008-08-01

A highly sensitive analytical method is required for the assessment of nanomolar perchlorate contamination in drinking water as an emerging environmental problem. We developed the novel approach based on a voltammetric ion-selective electrode to enable the electrochemical detection of "redox-inactive" perchlorate at a nanomolar level without its electrolysis. The perchlorate-selective electrode is based on the submicrometer-thick plasticized poly(vinyl chloride) membrane spin-coated on the poly(3-octylthiophene)-modified gold electrode. The liquid membrane serves as the first thin-layer cell for ion-transfer stripping voltammetry to give low detection limits of 0.2-0.5 nM perchlorate in deionized water, commercial bottled water, and tap water under a rotating electrode configuration. The detection limits are not only much lower than the action limit (approximately 246 nM) set by the U.S. Environmental Protection Agency but also are comparable to the detection limits of the most sensitive analytical methods for detecting perchlorate, that is, ion chromatography coupled with a suppressed conductivity detector (0.55 nM) or electrospray ionization mass spectrometry (0.20-0.25 nM). The mass transfer of perchlorate in the thin-layer liquid membrane and aqueous sample as well as its transfer at the interface between the two phases were studied experimentally and theoretically to achieve the low detection limits. The advantages of ion-transfer stripping voltammetry with a thin-layer liquid membrane against traditional ion-selective potentiometry are demonstrated in terms of a detection limit, a response time, and selectivity.

Distributed gas sensing with optical fibre photothermal interferometry.

PubMed

Lin, Yuechuan; Liu, Fei; He, Xiangge; Jin, Wei; Zhang, Min; Yang, Fan; Ho, Hoi Lut; Tan, Yanzhen; Gu, Lijuan

2017-12-11

We report the first distributed optical fibre trace-gas detection system based on photothermal interferometry (PTI) in a hollow-core photonic bandgap fibre (HC-PBF). Absorption of a modulated pump propagating in the gas-filled HC-PBF generates distributed phase modulation along the fibre, which is detected by a dual-pulse heterodyne phase-sensitive optical time-domain reflectometry (OTDR) system. Quasi-distributed sensing experiment with two 28-meter-long HC-PBF sensing sections connected by single-mode transmission fibres demonstrated a limit of detection (LOD) of ∼10 ppb acetylene with a pump power level of 55 mW and an effective noise bandwidth (ENBW) of 0.01 Hz, corresponding to a normalized detection limit of 5.5ppb⋅W/Hz. Distributed sensing experiment over a 200-meter-long sensing cable made of serially connected HC-PBFs demonstrated a LOD of ∼ 5 ppm with 62.5 mW peak pump power and 11.8 Hz ENBW, or a normalized detection limit of 312ppb⋅W/Hz. The spatial resolution of the current distributed detection system is limited to ∼ 30 m, but it is possible to reduce down to 1 meter or smaller by optimizing the phase detection system.

A simple and highly sensitive colorimetric detection method for gaseous formaldehyde.

PubMed

Feng, Liang; Musto, Christopher J; Suslick, Kenneth S

2010-03-31

A colorimetric detection method using amine-functionalized polymer films doped with a pH indicator has been developed for the rapid, sensitive, and quantitative detection of gaseous formaldehyde at concentrations well below the immediately dangerous to life or health (IDLH) limit. In 1 min, visible color changes are easily observed, even down to the permissible exposure limit (PEL) at 750 ppb. The limit of detection is below 50 ppb (7% of the PEL) after 10 min of exposure. This sensor is essentially unaffected by changes in humidity or temperature (4 to 50 degrees C) and is not sensitive to common interferents.

New improvements in methane detection using a Helmholtz resonant photoacoustic laser sensor: a comparison between near-IR diode lasers and mid-IR quantum cascade lasers.

PubMed

Grossel, Agnès; Zeninari, Virginie; Joly, Lilian; Parvitte, Bertrand; Courtois, Daniel; Durry, Georges

2006-04-01

Atmospheric methane was detected by combining a photoacoustic (PA) sensor with several lasers emitting in both the near- and mid-infrared spectral ranges to check the achievable detection limits. The PA spectrometer is based on differential Helmholtz resonance. Near-infrared telecommunication-type laser diodes of increasing power, from Sensors Unlimited Inc. and Anritsu, were first used to scan the 2 nu(3) band of CH(4) near 1.65 microm. The best achieved detection limit is 0.15 ppm of methane at atmospheric pressure and with a 1s integration time. The PA sensor was then operated in conjunction with a quantum cascade laser from Alpes Lasers emitting near 7.9 microm on the nu(4) band of CH(4). The achieved detection limit is then of 3 ppb. The dramatic improvement in the detection limit obtained with the QC laser is due to the stronger optical power as well as to the capability of reaching the fundamental bands of methane lying in the mid-infrared spectral range.

First Detected Arrival of a Quantum Walker on an Infinite Line

NASA Astrophysics Data System (ADS)

Thiel, Felix; Barkai, Eli; Kessler, David A.

2018-01-01

The first detection of a quantum particle on a graph is shown to depend sensitively on the distance ξ between the detector and initial location of the particle, and on the sampling time τ . Here, we use the recently introduced quantum renewal equation to investigate the statistics of first detection on an infinite line, using a tight-binding lattice Hamiltonian with nearest-neighbor hops. Universal features of the first detection probability are uncovered and simple limiting cases are analyzed. These include the large ξ limit, the small τ limit, and the power law decay with the attempt number of the detection probability over which quantum oscillations are superimposed. For large ξ the first detection probability assumes a scaling form and when the sampling time is equal to the inverse of the energy band width nonanalytical behaviors arise, accompanied by a transition in the statistics. The maximum total detection probability is found to occur for τ close to this transition point. When the initial location of the particle is far from the detection node we find that the total detection probability attains a finite value that is distance independent.

Gold nanoparticle-based low limit of detection Love wave biosensor for carcinoembryonic antigens.

PubMed

Li, Shuangming; Wan, Ying; Su, Yan; Fan, Chunhai; Bhethanabotla, Venkat R

2017-09-15

In this work, a Love wave biosensing platform is described for detecting cancer-related biomarker carcinoembryonic antigen (CEA). An ST 90°-X quartz Love wave device with a layer of SiO 2 waveguide was combined with gold nanoparticles (Au NPs) to amplify the mass loading effect of the acoustic wave sensor to achieve a limit of detection of 37pg/mL. The strategy involves modifying the Au NPs with anti-CEA antibody conjugates to form nanoprobes in a sandwich immunoassay. The unamplified detection limit of the Love wave biosensor is 9.4ng/mL. This 2-3 order of magnitude reduction in the limit of detection brings the SAW platform into the range useful for clinical diagnosis. Measurement electronics and microfluidics are easily constructed for acoustic wave biosensors, such as the Love wave device described here, allowing for robust platforms for point of care applications for cancer biomarkers in general. Copyright © 2017 Elsevier B.V. All rights reserved.

True detection limits in an experimental linearly heteroscedastic system. Part 1

NASA Astrophysics Data System (ADS)

Voigtman, Edward; Abraham, Kevin T.

2011-11-01

Using a lab-constructed laser-excited filter fluorimeter deliberately designed to exhibit linearly heteroscedastic, additive Gaussian noise, it has been shown that accurate estimates may be made of the true theoretical Currie decision levels ( YC and XC) and true Currie detection limits ( YD and XD) for the detection of rhodamine 6 G tetrafluoroborate in ethanol. The obtained experimental values, for 5% probability of false positives and 5% probability of false negatives, were YC = 56.1 mV, YD = 125. mV, XC = 0.132 μg /mL and XD = 0.294 μg /mL. For 5% probability of false positives and 1% probability of false negatives, the obtained detection limits were YD = 158. mV and XD = 0.372 μg /mL. These decision levels and corresponding detection limits were shown to pass the ultimate test: they resulted in observed probabilities of false positives and false negatives that were statistically equivalent to the a priori specified values.

Upper limits on the rates of BNS and NSBH mergers from Advanced LIGO's first observing run

NASA Astrophysics Data System (ADS)

Lackey, Benjamin; LIGO Collaboration

2017-01-01

Last year the Advanced LIGO detectors finished their first observing run and detected two binary black hole mergers with high significance but no binary neutron star (BNS) or neutron-star-black-hole (NSBH) mergers. We present upper limits on the rates of BNS and NSBH mergers in the universe based on their non-detection with two modeled searches. With zero detections, the upper limits depend on the choice of prior, but we find 90% upper limits using a conservative prior of 12 , 000 / Gpc3 / yr for BNS mergers and 1 , 000 - 3 , 000 / Gpc3 / yr for NSBH mergers depending on the black hole mass. Comparing these upper limits to several rates predictions in the literature, we find our upper limits are close to the more optimistic rates estimates. Further non-detections in the second and third observing runs should be able to rule out several rates predictions. Using the observed rate of short gamma ray bursts (GRBs), we can also place lower limits on the average beaming angle of short GRBs. Assuming all short GRBs come from BNS mergers, we find a 90% lower limit of 1-4 degrees on the GRB beaming angle, with the range coming from the uncertainty in short GRB rates.

Two-dimensional on-line detection of brominated and iodinated volatile organic compounds by ECD and ICP-MS after GC separation.

PubMed

Schwarz, A; Heumann, K G

2002-09-01

Inductively coupled plasma-mass spectrometry (ICP-MS) was coupled to a gas chromatographic (GC) system with electron capture detector (ECD), which enables relatively easy characterization and quantification of brominated and iodinated (halogenated) volatile organic compounds (HVOCs) in aquatic and air samples. The GC-ECD system is connected in series with an ICP-MS by a directly heated transfer line and an outlet port-hole for elimination of the ECD make-up gas during ignition of the plasma. The hyphenated GC-ECD/ICP-MS system provides high selectivity and sensitivity for monitoring individual HVOCs under fast chromatographic conditions. The ECD is most sensitive for the detection of chlorinated and brominated but the ICP-MS for iodinated compounds. The greatest advantage of the use of an ICP-MS is its element-specific detection, which allows clear identification of compounds in most cases. The absolute detection limits for ICP-MS are 0.5 pg for iodinated, 10 pg for brominated, and 50 pg for chlorinated HVOCs with the additional advantage that calibration is almost independent on different compounds of the same halogen. In contrast to that detection limits for ECD vary for the different halogenated compounds and lie in the range of 0.03-11 pg. The two-dimensional GC-ECD/ICP-MS instrumentation is compared with electron impact mass spectrometry (EI-MS) and microwave induced plasma atomic emission detection (MIP-AED). Even if EI-MS has additional power in identifying unknown peaks by its scan mode, the detection limits are much higher compared with GC-ECD/ICP-MS, whereas the selective ion monitoring mode (SIM) reaches similar detection limits. The MIP-AED detection limits are at the same level as EI-MS in the scan mode.

Direct questioning is more effective than patient-initiated report for the detection of sexually transmitted infections in a primary care HIV clinic in Western Kenya.

PubMed

Woo, Victoria Gah Hay; Cohen, Craig R; Bukusi, Elizabeth A; Huchko, Megan J

2013-02-01

In resource-limited settings, detection of sexually transmitted infections (STIs) often relies on self-reported symptoms to initiate management. We found self-report demonstrated poor sensitivity for STI detection. Adding clinician-initiated questions about symptoms improved detection rates. Vaginal examination further increased sensitivity. Including clinician-initiated screening in resource-limited settings would improve management of treatable STIs.

Evaluating 6 ricin field detection assays.

PubMed

Slotved, Hans-Christian; Sparding, Nadja; Tanassi, Julia Tanas; Steenhard, Nina R; Heegaard, Niels H H

2014-01-01

This study presents data showing the performance of 6 commercial detection assays against ricin around concentrations specified as detection limits by the producers. A 2-fold dilution series of 20 ng/ml ricin was prepared and used for testing the lateral-flow kits: BADD, Pro Strips™, ENVI, RAID DX, Ricin BioThreat Alert, and IMASS™ device. Three of the 6 tested field assays (IMASS™ device, ENVI assay, and the BioThreat Alert assay) were able to detect ricin, although differences in the measured detection limits compared to the official detection limits and false-negative results were observed. We were not able to get the BADD, Pro Strips™, and RAID assays to function in our laboratory. We conclude that when purchasing a field responder assay, there is large variation in the specificity of the assays, and a number of in-house tests must be performed to ensure functionality.

Field-effect amperometric immuno-detection of protein biomarker.

PubMed

Wang, Jiapeng; Yau, Siu-Tung

2011-11-15

The field-effect enzymatic detection technique has been applied to the amperometric immunoassay of the cancer biomarker, carcinoma antigen 125 (CA 125). The detection adopted a reagentless approach, in which the analyte, CA 125, was immobilized on the detecting electrode, which was modified using carbon nanotubes, and the detection signal was obtained by measuring the reduction peak current of the enzyme that was used to label the antibody. A gating voltage was applied to the detecting electrode, inducing increase in the signal current and therefore providing amplification of the detection signal. The voltage-controlled signal amplification of the detection system has increased the sensitivity and lowered the detection limit of the system. A detection limit of 0.9U/ml was obtained in the work. Copyright © 2011 Elsevier B.V. All rights reserved.

Detection limit of Mycobacterium chimaera in water samples for monitoring medical device safety: insights from a pilot experimental series.

PubMed

Schreiber, P W; Köhler, N; Cervera, R; Hasse, B; Sax, H; Keller, P M

2018-07-01

A growing number of Mycobacterium chimaera infections after cardiosurgery have been reported by several countries. These potentially fatal infections were traced back to contaminated heater-cooler devices (HCDs), which use water as a heat transfer medium. Aerosolization of water contaminated with M. chimaera from HCDs enables airborne transmission to patients undergoing open chest surgery. Infection control teams test HCD water samples for mycobacterial growth to guide preventive measures. The detection limit of M. chimaera in water samples, however, has not previously been investigated. To determine the detection limit of M. chimaera in water samples using laboratory-based serial dilution tests. An M. chimaera strain representative of the international cardiosurgery-associated M. chimaera outbreak was used to generate a logarithmic dilution series. Two different water volumes, 50 and 1000mL, were inoculated, and, after identical processing (centrifugation, decantation, and decontamination), seeded on mycobacteria growth indicator tube (MGIT) and Middlebrook 7H11 solid media. MGIT consistently showed a lower detection limit than 7H11 solid media, corresponding to a detection limit of ≥1.44 × 10 4 cfu/mL for 50mL and ≥2.4cfu/mL for 1000mL water samples. Solid media failed to detect M. chimaera in 50mL water samples. Depending on water volume and culture method, major differences exist in the detection limit of M. chimaera. In terms of sensitivity, 1000mL water samples in MGIT media performed best. Our results have important implications for infection prevention and control strategies in mitigation of the M. chimaera outbreak and healthcare water safety in general. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Quaternary ammonium promoted ultra selective and sensitive fluorescence detection of fluoride ion in water and living cells.

PubMed

Li, Long; Ji, Yuzhuo; Tang, Xinjing

2014-10-21

Highly selective and sensitive fluorescent probes with a quaternary ammonium moiety have been rationally designed and developed for fast and sensitive fluorescence detection of fluoride ion (F(-) from NaF, not TBAF) in aqueous solution and living cells. With the sequestration effect of quaternary ammonium, the detection time was less than 2 min and the detection limit of fluoride ion was as low as 0.57 ppm that is among the lowest detection limits in aqueous solutions of many fluoride fluorescence probes in the literature.

Highly selective luminescent sensing of picric acid based on a water-stable europium metal-organic framework

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xia, Tifeng; Zhu, Fengliang; Cui, Yuanjing, E-mail: cuiyj@zju.edu.cn

A water-stable metal-organic framework (MOF) EuNDC has been synthesized for selective detection of the well-known contaminant and toxicant picric acid (PA) in aqueous solution. Due to the photo-induced electron transfer and self-absorption mechanism, EuNDC displayed rapid, selective and sensitive detection of PA with a detection limit of 37.6 ppb. Recyclability experiments revealed that EuNDC retains its initial luminescent intensity and same quenching efficiency in each cycle, suggesting high photostability and reusability for long-term sensing applications. The excellent detection performance of EuNDC makes it a promising PA sensing material for practical applications. - Graphical abstract: A water-stable europium-based metal-organic framework hasmore » been reported for highly selective sensing of picric acid (PA) with a detection limit of 37.6 ppb in aqueous solution. - Highlights: • A water-stable metal-organic framework (MOF) EuNDC was synthesized. • The highly selective detection of picric acid with a detection limit of 37.6 ppb was realized. • The detection mechanism were also presented and discussed.« less

Detection of β-Lactams and Chloramphenicol Residues in Raw Milk-Development and Application of an HPLC-DAD Method in Comparison with Microbial Inhibition Assays.

PubMed

Karageorgou, Eftychia; Christoforidou, Sofia; Ioannidou, Maria; Psomas, Evdoxios; Samouris, Georgios

2018-06-01

The present study was carried out to assess the detection sensitivity of four microbial inhibition assays (MIAs) in comparison with the results obtained by the High Performance Liquid Chromatography with Diode-Array Detection (HPLC-DAD) method for antibiotics of the β-lactam group and chloramphenicol in fortified raw milk samples. MIAs presented fairly good results when detecting β-lactams, whereas none were able to detect chloramphenicol at or above the permissible limits. HPLC analysis revealed high recoveries of examined compounds, whereas all detection limits observed were lower than their respective maximum residue limits (MRL) values. The extraction and clean-up procedure of antibiotics was performed by a modified matrix solid phase dispersion procedure using a mixture of Plexa by Agilent and QuEChERS as a sorbent. The HPLC method developed was validated, determining the accuracy, precision, linearity, decision limit, and detection capability. Both methods were used to monitor raw milk samples of several cows and sheep, obtained from producers in different regions of Greece, for the presence of examined antibiotic residues. Results obtained showed that MIAs could be used effectively and routinely to detect antibiotic residues in several milk types. However, in some cases, spoilage of milk samples revealed that the kits' sensitivity could be strongly affected, whereas this fact does not affect the effectiveness of HPLC-DAD analysis.

Peripheral detection and resolution with mid-/long-wavelength and short-wavelength sensitive cone systems.

PubMed

Zhu, Hai-Feng; Zele, Andrew J; Suheimat, Marwan; Lambert, Andrew J; Atchison, David A

2016-08-01

This study compared neural resolution and detection limits of the human mid-/long-wavelength and short-wavelength cone systems with anatomical estimates of photoreceptor and retinal ganglion cell spacings and sizes. Detection and resolution limits were measured from central fixation out to 35° eccentricity across the horizontal visual field using a modified Lotmar interferometer. The mid-/long-wavelength cone system was studied using a green (550 nm) test stimulus to which S-cones have low sensitivity. To bias resolution and detection to the short-wavelength cone system, a blue (450 nm) test stimulus was presented against a bright yellow background that desensitized the M- and L-cones. Participants were three trichromatic males with normal visual functions. With green stimuli, resolution showed a steep central-peripheral gradient that was similar between participants, whereas the detection gradient was shallower and patterns were different between participants. Detection and resolution with blue stimuli were poorer than for green stimuli. The detection of blue stimuli was superior to resolution across the horizontal visual field and the patterns were different between participants. The mid-/long-wavelength cone system's resolution is limited by midget ganglion cell spacing and its detection is limited by the size of the M- and L-cone photoreceptors, consistent with previous observations. We found that no such simple relationships occur for the short-wavelength cone system between resolution and the bistratified ganglion cell spacing, nor between detection and the S-cone photoreceptor sizes.

Photoionization of environmentally polluting aromatic chlorides and nitrides on the water surface by laser and synchrotron radiations.

PubMed

Sato, Miki; Maeda, Yuki; Ishioka, Toshio; Harata, Akira

2017-11-20

The detection limits and photoionization thresholds of polycyclic aromatic hydrocarbons and their chlorides and nitrides on the water surface are examined using laser two-photon ionization and single-photon ionization, respectively. The laser two-photon ionization methods are highly surface-selective, with a high sensitivity for aromatic hydrocarbons tending to accumulate on the water surface in the natural environment due to their highly hydrophobic nature. The dependence of the detection limits of target aromatic molecules on their physicochemical properties (photoionization thresholds relating to excess energy, molar absorptivity, and the octanol-water partition coefficient) is discussed. The detection limit clearly depends on the product of the octanol-water partition coefficient and molar absorptivity, and no clear dependence was found on excess energy. The detection limits of laser two-photon ionization for these types of molecules on the water surface are formulated.

Estimation of descriptive statistics for multiply censored water quality data

USGS Publications Warehouse

Helsel, Dennis R.; Cohn, Timothy A.

1988-01-01

This paper extends the work of Gilliom and Helsel (1986) on procedures for estimating descriptive statistics of water quality data that contain “less than” observations. Previously, procedures were evaluated when only one detection limit was present. Here we investigate the performance of estimators for data that have multiple detection limits. Probability plotting and maximum likelihood methods perform substantially better than simple substitution procedures now commonly in use. Therefore simple substitution procedures (e.g., substitution of the detection limit) should be avoided. Probability plotting methods are more robust than maximum likelihood methods to misspecification of the parent distribution and their use should be encouraged in the typical situation where the parent distribution is unknown. When utilized correctly, less than values frequently contain nearly as much information for estimating population moments and quantiles as would the same observations had the detection limit been below them.

Evaluation of statistical treatments of left-censored environmental data using coincident uncensored data sets: I. Summary statistics

USGS Publications Warehouse

Antweiler, Ronald C.; Taylor, Howard E.

2008-01-01

The main classes of statistical treatment of below-detection limit (left-censored) environmental data for the determination of basic statistics that have been used in the literature are substitution methods, maximum likelihood, regression on order statistics (ROS), and nonparametric techniques. These treatments, along with using all instrument-generated data (even those below detection), were evaluated by examining data sets in which the true values of the censored data were known. It was found that for data sets with less than 70% censored data, the best technique overall for determination of summary statistics was the nonparametric Kaplan-Meier technique. ROS and the two substitution methods of assigning one-half the detection limit value to censored data or assigning a random number between zero and the detection limit to censored data were adequate alternatives. The use of these two substitution methods, however, requires a thorough understanding of how the laboratory censored the data. The technique of employing all instrument-generated data - including numbers below the detection limit - was found to be less adequate than the above techniques. At high degrees of censoring (greater than 70% censored data), no technique provided good estimates of summary statistics. Maximum likelihood techniques were found to be far inferior to all other treatments except substituting zero or the detection limit value to censored data.

Time course of collagen peak in bile duct-ligated rats.

PubMed

Tarcin, Orhan; Basaranoglu, Metin; Tahan, Veysel; Tahan, Gülgün; Sücüllü, Ilker; Yilmaz, Nevin; Sood, Gagan; Snyder, Ned; Hilman, Gilbert; Celikel, Cigdem; Tözün, Nurdan

2011-04-28

One of the most useful experimental fibrogenesis models is the "bile duct-ligated rats". Our aim was to investigate the quantitative hepatic collagen content by two different methods during the different stages of hepatic fibrosis in bile duct-ligated rats on a weekly basis. We questioned whether the 1-wk or 4-wk bile duct-ligated model is suitable in animal fibrogenesis trials. Of the 53 male Wistar rats, 8 (Group 0) were used as a healthy control group. Bile duct ligation (BDL) had been performed in the rest. Bile duct-ligated rates were sacrificed 7 days later in group 1 (10 rats), 14 days later in group 2 (9 rats), 21 days later in group 3(9 rats) and 28 days later in group 4 (9 rats). Eight rats underwent sham-operation (Sham). Hepatic collagen measurements as well as serum levels of liver enzymes and function tests were all analysed. The peak level of collagen was observed biochemically and histomorphometricly at the end of third week (P < 0.001 and P < 0.05). Suprisingly, collagen levels had decreased with the course of time such as at the end of fourth week (P < 0.01 and P < 0.05). We have shown that fibrosis in bile duct-ligated rats is transient, i.e. reverses spontaneously after 3 weeks. This contrasts any situation in patients where hepatic fibrosis is progressive and irreversible as countless studies performed by many investigators in the same animal model.

An optimized one-tube, semi-nested PCR assay for Paracoccidioides brasiliensis detection.

PubMed

Pitz, Amanda de Faveri; Koishi, Andrea Cristine; Tavares, Eliandro Reis; Andrade, Fábio Goulart de; Loth, Eduardo Alexandre; Gandra, Rinaldo Ferreira; Venancio, Emerson José

2013-01-01

Herein, we report a one-tube, semi-nested-polymerase chain reaction (OTsn-PCR) assay for the detection of Paracoccidioides brasiliensis. We developed the OTsn-PCR assay for the detection of P. brasiliensis in clinical specimens and compared it with other PCR methods. The OTsn-PCR assay was positive for all clinical samples, and the detection limit was better or equivalent to the other nested or semi-nested PCR methods for P. brasiliensis detection. The OTsn-PCR assay described in this paper has a detection limit similar to other reactions for the molecular detection of P. brasiliensis, but this approach is faster and less prone to contamination than other conventional nested or semi-nested PCR assays.

A comparative study evaluating the efficacy of IS_MAP04 with IS900 and IS_MAP02 as a new diagnostic target for the detection of Mycobacterium avium subspecies paratuberculosis from bovine faeces.

PubMed

de Kruijf, Marcel; Govender, Rodney; Yearsley, Dermot; Coffey, Aidan; O'Mahony, Jim

2017-05-01

The aim of this study was to investigate the efficacy of IS_MAP04 as a potential new diagnostic quantitative PCR (qPCR) target for the detection of Mycobacterium avium subspecies paratuberculosis from bovine faeces. IS_MAP04 primers were designed and tested negative against non-MAP strains. The detection limit of IS_MAP04 qPCR was evaluated on different MAP K-10 DNA concentrations and on faecal samples spiked with different MAP K-10 cell dilutions. A collection of 106 faecal samples was analysed and the efficacy of IS_MAP04 was statistically compared with IS900 and IS_MAP02. The detection limits observed for IS_MAP04 and IS900 on MAP DNA was 34 fg and 3.4 fg respectively. The detection limit of MAP from inoculated faecal samples was 10 2 CFU/g for both IS_MAP04 and IS900 targets and a detection limit of 10 2 CFU/g was also achieved with a TaqMan qPCR targeting IS_MAP04. The efficacy of IS_MAP04 to detect positive MAP faecal samples was 83.0% compared to 85.8% and 83.9% for IS900 and IS_MAP02 respectively. Strong kappa agreements were observed between IS_MAP04 and IS900 (κ=0.892) and between IS_MAP04 and IS_MAP02 (κ=0.897). As a new molecular target, IS_MAP04 showed that the detection limit was comparable to IS900 to detect MAP from inoculated faecal material. The MAP detection efficacy of IS_MAP04 from naturally infected faecal samples proved to be relatively comparable to IS_MAP02, but yielded efficacy results slightly less than IS900. Moreover, IS_MAP04 could be of significant value when used in duplex or multiplex qPCR assays. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of detection limits in environmental analysis--is it possible? An approach on quality assurance in the lower working range by verification.

PubMed

Geiss, S; Einax, J W

2001-07-01

Detection limit, reporting limit and limit of quantitation are analytical parameters which describe the power of analytical methods. These parameters are used for internal quality assurance and externally for competing, especially in the case of trace analysis in environmental compartments. The wide variety of possibilities for computing or obtaining these measures in literature and in legislative rules makes any comparison difficult. Additionally, a host of terms have been used within the analytical community to describe detection and quantitation capabilities. Without trying to create an order for the variety of terms, this paper is aimed at providing a practical proposal for answering the main questions for the analysts concerning quality measures above. These main questions and related parameters were explained and graphically demonstrated. Estimation and verification of these parameters are the two steps to get real measures. A rule for a practical verification is given in a table, where the analyst can read out what to measure, what to estimate and which criteria have to be fulfilled. In this manner verified parameters detection limit, reporting limit and limit of quantitation now are comparable and the analyst himself is responsible to the unambiguity and reliability of these measures.

A fuel-limited isothermal DNA machine for the sensitive detection of cellular deoxyribonucleoside triphosphates.

PubMed

Dong, Jiantong; Wu, Tongbo; Xiao, Yu; Xu, Lei; Fang, Simin; Zhao, Meiping

2016-09-29

A fuel-limited isothermal DNA machine has been built for the sensitive fluorescence detection of cellular deoxyribonucleoside triphosphates (dNTPs) at the fmol level, which greatly reduces the required sample cell number. Upon the input of the limiting target dNTP, the machine runs automatically at 37 °C without the need for higher temperature.

Stochastic fluctuations and the detectability limit of network communities.

PubMed

Floretta, Lucio; Liechti, Jonas; Flammini, Alessandro; De Los Rios, Paolo

2013-12-01

We have analyzed the detectability limits of network communities in the framework of the popular Girvan and Newman benchmark. By carefully taking into account the inevitable stochastic fluctuations that affect the construction of each and every instance of the benchmark, we come to the conclusion that the native, putative partition of the network is completely lost even before the in-degree/out-degree ratio becomes equal to that of a structureless Erdös-Rényi network. We develop a simple iterative scheme, analytically well described by an infinite branching process, to provide an estimate of the true detectability limit. Using various algorithms based on modularity optimization, we show that all of them behave (semiquantitatively) in the same way, with the same functional form of the detectability threshold as a function of the network parameters. Because the same behavior has also been found by further modularity-optimization methods and for methods based on different heuristics implementations, we conclude that indeed a correct definition of the detectability limit must take into account the stochastic fluctuations of the network construction.

Comparison of Electrochemical Immunosensors and Aptasensors for Detection of Small Organic Molecules in Environment, Food Safety, Clinical and Public Security.

PubMed

Piro, Benoit; Shi, Shihui; Reisberg, Steeve; Noël, Vincent; Anquetin, Guillaume

2016-02-29

We review here the most frequently reported targets among the electrochemical immunosensors and aptasensors: antibiotics, bisphenol A, cocaine, ochratoxin A and estradiol. In each case, the immobilization procedures are described as well as the transduction schemes and the limits of detection. It is shown that limits of detections are generally two to three orders of magnitude lower for immunosensors than for aptasensors, due to the highest affinities of antibodies. No significant progresses have been made to improve these affinities, but transduction schemes were improved instead, which lead to a regular improvement of the limit of detections corresponding to ca. five orders of magnitude over these last 10 years. These progresses depend on the target, however.

A multi-residue method for the analysis of pesticides and pesticide degradates in water using HLB solid-phase extraction and gas chromatography-ion trap mass spectrometry

USGS Publications Warehouse

Hladik, M.L.; Smalling, K.L.; Kuivila, K.M.

2008-01-01

A method was developed for the analysis of over 60 pesticides and degradates in water by HLB solid-phase extraction and gas-chromatography/mass spectrometry. Method recoveries and detection limits were determined using two surface waters with different dissolved organic carbon (DOC) concentrations. In the lower DOC water, recoveries and detection limits were 80%-108% and 1-12 ng/L, respectively. In the higher DOC water, the detection limits were slightly higher (1-15 ng/L). Additionally, surface water samples from four sites were analyzed and 14 pesticides were detected with concentrations ranging from 4 to 1,200 ng/L. ?? 2008 Springer Science+Business Media, LLC.

Pulsed CO2 characterization for lidar use

NASA Technical Reports Server (NTRS)

Jaenisch, Holger M.

1992-01-01

An account is given of a scaled functional testbed laser for space-qualified coherent-detection lidar applications which employs a CO2 laser. This laser has undergone modification and characterization for inherent performance capabilities as a model of coherent detection. While characterization results show good overall performance that is in agreement with theoretical predictions, frequency-stability and pulse-length limitations severely limit the laser's use in coherent detection.

Hill AFB, Utah Installation Restoration Program. Phase IIB, IRP Survey. Volume 1. Text. Volume 2. Appendices

DTIC Science & Technology

1984-09-11

5 EPA 625 . Endosulfan sulfate wg/L 5 EPA 625 Chlordane pg/L * Toxaphene Pg/L * Acid Extractable Detection Analytical Compound Units Limit Method...ND ND ND ND 4,4’-DDT 5 ND ND ND ND Endosuif an sulfate 5 ND ND ND ND Chlordane* Toxa phene* Detection Acid Extractable Compound Limit M4-2 M4-6 14-9 Ge...Endosulfan sulfate 5 ND ND Chlordane * Toxaphene * Detection Acid Extractable Compound Limit BPM-1 BPM-2 2-Chlorophenol 2 ND ND 2-Nitrophenol 2 ND ND

Heisenberg limit for displacements with semiclassical states

NASA Astrophysics Data System (ADS)

Luis, Alfredo

2004-04-01

We analyze the quantum limit to the sensitivity of the detection of small displacements. We focus on the case of free particles and harmonic oscillators as the systems experiencing the displacement. We show that the minimum displacement detectable is proportional to the inverse of the square root of the mean value of the energy in the state experiencing the displacement (Heisenberg limit). We present a measuring scheme that reaches this limit using semiclassical states. We examine the performance of this strategy under realistic practical conditions by computing the effect of imperfections such as losses and nonunit detection efficiencies. This analysis confirms the robustness of this measuring strategy by showing that the experimental imperfections can be suitably compensated by increasing the mean energy of the input state.

The solar-flare infrared continuum - Observational techniques and upper limits

NASA Technical Reports Server (NTRS)

Hudson, H. S.

1975-01-01

Exploratory observations at 20 microns and 350 microns have determined detection thresholds for solar flares in these wavelengths. In the 20-micron range, solar atmospheric fluctuations (the 'temperature field') set the basic limits on flare detectability at about 5 K; at 350 microns, extinction in the earth's atmosphere provides the basic limitation of about 30 K. These thresholds are low enough for the successful detection of several infrared-emitting components of large flares. The upper limits obtained for subflares indicate that the thickness of the H-alpha flare region does not exceed approximately 10 km. This result confirms the conclusion of Suemoto and Hiei (1959) regarding the small effective thickness of the H-alpha-emitting regions in solar flares.

Detection of Salmonella enterica Serovar Typhimurium by Using a Rapid, Array-Based Immunosensor

PubMed Central

Taitt, Chris Rowe; Shubin, Yura S.; Angel, Roselina; Ligler, Frances S.

2004-01-01

The multianalyte array biosensor (MAAB) is a rapid analysis instrument capable of detecting multiple analytes simultaneously. Rapid (15-min), single-analyte sandwich immunoassays were developed for the detection of Salmonella enterica serovar Typhimurium, with a detection limit of 8 × 104 CFU/ml; the limit of detection was improved 10-fold by lengthening the assay protocol to 1 h. S. enterica serovar Typhimurium was also detected in the following spiked foodstuffs, with minimal sample preparation: sausage, cantaloupe, whole liquid egg, alfalfa sprouts, and chicken carcass rinse. Cross-reactivity tests were performed with Escherichia coli and Campylobacter jejuni. To determine whether the MAAB has potential as a screening tool for the diagnosis of asymptomatic Salmonella infection of poultry, chicken excretal samples from a private, noncommercial farm and from university poultry facilities were tested. While the private farm excreta gave rise to signals significantly above the buffer blanks, none of the university samples tested positive for S. enterica serovar Typhimurium without spiking; dose-response curves of spiked excretal samples from university-raised poultry gave limits of detection of 8 × 103 CFU/g. PMID:14711637

Enhanced Detectability of Community Structure in Multilayer Networks through Layer Aggregation.

PubMed

Taylor, Dane; Shai, Saray; Stanley, Natalie; Mucha, Peter J

2016-06-03

Many systems are naturally represented by a multilayer network in which edges exist in multiple layers that encode different, but potentially related, types of interactions, and it is important to understand limitations on the detectability of community structure in these networks. Using random matrix theory, we analyze detectability limitations for multilayer (specifically, multiplex) stochastic block models (SBMs) in which L layers are derived from a common SBM. We study the effect of layer aggregation on detectability for several aggregation methods, including summation of the layers' adjacency matrices for which we show the detectability limit vanishes as O(L^{-1/2}) with increasing number of layers, L. Importantly, we find a similar scaling behavior when the summation is thresholded at an optimal value, providing insight into the common-but not well understood-practice of thresholding pairwise-interaction data to obtain sparse network representations.

An improved method for undertaking limiting dilution assays for in vitro cloning of Plasmodium falciparum parasites.

PubMed

Butterworth, Alice S; Robertson, Alan J; Ho, Mei-Fong; Gatton, Michelle L; McCarthy, James S; Trenholme, Katharine R

2011-04-18

Obtaining single parasite clones is required for many techniques in malaria research. Cloning by limiting dilution using microscopy-based assessment for parasite growth is an arduous and labor-intensive process. An alternative method for the detection of parasite growth in limiting dilution assays is using a commercial ELISA histidine-rich protein II (HRP2) detection kit. Detection of parasite growth was undertaken using HRP2 ELISA and compared to thick film microscopy. An HRP2 protein standard was used to determine the detection threshold of the HRP2 ELISA assay, and a HRP2 release model was used to extrapolate the amount of parasite growth required for a positive result. The HRP2 ELISA was more sensitive than microscopy for detecting parasite growth. The minimum level of HRP2 protein detection of the ELISA was 0.11 ng/ml. Modeling of HRP2 release determined that 2,116 parasites are required to complete a full erythrocytic cycle to produce sufficient HRP2 to be detected by the ELISA. Under standard culture conditions this number of parasites is likely to be reached between 8 to 14 days of culture. This method provides an accurate and simple way for the detection of parasite growth in limiting dilution assays, reducing time and resources required in traditional methods. Furthermore the method uses spent culture media instead of the parasite-infected red blood cells, enabling culture to continue. © 2011 Butterworth et al; licensee BioMed Central Ltd.

Estimating bergamot juice adulteration of lemon juice by high-performance liquid chromatography (HPLC) analysis of flavanone glycosides.

