Effects of Collagen Tripeptide Supplement on Photoaging and Epidermal Skin Barrier in UVB-exposed Hairless Mice

PubMed Central

Pyun, Hee-Bong; Kim, Minji; Park, Jieun; Sakai, Yasuo; Numata, Noriaki; Shin, Jin-Yeong; Shin, Hyun-Jung; Kim, Do-Un; Hwang, Jae-Kwan

2012-01-01

Collagen tripeptide (CTP) is a functional food material with several biological effects such as improving dry skin and wound and bone fracture healing. This study focused on the anti-photoaging effects of CTP on a hairless mouse model. To evaluate the effects of CTP on UVB-induced skin wrinkle formation in vivo, the hairless mice were exposed to UVB radiation with oral administration of CTP for 14 weeks. Compared with the untreated UVB control group, mice treated with CTP showed significantly reduced wrinkle formation, skin thickening, and transepidermal water loss (TEWL). Skin hydration and hydroxyproline were increased in the CTP-treated group. Moreover, oral administration of CTP prevented UVB-induced MMP-3 and -13 activities as well as MMP-2 and -9 expressions. Oral administration of CTP increased skin elasticity and decreased abnormal elastic fiber formation. Erythema was also decreased in the CTP-treated group. Taken together, these results strongly suggest that CTP has potential as an anti-photoaging agent. PMID:24471092

Mitochondrial and Plasma Membrane Citrate Transporters: Discovery of Selective Inhibitors and Application to Structure/Function Analysis

PubMed Central

Sun, Jiakang; Aluvila, Sreevidya; Kotaria, Rusudan; Mayor, June A.; Walters, D. Eric; Kaplan, Ronald S.

2010-01-01

Cytoplasmic citrate is the prime carbon source for fatty acid, triacylglycerol, and cholesterol biosyntheses, and also regulates glucose metabolism via its allosteric inhibition of phosphofructokinase. It originates either via the efflux of citrate from the mitochondrial matrix on the inner membrane citrate transport protein (CTP) or via the influx of extracellular citrate on the plasma membrane citrate transporter (PMCT). Despite their common substrate, the two transport proteins share little sequence similarity and they transport citrate via fundamentally different mechanisms. We tested the ability of a set of previously identified CTP inhibitors, to inhibit the PMCT. We found that of the top 10 CTP inhibitors only one substantially inhibited the PMCT. Conversely, we identified two other inhibitors that inhibited the PMCT but had little effect on the CTP. All three identified PMCT inhibitors displayed a noncompetitive mechanism. Furthermore, models to explain inhibitor interactions with the CTP are proposed. As part of the present studies a PMCT homology model has been developed based on the crystal structure of the leucine transporter, and a possible citrate binding site has been identified and its composition compared with the two known citrate binding sites present within the CTP. The ability to selectively inhibit the PMCT may prove key to the pharmacologic amelioration of metabolic disorders resulting from the synthesis of excess lipid, cholesterol, and glucose, including human obesity, hyperlipidemia, hyper-cholesterolemia, and Type 2 diabetes. PMID:20686672

Low dose CT perfusion in acute ischemic stroke.

PubMed

Murphy, Amanda; So, Aaron; Lee, Ting-Yim; Symons, Sean; Jakubovic, Raphael; Zhang, Liying; Aviv, Richard I

2014-12-01

The purpose of this investigation is to determine if CT perfusion (CTP) measurements at low doses (LD = 20 or 50 mAs) are similar to those obtained at regular doses (RD = 100 mAs), with and without the addition of adaptive statistical iterative reconstruction (ASIR). A single-center, prospective study was performed in patients with acute ischemic stroke (n = 37; 54% male; age = 74 ± 15 years). Two CTP scans were performed on each subject: one at 100 mAs (RD) and one at either 50 or 20 mAs (LD). CTP parameters were compared between the RD and LD scans in regions of ischemia, infarction, and normal tissue. Differences were determined using a within-subjects ANOVA (p < 0.05) followed by a paired t test post hoc analysis (p < 0.01). At 50 mAs, there was no significant difference between cerebral blood flow (CBF), cerebral blood volume (CBV), or time to maximum enhancement (Tmax) values for the RD and LD scans in the ischemic, infarcted, or normal contralateral regions (p < 0.05). At 20 mAs, there were significant differences between the RD and LD scans for all parameters in the ischemic and normal tissue regions (p > 0.05). CTP-derived CBF and CBV are not different at 50 mAs compared to 100 mAs, even without the addition of ASIR. Current CTP protocols can be modified to reduce the effective dose by 50 % without altering CTP measurements.

CTP synthase forms cytoophidia in the cytoplasm and nucleus

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

Gou, Ke-Mian; State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193; Chang, Chia-Chun

2014-04-15

CTP synthase is an essential metabolic enzyme responsible for the de novo synthesis of CTP. Multiple studies have recently showed that CTP synthase protein molecules form filamentous structures termed cytoophidia or CTP synthase filaments in the cytoplasm of eukaryotic cells, as well as in bacteria. Here we report that CTP synthase can form cytoophidia not only in the cytoplasm, but also in the nucleus of eukaryotic cells. Both glutamine deprivation and glutamine analog treatment promote formation of cytoplasmic cytoophidia (C-cytoophidia) and nuclear cytoophidia (N-cytoophidia). N-cytoophidia are generally shorter and thinner than their cytoplasmic counterparts. In mammalian cells, both CTP synthasemore » 1 and CTP synthase 2 can form cytoophidia. Using live imaging, we have observed that both C-cytoophidia and N-cytoophidia undergo multiple rounds of fusion upon glutamine analog treatment. Our study reveals the coexistence of cytoophidia in the cytoplasm and nucleus, therefore providing a good opportunity to investigate the intracellular compartmentation of CTP synthase. - Highlights: • CTP synthase forms cytoophidia not only in the cytoplasm but also in the nucleus. • Glutamine deprivation and Glutamine analogs promotes cytoophidium formation. • N-cytoophidia exhibit distinct morphology when compared to C-cytoophidia. • Both CTP synthase 1 and CTP synthase 2 form cytoophidia in mammalian cells. • Fusions of cytoophidia occur in the cytoplasm and nucleus.« less

Implementation of an anonymisation tool for clinical trials using a clinical trial processor integrated with an existing trial patient data information system.

PubMed

Aryanto, Kadek Y E; Broekema, André; Oudkerk, Matthijs; van Ooijen, Peter M A

2012-01-01

To present an adapted Clinical Trial Processor (CTP) test set-up for receiving, anonymising and saving Digital Imaging and Communications in Medicine (DICOM) data using external input from the original database of an existing clinical study information system to guide the anonymisation process. Two methods are presented for an adapted CTP test set-up. In the first method, images are pushed from the Picture Archiving and Communication System (PACS) using the DICOM protocol through a local network. In the second method, images are transferred through the internet using the HTTPS protocol. In total 25,000 images from 50 patients were moved from the PACS, anonymised and stored within roughly 2 h using the first method. In the second method, an average of 10 images per minute were transferred and processed over a residential connection. In both methods, no duplicated images were stored when previous images were retransferred. The anonymised images are stored in appropriate directories. The CTP can transfer and process DICOM images correctly in a very easy set-up providing a fast, secure and stable environment. The adapted CTP allows easy integration into an environment in which patient data are already included in an existing information system.

Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease: a multicentre, open-label, randomised, phase 2 trial.

PubMed

Manns, Michael; Samuel, Didier; Gane, Edward J; Mutimer, David; McCaughan, Geoff; Buti, Maria; Prieto, Martín; Calleja, José Luis; Peck-Radosavljevic, Markus; Müllhaupt, Beat; Agarwal, Kosh; Angus, Peter; Yoshida, Eric M; Colombo, Massimo; Rizzetto, Mario; Dvory-Sobol, Hadas; Denning, Jill; Arterburn, Sarah; Pang, Phillip S; Brainard, Diana; McHutchison, John G; Dufour, Jean-François; Van Vlierberghe, Hans; van Hoek, Bart; Forns, Xavier

2016-06-01

Treatment options are limited for patients infected by hepatitis C virus (HCV) with advanced liver disease. We assessed the safety and efficacy of ledipasvir, sofosbuvir, and ribavirin in patients with HCV genotype 1 or 4 and advanced liver disease. We did an open-label study at 34 sites in Europe, Canada, Australia, and New Zealand. Cohort A included patients with Child-Turcotte-Pugh class B (CTP-B) or CTP-C cirrhosis who had not undergone liver transplantation. Cohort B included post-transplantation patients who had either no cirrhosis; CTP-A, CTP-B, or CTP-C cirrhosis; or fibrosing cholestatic hepatitis. Patients in each group were randomly assigned (1:1) using a computer-generated randomisation sequence to receive 12 or 24 weeks of ledipasvir (90 mg) and sofosbuvir (400 mg) once daily (combination tablet), plus ribavirin (600-1200 mg daily). The primary endpoint was the proportion of patients achieving a sustained virological response 12 weeks after treatment (SVR12). All patients who received at least one dose of study drug were included in the safety analysis and all patients who received at least one dose of study drug and did not undergo liver transplantation during treatment were included in the efficacy analyses. Estimates of SVR12 and relapse rates and their two-sided 90% CI (Clopper-Pearson method) were provided. This exploratory phase 2 study was not powered for formal comparisons among treatment groups; no statistical hypothesis testing was planned or conducted. The trial is registered with EudraCT (number 2013-002802-30) and ClinicalTrials.gov (number NCT02010255). Between Jan 14, 2014, and Aug 19, 2014, 398 patients were screened. Of 333 patients who received treatment, 296 had genotype 1 HCV and 37 had genotype 4 HCV. In cohort A, among patients with genotype 1 HCV, SVR12 was achieved by 20 (87%, 90% CI 70-96) of 23 CTP-B patients with 12 weeks of treatment; 22 (96%, 81-100) of 23 CTP-B patients with 24 weeks of treatment; 17 (85%, 66-96) of 20 CTP-C patients (12 weeks treatment); and 18 (78%, 60-91) of 23 CTP-C patients (24 weeks treatment). In cohort B, among patients with genotype 1 HCV, SVR12 was achieved by 42 (93%, 84-98) of 45 patients without cirrhosis (12 weeks treatment); 44 (100%, 93-100) of 44 patients without cirrhosis (24 weeks treatment); 30 (100%, 91-100) of 30 CTP-A patients (12 weeks treatment); 27 (96%, 84-100) of 28 CTP-A patients (24 weeks treatment); 19 (95%, 78-100) of 20 CTP-B patients (12 weeks treatment); 20 (100%, 86-100) of 20 CTP-B patients (24 weeks treatment); one (50%, 3-98) of two CTP-C patients (12 weeks treatment); and four (80%, 34-99) of five CTP-C patients (24 weeks treatment). All five patients with fibrosing cholestatic hepatitis achieved SVR12 (100%, 90% CI 55-100). Among all patients with genotype 4 HCV, SVR12 was achieved by 14 (78%, 56-92) of 18 patients (12 weeks treatment) and 16 (94%, 75-100) of 17 patients (24 weeks treatment). Seven patients (2%) discontinued ledipasvir-sofosbuvir prematurely due to adverse events. 17 patients died, mainly from complications of hepatic decompensation. Ledipasvir-sofosbuvir and ribavirin provided high rates of SVR12 for patients with advanced liver disease, including those with decompensated cirrhosis before or after liver transplantation. Gilead Sciences. Copyright © 2016 Elsevier Ltd. All rights reserved.

Analytical similarity assessment of rituximab biosimilar CT-P10 to reference medicinal product

PubMed Central

Lee, Kyoung Hoon; Kim, Yeon Jung; Kang, Hyun Ah; Kim, Sung Hwan; Lee, So Jung; Lim, Ki Jung; Jung, Soon Kwan; Chang, Shin Jae

2018-01-01

ABSTRACT CT-P10 (Truxima™) was recently approved as the world's first rituximab biosimilar product in the European Union (EU) and South Korea. To demonstrate biosimilarity of CT-P10 with the reference medicinal product (RMP), extensive 3-way similarity assessment has been conducted between CT-P10, EU-Rituximab and US-Rituximab, focusing on the physicochemical and biological quality attributes. A multitude of state-of-the-art analyses revealed that CT-P10 has identical primary and higher order structures compared to the original product. Purity/impurity profiles of CT-P10 measured by the levels of aggregates, fragments, non-glycosylated form and process-related impurities were also found to be comparable with those of RMPs. In terms of the post-translational modification, CT-P10 contains slightly less N-terminal pyro-glutamate variant, which has been known not to affect product efficacy or safety. Oligosaccharide profiling has revealed that, although CT-P10 contains the same conserved glycan species and relative proportion with the RMPs, the content of total afucosylated glycan in CT-P10 was slightly higher than in EU- or US-Rituximab. Nevertheless, the effect of the observed level of afucosylation in CT-P10 drug product on Fc receptor binding affinity or antibody-dependent cell-mediated cytotoxicity was found to be negligible based on the spiking study with highly afucosylated sample. Arrays of biological assays representative of known and putative mechanisms of action for rituximab have shown that biological activities of CT-P10 are within the quality range of RMPs. Recent results of clinical studies have further confirmed that the CT-P10 exhibits equivalent clinical efficacy and safety profiles compared to EU- and US-Rituximab. The current 3-way similarity assessment together with clinical study results confidently demonstrate that CT-P10 is highly similar with EU- and US-Rituximab in terms of physicochemical properties, biological activities, efficacy, and safety for its final approval as a biosimilar product. PMID:29469653

Analytical similarity assessment of rituximab biosimilar CT-P10 to reference medicinal product.

PubMed

Lee, Kyoung Hoon; Lee, Jihun; Bae, Jin Soo; Kim, Yeon Jung; Kang, Hyun Ah; Kim, Sung Hwan; Lee, So Jung; Lim, Ki Jung; Lee, Jung Woo; Jung, Soon Kwan; Chang, Shin Jae

2018-04-01

CT-P10 (Truxima™) was recently approved as the world's first rituximab biosimilar product in the European Union (EU) and South Korea. To demonstrate biosimilarity of CT-P10 with the reference medicinal product (RMP), extensive 3-way similarity assessment has been conducted between CT-P10, EU-Rituximab and US-Rituximab, focusing on the physicochemical and biological quality attributes. A multitude of state-of-the-art analyses revealed that CT-P10 has identical primary and higher order structures compared to the original product. Purity/impurity profiles of CT-P10 measured by the levels of aggregates, fragments, non-glycosylated form and process-related impurities were also found to be comparable with those of RMPs. In terms of the post-translational modification, CT-P10 contains slightly less N-terminal pyro-glutamate variant, which has been known not to affect product efficacy or safety. Oligosaccharide profiling has revealed that, although CT-P10 contains the same conserved glycan species and relative proportion with the RMPs, the content of total afucosylated glycan in CT-P10 was slightly higher than in EU- or US-Rituximab. Nevertheless, the effect of the observed level of afucosylation in CT-P10 drug product on Fc receptor binding affinity or antibody-dependent cell-mediated cytotoxicity was found to be negligible based on the spiking study with highly afucosylated sample. Arrays of biological assays representative of known and putative mechanisms of action for rituximab have shown that biological activities of CT-P10 are within the quality range of RMPs. Recent results of clinical studies have further confirmed that the CT-P10 exhibits equivalent clinical efficacy and safety profiles compared to EU- and US-Rituximab. The current 3-way similarity assessment together with clinical study results confidently demonstrate that CT-P10 is highly similar with EU- and US-Rituximab in terms of physicochemical properties, biological activities, efficacy, and safety for its final approval as a biosimilar product.

Correction for Delay and Dispersion Results in More Accurate Cerebral Blood Flow Ischemic Core Measurement in Acute Stroke.

PubMed

Lin, Longting; Bivard, Andrew; Kleinig, Timothy; Spratt, Neil J; Levi, Christopher R; Yang, Qing; Parsons, Mark W

2018-04-01

This study aimed to assess how the ischemic core measured by perfusion computed tomography (CTP) was affected by the delay and dispersion effect. Ischemic stroke patients having CTP performed within 6 hours of onset were included. The CTP data were processed twice, generating standard cerebral blood flow (sCBF) and delay- and dispersion-corrected CBF (ddCBF), respectively. Ischemic core measured by the sCBF and ddCBF was then compared at the relative threshold <30% of normal tissue. Two references for ischemic core were used: acute diffusion-weighted imaging or 24-hour diffusion-weighted imaging in patients with complete recanalization. Difference of core volume between CTP and diffusion-weighted imaging was estimated by Mann-Whitney U test and limits of agreement. Patients were also classified into favorable and unfavorable CTP patterns. The imaging pattern classification by sCBF and ddCBF was compared by the χ 2 test; their respective ability to predict good clinical outcome (3-month modified Rankin Scale score) was tested in logistic regression. Fifty-five patients were included in this study. Median sCBF ischemic core volume was 38.5 mL (12.4-61.9 mL), much larger than the median core volume of 17.2 mL measured by ddCBF (interquartile range, 5.5-38.8; P <0.001). Moreover, compared with sCBF <30%, ddCBF <30% measured the ischemic core much closer to diffusion-weighted imaging core references, with the mean volume difference of -0.1 mL (95% limits of agreement, -25.4 to 25.2; P =0.97) and 16.7 mL (95% limits of agreement, -21.7 to 55.2; P <0.001), respectively. Imaging patterns defined by sCBF showed a difference to that defined by ddCBF ( P <0.001), with 12 patients classified as favorable imaging patterns by ddCBF but as unfavorable by sCBF. The favorable imaging pattern classified by ddCBF, compared with sCBF classification, had higher predictive power for good clinical outcome (odds ratio, 7.8 [2-30.5] and 3.1 [0.9-11], respectively). Delay and dispersion correction increases the accuracy of ischemic core measurement on CTP. © 2018 American Heart Association, Inc.

A disruption of ctpA encoding carboxy-terminal protease attenuates Burkholderia mallei and induces partial protection in CD1 mice.

PubMed

Bandara, Aloka B; DeShazer, David; Inzana, Thomas J; Sriranganathan, Nammalwar; Schurig, Gerhardt G; Boyle, Stephen M

2008-09-01

Burkholderia mallei is the etiologic agent of glanders in solipeds (horses, mules and donkeys), and incidentally in carnivores and humans. Little is known about the molecular mechanisms of B. mallei pathogenesis. The putative carboxy-terminal processing protease (CtpA) of B. mallei is a member of a novel family of endoproteases involved in the maturation of proteins destined for the cell envelope. All species and isolates of Burkholderia carry a highly conserved copy of ctpA. We studied the involvement of CtpA on growth, cell morphology, persistence, and pathogenicity of B. mallei. A sucrose-resistant strain of B. mallei was constructed by deleting a major portion of the sacB gene of the wild type strain ATCC 23344 by gene replacement, and designated as strain 23344DeltasacB. A portion of the ctpA gene (encoding CtpA) of strain 23344DeltasacB was deleted by gene replacement to generate strain 23344DeltasacBDeltactpA. In contrast to the wild type ATCC 23344 or the sacB mutant 23344DeltasacB, the ctpA mutant 23344DeltasacBDeltactpA displayed altered cell morphologies with partially or fully disintegrated cell envelopes. Furthermore, relative to the wild type, the ctpA mutant displayed slower growth in vitro and less ability to survive in J774.2 murine macrophages. The expression of mRNA of adtA, the gene downstream of ctpA was similar among the three strains suggesting that disruption of ctpA did not induce any polar effects. As with the wild type or the sacB mutant, the ctpA mutant exhibited a dose-dependent lethality when inoculated intraperitoneally into CD1 mice. The CD1 mice inoculated with a non-lethal dose of the ctpA mutant produced specific serum immunoglobulins IgG1 and IgG2a and were partially protected against challenge with wild type B. mallei ATCC 23344. These findings suggest that CtpA regulates in vitro growth, cell morphology and intracellular survival of B. mallei, and a ctpA mutant protects CD1 mice against glanders.

Extraction, purification, characterization and antioxidant activities of polysaccharides from Cistanche tubulosa.

PubMed

Zhang, Wiejie; Huang, Jing; Wang, Wei; Li, Qian; Chen, Yao; Feng, Weiwei; Zheng, Daheng; Zhao, Ting; Mao, Guanghua; Yang, Liuqing; Wu, Xiangyang

2016-12-01

An efficient ultrasonic-cellulase-assisted extraction (UCE) of Cistanche tubulosa polysaccharide (CTP) was established. The response surface methodology based on Box-Behnken Design was employed to further optimize extraction conditions. After quaternary ammonium salt precipitation, the polysaccharide of C. tubulosa was characterized by different techniques. The results showed that a maximum polysaccharide yield of 22.31±0.45% was achieved at a pH of 5.2 for 31.5min at 54.1°C. Compared to hot water extraction, the yield of CTP in UCE and polysaccharide content increased to 44.96% and 70.13±2.19%, respectively. There was no marked difference among polysaccharides extracted using different methods from the infrared spectrum. Ultrasonic-cellulase-assisted extraction polysaccharide showed a fibrous structure from scanning electron microscopy and was composed of rhamnose, mannose, glucose, and galactose in a molar ratio of 2.18:1:28.29:1.43 by gas chromatography. The circular dichroism results indicated that polysaccharides had a maximum positive peak around 210nm with different peak values. The thermogravimetric analysis and differential scanning calorimetry were used to test the thermostability of CTP. Besides, CTP demonstrated appreciable antioxidant potential on antioxidant experiments in vitro. The results suggested that UCE is an effective method for CTP extraction and its polysaccharide showed appreciable antioxidant activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of oral CTL vaccine using a CTP-integrated Sabin 1 poliovirus-based vector system.

PubMed

Han, Seung-Soo; Lee, Jinjoo; Jung, Yideul; Kang, Myeong-Ho; Hong, Jung-Hyub; Cha, Min-Suk; Park, Yu-Jin; Lee, Ezra; Yoon, Cheol-Hee; Bae, Yong-Soo

2015-09-11

We developed a CTL vaccine vector by modification of the RPS-Vax system, a mucosal vaccine vector derived from a poliovirus Sabin 1 strain, and generated an oral CTL vaccine against HIV-1. A DNA fragment encoding a cytoplasmic transduction peptide (CTP) was integrated into the RPS-Vax system to generate RPS-CTP, a CTL vaccine vector. An HIV-1 p24 cDNA fragment was introduced into the RPS-CTP vector system and a recombinant poliovirus (rec-PV) named vRPS-CTP/p24 was produced. vRPS-CTP/p24 was genetically stable and efficiently induced Th1 immunity and p24-specific CTLs in immunized poliovirus receptor-transgenic (PVR-Tg) mice. In challenge experiments, PVR-Tg mice that were pre-immunized orally with vRPS-CTP/p24 were resistant to challenge with a lethal dose of p24-expressing recombinant vaccinia virus (rMVA-p24). These results suggested that the RPS-CTP vector system had potential for developing oral CTL vaccines against infectious diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rust fungal effectors mimic host transit peptides to translocate into chloroplasts.

PubMed

Petre, Benjamin; Lorrain, Cécile; Saunders, Diane G O; Win, Joe; Sklenar, Jan; Duplessis, Sébastien; Kamoun, Sophien

2016-04-01

Parasite effector proteins target various host cell compartments to alter host processes and promote infection. How effectors cross membrane-rich interfaces to reach these compartments is a major question in effector biology. Growing evidence suggests that effectors use molecular mimicry to subvert host cell machinery for protein sorting. We recently identified chloroplast-targeted protein 1 (CTP1), a candidate effector from the poplar leaf rust fungus Melampsora larici-populina that carries a predicted transit peptide and accumulates in chloroplasts and mitochondria. Here, we show that the CTP1 transit peptide is necessary and sufficient for accumulation in the stroma of chloroplasts. CTP1 is part of a Melampsora-specific family of polymorphic secreted proteins. Two members of that family, CTP2 and CTP3, also translocate in chloroplasts in an N-terminal signal-dependent manner. CTP1, CTP2 and CTP3 are cleaved when they accumulate in chloroplasts, while they remain intact when they do not translocate into chloroplasts. Our findings reveal that fungi have evolved effector proteins that mimic plant-specific sorting signals to traffic within plant cells. © 2015 John Wiley & Sons Ltd.

Engineered cytidine triphosphate synthetase with reduced product inhibition.

PubMed

Zhu, Mengzhu; Sun, Wujin; Wang, Yan; Meng, Jie; Zhang, Dalu; Guo, Ting; Ouyang, Pingkai; Ying, Hanjie; Xie, Jingjing

2014-07-01

Cytidine triphosphate (CTP) synthetase (CTPS) (EC number 6.3.4.2) is a key enzyme involved in de novo synthesis of CTP. It catalyzes the rate-limiting step of the process due to the product inhibition effects on the enzyme. In this study, a novel CTPS from Corynebacterium glutamicum ATCC 13032 (CgCTPS) was cloned, expressed and characterized. A series of mutagenesis in its N-terminal ammonia ligase (ALase) domain was performed in order to reduce CTP product inhibition. All single mutation variants (D160E, E162A, E168K) lowered product inhibition by lowering the enzyme's binding affinity for CTP. The homology model of CgCTPS showed that D160E mutant caused steric hindrance for the pyrimidine ring of CTP stacking, E162A disrupted the hydrogen bond between CTP ribose and side chain and D168K caused minor localized structure perturbations of CTP binding pocket. The triple mutant of CTPS (D160E-E162A-E168K) with halved Km, doubled Vmax and the 23.5-fold increased IC50 for CTP shows a potential for use in industrial-scale CTP production by its better performance in enzyme kinetics and product inhibition. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Is cannabis an illicit drug or a medicine? A quantitative framing analysis of Israeli newspaper coverage.

PubMed

Sznitman, Sharon R; Lewis, Nehama

2015-05-01

Various countries and states, including Israel, have recently legalized cannabis for therapeutic purposes (CTP). These changes have received mass media coverage and prompted national and international dialogue about the status of cannabis and whether or not it can be defined as a (legitimate) medicine, illicit and harmful drug, or both. News media framing may influence, and be influenced by, public opinion regarding CTP and support for CTP license provisions for patients. This study examines the framing of CTP in Israeli media coverage and the association between media coverage and trends in the provision of CTP licenses in Israel over time. All published news articles relevant to CTP and the framing of cannabis (N=214) from the three highest circulation newspapers in Israel were content analyzed. Articles were published between January 2007 and June 2013, a period in which CTP licenses granted by the Ministry of Health increased substantially. In the majority of CTP news articles (69%), cannabis was framed as a medicine, although in almost one third of articles (31%) cannabis was framed as an illicit drug. The relative proportion of news items in which cannabis was framed as an illicit drug fluctuated during the study period, but was unrelated to linear or curvilinear trends in CTP licensing. The relatively large proportion of news items framing cannabis as a medicine is consistent with growing support for the expansion of the Israel's CTP program. Copyright © 2015 Elsevier B.V. All rights reserved.

Time-resolved perfusion imaging at the angiography suite: preclinical comparison of a new flat-detector application to computed tomography perfusion.

PubMed

Jürgens, Julian H W; Schulz, Nadine; Wybranski, Christian; Seidensticker, Max; Streit, Sebastian; Brauner, Jan; Wohlgemuth, Walter A; Deuerling-Zheng, Yu; Ricke, Jens; Dudeck, Oliver

2015-02-01

The objective of this study was to compare the parameter maps of a new flat-panel detector application for time-resolved perfusion imaging in the angiography room (FD-CTP) with computed tomography perfusion (CTP) in an experimental tumor model. Twenty-four VX2 tumors were implanted into the hind legs of 12 rabbits. Three weeks later, FD-CTP (Artis zeego; Siemens) and CTP (SOMATOM Definition AS +; Siemens) were performed. The parameter maps for the FD-CTP were calculated using a prototype software, and those for the CTP were calculated with VPCT-body software on a dedicated syngo MultiModality Workplace. The parameters were compared using Pearson product-moment correlation coefficient and linear regression analysis. The Pearson product-moment correlation coefficient showed good correlation values for both the intratumoral blood volume of 0.848 (P < 0.01) and the blood flow of 0.698 (P < 0.01). The linear regression analysis of the perfusion between FD-CTP and CTP showed for the blood volume a regression equation y = 4.44x + 36.72 (P < 0.01) and for the blood flow y = 0.75x + 14.61 (P < 0.01). This preclinical study provides evidence that FD-CTP allows a time-resolved (dynamic) perfusion imaging of tumors similar to CTP, which provides the basis for clinical applications such as the assessment of tumor response to locoregional therapies directly in the angiography suite.

Cannabis for therapeutic purposes and public health and safety: a systematic and critical review.

PubMed

Sznitman, Sharon R; Zolotov, Yuval

2015-01-01

The use of Cannabis for Therapeutic Purposes (CTP) has recently become legal in many places. These policy and legal modifications may be related to changes in cannabis perceptions, availability and use and in the way cannabis is grown and sold. This may in turn have effects on public health and safety. To better understand the potential effects of CTP legalization on public health and safety, the current paper synthesizes and critically discusses the relevant literature. Twenty-eight studies were identified by a comprehensive search strategy, and their characteristics and main findings were systematically reviewed according to the following content themes: CTP and illegal cannabis use; CTP and other public health issues; CTP, crime and neighbourhood disadvantage. The research field is currently limited by a lack of theoretical and methodological rigorous studies. The review shows that the most prevalent theme of investigation so far has been the relation between CTP and illegal cannabis use. In addition, the literature review shows that there is an absence of evidence to support many common concerns related to detrimental public health and safety effects of CTP legalization. Although lack of evidence provides some reassurance that CTP legalization may not have posed a substantial threat to public health and safety, this conclusion needs to be examined in light of the limitations of studies conducted so far. Furthermore, as CTP policy continues to evolve, including incorporation of greater commercialization, it is possible that the full effects of CTP legalization have yet to take place. Ensuring study quality will allow future research to better investigate the complex role that CTP plays in relation to society at large, and public health and safety in particular. Copyright © 2014 Elsevier B.V. All rights reserved.

Efficacy and safety of CT-P13 (biosimilar infliximab) in patients with rheumatoid arthritis: comparison between switching from reference infliximab to CT-P13 and continuing CT-P13 in the PLANETRA extension study

PubMed Central

Yoo, Dae Hyun; Prodanovic, Nenad; Jaworski, Janusz; Miranda, Pedro; Ramiterre, Edgar; Lanzon, Allan; Baranauskaite, Asta; Wiland, Piotr; Abud-Mendoza, Carlos; Oparanov, Boycho; Smiyan, Svitlana; Kim, HoUng; Lee, Sang Joon; Kim, SuYeon; Park, Won

2017-01-01

Objectives To assess the efficacy and safety of switching from the infliximab reference product (RP; Remicade) to its biosimilar CT-P13 (Remsima, Inflectra) or continuing CT-P13 in patients with rheumatoid arthritis (RA) for an additional six infusions. Methods This open-label extension study recruited patients with RA who had completed the 54-week, randomised, parallel-group study comparing CT-P13 with RP (PLANETRA; NCT01217086). CT-P13 (3 mg/kg) was administered intravenously every 8 weeks from weeks 62 to 102. All patients received concomitant methotrexate. Endpoints included American College of Rheumatology 20% (ACR20) response, ACR50, ACR70, immunogenicity and safety. Data were analysed for patients who received CT-P13 for 102 weeks (maintenance group) and for those who received RP for 54 weeks and then switched to CT-P13 (switch group). Results Overall, 302 of 455 patients who completed the PLANETRA study enrolled into the extension. Of these, 158 had received CT-P13 (maintenance group) and 144 RP (switch group). Response rates at week 102 for maintenance versus switch groups, respectively, were 71.7% vs 71.8% for ACR20, 48.0% vs 51.4% for ACR50 and 24.3% vs 26.1% for ACR70. The proportion of patients with antidrug antibodies was comparable between groups (week 102: 40.3% vs 44.8%, respectively). Treatment-emergent adverse events occurred in similar proportions of patients in the two groups during the extension study (53.5% and 53.8%, respectively). Conclusions Comparable efficacy and tolerability were observed in patients who switched from RP to its biosimilar CT-P13 for an additional year and in those who had long-term CT-P13 treatment for 2 years. Trial registration number NCT01571219; Results. PMID:27130908

Evaluation of the Cross-reactivity of Antidrug Antibodies to CT-P13 and Infliximab Reference Product (Remicade): An Analysis Using Immunoassays Tagged with Both Agents.

PubMed

Reinisch, Walter; Jahnsen, Jørgen; Schreiber, Stefan; Danese, Silvio; Panés, Julián; Balsa, Alejandro; Park, Won; Kim, JiSoo; Lee, Jee Un; Yoo, Dae Hyun

2017-06-01

During two pivotal clinical trials of the infliximab biosimilar CT-P13 (PLANETAS and PLANETRA), antidrug antibodies (ADAs) and neutralising antibodies (NAbs) were detected in the sera of patients treated with CT-P13 and the reference product (RP; Remicade). The aim was to assess the comparability of Remicade- and CT-P13-tagged immunoassays for the detection of ADAs and NAbs using data from these trials, in order to determine the cross-reactivity of CT-P13 and RP ADAs. Sera from patients with rheumatoid arthritis and ankylosing spondylitis were analysed using an electrochemiluminescence (ECL) bridging assay or Gyros immunoassay, tagged with Remicade or CT-P13 at screening, weeks 14, 30 and 54, and the end of study visit. NAb titre was compared at screening and weeks 14 and 30. The proportion of cross-reactive samples was determined and an inter-rater agreement analysis performed to assess the concordance of results between assays. In PLANETAS, 93.1% (94/101) of RP ADA-positive samples and 93.0% (93/100) of RP NAb-positive samples cross-reacted with CT-P13; 99.0% (103/104) of CT-P13 ADA-positive and 98.0% (98/100) of CT-P13 NAb-positive samples cross-reacted with the RP. In PLANETRA, 94.7% (426/450) of RP ADA-positive samples and 94.3% (415/440) of RP NAb-positive samples cross-reacted with CT-P13, and 96.6% (458/474) of CT-P13 ADA-positive and 96.4% (452/469) of CT-P13 NAb-positive samples cross-reacted with the RP. In both studies, there was strong agreement in outcome between assays at all post-screening time points (PLANETAS: Cohen's κ 0.89-0.98 for ADA, 0.86-0.98 for NAb; PLANETRA: 0.92-0.94 for both ADA and NAb, all p < 0.001). Significant concordance between assays was observed for NAb titre at weeks 14 and 30 (PLANETAS: Spearman's ρ 0.73 and 0.74, respectively; PLANETRA: 0.61 and 0.72, respectively; all p < 0.001). This study has demonstrated that ADAs and NAbs against CT-P13 and RP are cross-reactive, indicating that CT-P13 and RP share immunodominant epitopes.

Activation and inhibition of CTP synthase from Trypanosoma brucei, the causative agent of African sleeping sickness.

PubMed

Steeves, Craig H; Bearne, Stephen L

2011-09-15

CTP Synthase from Trypanosoma brucei (TbCTPS) catalyzes the conversion of UTP to CTP and is a recognized target for the development of antiprotozoal agents. GTP activates glutamine-dependent CTP formation catalyzed by TbCTPS at concentrations below 0.2 mM, but inhibits this activity at concentrations above 0.2 mM. TbCTPS catalyzes ammonia-dependent CTP formation, which is inhibited by purine derivatives such as GTP, guanosine, caffeine, and uric acid with IC(50) values of 460, 380, 480, and 100 μM, respectively. These observations suggest that the purine ring may serve as a useful scaffold for the development of inhibitors of trypanosomal CTP synthase. Copyright © 2011 Elsevier Ltd. All rights reserved.

Lexical retrieval in discourse: An early indicator of Alzheimer's dementia

PubMed Central

Pekkala, Seija; Wiener, Debra; Himali, Jayandra J.J.; Beiser, Alexa S.; Obler, Loraine K.; Liu, Yulin; McKee, Ann; Auerbach, Sanford; Seshadri, Sudha; Wolf, Philip A.; Au, Rhoda

2014-01-01

We examined the progression of lexical-retrieval deficits in individuals with neuropathologically determined Alzheimer's disease (AD; n = 23) and a comparison group without criteria for AD (n = 24) to determine whether linguistic changes were a significant marker of the disease. Our participants underwent multiple administrations of a neuropsychological battery, with initial administration occurring on average 16 years prior to death. The battery included the Boston Naming Test (BNT), a letter fluency task (FAS), and written description of the Cookie Theft Picture (CTP). Repeated measures analysis revealed that the AD-group showed progressively greater decline in FAS and CTP lexical performance than the comparison group. Cross-sectional time-specific group comparisons indicated that the CTP differentiated performance between the two groups at 7–9 years prior to death and FAS and BNT only at 2–4 years. These results suggest that lexical-retrieval deficits in written discourse serve as an early indicator of AD. PMID:23985011

Lexical retrieval in discourse: an early indicator of Alzheimer's dementia.

PubMed

Pekkala, Seija; Wiener, Debra; Himali, Jayandra J; Beiser, Alexa S; Obler, Loraine K; Liu, Yulin; McKee, Ann; Auerbach, Sanford; Seshadri, Sudha; Wolf, Philip A; Au, Rhoda

2013-12-01

We examined the progression of lexical-retrieval deficits in individuals with neuropathologically determined Alzheimer's disease (AD; n = 23) and a comparison group without criteria for AD (n = 24) to determine whether linguistic changes were a significant marker of the disease. Our participants underwent multiple administrations of a neuropsychological battery, with initial administration occurring on average 16 years prior to death. The battery included the Boston Naming Test (BNT), a letter fluency task (FAS) and written description of the Cookie Theft Picture (CTP). Repeated measures analysis revealed that the AD-group showed progressively greater decline in FAS and CTP lexical performance than the comparison group. Cross-sectional time-specific group comparisons indicated that the CTP differentiated performance between the two groups at 7-9 years prior to death and FAS and BNT only at 2-4 years. These results suggest that lexical-retrieval deficits in written discourse serve as an early indicator of AD.

Personalized assessment of radiation risks from the one-stop-shop myocardial 256-slice CT examination.

PubMed

Perisinakis, Kostas; Seimenis, Ioannis; Tzedakis, Antonis; Pagonidis, Kostas; Papadakis, Antonios E; Damilakis, John

2013-10-15

This study provides data on the cumulative life attributable risk (LAR) of radiation-induced cancer from the combination of coronary CT angiography (CCTA), dynamic CT perfusion (CTP) and delayed enhancement (DE) CT scans, required for reliable risk-benefit analysis of the one-stop-shop CCTA + CTP + DECT cardiac examination. Monte Carlo simulation of the dynamic CTP and DECT exposures on 62 adult individuals was employed to determine radiation absorbed dose to exposed radiosensitive organs. Corresponding data for CCTA were derived using patient chest circumference and previously published data. Individual-specific LARs of cancer were estimated using organ/tissue-specific radiogenic cancer risk factors. Total LAR from CCTA + CTP + DECT scans' sequence were estimated and compared to nominal intrinsic risk of cancer. The main contribution, up to 80%, to cumulative radiation burden from CCTA + CTP + DECT scan-sequence was found to originate from the CTP scan. The total LAR from CCTA + CTP + DECT for females was found 4-6 times higher, compared to males. The mean cumulative risk of radiogenic cancer associated with the complete CCTA + CTP + DECT scan sequence was found to marginally increase the intrinsic risk for cancer induction by less than 0.6% and 0.1% for females and males, respectively. The radiation risk from the 256-slice CCTA + CTP + DECT scan sequence may be considered low and should not constitute an obstacle for the clinical endorsement of the one-stop-shop cardiac CT examination, given that its clinical value has been well verified. Nevertheless, every effort should be made towards optimization of the dynamic CTP component which is the main contributor to patient radiation burden. © 2013.

Are dispensaries indispensable? Patient experiences of access to cannabis from medical cannabis dispensaries in Canada.

PubMed

Capler, Rielle; Walsh, Zach; Crosby, Kim; Belle-Isle, Lynne; Holtzman, Susan; Lucas, Philippe; Callaway, Robert

2017-09-01

In 2001, Canada established a federal program for cannabis for therapeutic purposes (CTP). Medical cannabis dispensaries (dispensaries) are widely accessed as a source of CTP despite storefront sales of cannabis being illegal. The discrepancy between legal status and social practice has fuelled active debate regarding the role of dispensaries. The present study aims to inform this debate by analysing CTP user experiences with different CTP sources, and comparing dispensary users to those accessing CTP from other sources. We compared sociodemographic characteristics, health related factors and patterns of cannabis use of 445 respondents, 215 who accessed CTP from dispensaries with 230 who accessed other sources. We compared patients' ratings of CTP sources (dispensaries, Health Canada's supplier, self-production, other producer, friend or acquaintance, street dealer) for quality and availability of product, safety and efficiency of access, cost, and feeling respected while accessing. Patients using dispensaries were older, more likely to have arthritis and HIV/AIDS, and less likely to have mental health conditions than those not using dispensaries. Those accessing dispensaries used larger quantities of cannabis, placed greater value on access to specific strains, and were more likely to have legal authorization for CTP. Dispensaries were rated equally to or more favourably than other sources of CTP for quality, safety, availability, efficiency and feeling respected, and less favourably than self-production and other producer for cost. Given the high endorsement of dispensaries by patients, future regulations should consider including dispensaries as a source of CTP and address known barriers to access such as cost and health care provider support. Further research should assess the impact of the addition of licensed producers on the role and perceived value of dispensaries within the Canadian medical cannabis system. Copyright © 2017 Elsevier B.V. All rights reserved.

Noise characteristics of CT perfusion imaging: how does noise propagate from source images to final perfusion maps?

NASA Astrophysics Data System (ADS)

Li, Ke; Chen, Guang-Hong

2016-03-01

Cerebral CT perfusion (CTP) imaging is playing an important role in the diagnosis and treatment of acute ischemic strokes. Meanwhile, the reliability of CTP-based ischemic lesion detection has been challenged due to the noisy appearance and low signal-to-noise ratio of CTP maps. To reduce noise and improve image quality, a rigorous study on the noise transfer properties of CTP systems is highly desirable to provide the needed scientific guidance. This paper concerns how noise in the CTP source images propagates to the final CTP maps. Both theoretical deviations and subsequent validation experiments demonstrated that, the noise level of background frames plays a dominant role in the noise of the cerebral blood volume (CBV) maps. This is in direct contradiction with the general belief that noise of non-background image frames is of greater importance in CTP imaging. The study found that when radiation doses delivered to the background frames and to all non-background frames are equal, lowest noise variance is achieved in the final CBV maps. This novel equality condition provides a practical means to optimize radiation dose delivery in CTP data acquisition: radiation exposures should be modulated between background frames and non-background frames so that the above equality condition is satisïnAed. For several typical CTP acquisition protocols, numerical simulations and in vivo canine experiment demonstrated that noise of CBV can be effectively reduced using the proposed exposure modulation method.

Perceptions of cannabis as a stigmatized medicine: a qualitative descriptive study

PubMed Central

2013-01-01

Background Despite its increasing prevalence and acceptance among the general public, cannabis use continues to be viewed as an aberrant activity in many contexts. However, little is known about how stigma associated with cannabis use affects individuals who use cannabis for therapeutic purposes (CTP) and what strategies these individuals employ to manage associated stigma. The aim of this Canadian study was to describe users’ perceptions of and responses to the stigma attached to using CTP. Methods Twenty-three individuals who were using CTP for a range of health problems took part in semi-structured interviews. Transcribed data were analyzed using an inductive approach and comparative strategies to explore participants’ perceptions of CTP and identify themes. Results Participant experiences of stigma were related to negative views of cannabis as a recreational drug, the current criminal sanctions associated with cannabis use, and using cannabis in the context of stigmatizing vulnerability (related to existing illness and disability). Strategies for managing the resulting stigma of using CTP included: keeping CTP ‘undercover’; educating those who did not approve of or understand CTP use; and using cannabis responsibly. Conclusions Understanding how individuals perceive and respond to stigma can inform the development of strategies aimed at reducing stigma associated with the use of CTP and thereby address barriers faced by those using this medicine. PMID:23414118

A benchmarking tool to evaluate computer tomography perfusion infarct core predictions against a DWI standard.

PubMed

Cereda, Carlo W; Christensen, Søren; Campbell, Bruce Cv; Mishra, Nishant K; Mlynash, Michael; Levi, Christopher; Straka, Matus; Wintermark, Max; Bammer, Roland; Albers, Gregory W; Parsons, Mark W; Lansberg, Maarten G

2016-10-01

Differences in research methodology have hampered the optimization of Computer Tomography Perfusion (CTP) for identification of the ischemic core. We aim to optimize CTP core identification using a novel benchmarking tool. The benchmarking tool consists of an imaging library and a statistical analysis algorithm to evaluate the performance of CTP. The tool was used to optimize and evaluate an in-house developed CTP-software algorithm. Imaging data of 103 acute stroke patients were included in the benchmarking tool. Median time from stroke onset to CT was 185 min (IQR 180-238), and the median time between completion of CT and start of MRI was 36 min (IQR 25-79). Volumetric accuracy of the CTP-ROIs was optimal at an rCBF threshold of <38%; at this threshold, the mean difference was 0.3 ml (SD 19.8 ml), the mean absolute difference was 14.3 (SD 13.7) ml, and CTP was 67% sensitive and 87% specific for identification of DWI positive tissue voxels. The benchmarking tool can play an important role in optimizing CTP software as it provides investigators with a novel method to directly compare the performance of alternative CTP software packages. © The Author(s) 2015.

Tetrameric Ctp1 coordinates DNA binding and DNA bridging in DNA double-strand-break repair

DOE PAGES

Andres, Sara N.; Appel, C. Denise; Westmoreland, James W.; ...

2015-01-12

Ctp1 (also known as CtIP or Sae2) collaborates with Mre11-Rad50-Nbs1 to initiate repair of DNA double-strand breaks (DSBs), but its functions remain enigmatic. In this paper, we report that tetrameric Schizosaccharomyces pombe Ctp1 contains multivalent DNA-binding and DNA-bridging activities. Through structural and biophysical analyses of the Ctp1 tetramer, we define the salient features of Ctp1 architecture: an N-terminal interlocking tetrameric helical dimer-of-dimers (THDD) domain and a central intrinsically disordered region (IDR) linked to C-terminal 'RHR' DNA-interaction motifs. The THDD, IDR and RHR are required for Ctp1 DNA-bridging activity in vitro, and both the THDD and RHR are required for efficientmore » DSB repair in S. pombe. Finally, our results establish non-nucleolytic roles of Ctp1 in binding and coordination of DSB-repair intermediates and suggest that ablation of human CtIP DNA binding by truncating mutations underlie the CtIP-linked Seckel and Jawad syndromes.« less

Computed Tomographic Perfusion Predicts Poor Outcomes in a Randomized Trial of Endovascular Therapy.

PubMed

Wannamaker, Robert; Guinand, Taurian; Menon, Bijoy K; Demchuk, Andrew; Goyal, Mayank; Frei, Donald; Bharatha, Aditya; Jovin, Tudor G; Shankar, Jai; Krings, Timo; Baxter, Blaise; Holmstedt, Christine; Swartz, Richard; Dowlatshahi, Dar; Chan, Richard; Tampieri, Donatella; Choe, Hana; Burns, Paul; Gentile, Nina; Rempel, Jeremy; Shuaib, Ashfaq; Buck, Brian; Bivard, Andrew; Hill, Michael; Butcher, Kenneth

2018-06-01

In the ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times), patients with large vessel occlusions and small infarct cores identified with computed tomography (CT)/CT angiography were randomized to endovascular therapy or standard of care. CT perfusion (CTP) was obtained in some cases but was not used to select patients. We tested the hypothesis that patients with penumbral CTP patterns have higher rates of good clinical outcome. All CTP data acquired in ESCAPE patients were analyzed centrally using a semiautomated perfusion threshold-based approach. A penumbral pattern was defined as an infarct core <70 mL, penumbral volume >15 mL, and a total hypoperfused volume:core volume ratio of >1.8. The primary outcome was good functional outcome at 90 days (modified Rankin Scale score, 0-2). CTP was acquired in 138 of 316 ESCAPE patients. Penumbral patterns were present in 116 of 128 (90.6%) of patients with interpretable CTP data. The rate of good functional outcome in penumbral pattern patients (53 of 114; 46%) was higher than that in nonpenumbral patients (2 of 12; 17%; P =0.041). In penumbral patients, endovascular therapy increased the likelihood of a good clinical outcome (34 of 58; 57%) compared with those in the control group (19 of 58; 33%; odds ratio, 2.68; 95% confidence interval, 1.25-5.76; P =0.011). Only 3 of 12 nonpenumbral patients were randomized to the endovascular group, preventing an analysis of treatment effect. The majority of patients with CTP imaging in the ESCAPE trial had penumbral patterns, which were associated with better outcomes overall. Patients with penumbra treated with endovascular therapy had the greatest odds of good functional outcome. Nonpenumbral patients were much less likely to achieve good outcomes. © 2018 American Heart Association, Inc.

Limited reliability of computed tomographic perfusion acute infarct volume measurements compared with diffusion-weighted imaging in anterior circulation stroke.

PubMed

Schaefer, Pamela W; Souza, Leticia; Kamalian, Shervin; Hirsch, Joshua A; Yoo, Albert J; Kamalian, Shahmir; Gonzalez, R Gilberto; Lev, Michael H

2015-02-01

Diffusion-weighted imaging (DWI) can reliably identify critically ischemic tissue shortly after stroke onset. We tested whether thresholded computed tomographic cerebral blood flow (CT-CBF) and CT-cerebral blood volume (CT-CBV) maps are sufficiently accurate to substitute for DWI for estimating the critically ischemic tissue volume. Ischemic volumes of 55 patients with acute anterior circulation stroke were assessed on DWI by visual segmentation and on CT-CBF and CT-CBV with segmentation using 15% and 30% thresholds, respectively. The contrast:noise ratios of ischemic regions on the DWI and CT perfusion (CTP) images were measured. Correlation and Bland-Altman analyses were used to assess the reliability of CTP. Mean contrast:noise ratios for DWI, CT-CBF, and CT-CBV were 4.3, 0.9, and 0.4, respectively. CTP and DWI lesion volumes were highly correlated (R(2)=0.87 for CT-CBF; R(2)=0.83 for CT-CBV; P<0.001). Bland-Altman analyses revealed little systemic bias (-2.6 mL) but high measurement variability (95% confidence interval, ±56.7 mL) between mean CT-CBF and DWI lesion volumes, and systemic bias (-26 mL) and high measurement variability (95% confidence interval, ±64.0 mL) between mean CT-CBV and DWI lesion volumes. A simulated treatment study demonstrated that using CTP-CBF instead of DWI for detecting a statistically significant effect would require at least twice as many patients. The poor contrast:noise ratios of CT-CBV and CT-CBF compared with those of DWI result in large measurement error, making it problematic to substitute CTP for DWI in selecting individual acute stroke patients for treatment. CTP could be used for treatment studies of patient groups, but the number of patients needed to identify a significant effect is much higher than the number needed if DWI is used. © 2014 American Heart Association, Inc.

Inventory of File WAFS_blended_2014102006f06.grib2

Science.gov Websites

) [%] 004 700 mb CTP 6 hour fcst In-Cloud Turbulence [%] spatial ave,code table 4.15=3,#points=1 005 700 mb CTP 6 hour fcst In-Cloud Turbulence [%] spatial max,code table 4.15=3,#points=1 006 600 mb CTP 6 hour fcst In-Cloud Turbulence [%] spatial ave,code table 4.15=3,#points=1 007 600 mb CTP 6 hour fcst In

Computed Tomography Perfusion Improves Diagnostic Accuracy in Acute Posterior Circulation Stroke.

PubMed

Sporns, Peter; Schmidt, Rene; Minnerup, Jens; Dziewas, Rainer; Kemmling, André; Dittrich, Ralf; Zoubi, Tarek; Heermann, Philipp; Cnyrim, Christian; Schwindt, Wolfram; Heindel, Walter; Niederstadt, Thomas; Hanning, Uta

2016-01-01

Computed tomography perfusion (CTP) has a high diagnostic value in the detection of acute ischemic stroke in the anterior circulation. However, the diagnostic value in suspected posterior circulation (PC) stroke is uncertain, and whole brain volume perfusion is not yet in widespread use. We therefore studied the additional value of whole brain volume perfusion to non-contrast CT (NCCT) and CT angiography source images (CTA-SI) for infarct detection in patients with suspected acute ischemic PC stroke. This is a retrospective review of patients with suspected stroke in the PC in a database of our stroke center (n = 3,011) who underwent NCCT, CTA and CTP within 9 h after stroke onset and CT or MRI on follow-up. Images were evaluated for signs and pc-ASPECTS locations of ischemia. Three imaging models - A (NCCT), B (NCCT + CTA-SI) and C (NCCT + CTA-SI + CTP) - were compared with regard to the misclassification rate relative to gold standard (infarction in follow-up imaging) using the McNemar's test. Of 3,011 stroke patients, 267 patients had a suspected stroke in the PC and 188 patients (70.4%) evidenced a PC infarct on follow-up imaging. The sensitivity of Model C (76.6%) was higher compared with that of Model A (21.3%) and Model B (43.6%). CTP detected significantly more ischemic lesions, especially in the cerebellum, posterior cerebral artery territory and thalami. Our findings in a large cohort of consecutive patients show that CTP detects significantly more ischemic strokes in the PC than CTA and NCCT alone. © 2016 S. Karger AG, Basel.

A Novel P1B-type Mn2+-transporting ATPase Is Required for Secreted Protein Metallation in Mycobacteria*

PubMed Central

Padilla-Benavides, Teresita; Long, Jarukit E.; Raimunda, Daniel; Sassetti, Christopher M.; Argüello, José M.

2013-01-01

Transition metals are central for bacterial virulence and host defense. P1B-ATPases are responsible for cytoplasmic metal efflux and play roles either in limiting cytosolic metal concentrations or in the maturation of secreted metalloproteins. The P1B-ATPase, CtpC, is required for Mycobacterium tuberculosis survival in a mouse model (Sassetti, C. M., and Rubin, E. J. (2003) Genetic requirements for mycobacterial survival during infection. Proc. Natl. Acad. Sci. U.S.A. 100, 12989–12994). CtpC prevents Zn2+ toxicity, suggesting a role in Zn2+ export from the cytosol (Botella, H., Peyron, P., Levillain, F., Poincloux, R., Poquet, Y., Brandli, I., Wang, C., Tailleux, L., Tilleul, S., Charriere, G. M., Waddell, S. J., Foti, M., Lugo-Villarino, G., Gao, Q., Maridonneau-Parini, I., Butcher, P. D., Castagnoli, P. R., Gicquel, B., de Chastellièr, C., and Neyrolles, O. (2011) Mycobacterial P1-type ATPases mediate resistance to zinc poisoning in human macrophages. Cell Host Microbe 10, 248–259). However, key metal-coordinating residues and the overall structure of CtpC are distinct from Zn2+-ATPases. We found that isolated CtpC has metal-dependent ATPase activity with a strong preference for Mn2+ over Zn2+. In vivo, CtpC is unable to complement Escherichia coli lacking a functional Zn2+-ATPase. Deletion of M. tuberculosis or Mycobacterium smegmatis ctpC leads to cytosolic Mn2+ accumulation but no alterations in other metals levels. Whereas ctpC-deficient M. tuberculosis is sensitive to extracellular Zn2+, the M. smegmatis mutant is not. Both ctpC mutants are sensitive to oxidative stress, which might explain the Zn2+-sensitive phenotype of the M. tuberculosis ctpC mutant. CtpC is a high affinity/slow turnover ATPase, suggesting a role in protein metallation. Consistent with this hypothesis, mutation of CtpC leads to a decrease of Mn2+ bound to secreted proteins and of the activity of secreted Fe/Mn-superoxide dismutase, particularly in M. smegmatis. Alterations in the assembly of metalloenzymes involved in redox stress response might explain the sensitivity of M. tuberculosis ctpC mutants to oxidative stress and growth and persistence defects in mice infection models. PMID:23482562

Identification of CtpL as a chromosomally encoded chemoreceptor for 4-chloroaniline and catechol in Pseudomonas aeruginosa PAO1.

PubMed

Vangnai, Alisa S; Takeuchi, Kazuki; Oku, Shota; Kataoka, Naoya; Nitisakulkan, Tisana; Tajima, Takahisa; Kato, Junichi

2013-12-01

Bacterial chemotaxis influences the ability of bacteria to survive and thrive in most environments, including polluted ones. Despite numerous reports of the phenotypic characterization of chemotactic bacteria, only a few molecular details of chemoreceptors for aromatic pollutants have been described. In this study, the molecular basis of chemotaxis toward an environmentally toxic chlorinated aromatic pollutant, 4-chloroaniline (4CA), was evaluated. Among the three Pseudomonas spp. tested, Pseudomonas aeruginosa PAO1 exhibited positive chemotaxis both to the nonmetabolizable 4CA, where 4-chloroacetanilide was formed as a dead-end transformation product, and to the metabolizable catechol. Molecular analysis of all 26 mutants with a disrupted methyl-accepting chemotaxis gene revealed that CtpL, a chromosomally encoded chemoreceptor, was responsible for the positive chemotactic response toward 4CA. Since CtpL has previously been described to be a major chemoreceptor for inorganic phosphate at low concentrations in PAO1, this report describes a fortuitous ability of CtpL to function toward aromatic pollutants. In addition, its regulation not only was dependent on the presence of the chemoattractant inducer but also was regulated by conditions of phosphate starvation. These results expand the range of known chemotactic transducers and their function in the environmental bacterium PAO1.

Prospective assessment of bone turnover and clinical bone diseases after allogeneic hematopoietic stem-cell transplantation.

PubMed

Petropoulou, Anna D; Porcher, Raphael; Herr, Andrée-Laure; Devergie, Agnès; Brentano, Thomas Funck; Ribaud, Patricia; Pinto, Fernando O; Rocha, Vanderson; Peffault de Latour, Régis; Orcel, Philippe; Socié, Gérard; Robin, Marie

2010-06-15

Bone complications after hematopoietic stem-cell transplantation (HSCT) are relatively frequent. Evaluation of biomarkers of bone turnover and dual energy x-ray absorptiometry (DEXA) are not known in this context. We prospectively evaluated bone mineral density, biomarkers of bone turnover, and the cumulative incidence of bone complications after allogeneic HSCT. One hundred forty-six patients were included. Bone mineral density was measured by DEXA 2-month and 1-year post-HSCT. The markers of bone turnover were serum C-telopeptide (C-TP), 5 tartrate-resistant acid phosphatase (bone resorption), and osteocalcin (bone formation) determined pre-HSCT and 2 months and 1 year thereafter. Potential association between osteoporosis at 2 months, osteoporotic fracture or avascular necrosis and, individual patient's characteristics and biologic markers were tested. C-TP was high before and 2 months after transplant. At 2 months, DEXA detected osteoporosis in more than half the patients tested. Male sex, median age less than or equal to 15 years, and abnormal C-TP before HSCT were risk factors significantly associated with osteoporosis. Three-year cumulative incidences of fractures and avascular necrosis were 8% and 11%, respectively. Children were at higher risk of fracture, whereas corticosteroid treatment duration was a significant risk factor for developing a clinical bone complication post-HSCT. Bone complications and osteoporosis are frequent after HSCT. Bone biologic markers and DEXA showed that subclinical bone abnormalities appeared early post-HSCT. The risk factors, age, gender, and C-TP easily available at the time of transplantation were identified. Biphosphonates should probably be given to patients with those risk factors.

Gemcitabine diphosphate choline is a major metabolite linked to the Kennedy pathway in pancreatic cancer models in vivo.

PubMed

Bapiro, T E; Frese, K K; Courtin, A; Bramhall, J L; Madhu, B; Cook, N; Neesse, A; Griffiths, J R; Tuveson, D A; Jodrell, D I; Richards, F M

2014-07-15

The modest benefits of gemcitabine (dFdC) therapy in patients with pancreatic ductal adenocarcinoma (PDAC) are well documented, with drug delivery and metabolic lability cited as important contributing factors. We have used a mouse model of PDAC: KRAS(G12D); p53(R172H); pdx-Cre (KPC) that recapitulates the human disease to study dFdC intra-tumoural metabolism. LC-MS/MS and NMR were used to measure drug and physiological analytes. Cytotoxicity was assessed by the Sulphorhodamine B assay. In KPC tumour tissue, we identified a new, Kennedy pathway-linked dFdC metabolite (gemcitabine diphosphate choline (GdPC)) present at equimolar amounts to its precursor, the accepted active metabolite gemcitabine triphosphate (dFdCTP). Utilising additional subcutaneous PDAC tumour models, we demonstrated an inverse correlation between GdPC/dFdCTP ratios and cytidine triphosphate (CTP). In tumour homogenates in vitro, CTP inhibited GdPC formation from dFdCTP, indicating competition between CTP and dFdCTP for CTP:phosphocholine cytidylyltransferase (CCT). As the structure of GdPC precludes entry into cells, potential cytotoxicity was assessed by stimulating CCT activity using linoleate in KPC cells in vitro, leading to increased GdPC concentration and synergistic growth inhibition after dFdC addition. GdPC is an important element of the intra-tumoural dFdC metabolic pathway in vivo.

Comparable Immune Function Inhibition by the Infliximab Biosimilar CT-P13: Implications for Treatment of Inflammatory Bowel Disease.

PubMed

Lim, Ki Jung; Lee, So Jung; Kim, Sunghwan; Lee, Su Yeon; Lee, Min Seob; Park, Yoon A; Choi, Eun Jin; Lee, Eun Beom; Jun, Hwang Keun; Cho, Jong Moon; Lee, SooYoung; Kwon, Ki Sung; Lim, Byung Pil; Jeon, Myung-Shin; Shin, Eui Cheol; Choi, Yong Sung; Fudim, Ella; Picard, Orit; Yavzori, Miri; Ben-Horin, Shomron; Chang, Shin Jae

2017-05-01

CT-P13 is the first biosimilar monoclonal antibody to infliximab, and was recently approved in the European Union, Japan, Korea, and USA for all six indications of infliximab. However, studies directly assessing the biologic activity of CT-P13 versus inflximab in the context of inflammatory bowel disease [IBD] are still scanty. In the present study, we aimed to compare the biological activities of CT-P13 and infliximab with specific focus on intestinal cells so as to gain insight into the potential biosimilarity of these two agents for treatment of IBD. CT-P13 and infliximab were investigated and compared by in vitro experiments for their neutralisation ability of soluble tumour necrosis factor alpha [sTNFα] and membrane-bound tumour necrosis factor alpha [mTNFα], suppression of cytokine release by reverse signalling, induction of regulatory macrophages and wound healing, and antibody-dependent cell cytotoxicity [ADCC]. CT-P13 showed similar biological activities to infliximab as gauged by neutralisation of soluble TNFα, as well as blockade of apoptosis and suppression of pro-inflammatory cytokines in intestinal Caco-2 cells. Infliximab and CT-P13 equally induced apoptosis and outside-to-inside signals through transmembrane TNFα [tmTNFα]. Moreover, regulatory macrophage induction and ensuing wound healing were similarly exerted by CT-P13 and infliximab. However, neither CT-P13 nor infliximab exerted any significant ADCC of ex vivo-stimulated peripheral blood monocytes or lamina propria mononuclear cells from IBD patients. These findings indicate that CT-P13 and infliximab exert highly similar biological activities in intestinal cells, and further support a mechanistic comparability of these two drugs in the treatment of IBD. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

Efficacy and safety of switching from reference infliximab to CT-P13 compared with maintenance of CT-P13 in ankylosing spondylitis: 102-week data from the PLANETAS extension study

PubMed Central

Park, Won; Yoo, Dae Hyun; Miranda, Pedro; Brzosko, Marek; Wiland, Piotr; Gutierrez-Ureña, Sergio; Mikazane, Helena; Lee, Yeon-Ah; Smiyan, Svitlana; Lim, Mie-Jin; Kadinov, Vladimir; Abud-Mendoza, Carlos; Kim, HoUng; Lee, Sang Joon; Bae, YunJu; Kim, SuYeon; Braun, Jürgen

2017-01-01

Objectives To investigate the efficacy and safety of switching from infliximab reference product (RP) to its biosimilar or maintaining biosimilar treatment in patients with ankylosing spondylitis (AS). Methods This open-label extension study recruited patients with AS who completed a 54-week, randomised controlled study comparing CT-P13 with RP (PLANETAS). CT-P13 (5 mg/kg) was administered intravenously every 8 weeks from week 62 to week 102. Efficacy end points included the proportion of patients achieving Assessment of SpondyloArthritis international Society (ASAS)20. Antidrug antibodies (ADAs) were measured using an electrochemiluminescent method. Data were analysed for patients treated with CT-P13 in the main PLANETAS study and the extension (maintenance group) and those who were switched to CT-P13 during the extension study (switch group). Results Overall, 174 (82.9%) of 210 patients who completed the first 54 weeks of PLANETAS and agreed to participate in the extension were enrolled. Among these, 88 were maintained on CT-P13 and 86 were switched to CT-P13 from RP. In these maintenance and switch groups, respectively, ASAS20 response rates at week 102 were 80.7% and 76.9%. ASAS40 and ASAS partial remission were also similar between groups. ADA positivity rates were comparable (week 102: 23.3% vs 27.4%). Adverse events led to treatment discontinuation during the extension study in 3 (3.3%) and 4 (4.8%) patients, respectively. Conclusions This is the first study to show that switching from RP to its biosimilar CT-P13 is possible without negative effects on safety or efficacy in patients with AS. In the maintenance group, CT-P13 was effective and well tolerated over 2 years of treatment. Trial registration number NCT01571206; Results. PMID:27117698

Diagnostic accuracy of semi-automatic quantitative metrics as an alternative to expert reading of CT myocardial perfusion in the CORE320 study.

PubMed

Ostovaneh, Mohammad R; Vavere, Andrea L; Mehra, Vishal C; Kofoed, Klaus F; Matheson, Matthew B; Arbab-Zadeh, Armin; Fujisawa, Yasuko; Schuijf, Joanne D; Rochitte, Carlos E; Scholte, Arthur J; Kitagawa, Kakuya; Dewey, Marc; Cox, Christopher; DiCarli, Marcelo F; George, Richard T; Lima, Joao A C

To determine the diagnostic accuracy of semi-automatic quantitative metrics compared to expert reading for interpretation of computed tomography perfusion (CTP) imaging. The CORE320 multicenter diagnostic accuracy clinical study enrolled patients between 45 and 85 years of age who were clinically referred for invasive coronary angiography (ICA). Computed tomography angiography (CTA), CTP, single photon emission computed tomography (SPECT), and ICA images were interpreted manually in blinded core laboratories by two experienced readers. Additionally, eight quantitative CTP metrics as continuous values were computed semi-automatically from myocardial and blood attenuation and were combined using logistic regression to derive a final quantitative CTP metric score. For the reference standard, hemodynamically significant coronary artery disease (CAD) was defined as a quantitative ICA stenosis of 50% or greater and a corresponding perfusion defect by SPECT. Diagnostic accuracy was determined by area under the receiver operating characteristic curve (AUC). Of the total 377 included patients, 66% were male, median age was 62 (IQR: 56, 68) years, and 27% had prior myocardial infarction. In patient based analysis, the AUC (95% CI) for combined CTA-CTP expert reading and combined CTA-CTP semi-automatic quantitative metrics was 0.87(0.84-0.91) and 0.86 (0.83-0.9), respectively. In vessel based analyses the AUC's were 0.85 (0.82-0.88) and 0.84 (0.81-0.87), respectively. No significant difference in AUC was found between combined CTA-CTP expert reading and CTA-CTP semi-automatic quantitative metrics in patient based or vessel based analyses(p > 0.05 for all). Combined CTA-CTP semi-automatic quantitative metrics is as accurate as CTA-CTP expert reading to detect hemodynamically significant CAD. Copyright © 2018 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

The Pseudomonas aeruginosa Periplasmic Protease CtpA Can Affect Systems That Impact Its Ability To Mount Both Acute and Chronic Infections

PubMed Central

Seo, Jin

2013-01-01

Proteases play important roles in the virulence of Pseudomonas aeruginosa. Some are exported to act on host targets and facilitate tissue destruction and bacterial dissemination. Others work within the bacterial cell to process virulence factors and regulate virulence gene expression. Relatively little is known about the role of one class of bacterial serine proteases known as the carboxyl-terminal processing proteases (CTPs). The P. aeruginosa genome encodes two CTPs annotated as PA3257/Prc and PA5134/CtpA in strain PAO1. Prc degrades mutant forms of the anti-sigma factor MucA to promote mucoidy in some cystic fibrosis lung isolates. However, nothing is known about the role or importance of CtpA. We have now found that endogenous CtpA is a soluble periplasmic protein and that a ctpA null mutant has specific phenotypes consistent with an altered cell envelope. Although a ctpA null mutation has no major effect on bacterial growth in the laboratory, CtpA is essential for the normal function of the type 3 secretion system (T3SS), for cytotoxicity toward host cells, and for virulence in a mouse model of acute pneumonia. Conversely, increasing the amount of CtpA above its endogenous level induces an uncharacterized extracytoplasmic function sigma factor regulon, an event that has been reported to attenuate P. aeruginosa in a rat model of chronic lung infection. Therefore, a normal level of CtpA activity is critical for T3SS function and acute virulence, whereas too much activity can trigger an apparent stress response that is detrimental to chronic virulence. PMID:24082078

Identification and Characterization of the Nuclear Isoform of Drosophila melanogaster CTP:Phosphocholine Cytidylyltransferase

USDA-ARS?s Scientific Manuscript database

CTP:phosphocholine cytidylyltransferase (CCT) catalyzes the conversion of phosphocholine and cytidine 5'-triphosphate (CTP) to CDP-choline for the eventual synthesis of phosphatidylcholine (PC). The enzyme is regulated by reversible association with cellular membranes, with the rate of catalysis in...

Gemcitabine diphosphate choline is a major metabolite linked to the Kennedy pathway in pancreatic cancer models in vivo

PubMed Central

Bapiro, T E; Frese, K K; Courtin, A; Bramhall, J L; Madhu, B; Cook, N; Neesse, A; Griffiths, J R; Tuveson, D A; Jodrell, D I; Richards, F M

2014-01-01

Background: The modest benefits of gemcitabine (dFdC) therapy in patients with pancreatic ductal adenocarcinoma (PDAC) are well documented, with drug delivery and metabolic lability cited as important contributing factors. We have used a mouse model of PDAC: KRASG12D; p53R172H; pdx-Cre (KPC) that recapitulates the human disease to study dFdC intra-tumoural metabolism. Methods: LC-MS/MS and NMR were used to measure drug and physiological analytes. Cytotoxicity was assessed by the Sulphorhodamine B assay. Results: In KPC tumour tissue, we identified a new, Kennedy pathway-linked dFdC metabolite (gemcitabine diphosphate choline (GdPC)) present at equimolar amounts to its precursor, the accepted active metabolite gemcitabine triphosphate (dFdCTP). Utilising additional subcutaneous PDAC tumour models, we demonstrated an inverse correlation between GdPC/dFdCTP ratios and cytidine triphosphate (CTP). In tumour homogenates in vitro, CTP inhibited GdPC formation from dFdCTP, indicating competition between CTP and dFdCTP for CTP:phosphocholine cytidylyltransferase (CCT). As the structure of GdPC precludes entry into cells, potential cytotoxicity was assessed by stimulating CCT activity using linoleate in KPC cells in vitro, leading to increased GdPC concentration and synergistic growth inhibition after dFdC addition. Conclusions: GdPC is an important element of the intra-tumoural dFdC metabolic pathway in vivo. PMID:24874484

Evaluating blood-brain barrier permeability in delayed cerebral infarction after aneurysmal subarachnoid hemorrhage.

PubMed

Ivanidze, J; Kesavabhotla, K; Kallas, O N; Mir, D; Baradaran, H; Gupta, A; Segal, A Z; Claassen, J; Sanelli, P C

2015-05-01

Patients with SAH are at increased risk of delayed infarction. Early detection and treatment of delayed infarction remain challenging. We assessed blood-brain barrier permeability, measured as permeability surface area product, by using CTP in patients with SAH with delayed infarction. We performed a retrospective study of patients with SAH with delayed infarction on follow-up NCCT. CTP was performed before the development of delayed infarction. CTP data were postprocessed into permeability surface area product, CBF, and MTT maps. Coregistration was performed to align the infarcted region on the follow-up NCCT with the corresponding location on the CTP maps obtained before infarction. Permeability surface area product, CBF, and MTT values were then obtained in the location of the subsequent infarction. The contralateral noninfarcted region was compared with the affected side in each patient. Wilcoxon signed rank tests were performed to determine statistical significance. Clinical data were collected at the time of CTP and at the time of follow-up NCCT. Twenty-one patients with SAH were included in the study. There was a statistically significant increase in permeability surface area product in the regions of subsequent infarction compared with the contralateral control regions (P < .0001). However, CBF and MTT values were not significantly different in these 2 regions. Subsequent follow-up NCCT demonstrated new delayed infarction in all 21 patients, at which time 38% of patients had new focal neurologic deficits. Our study reveals a statistically significant increase in permeability surface area product preceding delayed infarction in patients with SAH. Further investigation of early permeability changes in SAH may provide new insights into the prediction of delayed infarction. © 2015 by American Journal of Neuroradiology.

Efficacy and safety of switching from reference infliximab to CT-P13 compared with maintenance of CT-P13 in ankylosing spondylitis: 102-week data from the PLANETAS extension study.

PubMed

Park, Won; Yoo, Dae Hyun; Miranda, Pedro; Brzosko, Marek; Wiland, Piotr; Gutierrez-Ureña, Sergio; Mikazane, Helena; Lee, Yeon-Ah; Smiyan, Svitlana; Lim, Mie-Jin; Kadinov, Vladimir; Abud-Mendoza, Carlos; Kim, HoUng; Lee, Sang Joon; Bae, YunJu; Kim, SuYeon; Braun, Jürgen

2017-02-01

To investigate the efficacy and safety of switching from infliximab reference product (RP) to its biosimilar or maintaining biosimilar treatment in patients with ankylosing spondylitis (AS). This open-label extension study recruited patients with AS who completed a 54-week, randomised controlled study comparing CT-P13 with RP (PLANETAS). CT-P13 (5 mg/kg) was administered intravenously every 8 weeks from week 62 to week 102. Efficacy end points included the proportion of patients achieving Assessment of SpondyloArthritis international Society (ASAS)20. Antidrug antibodies (ADAs) were measured using an electrochemiluminescent method. Data were analysed for patients treated with CT-P13 in the main PLANETAS study and the extension (maintenance group) and those who were switched to CT-P13 during the extension study (switch group). Overall, 174 (82.9%) of 210 patients who completed the first 54 weeks of PLANETAS and agreed to participate in the extension were enrolled. Among these, 88 were maintained on CT-P13 and 86 were switched to CT-P13 from RP. In these maintenance and switch groups, respectively, ASAS20 response rates at week 102 were 80.7% and 76.9%. ASAS40 and ASAS partial remission were also similar between groups. ADA positivity rates were comparable (week 102: 23.3% vs 27.4%). Adverse events led to treatment discontinuation during the extension study in 3 (3.3%) and 4 (4.8%) patients, respectively. This is the first study to show that switching from RP to its biosimilar CT-P13 is possible without negative effects on safety or efficacy in patients with AS. In the maintenance group, CT-P13 was effective and well tolerated over 2 years of treatment. NCT01571206; Results. 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/.

Pilot study comparing the Childhood Arthritis & Rheumatology Research Alliance (CARRA) systemic Juvenile Idiopathic Arthritis Consensus Treatment Plans.

PubMed

Kimura, Yukiko; Grevich, Sriharsha; Beukelman, Timothy; Morgan, Esi; Nigrovic, Peter A; Mieszkalski, Kelly; Graham, T Brent; Ibarra, Maria; Ilowite, Norman; Klein-Gitelman, Marisa; Onel, Karen; Prahalad, Sampath; Punaro, Marilynn; Ringold, Sarah; Toib, Dana; Van Mater, Heather; Weiss, Jennifer E; Weiss, Pamela F; Schanberg, Laura E

2017-04-11

To assess the feasibility of studying the comparative effectiveness of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plans (CTPs) for systemic Juvenile Idiopathic Arthritis (JIA) using an observational registry. Untreated systemic JIA patients enrolled in the CARRA Registry were begun on one of 4 CTPs chosen by the treating physician and patient/family (glucocorticoid [GC] alone; methotrexate [MTX] ± GC; IL1 inhibitor [IL1i] ± GC; IL6 inhibitor [IL6i] ± GC). The primary outcome of clinical inactive disease (CID) without current GC use was assessed at 9 months. clinicaltrials.gov NCT01697254; first registered 9/28/12 (retrospectively enrolled). Thirty patients were enrolled at 13 sites; eight patients were started on a non-biologic CTP (2 GC, 6 MTX) and 22 patients on a biologic CTP (12 IL1i, 10 IL6i) at disease onset. Demographic and disease features were similar between CTP groups. CTP choice appeared to segregate by site preference. CID off GC was achieved by 37% (11 of 30) including 11/22 (50%) starting a biologic CTP compared to 0/8 starting a non-biologic CTP (p = 0.014). There were four serious adverse events: two infections, one appendicitis and one macrophage activation syndrome. The CARRA systemic JIA CTP pilot study demonstrated successful implementation of CTPs using the CARRA registry infrastructure. Having demonstrated feasibility, a larger study using CTP response to better determine the relative effectiveness of treatments for new-onset systemic JIA is now underway.

Quantification of myocardial blood flow using dynamic 320-row multi-detector CT as compared with ¹⁵O-H₂O PET.

PubMed

Kikuchi, Yasuka; Oyama-Manabe, Noriko; Naya, Masanao; Manabe, Osamu; Tomiyama, Yuuki; Sasaki, Tsukasa; Katoh, Chietsugu; Kudo, Kohsuke; Tamaki, Nagara; Shirato, Hiroki

2014-07-01

This study introduces a method to calculate myocardium blood flow (MBF) and coronary flow reserve (CFR) using the relatively low-dose dynamic 320-row multi-detector computed tomography (MDCT), validates the method against (15)O-H₂O positron-emission tomography (PET) and assesses the CFRs of coronary artery disease (CAD) patients. Thirty-two subjects underwent both dynamic CT perfusion (CTP) and PET perfusion imaging at rest and during pharmacological stress. In 12 normal subjects (pilot group), the calculation method for MBF and CFR was established. In the other 13 normal subjects (validation group), MBF and CFR obtained by dynamic CTP and PET were compared. Finally, the CFRs obtained by dynamic CTP and PET were compared between the validation group and CAD patients (n = 7). Correlation between MBF of MDCT and PET was strong (r = 0.95, P < 0.0001). CFR showed good correlation between dynamic CTP and PET (r = 0.67, P = 0.0126). CFRCT in the CAD group (2.3 ± 0.8) was significantly lower than that in the validation group (5.2 ± 1.8) (P = 0.0011). We established a method for measuring MBF and CFR with the relatively low-dose dynamic MDCT. Lower CFR was well demonstrated in CAD patients by dynamic CTP. • MBF and CFR can be calculated using dynamic CTP with 320-row MDCT. • MBF and CFR showed good correlation between dynamic CTP and PET. • Lower CFR was well demonstrated in CAD patients by dynamic CTP.

Assessing the short- and long-term prognosis of patients with cirrhosis and acute variceal bleeding.

PubMed

Sempere, L; Palazón, J M; Sánchez-Payá, J; Pascual, S; de Madaria, E; Poveda, M J; Carnicer, F; Zapater, P; Pérez-Mateo, M

2009-04-01

to evaluate the efficacy of various indicators in predicting short- and long-term survival in patients with cirrhosis and acute variceal bleeding. prognostic indicators were calculated for a cohort of 201 cirrhotic patients with acute variceal bleeding hospitalized in our center, a third-level teaching hospital. The studied variables were: age, sex, etiology of cirrhosis, endoscopic findings, previous variceal bleeding episodes, human immunodeficiency virus (HIV) infection, hepatocellular carcinoma (HCC), infection during episode, and Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) scores within 24 hours of bleeding onset. Patients were followed up for at least 6 months until death, liver transplantation, or end of observation. median follow-up was 66.85 weeks (range 0-432.4). The 6-week, 3-month, 12-month and 36-month mortality rates were 22.9, 24.9, 34.3, and 39.8%, respectively. Age >= 65 years, presence of HCC, CTP score >=10, and MELD score >= 18 were the variables associated with mortality in the multivariate analysis. The accuracy of MELD scores as predictors of 6-week, 3-month, 12-month, and 36-month mortality was better than that of CTP scores (c-statistics: 6 week MELD 0.804, CTP 0.762; 3-month MELD 0.794, CTP 0.760; 12-month MELD 0.766, CTP 0.741; 36 month MELD 0.737, CTP 0.717). MELD and CTP scores together with age and a diagnosis of hepatocellular carcinoma are useful indicators to assess the short- and long-term prognosis of patients with acute variceal bleeding.

Sugar-modified poly(propylene imine) dendrimers as drug delivery agents for cytarabine to overcome drug resistance.

PubMed

Szulc, Aleksandra; Pulaski, Lukasz; Appelhans, Dietmar; Voit, Brigitte; Klajnert-Maculewicz, Barbara

2016-11-20

Maltose-modified poly(propylene imine) glycodendrimers (PPI-m OS) of the 4th generation provide a promising strategy for leukemia treatment. Anticancer therapy with nucleoside analog drugs such as cytarabine (Ara-C) frequently has limited efficacy due to drug resistance, inefficient uptake and accumulation of the drug inside cancer cells where it has to be transformed into the active triphosphate congener. The cationic nature of PPI dendrimers makes it possible to form complexes with nucleotide Ara-C triphosphate forms (Ara-CTP). The aim of this work was to test the concept of applying PPI glycodendrimers as drug delivery devices in order to facilitate the delivery of activated cytarabine to cancer cells to overcome metabolic limitations of the drug. The study has been carried out using 1301 and HL-60 leukemic cell lines as well as peripheral blood mononuclear cells. The results of cytotoxicity and apoptosis assays showed enhanced activity of Ara-C triphosphate form (Ara-CTP) complexed with PPI-m dendrimers in relation to free Ara-C and Ara-CTP against 1301 leukemic cells. Secondly, enhanced uptake and cytotoxicity of Ara-CTP-dendrimers complexes toward 1301 cells with blocked human equilibrative nucleoside transporter - hENT1 suggested that this combination might be a versatile candidate for chemotherapy against resistant acute lymphoblastic leukemia cells with lower expression of hENT1. Copyright © 2016 Elsevier B.V. All rights reserved.

Phenotypes of gene disruptants in relation to a putative mitochondrial malate-citrate shuttle protein in citric acid-producing Aspergillus niger.

PubMed

Kirimura, Kohtaro; Kobayashi, Keiichi; Ueda, Yuka; Hattori, Takasumi

2016-09-01

The mitochondrial citrate transport protein (CTP) functions as a malate-citrate shuttle catalyzing the exchange of citrate plus a proton for malate between mitochondria and cytosol across the inner mitochondrial membrane in higher eukaryotic organisms. In this study, for functional analysis, we cloned the gene encoding putative CTP (ctpA) of citric acid-producing Aspergillus niger WU-2223L. The gene ctpA encodes a polypeptide consisting 296 amino acids conserved active residues required for citrate transport function. Only in early-log phase, the ctpA disruptant DCTPA-1 showed growth delay, and the amount of citric acid produced by strain DCTPA-1 was smaller than that by parental strain WU-2223L. These results indicate that the CTPA affects growth and thereby citric acid metabolism of A. niger changes, especially in early-log phase, but not citric acid-producing period. This is the first report showing that disruption of ctpA causes changes of phenotypes in relation to citric acid production in A. niger.

Accuracy of Computed Tomographic Perfusion in Diagnosis of Brain Death: A Prospective Cohort Study.

PubMed

Sawicki, Marcin; Sołek-Pastuszka, Joanna; Chamier-Ciemińska, Katarzyna; Walecka, Anna; Bohatyrewicz, Romuald

2018-05-04

BACKGROUND This study was designed to determine diagnostic accuracy of computed tomographic perfusion (CTP) compared to computed tomographic angiography (CTA) for the diagnosis of brain death (BD). MATERIAL AND METHODS Whole-brain CTP was performed in patients diagnosed with BD and in patients with devastating brain injury with preserved brainstem reflexes. CTA was derived from CTP datasets. Cerebral blood flow (CBF) and volume (CBV) were calculated in all brain regions. CTP findings were interpreted as confirming diagnosis of BD (positive) when CBF and CBV in all ROIs were below 10 mL/100 g/min and 1.0 mL/100 g, respectively. CTA findings were interpreted using a 4-point system. RESULTS Fifty brain-dead patients and 5 controls were included. In brain-dead patients, CTP results revealed CBF 0.00-9.98 mL/100 g/min and CBV 0.00-0.99 mL/100 g, and were thus interpreted as positive in all patients. CTA results suggested 7 negative cases, providing 86% sensitivity. In the non-brain-dead group, CTP results revealed CBF 2.37-37.59 mL/100 g/min and CBV 0.73-2.34 mL/100 g. The difference between values of CBF and CBV in the brain-dead and non-brain-dead groups was statistically significant (p=0.002 for CBF and p=0.001 for CBV). CTP findings in all non-brain-dead patients were interpreted as negative. This resulted in a specificity of 100% (95% CI, 0.31-1.00) for CTP in the diagnosis of BD. In all non-brain-dead patients, CTA revealed preserved intracranial filling and was interpreted as negative. This resulted in a specificity of 100% (95% CI, 0.31-1.00) for CTA in diagnosis of BD. CONCLUSIONS Whole-brain CTP seems to be a highly sensitive and specific method in diagnosis of BD.