PubMed

Cautela, Domenico; Laratta, Bruna; Santelli, Francesca; Trifirò, Antonio; Servillo, Luigi; Castaldo, Domenico

2008-07-09

The chemical composition of 30 samples of juices obtained from bergamot (Citrus bergamia Risso and Poit.) fruits is reported and compared to the genuineness parameters adopted by Association of the Industry of Juice and Nectars (AIJN) for lemon juice. It was found that the compositional differences between the two juices are distinguishable, although with difficulty. However, these differences are not strong enough to detect the fraudulent addition of bergamot juice to lemon juice. Instead, we found the high-performance liquid chromatography (HPLC) analysis of the flavanones naringin, neohesperidin, and neoeriocitrin, which are present in bergamot juice and practically absent in the lemon juice, is a convenient way to detect and quantify the fraudulent addition of bergamot juice. The method has been validated by calculating the detection and quantification limits according to Eurachem procedures. Employing neoeriocitrin (detection limit = 0.7 mg/L) and naringin (detection limit = 1 mg/L) as markers, it is possible to detect the addition of bergamot juice to lemon juice at the 1% level. When using neohesperidin as a marker (detection limit = 1 mg/L), the minimal percentage of detectable addition of bergamot juice was about 2%. Finally, it is reported that the pattern of flavonoid content of the bergamot juice is similar to those of chinotto (Citrus myrtifolia Raf) and bitter orange (Citrus aurantium L.) juices and that it is possible to distinguish the three kinds of juices by HPLC analysis.

Performance limitations of label-free sensors in molecular diagnosis using complex samples

NASA Astrophysics Data System (ADS)

Varma, Manoj

2016-03-01

Label-free biosensors promised a paradigm involving direct detection of biomarkers from complex samples such as serum without requiring multistep sample processing typical of labelled methods such as ELISA or immunofluorescence assays. Label-free sensors have witnessed decades of development with a veritable zoo of techniques available today exploiting a multitude of physical effects. It is appropriate now to critically assess whether label-free technologies have succeeded in delivering their promise with respect to diagnostic applications, particularly, ambitious goals such as early cancer detection using serum biomarkers, which require low limits of detection (LoD). Comparison of nearly 120 limits of detection (LoD) values reported by labelled and label-free sensing approaches over a wide range of detection techniques and target molecules in serum revealed that labeled techniques achieve 2-3 orders of magnitude better LoDs. Data from experiments where labelled and label-free assays were performed simultaneously using the same assay parameters also confirm that the LoD achieved by labelled techniques is 2 to 3 orders of magnitude better than that by label-free techniques. Furthermore, label-free techniques required significant signal amplification, for e.g. using nanoparticle conjugated secondary antibodies, to achieve LoDs comparable to labelled methods substantially deviating from the original "direct detection" paradigm. This finding has important implications on the practical limits of applying label-free detection methods for molecular diagnosis.

Detectability Thresholds and Optimal Algorithms for Community Structure in Dynamic Networks

NASA Astrophysics Data System (ADS)

Ghasemian, Amir; Zhang, Pan; Clauset, Aaron; Moore, Cristopher; Peel, Leto

2016-07-01

The detection of communities within a dynamic network is a common means for obtaining a coarse-grained view of a complex system and for investigating its underlying processes. While a number of methods have been proposed in the machine learning and physics literature, we lack a theoretical analysis of their strengths and weaknesses, or of the ultimate limits on when communities can be detected. Here, we study the fundamental limits of detecting community structure in dynamic networks. Specifically, we analyze the limits of detectability for a dynamic stochastic block model where nodes change their community memberships over time, but where edges are generated independently at each time step. Using the cavity method, we derive a precise detectability threshold as a function of the rate of change and the strength of the communities. Below this sharp threshold, we claim that no efficient algorithm can identify the communities better than chance. We then give two algorithms that are optimal in the sense that they succeed all the way down to this threshold. The first uses belief propagation, which gives asymptotically optimal accuracy, and the second is a fast spectral clustering algorithm, based on linearizing the belief propagation equations. These results extend our understanding of the limits of community detection in an important direction, and introduce new mathematical tools for similar extensions to networks with other types of auxiliary information.

Evaluation of PCR Approaches for Detection of Bartonella bacilliformis in Blood Samples.

PubMed

Gomes, Cláudia; Martinez-Puchol, Sandra; Pons, Maria J; Bazán, Jorge; Tinco, Carmen; del Valle, Juana; Ruiz, Joaquim

2016-03-01

The lack of an effective diagnostic tool for Carrion's disease leads to misdiagnosis, wrong treatments and perpetuation of asymptomatic carriers living in endemic areas. Conventional PCR approaches have been reported as a diagnostic technique. However, the detection limit of these techniques is not clear as well as if its usefulness in low bacteriemia cases. The aim of this study was to evaluate the detection limit of 3 PCR approaches. We determined the detection limit of 3 different PCR approaches: Bartonella-specific 16S rRNA, fla and its genes. We also evaluated the viability of dry blood spots to be used as a sample transport system. Our results show that 16S rRNA PCR is the approach with a lowest detection limit, 5 CFU/μL, and thus, the best diagnostic PCR tool studied. Dry blood spots diminish the sensitivity of the assay. From the tested PCRs, the 16S rRNA PCR-approach is the best to be used in the direct blood detection of acute cases of Carrion's disease. However its use in samples from dry blood spots results in easier management of transport samples in rural areas, a slight decrease in the sensitivity was observed. The usefulness to detect by PCR the presence of low-bacteriemic or asymptomatic carriers is doubtful, showing the need to search for new more sensible techniques.

Application of fluorescence spectroscopy and imaging in the detection of a photosensitizer in photodynamic therapy

NASA Astrophysics Data System (ADS)

Zang, Lixin; Zhao, Huimin; Zhang, Zhiguo; Cao, Wenwu

2017-02-01

Photodynamic therapy (PDT) is currently an advanced optical technology in medical applications. However, the application of PDT is limited by the detection of photosensitizers. This work focuses on the application of fluorescence spectroscopy and imaging in the detection of an effective photosenzitizer, hematoporphyrin monomethyl ether (HMME). Optical properties of HMME were measured and analyzed based on its absorption and fluorescence spectra. The production mechanism of its fluorescence emission was analyzed. The detection device for HMME based on fluorescence spectroscopy was designed. Ratiometric method was applied to eliminate the influence of intensity change of excitation sources, fluctuates of excitation sources and photo detectors, and background emissions. The detection limit of this device is 6 μg/L, and it was successfully applied to the diagnosis of the metabolism of HMME in the esophageal cancer cells. To overcome the limitation of the point measurement using fluorescence spectroscopy, a two-dimensional (2D) fluorescence imaging system was established. The algorithm of the 2D fluorescence imaging system is deduced according to the fluorescence ratiometric method using bandpass filters. The method of multiple pixel point addition (MPPA) was used to eliminate fluctuates of signals. Using the method of MPPA, SNR was improved by about 30 times. The detection limit of this imaging system is 1.9 μg/L. Our systems can be used in the detection of porphyrins to improve the PDT effect.

40 CFR 761.30 - Authorizations.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Current-limiting fuses or other equivalent technology must be used to detect sustained high current faults... fuses or other equivalent technology to avoid PCB Transformer ruptures from sustained high current... protection, such as current-limiting fuses or other equivalent technology, to detect sustained high current...

Sample-morphology effects on x-ray photoelectron peak intensities. II. Estimation of detection limits for thin-film materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Powell, Cedric J., E-mail: cedric.powell@nist.gov; Werner, Wolfgang S. M.; Smekal, Werner

2014-09-01

The authors show that the National Institute of Standards and Technology database for the simulation of electron spectra for surface analysis (SESSA) can be used to determine detection limits for thin-film materials such as a thin film on a substrate or buried at varying depths in another material for common x-ray photoelectron spectroscopy (XPS) measurement conditions. Illustrative simulations were made for a W film on or in a Ru matrix and for a Ru film on or in a W matrix. In the former case, the thickness of a W film at a given depth in the Ru matrix wasmore » varied so that the intensity of the W 4d{sub 5/2} peak was essentially the same as that for a homogeneous RuW{sub 0.001} alloy. Similarly, the thickness of a Ru film at a selected depth in the W matrix was varied so that the intensity of the Ru 3p{sub 3/2} peak matched that from a homogeneous WRu{sub 0.01} alloy. These film thicknesses correspond to the detection limits of each minor component for measurement conditions where the detection limits for a homogeneous sample varied between 0.1 at. % (for the RuW{sub 0.001} alloy) and 1 at. % (for the WRu{sub 0.01} alloy). SESSA can be similarly used to convert estimates of XPS detection limits for a minor species in a homogeneous solid to the corresponding XPS detection limits for that species as a thin film on or buried in the chosen solid.« less

White Light Heterodyne Interferometry SNR

DTIC Science & Technology

2015-04-09

interferometers in the visible- and near-IR, where shot - noise -limited detectors are available. In the LWIR, the advantage of a direct detection...wavebands where shot - noise -limited detection is possible with direct detection systems, the relationship changes in the mid-wave infrared (MWIR) and...flux, without either having to split the light N – 1 ways or take the extra shot - noise penalty from Fizeau beam combining light from all apertures

Transformative Colloidal Nanomaterials for Mid- Infrared Devices

DTIC Science & Technology

2015-06-11

like. Luminescence has been detected up to the detection limit of our MCT detector (11 microns). Inorganic ligand exchange using ammonium sulfide...biexciton lifetime is not changing significantly, being about 30-50 ps. One issue with CQDs films for mid-IR detection will be to achieve noise ...limited by generation/recombination. Our first studies showed that at 1kHz, 1/f noise dominated starting at temperatures of 100K and increased

Dark matter direct detection of a fermionic singlet at one loop

NASA Astrophysics Data System (ADS)

Herrero-García, Juan; Molinaro, Emiliano; Schmidt, Michael A.

2018-06-01

The strong direct detection limits could be pointing to dark matter - nucleus scattering at loop level. We study in detail the prototype example of an electroweak singlet (Dirac or Majorana) dark matter fermion coupled to an extended dark sector, which is composed of a new fermion and a new scalar. Given the strong limits on colored particles from direct and indirect searches we assume that the fields of the new dark sector are color singlets. We outline the possible simplified models, including the well-motivated cases in which the extra scalar or fermion is a Standard Model particle, as well as the possible connection to neutrino masses. We compute the contributions to direct detection from the photon, the Z and the Higgs penguins for arbitrary quantum numbers of the dark sector. Furthermore, we derive compact expressions in certain limits, i.e., when all new particles are heavier than the dark matter mass and when the fermion running in the loop is light, like a Standard Model lepton. We study in detail the predicted direct detection rate and how current and future direct detection limits constrain the model parameters. In case dark matter couples directly to Standard Model leptons we find an interesting interplay between lepton flavor violation, direct detection and the observed relic abundance.

Detection of proteolytic activity by covalent tethering of fluorogenic substrates in zymogram gels.

PubMed

Deshmukh, Ameya A; Weist, Jessica L; Leight, Jennifer L

2018-05-01

Current zymographic techniques detect only a subset of known proteases due to the limited number of native proteins that have been optimized for incorporation into polyacrylamide gels. To address this limitation, we have developed a technique to covalently incorporate fluorescently labeled, protease-sensitive peptides using an azido-PEG3-maleimide crosslinker. Peptides incorporated into gels enabled measurement of MMP-2, -9, -14, and bacterial collagenase. Sensitivity analysis demonstrated that use of peptide functionalized gels could surpass detection limits of current techniques. Finally, electrophoresis of conditioned media from cultured cells resulted in the appearance of several proteolytic bands, some of which were undetectable by gelatin zymography. Taken together, these results demonstrate that covalent incorporation of fluorescent substrates can greatly expand the library of detectable proteases using zymographic techniques.

Comparison of Electrochemical Immunosensors and Aptasensors for Detection of Small Organic Molecules in Environment, Food Safety, Clinical and Public Security

PubMed Central

Piro, Benoit; Shi, Shihui; Reisberg, Steeve; Noël, Vincent; Anquetin, Guillaume

2016-01-01

We review here the most frequently reported targets among the electrochemical immunosensors and aptasensors: antibiotics, bisphenol A, cocaine, ochratoxin A and estradiol. In each case, the immobilization procedures are described as well as the transduction schemes and the limits of detection. It is shown that limits of detections are generally two to three orders of magnitude lower for immunosensors than for aptasensors, due to the highest affinities of antibodies. No significant progresses have been made to improve these affinities, but transduction schemes were improved instead, which lead to a regular improvement of the limit of detections corresponding to ca. five orders of magnitude over these last 10 years. These progresses depend on the target, however. PMID:26938570

Investigation of detection limits for diffuse optical tomography systems: II. Analysis of slab and cup geometry for breast imaging.

PubMed

Ziegler, Ronny; Brendel, Bernhard; Rinneberg, Herbert; Nielsen, Tim

2009-01-21

Using a statistical (chi-square) test on simulated data and a realistic noise model derived from the system's hardware we study the performance of diffuse optical tomography systems for fluorescence imaging. We compare the predicted smallest size of detectable lesions at various positions in slab and cup geometry and model how detection sensitivity depends on breast compression and lesion fluorescence contrast. Our investigation shows that lesion detection is limited by relative noise in slab geometry and by absolute noise in cup geometry.

SU-D-BRD-07: Evaluation of the Effectiveness of Statistical Process Control Methods to Detect Systematic Errors For Routine Electron Energy Verification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parker, S

2015-06-15

Purpose: To evaluate the ability of statistical process control methods to detect systematic errors when using a two dimensional (2D) detector array for routine electron beam energy verification. Methods: Electron beam energy constancy was measured using an aluminum wedge and a 2D diode array on four linear accelerators. Process control limits were established. Measurements were recorded in control charts and compared with both calculated process control limits and TG-142 recommended specification limits. The data was tested for normality, process capability and process acceptability. Additional measurements were recorded while systematic errors were intentionally introduced. Systematic errors included shifts in the alignmentmore » of the wedge, incorrect orientation of the wedge, and incorrect array calibration. Results: Control limits calculated for each beam were smaller than the recommended specification limits. Process capability and process acceptability ratios were greater than one in all cases. All data was normally distributed. Shifts in the alignment of the wedge were most apparent for low energies. The smallest shift (0.5 mm) was detectable using process control limits in some cases, while the largest shift (2 mm) was detectable using specification limits in only one case. The wedge orientation tested did not affect the measurements as this did not affect the thickness of aluminum over the detectors of interest. Array calibration dependence varied with energy and selected array calibration. 6 MeV was the least sensitive to array calibration selection while 16 MeV was the most sensitive. Conclusion: Statistical process control methods demonstrated that the data distribution was normally distributed, the process was capable of meeting specifications, and that the process was centered within the specification limits. Though not all systematic errors were distinguishable from random errors, process control limits increased the ability to detect systematic errors using routine measurement of electron beam energy constancy.« less

Detection Limits for Spectro-fluorometry: A Case Study in the Region of Finstersee, Canton Zug, Northern Switzerland

NASA Astrophysics Data System (ADS)

Otz, M. H.; Otz, H. K.; Keller, P.

2002-05-01

Synthetic fluorescent dyes, applied below the visual detection limit (< 0.1 mg/L), have been used as tracers of ground water flow paths since the beginning of the 1950s. Since 1965, we have used spectro-fluorometers with photomultipliers to measure low concentrations of fluorescent dyes in ground water in Switzerland. In collaboration with the Engineering Geology Department of the ETH, we have separated uranine at 0.1 ng/L and Na-naphtionate at 1 ng/L from background fluorescence of spring water in the Finstersee region. These values are 10-100 times lower than postulated detection limits in the literature. The use of low dye concentrations prevents a study region from being contaminated by increased background levels due to remnant dye within the aquifer, thereby leaving the region available for future dye tracing studies. Lower detection limits also can solve particular hydraulic problems where conventional methods fail and enhance the possibility for using artificial dyes in environmentally sensitive aquifer settings.

Electrochemistry and Spectroelectrochemistry of Luminescent Europium Complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lines, Amanda M.; Wang, Zheming; Clark, Sue B.

Fast, cost effective, and robust means of detecting and quantifying lanthanides are needed for supporting more efficient tracking within the nuclear, medicinal, and industrial fields. Spectroelectrochemistry (SEC) is a powerful technique combining electrochemistry and spectroscopy that can meet those needs. The primary limitation of SEC as a detection method for lanthanides is their low molar absorptivity in absorbance based measurements and low emission intensities in fluorescence based measurements; both lead to high limits of detection. These limitations can be circumvented by complexing the lanthanides with sensitizing ligands that enhance fluorescence, thereby dropping the limits of detection. Complexation may also stabilizemore » the metal ions in solution and improve the electrochemical reversibility, or Nernstian behavior, of the redox couples. To demonstrate this concept, studies were completed using europium in complexes with four different sensitizing ligands. Initial work indicates Eu in the four complexes studied does display the necessary characteristics for SEC analysis, which was successfully and reproducibly applied to all Eu complexes.« less

Specific determination of bromate in bread by ion chromatography with ICP-MS.

PubMed

Akiyama, Takumi; Yamanaka, Michiko; Date, Yukiko; Kubota, Hiroki; Nagaoka, Megumi Hamano; Kawasaki, Yoko; Yamazaki, Takeshi; Yomota, Chikako; Maitani, Tamio

2002-12-01

A sensitive method for detecting bromate in bread by ion chromatography with inductively-coupled plasma mass spectrometry (IC/ICP-MS) was developed. Bromate was extracted from bread with water. The clean-up procedure included a 0.2 micron filter, a C18 cartridge for defatting, a silver cartridge to remove halogen anions, a centrifugal ultrafiltration unit to remove proteins, and a cation-exchange cartridge to remove silver ions. A 500 microL sample solution was applied to IC/ICP-MS. The detection limit and the quantitation limit of bromate in the solution were 0.3 ng/mL and 1.0 ng/mL, expressed as HBrO3, respectively, which corresponded to 2 ng/g and 5 ng/g, respectively, in bread. Recovery of bromate was about 90%, and the CV was about 2%. Based on the detection limit in solution and recovery from bread, the detection limit of bromate in bread was estimated to be 2 ng/g.

LITE microscopy: Tilted light-sheet excitation of model organisms offers high resolution and low photobleaching

PubMed Central

Gerbich, Therese M.; Rana, Kishan; Suzuki, Aussie; Schaefer, Kristina N.; Heppert, Jennifer K.; Boothby, Thomas C.; Allbritton, Nancy L.; Gladfelter, Amy S.; Maddox, Amy S.

2018-01-01

Fluorescence microscopy is a powerful approach for studying subcellular dynamics at high spatiotemporal resolution; however, conventional fluorescence microscopy techniques are light-intensive and introduce unnecessary photodamage. Light-sheet fluorescence microscopy (LSFM) mitigates these problems by selectively illuminating the focal plane of the detection objective by using orthogonal excitation. Orthogonal excitation requires geometries that physically limit the detection objective numerical aperture (NA), thereby limiting both light-gathering efficiency (brightness) and native spatial resolution. We present a novel live-cell LSFM method, lateral interference tilted excitation (LITE), in which a tilted light sheet illuminates the detection objective focal plane without a sterically limiting illumination scheme. LITE is thus compatible with any detection objective, including oil immersion, without an upper NA limit. LITE combines the low photodamage of LSFM with high resolution, high brightness, and coverslip-based objectives. We demonstrate the utility of LITE for imaging animal, fungal, and plant model organisms over many hours at high spatiotemporal resolution. PMID:29490939

Detection limit of a VCO based detection chain dedicated to particles recognition and tracking

NASA Astrophysics Data System (ADS)

Coulié, K.; Rahajandraibe, W.; Aziza, H.; Micolau, G.; Vauché, R.

2018-01-01

A particle detection chain based on CMOS-SOI VCO circuit is presented. The solution is used for the recognition and the tracking of a given particle at circuit level. TCAD simulation of the detector has been performed on a 3×3 matrix of diodes based detector for particles recognition and tracking. The current response of the detector has been used for a case study in order to determine the ability of the chain to recognize an alpha particle crossing a 3×3 detection cell. The detection limit of the proposed solution is investigated and discussed in this paper.

Sparse aperture masking at the VLT. II. Detection limits for the eight debris disks stars β Pic, AU Mic, 49 Cet, η Tel, Fomalhaut, g Lup, HD 181327 and HR 8799

NASA Astrophysics Data System (ADS)

Gauchet, L.; Lacour, S.; Lagrange, A.-M.; Ehrenreich, D.; Bonnefoy, M.; Girard, J. H.; Boccaletti, A.

2016-10-01

Context. The formation of planetary systems is a common, yet complex mechanism. Numerous stars have been identified to possess a debris disk, a proto-planetary disk or a planetary system. The understanding of such formation process requires the study of debris disks. These targets are substantial and particularly suitable for optical and infrared observations. Sparse aperture masking (SAM) is a high angular resolution technique strongly contributing to probing the region from 30 to 200 mas around the stars. This area is usually unreachable with classical imaging, and the technique also remains highly competitive compared to vortex coronagraphy. Aims: We aim to study debris disks with aperture masking to probe the close environment of the stars. Our goal is either to find low-mass companions, or to set detection limits. Methods: We observed eight stars presenting debris disks (β Pictoris, AU Microscopii, 49 Ceti, η Telescopii, Fomalhaut, g Lupi, HD 181327, and HR 8799) with SAM technique on the NaCo instrument at the Very Large Telescope (VLT). Results: No close companions were detected using closure phase information under 0.5'' of separation from the parent stars. We obtained magnitude detection limits that we converted to Jupiter masses detection limits using theoretical isochrones from evolutionary models. Conclusions: We derived upper mass limits on the presence of companions in the area of a few times the telescope's diffraction limits around each target star. Based on observations collected at the European Southern Observatory (ESO) during runs 087.C-0450(A), 087.C-0450(B) 087.C-0750(A), 088.C-0358(A).All magnitude detection limits maps are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/595/A31

Limited copy number - high resolution melting (LCN-HRM) enables the detection and identification by sequencing of low level mutations in cancer biopsies

PubMed Central

Do, Hongdo; Dobrovic, Alexander

2009-01-01

Background Mutation detection in clinical tumour samples is challenging when the proportion of tumour cells, and thus mutant alleles, is low. The limited sensitivity of conventional sequencing necessitates the adoption of more sensitive approaches. High resolution melting (HRM) is more sensitive than sequencing but identification of the mutation is desirable, particularly when it is important to discriminate false positives due to PCR errors or template degradation from true mutations. We thus developed limited copy number - high resolution melting (LCN-HRM) which applies limiting dilution to HRM. Multiple replicate reactions with a limited number of target sequences per reaction allow low level mutations to be detected. The dilutions used (based on Ct values) are chosen such that mutations, if present, can be detected by the direct sequencing of amplicons with aberrant melting patterns. Results Using cell lines heterozygous for mutations, we found that the mutations were not readily detected when they comprised 10% of total alleles (20% tumour cells) by sequencing, whereas they were readily detectable at 5% total alleles by standard HRM. LCN-HRM allowed these mutations to be identified by direct sequencing of those positive reactions. LCN-HRM was then used to review formalin-fixed paraffin-embedded (FFPE) clinical samples showing discordant findings between sequencing and HRM for KRAS exon 2 and EGFR exons 19 and 21. Both true mutations present at low levels and sequence changes due to artefacts were detected by LCN-HRM. The use of high fidelity polymerases showed that the majority of the artefacts were derived from the damaged template rather than replication errors during amplification. Conclusion LCN-HRM bridges the sensitivity gap between HRM and sequencing and is effective in distinguishing between artefacts and true mutations. PMID:19811662

Superhydrophobic SERS substrates based on silicon hierarchical nanostructures

NASA Astrophysics Data System (ADS)

Chen, Xuexian; Wen, Jinxiu; Zhou, Jianhua; Zheng, Zebo; An, Di; Wang, Hao; Xie, Weiguang; Zhan, Runze; Xu, Ningsheng; Chen, Jun; She, Juncong; Chen, Huanjun; Deng, Shaozhi

2018-02-01

Silicon nanostructures have been cultivated as promising surface enhanced Raman scattering (SERS) substrates in terms of their low-loss optical resonance modes, facile functionalization, and compatibility with today’s state-of-the-art CMOS techniques. However, unlike their plasmonic counterparts, the electromagnetic field enhancements induced by silicon nanostructures are relatively small, which restrict their SERS sensing limit to around 10-7 M. To tackle this problem, we propose here a strategy for improving the SERS performance of silicon nanostructures by constructing silicon hierarchical nanostructures with a superhydrophobic surface. The hierarchical nanostructures are binary structures consisted of silicon nanowires (NWs) grown on micropyramids (MPs). After being modified with perfluorooctyltriethoxysilane (PFOT), the nanostructure surface shows a stable superhydrophobicity with a high contact angle of ˜160°. The substrate can allow for concentrating diluted analyte solutions into a specific area during the evaporation of the liquid droplet, whereby the analytes are aggregated into a small volume and can be easily detected by the silicon nanostructure SERS substrate. The analyte molecules (methylene blue: MB) enriched from an aqueous solution lower than 10-8 M can be readily detected. Such a detection limit is ˜100-fold lower than the conventional SERS substrates made of silicon nanostructures. Additionally, the detection limit can be further improved by functionalizing gold nanoparticles onto silicon hierarchical nanostructures, whereby the superhydrophobic characteristics and plasmonic field enhancements can be combined synergistically to give a detection limit down to ˜10-11 M. A gold nanoparticle-functionalized superhydrophobic substrate was employed to detect the spiked melamine in liquid milk. The results showed that the detection limit can be as low as 10-5 M, highlighting the potential of the proposed superhydrophobic SERS substrate in practical food safety inspection applications.

ARE WE THERE YET? TIME TO DETECTION OF NANOHERTZ GRAVITATIONAL WAVES BASED ON PULSAR-TIMING ARRAY LIMITS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, S. R.; Vallisneri, M.; Ellis, J. A.

2016-03-01

Decade-long timing observations of arrays of millisecond pulsars have placed highly constraining upper limits on the amplitude of the nanohertz gravitational-wave stochastic signal from the mergers of supermassive black hole binaries (∼10{sup −15} strain at f = 1 yr{sup −1}). These limits suggest that binary merger rates have been overestimated, or that environmental influences from nuclear gas or stars accelerate orbital decay, reducing the gravitational-wave signal at the lowest, most sensitive frequencies. This prompts the question whether nanohertz gravitational waves (GWs) are likely to be detected in the near future. In this Letter, we answer this question quantitatively using simple statistical estimates,more » deriving the range of true signal amplitudes that are compatible with current upper limits, and computing expected detection probabilities as a function of observation time. We conclude that small arrays consisting of the pulsars with the least timing noise, which yield the tightest upper limits, have discouraging prospects of making a detection in the next two decades. By contrast, we find large arrays are crucial to detection because the quadrupolar spatial correlations induced by GWs can be well sampled by many pulsar pairs. Indeed, timing programs that monitor a large and expanding set of pulsars have an ∼80% probability of detecting GWs within the next 10 years, under assumptions on merger rates and environmental influences ranging from optimistic to conservative. Even in the extreme case where 90% of binaries stall before merger and environmental coupling effects diminish low-frequency gravitational-wave power, detection is delayed by at most a few years.« less

Determination of target detection limits in hyperspectral data using band selection and dimensionality reduction

NASA Astrophysics Data System (ADS)

Gross, W.; Boehler, J.; Twizer, K.; Kedem, B.; Lenz, A.; Kneubuehler, M.; Wellig, P.; Oechslin, R.; Schilling, H.; Rotman, S.; Middelmann, W.

2016-10-01

Hyperspectral remote sensing data can be used for civil and military applications to robustly detect and classify target objects. High spectral resolution of hyperspectral data can compensate for the comparatively low spatial resolution, which allows for detection and classification of small targets, even below image resolution. Hyperspectral data sets are prone to considerable spectral redundancy, affecting and limiting data processing and algorithm performance. As a consequence, data reduction strategies become increasingly important, especially in view of near-real-time data analysis. The goal of this paper is to analyze different strategies for hyperspectral band selection algorithms and their effect on subpixel classification for different target and background materials. Airborne hyperspectral data is used in combination with linear target simulation procedures to create a representative amount of target-to-background ratios for evaluation of detection limits. Data from two different airborne hyperspectral sensors, AISA Eagle and Hawk, are used to evaluate transferability of band selection when using different sensors. The same target objects were recorded to compare the calculated detection limits. To determine subpixel classification results, pure pixels from the target materials are extracted and used to simulate mixed pixels with selected background materials. Target signatures are linearly combined with different background materials in varying ratios. The commonly used classification algorithms Adaptive Coherence Estimator (ACE) is used to compare the detection limit for the original data with several band selection and data reduction strategies. The evaluation of the classification results is done by assuming a fixed false alarm ratio and calculating the mean target-to-background ratio of correctly detected pixels. The results allow drawing conclusions about specific band combinations for certain target and background combinations. Additionally, generally useful wavelength ranges are determined and the optimal amount of principal components is analyzed.

Limited copy number-high resolution melting (LCN-HRM) enables the detection and identification by sequencing of low level mutations in cancer biopsies.

PubMed

Do, Hongdo; Dobrovic, Alexander

2009-10-08

Mutation detection in clinical tumour samples is challenging when the proportion of tumour cells, and thus mutant alleles, is low. The limited sensitivity of conventional sequencing necessitates the adoption of more sensitive approaches. High resolution melting (HRM) is more sensitive than sequencing but identification of the mutation is desirable, particularly when it is important to discriminate false positives due to PCR errors or template degradation from true mutations.We thus developed limited copy number - high resolution melting (LCN-HRM) which applies limiting dilution to HRM. Multiple replicate reactions with a limited number of target sequences per reaction allow low level mutations to be detected. The dilutions used (based on Ct values) are chosen such that mutations, if present, can be detected by the direct sequencing of amplicons with aberrant melting patterns. Using cell lines heterozygous for mutations, we found that the mutations were not readily detected when they comprised 10% of total alleles (20% tumour cells) by sequencing, whereas they were readily detectable at 5% total alleles by standard HRM. LCN-HRM allowed these mutations to be identified by direct sequencing of those positive reactions.LCN-HRM was then used to review formalin-fixed paraffin-embedded (FFPE) clinical samples showing discordant findings between sequencing and HRM for KRAS exon 2 and EGFR exons 19 and 21. Both true mutations present at low levels and sequence changes due to artefacts were detected by LCN-HRM. The use of high fidelity polymerases showed that the majority of the artefacts were derived from the damaged template rather than replication errors during amplification. LCN-HRM bridges the sensitivity gap between HRM and sequencing and is effective in distinguishing between artefacts and true mutations.

Sensitive electrochemical sensors for simultaneous determination of ascorbic acid, dopamine, and uric acid based on Au@Pd-reduced graphene oxide nanocomposites

NASA Astrophysics Data System (ADS)

Jiang, Jingjing; Du, Xuezhong

2014-09-01

Sensitive electrochemical sensors were fabricated with reduced graphene oxide-supported Au@Pd (Au@Pd-RGO) nanocomposites by one-step synthesis for individual and simultaneous determination of ascorbic acid (AA), dopamine (DA), and uric acid (UA) with low detection limits and wide concentration ranges. From the Au@Pd-RGO-modified electrodes, well-separated oxidation peaks and enhanced peak currents of AA, DA, and UA were observed owing to the superior conductivity of RGO and the excellent catalytic activity of Au@Pd nanoparticles. For individual detection, the linear responses of AA, DA, and UA were in the concentration ranges of 0.1-1000, 0.01-100, and 0.02-500 μM with detection limits of 0.02, 0.002, and 0.005 μM (S/N = 3), respectively. For simultaneous detection by synchronous change of the concentrations of AA, DA, and UA, the linear response ranges were 1-800, 0.1-100, and 0.1-350 μM with detection limits of 0.28, 0.024, and 0.02 μM (S/N = 3), respectively. The fabricated sensors were further applied to the detection of AA, DA, and UA in urine samples. The Au@Pd-RGO nanocomposites have promising applications in highly sensitive and selective electrochemical sensing.Sensitive electrochemical sensors were fabricated with reduced graphene oxide-supported Au@Pd (Au@Pd-RGO) nanocomposites by one-step synthesis for individual and simultaneous determination of ascorbic acid (AA), dopamine (DA), and uric acid (UA) with low detection limits and wide concentration ranges. From the Au@Pd-RGO-modified electrodes, well-separated oxidation peaks and enhanced peak currents of AA, DA, and UA were observed owing to the superior conductivity of RGO and the excellent catalytic activity of Au@Pd nanoparticles. For individual detection, the linear responses of AA, DA, and UA were in the concentration ranges of 0.1-1000, 0.01-100, and 0.02-500 μM with detection limits of 0.02, 0.002, and 0.005 μM (S/N = 3), respectively. For simultaneous detection by synchronous change of the concentrations of AA, DA, and UA, the linear response ranges were 1-800, 0.1-100, and 0.1-350 μM with detection limits of 0.28, 0.024, and 0.02 μM (S/N = 3), respectively. The fabricated sensors were further applied to the detection of AA, DA, and UA in urine samples. The Au@Pd-RGO nanocomposites have promising applications in highly sensitive and selective electrochemical sensing. Electronic supplementary information (ESI) available: pH optimization, comparison of sensor performances, interference experiments, and detection in urine samples. See DOI: 10.1039/c4nr01774a

Less-simplified models of dark matter for direct detection and the LHC

NASA Astrophysics Data System (ADS)

Choudhury, Arghya; Kowalska, Kamila; Roszkowski, Leszek; Sessolo, Enrico Maria; Williams, Andrew J.

2016-04-01

We construct models of dark matter with suppressed spin-independent scattering cross section utilizing the existing simplified model framework. Even simple combinations of simplified models can exhibit interference effects that cause the tree level contribution to the scattering cross section to vanish, thus demonstrating that direct detection limits on simplified models are not robust when embedded in a more complicated and realistic framework. In general for fermionic WIMP masses ≳ 10 GeV direct detection limits on the spin-independent scattering cross section are much stronger than those coming from the LHC. However these model combinations, which we call less-simplified models, represent situations where LHC searches become more competitive than direct detection experiments even for moderate dark matter mass. We show that a complementary use of several searches at the LHC can strongly constrain the direct detection blind spots by setting limits on the coupling constants and mediators' mass. We derive the strongest limits for combinations of vector + scalar, vector + "squark", and "squark" + scalar mediator, and present the corresponding projections for the LHC 14 TeV for a number of searches: mono-jet, jets + missing energy, and searches for heavy vector resonances.

Amplification-free point of care immunosensor for detecting type V collagen at a concentration level of ng/ml

NASA Astrophysics Data System (ADS)

Chung, Pei-Yu; Bracho-Sanchez, Evelyn R.; Jiang, Peng; Seagrave, JeanClare; Duncan, Matthew R.; Grotendorst, Gary R.; Schultz, Gregory; Batich, Christopher

2011-06-01

Point-of-care testing (POCT) is applicable in the immediate vicinity of the patient, where timely diagnosis or prognostic information could help doctors decide the following treatment. Among types of developed POCT, gold nanoparticle based lateral flow strip technology provides advantages such as simple operation, cost-effectiveness, and a user-friendly platform. Therefore, this type of POCT is most likely to be used in battlefields and developing countries. However, conventional lateral flow strips suffer from low detection limits. Although enzyme-linked amplification was demonstrated to improve the detection limit and sensitivity by stronger visible lines or by permitting electrochemical analytical instrumentation, the enzyme labels have potential to cause interference with other enzymes in our body fluids. To eliminate this limitation, we developed an amplification-free gold nanoparticle-based immunosensor applied for detecting collagen type V, which is produced or released abnormally during rejection of lung transplants and sulfur mustard exposure. By using suitable blocking protein to stabilize gold nanoparticles as the reporter probe, a low detection limit of ng/ml was achieved. This strategy is a promising platform for clinical POCT, with potential applications in military or disaster response.

Real-Time Detection of Telomerase in a Microelectromechanical Systems Platform

DTIC Science & Technology

2005-05-01

contains color images. 14. ABSTRACT 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT UU 18. NUMBER OF PAGES 147 19a...Telomerase accomplishes this by alleviating the “end-replication problem” (6,10,14,23,33,43). First described by Hayflick in 1965, the end-replication...were produced to determine the minimum detection limit of the ABI Prism 7000 as an optical fluorescent detection device. In addition, I wanted to

Digital Holographic Microscopy, a Method for Detection of Microorganisms in Plume Samples from Enceladus and Other Icy Worlds

PubMed Central

Bedrossian, Manuel; Lindensmith, Chris

2017-01-01

Abstract Detection of extant microbial life on Earth and elsewhere in the Solar System requires the ability to identify and enumerate micrometer-scale, essentially featureless cells. On Earth, bacteria are usually enumerated by culture plating or epifluorescence microscopy. Culture plates require long incubation times and can only count culturable strains, and epifluorescence microscopy requires extensive staining and concentration of the sample and instrumentation that is not readily miniaturized for space. Digital holographic microscopy (DHM) represents an alternative technique with no moving parts and higher throughput than traditional microscopy, making it potentially useful in space for detection of extant microorganisms provided that sufficient numbers of cells can be collected. Because sample collection is expected to be the limiting factor for space missions, especially to outer planets, it is important to quantify the limits of detection of any proposed technique for extant life detection. Here we use both laboratory and field samples to measure the limits of detection of an off-axis digital holographic microscope (DHM). A statistical model is used to estimate any instrument's probability of detection at various bacterial concentrations based on the optical performance characteristics of the instrument, as well as estimate the confidence interval of detection. This statistical model agrees well with the limit of detection of 103 cells/mL that was found experimentally with laboratory samples. In environmental samples, active cells were immediately evident at concentrations of 104 cells/mL. Published estimates of cell densities for Enceladus plumes yield up to 104 cells/mL, which are well within the off-axis DHM's limits of detection to confidence intervals greater than or equal to 95%, assuming sufficient sample volumes can be collected. The quantitative phase imaging provided by DHM allowed minerals to be distinguished from cells. Off-axis DHM's ability for rapid low-level bacterial detection and counting shows its viability as a technique for detection of extant microbial life provided that the cells can be captured intact and delivered to the sample chamber in a sufficient volume of liquid for imaging. Key Words: In situ life detection—Extant microorganisms—Holographic microscopy—Ocean Worlds—Enceladus—Imaging. Astrobiology 17, 913–925. PMID:28708412

Limit of detection of 15{sub N} by gas-chromatography atomic emission detection: Optimization using an experimental design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deruaz, D.; Bannier, A.; Pionchon, C.

1995-08-01

This paper deals with the optimal conditions for the detection of {sup 15}N determined using a four-factor experimental design from [2{sup 13}C,-1,3 {sup 15}N] caffeine measured with an atomic emission detector (AED) coupled to gas chromatography (GC). Owing to the capability of a photodiodes array, AED can simultaneously detect several elements using their specific emission lines within a wavelength range of 50 nm. So, the emissions of {sup 15}N and {sup 14}N are simultaneously detected at 420.17 nm and 421.46 nm respectively. Four independent experimental factors were tested (1) helium flow rate (plasma gas); (2) methane pressure (reactant gas); (3)more » oxygen pressure; (4) hydrogen pressure. It has been shown that these four gases had a significant influence on the analytical response of {sup 15}N. The linearity of the detection was determined using {sup 15}N amounts ranging from 1.52 pg to 19 ng under the optimal conditions obtained from the experimental design. The limit of detection was studied using different methods. The limits of detection of {sup 15}N was 1.9 pg/s according to the IUPAC method (International-Union of Pure and Applied Chemistry). The method proposed by Quimby and Sullivan gave a value of 2.3 pg/s and that of Oppenheimer gave a limit of 29 pg/s. For each determination, and internal standard: 1-isobutyl-3.7 dimethylxanthine was used. The results clearly demonstrate that GC AED is sensitive and selective enough to detect and measure {sup 15}N-labelled molecules after gas chromatographic separation.« less

Graphene nanosheet mediated MALDI-MS (GN-MALDI-MS) for rapid, in situ detection of intact incipient biofilm on material surfaces.

PubMed

Wu, Bo Sgum; Gopal, Judy; Hua, Pei-Yang; Wu, Hui-Fen

2016-09-01

Detection is the first step to efficient treatment, therefore early detection of biofilm gains paramount importance for the initiation of mitigation protocols. A systematic study was conducted to detect the biofilm formation (1h to 2month period) on aluminium, titanium surfaces and their corresponding oxide film surfaces. The limit of detection (LOD) in case of traditional MALDI-MS was limited to a 6h old biofilm. Whereas, in case of the Graphene nanosheet mediated MALDI-MS (GN-MALDI-MS) approach, early detection of the biofilm was demonstrated to be 1h on titanium surfaces and 3h for Al surfaces. Copyright © 2016 Elsevier B.V. All rights reserved.

High-field modulated ion-selective field-effect-transistor (FET) sensors with sensitivity higher than the ideal Nernst sensitivity.

PubMed

Chen, Yi-Ting; Sarangadharan, Indu; Sukesan, Revathi; Hseih, Ching-Yen; Lee, Geng-Yen; Chyi, Jen-Inn; Wang, Yu-Lin

2018-05-29

Lead ion selective membrane (Pb-ISM) coated AlGaN/GaN high electron mobility transistors (HEMT) was used to demonstrate a whole new methodology for ion-selective FET sensors, which can create ultra-high sensitivity (-36 mV/log [Pb 2+ ]) surpassing the limit of ideal sensitivity (-29.58 mV/log [Pb 2+ ]) in a typical Nernst equation for lead ion. The largely improved sensitivity has tremendously reduced the detection limit (10 -10  M) for several orders of magnitude of lead ion concentration compared to typical ion-selective electrode (ISE) (10 -7  M). The high sensitivity was obtained by creating a strong filed between the gate electrode and the HEMT channel. Systematical investigation was done by measuring different design of the sensor and gate bias, indicating ultra-high sensitivity and ultra-low detection limit obtained only in sufficiently strong field. Theoretical study in the sensitivity consistently agrees with the experimental finding and predicts the maximum and minimum sensitivity. The detection limit of our sensor is comparable to that of Inductively-Coupled-Plasma Mass Spectrum (ICP-MS), which also has detection limit near 10 -10  M.

Evaluation of a single-item screening question to detect limited health literacy in peritoneal dialysis patients.

PubMed

Jain, Deepika; Sheth, Heena; Bender, Filitsa H; Weisbord, Steven D; Green, Jamie A

2014-01-01

Studies have shown that a single-item question might be useful in identifying patients with limited health literacy. However, the utility of the approach has not been studied in patients receiving maintenance peritoneal dialysis (PD). We assessed health literacy in a cohort of 31 PD patients by administering the Rapid Estimate of Adult Literacy in Medicine (REALM) and a single-item health literacy (SHL) screening question "How confident are you filling out medical forms by yourself?" (Extremely, Quite a bit, Somewhat, A little bit, or Not at all). To determine the accuracy of the single-item question for detecting limited health literacy, we performed sensitivity and specificity analyses of the SHL and plotted the area under the receiver operating characteristic (AUROC) curve using the REALM as a reference standard. Using a cut-off of "Somewhat" or less confident, the sensitivity of the SHL for detecting limited health literacy was 80%, and the specificity was 88%. The positive likelihood ratio was 6.9. The SHL had an AUROC of 0.79 (95% confidence interval: 0.52 to 1.00). Our results show that the SHL could be effective in detecting limited health literacy in PD patients.

Of Detection Limits and Effective Mitigation: The Use of Infrared Cameras for Methane Leak Detection

NASA Astrophysics Data System (ADS)

Ravikumar, A. P.; Wang, J.; McGuire, M.; Bell, C.; Brandt, A. R.

2017-12-01

Mitigating methane emissions, a short-lived and potent greenhouse gas, is critical to limiting global temperature rise to two degree Celsius as outlined in the Paris Agreement. A major source of anthropogenic methane emissions in the United States is the oil and gas sector. To this effect, state and federal governments have recommended the use of optical gas imaging systems in periodic leak detection and repair (LDAR) surveys to detect for fugitive emissions or leaks. The most commonly used optical gas imaging systems (OGI) are infrared cameras. In this work, we systematically evaluate the limits of infrared (IR) camera based OGI system for use in methane leak detection programs. We analyze the effect of various parameters that influence the minimum detectable leak rates of infrared cameras. Blind leak detection tests were carried out at the Department of Energy's MONITOR natural gas test-facility in Fort Collins, CO. Leak sources included natural gas wellheads, separators, and tanks. With an EPA mandated 60 g/hr leak detection threshold for IR cameras, we test leak rates ranging from 4 g/hr to over 350 g/hr at imaging distances between 5 ft and 70 ft from the leak source. We perform these experiments over the course of a week, encompassing a wide range of wind and weather conditions. Using repeated measurements at a given leak rate and imaging distance, we generate detection probability curves as a function of leak-size for various imaging distances, and measurement conditions. In addition, we estimate the median detection threshold - leak-size at which the probability of detection is 50% - under various scenarios to reduce uncertainty in mitigation effectiveness. Preliminary analysis shows that the median detection threshold varies from 3 g/hr at an imaging distance of 5 ft to over 150 g/hr at 50 ft (ambient temperature: 80 F, winds < 4 m/s). Results from this study can be directly used to improve OGI based LDAR protocols and reduce uncertainty in estimated mitigation effectiveness. Furthermore, detection limits determined in this study can be used as standards to compare new detection technologies.

Homeland Security and Contraband Detection

NASA Astrophysics Data System (ADS)

Lanza, R. C.

Detection of contraband and illicit materials has become increasingly important, especially since the terrorist attacks in the United States on September 11, 2001. The nature of the detection problem embodies both physics issues and a set of operational constraints that limit the practical application of neutrons. The issue under consideration is detection of materials that are considered serious threats; these may include explosives; radioactive materials, fissile materials, and other materials associated with nuclear weapons, often referred to as special nuclear material (SNM). The overriding constraint is in the physics: systems must be based on clean physics; but unlike physics experiments, detection systems work under the limitation that materials must be identified nonintrusively, without interrupting the normal flow of commerce and with a high probability of detection and a low probability of false alarms. A great deal of work has been reported in the literature on neutron-based techniques for detecting explosives and drugs. The largest impetus by far for detecting explosives comes from aviation industry requirements for inspecting luggage and, to a lesser extent, cargo. The major alternative techniques are either X-ray-based or chemical trace detection methods that look for small traces of explosive residues. The limitations of the X-ray and trace methods in detecting explosives are well known, but currently (2008) it is safe to say that no neutron- or nuclear-based technique is being used routinely for security inspection, despite extensive development of these methods. Smuggling of nuclear materials has become a concern, and neutron techniques are particularly attractive for detecting them. Given the limitations of X-ray techniques and the need for SNM detection, it is now useful to reexamine neutron methodologies, particularly imaging. A significant number of neutron-based techniques have been proposed and are under development for security applications, especially SNM detection, but describing how they work is beyond the scope of the chapter. Instead, one particular approach to neutron imaging, neutron resonance radiography (NRR), is discussed in detail as it illustrates many of the issues connected with imaging and detection.

Detection of placental alpha microglobulin-1 versus insulin-like growth factor-binding protein-1 in amniotic fluid at term: a comparative study.

PubMed

Pollet-Villard, Marie; Cartier, Régine; Gaucherand, Pascal; Doret, Muriel

2011-06-01

We compared two biochemical tests of premature rupture of membranes (PROM) in vitro: Actim PROM (Medix Biochemica, Kauniainen, Finland), which detects insulin-like growth factor binding protein-1, and AmniSure (AmniSure International LLC, Cambridge, MA), which detects placental alpha microglobulin-1. Samples of amniotic fluid were collected during caesarean section in 41 patients. A dilution series was prepared and both tests were performed twice at each dilution. Sensitivity, detection limit, response time, and reproducibility of both tests were compared. Both tests' sensitivity was 100% at dilution 1:10 and 1:20. AmniSure sensitivity was higher at dilution 1:40 and 1:80 ( P < 0.05). In 29 of 40 cases, AmniSure had a lower detection limit than Actim PROM. AmniSure response times were shorter and reproducibility was higher than Actim PROM ( P < 0.05). AmniSure had a lower detection limit of amniotic fluid than Actim PROM, with a shorter response time, a higher sensitivity, and a better reproducibility. © Thieme Medical Publishers.

Tin oxide quantum dots embedded iron oxide composite as efficient lead sensor

NASA Astrophysics Data System (ADS)

Dutta, Dipa; Bahadur, Dhirendra

2018-04-01

SnO2 quantum dots (QDs) embedded iron oxide (IO) nanocomposite is fabricated and explored as a capable sensor for lead detection. Square wave anodic stripping voltammetry (SWASV) and amperometry have been used to explore the proposed sensor's response towards lead detection. The modified electrode shows linear current response for concentration of lead ranging from 99 nM to 6.6 µM with limit of detection 0.42 µM (34 ppb). Amperometry shows a detection limit as low as 0.18 nM (0.015 ppb); which is far below the permissible limit of lead in drinking water by World Health Organization. This proposed sensor shows linear current response (R2 = 0.98) for the lead concentration ranging from 133 × 10-9 to 4.4 × 10-6M. It also exhibits rapid response time of 12 sec with an ultra high sensitivity of 5.5 µA/nM. These detection properties promise the use of SnO2 QDs -IO composite for detection of lead in environmental sample with great ease.

A Validation of Remotely Sensed Fires Using Ground Reports

NASA Astrophysics Data System (ADS)

Ruminski, M. G.; Hanna, J.

2007-12-01

A satellite based analysis of fire detections and smoke emissions for North America is produced daily by NOAA/NESDIS. The analysis incorporates data from the MODIS (Terra and Aqua) and AVHRR (NOAA-15/16/17) polar orbiting instruments and GOES East and West geostationary spacecraft with nominal resolutions of 1km and 4 km for the polar and geostationary platforms respectively. Automated fire detection algorithms are utilized for each of the sensors. Analysts perform a quality control procedure on the automated detects by deleting points that are deemed to be false detects and adding points that the algorithms did not detect. A limited validation of the final quality controlled product was performed using high resolution (30 m) ASTER data in the summer of 2006. Some limitations in using ASTER data are that each scene is only approximately 3600 square km, the data acquisition time is relatively constant at around 1030 local solar time and ASTER is another remotely sensed data source. This study expands on the ASTER validation by using ground reports of prescribed burns in Montana and Idaho for 2003 and 2004. It provides a non-remote sensing data source for comparison. While the ground data do not have the limitations noted above for ASTER there are still limitations. For example, even though the data set covers a much larger area (nearly 600,000 square km) than even several ASTER scenes, it still represents a single region of North America. And while the ground data are not restricted to a narrow time window, only a date is provided with each report, limiting the ability to make detailed conclusions about the detection capabilities for specific instruments, especially for the less temporally frequent polar orbiting MODIS and AVHRR sensors. Comparison of the ground data reports to the quality controlled fire analysis revealed a low rate of overall detection of 23.00% over the entire study period. Examination of the daily detection rates revealed a wide variation, with some days resulting in as little as 5 detects out of 107 reported fires while other days had as many as 84 detections out of 160 reports. Inspection of the satellite imagery from the days with very low detection rates revealed that extensive cloud cover prohibited satellite fire detection. On days when cloud cover was at a minimum, detection rates were substantially higher. An estimate of the fire size was also provided with the ground data set. Statistics will be presented for days with minimal cloud cover which will indicate the probability of detection for fires of various sizes.

Application of Twin Beams in Mach-Zehnder Interferometer

NASA Technical Reports Server (NTRS)

Zhang, J. X.; Xie, C. D.; Peng, K. C.

1996-01-01

Using the twin beams generated from parametric amplifier to drive the two port of a Mach-Zehnder interferometer, it is shown that the minimum detectable optical phase shift can be largly reduced to the Heisenberg limit(1/n) which is far below the Shot Noise Limit(1/square root of n) the large gain limit. The dependence of the minimum detectable phase shift on parametric gain and the inefficient photodetectors has been discussed.

Kernel-Phase Interferometry for Super-Resolution Detection of Faint Companions

NASA Astrophysics Data System (ADS)

Factor, Samuel M.; Kraus, Adam L.

2017-01-01

Direct detection of close in companions (exoplanets or binary systems) is notoriously difficult. While coronagraphs and point spread function (PSF) subtraction can be used to reduce contrast and dig out signals of companions under the PSF, there are still significant limitations in separation and contrast. Non-redundant aperture masking (NRM) interferometry can be used to detect companions well inside the PSF of a diffraction limited image, though the mask discards ˜95% of the light gathered by the telescope and thus the technique is severely flux limited. Kernel-phase analysis applies interferometric techniques similar to NRM to a diffraction limited image utilizing the full aperture. Instead of non-redundant closure-phases, kernel-phases are constructed from a grid of points on the full aperture, simulating a redundant interferometer. I have developed my own faint companion detection pipeline which utilizes an Bayesian analysis of kernel-phases. I have used this pipeline to search for new companions in archival images from HST/NICMOS in order to constrain planet and binary formation models at separations inaccessible to previous techniques. Using this method, it is possible to detect a companion well within the classical λ/D Rayleigh diffraction limit using a fraction of the telescope time as NRM. This technique can easily be applied to archival data as no mask is needed and will thus make the detection of close in companions cheap and simple as no additional observations are needed. Since the James Webb Space Telescope (JWST) will be able to perform NRM observations, further development and characterization of kernel-phase analysis will allow efficient use of highly competitive JWST telescope time.

Enhancement of laser-induced breakdown spectroscopy (LIBS) Detection limit using a low-pressure and short-pulse laser-induced plasma process.

PubMed

Wang, Zhen Zhen; Deguchi, Yoshihiro; Kuwahara, Masakazu; Yan, Jun Jie; Liu, Ji Ping

2013-11-01

Laser-induced breakdown spectroscopy (LIBS) technology is an appealing technique compared with many other types of elemental analysis because of the fast response, high sensitivity, real-time, and noncontact features. One of the challenging targets of LIBS is the enhancement of the detection limit. In this study, the detection limit of gas-phase LIBS analysis has been improved by controlling the pressure and laser pulse width. In order to verify this method, low-pressure gas plasma was induced using nanosecond and picosecond lasers. The method was applied to the detection of Hg. The emission intensity ratio of the Hg atom to NO (IHg/INO) was analyzed to evaluate the LIBS detection limit because the NO emission (interference signal) was formed during the plasma generation and cooling process of N2 and O2 in the air. It was demonstrated that the enhancement of IHg/INO arose by decreasing the pressure to a few kilopascals, and the IHg/INO of the picosecond breakdown was always much higher than that of the nanosecond breakdown at low buffer gas pressure. Enhancement of IHg/INO increased more than 10 times at 700 Pa using picosecond laser with 35 ps pulse width. The detection limit was enhanced to 0.03 ppm (parts per million). We also saw that the spectra from the center and edge parts of plasma showed different features. Comparing the central spectra with the edge spectra, IHg/INO of the edge spectra was higher than that of the central spectra using the picosecond laser breakdown process.

ROBUST ESTIMATION OF MEAN AND VARIANCE USING ENVIRONMENTAL DATA SETS WITH BELOW DETECTION LIMIT OBSERVATIONS

EPA Science Inventory

Scientists, especially environmental scientists often encounter trace level concentrations that are typically reported as less than a certain limit of detection, L. Type 1, left-censored data arise when certain low values lying below L are ignored or unknown as they cannot be mea...

40 CFR 86.1309-90 - Exhaust gas sampling system; Otto-cycle and non-petroleum-fueled engines.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., shall exceed either 2.5 mg/l or a concentration equal to 25 times the limit of detection for the HPLC..., shall exceed either 2.5 mg/l or a concentration equal to 25 times the limit of detection for the HPLC...

40 CFR 86.1309-90 - Exhaust gas sampling system; Otto-cycle and non-petroleum-fueled engines.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., shall exceed either 2.5 mg/l or a concentration equal to 25 times the limit of detection for the HPLC..., shall exceed either 2.5 mg/l or a concentration equal to 25 times the limit of detection for the HPLC...

Reducing health risk assigned to organic emissions from a chemical weapons incinerator.

PubMed

Laman, David M; Weiler, B Douglas; Skeen, Rodney S

2013-03-01

Organic emissions from a chemical weapons incinerator have been characterized with an improved set of analytical methods to reduce the human health risk assigned to operations of the facility. A gas chromatography/mass selective detection method with substantially reduced detection limits has been used in conjunction with scanning electron microscopy/energy dispersive X-ray spectrometry and Fourier transform infrared microscopy to improve the speciation of semi-volatile and non-volatile organics emitted from the incinerator. The reduced detection limits have allowed a significant reduction in the assumed polycyclic aromatic hydrocarbon (PAH) and aminobiphenyl (ABP) emission rates used as inputs to the human health risk assessment for the incinerator. A mean factor of 17 decrease in assigned human health risk is realized for six common local exposure scenarios as a result of the reduced PAH and ABP detection limits.

Bioelectrocatalytic application of titania nanotube array for molecule detection.

PubMed

Xie, Yibing; Zhou, Limin; Huang, Haitao

2007-06-15

A bioelectrocatalysis system based on titania nanotube electrode has been developed for the quantitative detection application. Highly ordered titania nanotube array with inner diameter of 60 nm and total length of 540 nm was formed by anodizing titanium foils. The functionalization modification was achieved by embedding glucose oxidases inside tubule channels and electropolymerizing pyrrole for interfacial immobilization. Morphology and microstructure characterization, electrochemical properties and bioelectrocatalytic reactivities of this composite were fully investigated. The direct detection of hydrogen peroxide by electrocatalytic reduction reaction was fulfilled on pure titania nanotube array with a detection limit up to 2.0 x 10(-4)mM. A biosensor based on the glucose oxidase-titania/titanium electrode was constructed for amperometric detection and quantitative determination of glucose in a phosphate buffer solution (pH 6.8) under a potentiostatic condition (-0.4V versus SCE). The resulting glucose biosensor showed an excellent performance with a response time below 5.6s and a detection limit of 2.0 x 10(-3)mM. The corresponding detection sensitivity was 45.5 microA mM(-1)cm(-2). A good operational reliability was also achieved with relative standard deviations below 3.0%. This novel biosensor exhibited quite high response sensitivity and low detection limit for potential applications.

Development of a β-Lactoglobulin Sensor Based on SPR for Milk Allergens Detection.

PubMed

Ashley, Jon; D'Aurelio, Roberta; Piekarska, Monika; Temblay, Jeff; Pleasants, Mike; Trinh, Linda; Rodgers, Thomas L; Tothill, Ibtisam E

2018-03-27

A sensitive and label-free surface plasmon resonance (SPR) based sensor was developed in this work for the detection of milk allergens. β-lactoglobulin (BLG) protein was used as the biomarker for cow milk detection. This is to be used directly in final rinse samples of cleaning in-place (CIP) systems of food manufacturers. The affinity assay was optimised and characterised before a standard curve was performed in pure buffer conditions, giving a detection limit of 0.164 µg mL -1 as a direct binding assay. The detection limit can be further enhanced through the use of a sandwich assay and amplification with nanomaterials. However, this was not required here, as the detection limit achieved exceeded the required allergen detection levels of 2 µg mL -1 for β-lactoglobulin. The binding affinities of the polyclonal antibody for BLG, expressed by the dissociation constant (K D ), were equal to 2.59 × 10 -9 M. The developed SPR-based sensor offers several advantages in terms of label-free detection, real-time measurements, potential on-line system and superior sensitivity when compared to ELISA-based techniques. The method is novel for this application and could be applied to wider food allergen risk management decision(s) in food manufacturing.

Lowering detection limits for 1,2,3-trichloropropane in water using solid phase extraction coupled to purge and trap sample introduction in an isotope dilution GC-MS method.

PubMed

Liao, Wenta; Ghabour, Miriam; Draper, William M; Chandrasena, Esala

2016-09-01

Purge and trap sample introduction (PTI) has been the premier sampling and preconcentration technique for gas chromatographic determination of volatile organic compounds (VOCs) in drinking water for almost 50 years. PTI affords sub parts-per-billion (ppb) detection limits for purgeable VOCs including fixed gases and higher boiling hydrocarbons and halocarbons. In this study the coupling of solid phase extraction (SPE) to PTI was investigated as a means to substantially increase enrichment and lower detection limits for the emerging contaminant, 1,2,3-trichloropropane (TCP). Water samples (500 mL) were dechlorinated, preserved with a biocide, and spiked with the isotope labeled internal standard, d5-TCP. The entire 500 mL sample was extracted with activated carbon or carbon molecular sieve SPE cartridges, and then eluted with dichloromethane -- excess solvent was removed in a nitrogen evaporator and diethylene glycol "keeper" remaining was dispersed in 5 mL of water for PTI GC-MS analysis. The experimental Method Detection Limit (MDL) for TCP was 0.11 ng/L (ppt) and accuracy was 95-103% in sub-ppt determinations. Groundwater samples including impaired California sources and treated water (n = 21) were analyzed with results ranging from below the method reporting limit (0.30 ng/L) to > 250 ng/L. Coupling of SPE with PTI may provide similar reductions in detection limits for other VOCs with appropriate physical-chemical properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rapid Detection of Ebola Virus with a Reagent-Free, Point-of-Care Biosensor

PubMed Central

Baca, Justin T.; Severns, Virginia; Lovato, Debbie; Branch, Darren W.; Larson, Richard S.

2015-01-01

Surface acoustic wave (SAW) sensors can rapidly detect Ebola antigens at the point-of-care without the need for added reagents, sample processing, or specialized personnel. This preliminary study demonstrates SAW biosensor detection of the Ebola virus in a concentration-dependent manner. The detection limit with this methodology is below the average level of viremia detected on the first day of symptoms by PCR. We observe a log-linear sensor response for highly fragmented Ebola viral particles, with a detection limit corresponding to 1.9 × 104 PFU/mL prior to virus inactivation. We predict greatly improved sensitivity for intact, infectious Ebola virus. This point-of-care methodology has the potential to detect Ebola viremia prior to symptom onset, greatly enabling infection control and rapid treatment. This biosensor platform is powered by disposable AA batteries and can be rapidly adapted to detect other emerging diseases in austere conditions. PMID:25875186

Detection method of flexion relaxation phenomenon based on wavelets for patients with low back pain

NASA Astrophysics Data System (ADS)

Nougarou, François; Massicotte, Daniel; Descarreaux, Martin

2012-12-01

The flexion relaxation phenomenon (FRP) can be defined as a reduction or silence of myoelectric activity of the lumbar erector spinae muscle during full trunk flexion. It is typically absent in patients with chronic low back pain (LBP). Before any broad clinical utilization of this neuromuscular response can be made, effective, standardized, and accurate methods of identifying FRP limits are needed. However, this phenomenon is clearly more difficult to detect for LBP patients than for healthy patients. The main goal of this study is to develop an automated method based on wavelet transformation that would improve time point limits detection of surface electromyography signals of the FRP in case of LBP patients. Conventional visual identification and proposed automated methods of time point limits detection of relaxation phase were compared on experimental data using criteria of accuracy and repeatability based on physiological properties. The evaluation demonstrates that the use of wavelet transform (WT) yields better results than methods without wavelet decomposition. Furthermore, methods based on wavelet per packet transform are more effective than algorithms employing discrete WT. Compared to visual detection, in addition to demonstrating an obvious saving of time, the use of wavelet per packet transform improves the accuracy and repeatability in the detection of the FRP limits. These results clearly highlight the value of the proposed technique in identifying onset and offset of the flexion relaxation response in LBP subjects.

Detection of HIV-1 p24 at Attomole Level by Ultrasensitive ELISA with Thio-NAD Cycling

PubMed Central

Nakatsuma, Akira; Kaneda, Mugiho; Kodama, Hiromi; Morikawa, Mika; Watabe, Satoshi; Nakaishi, Kazunari; Yamashita, Masakane; Yoshimura, Teruki; Miura, Toshiaki; Ninomiya, Masaki; Ito, Etsuro

2015-01-01

To reduce the window period between HIV-1 infection and the ability to diagnose it, a fourth-generation immunoassay including the detection of HIV-1 p24 antigen has been developed. However, because the commercially available systems for this assay use special, high-cost instruments to measure, for example, chemiluminescence, it is performed only by diagnostics companies and hub hospitals. To overcome this limitation, we applied an ultrasensitive ELISA coupled with a thio-NAD cycling, which is based on a usual enzyme immunoassay without special instruments, to detect HIV-1 p24. The p24 detection limit by our ultrasensitive ELISA was 0.0065 IU/assay (i.e., ca. 10-18 moles/assay). Because HIV-1 p24 antigen is thought to be present in the virion in much greater numbers than viral RNA copies, the value of 10-18 moles of the p24/assay corresponds to ca. 103 copies of the HIV-1 RNA/assay. That is, our ultrasensitive ELISA is chasing the detection limit (102 copies/assay) obtained by PCR-based nucleic acid testing (NAT) with a margin of only one different order. Further, the detection limit by our ultrasensitive ELISA is less than that mandated for a CE-marked HIV antigen/antibody assay. An additional recovery test using blood supported the reliability of our ultrasensitive ELISA. PMID:26098695

A search for SiO, OH, CO and HCN radio emission from silicate-carbon stars

NASA Technical Reports Server (NTRS)

Little-Marenin, I. R.; Sahai, R.; Wannier, P. G.; Benson, P. J.; Gaylard, M.; Omont, A.

1994-01-01

We report upper limits for radio emission of SiO at 86 and 43 GHz, of OH at 1612 and 1665/1667 MHz, of CO at 115 GHz and HCN at 88.6 GHz in the silicate-carbon stars. These upper limits of SiO imply that oxygen-rich material has not been detected within 2R(sub star) of a central star even though the detected emission from silicate dust grains, H2O and OH maser establishes the presence of oxygen-rich material from about tens to thousands of AU of a central star. The upper limit of the SiO abundance is consistent with that found in oxygen-rich envelopes. Upper limits of the mass loss rate (based on the CO data) are estimated to be between 10(exp -6) to 10(exp -7) solar mass/yr assuming a distance of 1.5 kpc for these stars. The absence of HCN microwave emission implies that no carbon-rich material can be detected at large distances (thousands of AU) from a central star. The lack of detections of SiO, CO, and HCN emission is most likely due to the large distances of these stars. A number of C stars were detected in CO and HCN, but only the M supergiant VX Sgr was detected in CO.

Acetylcholinesterase Immobilized on Magnetic Beads for Pesticides Detection: Application to Olive Oil Analysis

PubMed Central

Ben Oujji, Najwa; Bakas, Idriss; Istamboulié, Georges; Ait-Ichou, Ihya; Ait-Addi, Elhabib; Rouillon, Régis; Noguer, Thierry

2012-01-01

This work presents the development of bioassays and biosensors for the detection of insecticides widely used in the treatment of olive trees. The systems are based on the covalent immobilisation of acetylcholinesterase on magnetic microbeads using either colorimetry or amperometry as detection technique. The magnetic beads were immobilised on screen-printed electrodes or microtitration plates and tested using standard solutions and real samples. The developed devices showed good analytical performances with limits of detection much lower than the maximum residue limit tolerated by international regulations, as well as a good reproducibility and stability. PMID:22969377

A novel dicyanoisophorone based red-emitting fluorescent probe with a large Stokes shift for detection of hydrazine in solution and living cells

NASA Astrophysics Data System (ADS)

Lv, Hongshui; Sun, Haiyan; Wang, Shoujuan; Kong, Fangong

2018-05-01

A novel dicyanoisophorone based fluorescent probe HP was developed to detect hydrazine. Upon the addition of hydrazine, probe HP displayed turn-on fluorescence in the red region with a large Stokes shift (180 nm). This probe exhibited high selectivity and high sensitivity to hydrazine in solution. The detection limit of HP was found to be 3.26 ppb, which was lower than the threshold limit value set by USEPA (10 ppb). Moreover, the probe was successfully applied to detect hydrazine in different water samples and living cells.

Highly sensitive and selective liquid crystal optical sensor for detection of ammonia.

PubMed

Niu, Xiaofang; Zhong, Yuanbo; Chen, Rui; Wang, Fei; Luo, Dan

2017-06-12

Ammonia detection technologies are very important in environment monitoring. However, most existing technologies are complex and expensive, which limit the useful range of real-time application. Here, we propose a highly sensitive and selective optical sensor for detection of ammonia (NH 3 ) based on liquid crystals (LCs). This optical sensor is realized through the competitive binding between ammonia and liquid crystals on chitosan-Cu 2+ that decorated on glass substrate. We achieve a broad detection range of ammonia from 50 ppm to 1250 ppm, with a low detection limit of 16.6 ppm. This sensor is low-cost, simple, fast, and highly sensitive and selective for detection of ammonia. The proposal LC sensing method can be a sensitive detection platform for other molecule monitors such as proteins, DNAs and other heavy metal ions by modifying sensing molecules.

Sniper detection using infrared camera: technical possibilities and limitations

NASA Astrophysics Data System (ADS)

Kastek, M.; Dulski, R.; Trzaskawka, P.; Bieszczad, G.

2010-04-01

The paper discusses technical possibilities to build an effective system for sniper detection using infrared cameras. Descriptions of phenomena which make it possible to detect sniper activities in infrared spectra as well as analysis of physical limitations were performed. Cooled and uncooled detectors were considered. Three phases of sniper activities were taken into consideration: before, during and after the shot. On the basis of experimental data the parameters defining the target were determined which are essential in assessing the capability of infrared camera to detect sniper activity. A sniper body and muzzle flash were analyzed as targets. The simulation of detection ranges was done for the assumed scenario of sniper detection task. The infrared sniper detection system was discussed, capable of fulfilling the requirements. The discussion of the results of analysis and simulations was finally presented.

Electrophoretically mediated microanalysis of leucine aminopeptidase using two-photon excited fluorescence detection on a microchip.

PubMed

Zugel, S A; Burke, B J; Regnier, F E; Lytle, F E

2000-11-15

Two-photon excited fluorescence detection was performed on a microfabricated electrophoresis chip. A calibration curve of the fluorescent tag beta-naphthylamine was performed, resulting in a sensitivity of 2.5 x 10(9) counts M(-1) corresponding to a detection limit of 60 nM. Additionally, leucine aminopeptidase was assayed on the chip using electrophoretically mediated microanalysis. The differential electroosmotic mobilities of the enzyme and substrate, L-leucine beta-naphthylamide, allowed for efficient mixing in an open channel, resulting in the detection of a 30 nM enzyme solution under constant potential. A zero potential incubation for 1 min yielded a calculated detection limit of 4 nM enzyme.

Nanoplatforms for Detection, Remediation and Protection Against Chem-Bio Warfare

NASA Astrophysics Data System (ADS)

Denkbaş, E. B.; Bayram, C.; Kavaz, D.; Çirak, T.; Demirbilek, M.

Chemical and biological substances have been used as warfare agents by terrorists by varying degree of sophistication. It is critical that these agents be detected in real-time with high level of sensitively, specificity, and accuracy. Many different types of techniques and systems have been developed to detect these agents. But there are some limitations in these conventional techniques and systems. Limitations include the collection, handling and sampling procedures, detection limits, sample transfer, expensive equipment, personnel training, and detection materials. Due to the unique properties such as quantum effect, very high surface/volume ratio, enhanced surface reactivity, conductivity, electrical and magnetic properties of the nanomaterials offer great opportunity to develop very fast, sensitive, accurate and cost effective detection techniques and systems to detect chemical and biological (chem.-bio) warfare agents. Furthermore, surface modification of the materials is very easy and effective way to get functional or smart surfaces to be used as nano-biosensor platform. In that respect many different types of nanomaterials have been developed and used for the detection, remediation and protection, such as gold and silver nanoparticles, quantum dots, Nano chips and arrays, fluorescent polymeric and magnetic nanoparticles, fiber optic and cantilever based nanobiosensors, nanofibrillar nanostructures etc. This study summarizes preparation and characterization of nanotechnology based approaches for the detection of and remediation and protection against chem.-bio warfare agents.

Method for improving the limit of detection in a data signal

DOEpatents

Synovec, Robert E.; Yueng, Edward S.

1989-10-17

A method for improving the limit of detection for a data set in which experimental noise is uncorrelated along a given abscissa and an analytical signal is correlated to the abscissa, the steps comprising collecting the data set, converting the data set into a data signal including an analytical portion and the experimental noise portion, designating and adjusting a baseline of the data signal to center the experimental noise numerically about a zero reference, and integrating the data signal preserving the corresponding information for each point of the data signal. The steps of the method produce an enhanced integrated data signal which improves the limit of detection of the data signal.

Method for improving the limit of detection in a data signal

DOEpatents

Synovec, R.E.; Yueng, E.S.

1989-10-17

Disclosed is a method for improving the limit of detection for a data set in which experimental noise is uncorrelated along a given abscissa and an analytical signal is correlated to the abscissa, the steps comprising collecting the data set, converting the data set into a data signal including an analytical portion and the experimental noise portion, designating and adjusting a baseline of the data signal to center the experimental noise numerically about a zero reference, and integrating the data signal preserving the corresponding information for each point of the data signal. The steps of the method produce an enhanced integrated data signal which improves the limit of detection of the data signal. 8 figs.

Quantum-limited evanescent single molecule sensing.

NASA Astrophysics Data System (ADS)

Bowen, Warwick; Mauranyapin, Nicolas; Madsen, Lars; Taylor, Michael; Waleed, Muhammad

Sensors that are able to detect and track single unlabeled biomolecules are an important tool both to understand biomolecular dynamics and interactions, and for medical diagnostics operating at their ultimate detection limits. Recently, exceptional sensitivity has been achieved using the strongly enhanced evanescent fields provided by optical microcavities and plasmonic resonators. However, at high field intensities photodamage to the biological specimen becomes increasingly problematic. Here, we introduce a new approach that combines dark field illumination and heterodyne detection in an optical nanofibre. This allows operation at the fundamental precision limit introduced by quantisation of light. We achieve state-of-the-art sensitivity with a four order-of-magnitude reduction in optical intensity. This enables quantum noise limited tracking of single biomolecules as small as 3.5 nm and surface-molecule interactions to be montored over extended periods. By achieving quantum noise limited precision, our approach provides a pathway towards quantum-enhanced single-molecule biosensors. We acknkowledge financial support from AFOSR and AOARD.

[Exposure to organic halogen compounds in drinking water of 9 Italian regions: exposure to chlorites, chlorates, thrihalomethanes, trichloroethylene and tetrachloroethylene].

PubMed

Fantuzzi, G; Aggazzotti, G; Righi, E; Predieri, G; Giacobazzi, P; Kanitz, S; Barbone, F; Sansebastiano, G; Ricci, C; Leoni, V; Fabiani, L; Triassi, M

2007-01-01

This study investigated the exposure to organohalogens compounds in drinking water from 9 Italian towns (Udine, Genova, Parma, Modena, Siena, Roma, L'Aquila, Napoli and Catania). Overall, 1199 samples collected from 72 waterworks were analyzed. THMs, trichloroethylene and tetrachloroethylene were evaluated using the head-space gas chromatographic technique (detection limit of 0.01 microg/l; chlorite and chlorate analysis was performed by ion chromatography (detection limit of 20 microg/l). THMs were evidenced in 925 samples (77%) (median value: 1.12 micro/l; range: 0.01-54 mciro/l) and 7 were higher than the THMs Italian limit of 30 microg/l. Chlorite and chlorate levels were higher than the detection limit in 45% for chlorite and in 34% for chlorate samples; median values were 221 microg/l and 76 microg/l, respectively. Chlorite values were higher than the chlorite Italian limit (700 microg/l) in 35 samples (8.7%). Trichloroethylene and tetrachloroethylene were measured in 29% and 44% of the investigated samples and showed values lower than the Italian limit (highest levels of 6 microg/l and 9 microg/l, respectively). The low levels detected of THMs, trichloroethylene and tetrachloroethylene have no potentials effects on human health, whereas, the levels of chlorite and chlorates should be further evaluated and their potential effects for the populations using these drinking waters, better understood.