Evaluation of multifunctional imaging parameters in gastro-oesophageal cancer using F-18-FDG-PET/CT with integrated perfusion CT.

PubMed

Sah, Bert-Ram; Leissing, Christian A; Delso, Gaspar; Ter Voert, Edwin E; Krieg, Stefan; Leibl, Sebastian; Schneider, Paul M; Reiner, Cäcilia S; Hüllner, Martin W; Veit-Haibach, Patrick

2018-05-10

Positron emission tomography (PET) / computed tomography (CT) is among the most frequently used imaging modalities for initial staging of gastro-oesophageal (GE) cancer, whereas CT-perfusion (CTP) provides different multiparametric information. This proof of concept study compares CTP- and PET-parameters in patients with GE cancer to evaluate correlations and a possible prognostic value of a combined PET/CTP imaging procedure. A total of 31 patients with F-18-FDG-PET/CT and CTP studies were prospectively analysed. Patients had adenocarcinoma (n = 22) and oesophageal squamous cell carcinoma (SCC, n = 9). Imaging was performed before start of treatment. CTP parameters [blood flow (BF), blood volume (BV), mean transit time (MTT)] and metabolic parameters [(maximum and mean standardised uptake values and standard deviation (SUVmax, SUVmean, SUVsd), metabolic tumour volume (MTV) and tumour lesion glycolysis (TLG)], as well as flow metabolic product [FMP (BF × SUVmax)] were determined and their relationship was compared. Additionally their association to clinical parameters (differentiation grading, staging, HER2-status, follow-up status) and to histopathological regression (post-neoadjuvant regression grading) was evaluated. Correlation between parameters of both modalities was significant between MTT and MTV (r = 0.375, p = 0.038); no other significant correlation was found. Patients with complete histopathological regression showed significantly lower BF and BV than patients with nearly complete or partial response. TLG and regression grading showed significant correlation with staging. All other quantitative parameters for CTP and PET data did not correlate significantly with histopathological regression grading, differentiation or staging. The combination of PET and CTP parameters (FMP) showed no significant prognostic value. Significant correlations were only found between MTT and MTV, which indicates a possible perfusional/metabolic coupling. Therefore, pre-therapeutic CTP and PET- parameters provide complementary information about the pre-therapeutic tumour status and are not interchangeable. Only CTP parameters might be able to predict complete histopathological regression. On the other hand, only PET parameters are correlated with staging.

Integrated controls and health monitoring for chemical transfer propulsion

NASA Technical Reports Server (NTRS)

Millis, Marc G.; Binder, Michael P.

1990-01-01

NASA is reviewing various propulsion technologies for exploring space. The requirements are examined for one enabling propulsion technology: Integrated Controls and Health Monitoring (ICHM) for Chemical Transfer Propulsion (CTP). Functional requirements for a CTP-ICHM system are proposed from tentative mission scenarios, vehicle configurations, CTP specifications, and technical feasibility. These CTP-ICHM requirements go beyond traditional reliable operation and emergency shutoff control to include: (1) enhanced mission flexibility; (2) continuously variable throttling; (3) tank-head start control; (4) automated prestart and post-shutoff engine check; (5) monitoring of space exposure degradation; and (6) product evolution flexibility. Technology development plans are also discussed.

Direct comparison of rest and adenosine stress myocardial perfusion CT with rest and stress SPECT

PubMed Central

Okada, David R.; Ghoshhajra, Brian B.; Blankstein, Ron; Rocha-Filho, Jose A.; Shturman, Leonid D.; Rogers, Ian S.; Bezerra, Hiram G.; Sarwar, Ammar; Gewirtz, Henry; Hoffmann, Udo; Mamuya, Wilfred S.; Brady, Thomas J.; Cury, Ricardo C.

2010-01-01

Introduction We have recently described a technique for assessing myocardial perfusion using adenosine-mediated stress imaging (CTP) with dual source computed tomography. SPECT myocardial perfusion imaging (SPECT-MPI) is a widely utilized and extensively validated method for assessing myocardial perfusion. The aim of this study was to determine the level of agreement between CTP and SPECT-MPI at rest and under stress on a per-segment, per-vessel, and per-patient basis. Methods Forty-seven consecutive patients underwent CTP and SPECT-MPI. Perfusion images were interpreted using the 17 segment AHA model and were scored on a 0 (normal) to 3 (abnormal) scale. Summed rest and stress scores were calculated for each vascular territory and patient by adding corresponding segmental scores. Results On a per-segment basis (n = 799), CTP and SPECT-MPI demonstrated excellent correlation: Goodman-Kruskall γ = .59 (P < .0001) for stress and .75 (P < .0001) for rest. On a per-vessel basis (n = 141), CTP and SPECT-MPI summed scores demonstrated good correlation: Pearson r = .56 (P < .0001) for stress and .66 (P < .0001) for rest. On a per-patient basis (n = 47), CTP and SPECT-MPI demonstrated good correlation: Pearson r = .60 (P < .0001) for stress and .76 (P < .0001) for rest. Conclusions CTP compares favorably with SPECT-MPI for detection, extent, and severity of myocardial perfusion defects at rest and stress. PMID:19936863

Comprehensive Study of Educational Technology Programs Authorized from 1989-1992. Volume IV: California Technology Project.

ERIC Educational Resources Information Center

Far West Lab. for Educational Research and Development, San Francisco, CA.

This report, the fourth in a series of six, describes the evaluative studies conducted during Phase II of the California Educational Technology Assessment Program, the California Technology Project (CTP), and the CTP Regional Consortia. The report begins with background information on the CTP, starting with the earlier statewide network of…

Cerebral Blood Volume ASPECTS Is the Best Predictor of Clinical Outcome in Acute Ischemic Stroke: A Retrospective, Combined Semi-Quantitative and Quantitative Assessment.

PubMed

Padroni, Marina; Bernardoni, Andrea; Tamborino, Carmine; Roversi, Gloria; Borrelli, Massimo; Saletti, Andrea; De Vito, Alessandro; Azzini, Cristiano; Borgatti, Luca; Marcello, Onofrio; d'Esterre, Christopher; Ceruti, Stefano; Casetta, Ilaria; Lee, Ting-Yim; Fainardi, Enrico

2016-01-01

The capability of CT perfusion (CTP) Alberta Stroke Program Early CT Score (ASPECTS) to predict outcome and identify ischemia severity in acute ischemic stroke (AIS) patients is still questioned. 62 patients with AIS were imaged within 8 hours of symptom onset by non-contrast CT, CT angiography and CTP scans at admission and 24 hours. CTP ASPECTS was calculated on the affected hemisphere using cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) maps by subtracting 1 point for any abnormalities visually detected or measured within multiple cortical circular regions of interest according to previously established thresholds. MTT-CBV ASPECTS was considered as CTP ASPECTS mismatch. Hemorrhagic transformation (HT), recanalization status and reperfusion grade at 24 hours, final infarct volume at 7 days and modified Rankin scale (mRS) at 3 months after onset were recorded. Semi-quantitative and quantitative CTP ASPECTS were highly correlated (p<0.00001). CBF, CBV and MTT ASPECTS were higher in patients with no HT and mRS ≤ 2 and inversely associated with final infarct volume and mRS (p values: from p<0.05 to p<0.00001). CTP ASPECTS mismatch was slightly associated with radiological and clinical outcomes (p values: from p<0.05 to p<0.02) only if evaluated quantitatively. A CBV ASPECTS of 9 was the optimal semi-quantitative value for predicting outcome. Our findings suggest that visual inspection of CTP ASPECTS recognizes infarct and ischemic absolute values. Semi-quantitative CBV ASPECTS, but not CTP ASPECTS mismatch, represents a strong prognostic indicator, implying that core extent is the main determinant of outcome, irrespective of penumbra size.

Whole brain CT perfusion deficits using 320-detector-row CT scanner in TIA patients are associated with ABCD2 score.

PubMed

Mehta, Bijal K; Mustafa, Ghulam; McMurtray, Aaron; Masud, Mohammed W; Gunukula, Sameer K; Kamal, Haris; Kandel, Amit; Beltagy, Abdelrahman; Li, Ping

2014-01-01

Transient ischemic attacks (TIA) are cerebral ischemic events without infarction. The uses of CT perfusion (CTP) techniques such as cerebral blood volume (CBV), time to peak (TTP), mean transit time (MTT) and cerebral blood flow (CBF) provide real time data about ischemia. It has been shown that CTP changes occur in less sensitive CTP scanners in patients with TIA. Larger detector row CTP (whole brain perfusion studies) may show that CTP abnormalities are more prevalent than previously noted. It is also unclear if these changes are associated with TIA severity. To demonstrate that TIA patients are associated with perfusion deficits using whole brain 320-detector-row CT perfusion, and to determine an association between ABCD2 score and perfusion deficit using whole brain perfusion. We retrospectively reviewed all TIA patients for CTP deficits from 2008-2010. Perfusion imaging was reviewed at admission; and it was determined if a perfusion deficit was present along with vascular territory involved. Of 364 TIA patients, 62 patients had CTP deficits. The largest group of patients had MCA territory involved with 48 of 62 patients (77.42%). The most common perfusion abnormality was increased TTP with 46 patients (74.19%). The ABCD2 score was reviewed in association with perfusion deficit. Increased age >60, severe hypertension (>180/100 mmHg), patients with speech abnormalities, and duration of symptoms >10 min were associated with a perfusion deficit but history of diabetes or minimal/moderate hypertension (140/90-179/99 mmHg) was not. There was no association between motor deficit and perfusion abnormality. Perfusion deficits are found in TIA patients using whole brain CTP and associated with components of the ABCD2 score.

Early whole-brain CT perfusion for detection of patients at risk for delayed cerebral ischemia after subarachnoid hemorrhage.

PubMed

Malinova, Vesna; Dolatowski, Karoline; Schramm, Peter; Moerer, Onnen; Rohde, Veit; Mielke, Dorothee

2016-07-01

OBJECT This prospective study investigated the role of whole-brain CT perfusion (CTP) studies in the identification of patients at risk for delayed ischemic neurological deficits (DIND) and of tissue at risk for delayed cerebral infarction (DCI). METHODS Forty-three patients with aneurysmal subarachnoid hemorrhage (aSAH) were included in this study. A CTP study was routinely performed in the early phase (Day 3). The CTP study was repeated in cases of transcranial Doppler sonography (TCD)-measured blood flow velocity (BFV) increase of > 50 cm/sec within 24 hours and/or on Day 7 in patients who were intubated/sedated. RESULTS Early CTP studies revealed perfusion deficits in 14 patients, of whom 10 patients (72%) developed DIND, and 6 of these 10 patients (60%) had DCI. Three of the 14 patients (21%) with early perfusion deficits developed DCI without having had DIND, and the remaining patient (7%) had neither DIND nor DCI. There was a statistically significant correlation between early perfusion deficits and occurrence of DIND and DCI (p < 0.0001). A repeated CTP was performed in 8 patients with a TCD-measured BFV increase > 50 cm/sec within 24 hours, revealing a perfusion deficit in 3 of them (38%). Two of the 3 patients (67%) developed DCI without preceding DIND and 1 patient (33%) had DIND without DCI. In 4 of the 7 patients (57%) who were sedated and/or comatose, additional CTP studies on Day 7 showed perfusion deficits. All 4 patients developed DCI. CONCLUSIONS Whole-brain CTP on Day 3 after aSAH allows early and reliable identification of patients at risk for DIND and tissue at risk for DCI. Additional CTP investigations, guided by TCD-measured BFV increase or persisting coma, do not contribute to information gain.

Acute CT perfusion changes in seizure patients presenting to the emergency department with stroke-like symptoms: correlation with clinical and electroencephalography findings.

PubMed

Payabvash, S; Oswood, M C; Truwit, C L; McKinney, A M

2015-10-01

To determine acute computed tomography perfusion (CTP) changes in seizure patients presenting with stroke-like symptoms and to correlate those changes with clinical presentation and electroencephalography (EEG). The medical records of all patients who presented to the emergency department with acute stroke-like symptoms and underwent CTP (n=1085) over a 5.5-year period were reviewed. Patients were included who had primary seizure as the final diagnosis, and underwent CTP within 3 hours of symptom onset. A subset of patients had a follow-up EEG within 7 days. The perfusion changes and EEG findings were compared between different clinical presentations. Eighteen of 1085 patients (1.7%) who underwent CTP following an acute stroke-like presentation were included. The abnormality on CTP was usually focal, unilateral hyperperfusion - increased relative cerebral blood flow (rCBF) and volume (rCBV) (n=14/18), which most often affected the temporal lobe. Those patients who presented with a motor or speech deficit (n=12) had a higher temporal lobe rCBV, and rCBF, and lower relative mean transit time (rMTT) compared to those with non-focal neurological deficit at presentation. Early EEG was available in 13 patients; a sharp-spike epileptiform EEG discharge pattern (n=5) was associated with higher temporal lobe ipsilateral rCBF and rCBV, and lower rMTT on admission CTP examination. Seizure patients who present with a unilateral motor or speech deficit most commonly have contralateral hyperperfusion in the corresponding eloquent brain regions on the acute-stage CTP examination. In such patients, epileptiform discharges on the early follow-up EEG are associated with ipsilateral hyperperfusion on the admission CTP. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Cerebral Blood Volume ASPECTS Is the Best Predictor of Clinical Outcome in Acute Ischemic Stroke: A Retrospective, Combined Semi-Quantitative and Quantitative Assessment

PubMed Central

Padroni, Marina; Bernardoni, Andrea; Tamborino, Carmine; Roversi, Gloria; Borrelli, Massimo; Saletti, Andrea; De Vito, Alessandro; Azzini, Cristiano; Borgatti, Luca; Marcello, Onofrio; d’Esterre, Christopher; Ceruti, Stefano; Casetta, Ilaria; Lee, Ting-Yim; Fainardi, Enrico

2016-01-01

Introduction The capability of CT perfusion (CTP) Alberta Stroke Program Early CT Score (ASPECTS) to predict outcome and identify ischemia severity in acute ischemic stroke (AIS) patients is still questioned. Methods 62 patients with AIS were imaged within 8 hours of symptom onset by non-contrast CT, CT angiography and CTP scans at admission and 24 hours. CTP ASPECTS was calculated on the affected hemisphere using cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) maps by subtracting 1 point for any abnormalities visually detected or measured within multiple cortical circular regions of interest according to previously established thresholds. MTT-CBV ASPECTS was considered as CTP ASPECTS mismatch. Hemorrhagic transformation (HT), recanalization status and reperfusion grade at 24 hours, final infarct volume at 7 days and modified Rankin scale (mRS) at 3 months after onset were recorded. Results Semi-quantitative and quantitative CTP ASPECTS were highly correlated (p<0.00001). CBF, CBV and MTT ASPECTS were higher in patients with no HT and mRS≤2 and inversely associated with final infarct volume and mRS (p values: from p<0.05 to p<0.00001). CTP ASPECTS mismatch was slightly associated with radiological and clinical outcomes (p values: from p<0.05 to p<0.02) only if evaluated quantitatively. A CBV ASPECTS of 9 was the optimal semi-quantitative value for predicting outcome. Conclusions Our findings suggest that visual inspection of CTP ASPECTS recognizes infarct and ischemic absolute values. Semi-quantitative CBV ASPECTS, but not CTP ASPECTS mismatch, represents a strong prognostic indicator, implying that core extent is the main determinant of outcome, irrespective of penumbra size. PMID:26824672

Comparison of CT perfusion summary maps to early diffusion-weighted images in suspected acute middle cerebral artery stroke.

PubMed

Benson, John; Payabvash, Seyedmehdi; Salazar, Pascal; Jagadeesan, Bharathi; Palmer, Christopher S; Truwit, Charles L; McKinney, Alexander M

2015-04-01

To assess the accuracy and reliability of one vendor's (Vital Images, Toshiba Medical, Minnetonka, MN) automated CT perfusion (CTP) summary maps in identification and volume estimation of infarcted tissue in patients with acute middle cerebral artery (MCA) distribution infarcts. From 1085 CTP examinations over 5.5 years, 43 diffusion-weighted imaging (DWI)-positive patients were included who underwent both CTP and DWI <12 h after symptom onset, with another 43 age-matched patients as controls (DWI-negative). Automated delay-corrected postprocessing software (DC-SVD) generated both infarct "core only" and "core+penumbra" CTP summary maps. Three reviewers independently tabulated Alberta Stroke Program Early CT scores (ASPECTS) of both CTP summary maps and coregistered DWI. Of 86 included patients, 36 had DWI infarct volumes ≤70 ml, 7 had volumes >70 ml, and 43 were negative; the automated CTP "core only" map correctly classified each as >70 ml or ≤70 ml, while the "core+penumbra" map misclassified 4 as >70 ml. There were strong correlations between DWI volume with both summary map-based volumes: "core only" (r=0.93), and "core+penumbra" (r=0.77) (both p<0.0001). Agreement between ASPECTS scores of infarct core on DWI with summary maps was 0.65-0.74 for "core only" map, and 0.61-0.65 for "core+penumbra" (both p<0.0001). Using DWI-based ASPECTS scores as the standard, the accuracy of the CTP-based maps were 79.1-86.0% for the "core only" map, and 83.7-88.4% for "core+penumbra." Automated CTP summary maps appear to be relatively accurate in both the detection of acute MCA distribution infarcts, and the discrimination of volumes using a 70 ml threshold. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

CT myocardial perfusion imaging: current status and future perspectives.

PubMed

Yang, Dong Hyun; Kim, Young-Hak

2017-07-01

Computed tomography myocardial perfusion (CTP) combined with coronary computed tomography angiography (CCTA) may constitute a "1-stop shop" for the noninvasive diagnosis of hemodynamically significant coronary stenosis during a single CT examination. CTP shows high diagnostic performance and provides incremental value over CCTA for the detection of hemodynamically significant coronary stenosis in patients with a high Agatston calcium score or coronary artery stents. Future studies should determine the optimal protocol and clinical value of CTP for guiding revascularization strategy and prognostication. In this article, we review the current status and future perspectives of CTP, focusing on technical considerations, clinical applications, and future research topics.

A Statistical Study on the Effect of Hydrostatic Pressure on Metastable Pitting Corrosion of X70 Pipeline Steel.

PubMed

Yang, Zixuan; Kan, Bo; Li, Jinxu; Qiao, Lijie; Volinsky, Alex A; Su, Yanjing

2017-11-14

Hydrostatic pressure effects on pitting initiation and propagation in X70 steel are investigated by evaluating metastable pitting probability using electrochemical methods and immersion corrosion tests in containing chlorine ion solution. Potentiodynamic tests indicated that hydrostatic pressure can decrease the breakdown potential and lead to a reduced transpassivity region. Metastable test results revealed that hydrostatic pressure can increase metastable pitting formation frequency and promote stabilization of metastable pitting growth. Electrochemical impedance spectroscopy (EIS) results indicate that Hydrostatic pressure decreases the charge transfer resistance and increases the dissolution rate within the cavities. Corrosion test results also indicated that pitting initiation and propagation are accelerated by hydrostatic pressure. Result validity was verified by evaluating metastable pitting to predict pitting corrosion resistance.

A Statistical Study on the Effect of Hydrostatic Pressure on Metastable Pitting Corrosion of X70 Pipeline Steel

PubMed Central

Yang, Zixuan; Kan, Bo; Li, Jinxu; Su, Yanjing; Qiao, Lijie; Volinsky, Alex A.

2017-01-01

Hydrostatic pressure effects on pitting initiation and propagation in X70 steel are investigated by evaluating metastable pitting probability using electrochemical methods and immersion corrosion tests in containing chlorine ion solution. Potentiodynamic tests indicated that hydrostatic pressure can decrease the breakdown potential and lead to a reduced transpassivity region. Metastable test results revealed that hydrostatic pressure can increase metastable pitting formation frequency and promote stabilization of metastable pitting growth. Electrochemical impedance spectroscopy (EIS) results indicate that Hydrostatic pressure decreases the charge transfer resistance and increases the dissolution rate within the cavities. Corrosion test results also indicated that pitting initiation and propagation are accelerated by hydrostatic pressure. Result validity was verified by evaluating metastable pitting to predict pitting corrosion resistance. PMID:29135912

The Effects of Hot Corrosion Pits on the Fatigue Resistance of a Disk Superalloy

NASA Technical Reports Server (NTRS)

Gabb, Timothy P.; Telesman, Jack; Hazel, Brian; Mourer, David P.

2009-01-01

The effects of hot corrosion pits on low cycle fatigue life and failure modes of the disk superalloy ME3 were investigated. Low cycle fatigue specimens were subjected to hot corrosion exposures producing pits, then tested at low and high temperatures. Fatigue lives and failure initiation points were compared to those of specimens without corrosion pits. Several tests were interrupted to estimate the fraction of fatigue life that fatigue cracks initiated at pits. Corrosion pits significantly reduced fatigue life by 60 to 98 percent. Fatigue cracks initiated at a very small fraction of life for high temperature tests, but initiated at higher fractions in tests at low temperature. Critical pit sizes required to promote fatigue cracking were estimated, based on measurements of pits initiating cracks on fracture surfaces.

Collaborative trial validation studies of real-time PCR-based GMO screening methods for detection of the bar gene and the ctp2-cp4epsps construct.

PubMed

Grohmann, Lutz; Brünen-Nieweler, Claudia; Nemeth, Anne; Waiblinger, Hans-Ulrich

2009-10-14

Polymerase Chain Reaction (PCR)-based screening methods targeting genetic elements commonly used in genetically modified (GM) plants are important tools for the detection of GM materials in food, feed, and seed samples. To expand and harmonize the screening capability of enforcement laboratories, the German Federal Office of Consumer Protection and Food Safety conducted collaborative trials for interlaboratory validation of real-time PCR methods for detection of the phosphinothricin acetyltransferase (bar) gene from Streptomyces hygroscopicus and a construct containing the 5-enolpyruvylshikimate-3-phosphate synthase gene from Agrobacterium tumefaciens sp. strain CP4 (ctp2-cp4epsps), respectively. To assess the limit of detection, precision, and accuracy of the methods, laboratories had to analyze two sets of 18 coded genomic DNA samples of events LLRice62 and MS8 with the bar method and NK603 and GT73 with the ctp2-cp4epsps method at analyte levels of 0, 0.02, and 0.1% GM content, respectively. In addition, standard DNAs were provided to the laboratories to generate calibration curves for copy number quantification of the bar and ctp2-cp4epsps target sequences present in the test samples. The study design and the results obtained are discussed with respect to the difficult issue of developing general guidelines and concepts for the collaborative trial validation of qualitative PCR screening methods.

Dipyridamole stress myocardial perfusion by computed tomography in patients with left bundle branch block.

PubMed

Cabeda, Estêvan Vieira; Falcão, Andréa Maria Gomes; Soares, José; Rochitte, Carlos Eduardo; Nomura, César Higa; Ávila, Luiz Francisco Rodrigues; Parga, José Rodrigues

2015-12-01

Functional tests have limited accuracy for identifying myocardial ischemia in patients with left bundle branch block (LBBB). To assess the diagnostic accuracy of dipyridamole-stress myocardial computed tomography perfusion (CTP) by 320-detector CT in patients with LBBB using invasive quantitative coronary angiography (QCA) (stenosis ≥ 70%) as reference; to investigate the advantage of adding CTP to coronary computed tomography angiography (CTA) and compare the results with those of single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy. Thirty patients with LBBB who had undergone SPECT for the investigation of coronary artery disease were referred for stress tomography. Independent examiners performed per-patient and per-coronary territory assessments. All patients gave written informed consent to participate in the study that was approved by the institution's ethics committee. The patients' mean age was 62 ± 10 years. The mean dose of radiation for the tomography protocol was 9.3 ± 4.6 mSv. With regard to CTP, the per-patient values for sensitivity, specificity, positive and negative predictive values, and accuracy were 86%, 81%, 80%, 87%, and 83%, respectively (p = 0.001). The per-territory values were 63%, 86%, 65%, 84%, and 79%, respectively (p < 0.001). In both analyses, the addition of CTP to CTA achieved higher diagnostic accuracy for detecting myocardial ischemia than SPECT (p < 0.001). The use of the stress tomography protocol is feasible and has good diagnostic accuracy for assessing myocardial ischemia in patients with LBBB.

TU-EF-204-02: Hiigh Quality and Sub-MSv Cerebral CT Perfusion Imaging

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

Li, Ke; Niu, Kai; Wu, Yijing

2015-06-15

Purpose: CT Perfusion (CTP) imaging is of great importance in acute ischemic stroke management due to its potential to detect hypoperfused yet salvageable tissue and distinguish it from definitely unsalvageable tissue. However, current CTP imaging suffers from poor image quality and high radiation dose (up to 5 mSv). The purpose of this work was to demonstrate that technical innovations such as Prior Image Constrained Compressed Sensing (PICCS) have the potential to address these challenges and achieve high quality and sub-mSv CTP imaging. Methods: (1) A spatial-temporal 4D cascaded system model was developed to indentify the bottlenecks in the current CTPmore » technology; (2) A task-based framework was developed to optimize the CTP system parameters; (3) Guided by (1) and (2), PICCS was customized for the reconstruction of CTP source images. Digital anthropomorphic perfusion phantoms, animal studies, and preliminary human subject studies were used to validate and evaluate the potentials of using these innovations to advance the CTP technology. Results: The 4D cascaded model was validated in both phantom and canine stroke models. Based upon this cascaded model, it has been discovered that, as long as the spatial resolution and noise properties of the 4D source CT images are given, the 3D MTF and NPS of the final CTP maps can be analytically derived for a given set of processing methods and parameters. The cascaded model analysis also identified that the most critical technical factor in CTP is how to acquire and reconstruct high quality source images; it has very little to do with the denoising techniques often used after parametric perfusion calculations. This explained why PICCS resulted in a five-fold dose reduction or substantial improvement in image quality. Conclusion: Technical innovations generated promising results towards achieving high quality and sub-mSv CTP imaging for reliable and safe assessment of acute ischemic strokes. K. Li, K. Niu, Y. Wu: Nothing to disclose. G.-H. Chen: Research funded, GE Healthcare; Research funded, Siemens AX.« less

Configurable Multi-Purpose Processor

NASA Technical Reports Server (NTRS)

Valencia, J. Emilio; Forney, Chirstopher; Morrison, Robert; Birr, Richard

2010-01-01

Advancements in technology have allowed the miniaturization of systems used in aerospace vehicles. This technology is driven by the need for next-generation systems that provide reliable, responsive, and cost-effective range operations while providing increased capabilities such as simultaneous mission support, increased launch trajectories, improved launch, and landing opportunities, etc. Leveraging the newest technologies, the command and telemetry processor (CTP) concept provides for a compact, flexible, and integrated solution for flight command and telemetry systems and range systems. The CTP is a relatively small circuit board that serves as a processing platform for high dynamic, high vibration environments. The CTP can be reconfigured and reprogrammed, allowing it to be adapted for many different applications. The design is centered around a configurable field-programmable gate array (FPGA) device that contains numerous logic cells that can be used to implement traditional integrated circuits. The FPGA contains two PowerPC processors running the Vx-Works real-time operating system and are used to execute software programs specific to each application. The CTP was designed and developed specifically to provide telemetry functions; namely, the command processing, telemetry processing, and GPS metric tracking of a flight vehicle. However, it can be used as a general-purpose processor board to perform numerous functions implemented in either hardware or software using the FPGA s processors and/or logic cells. Functionally, the CTP was designed for range safety applications where it would ultimately become part of a vehicle s flight termination system. Consequently, the major functions of the CTP are to perform the forward link command processing, GPS metric tracking, return link telemetry data processing, error detection and correction, data encryption/ decryption, and initiate flight termination action commands. Also, the CTP had to be designed to survive and operate in a launch environment. Additionally, the CTP was designed to interface with the WFF (Wallops Flight Facility) custom-designed transceiver board which is used in the Low Cost TDRSS Transceiver (LCT2) also developed by WFF. The LCT2 s transceiver board demodulates commands received from the ground via the forward link and sends them to the CTP, where they are processed. The CTP inputs and processes data from the inertial measurement unit (IMU) and the GPS receiver board, generates status data, and then sends the data to the transceiver board where it is modulated and sent to the ground via the return link. Overall, the CTP has combined processing with the ability to interface to a GPS receiver, an IMU, and a pulse code modulation (PCM) communication link, while providing the capability to support common interfaces including Ethernet and serial interfaces boarding a relatively small-sized, lightweight package.

Adsorption of Dissolved Metals in the Berkeley Pit using Thiol-Functionalized Self-Assembled Monolayers on Mesoporous Supports (Thiol-SAMMS)

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

Betancourt, Amaury P.; Mattigod, Shas V.; Wellman, Dawn M.

2010-03-07

The Berkeley Pit in Butte, Montana, is heavily contaminated with dissolved metals. Adsorption and extraction of these metals can be accomplished through the use of a selective adsorbent. For this research, the adsorbent used was thiol-functionalized Self-Assembled Monolayers on Mesoporous Supports (thiol-SAMMS), which was developed at Pacific Northwest National Laboratory (PNNL). Thiol-SAMMS selectively binds to numerous types of dissolved metals. The objective of this research was to evaluate the loading and kinetics of aluminum, beryllium, copper, and zinc on thiol-SAMMS. For the loading tests, a series of Berkeley Pit water to thiol-SAMMS ratios (mL:g) were tested. These ratios were 1000:1,more » 500:1, 100:1, and 50:1. Berkeley Pit water is acidic (pH {approx} 2.5). This can affect the performance of SAMMS materials. Therefore, the effect of pH was evaluated by conducting parallel series of loading tests wherein the Berkeley Pit water was neutralized before or after addition of thiol-SAMMS, and a series of kinetics tests wherein the Berkeley Pit water was neutralized before addition of thiol-SAMMS for the first test and was not neutralized for the second test. For the kinetics tests, one Berkeley Pit water to thiol-SAMMS ratio was tested, which was 2000:1. The results of the loading and kinetics tests suggest that a significant decrease in dissolved metal concentration at Berkeley Pit could be realized through neutralization of Berkeley Pit water. Thiol-SAMMS technology has a limited application under the highly acidic conditions posed by the Berkeley Pit. However, thiol-SAMMS could provide a secondary remedial technique which would complete the remedial system and remove dissolved metals from the Berkeley Pit to below drinking water standards.« less

Comparison of the pharmacokinetics and safety of three formulations of infliximab (CT-P13, EU-approved reference infliximab and the US-licensed reference infliximab) in healthy subjects: a randomized, double-blind, three-arm, parallel-group, single-dose, Phase I study.

PubMed

Park, Won; Lee, Sang Joon; Yun, Jihye; Yoo, Dae Hyun

2015-01-01

To compare the pharmacokinetics (PK), safety and tolerability of biosimilar infliximab (CT-P13 [Remsima(®), Inflectra(®)]) with two formulations of the reference medicinal product (RMP) (Remicade(®)) from either Europe (EU-RMP) or the USA (US-RMP). This was a double-blind, three-arm, parallel-group study (EudraCT number: 2013-003173-10). Healthy subjects received single doses (5 mg/kg) of CT-P13 (n = 71), EU-RMP (n = 71) or US-RMP (n = 71). The primary objective was to compare the PK profiles for the three formulations. Assessments of comparative safety and tolerability were secondary objectives. Baseline demographics were well balanced across the three groups. Primary end points (Cmax, AUClast and AUCinf) were equivalent between all formulations (CT-P13 vs EU-RMP; CT-P13 vs US-RMP; EU-RMP vs US-RMP). All other PK end points supported the high similarity of the three treatments. Tolerability profiles of the formulations were similar. The PK profile of CT-P13 is highly similar to EU-RMP and US-RMP. All three formulations were equally well tolerated.

Simulation of Fatigue Crack Initiation at Corrosion Pits With EDM Notches

NASA Technical Reports Server (NTRS)

Smith, Stephen W.; Newman, John A.; Piascik, Robert S.

2003-01-01

Uniaxial fatigue tests were conducted to compare the fatigue life of laboratory produced corrosion pits, similar to those observed in the shuttle main landing gear wheel bolt-hole, and an electro-discharged-machined (EDM) flaw. EDM Jaws are used to simulate corrosion pits during shuttle wheel (dynamometer) testing. The aluminum alloy, (AA 7050) laboratory fatigue tests were conducted to simulate the local stress level contained in the wheel bolt-hole. Under this high local stress condition, the EDM notch produced a fatigue life similar to test specimens containing corrosion pits of similar size. Based on the laboratory fatigue test results, the EDM Jaw (semi-circular disc shaped) produces a local stress state similar to corrosion pits and can be used to simulate a corrosion pit during the shuttle wheel dynamometer tests.

A Phenotypic Based Target Screening Approach Delivers New Antitubercular CTP Synthetase Inhibitors.

PubMed

Esposito, Marta; Szadocka, Sára; Degiacomi, Giulia; Orena, Beatrice S; Mori, Giorgia; Piano, Valentina; Boldrin, Francesca; Zemanová, Júlia; Huszár, Stanislav; Barros, David; Ekins, Sean; Lelièvre, Joel; Manganelli, Riccardo; Mattevi, Andrea; Pasca, Maria Rosalia; Riccardi, Giovanna; Ballell, Lluis; Mikušová, Katarína; Chiarelli, Laurent R

2017-06-09

Despite its great potential, the target-based approach has been mostly unsuccessful in tuberculosis drug discovery, while whole cell phenotypic screening has delivered several active compounds. However, for many of these hits, the cellular target has not yet been identified, thus preventing further target-based optimization of the compounds. In this context, the newly validated drug target CTP synthetase PyrG was exploited to assess a target-based approach of already known, but untargeted, antimycobacterial compounds. To this purpose the publically available GlaxoSmithKline antimycobacterial compound set was assayed, uncovering a series of 4-(pyridin-2-yl)thiazole derivatives which efficiently inhibit the Mycobacterium tuberculosis PyrG enzyme activity, one of them showing low activity against the human CTP synthetase. The three best compounds were ATP binding site competitive inhibitors, with K i values ranging from 3 to 20 μM, but did not show any activity against a small panel of different prokaryotic and eukaryotic kinases, thus demonstrating specificity for the CTP synthetases. Metabolic labeling experiments demonstrated that the compounds directly interfere not only with CTP biosynthesis, but also with other CTP dependent biochemical pathways, such as lipid biosynthesis. Moreover, using a M. tuberculosis pyrG conditional knock-down strain, it was shown that the activity of two compounds is dependent on the intracellular concentration of the CTP synthetase. All these results strongly suggest a role of PyrG as a target of these compounds, thus strengthening the value of this kind of approach for the identification of new scaffolds for drug development.

Efficacy of Stent-Retriever Thrombectomy in Magnetic Resonance Imaging Versus Computed Tomographic Perfusion-Selected Patients in SWIFT PRIME Trial (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke).

PubMed

Menjot de Champfleur, Nicolas; Saver, Jeffrey L; Goyal, Mayank; Jahan, Reza; Diener, Hans-Christoph; Bonafe, Alain; Levy, Elad I; Pereira, Vitor M; Cognard, Christophe; Yavagal, Dileep R; Albers, Gregory W

2017-06-01

The majority of patients enrolled in SWIFT PRIME trial (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke) had computed tomographic perfusion (CTP) imaging before randomization; 34 patients were randomized after magnetic resonance imaging (MRI). Patients with middle cerebral artery and distal carotid occlusions were randomized to treatment with tPA (tissue-type plasminogen activator) alone or tPA+stentriever thrombectomy. The primary outcome was the distribution of the modified Rankin Scale score at 90 days. Patients with the target mismatch profile for enrollment were identified on MRI and CTP. MRI selection was performed in 34 patients; CTP in 139 patients. Baseline National Institutes of Health Stroke Scale score was 17 in both groups. Target mismatch profile was present in 95% (MRI) versus 83% (CTP). A higher percentage of the MRI group was transferred from an outside hospital ( P =0.02), and therefore, the time from stroke onset to randomization was longer in the MRI group ( P =0.003). Time from emergency room arrival to randomization did not differ in CTP versus MRI-selected patients. Baseline ischemic core volumes were similar in both groups. Reperfusion rates (>90%/TICI [Thrombolysis in Cerebral Infarction] score 3) did not differ in the stentriever-treated patients in the MRI versus CTP groups. The primary efficacy analysis (90-day mRS score) demonstrated a statistically significant benefit in both subgroups (MRI, P =0.02; CTP, P =0.01). Infarct growth was reduced in the stentriever-treated group in both MRI and CTP groups. Time to randomization was significantly longer in MRI-selected patients; however, site arrival to randomization times were not prolonged, and the benefits of endovascular therapy were similar. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461. © 2017 American Heart Association, Inc.

Treatment of hepatitis C virus infection in patients with cirrhosis and predictive value of model for end-stage liver disease: Analysis of data from the Hepa-C registry.

PubMed

Fernández Carrillo, Carlos; Lens, Sabela; Llop, Elba; Pascasio, Juan Manuel; Crespo, Javier; Arenas, Juan; Fernández, Inmaculada; Baliellas, Carme; Carrión, José Antonio; de la Mata, Manuel; Buti, Maria; Castells, Lluís; Albillos, Agustín; Romero, Manuel; Turnes, Juan; Pons, Clara; Moreno-Planas, José María; Moreno-Palomares, José Javier; Fernández-Rodriguez, Conrado; García-Samaniego, Javier; Prieto, Martín; Fernández Bermejo, Miguel; Salmerón, Javier; Badia, Ester; Salcedo, Magdalena; Herrero, José Ignacio; Granados, Rafael; Blé, Michel; Mariño, Zoe; Calleja, José Luis

2017-06-01

Direct-acting antiviral agents (DAAs) are highly effective and well tolerated in patients with chronic hepatitis C virus infection, including those with compensated cirrhosis. However, fewer data are available in patients with more advanced liver disease. Our retrospective, noninterventional, national, multicenter study in patients from the Spanish Hepa-C registry investigated the effectiveness and safety of interferon-free DAA regimens in patients with advanced liver disease, including those with decompensated cirrhosis, in routine practice (all currently approved regimens were registered). Patients transplanted during treatment or within 12 weeks of completing treatment were excluded. Among 843 patients with cirrhosis (Child-Turcotte-Pugh [CTP] class A, n = 564; CTP class B/C, n = 175), 90% achieved sustained virologic response 12 weeks after treatment (SVR12). Significant differences in SVR12 and relapse rates were observed between CTP class A and CTP class B/C patients (94% versus 78%, and 4% versus 14%, respectively; both P < 0.001). Serious adverse events (SAEs) were more common in CTP class B/C versus CTP class A patients (50% versus 12%, respectively; P < 0.001). Incident decompensation was the most common serious adverse event (7% overall). Death rate during the study period was 16/843 (2%), significantly higher among CTP class B/C versus CTP class A patients (6.4% versus 0.9%; P < 0.001). Baseline Model for End-Stage Liver Disease (MELD) score alone (cut-off 18) was the best predictor of survival. Patients with decompensated cirrhosis receiving DAAs present lower response rates and experience more SAEs. In this setting, a MELD score ≥18 may help clinicians to identify those patients with a higher risk of complications and to individualize treatment decisions. (Hepatology 2017;65:1810-1822). © 2017 by the American Association for the Study of Liver Diseases.

Assessment of bronchial and pulmonary blood supply in non-small cell lung cancer subtypes using computed tomography perfusion.

PubMed

Nguyen-Kim, Thi Dan Linh; Frauenfelder, Thomas; Strobel, Klaus; Veit-Haibach, Patrick; Huellner, Martin W

2015-03-01

The aim of this study was to investigate the dual blood supply of non-small cell lung cancer (NSCLC) and its association with tumor subtype, size, and stage, using computed tomography perfusion (CTP). A total of 54 patients (median age, 65 years; range, 42-79 years; 15 women, 39 men) with suspected lung cancer underwent a CTP scan of the lung tumor. Pulmonary and bronchial vasculature regions of interest were used to calculate independently CTP parameters (blood flow [BF], blood volume [BV], and mean transit time [MTT]) of the tumor tissue. The mean and maximum pulmonary and bronchial perfusion indexes (PImean and PImax) were calculated. The tumoral volume and the largest tumoral diameter were assessed. Differences in CTP parameters and indexes among NSCLC subtypes, tumor stages and tumor dimensions were analyzed using non-parametric tests. According to biopsy, 37 patients had NSCLC (22 adenocarcinomas [ACs], 8 squamous cell carcinomas [SCCs], 7 large-cell carcinomas [LCC]). The mean bronchial BF/pulmonary BF, bronchial BV/pulmonary BV, and bronchial MTT/pulmonary MTT was 41.2 ± 30.0/36.9 ± 24.2 mL/100 mL/min, 11.4 ± 9.7/10.4 ± 9.4 mL/100 mL, and 11.4 ± 4.3/14.9 ± 4.4 seconds, respectively. In general, higher bronchial BF than pulmonary BF was observed in NSCLC (P = 0.014). Using a tumoral volume cutoff of 3.5 cm, a significant difference in pulmonary PImax was found (P = 0.028). There was a significantly higher mean pulmonary BF in LCCs and SCCs compared with ACs (P = 0.018 and P = 0.044, respectively), whereas the mean bronchial BF was only significantly higher in LCCs compared with ACs (P = 0.024). Correspondingly, the PImax was significantly higher in LCCs and SCCs than in ACs (P = 0.001 for both). Differences between bronchial and pulmonary PImean and PImax among T stages and Union Internationale Contre le Cancer stages were not statistically significant (P values ranging from 0.691 to 0.753). The known dual blood supply of NSCLC, which depends on tumor size and histological subtype, is reflected in CTP parameters, with parameters depending both on tumor size and histological subtype. This has to be accounted for when analyzing NSCLC with CTP.

Evaluation of the Bangalore Project.

ERIC Educational Resources Information Center

Beretta, Alan; Davies, Alan

1985-01-01

Follows up an article by Brumfit on the Bangalore/Madras Communicational Teaching Project (CTP). Discusses the framework, tests, and results of a 1984 evaluation supporting the claim that grammar construction can take place through a focus on meaning alone. (SED)

Reversible hemispheric hypoperfusion in two cases of SMART syndrome.

PubMed

Wai, Karmen; Balabanski, Anna; Chia, Nicholas; Kleinig, Timothy

2017-09-01

Stroke-like migraine attacks after radiation therapy (SMART) syndrome manifests as prolonged episodes of cortical dysfunction, years after cranial irradiation. We present two cases demonstrating reversible hemispheric hypoperfusion. Case 1 presented with left hemispheric symptoms following previous similar episodes. CT perfusion (CTP) demonstrated reversible hemispheric hypoperfusion; subsequent investigations were consistent with SMART syndrome. Case 2 presented following the third episode of a hemispheric syndrome with near-identical CTP abnormalities. L-arginine was administered with rapid reversal of clinical and CTP abnormalities. We conclude that SMART syndrome may demonstrate significant hypoperfusion on hyperacute CTP without subsequent infarction. Impaired cerebrovascular autoregulation probably contributes to cortical dysfunction in SMART syndrome. L-arginine warrants investigation as a potential treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effect of sprinting after each set of heavy resistance training on the running speed and jumping performance of young basketball players.

PubMed

Tsimahidis, Konstantinos; Galazoulas, Christos; Skoufas, Dimitrios; Papaiakovou, Georgios; Bassa, Eleni; Patikas, Dimitrios; Kotzamanidis, Christos

2010-08-01

The purpose of this study was to investigate the effect of a 10-week heavy resistance combined with a running training program on the strength, running speed (RS), and vertical jump performance of young basketball players. Twenty-six junior basketball players were equally divided in 2 groups. The control (CON) group performed only technical preparation and the group that followed the combined training program (CTP) performed additionally 5 sets of 8-5 repetition maximum (RM) half squat with 1 30-m sprint after each set. The evaluation took place before training and after the 5th and 10th weeks of training. Apart from the 1RM half squat test, the 10- and 30-m running time was measured using photocells and the jump height (squat, countermovement jump, and drop jump) was estimated taking into account the flight time. The 1RM increased by 30.3 +/- 1.5% at the 10th week of training for the CTP group (p < 0.05), whereas the CON group showed no significant increase (1.1 +/- 1.6%, p > 0.05). In general, all measured parameters showed a statistically significant increase after the 5th and 10th weeks (p < 0.05), in contrast to the CON group (p > 0.05). This suggests that the applied CTP is beneficial for the strength, RS, and jump height of young basketball players. The observed adaptations in the CTP group could be attributed to learning factors and to a more optimal transfer of the strength gain to running and jumping performance.

Different CT perfusion algorithms in the detection of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

PubMed

Cremers, Charlotte H P; Dankbaar, Jan Willem; Vergouwen, Mervyn D I; Vos, Pieter C; Bennink, Edwin; Rinkel, Gabriel J E; Velthuis, Birgitta K; van der Schaaf, Irene C

2015-05-01

Tracer delay-sensitive perfusion algorithms in CT perfusion (CTP) result in an overestimation of the extent of ischemia in thromboembolic stroke. In diagnosing delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH), delayed arrival of contrast due to vasospasm may also overestimate the extent of ischemia. We investigated the diagnostic accuracy of tracer delay-sensitive and tracer delay-insensitive algorithms for detecting DCI. From a prospectively collected series of aSAH patients admitted between 2007-2011, we included patients with any clinical deterioration other than rebleeding within 21 days after SAH who underwent NCCT/CTP/CTA imaging. Causes of clinical deterioration were categorized into DCI and no DCI. CTP maps were calculated with tracer delay-sensitive and tracer delay-insensitive algorithms and were visually assessed for the presence of perfusion deficits by two independent observers with different levels of experience. The diagnostic value of both algorithms was calculated for both observers. Seventy-one patients were included. For the experienced observer, the positive predictive values (PPVs) were 0.67 for the delay-sensitive and 0.66 for the delay-insensitive algorithm, and the negative predictive values (NPVs) were 0.73 and 0.74. For the less experienced observer, PPVs were 0.60 for both algorithms, and NPVs were 0.66 for the delay-sensitive and 0.63 for the delay-insensitive algorithm. Test characteristics are comparable for tracer delay-sensitive and tracer delay-insensitive algorithms for the visual assessment of CTP in diagnosing DCI. This indicates that both algorithms can be used for this purpose.

Safety and feasibility of leadless pacemaker in patients undergoing atrioventricular node ablation for atrial fibrillation.

PubMed

Yarlagadda, Bharath; Turagam, Mohit K; Dar, Tawseef; Jangam, Pragna; Veerapaneni, Vaishnavi; Atkins, Donita; Bommana, Sudharani; Friedman, Paul; Deshmukh, Abhishek J; Doshi, Rahul; Reddy, Vivek Y; Dukkipati, Srinivas R; Natale, Andrea; Lakkireddy, Dhanunjaya

2018-03-01

Atrioventricular node (AVN) ablation and permanent pacing is an established strategy for rate control in the management of symptomatic atrial fibrillation (AF). Leadless pacemakers (LPs) can overcome some of the short-term and long-term limitations of conventional transvenous pacemakers (CTPs). The purpose of this study was to compare the feasibility and safety of LP with those of single-chamber CTP in patients with AF undergoing AVN ablation. We conducted a multicenter observational study of patients undergoing AVN ablation and pacemaker implantation (LP vs single-chamber CTP) between February 2014 and November 2016. The primary efficacy end points were acceptable sensing (R wave ≥5.0 mV) and pacing thresholds (≤2.0 V at 0.4 ms) at follow-up. Safety end points included device-related major and minor (early ≤1 month, late >1 month) adverse events. A total of 127 patients with LP (n = 60) and CTP (n = 67) were studied. The median follow-up was 12 months (interquartile range 12-18 months). Ninety-five percent of the LP group and 97% of the CTP group met the primary efficacy end point at follow-up (57 of 60 vs 65 of 67; P = .66). There was 1 major adverse event (loss of pacing and sensing) in the LP group and 2 (lead dislodgement) in the CTP group (1 of 60 vs 2 of 67; P = 1.00). There were 6 minor adverse events (5 early and 1 late) in the LP group and 3 (early) in the CTP group (6 of 60 vs 3 of 67; P = .30). Our results demonstrate the feasibility and safety of LP compared with CTP in patients undergoing AVN ablation for AF. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

A proposed procedure for derivation of regulatory values for carcinogenic airborne polycyclic aromatic hydrocarbons (PAHs) based on coal tar pitch (CTP) volatiles.

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

Foureman, G.L.; Smith, R.L.

A procedure for estimating upper bound lifetime human cancer risk from air levels of six common carcinogenic polycyclic aromatic hydrocarbons (PAHs), termed APAHs of concern, is proposed. These PAHs are benzo(a)pyrene, benz(a)anthracene, benzo(b)fluoranthene, benzo(k)fluoranthene, indeno(1,2,3-c,d)pyrene, and chrysene. In application, this proposed procedure would regard any given air level obtained for a APAH of concern to originate from a standard mixture of coal tar pitch (CTP). The given air level for the APAHs of concern is then related to a corresponding air level of CTP and thence, to an inhalation unit cancer risk calculated for CTP. Reference values for the proceduremore » are the relative and absolute PAH composition of a CTP standard (SRM-1597) and the inhalation unit cancer risk. Qualitative characterization of the results are a vital part of the procedure especially when more than one APAH of concern{at} is being considered. Toxic equivalency factors (TEFs) may be used as an evaluative tool in characterization of the procedure and outcome. Limitations of this proposed procedure include the uneven database for the reference values and the inability to consider air samples inclusive of another common carcinogenic PAH, dibenz(a,h)anthracene, due to its lack of documentation in CTP and high TEF« less

Clinical experience with infliximab biosimilar Remsima (CT-P13) in inflammatory bowel disease patients

PubMed Central

Jahnsen, Jørgen

2016-01-01

Many reference biological therapies have now reached or are near to patent expiry, and therefore a number of biosimilars have been or will be developed. The term biosimilar can be defined as a biotherapeutic product that is similar in efficacy, safety and quality to the licensed reference product. Biosimilars may lead to a reduced price and significant cost savings for the health community and hopefully more patients globally will have easier access to biological therapy when indicated. CT-P13, which is a TNF-alfa inhibitor, is the first monoclonal antibody biosimilar being used in clinical practice. The drug is approved for all indications as an innovator product although clinical efficacy has only been demonstrated in rheumatic diseases. Until now the number of patients with inflammatory bowel disease (IBD) treated with CT-P13 is confined, but experience is continuously growing. Based on current data, CT-P13 seems to be efficacious and generally well tolerated in IBD especially in patients who are naïve to biological therapy. Knowledge with regard to interchangeability between CT-P13 and the originator infliximab is however, still rather sparse and more data are desired. Immunogenicity and long-term safety related to CT-P13 are other areas of great importance and good and reliable postmarketing pharmacovigilance is therefore required in the coming years. PMID:27134662

Experimental validation of Critical Temperature-Pressure theory of scuffing

NASA Astrophysics Data System (ADS)

Lee, Si C.; Chen, Huanliang

1995-07-01

A series of experiments was conducted for validating a newly developed theory of scuffing. The Critical temperature-Pressure (CTP) theory is based on the physisorption behavior of lubricants and is capable of predicting the onset of scuffing failures over a wide range of operating conditions, including the contacts operating in the boundary lubrication and in the partial elastohydrodynamic lubrication (EHL) regimes. According to the CTP theory, failures occur when the contact temperature exceeds a certain critical value which is a function of the lubricant pressure generated by the hydrodynamic action of the EHL contact. A special device capable of simulating the ambient conditions of the partial EHL conjunctions (of contact temperature, pressure, and the lubricant pressure) was constructed. A ball-on-flat type wear tester was put inside a pressure vessel, completely immersed in a highly pressurized bath of mineral oil. The temperature on the flat specimen was gradually increased while the ball was slowly traversed. At a certain critical temmperature, the friction force abruptly jumped indicating the incipiency of the lubrication breakdown. This experiment was repeated for several levels of hydrostatic pressure and the corresponding critical temperatures were obtained. The test results showed an excellent correlation with the newly developed CTP theory.

Clinical development of CT-P10 and other biosimilar cancer therapeutics.

PubMed

Kim, Won Seog; Coiffier, Bertrand; Kwon, Hyuk-Chan; Kim, SuYeon

2017-05-01

Biosimilars are highly similar versions of approved biologic drugs that may confer equivalent efficacy at a reduced cost. Patents for several biological cancer therapeutics are past or approaching expiry, presenting an opportunity to increase affordability and global accessibility of key drugs through the development of biosimilars. To receive approval, a biosimilar must show no clinically meaningful differences from the reference product in terms of efficacy or safety. The first monoclonal antibody biosimilar cancer therapeutic to gain approval was CT-P10, a biosimilar of rituximab. Here, we review the oncology clinical development program for CT-P10, providing insights into the rationale for, and design of, CT-P10 clinical trials in patients with cancer. Trials of biosimilar cancer therapeutics in development are also discussed.

A Disruption of ctpA Encoding Carboxy-Terminal Protease Attenuates Burkholderia mallei and Induces Partial Protection in CD1 Mice

DTIC Science & Technology

2008-06-03

etiologic agent of glanders in solipeds (horses, mules and donkeys), and incidentally in carnivores and humans. Little is known about the molecular...disintegrated cell envelopes. Furthermore, relative to the wild type, the ctpA mutant displayed slower growth in vitro and less ability to survive in...IgG2a and were partially protected against chal- lenge with wild type B. mallei ATCC 23344. These findings suggest that CtpA regulates in vitro growth

Following DNA chain extension and protein conformational changes in crystals of a Y-family DNA polymerase via Raman crystallography.

PubMed

Espinoza-Herrera, Shirly J; Gaur, Vineet; Suo, Zucai; Carey, Paul R

2013-07-23

Y-Family DNA polymerases are known to bypass DNA lesions in vitro and in vivo. Sulfolobus solfataricus DNA polymerase (Dpo4) was chosen as a model Y-family enzyme for investigating the mechanism of DNA synthesis in single crystals. Crystals of Dpo4 in complexes with DNA (the binary complex) in the presence or absence of an incoming nucleotide were analyzed by Raman microscopy. (13)C- and (15)N-labeled d*CTP, or unlabeled dCTP, were soaked into the binary crystals with G as the templating base. In the presence of the catalytic metal ions, Mg(2+) and Mn(2+), nucleotide incorporation was detected by the disappearance of the triphosphate band of dCTP and the retention of *C modes in the crystal following soaking out of noncovalently bound C(or *C)TP. The addition of the second coded base, thymine, was observed by adding cognate dTTP to the crystal following a single d*CTP addition. Adding these two bases caused visible damage to the crystal that was possibly caused by protein and/or DNA conformational change within the crystal. When d*CTP is soaked into the Dpo4 crystal in the absence of Mn(2+) or Mg(2+), the primer extension reaction did not occur; instead, a ternary protein·template·d*CTP complex was formed. In the Raman difference spectra of both binary and ternary complexes, in addition to the modes of d(*C)CTP, features caused by ring modes from the template/primer bases being perturbed and from the DNA backbone appear, as well as features from perturbed peptide and amino acid side chain modes. These effects are more pronounced in the ternary complex than in the binary complex. Using standardized Raman intensities followed as a function of time, the C(*C)TP population in the crystal was maximal at ∼20 min. These remained unchanged in the ternary complex but declined in the binary complexes as chain incorporation occurred.

A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study

PubMed Central

Yoo, Dae Hyun; Hrycaj, Pawel; Miranda, Pedro; Ramiterre, Edgar; Piotrowski, Mariusz; Shevchuk, Sergii; Kovalenko, Volodymyr; Prodanovic, Nenad; Abello-Banfi, Mauricio; Gutierrez-Ureña, Sergio; Morales-Olazabal, Luis; Tee, Michael; Jimenez, Renato; Zamani, Omid; Lee, Sang Joon; Kim, HoUng; Park, Won; Müller-Ladner, Ulf

2013-01-01

Objectives To compare the efficacy and safety of innovator infliximab (INX) and CT-P13, an INX biosimilar, in active rheumatoid arthritis patients with inadequate response to methotrexate (MTX) treatment. Methods Phase III randomised, double-blind, multicentre, multinational, parallel-group study. Patients with active disease despite MTX (12.5–25 mg/week) were randomised to receive 3 mg/kg of CT-P13 (n=302) or INX (n=304) with MTX and folic acid. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 30. Therapeutic equivalence of clinical response according to ACR20 criteria was concluded if the 95% CI for the treatment difference was within ±15%. Secondary endpoints included ACR response criteria, European League Against Rheumatism (EULAR) response criteria, change in Disease Activity Score 28 (DAS28), Medical Outcomes Study Short-Form Health Survey (SF-36), Simplified Disease Activity Index, Clinical Disease Activity Index, as well as pharmacokinetic (PK) and pharmacodynamic (PD) parameters, safety and immunogenicity. Results At week 30, ACR20 responses were 60.9% for CT-P13 and 58.6% for INX (95% CI −6% to 10%) in the intention-to-treat population. The proportions in CT-P13 and INX groups achieving good or moderate EULAR responses (C reactive protein (CRP)) at week 30 were 85.8% and 87.1%, respectively. Low disease activity or remission according to DAS28–CRP, ACR–EULAR remission rates, ACR50/ACR70 responses and all other PK and PD endpoints were highly similar at week 30. Incidence of drug-related adverse events (35.2% vs 35.9%) and detection of antidrug antibodies (48.4% vs 48.2%) were highly similar for CT-P13 and INX, respectively. Conclusions CT-P13 demonstrated equivalent efficacy to INX at week 30, with a comparable PK profile and immunogenicity. CT-P13 was well tolerated, with a safety profile comparable with that of INX. ClinicalTrials.gov Identifier NCT01217086 PMID:23687260

California Transportation Plan 2025.

DOT National Transportation Integrated Search

2006-04-01

The California Transportation Plan 2025 (CTP) offers a blueprint for meeting : the States future mobility needs. The CTP is a long-range transportation : policy plan that explores the social, economic, and technological trends : and demographic ch...

A new sampling scheme for developing metamodels with the zeros of Chebyshev polynomials

NASA Astrophysics Data System (ADS)

Wu, Jinglai; Luo, Zhen; Zhang, Nong; Zhang, Yunqing

2015-09-01

The accuracy of metamodelling is determined by both the sampling and approximation. This article proposes a new sampling method based on the zeros of Chebyshev polynomials to capture the sampling information effectively. First, the zeros of one-dimensional Chebyshev polynomials are applied to construct Chebyshev tensor product (CTP) sampling, and the CTP is then used to construct high-order multi-dimensional metamodels using the 'hypercube' polynomials. Secondly, the CTP sampling is further enhanced to develop Chebyshev collocation method (CCM) sampling, to construct the 'simplex' polynomials. The samples of CCM are randomly and directly chosen from the CTP samples. Two widely studied sampling methods, namely the Smolyak sparse grid and Hammersley, are used to demonstrate the effectiveness of the proposed sampling method. Several numerical examples are utilized to validate the approximation accuracy of the proposed metamodel under different dimensions.

Isolation of a euryhaline microalgal strain, Tetraselmis sp. CTP4, as a robust feedstock for biodiesel production

PubMed Central

Pereira, Hugo; Gangadhar, Katkam N.; Schulze, Peter S. C.; Santos, Tamára; de Sousa, Carolina Bruno; Schueler, Lisa M.; Custódio, Luísa; Malcata, F. Xavier; Gouveia, Luísa; Varela, João C. S.; Barreira, Luísa

2016-01-01

Bioprospecting for novel microalgal strains is key to improving the feasibility of microalgae-derived biodiesel production. Tetraselmis sp. CTP4 (Chlorophyta, Chlorodendrophyceae) was isolated using fluorescence activated cell sorting (FACS) in order to screen novel lipid-rich microalgae. CTP4 is a robust, euryhaline strain able to grow in seawater growth medium as well as in non-sterile urban wastewater. Because of its large cell size (9–22 μm), CTP4 settles down after a six-hour sedimentation step. This leads to a medium removal efficiency of 80%, allowing a significant decrease of biomass dewatering costs. Using a two-stage system, a 3-fold increase in lipid content (up to 33% of DW) and a 2-fold enhancement in lipid productivity (up to 52.1 mg L−1 d−1) were observed upon exposure to nutrient depletion for 7 days. The biodiesel synthesized from the lipids of CTP4 contained high levels of oleic acid (25.67% of total fatty acids content) and minor amounts of polyunsaturated fatty acids with ≥4 double bonds (<1%). As a result, this biofuel complies with most of the European (EN14214) and American (ASTM D6751) specifications, which commonly used microalgal feedstocks are usually unable to meet. In conclusion, Tetraselmis sp. CTP4 displays promising features as feedstock with lower downstream processing costs for biomass dewatering and biodiesel refining. PMID:27767051

Comparable long-term efficacy, as assessed by patient-reported outcomes, safety and pharmacokinetics, of CT-P13 and reference infliximab in patients with ankylosing spondylitis: 54-week results from the randomized, parallel-group PLANETAS study.

PubMed

Park, Won; Yoo, Dae Hyun; Jaworski, Janusz; Brzezicki, Jan; Gnylorybov, Andriy; Kadinov, Vladimir; Sariego, Irmgadt Goecke; Abud-Mendoza, Carlos; Escalante, William Jose Otero; Kang, Seong Wook; Andersone, Daina; Blanco, Francisco; Hong, Seung Suh; Lee, Sun Hee; Braun, Jürgen

2016-01-20

CT-P13 (Remsima®, Inflectra®) is a biosimilar of the infliximab reference product (RP; Remicade®) and is approved in Europe and elsewhere, mostly for the same indications as RP. The aim of this study was to compare the 54-week efficacy, immunogenicity, pharmacokinetics (PK) and safety of CT-P13 with RP in patients with ankylosing spondylitis (AS), with a focus on patient-reported outcomes (PROs). This was a multinational, double-blind, parallel-group study in patients with active AS. Participants were randomized (1:1) to receive CT-P13 (5 mg/kg) or RP (5 mg/kg) at weeks 0, 2, 6 and then every 8 weeks up to week 54. To assess responses, standardized assessment tools were used with an intention-to-treat analysis of observed data. Anti-drug antibodies (ADAs), PK parameters, and safety outcomes were also assessed. Of 250 randomized patients (n = 125 per group), 210 (84.0 %) completed 54 weeks of treatment, with similar completion rates between groups. At week 54, Assessment of Spondylo Arthritis international Society (ASAS)20 response, ASAS40 response and ASAS partial remission were comparable between treatment groups. Changes from baseline in PROs such as mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; CT-P13 -3.1 versus RP -2.8), Bath Ankylosing Spondylitis Functional Index (BASFI; -2.9 versus -2.7), and Short Form Health Survey (SF-36) scores (9.26 versus 10.13 for physical component summary; 7.30 versus 6.54 for mental component summary) were similar between treatment groups. At 54 weeks, 19.5 % and 23.0 % of patients receiving CT-P13 and RP, respectively, had ADAs. All observed PK parameters of CT-P13 and RP, including maximum and minimum serum concentrations, were similar through 54 weeks. The influence of ADAs on PK was similar in the two treatment groups. Most adverse events were mild or moderate in severity. There was no notable difference between treatment groups in the incidence of adverse events, serious adverse events, infections and infusion-related reactions. CT-P13 and RP have highly comparable efficacy (including PROs) and PK up to week 54. Over a 1-year period, CT-P13 was well tolerated and displayed a safety profile comparable to RP; no differences in immunogenicity were observed. ClinicalTrials.gov identifier: NCT01220518 . Registered 4 October 2010.

Associations Between Serum Bone Biomarkers in Early Breast Cancer and Development of Bone Metastasis: Results From the AZURE (BIG01/04) Trial.

PubMed

Brown, Janet; Rathbone, Emma; Hinsley, Samantha; Gregory, Walter; Gossiel, Fatma; Marshall, Helen; Burkinshaw, Roger; Shulver, Helen; Thandar, Hasina; Bertelli, Gianfilippo; Maccon, Keane; Bowman, Angela; Hanby, Andrew; Bell, Richard; Cameron, David; Coleman, Robert

2018-02-07

Adjuvant therapies can prevent/delay bone metastasis development in breast cancer. We investigated whether serum bone turnover markers in early disease have clinical utility in identifying patients with a high risk of developing bone metastasis. Markers of bone formation (N-terminal propeptide of type-1 collagen [P1NP]) and bone resorption (C-telopeptide of type-1 collagen [CTX], pyridinoline cross-linked carboxy-terminal telopeptide of type-1 collagen [1-CTP]) were measured in baseline (pretreatment blood samples from 872 patients from a large randomized trial of adjuvant zoledronic acid (AZURE-ISRCTN79831382) in early breast cancer. Cox proportional hazards regression and cumulative incidence functions (adjusted for factors having a statistically significant effect on outcome) were used to investigate prognostic and predictive associations between recurrence events, bone marker levels, and clinical variables. All statistical tests were two-sided. When considered as continuous variables (log transformed), P1NP, CTX, and 1-CTP were each prognostic for future bone recurrence at any time (P = .006, P = .009, P = .008, respectively). Harrell's c-indices were a P1NP of 0.57 (95% confidence interval [CI] = 0.51 to 0.63), CTX of 0.57 (95% CI = 0.51 to 0.62), and 1-CTP of 0.57 (95% CI = 0.52 to 0.63). In categorical analyses based on the normal range, high baseline P1NP (>70 ng/mL) and CTX (>0.299 ng/mL), but not 1-CTP (>4.2 ng/mL), were also prognostic for future bone recurrence (P = .03, P = .03, P = .10, respectively). None of the markers were prognostic for overall distant recurrence; that is, they were bone metastasis specific, and none of the markers were predictive of treatment benefit from zoledronic acid. Serum P1NP, CTX, and 1-CTP are clinically useful, easily measured markers that show good prognostic ability (though low-to-moderate discrimination) for bone-specific recurrence and are worthy of further study. © The Author(s) 2018. Published by Oxford University Press.

The P-type ATPase CtpG preferentially transports Cd2+ across the Mycobacterium tuberculosis plasma membrane.

PubMed

López, Marcela; Quitian, Laudy-Viviana; Calderón, Martha-Nancy; Soto, Carlos-Y

2018-04-01

P 1B -type ATPases are involved in heavy metal transport across the plasma membrane. Some Mycobacterium tuberculosis P-type ATPases are induced during infection, suggesting that this type of transporter could play a critical role in mycobacterial survival. To date, the ion specificity of M. tuberculosis heavy metal-transporting P 1B -ATPases is not well understood. In this work, we observed that, although divalent heavy metal cations such as Cu 2+ , Co 2+ , Ni 2+ , Zn 2+ Cd 2+ and Pb 2+ stimulate the ATPase activity of the putative P 1B -type ATPase CtpG in the plasma membrane, whole cells of M. smegmatis expressing CtpG only tolerate high levels of Cd 2+ and Cu 2+ . As indicator of the catalytic constant, Michaelis-Menten kinetics showed that CtpG embedded in the mycobacterial cell membrane has a V max /K m ratio 7.4-fold higher for Cd 2+ than for Cu 2+ ions. Thus, although CtpG can accept different substrates in vitro, this P-type ATPase transports Cd 2+ more efficiently than other heavy metal cations across the mycobacterial plasma membrane.

Myocardial perfusion 320-row multidetector computed tomography-guided treatment strategy for the clinical management of patients with recent acute-onset chest pain: Design of the CArdiac cT in the treatment of acute CHest pain (CATCH)-2 randomized controlled trial.

PubMed

Sørgaard, Mathias; Linde, Jesper J; Hove, Jens D; Petersen, Jan R; Jørgensen, Tem B S; Abdulla, Jawdat; Heitmann, Merete; Kragelund, Charlotte; Hansen, Thomas Fritz; Udholm, Patricia M; Pihl, Christian; Kühl, J Tobias; Engstrøm, Thomas; Jensen, Jan Skov; Høfsten, Dan E; Kelbæk, Henning; Kofoed, Klaus F

2016-09-01

Patients admitted with chest pain are a diagnostic challenge because the majority does not have coronary artery disease (CAD). Assessment of CAD with coronary computed tomography angiography (CCTA) is safe, cost-effective, and accurate, albeit with a modest specificity. Stress myocardial computed tomography perfusion (CTP) has been shown to increase the specificity when added to CCTA, without lowering the sensitivity. This article describes the design of a randomized controlled trial, CATCH-2, comparing a clinical diagnostic management strategy of CCTA alone against CCTA in combination with CTP. Patients with acute-onset chest pain older than 50 years and with at least one cardiovascular risk factor for CAD are being prospectively enrolled to this study from 6 different clinical sites since October 2013. A total of 600 patients will be included. Patients are randomized 1:1 to clinical management based on CCTA or on CCTA in combination with CTP, determining the need for further testing with invasive coronary angiography including measurement of the fractional flow reserve in vessels with coronary artery lesions. Patients are scanned with a 320-row multidetector computed tomography scanner. Decisions to revascularize the patients are taken by the invasive cardiologist independently of the study allocation. The primary end point is the frequency of revascularization. Secondary end points of clinical outcome are also recorded. The CATCH-2 will determine whether CCTA in combination with CTP is diagnostically superior to CCTA alone in the management of patients with acute-onset chest pain. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of glioblastomas and lymphomas with whole-brain CT perfusion: Comparison between a delay-invariant singular-value decomposition algorithm and a Patlak plot.

PubMed

Hiwatashi, Akio; Togao, Osamu; Yamashita, Koji; Kikuchi, Kazufumi; Yoshimoto, Koji; Mizoguchi, Masahiro; Suzuki, Satoshi O; Yoshiura, Takashi; Honda, Hiroshi

2016-07-01

Correction of contrast leakage is recommended when enhancing lesions during perfusion analysis. The purpose of this study was to assess the diagnostic performance of computed tomography perfusion (CTP) with a delay-invariant singular-value decomposition algorithm (SVD+) and a Patlak plot in differentiating glioblastomas from lymphomas. This prospective study included 17 adult patients (12 men and 5 women) with pathologically proven glioblastomas (n=10) and lymphomas (n=7). CTP data were analyzed using SVD+ and a Patlak plot. The relative tumor blood volume and flow compared to contralateral normal-appearing gray matter (rCBV and rCBF derived from SVD+, and rBV and rFlow derived from the Patlak plot) were used to differentiate between glioblastomas and lymphomas. The Mann-Whitney U test and receiver operating characteristic (ROC) analyses were used for statistical analysis. Glioblastomas showed significantly higher rFlow (3.05±0.49, mean±standard deviation) than lymphomas (1.56±0.53; P<0.05). There were no statistically significant differences between glioblastomas and lymphomas in rBV (2.52±1.57 vs. 1.03±0.51; P>0.05), rCBF (1.38±0.41 vs. 1.29±0.47; P>0.05), or rCBV (1.78±0.47 vs. 1.87±0.66; P>0.05). ROC analysis showed the best diagnostic performance with rFlow (Az=0.871), followed by rBV (Az=0.771), rCBF (Az=0.614), and rCBV (Az=0.529). CTP analysis with a Patlak plot was helpful in differentiating between glioblastomas and lymphomas, but CTP analysis with SVD+ was not. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Feasibility of dual-low scheme combined with iterative reconstruction technique in acute cerebral infarction volume CT whole brain perfusion imaging.

PubMed

Wang, Tao; Gong, Yi; Shi, Yibing; Hua, Rong; Zhang, Qingshan

2017-07-01

The feasibility of application of low-concentration contrast agent and low tube voltage combined with iterative reconstruction in whole brain computed tomography perfusion (CTP) imaging of patients with acute cerebral infarction was investigated. Fifty-nine patients who underwent whole brain CTP examination and diagnosed with acute cerebral infarction from September 2014 to March 2016 were selected. Patients were randomly divided into groups A and B. There were 28 cases in group A [tube voltage, 100 kV; contrast agent, iohexol (350 mg I/ml), reconstructed by filtered back projection] and 31 cases in group B [tube voltage, 80 kV; contrast agent, iodixanol (270 mg I/ml), reconstructed by algebraic reconstruction technique]. The artery CT value, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), dose length product, effective dose (ED) of radiation and brain iodine intake of both groups were measured and statistically analyzed. Two physicians carried out kappa (κ) analysis on the consistency of image quality evaluation. The difference in subjective image quality evaluation between the groups was tested by χ 2 . The differences in CT value, SNR, CNR, CTP and CT angiography subjective image quality evaluation between both groups were not statistically significant (P>0.05); the diagnosis rate of the acute infarcts between the two groups was not significantly different; while the ED and iodine intake in group B (dual low-dose group) were lower than group A. In conclusion, combination of low tube voltage and iterative reconstruction technique, and application of low-concentration contrast agent (270 mg I/ml) in whole brain CTP examination reduced ED and iodine intake without compromising image quality, thereby reducing the risk of contrast-induced nephropathy.

Error-prone bypass of O6-methylguanine by DNA polymerase of Pseudomonas aeruginosa phage PaP1.

PubMed

Gu, Shiling; Xiong, Jingyuan; Shi, Ying; You, Jia; Zou, Zhenyu; Liu, Xiaoying; Zhang, Huidong

2017-09-01

O 6 -Methylguanine (O 6 -MeG) is highly mutagenic and is commonly found in DNA exposed to methylating agents, generally leads to G:C to A:T mutagenesis. To study DNA replication encountering O 6 -MeG by the DNA polymerase (gp90) of P. aeruginosa phage PaP1, we analyzed steady-state and pre-steady-state kinetics of nucleotide incorporation opposite O 6 -MeG by gp90 exo - . O 6 -MeG partially inhibited full-length extension by gp90 exo - . O 6 -MeG greatly reduces dNTP incorporation efficiency, resulting in 67-fold preferential error-prone incorporation of dTTP than dCTP. Gp90 exo - extends beyond T:O 6 -MeG 2-fold more efficiently than C:O 6 -MeG. Incorporation of dCTP opposite G and incorporation of dCTP or dTTP opposite O 6 -MeG show fast burst phases. The pre-steady-state incorporation efficiency (k pol /K d,dNTP ) is decreased in the order of dCTP:G>dTTP:O 6 -MeG>dCTP:O 6 -MeG. The presence of O 6 -MeG at template does not affect the binding affinity of polymerase to DNA but it weakened their binding in the presence of dCTP and Mg 2+ . Misincorporation of dTTP opposite O 6 -MeG further weakens the binding affinity of polymerase to DNA. The priority of dTTP incorporation opposite O 6 -MeG is originated from the fact that dTTP can induce a faster conformational change step and a faster chemical step than dCTP. This study reveals that gp90 bypasses O 6 -MeG in an error-prone manner and provides further understanding in DNA replication encountering mutagenic alkylation DNA damage for P. aeruginosa phage PaP1. Copyright © 2017 Elsevier B.V. All rights reserved.

Low dose dynamic myocardial CT perfusion using advanced iterative reconstruction

NASA Astrophysics Data System (ADS)

Eck, Brendan L.; Fahmi, Rachid; Fuqua, Christopher; Vembar, Mani; Dhanantwari, Amar; Bezerra, Hiram G.; Wilson, David L.

2015-03-01

Dynamic myocardial CT perfusion (CTP) can provide quantitative functional information for the assessment of coronary artery disease. However, x-ray dose in dynamic CTP is high, typically from 10mSv to >20mSv. We compared the dose reduction potential of advanced iterative reconstruction, Iterative Model Reconstruction (IMR, Philips Healthcare, Cleveland, Ohio) to hybrid iterative reconstruction (iDose4) and filtered back projection (FBP). Dynamic CTP scans were obtained using a porcine model with balloon-induced ischemia in the left anterior descending coronary artery to prescribed fractional flow reserve values. High dose dynamic CTP scans were acquired at 100kVp/100mAs with effective dose of 23mSv. Low dose scans at 75mAs, 50mAs, and 25mAs were simulated by adding x-ray quantum noise and detector electronic noise to the projection space data. Images were reconstructed with FBP, iDose4, and IMR at each dose level. Image quality in static CTP images was assessed by SNR and CNR. Blood flow was obtained using a dynamic CTP analysis pipeline and blood flow image quality was assessed using flow-SNR and flow-CNR. IMR showed highest static image quality according to SNR and CNR. Blood flow in FBP was increasingly over-estimated at reduced dose. Flow was more consistent for iDose4 from 100mAs to 50mAs, but was over-estimated at 25mAs. IMR was most consistent from 100mAs to 25mAs. Static images and flow maps for 100mAs FBP, 50mAs iDose4, and 25mAs IMR showed comparable, clear ischemia, CNR, and flow-CNR values. These results suggest that IMR can enable dynamic CTP at significantly reduced dose, at 5.8mSv or 25% of the comparable 23mSv FBP protocol.

Ceramics Technology Project database: September 1991 summary report. [Materials for piston ring-cylinder liner for advanced heat/diesel engines

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

Keyes, B.L.P.

1992-06-01

The piston ring-cylinder liner area of the internal combustion engine must withstand very-high-temperature gradients, highly-corrosive environments, and constant friction. Improving the efficiency in the engine requires ring and cylinder liner materials that can survive this abusive environment and lubricants that resist decomposition at elevated temperatures. Wear and friction tests have been done on many material combinations in environments similar to actual use to find the right materials for the situation. This report covers tribology information produced from 1986 through July 1991 by Battelle columbus Laboratories, Caterpillar Inc., and Cummins Engine Company, Inc. for the Ceramic Technology Project (CTP). All datamore » in this report were taken from the project's semiannual and bimonthly progress reports and cover base materials, coatings, and lubricants. The data, including test rig descriptions and material characterizations, are stored in the CTP database and are available to all project participants on request. Objective of this report is to make available the test results from these studies, but not to draw conclusions from these data.« less

Ceramics Technology Project database: September 1991 summary report

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

Keyes, B.L.P.

1992-06-01

The piston ring-cylinder liner area of the internal combustion engine must withstand very-high-temperature gradients, highly-corrosive environments, and constant friction. Improving the efficiency in the engine requires ring and cylinder liner materials that can survive this abusive environment and lubricants that resist decomposition at elevated temperatures. Wear and friction tests have been done on many material combinations in environments similar to actual use to find the right materials for the situation. This report covers tribology information produced from 1986 through July 1991 by Battelle columbus Laboratories, Caterpillar Inc., and Cummins Engine Company, Inc. for the Ceramic Technology Project (CTP). All datamore » in this report were taken from the project`s semiannual and bimonthly progress reports and cover base materials, coatings, and lubricants. The data, including test rig descriptions and material characterizations, are stored in the CTP database and are available to all project participants on request. Objective of this report is to make available the test results from these studies, but not to draw conclusions from these data.« less

Evaluation of the pharmacokinetic equivalence and 54-week efficacy and safety of CT-P13 and innovator infliximab in Japanese patients with rheumatoid arthritis

PubMed Central

Takeuchi, Tsutomu; Yamanaka, Hisashi; Tanaka, Yoshiya; Sakurai, Takeo; Saito, Kazuyoshi; Ohtsubo, Hideo; Lee, Sang Joon; Nambu, Yoshihiro

2015-01-01

Objectives. To demonstrate the pharmacokinetic equivalence of CT-P13 and its innovator infliximab (IFX) in Japanese patients with rheumatoid arthritis (RA), and to compare the efficacy and safety of these drugs, administered for 54 weeks. Methods. In a randomized, double-blind, parallel-group, multicenter study, 3 mg/kg of CT-P13 or IFX, in combination with methotrexate (MTX) (6–16 mg/week), was administered for 54 weeks to Japanese active RA patients with an inadequate response to MTX, to demonstrate the pharmacokinetic equivalence, based on the area under the curve (AUCτ) (weeks 6–14) and Cmax (week 6) of these drugs, and to compare their efficacy and safety. Results. The CT-P13-to-IFX ratios (90% confidence intervals) of the geometric mean AUCτ and Cmax values in patients negative for antibodies to infliximab at week 14 were 111.62% (100.24–124.29%) and 104.09% (92.12–117.61%), respectively, demonstrating the pharmacokinetic equivalence of these drugs. In the full analysis set, CT-P13 and IFX showed comparable therapeutic effectiveness, as measured by the American College of Rheumatology, Disease Activity Score in 28 joints, the European League Against Rheumatism, and other efficacy criteria, at weeks 14 and 30. The incidence of adverse events was similar for these drugs. Conclusion. CT-P13 and IFX, administered at a dose of 3 mg/kg in combination with MTX to active RA patients, were pharmacokinetically equivalent and comparable in efficacy and safety. PMID:25736355

Antibacterial, anti-inflammatory, and bone-regenerative dual-drug-loaded calcium phosphate nanocarriers-in vitro and in vivo studies.

PubMed

Madhumathi, K; Rubaiya, Y; Doble, Mukesh; Venkateswari, R; Sampath Kumar, T S

2018-05-01

A dual local drug delivery system (DDS) composed of calcium phosphate bioceramic nanocarriers aimed at treating the antibacterial, anti-inflammatory, and bone-regenerative aspects of periodontitis has been developed. Calcium-deficient hydroxyapatite (CDHA, Ca/P = 1.61) and tricalcium phosphate (β-TCP) were prepared by microwave-accelerated wet chemical synthesis method. The phase purity of the nanocarriers was confirmed by x-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR), while the transmission electron microscopy (TEM) confirmed their nanosized morphology. CDHA was selected as carrier for the antibiotic (tetracycline) while TCP was chosen as the anti-inflammatory drug (ibuprofen) carrier. Combined drug release profile was studied in vitro from CDHA/TCP (CTP) system and compared with a HA/TCP (BCP) biphasic system. The tetracycline and ibuprofen release rate was 71 and 23% from CTP system as compared to 63 and 20% from BCP system. CTP system also showed a more controlled drug release profile compared to BCP system. Modeling of drug release kinetics from CTP system indicated that the release follows Higuchi model with a non-typical Fickian diffusion profile. In vitro biological studies showed the CTP system to be biocompatible with significant antibacterial and anti-inflammatory activity. In vivo implantation studies on rat cranial defects showed greater bone healing and new bone formation in the drug-loaded CTP system compared to control (no carrier) at the end of 12 weeks. The in vitro and in vivo results suggest that the combined drug delivery platform can provide a comprehensive management for all bone infections requiring multi-drug therapy.

The Novel Zinc Finger Protein dASCIZ Regulates Mitosis in Drosophila via an Essential Role in Dynein Light-Chain Expression

PubMed Central

Zaytseva, Olga; Tenis, Nora; Mitchell, Naomi; Kanno, Shin-ichiro; Yasui, Akira; Heierhorst, Jörg; Quinn, Leonie M

2014-01-01

The essential zinc finger protein ASCIZ (also known as ATMIN, ZNF822) plays critical roles during lung organogenesis and B cell development in mice, where it regulates the expression of dynein light chain (DYNLL1/LC8), but its functions in other species including invertebrates are largely unknown. Here we report the identification of the Drosophila ortholog of ASCIZ (dASCIZ) and show that loss of dASCIZ function leads to pronounced mitotic delays with centrosome and spindle positioning defects during development, reminiscent of impaired dynein motor functions. Interestingly, similar mitotic and developmental defects were observed upon knockdown of the DYNLL/LC8-type dynein light chain Cutup (Ctp), and dASCIZ loss-of-function phenotypes could be suppressed by ectopic Ctp expression. Consistent with a genetic function of dASCIZ upstream of Ctp, we show that loss of dASCIZ led to reduced endogenous Ctp mRNA and protein levels and dramatically reduced Ctp–LacZ reporter gene activity in vivo, indicating that dASCIZ regulates development and mitosis as a Ctp transcription factor. We speculate that the more severe mitotic defects in the absence of ASCIZ in flies compared to mice may be due to redundancy with a second, ASCIZ-independent, Dynll2 gene in mammals in contrast to a single Ctp gene in Drosophila. Altogether, our data demonstrate that ASCIZ is an evolutionary highly conserved transcriptional regulator of dynein light-chain levels and a novel regulator of mitosis in flies. PMID:24336747

The effects of pitting on fatigue crack nucleation in 7075-T6 aluminum alloy

NASA Technical Reports Server (NTRS)

Ma, LI; Hoeppner, David W.

1994-01-01

A high-strength aluminum alloy, 7075-T6, was studied to quantitatively evaluate chemical pitting effects of its corrosion fatigue life. The study focused on pit nucleation, pit growth, and fatigue crack nucleation. Pitting corrosion fatigue experiments were conducted in 3.5 percent NaCl aqueous solution under constant amplitude sinusoidal loading at two frequencies, 5 and 20 Hz. Smooth and unnotched specimens were used in this investigation. A video recording system was developed to allow in situ observation of the surface changes of the specimens during testing. The results indicated that pitting corrosion considerably reduces the fatigue strength by accelerating fatigue crack nucleation. A metallographic examination was conducted on the specimens to evaluate the nature of corrosion pits. First, the actual shapes of the corrosion pits were evaluated by cross-sectioning the pits. Secondly, the relation between corrosion pits and microstructure was also investigated. Finally, the possibility of another corrosion mechanism that might be involved in pitting was explored in this investigation. The fractography of the tested specimens showed that corner corrosion pits were responsible for fatigue crack nucleation in the material due to the associated stress concentration. The pits exhibited variance of morphology. Fatigue life for the experimental conditions appeared to be strongly dependent on pitting kinetics and the crack nucleation stage.

Assessment of hemodynamics in a rat model of liver cirrhosis with precancerous lesions using multislice spiral CT perfusion imaging.