A sandwich-type optical immunosensor based on the alkaline phosphatase enzyme for Salmonella thypimurium detection

NASA Astrophysics Data System (ADS)

Widyastuti, E.; Puspitasari Schonherr, M. F.; Masruroh, A.; Anggraeni, R. A.; Nisak, Y. K.; Mursidah, S.

2018-03-01

Salmonella is pathogenic bacteria that caused foodborne diseases which being called Salmonellosis. Prevalence of Salmonellosis that being caused by Salmonella thypimurium in Indonesia is quite high. However, detection of Salmonella bacteria in food still limited, complicated, and required a lot time. Sensitive optical assay for Salmonella thypimurium paper based detection has been developed by integrating sandwich assay between antibody-antigen complex and alkaline phosphatase enzyme that produce visible bluish-purple colour with presence of NBT-BCIP substrate. The results showed that Limit of Quantitation of detection is 105 CFU mL-1 with detection time 15 minutes. Linearity test between Colour intensity that produced from Salmonella concentration presence on samples showed that detection has good linearity. Selectivity test exhibited excellent sensitivity with good discrimination against Escherichia coli.

Cycling temperature capillary electrophoresis: A quantitative, fast and inexpensive method to detect mutations in mixed populations of human mitochondrial DNA.

PubMed

Refinetti, Paulo; Morgenthaler, Stephan; Ekstrøm, Per O

2016-07-01

Cycling temperature capillary electrophoresis has been optimised for mutation detection in 76% of the mitochondrial genome. The method was tested on a mixed sample and compared to mutation detection by next generation sequencing. Out of 152 fragments 90 were concordant, 51 discordant and in 11 were semi-concordant. Dilution experiments show that cycling capillary electrophoresis has a detection limit of 1-3%. The detection limit of routine next generation sequencing was in the ranges of 15 to 30%. Cycling temperature capillary electrophoresis detect and accurate quantify mutations at a fraction of the cost and time required to perform a next generation sequencing analysis. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Detection of silver nanoparticles in seawater at ppb levels using UV-visible spectrophotometry with long path cells.

PubMed

Lodeiro, Pablo; Achterberg, Eric P; El-Shahawi, Mohammad S

2017-03-01

Silver nanoparticles (AgNPs) are emerging contaminants that are difficult to detect in natural waters. UV-visible spectrophotometry is a simple technique that allows detection of AgNPs through analysis of their characteristic surface plasmon resonance band. The detection limit for nanoparticles using up to 10cm path length cuvettes with UV-visible spectrophotometry is in the 0.1-10ppm range. This detection limit is insufficiently low to observe AgNPs in natural environments. Here we show how the use of capillary cells with an optical path length up to 200cm, forms an excellent technique for rapid detection and quantification of non-aggregated AgNPs at ppb concentrations in complex natural matrices such as seawater. Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical Contaminant and Decontaminant Test Methodology Source Document. Second Edition

DTIC Science & Technology

2012-07-01

performance as described in “A Statistical Overview on Univariate Calibration, Inverse Regression, and Detection Limits: Application to Gas Chromatography...Overview on Univariate Calibration, Inverse Regression, and Detection Limits: Application to Gas Chromatography/Mass Spectrometry Technique. Mass... APPLICATIONS INTERNATIONAL CORPORATION Gunpowder, MD 21010-0068 July 2012 Approved for public release; distribution is unlimited

78 FR 33110 - Certain Electronic Digital Media Devices and Components Thereof; Determination To Review a Remand...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-03

... construction of the claims added during reissue? In particular, please comment on the applicability of the... proffered claim construction argument that construes the claim limitation ``to detect that the signal path... proposed construction of the claimed detection circuitry limitation is adopted (see Apple Pet. at 69-76...

Polymer microchip CE of proteins either off- or on-chip labeled with chameleon dye for simplified analysis.

PubMed

Yu, Ming; Wang, Hsiang-Yu; Woolley, Adam T

2009-12-01

Microchip CE of proteins labeled either off- or on-chip with the "chameleon" CE dye 503 using poly(methyl methacrylate) microchips is presented. A simple dynamic coating using the cationic surfactant CTAB prevented nonspecific adsorption of protein and dye to the channel walls. The labeling reactions for both off- and on-chip labeling proceeded at room temperature without requiring heating steps. In off-chip labeling, a 9 ng/mL concentration detection limit for BSA, corresponding to a approximately 7 fg (100 zmol) mass detection limit, was obtained. In on-chip tagging, the free dye and protein were placed in different reservoirs of the microchip, and an extra incubation step was not needed. A 1 microg/mL concentration detection limit for BSA, corresponding to a approximately 700 fg (10 amol) mass detection limit, was obtained from this protocol. The earlier elution time of the BSA peak in on-chip labeling resulted from fewer total labels on each protein molecule. Our on-chip labeling method is an important part of automation in miniaturized devices.

Radiometric Short-Term Fourier Transform analysis of photonic Doppler velocimetry recordings and detectivity limit

NASA Astrophysics Data System (ADS)

Prudhomme, G.; Berthe, L.; Bénier, J.; Bozier, O.; Mercier, P.

2017-01-01

Photonic Doppler Velocimetry is a plug-and-play and versatile diagnostic used in dynamic physic experiments to measure velocities. When signals are analyzed using a Short-Time Fourier Transform, multiple velocities can be distinguished: for example, the velocities of moving particle-cloud appear on spectrograms. In order to estimate the back-scattering fluxes of target, we propose an original approach "PDV Radiometric analysis" resulting in an expression of time-velocity spectrograms coded in power units. Experiments involving micron-sized particles raise the issue of detection limit; particle-size limit is very difficult to evaluate. From the quantification of noise sources, we derive an estimation of the spectrogram noise leading to a detectivity limit, which may be compared to the fraction of the incoming power which has been back-scattered by the particle and then collected by the probe. This fraction increases with their size. At last, some results from laser-shock accelerated particles using two different PDV systems are compared: it shows the improvement of detectivity with respect to the Effective Number of Bits (ENOB) of the digitizer.

An adaptive confidence limit for periodic non-steady conditions fault detection

NASA Astrophysics Data System (ADS)

Wang, Tianzhen; Wu, Hao; Ni, Mengqi; Zhang, Milu; Dong, Jingjing; Benbouzid, Mohamed El Hachemi; Hu, Xiong

2016-05-01

System monitoring has become a major concern in batch process due to the fact that failure rate in non-steady conditions is much higher than in steady ones. A series of approaches based on PCA have already solved problems such as data dimensionality reduction, multivariable decorrelation, and processing non-changing signal. However, if the data follows non-Gaussian distribution or the variables contain some signal changes, the above approaches are not applicable. To deal with these concerns and to enhance performance in multiperiod data processing, this paper proposes a fault detection method using adaptive confidence limit (ACL) in periodic non-steady conditions. The proposed ACL method achieves four main enhancements: Longitudinal-Standardization could convert non-Gaussian sampling data to Gaussian ones; the multiperiod PCA algorithm could reduce dimensionality, remove correlation, and improve the monitoring accuracy; the adaptive confidence limit could detect faults under non-steady conditions; the fault sections determination procedure could select the appropriate parameter of the adaptive confidence limit. The achieved result analysis clearly shows that the proposed ACL method is superior to other fault detection approaches under periodic non-steady conditions.

Determination of bisphenol A in food-simulating liquids using LCED with a chemically modified electrode.

PubMed

D'Antuono, A; Dall'Orto, V C; Lo Balbo, A; Sobral, S; Rezzano, I

2001-03-01

Liquid chromatography with electrochemical detector (LC-ED), using a chemically modified electrode coated with a metalloporphyrin film, is reported for determination of bisphenol A (BPA) migration from polycarbonate baby bottles. The extraction process of the samples was performed according to regulations of the Southern Common Market (MERCOSUR), where certain food-simulating liquids [(A) distilled water, (B) acetic acid 3% V/V in distilled water, and (C) ethanol 15% V/V in distilled water] are defined along with controlled time and temperature conditions. The baseline obtained using the naked electrode showed a considerable drift which increased the detection limit. This effect was suppressed with the chemically modified electrode. A linear range up to 450 ppb along with a detection limit of 20 ppb for the amperometric detection technique was observed. The procedure described herein allowed lowering the detection limit of the method to 0.2 ppb. The value found for BPA in the food-simulating liquid is 1.2 ppb, which is below the tolerance limit for specific migration (4.8 ppm).

Statistical analysis of water-quality data containing multiple detection limits: S-language software for regression on order statistics

USGS Publications Warehouse

Lee, L.; Helsel, D.

2005-01-01

Trace contaminants in water, including metals and organics, often are measured at sufficiently low concentrations to be reported only as values below the instrument detection limit. Interpretation of these "less thans" is complicated when multiple detection limits occur. Statistical methods for multiply censored, or multiple-detection limit, datasets have been developed for medical and industrial statistics, and can be employed to estimate summary statistics or model the distributions of trace-level environmental data. We describe S-language-based software tools that perform robust linear regression on order statistics (ROS). The ROS method has been evaluated as one of the most reliable procedures for developing summary statistics of multiply censored data. It is applicable to any dataset that has 0 to 80% of its values censored. These tools are a part of a software library, or add-on package, for the R environment for statistical computing. This library can be used to generate ROS models and associated summary statistics, plot modeled distributions, and predict exceedance probabilities of water-quality standards. ?? 2005 Elsevier Ltd. All rights reserved.

Annual Report of Lawrence Livermore National Laboratory to the Federal Aviation Administration on the High Altitude Pollution Program - 1980.

DTIC Science & Technology

1980-12-01

calculated change in 03 at high altitude to statistical detection limits for change as developed from Umkehr data from Arosa , -• Switzerland, and we...from - . Arosa (Penner et al., 1981). The method used to derive these limits is similar to that described for total 03 by Hill et al. (1977). These...N limit, Arosa -10 I I IN. (b) Umkehr, level 8 (-38-43 km) 5-10 C ~~Statistical"/ 7 ’ detection -20- limit, Arosa 1970 1980 1990 2000 2010 2020 2030

The quantum limit for gravitational-wave detectors and methods of circumventing it

NASA Technical Reports Server (NTRS)

Thorne, K. S.; Caves, C. M.; Sandberg, V. D.; Zimmermann, M.; Drever, R. W. P.

1979-01-01

The Heisenberg uncertainty principle prevents the monitoring of the complex amplitude of a mechanical oscillator more accurately than a certain limit value. This 'quantum limit' is a serious obstacle to the achievement of a 10 to the -21st gravitational-wave detection sensitivity. This paper examines the principles of the back-action evasion technique and finds that this technique may be able to overcome the problem of the quantum limit. Back-action evasion does not solve, however, other problems of detection, such as weak coupling, large amplifier noise, and large Nyquist noise.

Detection of Hepatitis B Virus DNA among Chronic and potential Occult HBV patients in resource-limited settings by Loop-Mediated Isothermal Amplification assay.

PubMed

Akram, Arifa; Islam, S M Rashedul; Munshi, Saif Ullah; Tabassum, Shahina

2018-05-16

Transmission of Hepatitis B Virus (HBV) usually occurs due to the transfusion of blood or blood products from chronic HBV (CHB) or occult HBV infected (OBI) patients. Besides serological tests e.g. HBsAg and anti-HBc (total), detection of HBV-DNA is necessary for the diagnosis of OBI patients. Different nucleic acid tests (NATs) including real-time-Polymerase Chain Reaction (qPCR) are used for the detect HBV-DNA. The NATs are expensive and require technical expertise which are barriers to introducing them in resource-limited settings. This study was undertaken to evaluate the use of Loop-Mediated Isothermal Amplification (LAMP) assay as an alternative to qPCR for the detection of HBV-DNA in CHB and potential OBI patients in resource-limited settings. Following the published protocols with some modifications, a LAMP assay was developed for detection of HBV-DNA by either using a heat block followed by detection in an agarose gel or using a qPCR thermocycler. The LAMP assay was applied to supernatant prepared from heat treated serum collected from CHB and potential OBI patients. HBV viral load in serum was measured by qPCR using a single step HBV-DNA quantification kit. Among 200 samples tested, qPCR was capable to detect HBV-DNA in 25.5% of cases, whereas LAMP assay detected HBV-DNA in 43.5% cases. The qPCR was able to detect 11 (9.16%) potential OBI cases, whereas LAMP assay identified HBV-DNA in 43 (35.83%) cases. In addition to tests for HBsAg and/or anti-HBc (total), detection of HBV-DNA by LAMP assay may aid in preventing post-transfusion HBV infection in resource-limited settings. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Solid core dipoles and switching power supplies: Lower cost light sources?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benesch, Jay; Philip, Sarin

As a result of improvements in power semiconductors, moderate frequency switching supplies can now provide the hundreds of amps typically required by accelerators with zero-to-peak noise in the kHz region ~ 0.06% in current or voltage mode. Modeling was undertaken using a finite electromagnetic program to determine if eddy currents induced in the solid steel of CEBAF magnets and small supplemental additions would bring the error fields down to the 5ppm level needed for beam quality. The expected maximum field of the magnet under consideration is 0.85 T and the DC current required to produce that field is used inmore » the calculations. An additional 0.1% current ripple is added to the DC current at discrete frequencies 360 Hz, 720 Hz or 7200 Hz. Over the region of the pole within 0.5% of the central integrated BdL the resulting AC field changes can be reduced to less than 1% of the 0.1% input ripple for all frequencies, and a sixth of that at 7200 Hz. Doubling the current, providing 1.5 T central field, yielded the same fractional reduction in ripple at the beam for the cases checked. A small dipole was measured at 60, 120, 360 and 720 Hz in two conditions and the results compared to the larger model for the latter two frequencies with surprisingly good agreement. Thus, for light sources with aluminum vacuum vessels and full energy linac injection, the combination of solid core dipoles and switching power supplies may result in significant cost savings.« less

Graphene based chalcogenide fiber-optic evanescent wave sensor for detection of hemoglobin in human blood

NASA Astrophysics Data System (ADS)

Sharma, Anuj K.; Gupta, Jyoti

2018-03-01

Fiber optic evanescent wave sensor with graphene as an absorption-enhancing layer to measure hemoglobin concentration in human blood is proposed. Previous modal functions and experimental results describing the variation of optical constants of human blood with different hemoglobin concentrations in the near-infrared spectral region are considered for sensor design simulation. The sensor's performance is closely analyzed in terms of its absorption coefficient, sensitivity, and detection limit. It is found that the proposed sensor should be operated at longer light wavelength to get more enhanced sensitivity and smaller detection limit. At 1000 nm wavelength, a detection limit of 18 μg/dL and sensitivity of 6.71 × 10-4 per g/dL is achievable with the proposed sensor. The sensitivity is found to be better for larger hemoglobin concentrations. The results are correlated with the evanescent wave penetration depth.

Effects of capacity limits, memory loss, and sound type in change deafness.

PubMed

Gregg, Melissa K; Irsik, Vanessa C; Snyder, Joel S

2017-11-01

Change deafness, the inability to notice changes to auditory scenes, has the potential to provide insights about sound perception in busy situations typical of everyday life. We determined the extent to which change deafness to sounds is due to the capacity of processing multiple sounds and the loss of memory for sounds over time. We also determined whether these processing limitations work differently for varying types of sounds within a scene. Auditory scenes composed of naturalistic sounds, spectrally dynamic unrecognizable sounds, tones, and noise rhythms were presented in a change-detection task. On each trial, two scenes were presented that were same or different. We manipulated the number of sounds within each scene to measure memory capacity and the silent interval between scenes to measure memory loss. For all sounds, change detection was worse as scene size increased, demonstrating the importance of capacity limits. Change detection to the natural sounds did not deteriorate much as the interval between scenes increased up to 2,000 ms, but it did deteriorate substantially with longer intervals. For artificial sounds, in contrast, change-detection performance suffered even for very short intervals. The results suggest that change detection is generally limited by capacity, regardless of sound type, but that auditory memory is more enduring for sounds with naturalistic acoustic structures.

Development of an enzyme-linked immunosorbent assay for the detection of dicamba.

PubMed

Clegg, B S; Stephenson, G R; Hall, J C

2001-05-01

A competitive indirect enzyme-linked immunosorbent assay (CI-ELISA) was developed to quantitate the herbicide dicamba (3,6-dichloro-2-methoxybenzoic acid) in water. The CI-ELISA has a detection limit of 2.3 microg L(-1) and a linear working range of 10--10000 microg L(-1) with an IC(50) value of 195 microg L(-1). The dicamba polyclonal antisera did not cross-react with a number of other herbicides tested but did cross-react with a dicamba metabolite, 5-hydroxydicamba, and structurally related chlorobenzoic acids. The assay was used to estimate quantitatively dicamba concentrations in water samples. Water samples were analyzed directly, and no sample preparation was required. To improve detection limits, a C(18) (reversed phase) column concentration step was devised prior to analysis, and the detection limits were increased by at least by 10-fold. After the sample preconcentration, the detection limit, IC(50), and linear working range were 0.23, 19.5, and 5-200 microg L(-1), respectively. The CI-ELISA estimations in water correlated well with those from gas chromatography-mass spectrometry (GC-MS) analysis (r(2) = 0.9991). This assay contributes to reducing laboratory costs associated with the conventional GC-MS residue analysis techniques for the quantitation of dicamba in water.

Modeling of a Single-Notch Microfiber Coupler for High-Sensitivity and Low Detection-Limit Refractive Index Sensing.

PubMed

Zhang, Jiali; Shi, Lei; Zhu, Song; Xu, Xinbiao; Zhang, Xinliang

2016-05-11

A highly sensitive refractive index sensor with low detection limit based on an asymmetric optical microfiber coupler is proposed. It is composed of a silica optical microfiber and an As₂Se₃ optical microfiber. Due to the asymmetry of the microfiber materials, a single-notch transmission spectrum is demonstrated by the large refractive index difference between the two optical microfibers. Compared with the symmetric coupler, the bandwidth of the asymmetric structure is over one order of magnitude narrower than that of the former. Therefore, the asymmetric optical microfiber coupler based sensor can reach over one order of magnitude smaller detection limit, which is defined as the minimal detectable refractive index change caused by the surrounding analyte. With the advantage of large evanescent field, the results also show that a sensitivity of up to 3212 nm per refractive index unit with a bandwidth of 12 nm is achieved with the asymmetric optical microfiber coupler. Furthermore, a maximum sensitivity of 4549 nm per refractive index unit can be reached while the radii of the silica optical microfiber and As₂Se₃ optical microfiber are 0.5 μm and a 0.128 μm, respectively. This sensor component may have important potential for low detection-limit physical and biochemical sensing applications.

A fast stir bar sorptive extraction method for the analysis of geosmin and 2-methylisoborneol in source and drinking water.

PubMed

Bauld, T; Teasdale, P; Stratton, H; Uwins, H

2007-01-01

The presence of unpleasant taste and odour in drinking water is an ongoing aesthetic concern for water providers worldwide. The need for a sensitive and robust method capable of analysis in both natural and treated waters is essential for early detection of taste and odour events. The purpose of this study was to develop and optimise a fast stir bar sorptive extraction (SBSE) method for the analysis of geosmin and 2-methylisoborneol (MIB) in both natural water and drinking water. Limits of detection with the optimised fast method (45 min extraction time at 60 degrees C using 24 microL stir bars) were 1.1 ng/L for geosmin and 4.2 ng/L for MIB. Relative standard deviations at the detection limits were under 17% for both compounds. Use of multiple stir bars can be used to decrease the detection limits further. The use of 25% NaCl and 5% methanol sample modifiers decreased the experimental recoveries. Likewise, addition of 1 mg/L and 1.5 mg/L NaOCI decreased the recoveries and this effect was not reversed by addition of 10% thiosulphate. The optimised method was used to measure geosmin concentrations in treated and untreated drinking water. MIB concentrations were below the detection limits in these waters.

Chloride interference in the determination of bromate in drinking water by reagent free ion chromatography with mass spectrometry detection.

PubMed

Cavalli, Silvano; Polesello, Stefano; Valsecchi, Sara

2005-08-26

Bromate, a well known by-product of the ozonation of drinking water, has been included among the substances which have to be monitored in the drinking water according to the last EC Directive 251/98 on potable water with a regulated limit of 10 microg l(-1). The need of performing routine analysis at this limit is a driving force for the developing of new simple and sensitive methods of detection, which should be also able to overcome the effect of matrix composition. This work explored the use of mass spectrometry detection with electrospray ionisation hyphenated to a reagent free ion chromatograph with hydroxide gradient elution for the determination of bromate in drinking water. The use of a high capacity hydroxide selective column operated in gradient mode allowed to avoid the interference by carbonate peak, which moved to longer retention times. The effect of increasing chloride concentrations from 0 to 250 mg l(-1), which is the guideline limit for drinking water in Directive 251/98/EC, was to decrease absolute mass spectrometric response and chromatographic efficiency and, on the consequence, to increase the effective detection limits. The effect of the chloride concentration on the detection of bromate is discussed.

Effectiveness of a flow-based device using riboflavin photochemistry in damaging blood-borne viral nucleic acids.

PubMed

Zhu, Liguo; Tong, Hongli; Wang, Shufang; Yu, Yang; Liu, Zhong; Li, Changqing; Wang, Deqing

2018-05-03

Effectiveness of a flow-based treatment device using riboflavin photochemistry was demonstrated by cytopathic effect method using indicator viruses. However, inactivation efficacy against real blood-borne viruses needs to be evaluated, especially at nucleic acid level. Special plasma samples with varying concentrations of blood-borne virus were selected using a strict blood selection procedure and were treated with device treatment (DT). Nucleic acid test (NAT) using polymerase chain reaction fluorescence method was used to detect virus copies. The NAT value of 4325 in plasma with high Hepatitis B Virus (HBV) concentrations decreased to 1330 with DT. After 100-fold dilution, the NAT value was below the NAT detection limits with DT compared with 23.0 that without DT. The NAT value of 61.9 in plasma with medium HBV concentrations decreased to 37.8 with DT, and after 10-fold dilution, the NAT value was below the NAT detection limits with DT compared with below 20 that without DT. The Ct values of plasma with low concentrations of blood-borne viruses were below the NAT detection limits with DT. There was a dose effect with DT which was effective in blood-borne viruses damaging nucleic acids to a level below the NAT detection limits. Copyright © 2018 Elsevier B.V. All rights reserved.

Nanoporous Glass Integrated in Volumetric Bar-Chart Chip for Point-of-Care Diagnostics of Non-Small Cell Lung Cancer.

PubMed

Li, Ying; Xuan, Jie; Song, Yujun; Qi, Wenjin; He, Bangshun; Wang, Ping; Qin, Lidong

2016-01-26

Point-of-care (POC) testing has the potential to enable rapid, low-cost, and large-scale screening. POC detection of a multiplexed biomarker panel can facilitate the early diagnosis of non-small cell lung cancer (NSCLC) and, thus, may allow for more timely surgical intervention for life-saving treatment. Herein, we report the nanoporous glass (NPG) integrated volumetric bar-chart chip (V-Chip) for POC detection of the three NSCLC biomarkers CEA, CYFRA 21-1, and SCCA, by the naked eye. The 3D nanostructures in the NPG membrane efficiently increase the number of binding sites for antibodies and decrease the diffusion distance between antibody and antigen, enabling the low detection limit and rapid analysis time of the NPG-V-Chip. We utilized the NPG-V-Chip to test the NSCLC biomarker panel and found that the limit of detection can reach 50 pg/mL (10-fold improvement over the original V-Chip), and the total assay time can be decreased from 4 to 0.5 h. We then detected CEA in 21 serum samples from patients with common cancers, and the on-chip results showed good correlation with the clinical results. We further assayed 10 lung cancer samples using the device and confirmed the results obtained using conventional ELISA methods. In summary, the NPG-V-Chip platform has the ability of multiplex, low detection limit, low cost, lack of need for accessory equipment, and rapid analysis time, which may render the V-Chip a useful platform for quantitative POC detection in resource-limited settings and personalized diagnostics.

The limit of detection in scintigraphic imaging with I-131 in patients with differentiated thyroid carcinoma

NASA Astrophysics Data System (ADS)

Hänscheid, H.; Lassmann, M.; Buck, A. K.; Reiners, C.; Verburg, F. A.

2014-05-01

Radioiodine scintigraphy influences staging and treatment in patients with differentiated thyroid carcinoma. The limit of detection for fractional uptake in an iodine avid focus in a scintigraphic image was determined from the number of lesion net counts and the count density of the tissue background. The count statistics were used to calculate the diagnostic activity required to elevate the signal from a lesion with a given uptake significantly above a homogeneous background with randomly distributed counts per area. The dependences of the minimal uptake and the minimal size of lesions visible in a scan on several parameters of influence were determined by linking the typical biokinetics observed in iodine avid tissue to the lesion mass and to the absorbed dose received in a radioiodine therapy. The detection limits for fractional uptake in a neck lesion of a typical patient are about 0.001% after therapy with 7000 MBq, 0.01% for activities typically administered in diagnostic assessments (74-185 MBq), and 0.1% after the administration of 10 MBq I-131. Lesions at the limit of detection in a diagnostic scan with biokinetics eligible for radioiodine therapy are small with diameters of a few millimeters. Increasing the diagnostic activity by a factor of 4 reduces the diameter of visible lesions by 25% or about 1 mm. Several other determinants have a comparable or higher influence on the limit of detection than the administered activity; most important are the biokinetics in both blood pool and target tissue and the time of measurement. A generally valid recommendation for the timing of the scan is impossible as the time of the highest probability to detect iodine avid tissue depends on the administered activity as well as on the biokinetics in the lesion and background in the individual patient.

Effects of Kapton Sample Cell Windows on the Detection Limit of Smectite: Implications for CheMin on the Mars Science Laboratory Mission

NASA Technical Reports Server (NTRS)

Achilles, C. N.; Ming, Douglas W.; Morris, R. V.; Blake, D. F.

2012-01-01

The CheMin instrument on the Mars Science Laboratory (MSL) rover Curiosity is an X-ray diffraction (XRD) and X-ray fluorescence (XRF) instrument capable of providing the mineralogical and chemical compositions of rocks and soils on the surface of Mars. CheMin uses a microfocus X-ray tube with a Co target, transmission geometry, and an energy-discriminating X-ray sensitive CCD to produce simultaneous 2-D XRD patterns and energy-dispersive X-ray histograms from powdered samples. CheMin has two different window materials used for sample cells -- Mylar and Kapton. Instrument details are provided elsewhere. Fe/Mg-smectite (e.g., nontronite) has been identified in Gale Crater, the MSL future landing site, by CRISM spectra. While large quantities of phyllosilicate minerals will be easily detected by CheMin, it is important to establish detection limits of such phases to understand capabilities and limitations of the instrument. A previous study indicated that the (001) peak of smectite at 15 Ang was detectable in a mixture of 1 wt.% smectite with olivine when Mylar is the window material for the sample cell. Complications arise when Kapton is the window material because Kapton itself also has a diffraction peak near 15 Ang (6.8 deg 2 Theta). This study presents results of mineral mixtures of smectite and olivine to determine smectite detection limits for Kapton sample cells. Because the intensity and position of the smectite (001) peak depends on the hydration state, we also analyzed mixtures with "hydrated" and "dehydrated"h smectite to examine the effects of hydration state on detection limits.

Kernel-Phase Interferometry for Super-Resolution Detection of Faint Companions

NASA Astrophysics Data System (ADS)

Factor, Samuel M.; Kraus, Adam L.

2017-06-01

Direct detection of close in companions (exoplanets or binary systems) is notoriously difficult. While coronagraphs and point spread function (PSF) subtraction can be used to reduce contrast and dig out signals of companions under the PSF, there are still significant limitations in separation and contrast near λ/D. Non-redundant aperture masking (NRM) interferometry can be used to detect companions well inside the PSF of a diffraction limited image, though the mask discards ˜ 95% of the light gathered by the telescope and thus the technique is severely flux limited. Kernel-phase analysis applies interferometric techniques similar to NRM to a diffraction limited image utilizing the full aperture. Instead of non-redundant closure-phases, kernel-phases are constructed from a grid of points on the full aperture, simulating a redundant interferometer. I have developed a new, easy to use, faint companion detection pipeline which analyzes kernel-phases utilizing Bayesian model comparison. I demonstrate this pipeline on archival images from HST/NICMOS, searching for new companions in order to constrain binary formation models at separations inaccessible to previous techniques. Using this method, it is possible to detect a companion well within the classical λ/D Rayleigh diffraction limit using a fraction of the telescope time as NRM. Since the James Webb Space Telescope (JWST) will be able to perform NRM observations, further development and characterization of kernel-phase analysis will allow efficient use of highly competitive JWST telescope time. As no mask is needed, this technique can easily be applied to archival data and even target acquisition images (e.g. from JWST), making the detection of close in companions cheap and simple as no additional observations are needed.

Methods for the preparation and analysis of solids and suspended solids for methylmercury

USGS Publications Warehouse

DeWild, John F.; Olund, Shane D.; Olson, Mark L.; Tate, Michael T.

2004-01-01

This report presents the methods and method performance data for the determination of methylmercury concentrations in solids and suspended solids. Using the methods outlined here, the U.S. Geological Survey's Wisconsin District Mercury Laboratory can consistently detect methylmercury in solids and suspended solids at environmentally relevant concentrations. Solids can be analyzed wet or freeze dried with a minimum detection limit of 0.08 ng/g (as-processed). Suspended solids must first be isolated from aqueous matrices by filtration. The minimum detection limit for suspended solids is 0.01 ng per filter resulting in a minimum reporting limit ranging from 0.2 ng/L for a 0.05 L filtered volume to 0.01 ng/L for a 1.0 L filtered volume. Maximum concentrations for both matrices can be extended to cover nearly any amount of methylmercury by limiting sample size.

Centrifugal Microfluidic Platform for Rapid, Multiplexed Detection of TB and HIV Biomarkers in Whole Blood Samples

DOE Office of Scientific and Technical Information (OSTI.GOV)

Litvinov, Julia; Moen, Scott T.; Berry, Gregory J.

Infection with Mycobacterium Tuberculosis represents a significant threat to people with immune disorders, such as HIV-positive individuals, and can result in significant health complications or death if not diagnosed and treated early. We present a centrifugal microfluidic platform for multiplexed detection of tuberculosis and HIV biomarkers in human whole blood with minimal sample preparation and a sample-to-answer time of 30 minutes. This multiplexed assay was developed for the detection of two M.tuberculosis secreted proteins, whose secretion represents an active and ongoing infection, as well as detection of HIV p24 protein and human anti-p24 antibodies. The limit of detection for thismore » multiplex assay is in the pg/mL range for both HIV and M.tuberculosis proteins, making this assay potentially useful in the clinical diagnosis of both HIV and Tuberculosis proteins indicative of active infection. Antigen detection for the HIV assay sensitivity was 89%, the specificity 85%. Serological detection had 100% sensitivity and specificity for the limited sample pool. The centrifugal microfluidic platform presented here offers the potential for a portable, fast and inexpensive multiplexed diagnostic device that can be used in resource-limited settings for diagnosis of TB and HIV.« less

Development of an Electrochemical Paper-Based Analytical Device for Trace Detection of Virus Particles.

PubMed

Channon, Robert B; Yang, Yuanyuan; Feibelman, Kristen M; Geiss, Brian J; Dandy, David S; Henry, Charles S

2018-06-19

Viral pathogens are a serious health threat around the world, particularly in resource limited settings, where current sensing approaches are often insufficient and slow, compounding the spread and burden of these pathogens. Here, we describe a label-free, point-of-care approach toward detection of virus particles, based on a microfluidic paper-based analytical device with integrated microwire Au electrodes. The device is initially characterized through capturing of streptavidin modified nanoparticles by biotin-modified microwires. An order of magnitude improvement in detection limits is achieved through use of a microfluidic device over a classical static paper-based device, due to enhanced mass transport and capturing of particles on the modified electrodes. Electrochemical impedance spectroscopy detection of West Nile virus particles was carried out using antibody functionalized Au microwires, achieving a detection limit of 10.2 particles in 50 μL of cell culture media. No increase in signal is found on addition of an excess of a nonspecific target (Sindbis). This detection motif is significantly cheaper (∼$1 per test) and faster (∼30 min) than current methods, while achieving the desired selectivity and sensitivity. This sensing motif represents a general platform for trace detection of a wide range of biological pathogens.

Characterizing bio-optical and ecological features of algal bloom waters for detection and tracking from space

NASA Astrophysics Data System (ADS)

Ahmed, S.; Amin, R.; Gladkova, I.; Gilerson, A.; Grossberg, M.; Hlaing, S.; Shariar, F.; Alabi, P.

2010-04-01

The detection and monitoring of harmful algal blooms using in-situ field measurements is both labor intensive and is practically limited on achievable temporal and spatial resolutions, since field measurements are typically carried out at a series of discrete points and at discrete times, with practical limitations on temporal continuity. The planning and preparation of remedial measures to reduce health risks, etc., requires detection approaches which can effectively cover larger areas with contiguous spatial resolutions, and at the same time offer a more comprehensive and contemporaneous snapshot of entire blooms as they occur. This is beyond capabilities of in-situ measurements and it is in this context that satellite Ocean Color sensors offer potential advantages for bloom detection and monitoring. In this paper we examine the applications and limitations of an approach we have recently developed for the detection of K. brevis blooms from satellite Ocean Color Sensors measurements, the Red Band Difference Technique, and compare it to other detection algorithm approaches, including a new statistical based approach also proposed here. To achieve more uniform standards of comparisons, the performance of different techniques for detection are applied to the same specific verified blooms occurring off the West Florida Shelf (WFS) that have been verified by in-situ measurements.

Sensitivity and accuracy of high-throughput metabarcoding methods for early detection of invasive fish species

NASA Astrophysics Data System (ADS)

Hatzenbuhler, Chelsea; Kelly, John R.; Martinson, John; Okum, Sara; Pilgrim, Erik

2017-04-01

High-throughput DNA metabarcoding has gained recognition as a potentially powerful tool for biomonitoring, including early detection of aquatic invasive species (AIS). DNA based techniques are advancing, but our understanding of the limits to detection for metabarcoding complex samples is inadequate. For detecting AIS at an early stage of invasion when the species is rare, accuracy at low detection limits is key. To evaluate the utility of metabarcoding in future fish community monitoring programs, we conducted several experiments to determine the sensitivity and accuracy of routine metabarcoding methods. Experimental mixes used larval fish tissue from multiple “common” species spiked with varying proportions of tissue from an additional “rare” species. Pyrosequencing of genetic marker, COI (cytochrome c oxidase subunit I) and subsequent sequence data analysis provided experimental evidence of low-level detection of the target “rare” species at biomass percentages as low as 0.02% of total sample biomass. Limits to detection varied interspecifically and were susceptible to amplification bias. Moreover, results showed some data processing methods can skew sequence-based biodiversity measurements from corresponding relative biomass abundances and increase false absences. We suggest caution in interpreting presence/absence and relative abundance in larval fish assemblages until metabarcoding methods are optimized for accuracy and precision.

Centrifugal Microfluidic Platform for Rapid, Multiplexed Detection of TB and HIV Biomarkers in Whole Blood Samples

DOE PAGES

Litvinov, Julia; Moen, Scott T.; Berry, Gregory J.; ...

2017-05-30

Infection with Mycobacterium Tuberculosis represents a significant threat to people with immune disorders, such as HIV-positive individuals, and can result in significant health complications or death if not diagnosed and treated early. We present a centrifugal microfluidic platform for multiplexed detection of tuberculosis and HIV biomarkers in human whole blood with minimal sample preparation and a sample-to-answer time of 30 minutes. This multiplexed assay was developed for the detection of two M.tuberculosis secreted proteins, whose secretion represents an active and ongoing infection, as well as detection of HIV p24 protein and human anti-p24 antibodies. The limit of detection for thismore » multiplex assay is in the pg/mL range for both HIV and M.tuberculosis proteins, making this assay potentially useful in the clinical diagnosis of both HIV and Tuberculosis proteins indicative of active infection. Antigen detection for the HIV assay sensitivity was 89%, the specificity 85%. Serological detection had 100% sensitivity and specificity for the limited sample pool. The centrifugal microfluidic platform presented here offers the potential for a portable, fast and inexpensive multiplexed diagnostic device that can be used in resource-limited settings for diagnosis of TB and HIV.« less

Development of analytical method for ultrasensitive detection of salbutamol utilizing DNA labeled-immunoprobe.

PubMed

Lei, Yajing; Li, Xiaoyi; Akash, Muhammad Sajid Hamid; Zhou, Lifang; Tang, Xiaojing; Shi, Weixing; Liu, Zhiming; Chen, Shuqing

2015-03-25

Salbutamol (SAL) is known as quick-acting β-2 receptor agonist and its use in humans for pulmonary diseases and/or in animal feed is limited because of associated potential hazardous effects on health. Several techniques are available for the detection of SAL, but are expensive and time consuming. Here for the first time, a novel pre-assembled DNA immunoprobe-based immuno-PCR assay was developed to investigate the levels of SAL in human urine samples and compared the proposed immuno-PCR assay for the detection of SAL with that of direct competitive ELISA. Under the optimized conditions, the assay showed a linear range over seven orders of magnitude, whereas the limit of detection of SAL in buffer was found to be 21 fg/mL. Current immuno-PCR assay exhibited a 300-fold better detection limit for SAL as compared to one achieved with direct competitive ELISA using the same antibody. In conclusion, it has been found that the developed method is highly sensitive and simple method that can significantly enhance the detection sensitivity for small molecules. Moreover it can be modified and used for detecting other small molecules and/or chemicals that exist in the environment and are responsible for the environmental pollution. Copyright © 2014 Elsevier B.V. All rights reserved.

DNA detection and single nucleotide mutation identification using SERS for molecular diagnostics and global health

NASA Astrophysics Data System (ADS)

Ngo, Hoan T.; Gandra, Naveen; Fales, Andrew M.; Taylor, Steve M.; Vo-Dinh, Tuan

2017-02-01

Nucleic acid-based molecular diagnostics at the point-of-care (POC) and in resource-limited settings is still a challenge. We present a sensitive yet simple DNA detection method with single nucleotide polymorphism (SNP) identification capability. The detection scheme involves sandwich hybridization of magnetic beads conjugated with capture probes, target sequences, and ultrabright surface-enhanced Raman Scattering (SERS) nanorattles conjugated with reporter probes. Upon hybridization, the sandwich probes are concentrated at the detection focus controlled by a magnetic system for SERS measurements. The ultrabright SERS nanorattles, consisting of a core and a shell with resonance Raman reporters loaded in the gap space between the core and the shell, serve as SERS tags for ultrasensitive signal detection. Specific DNA sequences of the malaria parasite Plasmodium falciparum and dengue virus 1 (DENV1) were used as the model marker system. Detection limit of approximately 100 attomoles was achieved. Single nucleotide polymorphism (SNP) discrimination of wild type malaria DNA and mutant malaria DNA, which confers resistance to artemisinin drugs, was also demonstrated. The results demonstrate the molecular diagnostic potential of the nanorattle-based method to both detect and genotype infectious pathogens. The method's simplicity makes it a suitable candidate for molecular diagnosis at the POC and in resource-limited settings.

Detection methods and performance criteria for genetically modified organisms.

PubMed

Bertheau, Yves; Diolez, Annick; Kobilinsky, André; Magin, Kimberly

2002-01-01

Detection methods for genetically modified organisms (GMOs) are necessary for many applications, from seed purity assessment to compliance of food labeling in several countries. Numerous analytical methods are currently used or under development to support these needs. The currently used methods are bioassays and protein- and DNA-based detection protocols. To avoid discrepancy of results between such largely different methods and, for instance, the potential resulting legal actions, compatibility of the methods is urgently needed. Performance criteria of methods allow evaluation against a common standard. The more-common performance criteria for detection methods are precision, accuracy, sensitivity, and specificity, which together specifically address other terms used to describe the performance of a method, such as applicability, selectivity, calibration, trueness, precision, recovery, operating range, limit of quantitation, limit of detection, and ruggedness. Performance criteria should provide objective tools to accept or reject specific methods, to validate them, to ensure compatibility between validated methods, and be used on a routine basis to reject data outside an acceptable range of variability. When selecting a method of detection, it is also important to consider its applicability, its field of applications, and its limitations, by including factors such as its ability to detect the target analyte in a given matrix, the duration of the analyses, its cost effectiveness, and the necessary sample sizes for testing. Thus, the current GMO detection methods should be evaluated against a common set of performance criteria.

Anomaly detection in reconstructed quantum states using a machine-learning technique

NASA Astrophysics Data System (ADS)

Hara, Satoshi; Ono, Takafumi; Okamoto, Ryo; Washio, Takashi; Takeuchi, Shigeki

2014-02-01

The accurate detection of small deviations in given density matrices is important for quantum information processing. Here we propose a method based on the concept of data mining. We demonstrate that the proposed method can more accurately detect small erroneous deviations in reconstructed density matrices, which contain intrinsic fluctuations due to the limited number of samples, than a naive method of checking the trace distance from the average of the given density matrices. This method has the potential to be a key tool in broad areas of physics where the detection of small deviations of quantum states reconstructed using a limited number of samples is essential.

Pre-oxidation for Colorimetric Sensor Array Detection of VOCs

PubMed Central

Lin, Hengwei; Jang, Minseok; Suslick, Kenneth S.

2011-01-01

A disposable pre-oxidation technique is reported that dramatically improves the detection and identification of volatile organic compounds (VOCs) by a colorimetric sensor array. By passing a vapor stream through a tube packed with chromic acid on silica immediately before the colorimetric sensor array, the sensitivity to less reactive VOCs is substantially increased and limits of detection (LODs) are improved ~300-fold, permitting the detection, identification, and discrimination of 20 commonly found indoor VOC pollutants at both their immediately dangerous to life or health (IDLH) and at permissible exposure limits (PEL) concentrations. LODs of these pollutants were on average 1.4% of their respective PELs. PMID:21967478

Improvements of low-detection-limit filter-free fluorescence sensor developed by charge accumulation operation

NASA Astrophysics Data System (ADS)

Tanaka, Kiyotsugu; Choi, Yong Joon; Moriwaki, Yu; Hizawa, Takeshi; Iwata, Tatsuya; Dasai, Fumihiro; Kimura, Yasuyuki; Takahashi, Kazuhiro; Sawada, Kazuaki

2017-04-01

We developed a low-detection-limit filter-free fluorescence sensor by a charge accumulation technique. For charge accumulation, a floating diffusion amplifier (FDA), which included a floating diffusion capacitor, a transfer gate, and a source follower circuit, was used. To integrate CMOS circuits with the filter-free fluorescence sensor, we adopted a triple-well process to isolate transistors from the sensor on a single chip. We detected 0.1 nW fluorescence under the illumination of excitation light by 1.5 ms accumulation, which was one order of magnitude greater than that of a previous current detection sensor.

Detection of shigella in lettuce by the use of a rapid molecular assay with increased sensitivity

PubMed Central

Jiménez, Kenia Barrantes; McCoy², Clyde B.; Achí, Rosario

2010-01-01

A Multiplex Polymerase Chain Reaction (PCR) assay to be used as an alternative to the conventional culture method in detecting Shigella and enteroinvasive Escherichia coli (EIEC) virulence genes ipaH and ial in lettuce was developed. Efficacy and rapidity of the molecular method were determined as compared to the conventional culture. Lettuce samples were inoculated with different Shigella flexneri concentrations (from 10 CFU/ml to 107 CFU/ml). DNA was extracted directly from lettuce after inoculation (direct-PCR) and after an enrichment step (enrichment PCR). Multiplex PCR detection limit was 104CFU/ml, diagnostic sensitivity and specificity were 100% accurate. An internal amplification control (IAC) of 100 bp was used in order to avoid false negative results. This method produced results in 1 to 2 days while the conventional culture method required 5 to 6 days. Also, the culture method detection limit was 106 CFU/ml, diagnostic sensitivity was 53% and diagnostic specificity was 100%. In this study a Multiplex PCR method for detection of virulence genes in Shigella and EIEC was shown to be effective in terms of diagnostic sensitivity, detection limit and amount of time as compared to Shigella conventional culture. PMID:24031579

Qualitative Contrast between Knowledge-Limited Mixed-State and Variable-Resources Models of Visual Change Detection

ERIC Educational Resources Information Center

Nosofsky, Robert M.; Donkin, Chris

2016-01-01

We report an experiment designed to provide a qualitative contrast between knowledge-limited versions of mixed-state and variable-resources (VR) models of visual change detection. The key data pattern is that observers often respond "same" on big-change trials, while simultaneously being able to discriminate between same and small-change…

Surprise-Induced Blindness: A Stimulus-Driven Attentional Limit to Conscious Perception

ERIC Educational Resources Information Center

Asplund, Christopher L.; Todd, J. Jay; Snyder, A. P.; Gilbert, Christopher M.; Marois, Rene

2010-01-01

The cost of attending to a visual event can be the failure to consciously detect other events. This processing limitation is well illustrated by the attentional blink paradigm, in which searching for and attending to a target presented in a rapid serial visual presentation stream of distractors can impair one's ability to detect a second target…

Determining the 95% limit of detection for waterborne pathogen analyses from primary concentration to qPCR

USDA-ARS?s Scientific Manuscript database

The limit of detection (LOD) for qPCR-based analyses is not consistently defined or determined in studies on waterborne pathogens. Moreover, the LODs reported often reflect the qPCR assay rather than the entire sample process. Our objective was to develop a method to determine the 95% LOD (lowest co...

SUPPLEMENT TO EPA COMPENDIUM METHOD TO-15 - REDUCTION OF METHOD DETECTION LIMITS TO MEET VAPOR INTRUSION MONITORING NEEDS

EPA Science Inventory

The Supplement to EPA Compendium Method TO-15 provides guidance for reducing the method detection limit (MDL) for the compound 1,1- dichloroethene (1,1-DCE) and for other volatile organic compounds (VOCs) from 0.5 ppbv, as cited in Method TO-15, to much lower concentrations. R...

SUPPLEMENT TO EPA COMPENDIUM METHOD TO-15 - REDUCTION OF METHOD DETECTION LIMITS TO MEET VAPOR INTRUSION MONITORING NEEDS

EPA Science Inventory

The Supplement to EPA Compendium Method TO-15 provides guidance for reducing the method detection limit (MDL) for the compound 1,1-dichloroethene (1,1-DCE) and for other volatile organic compounds (VOCs) from 0.5 parts per billion by volume (ppbv), as cited in Method TO-15, to ...

Noninvasive Imaging of the Biliary System Relevant to Percutaneous Interventions

PubMed Central

Thomas, Stephen; Jahangir, Kayleen

2016-01-01

Clinical data such as history, physical examination, and laboratory tests are useful in identifying patients with biliary obstruction and biliary sources of infection. However, if intervention is planned, noninvasive imaging is needed to confirm the presence, location, and extent of the disease process. Currently, the most commonly available and used noninvasive modalities are ultrasound (US), computed tomography (CT), magnetic resonance (MR), and nuclear medicine hepatobiliary scintigraphy (HIDA). US is quick, portable, readily available, and is commonly the first imaging modality used when biliary pathology is suspected. It is excellent in the detection of cholelithiasis and acute cholecystitis but is limited in detecting choledocholithiasis. CT is excellent at detecting infected postoperative fluid collections, bilomas, biliary obstruction, and biliary infection but is limited in the detection of cholelithiasis. Therefore, US may be more useful than CT for the initial screening of acute biliary disease. MR has inherent advantages over CT, as it does not use ionizing radiation, can be done without intravenous contrast, and its detection of cholelithiasis is not affected by the internal composition of the stone. Magnetic resonance cholangiopancreatography can be used to determine the cause and location of biliary obstruction but is limited in the detection of small stones and the evaluation of the biliary tract near the ampulla. HIDA is used to evaluate for cholecystitis, biliary obstruction, and bile leaks. The main limitation is its lack of anatomical detail, and it is therefore frequently performed in conjunction with other described modalities. PMID:27904246

A Game Theoretic Fault Detection Filter

NASA Technical Reports Server (NTRS)

Chung, Walter H.; Speyer, Jason L.

1995-01-01

The fault detection process is modelled as a disturbance attenuation problem. The solution to this problem is found via differential game theory, leading to an H(sub infinity) filter which bounds the transmission of all exogenous signals save the fault to be detected. For a general class of linear systems which includes some time-varying systems, it is shown that this transmission bound can be taken to zero by simultaneously bringing the sensor noise weighting to zero. Thus, in the limit, a complete transmission block can he achieved, making the game filter into a fault detection filter. When we specialize this result to time-invariant system, it is found that the detection filter attained in the limit is identical to the well known Beard-Jones Fault Detection Filter. That is, all fault inputs other than the one to be detected (the "nuisance faults") are restricted to an invariant subspace which is unobservable to a projection on the output. For time-invariant systems, it is also shown that in the limit, the order of the state-space and the game filter can be reduced by factoring out the invariant subspace. The result is a lower dimensional filter which can observe only the fault to be detected. A reduced-order filter can also he generated for time-varying systems, though the computational overhead may be intensive. An example given at the end of the paper demonstrates the effectiveness of the filter as a tool for fault detection and identification.

Direct Detection Electron Energy-Loss Spectroscopy: A Method to Push the Limits of Resolution and Sensitivity.

PubMed

Hart, James L; Lang, Andrew C; Leff, Asher C; Longo, Paolo; Trevor, Colin; Twesten, Ray D; Taheri, Mitra L

2017-08-15

In many cases, electron counting with direct detection sensors offers improved resolution, lower noise, and higher pixel density compared to conventional, indirect detection sensors for electron microscopy applications. Direct detection technology has previously been utilized, with great success, for imaging and diffraction, but potential advantages for spectroscopy remain unexplored. Here we compare the performance of a direct detection sensor operated in counting mode and an indirect detection sensor (scintillator/fiber-optic/CCD) for electron energy-loss spectroscopy. Clear improvements in measured detective quantum efficiency and combined energy resolution/energy field-of-view are offered by counting mode direct detection, showing promise for efficient spectrum imaging, low-dose mapping of beam-sensitive specimens, trace element analysis, and time-resolved spectroscopy. Despite the limited counting rate imposed by the readout electronics, we show that both core-loss and low-loss spectral acquisition are practical. These developments will benefit biologists, chemists, physicists, and materials scientists alike.

Rapid detection of Ebola virus with a reagent-free, point-of-care biosensor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baca, Justin T.; Severns, Virginia; Lovato, Debbie

Surface acoustic wave (SAW) sensors can rapidly detect Ebola antigens at the point-of-care without the need for added reagents, sample processing, or specialized personnel. This preliminary study demonstrates SAW biosensor detection of the Ebola virus in a concentration-dependent manner. The detection limit with this methodology is below the average level of viremia detected on the first day of symptoms by PCR. We observe a log-linear sensor response for highly fragmented Ebola viral particles, with a detection limit corresponding to 1.9 × 10⁴ PFU/mL prior to virus inactivation. We predict greatly improved sensitivity for intact, infectious Ebola virus. This point-of-care methodologymore » has the potential to detect Ebola viremia prior to symptom onset, greatly enabling infection control and rapid treatment. This biosensor platform is powered by disposable AA batteries and can be rapidly adapted to detect other emerging diseases in austere conditions.« less

A Shadowing Problem in the Detection of Overlapping Communities: Lifting the Resolution Limit through a Cascading Procedure

PubMed Central

Young, Jean-Gabriel; Allard, Antoine; Hébert-Dufresne, Laurent; Dubé, Louis J.

2015-01-01

Community detection is the process of assigning nodes and links in significant communities (e.g. clusters, function modules) and its development has led to a better understanding of complex networks. When applied to sizable networks, we argue that most detection algorithms correctly identify prominent communities, but fail to do so across multiple scales. As a result, a significant fraction of the network is left uncharted. We show that this problem stems from larger or denser communities overshadowing smaller or sparser ones, and that this effect accounts for most of the undetected communities and unassigned links. We propose a generic cascading approach to community detection that circumvents the problem. Using real and artificial network datasets with three widely used community detection algorithms, we show how a simple cascading procedure allows for the detection of the missing communities. This work highlights a new detection limit of community structure, and we hope that our approach can inspire better community detection algorithms. PMID:26461919

Rapid detection of Ebola virus with a reagent-free, point-of-care biosensor

DOE PAGES

Baca, Justin T.; Severns, Virginia; Lovato, Debbie; ...

2015-04-14

Surface acoustic wave (SAW) sensors can rapidly detect Ebola antigens at the point-of-care without the need for added reagents, sample processing, or specialized personnel. This preliminary study demonstrates SAW biosensor detection of the Ebola virus in a concentration-dependent manner. The detection limit with this methodology is below the average level of viremia detected on the first day of symptoms by PCR. We observe a log-linear sensor response for highly fragmented Ebola viral particles, with a detection limit corresponding to 1.9 × 10⁴ PFU/mL prior to virus inactivation. We predict greatly improved sensitivity for intact, infectious Ebola virus. This point-of-care methodologymore » has the potential to detect Ebola viremia prior to symptom onset, greatly enabling infection control and rapid treatment. This biosensor platform is powered by disposable AA batteries and can be rapidly adapted to detect other emerging diseases in austere conditions.« less

Label-free peptide aptamer based impedimetric biosensor for highly sensitive detection of TNT with a ternary assembly layer.

PubMed

Li, Yanyan; Zhao, Manru; Wang, Haiyan

2017-11-01

We report a label-free peptide aptamer based biosensor for highly sensitive detection of TNT which was designed with a ternary assembly layer consisting of anti-TNT peptide aptamer (peptamer), dithiothreitol (DTT), and 6-mercaptohexanol (MCH), forming Au/peptamer-DTT/MCH. A linear relationship between the change in electron transfer resistance and the logarithm of the TNT concentration from 0.44 to 18.92 pM, with a detection limit of 0.15 pM, was obtained. In comparison, the detection limit of the aptasensor with a common binary assembly layer (Au/peptamer/MCH) was 0.15 nM. The remarkable improvement in the detection limit could be ascribed to the crucial role of the ternary assembly layer, providing an OH-richer hydrophilic environment and a highly compact surface layer with minimal surface defects, reducing the non-covalent binding (physisorption) of the peptamer and non-specific adsorption of TNT onto the electrode surface, leading to high sensitivity, and which can serve as a general sensing platform for the fabrication of other biosensors.

Detection, Size, Measurement, and Structural Analysis Limits for the 2MASS, UKIDSS-LAS, and VISTA VIKING Surveys

NASA Astrophysics Data System (ADS)

Andrews, Stephen K.; Kelvin, Lee S.; Driver, Simon P.; Robotham, Aaron S. G.

2014-01-01

The 2MASS, UKIDSS-LAS, and VISTA VIKING surveys have all now observed the GAMA 9hr region in the Ks band. Here we compare the detection rates, photometry, basic size measurements, and single-component GALFIT structural measurements for a sample of 37 591 galaxies. We explore the sensitivity limits where the data agree for a variety of issues including: detection, star-galaxy separation, photometric measurements, size and ellipticity measurements, and Sérsic measurements. We find that 2MASS fails to detect at least 20% of the galaxy population within all magnitude bins, however for those that are detected we find photometry is robust (± 0.2 mag) to 14.7 AB mag and star-galaxy separation to 14.8 AB mag. For UKIDSS-LAS we find incompleteness starts to enter at a flux limit of 18.9 AB mag, star-galaxy separation is robust to 16.3 AB mag, and structural measurements are robust to 17.7 AB mag. VISTA VIKING data are complete to approximately 20.0 AB mag and structural measurements appear robust to 18.8 AB mag.

Purgeable organic compounds at or near the Idaho Nuclear Technology and Engineering Center, Idaho National Laboratory, Idaho, 2015

USGS Publications Warehouse

Maimer, Neil V.; Bartholomay, Roy C.

2016-05-25

During 2015, the U.S. Geological Survey, in cooperation with the U.S. Department of Energy, collected groundwater samples from 31 wells at or near the Idaho Nuclear Technology and Engineering Center (INTEC) at the Idaho National Laboratory for purgeable organic compounds (POCs). The samples were collected and analyzed for the purpose of evaluating whether purge water from wells located inside an areal polygon established downgradient of the INTEC must be treated as a Resource Conservation and Recovery Act listed waste.POC concentrations in water samples from 29 of 31 wells completed in the eastern Snake River Plain aquifer were greater than their detection limit, determined from detection and quantitation calculation software, for at least one to four POCs. Of the 29 wells with concentrations greater than their detection limits, only 20 had concentrations greater than the laboratory reporting limit as calculated with detection and quantitation calculation software. None of the concentrations exceeded any maximum contaminant levels established for public drinking water supplies. Most commonly detected compounds were 1,1,1-trichoroethane, 1,1-dichloroethene, and trichloroethene.

Methods of analysis by the U.S. Geological Survey National Water Quality Laboratory; determination of 86 volatile organic compounds in water by gas chromatography/mass spectrometry, including detections less than reporting limits

USGS Publications Warehouse

Connor, Brooke F.; Rose, Donna L.; Noriega, Mary C.; Murtaugh, Lucinda K.; Abney, Sonja R.

1998-01-01

This report presents precision and accuracy data for volatile organic compounds (VOCs) in the nanogram-per-liter range, including aromatic hydrocarbons, reformulated fuel components, and halogenated hydrocarbons using purge and trap capillary-column gas chromatography/mass spectrometry. One-hundred-four VOCs were initially tested. Of these, 86 are suitable for determination by this method. Selected data are provided for the 18 VOCs that were not included. This method also allows for the reporting of semiquantitative results for tentatively identified VOCs not included in the list of method compounds. Method detection limits, method performance data, preservation study results, and blank results are presented. The authors describe a procedure for reporting low-concentration detections at less than the reporting limit. The nondetection value (NDV) is introduced as a statistically defined reporting limit designed to limit false positives and false negatives to less than 1 percent. Nondetections of method compounds are reported as ?less than NDV.? Positive detections measured at less than NDV are reported as estimated concentrations to alert the data user to decreased confidence in accurate quantitation. Instructions are provided for analysts to report data at less than the reporting limits. This method can support the use of either method reporting limits that censor detections at lower concentrations or the use of NDVs as reporting limits. The data-reporting strategy for providing analytical results at less than the reporting limit is a result of the increased need to identify the presence or absence of environmental contaminants in water samples at increasingly lower concentrations. Long-term method detection limits (LTMDLs) for 86 selected compounds range from 0.013 to 2.452 micrograms per liter (?g/L) and differ from standard method detection limits (MDLs) in that the LTMDLs include the long-term variance of multiple instruments, multiple operators, and multiple calibrations over a longer time. For these reasons, LTMDLs are expected to be slightly higher than standard MDLs. Recoveries for all of the VOCs tested ranged from 36 (tert-butyl formate) to 155 percent (pentachlorobenzene). The majority of the compounds ranged from 85 to 115 percent recovery and had less than 5 percent relative standard deviation for concentrations spiked between 1 to 500 ?g/L in volatile blank-, surface-, and ground-water samples. Recoveries of 60 set spikes at low concentrations ranged from 70 to 114 percent (1,2,3- trimethylbenzene and acetone). Recovery data were collected over 6 months with multiple instruments, operators, and calibrations. In this method, volatile organic compounds are extracted from a water sample by actively purging with helium. The VOCs are collected onto a sorbent trap, thermally desorbed, separated by a Megabore gas chromatographic capillary column, and finally determined by a full-scan quadrupole mass spectrometer. Compound identification is confirmed by the gas chromatographic retention time and by the resultant mass spectrum, typically identified by three unique ions. An unknown compound detected in a sample can be tentatively identified by comparing the unknown mass spectrum to reference spectra in the mass-spectra computer-data system library compiled by the National Institute of Standards and Technology.

The Need and Potential of Biosensors to Detect Dioxins and Dioxin-Like Polychlorinated Biphenyls along the Milk, Eggs and Meat Food Chain

PubMed Central

Chobtang, Jeerasak; de Boer, Imke J. M.; Hoogenboom, Ron L. A. P.; Haasnoot, Willem; Kijlstra, Aize; Meerburg, Bastiaan G.

2011-01-01

Dioxins and dioxin-like polychlorinated biphenyls (DL-PCBs) are hazardous toxic, ubiquitous and persistent chemical compounds, which can enter the food chain and accumulate up to higher trophic levels. Their determination requires sophisticated methods, expensive facilities and instruments, well-trained personnel and expensive chemical reagents. Ideally, real-time monitoring using rapid detection methods should be applied to detect possible contamination along the food chain in order to prevent human exposure. Sensor technology may be promising in this respect. This review gives the state of the art for detecting possible contamination with dioxins and DL-PCBs along the food chain of animal-source foods. The main detection methods applied (i.e., high resolution gas-chromatography combined with high resolution mass-spectrometry (HRGC/HRMS) and the chemical activated luciferase gene expression method (CALUX bioassay)), each have their limitations. Biosensors for detecting dioxins and related compounds, although still under development, show potential to overcome these limitations. Immunosensors and biomimetic-based biosensors potentially offer increased selectivity and sensitivity for dioxin and DL-PCB detection, while whole cell-based biosensors present interpretable biological results. The main shortcoming of current biosensors, however, is their detection level: this may be insufficient as limits for dioxins and DL-PCBs for food and feedstuffs are in pg per gram level. In addition, these contaminants are normally present in fat, a difficult matrix for biosensor detection. Therefore, simple and efficient extraction and clean-up procedures are required which may enable biosensors to detect dioxins and DL-PCBs contamination along the food chain. PMID:22247688

The need and potential of biosensors to detect dioxins and dioxin-like polychlorinated biphenyls along the milk, eggs and meat food chain.

PubMed

Chobtang, Jeerasak; de Boer, Imke J M; Hoogenboom, Ron L A P; Haasnoot, Willem; Kijlstra, Aize; Meerburg, Bastiaan G

2011-01-01

Dioxins and dioxin-like polychlorinated biphenyls (DL-PCBs) are hazardous toxic, ubiquitous and persistent chemical compounds, which can enter the food chain and accumulate up to higher trophic levels. Their determination requires sophisticated methods, expensive facilities and instruments, well-trained personnel and expensive chemical reagents. Ideally, real-time monitoring using rapid detection methods should be applied to detect possible contamination along the food chain in order to prevent human exposure. Sensor technology may be promising in this respect. This review gives the state of the art for detecting possible contamination with dioxins and DL-PCBs along the food chain of animal-source foods. The main detection methods applied (i.e., high resolution gas-chromatography combined with high resolution mass-spectrometry (HRGC/HRMS) and the chemical activated luciferase gene expression method (CALUX bioassay)), each have their limitations. Biosensors for detecting dioxins and related compounds, although still under development, show potential to overcome these limitations. Immunosensors and biomimetic-based biosensors potentially offer increased selectivity and sensitivity for dioxin and DL-PCB detection, while whole cell-based biosensors present interpretable biological results. The main shortcoming of current biosensors, however, is their detection level: this may be insufficient as limits for dioxins and DL-PCBs for food and feedstuffs are in pg per gram level. In addition, these contaminants are normally present in fat, a difficult matrix for biosensor detection. Therefore, simple and efficient extraction and clean-up procedures are required which may enable biosensors to detect dioxins and DL-PCBs contamination along the food chain.

Highly sensitive and specific on-site detection of serum cocaine by a low cost aptasensor.

PubMed

Oueslati, Rania; Cheng, Cheng; Wu, Jayne; Chen, Jiangang

2018-06-15

Cocaine is one of the most used illegal recreational drugs. Developing an on-site test for cocaine use detection has been a focus of research effort, since it is essential to the control and legal action against drug abuse. Currently most of cocaine detection methods are time-consuming and require special or expensive equipment, and the detection often suffers from high cross-reactivity with cocaine metabolites and relative low sensitivity with the best limit of detection reported at sub nanomolar (nM) level. In this work, an aptasensor has been developed using capacitive monitoring of sensor surface incorporating alternating current electrokinetics effects to speed up molecular transport and minimize matrix effects. The aptasensor is rapid, low cost, highly sensitive and specific as well as simple-to-use for the detection of cocaine from serum. The assay has a sample-to-result time of 30 s, a limit of detection of 7.8 fM, and a linear response for cocaine ranging from 14.5fM to 14.5pM in standard buffer, which are great improvements from other reported cocaine sensors. Special buffer is used for serum cocaine detection, and a limit of detection of 13.4 fM is experimentally demonstrated for cocaine spiked in human serum (equivalent to 1.34pM cocaine in neat serum). The specificity of the biosensor is also demonstrated with structurally similar chemicals, ecgonine ethyl ester and methylecgonidine. This biosensor shows high promise in detection of low levels of cocaine from complex matrices. Copyright © 2018 Elsevier B.V. All rights reserved.

Enhanced speed in fluorescence imaging using beat frequency multiplexing

NASA Astrophysics Data System (ADS)

Mikami, Hideharu; Kobayashi, Hirofumi; Wang, Yisen; Hamad, Syed; Ozeki, Yasuyuki; Goda, Keisuke

2016-03-01

Fluorescence imaging using radiofrequency-tagged emission (FIRE) is an emerging technique that enables higher imaging speed (namely, temporal resolution) in fluorescence microscopy compared to conventional fluorescence imaging techniques such as confocal microscopy and wide-field microscopy. It works based on the principle that it uses multiple intensity-modulated fields in an interferometric setup as excitation fields and applies frequency-division multiplexing to fluorescence signals. Unfortunately, despite its high potential, FIRE has limited imaging speed due to two practical limitations: signal bandwidth and signal detection efficiency. The signal bandwidth is limited by that of an acousto-optic deflector (AOD) employed in the setup, which is typically 100-200 MHz for the spectral range of fluorescence excitation (400-600 nm). The signal detection efficiency is limited by poor spatial mode-matching between two interfering fields to produce a modulated excitation field. Here we present a method to overcome these limitations and thus to achieve higher imaging speed than the prior version of FIRE. Our method achieves an increase in signal bandwidth by a factor of two and nearly optimal mode matching, which enables the imaging speed limited by the lifetime of the target fluorophore rather than the imaging system itself. The higher bandwidth and better signal detection efficiency work synergistically because higher bandwidth requires higher signal levels to avoid the contribution of shot noise and amplifier noise to the fluorescence signal. Due to its unprecedentedly high-speed performance, our method has a wide variety of applications in cancer detection, drug discovery, and regenerative medicine.

Reducing Uncertainty for Acute Febrile Illness in Resource-Limited Settings: The Current Diagnostic Landscape

PubMed Central

Robinson, Matthew L.; Manabe, Yukari C.

2017-01-01

Diagnosing the cause of acute febrile illness in resource-limited settings is important—to give the correct antimicrobials to patients who need them, to prevent unnecessary antimicrobial use, to detect emerging infectious diseases early, and to guide vaccine deployment. A variety of approaches are yielding more rapid and accurate tests that can detect more pathogens in a wider variety of settings. After decades of slow progress in diagnostics for acute febrile illness in resource-limited settings, a wave of converging advancements will enable clinicians in resource-limited settings to reduce uncertainty for the diagnosis of acute febrile illness. PMID:28719277

Detecting spatial regimes in ecosystems

EPA Science Inventory

Research on early warning indicators has generally focused on assessing temporal transitions with limited application of these methods to detecting spatial regimes. Traditional spatial boundary detection procedures that result in ecoregion maps are typically based on ecological ...

76 FR 73727 - Biweekly Notice; Applications and Amendments to Facility Operating Licenses Involving No...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-29

... Detection Instrumentation,'' to define a new time limit for restoring inoperable RCS leakage detection... Specifications Section 3.4.15 regarding reactor coolant leakage detection instrumentation to be consistent with... amendments revised the Technical Specifications (TSs) ``RCS [reactor coolant system] Leakage Detection...

46 CFR 161.002-2 - Types of fire-protective systems.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., but not be limited to, automatic fire and smoke detecting systems, manual fire alarm systems, sample extraction smoke detection systems, watchman's supervisory systems, and combinations of these systems. (b) Automatic fire detecting systems. For the purpose of this subpart, automatic fire and smoke detecting...

46 CFR 161.002-2 - Types of fire-protective systems.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., but not be limited to, automatic fire and smoke detecting systems, manual fire alarm systems, sample extraction smoke detection systems, watchman's supervisory systems, and combinations of these systems. (b) Automatic fire detecting systems. For the purpose of this subpart, automatic fire and smoke detecting...

Label-free optical biosensing with slot-waveguides.

PubMed

Barrios, Carlos A; Bañuls, María José; González-Pedro, Victoria; Gylfason, Kristinn B; Sánchez, Benito; Griol, Amadeu; Maquieira, A; Sohlström, H; Holgado, M; Casquel, R

2008-04-01

We demonstrate label-free molecule detection by using an integrated biosensor based on a Si(3)N(4)/SiO(2) slot-waveguide microring resonator. Bovine serum albumin (BSA) and anti-BSA molecular binding events on the sensor surface are monitored through the measurement of resonant wavelength shifts with varying biomolecule concentrations. The biosensor exhibited sensitivities of 1.8 and 3.2 nm/(ng/mm(2)) for the detection of anti-BSA and BSA, respectively. The estimated detection limits are 28 and 16 pg/mm(2) for anti-BSA and BSA, respectively, limited by wavelength resolution.

Addressing the Limit of Detectability of Residual Oxide Discontinuities in Friction Stir Butt Welds of Aluminum using Phased Array Ultrasound

NASA Technical Reports Server (NTRS)

Johnston, P. H.

2008-01-01

This activity seeks to estimate a theoretical upper bound of detectability for a layer of oxide embedded in a friction stir weld in aluminum. The oxide is theoretically modeled as an ideal planar layer of aluminum oxide, oriented normal to an interrogating ultrasound beam. Experimentally-measured grain scattering level is used to represent the practical noise floor. Echoes from naturally-occurring oxides will necessarily fall below this theoretical limit, and must be above the measurement noise to be potentially detectable.

Dual chamber arrhythmia detection in the implantable cardioverter defibrillator.

PubMed

Dijkman, B; Wellens, H J

2000-10-01

Dual chamber implantable cardioverter defibrillator (ICD) technology extended ICD therapy to more than termination of hemodynamically unstable ventricular tachyarrhythmias. It created the basis for dual chamber arrhythmia management in which dependable detection is important for treatment and prevention of both ventricular and atrial arrhythmias. Dual chamber detection algorithms were investigated in two Medtronic dual chamber ICDs: the 7250 Jewel AF (33 patients) and the 7271 Gem DR (31 patients). Both ICDs use the same PR Logic algorithm to interpret tachycardia as ventricular tachycardia (VT), supraventricular tachycardia (SVT), or dual (VT+ SVT). The accuracy of dual chamber detection was studied in 310 of 1,367 spontaneously occurring tachycardias in which rate criterion only was not sufficient for arrhythmia diagnosis. In 78 episodes there was a double tachycardia, in 223 episodes SVT was detected in the VT or ventricular fibrillation zone, and in 9 episodes arrhythmia was detected outside the boundaries of the PR Logic functioning. In 100% of double tachycardias the VT was correctly diagnosed and received priority treatment. SVT was seen in 59 (19%) episodes diagnosed as VT. The causes of inappropriate detection were (1) algorithm failure (inability to fulfill the PR

Experimental Study of the Detection Limit in Dual-Gate Biosensors Using Ultrathin Silicon Transistors.

PubMed

Wu, Ting; Alharbi, Abdullah; You, Kai-Dyi; Kisslinger, Kim; Stach, Eric A; Shahrjerdi, Davood

2017-07-25

Dual-gate field-effect biosensors (bioFETs) with asymmetric gate capacitances were shown to surpass the Nernst limit of 59 mV/pH. However, previous studies have conflicting findings on the effect of the capacitive amplification scheme on the sensor detection limit, which is inversely proportional to the signal-to-noise ratio (SNR). Here, we present a systematic experimental investigation of the SNR using ultrathin silicon transistors. Our sensors operate at low voltage and feature asymmetric front and back oxide capacitances with asymmetry factors of 1.4 and 2.3. We demonstrate that in the dual-gate configuration, the response of our bioFETs to the pH change increases proportional to the asymmetry factor and indeed exceeds the Nernst limit. Further, our results reveal that the noise amplitude also increases in proportion to the asymmetry factor. We establish that the commensurate increase of the noise amplitude originates from the intrinsic low-frequency characteristic of the sensor noise, dominated by number fluctuation. These findings suggest that this capacitive signal amplification scheme does not improve the intrinsic detection limit of the dual-gate biosensors.

Thermal detection thresholds in 5-year-old preterm born children; IQ does matter.

PubMed

de Graaf, Joke; Valkenburg, Abraham J; Tibboel, Dick; van Dijk, Monique

2012-07-01

Experiencing pain at newborn age may have consequences on one's somatosensory perception later in life. Children's perception for cold and warm stimuli may be determined with the Thermal Sensory Analyzer (TSA) device by two different methods. This pilot study in 5-year-old children born preterm aimed at establishing whether the TSA method of limits, which is dependent of reaction time, and the method of levels, which is independent of reaction time, would yield different cold and warm detection thresholds. The second aim was to establish possible associations between intellectual ability and the detection thresholds obtained with either method. A convenience sample was drawn from the participants in an ongoing 5-year follow-up study of a randomized controlled trial on effects of morphine during mechanical ventilation. Thresholds were assessed using both methods and statistically compared. Possible associations between the child's intelligence quotient (IQ) and threshold levels were analyzed. The method of levels yielded more sensitive thresholds than did the method of limits, i.e. mean (SD) cold detection thresholds: 30.3 (1.4) versus 28.4 (1.7) (Cohen'sd=1.2, P=0.001) and warm detection thresholds; 33.9 (1.9) versus 35.6 (2.1) (Cohen's d=0.8, P=0.04). IQ was statistically significantly associated only with the detection thresholds obtained with the method of limits (cold: r=0.64, warm: r=-0.52). The TSA method of levels, is to be preferred over the method of limits in 5-year-old preterm born children, as it establishes more sensitive detection thresholds and is independent of IQ. Copyright © 2011 Elsevier Ltd. All rights reserved.

Whispering-Gallery Mode Resonators for Detecting Cancer

PubMed Central

Pongruengkiat, Weeratouch; Pechprasarn, Suejit

2017-01-01

Optical resonators are sensors well known for their high sensitivity and fast response time. These sensors have a wide range of applications, including in the biomedical fields, and cancer detection is one such promising application. Sensor diagnosis currently has many limitations, such as being expensive, highly invasive, and time-consuming. New developments are welcomed to overcome these limitations. Optical resonators have high sensitivity, which enable medical testing to detect disease in the early stage. Herein, we describe the principle of whispering-gallery mode and ring optical resonators. We also add to the knowledge of cancer biomarker diagnosis, where we discuss the application of optical resonators for specific biomarkers. Lastly, we discuss advancements in optical resonators for detecting cancer in terms of their ability to detect small amounts of cancer biomarkers. PMID:28902169

Sensitivity of photoacoustic microscopy

PubMed Central

Yao, Junjie; Wang, Lihong V.