PubMed

Ma, Guolin; Bai, Rongjie; Jiang, Huijie; Hao, Xuejia; Ling, Zaisheng; Li, Kefeng

2013-01-01

To develop an optimal scanning protocol for multislice spiral CT perfusion (CTP) imaging to evaluate hemodynamic changes in liver cirrhosis with diethylnitrosamine- (DEN-) induced precancerous lesions. Male Wistar rats were randomly divided into the control group (n = 80) and the precancerous liver cirrhosis group (n = 40). The control group received saline injection and the liver cirrhosis group received 50 mg/kg DEN i.p. twice a week for 12 weeks. All animals underwent plain CT scanning, CTP, and contrast-enhanced CT scanning. Scanning parameters were optimized by adjusting the diatrizoate concentration, the flow rate, and the delivery time. The hemodynamics of both groups was further compared using optimized multislice spiral CTP imaging. High-quality CTP images were obtained with following parameters: 150 kV; 150 mAs; 5 mm thickness, 5 mm interval; pitch, 1; matrix, 512 × 512; and FOV, 9.6 cm. Compared to the control group, the liver cirrhosis group had a significantly increased value of the hepatic arterial fraction and the hepatic artery perfusion (P < 0.05) but significantly decreased hepatic portal perfusion and mean transit time (P < 0.05). Multislice spiral CTP imaging can be used to evaluate the hemodynamic changes in the rat model of liver cirrhosis with precancerous lesions.

Dependence of quantitative accuracy of CT perfusion imaging on system parameters

NASA Astrophysics Data System (ADS)

Li, Ke; Chen, Guang-Hong

2017-03-01

Deconvolution is a popular method to calculate parametric perfusion parameters from four dimensional CT perfusion (CTP) source images. During the deconvolution process, the four dimensional space is squeezed into three-dimensional space by removing the temporal dimension, and a prior knowledge is often used to suppress noise associated with the process. These additional complexities confound the understanding about deconvolution-based CTP imaging system and how its quantitative accuracy depends on parameters and sub-operations involved in the image formation process. Meanwhile, there has been a strong clinical need in answering this question, as physicians often rely heavily on the quantitative values of perfusion parameters to make diagnostic decisions, particularly during an emergent clinical situation (e.g. diagnosis of acute ischemic stroke). The purpose of this work was to develop a theoretical framework that quantitatively relates the quantification accuracy of parametric perfusion parameters with CTP acquisition and post-processing parameters. This goal was achieved with the help of a cascaded systems analysis for deconvolution-based CTP imaging systems. Based on the cascaded systems analysis, the quantitative relationship between regularization strength, source image noise, arterial input function, and the quantification accuracy of perfusion parameters was established. The theory could potentially be used to guide developments of CTP imaging technology for better quantification accuracy and lower radiation dose.

Rain Erosion Studies of Sapphire, Aluminum Oxynitride, Spinel, Lanthana- Doped Yttria, and TAF Glass

DTIC Science & Technology

1990-07-01

small , there is little change in average scatter for any material in any test. CONCLUSIONS AND DISCUSSION The principal conclusions are 1. ALON...20 Sample broke erosion damage 10 Slight pitting, 20 No change erosion damage 15 Pitting, cratering, 20 Small surface pits erosion damage 15 Pitting...Sample broke 10 No damage 15 Sample pitted, small edge fracture 15 Slight pitting, 1 crater, 20 Sample pitted, erosion damage small edge fracture 15 SUght

Force-displacement measurements of earlywood bordered pits using a mesomechanical tester.

PubMed

Zelinka, Samuel L; Bourne, Keith J; Hermanson, John C; Glass, Samuel V; Costa, Adriana; Wiedenhoeft, Alex C

2015-10-01

The elastic properties of pit membranes are reported to have important implications in understanding air-seeding phenomena in gymnosperms, and pit aspiration plays a large role in wood technological applications such as wood drying and preservative treatment. Here we present force-displacement measurements for pit membranes of circular bordered pits, collected on a mesomechanical testing system. The system consists of a quartz microprobe attached to a microforce sensor that is positioned and advanced with a micromanipulator mounted on an inverted microscope. Membrane displacement is measured from digital image analysis. Unaspirated pits from earlywood of never-dried wood of Larix and Pinus and aspirated pits from earlywood of dried wood of Larix were tested to generate force-displacement curves up to the point of membrane failure. Two failure modes were observed: rupture or tearing of the pit membrane by the microprobe tip, and the stretching of the pit membrane until the torus was forced out of the pit chamber through the pit aperture without rupture, a condition we refer to as torus prolapse. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Towards robust deconvolution of low-dose perfusion CT: sparse perfusion deconvolution using online dictionary learning.

PubMed

Fang, Ruogu; Chen, Tsuhan; Sanelli, Pina C

2013-05-01

Computed tomography perfusion (CTP) is an important functional imaging modality in the evaluation of cerebrovascular diseases, particularly in acute stroke and vasospasm. However, the post-processed parametric maps of blood flow tend to be noisy, especially in low-dose CTP, due to the noisy contrast enhancement profile and the oscillatory nature of the results generated by the current computational methods. In this paper, we propose a robust sparse perfusion deconvolution method (SPD) to estimate cerebral blood flow in CTP performed at low radiation dose. We first build a dictionary from high-dose perfusion maps using online dictionary learning and then perform deconvolution-based hemodynamic parameters estimation on the low-dose CTP data. Our method is validated on clinical data of patients with normal and pathological CBF maps. The results show that we achieve superior performance than existing methods, and potentially improve the differentiation between normal and ischemic tissue in the brain. Copyright © 2013 Elsevier B.V. All rights reserved.

De-agglomeration and homogenisation of nanoparticles in coal tar pitch-based carbon materials

NASA Astrophysics Data System (ADS)

Gubernat, Maciej; Tomala, Janusz; Frohs, Wilhelm; Fraczek-Szczypta, Aneta; Blazewicz, Stanislaw

2016-03-01

The aim of the work was to characterise coal tar pitch (CTP) modified with selected nanoparticles as a binder precursor for the manufacture of synthetic carbon materials. Different factors influencing the preliminary preparative steps in the preparation of homogenous nanoparticle/CTP composition were studied. Graphene flakes, carbon black and nano-sized silicon carbide were used to modify CTP. Prior to introducing them into liquid CTP, nanoparticles were subjected to sonication. Various dispersants were used to prepare the suspensions, i.e. water, ethanol, dimethylformamide (DMF) and N-methylpyrrolidone (NMP).The results showed that proper dispersant selection is one of the most important factors influencing the de-agglomeration process of nanoparticles. DMF and NMP were found to be effective dispersants for the preparation of homogenous nanoparticle-containing suspensions. The presence of SiC and carbon black nanoparticles in the liquid pitch during heat treatment up to 2000 °C leads to the inhibition of crystallite growth in carbon residue.

Post-marketing study of biosimilar infliximab (CT-P13) to evaluate its safety and efficacy in Korea.

PubMed

Park, Sang Hyoung; Kim, Young-Ho; Lee, Ji Hyun; Kwon, Hyeok Jin; Lee, Suck-Ho; Park, Dong Il; Kim, Hyung Kil; Cheon, Jae Hee; Im, Jong Pil; Kim, You Sun; Lee, Sung Young; Lee, Sang Joon

2015-01-01

To evaluate the safety and efficacy of CT-P13 (Remsima(®)) in patients with inflammatory bowel disease (IBD) in South Korea. This post-marketing study included patients with active moderate-to-severe Crohn's disease (CD), fistulizing CD (FCD), or moderate-to-severe ulcerative colitis (UC) treated with CT-P13 and followed for 30 weeks. Assessments included treatment-emergent adverse events (TEAEs) and disease-specific clinical response and remission. No unexpected TEAEs were observed in the 173 patients recruited to date. TEAEs occurred in 18.1, 16.7, and 26.9% of CD, FCD, and UC patients, respectively. Treatment-related TEAEs occurred in 10% of patients and were mostly mild-moderate in severity. There were five serious TEAEs (two infusion-related reactions, two infections, one abdominal pain) and no cases of malignancy, pneumonia, or death. Positive outcomes for response/remission were reported regardless of whether patients had received prior infliximab or not. CT-P13 was well tolerated and efficacious in patients with IBD.

Towards robust deconvolution of low-dose perfusion CT: Sparse perfusion deconvolution using online dictionary learning

PubMed Central

Fang, Ruogu; Chen, Tsuhan; Sanelli, Pina C.

2014-01-01

Computed tomography perfusion (CTP) is an important functional imaging modality in the evaluation of cerebrovascular diseases, particularly in acute stroke and vasospasm. However, the post-processed parametric maps of blood flow tend to be noisy, especially in low-dose CTP, due to the noisy contrast enhancement profile and the oscillatory nature of the results generated by the current computational methods. In this paper, we propose a robust sparse perfusion deconvolution method (SPD) to estimate cerebral blood flow in CTP performed at low radiation dose. We first build a dictionary from high-dose perfusion maps using online dictionary learning and then perform deconvolution-based hemodynamic parameters estimation on the low-dose CTP data. Our method is validated on clinical data of patients with normal and pathological CBF maps. The results show that we achieve superior performance than existing methods, and potentially improve the differentiation between normal and ischemic tissue in the brain. PMID:23542422

Electrochemical and pitting corrosion resistance of AISI 4145 steel subjected to massive laser shock peening treatment with different coverage layers

NASA Astrophysics Data System (ADS)

Lu, J. Z.; Han, B.; Cui, C. Y.; Li, C. J.; Luo, K. Y.

2017-02-01

The effects of massive laser shock peening (LSP) treatment with different coverage layers on residual stress, pitting morphologies in a standard corrosive solution and electrochemical corrosion resistance of AISI 4145 steel were investigated by pitting corrosion test, potentiodynamic polarisation test, and SEM observations. Results showed massive LSP treatment can effectively cause an obvious improvement of pitting corrosion resistance of AISI 4145 steel, and increased coverage layer can also gradually improve its corrosion resistance. Massive LSP treatment with multiple layers was shown to influence pitting corrosion behaviour in a standard corrosive solution.

CT-P13: design, development, and place in therapy

PubMed Central

Gabbani, Tommaso; Deiana, Simona; Annese, Vito

2017-01-01

The introduction of biological agents has revolutionized the management of many life-threatening and debilitating immune-mediated diseases. Because of the high cost of biological drugs and their patent expiration, the market has opened to biosimilar agents, copy versions of the originators, which can lead to reduced health care expenditure and increase treatment access worldwide. CT-P13 is the first biosimilar of infliximab (IFX) and has been approved for the same indications as its originator drug. It obtained regulatory approval by the European Medicines Agency in September 2013 and by the US Food and Drug Administration in April 2016. The Phase I and Phase III clinical trials conducted in ankylosing spondylitis and rheumatoid arthritis have demonstrated pharmacokinetic and efficacy equivalence with comparable safety and immunogenicity to IFX. For these reasons, the use of CT-P13 has been extrapolated also to inflammatory bowel disease. There have been some initial concerns regarding the use of CT-P13 in inflammatory bowel disease patients, because of the lack of randomized controlled trials. However, emerging real-world data have further confirmed the comparability between CT-P13 and its reference product in terms of efficacy, safety, and immunogenicity, in patients naïve to the anti-tumor necrosis factor alpha agents and after switching from IFX, and will be summarized in this review. PMID:28652703

Identification of a cardiac specific protein transduction domain by in vivo biopanning using a M13 phage peptide display library in mice.

PubMed

Zahid, Maliha; Phillips, Brett E; Albers, Sean M; Giannoukakis, Nick; Watkins, Simon C; Robbins, Paul D

2010-08-17

A peptide able to transduce cardiac tissue specifically, delivering cargoes to the heart, would be of significant therapeutic potential for delivery of small molecules, proteins and nucleic acids. In order to identify peptide(s) able to transduce heart tissue, biopanning was performed in cell culture and in vivo with a M13 phage peptide display library. A cardiomyoblast cell line, H9C2, was incubated with a M13 phage 12 amino acid peptide display library. Internalized phage was recovered, amplified and then subjected to a total of three rounds of in vivo biopanning where infectious phage was isolated from cardiac tissue following intravenous injection. After the third round, 60% of sequenced plaques carried the peptide sequence APWHLSSQYSRT, termed cardiac targeting peptide (CTP). We demonstrate that CTP was able to transduce cardiomyocytes functionally in culture in a concentration and cell-type dependent manner. Mice injected with CTP showed significant transduction of heart tissue with minimal uptake by lung and kidney capillaries, and no uptake in liver, skeletal muscle, spleen or brain. The level of heart transduction by CTP also was greater than with a cationic transduction domain. Biopanning using a peptide phage display library identified a peptide able to transduce heart tissue in vivo efficiently and specifically. CTP could be used to deliver therapeutic peptides, proteins and nucleic acid specifically to the heart.

Cannabis for therapeutic purposes: patient characteristics, access, and reasons for use.

PubMed

Walsh, Zach; Callaway, Robert; Belle-Isle, Lynne; Capler, Rielle; Kay, Robert; Lucas, Philippe; Holtzman, Susan

2013-11-01

The authorized and unauthorized use of cannabis for therapeutic purposes (CTP) has increased dramatically in recent years, and physicians have called for further research to better clarify the parameters of effective and appropriate use. We report findings from a large cross-sectional study of the use of CTP in Canada and compare use across medical conditions and across authorized and unauthorized users. We examined cannabis use history, medical conditions and symptoms, patterns of current use of CTP, modes of access and perceived effectiveness among 628 self-selected Canadians consumers of CTP. Participants were recruited from medical cannabis dispensaries and from organizations that assist users of CTP. Patients reported using cannabis to treat multiple symptoms, with sleep, pain, and anxiety being the most common. Cannabis was perceived to provide effective symptoms relief across medical conditions. Patterns of use were also consistent across medical conditions. Notable differences were observed with regard to modes of access. Across medical conditions respondents reported using cannabis to effectively address diverse symptoms. Results indicate a substantial disconnect between the therapeutic use of cannabis and research on the risks and benefits of such use; particularly with regard to the anxiolytic and sedative use of cannabis. Authorized and unauthorized users exhibited few meaningful differences with regard to medical conditions and patterns of use, but faced substantial differences regarding access. Copyright © 2013 Elsevier B.V. All rights reserved.

77 FR 21540 - Notice of Submission for OMB Review; Federal Student Aid; Comprehensive Transition Programs (CTP...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-10

... DEPARTMENT OF EDUCATION Notice of Submission for OMB Review; Federal Student Aid; Comprehensive Transition Programs (CTP) for Students With Intellectual Disabilities Expenditure Report SUMMARY: The Higher Education Opportunity Act, Public Law 110-315, added provisions for the Higher Education Act, as amended in...

Application of silver nanoparticles to the chemiluminescence determination of cefditoren pivoxil using the luminol-ferricyanide system.

PubMed

Alarfaj, Nawal A; Aly, Fatma A; El-Tohamy, Maha F

2015-02-01

A new simple, accurate and sensitive sequential injection analysis chemiluminescence (CL) detection method for the determination of cefditoren pivoxil (CTP) has been developed. The developed method was based on the enhancement effect of silver nanoparticles on the CL signal arising from a luminol-potassium ferricyanide reaction in the presence of CTP. The optimum conditions relevant to the effect of luminol, potassium ferricyanide and silver nanoparticle concentrations were investigated. The proposed method showed linear relationships between relative CL intensity and the investigated drug concentration at the range 0.001-5000 ng/mL, (r = 0.9998, n = 12) with a detection limit of 0.5 pg/mL and quantification limit of 0.001 ng/mL. The relative standard deviation was 1.6%. The proposed method was employed for the determination of CTP in bulk drug, in its pharmaceutical dosage forms and biological fluids such as human serum and urine. The interference of some common additive compounds such as glucose, lactose, starch, talc and magnesium stearate was investigated. In addition, the interference of some related cephalosporins was tested. No interference was recorded. The obtained sequential injection analysis-CL results were statistically compared with those from a reported method and did not show any significant differences. Copyright © 2014 John Wiley & Sons, Ltd.

A Comprehensive Pitting Study of High Velocity Oxygen Fuel Inconel 625 Coating by Using Electrochemical Testing Techniques

NASA Astrophysics Data System (ADS)

Niaz, Akbar; Khan, Sajid Ullah

2016-01-01

In the present work, Inconel 625 was coated on a mild steel substrate using a high velocity oxygen fuel coating process. The pitting propensity of the coating was tested by using open circuit potential versus time, potentiodynamic polarization, electrochemical potentiokinetic reactivation, and scanning electrochemical microscopy. The pitting propensity of the coating was compared with bulk Inconel 625 alloy. The results confirmed that there were regions of different electrochemical activities on the coating which have caused pitting corrosion.

Single and Multi-Pulse Low-Energy Conical Theta Pinch Inductive Pulsed Plasma Thruster Performance

NASA Technical Reports Server (NTRS)

Hallock, Ashley K.; Martin, Adam; Polzin, Kurt; Kimberlin, Adam; Eskridge, Richard

2013-01-01

Fabricated and tested CTP IPPTs at cone angles of 20deg, 38deg, and 60deg, and performed direct single-pulse impulse bit measurements with continuous gas flow. Single pulse performance highest for 38deg angle with impulse bit of approx.1 mN-s for both argon and xenon. Estimated efficiencies low, but not unexpectedly so based on historical data trends and the direction of the force vector in the CTP. Capacitor charging system assembled to provide rapid recharging of capacitor bank, permitting repetition-rate operation. IPPT operated at repetition-rate of 5 Hz, at maximum average power of 2.5 kW, representing to our knowledge the highest average power for a repetitively-pulsed thruster. Average thrust in repetition-rate mode (at 5 kV, 75 sccm argon) was greater than simply multiplying the single-pulse impulse bit and the repetition rate.

Ceramic Technology Project data base: September 1992 summary report

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

Keyes, B.L.P.

Data presented in this report represent an intense effort to improve processing methods, testing methods, and general mechanical properties (rupture modulus, tensile, creep, stress-rupture, dynamic and cyclic fatigue, fracture toughness) of candidate ceramics for use in advanced heat engines. This work was performed by many facilities and represents only a small part of the data generated by the Ceramic Technology Project (CTP) since 1986. Materials discussed include GTE PY6, GN-10, NT-154, NT-164, SN-260, SN-251, SN-252, AY6, silicon nitride combined with rare-earth oxides, Y-TZP, ZTA, NC-433, NT-230, Hexoloy SA, MgO-PSZ-to-MgO-PSZ joints, MgO-PSZ-to-cast iron, and a few whisker/fiber-reinforced ceramics. Information in thismore » report was taken from the project`s semiannual and bimonthly progress reports and from final reports summarizing the results of individual studies. Test results are presented in tabular form and in graphs. All data, including test rig descriptions and material characterizations, are stored in the CTP data base and are available to all project participants on request. The objective of this report is to make available the test results from these studies but not to draw conclusions from those data.« less

Common Grounds for Modelling Mathematics in Educational Software

ERIC Educational Resources Information Center

Neuper, Walther

2010-01-01

Two kinds of software, CAS and DGS, are starting to work towards mutual integration. This paper envisages common grounds for such integration based on principles of computer theorem proving (CTP). Presently, the CTP community seems to lack awareness as to which of their products' features might serve mathematics education from high-school to…

Attention to Form or Meaning? Error Treatment in the Bangalore Project.

ERIC Educational Resources Information Center

Beretta, Alan

1989-01-01

Reports on an evaluation of the Bangalore/Madras Communicational Teaching Project (CTP), a content-based approach to language learning. Analysis of 21 lesson transcripts revealed a greater incidence of error treatment of content than linguistic error, consonant with the CTP focus on meaning rather than form. (26 references) (Author/CB)

Evaluation of the Bangalore/Madras Communicational Teaching Project.

ERIC Educational Resources Information Center

Beretta, Alan; Davies, Alan

The Bangalore Communicational Teaching Project (CTP) in India operates on the central tenet that in English instruction, form can be acquired through a focus on meaning alone, that a grammatical system can be assimilated unconsciously if the mind is engaged in trying to understand or convey meaning. Linguistic specification is not used in CTP, and…

Genomic Sequence and Characterization of the Virulent Bacteriophage φCTP1 from Clostridium tyrobutyricum and Heterologous Expression of Its Endolysin▿

PubMed Central

Mayer, Melinda J.; Payne, John; Gasson, Michael J.; Narbad, Arjan

2010-01-01

The growth of Clostridium tyrobutyricum in developing cheese leads to spoilage and cheese blowing. Bacteriophages or their specific lytic enzymes may provide a biological control method for eliminating such undesirable organisms without affecting other microflora. We isolated the virulent bacteriophage φCTP1 belonging to the Siphoviridae and have shown that it is effective in causing lysis of sensitive strains. The double-stranded DNA genome of φCTP1 is 59,199 bp, and sequence analysis indicated that it has 86 open reading frames. orf29 was identified as the gene coding for the phage endolysin responsible for cell wall degradation prior to virion release. We cloned and expressed the ctp1l gene in E. coli and demonstrated that the partially purified protein induced lysis of C. tyrobutyricum cells and reduced viable counts both in buffer and in milk. The endolysin was inactive against a range of clostridial species but did show lysis of Clostridium sporogenes, another potential spoilage organism. Removal of the C-terminal portion of the endolysin completely abolished lytic activity. PMID:20581196

La-CTP: Loop-Aware Routing for Energy-Harvesting Wireless Sensor Networks.

PubMed

Sun, Guodong; Shang, Xinna; Zuo, Yan

2018-02-02

In emerging energy-harvesting wireless sensor networks (EH-WSN), the sensor nodes can harvest environmental energy to drive their operation, releasing the user's burden in terms of frequent battery replacement, and even enabling perpetual sensing systems. In EH-WSN applications, usually, the node in energy-harvesting or recharging state has to stop working until it completes the energy replenishment. However, such temporary departures of recharging nodes severely impact the packet routing, and one immediate result is the routing loop problem. Controlling loops in connectivity-intermittent EH-WSN in an efficient way is a big challenge in practice, and so far, users still lack of effective and practicable routing protocols with loop handling. Based on the Collection Tree Protocol (CTP) widely used in traditional wireless sensor networks, this paper proposes a loop-aware routing protocol for real-world EH-WSNs, called La-CTP, which involves a new parent updating metric and a proactive, adaptive beaconing scheme to effectively suppress the occurrence of loops and unlock unavoidable loops, respectively. We constructed a 100-node testbed to evaluate La-CTP, and the experimental results showed its efficacy and efficiency.

Use of MODIS Cloud Top Pressure to Improve Assimilation Yields of AIRS Radiances in GSI

NASA Technical Reports Server (NTRS)

Zavodsky, Bradley; Srikishen, Jayanthi

2014-01-01

Improvements to global and regional numerical weather prediction have been demonstrated through assimilation of data from NASA's Atmospheric Infrared Sounder (AIRS). Current operational data assimilation systems use AIRS radiances, but impact on regional forecasts has been much smaller than for global forecasts. Previously, it has been shown that cloud top designation associated with quality control procedures within the Gridpoint Statistical Interpolation (GSI) system used operationally by a number of Joint Center for Satellite Data Assimilation (JCSDA) partners may not provide the best representation of cloud top pressure (CTP). Because this designated CTP determines which channels are cloud-free and, thus, available for assimilation, ensuring the most accurate representation of this value is imperative to obtaining the greatest impact from satellite radiances. This paper examines the assimilation of hyperspectral sounder data used in operational numerical weather prediction by comparing analysis increments and numerical forecasts generated using operational techniques with a research technique that swaps CTP from the Moderate-resolution Imaging Spectroradiometer (MODIS) for the value of CTP calculated from the radiances within GSI.

Current status of biosimilars in the treatment of inflammatory bowel diseases

PubMed Central

2016-01-01

Introduction of biological therapies have led to dramatic changes in the management of debilitating immune-mediated inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease. However, the long term use of these agents may be very expensive, placing a significant burden on National Healthcare Systems. The development of first biosimilar to infliximab, CT-P13 (Remsima; Celltrion Inc., Incheon, Korea and Inflextra; Hospiral, Lake Forest, Illinois, USA) has become another way to decrease the medical care cost and increase patient treatment option, but, actual equivalence of efficacy and safety of CT-P13 was investigated in rheumatic diseases only. The extrapolation of outcome from rheumatic trials to IBD and the interchangeability of CT-P13 with infliximab have come to be a matter of concern. Two recent retrospective studies reported the similarity of CT-P13 in terms of efficacy and safety. Infliximab biosimilars may be promising new treatment options for IBD patients, however, well-designed, prospective randomized non-inferiority trials should be needed to confidently integrate infliximab biosimilars into IBD treatment. PMID:26884730

Shortened Mean Transit Time in CT Perfusion With Singular Value Decomposition Analysis in Acute Cerebral Infarction: Quantitative Evaluation and Comparison With Various CT Perfusion Parameters.

PubMed

Murayama, Kazuhiro; Katada, Kazuhiro; Hayakawa, Motoharu; Toyama, Hiroshi

We aimed to clarify the cause of shortened mean transit time (MTT) in acute ischemic cerebrovascular disease and examined its relationship with reperfusion. Twenty-three patients with acute ischemic cerebrovascular disease underwent whole-brain computed tomography perfusion (CTP). The maximum MTT (MTTmax), minimum MTT (MTTmin), ratio of maximum and minimum MTT (MTTmin/max), and minimum cerebral blood volume (CBV) (CBVmin) were measured by automatic region of interest analysis. Diffusion weighted image was performed to calculate infarction volume. We compared these CTP parameters between reperfusion and nonreperfusion groups and calculated correlation coefficients between the infarction core volume and CTP parameters. Significant differences were observed between reperfusion and nonreperfusion groups (MTTmin/max: P = 0.014; CBVmin ratio: P = 0.038). Regression analysis of CTP and high-intensity volume on diffusion weighted image showed negative correlation (CBVmin ratio: r = -0.41; MTTmin/max: r = -0.30; MTTmin ratio: r = -0.27). A region of shortened MTT indicated obstructed blood flow, which was attributed to the singular value decomposition method error.

Childhood Arthritis and Rheumatology Research Alliance Consensus Clinical Treatment Plans for Juvenile Dermatomyositis with Persistent Skin Rash.

PubMed

Huber, Adam M; Kim, Susan; Reed, Ann M; Carrasco, Ruy; Feldman, Brian M; Hong, Sandy D; Kahn, Philip; Rahimi, Homaira; Robinson, Angela Byun; Vehe, Richard K; Weiss, Jennifer E; Spencer, Charles

2017-01-01

Juvenile dermatomyositis (JDM) is the most common form of idiopathic inflammatory myopathy in children. While outcomes are generally thought to be good, persistence of skin rash is a common problem. The goal of this study was to describe the development of clinical treatment plans (CTP) for children with JDM characterized by persistent skin rash despite complete resolution of muscle involvement. The Childhood Arthritis and Rheumatology Research Alliance, a North American consortium of pediatric rheumatologists and other healthcare providers, used a combination of Delphi surveys and nominal group consensus meetings to develop CTP that reflected consensus on typical treatments for patients with JDM with persistent skin rash. Consensus was reached on patient characteristics and outcome assessment. Patients should have previously received corticosteroids and methotrexate (MTX). Three consensus treatment plans were developed. Plan A added intravenous immunoglobulin (IVIG) if it was not already being used. Plan B added mycophenolate mofetil, while Plan C added cyclosporine. Continuation of previous treatments, including corticosteroids, MTX, and IVIG, was permitted in plans B and C. Three consensus CTP were developed for use in children with JDM and persistent skin rash despite complete resolution of muscle disease. These CTP reflect typical treatment approaches and are not to be considered treatment recommendations or standard of care. Using prospective data collection and statistical methods to account for nonrandom treatment assignment, it is expected that these CTP will be used to allow treatment comparisons, and ultimately determine the best treatment for these patients.

Membrane penetrating peptides greatly enhance baculovirus transduction efficiency into mammalian cells

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

Chen, Hong-Zhang; Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan, ROC; Wu, Carol P.

2011-02-11

Research highlights: {yields} Ligation of CTP with GP64 enhances baculovirus transduction into mammalian cells. {yields} Fusion of PTD with VP39 enhances baculovirus transduction into mammalian cells. {yields} CTP and PTD-carrying viruses improve the transduction of co-transduced baculoviruses. {yields} Virus entry and gene expression can be separate events in different cell types. -- Abstract: The baculovirus group of insect viruses is widely used for foreign gene introduction into mammalian cells for gene expression and protein production; however, the efficiency of baculovirus entry into mammalian cells is in general still low. In this study, two recombinant baculoviruses were engineered and their abilitymore » to improve viral entry was examined: (1) cytoplasmic transduction peptide (CTP) was fused with baculovirus envelope protein, GP64, to produce a cytoplasmic membrane penetrating baculovirus (vE-CTP); and (2) the protein transduction domain (PTD) of HIV TAT protein was fused with the baculovirus capsid protein VP39 to form a nuclear membrane penetrating baculovirus (vE-PTD). Transduction experiments showed that both viruses had better transduction efficiency than vE, a control virus that only expresses EGFP in mammalian cells. Interestingly, vE-CTP and vE-PTD were also able to improve the transduction efficiency of a co-transduced baculovirus, resulting in higher levels of gene expression. Our results have described new routes to further enhance the development of baculovirus as a tool for gene delivery into mammalian cells.« less

Ischemic Volume and Neurological Deficit: Correlation of Computed Tomography Perfusion with the National Institutes of Health Stroke Scale Score in Acute Ischemic Stroke.

PubMed

Furlanis, Giovanni; Ajčević, Miloš; Stragapede, Lara; Lugnan, Carlo; Ridolfi, Mariana; Caruso, Paola; Naccarato, Marcello; Ukmar, Maja; Manganotti, Paolo

2018-04-30

The National Institutes of Health Stroke Scale (NIHSS) is the most adopted stroke patients' evaluation tool in emergency settings to assess the severity of stroke and to determine the patients' eligibility for specific treatments. Computed tomography perfusion (CTP) is crucial to identify salvageable tissue that can benefit from the reperfusion treatment. The aim of this study is to identify the relation between the NIHSS scores and the hypoperfused volumes evaluated by CTP in patients with hyperacute ischemic stroke. This retrospective study was conducted on 105 patients with ischemic stroke who underwent NIHSS assessment and CTP in the hyperacute phase. Hypoperfused volume was evaluated by CTP maps processed with semi-automatic algorithm. An analysis was conducted to determine the degree of correlation between the NIHSS scores and the ischemic lesion volumes and to investigate the relation between the anterior and the posterior circulation strokes, as well as between the right and the left hemispheric strokes. A significant correlation was found between ischemic volume and NIHSS score at baseline (r = .82; P < .0001) in the entire cohort. A high NIHSS-volume correlation was identified in the anterior circulation stroke (r = .76; P < .0001); whereas, it was nonsignificant in the posterior circulation stroke. NIHSS score and volume correlated for the left and the right hemispheric strokes (r = .83 and .81; P < .0001), showing a slightly higher slope in the left. This study showed a strong correlation between the baseline NIHSS score and the ischemic volume estimated by CTP. We confirmed that NIHSS is a reliable predictor of perfusion deficits in acute ischemic stroke. CTP allows fast imaging assessment in the hyperacute phase. The results highlight the importance of these diagnostic tools in the assessment of stroke severity and in acute decision-making. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Effect of increasing the sampling interval to 2 seconds on the radiation dose and accuracy of CT perfusion of the head and neck.

PubMed

Tawfik, Ahmed M; Razek, Ahmed A; Elhawary, Galal; Batouty, Nihal M

2014-01-01

To evaluate the effect of increasing the sampling interval from 1 second (1 image per second) to 2 seconds (1 image every 2 seconds) on computed tomographic (CT) perfusion (CTP) of head and neck tumors. Twenty patients underwent CTP studies of head and neck tumors with images acquired in cine mode for 50 seconds using sampling interval of 1 second. Using deconvolution-based software, analysis of CTP was done with sampling interval of 1 second and then 2 seconds. Perfusion maps representing blood flow, blood volume, mean transit time, and permeability surface area product (PS) were obtained. Quantitative tumor CTP values were compared between the 2 sampling intervals. Two blinded radiologists compared the subjective quality of CTP maps using a 3-point scale between the 2 sampling intervals. Radiation dose parameters were recorded for the 2 sampling interval rates. No significant differences were observed between the means of the 4 perfusion parameters generated using both sampling intervals; all P >0.05. The 95% limits of agreement between the 2 sampling intervals were -65.9 to 48.1) mL/min per 100 g for blood flow, -3.6 to 3.1 mL/100 g for blood volume, -2.9 to 3.8 seconds for mean transit time, and -10.0 to 12.5 mL/min per 100 g for PS. There was no significant difference between the subjective quality scores of CTP maps obtained using the 2 sampling intervals; all P > 0.05. Radiation dose was halved when sampling interval increased from 1 to 2 seconds. Increasing the sampling interval rate to 1 image every 2 seconds does not compromise the image quality and has no significant effect on quantitative perfusion parameters of head and neck tumors. The radiation dose is halved.

Preparation of Chitin-PLA laminated composite for implantable application.

PubMed

Nasrin, Romana; Biswas, Shanta; Rashid, Taslim Ur; Afrin, Sanjida; Jahan, Rumana Akhter; Haque, Papia; Rahman, Mohammed Mizanur

2017-12-01

The present study explores the possibilities of using locally available inexpensive waste prawn shell derived chitin reinforced and bioabsorbable polylactic acid (PLA) laminated composites to develop new materials with excellent mechanical and thermal properties for implantable application such as in bone or dental implant. Chitin at different concentration (1-20% of PLA) reinforced PLA films (CTP) were fabricated by solvent casting process and laminated chitin-PLA composites (LCTP) were prepared by laminating PLA film (obtained by hot press method) with CTP also by hot press method at 160 °C. The effect of variation of chitin concentration on the resulting laminated composite's behavior was investigated. The detailed physico-mechanical, surface morphology and thermal were assessed with different characterization technique such as FT-IR, XRD, SEM and TGA. The FTIR spectra showed the characteristic peaks for chitin and PLA in the composites. SEM images showed an excellent dispersion of chitin in the films and composites. Thermogravimetric analysis (TGA) showed that the complete degradation of chitin, PLA film, 5% chitin reinforced PLA film (CTP2) and LCTP are 98%, 95%, 87% and 98% respectively at temperature of 500 °C. The tensile strength of the LCTP was found 25.09 MPa which is significantly higher than pure PLA film (18.55 MPa) and CTP2 film (8.83 MPa). After lamination of pure PLA and CTP2 film, the composite (LCTP) yielded 0.265-1.061% water absorption from 30 min to 24 h immerse in water that is much lower than PLA and CTP. The increased mechanical properties of the laminated films with the increase of chitin content indicated good dispersion of chitin into PLA and strong interfacial actions between the polymer and chitin. The improvement of mechanical properties and the results of antimicrobial and cytotoxicity of the composites also evaluated and revealed the composite would be a suitable candidate for implant application in biomedical sector.

The influence of early psychosocial intervention on the long-term clinical outcomes of people suffering from schizophrenia.

PubMed

Cechnicki, Andrzej; Bielańska, Anna

2017-02-26

To compare the treatment outcomes of DSM-IV-TR schizophrenia patients in either a Community Treatment Program or an Individual Treatment Program (CTP vs. ITP). The assessment was made after the first hospitalization, and then after three and twelve years. Participants were randomly assigned to CTP (experimental) and ITP (traditional) group, with 40 people in each group. 67 people (84%) participated in all three assessments. The socio-demographic and clinical indicators were the same for both groups. In the first three years only the CTP group participated in day-care treatment, patient and family psychoeducation and community treatment. Later, both groups received this treatment. The following tools were used: Anamnestic and Catamnestic Questionnaire, the GAF scale, the BPRS LA and Lehman's Quality of Life Interview. It was only after twelve years that there was a significant beneficial improvement in the mean GAF score in the CTP group (p = 0.036), which was comparable with the results obtained by Watt and Shepherd for the course of the illness in favorable remission cases (p = 0.038). The difference in the number of relapses was also significantly in favor of the CTP group only after 12 years (p = 0.045), as was the difference in the number of rehospitalizations (p = 0.013). The general severity of symptoms was found to be significantly lower for the CPT group after 3 (p = 0.008) and 12 years (p = 0.030), whereas it was significantly lower in the case of positive syndrome only after 3 years (p = 0.044). 1. A greater number of favorable differences were identified for the CTP group at the twelve-year point than at the conclusion of the experiment. 2. The three-year delay in introducing psycho-social treatment was associated with a poorer long-term outcome for the clinical course of schizophrenia.

Antibodies against a peptide of cholera toxin differing in cross-reactivity with the toxin differ in their specific interactions with the peptide as observed by sup 1 H NMR spectroscopy

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

Anglister, J.; Zilber, B.

1990-01-30

The interactions between the aromatic residues of the monoclonal antibody TE34, and its peptide antigen CTP3, have been studied by 2D TRNOE difference spectroscopy. The sequence of CTP3 corresponds to residues 50-64 of the B subunit of cholera toxin (VEVPGSQHIDSQKKA). Unlike two previously studied anti-CTP3 antibodies (TE32 and TE33), the TE34 antibody does not bind the toxin. The off-rate of CTP3 from TE34 was found to be too slow to measure strong TRNOE cross-peaks between the antibody and the peptide. Much faster off-rates, resulting in a strong TRNOE, were obtained for two peptide analogues: (a) CTP3 with an amide inmore » the C-terminus (VEVPGSQHIDSQKKA-NH{sub 2}) and (b) a truncated version of the peptide (N-acetyl-IDSQKKA). These modifications do not interfere significantly either with the interactions of the unmodified part of the peptide with the antibody or with intramolecular interactions occurring in the epitope recognized by the antibody. The combined use of these peptides allows us to study the interactions between the antibody and the whole peptide. Two tyrosine residues and one or more tryptophan and phenylalanine residues have been found to interact with histidine-8, isoleucine-9, aspartate-10, lysine-13 and/or lysine-14, and alanine-15 of the peptide. The strong interaction of TE34 with the negatively charged C-terminus of CTP3 is one of the main reasons for its lack of cross-reactivity with the native toxin. Similar use of modified peptides may extend the applicability of 2D TRNOE difference spectroscopy to the study of other antibody-peptide complexes involving slow peptide off-rates.« less

Kinetic and Structural Impact of Metal Ions and Genetic Variations on Human DNA Polymerase ι.

PubMed

Choi, Jeong-Yun; Patra, Amritaj; Yeom, Mina; Lee, Young-Sam; Zhang, Qianqian; Egli, Martin; Guengerich, F Peter

2016-09-30

DNA polymerase (pol) ι is a Y-family polymerase involved in translesion synthesis, exhibiting higher catalytic activity with Mn 2+ than Mg 2+ The human germline R96G variant impairs both Mn 2+ -dependent and Mg 2+ -dependent activities of pol ι, whereas the Δ1-25 variant selectively enhances its Mg 2+ -dependent activity. We analyzed pre-steady-state kinetic and structural effects of these two metal ions and genetic variations on pol ι using pol ι core (residues 1-445) proteins. The presence of Mn 2+ (0.15 mm) instead of Mg 2+ (2 mm) caused a 770-fold increase in efficiency (k pol /K d ,dCTP ) of pol ι for dCTP insertion opposite G, mainly due to a 450-fold decrease in K d ,dCTP The R96G and Δ1-25 variants displayed a 53-fold decrease and a 3-fold increase, respectively, in k pol /K d ,dCTP for dCTP insertion opposite G with Mg 2+ when compared with wild type, substantially attenuated by substitution with Mn 2+ Crystal structures of pol ι ternary complexes, including the primer terminus 3'-OH and a non-hydrolyzable dCTP analogue opposite G with the active-site Mg 2+ or Mn 2+ , revealed that Mn 2+ achieves more optimal octahedral coordination geometry than Mg 2+ , with lower values in average coordination distance geometry in the catalytic metal A-site. Crystal structures of R96G revealed the loss of three H-bonds of residues Gly-96 and Tyr-93 with an incoming dNTP, due to the lack of an arginine, as well as a destabilized Tyr-93 side chain secondary to the loss of a cation-π interaction between both side chains. These results provide a mechanistic basis for alteration in pol ι catalytic function with coordinating metals and genetic variation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Kinetic and Structural Impact of Metal Ions and Genetic Variations on Human DNA Polymerase ι*

PubMed Central

Choi, Jeong-Yun; Patra, Amritaj; Yeom, Mina; Lee, Young-Sam; Zhang, Qianqian; Egli, Martin; Guengerich, F. Peter

2016-01-01

DNA polymerase (pol) ι is a Y-family polymerase involved in translesion synthesis, exhibiting higher catalytic activity with Mn2+ than Mg2+. The human germline R96G variant impairs both Mn2+-dependent and Mg2+-dependent activities of pol ι, whereas the Δ1–25 variant selectively enhances its Mg2+-dependent activity. We analyzed pre-steady-state kinetic and structural effects of these two metal ions and genetic variations on pol ι using pol ι core (residues 1–445) proteins. The presence of Mn2+ (0.15 mm) instead of Mg2+ (2 mm) caused a 770-fold increase in efficiency (kpol/Kd,dCTP) of pol ι for dCTP insertion opposite G, mainly due to a 450-fold decrease in Kd,dCTP. The R96G and Δ1–25 variants displayed a 53-fold decrease and a 3-fold increase, respectively, in kpol/Kd,dCTP for dCTP insertion opposite G with Mg2+ when compared with wild type, substantially attenuated by substitution with Mn2+. Crystal structures of pol ι ternary complexes, including the primer terminus 3′-OH and a non-hydrolyzable dCTP analogue opposite G with the active-site Mg2+ or Mn2+, revealed that Mn2+ achieves more optimal octahedral coordination geometry than Mg2+, with lower values in average coordination distance geometry in the catalytic metal A-site. Crystal structures of R96G revealed the loss of three H-bonds of residues Gly-96 and Tyr-93 with an incoming dNTP, due to the lack of an arginine, as well as a destabilized Tyr-93 side chain secondary to the loss of a cation-π interaction between both side chains. These results provide a mechanistic basis for alteration in pol ι catalytic function with coordinating metals and genetic variation. PMID:27555320

Assessment of pit latrines in a peri-urban community in KwaZulu-Natal (South Africa) as a source of antibiotic resistant E. coli strains.

PubMed

Beukes, Lorika S; King, Tracy L B; Schmidt, Stefan

2017-11-01

Due to the frequent use of antibiotics and recurring illnesses related to multidrug-resistant (MDR) bacteria in South Africa, we determined if MDR Escherichia coli were present in pit latrine fecal sludge samples obtained from a peri-urban community in KwaZulu-Natal, South Africa. The abundance of E. coli in pit latrine samples was established using a most probable number (MPN) method with species confirmation done using biochemical tests and polymerase chain reaction (PCR). Forty-four randomly selected E. coli pit latrine isolates were further characterized, using the European committee on antimicrobial susceptibility testing (EUCAST) disk diffusion method to establish antibiotic resistance profiles for these E. coli isolates. The resulting MPN values for E. coli ranged from one to 6.2 log 10 MPN per gram of fresh pit latrine fecal sludge. While only 3 out of 44 E. coli pit latrine isolates showed no resistance to any of the 12 tested antibiotics, most isolates were resistant to two or more antibiotics. The majority of isolates showed resistance to at least one of the two tested aminoglycosides, one isolate showed resistance to the carbapenem ertapenem, and although resistance was not detected for tigecycline four pit latrine E. coli isolates showed intermediate resistance to this antibiotic. However, about 14% of the E. coli pit latrine isolates were categorized as MDR, all of which showed resistance to four or more antibiotics. The presence of MDR E. coli strains in pit latrine samples demonstrates that these facilities are potential sources for MDR bacteria. Copyright © 2017 Elsevier GmbH. All rights reserved.

ORION Project-(SPLASH) Structural Passive Landing Attenuation fo

NASA Image and Video Library

2011-12-13

ORION Project-(SPLASH) Structural Passive Landing Attenuation for Survivability of Human Crew (BTA) Boiler Plate Test Article Water Impact Test-Pit Phase 4 Test or Pit 4 Tested at the Hydro Impact Basin at the Landing and Impact Research Facility (Gantry)

Technical Evaluation Motor No. 10 (TEM-10)

NASA Technical Reports Server (NTRS)

1993-01-01

Technical Evaluation Motor No. 10 (TEM-10) was static fired on 27 Apr. 1993 at the Thiokol Corporation full-scale motor static test bay, T-24. This final test report documents the procedures, performance, and results of the static test firing of TEM-10. All observations, discussions, conclusions, and recommendations contained are final. Included is a presentation and discussion of TEM-10 performance, anomalies, and test results in concurrence with the objectives outlined in CTP-0110, Revision D, Space Shuttle Technical Evaluation Motor No. 10 (TEM-10) Static Fire Test Plan.

Evolution of Scholarly Publishing and Library Services in Astronomy Its Impact, Challenges, and Opportunities

NASA Astrophysics Data System (ADS)

Wesley, Hema; Sheshadri, Geetha

2016-10-01

Scholarly publishing and its procedures have evolved rapidly, forcefully, and incredibly. Technical advances in the production and promotion of science content have dramatically augmented the visibility and reach, deepened the impact and intensified the thrust of science journal content. These changes range from checking text on perforated tapes to pit stop; from hot metal types to CTP; and from Gutenberg to colour digital printers. Intrinsic and inextricable to this revolutionary aspect of evolution in scholarly publishing is the evolution of library services in astronomy which catapulted library resources from preprints on shelves to customised digital repositories and from communicating observational data through postal telegrams to Tablets. What impact does this unique blend of revolutionary advances have on science and society, what are the consequent challenges, and what are the opportunities that can metamorphose from challenges inherent in the power and potential of the `published word'? The perspectives expressed in this paper stem from learning experiences of the authors at the Indian Academy of Sciences, publishers of ten science journals including the Journal of Astrophysics and Astronomy, and at the Raman Research Institute Library (in which Astronomy is one of the core subjects for research)

Outdoor Testing Areas | Energy Systems Integration Facility | NREL

Science.gov Websites

of engineers running tests on plug-in hybrid electric vehicles at the Medium-Voltage Outdoor Test large microgrids hub, located in the outdoor low-voltage test yard, includes underground trench access pits for full enclosure of rotating machinery under test. Key Infrastructure Secured underground pits

Record of Technical Change 2 for Closure Report for Corrective Action Unit 204: Storage Bunkers, Nevada Test Site, Nevada, Revision 0

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

Krauss, Mark J.; Birney, Cathleen

2006-04-01

CAS 05-33-01, Kay Blockhouse, consists of an area of approximately 11 acres and includes the Kay Blockhouse, two bum pits with steel frames, one bum pit with a soil berm, two open pits, two steel-lined subsurface pits, one berm with embedded piping, one berm with piping debris, a burn area with a large concrete block with an embedded steel prong, and one open pit with a concrete foundation at the north end. The Kay Blockhouse was constructed in 1951 and was used as an instrumentation bunker for Operation Ranger, a series of five atmospheric nuclear tests. The burn pits andmore » other surface features within the CAS boundary were not part of the nuclear testing. The Kay Blockhouse is constructed of concrete with a wooden entryway door. The details of the construction of the floor are unknown (NNSA/NSO, 2004b). During closure activities, lead- and radiologically impacted soil was removed, and verification samples were collected. Friable asbestos material was removed from the burn pits; the asbestos and steel frames from the bum pits were disposed of at the Area 23 Sanitary Landfill. In addition, the two steel-lined pits were filled with native soil and capped with 1.5 ft of concrete. The bunker was secured by installing security fencing and a gate around the entrance to the bunker. The RMA was reestablished and fenced with T-post and wire-rope fencing (NNSA/NSO, 2006a).« less

Reference materials for cellular therapeutics.

PubMed

Bravery, Christopher A; French, Anna

2014-09-01

The development of cellular therapeutics (CTP) takes place over many years, and, where successful, the developer will anticipate the product to be in clinical use for decades. Successful demonstration of manufacturing and quality consistency is dependent on the use of complex analytical methods; thus, the risk of process and method drift over time is high. The use of reference materials (RM) is an established scientific principle and as such also a regulatory requirement. The various uses of RM in the context of CTP manufacturing and quality are discussed, along with why they are needed for living cell products and the analytical methods applied to them. Relatively few consensus RM exist that are suitable for even common methods used by CTP developers, such as flow cytometry. Others have also identified this need and made proposals; however, great care will be needed to ensure any consensus RM that result are fit for purpose. Such consensus RM probably will need to be applied to specific standardized methods, and the idea that a single RM can have wide applicability is challenged. Written standards, including standardized methods, together with appropriate measurement RM are probably the most appropriate way to define specific starting cell types. The characteristics of a specific CTP will to some degree deviate from those of the starting cells; consequently, a product RM remains the best solution where feasible. Each CTP developer must consider how and what types of RM should be used to ensure the reliability of their own analytical measurements. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

A review of the literature analyzing benefits and concerns of infliximab biosimilar CT-P13 for the treatment of rheumatologic diseases: focus on interchangeability

PubMed Central

Becciolini, Andrea; Raimondo, Maria Gabriella; Crotti, Chiara; Agape, Elena; Biggioggero, Martina; Favalli, Ennio Giulio

2017-01-01

The introduction of biological agents drastically changed the treatment paradigm of inflammatory arthritides, ameliorating the natural history of the diseases but concomitantly increasing the drug costs due to the manufacturing process. On this concern, biosimilar drugs may represent a valid option for reducing this elevated cost and increasing the availability of these highly effective treatments. Recently, CT-P13, the first biosimilar of infliximab, has been approved with the same indications established for the reference product (RP), and its daily use is progressively increasing. However, the experience with biosimilar drugs in the field of rheumatology is still limited, raising potential doubts and concerns on their correct management in real-life settings. Comparability analysis between CT-P13 and its RP was evaluated in equivalence randomized controlled trials (RCTs) – PLANETRA and PLANETAS – performed on patients with rheumatoid arthritis and axial spondylitis, respectively. CT-P13 and RP showed similar profile in terms of quality, biological activity, safety, immunogenicity, and efficacy. However, the interchangeability between infliximab RP and its biosimilar still represents the most challenging issue because of a lack of a long-lasting experience. To date, reassuring preliminary data on this topic were reported in open-label extensions of PLANETRA and PLANETAS RCTs and in ongoing real-life observational studies. These findings, taken all together, significantly affect the landscape of biosimilar regulatory pathways and strongly support CT-P13 introduction as a great opportunity for expanding the accessibility to these very effective and high-cost therapies. PMID:28721016

A review of the literature analyzing benefits and concerns of infliximab biosimilar CT-P13 for the treatment of rheumatologic diseases: focus on interchangeability.

PubMed

Becciolini, Andrea; Raimondo, Maria Gabriella; Crotti, Chiara; Agape, Elena; Biggioggero, Martina; Favalli, Ennio Giulio

2017-01-01

The introduction of biological agents drastically changed the treatment paradigm of inflammatory arthritides, ameliorating the natural history of the diseases but concomitantly increasing the drug costs due to the manufacturing process. On this concern, biosimilar drugs may represent a valid option for reducing this elevated cost and increasing the availability of these highly effective treatments. Recently, CT-P13, the first biosimilar of infliximab, has been approved with the same indications established for the reference product (RP), and its daily use is progressively increasing. However, the experience with biosimilar drugs in the field of rheumatology is still limited, raising potential doubts and concerns on their correct management in real-life settings. Comparability analysis between CT-P13 and its RP was evaluated in equivalence randomized controlled trials (RCTs) - PLANETRA and PLANETAS - performed on patients with rheumatoid arthritis and axial spondylitis, respectively. CT-P13 and RP showed similar profile in terms of quality, biological activity, safety, immunogenicity, and efficacy. However, the interchangeability between infliximab RP and its biosimilar still represents the most challenging issue because of a lack of a long-lasting experience. To date, reassuring preliminary data on this topic were reported in open-label extensions of PLANETRA and PLANETAS RCTs and in ongoing real-life observational studies. These findings, taken all together, significantly affect the landscape of biosimilar regulatory pathways and strongly support CT-P13 introduction as a great opportunity for expanding the accessibility to these very effective and high-cost therapies.

Validation of motion correction techniques for liver CT perfusion studies

PubMed Central

Chandler, A; Wei, W; Anderson, E F; Herron, D H; Ye, Z; Ng, C S

2012-01-01

Objectives Motion in images potentially compromises the evaluation of temporally acquired CT perfusion (CTp) data; image registration should mitigate this, but first requires validation. Our objective was to compare the relative performance of manual, rigid and non-rigid registration techniques to correct anatomical misalignment in acquired liver CTp data sets. Methods 17 data sets in patients with liver tumours who had undergone a CTp protocol were evaluated. Each data set consisted of a cine acquisition during a breath-hold (Phase 1), followed by six further sets of cine scans (each containing 11 images) acquired during free breathing (Phase 2). Phase 2 images were registered to a reference image from Phase 1 cine using two semi-automated intensity-based registration techniques (rigid and non-rigid) and a manual technique (the only option available in the relevant vendor CTp software). The performance of each technique to align liver anatomy was assessed by four observers, independently and blindly, on two separate occasions, using a semi-quantitative visual validation study (employing a six-point score). The registration techniques were statistically compared using an ordinal probit regression model. Results 306 registrations (2448 observer scores) were evaluated. The three registration techniques were significantly different from each other (p=0.03). On pairwise comparison, the semi-automated techniques were significantly superior to the manual technique, with non-rigid significantly superior to rigid (p<0.0001), which in turn was significantly superior to manual registration (p=0.04). Conclusion Semi-automated registration techniques achieved superior alignment of liver anatomy compared with the manual technique. We hope this will translate into more reliable CTp analyses. PMID:22374283

Automated prediction of tissue outcome after acute ischemic stroke in computed tomography perfusion images

NASA Astrophysics Data System (ADS)

Vos, Pieter C.; Bennink, Edwin; de Jong, Hugo; Velthuis, Birgitta K.; Viergever, Max A.; Dankbaar, Jan Willem

2015-03-01

Assessment of the extent of cerebral damage on admission in patients with acute ischemic stroke could play an important role in treatment decision making. Computed tomography perfusion (CTP) imaging can be used to determine the extent of damage. However, clinical application is hindered by differences among vendors and used methodology. As a result, threshold based methods and visual assessment of CTP images has not yet shown to be useful in treatment decision making and predicting clinical outcome. Preliminary results in MR studies have shown the benefit of using supervised classifiers for predicting tissue outcome, but this has not been demonstrated for CTP. We present a novel method for the automatic prediction of tissue outcome by combining multi-parametric CTP images into a tissue outcome probability map. A supervised classification scheme was developed to extract absolute and relative perfusion values from processed CTP images that are summarized by a trained classifier into a likelihood of infarction. Training was performed using follow-up CT scans of 20 acute stroke patients with complete recanalization of the vessel that was occluded on admission. Infarcted regions were annotated by expert neuroradiologists. Multiple classifiers were evaluated in a leave-one-patient-out strategy for their discriminating performance using receiver operating characteristic (ROC) statistics. Results showed that a RandomForest classifier performed optimally with an area under the ROC of 0.90 for discriminating infarct tissue. The obtained results are an improvement over existing thresholding methods and are in line with results found in literature where MR perfusion was used.

Safe use of proton pump inhibitors in patients with cirrhosis.

PubMed

Weersink, Rianne A; Bouma, Margriet; Burger, David M; Drenth, Joost P H; Froukje Harkes-Idzinga, S; Hunfeld, Nicole G M; Metselaar, Herold J; Monster-Simons, Margje H; van Putten, Sandra A W; Taxis, Katja; Borgsteede, Sander D

2018-04-24

Proton pump inhibitors (PPIs) belong to the most frequently used drugs, also in patients with cirrhosis. PPIs are extensively metabolized by the liver, but practice guidance on prescribing in cirrhosis is lacking. We aim to develop practical guidance on the safe use of PPIs in cirrhosis. A systematic literature search identified studies about the safety (i.e. adverse events) and pharmacokinetics of PPIs in cirrhotic patients. This evidence and data from the product information was reviewed by an expert panel who classified drugs as safe; no additional risks known; additional risks known; unsafe; or unknown. Guidance was aimed at the oral use of PPIs and categorized by the severity of cirrhosis, using the Child-Turcotte-Pugh (CTP) classification. A total of 69 studies were included. Esomeprazole, omeprazole and rabeprazole were classified as having 'no additional risks known'. A reduction in maximum dose of omeprazole and rabeprazole is recommended for CTP A and B patients. For patients with CTP C cirrhosis, the only PPI advised is esomeprazole in a maximum dosage of 20 mg per day. Pantoprazole and lansoprazole were classified as unsafe, because of 4- to 8-fold increased exposure. The use of PPIs in cirrhotic patients has been associated with the development of infections and hepatic encephalopathy and should be carefully considered. We suggest using esomeprazole, omeprazole or rabeprazole in patients with CTP A or B cirrhosis and only esomeprazole in patients with CTP C. Pharmacokinetic changes are also important to consider when prescribing PPIs to vulnerable, cirrhotic patients. This article is protected by copyright. All rights reserved.

CTP synthase 1, a smooth muscle-sensitive therapeutic target for effective vascular repair

PubMed Central

Tang, Rui; Cui, Xiao-Bing; Wang, Jia-Ning; Chen, Shi-You

2013-01-01

Objective Vascular remodeling due to smooth muscle cell (SMC) proliferation and neointima formation is a major medical challenge in cardiovascular intervention. However, anti-neointima drugs often indistinguishably block re-endothelialization, an essential step toward successful vascular repair, due to their non-specific effect on endothelial cells (EC). The objective of this study was to identify a therapeutic target that differentially regulates SMC and EC proliferation. Approach and Results By using both rat balloon-injury and mouse wire-injury models, we identified CTP synthase (CTPS) as one of the potential targets that may be used for developing therapeutics for treating neointima-related disorders. CTPS1 was induced in proliferative SMCs in vitro and neointima SMCs in vivo. Blockade of CTPS1 expression by small hairpin RNA or activity by cyclopentenyl cytosine suppressed SMC proliferation and neointima formation. Surprisingly, cyclopentenyl cytosine had much less effect on EC proliferation. Of importance, blockade of CTPS1 in vivo sustained the re-endothelialization due to induction of CTP synthesis salvage pathway enzymes nucleoside diphosphate kinase A and B in ECs. Diphosphate kinase B appeared to preserve EC proliferation via utilization of extracellular cytidine to synthesize CTP. Indeed, blockade of both CTPS1 and diphosphate kinase B suppressed EC proliferation in vitro and the re-endothelization in vivo. Conclusions Our study uncovered a fundamental difference in CTP biosynthesis between SMCs and ECs during vascular remodeling, which provided a novel strategy by using cyclopentenyl cytosine or other CTPS1 inhibitors to selectively block SMC proliferation without disturbing or even promoting re-endothelialization for effective vascular repair following injury. PMID:24008161

Compliance through pollution prevention opportunity assessments at Edwards AFB -- Development, results and lessons learned

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

Beutelman, H.P.; Lawrence, A.

1999-07-01

Edwards Air Force Base (AFB), located in the Mojave Desert of southern California, is required to comply with environmental requirements for air pollution emissions, hazardous waste disposal, and clean water. The resources required to meet these many compliance requirements represents an ever increasing financial burden to the base, and to the Department of Defense. A recognized superior approach to environmental management is to achieve compliance through a proactive pollution prevention (P2) program which mitigates, and when possible, eliminates compliance requirements and costs, while at the same time reducing pollution released to the environment. At Edwards AFB, the Environmental Management Officemore » P2 Branch developed and implemented a strategy that addresses this concept, better known as Compliance Through Pollution Prevention (CTP2). At the 91st AWMA Annual Meeting and Exhibition, Edwards AFB presented a paper on its strategy and implementation of its CTP2 concept. Part of that strategy and implementation included accomplishment of process specific focused P2 opportunity assessments (OAs). Starting in 1998, Edwards AFB initiated a CTP2 OA project where OAs were targeted on those operational processes, identified as compliance sites, that contributed most to the compliance requirements and costs at Edwards AFB. The targeting of these compliance sites was accomplished by developing a compliance matrix that prioritized processes in accordance with an operational risk management approach. The Edwards AFB CTP2 PPOA project is the first of its kind within the Air Force Material Command, and is serving as a benchmark for establishment of the CTP2 OA process.« less

Comparison of Shear-wave Profiles for a Compacted Fill in a Geotechnical Test Pit

NASA Astrophysics Data System (ADS)

Sylvain, M. B.; Pando, M. A.; Whelan, M.; Bents, D.; Park, C.; Ogunro, V.

2014-12-01

This paper investigates the use of common methods for geological seismic site characterization including: i) multichannel analysis of surface waves (MASW),ii) crosshole seismic surveys, and iii) seismic cone penetrometer tests. The in-situ tests were performed in a geotechnical test pit located at the University of North Carolina at Charlotte High Bay Laboratory. The test pit has dimensions of 12 feet wide by 12 feet long by 10 feet deep. The pit was filled with a silty sand (SW-SM) soil, which was compacted in lifts using a vibratory plate compactor. The shear wave velocity values from the 3 techniques are compared in terms of magnitude versus depth as well as spatially. The comparison was carried out before and after inducing soil disturbance at controlled locations to evaluate which methods were better suited to captured the induced soil disturbance.

Pitting Initiation and Propagation of X70 Pipeline Steel Exposed to Chloride-Containing Environments

PubMed Central

Yang, Zixuan; Kan, Bo; Li, Jinxu; Su, Yanjing; Qiao, Lijie; Volinsky, Alex A.

2017-01-01

Inclusion-induced pitting initiation mechanisms in X70 steel were investigated by scanning electron microscopy, scanning Kelvin probe force microscopy (SKPFM), immersion and electrochemical polarization tests in chloride-containing ion solutions. There are three inclusion types in the X70 steel. Corrosion test results indicated that pitting corrosion resistance of type A inclusion < type C inclusion < type B inclusion, i.e., (Mn, Ca)S < matrix < (Al, Ca)O. SKPFM test results show that the type A inclusion exhibited both lower and higher potentials than the matrix, while the type B inclusion exhibited higher potential than the matrix. The corrosion test and the SKPFM potential test results are consistent. Potentiodynamic polarization results indicate that the type A and C are active inclusions, while the type B is an inactive inclusion. Three kinds of possible mechanisms of inclusion-induced pitting corrosion are established for the X70 steel. PMID:28902156

Collision and phonation threshold pressures before and after loud, prolonged vocalization in trained and untrained voices.

PubMed

Enflo, Laura; Sundberg, Johan; McAllister, Anita

2013-09-01

The phonation threshold pressure (PTP) is defined as the lowest subglottal pressure needed for obtaining and sustaining vocal fold oscillation. It has been found to increase during vocal fatigue. In the present study, PTP is measured together with the threshold pressure needed for vocal fold collision; henceforth, the collision threshold pressure (CTP). PTP and CTP are compared before and after loud, prolonged vocalization in singer and nonsinger voices. Ten subjects repeated the vowel sequence /a, e, i, o, u/ at a Sound Pressure Level of at least 80 dB at 0.3 m for 20 minutes. Audio and electroglottography signals were recorded before and after this exercise. At the same time, oral pressure was registered while the subjects produced a diminuendo repeating the syllable /pa:/, thus acquiring an approximate of the subglottal pressure. CTP and PTP increased significantly after the vocal loading in the nonsinger subjects. On the other hand, singers reported no substantial effect of the exercise, and most singers had a mean after-to-before ratio close to 1 for both CTP and PTP. Copyright © 2013 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

La-CTP: Loop-Aware Routing for Energy-Harvesting Wireless Sensor Networks

PubMed Central

Sun, Guodong; Shang, Xinna; Zuo, Yan

2018-01-01

In emerging energy-harvesting wireless sensor networks (EH-WSN), the sensor nodes can harvest environmental energy to drive their operation, releasing the user’s burden in terms of frequent battery replacement, and even enabling perpetual sensing systems. In EH-WSN applications, usually, the node in energy-harvesting or recharging state has to stop working until it completes the energy replenishment. However, such temporary departures of recharging nodes severely impact the packet routing, and one immediate result is the routing loop problem. Controlling loops in connectivity-intermittent EH-WSN in an efficient way is a big challenge in practice, and so far, users still lack of effective and practicable routing protocols with loop handling. Based on the Collection Tree Protocol (CTP) widely used in traditional wireless sensor networks, this paper proposes a loop-aware routing protocol for real-world EH-WSNs, called La-CTP, which involves a new parent updating metric and a proactive, adaptive beaconing scheme to effectively suppress the occurrence of loops and unlock unavoidable loops, respectively. We constructed a 100-node testbed to evaluate La-CTP, and the experimental results showed its efficacy and efficiency. PMID:29393876

Biosimilar Monoclonal Antibodies for Inflammatory Bowel Disease: Current Comfort and Future Prospects.

PubMed

Gecse, Krisztina B; Lakatos, Péter L

2016-10-01

Biosimilars are biologic medicines that enter the market after a patent for an original reference product expires. The European Medicines Agency (EMA) developed a stringent legislation process for biosimilar monoclonal antibodies, whereby similarity to the reference medicinal product in terms of quality characteristics, biological activity, clinical safety and efficacy must be demonstrated. Biosimilar infliximab CT-P13 was the first biosimilar monoclonal antibody to receive EMA marketing authorization, and further biosimilar molecules are being developed. The phase I and III clinical trials were conducted in ankylosing spondylitis and rheumatoid arthritis, and the use of CT-P13 in inflammatory bowel disease (IBD) was extrapolated on the results of these trials. Medical professionals were initially concerned about the reversed engineering process, the novel legal framework and the lack of clinical data in IBD. Emerging real-world data have confirmed the similarities between CT-P13 and the reference product in terms of efficacy, safety and immunogenicity in IBD. The cost reduction represented by biosimilars promotes industry competition and improves treatment access with sustained quality of care. This article reviews the existing and emerging clinical data for CT-P13 and a future perspective on biosimilar use in IBD.

Kinetic Basis of Nucleotide Selection Employed by a Protein Template-Dependent DNA Polymerase†

PubMed Central

Brown, Jessica A.; Fowler, Jason D.; Suo, Zucai

2010-01-01

Rev1, a Y-family DNA polymerase, contributes to spontaneous and DNA damage-induced mutagenic events. In this paper, we have employed pre-steady state kinetic methodology to establish a kinetic basis for nucleotide selection by human Rev1, a unique nucleotidyl transferase that uses a protein template-directed mechanism to preferentially instruct dCTP incorporation. This work demonstrated that the high incorporation efficiency of dCTP is dependent on both substrates: an incoming dCTP and a templating base dG. The extremely low base substitution fidelity of human Rev1 (100 to 10-5) was due to the preferred misincorporation of dCTP with templating bases dA, dT, and dC over correct dNTPs. Using non-natural nucleotide analogs, we showed that hydrogen bonding interactions between residue R357 of human Rev1 and an incoming dNTP are not essential for DNA synthesis. Lastly, human Rev1 discriminates between ribonucleotides and deoxyribonucleotides mainly by reducing the rate of incorporation, and the sugar selectivity of human Rev1 is sensitive to both the size and orientation of the 2′-substituent of a ribonucleotide. PMID:20518555

CT-P6 compared with reference trastuzumab for HER2-positive breast cancer: a randomised, double-blind, active-controlled, phase 3 equivalence trial.

PubMed

Stebbing, Justin; Baranau, Yauheni; Baryash, Valeriy; Manikhas, Alexey; Moiseyenko, Vladimir; Dzagnidze, Giorgi; Zhavrid, Edvard; Boliukh, Dmytro; Stroyakovskii, Daniil; Pikiel, Joanna; Eniu, Alexandru; Komov, Dmitry; Morar-Bolba, Gabriela; Li, Rubi K; Rusyn, Andriy; Lee, Sang Joon; Lee, Sung Young; Esteva, Francisco J

2017-07-01

CT-P6 is a proposed biosimilar to reference trastuzumab. In this study, we aimed to establish equivalence of CT-P6 to reference trastuzumab in neoadjuvant treatment of HER2-positive early-stage breast cancer. In this randomised, double-blind, active-controlled, phase 3 equivalence trial, we recruited women aged 18 years or older with stage I-IIIa operable HER2-positive breast cancer from 112 centres in 23 countries. Inclusion criteria were an Eastern Cooperative Oncology Group performance status score of 0 or 1; a normal left ventricular ejection fraction of at least 55%; adequate bone marrow, hepatic, and renal function; at least one measureable lesion; and known oestrogen and progesterone receptor status. Exclusion criteria included bilateral breast cancer, previous breast cancer treatment, previous anthracycline treatment, and pregnancy or lactation. We randomly allocated patients 1:1 to receive neoadjuvant CT-P6 or reference trastuzumab intravenously (eight cycles, each lasting 3 weeks, for 24 weeks; 8 mg/kg on day 1 of cycle 1 and 6 mg/kg on day 1 of cycles 2-8) in conjunction with neoadjuvant docetaxel (75 mg/m 2 on day 1 of cycles 1-4) and FEC (fluorouracil [500 mg/m 2 ], epirubicin [75 mg/m 2 ], and cyclophosphamide [500 mg/m 2 ]; day 1 of cycles 5-8) therapy. We stratified randomisation by clinical stage, receptor status, and country and used permuted blocks. We did surgery within 3-6 weeks of the final neoadjuvant study drug dose, followed by an adjuvant treatment period of up to 1 year. We monitored long-term safety and efficacy for 3 years after the last patient was enrolled. Participants and investigators were masked to treatment until study completion. The primary efficacy endpoint, analysed in the per-protocol population, was pathological complete response, assessed via specimens obtained during surgery, analysed by masked central review of local histopathology reports. The equivalence margin was -0·15 to 0·15. This trial is registered with ClinicalTrials.gov, number NCT02162667, and is ongoing, but no longer recruiting. Between Aug 7, 2014, and May 6, 2016, we randomly allocated 549 patients (271 [49%] to CT-P6 vs 278 [51%] to reference trastuzumab). A similar proportion of patients achieved pathological complete response with CT-P6 (116 [46·8%; 95% CI 40·4-53·2] of 248 patients) and reference trastuzumab (129 [50·4%; 44·1-56·7] of 256 patients). The 95% CI of the estimated treatment outcome difference (-0·04% [95% CI -0·12 to 0·05]) was within the equivalence margin. 19 (7%) of 271 patients in the CT-P6 group reported serious treatment-emergent adverse events versus 22 (8%) of 278 in the reference trastuzumab group; frequent (occurring in more than one patient) serious adverse events were febrile neutropenia (four [1%] vs one [<1%]) and neutropenia (one [<1%] vs two [1%]). Grade 3 or worse treatment-related adverse events occurred in 17 (6%) of 271 patients in the CT-P6 group versus 23 (8%) of 278 in the reference trastuzumab group; the most frequently reported adverse event was neutropenia in ten (4%) versus 14 (5%). CT-P6 showed equivalent efficacy to reference trastuzumab and adverse events were similar. Availability of trastuzumab biosimilars could increase access to this targeted therapy for HER2-positive early-stage cancer. Celltrion Inc. Copyright © 2017 Elsevier Ltd. All rights reserved.

NREL Collaborates with Trucking Industry to Prioritize R&D Opportunities |

Science.gov Websites

Department drive decision-making and improve efficiency, informing long-term, high-risk research such as the Rosa Using Data to Drive Decision Making NREL's fleet test and evaluation team conducts real-world 21CTP an example of NREL's data evaluation and decision support capabilities. Using data collected in

Reliable identification of deep sulcal pits: the effects of scan session, scanner, and surface extraction tool.

PubMed

Im, Kiho; Lee, Jong-Min; Jeon, Seun; Kim, Jong-Heon; Seo, Sang Won; Na, Duk L; Grant, P Ellen

2013-01-01

Sulcal pit analysis has been providing novel insights into brain function and development. The purpose of this study was to evaluate the reliability of sulcal pit extraction with respect to the effects of scan session, scanner, and surface extraction tool. Five subjects were scanned 4 times at 3 MRI centers and other 5 subjects were scanned 3 times at 2 MRI centers, including 1 test-retest session. Sulcal pits were extracted on the white matter surfaces reconstructed with both Montreal Neurological Institute and Freesurfer pipelines. We estimated similarity of the presence of sulcal pits having a maximum value of 1 and their spatial difference within the same subject. The tests showed high similarity of the sulcal pit presence and low spatial difference. The similarity was more than 0.90 and the spatial difference was less than 1.7 mm in most cases according to different scan sessions or scanners, and more than 0.85 and about 2.0 mm across surface extraction tools. The reliability of sulcal pit extraction was more affected by the image processing-related factors than the scan session or scanner factors. Moreover, the similarity of sulcal pit distribution appeared to be largely influenced by the presence or absence of the sulcal pits on the shallow and small folds. We suggest that our sulcal pit extraction from MRI is highly reliable and could be useful for clinical applications as an imaging biomarker.

Study on the corrosion residual strength of the 1.0 wt.% Ce modified AZ91 magnesium alloy

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

Li Chunfang; Liu Yaohui, E-mail: liuyaohui2005@yahoo.com; Wang Qiang

2010-01-15

The effect of corrosion on the tensile behaviour of the 1.0 wt.% Ce modified AZ91 magnesium alloy was investigated by the immersion of the test bar in 3.5 wt.% NaCl aqueous solution for 0, 12, 40, 108, 204, 372 and 468 h with the subsequent tensile tests in this paper. The fractography was analyzed by scanning electron microscopy. The results show that pitting corrosion should be responsible for the drop of the corrosion residual strength within the testing time. The depth of the corrosion pits was statistically and quantitatively obtained by an optical microscopy and the maximal value was recordedmore » as the extreme depth of the corrosion pit. Furthermore, the corrosion residual strength is linearly dependent on the extreme depth of the corrosion pit, which can be attributed to the loss of cross-sectional area and the emergence of stress concentration caused by the initiation and development of corrosion pits.« less

The effects of acute stress on Pavlovian-instrumental transfer in rats.

PubMed

Pielock, Steffi M; Braun, Stephanie; Hauber, Wolfgang

2013-03-01

Pavlovian stimuli invigorate ongoing instrumental action, a phenomenon termed the Pavlovian-instrumental transfer (PIT) effect. Acute stressors can markedly enhance the release of corticotropin-releasing factor (CRF), and CRF injection into the nucleus accumbens increases the PIT effect. However, it is unknown whether acute stressors by themselves would amplify the PIT effect. Here, we examined the effects of acute stressors on PIT. Rats first received Pavlovian and instrumental training, and then the impact of the Pavlovian stimuli on instrumental responding was analyzed in the subsequent PIT test. Acute stressors were applied prior to the PIT test. Because the effects of acute stressors critically depend on stressor type and time of day, we used two acute stressors that involved one or several distinct stressors (denoted here as "single" vs. "multiple" stressors) applied either in the light or the dark period of the light:dark cycle. The results revealed that single and multiple stressors applied in the light period did not alter the PIT effect--that is, the ability of an appetitive Pavlovian stimulus to enhance leverpressing--or the basal leverpress rate. When applied in the dark period, single and multiple stressors also did not alter the PIT effect, but they did markedly reduce the basal leverpress rate. Diazepam pretreatment did not counteract the declines in basal instrumental responding in the PIT test that were induced by either a single or multiple stressors. Our findings suggest that acute stressors were unable to amplify the incentive salience of reward-predictive Pavlovian stimuli to activate instrumental responding, but, depending on the time of day of stressor exposure, they did reduce basal instrumental responding.

How food cues can enhance and inhibit motivation to obtain and consume food.

PubMed

Colagiuri, Ben; Lovibond, Peter F

2015-01-01

Learning may play an important role in over-eating. One example is Pavlovian-to-instrumental transfer (PIT), whereby reward cues facilitate responding to obtain that reward. Whilst there is increasing research indicating PIT for food in humans, these studies have exclusively tested PIT under instrumental extinction (i.e. when the food is no longer available), which may reduce their ecological validity. To address this, we conducted two experiments exploring PIT for food in humans when tested under instrumental reinforcement. Participants first underwent Pavlovian discrimination training with an auditory cue paired with a chocolate reward (CS+) and another auditory cue unpaired (CS-). In instrumental training participants learnt to press a button to receive the chocolate reward on a VR10 schedule. In the test phase, each CS was presented whilst participants maintained the opportunity to press the button to receive chocolate. In Experiment 1, the PIT test was implemented after up to 20 min of instrumental training (satiation) whereas in Experiment 2 it was implemented after only 4 min of instrumental training. In both experiments there was evidence for differential PIT, but the pattern differed according to the rate of responding at the time of the PIT test. In low baseline responders the CS+ facilitated both button press responding and consumption, whereas in high baseline responders the CS- suppressed responding. These findings suggest that both excitatory and inhibitory associations may be learnt during PIT training and that the expression of these associations depends on motivation levels at the time the cues are encountered. Particularly concerning is that a food-paired cue can elicit increased motivation to obtain and consume food even when the participant is highly satiated and no longer actively seeking food, as this may be one mechanism by which over-consumption is maintained. Copyright © 2014 Elsevier Ltd. All rights reserved.

Oral administration of citrus pulp reduces gasrointestinal recovery of orally dosed Escherichia coli F18 in weaned pigs

USDA-ARS?s Scientific Manuscript database

The effects of citrus pulp (CTP), on the immune and cortisol responses to E. coli F18 inoculation and subsequent E. coli recovery were evaluated in newly weaned pigs (23.3 + 1.8 d of age). Barrows were assigned to 1 of 2 treatment groups; with (CTP; n = 15) and without (Control; n = 15) the in-feed ...

Structure-based Mechanism of CMP-2-keto-3-deoxymanno-octulonic Acid Synthetase

PubMed Central

Heyes, Derren J.; Levy, Colin; Lafite, Pierre; Roberts, Ian S.; Goldrick, Marie; Stachulski, Andrew V.; Rossington, Steven B.; Stanford, Deborah; Rigby, Stephen E. J.; Scrutton, Nigel S.; Leys, David

2009-01-01

The enzyme CMP-Kdo synthetase (KdsB) catalyzes the addition of 2-keto-3-deoxymanno-octulonic acid (Kdo) to CTP to form CMP-Kdo, a key reaction in the biosynthesis of lipopolysaccharide. The reaction catalyzed by KdsB and the related CMP-acylneuraminate synthase is unique among the sugar-activating enzymes in that the respective sugars are directly coupled to a cytosine monophosphate. Using inhibition studies, in combination with isothermal calorimetry, we show the substrate analogue 2β-deoxy-Kdo to be a potent competitive inhibitor. The ligand-free Escherichia coli KdsB and ternary complex KdsB-CTP-2β-deoxy-Kdo crystal structures reveal that Kdo binding leads to active site closure and repositioning of the CTP phosphates and associated Mg2+ ion (Mg-B). Both ligands occupy conformations compatible with an Sn2-type attack on the α-phosphate by the Kdo 2-hydroxyl group. Based on strong similarity with DNA/RNA polymerases, both in terms of overall chemistry catalyzed as well as active site configuration, we postulate a second Mg2+ ion (Mg-A) is bound by the catalytically competent KdsB-CTP-Kdo ternary complex. Modeling of this complex reveals the Mg-A coordinated to the conserved Asp100 and Asp235 in addition to the CTP α-phosphate and both the Kdo carboxylic and 2-hydroxyl groups. EPR measurements on the Mn2+-substituted ternary complex support this model. We propose the KdsB/CNS sugar-activating enzymes catalyze the formation of activated sugars, such as the abundant CMP-5-N-acetylneuraminic acid, by recruitment of two Mg2+ to the active site. Although each metal ion assists in correct positioning of the substrates and activation of the α-phosphate, Mg-A is responsible for activation of the sugar-hydroxyl group. PMID:19815542

Transition-state destabilization reveals how human DNA polymerase β proceeds across the chemically unstable lesion N7-methylguanine

PubMed Central

Ouzon-Shubeita, Hala; Lee, Seongmin

2014-01-01

N7-Methyl-2′-deoxyguanosine (m7dG) is the predominant lesion formed by methylating agents. A systematic investigation on the effect of m7dG on DNA replication has been difficult due to the chemical instability of m7dG. To gain insights into the m7dG effect, we employed a 2′-fluorine-mediated transition-state destabilzation strategy. Specifically, we determined kinetic parameters for dCTP insertion opposite a chemically stable m7dG analogue, 2′-fluoro-m7dG (Fm7dG), by human DNA polymerase β (polβ) and solved three X-ray structures of polβ in complex with the templating Fm7dG paired with incoming dCTP or dTTP analogues. The kinetic studies reveal that the templating Fm7dG slows polβ catalysis ∼300-fold, suggesting that m7dG in genomic DNA may impede replication by some DNA polymerases. The structural analysis reveals that Fm7dG forms a canonical Watson–Crick base pair with dCTP, but metal ion coordination is suboptimal for catalysis in the polβ-Fm7dG:dCTP complex, which partially explains the slow insertion of dCTP opposite Fm7dG by polβ. In addition, the polβ-Fm7dG:dTTP structure shows open protein conformations and staggered base pair conformations, indicating that N7-methylation of dG does not promote a promutagenic replication. Overall, the first systematic studies on the effect of m7dG on DNA replication reveal that polβ catalysis across m7dG is slow, yet highly accurate. PMID:24966350

Biased visualization of hypoperfused tissue by computed tomography due to short imaging duration: improved classification by image down-sampling and vascular models.

PubMed

Mikkelsen, Irene Klærke; Jones, P Simon; Ribe, Lars Riisgaard; Alawneh, Josef; Puig, Josep; Bekke, Susanne Lise; Tietze, Anna; Gillard, Jonathan H; Warburton, Elisabeth A; Pedraza, Salva; Baron, Jean-Claude; Østergaard, Leif; Mouridsen, Kim

2015-07-01

Lesion detection in acute stroke by computed-tomography perfusion (CTP) can be affected by incomplete bolus coverage in veins and hypoperfused tissue, so-called bolus truncation (BT), and low contrast-to-noise ratio (CNR). We examined the BT-frequency and hypothesized that image down-sampling and a vascular model (VM) for perfusion calculation would improve normo- and hypoperfused tissue classification. CTP datasets from 40 acute stroke patients were retrospectively analysed for BT. In 16 patients with hypoperfused tissue but no BT, repeated 2-by-2 image down-sampling and uniform filtering was performed, comparing CNR to perfusion-MRI levels and tissue classification to that of unprocessed data. By simulating reduced scan duration, the minimum scan-duration at which estimated lesion volumes came within 10% of their true volume was compared for VM and state-of-the-art algorithms. BT in veins and hypoperfused tissue was observed in 9/40 (22.5%) and 17/40 patients (42.5%), respectively. Down-sampling to 128 × 128 resolution yielded CNR comparable to MR data and improved tissue classification (p = 0.0069). VM reduced minimum scan duration, providing reliable maps of cerebral blood flow and mean transit time: 5 s (p = 0.03) and 7 s (p < 0.0001), respectively). BT is not uncommon in stroke CTP with 40-s scan duration. Applying image down-sampling and VM improve tissue classification. • Too-short imaging duration is common in clinical acute stroke CTP imaging. • The consequence is impaired identification of hypoperfused tissue in acute stroke patients. • The vascular model is less sensitive than current algorithms to imaging duration. • Noise reduction by image down-sampling improves identification of hypoperfused tissue by CTP.

Clinical Use of CT Perfusion For Diagnosis and Prediction of Lesion Growth in Acute Ischemic Stroke

PubMed Central

Huisa, Branko N; Neil, William P; Schrader, Ronald; Maya, Marcel; Pereira, Benedict; Bruce, Nhu T; Lyden, Patrick D

2012-01-01

Background and Purpose CT perfusion (CTP) mapping in research centers correlates well with diffusion weighted imaging (DWI) lesions and may accurately differentiate the infarct core from ischemic penumbra. The value of CTP in real-world clinical practice has not been fully established. We investigated the yield of CTP– derived cerebral blood volume (CBV) and mean transient time (MTT) for the detection of cerebral ischemia and ischemic penumbra in a sample of acute ischemic stroke (AIS) patients. Methods We studied 165 patients with initial clinical symptoms suggestive of AIS. All patients had an initial non-contrast head CT, CT Perfusion (CTP), CT angiogram (CTA) and follow up brain MRI. The obtained perfusion images were used for image processing. CBV, MTT and DWI lesion volumes were visually estimated and manually traced. Statistical analysis was done using R-2.14.and SAS 9.1. Results All normal DWI sequences had normal CBV and MTT studies (N=89). Seventy-three patients had acute DWI lesions. CBV was abnormal in 23.3% and MTT was abnormal in 42.5% of these patients. There was a high specificity (91.8%)but poor sensitivity (40.0%) for MTT maps predicting positive DWI. Spearman correlation was significant between MTT and DWI lesions (ρ=0.66, p>0.0001) only for abnormal MTT and DWI lesions>0cc. CBV lesions did not correlate with final DWI. Conclusions In real-world use, acute imaging with CTP did not predict stroke or DWI lesions with sufficient accuracy. Our findings argue against the use of CTP for screening AIS patients until real-world implementations match the accuracy reported from specialized research centers. PMID:23253533

Timing of Occurrence Is the Most Important Characteristic of Spot Sign.