2014-01-01

Building on its high spatial resolution, deep penetration depth and excellent image contrast, 3D photoacoustic microscopy (PAM) has grown tremendously since its first publication in 2005. Integrating optical excitation and acoustic detection, PAM has broken through both the optical diffusion and optical diffraction limits. PAM has 100% relative sensitivity to optical absorption (i.e., a given percentage change in the optical absorption coefficient yields the same percentage change in the photoacoustic amplitude), and its ultimate detection sensitivity is limited only by thermal noise. Focusing on the engineering aspects of PAM, this Review discusses the detection sensitivity of PAM, compares the detection efficiency of different PAM designs, and summarizes the imaging performance of various endogenous and exogenous contrast agents. It then describes representative PAM applications with high detection sensitivity, and outlines paths to further improvement. PMID:25302158

Study on methenamine detection in starch products through SERS technology

NASA Astrophysics Data System (ADS)

Cui, Yu; Qu, Zhou

2016-01-01

Using silver sol as a strengthened base, this paper concludes that l0ppb-0.1ppb methenamine aqueous solution has a better signal in 1052cm-1 Raman feature. And the lower limit of the aqueous solution is about 0.1ppb. Adding corresponding amount methenamine in vermicelli sample, the lower limit is about 10ppm. This is a safest and pollution-free detection process. Furthermore, the pretreatment process is simple, which will be finished in 20 minutes. Hence, it is better than other detection methods. SERS technology provides a simple, rapid and efficient detection method for field measurement and real time detection modulating disk of component, laser zooming system. Through the use of laser diode, Laser-beam riding guided system is likely to have smaller shape and very light.

Improved detection limits for electrospray ionization on a magnetic sector mass spectrometer by using an array detector.

PubMed

Cody, R B; Tamura, J; Finch, J W; Musselman, B D

1994-03-01

Array detection was compared with point detection for solutions of hen egg-white lysozyme, equine myoglobin, and ubiquitin analyzed by electrospray ionization with a magnetic sector mass spectrometer. The detection limits for samples analyzed by using the array detector system were at least 10 times lower than could be achieved by using a point detector on the same mass spectrometer. The minimum detectable quantity of protein corresponded to a signal-to-background ratio of approximately 2∶1 for a 500 amol/μL solution of hen egg-white lysozyme. However, the ultimate practical sample concentrations appeared to be in the 10-100 fmol/μL range for the analysis of dilute solutions of relatively pure proteins or simple mixtures.

Hapsite Gas Chromatography - Mass Spectrometry with Solid Phase Microextraction

DTIC Science & Technology

2005-07-18

Polydimethylsiloxane /Divinylbenzene (PDMS/DVB) 65um/partially crosslinked*** Polar volatiles 60urn/ partially crosslinked General purpose (for HPLC ... Polydimethylsiloxane (PDMS). The HAPSITE with tri-bed concentrator achieved the lowest detection limits. The HAPSITE and the field portable GCUMS... Polydimethylsiloxane (PDMS). The HAPSITE with tri-bed concentrator achieved the lowest detection limits. The HAPSITE and the field portable GC/MS instrument coupled

40 CFR 63.1453 - How do I demonstrate continuous compliance with the emission limitations, work practice standards...

Code of Federal Regulations, 2010 CFR

2010-07-01

... percent opacity. (c) Baghouses. For each baghouse subject to the operating limit for the bag leak... that the bag leak detection system alarm does not sound for more than 5 percent of the operating time... malfunction of the bag leak detection system are not included in the calculation. (ii) Alarms that occur...

40 CFR 60.4850 - What operating limits and requirements must I meet and by when?

Code of Federal Regulations, 2011 CFR

2011-07-01

...) If you use a fabric filter to comply with the emission limits, you must install the bag leak detection system specified in §§ 60.4880(b) and 60.4905(b)(3)(i) and operate the bag leak detection system... filter, electrostatic precipitator, or activated carbon injection are listed in Table 3 to this subpart...

40 CFR Appendix C to Part 425 - Definition and Procedure for the Determination of the Method Detection Limit 1

Code of Federal Regulations, 2010 CFR

2010-07-01

... Determination of the Method Detection Limit 1 C Appendix C to Part 425 Protection of Environment ENVIRONMENTAL... CATEGORY Pt. 425, App. C Appendix C to Part 425—Definition and Procedure for the Determination of the... reagent water. (c) The concentration value that corresponds to the region of the standard curve where...

Polymer microchip capillary electrophoresis of proteins either off- or on-chip labeled with chameleon dye for simplified analysis

PubMed Central

Yu, Ming; Wang, Hsiang-Yu; Woolley, Adam

2009-01-01

Microchip capillary electrophoresis of proteins labeled either off- or on-chip with the “chameleon” CE dye 503 using poly(methyl methacrylate) microchips is presented. A simple dynamic coating using the cationic surfactant cetyltrimethyl ammonium bromide prevented nonspecific adsorption of protein and dye to the channel walls. The labeling reactions for both off- and on-chip labeling proceeded at room temperature without requiring heating steps. In off-chip labeling, a 9 ng/mL concentration detection limit for bovine serum albumin (BSA), corresponding to a ~7 fg (100 zmol) mass detection limit, was obtained. In on-chip tagging, the free dye and protein were placed in different reservoirs of the microchip, and an extra incubation step was not needed. A 1 μg/mL concentration detection limit for BSA, corresponding to a ~700 fg (10 amol) mass detection limit, was obtained from this protocol. The earlier elution time of the BSA peak in on-chip labeling resulted from fewer total labels on each protein molecule. Our on-chip labeling method is an important part of automation in miniaturized devices. PMID:19924700

Predictive inference for best linear combination of biomarkers subject to limits of detection.

PubMed

Coolen-Maturi, Tahani

2017-08-15

Measuring the accuracy of diagnostic tests is crucial in many application areas including medicine, machine learning and credit scoring. The receiver operating characteristic (ROC) curve is a useful tool to assess the ability of a diagnostic test to discriminate between two classes or groups. In practice, multiple diagnostic tests or biomarkers are combined to improve diagnostic accuracy. Often, biomarker measurements are undetectable either below or above the so-called limits of detection (LoD). In this paper, nonparametric predictive inference (NPI) for best linear combination of two or more biomarkers subject to limits of detection is presented. NPI is a frequentist statistical method that is explicitly aimed at using few modelling assumptions, enabled through the use of lower and upper probabilities to quantify uncertainty. The NPI lower and upper bounds for the ROC curve subject to limits of detection are derived, where the objective function to maximize is the area under the ROC curve. In addition, the paper discusses the effect of restriction on the linear combination's coefficients on the analysis. Examples are provided to illustrate the proposed method. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Applying ISO 11929:2010 Standard to detection limit calculation in least-squares based multi-nuclide gamma-ray spectrum evaluation

NASA Astrophysics Data System (ADS)

Kanisch, G.

2017-05-01

The concepts of ISO 11929 (2010) are applied to evaluation of radionuclide activities from more complex multi-nuclide gamma-ray spectra. From net peak areas estimated by peak fitting, activities and their standard uncertainties are calculated by weighted linear least-squares method with an additional step, where uncertainties of the design matrix elements are taken into account. A numerical treatment of the standard's uncertainty function, based on ISO 11929 Annex C.5, leads to a procedure for deriving decision threshold and detection limit values. The methods shown allow resolving interferences between radionuclide activities also in case of calculating detection limits where they can improve the latter by including more than one gamma line per radionuclide. The co"mmon single nuclide weighted mean is extended to an interference-corrected (generalized) weighted mean, which, combined with the least-squares method, allows faster detection limit calculations. In addition, a new grouped uncertainty budget was inferred, which for each radionuclide gives uncertainty budgets from seven main variables, such as net count rates, peak efficiencies, gamma emission intensities and others; grouping refers to summation over lists of peaks per radionuclide.

Comparison of detection limit in fiber-based conventional, amplified, and gain-clamped cavity ring-down techniques

NASA Astrophysics Data System (ADS)

Sharma, K.; Abdul Khudus, M. I. M.; Alam, S. U.; Bhattacharya, S.; Venkitesh, D.; Brambilla, G.

2018-01-01

Relative performance and detection limit of conventional, amplified, and gain-clamped cavity ring-down techniques (CRDT) in all-fiber configurations are compared experimentally for the first time. Refractive index measurement using evanescent field in tapered fibers is used as a benchmark for the comparison. The systematic optimization of a nested-loop configuration in gain-clamped CRDT is also discussed, which is crucial for achieving a constant gain in a CRDT experiment. It is found that even though conventional CRDT has the lowest standard error in ring-down time (Δτ), the value of ring-down time (τ) is very small, thus leading to poor detection limit. Amplified CRDT provides an improvement in τ, albeit with two orders of magnitude higher Δτ due to amplifier noise. The nested-loop configuration in gain-clamped CRDT helps in reducing Δτ by an order of magnitude as compared to amplified CRDT whilst retaining the improvement in τ. A detection limit of 1 . 03 × 10-4 RIU at refractive index of 1.322 with a 3 mm long and 4.5 μm diameter tapered fiber is demonstrated with the gain-clamped CRDT.

Analysis of metalaxyl racemate using high performance liquid chromatography coupled with four kinds of detectors.

PubMed

Chen, Tao; Fan, Jun; Gao, Ruiqi; Wang, Tai; Yu, Ying; Zhang, Weiguang

2016-10-07

Chiral stationary phase-high performance liquid chromatography coupled with various detectors has been one of most commonly used methods for analysis and separation of chiral compounds over the past decades. Various detectors exhibit different characteristics in qualitative and quantitative studies under different chromatographic conditions. Herein, a comparative evaluation of HPLC coupled with ultraviolet, optical rotation, refractive index, and evaporative light scattering detectors has been conducted for qualitative and quantitative analyses of metalaxyl racemate. Effects of separation conditions on the peak area ratio between two enantiomers, including sample concentration, column temperature, mobile phase composition, as well as flow rate, have been investigated in detail. In addition, the limits of detection, the limits of quantitation, quantitative range and precision for these two enantiomers by using four detectors have been also studied. As indicated, the chromatographic separation conditions have been slight effects on ultraviolet and refractive index detections and the peak area ratio between two enantiomers remains almost unchanged, but the evaporative light scattering detection has been significantly affected by the above-mentioned chromatographic conditions and the corresponding peak area ratios varied greatly. Moreover, the limits of detection, the limits of quantitation, and the quantitative ranges of two enantiomers with UV detection were remarkably lower by 1-2 magnitudes than the others. Copyright © 2016 Elsevier B.V. All rights reserved.

CMOS-MEMS Chemiresistive and Chemicapacitive Chemical Sensor System

NASA Astrophysics Data System (ADS)

Lazarus, Nathan S.

Integrating chemical sensors with testing electronics is a powerful technique with the potential to lower power and cost and allow for lower system limits of detection. This thesis explores the possibility of creating an integrated sensor system intended to be embedded within respirator cartridges to notify the user that hazardous chemicals will soon leak into the face mask. For a chemical sensor designer, this application is particularly challenging due to the need for a very sensitive and cheap sensor that will be exposed to widely varying environmental conditions during use. An octanethiol-coated gold nanoparticle chemiresistor to detect industrial solvents is developed, focusing on characterizing the environmental stability and limits of detection of the sensor. Since the chemiresistor was found to be highly sensitive to water vapor, a series of highly sensitive humidity sensor topologies were developed, with sensitivities several times previous integrated capacitive humidity sensors achieved. Circuit techniques were then explored to reduce the humidity sensor limits of detection, including the analysis of noise, charge injection, jitter and clock feedthrough in a charge-based capacitance measurement (CBCM) circuit and the design of a low noise Colpitts LC oscillator. The characterization of high resistance gold nanoclusters for capacitive chemical sensing was also performed. In the final section, a preconcentrator, a heater element intended to release a brief concentrated pulse of analate, was developed and tested for the purposes of lowering the system limit of detection.

ENVIRONMENTAL APPLICATION OF GAS CHROMATOGRAPHY/ATOMIC EMISSION DETECTION

EPA Science Inventory

A gas chromatography/atomic emission detector (GC/AED) system has been evaluated for its applicability to environmental analysis. Detection limits, elemental response factors, and regression analysis data were determined for 58 semivolatile environmental contaminants. Detection l...

Rapid and sensitive detection of synthetic cannabinoids AMB-FUBINACA and α-PVP using surface enhanced Raman scattering (SERS)

NASA Astrophysics Data System (ADS)

Islam, Syed K.; Cheng, Yin Pak; Birke, Ronald L.; Green, Omar; Kubic, Thomas; Lombardi, John R.

2018-04-01

The application of surface enhanced Raman scattering (SERS) has been reported as a fast and sensitive analytical method in the trace detection of the two most commonly known synthetic cannabinoids AMB-FUBINACA and alpha-pyrrolidinovalerophenone (α-PVP). FUBINACA and α-PVP are two of the most dangerous synthetic cannabinoids which have been reported to cause numerous deaths in the United States. While instruments such as GC-MS, LC-MS have been traditionally recognized as analytical tools for the detection of these synthetic drugs, SERS has been recently gaining ground in the analysis of these synthetic drugs due to its sensitivity in trace analysis and its effectiveness as a rapid method of detection. This present study shows the limit of detection of a concentration as low as picomolar for AMB-FUBINACA while for α-PVP, the limit of detection is in nanomolar concentration using SERS.

Characterization of the hydrogeology and water quality at the Management Systems Evaluation Area near Princeton, Minnesota, 1991-92

USGS Publications Warehouse

Delin, G.N.; Landon, M.K.; Lamb, J.A.; Anderson, J.L.

1994-01-01

Atrazine was detected by gas chromatography mass spectroscopy in 2 of the 7 wells in the research area at concentrations of 0.04 and 0.17 micrograms per liter (ug/L), well below the U.S. Environmental Protection Agency's recommended maximum contaminant level of 3 ug/L. The median concentration in these Wells was less than the qualitative detection limit of 0.01 ug/L. Atrazine metabolite de-ethylatrazine was the most frequently detected herbicide or herbicide metabolite. De-ethylatrazine was detected in 5 of the 7 wells in the research area at concentrations ranging from 0.12 to 0.32 ug/L with a median concentration of 0.14 ug/L. Atrazine metabolite de-isopropylatrazine was not detected above the qualitative detection limit of 0.06 ug/L. The most likely sources of atrazine are applications to the research area during 1990 or from precipitation.

Photonic Crystal Enhanced Fluorescence for Early Breast Cancer Biomarker Detection

PubMed Central

Cunningham, Brian T.; Zangar, Richard C.

2013-01-01

Photonic crystal surfaces offer a compelling platform for improving the sensitivity of surface-based fluorescent assays used in disease diagnostics. Through the complementary processes of photonic crystal enhanced excitation and enhanced extraction, a periodic dielectric-based nanostructured surface can simultaneously increase the electric field intensity experienced by surface-bound fluorophores and increase the collection efficiency of emitted fluorescent photons. Through the ability to inexpensively fabricate photonic crystal surfaces over substantial surface areas, they are amenable to single-use applications in biological sensing, such as disease biomarker detection in serum. In this review, we will describe the motivation for implementing high-sensitivity, multiplexed biomarker detection in the context of breast cancer diagnosis. We will summarize recent efforts to improve the detection limits of such assays though the use of photonic crystal surfaces. Reduction of detection limits is driven by low autofluorescent substrates for photonic crystal fabrication, and detection instruments that take advantage of their unique features. PMID:22736539

Rapid and sensitive detection of canine parvovirus type 2 by recombinase polymerase amplification.

PubMed

Wang, Jianchang; Liu, Libing; Li, Ruiwen; Wang, Jinfeng; Fu, Qi; Yuan, Wanzhe

2016-04-01

A novel recombinase polymerase amplification (RPA)-based method for detection of canine parvovirus type 2 (CPV-2) was developed. Sensitivity analysis showed that the detection limit of RPA was 10 copies of CPV-2 genomic DNA. RPA amplified both CPV-2a and -2b DNA but did not amplify the template of other important dog viruses (CCoV, PRV or CDV), demonstrating high specificity. The method was further validated with 57 canine fecal samples. An outstanding advantage of RPA is that it is an isothermal reaction and can be performed in a water bath, making RPA a potential alternative method for CPV-2 detection in resource-limited settings.

Sensitive DNA detection and SNP discrimination using ultrabright SERS nanorattles and magnetic beads for malaria diagnostics.

PubMed

Ngo, Hoan T; Gandra, Naveen; Fales, Andrew M; Taylor, Steve M; Vo-Dinh, Tuan

2016-07-15

One of the major obstacles to implement nucleic acid-based molecular diagnostics at the point-of-care (POC) and in resource-limited settings is the lack of sensitive and practical DNA detection methods that can be seamlessly integrated into portable platforms. Herein we present a sensitive yet simple DNA detection method using a surface-enhanced Raman scattering (SERS) nanoplatform: the ultrabright SERS nanorattle. The method, referred to as the nanorattle-based method, involves sandwich hybridization of magnetic beads that are loaded with capture probes, target sequences, and ultrabright SERS nanorattles that are loaded with reporter probes. Upon hybridization, a magnet was applied to concentrate the hybridization sandwiches at a detection spot for SERS measurements. The ultrabright SERS nanorattles, composed of a core and a shell with resonance Raman reporters loaded in the gap space between the core and the shell, serve as SERS tags for signal detection. Using this method, a specific DNA sequence of the malaria parasite Plasmodium falciparum could be detected with a detection limit of approximately 100 attomoles. Single nucleotide polymorphism (SNP) discrimination of wild type malaria DNA and mutant malaria DNA, which confers resistance to artemisinin drugs, was also demonstrated. These test models demonstrate the molecular diagnostic potential of the nanorattle-based method to both detect and genotype infectious pathogens. Furthermore, the method's simplicity makes it a suitable candidate for integration into portable platforms for POC and in resource-limited settings applications. Copyright © 2016. Published by Elsevier B.V.

[Analysis of Cr in soil by LIBS based on conical spatial confinement of plasma].

PubMed

Lin, Yong-Zeng; Yao, Ming-Yin; Chen, Tian-Bing; Li, Wen-Bing; Zheng, Mei-Lan; Xu, Xue-Hong; Tu, Jian-Ping; Liu, Mu-Hua

2013-11-01

The present study is to improve the sensitivity of detection and reduce the limit of detection in detecting heavy metal of soil by laser induced breakdown spectroscopy (LIBS). The Cr element of national standard soil was regarded as the research object. In the experiment, a conical cavity with small diameter end of 20 mm and large diameter end of 45 mm respectively was installed below the focusing lens near the experiment sample to mainly confine the signal transmitted by plasma and to some extent to confine the plasma itself in the LIBS setup. In detecting Cr I 425.44 nm, the beast delay time gained from experiment is 1.3 micros, and the relative standard deviation is below 10%. Compared with the setup of non-spatial confinement, the spectral intensity of Cr in the soil sample was enhanced more than 7%. Calibration curve was established in the Cr concentration range from 60 to 400 microg x g(-1). Under the condition of spatial confinement, the liner regression coefficient and the limit of detection were 0.997 71 and 18.85 microg x g(-1) respectively, however, the regression coefficient and the limit of detection were 0.991 22 and 36.99 microg x g(-1) without spatial confinement. So, this shows that conical spatial confinement can/improve the sensitivity of detection and enhance the spectral intensity. And it is a good auxiliary function in detecting Cr in the soil by laser induced breakdown spectroscopy.

Using Metal Complex Ion-Molecule Reactions in a Miniature Rectilinear Ion Trap Mass Spectrometer to Detect Chemical Warfare Agents

NASA Astrophysics Data System (ADS)

Graichen, Adam M.; Vachet, Richard W.

2013-06-01

The gas-phase reactions of a series of coordinatively unsaturated [Ni(L)n]y+ complexes, where L is a nitrogen-containing ligand, with chemical warfare agent (CWA) simulants in a miniature rectilinear ion trap mass spectrometer were investigated as part of a new approach to detect CWAs. Results show that upon entering the vacuum system via a poly(dimethylsiloxane) (PDMS) membrane introduction, low concentrations of several CWA simulants, including dipropyl sulfide (simulant for mustard gas), acetonitrile (simulant for the nerve agent tabun), and diethyl phosphite (simulant for nerve agents sarin, soman, tabun, and VX), can react with metal complex ions generated by electrospray ionization (ESI), thereby providing a sensitive means of detecting these compounds. The [Ni(L)n]2+ complexes are found to be particularly reactive with the simulants of mustard gas and tabun, allowing their detection at low parts-per-billion (ppb) levels. These detection limits are well below reported exposure limits for these CWAs, which indicates the applicability of this new approach, and are about two orders of magnitude lower than electron ionization detection limits on the same mass spectrometer. The use of coordinatively unsaturated metal complexes as reagent ions offers the possibility of further tuning the ion-molecule chemistry so that desired compounds can be detected selectively or at even lower concentrations.

Hydrazinylpyridine based highly selective optical sensor for aqueous source of carbonate ions: Electrochemical and DFT studies

NASA Astrophysics Data System (ADS)

Thimaradka, Vikram; Pangannaya, Srikala; Mohan, Makesh; Trivedi, Darshak R.

2018-03-01

A series of new receptors PDZ1-3 based on 2-(arylidenehydrazinyl)pyridines have been designed and synthesized for the detection of biologically and environmentally important ions. The colorimetric detection of CO32 - using neutral organic receptor PDZ-1 has been achieved with characteristic visual colour change from yellow to green accompanied by a large redshift of 215 nm in absorption maxima. UV-Vis spectroscopic and cyclic voltammetric studies reveal the stoichiometry of binding and electrochemistry of host-guest complex formation. The binding constant was found to be 0.77 × 104 M- 2. In addition, electrochemical studies provide an insight into the stability of the complex. DFT studies performed on the PDZ-1 and PDZ-1 - CO32 - complex reveal the binding mechanism involved in the anion detection process. PDZ-1 is highly selective for carbonate and does not show any colorimetric response towards any other anions or cations, while PDZ-2 and PDZ-3 remain inactive in the ion detection process. The limit of detection (LOD) and limit of quantification (LOQ) of PDZ-1 for carbonate was found to be 0.11 mM and 0.36 mM respectively. Considerable binding constant and limit of detection make PDZ-1 to be used as a real time sensor for the detection of carbonate in environmental and biological samples.

Surface plasmon resonance biosensor for enzymatic detection of small analytes

NASA Astrophysics Data System (ADS)

Massumi Miyazaki, Celina; Makoto Shimizu, Flávio; Mejía-Salazar, J. R.; Oliveira, Osvaldo N., Jr.; Ferreira, Marystela

2017-04-01

Surface plasmon resonance (SPR) biosensing is based on the detection of small changes in the refractive index on a gold surface modified with molecular recognition materials, thus being mostly limited to detecting large molecules. In this paper, we report on a SPR biosensing platform suitable to detect small molecules by making use of the mediator-type enzyme microperoxidase-11 (MP11) in layer-by-layer films. By depositing a top layer of glucose oxidase or uricase, we were able to detect glucose or uric acid with limits of detection of 3.4 and 0.27 μmol l-1, respectively. Measurable SPR signals could be achieved because of the changes in polarizability of MP11, as it is oxidized upon interaction with the analyte. Confirmation of this hypothesis was obtained with finite difference time domain simulations, which also allowed us to discard the possible effects from film roughness changes observed in atomic force microscopy images. The main advantage of this mediator-type enzyme approach is in the simplicity of the experimental method that does not require an external potential, unlike similar approaches for SPR biosensing of small molecules. The detection limits reported here were achieved without optimizing the film architecture, and therefore the performance can in principle be further enhanced, while the proposed SPR platform may be extended to any system where hydrogen peroxide is generated in enzymatic reactions.

Enantioselective determination of the organochlorine pesticide bromocyclen in spiked fish tissue using solid-phase microextraction coupled to gas chromatography with ECD and ICP-MS detection.

PubMed

Fidalgo-Used, Natalia; Montes-Bayón, Maria; Blanco-González, Elisa; Sanz-Medel, Alfredo

2008-05-15

A method for enantioselective determination of bromocyclen enantiomers in fish tissue has been developed. The enantiomers were resolved by capillary gas chromatography (GC) using a commercial chiral column (CP-Chirasil-Dex CB) and a temperature program from 50 degrees C (held for 1 min), raised to 140 degrees C at 40 degrees C min(-1) and then raised at 0.2 degrees C min(-1) to 155 degrees C. This enantioselective gas chromatographic separation was combined with a clean-up/enrichment procedure based on solid-phase microextraction (SPME). Under SPME optimized conditions, precision, linearity range and detection limits of the developed SPME-enantioselective GC procedure were evaluated and compared using two different detection systems: a classical electron-capture detection (ECD) and an element specific detection using inductively coupled plasma mass spectrometry (ICP-MS). The SPME-GC-ECD method exhibited an excellent sensitivity, with detection limits of 0.2 ng L(-1) for each enantiomer of bromocyclen. Although ICP-MS offered poorer detection limits (7 ng L(-1) as Br, equivalent to 36 ng L(-1) of each enantiomer) than conventional ECD detector, it proved to be clearly superior in terms of selectivity. The relative potential and performance of the two compared methods for real-life analysis has been illustrated by the determination of enantiomers of bromocyclen in spiked tissue extracts of trout.

Step-scan T cell-based differential Fourier transform infrared photoacoustic spectroscopy (DFTIR-PAS) for detection of ambient air contaminants

NASA Astrophysics Data System (ADS)

Liu, Lixian; Mandelis, Andreas; Huan, Huiting; Melnikov, Alexander

2016-10-01

A step-scan differential Fourier transform infrared photoacoustic spectroscopy (DFTIR-PAS) using a commercial FTIR spectrometer was developed theoretically and experimentally for air contaminant monitoring. The configuration comprises two identical, small-size and low-resonance-frequency T cells satisfying the conflicting requirements of low chopping frequency and limited space in the sample compartment. Carbon dioxide (CO2) IR absorption spectra were used to demonstrate the capability of the DFTIR-PAS method to detect ambient pollutants. A linear amplitude response to CO2 concentrations from 100 to 10,000 ppmv was observed, leading to a theoretical detection limit of 2 ppmv. The differential mode was able to suppress the coherent noise, thereby imparting the DFTIR-PAS method with a better signal-to-noise ratio and lower theoretical detection limit than the single mode. The results indicate that it is possible to use step-scan DFTIR-PAS with T cells as a quantitative method for high sensitivity analysis of ambient contaminants.

Iron pentacarbonyl detection limits in the cigarette smoke matrix using FT-IR spectroscopy

NASA Astrophysics Data System (ADS)

Parrish, Milton E.; Plunkett, Susan E.; Harward, Charles N.

2005-11-01

Endogenous metals present in tobacco from agricultural practices have been purported to generate metal carbonyls in cigarette smoke. Transition metal catalysts, such as iron oxide, have been investigated for the reduction of carbon monoxide (CO) in cigarette smoke. These studies motivated the development of an analytical method to determine if iron pentacarbonyl [Fe(CO) 5] is present in mainstream smoke from cigarette models having cigarette paper made with iron oxide. An FT-IR puff-by-puff method was developed and the detection limit was determined using two primary reference spectra from different sources to estimate the amount of Fe(CO) 5 present in a high-pressure steel cylinder of CO. We do not detect Fe(CO) 5 in a single 35 mL puff from reference cigarettes or from those cigarette models having cigarette paper made with iron oxide, with a 30-ppbV limit of detection (LOD). Also, it was shown that a filter containing activated carbon would remove Fe(CO) 5.

Flower-like ZnO decorated polyaniline/reduced graphene oxide nanocomposites for simultaneous determination of dopamine and uric acid.

PubMed

Ghanbari, Kh; Moloudi, M

2016-11-01

A novel sensor was fabricated by electrochemical deposition of ZnO flower-like/polyaniline nanofiber/reduced graphene oxide nanocomposite (ZnO/PANI/RGO) on glassy carbon electrode (GCE) for direct detection of dopamine (DA) and uric acid (UA) in the presence of fixed concentration of ascorbic acid (AA). Surface morphology and characterization of the modified electrodes were confirmed by field emission scanning microscopy (FE-SEM), X-ray diffraction (XRD), Raman and FT-IR spectroscopies. For individual detection, the linear responses were in the two concentration ranges of 0.001-1 μM and 1-1000 μM with detection limit 0.8 nM (S/N = 3) for DA, and also 0.1-100 μM and 100-1000 μM with detection limit 0.042 μM (S/N = 3) for UA. Simultaneous determination of these species in their mixture solution showed the linear responses in the two concentration ranges of 0.1-90 μM and 90-1000 μM with detection limit 0.017 μM (S/N = 3) for DA and also showed two linear range of 0.5-90 μM and 100-1000 μM with detection limit 0.12 μM (S/N = 3) for UA, with coexistence of 1000 μM AA. The applicability of sensor for the analysis of DA, and UA in dopamine injection solution, human serum and human urine samples was successfully demonstrated. Copyright © 2016 Elsevier Inc. All rights reserved.

Kernel-Phase Interferometry for Super-Resolution Detection of Faint Companions

NASA Astrophysics Data System (ADS)

Factor, Samuel

2016-10-01

Direct detection of close in companions (binary systems or exoplanets) is notoriously difficult. While chronagraphs and point spread function (PSF) subtraction can be used to reduce contrast and dig out signals of companions under the PSF, there are still significant limitations in separation and contrast. While non-redundant aperture masking (NRM) interferometry can be used to detect companions well inside the PSF of a diffraction limited image, the mask discards 95% of the light gathered by the telescope and thus the technique is severely flux limited. Kernel-phase analysis applies interferometric techniques similar to NRM though utilizing the full aperture. Instead of closure-phases, kernel-phases are constructed from a grid of points on the full aperture, simulating a redundant interferometer. I propose to develop my own faint companion detection pipeline which utilizes an MCMC analysis of kernel-phases. I will search for new companions in archival images from NIC1 and ACS/HRC in order to constrain binary and planet formation models at separations inaccessible to previous techniques. Using this method, it is possible to detect a companion well within the classical l/D Rayleigh diffraction limit using a fraction of the telescope time as NRM. This technique can easily be applied to archival data as no mask is needed and will thus make the detection of close in companions cheap and simple as no additional observations are needed. Since the James Webb Space Telescope (JWST) will be able to perform NRM observations, further development and characterization of kernel-phase analysis will allow efficient use of highly competitive JWST telescope time.

A recombinase polymerase amplification-based assay for rapid detection of African swine fever virus.

PubMed

Wang, Jianchang; Wang, Jinfeng; Geng, Yunyun; Yuan, Wanzhe

2017-10-01

A recombinase polymerase amplification (RPA)-based method was developed for rapid and specific detection of African swine fever virus (ASFV), the etiologic agent of African swine fever, a devastating disease of swine. Primers and the exo probe targeting the conserved region of the P72 gene of ASFV were designed and the reaction was run on the Genie III scanner device. Using recombinant plasmid DNA containing the P72 gene as template, we showed that the amplified product could be detected in less than 10 min and that the detection limit was 10 2 copies DNA/reaction [same detection limit as real-time polymerase chain reaction (PCR)]. The RPA assay did not cross-detect CSFV, PCV-2, PRV, PRRSV, or FMDV, common viruses seen in pigs. Tests of recombinant plasmid-spiked serum samples revealed that RPA and real-time PCR had the same diagnostic rate. The RPA assay, which is simple, cost-effective, and fast, is a promising alternative to real-time PCR for ASFV detection.

A recombinase polymerase amplification-based assay for rapid detection of African swine fever virus

PubMed Central

Wang, Jianchang; Wang, Jinfeng; Geng, Yunyun; Yuan, Wanzhe

2017-01-01

A recombinase polymerase amplification (RPA)-based method was developed for rapid and specific detection of African swine fever virus (ASFV), the etiologic agent of African swine fever, a devastating disease of swine. Primers and the exo probe targeting the conserved region of the P72 gene of ASFV were designed and the reaction was run on the Genie III scanner device. Using recombinant plasmid DNA containing the P72 gene as template, we showed that the amplified product could be detected in less than 10 min and that the detection limit was 102 copies DNA/reaction [same detection limit as real-time polymerase chain reaction (PCR)]. The RPA assay did not cross-detect CSFV, PCV-2, PRV, PRRSV, or FMDV, common viruses seen in pigs. Tests of recombinant plasmid-spiked serum samples revealed that RPA and real-time PCR had the same diagnostic rate. The RPA assay, which is simple, cost-effective, and fast, is a promising alternative to real-time PCR for ASFV detection. PMID:29081590

Sensitive electrochemical sensors for simultaneous determination of ascorbic acid, dopamine, and uric acid based on Au@Pd-reduced graphene oxide nanocomposites.

PubMed

Jiang, Jingjing; Du, Xuezhong

2014-10-07

Sensitive electrochemical sensors were fabricated with reduced graphene oxide-supported Au@Pd (Au@Pd-RGO) nanocomposites by one-step synthesis for individual and simultaneous determination of ascorbic acid (AA), dopamine (DA), and uric acid (UA) with low detection limits and wide concentration ranges. From the Au@Pd-RGO-modified electrodes, well-separated oxidation peaks and enhanced peak currents of AA, DA, and UA were observed owing to the superior conductivity of RGO and the excellent catalytic activity of Au@Pd nanoparticles. For individual detection, the linear responses of AA, DA, and UA were in the concentration ranges of 0.1-1000, 0.01-100, and 0.02-500 μM with detection limits of 0.02, 0.002, and 0.005 μM (S/N = 3), respectively. For simultaneous detection by synchronous change of the concentrations of AA, DA, and UA, the linear response ranges were 1-800, 0.1-100, and 0.1-350 μM with detection limits of 0.28, 0.024, and 0.02 μM (S/N = 3), respectively. The fabricated sensors were further applied to the detection of AA, DA, and UA in urine samples. The Au@Pd-RGO nanocomposites have promising applications in highly sensitive and selective electrochemical sensing.

Ultrahigh-Sensitivity Piezoresistive Pressure Sensors for Detection of Tiny Pressure.

PubMed

Li, Hongwei; Wu, Kunjie; Xu, Zeyang; Wang, Zhongwu; Meng, Yancheng; Li, Liqiang

2018-06-20

High-sensitivity pressure sensors are crucial for the ultrasensitive touch technology and E-skin, especially at the tiny-pressure range below 100 Pa. However, it is highly challenging to substantially promote sensitivity beyond the current level at several to 200 kPa -1 and to improve the detection limit lower than 0.1 Pa, which is significant for the development of pressure sensors toward ultrasensitive and highly precise detection. Here, we develop an efficient strategy to greatly improve the sensitivity near to 2000 kPa -1 using short-channel coplanar device structure and sharp microstructure, which is systematically proposed for the first time and rationalized by the mathematic calculation and analysis. Significantly, benefiting from the ultrahigh sensitivity, the detection limit is improved to be as small as 0.075 Pa. The sensitivity and detection limit are both superior to the current levels and far surpass the function of human skin. Furthermore, the sensor shows fast response time (50 μs), excellent reproducibility and stability, and low power consumption. Remarkably, the sensor shows excellent detection capacity in the tiny-pressure range, including light-emitting diode switching with a pressure of 7 Pa, ringtone (2-20 Pa) recognition, and ultrasensitive (0.1 Pa) electronic glove. This work represents a performance and strategic progress in the field of pressure sensing.

Targeted Analyte Detection by Standard Addition Improves Detection Limits in MALDI Mass Spectrometry

PubMed Central

Eshghi, Shadi Toghi; Li, Xingde; Zhang, Hui

2014-01-01

Matrix-assisted laser desorption/ionization has proven an effective tool for fast and accurate determination of many molecules. However, the detector sensitivity and chemical noise compromise the detection of many invaluable low-abundance molecules from biological and clinical samples. To challenge this limitation, we developed a targeted analyte detection (TAD) technique. In TAD, the target analyte is selectively elevated by spiking a known amount of that analyte into the sample, thereby raising its concentration above the noise level, where we take advantage of the improved sensitivity to detect the presence of the endogenous analyte in the sample. We assessed TAD on three peptides in simple and complex background solutions with various exogenous analyte concentrations in two MALDI matrices. TAD successfully improved the limit of detection (LOD) of target analytes when the target peptides were added to the sample in a concentration close to optimum concentration. The optimum exogenous concentration was estimated through a quantitative method to be approximately equal to the original LOD for each target. Also, we showed that TAD could achieve LOD improvements on an average of 3-fold in a simple and 2-fold in a complex sample. TAD provides a straightforward assay to improve the LOD of generic target analytes without the need for costly hardware modifications. PMID:22877355

Targeted analyte detection by standard addition improves detection limits in matrix-assisted laser desorption/ionization mass spectrometry.

PubMed

Toghi Eshghi, Shadi; Li, Xingde; Zhang, Hui

2012-09-18

Matrix-assisted laser desorption/ionization (MALDI) has proven an effective tool for fast and accurate determination of many molecules. However, the detector sensitivity and chemical noise compromise the detection of many invaluable low-abundance molecules from biological and clinical samples. To challenge this limitation, we developed a targeted analyte detection (TAD) technique. In TAD, the target analyte is selectively elevated by spiking a known amount of that analyte into the sample, thereby raising its concentration above the noise level, where we take advantage of the improved sensitivity to detect the presence of the endogenous analyte in the sample. We assessed TAD on three peptides in simple and complex background solutions with various exogenous analyte concentrations in two MALDI matrices. TAD successfully improved the limit of detection (LOD) of target analytes when the target peptides were added to the sample in a concentration close to optimum concentration. The optimum exogenous concentration was estimated through a quantitative method to be approximately equal to the original LOD for each target. Also, we showed that TAD could achieve LOD improvements on an average of 3-fold in a simple and 2-fold in a complex sample. TAD provides a straightforward assay to improve the LOD of generic target analytes without the need for costly hardware modifications.

Comparative evaluation of the sensitivity of LAMP, PCR and in vitro culture methods for the diagnosis of equine piroplasmosis.