PubMed

Wang, Binli; Yan, Shenqiang; Xu, Mengjun; Zhang, Sheng; Liu, Keqin; Hu, Haitao; Selim, Magdy; Lou, Min

2016-05-01

Most previous studies have used single-phase computed tomographic angiography to detect the spot sign, a marker for hematoma expansion (HE) in spontaneous intracerebral hemorrhage. We investigated whether defining the spot sign based on timing on perfusion computed tomography (CTP) would improve its specificity for predicting HE. We prospectively enrolled supratentorial spontaneous intracerebral hemorrhage patients who underwent CTP within 6 hours of onset. Logistic regression was performed to assess the risk factors for HE and poor outcome. Predictive performance of individual CTP spot sign characteristics were examined with receiver operating characteristic analysis. Sixty-two men and 21 women with spontaneous intracerebral hemorrhage were included in this analysis. Spot sign was detected in 46% (38/83) of patients. Receiver operating characteristic analysis indicated that the timing of spot sign occurrence on CTP had the greatest area under receiver operating characteristic curve for HE (0.794; 95% confidence interval, 0.630-0.958; P=0.007); the cutoff time was 23.13 seconds. On multivariable analysis, the presence of early-occurring spot sign (ie, spot sign before 23.13 seconds) was an independent predictor not only of HE (odds ratio=28.835; 95% confidence interval, 6.960-119.458; P<0.001), but also of mortality at 3 months (odds ratio =22.377; 95% confidence interval, 1.773-282.334; P=0.016). Moreover, the predictive performance showed that the redefined early-occurring spot sign maintained a higher specificity for HE compared with spot sign (91% versus 74%). Redefining the spot sign based on timing of contrast leakage on CTP to determine early-occurring spot sign improves the specificity for predicting HE and 3-month mortality. The use of early-occurring spot sign could improve the selection of ICH patients for potential hemostatic therapy. © 2016 American Heart Association, Inc.

Timing of occurrence is the most important characteristic of spot sign

PubMed Central

Xu, Mengjun; Zhang, Sheng; Liu, Keqin; Hu, Haitao; Selim, Magdy; Lou, Min

2016-01-01

Background and Purpose Most previous studies have used single-phase CT angiography (CTA) to detect the spot sign, a marker for hematoma expansion (HE) in spontaneous intracerebral hemorrhage (SICH). We investigated whether defining the spot sign based on timing on perfusion CT (CTP) would improve its specificity for predicting HE. Methods We prospectively enrolled supratentorial SICH patients, who underwent CTP within 6 h of onset. Logistic regression were performed to assess the risk factors for HE and poor outcome. Predictive performance of individual CTP spot sign characteristics were examined with receiver operating characteristic (ROC) analysis. Results Sixty-two men and 21 women with SICH were included in this analysis. Spot sign was detected in 46% (38/83) patients. ROC analysis indicated that the timing of spot sign occurrence on CTP had the greatest AUC for HE (0.794; 95% CI, 0.630-0.958; P=0.007); the cutoff time was 23.13 seconds. On multivariable analysis, the presence of early-occurring spot sign (EOSS; i.e. spot sign before 23.13 seconds) was an independent predictor, not only of HE (OR=28.835; 95% CI, 6.960-119.458; P<0.001), but also of mortality at 3 months (OR=22.377; 95% CI, 1.773-282.334; P=0.016). Moreover, the predictive performance showed that the redefined EOSS maintained a higher specificity for HE compared to spot sign (91% vs 74%). Conclusions Redefining the spot sign based on timing of contrast leakage on CTP to determine EOSS, improves the specificity for predicting HE and 3-month mortality. The use of EOSS could improve the selection of ICH patients for potential hemostatic therapy. PMID:27026627

Prediction of Post-operative Mortality in Patients with HCV-related Cirrhosis Undergoing Non-Hepatic Surgeries

PubMed Central

Hemida, Khalid; Shabana, Sherif Sadek; Said, Hani; Ali-Eldin, Fatma

2016-01-01

Introduction Patients with chronic liver diseases are at great risk for both morbidity and mortality during the post-operative period due to the stress of surgery and the effects of general anaesthesia. Aim The main aim of this study was to evaluate the value of Model for End-stage Liver Disease (MELD) score, as compared to Child-Turcotte-Pugh (CTP) score, for prediction of 30- day post-operative mortality in Egyptian patients with liver cirrhosis undergoing non-hepatic surgery under general anaesthesia. Materials and Methods A total of 60 patients with Hepatitis C Virus (HCV) - related liver cirrhosis were included in this study. Sensitivity and specificity of MELD and CTP scores were evaluated for the prediction of post-operative mortality. A total of 20 patients who had no clinical, biochemical or radiological evidence of liver disease were included to serve as a control group. Results The highest sensitivity and specificity for detection of post-operative mortality was detected at a MELD score of 13.5. CTP score had a sensitivity of 75%, a specificity of 96.4%, and an overall accuracy of 95% for prediction of post-operative mortality. On the other side and at a cut-off value of 13.5, MELD score had a sensitivity of 100%, a specificity of 64.0%, and an overall accuracy of 66.6% for prediction of post-operative mortality in patients with HCV- related liver cirrhosis. Conclusion MELD score proved to be more sensitive but less specific than CTP score for prediction of post-operative mortality. CTP and MELD scores may be complementary rather than competitive in predicting post-operative mortality in patients with HCV- related liver cirrhosis. PMID:27891371

Algorithms for detecting cherry pits on the basis of transmittance mode hyperspectral data

NASA Astrophysics Data System (ADS)

Siedliska, Anna; Zubik, Monika; Baranowski, Piotr; Mazurek, Wojciech

2017-10-01

The suitability of the hyperspectral transmittance imaging technique was assessed in terms of detecting the internal intrusions (pits and their fragments) in cherries. Herein, hyperspectral transmission images were acquired in the visible and near-infrared range (450-1000 nm) from pitted and intact cherries of three popular cultivars: `Łutówka', `Pandy 103', and `Groniasta', differing by soluble solid content. The hyperspectral transmittance data of fresh cherries were used to determine the influence of differing soluble solid content in fruit tissues on pit detection effectiveness. Models for predicting the soluble solid content of cherries were also developed. The principal component analysis and the second derivative pre-treatment of the hyperspectral data were used to construct the supervised classification models. In this study, five classifiers were tested for pit detection. From all the classifiers studied, the best prediction accuracies for the whole pit or pit fragment detection were obtained via the backpropagation neural networks model (87.6% of correctly classified instances for the training/test set and 81.4% for the validation set). The accuracy of distinguishing between drilled and intact cherries was close to 96%. These results showed that the hyperspectral transmittance imaging technique is feasible and useful for the non-destructive detection of pits in cherries.

High-sensitivity chemiluminescence immunoassays for detection of growth hormone doping in sports.

PubMed

Bidlingmaier, Martin; Suhr, Jennifer; Ernst, Andrea; Wu, Zida; Keller, Alexandra; Strasburger, Christian J; Bergmann, Andreas

2009-03-01

Recombinant human growth hormone (rhGH) is abused in sports, but adequate routine doping tests are lacking. Analysis of serum hGH isoform composition has been shown to be effective in detecting rhGH doping. We developed and validated selective immunoassays for isoform analysis with potential utility for screening and confirmation in doping tests. Monoclonal antibodies with preference for pituitary hGH (phGH) or rhGH were used to establish 2 pairs of sandwich-type chemiluminescence assays with differential recognition of rhGH (recA and recB) and phGH (pitA and pitB). We analyzed specimens from volunteers before and after administration of rhGH and calculated ratios between the respective rec- and pit-assay results. Functional sensitivities were <0.05 microg/L, with intra- and interassay imprecision < or =8.4% and < or =13.7%, respectively. In 2 independent cohorts of healthy subjects, rec/pit ratios (median range) were 0.84 (0.09-1.32)/0.81 (0.27-1.21) (recA/pitA) and 0.68 (0.08-1.20)/0.80 (0.25-1.36) (recB/pitB), with no sex difference. In 20 recreational athletes, ratios (median SD) increased after a single injection of rhGH, reaching 350% (73%) (recA/pitA) and 400% (93%) (recB/pitB) of baseline ratios. At a moderate dose (0.033 mg/kg), mean recA/pitA and recB/pitB ratios remained significantly increased for 18 h (men) and 26 h (women). After high-dose rhGH (0.083 mg/kg), mean rec/pit ratios remained increased for 32 h (recA/pitA) and 34 h (recB/pitB) in men and were still increased after 36 h in women. Using sensitive chemiluminescence assays with preferential recognition of phGH or rhGH, detection of a single injection of rhGH was possible for up to 36 h.

Quantitative Correlation of 7B04 Aluminum Alloys Pitting Corrosion Morphology Characteristics with Stress Concentration Factor

NASA Astrophysics Data System (ADS)

Liu, Zhiguo; Yan, Guangyao; Mu, Zhitao; Li, Xudong

2018-01-01

The accelerated pitting corrosion test of 7B04 aluminum alloy specimen was carried out according to the spectrum which simulated airport environment, and the corresponding pitting corrosion damage was obtained and was defined through three parameters A and B and C which respectively denoted the corrosion pit surface length and width and corrosion pit depth. The ratio between three parameters could determine the morphology characteristics of corrosion pits. On this basis the stress concentration factor of typical corrosion pit morphology under certain load conditions was quantitatively analyzed. The research shows that the corrosion pits gradually incline to be ellipse in surface and moderate in depth, and most value of B/A and C/A lies in 1 between 4 and few maximum exceeds 4; The stress concentration factor Kf of corrosion pits is obviously affected by the its morphology, the value of Kf increases with corrosion pits depth increasement under certain corrosion pits surface geometry. Also, the value of Kf decreases with surface width increasement under certain corrosion pits depth. The research conclusion can set theory basis for corrosion fatigue life analysis of aircraft aluminum alloy structure.

Oral administration of citrus pulp reduces gastrointestinal recovery of orally dosed Escherichia coli F18 in weaned pigs

USDA-ARS?s Scientific Manuscript database

The effects of citrus pulp (CTP) on the immune and cortisol responses to E. coli F18 inoculation and subsequent E. coli recovery were evaluated in newly weaned pigs (23.3 + 1.8 d of age). Barrows were assigned to 1 of 2 treatment groups; with (CTP; n = 15) and without (Control; n = 15) the in-feed i...

Serum iron parameters in liver cirrhosis

NASA Astrophysics Data System (ADS)

Siregar, G. A.; Maail, W.

2018-03-01

The liver plays a fundamental role in iron homeostasis. Iron parameters change, especially ferritin, need to be evaluated in patients with liver cirrhosis. Serum ferritin could predict the prognosis of patients with decompensated cirrhosis since it reflects immunemediated and infectious stimuli. Ferritin could express the severity of liver disease and possible subsequent complications. Finally, it might reflect an iron overload condition resulting in significant morbidity and early mortality. 70 patients with decompensated liver cirrhosis divided into three Child-Pugh subgroups. Serum iron parameters include serum iron (SI), total iron binding capacity (TIBC) and ferritin was measured in these groups. From these 70 patients, 30 (42.9%) with HbsAg positive, 26 (37.1%) with anti-HCV positive and 14 (20%) with both HbsAg and anti-HCV positive. Of the 70 patients, 14 (20%) had CTP Class A cirrhosis, 17 (24.3%) had CTP Class B cirrhosis, and 39 (55.7%) had CTP C cirrhosis. The median (range) value of serum iron was 36 (10-345) μg/dl, TIBC was 160 (59-520) μg/dl, Ferritin was 253.5 (8-6078) ng/ml and the transferrin saturation was 22.9 (3.65-216.98) %.We found a significant difference in serum ferritin level with CTP score. Ferritin levels increased as Child-Pugh class progressed (p<0.001).

Detection of Alicyclobacillus species in fruit juice using a random genomic DNA microarray chip.

PubMed

Jang, Jun Hyeong; Kim, Sun-Joong; Yoon, Bo Hyun; Ryu, Jee-Hoon; Gu, Man Bock; Chang, Hyo-Ihl

2011-06-01

This study describes a method using a DNA microarray chip to rapidly and simultaneously detect Alicyclobacillus species in orange juice based on the hybridization of genomic DNA with random probes. Three food spoilage bacteria were used in this study: Alicyclobacillus acidocaldarius, Alicyclobacillus acidoterrestris, and Alicyclobacillus cycloheptanicus. The three Alicyclobacillus species were adjusted to 2 × 10(3) CFU/ml and inoculated into pasteurized 100% pure orange juice. Cy5-dCTP labeling was used for reference signals, and Cy3-dCTP was labeled for target genomic DNA. The molar ratio of 1:1 of Cy3-dCTP and Cy5-dCTP was used. DNA microarray chips were fabricated using randomly fragmented DNA of Alicyclobacillus spp. and were hybridized with genomic DNA extracted from Bacillus spp. Genomic DNA extracted from Alicyclobacillus spp. showed a significantly higher hybridization rate compared with DNA of Bacillus spp., thereby distinguishing Alicyclobacillus spp. from Bacillus spp. The results showed that the microarray DNA chip containing randomly fragmented genomic DNA was specific and clearly identified specific food spoilage bacteria. This microarray system is a good tool for rapid and specific detection of thermophilic spoilage bacteria, mainly Alicyclobacillus spp., and is useful and applicable to the fruit juice industry.

Progress in biosimilar monoclonal antibody development: the infliximab biosimilar CT-P13 in the treatment of rheumatic diseases.

PubMed

Braun, Jürgen; Kudrin, Alex

2015-01-01

Biosimilars are biologic medical products whose active drug substance is made by a living organism or derived from it. The term is used to describe a subsequent version of an innovator biopharmaceutical product aiming at approval following patent expiry on the reference product. Biosimilars of monoclonal need to demonstrate similar but not identical quality of nonclinical and clinical attributes. Not all data of the originator product need to be recapitulated, as large numbers of patient-years of exposure data are already available. Thus, biosimilar development is largely based on the safety profiles of the originator product. The evaluation of biosimilarity includes immunogenicity attributed risks. CT-P13 (Remsima™/Inflectra™, Celltrion/Hospira), a biosimilar of the innovator drug infliximab (INF), was the first approved complex biosimilar monoclonal antibody in the EU, within the framework of WHO, EMA and US FDA biosimilar guidelines. CT-P13 has shown analytical and nonclinical features highly similar to INF including pharmacokinetics, efficacy, safety and immunogenicity profiles in ankylosing spondylitis and rheumatoid arthritis. The objective of this article is to highlight the recent biosimilar development and to review the results from the studies PLANETRA and PLANETAS, which have supported the approval of CT-P13 for several indications.

An optimized transit peptide for effective targeting of diverse foreign proteins into chloroplasts in rice.

PubMed

Shen, Bo-Ran; Zhu, Cheng-Hua; Yao, Zhen; Cui, Li-Li; Zhang, Jian-Jun; Yang, Cheng-Wei; He, Zheng-Hui; Peng, Xin-Xiang

2017-04-11

Various chloroplast transit peptides (CTP) have been used to successfully target some foreign proteins into chloroplasts, but for other proteins these same CTPs have reduced localization efficiencies or fail completely. The underlying cause of the failures remains an open question, and more effective CTPs are needed. In this study, we initially observed that two E.coli enzymes, EcTSR and EcGCL, failed to be targeted into rice chloroplasts by the commonly-used rice rbcS transit peptide (rCTP) and were subsequently degraded. Further analyses revealed that the N-terminal unfolded region of cargo proteins is critical for their localization capability, and that a length of about 20 amino acids is required to attain the maximum localization efficiency. We considered that the unfolded region may alleviate the steric hindrance produced by the cargo protein, by functioning as a spacer to which cytosolic translocators can bind. Based on this inference, an optimized CTP, named RC2, was constructed. Analyses showed that RC2 can more effectively target diverse proteins, including EcTSR and EcGCL, into rice chloroplasts. Collectively, our results provide further insight into the mechanism of CTP-mediated chloroplastic localization, and more importantly, RC2 can be widely applied in future chloroplastic metabolic engineering, particularly for crop plants.

Copper Tube Pitting in Santa Fe Municipal Water Caused by Microbial Induced Corrosion.

PubMed

Burleigh, Thomas D; Gierke, Casey G; Fredj, Narjes; Boston, Penelope J

2014-06-05

Many copper water lines for municipal drinking water in Santa Fe, New Mexico USA, have developed pinhole leaks. The pitting matches the description of Type I pitting of copper, which has historically been attributed to water chemistry and to contaminants on the copper tubing surface. However, more recent studies attribute copper pitting to microbial induced corrosion (MIC). In order to test for microbes, the copper tubing was fixed in hexamethyldisilazane (HMDS), then the tops of the corrosion mounds were broken open, and the interior of the corrosion pits were examined with scanning electron microscopy (SEM). The analysis found that microbes resembling actinobacteria were deep inside the pits and wedged between the crystallographic planes of the corroded copper grains. The presence of actinobacteria confirms the possibility that the cause of this pitting corrosion was MIC. This observation provides better understanding and new methods for preventing the pitting of copper tubing in municipal water.

Copper Tube Pitting in Santa Fe Municipal Water Caused by Microbial Induced Corrosion

PubMed Central

Burleigh, Thomas D.; Gierke, Casey G.; Fredj, Narjes; Boston, Penelope J.

2014-01-01

Many copper water lines for municipal drinking water in Santa Fe, New Mexico USA, have developed pinhole leaks. The pitting matches the description of Type I pitting of copper, which has historically been attributed to water chemistry and to contaminants on the copper tubing surface. However, more recent studies attribute copper pitting to microbial induced corrosion (MIC). In order to test for microbes, the copper tubing was fixed in hexamethyldisilazane (HMDS), then the tops of the corrosion mounds were broken open, and the interior of the corrosion pits were examined with scanning electron microscopy (SEM). The analysis found that microbes resembling actinobacteria were deep inside the pits and wedged between the crystallographic planes of the corroded copper grains. The presence of actinobacteria confirms the possibility that the cause of this pitting corrosion was MIC. This observation provides better understanding and new methods for preventing the pitting of copper tubing in municipal water. PMID:28788679

Pressure Autoregulation Measurement Techniques in Adult Traumatic Brain Injury, Part I: A Scoping Review of Intermittent/Semi-Intermittent Methods.

PubMed

Zeiler, Frederick A; Donnelly, Joseph; Calviello, Leanne; Menon, David K; Smielewski, Peter; Czosnyka, Marek

2017-12-01

The purpose of this study was to perform a systematic, scoping review of commonly described intermittent/semi-intermittent autoregulation measurement techniques in adult traumatic brain injury (TBI). Nine separate systematic reviews were conducted for each intermittent technique: computed tomographic perfusion (CTP)/Xenon-CT (Xe-CT), positron emission tomography (PET), magnetic resonance imaging (MRI), arteriovenous difference in oxygen (AVDO 2 ) technique, thigh cuff deflation technique (TCDT), transient hyperemic response test (THRT), orthostatic hypotension test (OHT), mean flow index (Mx), and transfer function autoregulation index (TF-ARI). MEDLINE ® , BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library (inception to December 2016), and reference lists of relevant articles were searched. A two tier filter of references was conducted. The total number of articles utilizing each of the nine searched techniques for intermittent/semi-intermittent autoregulation techniques in adult TBI were: CTP/Xe-CT (10), PET (6), MRI (0), AVDO 2 (10), ARI-based TCDT (9), THRT (6), OHT (3), Mx (17), and TF-ARI (6). The premise behind all of the intermittent techniques is manipulation of systemic blood pressure/blood volume via either chemical (such as vasopressors) or mechanical (such as thigh cuffs or carotid compression) means. Exceptionally, Mx and TF-ARI are based on spontaneous fluctuations of cerebral perfusion pressure (CPP) or mean arterial pressure (MAP). The method for assessing the cerebral circulation during these manipulations varies, with both imaging-based techniques and TCD utilized. Despite the limited literature for intermittent/semi-intermittent techniques in adult TBI (minus Mx), it is important to acknowledge the availability of such tests. They have provided fundamental insight into human autoregulatory capacity, leading to the development of continuous and more commonly applied techniques in the intensive care unit (ICU). Numerous methods of intermittent/semi-intermittent pressure autoregulation assessment in adult TBI exist, including: CTP/Xe-CT, PET, AVDO 2 technique, TCDT-based ARI, THRT, OHT, Mx, and TF-ARI. MRI-based techniques in adult TBI are yet to be described, with the main focus of MRI techniques on metabolic-based cerebrovascular reactivity (CVR) and not pressure-based autoregulation.

Technical Evaluation Motor No. 7 (TEM-7)

NASA Technical Reports Server (NTRS)

Hughes, Phil

1991-01-01

The Technical Evaluation Motor No. 7 (TEM-7) test was a full-scale, full duration static test firing of a high performance motor-configuration solid rocket motor with nozzle vectoring. The final test report documents the procedures, performance, and results of the static test firing of TEM-7. All observations, discussions, conclusions, and recommendations included in the report are complete and final except for the TEM-7 fixed housing unbond investigation. A presentation and discussion of TEM-7 performance, anomalies, and test result concurrence with the objectives outlined in CTP-0107, Rev A, Space Shuttle Technical Evaluation Motor No. 7 (TEM-7) Static Fire Test Plan are included.

Project W-314 acceptance test report HNF-4647 for HNF-4646 241-B pit leak detection ANB-WT-LDSTA-231 for project W-314

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

HAMMERS, J.S.

The purpose of the test was to verify that the AN Tank Farm B Pit Leak Detector components are functionally integrated and operate in accordance with engineering design specifications. The Acceptance Test Procedure HNF-4646,241-AN-B-Pit Leak Detection ANB-WT-LDSTA-231 was conducted between 26 June and 02 July 1999 at the 200E AN Tank Farm. The test has been completed with no open test exceptions. The test was conducted prior to final engineering ''as built'' activities being completed this had no impact on the procedure or test results. All components, identified in the procedure were found to be labeled and identified as writtenmore » in the procedure.« less

Gradual plasmon evolution and huge infrared near-field enhancement of metallic bridged nanoparticle dimers.

PubMed

Huang, Yu; Ma, Lingwei; Hou, Mengjing; Xie, Zheng; Zhang, Zhengjun

2016-01-28

By three-dimensional (3D) finite element method (FEM) plasmon mapping, gradual plasmon evolutions of both bonding dipole plasmon (BDP) and charge transfer plasmon (CTP) modes are visualized. In particular, the evolved BDP mode provides a physical insight into the rapid degeneration of electromagnetic hot spots in practical applications, while the rising CTP mode enables a huge near-field enhancement for potential plasmonic devices at infrared wavelengths.

Crystallization and preliminary X-ray analysis of CTP:phosphoethanolamine cytidylyltransferase (ECT) from Saccharomyces cerevisiae

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

Ohtsuka, Jun; Nagata, Koji; Lee, Woo Cheol

2006-10-01

CTP:phosphoethanolamine cytidylyltransferase from S. cerevisiae has been expressed, purified and crystallized. CTP:phosphoethanolamine cytidylyltransferase (ECT) is the enzyme that catalyzes the conversion of phosphoethanolamine to CDP-ethanolamine in the phosphatidylethanolamine-biosynthetic pathway (Kennedy pathway). ECT from Saccharomyces cerevisiae was crystallized by the sitting-drop vapour-diffusion method using PEG 4000 as precipitant. The crystals diffracted X-rays from a synchrotron-radiation source to 1.88 Å resolution. The space group was assigned as primitive tetragonal, P4{sub 1}2{sub 1}2 or P4{sub 3}2{sub 1}2, with unit-cell parameters a = b = 66.3, c = 150.8 Å. The crystals contain one ECT molecule in the asymmetric unit (V{sub M} = 2.2more » Å{sup 3} Da{sup −1}), with a solvent content of 43%.« less

Stochastic theory of fatigue corrosion

NASA Astrophysics Data System (ADS)

Hu, Haiyun

1999-10-01

A stochastic theory of corrosion has been constructed. The stochastic equations are described giving the transportation corrosion rate and fluctuation corrosion coefficient. In addition the pit diameter distribution function, the average pit diameter and the most probable pit diameter including other related empirical formula have been derived. In order to clarify the effect of stress range on the initiation and growth behaviour of pitting corrosion, round smooth specimen were tested under cyclic loading in 3.5% NaCl solution.

Enhanced ID Pit Sizing Using Multivariate Regression Algorithm

NASA Astrophysics Data System (ADS)

Krzywosz, Kenji

2007-03-01

EPRI is funding a program to enhance and improve the reliability of inside diameter (ID) pit sizing for balance-of plant heat exchangers, such as condensers and component cooling water heat exchangers. More traditional approaches to ID pit sizing involve the use of frequency-specific amplitude or phase angles. The enhanced multivariate regression algorithm for ID pit depth sizing incorporates three simultaneous input parameters of frequency, amplitude, and phase angle. A set of calibration data sets consisting of machined pits of various rounded and elongated shapes and depths was acquired in the frequency range of 100 kHz to 1 MHz for stainless steel tubing having nominal wall thickness of 0.028 inch. To add noise to the acquired data set, each test sample was rotated and test data acquired at 3, 6, 9, and 12 o'clock positions. The ID pit depths were estimated using a second order and fourth order regression functions by relying on normalized amplitude and phase angle information from multiple frequencies. Due to unique damage morphology associated with the microbiologically-influenced ID pits, it was necessary to modify the elongated calibration standard-based algorithms by relying on the algorithm developed solely from the destructive sectioning results. This paper presents the use of transformed multivariate regression algorithm to estimate ID pit depths and compare the results with the traditional univariate phase angle analysis. Both estimates were then compared with the destructive sectioning results.

Corrective action plan for corrective action Unit 342: Area 23 Mercury Fire Training Pit, Nevada Test Site, Nevada

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

Nacht, S.

1999-08-01

The Mercury Fire Training Pit is a former fire training area located in Area 23 of the Nevada Test Site (NTS). The Mercury Fire Training Pit was used from approximately 1965 to the early 1990s to train fire-fighting personnel at the NTS, and encompasses an area approximately 107 meters (m) (350 feet [ft]) by 137 m (450 ft). The Mercury Fire Training Pit formerly included a bermed burn pit with four small burn tanks, four large above ground storage tanks an overturned bus, a telephone pole storage area, and areas for burning sheds, pallets, and cables. Closure activities will includemore » excavation of the impacted soil in the aboveground storage tank and burn pit areas to a depth of 1.5 m (5 ft), and excavation of the impacted surface soil downgradient of the former ASTs and burnpit areas to a depth of 0.3 m (1 ft). Excavated soil will be disposed in the Area 6 Hydrocarbon Landfill at the NTS.« less

Microstructure, Pitting Corrosion Resistance and Impact Toughness of Duplex Stainless Steel Underwater Dry Hyperbaric Flux-Cored Arc Welds

PubMed Central

Hu, Yu; Shen, Xiao-Qin; Wang, Zhong-Min

2017-01-01

Duplex stainless steel multi-pass welds were made at 0.15 MPa, 0.45 MPa, and 0.75 MPa pressure, simulating underwater dry hyperbaric welding by the flux-cored arc welding (FCAW) method, with welds of normal pressure as a benchmark. The purpose of this work was to estimate the effect of ambient pressure on the microstructure, pitting corrosion resistance and impact toughness of the weld metal. The microstructure measurement revealed that the ferrite content in the weld metal made at 0.45 MPa is the lowest, followed by that of 0.75 MPa and 0.15 MPa. The analysis of potentiodynamic polarization tests at 30 °C and 50 °C demonstrated that the pitting corrosion resistance depends on the phases of the lower pitting resistance equivalent numbers (PREN), secondary austenite and ferrite. The weld metal made at 0.45 MPa had the best resistance to pitting corrosion at 30 °C and 50 °C with the highest PRENs of secondary austenite and ferrite. The weld metal made at 0.15 MPa displayed the lowest pitting corrosion resistance at 30 °C with the lowest PREN of secondary austenite, while the weld metal made at 0.75 MPa was the most seriously eroded after being tested at 50 °C for the lowest PREN of ferrite, with large cluster pits seen in ferrite at 50 °C. The impact tests displayed a typical ductile-brittle transition because of the body-centered cubic (BCC) structure of the ferrite when the test temperature was lowered. All the weld metals met the required value of 34 J at −40 °C according to the ASTM A923. The highest ferrite content corresponded to the worst impact toughness, but the highest toughness value did not correspond to the greatest austenite content. With the decreasing of the test temperature, the drop value of absorbed energy was correlated to the ferrite content. Additionally, in this work, the weld metal made at 0.45 MPa had the best combined properties of pitting resistance and impact toughness. PMID:29258262

Microstructure, Pitting Corrosion Resistance and Impact Toughness of Duplex Stainless Steel Underwater Dry Hyperbaric Flux-Cored Arc Welds.

PubMed

Hu, Yu; Shi, Yong-Hua; Shen, Xiao-Qin; Wang, Zhong-Min

2017-12-18

Duplex stainless steel multi-pass welds were made at 0.15 MPa, 0.45 MPa, and 0.75 MPa pressure, simulating underwater dry hyperbaric welding by the flux-cored arc welding (FCAW) method, with welds of normal pressure as a benchmark. The purpose of this work was to estimate the effect of ambient pressure on the microstructure, pitting corrosion resistance and impact toughness of the weld metal. The microstructure measurement revealed that the ferrite content in the weld metal made at 0.45 MPa is the lowest, followed by that of 0.75 MPa and 0.15 MPa. The analysis of potentiodynamic polarization tests at 30 °C and 50 °C demonstrated that the pitting corrosion resistance depends on the phases of the lower pitting resistance equivalent numbers (PREN), secondary austenite and ferrite. The weld metal made at 0.45 MPa had the best resistance to pitting corrosion at 30 °C and 50 °C with the highest PRENs of secondary austenite and ferrite. The weld metal made at 0.15 MPa displayed the lowest pitting corrosion resistance at 30 °C with the lowest PREN of secondary austenite, while the weld metal made at 0.75 MPa was the most seriously eroded after being tested at 50 °C for the lowest PREN of ferrite, with large cluster pits seen in ferrite at 50 °C. The impact tests displayed a typical ductile-brittle transition because of the body-centered cubic (BCC) structure of the ferrite when the test temperature was lowered. All the weld metals met the required value of 34 J at -40 °C according to the ASTM A923. The highest ferrite content corresponded to the worst impact toughness, but the highest toughness value did not correspond to the greatest austenite content. With the decreasing of the test temperature, the drop value of absorbed energy was correlated to the ferrite content. Additionally, in this work, the weld metal made at 0.45 MPa had the best combined properties of pitting resistance and impact toughness.

Dependency of EBT2 film calibration curve on postirradiation time

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

Chang, Liyun, E-mail: liyunc@isu.edu.tw; Ding, Hueisch-Jy; Ho, Sheng-Yow

2014-02-15

Purpose: The Ashland Inc. product EBT2 film model is a widely used quality assurance tool, especially for verification of 2-dimensional dose distributions. In general, the calibration film and the dose measurement film are irradiated, scanned, and calibrated at the same postirradiation time (PIT), 1-2 days after the films are irradiated. However, for a busy clinic or in some special situations, the PIT for the dose measurement film may be different from that of the calibration film. In this case, the measured dose will be incorrect. This paper proposed a film calibration method that includes the effect of PIT. Methods: Themore » dose versus film optical density was fitted to a power function with three parameters. One of these parameters was PIT dependent, while the other two were found to be almost constant with a standard deviation of the mean less than 4%. The PIT-dependent parameter was fitted to another power function of PIT. The EBT2 film model was calibrated using the PDD method with 14 different PITs ranging from 1 h to 2 months. Ten of the fourteen PITs were used for finding the fitting parameters, and the other four were used for testing the model. Results: The verification test shows that the differences between the delivered doses and the film doses calculated with this modeling were mainly within 2% for delivered doses above 60 cGy, and the total uncertainties were generally under 5%. The errors and total uncertainties of film dose calculation were independent of the PIT using the proposed calibration procedure. However, the fitting uncertainty increased with decreasing dose or PIT, but stayed below 1.3% for this study. Conclusions: The EBT2 film dose can be modeled as a function of PIT. For the ease of routine calibration, five PITs were suggested to be used. It is recommended that two PITs be located in the fast developing period (1∼6 h), one in 1 ∼ 2 days, one around a week, and one around a month.« less

Detection probability of an in-stream passive integrated transponder (PIT) tag detection system for juvenile salmonids in the Klamath River, northern California, 2011

USGS Publications Warehouse

Beeman, John W.; Hayes, Brian; Wright, Katrina

2012-01-01

A series of in-stream passive integrated transponder (PIT) detection antennas installed across the Klamath River in August 2010 were tested using tagged fish in the summer of 2011. Six pass-by antennas were constructed and anchored to the bottom of the Klamath River at a site between the Shasta and Scott Rivers. Two of the six antennas malfunctioned during the spring of 2011 and two pass-through antennas were installed near the opposite shoreline prior to system testing. The detection probability of the PIT tag detection system was evaluated using yearling coho salmon implanted with a PIT tag and a radio transmitter and then released into the Klamath River slightly downstream of Iron Gate Dam. Cormack-Jolly-Seber capture-recapture methods were used to estimate the detection probability of the PIT tag detection system based on detections of PIT tags there and detections of radio transmitters at radio-telemetry detection systems downstream. One of the 43 PIT- and radio-tagged fish released was detected by the PIT tag detection system and 23 were detected by the radio-telemetry detection systems. The estimated detection probability of the PIT tag detection system was 0.043 (standard error 0.042). Eight PIT-tagged fish from other studies also were detected. Detections at the PIT tag detection system were at the two pass-through antennas and the pass-by antenna adjacent to them. Above average river discharge likely was a factor in the low detection probability of the PIT tag detection system. High discharges dislodged two power cables leaving 12 meters of the river width unsampled for PIT detections and resulted in water depths greater than the read distance of the antennas, which allowed fish to pass over much of the system with little chance of being detected. Improvements in detection probability may be expected under river discharge conditions where water depth over the antennas is within maximum read distance of the antennas. Improvements also may be expected if additional arrays of antennas are used.

20. Interior view of fuel storage pit or vault adjacent ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

20. Interior view of fuel storage pit or vault adjacent to Test Cell 9 in Component Test Laboratory (T-27), looking west. Photograph shows upgraded instrumentation, piping, tanks, and technological modifications installed in 1997-99 to accommodate component testing requirements for the Atlas V missile. - Air Force Plant PJKS, Systems Integration Laboratory, Components Test Laboratory, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

Diverse heterocyclic scaffolds as dCTP pyrophosphatase 1 inhibitors. Part 1: Triazoles, triazolopyrimidines, triazinoindoles, quinoline hydrazones and arylpiperazines.

PubMed

Llona-Minguez, Sabin; Häggblad, Maria; Martens, Ulf; Throup, Adam; Loseva, Olga; Jemth, Ann-Sofie; Lundgren, Bo; Scobie, Martin; Helleday, Thomas

2017-08-15

A high-throughput screening campaign using a commercial compound library (ChemBridge DiverSET) revealed diverse chemotypes as inhibitors of the human dCTP pyrophosphatase 1 (dCTPase). Triazole, triazolopyrimidine, triazinoindole, quinoline hydrazone and arylpiperazine hits were clustered, confirmed by IC 50 determinations, and their preliminary structure-activity-relationships (SAR) and ligand efficiency scores are discussed in this letter. Copyright © 2017. Published by Elsevier Ltd.

Characterization of a Dopaminergic Stimulatory Factor Derived from Monoclonal Cell Lines of Striatal Origin

DTIC Science & Technology

2006-12-01

other substrates for its biosynthesis would be effective in raising MN9D dopamine content. The pyrimidine, cytidine triphosphate (CTP) reacts with...phosphatidylethanolamine or phosphatidylcholine. MN9D cells were treated for 48 hrs with 2 mM CTP, cytidine diphosphate (CDP) or cytidine monophosphate (CMP), in the...presence or absence of 25 µM ethanolamine or 25 µM phosphoethanolamine. Cytidine alone did not alter the dopaminergic stimulatory effect of

Development of a realistic, dynamic digital brain phantom for CT perfusion validation

NASA Astrophysics Data System (ADS)

Divel, Sarah E.; Segars, W. Paul; Christensen, Soren; Wintermark, Max; Lansberg, Maarten G.; Pelc, Norbert J.

2016-03-01

Physicians rely on CT Perfusion (CTP) images and quantitative image data, including cerebral blood flow, cerebral blood volume, and bolus arrival delay, to diagnose and treat stroke patients. However, the quantification of these metrics may vary depending on the computational method used. Therefore, we have developed a dynamic and realistic digital brain phantom upon which CTP scans can be simulated based on a set of ground truth scenarios. Building upon the previously developed 4D extended cardiac-torso (XCAT) phantom containing a highly detailed brain model, this work consisted of expanding the intricate vasculature by semi-automatically segmenting existing MRA data and fitting nonuniform rational B-spline surfaces to the new vessels. Using time attenuation curves input by the user as reference, the contrast enhancement in the vessels changes dynamically. At each time point, the iodine concentration in the arteries and veins is calculated from the curves and the material composition of the blood changes to reflect the expected values. CatSim, a CT system simulator, generates simulated data sets of this dynamic digital phantom which can be further analyzed to validate CTP studies and post-processing methods. The development of this dynamic and realistic digital phantom provides a valuable resource with which current uncertainties and controversies surrounding the quantitative computations generated from CTP data can be examined and resolved.

Quantification of the Effect of Shuttling on Computed Tomography Perfusion Parameters by Investigation of Aortic Inputs on Different Table Positions From Shuttle-Mode Scans of Lung and Liver Tumors.

PubMed

Ghosh, Payel; Chandler, Adam G; Hobbs, Brian P; Sun, Jia; Rong, John; Hong, David; Subbiah, Vivek; Janku, Filip; Naing, Aung; Hwu, Wen-Jen; Ng, Chaan S

The aim of this study was to quantify the effect of shuttling on computed tomography perfusion (CTp) parameters derived from shuttle-mode body CT images using aortic inputs from different table positions. Axial shuttle-mode CT scans were acquired from 6 patients (10 phases, 2 nonoverlapping table positions 1.4 seconds apart) after contrast agent administration. Artifacts resulting from the shuttling motion were corrected with nonrigid registration before computing CTp maps from 4 aortic levels chosen from the most superior and inferior slices of each table position scan. The effect of shuttling on CTp parameters was estimated by mean differences in mappings obtained from aortic inputs in different table positions. Shuttling effect was also quantified using 95% limits of agreement of CTp parameter differences within-table and between-table aortic positions from the interaortic mean CTp values. Blood flow, permeability surface, and hepatic arterial fraction differences were insignificant (P > 0.05) for both within-table and between-table comparisons. The 95% limits of agreement for within-table blood volume (BV) value deviations obtained from lung tumor regions were less than 4.7% (P = 0.18) compared with less than 12.2% (P = 0.003) for between-table BV value deviations. The 95% limits of agreement of within-table deviations for liver tumor regions were less than 1.9% (P = 0.55) for BV and less than 3.2% (P = 0.23) for mean transit time, whereas between-table BV and mean transit time deviations were less than 11.7% (P < 0.01) and less than 14.6% (P < 0.01), respectively. Values for normal liver tissue regions were concordant. Computed tomography perfusion parameters acquired from aortic levels within-table positions generally yielded higher agreement than mappings obtained from aortic levels between-table positions indicating differences due to shuttling effect.

Biochemical Evaluation of the Inhibition Properties of Favipiravir and 2′-C-Methyl-Cytidine Triphosphates against Human and Mouse Norovirus RNA Polymerases

PubMed Central

Tucker, Kathryn; Lin, Xiaoyan; Kao, C. Cheng; Shaw, Ken; Tan, Hua; Symons, Julian; Behera, Ishani; Rajwanshi, Vivek K.; Dyatkina, Natalia; Wang, Guangyi; Beigelman, Leo

2015-01-01

Norovirus (NoV) is a positive-sense single-stranded RNA virus that causes acute gastroenteritis and is responsible for 200,000 deaths per year worldwide. No effective vaccine or treatment is available. Recent studies have shown that the nucleoside analogs favipiravir (T-705) and 2′-C-methyl-cytidine (2CM-C) inhibit NoV replication in vitro and in animal models, but their precise mechanism of action is unknown. We evaluated the molecular interactions between nucleoside triphosphates and NoV RNA-dependent RNA polymerase (NoVpol), the enzyme responsible for replication and transcription of NoV genomic RNA. We found that T-705 ribonucleoside triphosphate (RTP) and 2CM-C triphosphate (2CM-CTP) equally inhibited human and mouse NoVpol activities at concentrations resulting in 50% of maximum inhibition (IC50s) in the low micromolar range. 2CM-CTP inhibited the viral polymerases by competing directly with natural CTP during primer elongation, whereas T-705 RTP competed mostly with ATP and GTP at the initiation and elongation steps. Incorporation of 2CM-CTP into viral RNA blocked subsequent RNA synthesis, whereas T-705 RTP did not cause immediate chain termination of NoVpol. 2CM-CTP and T-705 RTP displayed low levels of enzyme selectivity, as they were both recognized as substrates by human mitochondrial RNA polymerase. The level of discrimination by the human enzyme was increased with a novel analog of T-705 RTP containing a 2′-C-methyl substitution. Collectively, our data suggest that 2CM-C inhibits replication of NoV by acting as a classic chain terminator, while T-705 may inhibit the virus by multiple mechanisms of action. Understanding the precise mechanism of action of anti-NoV compounds could provide a rational basis for optimizing their inhibition potencies and selectivities. PMID:26392512

Structural basis for proficient incorporation of dTTP opposite O6-methylguanine by human DNA polymerase iota.

PubMed

Pence, Matthew G; Choi, Jeong-Yun; Egli, Martin; Guengerich, F Peter

2010-12-24

O(6)-methylguanine (O(6)-methylG) is highly mutagenic and is commonly found in DNA exposed to methylating agents, even physiological ones (e.g. S-adenosylmethionine). The efficiency of a truncated, catalytic DNA polymerase ι core enzyme was determined for nucleoside triphosphate incorporation opposite O(6)-methylG, using steady-state kinetic analyses. The results presented here corroborate previous work from this laboratory using full-length pol ι, which showed that dTTP incorporation occurs with high efficiency opposite O(6)-methylG. Misincorporation of dTTP opposite O(6)-methylG occurred with ∼6-fold higher efficiency than incorporation of dCTP. Crystal structures of the truncated form of pol ι with O(6)-methylG as the template base and incoming dCTP or dTTP were solved and showed that O(6)-methylG is rotated into the syn conformation in the pol ι active site and that dTTP misincorporation by pol ι is the result of Hoogsteen base pairing with the adduct. Both dCTP and dTTP base paired with the Hoogsteen edge of O(6)-methylG. A single, short hydrogen bond formed between the N3 atom of dTTP and the N7 atom of O(6)-methylG. Protonation of the N3 atom of dCTP and bifurcation of the N3 hydrogen between the N7 and O(6) atoms of O(6)-methylG allow base pairing of the lesion with dCTP. We conclude that differences in the Hoogsteen hydrogen bonding between nucleotides is the main factor in the preferential selectivity of dTTP opposite O(6)-methylG by human pol ι, in contrast to the mispairing modes observed previously for O(6)-methylG in the structures of the model DNA polymerases Sulfolobus solfataricus Dpo4 and Bacillus stearothermophilus DNA polymerase I.

Stability of radiomic features in CT perfusion maps

NASA Astrophysics Data System (ADS)

Bogowicz, M.; Riesterer, O.; Bundschuh, R. A.; Veit-Haibach, P.; Hüllner, M.; Studer, G.; Stieb, S.; Glatz, S.; Pruschy, M.; Guckenberger, M.; Tanadini-Lang, S.

2016-12-01

This study aimed to identify a set of stable radiomic parameters in CT perfusion (CTP) maps with respect to CTP calculation factors and image discretization, as an input for future prognostic models for local tumor response to chemo-radiotherapy. Pre-treatment CTP images of eleven patients with oropharyngeal carcinoma and eleven patients with non-small cell lung cancer (NSCLC) were analyzed. 315 radiomic parameters were studied per perfusion map (blood volume, blood flow and mean transit time). Radiomics robustness was investigated regarding the potentially standardizable (image discretization method, Hounsfield unit (HU) threshold, voxel size and temporal resolution) and non-standardizable (artery contouring and noise threshold) perfusion calculation factors using the intraclass correlation (ICC). To gain added value for our model radiomic parameters correlated with tumor volume, a well-known predictive factor for local tumor response to chemo-radiotherapy, were excluded from the analysis. The remaining stable radiomic parameters were grouped according to inter-parameter Spearman correlations and for each group the parameter with the highest ICC was included in the final set. The acceptance level was 0.9 and 0.7 for the ICC and correlation, respectively. The image discretization method using fixed number of bins or fixed intervals gave a similar number of stable radiomic parameters (around 40%). The potentially standardizable factors introduced more variability into radiomic parameters than the non-standardizable ones with 56-98% and 43-58% instability rates, respectively. The highest variability was observed for voxel size (instability rate  >97% for both patient cohorts). Without standardization of CTP calculation factors none of the studied radiomic parameters were stable. After standardization with respect to non-standardizable factors ten radiomic parameters were stable for both patient cohorts after correction for inter-parameter correlations. Voxel size, image discretization, HU threshold and temporal resolution have to be standardized to build a reliable predictive model based on CTP radiomics analysis.

Hypotonic activation of short ClC3 isoform is modulated by direct interaction between its cytosolic C-terminal tail and subcortical actin filaments.

PubMed

McCloskey, Diana T; Doherty, Lynda; Dai, Yan-Ping; Miller, Lisa; Hume, Joseph R; Yamboliev, Ilia A

2007-06-08

Short ClC3 isoform (sClC3) functions as a volume-sensitive outwardly rectifying anion channel (VSOAC) in some cell types. In previous studies, we have shown that the hypotonic activation of sClC3 is linked to cell swelling-mediated remodeling of the actin cytoskeleton. In the present study, we have tested the hypothesis that the cytosolic tails of sClC3 bind to actin directly and that binding modulates the hypotonic activation of the channel. Co-sedimentation assays in vitro demonstrated a strong binding between the glutathione S-transferase-fused cytosolic C terminus of sClC3 (GST-sClC3-CT) to filamentous actin (F-actin) but not to globular monomeric actin (G-actin). The GST-fused N terminus (GST-sClC3-NT) exhibited low binding affinity to both G- and F-actin. Co-sedimentation experiments with progressively truncated GST-sClC3-CT indicated that the F-actin binding region is located between amino acids 690 and 760 of sClC3. Two synthetic peptides mapping basic clusters of the cytosolic sClC3-CT (CTP2, isoleucine 716 to leucine 734; and CTP3, proline 688 to proline 709) prevented binding of GST-sClC3-CT to F-actin in vitro. Dialysis into NIH/3T3 cells of these two peptides (but not of synthetic peptide CTP1 (isoleucine 737 to glutamine 748)) reduced the maximal current density by 60 and 38%, respectively. Based on these results, we have concluded that, by direct interaction with subcortical actin filaments, sClC3 contributes to the hypotonic stress-induced VSOACs in NIH/3T3 cells.

Predictors of hospital re-admissions among Hispanics with hepatitis C-related cirrhosis.

PubMed

Atla, Pradeep R; Sheikh, Muhammad Y; Gill, Firdose; Kundu, Rabindra; Choudhury, Jayanta

2016-01-01

Hospital re-admissions in decompensated cirrhosis are associated with worse patient outcomes. Hispanics have a disproportionately high prevalence of hepatitis C virus (HCV)-related morbidity and mortality. The goal of this study was to evaluate the factors affecting re-admission rates among Hispanics with HCV-related cirrhosis. A total of 292 consecutive HCV-related cirrhosis admissions (Hispanics 189, non-Hispanics 103) from January 2009 to December 2012 were retrospectively reviewed; 132 were cirrhosis-related re-admissions. The statistical analysis was performed using STATA version 11.1. Chi-square/Fisher's exact and Student's t-tests were used to compare categorical and continuous variables, respectively. Multivariate logistic regression analysis was performed to identify predictors for hospital readmissions. Among the 132 cirrhosis-related readmissions, 71% were Hispanics while 29% were non-Hispanics (P=0.035). Hepatic encephalopathy (HE) and esophageal variceal hemorrhage were the most frequent causes of the first and subsequent readmissions. Hispanics with readmissions had a higher Child-Turcotte-Pugh (CTP) class (B and C) and higher model for end-stage liver disease (MELD) scores (≥15), as well as a higher incidence of alcohol use, HE, spontaneous bacterial peritonitis, hepatocellular carcinoma, and varices (P<0.05). The majority of the study patients (81%) had MELD scores <15. Multivariate regression analysis identified alcohol use (OR 2.63; 95%CI 1.1-6.4), HE (OR 5.5; 95%CI 2-15.3), varices (OR 3.2; 95%CI 1.3-8.2), and CTP class (OR 3.3; 95%CI 1.4-8.1) as predictors for readmissions among Hispanics. CTP classes B and C, among other factors, were the major predictors for hospital readmissions in Hispanics with HCV-related cirrhosis. The majority of these readmissions were due to HE and variceal hemorrhage.

The Effect of Surface Patterning on Corrosion Resistance of Biomedical Devices

NASA Astrophysics Data System (ADS)

Guo, Mengnan; Toloei, Alisina; Rotermund, Harm H.

2016-10-01

In this study, two styles of surface topographies have been created on stainless steel wires to test their corrosion resistance as simulated implanted biomedical devices. Grade 316 LVM stainless steel wire was initially polished to G1500 surface finish before treatment to produce the two different topographies: 1. Unidirectional roughness was created using SiC papers and 2. Various patterns were created with specific hole diameter and inter-hole spacing using focused ion beam (FIB). In order to simulate the environment of implanted biomedical devices, a three-electrode electrochemical cell with 0.9% (by mass) NaCl solution has been used to test the corrosion resistance of the samples by potentiodynamic polarization test method. SEM and EDS analyzed the appearance and chemical composition of different elements including oxygen on the surface. The potential of stable pitting, time related to the initiation of the stable pitting, and the highest corrosion current associated with stable pitting have been compared for samples with the two styles of topography. It was found that surfaces with patterns have a relatively higher pitting potential and it takes longer time to initiate stable pitting than the surface without any patterns.

Influence of non-smooth surface on tribological properties of glass fiber-epoxy resin composite sliding against stainless steel under natural seawater lubrication

NASA Astrophysics Data System (ADS)

Wu, Shaofeng; Gao, Dianrong; Liang, Yingna; Chen, Bo

2015-11-01

With the development of bionics, the bionic non-smooth surfaces are introduced to the field of tribology. Although non-smooth surface has been studied widely, the studies of non-smooth surface under the natural seawater lubrication are still very fewer, especially experimental research. The influences of smooth and non-smooth surface on the frictional properties of the glass fiber-epoxy resin composite (GF/EPR) coupled with stainless steel 316L are investigated under natural seawater lubrication in this paper. The tested non-smooth surfaces include the surfaces with semi-spherical pits, the conical pits, the cone-cylinder combined pits, the cylindrical pits and through holes. The friction and wear tests are performed using a ring-on-disc test rig under 60 N load and 1000 r/min rotational speed. The tests results show that GF/EPR with bionic non-smooth surface has quite lower friction coefficient and better wear resistance than GF/EPR with smooth surface without pits. The average friction coefficient of GF/EPR with semi-spherical pits is 0.088, which shows the largest reduction is approximately 63.18% of GF/EPR with smooth surface. In addition, the wear debris on the worn surfaces of GF/EPR are observed by a confocal scanning laser microscope. It is shown that the primary wear mechanism is the abrasive wear. The research results provide some design parameters for non-smooth surface, and the experiment results can serve as a beneficial supplement to non-smooth surface study.

Pitting Behavior of L415 Pipeline Steel in Simulated Leaching Liquid Environment

NASA Astrophysics Data System (ADS)

Wan, H. X.; Yang, X. J.; Liu, Z. Y.; Song, D. D.; Du, C. W.; Li, X. G.

2017-02-01

The corrosion behavior and laws of the west-east gas pressure pipeline of L415 steel were studied in simulated leaching liquid. The failure of the L415 steel during the pressure testing process was investigated using electrochemical polarization, electrochemical impedance spectroscopy, and immersion test. The corrosion rate of the L415 steel increased with ion concentration in the leaching liquid. This rate reached about 0.8 mm a-1 and belonged to the severe corrosion grade. Pitting corrosion was observed in various simulated solutions with different aggressive species concentrations. The original ion concentration in the leaching liquid (1×) is the key factor influencing pitting initiation and development. Pitting showed easy nucleation, and its growth rate was relatively slow, in the basic simulating solution of the leach liquid (i.e., the ion content is compactable to the real condition in the rust on the inner steel pipe surface). Pitting was also highly sensitive and easily grew in the solution with doubled ion concentration in the basic simulating solution (2×). A uniform corrosion, instead of pitting, mainly occurred when the ion concentration was up to 10× of the basic solution.

Dose-Dependent Dual Role of PIT-1 (POU1F1) in Somatolactotroph Cell Proliferation and Apoptosis

PubMed Central

Jullien, Nicolas; Roche, Catherine; Brue, Thierry; Figarella-Branger, Dominique; Graillon, Thomas; Barlier, Anne; Herman, Jean-Paul

2015-01-01

To test the role of wtPIT-1 (PITWT) or PIT-1 (R271W) (PIT271) in somatolactotroph cells, we established, using inducible lentiviral vectors, sublines of GH4C1 somatotroph cells that allow the blockade of the expression of endogenous PIT-1 and/or the expression of PITWT or PIT271, a dominant negative mutant of PIT-1 responsible for Combined Pituitary Hormone Deficiency in patients. Blocking expression of endogenous PIT-1 induced a marked decrease of cell proliferation. Overexpressing PITWT twofold led also to a dose-dependent decrease of cell proliferation that was accompanied by cell death. Expression of PIT271 induced a strong dose-dependent decrease of cell proliferation accompanied by a very pronounced cell death. These actions of PIT271 are independent of its interaction/competition with endogenous PIT-1, as they were unchanged when expression of endogenous PIT-1 was blocked. All these actions are specific for somatolactotroph cells, and could not be observed in heterologous cells. Cell death induced by PITWT or by PIT271 was accompanied by DNA fragmentation, but was not inhibited by inhibitors of caspases, autophagy or necrosis, suggesting that this cell death is a caspase-independent apoptosis. Altogether, our results indicate that under normal conditions PIT-1 is important for the maintenance of cell proliferation, while when expressed at supra-normal levels it induces cell death. Through this dual action, PIT-1 may play a role in the expansion/regression cycles of pituitary lactotroph population during and after lactation. Our results also demonstrate that the so-called “dominant-negative” action of PIT271 is independent of its competition with PIT-1 or a blockade of the actions of the latter, and are actions specific to this mutant variant of PIT-1. PMID:25822178

Integrating Oil Debris and Vibration Gear Damage Detection Technologies Using Fuzzy Logic

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.; Afjeh, Abdollah A.

2002-01-01

A diagnostic tool for detecting damage to spur gears was developed. Two different measurement technologies, wear debris analysis and vibration, were integrated into a health monitoring system for detecting surface fatigue pitting damage on gears. This integrated system showed improved detection and decision-making capabilities as compared to using individual measurement technologies. This diagnostic tool was developed and evaluated experimentally by collecting vibration and oil debris data from fatigue tests performed in the NASA Glenn Spur Gear Fatigue Test Rig. Experimental data were collected during experiments performed in this test rig with and without pitting. Results show combining the two measurement technologies improves the detection of pitting damage on spur gears.

Pit formation observed in a multilayer dielectric coating as a result of simulated space environmental exposure

NASA Astrophysics Data System (ADS)

Fuqua, Peter D.; Presser, Nathan; Barrie, James D.; Meshishnek, Michael J.; Coleman, Dianne J.

2002-06-01

Certain spaceborne telescope designs require that dielectric-coated lenses be exposed to the energetic electrons and protons associated with the space environment. Test coupons that were exposed to a simulated space environment showed extensive pitting as a result of dielectric breakdown. A typical pit was 50-100 mum at the surface and extended to the substrate material, in which a 10-mum-diameter melt region was found. Pitting was not observed on similar samples that had also been overcoated with a transparent conductive thin film. Measurement of the bidirectional reflectance distribution transfer function showed that pitting caused a fivefold to tenfold increase in the scattering of visible light.

Technical Evaluation Motor No. 7 (TEM-07)

NASA Technical Reports Server (NTRS)

Hugh, Phil

1991-01-01

Technical Evaluation Motor Number 7 (TEM-7) was a full scale, full-duration static test firing of a high performance motor (HPM) configuration solid rocket motor (SRM) with nozzle vectoring. The static test fire occurred on 11 December 1990 at the Thiokol Corporation Static Test Bay T-97. Documented here are the procedures, performance, and results available through 22 January 1991. Critical post test hardware activities and assessment of the test data are not complete. A completed test report will be submitted 60 days after the test date. Included here is a presentation and discussion of the TEM-7 performance, anomalies, and test result concurrence with the objectives outlined in CTP-0107 Revision A, Space Shuttle Technical Evaluation Motor number 7 (TEM-07) Static Fire Test Plan.

Distributed fiber optic strain sensing to detect artificial pitting corrosion in stirrups

NASA Astrophysics Data System (ADS)

Zhang, Jiachen; Kancharla, Vinutha; Hoult, Neil A.

2017-04-01

Pitting corrosion is difficult to identify through visual inspection and can lead to sudden structural failures. As such, an experimental study was undertaken to investigate whether distributed fiber optic strain sensors are capable of detecting the locations and strain changes associated with stirrup corrosion in reinforced concrete beams. In comparison to conventional strain gauges, this type of sensor can measure the strain response along the entire length of the fiber optic cable. Two specimens were tested: a control and a deteriorated beam. The deteriorated beam was artificially corroded by reducing the cross sectional area of the closed stirrups by 50% on both sides of the stirrup at the mid-height. This level of area reduction represents severe pitting corrosion. The beams were instrumented with nylon coated fiber optic sensors to measure the distributed strains, and then tested to failure under three point bending. The load deflection behavior of the two specimens was compared to assess the impact of the artificial pitting corrosion on the capacity. Digital Image Correlation was used to locate the extent and trajectory of the crack paths. It was found that the pitting corrosion had no impact on capacity or stiffness. Also, in this investigation the fiber optic sensing system failed to detect the location and strain changes due to pitting corrosion since the shear cracks did not intersect with the pitting location.

Assessment of tumor vascularization with functional computed tomography perfusion imaging in patients with cirrhotic liver disease.

PubMed

Li, Jin-Ping; Zhao, De-Li; Jiang, Hui-Jie; Huang, Ya-Hua; Li, Da-Qing; Wan, Yong; Liu, Xin-Ding; Wang, Jin-E

2011-02-01

Hepatocellular carcinoma (HCC) is a common malignant tumor in China, and early diagnosis is critical for patient outcome. In patients with HCC, it is mostly based on liver cirrhosis, developing from benign regenerative nodules and dysplastic nodules to HCC lesions, and a better understanding of its vascular supply and the hemodynamic changes may lead to early tumor detection. Angiogenesis is essential for the growth of primary and metastatic tumors due to changes in vascular perfusion, blood volume and permeability. These hemodynamic and physiological properties can be measured serially using functional computed tomography perfusion (CTP) imaging and can be used to assess the growth of HCC. This study aimed to clarify the physiological characteristics of tumor angiogenesis in cirrhotic liver disease by this fast imaging method. CTP was performed in 30 volunteers without liver disease (control subjects) and 49 patients with liver disease (experimental subjects: 27 with HCC and 22 with cirrhosis). All subjects were also evaluated by physical examination, laboratory screening and Doppler ultrasonography of the liver. The diagnosis of HCC was made according to the EASL criteria. All patients underwent contrast-enhanced ultrasonography, pre- and post-contrast triple-phase CT and CTP study. A mathematical deconvolution model was applied to provide hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT), permeability of capillary vessel surface (PS), hepatic arterial index (HAI), hepatic arterial perfusion (HAP) and hepatic portal perfusion (HPP) data. The Mann-Whitney U test was used to determine differences in perfusion parameters between the background cirrhotic liver parenchyma and HCC and between the cirrhotic liver parenchyma with HCC and that without HCC. In normal liver, the HAP/HVP ratio was about 1/4. HCC had significantly higher HAP and HAI and lower HPP than background liver parenchyma adjacent to the HCC. The value of HBF at the tumor rim was significantly higher than that in the controls. HBF, HBV, HAI, HAP and HPP, but not MTT and PS, were significantly higher in the cirrhotic liver parenchyma involved with HCC than those of the controls. Perfusion parameters were not significantly different between the controls and the cirrhotic liver parenchyma not involved with HCC. CTP can clearly distinguish tumor from cirrhotic liver parenchyma and controls and can provide quantitative information about tumor-related angiogenesis, which can be used to assess tumor vascularization in cirrhotic liver disease.

How the CCA-Adding Enzyme Selects Adenine over Cytosine at Position 76 of tRNA

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

B Pan; Y Xiong; T Steitz

2011-12-31

CCA-adding enzymes [ATP(CTP):tRNA nucleotidyltransferases] add CCA onto the 3' end of transfer RNA (tRNA) precursors without using a nucleic acid template. Although the mechanism by which cytosine (C) is selected at position 75 of tRNA has been established, the mechanism by which adenine (A) is selected at position 76 remains elusive. Here, we report five cocrystal structures of the enzyme complexed with both a tRNA mimic and nucleoside triphosphates under catalytically active conditions. These structures suggest that adenosine 5'-monophosphate is incorporated onto the A76 position of the tRNA via a carboxylate-assisted, one-metal-ion mechanism with aspartate 110 functioning as a generalmore » base. The discrimination against incorporation of cytidine 5'-triphosphate (CTP) at position 76 arises from improper placement of the {alpha} phosphate of the incoming CTP, which results from the interaction of C with arginine 224 and prevents the nucleophilic attack by the 3' hydroxyl group of cytidine75.« less

Chiral Tricritical Point: A New Universality Class in Dirac Systems

NASA Astrophysics Data System (ADS)

Yin, Shuai; Jian, Shao-Kai; Yao, Hong

2018-05-01

Tricriticality, as a sister of criticality, is a fundamental and absorbing issue in condensed-matter physics. It has been verified that the bosonic Wilson-Fisher universality class can be changed by gapless fermionic modes at criticality. However, the counterpart phenomena at tricriticality have rarely been explored. In this Letter, we study a model in which a tricritical Ising model is coupled to massless Dirac fermions. We find that the massless Dirac fermions result in the emergence of a new tricritical point, which we refer to as the chiral tricritical point (CTP), at the phase boundary between the Dirac semimetal and the charge-density wave insulator. From functional renormalization group analysis of the effective action, we obtain the critical behaviors of the CTP, which are qualitatively distinct from both the tricritical Ising universality and the chiral Ising universality. We further extend the calculations of the chiral tricritical behaviors of Ising spins to the case of Heisenberg spins. The experimental relevance of the CTP in two-dimensional Dirac semimetals is also discussed.

Study on the Accident-causing of Foundation Pit Engineering

NASA Astrophysics Data System (ADS)

Shuicheng, Tian; Xinyue, Zhang; Pengfei, Yang; Longgang, Chen

2018-05-01

With the development of high-rise buildings and underground space, a large number of foundation pit projects have occurred. Frequent accidents of it cause great losses to the society, how to reduce the frequency of pit accidents has become one of the most urgent problems to be solved. Therefore, analysing the influencing factors of foundation pit engineering accidents and studying the causes of foundation pit accidents, which of great significance for improving the safety management level of foundation pit engineering and reducing the incidence of foundation pit accidents. Firstly, based on literature review and questionnaires, this paper selected construction management, survey, design, construction, supervision and monitoring as research factors, we used the AHP method and the Dematel method to analyze the weights of various influencing factors to screen indicators to determine the ultimate system of accidents caused by foundation pit accidents; Secondly, SPSS 21.0 software was used to test the reliability and validity of the recovered questionnaire data. AMOS 7.0 software was used to fit, evaluate, and explain the set model; Finally, this paper analysed the influencing factors of foundation pit engineering accidents, corresponding management countermeasures and suggestions were put forward.

Development of an aversive Pavlovian-to-instrumental transfer task in rat

PubMed Central

Campese, Vincent; McCue, Margaret; Lázaro-Muñoz, Gabriel; LeDoux, Joseph E.; Cain, Christopher K.

2013-01-01

Pavlovian-to-instrumental transfer (PIT) is an effect whereby a classically conditioned stimulus (CS) enhances ongoing instrumental responding. PIT has been extensively studied with appetitive conditioning but barely at all with aversive conditioning. Although it's been argued that conditioned suppression is a form of aversive PIT, this effect is fundamentally different from appetitive PIT because the CS suppresses, instead of facilitates, responding. Five experiments investigated the importance of a variety of factors on aversive PIT in a rodent Sidman avoidance paradigm in which ongoing shuttling behavior (unsignaled active avoidance or USAA) was facilitated by an aversive CS. Experiment 1 demonstrated a basic PIT effect. Experiment 2 found that a moderate amount of USAA extinction produces the strongest PIT with shuttling rates best at around 2 responses per minute prior to the CS. Experiment 3 tested a protocol in which the USAA behavior was required to reach the 2-response per minute mark in order to trigger the CS presentation and found that this produced robust and reliable PIT. Experiment 4 found that the Pavlovian conditioning US intensity was not a major determinant of PIT strength. Experiment 5 demonstrated that if the CS and US were not explicitly paired during Pavlovian conditioning, PIT did not occur, showing that CS-US learning is required. Together, these studies demonstrate a robust, reliable and stable aversive PIT effect that is amenable to analysis of neural circuitry. PMID:24324417

12. "TEST STAND; STRUCTURAL; DEFLECTOR PIT DETAILS, SHEET NO. 1." ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

12. "TEST STAND; STRUCTURAL; DEFLECTOR PIT DETAILS, SHEET NO. 1." Specifications No. ENG-04-353-55-72; Drawing No. 60-09-12; sheet 41 of 148; file no. 1320/92, Rev. A. Stamped: RECORD DRAWING - AS CONSTRUCTED. Below stamp: Contract no. 4338, no change. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Test Stand 1-A Terminal Room, Test Area 1-120, north end of Jupiter Boulevard, Boron, Kern County, CA

Structures of Bordered Pits Potentially Contributing to Isolation of a Refilled Vessel from Negative Xylem Pressure in Stems of Morus australis Poir.: Testing of the Pit Membrane Osmosis and Pit Valve Hypotheses.

PubMed

Ooeda, Hiroki; Terashima, Ichiro; Taneda, Haruhiko

2017-02-01

Two hypotheses have been proposed to explain the mechanism preventing the refilling vessel water from being drained to the neighboring functional vessels under negative pressure. The pit membrane osmosis hypothesis proposes that the xylem parenchyma cells release polysaccharides that are impermeable to the intervessel pit membranes into the refilling vessel; this osmotically counteracts the negative pressure, thereby allowing the vessel to refill. The pit valve hypothesis proposes that gas trapped within intervessel bordered pits isolates the refilling vessel water from the surrounding functional vessels. Here, using the single-vessel method, we assessed these hypotheses in shoots of mulberry (Morus australis Poir.). First, we confirmed the occurrence of xylem refilling under negative pressure in the potted mulberry saplings. To examine the pit membrane osmosis hypothesis, we estimated the semi-permeability of pit membranes for molecules of various sizes and found that the pit membranes were not semi-permeable to polyethylene glycol of molecular mass <20,000. For the pit valve hypothesis, we formed pit valves in the intervessel pits in the short stem segments and measured the maximum liquid pressure up to which gases in bordered pits were retained. The threshold pressure ranged from 0.025 to 0.10 MPa. These values matched the theoretical value calculated from the geometry of the pit chamber (0.0692-0.101 MPa). Our results suggest that gas in the pits is retained by surface tension, even under substantial positive pressure to resolve gases in the refilling vessel, whereas the molecule size required for the pit membrane osmosis mechanism in mulberry would be unrealistically large. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Effects of heat input on the pitting resistance of Inconel 625 welds by overlay welding

NASA Astrophysics Data System (ADS)

Kim, Jun Seok; Park, Young IL; Lee, Hae Woo

2015-03-01

The objective of this study was to establish the relationship between the dilution ratio of the weld zone and pitting resistance depending on the heat input to welding of the Inconel alloy. Each specimen was produced by electroslag welding using Inconel 625 as the filler metal. In the weld zone of each specimen, dendrite grains were observed near the fusion line and equiaxed grains were observed on the surface. It was also observed that a melted zone with a high Fe content was formed around the fusion line, which became wider as the welding heat input increased. In order to evaluate the pitting resistance, potentiodynamic polarization tests and CPT tests were conducted. The results of these tests confirmed that there is no difference between the pitting resistances of each specimen, as the structures of the surfaces were identical despite the effect of the differences in the welding heat input for each specimen and the minor dilution effect on the surface.

Pit Latrine Fecal Sludge Resistance Using a Dynamic Cone Penetrometer in Low Income Areas in Mzuzu City, Malawi

PubMed Central

Chirwa, Charles F. C.; Hall, Ralph P.; Krometis, Leigh-Anne H.; Vance, Eric A.; Edwards, Adam; Guan, Ting; Holm, Rochelle H.

2017-01-01

Pit latrines can provide improved household sanitation, but without effective and inexpensive emptying options, they are often abandoned once full and may pose a public health threat. Emptying techniques can be difficult, as the sludge contents of each pit latrine are different. The design of effective emptying techniques (e.g., pumps) is limited by a lack of data characterizing typical in situ latrine sludge resistance. This investigation aimed to better understand the community education and technical engineering needs necessary to improve pit latrine management. In low income areas within Mzuzu city, Malawi, 300 pit latrines from three distinct areas were assessed using a dynamic cone penetrometer to quantify fecal sludge strength, and household members were surveyed to determine their knowledge of desludging procedures and practices likely to impact fecal sludge characteristics. The results demonstrate that there is a significant difference in sludge strength between lined and unlined pits within a defined area, though sludge hardened with depth, regardless of the pit type or region. There was only limited association between cone penetration depth and household survey data. To promote the adoption of pit emptying, it is recommended that households be provided with information that supports pit emptying, such as latrine construction designs, local pit emptying options, and cost. This study indicates that the use of a penetrometer test in the field prior to pit latrine emptying may facilitate the selection of appropriate pit emptying technology. PMID:28165378

Effects of chloride ion concentration and pH values on the corrosion behavior of Cr12Ni3Co12Mo4W ultra-high-strength martensitic stainless steel

NASA Astrophysics Data System (ADS)

Li, Hui-yan; Dong, Chao-fang; Xiao, Kui; Li, Xiao-gang; Zhong, Ping

2016-11-01

The effects of Cl- ion concentration and pH values on the corrosion behavior of Cr12Ni3Co12Mo4W ultra-high-strength martensitic stainless steel (UHSMSS) were investigated by a series of electrochemical tests combined with observations by stereology microscopy and scanning electron microscopy. A critical Cl- ion concentration was found to exist (approximately 0.1wt%), above which pitting occurred. The pitting potential decreased with increasing Cl- ion concentration. A UHSMSS specimen tempered at 600°C exhibited a better pitting corrosion resistance than the one tempered at 400°C. The corrosion current density and passive current density of the UHSMSS tempered at 600°C decreased with increasing pH values of the corrosion solution. The pits developed a shallower dish geometry with increasing polarization potential. A lacy cover on the pits of the UHSMSS tempered at 400°C accelerated pitting, whereas corrosion products deposited in the pits of the UHSMSS tempered at 600°C hindered pitting.

Bordered pit structure and function determine spatial patterns of air-seeding thresholds in xylem of Douglas-fir (Pseudotsuga menziesii; Pinaceae) trees.

Treesearch

J.C. Domec; B. Lachenbruch; F.C. Meinzer

2006-01-01

The air-seeding hypothesis predicts that xylem embolism resistance is linked directly to bordered pit functioning. We tested this prediction in trunks, roots, and branches at different vertical and radial locations in young and old trees of Pseudotsuga menziesii. Dimensions of bordered pits were measured from light and scanning electron micrographs...

Geographic and demographic variabilities of quantitative parameters in stress myocardial computed tomography perfusion.

PubMed

Park, Jinoh; Kim, Hyun-Sook; Hwang, Hye Jeon; Yang, Dong Hyun; Koo, Hyun Jung; Kang, Joon-Won; Kim, Young-Hak

2017-09-01

To evaluate the geographic and demographic variabilities of the quantitative parameters of computed tomography perfusion (CTP) of the left ventricular (LV) myocardium in patients with normal coronary artery on computed tomography angiography (CTA). From a multicenter CTP registry of stress and static computed tomography, we retrospectively recruited 113 patients (mean age, 60 years; 57 men) without perfusion defect on visual assessment and minimal (< 20% of diameter stenosis) or no coronary artery disease on CTA. Using semiautomatic analysis software, quantitative parameters of the LV myocardium, including the myocardial attenuation in stress and rest phases, transmural perfusion ratio (TPR), and myocardial perfusion reserve index (MPRI), were evaluated in 16 myocardial segments. In the lateral wall of the LV myocardium, all quantitative parameters except for MPRI were significantly higher compared with those in the other walls. The MPRI showed consistent values in all myocardial walls (anterior to lateral wall: range, 25% to 27%; p = 0.401). At the basal level of the myocardium, all quantitative parameters were significantly lower than those at the mid- and apical levels. Compared with men, women had significantly higher values of myocardial attenuation and TPR. Age, body mass index, and Framingham risk score were significantly associated with the difference in myocardial attenuation. Geographic and demographic variabilities of quantitative parameters in stress myocardial CTP exist in healthy subjects without significant coronary artery disease. This information may be helpful when assessing myocardial perfusion defects in CTP.

The Phoneme Identification Test for Assessment of Spectral and Temporal Discrimination Skills in Children: Development, Normative Data, and Test-Retest Reliability Studies.

PubMed

Cameron, Sharon; Chong-White, Nicky; Mealings, Kiri; Beechey, Tim; Dillon, Harvey; Young, Taegan

2018-02-01

Previous research suggests that a proportion of children experiencing reading and listening difficulties may have an underlying primary deficit in the way that the central auditory nervous system analyses the perceptually important, rapidly varying, formant frequency components of speech. The Phoneme Identification Test (PIT) was developed to investigate the ability of children to use spectro-temporal cues to perceptually categorize speech sounds based on their rapidly changing formant frequencies. The PIT uses an adaptive two-alternative forced-choice procedure whereby the participant identifies a synthesized consonant-vowel (CV) (/ba/ or /da/) syllable. CV syllables differed only in the second formant (F2) frequency along an 11-step continuum (between 0% and 100%-representing an ideal /ba/ and /da/, respectively). The CV syllables were presented in either quiet (PIT Q) or noise at a 0 dB signal-to-noise ratio (PIT N). Development of the PIT stimuli and test protocols, and collection of normative and test-retest reliability data. Twelve adults (aged 23 yr 10 mo to 50 yr 9 mo, mean 32 yr 5 mo) and 137 typically developing, primary-school children (aged 6 yr 0 mo to 12 yr 4 mo, mean 9 yr 3 mo). There were 73 males and 76 females. Data were collected using a touchscreen computer. Psychometric functions were automatically fit to individual data by the PIT software. Performance was determined by the width of the continuum for which responses were neither clearly /ba/ nor /da/ (referred to as the uncertainty region [UR]). A shallower psychometric function slope reflected greater uncertainty. Age effects were determined based on raw scores. Z scores were calculated to account for the effect of age on performance. Outliers, and individual data for which the confidence interval of the UR exceeded a maximum allowable value, were removed. Nonparametric tests were used as the data were skewed toward negative performance. Across participants, the median value of the F2 range that resulted in uncertain responses was 33% in quiet and 40% in noise. There was a significant effect of age on the width of this UR (p < 0.00001) in both quiet and noise, with performance becoming adult like by age 9 on the PIT Q and age 10 on the PIT N. A skewed distribution toward negative performance occurred in both quiet (p = 0.01) and noise (p = 0.006). Median UR scores were significantly wider in noise than in quiet (T = 2041, p < 0.0000001). Performance (z scores) across the two tests was significantly correlated (r = 0.36, p = 0.000009). Test-retest z scores were significantly correlated in both quiet and noise (r = 0.4 and 0.37, respectively, p < 0.0001). The PIT normative data show that the ability to identify phonemes based on changes in formant transitions improves with age, and that some children in the general population have performance much worse than their age peers. In children, uncertainty increases when the stimuli are presented in noise. The test is suitable for use in planned studies in a clinical population. American Academy of Audiology

Variation in primary and culture-expanded cells derived from connective tissue progenitors in human bone marrow space, bone trabecular surface and adipose tissue.

PubMed

Qadan, Maha A; Piuzzi, Nicolas S; Boehm, Cynthia; Bova, Wesley; Moos, Malcolm; Midura, Ronald J; Hascall, Vincent C; Malcuit, Christopher; Muschler, George F

2018-03-01

Connective tissue progenitors (CTPs) embody the heterogeneous stem and progenitor cell populations present in native tissue. CTPs are essential to the formation and remodeling of connective tissue and represent key targets for tissue-engineering and cell-based therapies. To better understand and characterize CTPs, we aimed to compare the (i) concentration and prevalence, (ii) early in vitro biological behavior and (iii) expression of surface-markers and transcription factors among cells derived from marrow space (MS), trabecular surface (TS), and adipose tissues (AT). Cancellous-bone and subcutaneous-adipose tissues were collected from 8 patients. Cells were isolated and cultured. Colony formation was assayed using Colonyze software based on ASTM standards. Cell concentration ([Cell]), CTP concentration ([CTP]) and CTP prevalence (P CTP ) were determined. Attributes of culture-expanded cells were compared based on (i) effective proliferation rate and (ii) expression of surface-markers CD73, CD90, CD105, SSEA-4, SSEA-3, SSEA-1/CD15, Cripto-1, E-Cadherin/CD324, Ep-CAM/CD326, CD146, hyaluronan and transcription factors Oct3/4, Sox-2 and Nanog using flow cytometry. Mean [Cell], [CTP] and P CTP were significantly different between MS and TS samples (P = 0.03, P = 0.008 and P= 0.0003), respectively. AT-derived cells generated the highest mean total cell yield at day 6 of culture-4-fold greater than TS and more than 40-fold greater than MS per million cells plated. TS colonies grew with higher mean density than MS colonies (290 ± 11 versus 150 ± 11 cell per mm 2 ; P = 0.0002). Expression of classical-mesenchymal stromal cell (MSC) markers was consistently recorded (>95%) from all tissue sources, whereas all the other markers were highly variable. The prevalence and biological potential of CTPs are different between patients and tissue sources and lack variation in classical MSC markers. Other markers are more likely to discriminate differences between cell populations in biological performance. Understanding the underlying reasons for variation in the concentration, prevalence, marker expression and biological potential of CTPs between patients and source tissues and determining the means of managing this variation will contribute to the rational development of cell-based clinical diagnostics and targeted cell-based therapies. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Software Modules for the Proximity-1 Space Link Interleaved Time Synchronization (PITS) Protocol

NASA Technical Reports Server (NTRS)

Woo, Simon S.; Veregge, John R.; Gao, Jay L.; Clare, Loren P.; Mills, David

2012-01-01

The Proximity-1 Space Link Interleaved Time Synchronization (PITS) protocol provides time distribution and synchronization services for space systems. A software prototype implementation of the PITS algorithm has been developed that also provides the test harness to evaluate the key functionalities of PITS with simulated data source and sink. PITS integrates time synchronization functionality into the link layer of the CCSDS Proximity-1 Space Link Protocol. The software prototype implements the network packet format, data structures, and transmit- and receive-timestamp function for a time server and a client. The software also simulates the transmit and receive-time stamp exchanges via UDP (User Datagram Protocol) socket between a time server and a time client, and produces relative time offsets and delay estimates.

Testing Aerospace Gears for Bending Fatigue, Pitting, and Scuffing

NASA Technical Reports Server (NTRS)

Krantz, Timothy; Anderson, Cody; Shareef, Iqbal; Fetty, Jason

2017-01-01

This work was motivated by the goal to increase the power to weight ratio of rotorcraft drive systems. Experiments were conducted to establish the performance of gears made from an aerospace alloy used in production aircraft. Bending fatigue, pitting, and scuffing test procedures and results are documented. The data establishes a baseline for evaluation of new technologies. Recommendations are made to improve test procedures for future work.

ATHENA X-IFU 300 K-50 mK cryochain demonstrator cryostat

NASA Astrophysics Data System (ADS)

Prouvé, T.; Duval, J. M.; Charles, I.; Yamasaki, N. Y.; Mitsuda, K.; Nakagawa, T.; Shinozaki, K.; Tokoku, C.; Yamamoto, R.; Minami, Y.; Le Du, M.; Andre, J.; Daniel, C.; Linder, M.

2018-01-01

In the framework of the ESA X-ray mission ATHENA, scheduled for launch in 2028, an ESA Core Technology Program (CTP) was started in 2016 to build a flight like cryostat demonstrator in parallel with the phase A studies of the ATHENA/X-IFU instrument [1,2]. As part of this CTP, called the Detector Cooling System (DCS), design, manufacturing and test of a cryostat including existing space coolers will be done. In addition to the validation of thermal performance, a Focal Plan Assembly (FPA) demonstrator using Transition Edge Sensors (TES) detector technology will be also integrated and its performance characterized versus the environment provided by the cryostat. This is a unique opportunity to validate many crucial issues of the cryogenic part of such a sensitive instrument. A dedicated activity within this CTP-DCS is the demonstration of the 300 K-50 mK cooling chain in a Ground System Equipment (GSE) cryostat. The studies are focused on the operation of the space coolers, which is made possible by the use of a ground cooler for cooling cryogenic shields and mechanical supports. Thanks to the modularity of the cryostat, several cooling chains could be tested. In the base line configuration described here, the low temperature stage is the CEA hybrid sorption/ADR 50 mK cooler with thermal interfaces at 4 K and 2 K. 4 K cooling is accomplished by a 4 K Joule-Thomson (JT) cryocooler and its Stirling precooler provided by JAXA. Regarding the 2 K stage, at first a 2 K JT from JAXA will be used. Alternatively, a 2 K JT cooler from RAL could replace the JAXA 2 K JT. In both cases new prototype(s) of a 2 K JT will be implemented, precooled by the EM 15 K pule tube cooler from Air Liquide. This test program is also the opportunity to validate the operation of the cryochain with respect to various requirements, such as time constant and temperature stabilities. This would bring us valuable inputs to integrate the cryochain in DCS cryostat or for the X-IFU phase A studies. This cryochain demonstration is also a critical milestone for the SPICA mission [3]. The design of the cryostat and first thermal validations both before and after integration of the JAXA JT coolers are presented in this paper.

Genetics Home Reference: Emanuel syndrome

MedlinePlus

... skin just in front of the ears ( preauricular pits or sinuses). About half of all affected infants ... MedlinePlus Encyclopedia: Microcephaly MedlinePlus Encyclopedia: Preauricular Tag or Pit General Information from MedlinePlus (5 links) Diagnostic Tests ...

Localized corrosion behaviour in simulated human body fluids of commercial Ni-Ti orthodontic wires.

PubMed

Rondelli, G; Vicentini, B

1999-04-01

The corrosion performances in simulated human body fluids of commercial equiatomic Ni-Ti orthodontic wires having various shape and size and produced by different manufacturers were evaluated; for comparison purposes wires made of stainless steel and of cobalt-based alloy were also examined. Potentiodynamic tests in artificial saliva at 40 degrees C indicated a sufficient pitting resistance for the Ni-Ti wires, similar to that of cobalt-based alloy wire; the stainless steel wire, instead, exhibited low pitting potential. Potentiodynamic tests at 40 degrees C in isotonic saline solution (0.9% NaCl) showed, for Ni-Ti and stainless steel wires, pitting potential values in the range approximately 200-400 mV and approximately 350 mV versus SCE, respectively: consequently, according to literature data (Hoar TP, Mears DC. Proc Roy Soc A 1996;294:486-510), these materials should be considered potentially susceptible to pitting; only the cobalt-based alloy should be immune from pitting. The localized corrosion potentials determined in the same environment by the ASTM F746 test (approximately 0-200 mV and 130 mV versus SCE for Ni-Ti and stainless steel, respectively) pointed out that for these materials an even higher risk of localized corrosion. Slight differences in localized corrosion behaviour among the various Ni-Ti wires were detected.

Study on Electro-Polishing Process by Niobium-Plate Sample With Artificial Pits

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

T. Saeki, H. Hayano, S. Kato, M. Nishiwaki, M. Sawabe, W.A. Clemens, R.L. Geng, R. Manus, P.V. Tyagi

2011-07-01

The Electro-polishing (EP) process is the best candidate of final surface-treatment for the production of ILC cavities. Nevertheless, the development of defects on the inner-surface of the Superconducting RF cavity during EP process has not been studied by experimental method. We made artificial pits on the surface of a Nb-plate sample and observed the development of the pit-shapes after each step of 30um-EP process where 120um was removed by EP in total. This article describes the results of this EP-test of Nb-sample with artificial pits.

Hydrolase treatments help unravel the function of intervessel pits in xylem hydraulics.

PubMed

Dusotoit-Coucaud, Anaïs; Brunel, Nicole; Tixier, Aude; Cochard, Hervé; Herbette, Stéphane

2014-03-01

Intervessel pits are structures that play a key role in the efficiency and safety functions of xylem hydraulics. However, little is known about the components of the pit membrane (PM) and their role in hydraulic functions, especially in resistance to cavitation. We tested the effect of commercial chemicals including a cellulase, a hemicellulase, a pectolyase, a proteinase and DTT on xylem hydraulic properties: vulnerability to cavitation (VC) and conductance. The effects were tested on branch segments from Fagus sylvatica (where the effects on pit structure were analyzed using TEM) and Populus tremula. Cellulose hydrolysis resulted in a sharp increase in VC and a significant increase in conductance, related to complete breakdown of the PM. Pectin hydrolysis also induced a sharp increase in VC but with no effect on conductance or pit structure observable by TEM. The other treatments with hemicellulase, proteinase or DTT showed no effect. This study brings evidence that cellulose and pectins are critical components underpinning VC, and that PM components may play distinct roles in the xylem hydraulic safety and efficiency. © 2013 Scandinavian Plant Physiology Society.

Methodology of selecting dozers for lignite open pit mines in Serbia

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

Stojanovic, D.; Ignjatovic, D.; Kovacevic, S.