PubMed

Alhassan, Andy; Govind, Yadav; Tam, Nguyen Thanh; Thekisoe, Oriel M M; Yokoyama, Naoaki; Inoue, Noboru; Igarashi, Ikuo

2007-04-01

The sensitivity of LAMP, PCR and in vitro culture methods for the detection of Theileria equi and Babesia caballi was evaluated using tenfold serially diluted culture parasites. On day 1 post-culture, both T. equi and B. caballi parasites could only be observed at 1% parasite dilution from the in vitro culture method, whereas LAMP could detect up to 1 x 10(-3)% of both T. equi and B. caballi parasite dilutions, whilst PCR could detect 1 x 10(-3)% T. equi and 1 x 10(-1)% B. caballi parasite dilutions. On day 7 post-culture, the detection limit for T. equi and B. caballi in the in vitro culture increased up to 1 x 10(-6)%, whereas LAMP detection limit increased to 1 x 10(-10)% for both parasites, whilst the PCR detection limit increased to 1 x 10(-10)% and 1 x 10(-6)% for T. equi and B. caballi, respectively. Furthermore, LAMP and PCR amplified the T. equi DNA extracted from the organs of an experimentally infected horse. This study further validates LAMP as an alternative molecular diagnostic tool, which can be used in the diagnosis of early infections of equine piroplasmosis and together with PCR can also be used as supplementary methods during post-mortems.

Accounting for Limited Detection Efficiency and Localization Precision in Cluster Analysis in Single Molecule Localization Microscopy

PubMed Central

Shivanandan, Arun; Unnikrishnan, Jayakrishnan; Radenovic, Aleksandra

2015-01-01

Single Molecule Localization Microscopy techniques like PhotoActivated Localization Microscopy, with their sub-diffraction limit spatial resolution, have been popularly used to characterize the spatial organization of membrane proteins, by means of quantitative cluster analysis. However, such quantitative studies remain challenged by the techniques’ inherent sources of errors such as a limited detection efficiency of less than 60%, due to incomplete photo-conversion, and a limited localization precision in the range of 10 – 30nm, varying across the detected molecules, mainly depending on the number of photons collected from each. We provide analytical methods to estimate the effect of these errors in cluster analysis and to correct for them. These methods, based on the Ripley’s L(r) – r or Pair Correlation Function popularly used by the community, can facilitate potentially breakthrough results in quantitative biology by providing a more accurate and precise quantification of protein spatial organization. PMID:25794150

Selecting Power-Efficient Signal Features for a Low-Power Fall Detector.

PubMed

Wang, Changhong; Redmond, Stephen J; Lu, Wei; Stevens, Michael C; Lord, Stephen R; Lovell, Nigel H

2017-11-01

Falls are a serious threat to the health of older people. A wearable fall detector can automatically detect the occurrence of a fall and alert a caregiver or an emergency response service so they may deliver immediate assistance, improving the chances of recovering from fall-related injuries. One constraint of such a wearable technology is its limited battery life. Thus, minimization of power consumption is an important design concern, all the while maintaining satisfactory accuracy of the fall detection algorithms implemented on the wearable device. This paper proposes an approach for selecting power-efficient signal features such that the minimum desirable fall detection accuracy is assured. Using data collected in simulated falls, simulated activities of daily living, and real free-living trials, all using young volunteers, the proposed approach selects four features from a set of ten commonly used features, providing a power saving of 75.3%, while limiting the error rate of a binary classification decision tree fall detection algorithm to 7.1%.Falls are a serious threat to the health of older people. A wearable fall detector can automatically detect the occurrence of a fall and alert a caregiver or an emergency response service so they may deliver immediate assistance, improving the chances of recovering from fall-related injuries. One constraint of such a wearable technology is its limited battery life. Thus, minimization of power consumption is an important design concern, all the while maintaining satisfactory accuracy of the fall detection algorithms implemented on the wearable device. This paper proposes an approach for selecting power-efficient signal features such that the minimum desirable fall detection accuracy is assured. Using data collected in simulated falls, simulated activities of daily living, and real free-living trials, all using young volunteers, the proposed approach selects four features from a set of ten commonly used features, providing a power saving of 75.3%, while limiting the error rate of a binary classification decision tree fall detection algorithm to 7.1%.

Quartz-Seq2: a high-throughput single-cell RNA-sequencing method that effectively uses limited sequence reads.

PubMed

Sasagawa, Yohei; Danno, Hiroki; Takada, Hitomi; Ebisawa, Masashi; Tanaka, Kaori; Hayashi, Tetsutaro; Kurisaki, Akira; Nikaido, Itoshi

2018-03-09

High-throughput single-cell RNA-seq methods assign limited unique molecular identifier (UMI) counts as gene expression values to single cells from shallow sequence reads and detect limited gene counts. We thus developed a high-throughput single-cell RNA-seq method, Quartz-Seq2, to overcome these issues. Our improvements in the reaction steps make it possible to effectively convert initial reads to UMI counts, at a rate of 30-50%, and detect more genes. To demonstrate the power of Quartz-Seq2, we analyzed approximately 10,000 transcriptomes from in vitro embryonic stem cells and an in vivo stromal vascular fraction with a limited number of reads.

An assessment of ground-based techniques for detecting other planetary systems. Volume 1: An overview. [workshop conclusions

NASA Technical Reports Server (NTRS)

Black, D. C. (Editor); Brunk, W. E. (Editor)

1980-01-01

The feasibility and limitations of ground-based techniques for detecting other planetary systems are discussed as well as the level of accuracy at which these limitations would occur and the extent to which they can be overcome by new technology and instrumenation. Workshop conclusions and recommendations are summarized and a proposed high priority program is considered.

Partial Least Squares Calibration Modeling Towards the Multivariate Limit of Detection for Enriched Isotopic Mixtures via Laser Ablation Molecular Isotopic Spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harris, Candace; Profeta, Luisa; Akpovo, Codjo

The psuedo univariate limit of detection was calculated to compare to the multivariate interval. ompared with results from the psuedounivariate LOD, the multivariate LOD includes other factors (i.e. signal uncertainties) and the reveals the significance in creating models that not only use the analyte’s emission line but also its entire molecular spectra.

Highly selective optical fluoride ion sensor with submicromolar detection limit based on aluminum(III) octaethylporphyrin in thin polymeric film.

PubMed

Badr, Ibrahim H A; Meyerhoff, Mark E

2005-04-20

A highly selective, sensitive, and reversible fluoride optical sensing film based on aluminum(III)octaethylporphyrin as a fluoride ionophore and a lipophilic pH indicator as the optical transducer is described. The fluoride optical sensing films exhibit a submicromolar detection limit and high discrimination for fluoride over several lipophilic anions such as nitrate, perchlorate, and thiocyanate.

Dual fluorescence/contactless conductivity detection for microfluidic chip.

PubMed

Liu, Cui; Mo, Yun-yan; Chen, Zuan-guang; Li, Xiang; Li, Ou-lian; Zhou, Xie

2008-07-28

A new dual detection system for microchip is reported. Both fluorescence detector (FD) and contactless conductivity detector (CCD) were combined together and integrated on a microfluidic chip. They shared a common detection position and responded simultaneously. A blue light-emitting diode was used as excitation source and a small planar photodiode was used to collect the emitted fluorescence in fluorescence detection, which made the device more compact and portable. The coupling of the fluorescence and contactless conductivity modes at the same position of a single separation channel enhanced the detection characterization of sample and offered simultaneous detection information of both fluorescent and charged specimen. The detection conditions of the system were optimized. K(+), Na(+), fluorescein sodium, fluorescein isothiocyanate (FITC) and FITC-labeled amino acids were used to evaluate the performance of the dual detection system. The limits of detection (LOD) of FD for fluorescein Na(+), FITC, FITC-labeled arginine (Arg), glycine (Gly) and phenylalanine (Phe) were 0.02micromolL(-1), 0.05micromolL(-1), 0.16micromolL(-1), 0.15micromolL(-1), 0.12micromolL(-1) respectively, and the limits of detection (LOD) of CCD achieved 0.58micromolL(-1) and 0.39micromolL(-1) for K(+) and Na(+) respectively.

Detection of adenoviruses in shellfish by means of conventional-PCR, nested-PCR, and integrated cell culture PCR (ICC/PCR).

PubMed

Rigotto, C; Sincero, T C M; Simões, C M O; Barardi, C R M

2005-01-01

We tested three PCR based methodologies to detect adenoviruses associated with cultivated oysters. Conventional-PCR, nested-PCR, and integrated cell culture-PCR (ICC/PCR) were first optimized using oysters seeded with know amounts of Adenovirus serotype 5 (Ad5). The maximum sensitivity for Ad5 detection was determined for each method, and then used to detect natural adenovirus contamination in oysters from three aquiculture farms in Florianopolis, Santa Catarina State, Brazil, over a period of 6 months. The results showed that the nested-PCR was more sensitive (limit of detection: 1.2 PFU/g of tissue) than conventional-PCR and ICC-PCR (limit of detection for both: 1.2 x 10(2)PFU/g of tissue) for detection of Ad5 in oyster extracts. Nested-PCR was able to detect 90% of Ad5 contamination in harvested oyster samples, while conventional-PCR was unable to detect Ad5 in any of the samples. The present work suggests that detection of human adenoviruses can be used as a tool to monitor the presence of human viruses in marine environments where shellfish grow, and that nested-PCR is the method of choice.

Biosensor technology for the detection of illegal drugs II: antibody development and detection techniques

NASA Astrophysics Data System (ADS)

Hilpert, Reinhold; Bauer, Christian; Binder, Florian; Grol, Michael; Hallermayer, Klaus; Josel, Hans-Peter; Klein, Christian; Maier, Josef; Makower, Alexander; Oberpriller, Helmut; Ritter, Josef

1994-10-01

In a joint project of Deutsche Aerospace, Boehringer Mannheim and the University of Potsdam portable devices for the detection of illegal drugs, based on biosensor technology, are being developed. The concept enrichment of the drug from the gas phase and detection by immunological means. This publication covers the development of specific antibodies and various detection procedures. Antibodies with a high affinity for cocaine have been developed with the aid of specially synthesized immunogens. A competitive detection procedure with biosensors based on optical grating couplers and applying particulate labels has been established, showing a lower detection limit of 10-10 mol/l for cocaine. Additionally, a combination of a displacement-immunoreactor and an enzymatically amplified electrode was investigated, which at present still suffers from insufficient sensitivity of the immunoreactor. An alternative, fleece-matrix based test procedure, where enrichment and detection steps are integrated in a single unit, is promising in terms of simplicity and sensitivity. A simple swab-test for the detection of cocaine at surfaces has been developed, which has a lower detection limit of about 10 ng and which can be performed within one minute.

Long-wavelength TCF-based fluorescence probes for the detection and intracellular imaging of biological thiols.

PubMed

Sedgwick, Adam C; Gardiner, Jordan E; Kim, Gyoungmi; Yevglevskis, Maksims; Lloyd, Matthew D; Jenkins, A Toby A; Bull, Steven D; Yoon, Juyoung; James, Tony D

2018-05-08

Two 'turn on' TCF-based fluorescence probes were developed for the detection of biological thiols (TCF-GSH and TCFCl-GSH). TCF-GSH was shown to have a high sensitivity towards glutathione (GSH) with a 0.28 μM limit of detection. Unfortunately, at higher GSH concentrations the fluorescence intensity of TCF-GSH decreased and toxicity was observed for TCF-GSH in live cells. However, TCFCl-GSH was shown to be able to detect GSH at biologically relevant concentrations with a 0.45 μM limit of detection. No toxicity was found for TCFCl-GSH and a clear 'turn on' with good photostability was observed for the exogenous addition of GSH, Cys and HCys. Furthermore, TCFCl-GSH was used to evaluate the effects of drug treatment on the levels of GSH in live cells.

A Matched Filter Technique for Slow Radio Transient Detection and First Demonstration with the Murchison Widefield Array

NASA Astrophysics Data System (ADS)

Feng, L.; Vaulin, R.; Hewitt, J. N.; Remillard, R.; Kaplan, D. L.; Murphy, Tara; Kudryavtseva, N.; Hancock, P.; Bernardi, G.; Bowman, J. D.; Briggs, F.; Cappallo, R. J.; Deshpande, A. A.; Gaensler, B. M.; Greenhill, L. J.; Hazelton, B. J.; Johnston-Hollitt, M.; Lonsdale, C. J.; McWhirter, S. R.; Mitchell, D. A.; Morales, M. F.; Morgan, E.; Oberoi, D.; Ord, S. M.; Prabu, T.; Udaya Shankar, N.; Srivani, K. S.; Subrahmanyan, R.; Tingay, S. J.; Wayth, R. B.; Webster, R. L.; Williams, A.; Williams, C. L.

2017-03-01

Many astronomical sources produce transient phenomena at radio frequencies, but the transient sky at low frequencies (<300 MHz) remains relatively unexplored. Blind surveys with new wide-field radio instruments are setting increasingly stringent limits on the transient surface density on various timescales. Although many of these instruments are limited by classical confusion noise from an ensemble of faint, unresolved sources, one can in principle detect transients below the classical confusion limit to the extent that the classical confusion noise is independent of time. We develop a technique for detecting radio transients that is based on temporal matched filters applied directly to time series of images, rather than relying on source-finding algorithms applied to individual images. This technique has well-defined statistical properties and is applicable to variable and transient searches for both confusion-limited and non-confusion-limited instruments. Using the Murchison Widefield Array as an example, we demonstrate that the technique works well on real data despite the presence of classical confusion noise, sidelobe confusion noise, and other systematic errors. We searched for transients lasting between 2 minutes and 3 months. We found no transients and set improved upper limits on the transient surface density at 182 MHz for flux densities between ˜20 and 200 mJy, providing the best limits to date for hour- and month-long transients.

CAPILLARY ELECTROPHORESIS/LASER-INDUCED FLUORESCENCE DETECTION OF FLUORESCEIN AS A GROUNDWATER MIGRATION TRACER

EPA Science Inventory

Capillary electrophoresis (CE) has been applied to the determination of the groundwater migration tracer dye fluorescein based on laser-induced fluorescence (LIF) detection and compared to determinations obtained with traditional spectrofluorimetry. Detection limits of injected d...

[Rapid detection of four antipertensive chemicals adulterated in traditional Chinese medicine for hypertension using TLC-SERS].

PubMed

Zhu, Qing-Xia; Cao, Yong-Bing; Cao, Ying-Ying; Lu, Feng

2014-04-01

A novel facile method for on-site detection of antipertensive chemicals (e. g. nicardipine hydrochloride, doxazosin mesylate, propranolol hydrochloride, and hydrochlorothiazide) adulterated in traditional Chinese medicine for hypertension using thin layer chromatography (TLC) combined with surface enhanced Raman spectroscopy (SERS) was reported in the present paper. Analytes and pharmaceutical matrices was separated by TLC, then SERS method was used to complete qualitative identification of trace substances on TLC plate. By optimizing colloidal silver concentration and developing solvent, as well as exploring the optimal limits of detection (LOD), the initially established TLC-SERS method was used to detect real hypertension Chinese pharmaceuticals. The results showed that this method had good specificity for the four chemicals and high sensitivity with a limit of detection as lower as to 0.005 microg. Finally, two of the ten antipertensive drugs were detected to be adulterated with chemicals. This simple and fast method can realize rapid detection of chemicals illegally for doping in antipertensive Chinese pharmaceuticals, and would have good prospects in on-site detection of chemicals for doping in Chinese pharmaceuticals.

Detection of Landmines by Neutron Backscattering: Effects of Soil Moisture on the Detection System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baysoy, D. Y.; Subasi, M.

2010-01-21

Detection of buried land mines by using neutron backscattering technique (NBS) is a well established method. It depends on detecting a hydrogen anomaly in dry soil. Since a landmine and its plastic casing contain much more hydrogen atoms than the dry soil, this anomaly can be detected by observing a rise in the number of neutrons moderated to thermal or epithermal energy. But, the presence of moisture in the soil limits the effectiveness of the measurements. In this work, a landmine detection system using the NBS technique was designed. A series of Monte Carlo calculations was carried out to determinemore » the limits of the system due to the moisture content of the soil. In the simulations, an isotropic fast neutron source ({sup 252}Cf, 100 mug) and a neutron detection system which consists of five {sup 3}He detectors were used in a practicable geometry. In order to see the effects of soil moisture on the efficiency of the detection system, soils with different water contents were tested.« less

Ultra-sensitive in-situ detection of near-infrared persistent luminescent tracer nanoagents in crude oil-water mixtures.

PubMed

Chuang, Yen-Jun; Liu, Feng; Wang, Wei; Kanj, Mazen Y; Poitzsch, Martin E; Pan, Zhengwei

2016-06-15

Current fluorescent nanoparticles-based tracer sensing techniques for oilfield applications suffer from insufficient sensitivity, with the tracer detection limit typically at the several hundred ppm level in untreated oil/water mixtures, which is mainly caused by the interference of the background fluorescence from the organic residues in crude oil under constant external excitation. Here we report the use of a persistent luminescence phenomenon, which enables an external excitation-free and thus background fluorescence-free measurement condition, for ultrahigh-sensitivity crude oil sensing. By using LiGa5O8:Cr(3+) near-infrared persistent luminescent nanoparticles as a tracer nanoagent, we achieved a tracer detection limit at the single-digit ppb level (down to 1 ppb concentration of nanoparticles) in high oil fraction (up to 65 wt.%) oil/water mixtures via a convenient, CCD camera-based imaging technique without any pretreatment or phase separation of the fluid samples. This detection limit is about four to five orders of magnitude lower than that obtained using conventional spectral methods. This study introduces a new type of tracer nanoagents and a new detection method for water tracer sensing in oil reservoir characterization and management.

Detection of colloidal silver chloride near solubility limit

NASA Astrophysics Data System (ADS)

Putri, K. Y.; Adawiah, R.

2018-03-01

Detection of nanoparticles in solution has been made possible by several means; one of them is laser-induced breakdown detection (LIBD). LIBD is able to distinguish colloids of various sizes and concentrations. This technique has been used in several solubility studies. In this study, the formation of colloids in a mixed system of silver nitrate and sodium chloride was observed by acoustic LIBD. Silver chloride has low solubility limit, therefore LIBD measurement is appropriate. Silver and chloride solutions with equal concentrations, set at below and above the solubility of silver chloride as the expected solid product, were mixed and the resulting colloids were observed. The result of LIBD measurement showed that larger particles were present as more silver and chloride introduced. However, once the concentrations exceeded the solubility limit of silver chloride, the detected particle size seemed to be decreasing, hence suggested the occurrence of coprecipitation process. This phenomenon indicated that the ability of LIBD to detect even small changes in colloid amounts might be a useful tool in study on formation and stability of colloids, i.e. to confirm whether nanoparticles synthesis has been successfully performed and whether the system is stable or not.

A STATISTICAL SURVEY OF DIOXIN-LIKE COMPOUNDS IN ...

EPA Pesticide Factsheets

The USEPA and the USDA completed the first statistically designed survey of the occurrence and concentration of dibenzo-p-dioxins (CDDs), dibenzofurans (CDFs), and coplanar polychlorinated biphenyls (PCBs) in the fat of beef animals raised for human consumption in the United States. Back fat was sampled from 63 carcasses at federally inspected slaughter establishments nationwide. The sample design called for sampling beef animal classes in proportion to national annual slaughter statistics. All samples were analyzed using a modification of EPA method 1613, using isotope dilution, High Resolution GC/MS to determine the rate of occurrence of 2,3,7,8-substituted CDDs/CDFs/PCBs. The method detection limits ranged from 0.05 ng/kg for TCDD to 3 ng/kg for OCDD. The results of this survey showed a mean concentration (reported as I-TEQ, lipid adjusted) in U.S. beef animals of 0.35 ng/kg and 0.89 ng/kg for CDD/CDF TEQs when either non-detects are treated as 0 value or assigned a value of 1/2 the detection limit, respectively, and 0.51 ng/kg for coplanar PCB TEQs at both non-detect equal 0 and 1/2 detection limit. journal article

Automating quantum dot barcode assays using microfluidics and magnetism for the development of a point-of-care device.

PubMed

Gao, Yali; Lam, Albert W Y; Chan, Warren C W

2013-04-24

The impact of detecting multiple infectious diseases simultaneously at point-of-care with good sensitivity, specificity, and reproducibility would be enormous for containing the spread of diseases in both resource-limited and rich countries. Many barcoding technologies have been introduced for addressing this need as barcodes can be applied to detecting thousands of genetic and protein biomarkers simultaneously. However, the assay process is not automated and is tedious and requires skilled technicians. Barcoding technology is currently limited to use in resource-rich settings. Here we used magnetism and microfluidics technology to automate the multiple steps in a quantum dot barcode assay. The quantum dot-barcoded microbeads are sequentially (a) introduced into the chip, (b) magnetically moved to a stream containing target molecules, (c) moved back to the original stream containing secondary probes, (d) washed, and (e) finally aligned for detection. The assay requires 20 min, has a limit of detection of 1.2 nM, and can detect genetic targets for HIV, hepatitis B, and syphilis. This study provides a simple strategy to automate the entire barcode assay process and moves barcoding technologies one step closer to point-of-care applications.

Determination of diphacinone in sea water, vertebrates, invertebrates, and bait pellet formulations following aerial broadcast on Mokapu Island, Molokai, Hawai'i

USGS Publications Warehouse

Gale, Robert W.; Tanner, Michael; Orazio, Carl E.

2008-01-01

This report presents the results of a study to determine diphacinone concentrations in samples of sea water and in fillet samples of fish and in limpets from the ocean adjacent to Mokapu Island and from reference samples from Molokai, Hawai'i; concentrations of the active ingredient (diphacinone) were also determined in samples of the Ramik Green bait pellets used for the broadcast study. After preparation, diphacinone concentrations were determined with high-performance liquid chromatography with photodiode array detection. No detectable concentrations of diphacinone were found in the fish, limpets, or sea-water samples from Mokapu Island or from the reference sites. The limit of detection for diphacinone in sea water was 18 nanograms per milliliter (parts per billion); the limit of detection in fish fillets was 10 nanograms per gram (parts per billion); and the limit of detection in limpets was 17 nanograms per gram. The average concentration of diphacinone in the Ramik Green bait pellets was 45 micrograms per gram (parts per million), which represents 90 percent of the nominal concentration stated for the product by the manufacturer.

Restricted Replication of Xenotropic Murine Leukemia Virus-Related Virus in Pigtailed Macaques

PubMed Central

Del Prete, Gregory Q.; Kearney, Mary F.; Spindler, Jon; Wiegand, Ann; Chertova, Elena; Roser, James D.; Estes, Jacob D.; Hao, Xing Pei; Trubey, Charles M.; Lara, Abigail; Lee, KyeongEun; Chaipan, Chawaree; Bess, Julian W.; Nagashima, Kunio; Keele, Brandon F.; Macallister, Rhonda; Smedley, Jeremy; Pathak, Vinay K.; KewalRamani, Vineet N.; Coffin, John M.

2012-01-01

Although xenotropic murine leukemia virus-related virus (XMRV) has been previously linked to prostate cancer and myalgic encephalomyelitis/chronic fatigue syndrome, recent data indicate that results interpreted as evidence of human XMRV infection reflect laboratory contamination rather than authentic in vivo infection. Nevertheless, XMRV is a retrovirus of undefined pathogenic potential that is able to replicate in human cells. Here we describe a comprehensive analysis of two male pigtailed macaques (Macaca nemestrina) experimentally infected with XMRV. Following intravenous inoculation with >1010 RNA copy equivalents of XMRV, viral replication was limited and transient, peaking at ≤2,200 viral RNA (vRNA) copies/ml plasma and becoming undetectable by 4 weeks postinfection, though viral DNA (vDNA) in peripheral blood mononuclear cells remained detectable through 119 days of follow-up. Similarly, vRNA was not detectable in lymph nodes by in situ hybridization despite detectable vDNA. Sequencing of cell-associated vDNA revealed extensive G-to-A hypermutation, suggestive of APOBEC-mediated viral restriction. Consistent with limited viral replication, we found transient upregulation of type I interferon responses that returned to baseline by 2 weeks postinfection, no detectable cellular immune responses, and limited or no spread to prostate tissue. Antibody responses, including neutralizing antibodies, however, were detectable by 2 weeks postinfection and maintained throughout the study. Both animals were healthy for the duration of follow-up. These findings indicate that XMRV replication and spread were limited in pigtailed macaques, predominantly by APOBEC-mediated hypermutation. Given that human APOBEC proteins restrict XMRV infection in vitro, human XMRV infection, if it occurred, would be expected to be characterized by similarly limited viral replication and spread. PMID:22238316

A Liquid Chromatography – Tandem Mass Spectrometry Approach for the Identification of Mebendazole Residue in Pork, Chicken, and Horse

PubMed Central

Lee, Ji Sun; Cho, Soo Hee; Lim, Chae Mi; Chang, Moon Ik; Joo, Hyun Jin; Park, Hyun Jin

2017-01-01

A confirmatory and quantitative method of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the determination of mebendazole and its hydrolyzed and reduced metabolites in pork, chicken, and horse muscles was developed and validated in this study. Anthelmintic compounds were extracted with ethyl acetate after sample mixture was made alkaline followed by liquid chromatographic separation using a reversed phase C18 column. Gradient elution was performed with a mobile phase consisting of water containing 10 mM ammonium formate and methanol. This confirmatory method was validated according to EU requirements. Evaluated validation parameters included specificity, accuracy, precision (repeatability and within-laboratory reproducibility), analytical limits (decision limit and detection limit), and applicability. Most parameters were proved to be conforming to the EU requirements. The decision limit (CCα) and detection capability (CCβ) for all analytes ranged from 15.84 to 17.96 μgkg-1. The limit of detection (LOD) and the limit of quantification (LOQ) for all analytes were 0.07 μgkg-1 and 0.2 μgkg-1, respectively. The developed method was successfully applied to monitoring samples collected from the markets in major cities and proven great potential to be used as a regulatory tool to determine mebendazole residues in animal based foods. PMID:28085912

Identification of Patient Zero in Static and Temporal Networks: Robustness and Limitations

NASA Astrophysics Data System (ADS)

Antulov-Fantulin, Nino; Lančić, Alen; Šmuc, Tomislav; Štefančić, Hrvoje; Šikić, Mile

2015-06-01

Detection of patient zero can give new insights to epidemiologists about the nature of first transmissions into a population. In this Letter, we study the statistical inference problem of detecting the source of epidemics from a snapshot of spreading on an arbitrary network structure. By using exact analytic calculations and Monte Carlo estimators, we demonstrate the detectability limits for the susceptible-infected-recovered model, which primarily depend on the spreading process characteristics. Finally, we demonstrate the applicability of the approach in a case of a simulated sexually transmitted infection spreading over an empirical temporal network of sexual interactions.

[Detection of antibodies against Legionella pneumophila from pleural effusion--a case report of Legionnaire's pneumonia with pleural effusion].

PubMed

Xu, L; Wang, P; Chen, S

1994-06-01

Using TAT and ELISA, 50 samples of pleural effusion and sera from patients infected with non-Legionella pneumophila were detected for antibodies against Legionella pneumophila serogroups 1 and 6, respectively. The average titre and upper limit value (99%, mean + 2.326S) calculated. In addition, a pleural effusion and a serum from a patient with Legionnaire's pneumonia were also detected by TAT and ELISA. The result showed that the titre of this antibody in his pleural effusion was not only over the upper limit, but also higher than that in his serum.

Comparison of two fabricated aptasensors based on modified carbon paste/oleic acid and magnetic bar carbon paste/Fe3O4@oleic acid nanoparticle electrodes for tetracycline detection.

PubMed

Jahanbani, Shahriar; Benvidi, Ali

2016-11-15

In this research, we have improved two aptasensors based on a modified carbon paste electrode (CPE) with oleic acid (OA), and a magnetic bar carbon paste electrode (MBCPE) with Fe3O4 magnetic nanoparticles and oleic acid (OA). After the immobilization process of anti-TET at the electrode surfaces, the aptasensors were named CPE/OA/anti-TET and MBCPE/Fe3O4NPs/OA/anti-TET respectively. In this paper, the detection of tetracycline is compared using CPE/OA/anti-TET and MBCPE/Fe3O4NPs/OA/anti-TET aptasensors. These modified electrodes were characterized by infrared spectroscopy (IR), scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS), UV-vis spectroscopy, and voltammetric methods. The linear range and the detection limit for TET with the CPE/OA/anti-TET aptasensor were found to be 1.0×10(-12)-1.0×10(-7)M and 3.0×10(-13)M respectively by EIS method. The linear range and the detection limit for TET with the CPE/OA/anti-TET aptasensor were found to be 1.0×10(-10)-1.0×10(-7)M with a limit of detection of 2.9×10(-11)M using differential pulse voltammetry (DPV) technique. The MBCPE/Fe3O4NPs/OA/anti-TET aptasensor was used for determination of TET, and a liner range of 1.0×10(-14)-1.0×10(-6)M with a detection limit of 3.8×10(-15)M was obtained by EIS method. Also, the linear range and detection limit of 1.0×10(-12)-1.0×10(-6)M and 3.1×10(-13)M respectively, were obtained for MBCPE/Fe3O4NPs/OA/anti-TET aptasensor using DPV. The proposed aptasensors were applied for determination of tetracycline in some real samples such as drug, milk, honey and blood serum samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Global limits and interference patterns in dark matter direct detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Catena, Riccardo; Gondolo, Paolo

2015-08-13

We compare the general effective theory of one-body dark matter nucleon interactions to current direct detection experiments in a global multidimensional statistical analysis. We derive exclusion limits on the 28 isoscalar and isovector coupling constants of the theory, and show that current data place interesting constraints on dark matter-nucleon interaction operators usually neglected in this context. We characterize the interference patterns that can arise in dark matter direct detection from pairs of dark matter-nucleon interaction operators, or from isoscalar and isovector components of the same operator. We find that commonly neglected destructive interference effects weaken standard direct detection exclusion limitsmore » by up to one order of magnitude in the coupling constants.« less

Global limits and interference patterns in dark matter direct detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Catena, Riccardo; Gondolo, Paolo, E-mail: riccardo.catena@theorie.physik.uni-goettingen.de, E-mail: paolo.gondolo@utah.edu

2015-08-01

We compare the general effective theory of one-body dark matter nucleon interactions to current direct detection experiments in a global multidimensional statistical analysis. We derive exclusion limits on the 28 isoscalar and isovector coupling constants of the theory, and show that current data place interesting constraints on dark matter-nucleon interaction operators usually neglected in this context. We characterize the interference patterns that can arise in dark matter direct detection from pairs of dark matter-nucleon interaction operators, or from isoscalar and isovector components of the same operator. We find that commonly neglected destructive interference effects weaken standard direct detection exclusion limitsmore » by up to one order of magnitude in the coupling constants.« less

Laser desorption with corona discharge ion mobility spectrometry for direct surface detection of explosives.

PubMed

Sabo, M; Malásková, M; Matejčík, S

2014-10-21

We present a new highly sensitive technique for the detection of explosives directly from the surface using laser desorption-corona discharge-ion mobility spectrometry (LD-CD-IMS). We have developed LD based on laser diode modules (LDM) and the technique was tested using three different LDM (445, 532 and 665 nm). The explosives were detected directly from the surface without any further preparation. We discuss the mechanism of the LD and the limitations of this technique such as desorption time, transport time and desorption area. After the evaluation of experimental data, we estimated the potential limits of detection of this method to be 0.6 pg for TNT, 2.8 pg for RDX and 8.4 pg for PETN.

Spectroscopic Detection of Glyphosate in Water Assisted by Laser-Ablated Silver Nanoparticles

PubMed Central

De Góes, Rafael Eleodoro; Muller, Marcia; Fabris, José Luís

2017-01-01

Glyphosate is one of the most widely used herbicides in the world. Its safety for both human health and aquatic biomes is a subject of wide debate. There are limits to glyphosate’s presence in bodies of water, and it is usually detected through complex analytical procedures. In this work, the presence of glyphosate is detected directly through optical interrogation of aqueous solution. For this purpose, silver nanoparticles were produced by pulsed laser ablation in liquids. Limits of detection of 0.9 mg/L and 3.2 mg/L were obtained with UV-Vis extinction and Surface Enhanced Raman spectroscopies, respectively. The sensing mechanism was evaluated in the presence of potential interferents as well as with commercial glyphosate-based herbicides. PMID:28445394

Development of binding assays in microfabricated picoliter vials: an assay for biotin.

PubMed

Grosvenor, A L; Feltus, A; Conover, R C; Daunert, S; Anderson, K W

2000-06-01

A homogeneous binding assay for the detection of biotin in picoliter vials was developed using the photoprotein aequorin as the label. The binding assay was based on the competition of free biotin with biotinylated aequorin (AEQ-biotin) for avidin. A sequential protocol was used, and modification of the assay to reduce the number of steps was examined. Results showed that detection limits on the order of 10(-14) mol of biotin were possible. Reducing the number of steps provided similar detection limits but only if the amount of avidin used was decreased. These binding assays based on picoliter volumes have potential applications in a variety of fields, including microanalysis and single-cell analysis, where the amount of sample is limited. In addition, these assays are suitable for the high-throughput screening of biopharmaceuticals.

Gravitational wave emission from oscillating millisecond pulsars

NASA Astrophysics Data System (ADS)

Alford, Mark G.; Schwenzer, Kai

2015-02-01

Neutron stars undergoing r-mode oscillation emit gravitational radiation that might be detected on the Earth. For known millisecond pulsars the observed spin-down rate imposes an upper limit on the possible gravitational wave signal of these sources. Taking into account the physics of r-mode evolution, we show that only sources spinning at frequencies above a few hundred Hertz can be unstable to r-modes, and we derive a more stringent universal r-mode spin-down limit on their gravitational wave signal. We find that this refined bound limits the gravitational wave strain from millisecond pulsars to values below the detection sensitivity of next generation detectors. Young sources are therefore a more promising option for the detection of gravitational waves emitted by r-modes and to probe the interior composition of compact stars in the near future.

Presence and distribution of nitrate and selected pesticides in surficial-sand aquifers and selected lakes, 1983-94, East Otter Tail County, Minnesota

USGS Publications Warehouse

Smith, Shannon E.; Ruhl, James E.

1995-01-01

Lake water was sampled from 11 sites on Little Pine, Big Pine, Rush, and Otter Tail Lakes. Nitrate-nitrogen concentrations were all below the detection limit (0.05 mg/L). The concentration of triazine herbicide compounds, as determined by immunoassay, was at or below the detection limit (0.10 ug/L) at all 11 sites. Dissolved oxygen concentrations at the sites ranged from 7.3 to 10.1 mg/L at the water surface, and from 5.3 to 9.7 mg/L at depth. Secchi disk transparency readings ranged from 4.0 to 7.4 feet. Total phosphorus concentrations were generally near or below the detection limit (0.01 mg/L) except at one site where the water had a total phosphorus concentration of 0.06 mg/L.

A novel turn-on fluorescent probe for Al3 + and Fe3 + in aqueous solution and its imaging in living cells

NASA Astrophysics Data System (ADS)

Dai, Yanpeng; Fu, Jiaxin; Yao, Kun; Song, Qianqian; Xu, Kuoxi; Pang, Xiaobin

2018-03-01

A quinoline-based fluorescence probe has been prepared and characterized. Probe 1 showed a selective sensing ability for Al3 + and Fe3 + ions through fluorescence enhancement response at 515 nm when it was excited at 360 nm. In the presence of Fe3 + ion, probe 1 exhibited a detection limit of 2.10 × 10- 6 M. As for Al3 +, its detection limit of 3.58 × 10- 7 M was significantly lower than the highest limit of Al3 + in drinking water recommended by the WHO (7.41 μM), representing a rare example in reported fluorescent probe for Al3 + ion. The fluorescence microscopy experiments have demonstrated that probe 1 could be used in live cells for the detection of Al3 + and Fe3 + ions.

Analysis of nuclear resonance fluorescence excitation measured with LaBr3(Ce) detectors near 2 MeV

NASA Astrophysics Data System (ADS)

Omer, Mohamed; Negm, Hani; Ohgaki, Hideaki; Daito, Izuru; Hayakawa, Takehito; Bakr, Mahmoud; Zen, Heishun; Hori, Toshitada; Kii, Toshiteru; Masuda, Kai; Hajima, Ryoichi; Shizuma, Toshiyuki; Toyokawa, Hiroyuki; Kikuzawa, Nobuhiro

2013-11-01

The performance of LaBr3(Ce) to measure nuclear resonance fluorescence (NRF) excitations is discussed in terms of limits of detection and in comparison with high-purity germanium (HPGe) detectors near the 2 MeV region where many NRF excitation levels from special nuclear materials are located. The NRF experiment was performed at the High Intensity γ-ray Source (HIγS) facility. The incident γ-rays, of 2.12 MeV energy, hit a B4C target to excite the 11B nuclei to the first excitation level. The statistical-sensitive non-linear peak clipping (SNIP) algorithm was implemented to eliminate the background and enhance the limits of detection for the spectra measured with LaBr3(Ce). Both detection and determination limits were deduced from the experimental data.

Swept-source based, single-shot, multi-detectable velocity range Doppler optical coherence tomography

PubMed Central

Meemon, Panomsak; Rolland, Jannick P.

2010-01-01

Phase-Resolved Doppler Optical Coherence Tomography (PR-DOCT) allows visualization and characterization of the location, direction, velocity, and profile of flow activity embedded in a static sample structure. The detectable Velocity Dynamic Range (VDR) of each particular PR-DOCT system is governed by a detectable Doppler phase shift, a flow angle, and an acquisition time interval used to determine the Doppler phase shift. In general, the lower boundary of the detectable Doppler phase shift is limited by the phase stability of the system, while the upper boundary is limited by the π phase ambiguity. For a given range of detectable Doppler phase shift, shortening the acquisition duration will increase not only the maximum detectable velocity but unfortunately also the minimum detectable velocity, which may lead to the invisibility of a slow flow. In this paper, we present an alternative acquisition scheme for PR-DOCT that extends the lower limit of the velocity dynamic range, while maintaining the maximum detectable velocity, hence increasing the overall VDR of PR-DOCT system. The essence of the approach is to implement a technique of multi-scale measurement to simultaneously acquire multiple VDRs in a single measurement. We demonstrate an example of implementation of the technique in a dual VDR DOCT, where two Doppler maps having different detectable VDRs were simultaneously detected, processed, and displayed in real time. One was a fixed VDR DOCT capable of measuring axial velocity of up to 10.9 mm/s without phase unwrapping. The other was a variable VDR DOCT capable of adjusting its detectable VDR to reveal slow flow information down to 11.3 μm/s. The technique is shown to effectively extend the overall detectable VDR of the PR-DOCT system. Examples of real time Doppler imaging of an African frog tadpole are demonstrated using the dual-VDR DOCT system. PMID:21258521

Detection of long wavelength infrared at moderate temperatures

NASA Technical Reports Server (NTRS)

Tredwell, T. J.

1977-01-01

Technical approaches for the advanced development of 8-12 micrometer detectors operating at elevated temperatures were defined. The theoretical limits to performance of 8-12 micrometer quantum detectors (photoconductive and photovoltaic) and thermal detectors (pyroelectrics, bolometers etc). An analytic model of signal and noise in both quantum detectors and pyroelectric detectors was developed and candidate materials for both detector types were identified and examined. The present status of both quantum and thermal detectors was assessed as well as the parameters limiting operating temperature and detectivity. The areas of research and development likely to lead to detector performance near the theoretical limit are identified.

Method for early detection of cooling-loss events

DOEpatents

Bermudez, Sergio A.; Hamann, Hendrik; Marianno, Fernando J.

2015-06-30

A method of detecting cooling-loss event early is provided. The method includes defining a relative humidity limit and change threshold for a given space, measuring relative humidity in the given space, determining, with a processing unit, whether the measured relative humidity is within the defined relative humidity limit, generating a warning in an event the measured relative humidity is outside the defined relative humidity limit and determining whether a change in the measured relative humidity is less than the defined change threshold for the given space and generating an alarm in an event the change is greater than the defined change threshold.

Method for early detection of cooling-loss events

DOEpatents

Bermudez, Sergio A.; Hamann, Hendrik F.; Marianno, Fernando J.

2015-12-22

A method of detecting cooling-loss event early is provided. The method includes defining a relative humidity limit and change threshold for a given space, measuring relative humidity in the given space, determining, with a processing unit, whether the measured relative humidity is within the defined relative humidity limit, generating a warning in an event the measured relative humidity is outside the defined relative humidity limit and determining whether a change in the measured relative humidity is less than the defined change threshold for the given space and generating an alarm in an event the change is greater than the defined change threshold.

Compact binary merger rates: Comparison with LIGO/Virgo upper limits

DOE PAGES

Belczynski, Krzysztof; Repetto, Serena; Holz, Daniel E.; ...

2016-03-03

Here, we compare evolutionary predictions of double compact object merger rate densities with initial and forthcoming LIGO/Virgo upper limits. We find that: (i) Due to the cosmological reach of advanced detectors, current conversion methods of population synthesis predictions into merger rate densities are insufficient. (ii) Our optimistic models are a factor of 18 below the initial LIGO/Virgo upper limits for BH–BH systems, indicating that a modest increase in observational sensitivity (by a factor of ~2.5) may bring the first detections or first gravitational wave constraints on binary evolution. (iii) Stellar-origin massive BH–BH mergers should dominate event rates in advanced LIGO/Virgo and can be detected out to redshift z sime 2 with templates including inspiral, merger, and ringdown. Normal stars (more » $$\\lt 150\\;{M}_{\\odot }$$) can produce such mergers with total redshifted mass up to $${M}_{{\\rm{tot,z}}}\\simeq 400\\;{M}_{\\odot }$$. (iv) High black hole (BH) natal kicks can severely limit the formation of massive BH–BH systems (both in isolated binary and in dynamical dense cluster evolution), and thus would eliminate detection of these systems even at full advanced LIGO/Virgo sensitivity. We find that low and high BH natal kicks are allowed by current observational electromagnetic constraints. (v) The majority of our models yield detections of all types of mergers (NS–NS, BH–NS, BH–BH) with advanced detectors. Numerous massive BH–BH merger detections will indicate small (if any) natal kicks for massive BHs.« less

Active sampling technique to enhance chemical signature of buried explosives

NASA Astrophysics Data System (ADS)

Lovell, John S.; French, Patrick D.

2004-09-01

Deminers and dismounted countermine engineers commonly use metal detectors, ground penetrating radar and probes to locate mines. Many modern landmines have a very low metal content, which severely limits the effectiveness of metal detectors. Canines have also been used for landmine detection for decades. Experiments have shown that canines smell the explosives which are known to leak from most types of landmines. The fact that dogs can detect landmines indicates that vapor sensing is a viable approach to landmine detection. Several groups are currently developing systems to detect landmines by "sniffing" for the ultra-trace explosive vapors above the soil. The amount of material that is available to passive vapor sensing systems is limited to no more than the vapor in equilibrium with the explosive related chemicals (ERCs) distributed in the surface soils over and near the landmine. The low equilibrium vapor pressure of TNT in the soil/atmosphere boundary layer and the limited volume of the boundary layer air imply that passive chemical vapor sensing systems require sensitivities in the picogram range, or lower. ADA is working to overcome many of the limitations of passive sampling methods, by the use of an active sampling method that employs a high-powered (1,200+ joules) strobe lamp to create a highly amplified plume of vapor and/or ERC-bearing fine particulates. Initial investigations have demonstrated that this approach can amplify the detectability of TNT by two or three orders of magnitude. This new active sampling technique could be used with any suitable explosive sensor.

A radio monitoring survey of ultra-luminous X-ray sources

NASA Astrophysics Data System (ADS)

Körding, E.; Colbert, E.; Falcke, H.

2005-06-01

We present the results of a radio monitoring campaign to search for radio emission from nearby ultra-luminous X-ray sources (ULXs). These sources are bright off-nuclear X-ray point sources with luminosities exceeding LX > 1039 erg s-1. A well-defined sample of the 9 nearest ULXs has been monitored eight times over 5 months with the Very Large Array in A and B configuration. Our limiting sensitivity is ≈0.15 mJy (4σ) for radio flares and ≈60 μJy for continuous emission. In M 82 two ULXs seem to have coincident compact radio sources, which are probably supernova remnants. No continuous or flaring radio emission has been detected from any other ULX. Thus, ULXs do not generally emit steady-state radio emission above radio powers of 1.5 × 1017 W/Hz. The non-detections of the continuous emission are consistent with beamed or unbeamed radio emission from accreting black holes of ≤ 103 M⊙ based on the radio/X-ray correlation. Other published radio detections (M 82, NGC 5408) are also discussed in this context. Both detections are significantly above our detection limit. If ULXs have flaring radio emission above 4 × 1017 W/Hz we can give an upper limit on the duty cycle of the flares of 6%. This upper limit is in agreement with the observed number of flares in Galactic radio transients. Additionally we present a yet unreported radio double structure in the nearby low-luminosity AGN NGC 4736.

Experimental Study of the Detection Limit in Dual-Gate Biosensors Using Ultrathin Silicon Transistors

DOE PAGES

Wu, Ting; Alharbi, Abdullah; You, Kai-Dyi; ...

2017-06-21

Dual-gate field-effect biosensors (bioFETs) with asymmetric gate capacitances were shown to surpass the Nernst limit of 59 mV/pH. However, previous studies have conflicting findings on the effect of the capacitive amplification scheme on the sensor detection limit, which is inversely proportional to the signal-to-noise ratio (SNR). In this paper, we present a systematic experimental investigation of the SNR using ultrathin silicon transistors. Our sensors operate at low voltage and feature asymmetric front and back oxide capacitances with asymmetry factors of 1.4 and 2.3. We demonstrate that in the dual-gate configuration, the response of our bioFETs to the pH change increasesmore » proportional to the asymmetry factor and indeed exceeds the Nernst limit. Further, our results reveal that the noise amplitude also increases in proportion to the asymmetry factor. We establish that the commensurate increase of the noise amplitude originates from the intrinsic low-frequency characteristic of the sensor noise, dominated by number fluctuation. Finally, these findings suggest that this capacitive signal amplification scheme does not improve the intrinsic detection limit of the dual-gate biosensors.« less

Experimental Study of the Detection Limit in Dual-Gate Biosensors Using Ultrathin Silicon Transistors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Ting; Alharbi, Abdullah; You, Kai-Dyi

Dual-gate field-effect biosensors (bioFETs) with asymmetric gate capacitances were shown to surpass the Nernst limit of 59 mV/pH. However, previous studies have conflicting findings on the effect of the capacitive amplification scheme on the sensor detection limit, which is inversely proportional to the signal-to-noise ratio (SNR). In this paper, we present a systematic experimental investigation of the SNR using ultrathin silicon transistors. Our sensors operate at low voltage and feature asymmetric front and back oxide capacitances with asymmetry factors of 1.4 and 2.3. We demonstrate that in the dual-gate configuration, the response of our bioFETs to the pH change increasesmore » proportional to the asymmetry factor and indeed exceeds the Nernst limit. Further, our results reveal that the noise amplitude also increases in proportion to the asymmetry factor. We establish that the commensurate increase of the noise amplitude originates from the intrinsic low-frequency characteristic of the sensor noise, dominated by number fluctuation. Finally, these findings suggest that this capacitive signal amplification scheme does not improve the intrinsic detection limit of the dual-gate biosensors.« less

Quantitative analysis of trace levels of surface contamination by X-ray photoelectron spectroscopy Part I: statistical uncertainty near the detection limit.

PubMed

Hill, Shannon B; Faradzhev, Nadir S; Powell, Cedric J

2017-12-01

We discuss the problem of quantifying common sources of statistical uncertainties for analyses of trace levels of surface contamination using X-ray photoelectron spectroscopy. We examine the propagation of error for peak-area measurements using common forms of linear and polynomial background subtraction including the correlation of points used to determine both background and peak areas. This correlation has been neglected in previous analyses, but we show that it contributes significantly to the peak-area uncertainty near the detection limit. We introduce the concept of relative background subtraction variance (RBSV) which quantifies the uncertainty introduced by the method of background determination relative to the uncertainty of the background area itself. The uncertainties of the peak area and atomic concentration and of the detection limit are expressed using the RBSV, which separates the contributions from the acquisition parameters, the background-determination method, and the properties of the measured spectrum. These results are then combined to find acquisition strategies that minimize the total measurement time needed to achieve a desired detection limit or atomic-percentage uncertainty for a particular trace element. Minimization of data-acquisition time is important for samples that are sensitive to x-ray dose and also for laboratories that need to optimize throughput.

Background correction in forensic photography. II. Photography of blood under conditions of non-uniform illumination or variable substrate color--practical aspects and limitations.

PubMed

Wagner, John H; Miskelly, Gordon M

2003-05-01

The combination of photographs taken at wavelengths at and bracketing the peak of a narrow absorbance band can lead to enhanced visualization of the substance causing the narrow absorbance band. This concept can be used to detect putative bloodstains by division of a linear photographic image taken at or near 415 nm with an image obtained by averaging linear photographs taken at or near 395 and 435 nm. Nonlinear images can also be background corrected by substituting subtraction for the division. This paper details experimental applications and limitations of this technique, including wavelength selection of the illuminant and at the camera. Characterization of a digital camera to be used in such a study is also detailed. Detection limits for blood using the three wavelength correction method under optimum conditions have been determined to be as low as 1 in 900 dilution, although on strongly patterned substrates blood diluted more than twenty-fold is difficult to detect. Use of only the 435 nm photograph to estimate the background in the 415 nm image lead to a twofold improvement in detection limit on unpatterned substrates compared with the three wavelength method with the particular camera and lighting system used, but it gave poorer background correction on patterned substrates.

Detection of Stimulus Displacements Across Saccades is Capacity-Limited and Biased in Favor of the Saccade Target

PubMed Central

Irwin, David E.; Robinson, Maria M.

2015-01-01

Retinal image displacements caused by saccadic eye movements are generally unnoticed. Recent theories have proposed that perceptual stability across saccades depends on a local evaluation process centered on the saccade target object rather than on remapping and evaluating the positions of all objects in a display. In three experiments, we examined whether objects other than the saccade target also influence perceptual stability by measuring displacement detection thresholds across saccades for saccade targets and a variable number of non-saccade objects. We found that the positions of multiple objects are maintained across saccades, but with variable precision, with the saccade target object having priority in the perception of displacement, most likely because it is the focus of attention before the saccade and resides near the fovea after the saccade. The perception of displacement of objects that are not the saccade target is affected by acuity limitations, attentional limitations, and limitations on memory capacity. Unlike previous studies that have found that a postsaccadic blank improves the detection of displacement direction across saccades, we found that postsaccadic blanking hurt the detection of displacement per se by increasing false alarms. Overall, our results are consistent with the hypothesis that visual working memory underlies the perception of stability across saccades. PMID:26640430

Use of x-ray fluorescence for in-situ detection of metals

NASA Astrophysics Data System (ADS)

Elam, W. T. E.; Whitlock, Robert R.; Gilfrich, John V.

1995-01-01

X-ray fluorescence (XRF) is a well-established, non-destructive method of determining elemental concentrations at ppm levels in complex samples. It can operate in atmosphere with no sample preparation, and provides accuracies of 1% or better under optimum conditions. This report addresses two sets of issues concerning the use of x-ray fluorescence as a sensor technology for the cone penetrometer, for shipboard waste disposal, or for other in-situ, real- time environmental applications. The first issue concerns the applicability of XRF to these applications, and includes investigation of detection limits and matrix effects. We have evaluated the detection limits and quantitative accuracy of a sensor mock-up for metals in soils under conditions expected in the field. In addition, several novel ways of improving the lower limits of detection to reach the drinking water regulatory limits have been explored. The second issue is the engineering involved with constructing a spectrometer within the 1.75 inch diameter of the penetrometer pipe, which is the most rigorous physical constraint. Only small improvements over current state-of-the-art are required. Additional advantages of XRF are that no radioactive sources or hazardous materials are used in the sensor design, and no reagents or any possible sources of ignition are involved.

Thermodynamic framework to assess low abundance DNA mutation detection by hybridization.

PubMed

Willems, Hanny; Jacobs, An; Hadiwikarta, Wahyu Wijaya; Venken, Tom; Valkenborg, Dirk; Van Roy, Nadine; Vandesompele, Jo; Hooyberghs, Jef

2017-01-01

The knowledge of genomic DNA variations in patient samples has a high and increasing value for human diagnostics in its broadest sense. Although many methods and sensors to detect or quantify these variations are available or under development, the number of underlying physico-chemical detection principles is limited. One of these principles is the hybridization of sample target DNA versus nucleic acid probes. We introduce a novel thermodynamics approach and develop a framework to exploit the specific detection capabilities of nucleic acid hybridization, using generic principles applicable to any platform. As a case study, we detect point mutations in the KRAS oncogene on a microarray platform. For the given platform and hybridization conditions, we demonstrate the multiplex detection capability of hybridization and assess the detection limit using thermodynamic considerations; DNA containing point mutations in a background of wild type sequences can be identified down to at least 1% relative concentration. In order to show the clinical relevance, the detection capabilities are confirmed on challenging formalin-fixed paraffin-embedded clinical tumor samples. This enzyme-free detection framework contains the accuracy and efficiency to screen for hundreds of mutations in a single run with many potential applications in molecular diagnostics and the field of personalised medicine.

ATP-mediated intrinsic peroxidase-like activity of Fe3O4-based nanozyme: One step detection of blood glucose at physiological pH.

PubMed

Vallabani, N V Srikanth; Karakoti, Ajay S; Singh, Sanjay

2017-05-01

Fe 3 O 4 nanoparticles (Fe 3 O 4 NPs), demonstrating peroxidase-like activity has garnered attention in the detection of several biomolecules, therefore, emerged as an excellent nano-biosensing agent. The intrinsic peroxidase-like activity of Fe 3 O 4 NPs at acidic pH is the fundamental action driving the oxidation of substrates like TMB, resulting in a colorimetric product formation used in the detection of biomolecules. Hence, the detection sensitivity essentially depends on the ability of oxidation by Fe 3 O 4 NPs in presence of H 2 O 2 . However, the limited sensitivity and pH condition constraint have been identified as the major drawbacks in the detection of biomolecules at physiological pH. Herein, we report overwhelming of the fundamental limitation of acidic pH and tuning the peroxidase-like activity of Fe 3 O 4 NPs at physiological pH by using ATP. In presence of ATP, Fe 3 O 4 NPs exhibited enhanced peroxidase-like activity over a wide range of pH and temperatures. Mechanistically, it was found that the ability of ATP to participate in single electron transfer reaction, through complexation with Fe 3 O 4 NPs, results in the generation of hydroxyl radicals which are responsible for enhanced peroxidase activity at physiological pH. We utilized this ATP-mediated enhanced peroxidase-like activity of Fe 3 O 4 NPs for single step detection of glucose with a colorimetric detection limit of 50μM. Further, we extended this single step detection method to monitor glucose level in human blood serum and detected in a time span of <5min at pH 7.4. Copyright © 2017 Elsevier B.V. All rights reserved.

Sensitive molecular detection of small nodal metastasis in uterine cervical cancer using HPV16-E6/CK19/MUC1 cancer biomarkers.

PubMed

Samouëlian, Vanessa; Mechtouf, Nawel; Leblanc, Eric; Cardin, Guillaume B; Lhotellier, Valérie; Querleu, Denis; Révillion, Françoise; Rodier, Francis

2018-04-24

Metastatic nodal involvement is a critical prognostic factor in uterine cervical cancer (UCC). To improve current methods of detecting UCC metastases in lymph nodes (LNs), we used quantitative PCR (qPCR) to assess mRNA expression of potential metastatic biomarkers. We found that expression of HPV16-E6, cytokeratin19 (CK19), and mucin1 (MUC1) is consistently upregulated in tumors and metastatic tissues, supporting a role for these genes in UCC progression. These putative biomarkers were able to predict the presence of histologically positive metastatic LNs with respective sensitivities and specificities of 82% and 99% (CK19), 76% and 95% (HPV16-E6), and 76% and 78% (MUC1). While the biomarkers failed to detect 1.7% to 2.2% of the histologically positive LNs when used individually, combining CK19 and HPV16-E6 enhanced sensitivity and specificity to 100% and 94%, respectively. To explore the sensitivity of qPCR-based detection of varying proportions of invading HPV16-positive UCC cells, we designed a LN metastasis model that achieved a fresh cell detection limit of 0.008% (1:12500 HPV16-positive to HPV16-negative cells), and a paraffin-embedded, formalin-fixed (PEFF) detection limit of 0.02% (1:5000 HPV16-positive to HPV16-negative cells), both of which are within the theoretical detection limit for micrometastasis. Thus, HPV E6/E7 oncogenes may be useful targets for the ultrasensitive detection of nodal involvements like micrometastases in fresh or archived tissue samples. Moreover, our results suggest that the biomarker combination of CK19/HPV-E6 could support a real-time intraoperative strategy for the detection of small, but potentially lethal, metastatic nodal involvements in fresh UCC tissues.

Limitations of Mass Spectrometry-Based Peptidomic Approaches

NASA Astrophysics Data System (ADS)

Fricker, Lloyd D.

2015-12-01

Mass spectrometry-based peptidomic approaches are powerful techniques to detect and identify the peptide content of biological samples. The present study investigated the limitations of peptidomic approaches using trimethylammonium butyrate isotopic tags to quantify relative peptide levels and Mascot searches to identify peptides. Data were combined from previous studies on human cell lines or mouse tissues. The combined databases contain 2155 unique peptides ranging in mass from 444 to 8765 Da, with the vast majority between 1 and 3 kDa. The amino acid composition of the identified peptides generally reflected the frequency in the Eukaryotic proteome with the exception of Cys, which was not present in any of the identified peptides in the free-SH form but was detected at low frequency as a disulfide with Cys residues, a disulfide with glutathione, or as S-cyanocysteine. To test if the low detection rate of peptides smaller than 500 Da, larger than 3 kDa, or containing Cys was a limitation of the peptidomics procedure, tryptic peptides of known proteins were processed for peptidomics using the same approach used for human cell lines and mouse tissues. The identified tryptic peptides ranged from 516 to 2418 Da, whereas the theoretical digest ranged from 217 to 7559 Da. Peptides with Cys were rarely detected and, if present, the Cys was usually modified S-cyanocysteine. Additionally, peptides with mono- and di-iodo Tyr and His were identified. Taken together, there are limitations of peptidomic techniques, and awareness of these limitations is important to properly use and interpret results.

Detection of BCG bacteria using a magnetoresistive biosensor: A step towards a fully electronic platform for tuberculosis point-of-care detection.

PubMed

Barroso, Teresa G; Martins, Rui C; Fernandes, Elisabete; Cardoso, Susana; Rivas, José; Freitas, Paulo P

2018-02-15

Tuberculosis is one of the major public health concerns. This highly contagious disease affects more than 10.4 million people, being a leading cause of morbidity by infection. Tuberculosis is diagnosed at the point-of-care by the Ziehl-Neelsen sputum smear microscopy test. Ziehl-Neelsen is laborious, prone to human error and infection risk, with a limit of detection of 10 4 cells/mL. In resource-poor nations, a more practical test, with lower detection limit, is paramount. This work uses a magnetoresistive biosensor to detect BCG bacteria for tuberculosis diagnosis. Herein we report: i) nanoparticle assembly method and specificity for tuberculosis detection; ii) demonstration of proportionality between BCG cell concentration and magnetoresistive voltage signal; iii) application of multiplicative signal correction for systematic effects removal; iv) investigation of calibration effectiveness using chemometrics methods; and v) comparison with state-of-the-art point-of-care tuberculosis biosensors. Results present a clear correspondence between voltage signal and cell concentration. Multiplicative signal correction removes baseline shifts within and between biochip sensors, allowing accurate and precise voltage signal between different biochips. The corrected signal was used for multivariate regression models, which significantly decreased the calibration standard error from 0.50 to 0.03log 10 (cells/mL). Results show that Ziehl-Neelsen detection limits and below are achievable with the magnetoresistive biochip, when pre-processing and chemometrics are used. Copyright © 2017 Elsevier B.V. All rights reserved.

Co-occurrence of the cyanotoxins BMAA, DABA and anatoxin-a in Nebraska reservoirs, fish, and aquatic plants.

PubMed

Al-Sammak, Maitham Ahmed; Hoagland, Kyle D; Cassada, David; Snow, Daniel D

2014-01-28

Several groups of microorganisms are capable of producing toxins in aquatic environments. Cyanobacteria are prevalent blue green algae in freshwater systems, and many species produce cyanotoxins which include a variety of chemical irritants, hepatotoxins and neurotoxins. Production and occurrence of potent neurotoxic cyanotoxins β-N-methylamino-L-alanine (BMAA), 2,4-diaminobutyric acid dihydrochloride (DABA), and anatoxin-a are especially critical with environmental implications to public and animal health. Biomagnification, though not well understood in aquatic systems, is potentially relevant to both human and animal health effects. Because little is known regarding their presence in fresh water, we investigated the occurrence and potential for bioaccumulation of cyanotoxins in several Nebraska reservoirs. Collection and analysis of 387 environmental and biological samples (water, fish, and aquatic plant) provided a snapshot of their occurrence. A sensitive detection method was developed using solid phase extraction (SPE) in combination with high pressure liquid chromatography-fluorescence detection (HPLC/FD) with confirmation by liquid chromatography-tandem mass spectrometry (LC/MS/MS). HPLC/FD detection limits ranged from 5 to 7 µg/L and LC/MS/MS detection limits were <0.5 µg/L, while detection limits for biological samples were in the range of 0.8-3.2 ng/g depending on the matrix. Based on these methods, measurable levels of these neurotoxic compounds were detected in approximately 25% of the samples, with detections of BMAA in about 18.1%, DABA in 17.1%, and anatoxin-a in 11.9%.

Co-occurrence of the Cyanotoxins BMAA, DABA and Anatoxin-a in Nebraska Reservoirs, Fish, and Aquatic Plants

PubMed Central

Al-Sammak, Maitham Ahmed; Hoagland, Kyle D.; Cassada, David; Snow, Daniel D.

2014-01-01

Several groups of microorganisms are capable of producing toxins in aquatic environments. Cyanobacteria are prevalent blue green algae in freshwater systems, and many species produce cyanotoxins which include a variety of chemical irritants, hepatotoxins and neurotoxins. Production and occurrence of potent neurotoxic cyanotoxins β-N-methylamino-l-alanine (BMAA), 2,4-diaminobutyric acid dihydrochloride (DABA), and anatoxin-a are especially critical with environmental implications to public and animal health. Biomagnification, though not well understood in aquatic systems, is potentially relevant to both human and animal health effects. Because little is known regarding their presence in fresh water, we investigated the occurrence and potential for bioaccumulation of cyanotoxins in several Nebraska reservoirs. Collection and analysis of 387 environmental and biological samples (water, fish, and aquatic plant) provided a snapshot of their occurrence. A sensitive detection method was developed using solid phase extraction (SPE) in combination with high pressure liquid chromatography-fluorescence detection (HPLC/FD) with confirmation by liquid chromatography-tandem mass spectrometry (LC/MS/MS). HPLC/FD detection limits ranged from 5 to 7 µg/L and LC/MS/MS detection limits were <0.5 µg/L, while detection limits for biological samples were in the range of 0.8–3.2 ng/g depending on the matrix. Based on these methods, measurable levels of these neurotoxic compounds were detected in approximately 25% of the samples, with detections of BMAA in about 18.1%, DABA in 17.1%, and anatoxin-a in 11.9%. PMID:24476710

Colorimetric Detection of Small Molecules in Complex Matrixes via Target-Mediated Growth of Aptamer-Functionalized Gold Nanoparticles.

PubMed

Soh, Jun Hui; Lin, Yiyang; Rana, Subinoy; Ying, Jackie Y; Stevens, Molly M

2015-08-04

A versatile and sensitive colorimetric assay that allows the rapid detection of small-molecule targets using the naked eye is demonstrated. The working principle of the assay integrates aptamer-target recognition and the aptamer-controlled growth of gold nanoparticles (Au NPs). Aptamer-target interactions modulate the amount of aptamer strands adsorbed on the surface of aptamer-functionalized Au NPs via desorption of the aptamer strands when target molecules bind with the aptamer. Depending on the resulting aptamer coverage, Au NPs grow into morphologically varied nanostructures, which give rise to different colored solutions. Au NPs with low aptamer coverage grow into spherical NPs, which produce red-colored solutions, whereas Au NPs with high aptamer coverage grow into branched NPs, which produce blue-colored solutions. We achieved visible colorimetric response and nanomolar detection limits for the detection of ochratoxin A (1 nM) in red wine samples, as well as cocaine (1 nM) and 17β-estradiol (0.2 nM) in spiked synthetic urine and saliva, respectively. The detection limits were well within clinically and physiologically relevant ranges, and below the maximum food safety limits. The assay is highly sensitive, specific, and able to detect an array of analytes rapidly without requiring sophisticated equipment, making it relevant for many applications, such as high-throughput drug and clinical screening, food sampling, and diagnostics. Furthermore, the assay is easily adapted as a chip-based platform for rapid and portable target detection.

Cost-effective flow-through nanohole array-based biosensing platform for the label-free detection of uropathogenic E. coli in real time.

PubMed

Gomez-Cruz, Juan; Nair, Srijit; Manjarrez-Hernandez, Angel; Gavilanes-Parra, Sandra; Ascanio, Gabriel; Escobedo, Carlos

2018-05-30

Rapid, inexpensive and sensitive detection of uropathogenic Escherichia coli (UPEC), a common cause of ascending urinary tract infections (UTIs) including cystitis and pyelonephritis, is critical given the increasing number of cases and its recurrence worldwide. In this paper, we present a label-free nanoplasmonic sensing platform, built with off-the-shelf optical and electronic components, which can detect intact UPEC at concentrations lower than the physiological limit for UTI diagnosis, in real time. The sensing platform consists of a red LED light source, lens assembly, CMOS detector, Raspberry Pi interface in conjugation with a metallic flow-through nanohole array-based sensor. Detection is achieved exploiting nanoplasmonic phenomena from the nanohole arrays through surface plasmon resonance imaging (SPRi) technique. The platform has a bulk sensitivity of 212 pixel intensity unit (PIU)/refractive index unit (RIU), and a resolution in the order of 10 -6 RIU. We demonstrate capture and detection of UPEC with a detection limit of ~100 CFU/ml - a concentration well below the threshold limit for UTI diagnosis in clinical samples. We also demonstrate detection of UPEC in spiked human urine samples for two different concentrations of bacteria. This work is particularly relevant for point-of-care applications, especially for regions around the world where accessibility to medical facilities is heavily dependent upon economy, and availability. Copyright © 2018 Elsevier B.V. All rights reserved.

On-Chip Photothermal Analyte Detection Using Integrated Luminescent Temperature Sensors.

PubMed

Pfeiffer, Simon A; Nagl, Stefan

2017-09-05

Optical absorbance detection based on attenuated light transmission is limited in sensitivity due to short path lengths in microfluidic and other miniaturized platforms. An alternative is detection using the photothermal effect. Herein we introduce a new kind of photothermal absorbance measurement using integrated luminescent temperature sensor spots inside microfluidic channels. The temperature sensors were photopolymerized inside the channels from NOA 81 UV-curable thiolene prepolymer doped with a tris(1,10-phenanthroline)ruthenium(II) temperature probe. The polymerized sensing structures were as small as 26 ± 3 μm in diameter and displayed a temperature resolution of better than 0.3 K between 20 and 50 °C. The absorbance from 532 nm laser excitation of the food dye Amaranth as a model analyte was quantified using these spots, and the influence of the flow rate, laser power, and concentration was investigated. Calibration yielded a linear relationship between analyte concentration and the temperature signal in the channels. The limit of detection for the azo-dye Amaranth (E123) in this setup was 13 μM. A minimal detectable absorbance of 3.2 × 10 -3 AU was obtained using an optical path length of 125 μm in this initial study. A microreactor with integrated temperature sensors was then employed for an absorbance-based miniaturized nitrite analysis, yielding a detection limit of 26 μM at a total assay time of only 75 s. This technique is very promising for sensitive, and potentially spatially resolved, optical absorbance detection on the micro- and nanoscale.

A model system for pathogen detection using a two-component bacteriophage/bioluminescent signal amplification assay

NASA Astrophysics Data System (ADS)

Bright, Nathan G.; Carroll, Richard J.; Applegate, Bruce M.

2004-03-01

Microbial contamination has become a mounting concern the last decade due to an increased emphasis of minimally processed food products specifically produce, and the recognition of foodborne pathogens such as Campylobacter jejuni, Escherichia coli O157:H7, and Listeria monocytogenes. This research investigates a detection approach utilizing bacteriophage pathogen specificity coupled with a bacterial bioluminescent bioreporter utilizing the quorum sensing molecule from Vibrio fischeri, N-(3-oxohexanoyl)-homoserine lactone (3-oxo-C6-HSL). The 3-oxo-C6-HSL molecules diffuse out of the target cell after infection and induce bioluminescence from a population of 3-oxo-C6-HSL bioreporters (ROLux). E. coli phage M13, a well-characterized bacteriophage, offers a model system testing the use of bacteriophage for pathogen detection through cell-to-cell communication via a LuxR/3-oxo-C6-HSL system. Simulated temperate phage assays tested functionality of the ROLux reporter and production of 3-oxo-C6-HSL by various test strains. These assays showed detection limits of 102cfu after 24 hours in a varietry of detection formats. Assays incorporating the bacteriophage M13-luxI with the ROLux reporter and a known population of target cells were subsequently developed and have shown consistent detection limits of 105cfu target organisms. Measurable light response from high concentrations of target cells was almost immediate, suggesting an enrichment step to further improve detection limits and reduce assay time.

Detection of trace amount of arsenic in groundwater by laser-induced breakdown spectroscopy and adsorption

NASA Astrophysics Data System (ADS)

Haider, A. F. M. Y.; Hedayet Ullah, M.; Khan, Z. H.; Kabir, Firoza; Abedin, K. M.

2014-03-01

LIBS technique coupled with adsorption has been applied for the efficient detection of arsenic in liquid. Several adsorbents like tea leaves, bamboo slice, charcoal and zinc oxide have been used to enable sensitive detection of arsenic presence in water using LIBS. Among these, zinc oxide and charcoal show the better results. The detection limits for arsenic in water were 1 ppm and 8 ppm, respectively, when ZnO and charcoal were used as adsorbents of arsenic. To date, the determination of 1 ppm of As in water is the lowest concentration of detected arsenic in water by the LIBS technique. The detection limit of As was lowered to even less than 100 ppb by a combination of LIBS technique, adsorption by ZnO and concentration enhancement technique. Using the combination of these three techniques the ultimate concentration of arsenic was found to be 0.083 ppm (83 ppb) for arsenic polluted water collected from a tube-well of Farajikandi union (longitude 90.64°, latitude 23.338° north) of Matlab Upozila of Chandpur district in Bangladesh. This result compares fairly well with the finding of arsenic concentration of 0.078 ppm in the sample by the AAS technique at the Bangladesh Council of Scientific and Industrial Research (BCSIR) lab. Such a low detection limit (1 ppm) of trace elements in liquid matrix has significantly enhanced the scope of LIBS as an analytical tool.

Detection limits of the strip test and PCR for genetically modified corn in Brazil.

PubMed

Nascimento, V E; Von Pinho, É V R; Von Pinho, R G; do Nascimento, A D

2012-08-16

Brazilian legislation establishes a labeling limit for products that contain more than 1% material from genetically modified organisms (GMOs). We assessed the sensitivity of the lateral flow strip test in detection of the GMO corn varieties Bt11 and MON810 and the specificity and sensitivity of PCR techniques for their detection. For the strip test, the GMO seeds were mixed with conventional seeds at levels of 0.2, 0.4 and 0.8% for Bt11, and 0.4, 0.8 and 1.6% for MON810. Three different methodologies were assessed and whole seeds, their endosperm and embryonic axis were used. For the PCR technique, the GMO seeds of each of the two varieties were mixed with conventional seeds at levels of 20, 10, 5, 2, 1, and 0.5%. The seeds were ground and the DNA extracted. For detection of the GMO material, specific primers were used for MON810 and Bt11 and maize zein as an endogenous control. The sensitivity of the strip test varied for both maize varieties and methodologies. The test was positive for Bt11 only at 0.8%, in contrast with the detection limit of 0.4% indicated by the manufacturer. In the multiplex PCR, the primers proved to be specific for the different varieties. These varieties were detected in samples with one GMO seed in 100. Thus, this technique proved to be efficient in detecting contaminations equal to or greater than 1%.

Solid core dipoles and switching power supplies: lower cost light sources?

NASA Astrophysics Data System (ADS)

Benesch, J.; Philip, S.

2015-05-01

As a result of improvements in power semiconductors, moderate frequency switching supplies can now provide the hundreds of amps typically required by accelerators with zero-to-peak noise in the kHz region ~ 0.06% in current or voltage mode. Modeling was undertaken using a finite electromagnetic program to determine if eddy currents induced in the solid steel of CEBAF magnets and small supplemental additions would bring the error fields down to the 5ppm level needed for beam quality. The expected maximum field of the magnet under consideration is 0.85 T and the DC current required to produce that field is used in the calculations. An additional 0.1% current ripple is added to the DC current at discrete frequencies 360 Hz, 720 Hz or 7200 Hz. Over the region of the pole within 0.5% of the central integrated BdL the resulting AC field changes can be reduced to less than 1% of the 0.1% input ripple for all frequencies, and a sixth of that at 7200 Hz. Doubling the current, providing 1.5 T central field, yielded the same fractional reduction in ripple at the beam for the cases checked. A small dipole was measured at 60, 120, 360 and 720 Hz in two conditions and the results compared to the larger model for the latter two frequencies with surprisingly good agreement. For light sources with aluminum vacuum vessels and full energy linac injection, the combination of solid core dipoles and switching power supplies may result in significant cost savings. The work may also be used to guide retrofit of existing machines to reduce the level of ripple in the particle beam path.

The renal effects of droxidopa are maintained in propranolol treated cirrhotic rats.

PubMed

Rodríguez, Sarai; Raurell, Imma; Ezkurdia, Nahia; Augustin, Salvador; Esteban, Rafael; Genescà, Joan; Martell, María

2015-02-01

Droxidopa improves hemodynamic and renal alterations of cirrhotic rats without changing portal pressure. We aimed to evaluate the effects of a combined treatment with droxidopa and non-selective beta-blockers or statins in order to decrease portal pressure, while maintaining droxidopa beneficial effects. Acute studies combining droxidopa with carvedilol, propranolol or atorvastatin in four-week bile-duct ligated (BDL) rats and a chronic study combining propranolol and droxidopa for 5 days in CCl4 -cirrhotic rats were performed. Hemodynamic values were registered and biochemical parameters from blood and urine samples analyzed. Bile-duct ligated rats treated with carvedilol + droxidopa showed no changes in mean arterial pressure (MAP) and portal pressure (PP) compared to vehicles. Atorvastatin + droxidopa combination also failed to reduce PP, but maintained the beneficial increase in MAP and superior mesenteric artery resistance (SMAR) and decrease in blood flow (SMABF) caused by droxidopa. In contrast, the acute administration of propranolol + droxidopa significantly reduced PP maintaining a mild increase in MAP and improving, in an additive way, the decrease in SMABF and increase in SMAR caused by droxidopa. This combination also preserved droxidopa diuretic effect. When chronically administered to CCl4 -cirrhotic rats, propranolol + droxidopa caused a decrease in PP, a significant reduction in SMABF and an increase in SMAR. The combination did not alter liver function and droxidopa diuretic and natriuretic effect, and even improved free water clearance. Droxidopa could be effective for the renal alterations of cirrhotic patients on propranolol therapy and the combination of both drugs may balance the adverse effects of each treatment. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.