1996-12-31

Apart from the main production processes (coal and overburden mining, rail conveyors transportation and storage of excavated masses) performed by great-capacity mechanization at open pit mines, numerous and different auxiliary works, that often have crucial influence on both the work efficiency of main equipment and the maintenance of optimum technical conditions of machines and plants covering technological system of open pit, are present. Successful realization of work indispensably requires a proper and adequate selection of auxiliary machines according to their type quantity, capacity, power etc. thus highly respecting specific conditions existing at each and every open pit mine. A dozermore » is certainly the most important and representative auxiliary machine at single open pit mine. It is widely used in numerous works that, in fact, are preconditions for successful work of the main mechanization and consequently the very selection of a dozer ranges among the most important operations when selecting mechanization. This paper presents the methodology of dozers selection when lignite open pit mines are concerned. A mathematical model defining the volume of work required for dozers to perform at open pit mines and consequently the number of necessary dozers was designed. The model underwent testing in practice at big open pit mines and can be used in design of future open pits mines.« less

Effects of transcriptional start site sequence and position on nucleotide-sensitive selection of alternative start sites at the pyrC promoter in Escherichia coli.

PubMed Central

Liu, J; Turnbough, C L

1994-01-01

In Escherichia coli, expression of the pyrC gene is regulated primarily by a translational control mechanism based on nucleotide-sensitive selection of transcriptional start sites at the pyrC promoter. When intracellular levels of CTP are high, pyrC transcripts are initiated predominantly with CTP at a site 7 bases downstream of the Pribnow box. These transcripts form a stable hairpin at their 5' ends that blocks ribosome binding. When the CTP level is low and the GTP level is high, conditions found in pyrimidine-limited cells, transcripts are initiated primarily with GTP at a site 9 bases downstream of the Pribnow box. These shorter transcripts are unable to form a hairpin at their 5' ends and are readily translated. In this study, we examined the effects of nucleotide sequence and position on the selection of transcriptional start sites at the pyrC promoter. We characterized promoter mutations that systematically alter the sequence at position 7 or 9 downstream of the Pribnow box or vary the spacing between the Pribnow box and wild-type transcriptional initiation region. The results reveal preferences for particular initiating nucleotides (ATP > or = GTP > UTP >> CTP) and for starting positions downstream of the Pribnow box (7 >> 6 and 8 > 9 > 10). The results indicate that optimal nucleotide-sensitive start site switching at the wild-type pyrC promoter is the result of competition between the preferred start site (position 7) that uses the poorest initiating nucleotide (CTP) and a weak start site (position 9) that uses a good initiating nucleotide (GTP). The sequence of the pyrC promoter also minimizes the synthesis of untranslatable transcripts and provides for maximum stability of the regulatory transcript hairpin. In addition, the results show that the effects of the mutations on pyrC expression and regulation are consistent with the current model for translational control. Possible effects of preferences for initiating nucleotides and start sites on the expression and regulation of other genes are discussed. Images PMID:7910603

Farnesol is utilized for isoprenoid biosynthesis in plant cells via farnesyl pyrophosphate formed by successive monophosphorylation reactions

PubMed Central

Thai, Long; Rush, Jeffrey S.; Maul, Jude E.; Devarenne, Timothy; Rodgers, Dana L.; Chappell, Joseph; Waechter, Charles J.

1999-01-01

The ability of Nicotiana tabacum cell cultures to utilize farnesol (F-OH) for sterol and sesquiterpene biosynthesis was investigated. [3H]F-OH was readily incorporated into sterols by rapidly growing cell cultures. However, the incorporation rate into sterols was reduced by greater than 70% in elicitor-treated cell cultures whereas a substantial proportion of the radioactivity was redirected into capsidiol, an extracellular sesquiterpene phytoalexin. The incorporation of [3H]F-OH into sterols was inhibited by squalestatin 1, suggesting that [3H]F-OH was incorporated via farnesyl pyrophosphate (F-P-P). Consistent with this possibility, N. tabacum proteins were metabolically labeled with [3H]F-OH or [3H]geranylgeraniol ([3H]GG-OH). Kinase activities converting F-OH to farnesyl monophosphate (F-P) and, subsequently, F-P-P were demonstrated directly by in vitro enzymatic studies. [3H]F-P and [3H]F-P-P were synthesized when exogenous [3H]F-OH was incubated with microsomal fractions and CTP. The kinetics of formation suggested a precursor–product relationship between [3H]F-P and [3H]F-P-P. In agreement with this kinetic pattern of labeling, [32P]F-P and [32P]F-P-P were synthesized when microsomal fractions were incubated with F-OH and F-P, respectively, with [γ-32P]CTP serving as the phosphoryl donor. Under similar conditions, the microsomal fractions catalyzed the enzymatic conversion of [3H]GG-OH to [3H]geranylgeranyl monophosphate and [3H]geranylgeranyl pyrophosphate ([3H]GG-P-P) in CTP-dependent reactions. A novel biosynthetic mechanism involving two successive monophosphorylation reactions was supported by the observation that [3H]CTP was formed when microsomes were incubated with [3H]CDP and either F-P-P or GG-P-P, but not F-P. These results document the presence of at least two CTP-mediated kinases that provide a mechanism for the utilization of F-OH and GG-OH for the biosynthesis of isoprenoid lipids and protein isoprenylation. PMID:10557276

Absolute Cerebral Blood Flow Infarction Threshold for 3-Hour Ischemia Time Determined with CT Perfusion and 18F-FFMZ-PET Imaging in a Porcine Model of Cerebral Ischemia

PubMed Central

Cockburn, Neil; Kovacs, Michael

2016-01-01

CT Perfusion (CTP) derived cerebral blood flow (CBF) thresholds have been proposed as the optimal parameter for distinguishing the infarct core prior to reperfusion. Previous threshold-derivation studies have been limited by uncertainties introduced by infarct expansion between the acute phase of stroke and follow-up imaging, or DWI lesion reversibility. In this study a model is proposed for determining infarction CBF thresholds at 3hr ischemia time by comparing contemporaneously acquired CTP derived CBF maps to 18F-FFMZ-PET imaging, with the objective of deriving a CBF threshold for infarction after 3 hours of ischemia. Endothelin-1 (ET-1) was injected into the brain of Duroc-Cross pigs (n = 11) through a burr hole in the skull. CTP images were acquired 10 and 30 minutes post ET-1 injection and then every 30 minutes for 150 minutes. 370 MBq of 18F-FFMZ was injected ~120 minutes post ET-1 injection and PET images were acquired for 25 minutes starting ~155–180 minutes post ET-1 injection. CBF maps from each CTP acquisition were co-registered and converted into a median CBF map. The median CBF map was co-registered to blood volume maps for vessel exclusion, an average CT image for grey/white matter segmentation, and 18F-FFMZ-PET images for infarct delineation. Logistic regression and ROC analysis were performed on infarcted and non-infarcted pixel CBF values for each animal that developed infarct. Six of the eleven animals developed infarction. The mean CBF value corresponding to the optimal operating point of the ROC curves for the 6 animals was 12.6 ± 2.8 mL·min-1·100g-1 for infarction after 3 hours of ischemia. The porcine ET-1 model of cerebral ischemia is easier to implement then other large animal models of stroke, and performs similarly as long as CBF is monitored using CTP to prevent reperfusion. PMID:27347877

Progenitor cells from different zones of human cartilage and their correlation with histopathological osteoarthritis progression.

PubMed

Mantripragada, Venkata P; Bova, Wesley A; Boehm, Cynthia; Piuzzi, Nicolas S; Obuchowski, Nancy A; Midura, Ronald J; Muschler, George F

2018-06-01

Cell-based therapies development for the treatment of osteoarthritis (OA) requires an understanding of the disease progression and attributes of the cells resident in cartilage. This study focused on quantitative assessment of the concentration and biological potential of stem and progenitor cells resident in different zones of cartilage displaying macroscopic Outerbridge grade 1-2 OA, and their correlation with OA progression based on established histologic scoring system. Lateral femoral condyles were collected from 15 patients with idiopathic OA and varus knees undergoing total knee arthroplasty. Superficial(C sp , top ∼ 500 µm) and deep cartilage(C dp ) was separated. Chondrogenic Connective Tissue Progenitors (CTP-C) were assayed by standardized Colony-Forming-Unit assay using automated image analysis (Colonyze TM ) based on ASTM standard F-2944-12. Cell concentration (cells/mg) was significantly greater in C sp (median: 7,000; range: 3,440-17,600) than C dp (median: 5,340; range: 3,393-9,660), p = 0.039. Prevalence (CTPs/million cells) was not different between C sp (median: 1,274; range: 0-3,898) and C dp (median:1,365; range:0-6,330), p = 0.42. In vitro performance of CTP-C progeny varied widely within and between patients, manifest by variation in colony size and morphology. Mean histopathological Mankin score was 4.7 (SD = 1.2), representing mild to moderate OA. Tidemark breach by blood vessels was associated with lower C sp cell concentration (p = 0.02). Matrix degradation was associated with lower C dp cell and CTP-C concentration (p = 0.015 and p = 0.095, respectively), independent of articular surface changes. These findings suggest that the initiation of OA may occur in either superficial or deep zones. The pathological changes affect CTP-Cs in C sp and C dp cartilage zones differently. The heterogeneity among the available CTP-Cs in C sp and C dp suggests performance-based selection to optimize cell-sourcing strategies for therapy. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1728-1738, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Structural Basis for Proficient Incorporation of dTTP Opposite O[superscript 6]-Methylguanine by Human DNA Polymerase [iota

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

Pence, Matthew G.; Choi, Jeong-Yun; Egli, Martin

2012-03-15

O{sup 6}-Methylguanine (O{sup 6}-methylG) is highly mutagenic and is commonly found in DNA exposed to methylating agents, even physiological ones (e.g. S-adenosylmethionine). The efficiency of a truncated, catalytic DNA polymerase L core enzyme was determined for nucleoside triphosphate incorporation opposite O{sup 6}-methylG, using steady-state kinetic analyses. The results presented here corroborate previous work from this laboratory using full-length pol L, which showed that dTTP incorporation occurs with high efficiency opposite O{sup 6}-methylG. Misincorporation of dTTP opposite O{sup 6}-methylG occurred with {approx}6-fold higher efficiency than incorporation of dCTP. Crystal structures of the truncated form of pol L with O{sup 6}-methylG asmore » the template base and incoming dCTP or dTTP were solved and showed that O{sup 6}-methylG is rotated into the syn conformation in the pol L active site and that dTTP misincorporation by pol L is the result of Hoogsteen base pairing with the adduct. Both dCTP and dTTP base paired with the Hoogsteen edge of O{sup 6}-methylG. A single, short hydrogen bond formed between the N3 atom of dTTP and the N7 atom of O{sup 6}-methylG. Protonation of the N3 atom of dCTP and bifurcation of the N3 hydrogen between the N7 and O{sup 6} atoms of O{sup 6}-methylG allow base pairing of the lesion with dCTP. We conclude that differences in the Hoogsteen hydrogen bonding between nucleotides is the main factor in the preferential selectivity of dTTP opposite O{sup 6}-methylG by human pol L, in contrast to the mispairing modes observed previously for O{sup 6}-methylG in the structures of the model DNA polymerases Sulfolobus solfataricus Dpo4 and Bacillus stearothermophilus DNA polymerase I.« less

Farnesol is utilized for isoprenoid biosynthesis in plant cells via farnesyl pyrophosphate formed by successive monophosphorylation reactions.

PubMed

Thai, L; Rush, J S; Maul, J E; Devarenne, T; Rodgers, D L; Chappell, J; Waechter, C J

1999-11-09

The ability of Nicotiana tabacum cell cultures to utilize farnesol (F-OH) for sterol and sesquiterpene biosynthesis was investigated. [(3)H]F-OH was readily incorporated into sterols by rapidly growing cell cultures. However, the incorporation rate into sterols was reduced by greater than 70% in elicitor-treated cell cultures whereas a substantial proportion of the radioactivity was redirected into capsidiol, an extracellular sesquiterpene phytoalexin. The incorporation of [(3)H]F-OH into sterols was inhibited by squalestatin 1, suggesting that [(3)H]F-OH was incorporated via farnesyl pyrophosphate (F-P-P). Consistent with this possibility, N. tabacum proteins were metabolically labeled with [(3)H]F-OH or [(3)H]geranylgeraniol ([(3)H]GG-OH). Kinase activities converting F-OH to farnesyl monophosphate (F-P) and, subsequently, F-P-P were demonstrated directly by in vitro enzymatic studies. [(3)H]F-P and [(3)H]F-P-P were synthesized when exogenous [(3)H]F-OH was incubated with microsomal fractions and CTP. The kinetics of formation suggested a precursor-product relationship between [(3)H]F-P and [(3)H]F-P-P. In agreement with this kinetic pattern of labeling, [(32)P]F-P and [(32)P]F-P-P were synthesized when microsomal fractions were incubated with F-OH and F-P, respectively, with [gamma-(32)P]CTP serving as the phosphoryl donor. Under similar conditions, the microsomal fractions catalyzed the enzymatic conversion of [(3)H]GG-OH to [(3)H]geranylgeranyl monophosphate and [(3)H]geranylgeranyl pyrophosphate ([(3)H]GG-P-P) in CTP-dependent reactions. A novel biosynthetic mechanism involving two successive monophosphorylation reactions was supported by the observation that [(3)H]CTP was formed when microsomes were incubated with [(3)H]CDP and either F-P-P or GG-P-P, but not F-P. These results document the presence of at least two CTP-mediated kinases that provide a mechanism for the utilization of F-OH and GG-OH for the biosynthesis of isoprenoid lipids and protein isoprenylation.

Correlation between evolution of inclusions and pitting corrosion in 304 stainless steel with yttrium addition.

PubMed

Shi, Weining; Yang, Shufeng; Li, Jingshe

2018-03-19

Effects of the evolution of inclusions on the pitting corrosion resistance of 304 stainless steel with different contents of the rare-earth element yttrium (Y) were studied using thermodynamic calculations, accelerated immersion tests, and electrochemical measurements. The experimental results showed that regular Y 2 O 3 inclusions demonstrated the best pitting resistance, followed in sequence by (Al,Mn)O inclusions, the composite inclusions, and irregular Y 2 O 3 inclusions. The pitting resistance first decreased, then increased, and then decreased again with increasing Y content, because sulfide inclusions were easily generated when the Y content was low and YN inclusions were easily generated at higher Y contents. The best pitting corrosion resistance was obtained for 304 stainless steel with addition of 0.019% Y.

The spontaneous replication error and the mismatch discrimination mechanisms of human DNA polymerase β

PubMed Central

Koag, Myong-Chul; Nam, Kwangho; Lee, Seongmin

2014-01-01

To provide molecular-level insights into the spontaneous replication error and the mismatch discrimination mechanisms of human DNA polymerase β (polβ), we report four crystal structures of polβ complexed with dG•dTTP and dA•dCTP mismatches in the presence of Mg2+ or Mn2+. The Mg2+-bound ground-state structures show that the dA•dCTP-Mg2+ complex adopts an ‘intermediate’ protein conformation while the dG•dTTP-Mg2+ complex adopts an open protein conformation. The Mn2+-bound ‘pre-chemistry-state’ structures show that the dA•dCTP-Mn2+ complex is structurally very similar to the dA•dCTP-Mg2+ complex, whereas the dG•dTTP-Mn2+ complex undergoes a large-scale conformational change to adopt a Watson–Crick-like dG•dTTP base pair and a closed protein conformation. These structural differences, together with our molecular dynamics simulation studies, suggest that polβ increases replication fidelity via a two-stage mismatch discrimination mechanism, where one is in the ground state and the other in the closed conformation state. In the closed conformation state, polβ appears to allow only a Watson–Crick-like conformation for purine•pyrimidine base pairs, thereby discriminating the mismatched base pairs based on their ability to form the Watson–Crick-like conformation. Overall, the present studies provide new insights into the spontaneous replication error and the replication fidelity mechanisms of polβ. PMID:25200079

The carboxyl-terminal region is a determinant for the intracellular behavior of the chorionic gonadotropin beta subunit: effects on the processing of the Asn-linked oligosaccharides.

PubMed

Muyan, M; Boime, I

1998-05-01

The placental hormone human CG (hCG) consists of two noncovalently linked alpha- and beta-subunits similar to the other glycoprotein hormones LH, FSH, and TSH. These heterodimers share a common alpha subunit but differ in their structurally distinct beta subunits. The CGbeta subunit is distinguished among the beta subunits by the presence of a C-terminal extension with four serine-linked oligosaccharides (carboxyl terminal peptide or CTP). In previous studies we observed that deleting this sequence decreased assembly of the truncated CGbeta subunit (CGbeta114) with the alpha-subunit and increased the heterogeneity of the secreted forms of the uncombined subunit synthesized in transfected Chinese hamster ovary (CHO) cells. The latter result was attributed to alterations in the processing of the two N-linked oligosaccharides. To examine at what step this heterogeneity occurs, the CGbeta and CGbeta114 genes were transfected into wild-type and mutant CHO cell lines that are defective in the late steps of the N-linked carbohydrate-processing pathway. We show here that removal of the CTP alters the processing of the core mannosyl unit of the subunit to complex forms at both glycosylation sites and that the oligosaccharides contain polylactosamine. Although it has been presumed that there is little intramolecular interaction between the CTP and the proximal domains of the subunit, our data suggest that the CTP sequence participates in the folding of the newly synthesized subunit, which is manifest by the posttranslational changes observed here.

The effect of tempering temperature on pitting corrosion resistance of 420 stainless steels

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

Anwar, Moch Syaiful, E-mail: moch026@lipi.go.id; Prifiharni, Siska, E-mail: sisk002@lipi.go.id; Mabruri, Efendi, E-mail: effe004@lipi.go.id

2016-04-19

The AISI Type 420 stainless steels are commonly used to steam generators, mixer blades, etc. These stainless steels are most prone to pitting in dissolved Cl{sup −} containing environments. In this paper, the effect of tempering temperature on pitting corrosion resistance of AISI Type 420 stainless steels was studied. The AISI Type 420 stainless steels specimens were heat treated at the temperature of 1050°C for 1 hour to reach austenite stabilization and then quench in the oil. After that, the specimens were tempered at the temperature of 150, 250, 350 and 450°C for 30 minutes and then air cooled tomore » the room temperature. The electrochemical potentiodynamic polarization test was conducted at 3.5% sodium chloride solution to evaluate corrosion rate and pitting corrosion behaviour. The Scanning Electron Microscope (SEM), Energy Dispersive X-Ray Spectroscopy (EDS) were used to evaluate the pitting corrosion product. The result have shown that highest pitting potential was found in the sample tempered at 250°C and corrosion pits were found to initiate preferentially around chromium carbides.« less

Near-Field Microwave Detection of Corrosion Precursor Pitting under Thin Dielectric Coatings in Metallic Substrate

NASA Astrophysics Data System (ADS)

Hughes, D.; Zoughi, R.; Austin, R.; Wood, N.; Engelbart, R.

2003-03-01

Detection of corrosion precursor pitting on metallic surfaces under various coatings and on bare metal is of keen interest in evaluation of aircraft fuselage. Near-field microwave nondestructive testing methods, utilizing open-ended rectangular waveguides and coaxial probes, have been used extensively for detection of surface flaws in metals, both on bare metal and under a dielectric coating. This paper presents the preliminary results of using microwave techniques to detect corrosion precursor pitting under paint and primer, applique and on bare metal. Machined pits of 500 μm diameter were detected using open-ended rectangular waveguides at V-Band under paint and primer and applique, and on bare metal. Using coaxial probes, machined pits with diameters down to 150 μm on bare metal were also detected. Relative pit size and density were shown on a corrosion-pitted sample using open-ended rectangular waveguides at frequencies of 35 GHz to 70 GHz. The use of Boeing's MAUS™ scanning systems provided improved results by alleviating standoff variation and scanning artifact. Typical results of this investigation are also presented.

Erosion of phosphor bronze under cavitation attack in a mineral oil

NASA Technical Reports Server (NTRS)

Rao, B. C. S.; Buckley, D. H.

1986-01-01

Experimental investigations on erosion of a copper alloy, phosphor bronze, under cavitation attack in a viscous mineral oil are presented. The details of pit formation and erosion were studied using scanning electron microscopy. The mean depth of penetration, the variations in surface roughness, and the changes in erosion pit size were studied. Cavitation pits formed initially over the grain boundaries while the surface grains were plastically deformed. Erosion of surface grains occurred largely by ductile fracture involving microcracking and removal in layers. The ratio h/a of the depth h to half width a of cavitation pits increased with test duration from 0.047 to 0.55.

Inconsistent identification of pit bull-type dogs by shelter staff.

PubMed

Olson, K R; Levy, J K; Norby, B; Crandall, M M; Broadhurst, J E; Jacks, S; Barton, R C; Zimmerman, M S

2015-11-01

Shelter staff and veterinarians routinely make subjective dog breed identification based on appearance, but their accuracy regarding pit bull-type breeds is unknown. The purpose of this study was to measure agreement among shelter staff in assigning pit bull-type breed designations to shelter dogs and to compare breed assignments with DNA breed signatures. In this prospective cross-sectional study, four staff members at each of four different shelters recorded their suspected breed(s) for 30 dogs; there was a total of 16 breed assessors and 120 dogs. The terms American pit bull terrier, American Staffordshire terrier, Staffordshire bull terrier, pit bull, and their mixes were included in the study definition of 'pit bull-type breeds.' Using visual identification only, the median inter-observer agreements and kappa values in pair-wise comparisons of each of the staff breed assignments for pit bull-type breed vs. not pit bull-type breed ranged from 76% to 83% and from 0.44 to 0.52 (moderate agreement), respectively. Whole blood was submitted to a commercial DNA testing laboratory for breed identification. Whereas DNA breed signatures identified only 25 dogs (21%) as pit bull-type, shelter staff collectively identified 62 (52%) dogs as pit bull-type. Agreement between visual and DNA-based breed assignments varied among individuals, with sensitivity for pit bull-type identification ranging from 33% to 75% and specificity ranging from 52% to 100%. The median kappa value for inter-observer agreement with DNA results at each shelter ranged from 0.1 to 0.48 (poor to moderate). Lack of consistency among shelter staff indicated that visual identification of pit bull-type dogs was unreliable. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

How the CCA-Adding Enzyme Selects Adenine over Cytosine at Position 76 of tRNA

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

Pan, Baocheng; Xiong, Yong; Steitz, Thomas A.

2010-11-22

CCA-adding enzymes [ATP(CTP):tRNA nucleotidyltransferases] add CCA onto the 3{prime} end of transfer RNA (tRNA) precursors without using a nucleic acid template. Although the mechanism by which cytosine (C) is selected at position 75 of tRNA has been established, the mechanism by which adenine (A) is selected at position 76 remains elusive. Here, we report five cocrystal structures of the enzyme complexed with both a tRNA mimic and nucleoside triphosphates under catalytically active conditions. These structures suggest that adenosine 5{prime}-monophosphate is incorporated onto the A76 position of the tRNA via a carboxylate-assisted, one-metal-ion mechanism with aspartate 110 functioning as a generalmore » base. The discrimination against incorporation of cytidine 5{prime}-triphosphate (CTP) at position 76 arises from improper placement of the {alpha} phosphate of the incoming CTP, which results from the interaction of C with arginine 224 and prevents the nucleophilic attack by the 3{prime} hydroxyl group of cytidine75.« less

Computed Tomography Perfusion Imaging for the Diagnosis of Hepatic Alveolar Echinococcosis

PubMed Central

Sade, Recep; Kantarci, Mecit; Genc, Berhan; Ogul, Hayri; Gundogdu, Betul; Yilmaz, Omer

2018-01-01

Objective: Alveolar echinococcosis (AE) is a rare life-threatening parasitic infection. Computed tomography perfusion (CTP) imaging has the potential to provide both quantitative and qualitative information about the tissue perfusion characteristics. The purpose of this study was the examination of the characteristic features and feasibility of CTP in AE liver lesions. Material and Methods: CTP scanning was performed in 25 patients who had a total of 35 lesions identified as AE of the liver. Blood flow (BF), blood volume (BV), portal venous perfusion (PVP), arterial liver perfusion (ALP), and hepatic perfusion indexes (HPI) were computed for background liver parenchyma and each AE lesion. Results: Significant differences were detected between perfusion values of the AE lesions and background liver tissue. The BV, BF, ALP, and PVP values for all components of the AE liver lesions were significantly lower than the normal liver parenchyma (p<0.01). Conclusions: We suggest that perfusion imaging can be used in AE of the liver. Thus, the quantitative knowledge of perfusion parameters are obtained via CT perfusion imaging. PMID:29531482

Effect of yeast strain and some nutritional factors on tannin composition and potential astringency of model wines.

PubMed

Rinaldi, Alessandra; Blaiotta, Giuseppe; Aponte, Maria; Moio, Luigi

2016-02-01

Nine Saccharomyces cerevisiae cultures, isolated from different sources, were tested for their ability to reduce tannins reactive towards salivary proteins, and potentially responsible for wine astringency. Strains were preliminary genetically characterized and evaluated for physiological features of technological interest. Laboratory-scale fermentations were performed in three synthetic media: CT) containing enological grape tannin; CTP) CT supplemented with organic nitrogen sources; CTPV) CTP supplemented with vitamins. Adsorption of total tannins, tannins reactive towards salivary proteins, yellow pigments, phenolics having antioxidant activity, and total phenols, characterizing the enological tannin, was determined by spectrophotometric methods after fermentation. The presence of vitamins and peptones in musts greatly influenced the adsorption of tannins reactive towards salivary proteins (4.24 g/L gallic acid equivalent), thus promoting the reduction of the potential astringency of model wines. With reference to the different phenolic classes, yeast strains showed different adsorption abilities. From a technological point of view, the yeast choice proved to be crucial in determining changes in gustative and mouthfeel profile of red wines and may assist winemakers to modulate colour and astringency of wine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Measurements of evaporation from a mine void lake and testing of modelling approaches

NASA Astrophysics Data System (ADS)

McJannet, David; Hawdon, Aaron; Van Niel, Tom; Boadle, Dave; Baker, Brett; Trefry, Mike; Rea, Iain

2017-12-01

Pit lakes often form in the void that remains after open cut mining operations cease. As pit lakes fill, hydrological and geochemical processes interact and these need to be understood for appropriate management actions to be implemented. Evaporation is important in the evolution of pit lakes as it acts to concentrate various constituents, controls water level and changes the thermal characteristics of the water body. Despite its importance, evaporation from pit lakes is poorly understood. To address this, we used an automated floating evaporation pan and undertook measurements at a pit lake over a 12 month period. We also developed a new procedure for correcting floating pan evaporation estimates to lake evaporation estimates based on surface temperature differences. Total annual evaporation was 2690 mm and reflected the strong radiation inputs, high temperatures and low humidity experienced in this region. Measurements were used to test the performance of evaporation estimates derived using both pan coefficient and aerodynamic modelling techniques. Daily and monthly evaporation estimates were poorly reproduced using pan coefficient techniques and their use is not recommended for such environments. Aerodynamic modelling was undertaken using a range of input datasets that may be available to those who manage pit lake systems. Excellent model performance was achieved using over-water or local over-land meteorological observations, particularly when the sheltering effects of the pit were considered. Model performance was reduced when off-site data were utilised and differences between local and off-site vapor pressure and wind speed were found to be the major cause.

Spiral Bevel Gear Damage Detection Using Decision Fusion Analysis

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.; Handschuh, Robert F.; Afjeh, Abdollah A.

2002-01-01

A diagnostic tool for detecting damage to spiral bevel gears was developed. Two different monitoring technologies, oil debris analysis and vibration, were integrated using data fusion into a health monitoring system for detecting surface fatigue pitting damage on gears. This integrated system showed improved detection and decision-making capabilities as compared to using individual monitoring technologies. This diagnostic tool was evaluated by collecting vibration and oil debris data from fatigue tests performed in the NASA Glenn Spiral Bevel Gear Fatigue Rigs. Data was collected during experiments performed in this test rig when pitting damage occurred. Results show that combining the vibration and oil debris measurement technologies improves the detection of pitting damage on spiral bevel gears.

Gear Damage Detection Using Oil Debris Analysis

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.

2001-01-01

The purpose of this paper was to verify, when using an oil debris sensor, that accumulated mass predicts gear pitting damage and to identify a method to set threshold limits for damaged gears. Oil debris data was collected from 8 experiments with no damage and 8 with pitting damage in the NASA Glenn Spur Gear Fatigue Rig. Oil debris feature analysis was performed on this data. Video images of damage progression were also collected from 6 of the experiments with pitting damage. During each test, data from an oil debris sensor was monitored and recorded for the occurrence of pitting damage. The data measured from the oil debris sensor during experiments with damage and with no damage was used to identify membership functions to build a simple fuzzy logic model. Using fuzzy logic techniques and the oil debris data, threshold limits were defined that discriminate between stages of pitting wear. Results indicate accumulated mass combined with fuzzy logic analysis techniques is a good predictor of pitting damage on spur gears.

Corrosion study of bare and coated stainless steel

NASA Technical Reports Server (NTRS)

Morrison, J. D.

1972-01-01

A program was conducted at Kennedy Space Center from February 1968 to February 1971 to evaluate the performance of austenitic stainless steel alloys used in fluid systems lines. For several years, there had been numerous failures of stainless steel hardware caused by pitting and stress corrosion cracking. Several alloys were evaluated for effectiveness of certain sacrificial-type protective coverings in preventing corrosion failures. Samples were tested in specially designed racks placed 91 meters (100 yards) above high-tide line at Cape Kennedy. It is concluded that: (1) unprotected tubing samples showed evidence of pitting initiation after 2 weeks; (2) although some alloys develop larger pits than others, it is probable that the actual pitting rate is independent of alloy type; (3) the deepest pitting occurred in the sheltered part of the samples; and (4) zinc-rich coatings and an aluminum-filled coating have afforded sacrificial protection against pitting for at least 28 months. It is believed that a much longer effective coating life can be expected.

A new C-terminal located mutation (V272ter) in the PIT-1 gene manifesting with severe congenital hypothyroidism. Possible functionality of the PIT-1 C-terminus.

PubMed

Blankenstein, O; Mühlenberg, R; Kim, C; Wüller, S; Pfäffle, R; Heimann, G

2001-01-01

We describe a newborn with clinical signs of severe hypothyroidism and combined pituitary hormone deficiency due to a new mutation in the PIT-1 gene. Endocrine stimulation test revealed a deficiency for PRL, TSH and GH, suggesting a defect in the pituitary transcription factor PIT-1. Genetic analysis of the PIT-1 gene was performed by exon-specific PCR, followed by SSCP mutation screening and DNA sequencing of the abnormal migrating fragments. DNA sequencing revealed a new mutation (V272ter) in direct neighborhood to a known mutational hot spot (R271W) in the C-terminal part of the PIT-1 molecule. Whereas the R271W mutation has a dominant negative effect on the mutant protein, the newly described mutation is inherited in an autosomal-recessive way. The biological consequences of these two different mutations are discussed. Copyright 2002 S. Karger AG, Basel

A non-linear regression method for CT brain perfusion analysis

NASA Astrophysics Data System (ADS)

Bennink, E.; Oosterbroek, J.; Viergever, M. A.; Velthuis, B. K.; de Jong, H. W. A. M.

2015-03-01

CT perfusion (CTP) imaging allows for rapid diagnosis of ischemic stroke. Generation of perfusion maps from CTP data usually involves deconvolution algorithms providing estimates for the impulse response function in the tissue. We propose the use of a fast non-linear regression (NLR) method that we postulate has similar performance to the current academic state-of-art method (bSVD), but that has some important advantages, including the estimation of vascular permeability, improved robustness to tracer-delay, and very few tuning parameters, that are all important in stroke assessment. The aim of this study is to evaluate the fast NLR method against bSVD and a commercial clinical state-of-art method. The three methods were tested against a published digital perfusion phantom earlier used to illustrate the superiority of bSVD. In addition, the NLR and clinical methods were also tested against bSVD on 20 clinical scans. Pearson correlation coefficients were calculated for each of the tested methods. All three methods showed high correlation coefficients (>0.9) with the ground truth in the phantom. With respect to the clinical scans, the NLR perfusion maps showed higher correlation with bSVD than the perfusion maps from the clinical method. Furthermore, the perfusion maps showed that the fast NLR estimates are robust to tracer-delay. In conclusion, the proposed fast NLR method provides a simple and flexible way of estimating perfusion parameters from CT perfusion scans, with high correlation coefficients. This suggests that it could be a better alternative to the current clinical and academic state-of-art methods.

Pitting and Stress Corrosion Cracking Susceptibility of Nanostructured Al-Mg Alloys in Natural and Artificial Environments

NASA Astrophysics Data System (ADS)

Sharma, Mala M.; Ziemian, Constance W.

2008-12-01

The stress corrosion cracking (SCC) behavior of two developmental nanocrystalline 5083 alloys with varied composition and processing conditions was studied. The results were compared to a commercial aluminum AA 5083 (H111) alloy. The pitting densities, size and depths, and residual tensile strengths were measured after alternate immersion in artificial seawater and atmospheric exposure under different loading conditions. Optical and scanning electron microscopy (SEM) with EDX was used to analyze the fracture surfaces of failed specimen after removal at selected intervals and tensile testing. One of the nanostructured Al-Mg alloys exhibited significantly superior pitting resistance when compared to conventional microstructured AA 5083. Under conditions where pitting corrosion showed up as local tunnels toward phase inclusions, transgranular cracking was observed, whereas under conditions when pitting corrosion evolved along grain boundaries, intergranular cracking inside the pit was observed. Pit initiation resistance of the nano alloys appears to be better than that of the conventional alloys. However, long-term pit propagation is a concern and warrants further study. The objective of this investigation was to obtain information regarding the role that ultra-fine microstructures play in their degradation in marine environments and to provide insight into the corrosion mechanisms and damage processes of these alloys.

Loss of PiT-1 Results in Abnormal Endocytosis in the Yolk Sac Visceral Endoderm

PubMed Central

Wallingford, Mary C.; Giachelli, Cecilia M.

2014-01-01

PiT-1 protein is a transmembrane sodium-dependent phosphate (Pi) transporter. PiT-1 knock out (KO) embryos die from largely unknown causes by embryonic day (E) 12.5. We tested the hypothesis that PiT-1 is required for endocytosis in the embryonic yolk sac (YS) visceral endoderm (VE). Here we present data supporting that PiT-1 KO results in a YS remodeling defect and decreased endocytosis in the YS VE. The remodeling defect is not due to an upstream cardiomyocyte requirement for PiT-1, as SM22αCre-specific KO of PiT-1 in the developing heart and the YS mesodermal layer (ME) does not recapitulate the PiT-1 global KO phenotype. Furthermore, we find that high levels of PiT-1 protein localize to the YS VE apical membrane. Together these data support that PiT-1 is likely required in YS VE. During normal development maternal immunoglobulin (IgG) is endocytosed into YS VE and accumulates in the apical side of the VE in a specialized lysosome termed the apical vacuole (AV). We have identified a reduction in PiT-1 KO VE cell height and a striking loss of IgG accumulation in the PiT-1 KO VE. The endocytosis genes Tfeb, Lamtor2 and Snx2 are increased at the RNA level. Lysotracker Red staining reveals a loss of distinct AVs, and yolk sacs incubated ex vivo with phRODO Green Dextran for Endocytosis demonstrate a functional loss of endocytosis. As yolk sac endocytosis is controlled in part by microautophagy, but expression of LC3 had not been examined, we investigated LC3 expression during yolk sac development and found stage-specific LC3 RNA expression that is predominantly from the YS VE layer at E9.5. Normalized LC3-II protein levels are decreased in the PiT-1 KO YS, supporting a requirement for PiT-1 in autophagy in the YS. Therefore, we propose the novel idea that PiT-1 is central to the regulation of endocytosis and autophagy in the YS VE. PMID:25138534

Long term storage test of titanium material with liquid fluorine propellant

NASA Technical Reports Server (NTRS)

Denson, J. R.; English, W. D.; Roth, J.; Toy, A.

1979-01-01

The compatibility of 6AL-4V Ti with propellant grade GF2 and LF2 at 77 K for up to 3 years was investigated. Titanium double coupons, annealed or heat treated, with 16 or 64 RMS finishes, were immersed in F2 in individual Pyrex capsules and stored under LN2 for 29 and 39 months. Pre and post immersion tests were performed on the propellant and coupons. Chemical analysis of the propellant did not reveal any significant changes due to titanium corrosion. Gravimetric, visual, microscopic, and metallurgical examination with pitting analysis did not reveal gross corrosion of the titanium although pitting appears to be greater after 39 months exposure. The increase in pit size and number raises the possibility of unpredictable crack propagation instability. Fracture toughness tests are necessary to define this possibility.

Corrosion behavior in high heat input welded heat-affected zone of Ni-free high-nitrogen Fe–18Cr–10Mn–N austenitic stainless steel

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

Moon, Joonoh, E-mail: mjo99@kims.re.kr; Ha, Heon-Young; Lee, Tae-Ho

2013-08-15

The pitting corrosion and interphase corrosion behaviors in high heat input welded heat-affected zone (HAZ) of a metastable high-nitrogen Fe–18Cr–10Mn–N austenitic stainless steel were explored through electrochemical tests. The HAZs were simulated using Gleeble simulator with high heat input welding condition of 300 kJ/cm and the peak temperature of the HAZs was changed from 1200 °C to 1350 °C, aiming to examine the effect of δ-ferrite formation on corrosion behavior. The electrochemical test results show that both pitting corrosion resistance and interphase corrosion resistance were seriously deteriorated by δ-ferrite formation in the HAZ and their aspects were different with increasingmore » δ-ferrite fraction. The pitting corrosion resistance was decreased by the formation of Cr-depleted zone along δ-ferrite/austenite (γ) interphase resulting from δ-ferrite formation; however it didn't depend on δ-ferrite fraction. The interphase corrosion resistance depends on the total amount of Cr-depleted zone as well as ferrite area and thus continuously decreased with increasing δ-ferrite fraction. The different effects of δ-ferrite fraction on pitting corrosion and interphase corrosion were carefully discussed in terms of alloying elements partitioning in the HAZ based on thermodynamic consideration. - Highlights: • Corrosion behavior in the weld HAZ of high-nitrogen austenitic alloy was studied. • Cr{sub 2}N particle was not precipitated in high heat input welded HAZ of tested alloy. • Pitting corrosion and interphase corrosion show a different behavior. • Pitting corrosion resistance was affected by whether or not δ-ferrite forms. • Interphase corrosion resistance was affected by the total amount of δ-ferrite.« less

Hot corrosion attack and strength degradation of SiC and Si(sub)3N(sub)4

NASA Technical Reports Server (NTRS)

Smialek, James L.; Fox, Dennis S.; Jacobson, Nathan S.

1987-01-01

Thin films of Na2SO4 and Na2CO3 molten salt deposits were used to corrode sintered SiC and Si3N4 at 1000 C. The resulting attack produced pitting and grain boundary etching resulting in strength decreases ranging from 15 to 50 percent. Corrosion pits were the predominant sources of fracture. The degree of strength decrease was found to be roughly correlated with the depth of the pit, as predicted from fracture toughness considerations. Gas evolution and bubble formation were key aspects of pit formation. Many of the observations of furnace exposures held true in a more realistic burner rig test.

ETR, TRA642. ON GROUND FLOOR, CAMERA LOOKS SOUTHWEST INTO PIT. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

ETR, TRA-642. ON GROUND FLOOR, CAMERA LOOKS SOUTHWEST INTO PIT. CANAL STRUCTURE IS AT RIGHT OF CENTER WITH RECTANGULAR OPENING TO BE MATED WITH THE DE-FUELING MECHANISM THAT WILL DEPOSIT FUEL RODS INTO THE WORKING CANAL. INL NEGATIVE NO. 56-3710. R.G. Larsen, Photographer, 11/13/1956 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

Effect of post weld impact treatment (PWIT) on mechanical properties of spot-welded joint

NASA Astrophysics Data System (ADS)

Ghazali, F. A.; Salleh, Z.; Hyie, K. M.; Rozlin, N. M. Nik; Hamidi, S. H. Ahmad; Padzi, M. M.

2017-12-01

This paper focuses on the study of improvement for spot welding on the tensile shear and hardness by applying post weld impact treatment (PWIT) on the welded joint. The main objective of the research is to characterize and improve the mechanical properties of the joint. The method of PWIT used on the welded joint was Pneumatic Impact Treatment (PIT). The concept of PIT on spot welding is that it improves the mechanical properties of the welded zone. The working sample was undergoing a resistance spot welding of joining two similar in dimension and material of a steel plate before treated. The dimension of both plate are 110 mm × 45 mm × 1.2 mm and the material used were low carbon steel (LCS). All the welded samples were tested for its mechanical properties by performing the tensile-shear and hardness test. Tensile-shear test was conducted on the spot welded, both treated and as-welded samples using crosshead speed of 2 mm/min, while hardness test was performed using 1kgf load via Vickers hardness indenter. The effects of PIT on tensile-shear properties and hardness were evaluated and found that the implementation of PIT has increased tensile shear and hardness significantly.

105. ARAIII. Interior view of ARA608 highbay pit in 1983 ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

105. ARA-III. Interior view of ARA-608 high-bay pit in 1983 modified to contain high-temperature, high-pressure autoclave and furnace test area. Ineel photo no. 81-109. - Idaho National Engineering Laboratory, Army Reactors Experimental Area, Scoville, Butte County, ID

62. Historic propellant piping diagram of oxidant pit at Building ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

62. Historic propellant piping diagram of oxidant pit at Building 202, January 6, 1956. NASA GRC drawing no. CF-101644. (On file at NASA Glenn Research Center). - Rocket Engine Testing Facility, GRC Building No. 202, NASA Glenn Research Center, Cleveland, Cuyahoga County, OH

Determination of lateral effects of borrow pits on hydrology of adjacent wetlands.

DOT National Transportation Integrated Search

2007-09-28

A three year research project was conducted to develop and test a method to predict the distance borrow pits should : be set back from adjacent wetlands to avoid detrimental impacts on wetland hydrology. The method is based on the : Boussinesq equati...

Sex, Parity, and Scars: A Meta-analytic Review.

PubMed

McFadden, Clare; Oxenham, Marc F

2018-01-01

The ability to identify whether a female has been pregnant or has given birth has significant implications for forensic investigations and bioarcheological research. The meaning of "scars of parturition," their causes, and their significance are a matter of contention, with a substantial literature of re-evaluations and tests of the relationship between pelvic scarring and parity. The aim of this study was to use meta-analytic techniques (the methodological approach) to test whether pelvic scarring, namely dorsal pubic pitting and the preauricular groove, is a predictor of parity and sex. Meta-analyses indicated that neither dorsal pubic pitting nor the preauricular groove are predictors of parity status, while dorsal pubic pitting is a moderate predictor of sex. A weak relationship between dorsal pubic pitting and parity was identified, but this is believed to be a product of the moderate relationship with sex. This calls into question whether any causal relationship between parity and pelvic scarring exists. © 2017 American Academy of Forensic Sciences.

Synergistic Use of MODIS and AIRS in a Variational Retrieval of Cloud Parameters.

NASA Astrophysics Data System (ADS)

Li, Jun; Menzel, W. Paul; Zhang, Wenjian; Sun, Fengying; Schmit, Timothy J.; Gurka, James J.; Weisz, Elisabeth

2004-11-01

The Moderate Resolution Imaging Spectroradiometer (MODIS) and the Atmospheric Infrared Sounder (AIRS) measurements from the Earth Observing System's (EOS's) Aqua satellite enable global monitoring of the distribution of clouds. MODIS is able to provide a cloud mask, surface and cloud types, cloud phase, cloud-top pressure (CTP), effective cloud amount (ECA), cloud particle size, and cloud optical thickness at high spatial resolution (1 5 km). The combined MODIS AIRS system offers the opportunity for improved cloud products, better than from either system alone; this improvement is demonstrated in this paper with both simulated and real radiances. A one-dimensional variational (1DVAR) methodology is used to retrieve the CTP and ECA from AIRS longwave (650 790 cm-1 or 15.38 12.65 μm) cloudy radiance measurements (hereinafter referred to as MODIS AIRS 1DVAR). The MODIS AIRS 1DVAR cloud properties show significant improvement over the MODIS-alone cloud properties and slight improvement over AIRS-alone cloud properties in a simulation study, while MODIS AIRS 1DVAR is much more computationally efficient than the AIRS-alone 1DVAR; comparisons with radiosonde observations show that CTPs improve by 10 40 hPa for MODIS AIRS CTPs over those from MODIS alone. The 1DVAR approach is applied to process the AIRS longwave cloudy radiance measurements; results are compared with MODIS and Geostationary Operational Environmental Satellite sounder cloud products. Data from ground-based instrumentation at the Atmospheric Radiation Measurement Program Cloud and Radiation Test Bed in Oklahoma are used for validation; results show that MODIS AIRS improves the MODIS CTP, especially in low-level clouds. The operational use of a high-spatial-resolution imager, along with information from a high-spectral-resolution sounder will be possible with instruments planned for the next-generation geostationary operational instruments.

Predictors of hospital re-admissions among Hispanics with hepatitis C-related cirrhosis

PubMed Central

Atla, Pradeep R.; Sheikh, Muhammad Y.; Gill, Firdose; Kundu, Rabindra; Choudhury, Jayanta

2016-01-01

Background Hospital re-admissions in decompensated cirrhosis are associated with worse patient outcomes. Hispanics have a disproportionately high prevalence of hepatitis C virus (HCV)-related morbidity and mortality. The goal of this study was to evaluate the factors affecting re-admission rates among Hispanics with HCV-related cirrhosis. Methods A total of 292 consecutive HCV-related cirrhosis admissions (Hispanics 189, non-Hispanics 103) from January 2009 to December 2012 were retrospectively reviewed; 132 were cirrhosis-related re-admissions. The statistical analysis was performed using STATA version 11.1. Chi-square/Fisher’s exact and Student’s t-tests were used to compare categorical and continuous variables, respectively. Multivariate logistic regression analysis was performed to identify predictors for hospital readmissions. Results Among the 132 cirrhosis-related readmissions, 71% were Hispanics while 29% were non-Hispanics (P=0.035). Hepatic encephalopathy (HE) and esophageal variceal hemorrhage were the most frequent causes of the first and subsequent readmissions. Hispanics with readmissions had a higher Child-Turcotte-Pugh (CTP) class (B and C) and higher model for end-stage liver disease (MELD) scores (≥15), as well as a higher incidence of alcohol use, HE, spontaneous bacterial peritonitis, hepatocellular carcinoma, and varices (P<0.05). The majority of the study patients (81%) had MELD scores <15. Multivariate regression analysis identified alcohol use (OR 2.63; 95%CI 1.1-6.4), HE (OR 5.5; 95%CI 2-15.3), varices (OR 3.2; 95%CI 1.3-8.2), and CTP class (OR 3.3; 95%CI 1.4–8.1) as predictors for readmissions among Hispanics. Conclusion CTP classes B and C, among other factors, were the major predictors for hospital readmissions in Hispanics with HCV-related cirrhosis. The majority of these readmissions were due to HE and variceal hemorrhage. PMID:27708520

Modified CLIP with objective liver reserve assessment retains prognosis prediction for patients with advanced hepatocellular carcinoma.

PubMed

Shao, Yu-Yun; Liu, Tsung-Hao; Lee, Ying-Hui; Hsu, Chih-Hung; Cheng, Ann-Lii

2016-07-01

The Cancer of the Liver Italian Program (CLIP) score is a commonly used staging system for hepatocellular carcinoma (HCC) helpful with predicting prognosis of advanced HCC. CLIP uses the Child-Turcotte-Pugh (CTP) score to evaluate liver reserve. A new scoring system, the albumin-bilirubin (ALBI) grade, has been proposed as they objectively evaluate liver reserve. We examined whether the modification of CLIP with ALBI retained its prognosis prediction for patients with advanced HCC. We included patients who received first-line antiangiogenic therapy for advanced HCC. Liver reserve was assessed using CTP and ALBI scores, which were then incorporated into CLIP and ALBI-CLIP, respectively. To assess their efficacies of prognostic prediction, the Cox's proportional hazard model and concordance indexes were used. A total of 142 patients were included; 137 of them were classified CTP A and 5 patients CTP B. Patients could be divided into four or five groups with different prognosis according to CLIP and ALBI-CLIP, respectively. Higher R(2) (0.249 vs 0.216) and lower Akaike information criterion (995.0 vs 1001.1) were observed for ALBI-CLIP than for CLIP in the Cox's model predicting overall survival. ALBI-CLIP remained an independent predictor for overall survival when CLIP and ALBI-CLIP were simultaneously incorporated in Cox's models allowing variable selection with adjustment for hepatitis etiology, treatment, and performance status. The concordance index was also higher for ALBI-CLIP than for CLIP (0.724 vs 0.703). Modification of CLIP scoring with ALBI, which objectively assesses liver reserve, retains and might have improved prognosis prediction for advanced HCC. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Antipyrimidine effects of five different pyrimidine de novo synthesis inhibitors in three head and neck cancer cell lines.

PubMed

Peters, Godefridus J

2018-05-03

The pyrimidine de novo nucleotide synthesis consists of 6 sequential steps. Various inhibitors against these enzymes have been developed and evaluated in the clinic for their potential anticancer activity: acivicin inhibits carbamoyl-phosphate-synthase-II, N-(phosphonacetyl)-L- aspartate (PALA) inhibits aspartate-transcarbamylase, Brequinar sodium and dichloroallyl-lawsone (DCL) inhibit dihydroorotate-dehydrogenase, and pyrazofurin (PF) inhibits orotate-phosphoribosyltransferase. We compared their growth inhibition against 3 cell lines from head-and-neck-cancer (HEP-2, UMSCC-14B and UMSCC-14C) and related the sensitivity to their effects on nucleotide pools. In all cell lines Brequinar and PF were the most active compounds with IC50 (50% growth inhibition) values between 0.06-0.37 µM, Acivicin was as potent (IC50s 0.26-1 µM), but DCL was 20-31-fold less active. PALA was most inactive (24-128 µM). At equitoxic concentrations, all pure antipyrimidine de novo inhibitors depleted UTP and CTP after 24 hr exposure, which was most pronounced for Brequinar (between 6-10% of UTP left, and 12-36% CTP), followed by DCL and PF, which were almost similar (6-16% UTP and 12-27% CTP), while PALA was the least active compound (10-70% UTP and 13-68% CTP). Acivicin is a multi-target inhibitor of more glutamine requiring enzymes (including GMP synthetase) and no decrease of UTP was found, but a pronounced decrease in GTP (31-72% left). In conclusion, these 5 inhibitors of the pyrimidine de novo nucleotide synthesis varied considerably in their efficacy and effect on pyrimidine nucleotide pools. Inhibitors of DHO-DH were most effective suggesting a primary role of this enzyme in controlling pyrimidine nucleotide pools.

Radiation concurrent with gemcitabine for locally advanced head and neck cancer: a phase I trial and intracellular drug incorporation study.

PubMed

Eisbruch, A; Shewach, D S; Bradford, C R; Littles, J F; Teknos, T N; Chepeha, D B; Marentette, L J; Terrell, J E; Hogikyan, N D; Dawson, L A; Urba, S; Wolf, G T; Lawrence, T S

2001-02-01

To examine the feasibility and dose-limiting toxicity (DLT) of once-weekly gemcitabine at doses predicted in preclinical studies to produce radiosensitization, concurrent with a standard course of radiation for locally advanced head and neck cancer. Tumor incorporation of gemcitabine triphosphate (dFdCTP) was measured to assess whether adequate concentrations were achieved at each dose level. Twenty-nine patients with unresectable head and neck cancer received a course of radiation (70 Gy over 7 weeks, 5 days weekly) concurrent with weekly infusions of low-dose gemcitabine. Tumor biopsies were performed after the first gemcitabine infusion (before radiation started), and the intracellular concentrations of dFdCTP were measured. Severe acute and late mucosal and pharyngeal-related DLT required de-escalation of gemcitabine dose in successive patient cohorts receiving dose levels of 300 mg/m(2)/wk, 150 mg/m(2)/wk, and 50 mg/m(2)/wk. No DLT was observed at 10 mg/m(2)/wk. The rate of endoscopy- and biopsy-assessed complete tumor response was 66% to 87% in the various cohorts. Tumor dFdCTP levels were similar in patients receiving 50 to 300 mg/m(2) (on average, 1.55 pmol/mg, SD 1.15) but were barely or not detectable at 10 mg/m(2). A high rate of acute and late mucosa-related DLT and a high rate of complete tumor response were observed in this regimen at the dose levels of 50 to 300 mg/m(2), which also resulted in similar, subcytotoxic intracellular dFdCTP concentrations. These results demonstrate significant tumor and normal tissue radiosensitization by low-dose gemcitabine. Different regimens of combined radiation and gemcitabine should be evaluated, based on newer preclinical data promising an improved therapeutic ratio.

Efficacy and Safety of the Biosimilar Infliximab CT-P13 Treatment in Inflammatory Bowel Diseases: A Prospective, Multicentre, Nationwide Cohort.

PubMed

Gecse, Krisztina B; Lovász, Barbara D; Farkas, Klaudia; Banai, János; Bene, László; Gasztonyi, Beáta; Golovics, Petra Anna; Kristóf, Tünde; Lakatos, László; Csontos, Ágnes Anna; Juhász, Márk; Nagy, Ferenc; Palatka, Károly; Papp, Mária; Patai, Árpád; Lakner, Lilla; Salamon, Ágnes; Szamosi, Tamás; Szepes, Zoltán; Tóth, Gábor T; Vincze, Áron; Szalay, Balázs; Molnár, Tamás; Lakatos, Péter L

2016-02-01

Biosimilar infliximab CT-P13 is approved for all indications of the originator product in Europe. Prospective data on its efficacy, safety, and immunogenicity in inflammatory bowel diseases are lacking. A prospective, nationwide, multicentre, observational cohort was designed to examine the efficacy, safety, and immunogenicity of CT-P13 infliximab biosimilar in the induction treatment of Crohn's disease [CD] and ulcerative colitis [UC]. Demographic data were collected and a harmonised monitoring strategy was applied. Early clinical remission, response, and early biochemical response were evaluated at Week 14, steroid-free clinical remission was evaluated at Week 30. Therapeutic drug level was monitored using a conventional enzyme-linked immunosorbent assay. In all, 210 consecutive inflammatory bowel disease [126 CD and 84 UC] patients were included in the present cohort. At Week 14, 81.4% of CD and 77.6% of UC patients showed clinical response and 53.6% of CD and 58.6% of UC patients were in clinical remission. Clinical remission rates at Week 14 were significantly higher in CD and UC patients who were infliximab naïve, compared with those with previous exposure to the originator compound [p < 0.05]. Until Week 30, adverse events were experienced in 17.1% of all patients. Infusion reactions and infectious adverse events occurred in 6.6% and 5.7% of all patients, respectively. This prospective multicentre cohort shows that CT-P13 is safe and effective in the induction of clinical remission and response in both CD and UC. Patients with previous infliximab exposure exhibited decreased response rates and were more likely to develop allergic reactions. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Intravenous thrombolysis in ischemic stroke with unknown onset using CT perfusion.

PubMed

Cortijo, E; García-Bermejo, P; Calleja, A I; Pérez-Fernández, S; Gómez, R; del Monte, J M; Reyes, J; Arenillas, J F

2014-03-01

Acute ischemic stroke patients with unclear onset time presenting >4.5 h from last-seen-normal (LSN) time are considered late patients and excluded from i.v. thrombolysis. We aimed to evaluate whether this subgroup of patients is different from patients presenting >4.5 h from a witnessed onset, in terms of eligibility and response to computed tomography perfusion (CTP)-guided i.v. thrombolysis. We prospectively studied consecutive acute non-lacunar middle cerebral artery (MCA) ischemic stroke patients presenting >4.5 h from LSN. All patients underwent multimodal CT and were considered eligible for i.v. thrombolysis according to CTP criteria. Two patient groups were established based on the knowledge of the stroke onset time. We compared the proportion of candidates suitable for intravenous thrombolysis between both groups, and their outcome after thrombolytic therapy. Among 147 MCA ischemic stroke patients presenting >4.5 h from LSN, stroke onset was witnessed in 74 and unknown in 73. Thirty-seven (50%) patients in the first group and 32 (44%) in the second met CTP criteria for thrombolysis (P = 0.7). Baseline variables were comparable between both groups with the exception of age, which was higher in the unclear onset group. The rates of early neurological improvement (54.1% vs 46.9%), 2-h MCA recanalization (43.5% vs 37%), symptomatic hemorrhagic transformation (3% vs 0%) and good 3-month functional outcome (62.2% vs 56.3%) did not differ significantly between both groups. Delayed stroke patients with unknown onset time were no different than patients >4.5 h regarding eligibility and response to CTP-based i.v. thrombolysis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Gear Fault Detection Effectiveness as Applied to Tooth Surface Pitting Fatigue Damage

NASA Technical Reports Server (NTRS)

Lewicki, David G.; Dempsey, Paula J.; Heath, Gregory F.; Shanthakumaran, Perumal

2009-01-01

A study was performed to evaluate fault detection effectiveness as applied to gear tooth pitting fatigue damage. Vibration and oil-debris monitoring (ODM) data were gathered from 24 sets of spur pinion and face gears run during a previous endurance evaluation study. Three common condition indicators (RMS, FM4, and NA4) were deduced from the time-averaged vibration data and used with the ODM to evaluate their performance for gear fault detection. The NA4 parameter showed to be a very good condition indicator for the detection of gear tooth surface pitting failures. The FM4 and RMS parameters performed average to below average in detection of gear tooth surface pitting failures. The ODM sensor was successful in detecting a significant amount of debris from all the gear tooth pitting fatigue failures. Excluding outliers, the average cumulative mass at the end of a test was 40 mg.

Pitting failure of copper pipings for emergency fire sprinkler in ground water

NASA Astrophysics Data System (ADS)

Baek, Seung-won; Lee, Jong-kwon; Kim, Jong-jip; Kim, Kyung-ja

2015-05-01

The possibility of microbiologically influenced corrosion was investigated in the early pitted copper pipes. The pipes were installed for less than 6 months as an immergency fire sprinkler. The bacteria were cultured by sampling of corrosion by-product near pits on failed copper pipes for the aerobic as well as anaerobic bacteria. However, only aerobic bacteria was found, which were Micrococcus Luteus and Bacillus sp.. The corrosion rate of copper pipes were studied by weight loss in the groundwater and polarization method. In immersion test as well as the electrochemical polarization test in ground water, only Micrococcus Luteus could activate corrosion of copper by 20% and 15%, respectively. On the other hand, Bacillus sp. showed little effect on corrosion in the above two tests. The shape and characteristics of failed copper pipes as well as simulated copper were investigated using stereoscope, optical microscopy, scanning electron microscope and EDS. The cause of pits were discussed, related with the dissolved copper concentrations, pH, and optical density. It could be concluded that the early failure of copper pipings could be ascribed to the acceration of copper in the presence of bacteria, i.e., Micrococcus Luteus.

The Python pit organ: imaging and immunocytochemical analysis of an extremely sensitive natural infrared detector.

PubMed

Grace, M S; Church, D R; Kelly, C T; Lynn, W F; Cooper, T M

1999-01-01

The Python infrared-sensitive pit organ is a natural infrared imager that combines high sensitivity, ambient temperature function, microscopic dimensions, and self-repair. We are investigating the spectral sensitivity and signal transduction process in snake infrared-sensitive neurons, neither of which is understood. For example, it is unknown whether infrared receptor neurons function on a thermal or a photic mechanism. We imaged pit organs in living Python molurus and Python regius using infrared-sensitive digital video cameras. Pit organs were significantly more absorptive and/or emissive than surrounding tissues in both 3-5 microns and 8-12 microns wavelength ranges. Pit organs exhibited greater absorption/emissivity in the 8-12 microns range than in the 3-5 microns range. To directly test the relationship between photoreceptors and pit organ infrared-sensitive neurons, we performed immunocytochemistry using antisera directed against retinal photoreceptor opsins. Retinal photoreceptors were labeled with antisera specific for retinal opsins, but these antisera failed to label terminals of infrared-sensitive neurons in the pit organ. Infrared-receptive neurons were also distinguished from retinal photoreceptors on the basis of their calcium-binding protein content. These results indicate that the pit organ absorbs infrared radiation in two major atmospheric transmission windows, one of which (8-12 microns) matches emission of targeted prey, and that infrared receptors are biochemically distinct from retinal photoreceptors. These results also provide the first identification of prospective biochemical components of infrared signal transduction in pit organ receptor neurons.

Taguchi Optimization of Pulsed Current GTA Welding Parameters for Improved Corrosion Resistance of 5083 Aluminum Welds

NASA Astrophysics Data System (ADS)

Rastkerdar, E.; Shamanian, M.; Saatchi, A.

2013-04-01

In this study, the Taguchi method was used as a design of experiment (DOE) technique to optimize the pulsed current gas tungsten arc welding (GTAW) parameters for improved pitting corrosion resistance of AA5083-H18 aluminum alloy welds. A L9 (34) orthogonal array of the Taguchi design was used, which involves nine experiments for four parameters: peak current ( P), base current ( B), percent pulse-on time ( T), and pulse frequency ( F) with three levels was used. Pitting corrosion resistance in 3.5 wt.% NaCl solution was evaluated by anodic polarization tests at room temperature and calculating the width of the passive region (∆ E pit). Analysis of variance (ANOVA) was performed on the measured data and S/ N (signal to noise) ratios. The "bigger is better" was selected as the quality characteristic (QC). The optimum conditions were found as 170 A, 85 A, 40%, and 6 Hz for P, B, T, and F factors, respectively. The study showed that the percent pulse-on time has the highest influence on the pitting corrosion resistance (50.48%) followed by pulse frequency (28.62%), peak current (11.05%) and base current (9.86%). The range of optimum ∆ E pit at optimum conditions with a confidence level of 90% was predicted to be between 174.81 and 177.74 mVSCE. Under optimum conditions, the confirmation test was carried out, and the experimental value of ∆ E pit of 176 mVSCE was in agreement with the predicted value from the Taguchi model. In this regard, the model can be effectively used to predict the ∆ E pit of pulsed current gas tungsten arc welded joints.

The Western Environmental Technology Office (WETO), Butte, Montana. Technology summary

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

NONE

1996-03-01

The Western Environmental Technology Office (WETO) is a multi-purpose engineering test facility located in Butte, Montana, and is managed by MSE, Inc. WETO seeks to contribute to environmental research by emphasizing projects to develop heavy metals removal and recovery processes, thermal vitrification systems, and waste minimization/pollution prevention technologies. WETO`s environmental technology research and testing activities focus on the recovery of usable resources from waste. In one of WETO`s areas of focus, groundwater contamination, water from the Berkeley Pit, located near the WETO site, is being used in demonstrations directed toward the recovery of potable water and metal from the heavymore » metal-bearing water. The Berkeley Pit is part of an inactive copper mine near Butte that was once part of the nation`s largest open-pit mining operation. The Pit contains approximately 25 billion gallons of Berkeley Pit groundwater and surface water containing many dissolved minerals. As part of DOE/OST`s Resource Recovery Project (RRP), technologies are being demonstrated to not only clean the contaminated water but to recover metal values such as copper, zinc, and iron with an estimated gross value of more than $100 million. When recovered, the Berkeley Pit waters could benefit the entire Butte valley with new water resources for fisheries, irrigation, municipal, and industrial use. At WETO, the emphasis is on environmental technology development and commercialization activities, which will focus on mine cleanup, waste treatment, resource recovery, and water resource management.« less

Simulations and measurements of artificial cracks and pits in flat stainless steel plates using tone burst eddy-current thermography (TBET)

NASA Astrophysics Data System (ADS)

Libin, M. N.; Balasubramaniam, Krishnan; Maxfield, B. W.; Krishnamurthy, C. V.

2013-01-01

Tone Burst Eddy current Thermography (TBET) is a new hybrid, non-contacting, Non-Destructive Evaluation (NDE) method which employs a combination of Pulsed Eddy current Thermography (PEC) and Thermographic Non-Destructive Evaluation (TNDE). For understanding the influence of cracking and pitting on heat generation and flow within a metallic body, a fundamental knowledge of the detailed induced current density distribution in the component under test is required. This information enables us to calculate the amount of heat produced by the defects and how that heat diffuses to the surface where it is imaged. This paper describes simulation work done for artificial pits and cracks within pits on the far surface of poorly conducting metals like stainless steel. The first phase of this investigation simulates the transient thermal distribution for artificial 2D pit and crack-like defects using the finite element package COMSOL multi-physics with the AC/DC module and general heat transfer. Considering the reflection measurement geometry where thermal excitation and temperature monitoring are on the same surface, pitting reduces the material volume thereby contributing to a larger temperature rise for the same thermal energy input. A crack within a pit gives a further increase in temperature above the pure pit baseline. The tone burst frequency can be changed to obtain approximately uniform heating (low frequency) or heating of a thin region at the observation surface. Although front surface temperature changes due to 10% deep far-side pits in a 6 mm thick plate can be measured, it is not yet clear whether a 20% deep crack within this pit can be discriminated against the background. Both simulations and measurements will be presented. The objective of this work is to determine whether the TBET method is suitable for the detection and characterization of far side pitting, cracking and cracks within those pits.

Influence of Stepped Osteotomy on Primary Stability of Implants Inserted in Low-Density Bone Sites: An In Vitro Study.

PubMed

Degidi, Marco; Daprile, Giuseppe; Piattelli, Adriano

The aims of this study were to evaluate the ability of a stepped osteotomy to improve dental implant primary stability in low-density bone sites and to investigate possible correlations between primary stability parameters. The study was performed on fresh humid bovine bone classified as type III. The test group consisted of 30 Astra Tech EV implants inserted following the protocol provided by the manufacturer. The first control group consisted of 30 Astra Tech EV implants inserted in sites without the underpreparation of the apical portion. The second control group consisted of 30 Astra Tech TX implants inserted following the protocol provided by the manufacturer. Implant insertion was performed at the predetermined 30 rpm. The insertion torque data were recorded and exported as a curve; using a trapezoidal integration technique, the area underlying the curve was calculated: this area represents the variable torque work (VTW). Peak insertion torque (pIT) and resonance frequency analysis (RFA) were also recorded. A Mann-Whitney test showed that the mean VTW was significantly higher in the test group compared with the first control and second control groups; furthermore, statistical analysis showed that pIT also was significantly higher in the test group compared with the first and second control groups. Analyzing RFA values, only the difference between the test group and second control group showed statistical significance. Pearson correlation analysis showed a very strong positive correlation between pIT and VTW values in all groups; furthermore, it showed a positive correlation between pIT and RFA values and between VTW and RFA values only in the test group. Within the limitations of an in vitro study, the results show that stepped osteotomy can be a viable method to improve implant primary stability in low-density bone sites, and that, when a traditional osteotomy method is performed, RFA presents no correlation with pIT and VTW.

Geophysical investigation, Salmon Site, Lamar County, Mississippi

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

NONE

Geophysical surveys were conducted in 1992 and 1993 on 21 sites at the Salmon Site (SS) located in Lamar County, Mississippi. The studies are part of the Remedial Investigation/Feasibility Study (RI/FS) being conducted by IT Corporation for the U.S. Department of Energy (DOE). During the 1960s, two nuclear devices and two chemical tests were detonated 826 meters (in) (2710 feet [ft]) below the ground surface in the salt dome underlying the SS. These tests were part of the Vela Uniform Program conducted to improve the United States capability to detect, identify, and locate underground nuclear detonations. The RI/FS is beingmore » conducted to determine if any contamination is migrating from the underground shot cavity in the salt dome and if there is any residual contamination in the near surface mud and debris disposal pits used during the testing activities. The objective of the surface geophysical surveys was to locate buried debris, disposal pits, and abandoned mud pits that may be present at the site. This information will then be used to identify the locations for test pits, cone penetrometer tests, and drill hole/monitor well installation. The disposal pits were used during the operation of the test site in the 1960s. Vertical magnetic gradient (magnetic gradient), electromagnetic (EM) conductivity, and ground-penetrating radar (GPR) surveys were used to accomplish these objectives. A description of the equipment used and a theoretical discussion of the geophysical methods are presented Appendix A. Because of the large number of figures relative to the number of pages of text, the geophysical grid-location maps, the contour maps of the magnetic-gradient data, the contour maps of the EM conductivity data, and the GPR traverse location maps are located in Appendix B, Tabs I through 22. In addition, selected GPR records are located in Appendix C.« less

Fabrication of Nanoscale Pits with High Throughput on Polymer Thin Film Using AFM Tip-Based Dynamic Plowing Lithography

NASA Astrophysics Data System (ADS)

He, Yang; Geng, Yanquan; Yan, Yongda; Luo, Xichun

2017-09-01

We show that an atomic force microscope (AFM) tip-based dynamic plowing lithography (DPL) approach can be used to fabricate nanoscale pits with high throughput. The method relies on scratching with a relatively large speed over a sample surface in tapping mode, which is responsible for the separation distance of adjacent pits. Scratching tests are carried out on a poly(methyl methacrylate) (PMMA) thin film using a diamond-like carbon coating tip. Results show that 100 μm/s is the critical value of the scratching speed. When the scratching speed is greater than 100 μm/s, pit structures can be generated. In contrast, nanogrooves can be formed with speeds less than the critical value. Because of the difficulty of breaking the molecular chain of glass-state polymer with an applied high-frequency load and low-energy dissipation in one interaction of the tip and the sample, one pit requires 65-80 penetrations to be achieved. Subsequently, the forming process of the pit is analyzed in detail, including three phases: elastic deformation, plastic deformation, and climbing over the pile-up. In particular, 4800-5800 pits can be obtained in 1 s using this proposed method. Both experiments and theoretical analysis are presented that fully determine the potential of this proposed method to fabricate pits efficiently.

Fabrication of Nanoscale Pits with High Throughput on Polymer Thin Film Using AFM Tip-Based Dynamic Plowing Lithography.

PubMed

He, Yang; Geng, Yanquan; Yan, Yongda; Luo, Xichun

2017-09-22

We show that an atomic force microscope (AFM) tip-based dynamic plowing lithography (DPL) approach can be used to fabricate nanoscale pits with high throughput. The method relies on scratching with a relatively large speed over a sample surface in tapping mode, which is responsible for the separation distance of adjacent pits. Scratching tests are carried out on a poly(methyl methacrylate) (PMMA) thin film using a diamond-like carbon coating tip. Results show that 100 μm/s is the critical value of the scratching speed. When the scratching speed is greater than 100 μm/s, pit structures can be generated. In contrast, nanogrooves can be formed with speeds less than the critical value. Because of the difficulty of breaking the molecular chain of glass-state polymer with an applied high-frequency load and low-energy dissipation in one interaction of the tip and the sample, one pit requires 65-80 penetrations to be achieved. Subsequently, the forming process of the pit is analyzed in detail, including three phases: elastic deformation, plastic deformation, and climbing over the pile-up. In particular, 4800-5800 pits can be obtained in 1 s using this proposed method. Both experiments and theoretical analysis are presented that fully determine the potential of this proposed method to fabricate pits efficiently.

Optimizing the physical conditioning of the NASCAR sprint cup pit crew athlete.

PubMed

Ferguson, David P; Davis, Adam M; Lightfoot, J Timothy

2015-03-01

Stock car racing is the largest spectator sport in the United States. As a result, National Association for Stock Car Automobile Racing (NASCAR) Sprint Cup teams have begun to invest in strength and conditioning programs for their pit crew athletes. However, there is limited knowledge regarding the physical characteristics of elite NASCAR pit crew athletes, how the NASCAR Sprint Cup season affects basic physiological parameters such as body composition, and what is the most appropriate physical training program that meets the needs of a pit crew athlete. We conducted 3 experiments involving Sprint Cup motorsport athletes to determine predictors of success at the elite level, seasonal physiological changes, and appropriate physical training programs. Our results showed that hamstring flexibility (p = 0.015) and the score on the 2-tire front run test (p = 0.012) were significant predictors of NASCAR Sprint Cup Pit Crew athlete performance. Additionally, during the off season, pit crew athletes lost lean body mass, which did not return until the middle of the season. Therefore, a strength and conditioning program was developed to optimize pit crew athlete performance throughout the season. Implementation of this strength and conditioning program in 1 NASCAR Sprint Cup team demonstrated that pit crew athletes were able to prevent lean body mass loss and have increased muscle power output from the start of the season to the end of the season.

Molecular characterization of the Salmonella typhi StpA protein that is related to both Yersinia YopE cytotoxin and YopH tyrosine phosphatase.

PubMed

Arricau, N; Hermant, D; Waxin, H; Popoff, M Y

1997-01-01

Analysis of the nucleotide sequence of a 4-kb DNA fragment located between the sip and iag loci on Salmonella typhi chromosome revealed three open reading frames, termed sipF, ctpA and stpA. The 82-amino-acid (aa) sipF product showed extensive similarity to the lacP protein from S. typhimurium. The StpA protein (535 aa) exhibited significant similarity to both Yersinia enterocolitica YopE cytotoxin and YopH tyrosine phosphatase. The CtpA polypeptide (130 aa) might be the molecular chaperone of the StpA protein.

Mechanism of error-free DNA synthesis across N1-methyl-deoxyadenosine by human DNA polymerase-ι

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

Jain, Rinku; Choudhury, Jayati Roy; Buku, Angeliki

N1-methyl-deoxyadenosine (1-MeA) is formed by methylation of deoxyadenosine at the N1 atom. 1-MeA presents a block to replicative DNA polymerases due to its inability to participate in Watson-Crick (W-C) base pairing. Here we determine how human DNA polymerase-ι (Polι) promotes error-free replication across 1-MeA. Steady state kinetic analyses indicate that Polι is ~100 fold more efficient in incorporating the correct nucleotide T versus the incorrect nucleotide C opposite 1-MeA. To understand the basis of this selectivity, we determined ternary structures of Polι bound to template 1-MeA and incoming dTTP or dCTP. In both structures, template 1-MeA rotates to the synmore » conformation but pairs differently with dTTP versus dCTP. Thus, whereas dTTP partakes in stable Hoogsteen base pairing with 1-MeA, dCTP fails to gain a “foothold” and is largely disordered. Together, our kinetic and structural studies show how Polι maintains discrimination between correct and incorrect incoming nucleotide opposite 1-MeA in preserving genome integrity.« less

Frequency and Voltage Dependence of the Dielectrophoretic Trapping of Short Lengths of DNA and dCTP in a Nanopipette

PubMed Central

Ying, Liming; White, Samuel S.; Bruckbauer, Andreas; Meadows, Lisa; Korchev, Yuri E.; Klenerman, David

2004-01-01

The study of the properties of DNA under high electric fields is of both fundamental and practical interest. We have exploited the high electric fields produced locally in the tip of a nanopipette to probe the motion of double- and single-stranded 40-mer DNA, a 1-kb single-stranded DNA, and a single-nucleotide triphosphate (dCTP) just inside and outside the pipette tip at different frequencies and amplitudes of applied voltages. We used dual laser excitation and dual color detection to simultaneously follow two fluorophore-labeled DNA sequences with millisecond time resolution, significantly faster than studies to date. A strong trapping effect was observed during the negative half cycle for all DNA samples and also the dCTP. This effect was maximum below 1 Hz and decreased with higher frequency. We assign this trapping to strong dielectrophoresis due to the high electric field and electric field gradient in the pipette tip. Dielectrophoresis in electrodeless tapered nanostructures has potential applications for controlled mixing and manipulation of short lengths of DNA and other biomolecules, opening new possibilities in miniaturized biological analysis. PMID:14747337

Advances in Behavioral Laboratory Methods that Inform Tobacco Regulatory Science: A TCORS Working Group Special Issue

PubMed Central

Wright, M. Jerry; Valentine, Gerald

2017-01-01

Objective The 2009 Family Smoking Prevention and Tobacco Control Act (TCA) created unprecented enabling conditions for establishing national regulatory policy that reduces the burden of public health and societal problems associated with tobacco product use. The Center for Tobacco Products (CTP), created by the FDA to implement the TCA, developed a first-of-its-kind FDA/National Institutes of Health (NIH) collaborative program to fund Tobacco Centers of Regulatory Science (TCORS). Methods To assist the TCORS with addressing research priorites, working groups (WGs) comprised of FDA-CTP liasions and TCORS investigators were formed. Under the direction of the Center for Evaluation and Coordination of Trainin and Research (CECTR), the TCORS WGs seek to develop tangible work products in their respective areas of focus. Results The focus of the behavioral pharmacology WG evolved from publishing a narrow paper on behavioral methods in electronic cigarette research to a collection of papers on advances in behavioral laboratory methods that may inform tobacco regulatory science. Conclusion This Special Issue contains articles that address all of the CTP research priorities and demonstrates how advances in behavioral laboratory methods made by TCORS investigators can inform FDA efforst to regulate tobacco products. PMID:29152546

Assessment of Pre- and Post-Operative Cerebral Perfusion in Anterior Circulation Intracranial Aneurysm Clipping Patients at Hospital Sungai Buloh Using CT Perfusion Scan and Correlations to Fisher, Navarro and WFNS Scores.

PubMed

Ghani, Ailani Ab; Nayan, Saiful Azli Mat; Kandasamy, Regunath; Ghani, Abdul Rahman Izani; Rosman, Azmin Kass

2017-02-01

Intracranial aneurysms may rupture and are typically associated with high morbidity and mortality, commonly due to vasospasm after rupture. Once the aneurysm ruptures, the patient's cerebral blood flow may be disturbed during the acute phase, affecting cerebral circulation and thus cerebral perfusion prior to the onset of vasospasm. Fisher and Navarro scores are used to predict vasospasm, while World Federation of Neurosurgical Societies (WFNS) scores are used to predict patient outcomes. Several score modifications are available to obtain higher sensitivity and specificity for the prediction of vasospasm development, but these scores are still unsuccessful. Alternatively, cerebral CT perfusion scan (CTP) is a non-invasive method for measuring cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) in regions of interests (ROI) to obtain the cerebral perfusion status as well as detecting vasospasm. A total of 30 patients' data with clipped anterior circulation intracranial aneurysms admitted to the hospital between 1 January 2013 and 30 June 2014, were collected from the hospital's electronic database. The data collected included patients' admissions demographic profiles, Fisher, Navarro and WFNS scores; and their immediate pre- and post-operative CTP parameters. This study found a significant increase in post-operative MTT (pre- and post-operative MTT) were 9.75 (SD = 1.31) and 10.44 (SD = 1.56) respectively, ( P < 0.001)) as well as a significant reduction in post-operative CBF (pre- and post-operative mean CBF were 195.29 (SD = 24.92) and 179.49 (SD = 31.17) respectively ( P < 0.001)). There were no significant differences in CBV. There were no significant correlations between the pre- and post-operative CTP parameters and Fisher, Navarro or WFNS scores. Despite the interest in using Fisher, Navarro and WFNS scores to predict vasospasm and patient outcomes for ruptured intracranial aneurysms, this study found no significant correlations between these scores in either pre- or post-operative CTP parameters. These results explain the disagreement in the field regarding the multiple proposed grading systems for vasospasm prediction. CTP measures more than just anatomical structures; therefore, it is more sensitive towards minor changes in cerebral perfusion that would not be detected by WFNS, Fisher or Navarro scores.

Learning From Falling

ERIC Educational Resources Information Center

Joh, Amy, S.; Adolph, Karen, E.

2006-01-01

Walkers fall frequently, especially during infancy. Children (15, 21, 27, 33, and 39 month-olds) and adults were tested in a novel foam pit paradigm to examine age-related changes in the relationship between falling and prospective control of locomotion. In trial 1, participants walked and fell into a deformable foam pit marked with distinct…

Modeling pitting corrosion of iron exposed to alkaline solutions containing nitrate and nitrite

NASA Astrophysics Data System (ADS)

Chen, Lifeng

2001-07-01

Pitting corrosion could be extremely serious for dilute high-level radioactive waste stored or processed in carbon steel tanks at the Savannah River Site. In these solutions, nitrate is an aggressive ion with respect to pitting of carbon steel while nitrite can be used as an inhibitor. Excessive additions of nitrite increase the risk of generating unstable nitrogen compounds during waste processing, and insufficient additions of nitrite could increase the risk of corrosion-induced failure. Thus there are strong incentives to obtain a fundamental understanding of the role of nitrite in pitting corrosion prevention with these solution chemistries. In this dissertation, both a 1-D and a 2-D model are used to study the pitting mechanism as a function of nitrite/nitrate ratios. The 1-D model used BAND(J) to test a reaction mechanism for the passivation behavior by comparing the predicted Open Circuit Potential (OCP) with OCP data from experiments at different NO2-/NO3- ratio. The model predictions are compared with Cyclic Potentiodynamic Polarization (CPP) experiments. A 2-D model was developed for the propagation of a pit in iron by writing subroutines for finite element software of GAMBIT and FIDAP. Geometrically distributed anodic and cathodic reactions are assumed. The results show three partial explanations describing the inhibition influence of nitrite to iron corrosion: the competing reduction reaction of nitrate to nitrite, the formation of Fe(OH)+, and the function of the porous film. The current distributions and the effect of porosity of the film on pH are also explained. The calculation results also show that rate of pit growth decreases as the pit diameter increases until it reaches a constant value. The profile of the local current density on the pit wall is parabolic for small pits and it changes to a linear distribution for large pits. The model predicts that addition of nitrite will decrease the production of ferrous ions and those can prevent iron from dissolving. Also nitrate ion will accumulate in the pit if not enough inhibitor is added to the solution, and this will accelerate pit growth.

A literature review of clinical tests for lumbar instability in low back pain: validity and applicability in clinical practice.

PubMed

Ferrari, Silvano; Manni, Tiziana; Bonetti, Francesca; Villafañe, Jorge Hugo; Vanti, Carla

2015-01-01

Several clinical tests have been proposed on low back pain (LBP), but their usefulness in detecting lumbar instability is not yet clear. The objective of this literature review was to investigate the clinical validity of the main clinical tests used for the diagnosis of lumbar instability in individuals with LBP and to verify their applicability in everyday clinical practice. We searched studies of the accuracy and/or reliability of Prone Instability Test (PIT), Passive Lumbar Extension Test (PLE), Aberrant Movements Pattern (AMP), Posterior Shear Test (PST), Active Straight Leg Raise Test (ASLR) and Prone and Supine Bridge Tests (PB and SB) in Medline, Embase, Cinahl, PubMed, and Scopus databases. Only the studies in which each test was investigated by at least one study concerning both the accuracy and the reliability were considered eligible. The quality of the studies was evaluated by QUADAS and QAREL scales. Six papers considering 333 LBP patients were included. The PLE was the most accurate and informative clinical test, with high sensitivity (0.84, 95% CI: 0.69 - 0.91) and high specificity (0.90, 95% CI: 0.85 -0.97). The diagnostic accuracy of AMP depends on each singular test. The PIT and the PST demonstrated by fair to moderate sensitivity and specificity [PIT sensitivity = 0.71 (95% CI: 0.51 - 0.83), PIT specificity = 0.57 (95% CI: 039 - 0.78); PST sensitivity = 0.50 (95% CI: 0.41 - 0.76), PST specificity = 0.48 (95% CI: 0.22 - 0.58)]. The PLE showed a good reliability (k = 0.76), but this result comes from a single study. The inter-rater reliability of the PIT ranged by slight (k = 0.10 and 0.04), to good (k = 0.87). The inter-rater reliability of the AMP ranged by slight (k = -0.07) to moderate (k = 0.64), whereas the inter-rater reliability of the PST was fair (k = 0.27). The data from the studies provided information on the methods used and suggest that PLE is the most appropriate tests to detect lumbar instability in specific LBP. However, due to the lack of available papers on other lumbar conditions, these findings should be confirmed with studies on non-specific LBP patients.

[Investigation on the phenomena of bacteria exceeding standards in rural pit water treated by ultrafiltration membrane].

PubMed

Yue, Yinling; Zhang, Lan; Ling, Bo

2011-11-01

To investigate the phenomenon of bacteria exceeding standards in rural pit water, which was intermittently operated by water pump equipped with ultrafiltration membrane, and to explore the solutions. Polyvinyl chloride (PVC) alloy capillary membranes combined with UV, disinfectant, one-way valve, water-seal, high water level-water tank and direct outlet were tested. The operation on water treatment was intermittent, simulating the ways of treating pit water in the rural. The combination modes of ultrafiltration membrane with UV, disinfectant and high water level-water tank are valid in solving the problem of high turbidity and microorganism of pit water stored in cellars, the quality of effluents was consistent with the requirements of the national standards. While the combination modes of ultrafiltration membrane with one-way valve or water-seal were less desirable, more bacteria in treated water than raw water were observed because of bacteria breeding on the membrane component. In order to avoid excessive bacteria in filtered pit water caused by intermittent operation, it is recommended that for the pit water in high water level water tanks, the ultrafiltration membranes should be cleaned with disinfectants on a regular basis. The effluent pit water from underground cellars should be disinfected with UV after ultrafiltration.

Nuclear Weapons: Comprehensive Test Ban Treaty

DTIC Science & Technology

2006-11-15

Unicorn ,” was conducted in a “down-hole” or vertical CRS-18 58 “Nanos Tours Nevada Test Site,” Daily Newsbulletin, Los Alamos National Laboratory...radioactive decay of aged plutonium would degrade weapon performance. Several SCEs have been used to support certification of the W88 pit. (A pit is the...tools and data that assess age -related complications and maintain the reliability and safety of the nation’s nuclear deterrent.”59 As they produce no

The effects of amphetamine sensitization on conditioned inhibition during a Pavlovian-instrumental transfer task in rats.

PubMed

Shiflett, Michael W; Riccie, Meaghan; DiMatteo, RoseMarie

2013-11-01

Psychostimulant sensitization heightens behavioral and motivational responses to reward-associated stimuli; however, its effects on stimuli associated with reward absence are less understood. We examined whether amphetamine sensitization alters performance during Pavlovian-instrumental transfer (PIT) to conditioned excitors and inhibitors. We further sought to characterize the effects of amphetamine sensitization on learning versus performance by exposing rats to amphetamine prior to Pavlovian training or between training and test. Adult male Long-Evans rats were given conditioned inhibition (A+/AX-) and Pavlovian (B+) training, followed by variable-interval instrumental conditioning. Rats were sensitized to D-amphetamine (2 mg/kg daily injections for 7 days) or served as non-exposed controls. Rats were given a PIT test, in which they were presented with stimulus B alone or in compound with the conditioned inhibitor (BX). During the PIT test, control rats significantly reduced instrumental responding on BX trials (to approximately 50 % of responding to B). Amphetamine sensitization prior to Pavlovian conditioning increased lever pressing on BX trials and reduced lever pressing on B trials compared to controls. Amphetamine sensitization between training and test increased lever pressing on B and BX trials compared to controls. No effects of sensitization were observed on conditioned food cup approach. Amphetamine sensitization increases instrumental responding during PIT to a conditioned inhibitor by enhancing the excitation of conditioned stimuli and reducing the inhibition of conditioned inhibitors.

MR imaging biomarkers for evaluating therapeutic effects shortly after near infrared photoimmunotherapy

PubMed Central

Nakamura, Yuko; Bernardo, Marcelino; Nagaya, Tadanobu; Sato, Kazuhide; Harada, Toshiko; Choyke, Peter L.; Kobayashi, Hisataka

2016-01-01

Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of antibodies for targeting tumors with the toxicity induced by photon absorbers after irradiation with NIR light. The purpose of this study was to determine if MR imaging can detect changes in the MR properties of tumor within several hours of NIR-PIT. A431 cells were injected subcutaneously in the right and left dorsi of 12 mice. Six days later, the mice were injected with a photon absorber, IR700, conjugated to panitumumab, an antibody targeting epidermal growth factor receptor. One day later, only right sided tumor was exposed to NIR light (treated tumor). MRI was performed 1 day before and 1-2 hours after NIR-PIT using gadofosveset for six mice and gadopentetate dimeglumine for another six mice. T2 relaxation times, the apparent diffusion coefficient (ADC) for the following combinations of b-values: 0-1000, 200-1000 and 500-1000 s/mm2 and enhancement indices were compared before and after NIR-PIT using a two-sided paired t-test. For treated tumors, T2 relaxation time increased after NIR-PIT (p < 0.01) and all three ADC values decreased after NIR-PIT (p < 0.01). Moreover, the enhancement area under the curve (AUC) using gadofosveset increased after NIR-PIT (p = 0.02). In conclusion, prolongation of T2, reductions in ADC and increased enhancement using gadofosveset are seen within 2 hours of NIR-PIT treatment of tumors. Thus, MRI can be a useful imaging biomarker for detecting early therapeutic changes after NIR-PIT. PMID:26885619

Limitation of the Cavitron technique by conifer pit aspiration.

PubMed

Beikircher, B; Ameglio, T; Cochard, H; Mayr, S

2010-07-01

The Cavitron technique facilitates time and material saving for vulnerability analysis. The use of rotors with small diameters leads to high water pressure gradients (DeltaP) across samples, which may cause pit aspiration in conifers. In this study, the effect of pit aspiration on Cavitron measurements was analysed and a modified 'conifer method' was tested which avoids critical (i.e. pit aspiration inducing) DeltaP. Four conifer species were used (Juniperus communis, Picea abies, Pinus sylvestris, and Larix decidua) for vulnerability analysis based on the standard Cavitron technique and the conifer method. In addition, DeltaP thresholds for pit aspiration were determined and water extraction curves were constructed. Vulnerability curves obtained with the standard method showed generally a less negative P for the induction of embolism than curves of the conifer method. Differences were species-specific with the smallest effects in Juniperus. Larix showed the most pronounced shifts in P(50) (pressure at 50% loss of conductivity) between the standard (-1.5 MPa) and the conifer (-3.5 MPa) methods. Pit aspiration occurred at the lowest DeltaP in Larix and at the highest in Juniperus. Accordingly, at a spinning velocity inducing P(50), DeltaP caused only a 4% loss of conductivity induced by pit aspiration in Juniperus, but about 60% in Larix. Water extraction curves were similar to vulnerability curves indicating that spinning itself did not affect pits. Conifer pit aspiration can have major influences on Cavitron measurements and lead to an overestimation of vulnerability thresholds when a small rotor is used. Thus, the conifer method presented here enables correct vulnerability analysis by avoiding artificial conductivity losses.

A web-based institutional DICOM distribution system with the integration of the Clinical Trial Processor (CTP).

PubMed

Aryanto, K Y E; Broekema, A; Langenhuysen, R G A; Oudkerk, M; van Ooijen, P M A

2015-05-01

To develop and test a fast and easy rule-based web-environment with optional de-identification of imaging data to facilitate data distribution within a hospital environment. A web interface was built using Hypertext Preprocessor (PHP), an open source scripting language for web development, and Java with SQL Server to handle the database. The system allows for the selection of patient data and for de-identifying these when necessary. Using the services provided by the RSNA Clinical Trial Processor (CTP), the selected images were pushed to the appropriate services using a protocol based on the module created for the associated task. Five pipelines, each performing a different task, were set up in the server. In a 75 month period, more than 2,000,000 images are transferred and de-identified in a proper manner while 20,000,000 images are moved from one node to another without de-identification. While maintaining a high level of security and stability, the proposed system is easy to setup, it integrate well with our clinical and research practice and it provides a fast and accurate vendor-neutral process of transferring, de-identifying, and storing DICOM images. Its ability to run different de-identification processes in parallel pipelines is a major advantage in both clinical and research setting.

Synergistic use of MODIS cloud products and AIRS radiance measurements for retrieval of cloud parameters

NASA Astrophysics Data System (ADS)

Li, J.; Menzel, W.; Sun, F.; Schmit, T.

2003-12-01

The Moderate-Resolution Imaging Spectroradiometer (MODIS) and Atmospheric Infrared Sounder (AIRS) measurements from the Earth Observing System's (EOS) Aqua satellite will enable global monitoring of the distribution of clouds. MODIS is able to provide at high spatial resolution (1 ~ 5km) the cloud mask, surface and cloud types, cloud phase, cloud-top pressure (CTP), effective cloud amount (ECA), cloud particle size (CPS), and cloud water path (CWP). AIRS is able to provide CTP, ECA, CPS, and CWP within the AIRS footprint with much better accuracy using its greatly enhanced hyperspectral remote sensing capability. The combined MODIS / AIRS system offers the opportunity for cloud products improved over those possible from either system alone. The algorithm developed was applied to process the AIRS longwave cloudy radiance measurements; results are compared with MODIS cloud products, as well as with the Geostationary Operational Environmental Satellite (GOES) sounder cloud products, to demonstrate the advantage of synergistic use of high spatial resolution MODIS cloud products and high spectral resolution AIRS sounder radiance measurements for optimal cloud retrieval. Data from ground-based instrumentation at the Atmospheric Radiation Measurement (ARM) Program Cloud and Radiation Test Bed (CART) in Oklahoma were used for the validation; results show that AIRS improves the MODIS cloud products in certain cases such as low-level clouds.

Prevention of neural hypersensitivity after acute upper limb burns: Development and pilot of a cortical training protocol.

PubMed

Edgar, Dale; Zorzi, Lisa M; Wand, Ben M; Brockman, Nathalie; Griggs, Carolyn; Clifford, Matthew; Wood, Fiona

2011-06-01

Acute burn patients suffer pain and secondary hyperalgesia. This alters movement patterns and impairs function. Non-pharmacological methods of treatment are limited and lack rigorous testing and evidence for use. The treatment in this case series was designed to direct conscious attention to, and normalise sensation of, the injured limb in pain free way. The aim of the study was to describe a cortical training programme (CTP) in acute upper limb burn patients and to investigate the efficacy, safety and feasibility of the protocol. The study is a descriptive case series (n=6). Study tasks engaged sensory and motor nerves to influence the perception of the injured area. Visual and tactile inputs to maintain and, or normalise the homuncular map were central to the intervention. One patient, who commenced the study without resting pain, responded negatively. The remaining five patients had reduced pain and fear avoidance behaviours with associated improvement in arm function. The CTP approach is safe and feasible for use with acute burn patients where pain is reported at rest. Comparative studies are required to determine the relative efficacy of the program to usual interventions and the patients who may benefit from the technique. Copyright © 2011 Elsevier Ltd and ISBI. All rights reserved.

Cyclic Polarization Behavior of ASTM A537-Cl.1 Steel in the Vapor Space Above Simulated Waste

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

Wiersma, B

2004-11-01

An assessment of the potential degradation mechanisms of Types I and II High-Level Waste (HLW) Tanks determined that pitting corrosion and stress corrosion cracking were the two most significant degradation mechanisms. Specifically, nitrate induced stress corrosion cracking was determined to be the principal degradation mechanism for the primary tank steel of non-stress relieved tanks. Controls on the solution chemistry have been in place to preclude the initiation and propagation of degradation in the tanks. However, recent experience has shown that steel not in contact with the bulk waste solution or slurry, but exposed to the ''vapor space'' above the bulkmore » waste, may be vulnerable to the initiation and propagation of degradation, including pitting and stress corrosion cracking. A program to resolve the issues associated with potential vapor space corrosion is in place. The objective of the program is to develop understanding of vapor space (VSC) and liquid/air interface (LAIC) corrosion to ensure a defensible technical basis to provide accurate corrosion evaluations with regard to vapor space and liquid/air interface corrosion (similar to current evaluations). There are several needs for a technically defensible basis with sufficient understanding to perform these evaluations. These include understanding of the (1) surface chemistry evolution, (2) corrosion response through coupon testing, and (3) mechanistic understanding through electrochemical studies. Experimentation performed in FY02 determined the potential for vapor space and liquid/air interface corrosion of ASTM A285-70 and ASTM A537-Cl.1 steels. The material surface characteristics, i.e. mill-scale, polished, were found to play a key role in the pitting response. The experimentation indicated that the potential for limited vapor space and liquid/air interface pitting exists at 1.5M nitrate solution when using chemistry controls designed to prevent stress corrosion cracking. Experimentation performed in FY03 quantified pitting rates as a function of material surface characteristics, including mill-scale and defects within the mill-scale. Testing was performed on ASTM A537-Cl.1 (normalized) steel, the material of construction of the Type III HLW tanks. The pitting rates were approximately 3 mpy for exposure above inhibited solutions, as calculated from the limited exposure times. This translates to a penetration time of 166 years for a 0.5-in tank wall provided that the pitting rate remains constant and the bulk solution chemistry is maintained within the L3 limit. The FY04 testing consisted of electrochemical testing to potentially lend insight into the surface chemistry and further understand the corrosion mechanism in the vapor space. Electrochemical testing lends insight into the corrosion processes through the determination of current potential relationships. The results of the electrochemical testing performed during FY04 are presented here.« less

The Relationship Between Specific Pavlovian Instrumental Transfer and Instrumental Reward Probability

PubMed Central

Cartoni, Emilio; Moretta, Tania; Puglisi-Allegra, Stefano; Cabib, Simona; Baldassarre, Gianluca

2015-01-01

Goal-directed behavior is influenced by environmental cues: in particular, cues associated with a reward can bias action choice toward actions directed to that same reward. This effect is studied experimentally as specific Pavlovian-instrumental transfer (specific PIT). We have investigated the hypothesis that cues associated to an outcome elicit specific PIT by rising the estimates of reward probability of actions associated to that same outcome. In other words, cues reduce the uncertainty on the efficacy of instrumental actions. We used a human PIT experimental paradigm to test the effects of two different instrumental contingencies: one group of participants had a 33% chance of being rewarded for each button press, while another had a 100% chance. The group trained with 33% reward probability showed a stronger PIT effect than the 100% group, in line with the hypothesis that Pavlovian cues linked to an outcome work by reducing the uncertainty of receiving it. The 100% group also showed a significant specific PIT effect, highlighting additional factors that could contribute to specific PIT beyond the instrumental training contingency. We hypothesize that the uncertainty about reward delivery due to testing in extinction might be one of these factors. These results add knowledge on how goal-directed behavior is influenced by the presence of environmental cues associated with a reward: such influence depends on the probability that we have to reach a reward, namely when there is less chance of getting a reward we are more influenced by cues associated with it, and vice versa. PMID:26635645

The effects of amphetamine exposure on outcome-selective Pavlovian-instrumental transfer in rats

PubMed Central

Shiflett, Michael W.

2012-01-01

Rationale Repeated exposure to psychostimulants alters behavioral responses to reward-related cues; however, the motivational underpinnings of this effect have not been fully characterized. Objectives The following study was designed to examine how amphetamine sensitization affects performance in rats on a series of Pavlovian and operant tasks that distinguish between general-incentive and outcome-selective forms of conditioned responses. Methods Adult male rats underwent Pavlovian and instrumental training for food pellet rewards. Following training, rats were sensitized to d-amphetamine (2 mg/kg for 7 days). Rats were subsequently tested on an outcome-selective Pavlovian-instrumental transfer (PIT) task, an outcome-reinstatement task, and an outcome devaluation task. Additionally, in a separate experiment PIT was assessed in amphetamine-sensitized and control rats using a Pavlovian backward-conditioned stimulus. Results Repeated amphetamine exposure sensitized locomotor activity to acute amphetamine challenge. Amphetamine altered responses to CS presentations by increasing conditioned approach. During tests of PIT amphetamine-treated rats showed no outcome-selectivity in their responding, responding to a CS whether or not it shared a common outcome with the instrumental response. No effect of amphetamine sensitization was observed on tests of outcome-selective reinstatement by outcome delivery, or action selection based on outcome value. Amphetamine-sensitized rats showed impaired outcome-selective PIT to a backward CS but were unaltered in conditioned approach. Conclusions Amphetamine sensitization prevents outcome-selective responding during PIT, which is dissociable from amphetamine’s effects on conditioned approach. These data suggest fundamental alterations in how stimuli motivate action in addiction. PMID:22562522

The PIT-trap-A "model-free" bootstrap procedure for inference about regression models with discrete, multivariate responses.

PubMed

Warton, David I; Thibaut, Loïc; Wang, Yi Alice

2017-01-01

Bootstrap methods are widely used in statistics, and bootstrapping of residuals can be especially useful in the regression context. However, difficulties are encountered extending residual resampling to regression settings where residuals are not identically distributed (thus not amenable to bootstrapping)-common examples including logistic or Poisson regression and generalizations to handle clustered or multivariate data, such as generalised estimating equations. We propose a bootstrap method based on probability integral transform (PIT-) residuals, which we call the PIT-trap, which assumes data come from some marginal distribution F of known parametric form. This method can be understood as a type of "model-free bootstrap", adapted to the problem of discrete and highly multivariate data. PIT-residuals have the key property that they are (asymptotically) pivotal. The PIT-trap thus inherits the key property, not afforded by any other residual resampling approach, that the marginal distribution of data can be preserved under PIT-trapping. This in turn enables the derivation of some standard bootstrap properties, including second-order correctness of pivotal PIT-trap test statistics. In multivariate data, bootstrapping rows of PIT-residuals affords the property that it preserves correlation in data without the need for it to be modelled, a key point of difference as compared to a parametric bootstrap. The proposed method is illustrated on an example involving multivariate abundance data in ecology, and demonstrated via simulation to have improved properties as compared to competing resampling methods.

The PIT-trap—A “model-free” bootstrap procedure for inference about regression models with discrete, multivariate responses

PubMed Central

Thibaut, Loïc; Wang, Yi Alice

2017-01-01

Bootstrap methods are widely used in statistics, and bootstrapping of residuals can be especially useful in the regression context. However, difficulties are encountered extending residual resampling to regression settings where residuals are not identically distributed (thus not amenable to bootstrapping)—common examples including logistic or Poisson regression and generalizations to handle clustered or multivariate data, such as generalised estimating equations. We propose a bootstrap method based on probability integral transform (PIT-) residuals, which we call the PIT-trap, which assumes data come from some marginal distribution F of known parametric form. This method can be understood as a type of “model-free bootstrap”, adapted to the problem of discrete and highly multivariate data. PIT-residuals have the key property that they are (asymptotically) pivotal. The PIT-trap thus inherits the key property, not afforded by any other residual resampling approach, that the marginal distribution of data can be preserved under PIT-trapping. This in turn enables the derivation of some standard bootstrap properties, including second-order correctness of pivotal PIT-trap test statistics. In multivariate data, bootstrapping rows of PIT-residuals affords the property that it preserves correlation in data without the need for it to be modelled, a key point of difference as compared to a parametric bootstrap. The proposed method is illustrated on an example involving multivariate abundance data in ecology, and demonstrated via simulation to have improved properties as compared to competing resampling methods. PMID:28738071

Gear Fault Detection Effectiveness as Applied to Tooth Surface Pitting Fatigue Damage

NASA Technical Reports Server (NTRS)

Lewicki, David G.; Dempsey, Paula J.; Heath, Gregory F.; Shanthakumaran, Perumal

2010-01-01

A study was performed to evaluate fault detection effectiveness as applied to gear-tooth-pitting-fatigue damage. Vibration and oil-debris monitoring (ODM) data were gathered from 24 sets of spur pinion and face gears run during a previous endurance evaluation study. Three common condition indicators (RMS, FM4, and NA4 [Ed. 's note: See Appendix A-Definitions D were deduced from the time-averaged vibration data and used with the ODM to evaluate their performance for gear fault detection. The NA4 parameter showed to be a very good condition indicator for the detection of gear tooth surface pitting failures. The FM4 and RMS parameters perfomu:d average to below average in detection of gear tooth surface pitting failures. The ODM sensor was successful in detecting a significant 8lDOunt of debris from all the gear tooth pitting fatigue failures. Excluding outliers, the average cumulative mass at the end of a test was 40 mg.

National Program for Inspection of Non-Federal Dams. Pomeroy Dam (CT 00479), Thames River Basin, Stafford, Connecticut. Phase I Inspection Report.

DTIC Science & Technology

1981-02-01

probable maximum rainfall for this area is 24 inches in 6 hours for 10 square miles. Using Corps of Engineers I methods , this results in a PMF of...TES rrs r 5 TEST PIT 4 TEST PIT 5 & WACE ELEV 6ai0 XowACfe (LV 5?O.O SLIRFAC EL LV M547 SURfACE ELEVUEDO SunRFdCE ELEV4 jiimv af 09- 0-4 am to-~ rame wro

PiTS-1: Carbon Partitioning in Loblolly Pine after 13C Labeling and Shade Treatments

DOE Data Explorer

Warren, J. M.; Iversen, C. M.; Garten, Jr., C. T.; Norby, R. J.; Childs, J.; Brice, D.; Evans, R. M.; Gu, L.; Thornton, P.; Weston, D. J.

2013-01-01

The PiTS task was established with the objective of improving the C partitioning routines in existing ecosystem models by exploring mechanistic model representations of partitioning tested against field observations. We used short-term field manipulations of C flow, through 13CO2 labeling, canopy shading and stem girdling, to dramatically alter C partitioning, and resultant data are being used to test model representation of C partitioning processes in the Community Land Model (CLM4 or CLM4.5).

Genome-wide re-sequencing of multidrug-resistant Mycobacterium leprae Airaku-3.

PubMed

Singh, P; Benjak, A; Carat, S; Kai, M; Busso, P; Avanzi, C; Paniz-Mondolfi, A; Peter, C; Harshman, K; Rougemont, J; Matsuoka, M; Cole, S T

2014-10-01

Genotyping and molecular characterization of drug resistance mechanisms in Mycobacterium leprae enables disease transmission and drug resistance trends to be monitored. In the present study, we performed genome-wide analysis of Airaku-3, a multidrug-resistant strain with an unknown mechanism of resistance to rifampicin. We identified 12 unique non-synonymous single-nucleotide polymorphisms (SNPs) including two in the transporter-encoding ctpC and ctpI genes. In addition, two SNPs were found that improve the resolution of SNP-based genotyping, particularly for Venezuelan and South East Asian strains of M. leprae. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

Tunable multiband plasmonic response of indium antimonide touching microrings in the terahertz range.

PubMed

Moridsadat, Maryam; Golmohammadi, Saeed; Baghban, Hamed

2018-06-01

In this paper, we propose a terahertz (THz) plasmonic structure that supports three resonance modes, including the charge transfer plasmon (CTP), the bonding dipole-dipole plasmon, and the antibonding dipole-dipole plasmon, which can be strongly tuned by geometrical parameters, passively, and the temperature, actively. The structure exhibits a considerable thermal sensitivity of more than 0.01 THz/K. The introduced multiband and tunable THz plasmonic structures offer important applications in thermal switches, thermo-optical modulators, broadband filters, design of multifunctional molecules originating from the multiband specification of the proposed structure, and improvement in plasmonic sensor applications stemming from a detailed study of the CTP mode.

Space Shuttle Flight Support Motor no. 1 (FSM-1)

NASA Technical Reports Server (NTRS)

Hughes, Phil D.

1990-01-01

Space Shuttle Flight Support Motor No. 1 (FSM-1) was static test fired on 15 Aug. 1990 at the Thiokol Corporation Static Test Bay T-24. FSM-1 was a full-scale, full-duration static test fire of a redesigned solid rocket motor. FSM-1 was the first of seven flight support motors which will be static test fired. The Flight Support Motor program validates components, materials, and manufacturing processes. In addition, FSM-1 was the full-scale motor for qualification of Western Electrochemical Corporation ammonium perchlorate. This motor was subjected to all controls and documentation requirements CTP-0171, Revision A. Inspection and instrumentation data indicate that the FSM-1 static test firing was successful. The ambient temperature during the test was 87 F and the propellant mean bulk temperature was 82 F. Ballistics performance values were within the specified requirements. The overall performance of the FSM-1 components and test equipment was nominal.

Fabrication of anatomically tapered foveal pits for retinal phantoms for optical coherence tomography

NASA Astrophysics Data System (ADS)

Lee, Gary C. F.; Smith, Gennifer T.; Agrawal, Monica; Ellerbee, Audrey K.

2015-03-01

Optical Coherence Tomography (OCT) has become a standard tool for diagnosing retinal disease in many ophthalmology clinics. Nonetheless, the technical and clinical research communities still lack a standardized phantom that could aid in evaluating and normalizing the various scan protocols and OCT machines employed at different institutions. Existing retinal phantoms designed for OCT imaging mimic some important features of the retina, such as the thickness and scattering properties of its many layers. However, the morphology of the foveal pit and the visible tapering of the retinal layers underlying the surface surrounding the pit remains a challenge to replicate in current phantoms. Recent attempts at creating a realistic foveal pit include molding, ablation and laser etching but have not proved sufficient to replicate this particular anatomical feature. In this work, we demonstrate a new fabrication procedure that is capable of replicating the tapered appearance of the retinal layers near the foveal pit using a combination of spin-coating and replica molding. The ability to create an anatomically correct foveal pit will allow for a new phantom better suited for intra- and inter-system evaluation and for improved testing of retinal segmentation algorithms.

Fabrication of spherical mitigation pit on KH2PO4 crystal by micro-milling and modeling of its induced light intensification.

PubMed

Cheng, Jian; Chen, Mingjun; Liao, Wei; Wang, Haijun; Xiao, Yong; Li, Mingquan

2013-07-15

Micro-machining is the most promising method for KH(2)PO(4) crystal to mitigate the surface damage growth in high power laser system. In this work, spherical mitigation pit is fabricated by micro-milling with an efficient machining procedure. The light intensification caused by rear surface features before and after mitigation is numerically modeled based on the finite-difference time-domain method. The results indicate that the occurrence of total internal reflections should be responsible for the largest light intensification inside the crystal. For spherical pits after mitigation, the light intensification can be greatly alleviated by preventing the occurrence of total internal reflections. The light intensification caused by spherical mitigation pit is strongly dependent on the width-depth ratio and it is suggested that the width-depth ratio of spherical mitigation pit must be devised to be larger than 5.0 to achieve the minimal light intensification for the mitigation of surface damage growth. Laser damage tests for KH(2)PO(4) crystal validate that the laser damage resistance of initially damaged surface can be retrieved to near the level of ideal surface by replacing initial damage site with predesigned mitigation pit.

Selectable-Tip Corrosion-Testing Electrochemical Cell

NASA Technical Reports Server (NTRS)

Lomness, Janice; Hintze, Paul

2008-01-01

The figure depicts aspects of an electrochemical cell for pitting- corrosion tests of material specimens. The cell is designed to generate a region of corrosion having a pit diameter determined by the diameter of a selectable tip. The average depth of corrosion is controlled by controlling the total electric charge passing through the cell in a test. The cell is also designed to produce minimal artifacts associated with crevice corrosion. There are three selectable tips, having diameters of 0.1 in. (0.254 cm), 0.3 in. (0.762 cm), and 0.6 in. (1.524 cm), respectively.

Designing local solutions for emptying pit latrines in low-income urban settlements (Malawi)

NASA Astrophysics Data System (ADS)

Chipeta, W. C.; Holm, R. H.; Kamanula, J. F.; Mtonga, W. E.; de los Reyes, F. L.

2017-08-01

A lack of effective options in local technology poses challenges when onsite household sanitation facilities are eventually filled to capacity in unplanned settlement areas within Mzuzu City, located in northern Malawi. Vacuum trucks currently dominate the market but focus on emptying septic tanks in the more easily accessible planned settlement areas, rather than servicing the pit latrines common in unplanned settlement areas. As a result, households in the unplanned settlement areas within Mzuzu rely primarily on manual pit emptying (i.e., shoveling by hand) or digging a new pit latrine. These practices have associated health risks and are limited by space constraints. This research focused on filling the technological gap through the design, development, and testing of a pedal powered modified Gulper pump using locally available materials and fabrication. A modified pedal powered Gulper technology was developed and demonstrated to be capable of lifting fecal sludge from a depth of 1.5 m with a mean flow rate of 0.00058 m3/s. If the trash content was low, a typical pit latrine with a volume of 1-4 m3 could be emptied within 1-2 h. Based on the findings in our research Phase IV, the pedal powered Gulper modification is promising as a potential emptying technology for lined pit latrines in unplanned settlement areas. The success rate of the technology is about 17% (5 out 30 sampled lined pit latrines were successful) and reflects the difficulty in finding a single technology that can work well in all types of pit latrines with varying contents. We note that cost should not be the only design criteria and acknowledge the challenge of handling trash in pit latrines.

Effect of sulfur and magnesium on hot ductility and pitting corrosion for Inconel 690 alloy

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

Liu, K.; Zhang, B.; Zhang, S.

1995-12-31

A series of hot tensile tests has been performed to study the effect of sulfur and magnesium on hot ductility of Inconel 690 alloy. The hot ductility has been evaluated from the reduction of area in hot tensile tests using a Gleeble testing machine. The value of reduction in area decreased with increasing sulfur content in the temperature range from 900 C to 1,200 C. When sulfur content was larger than 0.0025%, a ductility dip appeared, and the greater the sulfur content, the deeper and wider the ductility dip. The Scanning Electron Microscope (SEM) analyses showed that the fracture appearancesmore » changed gradually from transgranular to intergranular with increasing sulfur content, meanwhile sulfur and titanium segregation were observed at grain boundaries. The ductility dip of 690 alloy with relatively higher sulfur content could be inhibited by adding appropriate amount of magnesium. However, excessive addition led to magnesium precipitation, which was detrimental to hot ductility. The pitting test has also been conducted and the results showed that pitting rate obviously increased with increasing sulfur content.« less

Optical Switching Using Transition from Dipolar to Charge Transfer Plasmon Modes in Ge2Sb2Te5 Bridged Metallodielectric Dimers

PubMed Central

Ahmadivand, Arash; Gerislioglu, Burak; Sinha, Raju; Karabiyik, Mustafa; Pala, Nezih

2017-01-01

Capacitive coupling and direct shuttling of charges in nanoscale plasmonic components across a dielectric spacer and through a conductive junction lead to excitation of significantly different dipolar and charge transfer plasmon (CTP) resonances, respectively. Here, we demonstrate the excitation of dipolar and CTP resonant modes in metallic nanodimers bridged by phase-change material (PCM) sections, material and electrical characteristics of which can be controlled by external stimuli. Ultrafast switching (in the range of a few nanoseconds) between amorphous and crystalline phases of the PCM section (here Ge2Sb2Te5 (GST)) allows for designing a tunable plasmonic switch for optical communication applications with significant modulation depth (up to 88%). Judiciously selecting the geometrical parameters and taking advantage of the electrical properties of the amorphous phase of the GST section we adjusted the extinction peak of the dipolar mode at the telecommunication band (λ~1.55 μm), which is considered as the OFF state. Changing the GST phase to crystalline via optical heating allows for direct transfer of charges through the junction between nanodisks and formation of a distinct CTP peak at longer wavelengths (λ~1.85 μm) far from the telecommunication wavelength, which constitutes the ON state. PMID:28205643

Optical Switching Using Transition from Dipolar to Charge Transfer Plasmon Modes in Ge2Sb2Te5 Bridged Metallodielectric Dimers.

PubMed

Ahmadivand, Arash; Gerislioglu, Burak; Sinha, Raju; Karabiyik, Mustafa; Pala, Nezih

2017-02-16

Capacitive coupling and direct shuttling of charges in nanoscale plasmonic components across a dielectric spacer and through a conductive junction lead to excitation of significantly different dipolar and charge transfer plasmon (CTP) resonances, respectively. Here, we demonstrate the excitation of dipolar and CTP resonant modes in metallic nanodimers bridged by phase-change material (PCM) sections, material and electrical characteristics of which can be controlled by external stimuli. Ultrafast switching (in the range of a few nanoseconds) between amorphous and crystalline phases of the PCM section (here Ge 2 Sb 2 Te 5 (GST)) allows for designing a tunable plasmonic switch for optical communication applications with significant modulation depth (up to 88%). Judiciously selecting the geometrical parameters and taking advantage of the electrical properties of the amorphous phase of the GST section we adjusted the extinction peak of the dipolar mode at the telecommunication band (λ~1.55 μm), which is considered as the OFF state. Changing the GST phase to crystalline via optical heating allows for direct transfer of charges through the junction between nanodisks and formation of a distinct CTP peak at longer wavelengths (λ~1.85 μm) far from the telecommunication wavelength, which constitutes the ON state.

An 80-year summer temperature history from the Xiao Dongkemadi ice core in the central Tibetan Plateau and its association with atmospheric circulation

NASA Astrophysics Data System (ADS)

Li, Xiangying; Ding, Yongjian; Yu, Zhongbo; Mika, Sillanpää; Liu, Shiyin; Shangguan, Donghui; Lu, Chengyang

2015-02-01

The climate significance of oxygen isotopes from the central Tibetan Plateau (cTP) ice cores is a debated issue because of large scale atmospheric circulation. A high-resolution δ18O record was recovered from the Xiao Dongkemadi (XD) ice core, which expanded the spatial coverage of δ18O data in this region. Annual average δ18O correlated significantly with nearby MJJAS air temperatures, suggesting the δ18O can be used as a proxy to reconstruct regional climate change. The reconstructed temperature anomaly is related to the regional and global warming trends, and the greater warming amplitude since 1970s is related to the elevation dependency of the warming signal. The close relationship of the warming to variations in glacier mass balances and discharge reveal that recent warming has led to obvious glacier shrinkage and runoff increase. Correlation analysis suggests that monsoon and westerly moisture substantially influence the cTP ice core records, along with an increase in their level of contribution to the XD core accumulation in recent decades, and confirms a teleconnection of regional climate of the cTP ice cores with climate parameters in the Indian and North Atlantic Oceans.

Crystal Structure of the CTP1L Endolysin Reveals How Its Activity Is Regulated by a Secondary Translation Product*

PubMed Central

Dunne, Matthew; Leicht, Stefan; Krichel, Boris; Thompson, Andrew; Gómez-Torres, Natalia; Garde, Sonia; Narbad, Arjan; Mayer, Melinda J.

2016-01-01

Bacteriophages produce endolysins, which lyse the bacterial host cell to release newly produced virions. The timing of lysis is regulated and is thought to involve the activation of a molecular switch. We present a crystal structure of the activated endolysin CTP1L that targets Clostridium tyrobutyricum, consisting of a complex between the full-length protein and an N-terminally truncated C-terminal cell wall binding domain (CBD). The truncated CBD is produced through an internal translation start site within the endolysin gene. Mutants affecting the internal translation site change the oligomeric state of the endolysin and reduce lytic activity. The activity can be modulated by reconstitution of the full-length endolysin-CBD complex with free CBD. The same oligomerization mechanism applies to the CD27L endolysin that targets Clostridium difficile and the CS74L endolysin that targets Clostridium sporogenes. When the CTP1L endolysin gene is introduced into the commensal bacterium Lactococcus lactis, the truncated CBD is also produced, showing that the alternative start codon can be used in other bacterial species. The identification of a translational switch affecting oligomerization presented here has implications for the design of effective endolysins for the treatment of bacterial infections. PMID:26683375

The Effect of Heart Rate on Exposure Window and Best Phase for Stress Perfusion Computed Tomography: Lessons From the CORE320 Study.

PubMed

Steveson, Chloe; Schuijf, Joanne D; Vavere, Andrea L; Mather, Richard T; Caton, Teresa; Mehra, Vishal; Betoko, Aisha; Cox, Christopher; Lima, Joao Ac; George, Richard T

The aim of this study is to evaluate the effect of heart rate on exposure window, best phase, and image quality for stress computed tomography perfusion (CTP) in the CORE320 study. The CTP data sets were analyzed to determine the best phase for perfusion analysis. A predefined exposure window covering 75% to 95% of the R-R cycle was used. Of the 368 patients included in the analysis, 93% received oral β blockade before the rest scan. The median heart rate during the stress acquisition was 69 bpm (interquartile range [IQR], 60-77). The median best phase was 81% (IQR, 76-90), and length of exposure window was 22% (IQR, 19-24). The best phase was significantly later in the cardiac cycle with higher heart rates (P < 0.001), and higher heart rates resulted in a small, but higher number of poor quality scans (6%, P < 0.001). The median effective dose of the stress scan was 5.3 mSv (IQR, 3.8-6.1). Stress myocardial CTP imaging can be performed using prospective electrocardiography triggering, an exposure window of 75% to 95%, and β-blockade resulting in good or excellent image quality in the majority (80%) of patients while maintaining a low effective radiation dose.

Optical Switching Using Transition from Dipolar to Charge Transfer Plasmon Modes in Ge2Sb2Te5 Bridged Metallodielectric Dimers

NASA Astrophysics Data System (ADS)

Ahmadivand, Arash; Gerislioglu, Burak; Sinha, Raju; Karabiyik, Mustafa; Pala, Nezih

2017-02-01

Capacitive coupling and direct shuttling of charges in nanoscale plasmonic components across a dielectric spacer and through a conductive junction lead to excitation of significantly different dipolar and charge transfer plasmon (CTP) resonances, respectively. Here, we demonstrate the excitation of dipolar and CTP resonant modes in metallic nanodimers bridged by phase-change material (PCM) sections, material and electrical characteristics of which can be controlled by external stimuli. Ultrafast switching (in the range of a few nanoseconds) between amorphous and crystalline phases of the PCM section (here Ge2Sb2Te5 (GST)) allows for designing a tunable plasmonic switch for optical communication applications with significant modulation depth (up to 88%). Judiciously selecting the geometrical parameters and taking advantage of the electrical properties of the amorphous phase of the GST section we adjusted the extinction peak of the dipolar mode at the telecommunication band (λ~1.55 μm), which is considered as the OFF state. Changing the GST phase to crystalline via optical heating allows for direct transfer of charges through the junction between nanodisks and formation of a distinct CTP peak at longer wavelengths (λ~1.85 μm) far from the telecommunication wavelength, which constitutes the ON state.

Tobacco regulatory science: research to inform regulatory action at the Food and Drug Administration's Center for Tobacco Products.

PubMed

Ashley, David L; Backinger, Cathy L; van Bemmel, Dana M; Neveleff, Deborah J

2014-08-01

The U.S. Food and Drug Administration (FDA) promotes the development of regulatory science to ensure that a strong evidence base informs all of its regulatory activities related to the manufacture, marketing, and distribution of tobacco products as well as public education about tobacco product constituents and effects. Toward that end, the FDA's Center for Tobacco Products (CTP) provides funding for research studies with scientific aims that fall within its defined regulatory authority. However, given their traditional biomedical focus on basic and applied research, some researchers may not understand the principles of regulatory science or the types of studies CTP funds. The purpose of this paper is (1) to clarify the definition of regulatory science as a distinct scientific discipline, (2) to explore the role of tobacco regulatory science in order to help researchers understand the parameters and types of research that can be funded by CTP, and (3) to describe the types of research efforts that will inform the FDA's public health framework for tobacco product regulation. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Effects of pyrimidines on the guinea-pig coronary vasculature.

PubMed Central

Vials, A. J.; Burnstock, G.

1993-01-01

1. The effects of the pyrimidines, uridine 5'-triphosphate (UTP), thymidine 5'-triphosphate (TTP) and cytidine 5'-triphosphate (CTP), were examined in the guinea-pig coronary bed, by use of a Langendorff technique. Comparisons were made with the actions of the purines adenosine 5'-triphosphate (ATP), inosine 5'-triphosphate (ITP) and guanosine 5'-triphosphate (GTP). The effect of, the nitric oxide synthase inhibitor, L-NG-nitroarginine methyl ester (L-NAME) and, the prostaglandin synthesis inhibitor, indomethacin on the vasodilator response to these purines and pyrimidines was examined. The effects of these inhibitors were assessed on their ability to inhibit both the amplitude and the area of the vasodilator response. 2. The relative order of potency of the purines and pyrimidines studied was ATP > UTP > ITP >> GTP, TTP, CTP. 3. The maximum amplitude and area of the vasodilator response to the pyrimidines, UTP (5 x 10(-10)-5 x 10(-7) mol), TTP (5 x 10(-8)-5 x 10(-7) mol) and CTP (5 x 10(-7) mol), and purines, ITP (5 x 10(-9)-5 x 10(-7) mol) and GTP (5 x 10(-8)-5 x 10(-7) mol), were significantly reduced by L-NAME (3 x 10(-5) and 10(-4) M).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8298797

The chemical identity of intervessel pit membranes in Acer challenges hydrogel control of xylem hydraulic conductivity

PubMed Central

Klepsch, Matthias M.; Schmitt, Marco; Paul Knox, J.; Jansen, Steven

2016-01-01

Ion-mediated enhancement of the hydraulic conductivity of xylem tissue (i.e. the ionic effect) has been reported for various angiosperm species. One explanation of the ionic effect is that it is caused by the swelling and shrinking of intervessel pit membranes due to the presence of pectins and/or other cell-wall matrix polymers such as heteroxylans or arabinogalactan–proteins (AGPs) that may contain acidic sugars. Here, we examined the ionic effect for six Acer species and their pit membrane chemistry using immunocytochemistry, including antibodies against glycoproteins. Moreover, anatomical features related to the bordered pit morphology and vessel dimensions were investigated using light and electron microscopy. The ionic effect varied from 18 % (± 9) to 32 % (± 13). Epitopes of homogalacturonan (LM18) and xylan (LM11) were not detected in intervessel pit membranes. Negative results were also obtained for glycoproteins (extensin: LM1, JIM20; AGP glycan: LM2), although AGP (JIM13)-related epitopes were detected in parenchyma cells. The mean vessel length was significantly correlated with the magnitude of the ionic effect, unlike other pit or vessel-related characteristics. Our results suggest that intervessel pit membranes of Acer are unlikely to contain pectic or other acidic polysaccharides. Therefore, alternative explanations should be tested to clarify the ionic effect. PMID:27354661

Near infrared photoimmunotherapy prevents lung cancer metastases in a murine model

PubMed Central

Sato, Kazuhide; Nagaya, Tadanobu; Nakamura, Yuko; Harada, Toshiko; Choyke, Peter L.; Kobayashi, Hisataka

2015-01-01

Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of intravenously injected antibodies with the acute toxicity induced by photosensitizers after exposure to NIR-light. Herein, we evaluate the efficacy of NIR-PIT in preventing lung metastases in a mouse model. Lung is one of the most common sites for developing metastases, but it also has the deepest tissue light penetration. Thus, lung is the ideal site for treating early metastases by using a light-based strategy. In vitro NIR-PIT cytotoxicity was assessed with dead cell staining, luciferase activity, and a decrease in cytoplasmic GFP fluorescence in 3T3/HER2-luc-GFP cells incubated with an anti-HER2 antibody photosensitizer conjugate. Cell-specific killing was demonstrated in mixed 2D/3D cell cultures of 3T3/HER2-luc-GFP (target) and 3T3-RFP (non-target) cells. In vivo NIR-PIT was performed in the left lung in a mouse model of lung metastases, and the number of metastasis nodules, tumor fluorescence, and luciferase activity were all evaluated. All three evaluations demonstrated that the NIR-PIT-treated lung had significant reductions in metastatic disease (*p < 0.0001, Mann-Whitney U-test) and that NIR-PIT did not damage non-target tumors or normal lung tissue. Thus, NIR-PIT can specifically prevent early metastases and is a promising anti-metastatic therapy. PMID:25992770

Streamlined Approach for Environmental Restoration (SAFER) Plan for Corrective Action Unit 544: Cellars, Mud Pits, and Oil Spills, Nevada Test Site, Nevada, Revision 0

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

Mark Krauss

2010-07-01

This Streamlined Approach for Environmental Restoration (SAFER) Plan addresses the actions needed to achieve closure for Corrective Action Unit (CAU) 544, Cellars, Mud Pits, and Oil Spills, identified in the Federal Facility Agreement and Consent Order (FFACO). Corrective Action Unit 544 comprises the following 20 corrective action sites (CASs) located in Areas 2, 7, 9, 10, 12, 19, and 20 of the Nevada Test Site (NTS): • 02-37-08, Cellar & Mud Pit • 02-37-09, Cellar & Mud Pit • 07-09-01, Mud Pit • 09-09-46, U-9itsx20 PS #1A Mud Pit • 10-09-01, Mud Pit • 12-09-03, Mud Pit • 19-09-01, Mudmore » Pits (2) • 19-09-03, Mud Pit • 19-09-04, Mud Pit • 19-25-01, Oil Spill • 19-99-06, Waste Spill • 20-09-01, Mud Pits (2) • 20-09-02, Mud Pit • 20-09-03, Mud Pit • 20-09-04, Mud Pits (2) • 20-09-06, Mud Pit • 20-09-07, Mud Pit • 20-09-10, Mud Pit • 20-25-04, Oil Spills • 20-25-05, Oil Spills This plan provides the methodology for field activities needed to gather the necessary information for closing each CAS. There is sufficient information and process knowledge from historical documentation and investigations of similar sites regarding the expected nature and extent of potential contaminants to recommend closure of CAU 544 using the SAFER process. Using the approach approved for previous mud pit investigations (CAUs 530–535), 14 mud pits have been identified that • are either a single mud pit or a system of mud pits, • are not located in a radiologically posted area, and • have no evident biasing factors based on visual inspections. These 14 mud pits are recommended for no further action (NFA), and further field investigations will not be conducted. For the sites that do not meet the previously approved closure criteria, additional information will be obtained by conducting a field investigation before selecting the appropriate corrective action for each CAS. The results of the field investigation will support a defensible recommendation for closure of the remaining CASs in CAU 544. This will be presented in a closure report (CR) that will be prepared and submitted to the Nevada Division of Environmental Protection (NDEP) for review and approval. The sites will be investigated based on the data quality objectives (DQOs) developed on April 27, 2010, by representatives of NDEP and the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Site Office (NNSA/NSO). The DQO process was used to identify and define the type, amount, and quality of data needed to determine and implement appropriate corrective actions for each CAS in CAU 544. The DQO process developed for this CAU identified the following expected closure options: (1) investigation and confirmation that no contamination exists above the final action levels (FALs) leading to an NFA declaration, (2) characterization of the nature and extent of contamination leading to closure in place with use restrictions, (3) clean closure by remediation and verification, (4) closure in place with use restrictions with no investigation if CASs are in crater areas that have been determined to be unsafe to enter, or (5) NFA if the mud pit CAS meets the criteria established during the CAUs 530–535 SAFER investigation. The following summarizes the SAFER activities that will support the closure of CAU 544: • Perform visual inspection of all CASs. • Perform site preparation activities (e.g., utilities clearances, construction of temporary site exclusion zones). • Removal of easily managed, nonhazardous, and nonradioactive debris, including vegetation (e.g., tumbleweeds), at various CASs that interfere with sampling, if required to inspect soil surface or collect soil sample. • Collect environmental samples from designated target populations (e.g., mud pits, cellars, stained soil) to confirm or disprove the presence of contaminants of concern (COCs) as necessary to supplement existing information. • If no COCs are present at a CAS, establish NFA as the corrective action. • If COCs exist, collect environmental samples from designated target populations (e.g., clean soil adjacent to contaminated soil) and submit for laboratory analyses to define the extent of COC contamination. • If a COC is present at a CAS, either - Establish clean closure as the corrective action. The material to be remediated will be removed, disposed of as waste, and verification samples will be collected from remaining soil, or - Establish closure in place as the corrective action and implement the appropriate use restrictions. • Confirm the preferred closure option is sufficient to protect human health and the environment.« less

The effects of amphetamine sensitization on conditioned inhibition during a Pavlovian-instrumental transfer task in rats

PubMed Central

Shiflett, Michael W.; Riccie, Meaghan; DiMatteo, RoseMarie

2013-01-01

Rationale Psychostimulant sensitization heightens behavioral and motivational responses to reward-associated stimuli; however, its effects on stimuli associated with reward absence are less understood. Objectives We examined whether amphetamine sensitization alters performance during Pavlovian-instrumental transfer (PIT) to conditioned excitors and inhibitors. We further sought to characterize the effects of amphetamine sensitization on learning versus performance by exposing rats to amphetamine prior to Pavlovian training or between training and test. Methods Adult male Long Evans rats were given conditioned inhibition (A+/AX−) and Pavlovian (B+) training, followed by variable-interval instrumental conditioning. Rats were sensitized to d-amphetamine (2 mg/kg daily injections for seven days), or served as non-exposed controls. Rats were given a PIT test, in which they were presented with stimulus B alone or in compound with the conditioned inhibitor (BX). Results During the PIT test, control rats significantly reduced instrumental responding on BX trials (to approximately 50% of responding to B). Amphetamine sensitization prior to Pavlovian conditioning increased lever-pressing on BX trials and reduced lever-pressing on B trials compared to controls. Amphetamine sensitization between training and test increased lever-pressing on B and BX trials compared to controls. No effects of sensitization were observed on conditioned food-cup approach. Conclusions Amphetamine sensitization increases instrumental responding during PIT to a conditioned inhibitor, by enhancing excitation of conditioned stimuli and reducing inhibition of conditioned inhibitors. PMID:23715640

Mechanistic Basis for the Bypass of a Bulky DNA Adduct Catalyzed by a Y-Family DNA Polymerase

PubMed Central

Vyas, Rajan; Efthimiopoulos, Georgia; Tokarsky, E. John; Malik, Chanchal K.; Basu, Ashis K.; Suo, Zucai

2015-01-01

1-Nitropyrene (1-NP), an environmental pollutant, induces DNA damage in vivo and is considered to be carcinogenic. The DNA adducts formed by the 1-NP metabolites stall replicative DNA polymerases but are presumably bypassed by error-prone Y-family DNA polymerases at the expense of replication fidelity and efficiency in vivo. Our running start assays confirmed that a site-specifically placed 8-(deoxyguanosin-N2-yl)-1-aminopyrene (dG1,8), one of the DNA adducts derived from 1-NP, can be bypassed by Sulfolobus solfataricus DNA polymerase IV (Dpo4), although this representative Y-family enzyme was paused strongly by the lesion. Pre-steady-state kinetic assays were employed to determine the low nucleotide incorporation fidelity and establish a minimal kinetic mechanism for the dG1,8 bypass by Dpo4. To reveal a structural basis for dCTP incorporation opposite dG1,8, we solved the crystal structures of the complexes of Dpo4 and DNA containing a templating dG1,8 lesion in the absence or presence of dCTP. The Dpo4·DNA-dG1,8 binary structure shows that the aminopyrene moiety of the lesion stacks against the primer/template junction pair, while its dG moiety projected into the cleft between the Finger and Little Finger domains of Dpo4. In the Dpo4·DNA-dG1,8·dCTP ternary structure, the aminopyrene moiety of the dG1,8 lesion, is sandwiched between the nascent and junction base pairs, while its base is present in the major groove. Moreover, dCTP forms a Watson–Crick base pair with dG, two nucleotides upstream from the dG1,8 site, creating a complex for “-2” frameshift mutation. Mechanistically, these crystal structures provide additional insight into the aforementioned minimal kinetic mechanism. PMID:26327169

Inactivation of Lactobacillus leichmannii ribonucleotide reductase by 2',2'-difluoro-2'-deoxycytidine 5'-triphosphate: adenosylcobalamin destruction and formation of a nucleotide-based radical.

PubMed

Lohman, Gregory J S; Gerfen, Gary J; Stubbe, Joanne

2010-02-23

Ribonucleotide reductase (RNR, 76 kDa) from Lactobacillus leichmannii is a class II RNR that requires adenosylcobalamin (AdoCbl) as a cofactor. It catalyzes the conversion of nucleoside triphosphates to deoxynucleotides and is 100% inactivated by 1 equiv of 2',2'-difluoro-2'-deoxycytidine 5'-triphosphate (F(2)CTP) in <2 min. Sephadex G-50 chromatography of the inactivation reaction mixture for 2 min revealed that 0.47 equiv of a sugar moiety is covalently bound to RNR and 0.25 equiv of a cobalt(III) corrin is tightly associated, likely through a covalent interaction with C(419) (Co-S) in the active site of RNR [Lohman, G. J. S., and Stubbe, J. (2010) Biochemistry 49, DOI: 10.1021/bi902132u ]. After 1 h, a similar experiment revealed 0.45 equiv of the Co-S adduct associated with the protein. Thus, at least two pathways are associated with RNR inactivation: one associated with alkylation by the sugar of F(2)CTP and the second with AdoCbl destruction. To determine the fate of [1'-(3)H]F(2)CTP in the latter pathway, the reaction mixture at 2 min was reduced with NaBH(4) (NaB(2)H(4)) and the protein separated from the small molecules using a centrifugation device. The small molecules were dephosphorylated and analyzed by HPLC to reveal 0.25 equiv of a stereoisomer of cytidine, characterized by mass spectrometry and NMR spectroscopy, indicating the trapped nucleotide had lost both of its fluorides and gained an oxygen. High-field ENDOR studies with [1'-(2)H]F(2)CTP from the reaction quenched at 30 s revealed a radical that is nucleotide-based. The relationship between this radical and the trapped cytidine analogue provides insight into the nonalkylative pathway for RNR inactivation relative to the alkylative pathway.

A novel method for quantification of gemcitabine and its metabolites 2',2'-difluorodeoxyuridine and gemcitabine triphosphate in tumour tissue by LC-MS/MS: comparison with (19)F NMR spectroscopy.

PubMed

Bapiro, Tashinga E; Richards, Frances M; Goldgraben, Mae A; Olive, Kenneth P; Madhu, Basetti; Frese, Kristopher K; Cook, Natalie; Jacobetz, Michael A; Smith, Donna-Michelle; Tuveson, David A; Griffiths, John R; Jodrell, Duncan I

2011-11-01

To develop a sensitive analytical method to quantify gemcitabine (2',2'-difluorodeoxycytidine, dFdC) and its metabolites 2',2'-difluorodeoxyuridine (dFdU) and 2',2'-difluorodeoxycytidine-5'-triphosphate (dFdCTP) simultaneously from tumour tissue. Pancreatic ductal adenocarcinoma tumour tissue from genetically engineered mouse models of pancreatic cancer (KP ( FL/FL ) C and KP ( R172H/+) C) was collected after dosing the mice with gemcitabine. (19)F NMR spectroscopy and LC-MS/MS protocols were optimised to detect gemcitabine and its metabolites in homogenates of the tumour tissue. A (19)F NMR protocol was developed, which was capable of distinguishing the three analytes in tumour homogenates. However, it required at least 100 mg of the tissue in question and a long acquisition time per sample, making it impractical for use in large PK/PD studies or clinical trials. The LC-MS/MS protocol was developed using porous graphitic carbon to separate the analytes, enabling simultaneous detection of all three analytes from as little as 10 mg of tissue, with a sensitivity for dFdCTP of 0.2 ng/mg tissue. Multiple pieces of tissue from single tumours were analysed, showing little intra-tumour variation in the concentrations of dFdC or dFdU (both intra- and extra-cellular). Intra-tumoural variation was observed in the concentration of dFdCTP, an intra-cellular metabolite, which may reflect regions of different cellularity within a tumour. We have developed a sensitive LC-MS/MS method capable of quantifying gemcitabine, dFdU and dFdCTP in pancreatic tumour tissue. The requirement for only 10 mg of tissue enables this protocol to be used to analyse multiple areas from a single tumour and to spare tissue for additional pharmacodynamic assays.

Systematic review with meta-analysis: the efficacy and safety of CT-P13, a biosimilar of anti-tumour necrosis factor-α agent (infliximab), in inflammatory bowel diseases.

PubMed

Komaki, Y; Yamada, A; Komaki, F; Micic, D; Ido, A; Sakuraba, A

2017-04-01

Biosimilars of anti-tumour necrosis factor (TNF)-α agents have now become clinically available for the treatment of inflammatory bowel diseases (IBD). To perform a systematic review and meta-analysis to evaluate the efficacy and safety of biosimilars of anti-TNF-α agents in patients with IBD. Electronic databases were searched. The outcomes were the pooled rates of clinical response or remission, sustained clinical response or remission, and adverse events in patients with IBD induced with or switched to biosimilars of anti-TNF-α agents. Eleven observational studies reporting outcomes in 829 patients treated with biosimilar of infliximab (CT-P13) were identified. The pooled rates of clinical response among Crohn's disease (CD) and ulcerative colitis (UC) at 8-14 weeks were 0.79 (95% confidence interval (CI) = 0.65-0.88) and 0.74 (95% CI = 0.65-0.82), respectively, and at 24-30 weeks were 0.77 (95% CI = 0.63-0.86) and 0.77 (95% CI = 0.67-0.85) respectively. Adverse events were rare (CD, 0.08 (95% CI = 0.02-0.26); UC, 0.08 (95% CI = 0.03-0.17)). The pooled rates of sustained clinical response among CD and UC after switching from infliximab to CT-P13 at 30-32 weeks were 0.85 (95% CI = 0.71-0.93) and 0.96 (95% CI = 0.58-1.00), respectively, and at 48-63 weeks were 0.75 (95% CI = 0.44-0.92) and 0.83 (95% CI = 0.19-0.99) respectively. Adverse events were rare (CD, 0.10, 95% CI = 0.02-0.31; UC, 0.22, 95% CI = 0.04-0.63). CT-P13 was associated with excellent clinical efficacy and safety profile, supporting its use in the treatment of IBD. © 2017 John Wiley & Sons Ltd.

Basis of Miscoding of the DNA Adduct N2,3-Ethenoguanine by Human Y-family DNA Polymerases*

PubMed Central

Zhao, Linlin; Pence, Matthew G.; Christov, Plamen P.; Wawrzak, Zdzislaw; Choi, Jeong-Yun; Rizzo, Carmelo J.; Egli, Martin; Guengerich, F. Peter

2012-01-01

N2,3-Ethenoguanine (N2,3-ϵG) is one of the exocyclic DNA adducts produced by endogenous processes (e.g. lipid peroxidation) and exposure to bioactivated vinyl monomers such as vinyl chloride, which is a known human carcinogen. Existing studies exploring the miscoding potential of this lesion are quite indirect because of the lability of the glycosidic bond. We utilized a 2′-fluoro isostere approach to stabilize this lesion and synthesized oligonucleotides containing 2′-fluoro-N2,3-ϵ-2′-deoxyarabinoguanosine to investigate the miscoding potential of N2,3-ϵG by Y-family human DNA polymerases (pols). In primer extension assays, pol η and pol κ replicated through N2,3-ϵG, whereas pol ι and REV1 yielded only 1-base incorporation. Steady-state kinetics revealed that dCTP incorporation is preferred opposite N2,3-ϵG with relative efficiencies in the order of pol κ > REV1 > pol η ≈ pol ι, and dTTP misincorporation is the major miscoding event by all four Y-family human DNA pols. Pol ι had the highest dTTP misincorporation frequency (0.71) followed by pol η (0.63). REV1 misincorporated dTTP and dGTP with much lower frequencies. Crystal structures of pol ι with N2,3-ϵG paired to dCTP and dTTP revealed Hoogsteen-like base pairing mechanisms. Two hydrogen bonds were observed in the N2,3-ϵG:dCTP base pair, whereas only one appears to be present in the case of the N2,3-ϵG:dTTP pair. Base pairing mechanisms derived from the crystal structures explain the slightly favored dCTP insertion for pol ι in steady-state kinetic analysis. Taken together, these results provide a basis for the mutagenic potential of N2,3-ϵG. PMID:22910910

The Corrosion Characteristics and Tensile Behavior of Reinforcement under Coupled Carbonation and Static Loading

PubMed Central

Xu, Yidong

2015-01-01

This paper describes the non-uniform corrosion characteristics and mechanical properties of reinforcement under coupled action of carbonation and static loading. The two parameters, namely area-box (AB) value and arithmetical mean deviation (Ra), are adopted to characterize the corrosion morphology and pitting distribution from experimental observations. The results show that the static loading affects the corrosion characteristics of reinforcement. Local stress concentration in corroded reinforcement caused by tensile stress drives the corrosion pit pattern to be more irregular. The orthogonal test results from finite element simulations show that pit shape and pit depth are the two significant factors affecting the tensile behavior of reinforcement. Under the condition of similar corrosion mass loss ratio, the maximum plastic strain of corroded reinforcement increases with the increase of Ra and load time-history significantly. PMID:28793729

The stress-corrosion behavior of Al-Li-Cu alloys: A comparison of test methods

NASA Technical Reports Server (NTRS)

Rizzo, P. P.; Galvin, R. P.; Nelson, H. G.

1982-01-01

Two powder metallurgy processed (Al-Li-Cu) alloys with and without Mg addition were studied in aqueous 3.5% NaCl solution during the alternate immersion testing of tuning fork specimens, slow crack growth tests using fracture mechanics specimens, and the slow strain rate testing of straining electrode specimens. Scanning electron microscopy and optical metallography were used to demonstrate the character of the interaction between the Al-Li-Cu alloys and the selected environment. Both alloys are susceptible to SC in an aqueous 3.5% NaCl solution under the right electrochemical and microstructural conditions. Each test method yields important information on the character of the SC behavior. Under all conditions investigated, second phase particles strung out in rows along the extrusion direction in the alloys were rapidly attacked, and played principal role in the SC process. With time, larger pits developed from these rows of smaller pits and under certain electrochemical conditions surface cracks initiated from the larger pits and contributed directly to the fracture process. Evidence to support slow crack growth was observed in both the slow strain rate tests and the sustained immersion tests of precracked fracture mechanics specimens. The possible role of H2 in the stress corrosion cracking process is suggested.

Is the ipsilateral cortex surrounding the lesion or the non-injured contralateral cortex important for motor recovery in rats with photochemically induced cortical lesions?

PubMed

Takata, Kotaro; Yamauchi, Hideki; Tatsuno, Hisashi; Hashimoto, Keiji; Abo, Masahiro

2006-01-01

To determine whether the ipsilateral cortex surrounding the lesion or the non-injured contralateral cortex is important for motor recovery after brain damage in the photochemically initiated thrombosis (PIT) model. We induced PIT in the sensorimotor cortex in rats and examined the recovery of motor function using the beam-walking test. In 24 rats, the right sensorimotor cortex was lesioned after 2 days of training for the beam-walking test (group 1). After 10 days, PIT was induced in the left sensorimotor cortex. Eight additional rats (group 2) received 2 days training in beam walking, then underwent the beam-walking test to evaluate function. After 10 days of testing, the left sensorimotor cortex was lesioned and recovery was monitored by the beam-walking test for 8 days. In group 1 animals, left hindlimb function caused by a right sensorimotor cortex lesion recovered within 10 days after the operation. Right hindlimb function caused by the left-side lesion recovered within 6 days. In group 2, right hindlimb function caused by induction of the left-side lesion after a total of 12 days of beam-walking training and testing recovered within 6 days as with the double PIT model. The training effect may be relevant to reorganization and neuromodulation. Motor recovery patterns did not indicate whether motor recovery was dependent on the ipsilateral cortex surrounding the lesion or the cortex of the contralateral side. The results emphasize the need for selection of appropriate programs tailored to the area of cortical damage in order to enhance motor functional recovery in this model. Copyright 2006 S. Karger AG, Basel.

Relationship between Microstructure and Corrosion Behavior of Martensitic High Nitrogen Stainless Steel 30Cr15Mo1N at Different Austenitizing Temperatures.

PubMed

Jiang, Zhouhua; Feng, Hao; Li, Huabing; Zhu, Hongchun; Zhang, Shucai; Zhang, Binbin; Han, Yu; Zhang, Tao; Xu, Dake

2017-07-27

The relationship between microstructure and corrosion behavior of martensitic high nitrogen stainless steel 30Cr15Mo1N at different austenitizing temperatures was investigated by microscopy observation, electrochemical measurement, X-ray photoelectron spectroscopy analysis and immersion testing. The results indicated that finer Cr-rich M₂N dispersed more homogeneously than coarse M 23 C₆, and the fractions of M 23 C₆ and M₂N both decreased with increasing austenitizing temperature. The Cr-depleted zone around M 23 C₆ was wider and its minimum Cr concentration was lower than M₂N. The metastable pits initiated preferentially around coarse M 23 C₆ which induced severer Cr-depletion, and the pit growth followed the power law. The increasing of austenitizing temperature induced fewer metastable pit initiation sites, more uniform element distribution and higher contents of Cr, Mo and N in the matrix. In addition, the passive film thickened and Cr₂O₃, Cr 3+ and CrN enriched with increasing austenitizing temperature, which enhanced the stability of the passive film and repassivation ability of pits. Therefore, as austenitizing temperature increased, the metastable and stable pitting potentials increased and pit growth rate decreased, revealing less susceptible metastable pit initiation, larger repassivation tendency and higher corrosion resistance. The determining factor of pitting potentials could be divided into three stages: dissolution of M 23 C₆ (below 1000 °C), dissolution of M₂N (from 1000 to 1050 °C) and existence of a few undissolved precipitates and non-metallic inclusions (above 1050 °C).

Extinction of specific stimulus-outcome (S-O) associations in Pavlovian learning with an extended CS procedure.

PubMed

Delamater, Andrew R; Schneider, Kevin; Derman, Rifka C

2017-07-01

Three experiments with male and female rats were conducted to examine the effects of Pavlovian extinction training on Pavlovian-to-instrumental transfer (PIT) in a task in which the unconditioned stimulus (US) was presented at an early time point within an extended conditioned stimulus (CS). Two instrumental responses were trained with different reinforcing outcomes (R1-O1, R2-O2) and then, independently, 2 stimuli were trained with those outcomes (S1-O1, S2-O2). One group then underwent an extinction treatment (S1-, S2-) and a second was merely exposed to the experimental contexts without any stimulus events. Finally, the effects of the 2 stimuli on instrumental responding were assessed in PIT tests. Across experiments we varied the number of Pavlovian training trials prior to extinction (8, 16, or 64 trials) and the length of time following extinction prior to test (i.e., 1 or 21 days, in a test for spontaneous recovery). We observed that outcome-specific PIT was reduced by extinction in all of our training conditions and that this extinction effect was durable, surviving a 3-week spontaneous recovery interval even though conditioned magazine approach spontaneously recovered over this interval. Although extinction reduced the magnitude of PIT, the temporal expression of PIT was mostly unaffected. We found these effects in both male and female rats, though in 1 study females were extinction-resistant. These data suggest that under the conditions studied here Pavlovian extinction may permanently weaken the ability of Pavlovian cues to retrieve a representation of their associated outcomes without impacting the temporal organization of responding. This suggests that different features of learning may be differentially sensitive to extinction. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Limited mobility of dioxins near San Jacinto super fund site (waste pit) in the Houston Ship Channel, Texas due to strong sediment sorption.

PubMed

Louchouarn, Patrick; Seward, Shaya M; Cornelissen, Gerard; Arp, Hans Peter H; Yeager, Kevin M; Brinkmeyer, Robin; Santschi, Peter H

2018-07-01

Sediments from a waste pit in Houston Ship Channel (HSC) were characterized using a number of molecular markers of natural organic matter fractions (e.g., pyrogenic carbon residues, PAHs, lignins), in addition to dioxins, in order to test the hypothesis that the dispersal and mobility of dioxins from the waste pit in the San Jacinto River is minimal. Station SG-6, sampled at the site of the submerged waste pit, had the highest dioxin/furan concentrations reported for the Houston Ship Channel/Galveston Bay (HSC/GB) system (10,000-46,000 pg/g), which translated into some of the highest reported World Health Organization Toxic Equivalents (TEQs: 2000-11,000 pg/g) in HSC sediments. Using a multi-tracer approach, this study confirmed our hypothesis that sludges from chlorinated pulps are a very likely source of dioxins/furans to this pit. However, this material also contained large quantities of additional hydrophobic organic contaminants (PAHs) and pyrogenic markers (soot-BC, levoglucosan), pointing to the co-occurrence of petroleum hydrocarbons and combustion byproducts. Comparison of dioxin/furan signatures in the waste pit with those from sediments of the HSC and a control site suggests that the remobilization of contaminated particles did not occur beyond the close vicinity of the pit itself. The dioxins/furans in sediments outside the waste pit within the HSC are rather from other diffuse inputs, entering the sedimentary environment through the air and water, and which are comprised of a mixture of industrial and municipal sources. Fingerprinting of waste pit dioxins indicates that their composition is typical of pulp and paper sources. Measured pore water concentrations were 1 order of magnitude lower than estimated values, calculated from a multiphase sorption model, indicating low mobility of dioxins within the waste pit. This is likely accomplished by co-occurring and strong sorbing pyrogenic and petrogenic residues in the waste pit, which tend to keep dioxins strongly sorbed to particles. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

An investigation of gear mesh failure prediction techniques. M.S. Thesis - Cleveland State Univ.

NASA Technical Reports Server (NTRS)

Zakrajsek, James J.

1989-01-01

A study was performed in which several gear failure prediction methods were investigated and applied to experimental data from a gear fatigue test apparatus. The primary objective was to provide a baseline understanding of the prediction methods and to evaluate their diagnostic capabilities. The methods investigated use the signal average in both the time and frequency domain to detect gear failure. Data from eleven gear fatigue tests were recorded at periodic time intervals as the gears were run from initiation to failure. Four major failure modes, consisting of heavy wear, tooth breakage, single pits, and distributed pitting were observed among the failed gears. Results show that the prediction methods were able to detect only those gear failures which involved heavy wear or distributed pitting. None of the methods could predict fatigue cracks, which resulted in tooth breakage, or single pits. It is suspected that the fatigue cracks were not detected because of limitations in data acquisition rather than in methodology. Additionally, the frequency response between the gear shaft and the transducer was found to significantly affect the vibration signal. The specific frequencies affected were filtered out of the signal average prior to application of the methods.

The role of the vomeronasal organ of crotalines (Reptilia: Serpentes: Viperidae) in predator detection.

PubMed

Miller; Gutzke

1999-07-01

Most reptiles and mammals, with the exceptions of crocodilians, aquatic mammals and some primates, have a functional vomeronasal organ that detects and perceives semi-volatile chemicals in the environment. This organ is used in detection of prey and is also important for recognition of conspecifics and potential predators. We tested eight species of North American pit vipers for behavioural responses to an ophiophagous (snake-eating) predator, the common kingsnake, Lampropeltis getula. Kingsnakes have a substance in their skin that is recognized by crotalines, which react with a series of defensive responses including, but not limited to, avoidance, fleeing, body bridging and head hiding. The vomeronasal duct of the pit vipers was sutured closed to determine the role of this organ in detection of kingsnakes. Pit vipers with intact and sutured vomeronasal ducts were tested in a neutral cage with a kingsnake and monitored for behavioural responses. Results demonstrated that the vomeronasal organ is important in the recognition of kingsnakes by pit vipers and raises doubts that any other sense plays a major role in this behaviour. Copyright 1999 The Association for the Study of Animal Behaviour.

48 CFR 52.236-4 - Physical Data.

Code of Federal Regulations, 2014 CFR

2014-10-01

... fixed-price construction contract is contemplated and physical data (e.g., test borings, hydrographic..., such as surveys, auger borings, core borings, test pits, probings, test tunnels]. (b) Weather...

48 CFR 52.236-4 - Physical Data.

Code of Federal Regulations, 2013 CFR

2013-10-01

... fixed-price construction contract is contemplated and physical data (e.g., test borings, hydrographic..., such as surveys, auger borings, core borings, test pits, probings, test tunnels]. (b) Weather...

48 CFR 52.236-4 - Physical Data.

Code of Federal Regulations, 2012 CFR

2012-10-01

... fixed-price construction contract is contemplated and physical data (e.g., test borings, hydrographic..., such as surveys, auger borings, core borings, test pits, probings, test tunnels]. (b) Weather...

48 CFR 52.236-4 - Physical Data.

Code of Federal Regulations, 2011 CFR

2011-10-01

... fixed-price construction contract is contemplated and physical data (e.g., test borings, hydrographic..., such as surveys, auger borings, core borings, test pits, probings, test tunnels]. (b) Weather...

48 CFR 52.236-4 - Physical Data.

Code of Federal Regulations, 2010 CFR

2010-10-01

... fixed-price construction contract is contemplated and physical data (e.g., test borings, hydrographic..., such as surveys, auger borings, core borings, test pits, probings, test tunnels]. (b) Weather...

Toxicity of acid mine pit lake water remediated with limestone and phosphorus.

PubMed

Neil, Luke L; McCullough, Clint D; Lund, Mark A; Evans, Louis H; Tsvetnenko, Yuri

2009-11-01

Pit lakes are increasingly common worldwide and have potential to provide many benefits. However, lake water toxicity may require remediation before beneficial end uses can be realised. Three treatments to remediate AMD (pH approximately 4.8) pit lake water containing elevated concentrations of Al and Zn from Collie, Western Australia were tested in mesocosms. Treatments were: (a) limestone neutralisation (L), (b) phosphorus amendment (P), and (c) combined limestone neutralisation and phosphorus amendment (L+P). Laboratory bioassays with Ceriodaphnia cf. dubia, Chlorella protothecoides and Tetrahymena thermophila assessed remediation. Limestone neutralisation increased pH and reduced heavy metal concentrations by 98% (Al) to 14% (Mg), removing toxicity to the three test species within 2 months. Phosphorus amendment removed toxicity after 6 months of treatment. However, phosphorus amendment to prior limestone neutralisation failed to reduce toxicity more than limestone neutralisation alone. Low concentrations of both phosphorus and nitrogen appear to limit phytoplankton population growth in all treatments.

Corrosion of carbon steels, stainless steels, and titanium in aqueous lithium bromide solution

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

Guinon, J.L.; Garcia-Anton, J.; Perez-Herranz, V.

1994-03-01

Effects of lithium bromide (LiBr) concentration, pH, temperature, exposure time, and the action of some inhibitors on corrosion of several carbon (C) steels, stainless steels (SS), and a titanium (Ti) alloy were studied. Corrosion rates were determined by the polarization resistance method and compared to rates determined by weight-loss measurements. Pitting potentials (E[sub p]) were evaluated in neutral LiBr solution and with different inhibitors. Pit density and average pit depth depended on the metal tested, with lowest values for Ti, the next lowest values for type 316 SS (UNS S31600), and the highest values for UNS G41350 tempered steel.

Project W-314 specific test and evaluation plan for AZ tank farm upgrades

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

Hays, W.H.

1998-08-12

The purpose of this Specific Test and Evaluation Plan (STEP) is to provide a detailed written plan for the systematic testing of modifications made by the addition of the SN-631 transfer line from the AZ-O1A pit to the AZ-02A pit by the W-314 Project. The STEP develops the outline for test procedures that verify the system`s performance to the established Project design criteria. The STEP is a lower tier document based on the W-314 Test and Evaluation P1 an (TEP). Testing includes Validations and Verifications (e.g., Commercial Grade Item Dedication activities, etc), Factory Tests and Inspections (FTIs), installation tests andmore » inspections, Construction Tests and Inspections (CTIs), Acceptance Test Procedures (ATPs), Pre-Operational Test Procedures (POTPs), and Operational Test Procedures (OTPs). The STEP will be utilized in conjunction with the TEP for verification and validation.« less

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

K.E. Rasmuson

The U.S. Department of Energy has implemented a program to reclaim lands disturbed by site characterization at Yucca Mountain. Long term goals of the program are to re-establish processes on disturbed sites that will lead to self-sustaining plant communities. The Biological Opinion for Yucca Mountain Site Characterization Studies required that the U.S. Department of Energy develop a Reclamation Standards and Monitoring Plan to evaluate the success of reclamation efforts. According to the Reclamation Standards and Monitoring Plan, reclaimed sites will be monitored periodically, remediated if necessary, and eventually compared to an appropriate reference area to determine whether reclamation goals havemore » been achieved and the site can be released from further monitoring. Plant cover, density, and species richness (success parameters) on reclaimed sites are compared to 60 percent of the values (success criteria) for the same parameters on the reference area. Small sites (less than 0.1 ha) are evaluated for release using qualitative methods while large sites (greater than 0.1 ha) are evaluated using quantitative methods. In the summer of 2000, 31 small sites reclaimed in 1993 and 1994 were evaluated for reclamation success and potential release from further monitoring. Plant density, cover, and species richness were estimated on the C-Well Pipeline, UE-25 Large Rocks test site, and 29 ground surface facility test pits. Evidence of erosion, reproduction and natural recruitment, exotic species abundance, and animal use (key attributes) also were recorded for each site and used in success evaluations. The C-Well Pipeline and ground surface facility test pits were located in a ''Larrea tridentata - Ephedra nevadensis'' vegetation association while the UE-25 Large Rocks test site was located in an area dominated by ''Coleogyne ramosissima and Ephedra nevadensis''. Reference areas in the same vegetation associations with similar slope and aspect were chosen for comparison to the reclaimed sites. Sixty percent of the reference area means for density, cover, and species richness were compared to the estimated means for the reclaimed sites. Plant density, cover, and species richness at the C-Well Pipeline and UE-25 Large Rocks test site were greater than the success criteria and all key attributes indicated the sites were in acceptable condition. Therefore, these two sites were recommended for release from further monitoring. Of the 29 ground surface facility test pits, 26 met the criterion for density, 21 for cover, and 23 for species richness. When key attributes and conditions of the plant community near each pit were taken into account, 27 of these pits were recommended for release. Success parameters and key attributes at ground surface facility test pits 19 and 20 were inadequate for site release. Transplants of native species were added to these two sites in 2001 to improve density, cover, and species richness.« less

Cost-effectiveness analysis of ibrutinib in patients with Waldenström macroglobulinemia in Italy.

PubMed

Aiello, Andrea; D'Ausilio, Anna; Lo Muto, Roberta; Randon, Francesca; Laurenti, Luca

2017-01-01

Background and Objective: Ibrutinib has recently been approved in Europe for Waldenström Macroglobulinemia (WM) in symptomatic patients who have received at least one prior therapy, or in first-line treatment for patients unsuitable for chemo-immunotherapy. The aim of the study is to estimate the incremental cost-effectiveness ratio (ICER) of ibrutinib in relapse/refractory WM, compared with the Italian current therapeutic pathways (CTP). Methods: A Markov model was adapted for Italy considering the National Health System perspective. Input data from literature as well as global trials were used. The percentage use of therapies, and healthcare resources consumption were estimated according to expert panel advice. Drugs ex-factory prices and national tariffs were used for estimating costs. The model had a 15-year time horizon, with a 3.0% discount rate for both clinical and economic data. Deterministic and probabilistic sensitivity analyses were performed to test the results strength. Results: Ibrutinib resulted in increased Life Years Gained (LYGs) and increased costs compared to CTP, with an ICER of €52,698/LYG. Sensitivity analyses confirmed the results of the BaseCase. Specifically, in the probabilistic analysis, at a willingness to pay threshold of €60,000/LYG ibrutinib was cost-effective in 84% of simulations. Conclusions: Ibrutinib has demonstrated a positive cost-effectiveness profile in Italy.

Effects of an ethanol-paired CS on responding for ethanol and food: Comparisons with a stimulus in a Truly-Random-Control group and to a food-paired CS on responding for food.

PubMed

Lamb, R J; Ginsburg, Brett C; Schindler, Charles W

2016-12-01

Motivational increases due to exposure to alcohol-paired Conditioned Stimuli (CS) are central to some accounts of alcoholism. However, few studies isolate a stimulus's function as a CS from its other potential functions. Pavlovian-Instrumental-Transfer (PIT) procedures isolate a stimulus's function as a CS from its other functions. Though there are several relevant studies using PIT, knowledge gaps exist. Particularly, it is not clear that an alcohol-paired CS will increase alcohol seeking compared to the same stimulus in a Truly-Random-Control group, nor whether such increases are specific to alcohol seeking. To address these knowledge gaps in Experiment 1, rats responded for ethanol (0.1 ml 8% w/v) under an RI 30-sec schedule, then the lever was removed and half the rats had ethanol delivered during occasional 120-sec light presentations, while the remainder had ethanol and the light presented under independent RT schedules. Later the lever was returned and the light was presented during responding in extinction (PIT test). Following this test, levers were again removed and the light was presented without ethanol (light extinction), following again by a PIT test. Responding in the two groups during light presentations did not differ in either PIT test. Experiment 2 repeated Experiment 1 using food instead of ethanol. In Experiment 2, responding during light presentations increased in the paired group. In Experiment 3, rats were trained on a concurrent FR schedule of food and ethanol delivery. Ethanol was delivered following 5 responses and the response requirement for food adjusted so that similar numbers of food and ethanol deliveries were obtained. Subsequently, rats underwent conditioning, control and testing procedures identical to those in Experiment 1. In Experiment 3, the ethanol-paired CS increased ethanol-responding, but not food-responding. These results are most easily interpreted as changes in responding resulting from CS-elicited behavior rather than motivational changes. This interpretation is more compatible with some descriptions of the role of an alcohol-paired CS in alcoholism than others. Copyright © 2016 Elsevier Inc. All rights reserved.

Ventral pallidal projections to mediodorsal thalamus and ventral tegmental area play distinct roles in outcome-specific Pavlovian-instrumental transfer.

PubMed

Leung, Beatrice K; Balleine, Bernard W

2015-03-25

Outcome-specific Pavlovian-instrumental transfer (PIT) demonstrates the way that reward-related cues influence choice between instrumental actions. The nucleus accumbens shell (NAc-S) contributes critically to this effect, particularly through its output to the rostral medial ventral pallidum (VP-m). Using rats, we investigated in two experiments the role in the PIT effect of the two major outputs of this VP-m region innervated by the NAc-S, the mediodorsal thalamus (MD) and the ventral tegmental area (VTA). First, two retrograde tracers were injected into the MD and VTA to compare the neuronal activity of the two populations of projection neurons in the VP-m during PIT relative to controls. Second, the functional role of the connection between the VP-m and the MD or VTA was assessed using asymmetrical pharmacological manipulations before a PIT test. It was found that, whereas neurons in the VP-m projecting to the MD showed significantly more neuronal activation during PIT than those projecting to the VTA, neuronal activation of these latter neurons correlated with the size of the PIT effect. Disconnection of the two pathways during PIT also revealed different deficits in performance: disrupting the VP-m to MD pathway removed the response biasing effects of reward-related cues, whereas disrupting the VP-m to VTA pathway preserved the response bias but altered the overall rate of responding. The current results therefore suggest that the VP-m exerts distinct effects on the VTA and MD and that these latter structures mediate the motivational and cognitive components of specific PIT, respectively. Copyright © 2015 the authors 0270-6474/15/354953-12$15.00/0.

Relationship between Microstructure and Corrosion Behavior of Martensitic High Nitrogen Stainless Steel 30Cr15Mo1N at Different Austenitizing Temperatures

PubMed Central

Jiang, Zhouhua; Feng, Hao; Zhu, Hongchun; Zhang, Shucai; Zhang, Binbin; Han, Yu; Zhang, Tao; Xu, Dake

2017-01-01

The relationship between microstructure and corrosion behavior of martensitic high nitrogen stainless steel 30Cr15Mo1N at different austenitizing temperatures was investigated by microscopy observation, electrochemical measurement, X-ray photoelectron spectroscopy analysis and immersion testing. The results indicated that finer Cr-rich M2N dispersed more homogeneously than coarse M23C6, and the fractions of M23C6 and M2N both decreased with increasing austenitizing temperature. The Cr-depleted zone around M23C6 was wider and its minimum Cr concentration was lower than M2N. The metastable pits initiated preferentially around coarse M23C6 which induced severer Cr-depletion, and the pit growth followed the power law. The increasing of austenitizing temperature induced fewer metastable pit initiation sites, more uniform element distribution and higher contents of Cr, Mo and N in the matrix. In addition, the passive film thickened and Cr2O3, Cr3+ and CrN enriched with increasing austenitizing temperature, which enhanced the stability of the passive film and repassivation ability of pits. Therefore, as austenitizing temperature increased, the metastable and stable pitting potentials increased and pit growth rate decreased, revealing less susceptible metastable pit initiation, larger repassivation tendency and higher corrosion resistance. The determining factor of pitting potentials could be divided into three stages: dissolution of M23C6 (below 1000 °C), dissolution of M2N (from 1000 to 1050 °C) and existence of a few undissolved precipitates and non-metallic inclusions (above 1050 °C). PMID:28773221

Effect of Bearing Defects

DTIC Science & Technology

1974-12-01

defect types were tested at various levels: Comet- Tail, Dig-Nick, Dirt Brinell, Grind-Skip Lines, Impingement, Orange Peel , Pit, Scratch and "Liney...Shallow irregular indentation of surface. <.0015 max. dim. -(<.0008)*’ Otange Peel Pebbly appearance of raceway surface. Small ** Comet Tail Pit...scratch; dig-nick; impingement; grind-skip lines; and orange peel . The data obtained indicated that these defects in most cases, affected bearing

Cavitation damage prediction for spallation target vessels by assessment of acoustic vibration

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

Futakawa, Masatoshi; Kogawa, Hiroyuki; Hasegawa, Shoichi

2008-01-01

Liquid-mercury target systems for MW-class spallation neutron sources are being developed around the world. Proton beams are used to induce the spallation reaction. At the moment the proton beam hits the target, pressure waves are generated in the mercury because of the abrupt heat deposition. The pressure waves interact with the target vessel leading to negative pressure that may cause cavitation along the vessel wall. In order to estimate the cavitation erosion, i.e. the pitting damage formed by the collapse of cavitation bubbles, off-beam tests were performed by using an electric magnetic impact testing machine (MIMTM), which can impose equivalentmore » pressure pulses in mercury. The damage potential was defined based on the relationship between the pitting damage and the time-integrated acoustic vibration induced by impact due to the bubble collapses. Additionally, the damage potential was measured in on-beam tests carried out by using the proton beam at WNR (Weapons Neutron Research) facility in Los Alamos Neutron Science Center (LANSCE). In this paper, the concept of the damage potential, the relationship between the pitting damage formation and the damage potential both in off-beam and on-beam tests is shown.« less

A potyvirus vector efficiently targets recombinant proteins to chloroplasts, mitochondria and nuclei in plant cells when expressed at the amino terminus of the polyprotein.

PubMed

Majer, Eszter; Navarro, José-Antonio; Daròs, José-Antonio

2015-09-01

Plant virus-based expression systems allow quick and efficient production of recombinant proteins in plant biofactories. Among them, a system derived from tobacco etch virus (TEV; genus potyvirus) permits coexpression of equimolar amounts of several recombinant proteins. This work analyzed how to target recombinant proteins to different subcellular localizations in the plant cell using this system. We constructed TEV clones in which green fluorescent protein (GFP), with a chloroplast transit peptide (cTP), a nuclear localization signal (NLS) or a mitochondrial targeting peptide (mTP) was expressed either as the most amino-terminal product or embedded in the viral polyprotein. Results showed that cTP and mTP mediated efficient translocation of GFP to the corresponding organelle only when present at the amino terminus of the viral polyprotein. In contrast, the NLS worked efficiently at both positions. Viruses expressing GFP in the amino terminus of the viral polyprotein produced milder symptoms. Untagged GFPs and cTP and NLS tagged amino-terminal GFPs accumulated to higher amounts in infected tissues. Finally, viral progeny from clones with internal GFPs maintained the extra gene better. These observations will help in the design of potyvirus-based vectors able to coexpress several proteins while targeting different subcellular localizations, as required in plant metabolic engineering. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and polymerase activity of a fluorescent cytidine TNA triphosphate analogue

PubMed Central

Mei, Hui; Shi, Changhua; Jimenez, Randi M.; Wang, Yajun; Kardouh, Miramar

2017-01-01

Abstract Threose nucleic acid (TNA) is an artificial genetic polymer capable of undergoing Darwinian evolution to produce aptamers with affinity to specific targets. This property, coupled with a backbone structure that is refractory to nuclease digestion, makes TNA an attractive biopolymer system for diagnostic and therapeutic applications. Expanding the chemical diversity of TNA beyond the natural bases would enable the development of functional TNA molecules with enhanced physiochemical properties. Here, we describe the synthesis and polymerase activity of a fluorescent cytidine TNA triphosphate analogue (1,3-diaza-2-oxo-phenothiazine, tCfTP) that maintains Watson-Crick base pairing with guanine. Polymerase-mediated primer-extension assays reveal that tCfTP is efficiently added to the growing end of a TNA primer. Detailed kinetic assays indicate that tCfTP and tCTP have comparable rates for the first nucleotide incorporation step (kobs1). However, addition of the second nucleotide (kobs2) is 700-fold faster for tCfTP than tCTP due the increased effects of base stacking. Last, we found that TNA replication using tCfTP in place of tCTP exhibits 98.4% overall fidelity for the combined process of TNA transcription and reverse transcription. Together, these results expand the chemical diversity of enzymatically generated TNA molecules to include a hydrophobic base analogue with strong fluorescent properties that is compatible with in vitro selection. PMID:28472363

The USC Adult Twin Cohorts: International Twin Study and California Twin Program.

PubMed

Cozen, Wendy; Hwang, Amie E; Cockburn, Myles G; Hamilton, Ann S; Zadnick, John; Mack, Thomas M

2013-02-01

The study of twin subjects permits the documentation of crude heritability and may promote the identification of specific causal alleles. We believe that at the current time, the chief research advantage of twins as subjects, especially monozygotic twins, is that the commonality of their genetic and cultural identity simplifies the interpretation of biological associations. In order to study genetic and environmental determinants of cancer and chronic diseases, we developed two twin registries, maintained at the University of Southern California: The International Twin Study (ITS) and the California Twin Program (CTP). The ITS is a volunteer registry of twins with cancer and chronic disease consisting of 17,245 twin pairs affected by cancer and chronic disease, respectively, ascertained by advertising in periodicals from 1980-1991. The CTP is a population-based registry of California-born twin pairs ascertained by linking the California birth records to the State Department of Motor Vehicles. Over 51,000 individual California twins representing 36,965 pairs completed and returned 16-page questionnaires. Cancer diagnoses in the California twins are updated by regular linkage to the California Cancer Registry. Over 5,000 cancer patients are represented in the CTP. Twins from both registries have participated extensively in studies of breast cancer, melanoma, lymphoma, multiple sclerosis, systemic lupus erythematosus, diabetes mellitus type 1, mammographic density, smoking, and other traits and conditions.

Relative cerebral blood volume is associated with collateral status and infarct growth in stroke patients in SWIFT PRIME.

PubMed

Arenillas, Juan F; Cortijo, Elisa; García-Bermejo, Pablo; Levy, Elad I; Jahan, Reza; Goyal, Mayank; Saver, Jeffrey L; Albers, Gregory W

2017-01-01

We aimed to evaluate how predefined candidate cerebral perfusion parameters correlate with collateral circulation status and to assess their capacity to predict infarct growth in patients with acute ischemic stroke (AIS) eligible for endovascular therapy. Patients enrolled in the SWIFT PRIME trial with baseline computed tomography perfusion (CTP) scans were included. RAPID software was used to calculate mean relative cerebral blood volume (rCBV) in hypoperfused regions, and hypoperfusion index ratio (HIR). Blind assessments of collaterals were performed using CT angiography in the whole sample and cerebral angiogram in the endovascular group. Reperfusion was assessed on 27-h CTP; infarct volume was assessed on 27-h magnetic resonance imaging/CT scans. Logistic and rank linear regression models were conducted. We included 158 patients. High rCBV ( p = 0.03) and low HIR ( p = 0.03) were associated with good collaterals. A positive association was found between rCBV and better collateral grades on cerebral angiography ( p = 0.01). Baseline and 27-h follow-up CTP were available for 115 patients, of whom 74 (64%) achieved successful reperfusion. Lower rCBV predicted a higher infarct growth in successfully reperfused patients ( p = 0.038) and in the endovascular treatment group ( p = 0.049). Finally, rCBV and HIR may serve as markers of collateral circulation in AIS patients prior to endovascular therapy. Unique identifier: NCT0165746.

Evaluation of Remote Delivery of Passive Integrated Transponder (PIT) Technology to Mark Large Mammals

PubMed Central

Walter, W. David; Anderson, Charles W.; VerCauteren, Kurt C.

2012-01-01

Methods to individually mark and identify free-ranging wildlife without trapping and handling would be useful for a variety of research and management purposes. The use of Passive Integrated Transponder technology could be an efficient method for collecting data for mark-recapture analysis and other strategies for assessing characteristics about populations of various wildlife species. Passive Integrated Transponder tags (PIT) have unique numbered frequencies and have been used to successfully mark and identify mammals. We tested for successful injection of PIT and subsequent functioning of PIT into gelatin blocks using 4 variations of a prototype dart. We then selected the prototype dart that resulted in the least depth of penetration in the gelatin block to assess the ability of PIT to be successfully implanted into muscle tissue of white-tailed deer (Odocoileus virginianus) post-mortem and long-term in live, captive Rocky Mountain elk (Cervus elaphus). The prototype dart with a 12.7 mm (0.5 inch) needle length and no powder charge resulted in the shallowest mean (± SD) penetration depth into gelatin blocks of 27.0 mm (±5.6 mm) with 2.0 psi setting on the Dan-Inject CO2-pressured rifle. Eighty percent of PIT were successfully injected in the muscle mass of white-tailed deer post-mortem with a mean (± SD) penetration depth of 22.2 mm (±3.8 mm; n = 6). We injected PIT successfully into 13 live, captive elk by remote delivery at about 20 m that remained functional for 7 months. We successfully demonstrated that PIT could be remotely delivered in darts into muscle mass of large mammals and remain functional for >6 months. Although further research is warranted to fully develop the technique, remote delivery of PIT technology to large mammals is possible using prototype implant darts. PMID:22984572

δ-Opioid and Dopaminergic Processes in Accumbens Shell Modulate the Cholinergic Control of Predictive Learning and Choice

PubMed Central

Laurent, Vincent; Bertran-Gonzalez, Jesus; Chieng, Billy C.

2014-01-01

Decision-making depends on the ability to extract predictive information from the environment to guide future actions. Outcome-specific Pavlovian-instrumental transfer (PIT) provides an animal model of this process in which a stimulus predicting a particular outcome biases choice toward actions earning that outcome. Recent evidence suggests that cellular adaptations of δ-opioid receptors (DORs) on cholinergic interneurons (CINs) in the nucleus accumbens shell (NAc-S) are necessary for PIT. Here we found that modulation of DORs in CINs critically influences D1-receptor (D1R)-expressing projection neurons in the NAc-S to promote PIT. First, we assessed PIT-induced changes in signaling processes in dopamine D1- and D2-receptor-expressing neurons using drd2-eGFP mice, and found that PIT-related signaling was restricted to non-D2R-eGFP-expressing neurons, suggesting major involvement of D1R-neurons. Next we confirmed the role of D1Rs pharmacologically: the D1R antagonist SCH-23390, but not the D2R antagonist raclopride, infused into the NAc-S abolished PIT in rats, an effect that depended on DOR activity. Moreover, asymmetrical infusion of SCH-23390 and the DOR antagonist naltrindole into the NAc-S also abolished PIT. DOR agonists were found to sensitize the firing responses of CINs in brain slices prepared immediately after the PIT test. We confirmed the opioid-acetylcholinergic influence over D1R-neurons by selectively blocking muscarinic M4 receptors in the NAc-S, which tightly regulate the activity of D1Rs, a treatment that rescued the deficit in PIT induced by naltrindole. We describe a model of NAc-S function in which DORs modulate CINs to influence both D1R-neurons and stimulus-guided choice between goal-directed actions. PMID:24453326

Report on Electrochemcial Corrosion Testing of 241-SY-102 Grab Samples from the 2012 Grab Sampling Campaign

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

Wyrwas, Richard B.; Lamothe, Margaret E.

2013-05-30

This report describes the results of the electrochemical testing performed on tank 241-SY-102 (SY-102) grab samples that were collected in support of corrosion mitigation. The objective of the work presented here was to determine corrosion resistance of tank SY-102 to the grab samples collected using electrochemical methods up to 50°C as well as to satisfy data quality objectives. Grab samples were collected at multiple elevations from Riser 003. The electrochemical corrosion testing was planned to consist of linear polarization resistance testing (LPR) and cyclic potentiodynamic polarization (CPP) testing at 50°C. The temperature would be lowered to 40 °C and themore » test repeated if the CPP curve indicated pitting corrosion at 50°C. Ifno pitting was indicated by the CPP curve, then a duplicate scan would be repeated at 50°C to confirm the first result. The testing would be complete if the duplicate CPP scan was consistent with the first. This report contains the CPP results of the testing of grab sample 2SY-12-03 and 2SY-12-03DUP composite sample tested under these conditions. There was no indication of pitting at 50°C, and the duplicate scan was in agreement with the first scan. Since no further testing was required, a third scan with a shorter rest time was performed and is present in this report.« less

Is there a difference in prevalence of helminths between households using ecological sanitation and those using traditional pit latrines? A latrine based cross sectional comparative study in Malawi.

PubMed

Kumwenda, Save; Msefula, Chisomo; Kadewa, Wilfred; Diness, Yohane; Kato, Charles; Morse, Tracy; Ngwira, Bagrey

2017-06-09

Studies have shown that households using sludge from human excreta for agriculture are at an increased risk of soil transmitted helminths. However, while use of ecological sanitation (EcoSan) latrines is increasing in most African countries including Malawi, few studies have been done to check whether use of such sludge could potentially increase the prevalence of helminthic infections among household members as a results of exposure to faecal sludge/compared to use of traditional latrines. A cross sectional study was done targeting households using EcoSan and traditional pit latrines. Samples were collected from both types of latrines in Chikwawa (rural) and Blantyre (urban) districts. These two districts have a high number of EcoSan latrines in southern region of Malawi. 156 latrines were sampled (n = 95 traditional; n = 61 EcoSan), and processed following standard guidelines using modified triple floatation method. Identification of helminth ova (Ascaris lumbricoides, hookworms, Trichuris trichiura, Taenia spp. and Diphyllobothrium latum) was done using standard microscopy methods. The difference between the prevalence and mean concentration of helminths between the two types of latrines was tested using Chi Square and t test respectively. Of the total latrines tested, 85.9% (n = 134) had at least one species of helminth while 84.6% (n = 132) had at least a STH, with 82.0% (n = 50) in EcoSan and 86.3% (n = 82) in traditional pit latrines. There was no significant difference between the prevalence of helminths in EcoSan and traditional pit latrines [χ 2  = 0.43 (1), P = 0.5]. The prevalence of Ascaris lumbricoides was significantly higher in EcoSan than in traditional pit latrines [χ 2  = 5.44 (1) p = 0.02] while prevalence of hookworms was significantly higher in traditional pit latrines than in EcoSan latrines [χ 2  = 13.98 (1) p < 0.001]. The highest concentration of helminths per gram of faecal sludge was in traditional pit latrines [31.2 (95% CI 19.1-43.2)] than in EcoSan latrines [26.4 (95% CI 16.5-36.3)]. There was no significant difference between overall prevalence of helminths between households using EcoSan and those using traditional pit latrines. However, Ascaris lumbricoides was significantly higher in households using EcoSan latrines. EcoSan users need awareness on safe ways of handling faecal sludge in order to reduce chances of reinfection from Ascaris lumbricoides. Further research should be undertaken on household members to identify those infected and potential routes of infection to enable preventive targeting.

An investigation of rolling-sliding contact fatigue damage of carburized gear steels

NASA Astrophysics Data System (ADS)

Kramer, Patrick C.

The goal of this study was to evaluate the differences in RSCF performance between vacuum and gas carburized steels as well as to investigate the evolution of damage (wear and microstructure changes) leading to pitting. Vacuum and gas carburizing was performed on two gear steels (4120 and 4320) at 1010°C. The carburized specimens were tested in the as-carburized condition using a RSCF machine designed and built at the Colorado School of Mines. The tests were conducted at 3.2 GPa nominal Hertzian contact stress, based on pure rolling, 100°C, and using a negative twenty percent slide ratio. Tests were conducted to pitting failure for each condition for a comparison of the average fatigue lives. Pure rolling tests were also conducted, and were suspended at the same number of cycles as the average RSCF life for a comparison of fatigue damage developed by RCF and RSCF. Incremental tests were suspended at 1,000, 10,000, 100,000, and 200,000 cycles for the vacuum carburized steels to evaluate the wear and damage developed during the initial cycles of RSCF testing and to relate the wear and damage to pitting resistance. Incremental damage was not investigated for gas carburizing due to the limited number of available specimens. The vacuum carburized samples showed a decreased pitting fatigue resistance over the gas carburized samples, possibly due to the presence of bainite in the vacuum carburized cases. Pitting was observed to initiate from surface micropitting and microcracking. A microstructural change induced by contact fatigue, butterflies, was shown to contribute to micropitting and microcracking. Incremental testing revealed that the formation of a microcrack preceded and was necessary for the formation of the butterfly features, and that the butterfly features developed between 10,000 and 100,000 cycles. The orientation and depth of butterfly formation was shown to be dependent upon the application of traction stresses from sliding. RSCF butterflies formed nearly parallel to the rolling direction at a large range of depths. RCF butterflies formed at about 45° to the rolling direction in a more narrow range of depths. The surface roughness and surface profile were observed to change quickly in the first several thousand cycles of RSCF testing leading to a reduction in contact stress and increase in lambda ratio (ratio of lubricant fluid film thickness to composite surface roughness). The ability of a carburized sample wear track to reach and maintain a steady state morphology (run-in condition) during testing is postulated to translate to increased RSCF resistance.

Mitigating Localized Corrosion Using Thermally Sprayed Aluminum (TSA) Coatings on Welded 25% Cr Superduplex Stainless Steel

NASA Astrophysics Data System (ADS)

Paul, S.; Lu, Q.; Harvey, M. D. F.

2015-04-01

Thermally sprayed aluminum (TSA) coating has been increasingly used for the protection of carbon steel offshore structures, topside equipment, and flowlines/pipelines exposed to both marine atmospheres and seawater immersion conditions. In this paper, the effectiveness of TSA coatings in preventing localized corrosion, such as pitting and crevice corrosion of 25% Cr superduplex stainless steel (SDSS) in subsea applications, has been investigated. Welded 25% Cr SDSS (coated and uncoated) with and without defects, and surfaces coated with epoxy paint were also examined. Pitting and crevice corrosion tests, on welded 25% Cr SDSS specimens with and without TSA/epoxy coatings, were conducted in recirculated, aerated, and synthetic seawater at 90 °C for 90 days. The tests were carried out at both the free corrosion potentials and an applied cathodic potential of -1100 mV saturated calomel electrode. The acidity (pH) of the test solution was monitored daily and adjusted to between pH 7.5 and 8.1, using dilute HCl solution or dilute NaOH, depending on the pH of the solution measured during the test. The test results demonstrated that TSA prevented pitting and crevice corrosion of 25% Cr SDSS in artificial seawater at 90 °C, even when 10-mm-diameter coating defect exposing the underlying steel was present.

Skeletal mineralization deficits and impaired biogenesis and function of chondrocyte-derived matrix vesicles in Phospho1−/− and Phospho1/Pit1 double knockout mice

PubMed Central

Yadav, Manisha C.; Bottini, Massimo; Cory, Esther; Bhattacharya, Kunal; Kuss, Pia; Narisawa, Sonoko; Sah, Robert L.; Beck, Laurent; Fadeel, Bengt; Farquharson, Colin; Millán, José Luis

2016-01-01

We have previously shown that ablation of either the Phospho1 or Alpl gene, encoding PHOSPHO1 and tissue-nonspecific alkaline phosphatase (TNAP) respectively, lead to hyperosteoidosis but that their chondrocyte- and osteoblast-derived matrix vesicles (MVs) are able to initiate mineralization. In contrast, the double ablation of Phospho1 and Alpl completely abolish initiation and progression of skeletal mineralization. We argued that MVs initiate mineralization by a dual mechanism: PHOSPHO1-mediated intravesicular generation of Pi and phosphate transporter-mediated influx of Pi. To test this hypothesis, we generated mice with col2a1-driven cre-mediated ablation of Slc20a1, hereafter referred to as Pit1, alone or in combination with a Phospho1 gene deletion. Pit1col2/col2 mice did not show any major phenotypic abnormalities, while severe skeletal deformities were observed in the [Phospho1−/−; Pit1col2/col2] double knockout mice that were more pronounced than those observed in the Phospho1−/− mice. Histological analysis of [Phospho1−/−; Pit1col2/col2] bones showed growth plate abnormalities with a shorter hypertrophic chondrocyte zone and extensive hyperosteoidosis. The [Phospho1−/−; Pit1col2/col2] skeleton displayed significantly decreases in BV/TV%, trabecular number and bone mineral density, as well as decreased stiffness, decreased strength, and increased post-yield deflection compared to Phospho1−/− mice. Using atomic force microscopy we found that ~80% of [Phospho1−/−; Pit1col2/col2] MVs were devoid of mineral in comparison to ~50 % for the Phospho1−/− MVs and ~25% for the WT and Pit1col2/col2 MVs. We also found a significant decrease in the number of MVs produced by both Phospho1−/− and [Phospho1−/−; Pit1col2/col2] chondrocytes. These data support the involvement of PiT-1 in the initiation of skeletal mineralization and provide compelling evidence that PHOSPHO1 function is involved in MV biogenesis. PMID:26773408

38. 100,000 POUND STATIC TEST FACILITY: GENERAL VIEW OF TEST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

38. 100,000 POUND STATIC TEST FACILITY: GENERAL VIEW OF TEST BAY AND EXHAUST PIT, LOOKING WEST - White Sands Missile Range, V-2 Rocket Facilities, Near Headquarters Area, White Sands, Dona Ana County, NM

37. 100,000 POUND STATIC TEST FACILITY: GENERAL VIEW OF TEST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

37. 100,000 POUND STATIC TEST FACILITY: GENERAL VIEW OF TEST BAY AND EXHAUST PIT, LOOKING SOUTHWEST - White Sands Missile Range, V-2 Rocket Facilities, Near Headquarters Area, White Sands, Dona Ana County, NM

Comparison of TOF MRA, Contrast-Enhanced MRA and Subtracted CTA from CTP in Residue Evaluation of Treated Intracranial Aneurysms.

PubMed

Dündar, Tolga Turan; Aralaşmak, Ayşe; Özdemir, Hüseyin; Seyithanoğlu, Mehmet Hakan; Uysal, Ömer; Toprak, Hüseyin; Kitiş, Serkan; Özek, Erdinç; Alkan, Alpay

2017-10-18

To compare effectiveness of contrast-enhanced MRA (CE-MRA), 3D-Time-of-flight MRA (3D-TOF-MRA) and subtracted CTA from CTP (sub-CTA) in residue evaluation of intracranial aneurysms treated either with coiling or clipping. Sixteen treated aneurysms, which were evaluated with three methods within two weeks after the operation, were enrolled. The success of each imaging techniques in demonstration of residue aneurysm and nearby vessels was compared by Fisher\\'s Exact Test. The differences among three was evaluated by Cochran\\'s Q test (p ≤ 0.05). Perfusion abnormality was noted in % 81 of clipped and none of coiled patients. Vessel visualization in the vicinity of aneurysm was better in sub-CTA, followed by CE-MRA. In clipped aneurysms, sub-CTA revealed residue aneurysms in % 16,7 of the patients while 3D-TOF-MRA and CE-MRA revealed none. In coiled aneurysms, CE-MRA revealed residue aneurysms in 100 %, and TOF-MRA in 33,3 % while sub-CTA revealed none. Although dramatic differences were noted in the evaluation of residue aneurysm as well as nearby vessel visualization, no statistical significance noted due to very few patients in subcategories Conclusion: This is first study comparing the effectiveness of CE-MRA, 3D-TOF MRA and sub-CTA in residue aneurysms evaluation. Vessel visualization in the vicinity of aneurysm was better in sub-CTA in all regardless of coiling or clipping. Residue aneurysms were more commonly revealed by CE-MRA in coiled patients and more commonly and better shown by sub-CTA in clipped patients in addition of showing perfusion abnormality that's is more common in clipped patients.

CTP synthase forms the cytoophidium in human hepatocellular carcinoma.

PubMed

Chang, Chia-Chun; Jeng, Yung-Ming; Peng, Min; Keppeke, Gerson Dierley; Sung, Li-Ying; Liu, Ji-Long

2017-12-15

CTP synthase (CTPS) can aggregate into an intracellular macrostructure, the cytoophidium, in various organisms including human cells. Previous studies have shown that assembly of human CTPS cytoophidia may be correlated with the cellular metabolic status, and is able to promote the activity of CTPS. A correlation between the cytoophidium and cancer metabolism has been proposed but not yet been revealed. In the current study we provide clear evidence of the presence of CTPS cytoophidia in various human cancers and some non-cancerous tissues. Moreover, among 203 tissue samples of hepatocellular carcinoma, 56 (28%) samples exhibited many cytoophidia, whereas no cytoophidia were detected in adjacent non-cancerous hepatocytes for all samples. Our findings suggest that the CTPS cytoophidium may participate in the adaptive metabolism of human hepatocellular carcinoma. Copyright © 2017. Published by Elsevier Inc.

Detection of fungal infectous agent of wheat grains in store-pits of Markazi province, Iran.

PubMed

Saberi-Riseh, R; Javan-Nikkhah, M; Heidarian, R; Hosseini, S; Soleimani, P

2004-01-01

Wheat is an economic and important crop that provides approximately 20% of food calorie in the world. It is first crop in Iran and cultivated in the most areas of this country. Store-pit fungi make undesirable changes in quality and appearance of wheat grains. Even, some fungi produce different mycotoxins which are toxic to human and livestock's that use wheat grains as source of food. In this study, several samples were randomly collected from each of five store-pits located in different areas of Markazi Province including: Arak, Mahallat, Khomein, Saveh and Sarband. Grains were treated on PDA, and blotter, agar and washing test also used for isolating and detection of fungi. At least 100 grains per each sample were randomly used for each test and treatment. The fungi that determined in this study were Cochliobolus australiensis, Cladosporium herbarum, Epicoccum sp., Tilletia leavis, Aspergillus flavus, A. niger, A. fumigatus, Alternaria alternata, Alternaria sp., Penicillium italicum, P. digitatum, Fusarium sp., Rhizopus sp., Ustilago tritici, Scytalidium sp. Among these fungi the most isolates were belonged to Cladosporium, Alternaria, Rhizopus and Fusarium. Cladosporium herbarum was the most common in different sampling areas. Tilletia laevis and Ustilago tritici were just recovered in washing test. This study revealed that different fungi are associated with wheat grains in store-pits in Markazi Province. Some of them like Aspergillus flavus normally produce aflatoxin, a very toxic and carcinogenic mycotoxin that is harmful for human.

In Situ Corrosion and Heat Loss Assessment of Two Nonstandard Underground Heat Distribution System Piping Designs: Supplement-Appendices for Final Report on Project F07-AR01

DTIC Science & Technology

2011-06-01

negative mission impacts . This report documents the assessment of two similar nonstandard UHDS piping system designs — one at Fort Carson, CO, and one at...psig and monitored for 2 hours to determine whether the conduit piping system is protected from ground water infiltration and its degrading impacts ...Conduits to/from this pit were tested from adjacent pits. 2. Supply, Return drains tested on 8/15/07: All Dry N S EW MH-3N ERDC/CERL TR-11-14 H13

Analytical and experimental vibration analysis of a faulty gear system

NASA Astrophysics Data System (ADS)

Choy, F. K.; Braun, M. J.; Polyshchuk, V.; Zakrajsek, J. J.; Townsend, D. P.; Handschuh, R. F.

1994-10-01

A comprehensive analytical procedure was developed for predicting faults in gear transmission systems under normal operating conditions. A gear tooth fault model is developed to simulate the effects of pitting and wear on the vibration signal under normal operating conditions. The model uses changes in the gear mesh stiffness to simulate the effects of gear tooth faults. The overall dynamics of the gear transmission system is evaluated by coupling the dynamics of each individual gear-rotor system through gear mesh forces generated between each gear-rotor system and the bearing forces generated between the rotor and the gearbox structures. The predicted results were compared with experimental results obtained from a spiral bevel gear fatigue test rig at NASA Lewis Research Center. The Wigner-Ville Distribution (WVD) was used to give a comprehensive comparison of the predicted and experimental results. The WVD method applied to the experimental results were also compared to other fault detection techniques to verify the WVD's ability to detect the pitting damage, and to determine its relative performance. Overall results show good correlation between the experimental vibration data of the damaged test gear and the predicted vibration from the model with simulated gear tooth pitting damage. Results also verified that the WVD method can successfully detect and locate gear tooth wear and pitting damage.

Analytical and experimental vibration analysis of a faulty gear system

NASA Astrophysics Data System (ADS)

Choy, F. K.; Braun, M. J.; Polyshchuk, V.; Zakrajsek, J. J.; Townsend, D. P.; Handschuh, R. F.

1994-10-01

A comprehensive analytical procedure was developed for predicting faults in gear transmission systems under normal operating conditions. A gear tooth fault model is developed to simulate the effects of pitting and wear on the vibration signal under normal operating conditions. The model uses changes in the gear mesh stiffness to simulate the effects of gear tooth faults. The overall dynamics of the gear transmission system is evaluated by coupling the dynamics of each individual gear-rotor system through gear mesh forces generated between each gear-rotor system and the bearing forces generated between the rotor and the gearbox structure. The predicted results were compared with experimental results obtained from a spiral bevel gear fatigue test rig at NASA Lewis Research Center. The Wigner-Ville distribution (WVD) was used to give a comprehensive comparison of the predicted and experimental results. The WVD method applied to the experimental results were also compared to other fault detection techniques to verify the WVD's ability to detect the pitting damage, and to determine its relative performance. Overall results show good correlation between the experimental vibration data of the damaged test gear and the predicted vibration from the model with simulated gear tooth pitting damage. Results also verified that the WVD method can successfully detect and locate gear tooth wear and pitting damage.

Analytical and Experimental Vibration Analysis of a Faulty Gear System

NASA Technical Reports Server (NTRS)

Choy, F. K.; Braun, M. J.; Polyshchuk, V.; Zakrajsek, J. J.; Townsend, D. P.; Handschuh, R. F.

1994-01-01

A comprehensive analytical procedure was developed for predicting faults in gear transmission systems under normal operating conditions. A gear tooth fault model is developed to simulate the effects of pitting and wear on the vibration signal under normal operating conditions. The model uses changes in the gear mesh stiffness to simulate the effects of gear tooth faults. The overall dynamics of the gear transmission system is evaluated by coupling the dynamics of each individual gear-rotor system through gear mesh forces generated between each gear-rotor system and the bearing forces generated between the rotor and the gearbox structure. The predicted results were compared with experimental results obtained from a spiral bevel gear fatigue test rig at NASA Lewis Research Center. The Wigner-Ville distribution (WVD) was used to give a comprehensive comparison of the predicted and experimental results. The WVD method applied to the experimental results were also compared to other fault detection techniques to verify the WVD's ability to detect the pitting damage, and to determine its relative performance. Overall results show good correlation between the experimental vibration data of the damaged test gear and the predicted vibration from the model with simulated gear tooth pitting damage. Results also verified that the WVD method can successfully detect and locate gear tooth wear and pitting damage.

Sjogren's syndrome presenting as remitting seronegative symmetric synovitis with pitting edema (RS3PE).

PubMed Central

Choi, Young Mi; Sheen, Dong Hyuk; Lee, Yun Jong; Lee, Eun Bong; Song, Yeong Wook

2003-01-01

Remitting seronegative symmetric synovitis with pitting edema (RS3PE) syndrome is characterized by symmetrical and acute synovitis, pitting edema, the absence of rheumatoid factor, increased acute phase reactants, lack of bony erosions on radiography, and benign and short clinical course. Half of all patients with Sjogren's syndrome experience arthritis during the disease course. We here describe the first case of Sjogren's syndrome presenting as RS3PE. She had swelling in knees, ankles, and wrists. After then the swelling spread to her lower legs, feet, face, and both hands. She was admitted to another hospital and was suspected of lupus or rheumatoid arthritis. Three months later, she had dry mouth and had lower lip biopsy. She was admitted to this hospital due to development of swelling in face and lower legs for 3 days. On physical examination, she had pitting edema in both hands and feet dorsum. Laboratory test showed elevated erythrocyte sedimentation rate, positivity of rheumatoid factor, anti-nuclear antibody, and anti-Ro antibody. There was no erosion in the hands radiography. Schirmer's test and lip biopsy was compatible with Sjogren's syndrome. She was diagnosed RS3PE and Sjogren's syndrome. She was begun with prednisolone and her symptoms improved gradually. PMID:12923344

Sjogren's syndrome presenting as remitting seronegative symmetric synovitis with pitting edema (RS3PE).

PubMed

Choi, Young Mi; Sheen, Dong Hyuk; Lee, Yun Jong; Lee, Eun Bong; Song, Yeong Wook

2003-08-01

Remitting seronegative symmetric synovitis with pitting edema (RS3PE) syndrome is characterized by symmetrical and acute synovitis, pitting edema, the absence of rheumatoid factor, increased acute phase reactants, lack of bony erosions on radiography, and benign and short clinical course. Half of all patients with Sjogren's syndrome experience arthritis during the disease course. We here describe the first case of Sjogren's syndrome presenting as RS3PE. She had swelling in knees, ankles, and wrists. After then the swelling spread to her lower legs, feet, face, and both hands. She was admitted to another hospital and was suspected of lupus or rheumatoid arthritis. Three months later, she had dry mouth and had lower lip biopsy. She was admitted to this hospital due to development of swelling in face and lower legs for 3 days. On physical examination, she had pitting edema in both hands and feet dorsum. Laboratory test showed elevated erythrocyte sedimentation rate, positivity of rheumatoid factor, anti-nuclear antibody, and anti-Ro antibody. There was no erosion in the hands radiography. Schirmer's test and lip biopsy was compatible with Sjogren's syndrome. She was diagnosed RS3PE and Sjogren's syndrome. She was begun with prednisolone and her symptoms improved gradually.

Effect of Annealing Temperature on the Mechanical and Corrosion Behavior of a Newly Developed Novel Lean Duplex Stainless Steel.

PubMed

Guo, Yanjun; Hu, Jincheng; Li, Jin; Jiang, Laizhu; Liu, Tianwei; Wu, Yanping

2014-09-12

The effect of annealing temperature (1000-1150 °C) on the microstructure evolution, mechanical properties, and pitting corrosion behavior of a newly developed novel lean duplex stainless steel with 20.53Cr-3.45Mn-2.08Ni-0.17N-0.31Mo was studied by means of optical metallographic microscopy (OMM), scanning electron microscopy (SEM), magnetic force microscopy (MFM), scanning Kelvin probe force microscopy (SKPFM), energy dispersive X-ray spectroscopy (EDS), uniaxial tensile tests (UTT), and potentiostatic critical pitting temperature (CPT). The results showed that tensile and yield strength, as well as the pitting corrosion resistance, could be degraded with annealing temperature increasing from 1000 up to 1150 °C. Meanwhile, the elongation at break reached the maximum of 52.7% after annealing at 1050 °C due to the effect of martensite transformation induced plasticity (TRIP). The localized pitting attack preferentially occurred at ferrite phase, indicating that the ferrite phase had inferior pitting corrosion resistance as compared to the austenite phase. With increasing annealing temperature, the pitting resistance equivalent number (PREN) of ferrite phase dropped, while that of the austenite phase rose. Additionally, it was found that ferrite possessed a lower Volta potential than austenite phase. Moreover, the Volta potential difference between ferrite and austenite increased with the annealing temperature, which was well consistent with the difference of PREN.

Effect of Annealing Temperature on the Mechanical and Corrosion Behavior of a Newly Developed Novel Lean Duplex Stainless Steel

PubMed Central

Guo, Yanjun; Hu, Jincheng; Li, Jin; Jiang, Laizhu; Liu, Tianwei; Wu, Yanping

2014-01-01

The effect of annealing temperature (1000–1150 °C) on the microstructure evolution, mechanical properties, and pitting corrosion behavior of a newly developed novel lean duplex stainless steel with 20.53Cr-3.45Mn-2.08Ni-0.17N-0.31Mo was studied by means of optical metallographic microscopy (OMM), scanning electron microscopy (SEM), magnetic force microscopy (MFM), scanning Kelvin probe force microscopy (SKPFM), energy dispersive X-ray spectroscopy (EDS), uniaxial tensile tests (UTT), and potentiostatic critical pitting temperature (CPT). The results showed that tensile and yield strength, as well as the pitting corrosion resistance, could be degraded with annealing temperature increasing from 1000 up to 1150 °C. Meanwhile, the elongation at break reached the maximum of 52.7% after annealing at 1050 °C due to the effect of martensite transformation induced plasticity (TRIP). The localized pitting attack preferentially occurred at ferrite phase, indicating that the ferrite phase had inferior pitting corrosion resistance as compared to the austenite phase. With increasing annealing temperature, the pitting resistance equivalent number (PREN) of ferrite phase dropped, while that of the austenite phase rose. Additionally, it was found that ferrite possessed a lower Volta potential than austenite phase. Moreover, the Volta potential difference between ferrite and austenite increased with the annealing temperature, which was well consistent with the difference of PREN. PMID:28788201

Impairments in proverb interpretation following focal frontal lobe lesions☆

PubMed Central

Murphy, Patrick; Shallice, Tim; Robinson, Gail; MacPherson, Sarah E.; Turner, Martha; Woollett, Katherine; Bozzali, Marco; Cipolotti, Lisa

2013-01-01

The proverb interpretation task (PIT) is often used in clinical settings to evaluate frontal “executive” dysfunction. However, only a relatively small number of studies have investigated the relationship between frontal lobe lesions and performance on the PIT. We compared 52 patients with unselected focal frontal lobe lesions with 52 closely matched healthy controls on a proverb interpretation task. Participants also completed a battery of neuropsychological tests, including a fluid intelligence task (Raven’s Advanced Progressive Matrices). Lesions were firstly analysed according to a standard left/right sub-division. Secondly, a finer-grained analysis compared the performance of patients with medial, left lateral and right lateral lesions with healthy controls. Thirdly, a contrast of specific frontal subgroups compared the performance of patients with medial lesions with patients with lateral frontal lesions. The results showed that patients with left frontal lesions were significantly impaired on the PIT, while in patients with right frontal lesions the impairments approached significance. Medial frontal patients were the only frontal subgroup impaired on the PIT, relative to healthy controls and lateral frontal patients. Interestingly, an error analysis indicated that a significantly higher number of concrete responses were found in the left lateral subgroup compared to healthy controls. We found no correlation between scores on the PIT and on the fluid intelligence task. Overall our results suggest that specific regions of the frontal lobes contribute to the performance on the PIT. PMID:23850600

Determination on Damage Mechanism of the Planet Gear of Heavy Vehicle Final Drive

NASA Astrophysics Data System (ADS)

Ramdan, RD; Setiawan, R.; Sasmita, F.; Suratman, R.; Taufiqulloh

2018-02-01

The works focus on the investigation of damage mechanism of fractured in the form of spalling of the planet gears from the final drive assembly of 160-ton heavy vehicles. The objective of this work is to clearly understand the mechanism of damage. The work is the first stage of the on-going research on the remaining life estimation of such gears. The understanding of the damage mechanism is critical in order to provide accurate estimate of the gear’s remaining life with observed initial damage. The analysis was performed based on the metallurgy laboratory works, including visual observation, macro-micro fractography by optical stereo and optical microscope and micro-vickers hardness test. From visual observation it was observed pitting that form lining defect at common position, which is at gear flank position. From spalling sample it was observed ratchet mark at the boundary between macro pitting and the edge of fractured parts. Further observation on the cross-section of the samples by optical microscope confirm that initial micro pitting occur without spalling of the case hardened surface. Spalling occur when pitting achieve certain critical size, and occur at multiple initiation site of crack propagation. From the present research it was concluded that pitting was resulted due to repeated contact fatigue. In addition, development of micro to macro pitting as well as spalling occur at certain direction towards the top of the gear teeth.

The thermal background determines how the infrared and visual systems interact in pit vipers.

PubMed

Chen, Qin; Liu, Yang; Brauth, Steven E; Fang, Guangzhan; Tang, Yezhong

2017-09-01

The thermal infrared (IR) sensing system of pit vipers is believed to complement vision and provide a substitute imaging system in dark environments. Theoretically, the IR system would best image a scene consisting of a homothermal target in cold surroundings as a bright spot on a dark background. To test this hypothesis, we evaluated how the pit viper ( Gloydius brevicaudus ) discriminates and strikes prey when the background temperature is either higher or lower than that of the prey (approximately 32-33°C) in different parts of the scene. Snakes were tested in a modified predation cage in which background temperatures were set to 26°C on one side and either 33 or 40°C on the opposite side when the eyes, the pit organs or neither sensory system was occluded. When the eyes were blocked, snakes preferred to strike prey on the 26°C side rather than on the 33°C side but showed no bias in the other conditions. Snakes showed no preference for 26 versus 40°C background temperature, although more missed strikes occurred when the eyes were occluded. The results thus revealed that the pit viper IR system can accomplish a 'brightness constancy' computation reflecting the difference between the target and background temperatures, much as the visual system compares the luminance of a figure and the background. Furthermore, the results show that the IR system performs less well for locating prey when the background is warmer than the target. © 2017. Published by The Company of Biologists Ltd.

How Y-Family DNA polymerase IV is more accurate than Dpo4 at dCTP insertion opposite an N2-dG adduct of benzo[a]pyrene.

PubMed

Sholder, Gabriel; Creech, Amanda; Loechler, Edward L

2015-11-01

To bypass DNA damage, cells have Y-Family DNA polymerases (DNAPs). One Y-Family-class includes DNAP κ and DNAP IV, which accurately insert dCTP opposite N(2)-dG adducts, including from the carcinogen benzo[a]pyrene (BP). Another class includes DNAP η and DNAP V, which insert accurately opposite UV-damage, but inaccurately opposite BP-N(2)-dG. To investigate structural differences between Y-Family-classes, regions are swapped between DNAP IV (a κ/IV-class-member) and Dpo4 (a η/V-class-member); the kinetic consequences are evaluated via primer-extension studies with a BP-N(2)-dG-containing template. Four key structural elements are revealed. (1) Y-Family DNAPs have discreet non-covalent contacts between their little finger-domain (LF-Domain) and their catalytic core-domain (CC-Domain), which we call "non-covalent bridges" (NCBs). Arg37 and Arg38 in DNAP IV's CC-Domain near the active site form a non-covalent bridge (AS-NCB) by interacting with Glu251 and Asp252, respectively, in DNAP IV's LF-Domain. Without these interactions dATP/dGTP/dTTP misinsertions increase. DNAP IV's AS-NCB suppresses misinsertions better than Dpo4's equivalent AS-NCB. (2) DNAP IV also suppresses dATP/dGTP/dTTP misinsertions via a second non-covalent bridge, which is ∼8Å from the active site (Distal-NCB). Dpo4 has no Distal-NCB, rendering it inferior at dATP/dGTP/dTTP suppression. (3) dCTP insertion is facilitated by the larger minor groove opening near the active site in DNAP IV versus Dpo4, which is sensible given that Watson/Crick-like [dCTP:BP-N(2)-dG] pairing requires the BP-moiety to be in the minor groove. (4) Compared to Dpo4, DNAP IV has a smaller major groove opening, which suppresses dGTP misinsertion, implying BP-N(2)-dG bulk in the major groove during Hoogsteen syn-adduct-dG:dGTP pairing. In summary, DNAP IV has a large minor groove opening to enhance dCTP insertion, a plugged major groove opening to suppress dGTP misinsertion, and two non-covalent bridges (near and distal to the active site) to suppress dATP/dGTP/dTTP misinsertions; collectively these four structural features enhance DNAP IV's dNTP insertion fidelity opposite a BP-N(2)-dG adduct compared to Dpo4. Copyright © 2015 Elsevier B.V. All rights reserved.

Detecting gear tooth fracture in a high contact ratio face gear mesh

NASA Technical Reports Server (NTRS)

Zakrajsek, James J.; Handschuh, Robert F.; Lewicki, David G.; Decker, Harry J.

1995-01-01

This paper summarized the results of a study in which three different vibration diagnostic methods were used to detect gear tooth fracture in a high contact ratio face gear mesh. The NASA spiral bevel gear fatigue test rig was used to produce unseeded fault, natural failures of four face gear specimens. During the fatigue tests, which were run to determine load capacity and primary failure mechanisms for face gears, vibration signals were monitored and recorded for gear diagnostic purposes. Gear tooth bending fatigue and surface pitting were the primary failure modes found in the tests. The damage ranged from partial tooth fracture on a single tooth in one test to heavy wear, severe pitting, and complete tooth fracture of several teeth on another test. Three gear fault detection techniques, FM4, NA4*, and NB4, were applied to the experimental data. These methods use the signal average in both the time and frequency domain. Method NA4* was able to conclusively detect the gear tooth fractures in three out of the four fatigue tests, along with gear tooth surface pitting and heavy wear. For multiple tooth fractures, all of the methods gave a clear indication of the damage. It was also found that due to the high contact ratio of the face gear mesh, single tooth fractures did not significantly affect the vibration signal, making this type of failure difficult to detect.

Pits, rifts and slumps: the summit structure of Piton de la Fournaise

NASA Astrophysics Data System (ADS)

Carter, Adam; van Wyk de Vries, Benjamin; Kelfoun, Karim; Bachèlery, Patrick; Briole, Pierre

2007-06-01

A clear model of structures and associated stress fields of a volcano can provide a framework in which to study and monitor activity. We propose a volcano-tectonic model for the dynamics of the summit of Piton de la Fournaise (La Reunion Island, Indian Ocean). The summit contains two main pit crater structures (Dolomieu and Bory), two active rift zones, and a slumping eastern sector, all of which contribute to the actual fracture system. Dolomieu has developed over 100 years by sudden large collapse events and subsequent smaller drops that include terrace formation. Small intra-pit collapse scars and eruptive fissures are located along the southern floor of Dolomieu. The western pit wall of Dolomieu has a superficial inward dipping normal fault boundary connected to a deeper ring fault system. Outside Dolomieu, an oval extension zone containing sub-parallel pit-related fractures extends to a maximum distance of 225 m from the pit. At the summit the main trend for eruptive fissures is N80°, normal to the north south rift zone. The terraced structure of Dolomieu has been reproduced by analogue models with a roof to width ratio of approximately 1, suggesting an original magma chamber depth of about 1 km. Such a chamber may continue to act as a storage location today. The east flank has a convex concave profile and is bounded by strike-slip fractures that define a gravity slump. This zone is bound to the north by strike-slip fractures that may delineate a shear zone. The southern reciprocal shear zone is probably marked by an alignment of large scoria cones and is hidden by recent aa lavas. The slump head intersects Dolomieu pit and may slide on a hydrothermally altered layer known to be located at a depth of around 300 m. Our model has the summit activity controlled by the pit crater collapse structure, not the rifts. The rifts become important on the mid-flanks of the cone, away from pit-related fractures. On the east flank the superficial structures are controlled by the slump. We suggest that during pit subsidence intra-pit eruptions may occur. During tumescence, however, the pit system may become blocked and a flank eruption is more likely. Intrusions along the rift may cause deformation that subsequently increases the slump’s potential to deform. Conversely, slumping may influence the east flank stress distribution and locally control intrusion direction. These predictions can be tested with monitoring data to validate the model and, eventually, improve monitoring.

Comparison between target magnetic resonance imaging (MRI) in-gantry and cognitively directed transperineal or transrectal-guided prostate biopsies for Prostate Imaging-Reporting and Data System (PI-RADS) 3-5 MRI lesions.

PubMed

Yaxley, Anna J; Yaxley, John W; Thangasamy, Isaac A; Ballard, Emma; Pokorny, Morgan R

2017-11-01

To compare the detection rates of prostate cancer (PCa) in men with Prostate Imaging-Reporting and Data System (PI-RADS) 3-5 abnormalities on 3-Tesla multiparametric (mp) magnetic resonance imaging (MRI) using in-bore MRI-guided biopsy compared with cognitively directed transperineal (cTP) biopsy and transrectal ultrasonography (cTRUS) biopsy. This was a retrospective single-centre study of consecutive men attending the private practice clinic of an experienced urologist performing MRI-guided biopsy and an experienced urologist performing cTP and cTRUS biopsy techniques for PI-RADS 3-5 lesions identified on 3-Tesla mpMRI. There were 595 target mpMRI lesions from 482 men with PI-RADS 3-5 regions of interest during 483 episodes of biopsy. The abnormal mpMRI target lesion was biopsied using the MRI-guided method for 298 biopsies, the cTP method for 248 biopsies and the cTRUS method for 49 biopsies. There were no significant differences in PCa detection among the three biopsy methods in PI-RADS 3 (48.9%, 40.0% and 44.4%, respectively), PI-RADS 4 (73.2%, 81.0% and 85.0%, respectively) or PI-RADS 5 (95.2, 92.0% and 95.0%, respectively) lesions, and there was no significant difference in detection of significant PCa among the biopsy methods in PI-RADS 3 (42.2%, 30.0% and 33.3%, respectively), PI-RADS 4 (66.8%, 66.0% and 80.0%, respectively) or PI-RADS 5 (90.5%, 89.8% and 90.0%, respectively) lesions. There were also no differences in PCa or significant PCa detection based on lesion location or size among the methods. We found no significant difference in the ability to detect PCa or significant PCa using targeted MRI-guided, cTP or cTRUS biopsy methods. Identification of an abnormal area on mpMRI appears to be more important in increasing the detection of PCa than the technique used to biopsy an MRI abnormality. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Different scoring systems to predict 6-week mortality in cirrhosis patients with acute variceal bleeding: a retrospective analysis of 202 patients.

PubMed

Wang, Fang; Cui, Shu; Wang, Fengmei; Li, Fenghui; Tang, Fei; Zhang, Xu; Gao, Yanying; Lv, Hongmin

2018-06-17

Determine the optimal scoring system for evaluation of 6-week bleeding-related mortality in liver cirrhosis patients with acute variceal bleeding (AVB). Prediction effects of six scoring systems, AIMS65 score, Glasgow-Blatchford (GBS) score, full Rockall (FRS) score, the model for end-stage liver disease (MELD), the MELD-Na model and the Child-Turcotte-Pugh (CTP) score were analyzed in this study. A total of 202 liver cirrhosis patients with AVB were enrolled between 1 January 2014, and 31 December 2014. All subjects were scored according to AIMS65, GBS, FRS, MELD, MELD-Na and CTP scoring systems on the first day of admission. The primary endpoint of the study was 6-week mortality. The prediction effect of these scoring systems for 6-week mortality was compared by ROC curve and the area under the curve (AUC). The scores of nonsurvival group evaluated by the AIMS65, GBS, FRS, MELD, MELD-Na and CTP (2.6 ± 1.1, 12.9 ± 2.7, 6.6 ± 1.8, 26.9 ± 6.5, 31.6 ± 9.3, 9.6 ± 2.2, respectively) were higher than those of the survival group (1.2 ± 1.1, 10.2 ± 3.4, 5.1 ± 1.6, 21.0 ± 6.4, 22.8 ± 8.2, 7.7 ± 2.0, respectively) (p < .01). The values of AUC and Youden index of AIMS65 and MELD-Na scoring systems [(0.808, 0.453) and (0.781, 0.516), respectively] were superior to those of MELD (0.761, 0.454), CTP (0.748, 0.399), FRS (0.738, 0.358) and GBS scoring systems (0.726, 0.370). AIMS65 and MELD-Na scoring systems are recommended for evaluation of 6-week bleeding-related mortality in liver cirrhosis patients with AVB.

Iterative reconstruction for CT perfusion with a prior-image induced hybrid nonlocal means regularization: Phantom studies

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

Li, Bin; Lyu, Qingwen; Ma, Jianhua

2016-04-15

Purpose: In computed tomography perfusion (CTP) imaging, an initial phase CT acquired with a high-dose protocol can be used to improve the image quality of later phase CT acquired with a low-dose protocol. For dynamic regions, signals in the later low-dose CT may not be completely recovered if the initial CT heavily regularizes the iterative reconstruction process. The authors propose a hybrid nonlocal means (hNLM) regularization model for iterative reconstruction of low-dose CTP to overcome the limitation of the conventional prior-image induced penalty. Methods: The hybrid penalty was constructed by combining the NLM of the initial phase high-dose CT inmore » the stationary region and later phase low-dose CT in the dynamic region. The stationary and dynamic regions were determined by the similarity between the initial high-dose scan and later low-dose scan. The similarity was defined as a Gaussian kernel-based distance between the patch-window of the same pixel in the two scans, and its measurement was then used to weigh the influence of the initial high-dose CT. For regions with high similarity (e.g., stationary region), initial high-dose CT played a dominant role for regularizing the solution. For regions with low similarity (e.g., dynamic region), the regularization relied on a low-dose scan itself. This new hNLM penalty was incorporated into the penalized weighted least-squares (PWLS) for CTP reconstruction. Digital and physical phantom studies were performed to evaluate the PWLS-hNLM algorithm. Results: Both phantom studies showed that the PWLS-hNLM algorithm is superior to the conventional prior-image induced penalty term without considering the signal changes within the dynamic region. In the dynamic region of the Catphan phantom, the reconstruction error measured by root mean square error was reduced by 42.9% in PWLS-hNLM reconstructed image. Conclusions: The PWLS-hNLM algorithm can effectively use the initial high-dose CT to reconstruct low-dose CTP in the stationary region while reducing its influence in the dynamic region.« less

SU-E-J-26: Analysis of Image Quality in CBCT QA Using a Treatment Planning System

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

Xu, M

2014-06-01

Purpose: The objective of this study is to propose an alternative QA technique that analyzes imaging quality(IQ) in CBCT-QA processing. Methods: A catphan phantom was used to take CT imaging data set that were imported into a treatment planning system - Eclipse. The image quality was analyzed in terms of in-slice geometry resolution, Hounsfield numbers(HU) accuracy, mean-slice thickness, edge-to-center uniformity, low contrast resolution, and high contrast spatial resolution in Eclipse workstation. The CBCT-QA was also analyzed by OBI-workstation and a commercial software. Comparison was made to evaluation feasibility in a TPS environment. Results: The analysis of IQ was conducted inmore » Eclipse v10.0 TPS. In-slice geometric resolution was measured between 2-rods in section CTP404 and repeated for all 4 rods with the difference between expected and measured values less than +/−0.1 cm. For HU, the difference between expected and measured values in HU was found much less than +/−40. Mean slice thickness measured by a distance on the wire proportional to scanner increment multiplying by a factor of 0.42. After repeating measurements to 4 wires, the average difference between expected and measured values was less +/−0.124 mm in slice thickness. HU uniformity was measured in section CTP486 with the tolerance less than +/−40 HU. Low contrast resolution in section CTP515 and high contrast resolution in section CTP528 were found to be 7 disks in diameter of 4 mm and 6 lp/cm, respectively. Eclipse TPS results indicated a good agreement to those obtained in OBI workstation and ImagePro software for major parameters. Conclusion: An analysis of IQ was proposed as an alternative CBCT QA processing. Based upon measured data assessment, proposed method was accurate and consistent to IQ evaluation and TG142 guideline. The approach was to utilize TPS resource, which can be valuable to re-planning, verification, and delivery in adaptive therapy.« less

“Gate-keeper” Residues and Active-Site Rearrangements in DNA Polymerase μ Help Discriminate Non-cognate Nucleotides

PubMed Central

Li, Yunlang; Schlick, Tamar

2013-01-01

Incorporating the cognate instead of non-cognate substrates is crucial for DNA polymerase function. Here we analyze molecular dynamics simulations of DNA polymerase μ (pol μ) bound to different non-cognate incoming nucleotides including A:dCTP, A:dGTP, A(syn):dGTP, A:dATP, A(syn):dATP, T:dCTP, and T:dGTP to study the structure-function relationships involved with aberrant base pairs in the conformational pathway; while a pol μ complex with the A:dTTP base pair is available, no solved non-cognate structures are available. We observe distinct differences of the non-cognate systems compared to the cognate system. Specifically, the motions of active-site residue His329 and Asp330 distort the active site, and Trp436, Gln440, Glu443 and Arg444 tend to tighten the nucleotide-binding pocket when non-cognate nucleotides are bound; the latter effect may further lead to an altered electrostatic potential within the active site. That most of these “gate-keeper” residues are located farther apart from the upstream primer in pol μ, compared to other X family members, also suggests an interesting relation to pol μ's ability to incorporate nucleotides when the upstream primer is not paired. By examining the correlated motions within pol μ complexes, we also observe different patterns of correlations between non-cognate systems and the cognate system, especially decreased interactions between the incoming nucleotides and the nucleotide-binding pocket. Altered correlated motions in non-cognate systems agree with our recently proposed hybrid conformational selection/induced-fit models. Taken together, our studies propose the following order for difficulty of non-cognate system insertions by pol μ: T:dGTP

Toxicity of acid mine pit lake water remediated with limestone and phosphorus

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

Neil, L.L.; McCullough, C.D.; Lund, M.A.

2009-11-15

Pit lakes are increasingly common worldwide and have potential to provide many benefits. However, lake water toxicity may require remediation before beneficial end uses can be realised. Three treatments to remediate AMD (pH similar to 4.8) pit lake water containing elevated concentrations of Al and Zn from Collie, Western Australia were tested in mesocosms. Treatments were: (a) limestone neutralisation (L), (b) phosphorus amendment (P), and c) combined limestone neutralisation and phosphorus amendment (L+P). Laboratory bioassays with Ceriodaphnia cf. dubia, Chlorella protothecoides and Tetrahymena thermophila assessed remediation. Limestone neutralisation increased pH and reduced heavy metal concentrations by 98% (Al) to 14%more » (Mg), removing toxicity to the three test species within 2 months. Phosphorus amendment removed toxicity after 6 months of treatment. However, phosphorus amendment to prior limestone neutralisation failed to reduce toxicity more than limestone neutralisation alone. Low concentrations of both phosphorus and nitrogen appear to limit phytoplankton population growth in all treatments.« less

Erosion of aluminum 6061-T6 under cavitation attack in mineral oil and water

NASA Technical Reports Server (NTRS)

Rao, B. C. S.; Buckley, D. H.

1985-01-01

Studies of the erosion of aluminum 6061-T6 under cavitation attack in distilled water, ordinary tap water and a viscous mineral oil are presented. The mean depth of penetration for the mineral oil was about 40 percent of that for water at the end of a 40 min test. The mean depth of penetration and its rate did not differ significantly for distilled and tap water. The mean depth of penetration rate for both distilled and tap water increased to a maximum and then decreased with test duration, while that for mineral oil had a maximum during the initial period. The ratio h/2a of the pit depth h to the pit diameter 2a varied from 0.04 to 0.13 in water and from 0.06 to 0.20 in mineral oil. Scanning electron microscopy indicates that the pits are initially formed over the grain boundaries and precipitates while the surface grains are deformed under cavitation attack.

Influence of Sulfate-Reducing Bacteria on the Corrosion Residual Strength of an AZ91D Magnesium Alloy

PubMed Central

Zhu, Xianyong; Liu, Yaohui; Wang, Qiang; Liu, Jiaan

2014-01-01

In this paper, the corrosion residual strength of the AZ91D magnesium alloy in the presence of sulfate-reducing bacteria is studied. In the experiments, the chemical composition of corrosion film was analyzed by a scanning electron microscope with energy dispersive X-ray spectroscopy. In addition, a series of instruments, such as scanning electronic microscope, pH-meter and an AG-10TA materials test machine, were applied to test and record the morphology of the corrosion product, fracture texture and mechanical properties of the AZ91D magnesium alloy. The experiments show that the sulfate-reducing bacteria (SRB) play an important role in the corrosion process of the AZ91D magnesium alloy. Pitting corrosion was enhanced by sulfate-reducing bacteria. Corrosion pits are important defects that could lead to a significant stress concentration in the tensile process. As a result, sulfate-reducing bacteria influence the corrosion residual strength of the AZ91D magnesium alloy by accelerating pitting corrosion. PMID:28788236

GRC-2005-C-01066

NASA Image and Video Library

2001-07-28

Photographic documentation of the High Power Engine Propulsion HiPEP after a duration test. Also photographed are the instrumentation and installation articles to reveal post test conditions such as corrosion and pitting.

GRC-2005-C-01076

NASA Image and Video Library

2001-07-28

Photographic documentation of the High Power Engine Propulsion HiPEP after a duration test. Also photographed are the instrumentation and installation articles to reveal post test conditions such as corrosion and pitting.

GRC-2005-C-01036

NASA Image and Video Library

2001-07-28

Photographic documentation of the High Power Engine Propulsion HiPEP after a duration test. Also photographed are the instrumentation and installation articles to reveal post test conditions such as corrosion and pitting.

Corrective Action Investigation Plan for Corrective Action Unit 140: Waste Dumps, Burn Pits, and Storage Area, Nevada Test Site, Nevada, July 2002, Rev. No. 0

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

NNSA /NV

This Corrective Action Investigation Plan contains the U.S. Department of Energy, National Nuclear Security Administration Nevada Operations Office's approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 140 under the Federal Facility Agreement and Consent Order. Corrective Action Unit 140 consists of nine Corrective Action Sites (CASs): 05-08-01, Detonation Pits; 05-08-02, Debris Pits; 05-17-01, Hazardous Waste Accumulation Site (Buried); 05-19-01, Waste Disposal Site; 05-23-01, Gravel Gertie; 05-35-01, Burn Pit; 05-99-04, Burn Pit; 22-99-04, Radioactive Waste Dump; 23-17-01, Hazardous Waste Storage Area. All nine of these CASs are located withinmore » Areas 5, 22, and 23 of the Nevada Test Site (NTS) in Nevada, approximately 65 miles northwest of Las Vegas. This CAU is being investigated because disposed waste may be present without appropriate controls (i.e., use restrictions, adequate cover) and hazardous and/or radioactive constituents may be present or migrating at concentrations and locations that could potentially pose a threat to human health and the environment. The NTS has been used for various research and development projects including nuclear weapons testing. The CASs in CAU 140 were used for testing, material storage, waste storage, and waste disposal. A two-phase approach has been selected to collect information and generate data to satisfy needed resolution criteria and resolve the decision statements. Phase I will determine if contaminants of potential concern (COPCs) are present in concentrations exceeding preliminary action levels. This data will be evaluated at all CASs. Phase II will determine the extent of the contaminant(s) of concern (COCs). This data will only be evaluated for CASs with a COC identified during Phase I. Based on process knowledge, the COPCs for CAU 140 include volatile organics, semivolatile organics, petroleum hydrocarbons, explosive residues, herbicides, pesticides, polychlorinated biphenyls, metals, and radionuclides. The results of this field investigation will support a defensible evaluation of corrective action alternatives in the corrective action decision document.« less

Transit management certificate program.

DOT National Transportation Integrated Search

2012-07-01

TTI worked closely with the Landscape Architecture and Urban Planning Department : (LAUP) of Texas A&M University (TAMU) to develop a transit management certificate : focus for the current Graduate Certificate in Transportation Planning (CTP) housed ...

Thermo-Chemical Convection in Europa's Icy Shell with Salinity

NASA Technical Reports Server (NTRS)

Han, L.; Showman, A. P.

2005-01-01

Europa's icy surface displays numerous pits, uplifts, and chaos terrains that have been suggested to result from solid-state thermal convection in the ice shell, perhaps aided by partial melting. However, numerical simulations of thermal convection show that plumes have insufficient buoyancy to produce surface deformation. Here we present numerical simulations of thermochemical convection to test the hypothesis that convection with salinity can produce Europa's pits and domes. Our simulations show that domes (200-300 m) and pits (300-400 m) comparable to the observations can be produced in an ice shell of 15 km thick with 5-10% compositional density variation if the maximum viscosity is less than 10(exp 18) Pa sec. Additional information is included in the original extended abstract.

Preliminary study on combined pharmacological and laser treatment in optic pit serous maculopathy after literature review.

PubMed

Nebbioso, M; Dapoto, L; Lenarduzzi, F; Belcaro, G; Malagola, R

2012-12-01

The pit of the optic nerve head (ON) is a rare congenital defect that sometimes presents itself with a maculopathy of various neuroretinal layers for unknown reason. This study was focused, before and after pharmacological and parasurgical treatment, on the structural and functional visual assessment in a patient with optic pit maculopathy (OPM). In order to achieve this the latest generation of hi-tech diagnostic tests were used, such as Spectral-Domain Optical Coherence Tomography (SD-OCT), Visual Evoked Potentials (VEP), full-field Electroretinography (ERG), multifocal ERG (mfERG), Microperimetry (MP-1), Standard Automated Perimetry (SAP), Fluorescein Angiography (FA) and Indocyanine Green Angiography (ICG). The research was conducted through a review of past and recent literature.

Addendum to the Closure Report for Corrective Action Unit 355: Area 2 Cellars/Mud Pits Nevada Test Site, Nevada, Revision 0

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

Lynn Kidman

This document constitutes an addendum to the November 2003, Closure Report for Corrective Action Unit 355: Area 2 Cellars/Mud Pits as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modification document, this addendum consists of: • Thismore » cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the cancellation of the URs for: • CAS 02-37-01, Cellar & Mud Pit • CAS 02-37-03, Cellar & Mud Pit • CAS 02-37-04, Cellar & Mud Pit • CAS 02-37-05, Cellar & Mud Pit • CAS 02-37-06, Cellar & Mud Pit • CAS 02-37-07, Cellar & Mud Pit • CAS 02-37-10, Cellar & Mud Pit • CAS 02-37-11, Cellar & Mud Pit • CAS 02-37-12, Cellar & Mud Pit • CAS 02-37-13, Cellar & Mud Pit • CAS 02-37-14, Cellar & Mud Pit • CAS 02-37-15, Cellar & Mud Pit • CAS 02-37-16, Cellar & Mud Pit • CAS 02-37-17, Cellar • CAS 02-37-18, Cellar & Tanks These URs were established as part of Federal Facility Agreement and Consent Order (FFACO) corrective actions and were based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since these URs were established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, these URs were re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data (used to define the need for the URs) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove these URs because contamination is not present at these sites above the risk-based FALs. Requirements for inspecting and maintaining these URs will be canceled, and the postings and signage at each site will be removed. Fencing and posting may be present at these sites that are unrelated to the FFACO URs such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004f). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at these sites.« less

Regulation of PRPP and nucleoside tri and tetraphosphate pools in Escherichia coli under conditions of nitrogen starvation.

PubMed Central

Villadsen, I S; Michelsen, O

1977-01-01

The ribonucleoside triphosphate, deoxyribonucleoside triphosphate, 3' -diphosphate guanosine 5' -diphosphate (ppGpp), and 5-phosphoribosyl 1-pyrophosphate (PRPP) pools in Escherichia coli B were determined by thin-layer chromatography during changing conditions to ammonium starvation. The intracellular concentrations of all nucleotides were found to change in a well-defined order several minutes before andy observed change in the optical density of the culture. The levels of purine nucleoside triphosphates (adenosine 5' -triphosphate [CTP], dCTP) and uridine nucleotides (uridine 5' -triphosphate, deoxythymidine 5'-triphosphate). The deoxyribonucleotides thus behaved as the ribonucleotides. The levels of ppGpp increased 11-fold after the decrease in uridine nucleotides, when the accumulation of stable ribonucleic acid (RNA) stopped. The level of the nucleotide pool did not stabilize until 30 min after the change in optical density. The pool of dGTP dropped concomitantly with the pool of CTP. The nucleotide precursor PRPP exhibited a transient increase, wtih maximum value of four times the exponential levels at the onset of starvation. Apparently the cell adjusts early to starvation by reducing either the phosphorylating activity or the nucleotide biosynthetic activity. As in other downshift systems, the accumulation of stable RNA stopped before the break in optical density and before the stop in protein accumulation. Cell divisions were quite insensitive to the control mechanisms operating on RNA and protein accumulation under ammonium starvation, since the cells continued to divide for 21 min without any net accumulation of RNA. Images PMID:323222

Cerebral Hypoperfusion in Posterior Reversible Encephalopathy Syndrome is Different from Transient Ischemic Attack on CT Perfusion.

PubMed

Vanacker, Peter; Matias, Gonçalo; Hagmann, Patric; Michel, Patrik

2015-01-01

PRES is a reversible neurotoxic state presenting with headache, altered mental status, visual loss, and seizures. Delayed diagnosis can be avoided if radiological patterns could distinguish PRES from cerebral ischemia. Clinical and radiological data were collected on all hospitalized patients who had (1) discharge diagnosis of PRES and (2) acute CTP/CTA. Data were compared with 10 TIA patients with proven cytotoxic edema on MRI. Of the four PRES patients found, three were correlated with acute blood pressure and one with chemotherapy. At the radiological level, quantitative analyses of the CTP parameters showed that 2 out of 4 patients had bilaterally reduced CBF-values (23.2-47.1 ml/100g/min) in occipital regions, as seen in the pathological regions of TIA patients (27.3 ± 13.5 ml/100g/min). When compared with TIA patients, the pathological ROI's demonstrated decreased CBV-values (3.4-5.6 ml/100g). Vasogenic edema on MRI FLAIR imaging was seen in only one PRES patient, and cytotoxic edema on DWI-imaging was never found. CT angiography showed in one PRES patient a vasospasm-like unilateral posterior cerebral artery. If confirmed by other groups, CTP and CTA imaging in patients with acute visual loss and confusion may help to distinguish PRES from bi-occipital ischemia. These radiological parameters may identify PRES patients at risk for additional tissue infarction. Copyright © 2014 by the American Society of Neuroimaging.

Potency assay development for cellular therapy products: an ISCT review of the requirements and experiences in the industry.

PubMed

Bravery, Christopher A; Carmen, Jessica; Fong, Timothy; Oprea, Wanda; Hoogendoorn, Karin H; Woda, Juliana; Burger, Scott R; Rowley, Jon A; Bonyhadi, Mark L; Van't Hof, Wouter

2013-01-01

The evaluation of potency plays a key role in defining the quality of cellular therapy products (CTPs). Potency can be defined as a quantitative measure of relevant biologic function based on the attributes that are linked to relevant biologic properties. To achieve an adequate assessment of CTP potency, appropriate in vitro or in vivo laboratory assays and properly controlled clinical data need to be created. The primary objective of a potency assay is to provide a mechanism by which the manufacturing process and the final product for batch release are scrutinized for quality, consistency and stability. A potency assay also provides the basis for comparability assessment after process changes, such as scale-up, site transfer and new starting materials (e.g., a new donor). Potency assays should be in place for early clinical development, and validated assays are required for pivotal clinical trials. Potency is based on the individual characteristics of each individual CTP, and the adequacy of potency assays will be evaluated on a case-by-case basis by regulatory agencies. We provide an overview of the expectations and challenges in development of potency assays specific for CTPs; several real-life experiences from the cellular therapy industry are presented as illustrations. The key observation and message is that aggressive early investment in a solid potency evaluation strategy can greatly enhance eventual CTP deployment because it can mitigate the risk of costly product failure in late-stage development. Copyright © 2013. Published by Elsevier Inc.

Effect of oxybuprocaine eye drops on corneal volume and thickness measurements.

PubMed

Rosa, Nicola; De Bernardo, Maddalena; Borrelli, Maria; Filosa, Maria Luisa; Lanza, Michele

2011-05-01

To investigate the effect of oxybuprocaine eye drops on corneal volume (CV) and corneal thickness measurements. Central corneal thickness (CCT), corneal thinnest point (CTP), and CV of 78 eyes of 78 healthy volunteers were measured with Pentacam, before and 5 min after the administration of oxybuprocaine eye drops. The fellow non-anesthetized eyes were used as control. Before topical anesthesia, the mean CCT was 546.76 ± 35.3 μm, after anesthesia, it was 547.76 ± 36.56 μm (p = 0.86). In the fellow eyes, the first mean CCT was 548.82 ± 35.2 μm and the second was 547.55 ± 35.9 μm (p = 0.82). The mean CTP before anesthesia was 543.99 ± 35.23 μm, after it was 544.89 ± 36.3 μm (p = 0.88). In the fellow eyes, the first mean CTP was 544.15 ± 35.35 μm and the second was 542.81 ± 36 μm (p = 0.81). Before topical anesthesia, the mean CV was 60.55 ± 3.84 mm, after it was 60.66 ± 3.97 mm (p = 0.86). In the fellow eyes, the first mean CV was 60.93 ± 3.87 mm and the second was 60.73 ± 4 mm (p = 0.75). Oxybuprocaine eye drops do not appear to induce a significant corneal swelling and do not affect the measurements when comparing CCT measured with optical or ultrasound devices.

Improvement in thin cirrus retrievals using an emissivity-adjusted CO2 slicing algorithm

NASA Astrophysics Data System (ADS)

Zhang, Hong; Menzel, W. Paul

2002-09-01

CO2 slicing has been generally accepted as a useful algorithm for determining cloud top pressure (CTP) and effective cloud amount (ECA) for tropospheric clouds above 600 hPa. To date, the technique has assumed that the surface emissivity is that of a blackbody in the long-wavelength infrared radiances and that the cloud emissivities in spectrally close bands are approximately equal. The modified CO2 slicing algorithm considers adjustments of both surface emissivity and cloud emissivity ratio. Surface emissivity is adjusted according to the surface types. The ratio of cloud emissivities in spectrally close bands is adjusted away from unity according to radiative transfer calculations. The new CO2 slicing algorithm is examined with Moderate Resolution Imaging Spectroradiometer (MODIS) Airborne Simulator (MAS) CO2 band radiance measurements over thin clouds and validated against Cloud Lidar System (CLS) measurements of the same clouds; it is also applied to Geostationary Operational Environmental Satellite (GOES) Sounder data to study the overall impact on cloud property determinations. For high thin clouds an improved product emerges, while for thick and opaque clouds there is little change. For very thin clouds, the CTP increases by about 10-20 hPa and RMS (root mean square bias) difference is approximately 50 hPa; for thin clouds, the CTP increase is about 10 hPa bias and RMS difference is approximately 30 hPa. The new CO2 slicing algorithm places the clouds lower in the troposphere.

Review article: scoring systems for assessing prognosis in critically ill adult cirrhotics.

PubMed

Cholongitas, E; Senzolo, M; Patch, D; Shaw, S; Hui, C; Burroughs, A K

2006-08-01

Cirrhotic patients admitted to intensive care units (ICU) still have poor outcomes. Some current ICU prognostic models [Acute Physiology and Chronic Health Evaluation (APACHE), Organ System Failure (OSF) and Sequential Organ Failure Assessment (SOFA)] were used to stratify cirrhotics into risk categories, but few cirrhotics were included in the original model development. Liver-specific scores [Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD)] could be useful in this setting. To evaluate whether ICU prognostic models perform better compared with liver-disease specific ones in cirrhotics admitted to ICU. We performed a structured literature review identifying clinical studies focusing on prognosis and risk factors for mortality in adult cirrhotics admitted to ICU. We found 21 studies (five solely dealing with gastrointestinal bleeding) published during the last 20 years (54-420 patients in each). APACHE II and III, SOFA and OSF had better discrimination for correctly predicting death compared with the CTP score. The MELD score was evaluated only in one study and had good predictive accuracy [receiver operator characteristic (ROC) curve: 0.81). Organ dysfunction models (OSF, SOFA) were superior compared with APACHE II and III (ROC curve: range 0.83-0.94 vs. 0.66-0.88 respectively). Cardiovascular, liver and renal system dysfunction were more frequently independently associated with mortality. General-ICU models had better performance in cirrhotic populations compared with CTP score; OSF and SOFA had the best predictive ability. Further prospective and validation studies are needed.

Numerical modelling of the groundwater inflow to an advancing open pit mine: Kolahdarvazeh pit, Central Iran.

PubMed

Bahrami, Saeed; Doulati Ardejani, Faramarz; Aslani, Soheyla; Baafi, Ernest

2014-12-01

The groundwater inflow into a mine during its life and after ceasing operations is one of the most important concerns of the mining industry. This paper presents a hydrogeological assessment of the Irankuh Zn-Pb mine at 20 km south of Esfahan and 1 km northeast of Abnil in west-Central Iran. During mine excavation, the upper impervious bed of a confined aquifer was broken and water at high-pressure flowed into an open pit mine associated with the Kolahdarvazeh deposit. The inflow rates were 6.7 and 1.4 m(3)/s at the maximum and minimum quantities, respectively. Permeability, storage coefficient, thickness and initial head of the fully saturated confined aquifer were 3.5 × 10(-4) m/s, 0.2, 30 m and 60 m, respectively. The hydraulic heads as a function of time were monitored at four observation wells in the vicinity of the pit over 19 weeks and at an observation well near a test well over 21 h. In addition, by measuring the rate of pumping out from the pit sump, at a constant head (usually equal to height of the pit floor), the real inflow rates to the pit were monitored. The main innovations of this work were to make comparison between numerical modelling using a finite element software called SEEP/W and actual data related to inflow and extend the applicability of the numerical model. This model was further used to estimate the hydraulic heads at the observation wells around the pit over 19 weeks during mining operations. Data from a pump-out test and observation wells were used for model calibration and verification. In order to evaluate the model efficiency, the modelling results of inflow quantity and hydraulic heads were compared to those from analytical solutions, as well as the field data. The mean percent error in relation to field data for the inflow quantity was 0.108. It varied between 1.16 and 1.46 for hydraulic head predictions, which are much lower values than the mean percent errors resulted from the analytical solutions (from 1.8 to 5.3 for inflow and from 2.16 to 3.5 for hydraulic head predictions). The analytical solutions underestimated the inflow compared to the numerical model for the time period of 2-19 weeks. The results presented in this paper can be used for developing an effective dewatering program.

Case history of controlling a landslide at Panluo open-pit mine in China

NASA Astrophysics Data System (ADS)

Wei, Zuoan; Yin, Guangzhi; Wan, Ling; Shen, Louyan

2008-04-01

Controlling of landsides safely and economically is a great challenge to mine operators because landslides are major geological problems especially in open-pit mines. In this paper, a case history at Panluo open-pit mine is presented in detail to share the experiences and lessons with mine operators. Panluo open-pit mine is located in the southwestern Fujian province of China. It is the largest open-pit iron mine in the Fujian province and was planned in 1965 and is in full operation from 1978. In July 1990, an earthquake of magnitude 5.3 in Taiwan Strait and big rainstorms impacted the mine slope, causing tension cracks and rather large-scale failures, and forming a U-shaped landslide. Total potential volume was estimated to be up to 1.0 × 106 m3. This directly threatened the mine production. In order to protect the mine production and the dwellers’ safety around, a dynamic comprehensive method was implemented including geotechnical investigations, in-situ testing and monitoring, stability analysis, and many mitigation and preventive measures. These measures slowed down the development and further occurrence of the landslide. The results showed that the landslides were still active, it was slowed with the control measures and moved rapidly with rainfall and mining down. However, no catastrophic accidents occurred and the pit mining was continued till it was closed at the elevation of 887 m in 2000. As a successful case of landslide control at an open-pit mine for 10 years, this paper reports the controlling measures in details. These experiences of landslide control may be beneficial to other similar mines for landslide control.

Investigations of Air-cooled Turbine Rotors for Turbojet Engines II : Mechanical Design, Stress Analysis, and Burst Test of Modified J33 Split-disk Rotor / Richard H. Kemp and Merland L. Moseson

NASA Technical Reports Server (NTRS)

Kemp, Richard H; Moseson, Merland L

1952-01-01

A full-scale J33 air-cooled split turbine rotor was designed and spin-pit tested to destruction. Stress analysis and spin-pit results indicated that the rotor in a J33 turbojet engine, however, showed that the rear disk of the rotor operated at temperatures substantially higher than the forward disk. An extension of the stress analysis to include the temperature difference between the two disks indicated that engine modifications are required to permit operation of the two disks at more nearly the same temperature level.

Autonomous execution of the Precision Immobilization Technique

NASA Astrophysics Data System (ADS)

Mascareñas, David D. L.; Stull, Christopher J.; Farrar, Charles R.

2017-03-01

Over the course of the last decade great advances have been made in autonomously driving cars. The technology has advanced to the point that driverless car technology is currently being tested on publicly accessed roadways. The introduction of these technologies onto publicly accessed roadways not only raises questions of safety, but also security. Autonomously driving cars are inherently cyber-physical systems and as such will have novel security vulnerabilities that couple both the cyber aspects of the vehicle including the on-board computing and any network data it makes use of, with the physical nature of the vehicle including its sensors, actuators, and the vehicle chassis. Widespread implementation of driverless car technology will require that both the cyber, as well as physical security concerns surrounding these vehicles are addressed. In this work, we specifically developed a control policy to autonomously execute the Precision Immobilization Technique, a.k.a. the PIT maneuver. The PIT maneuver was originally developed by law enforcement to end high-speed vehicular pursuits in a quasi-safe manner. However, there is still a risk of damage/roll-over to both the vehicle executing the PIT maneuver as well as to the vehicle subject to the PIT maneuver. In law enforcement applications, it would be preferable to execute the PIT maneuver using an autonomous vehicle, thus removing the danger to law-enforcement officers. Furthermore, it is entirely possible that unscrupulous individuals could inject code into an autonomously-driving car to use the PIT maneuver to immobilize other vehicles while maintaining anonymity. For these reasons it is useful to know how the PIT maneuver can be implemented on an autonomous car. In this work a simple control policy based on velocity pursuit was developed to autonomously execute the PIT maneuver using only a vision and range measurements that are both commonly collected by contemporary driverless cars. The ability of this control policy to execute the PIT maneuver was demonstrated both in simulation and experimentally. The results of this work can help inform the design of autonomous car with regards to ensuring their cyber-physical security.

Pitting and stress corrosion cracking of stainless steel

NASA Astrophysics Data System (ADS)

Saithala, Janardhan R.

An investigation has been performed to determine the pitting resistance of stainless steels and stress corrosion cracking of super duplex stainless steels in water containing chloride ions from 25 - 170°C. The steels studied are 12% Cr, FV520B, FV566, 304L, Uranus65, 2205, Ferallium Alloy 255, and Zeron 100. All these commercial materials used in very significant industrial applications and suffer from pitting and stress corrosion failures. The design of a new experimental setup using an autoclave enabled potentiodynamic polarisation experiments and slow strain rate tests in dilute environments to be conducted at elevated temperatures. The corrosion potentials were controlled using a three electrode cell with computer controlled potentiostat.The experimental programme to determine pitting potentials was designed to simulate the service conditions experienced in most industrial plants and develop mathematical model equations to help a design engineer in material selection decision. Stress corrosion resistance of recently developed Zeron100 was evaluated in dilute environments to propose a mechanism in chloride solutions at high' temperatures useful for the nuclear and power generation industry. Results have shown the significance of the composition of alloying elements across a wide range of stainless steels and its influence on pitting. Nitrogen and molybdenum added to modern duplex stainless steels was found to be unstable at higher temperatures. The fractographic results obtained using the scanning electron microscope (SEM) has given insight in the initiation of pitting in modem duplex and super duplex stainless steels. A mathematical model has been proposed to predict pitting in stainless steels based on the effect of environmental factors (temperature, chloride concentration, and chemical composition). An attempt has been made to identify the mechanism of SCC in Zeron100 super duplex stainless steel.The proposed empirical models have shown good correlation between predicted pitting potential values with experimental results. It has been shown that the SCC mechanism in Zeron100 supports the slip assisted anodic dissolution model of SCC. The relationship between pitting and stress corrosion in dilute environments is established and empirical equations have been proposed to determine the damage region for wide range of stainless steels.

Survival of Seaward-Migrating PIT and Acoustic-Tagged Juvenile Chinook Salmon in the Snake and Columbia Rivers: An Evaluation of Length-Specific Tagging Effects

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

Brown, Richard S.; Oldenburg, Eric W.; Seaburg, Adam

Studies examining the survival of juvenile salmon as they emigrate to the ocean provide important information regarding the management of regulated river systems. Acoustic telemetry is a widely used tool for evaluating the behavior and survival of juvenile salmonids in the Columbia River basin. Thus, it is important to understand how the surgical tagging process and the presence of a transmitter affect survival so any biases can be accounted for or eliminated. This study evaluated the effects of fish length and tag type on the survival of yearling and subyearling Chinook salmon during their seaward migrations through the Snake andmore » Columbia rivers during 2006, 2007, and 2008. Fish were collected at Lower Granite Dam on the Snake River (river kilometer 695) and implanted with either only a passive integrated transponder (PIT) tag (PIT fish) or both a PIT tag and an acoustic transmitter (AT fish). Survival was estimated from release at Lower Granite Dam to multiple downstream locations (dams) using the Cormack–Jolly–Seber single release model, and analysis of variance was used to test for differences among length-classes and between tag types. No length-specific tag effect was detected between PIT and AT fish (i.e., length affected the survival of PIT fish in a manner similar to which it affected the survival of AT fish). Survival among the smallest length class (i.e., 80–89 mm) of both PIT and AT subyearling Chinook salmon was markedly low (i.e., 4%). Fish length was positively correlated with the survival of both PIT and AT fish. Significant differences in survival were detected between tag types; the survival of PIT fish was generally greater than that of AT fish. However, confounding variables warrant caution in making strong inferences regarding this factor. Further, results suggest that tag effects may be due to the process of surgically implanting the transmitter rather than the presence of the transmitter.« less

Pharmacology of biosimilar candidate drugs in rheumatology: a literature review.

PubMed

Araújo, F; Cordeiro, I; Teixeira, F; Gonçalves, J; Fonseca, J E

2014-01-01

To review current evidence concerning pharmacology of biosimilar candidates to be used in rheumatology. A PubMed search up to August 2013 was performed using relevant search terms to include all studies assessing pharmacological properties of biosimilar candidates to be used in rheumatology. Data on study characteristics, type of intervention, pharmacokinetics (PK), pharmacodynamics (PD) and bioequivalence ratios was extracted. Of 280 articles screened, 5 fulfilled our inclusion criteria. Two trials, PLANETAS and PLANETRA, compared CT-P13 and infliximab in patients with active ankylosing spondylitis and rheumatoid arthritis, respectively. PK bioequivalence was demonstrated in the phase 1 PLANETAS trial by highly comparable area under the curve (AUC) and maximum drug concentrations (Cmax), whose geometric mean ratios fell between the accepted bioequivalence range of 80-125%. Equivalence in efficacy and safety was demonstrated in the phase 3 PLANETRA trial. Two phase 1 trials comparing etanercept biosimilar candidates TuNEX and HD203 in healthy volunteers showed a high degree of similarity in AUC and Cmax, with respective geometric mean ratios between PK bioequivalence range. The last included trial referred to GP2013, a rituximab biosimilar candidate, which demonstrated PK and PD bioequivalence to reference product in three different dosing regimens in cynomolgus monkeys. Infliximab, etanercept and rituximab biosimilar candidates have demonstrated PK bioequivalence in the trials included in this review. CT-P13 has recently been approved for use in the European market and the remaining biosimilar candidates are currently being tested in patients with rheumatoid arthritis.

Influence of etching time and bonding strategies on the microshear bond strength of self- and light-cured pit-and-fissure sealants.

PubMed

Souza-Junior, Eduardo José; Borges, Boniek Castillo Dutra; Montes, Marcos Antônio Japiassú Resende; Alonso, Roberta Caroline Bruschi; Ambrosano, Glaucia Maria Bovi; Sinhoreti, Mário Alexandre Coelho

2012-01-01

This study evaluated the impact of extended etching and bonding strategies on the microshear bond strength of three sealant materials. Two pit-and-fissure sealants [FluroShield, Dentsply (light-cured) and AlphaSeal, DFL (self-cured)] and one light-cured flowable composite resin (Permaflo, Ultradent) were evaluated according to different enamel etching times (15 s or 30 s) and bonding procedures (no adhesive application, application of primer/hydrophobic resin or hydrophobic resin only). Intact enamel blocks were obtained from bovine teeth and sealed via the tested protocols. After 24 h, the microshear bond strength test was performed in a universal testing machine at a crosshead speed of 0.5 mm/min. Failure modes were classified by stereomicroscopy. Data were submitted to a three-way ANOVA and to Tukey's test (α=0.05). There was no statistically significant difference (p>0.05) among the materials. Permaflo showed higher bond strength when etched for 30 s alone. Enamel overetching decreased the bond strength of the light-cured sealant. Primer/bond previous treatment improved bond performance for AlphaSeal. In conclusion, from the tested conditions, all sealant materials presented similar bond strength values in relation to bonding protocol and etching time. The flowable composite can be used as a pit-and-fissure sealant. The use of a three-step adhesive system was essential for the self-cured sealant application.

Investigation of corrosion of welded joints of austenitic and duplex stainless steels

NASA Astrophysics Data System (ADS)

Topolska, S.

2016-08-01

Investigation of corrosion resistance of materials is one of the most important tests that allow determining their functional properties. Among these tests the special group consist electrochemical investigations, which let to accelerate the course of the process. These investigations allow rapidly estimating corrosion processes occurring in metal elements under the influence of the analysed environment. In the paper are presented results of investigations of the resistance to pitting corrosion of the steel of next grades: austenitic 316L and duplex 2205. It was also analysed the corrosion resistance of welded joints of these grades of steel. The investigations were conducted in two different corrosion environments: in the neutral one (3.5 % sodium chloride) and in the aggressive one (0.1 M sulphuric acid VI). The obtained results indicate different resistance of analysed grades of steel and their welded joints in relation to the corrosion environment. The austenitic 316L steel characterizes by the higher resistance to the pitting corrosion in the aggressive environment then the duplex 2205 steel. In the paper are presented results of potentiodynamic tests. They showed that all the specimens are less resistant to pitting corrosion in the environment of sulphuric acid (VI) than in the sodium chloride one. The 2205 steel has higher corrosion resistance than the 316L stainless steel in 3.5% NaCl. On the other hand, in 0.1 M H2SO4, the 316L steel has a higher corrosion resistance than the 2205 one. The weld has a similar, very good resistance to pitting corrosion like both steels.

Impairments in proverb interpretation following focal frontal lobe lesions.

PubMed

Murphy, Patrick; Shallice, Tim; Robinson, Gail; MacPherson, Sarah E; Turner, Martha; Woollett, Katherine; Bozzali, Marco; Cipolotti, Lisa

2013-09-01

The proverb interpretation task (PIT) is often used in clinical settings to evaluate frontal "executive" dysfunction. However, only a relatively small number of studies have investigated the relationship between frontal lobe lesions and performance on the PIT. We compared 52 patients with unselected focal frontal lobe lesions with 52 closely matched healthy controls on a proverb interpretation task. Participants also completed a battery of neuropsychological tests, including a fluid intelligence task (Raven's Advanced Progressive Matrices). Lesions were firstly analysed according to a standard left/right sub-division. Secondly, a finer-grained analysis compared the performance of patients with medial, left lateral and right lateral lesions with healthy controls. Thirdly, a contrast of specific frontal subgroups compared the performance of patients with medial lesions with patients with lateral frontal lesions. The results showed that patients with left frontal lesions were significantly impaired on the PIT, while in patients with right frontal lesions the impairments approached significance. Medial frontal patients were the only frontal subgroup impaired on the PIT, relative to healthy controls and lateral frontal patients. Interestingly, an error analysis indicated that a significantly higher number of concrete responses were found in the left lateral subgroup compared to healthy controls. We found no correlation between scores on the PIT and on the fluid intelligence task. Overall our results suggest that specific regions of the frontal lobes contribute to the performance on the PIT. © 2013 The Authors. Published by Elsevier Ltd. All rights reserved.

Sodium-dependent phosphate cotransporters and phosphate-induced calcification of vascular smooth muscle cells: Redundant roles for PiT-1 and PiT-2

PubMed Central

Crouthamel, Matthew H.; Lau, Wei Ling; Leaf, Elizabeth M.; Chavkin, Nick; Wallingford, Mary C.; Peterson, Danielle F.; Li, Xianwu; Liu, Yonggang; Chin, Michael T.; Levi, Moshe; Giachelli, Cecilia M.

2014-01-01

Objective Elevated serum phosphate has emerged as a major risk factor for vascular calcification. The sodium-dependent phosphate cotransporter, PiT-1, was previously shown to be required for phosphate-induced osteogenic differentiation and calcification of cultured human VSMCs, but its importance in vascular calcification in vivo, as well as the potential role of its homologue, PiT-2, have not been determined. We investigated the in vivo requirement for PiT-1 in vascular calcification using a mouse model of chronic kidney disease, and the potential compensatory role of PiT-2 using in vitro knockdown and over-expression strategies. Approach and Results Mice with targeted deletion of PiT-1 in VSMCs were generated (PiT-1Δsm). PiT-1 mRNA levels were undetectable whereas PiT-2 mRNA levels were increased 2 fold in the vascular aortic media of PiT-1Δsm compared to PiT-1flox/flox control. When arterial medial calcification was induced in PiT-1Δsm and PiT-1flox/flox by chronic kidney disease followed by dietary phosphate loading, the degree of aortic calcification was not different between genotypes, suggesting compensation by PiT-2. Consistent with this possibility, VSMCs isolated from PiT-1Δsm mice had no PiT-1 mRNA expression, increased PiT-2 mRNA levels, and no difference in sodium-dependent phosphate uptake or phosphate-induced matrix calcification compared to PiT-1flox/flox VSMCs. Knockdown of PiT-2 decreased phosphate uptake and phosphate-induced calcification of PiT-1Δsm VSMCs. Furthermore, over-expression of PiT-2 restored these parameters in human PiT-1-deficient VSMCs. Conclusions PiT-2 can mediate phosphate uptake and calcification of VSMCs in the absence of PiT-1. Mechanistically, PiT-1 and PiT-2 appear to serve redundant roles in phosphate-induced calcification of vascular smooth muscle cells. PMID:23968976

Environmental Assessment for Explosives Ordnance Disposal Proficiency Training Range at Wright-Patterson Air Force Base, Ohio

DTIC Science & Technology

2010-06-01

s) __ Test Plt(s) __ Test Trench(es) __ Deep Test(s) __ PZ or Humus Removal __ Testing/Excav. (strategy unknown) __ Mitigation/Block Excavation...Collection __ Surface Collection _Auger/Soil Corer _Shovel Test (s) .lL... Test Pit (s) _Test Trench (es) __ Deep Test (s) _ PZ or Humus Removal

Evolution of mud-capped dredge pits following excavation: sediment trapping and slope instability

NASA Astrophysics Data System (ADS)

Obelcz, J.; Xu, K.; Bentley, S. J.; Li, C.; Miner, M. D.; O'Connor, M. C.; Wang, J.

2016-02-01

Many fluvial channels incised the Northern Gulf of Mexico inner continental shelf during the late Quaternary. Mud-capped dredge pits (MCDPs), which are generally elongate and deep (8-10 m) excavations, target sandy fluvial channel deposits for coastal restoration projects. The morphological evolution of dredge excavations in noncohesive sandy substrate is well studied, but MCDPs have up to a several-meter-thick veneer of Holocene shelf mud overlying sandy channel deposits. This stratigraphy is hypothesized to result in more complex post-dredge morphology than pit walls simply slumping to the angle of repose shortly after excavation. Numerical modeling of MCDP post-dredge response conducted prior to excavation indicates pit walls may retrogressively fail, which is accounted for in pit design by assigning no-dredge setback buffers from pipelines or cultural and environmental resources. To validate model results and test effectiveness of setback buffers, a geophysical survey of the Sandy Point MCDP (20 km west of the Mississippi River Delta in 10m deep water), where 1.7 million m3 of sandy sediment was excavated in 2012, was conducted May 2015. A total of 84 line-km of high-resolution chirp subbottom and a 27 km2 grid of swath bathymetry and sidescan sonar were collected. The data indicate the dredge pit walls are differentially slumping, with the western pit wall in a more active state of failure than the eastern wall. The western failures morphologically resemble features observed along the muddy Mississippi River Delta Front at water depths of 20-100 m, including bowl-shaped collapse failures and retrogressive stair-stepped slumps; these failures may play a key role in evaluating the distance of setback buffer zone to pipelines. These features indicate the cohesive mud overlying the sandy infill has a prominent role in pit wall stability. A 0.5-1 m thick acoustically transparent package overlies the entire pit floor (interpreted as a possible fluid mud layer), overlying 1-3 m of post-dredge deposition that is concentrated along the western wall and center of the pit. The Sandy Point MCDP lies within a clockwise gyre, and its relief may serve as a significant trap of suspended sediment. These findings emphasize the role MCDPs play in sediment dynamics as well as their potential for submarine geohazards.

Assessment of Mud-Capped Dredge Pit Evolution Offshore Louisiana: Implications to Sand Excavation and Coastal Restoration

NASA Astrophysics Data System (ADS)

Xu, K.; Miner, M. D.; Bentley, S. J.; Li, C.; Obelcz, J.; O'Connor, M. C.

2016-02-01

The shelf offshore Louisiana is characterized by a dominantly muddy seafloor with a paucity of restoration-quality sand proximal to shore. Discrete sand deposits associated with ancient rivers that incised the shelf during lower sea-level positions occur close to shore. These shelf channel sands have been targeted for coastal restoration projects resulting in significant cost savings over more distal deposits. Several recent projects targeted shelf paleo-fluvial deposits comprising relatively deep (10 m) channel sands underlying a muddy overburden. Because of contrasting characteristics of cohesive mud vs. non-cohesive sand and potential modern fluvial mud supply from the Mississippi and Atchafalaya Rivers, long term pit evolution is poorly understood relative to their more common sand-only counterparts. Alterations to seafloor topography from dredging shelf sediment resources can potentially affect oil and gas infrastructure or other resources of concern (i.e. historic shipwrecks) located proximal to dredge pits. Site-specific data required to make accurate predictions and empirical measurements to test and validate predictive models were only available for Peveto Channel offshore Holly Beach, Louisiana. Here we present new geophysical and geological data (bathymetry, sidescan, subbottom, and radionuclide of sediment cores) and physical oceanographic observations (hydrodynamics and sediment dynamics) collected at Raccoon Island (dredged in 2013) dredge pit in Louisiana. These field data collections along with pre-existing data provide a time-series to capture evolution at Raccoon Island post-excavation. Conceptual morphological models will be developed for dredge pit evolution and testing effectiveness of setback buffers protecting pipelines, habitats, and cultural resources. Our results will increase decision making ability regarding safety and protecting environmental and cultural resources, and better management of valuable sand resources.

Nobody’s perfect: can irregularities in pit structure influence vulnerability to cavitation?

PubMed Central

Plavcová, Lenka; Jansen, Steven; Klepsch, Matthias; Hacke, Uwe G.

2013-01-01

Recent studies have suggested that species-specific pit properties such as pit membrane thickness, pit membrane porosity, torus-to-aperture diameter ratio and pit chamber depth influence xylem vulnerability to cavitation. Despite the indisputable importance of using mean pit characteristics, considerable variability in pit structure within a single species or even within a single pit field should be acknowledged. According to the rare pit hypothesis, a single pit that is more air-permeable than many neighboring pits is sufficient to allow air-seeding. Therefore, any irregularities or morphological abnormalities in pit structure allowing air-seeding should be associated with increased vulnerability to cavitation. Considering the currently proposed models of air-seeding, pit features such as rare, large pores in the pit membrane, torus extensions, and plasmodesmatal pores in a torus can represent potential glitches. These aberrations in pit structure could either result from inherent developmental flaws, or from damage caused to the pit membrane by chemical and physical agents. This suggests the existence of interesting feedbacks between abiotic and biotic stresses in xylem physiology. PMID:24273549

Analytical and Experimental Vibration Analysis of a Faulty Gear System.

DTIC Science & Technology

1994-10-01

Wigner - Ville Distribution ( WVD ) was used to give a comprehensive comparison of the predicted and...experimental results. The WVD method applied to the experimental results were also compared to other fault detection techniques to verify the WVD’s ability to...of the damaged test gear and the predicted vibration from the model with simulated gear tooth pitting damage. Results also verified that the WVD method can successfully detect and locate gear tooth wear and pitting damage.

Fatigue Testing of AA7050-T7451 with Various Corrosion Prevention Surface Treatments

DTIC Science & Technology

2013-06-01

UNCLASSIFIED Authors Marcus McDonald Air Vehicles Division Marcus McDonald initially spent 3 years working in the oil & gas, steel and...treatments: caustic degreasing, de-oxidising or anodising. The pits in the anodised coupons were larger than the pits caused by the pre-IVD etching...those fatigue cracks that grew from them spent less time in growing whilst they were small, because the crack started at what was a larger effective

Effect of polymorphic variants of GH, Pit-1, and beta-LG genes on milk production of Holstein cows.

PubMed

Heidari, M; Azari, M A; Hasani, S; Khanahmadi, A; Zerehdaran, S

2012-04-01

Effect of polymorphic variants of growth hormone (GH), beta-lactoglobulin (beta-LG), and Pit-1 genes on milk yield was analyzed in a Holstein herd. Genotypes of the cows for these genes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Allele frequencies were 0.884 and 0.116 for L and V variants of GH, 0.170 and 0.830 for A and B variants of Pit-1, and 0.529 and 0.471 for A and B variants of beta-LG, respectively. GLM procedure of SAS software was used to test the effects of these genes on milk yield. Results indicated significant effects of these genes on milk yield (P < 0.05). Cows with LL genotype of GH produced more milk than cows with LVgenotype (P < 0.05). Also, for Pit-1 gene, animals with AB genotype produced more milk than BB genotype (P < 0.05). In the case of beta-LG gene, milk yield of animals with AA genotype was more than BB genotype (P < 0.01). Therefore, it might be concluded that homozygote genotypes of GH (LL) and beta-LG (AA) were superior compared to heterozygote genotypes, whereas, the heterozygote genotype of Pit-1 gene (AB) was desirable.

Effect of Pollen, Pit Powder, and Gemmule Extract of Date Palm on Male Infertility: A Systematic Review.

PubMed

Tatar, Tuğba; Akdevelioğlu, Yasemin

2018-02-01

Pollen, pit powder, and gemmule extract of the date palm are rich in flavonoids. Antioxidant characteristics of the flavonoids have a significant effect on prevention and treatment of infertility. The aim of the present study was to review studies investigating the effects of pollen, pit powder, and gemmule extract of the date palm on male infertility. Articles that were published about the topic between 2005 and 2016 were reviewed from different databases in Turkish and English. The search engines used included PubMed, Science Direct, Clinical Key, Google Scholar, Springer, Dergipark, Ulakbim, and Akademik Dizin. The studies found that pollen, pit powder, and gemmule extract of the date palm created positive changes in hormone levels that have a role in male fertility and increased sperm motility and quality, spermatogenesis, and weights of testes and epididymis. Date palm pollen, pit powder, and gemmule extract have a high antioxidant capacity because of phenolic formations in the composition. Such characteristics have a positive effect on prevention and treatment of male infertility. Furthermore, gonadotropic and steroidal compounds within date palm pollen play a role in treatment of male infertility. The limited number of studies conducted on this topic indicates that more research is needed.

63. Photocopied August 1978. TESTING TURBINES AT HOLYOKE. INSTALLING A ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

63. Photocopied August 1978. TESTING TURBINES AT HOLYOKE. INSTALLING A PAIR OF THE JOLLY-McCORMICK RUNNERS AND CONTROL GATES IN THE TEST PIT. (343) - Michigan Lake Superior Power Company, Portage Street, Sault Ste. Marie, Chippewa County, MI

The effect of inhibitor sodium nitrate on pitting corrosion of dissimilar material weldment joint of stainless steel AISI 304 and mild steel SS 400

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

Hilca, B. R., E-mail: bangkithilca@yahoo.com; Triyono, E-mail: triyonomesin@uns.ac.id

This study experimentally evaluated the effect of Sodium Nitrate inhibitor (NaNO{sub 3}) of 0.1%, 0.3%, and 0.5% on NaCl 3.5% toward pitting corrosion of dissimilar metal welding joint between stainless steel AISI 304 and mild steel SS 400. Electrochemical corrosion was tested using potentiodynamic polarization. Further the Scanning Electron Microscope (SEM) conducted to analyze the specimen. Chemical composition analysis used Energy Dispersive X-ray Spectrometry (EDS). The highest efficiency of sodium nitrate for ER 308 attained 63.8% and 64.89%for ER 309L. The specimen surface which observed through SEM showed decrease of pitting corrosion respectively with the addition of sodium nitrate contentmore » as inhibitor.« less

Evaluation of candidate alloys for the construction of metal flex hoses in the STS launch environment

NASA Technical Reports Server (NTRS)

Ontiveros, Cordelia

1988-01-01

Various vacuum jacketed cryogenic supply lines at the Shuttle launch site use convoluted flexible expansion joints. The atmosphere at the launch site has a very high salt content, and during a launch, fuel combustion products include hydrochloric acid. This extremely corrosive environment has caused pitting corrosion failure in the flex hoses, which were made of 304L stainless steel. A search was done to find a more corrosion resistant replacement material. This study focused on 19 metal alloys. Tests which were performed include electrochemical corrosion testing, accelerated corrosion testing in a salt fog chamber, long term exposure at the beach corrosion testing site, and pitting corrosion tests in ferric chloride solution. Based on the results of these tests, the most corrosion resistant alloys were found to be (in order) Hastelloy C-22, Inconel 625, Hastelloy C-276, Hastelloy C-4, and Inco Alloy G-3. Of these top five alloys, the Hastelloy C-22 stands out as being the best of those tested for this application.

Evaluation of candidate alloys for the construction of metal flex hoses in the STS launch environment

NASA Technical Reports Server (NTRS)

Macdowell, Louis G., III; Ontiveros, Cordelia

1988-01-01

Various vacuum jacketed cryogenic supply lines at the Shuttle launch site use convoluted flexible expansion joints. The atmosphere at the launch site has a very high salt content, and during a launch fuel combustion products include hydrochloric acid. This extremely corrosive environment has caused pitting corrosion failure in the flex hoses, which were made out of 304L stainless steel. A search was done to find a more corrosion resistant replacement material. Nineteen metal alloys were tested. Tests which were performed include electrochemical corrosion testing, accelerated corrosion testing in a salt fog chamber, long term exposure at the beach corrosion testing site, and pitting corrosion tests in ferric chloride solution. Based on the results, the most corrosion resistant alloys were found to be, in order, Hastelloy C-22, Inconel 625, Hastelloy C-276, Hastelloy C-4, and Inco Alloy G-3. Of these top five alloys, the Hastelloy C-22 stands out as being the best of the alloys tested.

Endurance and failure characteristics of modified Vasco X-2, CBS 600 and AISI 9310 spur gears. [aircraft construction materials

NASA Technical Reports Server (NTRS)

Townsend, D. P.; Zaretsky, E. V.

1980-01-01

Gear endurance tests and rolling-element fatigue tests were conducted to compare the performance of spur gears made from AISI 9310, CBS 600 and modified Vasco X-2 and to compare the pitting fatigue lives of these three materials. Gears manufactured from CBS 600 exhibited lives longer than those manufactured from AISI 9310. However, rolling-element fatigue tests resulted in statistically equivalent lives. Modified Vasco X-2 exhibited statistically equivalent lives to AISI 9310. CBS 600 and modified Vasco X-2 gears exhibited the potential of tooth fracture occurring at a tooth surface fatigue pit. Case carburization of all gear surfaces for the modified Vasco X-2 gears results in fracture at the tips of the gears.

Direct detection of ligand binding to Sepharose-immobilised protein using saturation transfer double difference (STDD) NMR spectroscopy

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

Haselhorst, Thomas; Muenster-Kuehnel, Anja K.; Oschlies, Melanie

2007-08-10

We report an easy and direct application of 'Saturation Transfer Double Difference' (STDD) NMR spectroscopy to identify ligands that bind to a Sepharose-immobilised target protein. The model protein, cytidine 5'-monophosphate sialic acid (CMP-Sia) synthetase, was expressed as a Strep-Tag II fusion protein and immobilised on Strep-Tactin Sepharose. STD NMR experiments of the protein-enriched Sepharose matrix in the presence of a binding ligand (cytidine 5'-triphosphate, CTP) and a non-binding ligand ({alpha}/{beta}-glucose) clearly show that CTP binds to the immobilised enzyme, whereas glucose has no affinity. This approach has three major advantages: (a) only low quantities of protein are required, (b) nomore » specialised NMR technology or the application of additional data analysis by non-routine methods is required, and (c) easy multiple use of the immobilised protein is available.« less

Systematic design for trait introgression projects.

PubMed

Cameron, John N; Han, Ye; Wang, Lizhi; Beavis, William D

2017-10-01

Using an Operations Research approach, we demonstrate design of optimal trait introgression projects with respect to competing objectives. We demonstrate an innovative approach for designing Trait Introgression (TI) projects based on optimization principles from Operations Research. If the designs of TI projects are based on clear and measurable objectives, they can be translated into mathematical models with decision variables and constraints that can be translated into Pareto optimality plots associated with any arbitrary selection strategy. The Pareto plots can be used to make rational decisions concerning the trade-offs between maximizing the probability of success while minimizing costs and time. The systematic rigor associated with a cost, time and probability of success (CTP) framework is well suited to designing TI projects that require dynamic decision making. The CTP framework also revealed that previously identified 'best' strategies can be improved to be at least twice as effective without increasing time or expenses.

Dry Sintering Meets Wet Silver-Ion "Soldering": Charge-Transfer Plasmon Engineering of Solution-Assembled Gold Nanodimers From Visible to Near-Infrared I and II Regions.

PubMed

Fang, Lingling; Wang, Yueliang; Liu, Miao; Gong, Ming; Xu, An; Deng, Zhaoxiang

2016-11-07

Achieving highly tunable and localized surface plasmon resonance up to near infrared (NIR) regions is a key target in nanoplasmonics. In particular, a self-assembly process capable of producing highly uniform and solution-processable nanomaterials with tailor-made plasmonic properties is lacking. We herein address this problem through a conjunctive use of wet Ag + soldering and dry thermal sintering to produce nanodimer-derived structures with precisely engineered charge-transfer plasmon (CTP). The sintered dimers are water soluble, featuring gradually shifted CTP spanning an 800 nm wavelength range (up to NIR II). Upon silica removal, the products are grafted by DNA to offer surface functionality. This process is also adaptable to DNA-linked AuNP dimers toward plasmonic meta-materials via DNA-guided soldering and sintering. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Marengo, Barbara; Bottini, Consuelo; La Porta, C.A.M.

Phosphatidylethanolamine N-methyltransferase (PEMT) is the enzyme that converts phosphatidylethanolamine (PE) into phosphatidylcholine. We have previously shown that PEMT suppressed hepatoma growth by triggering apoptosis. We investigate whether PEMT controlled cell death and cell proliferation triggered by fasting/refeeding and whether it is a marker of early preneoplastic lesions. The induction of programmed cell death and suppression of cell proliferation by fasting were associated with enhanced PEMT expression and activity, and with a decrease in CTP:phosphocholine cytidylyltransferase expression. Refeeding returned the liver growth and expression of CTP:phosphocholine cytidylyltransferase to control levels, while the expression of PEMT decreased to below control values. Aftermore » DENA administration, PEMT protein, evaluated by Western blotting, slightly increased, but it remained below control levels. The treatment with 20 mg/kg DENA to refed rats induced the appearance of initiated hepatocytes that were negative for PEMT expression. Present findings indicate that PEMT is a novel tumour marker for early liver preneoplastic lesions.« less

The Coast Artillery Journal. Volume 65, Number 6, December 1926

DTIC Science & Technology

1926-12-01

both mortars are fired from the same pit, due to the increased concussion and general pit activity. A more thorough test of the system will result...Chiiteau-Salins. This result will be attained by the occupation of the heights of Baronville-~forhange. Also to begin the encirclement of Metz on the right...assure its full success. The enemy, in fact, considers that Metz and the Lorraine front constitute the left pillar of his dispositions, and we must seek

Hot Corrosion of Single-Crystal NiAl-X Alloys

NASA Technical Reports Server (NTRS)

Nesbitt, James A.

1998-01-01

Several single-crystal NiAl-X alloys (X=Hf, Ti, Cr, Ga) underwent hot corrosion testing in a Mach 0.3 burner rig at 900 deg. C for 300 1-hr cycles. The surface morphology after testing consisted of either mounds or an inward, uniform-type of attack which preserved surface features. It was observed that the surface morphology was affected by the surface preparation treatments. Microstructurally, the hot corrosion attack initiated as pits but evolved to a rampant attack consisting of the rapid inward growth of Al2O3. Electropolishing and chemical milling produced many pits and grooves on the surface. However, the presence of pits and grooves did not appear to strongly influence the hot corrosion response. Attack on many samples was strongly localized which was attributed to compositional inhomogeneity within the samples. It was found that increasing the Ti content from 1% to 5 % degraded the hot corrosion response of these alloys. In contrast, the addition of 1-2% Cr reduced the susceptibility of these alloys to hot corrosion attack and negated the deleterious effect of the 4-5% Ti addition.

Single crystal silicon filaments fabricated in SOI: A potential IR source for a microfabricated photometric CO2 sensor

NASA Technical Reports Server (NTRS)

Tu, Juliana; Smith, Rosemary L.

1995-01-01

The objective of this project was to design, fabricate, and test single crystal silicon filaments as potential black body IR sources for a spectrophotometric CO2 sensing microsystem. The design and fabrication of the silicon-on-insulator (SOI) filaments are summarized and figures showing the composite layout of the filament die (which contains four filaments of different lengths -- 500 microns, 1 mm, 1.5 mm and 2 mm -- and equal widths of 15 microns) are presented. The composite includes four mask layers: (1) silicon - defines the filament dimensions and contact pads; (2) release pit - defines the oxide removed from under the filament and hence, the length of the released filament; (3) Pyrex pit - defines the pit etched in the Pyrex cap (not used); and (4) metal - defines a metal pattern on the contact pads or used as a contact hole etch. I/V characteristics testing of the fabricated SOI filaments is described along with the nitride-coating procedures carried out to prevent oxidation and resistance instability.

Nucleation sites of Ge nanoislands grown on pit-patterned Si substrate prepared by electron-beam lithography

NASA Astrophysics Data System (ADS)

Smagina, Zh. V.; Zinovyev, V. A.; Rudin, S. A.; Novikov, P. L.; Rodyakina, E. E.; Dvurechenskii, A. V.

2018-04-01

Regular pit-patterned Si(001) substrates were prepared by electron-beam lithography followed by plasma chemical etching. The geometry of the pits was controlled by varying the etching conditions and the electron-beam exposure duration. It was shown that the location of three-dimensional (3D) Ge nanoislands subsequently grown on the pit-patterned Si substrates depends on the shape of the pit bottom. In the case of pits having a sharp bottom, 3D Ge islands nucleate inside the pits. For pits with a wide flat bottom, the 3D Ge island nucleation takes place at the pit periphery. This effect is attributed to the strain relaxation depending not only on the initial pit shape, but also on its evolution during the Ge wetting layer deposition. It was shown by Monte Carlo simulations that in the case of a pit with a pointed bottom, the relaxation is most effective inside the pit, while for a pit with a wide bottom, the most relaxed area migrates during Ge deposition from the pit bottom to its edges, where 3D Ge islands nucleate.

Successful remediation of four uranium calibration pits at Technical Area II, Sandia National Laboratories, Albuquerque, New Mexico, USA

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

Conway, R.; Wade, M.; Tharp, T.

1994-12-31

The first remediation of an Environmental Restoration (ER) Project site at Sandia National Laboratories (SNL) was successfully conducted in May and June 1994 at Technical Area II. The removal action involved four Uranium Calibration Pits (UCPs) filled with radioactive or hazardous materials. The concrete culvert pits were used to test and calibrate borehole radiometric logging tools for uranium exploration. The removal action consisted of excavating and containerizing the pit contents and contaminated soil beneath the culverts, removing the four culverts, and backfilling the excavation. Each UCP removal had unique complexities. Sixty 208-L drums of solid radioactive waste and eight 208-Lmore » drums of liquid hazardous waste were generated during the VCM. Two of the concrete culverts will be disposed as radioactive waste and two as solid waste. Uranium-238 was detected in UCP-2 ore material at 746 pci/g, and at 59 pci/g in UCP-1 silica sand. UCP-4 was empty; sludge from UCP-3 contained 122 mg/L (ppm) chromium.« less

Determination of precursor sites for pitting corrosion of polycrystalline titanium by using different techniques

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

Garfias-Mesias, L.F.; Alodan, M.; James, P.I.

1998-06-01

Scanning electrochemical microscopy (SECM) in ferrocyanide and bromide solutions was used to locate active sites (pitting precursors) on polycrystalline Ti where oxidation of Br{sup {minus}} and Fe(CN){sub 6}{sup 4{minus}} was possible. Analysis of the electrochemically active sites was done by using electron microscopy (SEM), energy dispersive X-ray analysis (EDX), atomic force microscopy (AFM), and in situ confocal laser scanning microscopy (CLSM). In most cases, the active sites were found to be associated with particles (inclusions) which contained mainly Al and Si; however, some other areas not associated with particles were also found to be active. Although the size of themore » inclusions was normally smaller than 20 {micro}m, as revealed by SEM and AFM imaging, in some cases larger particles were also found. Pitting corrosion tests in bromide solution at potentials above 1.5 V{sub SCE} followed by EDX analysis inside the pits and in situ CLSM observation, confirmed that most of the localized attack started in the areas where particles had been located.« less

[Vitrectomy and gas-fluid exchange for the treatment of serous macular detachment due to optic disc pit: long-term evaluation].

PubMed

Moreira Neto, Carlos Augusto; Moreira Junior, Carlos Augusto

2013-01-01

To evaluate 5 patients with serous macular detachment due to optic disc pit that were submitted to pars plana vitrectomy and were followed for at least 7 years. Patients were submitted to pars plana vitrectomy, posterior hyaloid removal, autologous serum injection and gas-fluid exchange, without laser photocoagulation, and were evaluated pre and post-operatively with visual acuity and Amsler grid testing, retinography, and recently, with autofluorescence imaging and high resolution OCT. All 5 eyes improved visual acuity significantly following the surgical procedure maintaining good vision throughout the follow-up period. Mean pre-operative visual acuity was 20/400 and final visual acuity was 20/27 with a mean follow-up time of 13.6 years. No recurrences of serous detachments were observed. OCT examinations demonstrated an attached retina up to the margin of the pit. Serous macular detachments due to optic disc pits were adequately treated with pars plana vitrectomy and gas fluid exchange, without the need for laser photocoagulation, maintaining excellent visual results for a long period of time.

Kinetics of Accumulation of Damage in Surface Layers of Lithium-Containing Aluminum Alloys in Fatigue Tests with Rigid Loading Cycle and Corrosive Effect of Environment

NASA Astrophysics Data System (ADS)

Morozova, L. V.; Zhegina, I. P.; Grigorenko, V. B.; Fomina, M. A.

2017-07-01

High-resolution methods of metal physics research including electron, laser and optical microscopy are used to study the kinetics of the accumulation of slip lines and bands and the corrosion damage in the plastic zone of specimens of aluminum-lithium alloys 1441 and B-1469 in rigid-cycle fatigue tests under the joint action of applied stresses and corrosive environment. The strain parameters (the density of slip bands, the sizes of plastic zones near fracture, the surface roughness in singled-out zones) and the damage parameters (the sizes of pits and the pitting area) are evaluated.

Morphogenesis and grain size variation of alluvial gold recovered in auriferous sediments of the Tormes Basin (Iberian Peninsula) using a simple correspondence analysis

NASA Astrophysics Data System (ADS)

Barrios, S.; Merinero, R.; Lozano, R.; Orea, I.

2015-12-01

With present techniques it is difficult to determine whether the gold particles present at fluvial placers have come from one or multiple sources. Knowledge of this would be useful in prospecting for larger gold deposits. The aim of the present work was to test the potential of a technique based on modern visual and classic statistical methods to determine the single or multisource origin of gold particles at different sites in the Tormes Basin (Central Iberian Zone of the Iberian Massif, Iberian Peninsula). This basin contains numerous lode and placer gold deposits that have been exploited since ancient times. Today, gold nuggets (usually associated with quartz, 0.2-6 g in weight, 0.53-3.74 cm long and mostly discoidal in shape and of intermediate roundness) can be recovered from the sediments of the upper reaches of the River Tormes. These nuggets, as well as small gold particles collected at three gravel pits from across the basin (all of which showed abrasion marks) were examined by optical and/or environmental scanning electron microscopy, and the differences in their dimensions and morphological features noted. Simple correspondence analysis of the sphericity and roundness of the nuggets and particles was used to morphologically classify the gold samples collected at each location. The gold nuggets were best classified as elongated rods of intermediate roundness. Surprisingly, the gold particles from the most upstream and downstream gravel pits were best described as discs/sub-discs of rounded appearance, while those from the intermediate gravel pit were discs of intermediate roundness. Analysis of the variance followed by the Tukey honest significant differences test revealed the particles from the most upstream gravel pit to be significantly more flattened and smaller. These were therefore transported further from their source than the particles collected at the other two pits. These results suggest that multiple sources of sedimentary gold exist in the Tormes Basin and that these feed these different gravel pits. Present techniques for classifying gold would not have detected these differences.

Closure Report for Corrective Action Unit 356: Mud Pits and Disposal Sites, Nevada Test Site, Nevada with Errata Sheet

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

NNSA /NV

2002-11-12

This Closure Report (CR) has been prepared for Corrective Action Unit (CAU) 356, Mud Pits and Disposal Sites, in accordance with the Federal Facility Agreement and Consent Order. This CAU is located in Areas 3 and 20 of the Nevada Test Site (NTS) approximately 65 miles northwest of Las Vegas, Nevada. Corrective Action Unit 356 consists of seven Corrective Action Sites (CASs): 03-04-01, Area 3 Change House Septic System; 03-09-01, Mud Pit Spill Over; 03-09-03, Mud Pit; 03-09-04, Mud Pit; 03-09-05, Mud Pit; 20-16-01, Landfill; and 20-22-21, Drums. This CR identifies and rationalizes the U.S. Department of Energy (DOE), Nationalmore » Nuclear Security Administration Nevada Operations Office's (NNSA/NV's) recommendation that no further corrective action and closure in place is deemed necessary for CAU 356. This recommendation is based on the results of field investigation/closure activities conducted November 20, 2001, through January 3, 2002, and March 11 to 14, 2002. These activities were conducted in accordance with the Streamlined Approach for Environmental Restoration Plan (SAFER) for CAU 356. For CASs 03-09-01, 03-09-03, 20-16-01, and 22-20-21, analytes detected in soil during the corrective action investigation were evaluated against Preliminary Action Levels (PALs) and it was determined that no Contaminants of Concern (COCs) were present. Therefore, no further action is necessary for the soil at these CASs. For CASs 03-04-01, 03-09-04, and 03-09-05, analytes detected in soil during the corrective action investigation were evaluated against PALs and identifies total petroleum hydrocarbons (TPHs) and radionuclides (i.e., americium-241 and/or plutonium 239/240) as COCs. The nature, extent, and concentration of the TPH and radionuclide COCs were bounded by sampling and shown to be relatively immobile. Therefore, closure in place is recommended for these CASs in CAU 356. Further, use restrictions are not required at this CAU beyond the NTS use restrictions identified in the SAFER Plan. In addition, the septic tank associated with CAU 356 will be closed in accordance with applicable regulations.« less

Martian Central Pit Craters

NASA Technical Reports Server (NTRS)

Hillman, E.; Barlow, N. G.

2005-01-01

Impact craters containing central pits are rare on the terrestrial planets but common on icy bodies. Mars is the exception among the terrestrial planets, where central pits are seen on crater floors ( floor pits ) as well as on top of central peaks ( summit pits ). Wood et al. [1] proposed that degassing of subsurface volatiles during crater formation produced central pits. Croft [2] argued instead that central pits might form during the impact of volatile-rich comets. Although central pits are seen in impact craters on icy moons such as Ganymede, they do show some significant differences from their martian counterparts: (a) only floor pits are seen on Ganymede, and (b) central pits begin to occur at crater diameters where the peak ring interior morphology begins to appear in terrestrial planet craters [3]. A study of craters containing central pits was conducted by Barlow and Bradley [4] using Viking imagery. They found that 28% of craters displaying an interior morphology on Mars contain central pits. Diameters of craters containing central pits ranged from 16 to 64 km. Barlow and Bradley noted that summit pit craters tended to be smaller than craters containing floor pits. They also noted a correlation of central pit craters with the proposed rings of large impact basins. They argued that basin ring formation fractured the martian crust and allowed subsurface volatiles to concentrate in these locations. They favored the model that degassing of the substrate during crater formation was responsible for central pit formation due to the preferential location of central pit craters along these basin rings.

SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia.

PubMed

Schneider, Constanze; Oellerich, Thomas; Baldauf, Hanna-Mari; Schwarz, Sarah-Marie; Thomas, Dominique; Flick, Robert; Bohnenberger, Hanibal; Kaderali, Lars; Stegmann, Lena; Cremer, Anjali; Martin, Margarethe; Lohmeyer, Julian; Michaelis, Martin; Hornung, Veit; Schliemann, Christoph; Berdel, Wolfgang E; Hartmann, Wolfgang; Wardelmann, Eva; Comoglio, Federico; Hansmann, Martin-Leo; Yakunin, Alexander F; Geisslinger, Gerd; Ströbel, Philipp; Ferreirós, Nerea; Serve, Hubert; Keppler, Oliver T; Cinatl, Jindrich

2017-02-01

The nucleoside analog cytarabine (Ara-C) is an essential component of primary and salvage chemotherapy regimens for acute myeloid leukemia (AML). After cellular uptake, Ara-C is converted into its therapeutically active triphosphate metabolite, Ara-CTP, which exerts antileukemic effects, primarily by inhibiting DNA synthesis in proliferating cells. Currently, a substantial fraction of patients with AML fail to respond effectively to Ara-C therapy, and reliable biomarkers for predicting the therapeutic response to Ara-C are lacking. SAMHD1 is a deoxynucleoside triphosphate (dNTP) triphosphohydrolase that cleaves physiological dNTPs into deoxyribonucleosides and inorganic triphosphate. Although it has been postulated that SAMHD1 sensitizes cancer cells to nucleoside-analog derivatives through the depletion of competing dNTPs, we show here that SAMHD1 reduces Ara-C cytotoxicity in AML cells. Mechanistically, dGTP-activated SAMHD1 hydrolyzes Ara-CTP, which results in a drastic reduction of Ara-CTP in leukemic cells. Loss of SAMHD1 activity-through genetic depletion, mutational inactivation of its triphosphohydrolase activity or proteasomal degradation using specialized, virus-like particles-potentiates the cytotoxicity of Ara-C in AML cells. In mouse models of retroviral AML transplantation, as well as in retrospective analyses of adult patients with AML, the response to Ara-C-containing therapy was inversely correlated with SAMHD1 expression. These results identify SAMHD1 as a potential biomarker for the stratification of patients with AML who might best respond to Ara-C-based therapy and as a target for treating Ara-C-refractory AML.

Central Equatorial Pacific Sea Surface Temperatures During the Last Glacial Maximum

NASA Astrophysics Data System (ADS)

Monteagudo, M. M.; Lynch-Stieglitz, J.; Schmidt, M. W.

2017-12-01

The state of the tropical Pacific ocean-atmosphere system during the Last Glacial Maximum (LGM, 19,000-23,000 years BP) remains an area of uncertainty. Spatial patterns of tropical Pacific sea surface temperature (SST) offer insight into atmospheric circulation (i.e. Walker Circulation), however, few records exist for the Central Tropical Pacific (CTP). The few existing glacial CTP SST reconstructions indicate 1-2 °C of warming based on foraminiferal transfer functions (CLIMAP Project Members, 1976). In contrast, evidence from geochemical proxies (Mg/Ca, UK'37, TEX86) show 1-3.5 °C cooling in the eastern and western tropical Pacific (e.g. MARGO Project Members, 2009). In this study we present the first Mg/Ca estimates of glacial CTP SST from a meridional sediment core transect along the Line Islands Ridge (0-7°N, 156-162 °W). We use a time slice approach to establish the magnitude of glacial-interglacial SST change between the LGM (19,000-23,0000 years BP) and the Holocene (0-10,000 years BP) using Mg/Ca in the surface-dwelling foraminifera Globigerinoides ruber. Our results indicate cooling at all latitudes, ranging between 1.2-2.7 °C (Holocene-LGM SST). Northern cores (6.83-2.77 °N) exhibit a smaller glacial-interglacial SST difference than equatorial site 20BB at 1.27 °N. The data generated thus far suggest the glacial meridional SST gradient may have been steeper, possibly as a result of increased zonal winds, equatorial upwelling, or westward expansion of the Eastern Pacific Cold Tongue.

[Etiology and complications of liver cirrhosis: data from a German centre].

PubMed

Sivanathan, V; Kittner, J M; Sprinzl, M F; Weinmann, A; Koch, S; Wiltink, J; Nguyen-Tat, M; Marquardt, J U; Wörns, M A; Zimmermann, T; Lang, H; Galle, P R; Schattenberg, J M

2014-09-01

Liver cirrhosis develops as a terminal complication of chronic liver disease. The clinical course is determined by the underlying etiology and the accompanying risk factors, which are influenced by the geographic and cultural background. A total of 236 patients (159 men, 77 women, median age 57 [22-81] years) were included for retrospective analysis between July 2012 and February 2014 using standardized questionnaires during an outpatient visit at a hepatology clinic. The most common etiologies of liver cirrhosis were related to alcohol consumption (52 %), chronic hepatitis C (28 %) or hepatitis B (14 %) infection and NASH (nonalcoholic steatohepatitis, 6 %). At the time of presentation 55 % patients had compensated cirrhosis corresponding to Child-Turcotte-Pugh (CTP) stage A, while 45 % were in a decompensated stage (30 % CTP B and 15 % CTP C). Subgroups were analyzed for the incidence of complications and the emergence of infections. Most frequently esophageal varices (60 %) and ascites (49 %) were observed, followed by pleural effusion (14 %), hepatic encephalopathy (25 %) or hepatorenal syndrome (18 %). 16 % of patients exhibited infection based on clinical criteria. An infective agent was isolated in 38 % of all cases with infection and of those 50 % were gram positive bacteria. In multivariate analysis only the presence of ascites was an independent risk factor for infection. Despite improved medical therapies for viral hepatitis, these were the most frequent causes of liver cirrhosis, closely followed by alcoholic cirrhosis. The observed complications included bacterial infection and complication related to portal hypertension. © Georg Thieme Verlag KG Stuttgart · New York.

SU-G-IeP2-06: Evaluation of Registration Accuracy for Cone-Beam CT Reconstruction Techniques

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

Li, J; Wang, P; Zhang, H

2016-06-15

Purpose: Cone-beam (CB) computed tomography (CT) is used for image guidance during radiotherapy treatment delivery. Conventional Feldkamp and compressed sensing (CS) based CBCT recon-struction techniques are compared for image registration. This study is to evaluate the image registration accuracy of conventional and CS CBCT for head-and-neck (HN) patients. Methods: Ten HN patients with oropharyngeal tumors were retrospectively selected. Each HN patient had one planning CT (CTP) and three CBCTs were acquired during an adaptive radiotherapy proto-col. Each CBCT was reconstructed by both the conventional (CBCTCON) and compressed sens-ing (CBCTCS) methods. Two oncologists manually labeled 23 landmarks of normal tissue andmore » implanted gold markers on both the CTP and CBCTCON. Subsequently, landmarks on CTp were propagated to CBCTs, using a b-spline-based deformable image registration (DIR) and rigid registration (RR). The errors of these registration methods between two CBCT methods were calcu-lated. Results: For DIR, the mean distance between the propagated and the labeled landmarks was 2.8 mm ± 0.52 for CBCTCS, and 3.5 mm ± 0.75 for CBCTCON. For RR, the mean distance between the propagated and the labeled landmarks was 6.8 mm ± 0.92 for CBCTCS, and 8.7 mm ± 0.95 CBCTCON. Conclusion: This study has demonstrated that CS CBCT is more accurate than conventional CBCT in image registration by both rigid and non-rigid methods. It is potentially suggested that CS CBCT is an improved image modality for image guided adaptive applications.« less

Numerical and experimental investigations on cavitation erosion

NASA Astrophysics Data System (ADS)

Fortes Patella, R.; Archer, A.; Flageul, C.

2012-11-01

A method is proposed to predict cavitation damage from cavitating flow simulations. For this purpose, a numerical process coupling cavitating flow simulations and erosion models was developed and applied to a two-dimensional (2D) hydrofoil tested at TUD (Darmstadt University of Technology, Germany) [1] and to a NACA 65012 tested at LMH-EPFL (Lausanne Polytechnic School) [2]. Cavitation erosion tests (pitting tests) were carried out and a 3D laser profilometry was used to analyze surfaces damaged by cavitation [3]. The method allows evaluating the pit characteristics, and mainly the volume damage rates. The paper describes the developed erosion model, the technique of cavitation damage measurement and presents some comparisons between experimental results and numerical damage predictions. The extent of cavitation erosion was correctly estimated in both hydrofoil geometries. The simulated qualitative influence of flow velocity, sigma value and gas content on cavitation damage agreed well with experimental observations.

Mapping of the minimal inorganic phosphate transporting unit of human PiT2 suggests a structure universal to PiT-related proteins from all kingdoms of life

PubMed Central

2011-01-01

Background The inorganic (Pi) phosphate transporter (PiT) family comprises known and putative Na+- or H+-dependent Pi-transporting proteins with representatives from all kingdoms. The mammalian members are placed in the outer cell membranes and suggested to supply cells with Pi to maintain house-keeping functions. Alignment of protein sequences representing PiT family members from all kingdoms reveals the presence of conserved amino acids and that bacterial phosphate permeases and putative phosphate permeases from archaea lack substantial parts of the protein sequence when compared to the mammalian PiT family members. Besides being Na+-dependent Pi (NaPi) transporters, the mammalian PiT paralogs, PiT1 and PiT2, also are receptors for gamma-retroviruses. We have here exploited the dual-function of PiT1 and PiT2 to study the structure-function relationship of PiT proteins. Results We show that the human PiT2 histidine, H502, and the human PiT1 glutamate, E70, - both conserved in eukaryotic PiT family members - are critical for Pi transport function. Noticeably, human PiT2 H502 is located in the C-terminal PiT family signature sequence, and human PiT1 E70 is located in ProDom domains characteristic for all PiT family members. A human PiT2 truncation mutant, which consists of the predicted 10 transmembrane (TM) domain backbone without a large intracellular domain (human PiT2ΔR254-V483), was found to be a fully functional Pi transporter. Further truncation of the human PiT2 protein by additional removal of two predicted TM domains together with the large intracellular domain created a mutant that resembles a bacterial phosphate permease and an archaeal putative phosphate permease. This human PiT2 truncation mutant (human PiT2ΔL183-V483) did also support Pi transport albeit at very low levels. Conclusions The results suggest that the overall structure of the Pi-transporting unit of the PiT family proteins has remained unchanged during evolution. Moreover, in combination, our studies of the gene structure of the human PiT1 and PiT2 genes (SLC20A1 and SLC20A2, respectively) and alignment of protein sequences of PiT family members from all kingdoms, along with the studies of the dual functions of the human PiT paralogs show that these proteins are excellent as models for studying the evolution of a protein's structure-function relationship. PMID:21586110

Mapping of the minimal inorganic phosphate transporting unit of human PiT2 suggests a structure universal to PiT-related proteins from all kingdoms of life.

PubMed

Bøttger, Pernille; Pedersen, Lene

2011-05-17

The inorganic (Pi) phosphate transporter (PiT) family comprises known and putative Na(+)- or H(+)-dependent Pi-transporting proteins with representatives from all kingdoms. The mammalian members are placed in the outer cell membranes and suggested to supply cells with Pi to maintain house-keeping functions. Alignment of protein sequences representing PiT family members from all kingdoms reveals the presence of conserved amino acids and that bacterial phosphate permeases and putative phosphate permeases from archaea lack substantial parts of the protein sequence when compared to the mammalian PiT family members. Besides being Na(+)-dependent P(i) (NaP(i)) transporters, the mammalian PiT paralogs, PiT1 and PiT2, also are receptors for gamma-retroviruses. We have here exploited the dual-function of PiT1 and PiT2 to study the structure-function relationship of PiT proteins. We show that the human PiT2 histidine, H(502), and the human PiT1 glutamate, E(70),--both conserved in eukaryotic PiT family members--are critical for P(i) transport function. Noticeably, human PiT2 H(502) is located in the C-terminal PiT family signature sequence, and human PiT1 E(70) is located in ProDom domains characteristic for all PiT family members.A human PiT2 truncation mutant, which consists of the predicted 10 transmembrane (TM) domain backbone without a large intracellular domain (human PiT2ΔR(254)-V(483)), was found to be a fully functional P(i) transporter. Further truncation of the human PiT2 protein by additional removal of two predicted TM domains together with the large intracellular domain created a mutant that resembles a bacterial phosphate permease and an archaeal putative phosphate permease. This human PiT2 truncation mutant (human PiT2ΔL(183)-V(483)) did also support P(i) transport albeit at very low levels. The results suggest that the overall structure of the P(i)-transporting unit of the PiT family proteins has remained unchanged during evolution. Moreover, in combination, our studies of the gene structure of the human PiT1 and PiT2 genes (SLC20A1 and SLC20A2, respectively) and alignment of protein sequences of PiT family members from all kingdoms, along with the studies of the dual functions of the human PiT paralogs show that these proteins are excellent as models for studying the evolution of a protein's structure-function relationship. © 2011 Bøttger and Pedersen; licensee BioMed Central Ltd.

Impaired limb reaction to displacement of center of gravity in rats with unilateral striatal ischemic injury.

PubMed

Nobile, Cameron W; Palmateer, Julie M; Kane, Jackie; Hurn, Patricia D; Schallert, Timothy; Adkins, DeAnna L

2014-10-01

Clinical stroke often results in impaired balance and increased vulnerability to severe injuries due to falling. To evaluate potential preclinical treatments that might target these deficits, it will be important to include tests capable of assessing these impairments chronically in animal models. Previously, we developed a postural instability test (PIT) that revealed chronic, unilateral impairments in postural stability in rat models of hemi-Parkinson's disease (PD) and of unilateral cervical spinal cord injury. Here, we investigated whether this test was also capable of revealing long-term stroke-induced impairments in postural support in rats. Additionally, we examined the ability of more common tests of sensorimotor function to detect chronic impairments. We found that the PIT detected chronic deficits in postural stability/balance enduring for up to 6 weeks post-stroke, outlasting impairments detected in other tests of forelimb sensorimotor function, including asymmetries in upright postural support (cylinder test) and vibrissae-evoked forelimb placing.

Cigarette smoke disrupts the integrity of airway adherens junctions through the aberrant interaction of p120-catenin with the cytoplasmic tail of MUC1

PubMed Central

Zhang, Lili; Gallup, Marianne; Zlock, Lorna; Basbaum, Carol; Finkbeiner, Walter E.; McNamara, Nancy A.

2014-01-01

Adherens junctions (AJs) containing epithelial cadherin (E-cad) bound to p120-catenin (p120ctn) and β-catenin (β-ctn) play a crucial role in regulating cell–cell adhesion. Cigarette smoke abrogates cell–cell adhesion between epithelial cells by disrupting E-cad, a hallmark of epithelial–mesenchymal transition (EMT), yet the underlying mechanism remains unknown. We used an organotypic culture of primary human bronchial epithelial (HBE) cells treated with smoke-concentrated medium (Smk) to establish an essential role for the interaction between p120ctn and the cytoplasmic tail of MUC1 (MUC1-CT) in regulating E-cad disruption. Within the first 4 h of smoke exposure, apical MUC1-CT repositioned to the basolateral membrane of pseudo-stratified HBE cells, where it interacted with p120ctn. A time-dependent increase in MUC1-CT/p120ctn complexes occurred in conjunction with a time-dependent dissociation of p120ctn/E-cad/β-ctn complexes, as well as the coordinated degradation of p120ctn and E-cad. Interestingly, Smk induced a similar interaction between MUC1-CT and β-ctn, but this occurred 44 h after MUC1-CT’s initial interaction with p120ctn, and well after the AJs were destroyed. Blocking MUC1-CT’s interaction with p120ctn using a MUC1-CT dominant-negative peptide, PMIP, successfully abolished Smk’s disruptive effects on AJs and recovered apical-basolateral polarity of HBE cells. The MUC1-CT/p120ctn interaction was highly dependent on EGFR/Src/Jnk-mediated tyrosine phosphorylation (TyrP) of MUC1-CT. Accordingly, EGFR, Src or Jnk inhibitors (AG1478, PP2, SP600125, respectively) abrogated Smk-induced MUC1-CT-TyrP, MUC1-CT/p120ctn interaction, AJ disruption, and loss of cellular polarity. Our work identified MUC1-CT and p120ctn as important regulators of epithelial polarity and cell-cell adhesion during a smoke-induced EMT-like process. Novel therapeutics designed to inhibit MUC1-CT/p120ctn complex formation may prevent EMT in the smoker’s airway. PMID:22833523

The three principles of action: a Pavlovian-instrumental transfer hypothesis

PubMed Central

Cartoni, Emilio; Puglisi-Allegra, Stefano; Baldassarre, Gianluca

2013-01-01

Pavlovian conditioned stimuli can influence instrumental responding, an effect called Pavlovian-instrumental transfer (PIT). During the last decade, PIT has been subdivided into two types: specific PIT and general PIT, each having its own neural substrates. Specific PIT happens when a conditioned stimulus (CS) associated with a reward enhances an instrumental response directed to the same reward. Under general PIT, instead, the CS enhances a response directed to a different reward. While important progress has been made into identifying the neural substrates, the function of specific and general PIT and how they interact with instrumental responses are still not clear. In the experimental paradigm that distinguishes specific and general PIT an effect of PIT inhibition has also been observed and is waiting for an explanation. Here we propose an hypothesis that links these three PIT effects (specific PIT, general PIT and PIT inhibition) to three aspects of action evaluation. These three aspects, which we call “principles of action”, are: context, efficacy, and utility. In goal-directed behavior, an agent has to evaluate if the context is suitable to accomplish the goal, the efficacy of his action in getting the goal, and the utility of the goal itself: we suggest that each of the three PIT effects is related to one of these aspects of action evaluation. In particular, we link specific PIT with the estimation of efficacy, general PIT with the evaluation of utility, and PIT inhibition with the adequacy of context. We also provide a latent cause Bayesian computational model that exemplifies this hypothesis. This hypothesis and the model provide a new framework and new predictions to advance knowledge about PIT functioning and its role in animal adaptation. PMID:24312025

Raft and floating radio frequency identification (RFID) antenna systems for detecting and estimating abundance of PIT-tagged fish in rivers

USGS Publications Warehouse

Fetherman, Eric R.; Avila, Brian W.; Winkelman, Dana L.

2016-01-01

Portable radio frequency identification (RFID) PIT tag antenna systems are increasingly being used in studies examining aquatic animal movement, survival, and habitat use, and their design flexibility permits application in a wide variety of settings. We describe the construction, use, and performance of two portable floating RFID PIT tag antenna systems designed to detect fish that were unavailable for recapture using stationary antennas or electrofishing. A raft antenna system was designed to detect and locate PIT-tagged fish in relatively long (i.e., ≥10 km) river reaches, and consisted of two antennas: (1) a horizontal antenna (4 × 1.2 m) installed on the bottom of the raft and used to detect fish in shallower river reaches (<1 m), and (2) a vertical antenna (2.7 × 1.2 m) for detecting fish in deeper pools (≥1 m). Detection distances of the horizontal antenna were between 0.7 and 1.0 m, and detection probability was 0.32 ± 0.02 (mean ± SE) in a field test using rocks marked with 32-mm PIT tags. Detection probability of PIT-tagged fish in the Cache la Poudre River, Colorado, using the raft antenna system, which covered 21% of the wetted area, was 0.14 ± 0.14. A shore-deployed floating antenna (14.6 × 0.6 m), which covered 100% of the wetted area, was designed for use by two operators for detecting and locating PIT-tagged fish in shorter (i.e., <2 km) river reaches. Detection distances of the shore-deployed floating antenna were between 0.7 and 0.8 m, and detection probabilities during field deployment in the St. Vrain River exceeded 0.52. The shore-deployed floating antenna was also used to estimate abundance of PIT-tagged fish. Results suggest that the shore-deployed floating antenna could be used as an alternative to estimating abundance using traditional sampling methods such as electrofishing.

Paraneoplastic remitting seronegative symmetrical synovitis with pitting edema (RS3PE syndrome): a report of two cases and review of the literature.

PubMed

Tunc, S Ercan; Arslan, Cagatay; Ayvacioglu, Naime Bayram; Sahin, Mehmet; Akkus, Selami; Yorgancigil, Huseyin

2004-07-01

We report two cases of paraneoplastic remitting seronegative symmetrical synovitis with pitting edema (RS3PE) associated with prostatic adenocarcinoma. One of the patients was positive for Helicobacter pylori and the other had secondary bone metastases. In the latter, the clinical picture of RS3PE developed after surgical intervention for the primary lesion. On physical examination, while the hands and feet were swollen in the first patient, pitting edema was present only at the feet of the other. All joints of the affected hands and feet were painful. Serological tests including rheumatoid factor, antinuclear antibody, and human leukocyte antigen B27 were all negative. Response to low-dose corticosteroid treatment was delayed in the first patient, but the symptoms were relieved better in the second one.

Performance of OTEC Heat Exchanger Materials in Tropical Seawaters

NASA Astrophysics Data System (ADS)

Larsen-Basse, Jorn

1985-03-01

The corrosion of several aluminum alloys in flowing Hawaiian surface seawater and water from 600 m depth for exposure periods up to three years has been studied. The alloys tested in cold water were Alclad (7072) 3003 and 3004; and bare 3004 and 5052). All show some pitting. Pit growth is slow, and pits do not penetrate the cladding. In the warm water, only uniform corrosion has been found. All alloys corrode at the same, low rate of˜3 μm/year after an initial short period of more rapid corrosion. This behavior is closely linked to the formation of a protective inorganic scale film on the surface. It consists of precipitated scale minerals from the seawater and aluminum corrosion products. The results indicate that OTEC evaporator heat exchangers constructed of aluminum alloys should have acceptable service lives.

A probability distribution model of tooth pits for evaluating time-varying mesh stiffness of pitting gears

NASA Astrophysics Data System (ADS)

Lei, Yaguo; Liu, Zongyao; Wang, Delong; Yang, Xiao; Liu, Huan; Lin, Jing

2018-06-01

Tooth damage often causes a reduction in gear mesh stiffness. Thus time-varying mesh stiffness (TVMS) can be treated as an indication of gear health conditions. This study is devoted to investigating the mesh stiffness variations of a pair of external spur gears with tooth pitting, and proposes a new model for describing tooth pitting based on probability distribution. In the model, considering the appearance and development process of tooth pitting, we model the pitting on the surface of spur gear teeth as a series of pits with a uniform distribution in the direction of tooth width and a normal distribution in the direction of tooth height, respectively. In addition, four pitting degrees, from no pitting to severe pitting, are modeled. Finally, influences of tooth pitting on TVMS are analyzed in details and the proposed model is validated by comparing with a finite element model. The comparison results show that the proposed model is effective for the TVMS evaluations of pitting gears.

Some properties of the walls of metaxylem vessels of maize roots, including tests of the wettability of their lumenal wall surfaces

PubMed Central

McCully, Margaret; Canny, Martin; Baker, Adam; Miller, Celia

2014-01-01

Background and Aims Since the proposal of the cohesion theory there has been a paradox that the lumenal surface of vessels is rich in hydrophobic lignin, while tension in the rising sap requires adhesion to a hydrophilic surface. This study sought to characterize the strength of that adhesion in maize (Zea mays), the wettability of the vessel surface, and to reconcile this with its histochemical and physical nature. Methods Wettability was assessed by emptying the maize root vessels of sap, perfusing them with either water or oil, and examining the adhesion (as revealed by contact angles) of the two liquids to vessel walls by cryo-scanning electron microscopy. The phobicity of the lumenal surface was also assessed histochemically with hydrophilic and hydrophobic probes. Key Results Pit borders in the lumen-facing vessel wall surface were wetted by both sap/water and oil. The attraction for oil was weaker: water could replace oil but not vice versa. Pit apertures repelled oil and were strongly stained by hydrophilic probes. Pit chambers were probably hydrophilic. Oil never entered the pits. When vessels were emptied and cryo-fixed immediately, pit chambers facing away from the vessels were always sap-filled. Pit chambers facing vessel lumens were either sap- or gas-filled. Sap from adjoining tracheary elements entering empty vessels accumulated on the lumenal surface in hemispherical drops, which spread out with decreasing contact angles to fill the lumen. Conclusions The vessel lumenal surface has a dual nature, namely a mosaic of hydrophilic and hydrophobic patches at the micrometre scale, with hydrophilic predominating. A key role is shown, for the first time, of overarching borders of pits in determining the dual nature of the surface. In gas-filled (embolized) vessels they are hydrophobic. When wetted by sap (vessels refilling or full) they are hydrophilic. A hypothesis is proposed to explain the switch between the two states. PMID:24709790

Feedback Limiting the Coastal Response to Irregularities in Shelf Bathymetry

NASA Astrophysics Data System (ADS)

List, J. H.; Benedet, L.

2007-12-01

Observations and engineering studies have shown that non-uniform inner shelf bathymetry can influence longshore sediment transport gradients and create patterns of shoreline change. One classic example is from Grand Isle, Louisiana, where two offshore borrow pits caused two zones of shoreline accretion landward of the pits. In addition to anthropogenic cases, many natural situations exist in which irregularities in coastal planform are thought to result from offshore shoals or depressions. Recent studies using the hydrodynamic model Delft3D have successfully simulated the observed nearshore erosion and accretion patterns landward of an inner shelf borrow pit. An analysis of the momentum balance in a steady-state simulation has demonstrated that both alongshore pressure gradients (due to alongshore variations in wave setup) and radiation stress gradients (terms relevant to alongshore forcing) are important for forcing the initial pattern of nearshore sedimentation in response to the borrow pit. The response of the coast to non-uniform inner shelf bathymetry appears to be limited, however, because observed shoreline undulations are often rather subtle. (An exception may exist in the case of a very high angle wave climate.) Therefore, feedbacks in processes must exist such that growth of the shoreline salient itself modifies the transport processes in a way that limits further growth (assuming the perturbation in inner shelf bathymetry itself remains unchanged). Examination of the Delft3D momentum balance for an inner shelf pit test case demonstrates that after a certain degree of morphologic development the forcing associated with the well-known shoreline smoothing process (a.k.a., diffusion) counteracts the forcing associated with the inner shelf pit, producing a negative feedback which arrests further growth of the shoreline salient. These results provide insights into the physical processes that control shoreline changes behind inner shelf bathymetric anomalies (i.e. man-made dredge pits and natural bathymetric features) and are therefore relevant to the understanding and prediction of shoreline change on many coasts.

NIR detection of pits and pit fragments in fresh cherries (abstract)

USDA-ARS?s Scientific Manuscript database

The feasibility of using near infrared (NIR) diffuse reflectance spectroscopy for the detection of pits and pit fragments in cherries was demonstrated. For detection of whole pits, 300 cherries were obtained locally and pits were removed from half. NIR reflectance spectra were obtained in triplicate...

7 CFR 52.779 - Freedom from pits.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Freedom from pits. 52.779 Section 52.779 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Freedom from pits. (a) General. The factor of freedom from pits refers to the incidence of pits and pit...

Transmission Bearing Damage Detection Using Decision Fusion Analysis

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.; Lewicki, David G.; Decker, Harry J.

2004-01-01

A diagnostic tool was developed for detecting fatigue damage to rolling element bearings in an OH-58 main rotor transmission. Two different monitoring technologies, oil debris analysis and vibration, were integrated using data fusion into a health monitoring system for detecting bearing surface fatigue pitting damage. This integrated system showed improved detection and decision-making capabilities as compared to using individual monitoring technologies. This diagnostic tool was evaluated by collecting vibration and oil debris data from tests performed in the NASA Glenn 500 hp Helicopter Transmission Test Stand. Data was collected during experiments performed in this test rig when two unanticipated bearing failures occurred. Results show that combining the vibration and oil debris measurement technologies improves the detection of pitting damage on spiral bevel gears duplex ball bearings and spiral bevel pinion triplex ball bearings in a main rotor transmission.

GPS Metric Tracking Unit

NASA Technical Reports Server (NTRS)

2008-01-01

As Global Positioning Satellite (GPS) applications become more prevalent for land- and air-based vehicles, GPS applications for space vehicles will also increase. The Applied Technology Directorate of Kennedy Space Center (KSC) has developed a lightweight, low-cost GPS Metric Tracking Unit (GMTU), the first of two steps in developing a lightweight, low-cost Space-Based Tracking and Command Subsystem (STACS) designed to meet Range Safety's link margin and latency requirements for vehicle command and telemetry data. The goals of STACS are to improve Range Safety operations and expand tracking capabilities for space vehicles. STACS will track the vehicle, receive commands, and send telemetry data through the space-based asset, which will dramatically reduce dependence on ground-based assets. The other step was the Low-Cost Tracking and Data Relay Satellite System (TDRSS) Transceiver (LCT2), developed by the Wallops Flight Facility (WFF), which allows the vehicle to communicate with a geosynchronous relay satellite. Although the GMTU and LCT2 were independently implemented and tested, the design collaboration of KSC and WFF engineers allowed GMTU and LCT2 to be integrated into one enclosure, leading to the final STACS. In operation, GMTU needs only a radio frequency (RF) input from a GPS antenna and outputs position and velocity data to the vehicle through a serial or pulse code modulation (PCM) interface. GMTU includes one commercial GPS receiver board and a custom board, the Command and Telemetry Processor (CTP) developed by KSC. The CTP design is based on a field-programmable gate array (FPGA) with embedded processors to support GPS functions.

Acute-On-Chronic Liver Failure: Causes, Clinical Characteristics and Predictors of Mortality.

PubMed

Tasneem, Abbas Ali; Luck, Nasir Hassan

2017-01-01

To determine the causes, characteristics and predictors of mortality in patients with acute-on-chronic liver failure (ACLF). Cross-sectional study. Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, from July 2014 to June 2016. All patients with acute-on-chronic liver disease (ACLD) with ages > 12 were included. Patients with ACLF, as defined by the Asian Pacific Association for the Study of Liver (APASL, 2014) were identified. Predictors of mortality were identified using chi-square or Fisher's exact test. Included in the study were 72 patients with mean age of 36.71 years, 46 (63.9%) being males. Among them, 61 developed ACLF. Commonest causes of chronic liver disease (CLD) were chronic viral hepatitis (37, 51.4%) and autoimmune hepatitis (14, 19.4%). Commonest causes of acute liver injury (ALI) were acute viral hepatitis (24, 33.3%) and drug induced liver injury (DILI) (17, 23.6%). Among those with ACLF, 24 (39.3%) patients died with median survival of 17.1 ±13.5 days. Mortality was significantly associated with Child Turcotte Pugh (CTP) score ≥13 (p=0.010), model for end-stage liver disease (MELD) score ≥30 (p=0.001), age >40 years (p=0.036), organ failures (OF) ≥3 (p <0.0001), portosystemic encephalopathy (PSE) (p <0.0001), renal failure (p <0.0001) and urosepsis (p <0.0001). Acute viral hepatitis and DILI are commonest causes of ACLF. Mortality is high in ACLF patients having OF ≥3, CTP ≥13, MELD ≥30, age >40 years, PSE, renal failure and urosepsis.

SRNL SHELF LIFE STUDIES - SCC STUDIES AT ROOM TEMPERTURE [stress corrosion cracking

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

Mickalonis, J.; Duffey, J.

Phase II, Series 2 corrosion testing performed by the Savannah River National Laboratory (SRNL) for the Department of Energy 3013 container has been completed. The corrosion tests are part of an integrated plan conducted jointly by Los Alamos National Laboratory and the Savannah River Site. SRNL was responsible for conducting corrosion studies in small-scale vessels to address the influence of salt composition, water loading, and type of oxide/salt contact on the relative humidity inside a 3013 container and on the resulting corrosion of Type 304L and 316L stainless steel (304L and 316L). This testing was conducted in two phases: Phasemore » I evaluated a broad spectrum of salt compositions and initial water loadings on the salt mixtures exposed to 304L and 316L and the resulting corrosion; Phase II evaluated the corrosion of 304L at specific water loadings and a single salt composition. During Phase I testing at high initial moisture levels (0.35 to 1.24 wt%)a, the roomtemperature corrosion of 304L exposed to a series of plutonium oxide/chloride salt mixtures ranged from superficial staining to pitting and stress corrosion cracking (SCC). 304L teardrop coupons that exhibited SCC were directly exposed to a mixture composed of 98 wt % PuO2, 0.9 wt % NaCl, 0.9 wt % KCl, and 0.2 wt % CaCl2. Cracking was not observed in a 316L teardrop coupon. Pitting was also observed in this environment for both 304L and 316L with depths ranging from 20 to 100 μm. Neither pitting nor SCC was observed in mixtures with a greater chloride salt concentration (5 and 28 wt%). These results demonstrated that for a corrosive solution to form a balance existed between the water loading and the salt chloride concentration. This chloride solution results from the interaction of loaded water with the hydrating CaCl2 salt. In Phase II, Series 1 tests, the SCC results were shown to be reproducible with cracking occurring in as little as 85 days. The approximate 0.5 wt% moisture level was found to result in an initial relative humidity of ~55% within the small-scale vessels. Pits were found to be associated with cracks and appeared to act as initiators for the cracking. In a vapor-space only exposure, the weld oxide, which results from the TIG closure weld used to fabricate the teardrop coupon, was also shown to be more susceptible to pitting corrosion than a surface free from weld oxide. This result has important implications for the closure weld of the 3013 inner can since the weld oxide on the can internal surface cannot be removed. The results from the Phase II, Series 2 tests further demonstrated the significance of forming a solution with a critical chloride concentration for corrosion to proceed. 304L teardrop coupons were found to corrode only by pitting with a similar oxide/salt mixture as used in Series 1 testing but with a lower water loading of 0.2 wt%, which resulted in an initial relative humidity of 35-38%. These tests ran twice as long as those for Series 1 testing. The exposure condition was also found to impact the corrosion with salt-exposed surfaces showing lower corrosion resistance. Additional analyses of the Series 2 coupons are recommended especially for determining if cracks emanate from the bottom of pits. Data generated under the 2009 3013 corrosion test plan, as was presented here, increased the understanding of the corrosion process within a sealed 3013 container. Along with the corrosion data from destructive evaluations of 3013 containers, the inner can closure weld region (ICCWR) has been identified as the most vulnerable area of the inner can where corrosion may lead to corrosive species leaking to the interior surface of the outer container, thereby jeopardizing the integrity of the 3013 container. A new corrosion plan has been designed that will characterize the corrosion at the ICCWR of 3013 DEs as well as parameters affecting this corrosion.« less

Effect of Host Media on Microbial Influenced Corrosion due to Desulfotomaculum nigrificans

NASA Astrophysics Data System (ADS)

Lata, Suman; Sharma, Chhaya; Singh, Ajay K.

2013-04-01

This article reports about the tests carried to investigate microbial-induced corrosion on stainless steels due to sulfate-reducing bacteria sp. Desulfotomaculum nigrificans in different host media. Stainless steel 304L, 316L, and 2205 were selected for the test. Modified Baar's media (BM), sodium chloride solution, and artificial sea water (SW) were used as test solutions in anaerobic conditions. Electrochemical polarization and immersion test were performed to estimate the extent of corrosion rate and pitting on stainless steels. SEM/EDS were used to study the details inside/outside pits formed on the corroded samples. Biofilm formed on corroded coupons was analyzed for its components by UV/Visible spectroscopy. Corrosion attack on the test samples was observed maximum in case of exposure to SW followed by NaCl solution, both having sulfide and chloride whereas stainless steel exposed to BM, having sulfide, showed minimum attack. Tendency of extracellular polymeric substances to bind metal ions is observed to be responsible for governing the extent of corrosion attack.

Effects of Variations in Salt-Spray Conditions on the Corrosion Mechanisms of an AE44 Magnesium Alloy

DOE PAGES

Martin, Holly J.; Horstemeyer, M. F.; Wang, Paul T.

2010-01-01

The understanding of how corrosion affects magnesium alloys is of utmost importance as the automotive and aerospace industries have become interested in the use of these lightweight alloys. However, the standardized salt-spray test does not produce adequate corrosion results when compared with field data, due to the lack of multiple exposure environments. This research explored four test combinations through three sets of cycles to determine how the corrosion mechanisms of pitting, intergranular corrosion, and general corrosion were affected by the environment. Of the four test combinations, Humidity-Drying was the least corrosive, while the most corrosive test condition was Salt Spray-Humidity-Drying.more » The differences in corrosivity of the test conditions are due to the various reactions needed to cause corrosion, including the presence of chloride ions to cause pit nucleation, the presence of humidity to cause galvanic corrosion, and the drying phase which trapped chloride ions beneath the corrosion by-products.« less

Quality Assurance Project Plan for the treatability study of in situ vitrification of Seepage Pit 1 in Waste Area Grouping 7 at Oak Ridge National Laboratory

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

NONE

This Quality Assurance Project Plan (QAPjP) establishes the quality assurance procedures and requirements to be implemented for the control of quality-related activities for Phase 3 of the Treatability Study (TS) of In Situ Vitrification (ISV) of Seepage Pit 1, ORNL Waste Area Grouping 7. This QAPjP supplements the Quality Assurance Plan for Oak Ridge National Laboratory Environmental Restoration Program by providing information specific to the ISV-TS. Phase 3 of the TS involves the actual ISV melt operations and posttest monitoring of Pit 1 and vicinity. Previously, Phase 1 activities were completed, which involved determining the boundaries of Pit 1, usingmore » driven rods and pipes and mapping the distribution of radioactivity using logging tools within the pipes. Phase 2 involved sampling the contents, both liquid and solids, in and around seepage Pit 1 to determine their chemical and radionuclide composition and the spatial distribution of these attributes. A separate QAPjP was developed for each phase of the project. A readiness review of the Phase 3 activities presented QAPjP will be conducted prior to initiating field activities, and an Operational Acceptance, Test (OAT) will also be conducted with no contamination involved. After, the OAT is complete, the ISV process will be restarted, and the melt will be allowed to increase with depth and incorporate the radionuclide contamination at the bottom of Pit 1. Upon completion of melt 1, the equipment will be shut down and mobilized to an adjacent location at which melt 2 will commence.« less

Effect of IGF1, GH, and PIT1 markers on the genetic parameters of growth and reproduction traits in Canchim cattle.

PubMed

Grossi, Daniela do Amaral; Buzanskas, Marcos Eli; Grupioni, Natalia Vinhal; de Paz, Claudia Cristina Paro; Regitano, Luciana Correia de Almeida; de Alencar, Maurício Mello; Schenkel, Flávio Schramm; Munari, Danísio Prado

2015-01-01

The availability of dense genomic information has increased genome-wide association studies for the bovine species; however research to assess the effect of single genes on production traits is still important to elucidate the genes functions. On this study the association of IGF1, GH, and PIT1 markers with growth and reproductive traits (birth weight, weaning weight, weight at 12 and 18 months of age, preweaning average daily weight gain, age and weight at first calving, and scrotal circumference at 12 and 18 months of age) were assessed by means of the variance component approach. The phenotypes were adjusted and then analyzed under two animal models, one which considered the polygenic and genotype (IGF1, GH or PIT1 markers) effects (Model 1), and the other which considers only the polygenic effect (Model 2). When the likelihood ratio test and the Bonferroni correction was applied at 5 % significance level, the genetic markers for the IGF1, GH, and PIT1 genes did not influence significantly the traits (p > 0.002). However, evidence of association of IGF1 with birth weight (p = 0.06) and GH with weight at first calving (p = 0.03) and with weight at 12 months of age (p = 0.08) was observed. In conclusion we could not confirm the associations between IGF1, GH, and PIT1 and growth traits that were previously reported in Canchim cattle, and no association was observed between these genes and reproductive traits. Future studies involving functional markers of IGF1, GH and PIT1 genes may help to clarify the role of these genes in growth and reproductive processes.

A distinct section of the Early Bronze Age society? Stable isotope investigations of burials in settlement pits and multiple inhumations of the Únětice culture in central Germany.

PubMed

Knipper, Corina; Fragata, Matthias; Nicklisch, Nicole; Siebert, Angelina; Szécsényi-Nagy, Anna; Hubensack, Vera; Metzner-Nebelsick, Carola; Meller, Harald; Alt, Kurt W

2016-03-01

Inhumations in so-called settlement pits and multiple interments are subordinate burial practices of the Early Bronze Age Únětice culture in central Germany (2200-1700/1650 BC). The majority of the Únětice population was entombed as single inhumations in rectangular grave pits with a normative position of the body. The goal of the study was to test archaeological hypotheses that the deviant burials may represent socially distinct or nonlocal individuals. The study comprised up to two teeth and one bone each of 74 human individuals from eight sites and faunal comparative samples. The inhumations included regular, deviant burials in so-called settlement or storage pits, and multiple burials. We investigated radiogenic strontium isotope compositions of tooth enamel ((87) Sr/(86) Sr) and light stable isotope ratios of carbon and nitrogen of bone collagen (δ(13) C, δ(15) N) aiming at the disclosure of residential changes and dietary patterns. Site-specific strontium isotope data ranges mirror different geological properties including calcareous bedrock, loess, and glacial till. Independent from burial types, they disclose low portions of nonlocal individuals of up to some 20% at the individual sites. The light stable isotope ratios of burials in settlement pits and rectangular graves overlap widely and indicate highly similar dietary habits. The analytical results let to conclude that inhumations in settlement pits and multiple burials were two of the manifold burial practices of the Early Bronze Age. The selection criteria of the individuals for the different forms of inhumation remained undisclosed. © 2015 Wiley Periodicals, Inc.

Repeatability of quantitative parameters of 18F-fluoride PET/CT and biochemical tumour and specific bone remodelling markers in prostate cancer bone metastases.

PubMed

Wassberg, Cecilia; Lubberink, Mark; Sörensen, Jens; Johansson, Silvia

2017-12-01

18F-fluoride PET/CT exhibits high sensitivity to delineate and measure the extent of bone metastatic disease in patients with prostate cancer. 18F-fluoride PET/CT could potentially replace traditional bone scintigraphy in clinical routine and trials. However, more studies are needed to assess repeatability and biological uptake variation. The aim of this study was to perform test-retest analysis of quantitative PET-derived parameters and blood/serum bone turnover markers at the same time point. Ten patients with prostate cancer and verified bone metastases were prospectively included. All underwent two serial 18F-fluoride PET/CT at 1 h post-injection. Up to five dominant index lesions and whole-body 18F-fluoride skeletal tumour burden were recorded per patient. Lesion-based PET parameters were SUVmax, SUVmean and functional tumour volume applying a VOI with 50% threshold (FTV 50% ). The total skeletal tumour burden, total lesion 18F-fluoride (TLF), was calculated using a threshold of SUV of ≥15. Blood/serum biochemical bone turnover markers obtained at the time of each PET were PSA, ALP, S-osteocalcin, S-beta-CTx, 1CTP and BAP. A total of 47 index lesions and a range of 2-122 bone metastases per patient were evaluated. Median time between 18F-fluoride PET/CT was 7 days (range 6-8 days). Repeatability coefficients were for SUVmax 26%, SUVmean 24%, FTV 50% for index lesions 23% and total skeletal tumour burden (TLF) 35%. Biochemical bone marker repeatability coefficients were for PSA 19%, ALP 23%, S-osteocalcin 18%, S-beta-CTx 22%, 1CTP 18% and BAP 23%. Quantitative 18F-fluoride uptake and simultaneous biochemical bone markers measurements are reproducible for prostate cancer metastases and show similar magnitude in test-retest variation.

Preliminary studies developing methods for the control of Chrysomya putoria, the African latrine fly, in pit latrines in The Gambia

PubMed Central

Lindsay, T C; Jawara, M; D'Alessandro, U; Pinder, M; Lindsay, S W

2013-01-01

Objective To explore ways of controlling Chrysomya putoria, the African latrine fly, in pit latrines. As pit latrines are a major source of these flies, eliminating these important breeding sites is likely to reduce village fly populations, and may reduce the spread of diarrhoeal pathogens. Methods We treated 24 latrines in a Gambian village: six each with (i) pyriproxyfen, an insect juvenile hormone mimic formulated as Sumilarv® 0.5G, a 0.5% pyriproxyfen granule, (ii) expanded polystyrene beads (EPB), (iii) local soap or (iv) no treatment as controls. Flies were collected using exit traps placed over the drop holes, weekly for five weeks. In a separate study, we tested whether latrines also function as efficient flytraps using the faecal odours as attractants. We constructed six pit latrines each with a built-in flytrap and tested their catching efficiency compared to six fish-baited box traps positioned 10 m from the latrine. Focus group discussions conducted afterwards assessed the acceptability of the flytrap latrines. Results Numbers of emerging C. putoria were reduced by 96.0% (95% CIs: 94.5–97.2%) 4–5 weeks after treatment with pyriproxyfen; by 64.2% (95% CIs: 51.8–73.5%) after treatment with local soap; by 41.3% (95% CIs = 24.0–54.7%) after treatment with EPB 3–5 weeks after treatment. Flytraps placed on latrines collected C. putoria and were deemed acceptable to local communities. Conclusions Sumilarv 0.5G shows promise as a chemical control agent, whilst odour-baited latrine traps may prove a useful method of non-chemical fly control. Both methods warrant further development to reduce fly production from pit latrines. A combination of interventions may prove effective for the control of latrine flies and the diseases they transmit. PMID:23198767

Association between self-reported bruxism activity and occurrence of dental attrition, abfraction, and occlusal pits on natural teeth.

PubMed

Tsiggos, Nikolaos; Tortopidis, Dimitrios; Hatzikyriakos, Andreas; Menexes, George

2008-07-01

It is unclear whether subjects who report tooth clenching and/or grinding have more noticeable clinical signs of dental attrition, abfractions, and occlusal pits on their natural teeth than subjects who do not report bruxism activity. The purpose of this study was to determine whether there was an association between self-reported (or not reported) bruxism activity and occurrence of dental attrition (anterior, posterior), abfractions, and occlusal pits on natural teeth. One hundred and two volunteer adult Greek subjects (mean age 44.6 +/-5.7 years) were classified into 2 groups (50 self-reported bruxers and 52 nonbruxers) according to 2 inquires regarding grinding and/or clenching of their teeth. Dental attrition (anterior, posterior) was assessed by 2 calibrated experienced examiners on diagnostic casts on a tooth-by-tooth basis, using a previously well established ordinal scale. Abfraction lesions (V-shaped, in the cervical region) and occlusal pits were recorded if these clinical signs were found on at least 2 natural teeth. Statistical comparisons between the 2 groups relative to the distribution of the occurrence of the 4 clinical signs were performed by means of the exact version of the chi-square test. The Fisher's exact test was used for the comparison of percentages. The intra- and interexaminer reliability was assessed by means of the Cohen's kappa coefficient (alpha=.05). The results demonstrated that there was a significant association between self-reported bruxism and occurrence of the 4 clinical signs. Although the 2 groups were significantly different according to the distribution of the 4 clinical signs, the greatest differences occurred for the anterior and posterior attrition signs. In this study, the occurrence of 4 clinical signs (posterior or anterior dental attrition, abfractions, and occlusal pits) was associated with self-reported bruxers. It is suggested that, primarily, signs of dental attrition may differentiate self-reported bruxers from nonbruxer subjects.

Phosphate (Pi)-regulated heterodimerization of the high-affinity sodium-dependent Pi transporters PiT1/Slc20a1 and PiT2/Slc20a2 underlies extracellular Pi sensing independently of Pi uptake.

PubMed

Bon, Nina; Couasnay, Greig; Bourgine, Annabelle; Sourice, Sophie; Beck-Cormier, Sarah; Guicheux, Jérôme; Beck, Laurent

2018-02-09

Extracellular phosphate (P i ) can act as a signaling molecule that directly alters gene expression and cellular physiology. The ability of cells or organisms to detect changes in extracellular P i levels implies the existence of a P i -sensing mechanism that signals to the body or individual cell. However, unlike in prokaryotes, yeasts, and plants, the molecular players involved in P i sensing in mammals remain unknown. In this study, we investigated the involvement of the high-affinity, sodium-dependent P i transporters PiT1 and PiT2 in mediating P i signaling in skeletal cells. We found that deletion of PiT1 or PiT2 blunted the P i -dependent ERK1/2-mediated phosphorylation and subsequent gene up-regulation of the mineralization inhibitors matrix Gla protein and osteopontin. This result suggested that both PiTs are necessary for P i signaling. Moreover, the ERK1/2 phosphorylation could be rescued by overexpressing P i transport-deficient PiT mutants. Using cross-linking and bioluminescence resonance energy transfer approaches, we found that PiT1 and PiT2 form high-abundance homodimers and P i -regulated low-abundance heterodimers. Interestingly, in the absence of sodium-dependent P i transport activity, the PiT1-PiT2 heterodimerization was still regulated by extracellular P i levels. Of note, when two putative P i -binding residues, Ser-128 (in PiT1) and Ser-113 (in PiT2), were substituted with alanine, the PiT1-PiT2 heterodimerization was no longer regulated by extracellular P i These observations suggested that P i binding rather than P i uptake may be the key factor in mediating P i signaling through the PiT proteins. Taken together, these results demonstrate that P i -regulated PiT1-PiT2 heterodimerization mediates P i sensing independently of P i uptake. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Analysis of the bacterial community in aged and aging pit mud of Chinese Luzhou-flavour liquor by combined PCR-DGGE and quantitative PCR assay.

PubMed

Liang, Huipeng; Li, Wenfang; Luo, Qingchun; Liu, Chaolan; Wu, Zhengyun; Zhang, Wenxue

2015-10-01

The community structure of bacteria in aged and aging pit mud, which was judged according to their sensory and physicochemical characteristics, was analysed using polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE) and quantitative real-time PCR (qPCR). The phyla Firmicutes, Actinobacteria, Proteobacteria, Synergistetes and Unclassified Bacteria were detected and the fermentative Firmicutes was predominant in both types of pit mud in the PCR-DGGE analysis. Among Firmicutes, Clostridiales was dominant in aged pit mud while Bacillales and Lactobacillales were dominant in aging pit mud. The diversity of bacterial communities in aged pit mud was higher than that in aging pit mud. In the qPCR analysis the abundance of Clostridium IV in aged pit mud was higher than that in aging pit mud and there were significant differences in the quantity of Clostridium IV between aged and aging pit mud of the same cellar (P < 0.05). There were some significant differences in the microbial community structure between aged and aging pit mud. The differences in the quantity of Clostridium IV might be involved in the distinction that the aged pit mud has a strong aroma while the aging pit mud does not. © 2014 Society of Chemical Industry.